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[0] Suner S, Fellows MR, Vargas-Irwin C, Nakata GK, Donoghue JP, Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex.IEEE Trans Neural Syst Rehabil Eng 13:4, 524-41 (2005 Dec)

[0] Westby GW, Wang H, A floating microwire technique for multichannel chronic neural recording and stimulation in the awake freely moving rat.J Neurosci Methods 76:2, 123-33 (1997 Oct 3)

[0] Rousche PJ, Normann RA, Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.J Neurosci Methods 82:1, 1-15 (1998 Jul 1)

[0] Isoda M, Hikosaka O, Role for subthalamic nucleus neurons in switching from automatic to controlled eye movement.J Neurosci 28:28, 7209-18 (2008 Jul 9)

[0] Kipke DR, Vetter RJ, Williams JC, Hetke JF, Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex.IEEE Trans Neural Syst Rehabil Eng 11:2, 151-5 (2003 Jun)

[0] Kennedy PR, Bakay RA, Moore MM, Adams K, Goldwaithe J, Direct control of a computer from the human central nervous system.IEEE Trans Rehabil Eng 8:2, 198-202 (2000 Jun)[1] Kennedy PR, Mirra SS, Bakay RA, The cone electrode: ultrastructural studies following long-term recording in rat and monkey cortex.Neurosci Lett 142:1, 89-94 (1992 Aug 3)

[0] Porada I, Bondar I, Spatz WB, Kruger J, Rabbit and monkey visual cortex: more than a year of recording with up to 64 microelectrodes.J Neurosci Methods 95:1, 13-28 (2000 Jan 31)

[0] Nicolelis MA, Dimitrov D, Carmena JM, Crist R, Lehew G, Kralik JD, Wise SP, Chronic, multisite, multielectrode recordings in macaque monkeys.Proc Natl Acad Sci U S A 100:19, 11041-6 (2003 Sep 16)

[0] Sodagar AM, Wise KD, Najafi K, A fully integrated mixed-signal neural processor for implantable multichannel cortical recording.IEEE Trans Biomed Eng 54:6 Pt 1, 1075-88 (2007 Jun)

[0] Aflalo TN, Graziano MS, Relationship between unconstrained arm movements and single-neuron firing in the macaque motor cortex.J Neurosci 27:11, 2760-80 (2007 Mar 14)

[0] Moran DW, Schwartz AB, Motor cortical representation of speed and direction during reaching.J Neurophysiol 82:5, 2676-92 (1999 Nov)

[0] Csicsvari J, Henze DA, Jamieson B, Harris KD, Sirota A, Bartho P, Wise KD, Buzsaki G, Massively parallel recording of unit and local field potentials with silicon-based electrodes.J Neurophysiol 90:2, 1314-23 (2003 Aug)

[1] Obeid I, Nicolelis MA, Wolf PD, A low power multichannel analog front end for portable neural signal recordings.J Neurosci Methods 133:1-2, 27-32 (2004 Feb 15)

[0] Kennedy PR, Mirra SS, Bakay RA, The cone electrode: ultrastructural studies following long-term recording in rat and monkey cortex.Neurosci Lett 142:1, 89-94 (1992 Aug 3)

[0] Boline J, Ashe J, On the relations between single cell activity in the motor cortex and the direction and magnitude of three-dimensional dynamic isometric force.Exp Brain Res 167:2, 148-59 (2005 Nov)

[0] Ashe J, Georgopoulos AP, Movement parameters and neural activity in motor cortex and area 5.Cereb Cortex 4:6, 590-600 (1994 Nov-Dec)

[0] Maier MA, Bennett KM, Hepp-Reymond MC, Lemon RN, Contribution of the monkey corticomotoneuronal system to the control of force in precision grip.J Neurophysiol 69:3, 772-85 (1993 Mar)[1] Smith AM, Hepp-Reymond MC, Wyss UR, Relation of activity in precentral cortical neurons to force and rate of force change during isometric contractions of finger muscles.Exp Brain Res 23:3, 315-32 (1975 Sep 29)

[0] Hepp-Reymond M, Kirkpatrick-Tanner M, Gabernet L, Qi HX, Weber B, Context-dependent force coding in motor and premotor cortical areas.Exp Brain Res 128:1-2, 123-33 (1999 Sep)

[0] Thach WT, Correlation of neural discharge with pattern and force of muscular activity, joint position, and direction of intended next movement in motor cortex and cerebellum.J Neurophysiol 41:3, 654-76 (1978 May)

[0] Amirikian B, Georgopoulos AP, Directional tuning profiles of motor cortical cells.Neurosci Res 36:1, 73-9 (2000 Jan)

[0] Teich MC, Heneghan C, Lowen SB, Ozaki T, Kaplan E, Fractal character of the neural spike train in the visual system of the cat.J Opt Soc Am A Opt Image Sci Vis 14:3, 529-46 (1997 Mar)

[0] Afanas'ev SV, Tolkunov BF, Rogatskaya NB, Orlov AA, Filatova EV, Sequential rearrangements of the ensemble activity of putamen neurons in the monkey brain as a correlate of continuous behavior.Neurosci Behav Physiol 34:3, 251-8 (2004 Mar)

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ref: -2021 tags: FIBSEM electron microscopy presynaptic plasticity activity Funke date: 10-12-2021 17:03 gmt revision:0 [head]

Ultrastructural readout of in vivo synaptic activity for functional connectomics

  • Anna Simon, Arnd Roth, Arlo Sheridan, Mehmet Fişek, Vincenzo Marra, Claudia Racca, View ORCID ProfileJan Funke, View ORCID ProfileKevin Staras, Michael Häusser
  • Did FIB-SEM on FM1-43 dye labeled synapses, then segmented the cells using machine learning, as Jan has pioneered.
    • FM1-43FX is membrane impermeable, and labels only synaptic vesicles that have been recycled after dye loading. (Invented in 1992!)
    • FM1-43FX is also able to photoconvert diaminobenzidene (DAB) into a amorphous highly conjugated polymer with high affinity for osmium tetroxide
  • This allows for a snapshot of ultrastructural presynaptic plasticity / activity.
  • N=84 boutons, but n=7 pairs / triples of boutons from the same axon.
    • These boutons have the same presynaptic spiking activity, and hence are expected to have the same release probability, and hence the same photoconversion (PC) labeling.
      • But they don't! The ratio of PC+ vesicle numbers between boutons on the same neuron is low, mean < 0.4, which suggests some boutons have high neurotransmitter release and recycling, others have low...
  • Quote in the abstract: We also demonstrate that neighboring boutons of the same axon, which share the same spiking activity, can differ greatly in their presynaptic release probability.
    • Well, sorta, the data here is a bit weak. It might all be lognormal fluctuations, as has been well demonstrated.
    • When I read it I was excited to think of the influence of presynaptic inhibition / modulation, which has not been measured here, but is likely to be important.

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ref: -2015 tags: conjugate light electron tomography mouse visual cortex fluorescent label UNC cryoembedding date: 03-11-2019 19:37 gmt revision:1 [0] [head]

PMID-25855189 Mapping Synapses by Conjugate Light-Electron Array Tomography

  • Use aligned interleaved immunofluorescence imaging follwed by array EM (FESEM). 70nm thick sections.
  • Of IHC, tissue must be dehydrated & embedded in a resin.
  • However, the dehydration disrupts cell membranes and ultrastructural details viewed via EM ...
  • Hence, EM microscopy uses osmium tetroxide to cross-link the lipids.
  • ... Yet that also disrupt / refolds the poteins, making IHC fail.
  • Solution is to dehydrate & embed at cryo temp, -70C, where the lipids do not dissolve. They used Lowicryl HM-20.
  • We show that cryoembedding provides markedly improved ultrastructure while still permitting multiplexed immunohistochemistry.

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ref: -0 tags: insertion speed needle neural electrodes force damage injury cassanova date: 06-01-2018 23:51 gmt revision:0 [head]

Effect of Needle Insertion Speed on Tissue Injury, Stress, and Backflow Distribution for Convection-Enhanced Delivery in the Rat Brain

  • Tissue damage, evaluated as the size of the hole left by the needle after retraction, bleeding, and tissue fracturing, was found to increase for increasing insertion speeds and was higher within white matter regions.
    • A statistically significant difference in hole areas with respect to insertion speed was found.
  • While there are no previous needle insertion speed studies with which to directly compare, previous electrode insertion studies have noted greater brain surface dimpling and insertion forces with increasing insertion speed [43–45]. These higher deformation and force measures may indicate greater brain tissue damage which is in agreement with the present study.
  • There are also studies which have found that fast insertion of sharp tip electrodes produced less blood vessel rupture and bleeding [28,29].
    • These differences in rate dependent damage may be due to differences in tip geometry (diameter and tip) or tissue region, since these electrode studies focus mainly on the cortex [28,29].
    • In the present study, hole measurements were small in the cortex, and no substantial bleeding was observed in the cortex except when it was produced during dura mater removal.
    • Any hemorrhage was observed primarily in white matter regions of the external capsule and the CPu.

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ref: -0 tags: insertion speed neural electrodes force damage date: 06-01-2018 23:38 gmt revision:2 [1] [0] [head]

In vivo evaluation of needle force and friction stress during insertion at varying insertion speed into the brain

  • Targeted at CED procedures, but probably applicable elsewhere.
  • Used a blunted 32ga CA glue filled hypodermic needle.
  • Sprague-dawley rats.
  • Increased insertion speed corresponds with increased force, unlike cardiac tissue.
  • Greatuer surface dimpling before failure results in larger regions of deformed tissue and more energy storage before needle penetration.
  • In this study (blunt needle) dimpling increased with insertion speed, indicating that more energy was transferred over a larger region and increasing the potential for injury.
  • However, friction stresses likely decrease with insertion speed since larger tissue holes were measured with increasing insertion speeds indicating lower frictional stresses.
    • Rapid deformation results in greater pressurization of fluid filled spaces if fluid does not have time to redistribute, making the tissue effectively stiffer. This may occur in compacted tissues below or surrounding the needle and result in increasing needle forces with increasing needle speed.

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ref: -0 tags: NET probes SU-8 microfabrication sewing machine carbon fiber electrode insertion mice histology 2p date: 12-29-2017 04:38 gmt revision:1 [0] [head]

PMID-28246640 Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration

  • SU-8 asymptotic H2O absorption is 3.3% in PBS -- quite a bit higher than I expected, and higher than PI.
  • Faced yield problems with contact litho at 2-3um trace/space.
  • Good recordings out to 4 months!
  • 3 minutes / probe insertion.
  • Fab:
    • Ni release layer, Su-8 2000.5. "excellent tensile strength" --
      • Tensile strength 60 MPa
      • Youngs modulus 2.0 GPa
      • Elongation at break 6.5%
      • Water absorption, per spec sheet, 0.65% (but not PBS)
    • 500nm dielectric; < 1% crosstalk; see figure S12.
    • Pt or Au rec sites, 10um x 20um or 30 x 30um.
    • FFC connector, with Si substrate remaining.
  • Used transgenic mice, YFP expressed in neurons.
  • CA glue used before metabond, followed by Kwik-sil silicone.
  • Neuron yield not so great -- they need to plate the electrodes down to acceptable impedance. (figure S5)
    • Measured impedance ~ 1M at 1khz.
  • Unclear if 50um x 1um is really that much worse than 10um x 1.5um.
  • Histology looks realyl great, (figure S10).
  • Manuscript did not mention (though the did at the poster) problems with electrode pull-out; they deal with it in the same way, application of ACSF.

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ref: Salcman-1973.07 tags: Salcman MEA microelectrodes chronic recording glass cyanocrylate date: 12-29-2017 04:33 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-4708761 Design, Fabrication, and In Vivo Behavior of Chronic Recording Intracortical Microelectrodes

  • Teflon-coated 25um Pt-Ir (90/10)
  • Heat fuse this with a glass micropipette & backfill with cyanoacrylate. {1011}
    • Isobutyl acrylate is hydrolysed more slowly and hence is less toxic to the surronding tissue
    • cyanoacrylate is apparently biodegradable.
  • Durable, stable: one electrode displayed a single cortical spike (though not necessarily the same one) for more than 90 consecutive days.
  • unacceptably low impedance = 100K or less
  • Unit activity was present only 10-24H after surgery.
  • formal review of even older microelectrode studies.
  • 10nA should be 100x too small to have any effect on a platinum tip [17]
  • A seperable cell with a SNR of 3:1 would become lost if the electrode tip moved 15um away from a 20um soma.
    • "It becomes clear that the problem of holding single units for prolonged periods in the unrestrained animal is not achieved without considerable difficulty". Yet they think they have solved it.

____References____

Salcman, Michael and Bak, Martin J. Design, Fabrication, and In Vivo Behavior of Chronic Recording Intracortical Microelectrodes Biomedical Engineering, IEEE Transactions on BME-20 4 253 -260 (1973)

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ref: -0 tags: robinson pasquali carbon nanotube fiber fluidic injection dextran neural electrode date: 12-28-2017 04:20 gmt revision:0 [head]

PMID-29220192 Fluidic Microactuation of Flexible Electrodes for Neural Recording.

  • Use viscous dextran solution + PDMS channel system
  • Durotomy (of course)
  • Parylene-C insulated carbon fiber electrodes, cut with FIB or razor blade
  • Used silver ink to electrically / mechanically attach for recordings.
  • Tested in hydra, rat brain slice (reticular formation of thalamus), and in-vivo rat.
  • Electrodes, at 12um diameter, E=120GPa, are approximately 127x stiffer than one 4x20um PI (E=9GPa) probe. Less damage though.

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ref: Gilgunn-2012 tags: kozai neural recording electrodes compliant parylene flexible dissolve date: 12-28-2017 03:50 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-6170092 (pdf) An ultra-compliant, scalable neural probe with molded biodissolvable delivery vehicle

    • Optical coherence tomography is cool.
  • Large footprint - 150 or 300um, 135um thick (13500 or 40500 um^2; c.f. tungsten needle 1963 (50um) or 490 (25um) um^2.)
  • Delivery vehicle is fabricated from biodissolvable carboxy-methylcellulose (CMC).
    • Device dissolves within three minutes of implantation.
    • Yet stiff enough to penetrate the dura of rats (with what degree of dimpling?)
    • Lithographic patterning process pretty clever, actually.
    • Parylene-X is ~ 1.1 um thick.
    • 500nm Pt is patterned via ion milling with a photoresist mask.
    • Use thin 20nm Cr etch mask for both DRIE (STS ICP) and parylene etch.
  • Probes are tiny -- 10um wide, 2.7um thick, coated in parylene-X.
  • CMC polymer tends to bend and warp due to stress -- must be clamped in a special jig.
  • No histology. Follow-up: {1399}

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ref: -0 tags: optogenetics micro LED flexible electrodes PET rogers date: 12-28-2017 03:24 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-23580530 Injectable, cellular-scale optoelectronics with applications for wireless optogenetics.

  • Supplementary materials
  • 21 authors, University Illinois at Urbana-Champaign, Tufts, China, Northwestern, Miami ..
  • GaN blue and green LEDs fabricated on a flexible substrate with stiff inserter.
    • Inserter is released in 15 min with a dissolving silk fibrin.
    • made of 250um thick SU-8 epoxy, reverse photocured on a glass slide.
  • GaN LEDS fabricated on a sapphire substrate & transfer printed via modified Karl-Suss mask aligner.
    • See supplemental materials for the intricate steps.
    • LEDs are 50um x 50um x 6.75um
  • Have integrated:
    • Temperature sensor (Pt serpentine resistor) / heater.
    • inorganic photodetector (IPD)
      • ultrathin silicon photodiode 1.25um thick, 200 x 200um^2, made on a SOI wafer
    • Pt extracellular recording electrode.
        • This insulated via 2um thick more SU-8.
  • Layers are precisely aligned and assembled via 500nm layer of epoxy.
    • Layers made of 6um or 2.5um thick mylar (polyethylene terephthalate (PET))
    • Layers joined with SU-8.
    • Wiring patterned via lift-off.
  • Powered via RF scavenging at 910 Mhz.
    • appeared to be simple, power in = light out; no data connection.
  • Tested vs control and fiber optic stimulation, staining for:
    • Tyrosine hydroxylase (makes l-DOPA)
    • c-fos, a neural activity marker
    • u-LEDs show significant activation.
  • Also tested for GFAP (astrocytes) and Iba1 (activated microglia); flexible & smaller devices had lower gliosis.
  • Next tested for behavior using a self-stimulation protocol; mice learned to self-stimulate to release DA.
  • Devices are somewhat reliable to 250 days!

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ref: Kozai-2009.11 tags: electrodes insertion Kozai flexible polymer momolayer date: 12-28-2017 02:59 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

PMID-19666051[0] Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain.

  • This study investigated the use of an electronegative (hydrophillic) self-assembled monolayer (SAM) as a coating on a stiff insertion shuttle to carry a polymer probe into the cerebral cortex, and then the detachment of the shuttle from the probe by altering the shuttle's hydrophobicity.
    • Used 11-mercaptoundecanoic acid.
    • Cr/Au (of course) evaporated on 15um thick Si shuttle.
    • SAM attracts water once inserted, causing the hydrophobic polymer to move away.
      • Why not make the polymer hydrophillic?
      • Is this just soap?
  • Used agarose brain model.
  • Good list of references for the justification of soft electrodes, and researched means for addressing this, mostly usnig polymer stiffeners.
    • "Computer models and experimental studies of the probe–tissue interface suggest that flexible and soft probes that approach the brain’s bulk material characteristics may help to minimize micromotion between the probe and surrounding tissue ({737}; {1203}; {1102}; {1200}; LaPlaca et al., 2005; {1216}; Neary et al., 2003 PMID-12657694; {1198})"
  • "However, polymer probes stick to metallic and silicon surfaces through hydrophobic interactions, causing the polymer probe to be carried out of the brain when the insertion shuttle is removed. The solution is to use a highly hydrophillic, electronegative, self-assembled monolayer coating on the shuttle.
  • Biran et al 2005 suggests that incremental damage due to stab wounds from the shuttle (needle) should be minor.
  • Probes: 12.5 um thick, 196 um wide, and 1.2cm long, polymide substrate and custom designed lithographed PDMS probes.
  • Polymer probes were inserted deep - 8.5 mm.
  • PDMS probes inserted with non-coated insertion shuttle resulted in explantation of the PDMS probe.

____References____

[0] Kozai TD, Kipke DR, Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain.J Neurosci Methods 184:2, 199-205 (2009 Nov 15)

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ref: -0 tags: platinum parylene electrodes brush dissolving stiffener gelatin date: 12-28-2017 02:44 gmt revision:0 [head]

PMID-27159159 Embedded Ultrathin Cluster Electrodes for Long-Term Recordings in Deep Brain Centers.

  • 12.5um pure Pt wires
  • Coated in 4um parylene-C
  • stiffened with gelatin
  • further protected with Kollicoat to retard dissolution.
  • Used a pulsed UV laser to ablate parylene, cut the platinum, and roughen the recording site.
  • See also {311}

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ref: -0 tags: polyimide electrodes immune response foreign body inflammation stiffener steiglitz date: 12-28-2017 02:37 gmt revision:0 [head]

PMID-27534649 Intracortical polyimide electrodes with a bioresorbable coating.

  • Molten saccharose was used as coating material.
  • 270 x 10um polyimide recording probes. (large!)
  • Tissue reaction seems to peak at 2 weeks-4weeks, and decline somewhere thereafter. (though there were not a great number of samples.)

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ref: -2001 tags: polyimide Kipke bioactive flexible electrode arrays date: 12-22-2017 01:16 gmt revision:2 [1] [0] [head]

PMID-11327505 Flexible polyimide-based intracortical electrode arrays with bioactive capability.

  • Appears to be the first or one of the first use of thin-film polyimide for intracortical recording; will have to cite.
  • Fab protocol: 500nm release thermal oxide, photo-paternable PI, Cr-Au metalization, O2 plasma de-scum for adhesion (ish?), <20um total thickness.
  • Conductive epoxy attachment to connector.

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ref: -0 tags: lieber mesh electronics SU-8 recording electrodes flexible polymer glass capillary date: 12-22-2017 00:14 gmt revision:0 [head]

PMID-29109247 Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology

  • Key change was the addition of multiple conductor traces per longitudinal mesh line; this allows them to get 64 or 128 channels per mesh without a dramatic increase in modulus.
  • The latitudinal / diagonal lines still displace tissue ...
  • And the injection mechanism, glass pipette, 650um OD, 400um ID, is pretty large, even for 128 channels.
  • Use carbon nanotube ink, custom CNC printer, to connect to FPC.
    • Pretty impressive that they can manipulate ~800nm thick Su-8 film intraop and have it work well!

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ref: -0 tags: electrode area review impedance date: 04-28-2017 17:55 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

Quick review of electrode area / impedance within m8ta:

  • {895} 500um^2
  • {311} 490um^2 nominal; 900k
  • {1040} 108um^2, plated from 5M to 1M.
  • Neuronexus: 177, 413um, 700um, and 1250um.
    • Suggest 177um for SUA, 413um for MUA.
    • Community consensus seems to be that these electrodes don't last as long, though.
    • Electroplating 177um^2 sites with PEDOT:PSS reduces impedance to 23k {1388}
  • {823} 122um^2 nominal
  • {736} 500um^2
  • {1027} (Utah) 1600um^2
    • Impedance: ~ 220K +-91K (in vivo -- large variance)
    • Blackrock site lists impedance @ 400k
  • SIrOF Utah array -- 3100um^2 (3.1e-5cm^2) -- large!
    • Impedance ~50K according to [www.blackrockmicro.com/userfiles/file/Microelectrode%20Arrays.pdf Blackrock product brochure].
  • PMID-20124668 (Utah again) 2000um^2, 125k Pt, 6k SIROF.
  • Neuropixel: 144um^2 acid-etched TiN
  • Carbon fiber: ~38 um^2, PEDOT:PSS or PEDOT:pTS started ~ 4M, plated down to ~ 130k initial, went up to 2M pSS, 840k pTS.

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ref: -2016 tags: Kozai carbon fiber microelectrodes JNE PEDOT PSS pTS date: 04-27-2017 01:42 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-27705958 Chronic in vivo stability assessment of carbon fiber microelectrode arrays.

  • showed excellent recording characteristics and nearly zero glial scarring.
  • 6.4um carbon fiber + 800nm parylene-C = 8.4um.
    • Cytec Thoronel T-650 CF, Youngs modulus = 255 GPa, tensile strength = 4.28 GPa, PAN-based.
  • Everything protected with our wonderful phenol epoxy 353NDT, heat-cure.
  • Used two coating solutions:
    • Solution of 0.01 M 3,4-ethylenedioxythiophene (483028, Sigma-Aldrich, St. Louis, MO): 0.1 M sodium p-toluenesulfonate (152536, Sigma-Aldrich, St. Louis, MO).
      • pTS is not that dissimilar from it's alkyl cousin, SPS, {1353}. Likely a soapy chemical due to the opposed methyl and sulfonic acid group; benzine will take up less room in the polymer c.f. SDS & may lower the oxidation potential of EDOT.
      • Tosylates have been explored as a EDOT counterion : PMID-22383043 Characterization of poly(3,4-ethylenedioxythiophene):tosylate conductive polymer microelectrodes for transmitter detection. and PEDOT-TMA
    • Solution was composed of 0.01 M 3,4-ethylene-dioxythiophene (483028, Sigma-Aldrich, St. Louis, MO):0.1 M polystyrene sulfonate (m.w. 70.000, 222271000, Acros, NJ).
    • For each solution the electrodeposition was carried out by applying 100 pA/channel for 600 s to form a layer of poly(3,4-ethylenedioxythiophene):sodium p-toluenesulfonate (PEDOT:pTS) or poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS).
      • Weird, would use voltage control here..
  • According to works by Green et al [45] and Hukins et al [46], equation (1) can be used to determine the aging time that
the fibers have undergone: t 37=t TQ10 T37)/10 t_{ 37} = t_T Q10^{T-37)/10} where t 37 t_{ 37} is the simulated aging time at 37 °C, t T t_T is the amount of real time that the samples have been kept at the elevated temperature, T T , and Q10 Q10 is an aging factor that is equal to 2, according to ASTM guidelines for polymer aging [47].
  • Show > 2MOhm impedance of the small-area electrodes. At the aging endpoint, PEDOT:pTS had about half the impedance of PEDOT:PSS.
    • 4M PSS, 7M pTS, both plated down to ~ 130k initial, went up to 2M pSS, 840k pTS.
  • Recording capability quite stellar
  • Likewise for the glial response.

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ref: -0 tags: PEDOT PSS electroplate eletrodeposition neural recording michigan probe stimulation CSC date: 04-27-2017 01:36 gmt revision:1 [0] [head]

PMID-19543541 Poly(3,4-ethylenedioxythiophene) as a micro-neural interface material for electrostimulation

  • 23k on a 177um^2 site.
  • demonstrated in-vitro durable stimulation.
  • Electrodeposited with 6na for 900 seconds per electrode.
    • Which is high -- c.f. 100pA for 600 seconds {1356}
  • Greater CSC and lower impedance / phase than (comparable?) Ir or IrOx plating.

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ref: -1977 tags: polyethylene surface treatment plasma electron irradiation mechanical testing saline seawater accelerated lifetime date: 04-15-2017 06:06 gmt revision:0 [head]

Enhancement of resistance of polyethylene to seawater-promoted degradation by surface modification

  • Polyethylene, when repeatedly stressed and exposed to seawater (e.g. ships' ropes), undergoes mechanical and chemical degradation.
  • Surface treatments of the polyethlyene can improve resistance to this degradation.
  • The author studied two methods of surface treatment:
    • Plasma (glow discharge, air) followed by diacid (adipic acid) or triisocyanate (DM100, = ?) co-polymerization
    • Electron irradiation with 500 kEV electrons.
  • Also mention CASING (crosslinking by activated species of inert gasses) as a popular method of surface treatment.
    • Diffuse-in crosslinkers is a third, popular these days ...
    • Others diffuse in at temperature e.g. a fatty acid - derived molecule, which is then bonded to e.g. heparin to reduce the thrombogenicity of a plastic.
  • Measured surface modifications via ATR IR (attenuated total reflectance, IR) and ESCA (aka XPS)
    • Expected results, carbonyl following the air glow discharge ...
  • Results:
    • Triisocyanate, ~ 6x improvement
    • diacid, ~ 50 x improvement.
    • electron irradiation, no apparent degradation!
      • Author's opinion that this is due to carbon-carbon crosslink leading to mechanical toughening (hmm, evidence?)
  • Quote: since the PE formulation studied here was low-weight, it was expected to lose crystallinity upon cyclic flexing; high density PE's have in fact been observed to become more crystalline with working.
    • Very interesting, kinda like copper. This could definitely be put to good use.
  • Low density polyethylene has greater chain branching and entanglement than high-density resins; when stressed the crystallites are diminished in total bulk, degrading tensile properties ... for high-density resins, mechanical working loosens up the structure enough to allow new crystallization to exceed stress-induced shrinkage of crystallites; hence, the crystallinity increases.

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ref: -0 tags: polyimide electrodes thermosonic bonding Stieglitz adhesion delamination date: 03-06-2017 21:58 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

IEEE-6347149 (pdf) Improved polyimide thin-film electrodes for neural implants 2012

  • Tested adhesion to Pt / SiC using accelerated aging in saline solution.
  • Targeted at retinal prostheses.
  • Layer stack:
    • 50nm SiC deposited through PECVD @ 100C using SPS, with low frequency RF modulation.
    • 100nm Pt
    • 100nm Au
    • 100nm Pt
      • These layers will alloy during cure, and hence reduce stress.
    • 30nm SiC
    • 10nm DLC (not needed, imho; PI sticks exceptionally well to clean SiC)
  • Recent studies have concluded that adhesion to PI is through carbon bindings and not through oxide formation.
    • Adhesion of polyimide to amorphous diamond-like carbon and SiC deteriorates at a minimal rate.
  • Delamination is caused by residual stress, which is not only inevetable but a major driving force for cracking in thin films.
    • Different CTE in layer stack -> different contraction when cooling from process temperature.
  • Platinum, which evaporates at 1770C, and is deposited ~100C (photoresists only withstand ~115C) results in a high-stress interface.
    • Pt - Carbon bonds only occur above 1000C
  • After 9 and 13 days of incubation the probes with 400 nm and 300nm of SiC, respectively, which were not tempered, showed complete delamination of the Pt from the SiC.
    • 60C, 0.9 M NaCl, 1 year.
    • The SiC remained attached to the PI.
      • Tempering: repeated treatment at 450C for 15 min in a N2 atmosphere.
    • All other probes remained stable.
  • Notably, used thermosonic bonding to the PI films, using sputtered (seed layer) then 12um electroplated Au.
  • Also: fully cured the base layer PI film.
  • Used oxygen plasma de-scum after patterning with resists to get better SiC adhesion to PI.
    • And better inter-layer adhesion (fully cured the first polyimide layer @ 450C).
  • Conclusion: "The fact that none of the tempered samples delaminated even after ~5 years of lifetime (extrapolated for 37 C) shows a tremendous increase in adhesion.

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ref: Schmidt-1993.11 tags: Normann utah array histology silicon electrode array cats date: 02-23-2017 22:03 gmt revision:4 [3] [2] [1] [0] [head]

PMID-8263001[0] Biocompatibility of silicon-based electrode arrays implanted in feline cortical tissue.

  • Tried two different times:
    • one day before euthanasia
    • 6 month implant.
  • Tried three different implants:
    • Uncoated silicon,
    • polymide coating
    • polymide coating with SiO2 adhesion layer / primer.
  • The last was the worst in terms of histopathological response.
  • Chronic implants showed relatively restrained immune response,
    • Gliosis was found around all tracks, 20-40um.
  • Encapsulation was less than 9um.
  • Edema and hemorrhage was minor but present on a subset of all implants.
  • Acute (24h) hemorrhage was more severe -- ~ 60%; edema ~ 20%.
  • Chronic histology revealed considerable macrophages w/ hemosiderin (a complex including ferritin)
  • See also [1]

____References____

[0] Schmidt S, Horch K, Normann R, Biocompatibility of silicon-based electrode arrays implanted in feline cortical tissue.J Biomed Mater Res 27:11, 1393-9 (1993 Nov)
[1] Jones KE, Campbell PK, Normann RA, A glass/silicon composite intracortical electrode array.Ann Biomed Eng 20:4, 423-37 (1992)

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ref: -0 tags: iridium oxide nanotube intracellular recording electroplate MEA date: 02-22-2017 22:41 gmt revision:0 [head]

PMID-24487777 Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials.

  • Electrodeposition of IrOx "magically" forms 500nm tubes.
  • Holes in Si3N4 / SiO2 were formed via e-beam lithography; underlying Pt wires via liftoff.
  • Showed long (minutes) intracellular access, though it tended to dip with time.

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ref: -0 tags: glassy carbon SU-8 pyrolysis CEC microelectrode stimulation stability platinum PEDOT date: 02-17-2017 00:05 gmt revision:2 [1] [0] [head]

A novel pattern transfer technique for mounting glassy carbon microelectrodes on polymeric flexible substrates

  • Use inert-atmosphere pyrolysis @ 900 - 1000 C of 20um SU-8 (which is aromatic) on a thermal oxide wafer.
  • Followed by spin & cure of PI.
  • Demonstrate strong carbonyl bonding of the glassy carbon with mechanical and FTIR testing.
  • Use of photosensitive PI allows through-vias to connect Cr/Au conductive traces.

PMID-28084398 Highly Stable Glassy Carbon Interfaces for Long-Term Neural Stimulation and Low-Noise Recording of Brain Activity

  • Use EIS to show superior charge-injection properties + stability of glassy carbon electrodes vs. Pt electrodes.
    • GC lasted > 5e6 pulses; Pt electrodes delaminated after 1e6 pulses.
    • Hydrogen bonding (above) clearly superior than neat PI-Pt interface
  • GC electrodes were, true to their name, glassy and much smoother than the platinum electrodes.
  • Further reduced impedance with PEDOT-PSS coating.
    • PEDOT-PSS coating on glassy carbon was, in their hands, far more stable than PEDOT-PSS on platinum.
  • All devices, GC, PEDOT:PSS, and Pt, had similar biocompatibility in their assay (figure 7)

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ref: -0 tags: bone marrow transplant chimera immune response to indwelling electrode implant capadona inflammation date: 02-02-2017 23:24 gmt revision:1 [0] [head]

PMID-24973296 The roles of blood-derived macrophages and resident microglia in the neuroinflammatory response to implanted intracortical microelectrodes.

  • Quite good introductory review on current understanding of immune / inflammatory / BBB breakdown response to indwelling neural implants.
  • Used chimera mice with marrow from CFP mice transplanted into irradiated hosts, so myeloid cells were labeled (including macrophages and monocytes).
    • Details of this process are properly fascinating ... there are clever ways of isolating and selecting the right marrow cells.
  • Implanted with a dummy Michigan style probe, 2mm x 123 um x 15um.
  • Histological processes and cell sorting / labeling also highly detailed.
  • 60% of the infiltrating cells (CFP+) are macrophages.
    • Within the total IBA1+ population (macrophages + microglia), we saw that only 20% of the total IBA1+ population was comprised of microglia at two weeks post implantation (Fig. 9G).
    • Additionally, at chronic time points (four, eight and sixteen weeks), we observed that less than 40% of the total IBA1+ population was comprised of microglia (Fig. 9G).
    • On the other hand, no significant differences were observed in microglia populations over time (Fig. 9G, Table 4). Together, our results suggest a predominant role of infiltrating macrophages surrounding implanted microelectrodes over time.
  • IBA1 = marker for ionized calcium binding adapter molecule, to label the total population of microglia/ macrophages (both resting and activated)
  • CD68 = activated microglia / macrophage.
    • Hard to discriminate microglia and infiltrating macrophages.
  • Interestingly, fluctuations in GFAP+ immunoreactivity correlated well with neuronal density and CFP+ immunoreactivty, suggesting a possible role of astrocytes in facilitating trafficking of blood-derived cells.
  • Contrary to what has been suggested by many intracortical microelectrode studies, a consistent connection was not found between activated microglia/macrophages and neuron density in our chimera models

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ref: Bartels-2008.09 tags: neurotrophic kennedy speech FM transmitter wireless Georga recording electrophysiology electrode date: 01-19-2017 02:18 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-18672003[0] Neurotrophic electrode: method of assembly and implantation into human motor speech cortex.

  • Glass electrode with 3-4 2mil Teflon insulated Au wires within it to record spiking.
  • Induce neurites (e.g. dendrites, axons, blood vessels, oligodendrocytes) to grow up into it using autologous sciatic nerve, and stay for the lifetime of the patient (Kennedy 1989) [1].
    • Histology has revealed axons, but not neurons, within the tissue inside the tip. (Kennedy 1989, 1992a.)
    • No glia in rat and monkey tests; PMID-1421115
    • Inserted 5-6mm into the cortex at an angle of 45 deg. far!?
  • Bipolar amplification on pairs of the Au wires.
  • patients damaged their electrodes due to spasms; same for monkeys, presumably. Seems the electronice and gold wires are also highly fragile. I'm quite familiar with this.
  • Includes a sine wave source for calibration. good idea!
  • Inductively powered @ 1Mhz.
  • FM modulation at 39.2Mz and 43.9Mhz. COTS?
    • The implantable electronics are bulky as can be seen in Figs. 14 and ​and 19. (what a mess?!)
  • 3 patients, 4 years in 2 patients that dies from unrelated causes, over 3 years in a third.
  • describe construction of electrode -- not complicated.

____References____

[0] Bartels J, Andreasen D, Ehirim P, Mao H, Seibert S, Wright EJ, Kennedy P, Neurotrophic electrode: method of assembly and implantation into human motor speech cortex.J Neurosci Methods 174:2, 168-76 (2008 Sep 30)
[1] Kennedy PR, The cone electrode: a long-term electrode that records from neurites grown onto its recording surface.J Neurosci Methods 29:3, 181-93 (1989 Sep)

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ref: -0 tags: kennedy neurotropic electrode date: 01-19-2017 01:47 gmt revision:2 [1] [0] [head]

PMID-9237542 Activity of single action potentials in monkey motor cortex during long-term task learning. Kennedy PR1, Bakay RA.'''

  • 2mm glass cone electrode, filled with matrigel and nerve growth factor, was implanted into layer 5/6 of the monkey motor cortex.
    • Matrigel: a solubilized basement membrane preparation extracted from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma, a tumor rich in such ECM proteins as laminin (a major component), collagen IV, heparin sulfate proteoglycans, entactin/nidogen, and a number of growth factors.
      • Used extensively in cell culture work.
      • Previous studies used 'autologous sciatic nerve'.
    • Of note, this was no less invasive than a Utah array; it's virtue lies in stability.
  • Incgrowing cells became mylenated [4]
  • Recording quality about the same as extracellular recordings: 40 to 80um amplitude.
    • Makes sense, as there was no reason for the neurites (no somas grew in!) to attach to the gold microwires.
  • Rather short communication describing what appears to be the idiosyncratic behavior of 3 neurons...

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ref: -0 tags: serial electron microscopy Lichtman reconstruction nervous tissue date: 01-17-2017 23:32 gmt revision:0 [head]

PMID-26232230 Saturated Reconstruction of a Volume of Neocortex.

  • Data presented at Cell "Big Questions in Neuroscience", perhaps the most impressive of the talks.

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ref: -0 tags: PEDOT electropolymerization electroplating gold TFB borate counterion acetonitrile date: 10-18-2016 07:49 gmt revision:3 [2] [1] [0] [head]

Electrochemical and Optical Properties of the Poly(3,4-ethylenedioxythiophene) Film Electropolymerized in an Aqueous Sodium Dodecyl Sulfate and Lithium Tetrafluoroborate Medium

  • EDOT has a higher oxidation potential than water, which makes polymers electropolymerized from water "poorly defined".
  • Addition of SDS lowers the oxidation potential to 0.76V, below that of EDOT in acetonitrile at 1.1V.
  • " The potential was first switched from open circuit potential to 0.5 V for 100 s before polarizing the electrode to the desired potential. This initial step was to allow double-layer charging of the Au electrode|solution interface, which minimizes the distortion of the polymerization current transient by double-layer capacitance charging.17,18 "
    • Huh, interesting.
  • Plated at 0.82 - 0.84V, 0.03M EDOT conc.
  • 0.1M LiBF4 anion / electrolyte; 0.07M SDS sufactant.
    • This SDS is incorporated into the film, and affects redox reactions as shown in the cyclic voltammagram (fig 4)
      • Doping level 0.36
    • BF4-, in comparison, can be driven out of the film.

Improvement of the Electrosynthesis and Physicochemical Properties of Poly(3,4-ethylenedioxythiophene) Using a Sodium Dodecyl Sulfate Micellar Aqueous Medium

  • "The oxidation potential of thiopene = 1.8V; water = 1.23V.
  • Claim: "The polymer films prepared in micellar medium [SDS] are more stable than those obtained in organic solution as demonstrated by the fact that, when submitted to a great number of redox cycles (n ≈ 50), there is no significant loss of their electroactivity (<10%). These electrochemical properties are accompanied by color changes of the film which turns from blue-black to red-purple upon reduction."
  • Estimate that there is about 21% DS- anions in the PEDOT - SDS films.
    • Cl - was at ~ 7%.
  • I'm still not sure about incorporating soap into the electroplating solution.. !

Electrochemical Synthesis of Poly(3,4-ethylenedioxythiophene) on Steel Electrodes: Properties and Characterization

  • 0.01M EDOT and 0.1M LiClO4 in acetonitrile.
  • Claim excellent adhesion & film properties to 316 SS.
  • Oxidation / electrodeposition at 1.20V; voltages higher than 1.7V resulted in flaky films.

PMID-20715789 Investigation of near ohmic behavior for poly(3,4-ethylenedioxythiophene): a model consistent with systematic variations in polymerization conditions.

  • Again use acetonitrile.
  • 1.3V vs Ag/AgCl electrode.
  • Perchlorate and tetraflouroborate both seemed the best counterions (figure 4).
  • Figure 5: Film was difficult to remove from surface.
    • They did use a polycrystaline Au layer:
    • "The plating process was allowed to run for 1 min (until approximately 100 mC had passed) at a constant potential of 0.3 V versus Ag/AgCl in 50 mM HAuCl4 prepared in 0.1 M NaCl."
  • Claim that the counterions are trapped; not in agreement with the SDS study above.
  • "Conditions for the consistent production of conducting polymer films employing potentiostatic deposition at 1.3 V for 60-90 s have been determined. The optimal concentration of the monomer is 0.0125 M, and that of the counterion is 0.05 M. "

PMID-24576579 '''Improving the performance of poly(3,4-ethylenedioxythiophene) for brain–machine interface applications"

  • Show that TFB (BF4-) is a suitable counterion for EDOT electropolymerization.
  • Comparison is between PEDOT:TFB deposited in an anhydrous acetronitrile solution, and PEDOT:PSS deposited in an aqueous solution.
    • Presumably the PSS brings the EDOT into solution (??).
  • figure 3 is compelling, but long-term, electrodes are not that much better than Au!
    • Maybe we should just palate with that.

PEDOT-modified integrated microelectrodes for the detection of ascorbic acid, dopamine and uric acid

  • Direct comparison of acetonitrile and water solvents for electropolymerization of EDOT.
  • "PEDOT adhesion is best on gold surface due to the strong interactions between gold and sulphur atoms.
  • images/1353_2.pdf
    • Au plating is essential!

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ref: -0 tags: gold micrograin recording electrodes electroplating impedance date: 10-17-2016 20:28 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-23071004 Gold nanograin microelectrodes for neuroelectronic interfaces.

  • We report a single-cell sized microelectrode, which has unique gold nanograin structures, using a simple electrochemical deposition method.
  • Fabricated microelectrode had a sunflower shape with 1-5 (um of micropetals along the circumference of the microelectrode and 500 nm nanograins at the center.
  • The nanograin electrodes had 69-fold decrease of impedance and 10-fold increase in electrical stimulation capability compared to unmodified flat gold microelectrodes.
  • images/1270_1.pdf pdf
  • The deposition was conducted with an aqueous solution containing 25 mM HAuCl (HAuCl · 3H O, Sigma-Aldrich, MO, 4 4 2USA) and 20 g/L polyvinylpyrrolidone (surfactant, stabilizing agent)

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ref: -0 tags: Charles Lieber syringe-injectable electronics SU-8 chronic flexible date: 10-14-2016 23:30 gmt revision:1 [0] [head]

PMID-27571550 Stable long-term chronic brain mapping at the single-neuron level.

  • Fu TM, Hong G1, Zhou T1, Schuhmann TG, Viveros RD2, Lieber CM.
  • 8 months with only 800nm of Su-8 (400nm of insulation!!). This is both surprising and very impressive; we have to step up our game!
  • In a mouse, too - their surgical technique must be very good. Mice only live ~ 2 years anyway.
  • Figure 3 -- stability -- incredible.
  • Recording sites were bare platinum, 20um diameter; stimulation sites were also bare Pt, 150um dia.
    • No plating or mircowire-fets, so far as I can see; electrode impedances were stable at 200 - 600k (supplementary figure 12).

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ref: Linsmeier-2011.01 tags: histology lund electrodes immune response fine flexible review Thelin date: 12-08-2015 23:57 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-21867803[0] Can histology solve the riddle of the nonfunctioning electrode? Factors influencing the biocompatibility of brain machine interfaces.

  • We show results from an ultrathin multichannel wire electrode that has been implanted in the rat cerebral cortex for 1 year.
    • 12um Pt-Ir wires in a 200um bundle coated with gelatin. See PMID-20551508[1]
    • Electrode was left in the rat cortex for 354 days
    • no clear GFAP staining or ED1 positive cells at the electrode tips.
  • To improve biocompatibility of implanted electrodes, we would like to suggest that free-floating, very small, flexible, and, in time, wireless electrodes would elicit a diminished cell encapsulation.
  • Suggest standardized methods for the electrode design, the electrode implantation method, and the analyses of cell reactions after implantation
  • somewhat of a review -- Stice, Biran 2005 [2] 2007 [3].
  • 50um is the recording distance Purcell 2009.
  • See also [4]
  • Study of neuronal density and ED1 reactivity / GFAP:
    • Even at 12 weeks the correlation between NeuN density and GFAP / ED1 was small -- r 2=0.12r^2 = 0.12
    • Note that DAPI labels many unknown cells in the vicinity of the electrode.

____References____

[0] Linsmeier CE, Thelin J, Danielsen N, Can histology solve the riddle of the nonfunctioning electrode? Factors influencing the biocompatibility of brain machine interfaces.Prog Brain Res 194no Issue 181-9 (2011)
[1] Lind G, Linsmeier CE, Thelin J, Schouenborg J, Gelatine-embedded electrodes--a novel biocompatible vehicle allowing implantation of highly flexible microelectrodes.J Neural Eng 7:4, 046005 (2010 Aug)
[2] Biran R, Martin DC, Tresco PA, Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.Exp Neurol 195:1, 115-26 (2005 Sep)
[3] Biran R, Martin DC, Tresco PA, The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.J Biomed Mater Res A 82:1, 169-78 (2007 Jul)
[4] Thelin J, Jörntell H, Psouni E, Garwicz M, Schouenborg J, Danielsen N, Linsmeier CE, Implant size and fixation mode strongly influence tissue reactions in the CNS.PLoS One 6:1, e16267 (2011 Jan 26)

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ref: -0 tags: alumina utah array electrode parylene encapsulation date: 10-23-2015 21:28 gmt revision:1 [0] [head]

Utah/blackrock group has been working on improving the longevity of their parlyene encapsulation with the addition of ~50nm Al2O3.

  • PMID-24771981 '''Self-aligned tip deinsulation of atomic layer deposited Al2O3 and parylene C coated Utah electrode array based neural interfaces
    • Process:
      • Normal Utah array dicing saw / glass frit / thinning and etch fabrication for the Utah probe.
      • Sputtered Ti, Sputtered Pt. (not sure how they mask this?)
      • Sputtered iridium oxide (SIROF, sputtered in an Ar + O2 plasma) electrode tips (again, not sure about the mask..)
      • ALD Al2O3 passivation, 50nm. Cambridge Fiji system, same as nanolab. Must take a long time!
      • A-174, aka 3-Methacryloxypropyltrimethoxysilane adhesion promoter (which presumably acts by pulling hydroxy groups off the alumina substrate; Al-O bonds have higher energy than Si-O)
      • 6um parylene.
      • Laser ablation of tips with 1000 pulses from KrF 5ns 100Hz excimer laser. Works much better than poking the electrode tips through thin aluminum foil.
      • O2 plasma descum / removal of carbon residues.
      • BOE removal of Al2O3 above the SIROF
    • Of note, ALD Al2O3 has included hydroxy bonds, which means that it gradually etches in PBS. (Pure Al2O3, as passivates aluminum parts exposed to seawater, does not?)
    • PBS also etches Si3N4, and crystaline Si.
  • IEEE-6627006 (pdf) Bi-layer encapsulation of utah array based neural interfaces by atomic layer deposited Al2O3 and parylene C
    • Atomic layer deposited (ALD) alumina is an excellent moisture barrier with WVTR at the order of ~ 10e-10 g·mm/m2·day [10-13]. But alumina alone is not suitable for encapsulation since it dissolves in water [14].
    • Demonstrated stable power-up of RF encapsulated devices for up to 600 equivalent days in 37C PBS.
      • Actual testing carried out at 57C, 4x accelerated.
  • PMID-24658358 Long-term reliability of Al2O3 and Parylene C bilayer encapsulated Utah electrode array based neural interfaces for chronic implantation.
    • Demonstrated good barrier longevity with wired Utah probes, active probes with flip-chip (Au/Sn eutectic reflow) record/stimulate circuits, and ones with bonded RF stimulation chips, INIR-6. (6th version!)
    • PBS etching of Si lead to undercutting & eventual flake-off of the SIROF, leading to dramatic impedance increase. (Figure 5 and 7).
      • no Pt under the SIROF?

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ref: -0 tags: polyimide silicon carbide adhesion DBS syle electrodes date: 07-22-2015 18:01 gmt revision:0 [head]

PMID-25571176 Fabrication and characterization of a high-resolution neural probe for stereoelectroencephalography and single neuron recording.

  • Layer stack:
    • 5um PI (UBE U-varnish S)
    • 50nm SiC
      • Deposited at 100C.
    • 300nm Pt
    • 30nm SiC
    • 10nm DLC
    • 5um PI
      • Cured at 450C
    • 100nm Al hard mask (removed)
    • Cytop dry adhesion layer
      • softbake to remove solvent,
      • then hardbake at 290C for 4 hours to anneal the PI and adhere the Cytop to it.

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ref: -2000 tags: polyimide acrylic aluminum electro deposition imide insulation ultra thin date: 02-27-2015 19:42 gmt revision:0 [head]

Ultrathin, Layered Polyamide and Polyimide Coatings on Aluminum

  • Alternating polyelectrolyte deposition of layered poly(acrylic acid)/poly(allylamine hydrochloride) (PAA/PAH) films on Al produces ultrathin coatings that protect Al from Cl--induced corrosion.
  • Resistance goes from 5 MOhm/cm^2 at 10nm thickness to ~50MOhm/cm^2 following imidization of the monolayer-applied polymer films.

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ref: -0 tags: gold carbon nanotube electroplating impedance PEG date: 10-24-2014 22:25 gmt revision:1 [0] [head]

PMID-21379404 Creating low-impedance tetrodes by electroplating with additives

  • Electroplated tetrodes to 30-70 kΩ by adding polyethylene glycol (PEG) or multi-walled carbon nanotube (MWCNT) solutions to a commercial gold-plating solution.
  • Cui and Martin [12] showed that altering the concentration of gold-plating solution and electroplating current can change the morphology of a gold-plated microelectrode coating.
  • Additionally, Keefer et al. [13] found that adding multi-walled carbon nanotubes (MWCNTs) to a gold-plating solution created microelectrode coatings with a “rice-like” texture and very low impedances.
  • Au electroplating solution made of non-cyanide, gold-plating solution (5355, SIFCO Selective Plating, Cleveland, OH).
  • A one-second, reversed-polarity pulse helped to clean the surface of the tetrode tip and lowered the impedances to 2MΩ to 3 MΩ before electroplating.
  • Electroplating pulses were one to five seconds long and were repeated until the tetrodes reached the desired impedances. After electroplating, the tetrodes were soaked in DI, air dried, and checked for shorts.

Conclusion: 75% PEG, commercial electropating solution, 0.1ua current pluses to 250K or less.

  • Though the Caswell Au plating solution will likely behave differently ..

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ref: -0 tags: kevlar electrodes flexible polymer 12um McNaughton Utah date: 10-11-2014 00:19 gmt revision:0 [head]

PMID-8982987 Metallized polymer fibers as leadwires and intrafascicular microelectrodes

  • McNaughton TG1, Horch KW.
  • Ti/W, Au, Pt metalization via sputtering.
  • 12um core diamater.
  • demonstrate 8 month reliability.
  • 1um dipped silicone elastomer insulation.
  • note difficulty in manufactuing the fibers. No kidding!
  • Tensile strength the same as a 25um Pt-Ir wire, 90x more flexible.

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ref: -0 tags: wirebonding finishes gold nickel palladium electroless electrolytic date: 09-21-2014 02:53 gmt revision:3 [2] [1] [0] [head]

Why palladium?


To prevent black nickel: http://tayloredge.com/reference/Electronics/PWB/BlackPad_ITRI_Round1.PD

Introduction The use of electroless nickel / immersion gold (E.Ni/I.Au) as a circuit board finish has grown significantly in the last few years. It provides a flat board finish, is very solderable, provides a precious metal contact surface and the nickel strengthens the plated holes. However, as the usage of E.Ni/I.Au increased, a problem was found on BGA (Ball Grid Array) components. An open or fractured solder joint sometimes appears after board assembly on the occasional BGA pad. The solder had wet and dissolved the gold and formed a weak intermetallic bond to the nickel. This weak bond to the nickel readily fractures under stress or shock, leaving an open circuit. The incidence of this problem appears to be very sporadic and a low ppm level problem, but it is very unpredictable. A BGA solder joint cannot be touched-up without the component being removed. After the BGA component is removed, a black pad is observed at the affected pad site. This black pad is not readily solderable, but it can be repaired.


From: http://www.smtnet.com/Forums/index.cfm?fuseaction=view_thread&Thread_ID=4430

You don't have enough gold. Your 2uin is too porous and is allowing the nickel to corrode. Prove that this by hand soldering to these pads with a more active flux, like a water soluble solder paste, than you are using.

You must have at least 3uin of immersion gold. Seriously consider >5uin.

Your nickel thickness is fine. Although if you wanted to trade costs, consider giving-up nickel to 150uin thickness, while increasing the gold thickness. Gold over electroless nickel creates brittle joints because of phosphorous in the nickel plating bath. The phosphorous migrates into the over-plating. Electrolytic nickel and gold plating should not be a problem.

If you stay with the electroless nickel, keep the phosphorous at a mid [7 - 9%] level. Just as important, don't let the immersion gold get too aggressive. The immersion gold works by corroding the nickel. If it is too aggressive it takes away the nickel and leave phosphorous behind. This makes it look like the phosphorous level is too high in the nickel bath.

Gold purity is very important for any type of wire bonding process. For aluminum wedge bonding, gold should have a purity of 99. 99% [no thalium] and the nickel becomes critical. No contaminates and the nickel wants to be plated a soft as possible. This requires good control of Ph and plating chemicals in the nickel-plating bath.

Harman "Wire Bonding In Microelectronics" McGraw-Hill is a good resource for troubleshooting wire bonding. I reviewed it in the SMTnet Newsletter a couple of months ago.


That said, electrolytic nickel + electrolytic gold does work well -- perhaps even better than ENEPIG:

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ref: Nordhausen-1994.02 tags: Utah array electrodes optimization date: 08-14-2014 01:24 gmt revision:2 [1] [0] [head]

PMID-8180807[0] Optimizing recording capabilities of the Utah Intracortical Electrode Array.

  • Nordhausen, Rousch, Normann (1993)
  • Originally it was designed for stimulation in a visual prosthesis.
  • Thought that the large surface area would securely anchor it to the cortex
    • Turns out you need to put gore-tex on top to keep it from being expelled.
  • Varied the exposed electrode tip to determine the optimum area.
  • Oldschool computer plots ...

____References____

[0] Nordhausen CT, Rousche PJ, Normann RA, Optimizing recording capabilities of the Utah Intracortical Electrode Array.Brain Res 637:1-2, 27-36 (1994 Feb 21)

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ref: Seymour-2011.06 tags: PEDOT Seymour electrode recording parylene date: 08-06-2014 22:39 gmt revision:3 [2] [1] [0] [head]

PMID-21301965[0] Novel multi-sided, microelectrode arrays for implantable neural applications.

  • There are problems with parylene multielectrode arrays:
    • water and salts will rapidly diffuse into the various interfacial boundaries
    • Interfacial delamination due to poor wet adhesion of parylene on metal
      • This possibly due to mechanical stress
      • causes excessive cross-talk or noise.
    • Parylene-C devices are prone to poor adhesion at either the dielectric to dielectric interface or at the dielectric to metal interface *** (Sharma and Yasuda 1982; Yasuda et al 2001)
  • solution: PPXCH 2NH 2PPX-CH_2NH_2 and PPXCHOPPX-CHO -- reactive parylene (amine bonds?!)
  • PEDOT is absolutely essential for attaining reasonable performance / impedance from the 85um^2 gold electrodes.
    • Thermal noise on 280um^2 and 170um^2 Au electrodes was too high to record neurons.
    • AU thickness 0.5um.
  • Performed soak tests on their electrodes; the reactive parylene is good, but not sure if it's a worthy improvement.

____References____

[0] Seymour JP, Langhals NB, Anderson DJ, Kipke DR, Novel multi-sided, microelectrode arrays for implantable neural applications.Biomed Microdevices 13:3, 441-51 (2011 Jun)

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ref: -0 tags: microelectrode patents date: 05-02-2014 00:07 gmt revision:1 [0] [head]

Various microelectrode patents:

Microelectronics:

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ref: -0 tags: carbon fiber electrode array parylene fire sharpening microthread date: 03-20-2014 19:57 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-23860226 A carbon-fiber electrode array for long-term neural recording.

  • Guitchounts G1, Markowitz JE, Liberti WA, Gardner TJ.
  • We describe an assembly method for a 16-channel electrode array consisting of carbon fibers (<5 µm diameter) individually insulated with Parylene-C and fire-sharpened. The diameter of the array is approximately 26 µm along the full extent of the implant.
  • Fibers from http://www.goodfellowusa.com/
    • young's modulus of 380GPa vs. tungsten 400GPa.
    • Data available from Toho Tenax
  • The absence of any report of single neuron isolation in HVC with a fixed chronic electrode implant underscores the difficulty of recording small cells (8-15um soma) with an implant whose damage length scale is large relative to the target neurons. (!!)

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ref: Cheung-2007.03 tags: flexible electrode array Michigan probe histology Vancouver current source density EPFL polyimide date: 12-21-2013 21:07 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-17027251[0] Flexible polyimide microelectrode array for in vivo recordings and current source density analysis.

  • Polyimide -- PI-2611 precusor.
  • 50nm Ti adhesion, 200nm Pt, both sputtered.
  • Electrodes etched via RIE in Cl2.
    • Sputtered and photo-patterned SiO2 etch mask.
  • Used regular solder to connect to a Samtec.
  • 15um total thickness.
  • 25um electrode diameter.
  • They were inserted directly (no carrier nor guide) into the brain; can be re-used.
  • Tested to 8 weeks.
  • No figure comparing silicon and polyimide, though they claim minimal GFAP response to the electrodes.

____References____

[0] Cheung KC, Renaud P, Tanila H, Djupsund K, Flexible polyimide microelectrode array for in vivo recordings and current source density analysis.Biosens Bioelectron 22:8, 1783-90 (2007 Mar 15)

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ref: -0 tags: polyimide platinum electrodes Spain longitudinal intrafasicular adhesion delamination date: 10-05-2013 22:24 gmt revision:4 [3] [2] [1] [0] [head]

PMID-17278585 Assessment of biocompatibility of chronically implanted polyimide and platinum intrafascicular electrodes. 2007

  • Designed platinum/polyimide longitudinal intrafasicular electrodes (LIFEs)
    • 25um PT/Ir, insulated to 60-75um diameter. PT/IR has a young's modulus of 202 Gpa.
      • Plated with platinum black under sonication, as this forms a tougher surface than without sonication.
      • See also: PMID-20485478 Improving impedance of implantable microwire multi-electrode arrays by ultrasonic electroplating of durable platinum black. Desai SA, Rolston JD, Guo L, Potter SM. 2010
    • Polyimide PI2611, 10um thick, 50mm long, 220um wide in the electrode segment.
  • Implanted into rat sciatic nerve for 3 months.
  • These electrodes have been tested in people for two days:
    • Electrical stimulation through the implanted electrodes elicited graded sensations of touch, joint movement, and position, referring to the missing limb. This suggested that peripheral nerve interfaces could be used to provide amputees with prosthetic limbs with sensory feedback and volitional control that is more natural than what is possible with current myoelectric and body-powered prostheses.
  • CMAPs = compound muscle action potentials.
  • CNAPs = compound nerve action potentials.
  • Platinum wire LIFE performed very similarly to the thin-film polyimide LIFE in most all tests, with slightly higher potentials recorded by the larger polyimide probe.
  • 'Higher encapsulation with the polyimide probes! Geometry?
  • However, the polyimide LIFEs induced less functional decline than the wire LIFEs.
  • Other polyimide studies [14] [16] [24] -- one of which they observed a 70% reduction of tensile strength after 11 months of implantation.
    • [14] F. J. Rodríguez, D. Ceballos, M. Schüttler, E. Valderrama, T. Stieglitz, and X. Navarro, “Polyimide cuff electrodes for peripheral nerve stimulation,” J. Neurosci. Meth., vol. 98, pp. 105–118, 2000.
    • [16] N. Lago, D. Ceballos, F. J. Rodríguez, T. Stieglitz, and X. Navarro, “Long term assessment of axonal regeneration through polyimide regenerative electrodes to interface the peripheral nerve,” Biomaterials, vol. 26, pp. 2021–2031, 2005.
    • [24] M. Schuettler, K. P. Koch, and T. Stieglitz, “Investigations on explanted micromachined nerve electrodes,” in Proc. 8th Annu. Int. Conf. Int. Functional Electrical Stimulation Soc., Maroochydore, Australia, 2003, pp. 306–310.
      • The technology of sandwiching a metallization layer between two layers of polyimide seems to be suitable, because no delamination of the polyimide layers was observed even after 11 months. The right choice of metals for building the electrical conductive elements of the microelectrodes is crucial. Ti/Au/Ti/Pt layers tend to flake off from polyimide while delamination of Ti/Pt layers was not observed. However, adhesion of Ti/Pt layers was investigated after 2.5 months of implantation while Ti/Au/Ti/Pt layers were exposed after 11 months to the biological system. In previous research projects, surgeons also reported on delamination of Ti/Au layers from polyimide substrate after three months. Unfortunately, we had no possibility of inspecting these microelectrodes in our laboratory.
      • See also {1250}

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ref: -0 tags: Kozai carbon nanotube electrode rcording histology date: 08-02-2013 05:42 gmt revision:1 [0] [head]

PMID-23142839 Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces.

  • Here, we report the development of an integrated composite electrode consisting of a carbon-fibre core, a poly(p-xylylene)-based thin-film coating that acts as a dielectric barrier and that is functionalized to control intrinsic biological processes, and a poly(thiophene)-based recording pad.
  • 7um diameter carbon nanotubes slide easily into cortex & yield good recording.
  • only 0.8um of parlyene-N coating.
    • Does it stick well? Does it crack?
  • Functionalized the parylene with 50nm of bromine / oxygen complex, bromoisobutyrate.
  • PEDOT recording surface drastically lowered impedance.
  • Difficult to assemble these little buggers!

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ref: -0 tags: Utah parylene cracking encapsulation electrode date: 06-28-2013 18:26 gmt revision:4 [3] [2] [1] [0] [head]

Characterization of parylene-C film as an encapsulation material for neural interface devices

  • Hsu, Jui-Meia; Kammer, Saschab; Jung, Erikc; Rieth, Lorend; Normann,A. Richarde; Solzbacher, Florianade (Utah)
  • lists Tg 35-80C for parylene-C;
  • 3um films applied.
  • Parylene samples were subjected to accelerated lifetime testing (85 % relative humidity (RH) and 85 ÌŠC) for 20 days, and the film did not show appearance changes as observed by optical microscopy. However, X-ray diffractograms show that the film crystallinity increased during this test.
  • 120C 100%RH for 2 hours released parylene from the silicon.
  • Soldering @ 350C backside of Utah array caused parylene to crack.
  • X-ray diffraction shows that heat causes parylene to crystalize:

___Low Dielectric Constant Materials for Ic Applications___ edited by Paul Shin Ho, Jihperng Leu, Wei William Lee

  • Aging and annealing increase crystalinity and thus lower the elongation to break and increase the modulus and mechanical strength of the films.
  • parylene-N is considerably more crystaline (57%), Tg 13C. (low!)
  • Bulk barrier properties are among the best of the organic polymeric coatings.

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ref: -0 tags: polyimide electrodes ecog japan photosensitive date: 06-28-2013 01:50 gmt revision:0 [head]

PMID-22719725 Photosensitive-polyimide based method for fabricating various neural electrode architectures

  • Yasuhiro X. Kato,1,* Shigeto Furukawa,2 Kazuyuki Samejima,1 Naoyuki Hironaka,2 and Makio Kashino2
  • many typos in this paper (not that I should talk..) Yet still, it's informative.
  • 12um thick photosensitive polyimide + Cr/Au fabrication.
  • Wet etch (photodeveloper).
  • Wet release (ferric chloride) from glass substrate.
  • Soldered a connector to the polyimide w/ stiffener.
  • Note that polyimide tends to shrink (up to 29%) during baking, unlike parylene!
  • Suggest 20-40um diameter neural recording sites; they did not coat.

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ref: -0 tags: polyimide platinum nanowire recording electrode plating date: 06-28-2013 00:46 gmt revision:2 [1] [0] [head]

IEEE-5734597 (pdf) A novel platinum nanowire-coated neural electrode and its electrochemical and biological characterization

  • Young-Hyun Jin ; IMTEK, Univ. of Freiburg, Freiburg, Germany ; Daubinger, P. ; Fiebich, B.L. ; Stieglitz, T.
  • 10um thick RIE etched polyimide and platinum electrodes.
  • polyimide was spin coated onto wafers.
  • Used relatively simple wet chemistry to plate platinum onto electrodes:
    • 0.14 M-% chloroplatin acid hexahydrate (H2PtCl6·6H2O, Sigma-Aldrich) and 7.4 M-% formic acid (HCOOH, Sigma-Aldrich) were mixed in de-ionized (DI) water. The fabricated device was floated upside down on the solution.
  • Let this plate for 7 days & effective site was enlarged by 617 times!

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ref: Prasad-2012.1 tags: tungsten microwire electrodes histology insulation failure sanchez microwire tungsten date: 06-27-2013 22:40 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

PMID-23010756[0] Comprehensive characterization and failure modes of tungsten microwire arrays in chronic neural implants.

  • c.f. [1]
  • microwire implant, durations that ranged from acute to up to 9 months in 25 rats.
  • First 2-3 weeks electrode impedance + recording quality fluctuated the most widely.
  • Electrode recording site deterioration continued for the long-term animals as insulation damage occurred and recording surface became more recessed over time.
  • Activated microglia were found near electrode tracts in all chronic animals.
    • High ferritin expression, intraparenchymal bleeding, microglial degeneration suggesting presence of excessive oxidative stress via Fenton chemistry.
      • Wikipedia: Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species via the Fenton Reaction.[11] Hence vertebrates use an elaborate set of protective mechanisms to bind iron in various tissue compartments.
  • Ferritin expression sometimes associated with blebbing / cytorrhexis. (in figures 7-8)
    • Interestingly, during the first few hours after implantation many microglial cells are undergoing cytoplasmic fragmentation (cytorrhexis) which indicates ongoing degeneration of these cells as their cytoplasm literally breaks apart. Cytorrhexis has been previously observed in the aged human brain where it becomes particular prominent in subjects with Alzheimer’s disease.
  • Could not discriminate abiotic (insulation, recording site size) and biotic (inflammatory response) causes of failure.
    • Microglial response not correlated with prolonged performance.
  • Tungsten TDT microwire arrays. 50um diameter, 10um polyimide insulation.
  • SEM imaging pre and prior implantation.
  • Antibodies marking microglia:
    • Iba1 marks all microglia.
    • ED1 stain against CD68 to identify active macrophages [80], but not necessarily all activated microglia since many activated cells are not engaged in phagocytosis and thus are ED1-negative.
    • Anti-ferritin staining to identify those microglia involved in the sequestration of free iron that may leak as a result of BBB compromize.
      • Issue: ferritin is expressed in all tissues ..
    • OX-6 to identify antigen-presenting MHC-II (immune) cells, e.g. microglia or blood-borne immune cells.
  • Found the immunohistoheamistry not terribly convincing.
    • Above, arrows show withdrawn electrode tips.
  • Working with the FDA to promote good laboratory practice (GLP) and good manufacturing practice (GMP). Can mention the same.
  • No evidence of infection in rats.
    • Not true in monkeys..

____References____

[0] Prasad A, Xue QS, Sankar V, Nishida T, Shaw G, Streit WJ, Sanchez JC, Comprehensive characterization and failure modes of tungsten microwire arrays in chronic neural implants.J Neural Eng 9:5, 056015 (2012 Oct)
[1] Freire MA, Morya E, Faber J, Santos JR, Guimaraes JS, Lemos NA, Sameshima K, Pereira A, Ribeiro S, Nicolelis MA, Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.PLoS One 6:11, e27554 (2011)

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ref: -0 tags: silicon electrode histology Michigan tip shape shear force date: 04-24-2013 20:02 gmt revision:3 [2] [1] [0] [head]

PMID-1601445 Factors influencing the biocompatibility of insertable silicon microshafts in cerebral cortex.

  • Relatively early assessment of tissue reaction to silicon electrodes.
  • Noted 'severe' reaction at electrode tip; recommend recording along the shaft, Michigan style.
  • Noted microhematoma formation.
  • Recommend fast insertion.
  • Bending of the shafts (e.g. they exert lateral force) causes lateral tissue damage.
    • Problem with fast insertion is that it may cause the needle to bend a bit -- resulting in lateral 'kill zone'.
    • Ultimate speed must be a compromise.
  • Advocate shearing blade tip or chisel point to sever microtubules, rather than a conical tip pushing them to a annular ring that can grab to the sides of the needle.
  • Good paper, reviews the relevant cellular anatomy...

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ref: -0 tags: electrode carbon fiber MEA date: 04-22-2013 18:19 gmt revision:2 [1] [0] [head]

PMID-21228307 Ultrasmall and customizable multichannel electrodes for extracellular recordings

  • 7um carbon fiber electrodes.
  • It has been estimated that insertion of a 50 um wire in the adult rat hippocampus CA1 area could damage 90% of the neurons that would otherwise be recordable by the electrode (Claverol-Tinture and Nadasdy 2004)
  • Highlight the tetrode effect: it's like beam forming.
  • Carbon fibers from Goodfellow Cambridge.
  • Insulated with a pulled micropipette.
  • Added insulation with cathodic electrodeposition paint (Claerclad HSR)
  • focused ion beam milling (FIB) (Qiao et al 2005) -- working resolution below 10nm.
  • The carbon fibers were fond to be stiff enough to penetrate the fly 'dura'.

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ref: -0 tags: histology immune response otto indiana electrodes gfap inflamation transparent clearing vimentin date: 04-19-2013 23:59 gmt revision:4 [3] [2] [1] [0] [head]

PMID-23428842 Chronic intracortical microelectrode arrays induce non-uniform, depth-related tissue responses.

  • Woolley AJ, Desai HA, Otto KJ.
  • One timepoint, 4 weeks.
  • Laser confocal microscopy
    • after tissue clearing (optical index of refraction matching) in a 60% sucrose solution.
  • Single-shank iridium contact silicon substrate MEA.
    • Device cut level with surface of brain after insertion.
  • Intact MEAs via device-capture histology, DHhist (Woolley et al 2011)
    • 350-450um tissue explanted with device.
    • They promote their technique.
  • Tissue surrounding microdevices exhibited two major depth-related phenomena:
    • a non-uniform microglial coating along the device length and
    • a dense mass of cells surrounding the implant in cerebral cortical layers I and II.
      • The dense mass of cells contained vimentin, a protein not typically expressed highly in CNS cells, evidence that non-CNS cells likely descended down the face of the penetrating devices from the pial surface.
        • But no Iba1 (activated microglia) per se in the tissue mass.
    • Hoe342 -- cell marker.
    • This mass was apparently consistent across animals!
    • Cells in the mass were VIM positive -- fibroblasts -- meninges?
  • low GFAP = not an astrocytic scar.
  • This study provides further evidence that a progressive invasion of non-CNS cells contributes substantially to the chronic phase of the tissue response around intracortical MEAs.
    • Again, might be from BBB distruption {1237}


This result is supported by previous papers:
  • {1193} -- microglia response not correlated to electrode failure, but correlated to ferritin immunoresponse
  • {781} -- also note that menigeal fibroblasts migrate down electrode tracts.
  • {1028} -- measured vimentin, GFAP, and ED1 (not Iba1). Found Vim+ and GFAP+, suggesting reactive astrocytes and not meningeal cells. ED1 aka CD68 is specific to macrophages and not microglia, so these may be blood-derived cells.
  • {1200} -- chronic contact with the meninges v.s intraparenchymal correlated with Vim+ encapsulation.
  • {1210} -- old paper showing the same result near surface of implant.
  • {1196} -- more against GFAP & pro BBB disruption
  • {1204} -- GFAP uncorrelated (!) with NeuN intensity
  • {307} -- all initial tests of utah arrays showed fibrous encapsulation; one array was completely explanted. This is why now they put gore-tex over the implant -- to prevent fibroblast migration (i guess).

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ref: -0 tags: winslow Tresco 2010 BBB histology immune response microelectrodes date: 04-19-2013 23:25 gmt revision:0 [head]

PMID-19963267 Quantitative analysis of the tissue response to chronically implanted microwire electrodes in rat cortex.

  • Winslow BD, Tresco PA.
  • The spatial distribution of biomarkers associated with the foreign body response to insulated microwires placed in rat cerebral cortex was analyzed 2, 4, and 12 weeks after implantation using quantitative methods.
  • We found no evidence that reactive gliosis increases over time or that neuronal loss is progressive, we did find evidence of persistent inflammation and enhanced BBB permeability at the electrode brain tissue interface that extended over the 3 month indwelling period and that exhibited more animal to animal variability at 3 months than at 2 and 4 weeks.

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ref: -0 tags: dissertation interconnect parylene flexible electrodes date: 02-26-2013 00:30 gmt revision:2 [1] [0] [head]

http://docs.lib.purdue.edu/dissertations/AAI3444877/

  • Several different projects --
    • Stretchable PDMS electrodes
    • PDMS-parylene ECoG
    • Transmitting parallel neural data via free-space optical link
    • semi-flexible hydrogel-parylene neural electrode.
    • The parylene electrodes with selectively patterned hydrogel provide stiff mechanical properties for easy penetration into the brain tissues and subsequent flexibility after insertion upon swelling of the hydrogel.
    • advanced packaging system with using a composite inorganic parylene combination.
      • Atomic layer deposited alumina-zirconia (Al2O3–ZrO2) composite layer can provide a conformal and nano-laminated coating on parylene surface in neural packaging systems in order to improve the hermeticity for long term implantations
  • Can't get the entire PDF. annoying.

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ref: Suner-2005.12 tags: Suner Utah probe electrophysiology reliability chronic electrode recording longevity histology MEA date: 01-31-2013 22:27 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-16425835Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex

  • claim that they have done a logitudinal development series that included 39 array implants in 18 monkeys.
  • can get reliable recordings out to 3 months (only? probably the array was forced out of the brain?)
    • however, it seems that their recording quality did not decrease dramatically over those 3 months.
  • excellent methods section.
  • also {1027}

____References____

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ref: -0 tags: microelectrodes original metal pipette glass recording MEA date: 01-31-2013 19:46 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-4065599 (pdf) Comments on Microelectrodes

  • The amplifiers themselves, even back in 1950's, posed no problems -- low bandwidth. All that is required is low noise and high input impedance.
  • KCl Glass electrodes are LPF (10M resistive + 10pf parasitic capacitance); metal HPF (capacitive).
    • The fluid tip will not see external triphasic spikes of vertebrate axons above the noise level.
  • Metal probe the most useful.
  • Pt electrode in CSF behaves like a capacitor at low voltage across a broad frequency range. CSF has compounds that retard oxidation; impedance is more resistive with physiological saline.
  • Noise voltage generated by a metal electrode best specified by equivalent noise resistance at room temperature, E rmsnoise=4kTR nδF E_{rms noise} = \sqrt{4 k T R_{n} \delta F} R_n should equal the real part of the electrode impedance at the same frequency.
  • Much of electrochemistry: solid AgCl diffuses away from an electrode tip with great speed and can hardly be continuously formed with an imposed current. Silver forms extremely stable complexes with organic molecules having attached amino and sulfhydril groups which occur in plenty where the electrode damages the tissue. Finally, the reduction-oxidation potential of axoplasm is low enough to reduce methylene blue, which places it below hydrogen. AgCl and HgCl are reduced.
  • The external current of nerve fibers is the second derivative of the traveling spike, the familiar triphasic (??) transient.
  • Svaetichin [1] and Dowben and Rose [3] plated with Platinum black. This increases the surface area.
    • Very quickly it burns onto itself a shell of very adherent stuff. It is kept from intimate contact with the tissue around it by a shell.
    • We found that if we add gelatin to the chloroplatinic acid bath from which we plate the Pt, the ball is not only made adherent to the tip but is, in a sense, prepoisoned and does not burn a shell into itself.
  • glass insulation using woods metal (which melts at a very low temperature). Platinum ball was plated onto 2-3um pipette tip. 3um gelatinized platinum black ball, impedance 100kOhm at 1kHz.
    • Highly capacitive probe: can be biased to 1 volt by a polarizing current of 1e-10 amp. (0.1nA).
  • Getting KCl solution into 1um pipettes is quite hard! They advise vacuum boiling to remove the air bubbles.
  • Humble authors, informative paper.

____References____

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ref: -0 tags: polymide flexible electrode Rousche incision needle assist date: 01-30-2013 06:38 gmt revision:3 [2] [1] [0] [head]

PMID-11327505 Flexible Polyimide-Based Intracortical Electrode Arrays with Bioactive Capability

  • Use gold / polymide fabrication; electrode is 20um thick, 160um wide.
  • Still quite flexible -- buckles at 0.003 N.
  • Successfully recorded by inserting it in an incision in rat barrel cortex -- needle assist.
    • Well, not too successfully.
  • Suggest that bioactive components can be applied to the permeable polymide surface.

____References____

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ref: Kruger-2010.05 tags: microelectrode array nichrome 7 years rhesus electrophysiology MEA Kruger oblique inverted date: 01-29-2013 07:54 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-20577628[0] Seven years of recording from monkey cortex with a chronically implanted multiple electrode.

  • Seven years!! good recordings the whole time, too. As they say, this is a clinically realistic time period. Have they solved the problem?
  • Used 12.5um Ni-Cr-Al wire insulated with 3um of polymide.
    • Wires were then glued to an 8x8 connector block using conductive epoxy.
    • Glued the bundle together with a solution of plexiglas in dichloroethane.
    • Then introduced the 0.3mm bundle into a j-shaped cannula. This allowed them to approach the gray matter inverted, from below (the white matter).
    • implanted 64 ch array into ventral premotor cortex (arm representation?).
  • No apparent degradation of recording quality over that time.
  • Had some serious problems with the quality of their connector.
    • They recommend: "Rather, the contacts on the head should be made from noble metals and be flat or shallowly hollow, so that they can be easily cleaned, and no male contacts can break."
    • Really need to amplify and multiplex prior connector (imho).
  • Claim that them managed to record from two neurons on one channel for nearly 7 years (ch 54).
  • They cite us, but only to indicate that we recommend slow penetration of the brain. They agree with our results that lowering of individual electrodes is better than all at once.

____References____

[0] Kruger J, Caruana F, Volta RD, Rizzolatti G, Seven years of recording from monkey cortex with a chronically implanted multiple microelectrode.Front Neuroengineering 3 Issue 6 (2010 May 28)

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ref: Wester-2009.04 tags: parylene flexible electrode gold Georgia date: 01-29-2013 03:14 gmt revision:4 [3] [2] [1] [0] [head]

PMID-19255461[0] Development and characterization of in vivo flexible electrodes compatible with large tissue displacements.

  • Device was 100um wide and 25um thick, and was stiff enough to enter directly.
    • carefully calibrated this stiffness -- good! we should do the same.
  • parylene composition.
  • brain tissue force on the order of 2mN.
  • No histology.
  • [http://www.ncbi.nlm.nih.gov/pubmed?term=LaPlaca%20MC[Author]&cauthor=true&cauthor_uid=19255461 laPlaca] has a good number of publications on shear stress in brain tissue.

____References____

[0] Wester BA, Lee RH, LaPlaca MC, Development and characterization of in vivo flexible electrodes compatible with large tissue displacements.J Neural Eng 6:2, 024002 (2009 Apr)

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ref: Polikov-2005.1 tags: neural response glia histology immune electrodes recording 2005 Tresco Michigan microglia date: 01-29-2013 00:34 gmt revision:10 [9] [8] [7] [6] [5] [4] [head]

PMID-16198003[0] Response of brain tissue to chronically implanted neural electrodes

  • Good review (the kind where figures are taken from other papers). Nothing terribly new (upon a very cursory inspection)
  • When CNS damage severs blood vessels, microglia are indistinguishable from the blood borne, monocyte-derived macrophages that are recruited by the degranulation of platelets and the cellular release of cytokines.
  • Furthermore, microglia are known to secrete, either constitutively, or in response to pathological stimuli, neurotrophic factors that aid in neuronal survival and growth.
    • Also release cytotoxic and neurotoxic factors that can lead to neuronal death in vitro.
    • It has been suggested that the presence of insoluble materials in the brain may lead to a state of 'frustrated phagocytosis' or inability of the macrophages to remove the foreign body, resulting in persistent release of neurotoxic substances.
  • When a 10x10 array of silicon probes was implanted in feline cortex, 60% of the needle tracks showed evidence of hemorrhage and 25% showed edema upon explantation of the probes after one day (Schmidt et al 1993) {1163}
    • Although a large number of the tracks were affected, only 3-5% of the area was actually covered by hemorrhages and edema, suggesting the actual damage to blood vessels may have been relatively minor. (!!)
  • Excess fluid and cellular debris diminishes 6-8 days due to the action of activated microglia and re-absorption.
  • As testament to the transitory nature of this mechanically induced wound healing response, electrode tracks could not be found in animals after several months when the electrode was inerted and quickly removed (Yuen and Agnew 1995, Rousche et al 2001; Csicsvari et al 2003, Biran et al 2005).
  • Biran et al 2005: observed persistent ED-1 immunoreactivity around silicon microelectrode arrays implanted in rat cortex at 2 and 4 weeks following implantation; not seen in microelectrode stab wound controls.
  • On the glial scar:
    • observed in the CNS of all vertebrates, presumably to isolate damaged parts of the nervous system and maintain the integrity of the blood-brain barrier.
    • mostly composed of reactive astrocytes.
    • presumably the glial scar insulates electrodes from nearby neurons, hindering diffusion and increasing impedance.
  • On the meninges:
    • Meningeal fibroblasts, which also stain for vimentin, but not for GFAP, may migrate down the electrode shaft from the brain surface and form the early basis for the glial scar.
  • On recording quality:
    • Histological examination upon explantation revealed that every electrode with stable unit recordings had at least one large neuron near the electrode tip, while every electrode that was not able to record resolvable action potentials was explanted from a site with no large neurons nearby.
  • Perhaps the clearest example of this variability was observed in the in vivo response to plastic “mock electrodes” implanted in rabbit brain by Stensaas and Stensaas (1976) {1210} and explanted over the course of 2 years. They separated the response into three types: Type 1 was characterized by little to no gliosis with neurons adjacent to the implant, Type 2 had a reactive astrocyte zone, and Type 3 exhibited a layer of connective tissue between the reactive astrocyte layer and the implant, with neurons pushed more than 100 um away. All three responses are well documented in the literature; however this study found that the model electrodes produced all three types of reactions simultaneously,depending on where along the electrode one looked.

____References____

[0] Polikov VS, Tresco PA, Reichert WM, Response of brain tissue to chronically implanted neural electrodes.J Neurosci Methods 148:1, 1-18 (2005 Oct 15)

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ref: Salcman-1976.01 tags: Salcman electrodes recording chronic microelectrode array MEA original parylene date: 01-28-2013 22:18 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-1256090[0] A new chronic recording intracortical microelectrode

  • maintain that tethering is the rational way to go: it "re-establishes the normal biomechanics of the intact cranial vault". (Salcman 1972, 1973) {1010}
    • have model of electrode tip motion in response to brain-skull displacements (Goldstein and Salcman 1973) {1011}
      • Electrode would have a tip displacement of about 5um in response to a 1mm displacement of the electrode's point of entry into the skull.
      • Exponential dependence on recording amplitude and distance (Rall, 1962). Gradient: 7.5uv/um; movements of more than 1-2um can radically alter the recordnig shape.
      • Probably our electrodes work because the dura & gliosis becomes firmly attached to the electrode shafts.
    • not really an array so much as a number (10-12) of single-unit electrodes.
  • Details the process of parylene-C deposition, electrode microwelding, etc. Pretty cool stuff -- what has happened to this technology?
  • Each bubble is glued with cyanocrylate to the pia. (they too question the safety of this).
  • arrays can be manually inserted via forceps.
  • 25um iridium wire electroplated in 1-2um of gold
    • then electo-etched until the desired tip geometry is achieved, 1-3um diameter
    • and vacuum coated in 3um of parylene-C.
    • Impedance 1-2M with a 1kHz sine wave at 10nA. Impedance is inversely related to the frequency of the test current, phase angle of 70-80deg.
      • Ref Robinson, 1968.
    • We must emphasize the extreme sensitivity of electrode measurements to the test conditions. Measured values of Z eZ_e are usually increased 1-3M when the electrode has been stored away for a few days. Removing the electrode from the test bath for a few minutes in air can lead to equally large increases when the electrode is tested upon remersion. [...] might be oxide.
    • Pinholes are the usual failure mechanism (KD Wise 2004), {149}; parylene is 'pinhole-free'.
  • The connecting 25um Au lead is very flexible and imposes little stress on the iridium electrode.
    • Connecting wire coated in 12um of parylene C
    • Would prefer even finer wire, 12um.
  • Perspex window over the craniotomy; had a vent in this window which they could open.
  • Opening the vent would cause the brain to pulse, moving the electrodes through the cortex and changing neural activity.
  • Size of an electrode is limited by ability to introduce it into the brain.
    • Electrode must be introduced through the pia; as the pial vessels supply the cortex (or drain the cortex).
    • For their electrodes, P crit=0.9gP_{crit} = 0.9 g ; the force necessary to penetrate the pia is 0.05 - 0.2g.
  • pure iridium is stiffer than Pt-Ir by a factor of 3 or so. (521 G N/m^2 = 521 GPa, higher than tungsten, which is 400 Gpa)
    • Pure iridium is apparently the stiffest metallic element ref
  • Interesting: "Once again we are impressed by the fact that passive recording electrodes exhibit drops in impedance in the living system which they never show on in vitro testing in protein solutions at 37C.
    • Between 40 and 50 days, a slow downward trend becomes noticeable; this trend continues for the life of the animal and asymptotically approaches values below 500k. Electrodes still record.
    • See {999}
    • Surmise that pure iridium electrodes have a different metal-electrolyte interface than more conventional metals (Pl and W).
  • Mention that the ultimate purpose is for a neural prosthesis.
    • Their then use was for recordings from M1 in monkeys and V1 from cats. (Schmidt, Bak, McIntosh 1974)
  • Ref Wise et al {1012}.

____References____

[0] Salcman M, Bak MJ, A new chronic recording intracortical microelectrode.Med Biol Eng 14:1, 42-50 (1976 Jan)

{1036}
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ref: -0 tags: decoding recording todo read biocompatibility histology electrodes future date: 01-28-2013 20:52 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

Things to read!

decoding:

  • PMID-20359500 Population decoding of motor cortical activity using a generalized linear model with hidden states
  • Robust satisficing linear regression: Performance/robustness trade-off and consistency criterion
  • PMID-15813408 Closed-loop cortical control of direction using support vector machines
  • Efficient Decoding With Steady-State Kalman Filter in Neural Interface Systems
    • Fixed gain: We analyze a low-complexity Kalman filter implementation in which the filter gain is approximated by its steady-state form, computed offline before real-time decoding commences.
    • We also find that the steady-state Kalman filter reduces the computational load (algorithm execution time) for decoding the firing rates of 25±3 single units by a factor of 7.0±0.9.

electrodes:

other random scribblings: Vascularization {1027} histology {736},{737} and size {1028},{747},{1026}, insulation {1033}. How very very important -- as important or moreso than the recording technology. What has happened to {149} ?

{1220}
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ref: -0 tags: histology review electrode response bioactive coatings date: 01-28-2013 20:16 gmt revision:0 [head]

PMID-20577634 Biocompatibility of intracortical microelectrodes: current status and future prospects.

  • ... but the most widely used method to enhance biocompatibility is the chemical modification of neural probe surfaces with anti-inflammatory compounds, adhesion proteins, or bioactive molecules (Heiduschka and Thanos, 1998; He et al., 2006; Ludwig et al., 2006; Moxon et al., 2007; Rennaker et al., 2007; Seymour and Kipke, 2007; Zhong and Bellamkonda, 2007; Leung et al., 2008; Williams, 2008; Grill et al., 2009)
    • Have any of these achieved success?
    • Many other polymers are basically biocompatible, provided they still insulate after equilibriating with the surrounding vapor pressure.
    • Personally I don't think biocoatings wil lmatter much if there is persistent shear at the interface.
  • Does make sense to have the electrode surface attractive to neurons (Kennedy..). For a later date.

{1219}
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ref: Williams-2007.12 tags: electrode impedance spectroscopy histology date: 01-28-2013 19:12 gmt revision:3 [2] [1] [0] [head]

PMID-18057508[0] Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants.

  • In general, impedance magnitude at 1 kHz was significantly increased in extensive reactions, starting about 4 days post-implant
    • Impedance is hence predictive of performance.
  • Electrodes with extensive reactions also displayed impedance spectra with a characteristic change at high frequencies. This change was manifested in the formation of a semi-circular arc in the Nyquist space, suggestive of increased cellular density in close proximity to the electrode site.
    • Interesting! Usefull!

____References____

[0] Williams JC, Hippensteel JA, Dilgen J, Shain W, Kipke DR, Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants.J Neural Eng 4:4, 410-23 (2007 Dec)

{1177}
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ref: -0 tags: magnetic flexible insertion japan neural recording electrodes date: 01-28-2013 03:54 gmt revision:2 [1] [0] [head]

IEEE-1196780 (pdf) 3D flexible multichannel neural probe array

  • Shoji Takeuchi1, Takafumi Suzuki2, Kunihiko Mabuchi2 and Hiroyuki Fujita
  • wild -- they use a magnetic field to make the electrodes stand up!
  • Electrodes released with DRIE, as with Michigan probes.
  • As with many other electrodes, pretty high electrical impedance - 1.5M @ 1kHz.
    • 20x20um recording sites on 10um parylene.
  • Could push these into a rat and record extracellular APs, but nothing quantitative, no histology either.
  • Used a PEG coating to make them stiff enough to insert into the ctx (phantom in IEEE conference proceedings.)

{1200}
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ref: Kim-2004.05 tags: histology electrode immune response Tresco hollow fiber membranes GFAP vimentin ED1 date: 01-28-2013 03:08 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-14741588[0] Chronic response of adult rat brain tissue to implants anchored to the skull.

  • The increase in tissue reactivity observed with transcranially implanted HFMs may be influenced by several mechanisms including chronic contact with the meninges and possibly motion of the device within brain tissue.
  • Broadly speaking, our results suggest that any biomaterial, biosensor or device that is anchored to the skull and in chronic contact with meningeal tissue will have a higher level of tissue reactivity than the same material completely implanted within brain tissue.
  • See also [1]
  • Could slice through the hollow fiber membrane for histology. (as we shall).
  • Good list of references.

____References____

[0] Kim YT, Hitchcock RW, Bridge MJ, Tresco PA, Chronic response of adult rat brain tissue to implants anchored to the skull.Biomaterials 25:12, 2229-37 (2004 May)
[1] Biran R, Martin DC, Tresco PA, The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.J Biomed Mater Res A 82:1, 169-78 (2007 Jul)

{895}
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ref: XindongLiu-2006.03 tags: neural recording electrodes stability cat parlene McCreery MEA date: 01-28-2013 02:50 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

IEEE-1605268 (pdf) Evaluation of the Stability of Intracortical Microelectrode Arrays

  • 35-50um IR electrodes, electrolytically sharpened at a 10 deg angle, with a 5um blunted tip.
  • Electrodes coated in parylene, and exposed at the tip with an eximer laser. Surface area of tip ~500um^2.
  • Sorted based on features (duration, pk-pk, ratio of + to -, ratio of + time to - time), followed by a demixing matrix (PCA?)
  • Did experiments in 25 cats with some task (for another paper?); got recordings for up to 800 days. Seems consistent with our results.
  • Neurons were stable (by their metrics) for up to 60 days.
  • sparse arrays showed stable recordings sooner than dense arrays, perhaps because they are larger and more qucikly become attached to the dura.
  • Electrodes were always unstable for the first 2-3 months. Stability index is as high as 30-40 days.
  • Average electrode yield was ~ 25%.
  • no histology.

____References____

Xindong Liu and McCreery, D.B. and Bullara, L.A. and Agnew, W.F. Evaluation of the stability of intracortical microelectrode arrays Neural Systems and Rehabilitation Engineering, IEEE Transactions on 14 1 91 -100 (2006)

{1114}
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ref: Feingold-2012.04 tags: Feingold Graybeil electrode moveable recording date: 01-28-2013 02:13 gmt revision:1 [0] [head]

PMID-22170970[0] A system for recording neural activity chronically and simultaneously from multiple cortical and subcortical regions in non-human primates.

  • Up to 127 electrodes in 14 brain areas for up to a year at a time.

____References____

[0] Feingold J, Desrochers TM, Fujii N, Harlan R, Tierney PL, Shimazu H, Amemori K, Graybiel AM, A system for recording neural activity chronically and simultaneously from multiple cortical and subcortical regions in nonhuman primates.J Neurophysiol 107:7, 1979-95 (2012 Apr)

{898}
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ref: Ward-2009.07 tags: microelectrode arrays immune response recording MEA Purdue date: 01-28-2013 01:52 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-19486899[0] Toward a comparison of microelectrodes for acute and chronic recordings.

  • Good research, paper well written.
  • Results suggest significant variability within and between microelectrode types with no clearly superior array (from the abstract).
  • As Miguel mantains, "Much of the new technology, however, does not supersede traditional microwire technology in its ability to evade a host immune response".
  • Initial implantation wound initiates a cascade of immune responses which culminates in a sheath of microglia, astrocytes, various ectracellular matrix constituents, and macrophages.
    • Decent citation list -- many people have been working on MEAs.
  • Fibrous encapusulation of the electrode is much less conductive than healthy nervous tissue, hence impedance measurements can be used to track tissue response.
  • Used Osort to sort the recorded neurons.
  • "Despite differing implant locations, and thus potentially differing levels of background neural activity, and differing scarring responses, which relates to the level of thermal noise in the observed signal (Ludwig et al., 2006), no significant SNR differences were observed among the MEA types for the duration of the study."
  • SNR trends did not seem to relate to site impedance trends over the 31-day period, and by inference, the extent of tissue encapsulation and neuronal density loss.
    • SNR is likely controlled by background neural noise, not thermal noise (which would be linked to impedance).
  • Electrodes with lower impedance generally recorded units from more sites than arrays with higher impedance.

____References____

[0] Ward MP, Rajdev P, Ellison C, Irazoqui PP, Toward a comparison of microelectrodes for acute and chronic recordings.Brain Res 1282no Issue 183-200 (2009 Jul 28)

{1213}
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ref: Chhatbar-2010.05 tags: Lee von Kraus Francis SUNY downstate electrode floating headpost date: 01-28-2013 01:06 gmt revision:1 [0] [head]

PMID-20153370[0] A bio-friendly and economical technique for chronic implantation of multiple microelectrode arrays

  • Nesting design -- the headpost is the only transcutaneous object.

____References____

[0] Chhatbar PY, von Kraus LM, Semework M, Francis JT, A bio-friendly and economical technique for chronic implantation of multiple microelectrode arrays.J Neurosci Methods 188:2, 187-94 (2010 May 15)

{78}
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ref: Musallam-2007.02 tags: Musallam MEA floating rats electrodes date: 01-28-2013 00:42 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-17067683[0] A floating metal microelectrode array for chronic implantation

  • Cite Gualtierotti and Bailey (1968) for a neutral-boyancy electrode w/ rigid shaft.
  • Alumina ceramic base, laser drilled.
  • insulated with silane follwed by parylene-C, 3um.
  • Tips exposed by eximer laser. (Schmidt et al, 1995)
  • Electrophysiology, but not histology.
  • Earlier conference proceedings: PMID-17946982[1] Active floating micro electrode arrays (AFMA).

____References____

[0] Musallam S, Bak MJ, Troyk PR, Andersen RA, A floating metal microelectrode array for chronic implantation.J Neurosci Methods 160:1, 122-7 (2007 Feb 15)
[1] Kim T, Troyk PR, Bak M, Active floating micro electrode arrays (AFMA).Conf Proc IEEE Eng Med Biol Soc 1no Issue 2807-10 (2006)

{311}
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ref: Westby-1997.1 tags: recording microwire electrode MEA sweet sucrose saliva dissolving FET floating date: 01-28-2013 00:28 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-9350963 A floating microwire technique for multichannel neural recording and stimulation in the awake rat

  • sweet electrodes -- attached to glass micropipette with sucrose or saliva.
    • Chorover and DeLuca 1972 "A sweet new multiple electrode for chronic single unit recording". {1019}
  • 42 implanted rats, 252 implanted wires, 79% yield. 62% of electrodes still working at 5 weeks.
    • Targeting an area with really large somas (50um).
  • fully-floating 25um microwire ellectrodes.
  • platinum iridium, 25um, teflon coated, handled only with silastic-protected pliers & tweezers to prevent damage to the insulation.
  • electrode impdance range 200-900kOhms; check insulation by applying -3V to each electrode & looking for hydrogen bubbles.
  • soldering hardens platinum iridium alloy (huh).
  • (!!!) wires are stiffened for implantation by temporarily attaching them to a micropipette guide with sucrose which subsequently dissolves in the brain!
  • the smooth sucrose (40 grams in 50ml of water heated to 118C) coating requires about a week of desiccation to become hard enough for insertion into the brain without premature softening. Sucrose becomes clear like glass once fully desiccated.
  • the air above the craniotomy is sufficiently humid to dissolve the sucrose if left there for more than a few seconds.
  • used a miniature single-channel FET amplifier as a headstage - only one channel out of 6 could be recorded at once :( Thus their reults only apply to the best of the microwires implanted - not to all of them.
  • recorded onto a mac quadra (hahah) 20khz 12 bit
  • applying 160ua microstimulation pulses can restore low (200kohm) electrode impedance. Recording quality was generally improved for a few days following stimulation but then returned to an asymptotic level with the impedance at approximately 900kOhm.
  • electrodes only seemed to last 5 weeks, whence they declined to about 27% yeild - see figure 8.
  • good review of microelectrode recording up to that point (1997).

____References____

{1105}
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ref: Bullara-1983.09 tags: electrode grinding insulation stimulation date: 01-28-2013 00:27 gmt revision:1 [0] [head]

PMID-6632958[0] A microelectrode for delivery of defined charge densities.

  • Details the diamond impregnated lead grinding and epoxy insulation of 75um Pt-Ir wires;
  • Encapsulate the whole thing in Dacron mesh;
  • Electrodes are good for stimulating up to 300 uC / cm^2 * phase;
  • Charge balanced pulses 5-20ua in amplitude, 200us/phase, 20Hz repetition are sufficient to activate nearby cortical neurons.

____References____

[0] Bullara LA, McCreery DB, Yuen TG, Agnew WF, A microelectrode for delivery of defined charge densities.J Neurosci Methods 9:1, 15-21 (1983 Sep)

{736}
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ref: Liu-1999.09 tags: electrodes recording tissue response MEA histology date: 01-28-2013 00:24 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-10498377[0] Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes.

  • implanted 7-shaft 35um iridium electrodes into the pericruciate gyrus of cats & measured the stability of recordings over several months.
  • electrodes were floating, under the dura; they note that connective tissue can force these floating arrays out of the brain, in further, or can encapsulate the electrodes.
    • electrodes activated by 'potentiodynamic cycling' to remove the insulation from the tip, I guess.
    • Insulation is epoxylite epoxy (5-10um thick) which is baked for curing and degassing at 100 and 170C each for 30 minutes.
    • more information on their fabrication in {1105}
  • Used the now-standard techniques for recording & analysis - amazing that this was all very new 10 years ago!
  • Measure stability not only on waveform shape (which will change as the position of the electrode relative to the neuron changes) but also neural tuning.
  • Lymphocytes were found to accumulate around the tips of the microstimulated sites.
  • Electrode sites that yielded recordings ('active') were all clean, with large neurons near the end, and with minimal connective tissue sheath (2-8 um; distance to nearby neurons was 30-50um).
    • Longest period for an active electrode was 242 days.
    • Electrode impedance was usually between 50 and 75 kOhm; there was no insulation failure.
  • Electrodes were stable even when the cat vigorously shook it's head in response to water placed on the head (!).
  • Electrodes were very unstable the first 2 weeks - 1 month ; rather stable thereafter.
    • Active electrodes tended to remain active ; inactive electrodes tended to remain inactive.

____References____

[0] Liu X, McCreery DB, Carter RR, Bullara LA, Yuen TG, Agnew WF, Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes.IEEE Trans Rehabil Eng 7:3, 315-26 (1999 Sep)
[1] Bullara LA, McCreery DB, Yuen TG, Agnew WF, A microelectrode for delivery of defined charge densities.J Neurosci Methods 9:1, 15-21 (1983 Sep)

{746}
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ref: Sanders-2000.1 tags: polymer fiber immune reaction biocompatibility rats polycaprolactone recording electrodes histology MEA date: 01-28-2013 00:01 gmt revision:11 [10] [9] [8] [7] [6] [5] [head]

PMID-10906696[0] Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.

  • Fibers smaller than 6μm6 \mu m show reduced immune response.
    • Fibers implanted in the subcutaneous dorsum (below the skin in the back of rats).
    • Polypropylene. (like rope).
    • Wish the result extended to small beads & small electrodes. 7μm7 \mu m is tiny, but possible with insulated Au wires.
      • Beads: try PMID-1913150 -- shows that the 600um - 50um beads ('microspheres') are well tolerated.
      • Also {750}.
  • Macrophage density in tissue with fiber diameters 2.1-5.9um comparable to that of unoperated contralateral control.

"

fiber diametercapsule thickness
2.1-5.90.6
6.5-10.611.7
11.1-15.820.3
16.7-26.725.5

____References____

[0] Sanders JE, Stiles CE, Hayes CL, Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.J Biomed Mater Res 52:1, 231-7 (2000 Oct)

{897}
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ref: Harris-2011.08 tags: microelectrodes nanocomposite immune response glia recording MEA date: 01-27-2013 22:19 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21654037[0] In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes

  • J P Harris, A E Hess, S J Rowan, C Weder, C A Zorman, D J Tyler and J R Capadona Case Western University.
  • Simple idea: electrodes should be rigid enough to penetrate the brain, yet soft enough to not damage it once implanted.
  • Many studies have shown that shear stress around a microelectrode shaft causes neural die-off and glial response.
  • You can only record from neurons if they are < 100um from the electrode tip.
  • Nanocomposite material is inspired by sea cucumber skin.
    • Our materials exhibit this behaviour by mimicking the architecture and proposed switching mechanism at play in the sea cucumber dermis by utilizing a polymer NC consisting of a controllable structural scaffold of rigid cellulose nanofibres embedded within a soft polymeric matrix. When the nanofibres percolate, they interact with each other through hydrogen bonding and form a nanofibre network that becomes the load-bearing element, leading to a high overall stiffness of the NC. When combined with a polymer system which additionally undergoes a phase transition at physiologically relevant temperatures, a contrast of over two orders of magnitude for the tensile elastic modulus is exhibited.
  • Probes were 200um wide, 100um thick, and had a point sharpened to 45deg.
  • Buckle force testing was done on 53um thick, 125um wide probes sharpened to a 30deg point.
  • Penetration stress through the rat pia is 1.2e7 dynes/cm^2 for a Si probe 40um thick and 80um wide.
  • See also {1198}

____References____

[0] Harris JP, Hess AE, Rowan SJ, Weder C, Zorman CA, Tyler DJ, Capadona JR, In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes.J Neural Eng 8:4, 046010 (2011 Aug)

{1210}
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ref: Stensaas-1976.01 tags: histology implant electrodes immune response date: 01-25-2013 02:52 gmt revision:1 [0] [head]

PMID-782142[0] The reaction of the cerebral cortex to chronically implanted plastic needles.

  • Three different classes of result:
    • Type I is characterized by little or no gliosis and synapses within 1-5mu of the implant;
    • type II contains a pronounced zone of reactive astrocytes;
    • type III is typified by a zone of connective tissue near the implant surface
      • One implant can evince all 3 different types!
  • Already were thinking of neuroprosthetic devices.

____References____

[0] Stensaas SS, Stensaas LJ, The reaction of the cerebral cortex to chronically implanted plastic needles.Acta Neuropathol 35:3, 187-203 (1976)

{1196}
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ref: Skousen-2011.01 tags: electrodes immune response Tresco Wise Michigan histology GFAP atrocyte surface area foreign body response date: 01-25-2013 01:44 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21867802[0] Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays.

  • We studied the chronic brain foreign body response to planar solid silicon microelectrode arrays and planar lattice arrays with identical penetrating profiles but with reduced surface area in rats after an 8-week indwelling period.
  • Using quantitative immunohistochemistry, we found that presenting less surface area after equivalent iatrogenic injury is accompanied by significantly less
    • persistent macrophage activation,
    • decreased blood brain barrier leakiness,
    • and reduced neuronal cell loss.
  • Could be a factor of micromotion, too -- the lattice array has more anchoring points (?)
  • They propose it's a factor of TNF- α\alpha concentration around the implants. This, and other proinflammatory and cytoxic cytokines, is released by macrophages.
  • "Recent studies from our lab have described disruption of BBB integrity, indicated by the presence of autologous IgG in the brain parenchyma, surrounding both microwire and planar silicon recording devices ([1][2]. Under normal conditions, autologous IgG is excluded from the brain parenchyma (Azzi et al., 1990; Seitz et al., 1985) but has been observed following BBB disruption (Aihara et al., 1994).
    • E.g. the presence of IgG proves that the BBB was compromised.
      • Less so with the lattice implants.
  • Previous work from our lab using single microwires and single shaft, planar silicon microelectrode arrays indicated that the spatial distribution of GFAP does not increase with time over the indwelling period and did not support the “increase in astrogliosis over time hypothesis” as a dominant or general biologically related failure mechanism for this type of microelectrode recording device {1197}.

____References____

[0] Skousen JL, Merriam SM, Srivannavit O, Perlin G, Wise KD, Tresco PA, Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays.Prog Brain Res 194no Issue 167-80 (2011)
[1] Winslow BD, Christensen MB, Yang WK, Solzbacher F, Tresco PA, A comparison of the tissue response to chronically implanted Parylene-C-coated and uncoated planar silicon microelectrode arrays in rat cortex.Biomaterials 31:35, 9163-72 (2010 Dec)
[2] Winslow BD, Tresco PA, Quantitative analysis of the tissue response to chronically implanted microwire electrodes in rat cortex.Biomaterials 31:7, 1558-67 (2010 Mar)

{1198}
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ref: Harris-2011.12 tags: mechanically adaptive electrodes implants case western dissolving flexible histology Harris date: 01-25-2013 01:39 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-22049097[0] Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies.

  • See also [1]
  • Initial tensile modulus of 5GPa dropped to 12MPa. (almost 500-fold!)
    • Their polymer nanocomposite (NC) still swells 65-70% (with water?)
    • Implant size 100 x 200um.
  • Controlled with tungsten of identical size and coating.
  • Tethered to skull.
  • Interesting:
    • The neuronal nuclei density within 100 µm of the device at four weeks post-implantation was greater for the compliant nanocomposite compared to the stiff wire.
    • At eight weeks post-implantation, the neuronal nuclei density around the nanocomposite was maintained, but the density around the wire recovered to match that of the nanocomposite.
    • Hypothesis, in discussion: softer implants are affecting the time-course of the response rather that final results
  • The glial scar response to the compliant nanocomposite was less vigorous than it was to the stiffer wire
  • Cultured astrocytes have been shown to respond to mechanical stimuli via calcium signaling (Ostrow and Sachs, 2005).
  • Substrate stiffness is also known to shift cell differentiation in mesenchymal stem cells to be neurogenic, myogenic, or osteogenic (Engler et al., 2006).
  • In vivo studies which focus on the effects of electrode tethering have shown that untethered implants reduce the extent of the glial scar (Biran et al., 2007; Kim et al., 2004; Subbaroyan, 2007)
  • Parylene, polymide, and PDMS still each have moduli 6 orders of mangitude larger than that of the brain.
  • In some of their plots, immune response is higher around the nanocomposites!
    • Could be that their implant is still too large / stiff?
  • Note that recent research shows that vitemin may have neuroprotective effects --
    • Research has linked vimentin expression to rapid neurite extension in response to damage (Levin et al., 2009)
    • NG2+ cells that express vimentin have been proposed to support repair of central nervous system (CNS) damage, and stabilize axons in response to dieback from ED1+ cells (Alonso, 2005; Nishiyama, 2007; Busch et al., 2010)
  • Prior work (Frampton et al., 2010 PMID-20336824[2]) hypothesizes that a more compact GFAP response increases the impedance of an electrode which may decrease the quality of electrode recordings.

____References____

[0] Harris JP, Capadona JR, Miller RH, Healy BC, Shanmuganathan K, Rowan SJ, Weder C, Tyler DJ, Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies.J Neural Eng 8:6, 066011 (2011 Dec)
[1] Harris JP, Hess AE, Rowan SJ, Weder C, Zorman CA, Tyler DJ, Capadona JR, In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes.J Neural Eng 8:4, 046010 (2011 Aug)
[2] Frampton JP, Hynd MR, Shuler ML, Shain W, Effects of glial cells on electrode impedance recorded from neuralprosthetic devices in vitro.Ann Biomed Eng 38:3, 1031-47 (2010 Mar)

{1208}
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ref: Lewitus-2011.08 tags: dissolving polymer electrodes histology degrading date: 01-25-2013 01:31 gmt revision:2 [1] [0] [head]

PMID-21609850[0] The fate of ultrafast degrading polymeric implants in the brain.

  • Tyrosene-derived terpolymer (protein?) dissolves within hours & was re-absorbed.
  • Second terpolymer degrades quickly but is not resorbed.
    • This type resulted in continuous glial activation and loss of neural tissue compared to first.
  • Makes sense, not unexpected.

____References____

[0] Lewitus DY, Smith KL, Shain W, Bolikal D, Kohn J, The fate of ultrafast degrading polymeric implants in the brain.Biomaterials 32:24, 5543-50 (2011 Aug)

{1205}
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ref: Rennaker-2005.03 tags: electrode recording longevity mechanical insertion Oklahoma MEA date: 01-25-2013 01:21 gmt revision:3 [2] [1] [0] [head]

PMID-15698656[0] A comparison of chronic multi-channel cortical implantation techniques: manual versus mechanical insertion.

  • Over 60% of the animals implanted with the mechanical insertion device had driven activity at week 6
    • whereas none of the animals with manually inserted arrays exhibited functional responses after 3 weeks.
      • Roughly identical responses immediately following surgery.
      • Could be that the manual inserter had horizontal movement / shear. (This is solveable with a stereotax).
      • Other research showed little difference in tissue response at 10um/s or 100um/s PMID-21896383[1]
  • Multi-wire electrodes.
  • Mechanical insertion device was capable of rapidly inserting the electrode without visible compression of the brain.
  • Response measured relative to auditory stimulus.
  • Their insertion device looks like a pen.

____References____

[0] Rennaker RL, Street S, Ruyle AM, Sloan AM, A comparison of chronic multi-channel cortical implantation techniques: manual versus mechanical insertion.J Neurosci Methods 142:2, 169-76 (2005 Mar 30)
[1] Welkenhuysen M, Andrei A, Ameye L, Eberle W, Nuttin B, Effect of insertion speed on tissue response and insertion mechanics of a chronically implanted silicon-based neural probe.IEEE Trans Biomed Eng 58:11, 3250-9 (2011 Nov)

{1206}
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ref: -0 tags: flexible polymer electrode recording polypyrrole Bizzi date: 01-25-2013 00:39 gmt revision:0 [head]

PMID-19164034 Cortical recording with polypyrrole microwire electrodes.

  • http://web.mit.edu/bcs/bizzilab/publications/bae2008.pdf
  • Electropolymerization of PPy on a glassy carbon electrode in solution.
  • Polypyrrole microwires were prepared by mounting a PPy film perpendicular to the stage of a cryo-microtome and slicing it in 20um sections.
  • Electrode mounted inside a glass capillary tube.
  • Impedance: 1e5 @ 1kHz.

{1202}
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ref: -0 tags: saccarose sugar sweet electrode implantation force germany date: 01-24-2013 21:46 gmt revision:0 [head]

PMID-22254391 Chronic intracortical implantation of saccharose-coated flexible shaft electrodes into the cortex of rats.

  • measured forces of about 6mN inserting the 75um diameter saccharose-coated electrode.
    • Individual wires were 40um in diameter.
  • Limited longitudinal histology or electrophysiology

{1111}
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ref: Stice-2007.06 tags: electrodes recording small rats S1 PGA histology GFAP date: 01-24-2013 21:07 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-17409479[0] Thin microelectrodes reduce GFAP expression in the implant site in rodent somatosensory cortex.

  • Implanted 12 um and 25 um polymide coated stainless steel
    • Wires coated with poly-glycolic acid (PGA) to facilitate implantation.
  • Only looked to 4 weeks.
  • 12 um implants significantly less GFAP (astrocyte) reactivity at 4 weeks, no difference at 2 weeks (figure 9 & 10).
    • B = bare, P = PGA coated.
  • Can use to bolster the idea that smaller implants are less irritating.

____References____

[0] Stice P, Gilletti A, Panitch A, Muthuswamy J, Thin microelectrodes reduce GFAP expression in the implant site in rodent somatosensory cortex.J Neural Eng 4:2, 42-53 (2007 Jun)

{737}
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ref: Biran-2005.09 tags: microelectrode Michigan probe glia tissue response electrode immune histology MEA Biran date: 01-24-2013 20:49 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-16045910[0] Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.

  • See also {1190} (wow, I'm redundant!)
  • Important point: ED1 up-regulation and neuronal loss were not observed in microelectrode stab controls, indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response.
    • CD68 = ED1 is a marker for microglia and other macrophages. (wikipedia article is informative).
    • GFAP = glial fibrillary acidic protein, marker for astrocytes.
  • Recording failure is caused by chronic inflammation (mostly activated microglia) at the microelectrode brain tissue interface.
  • Only tested response 2 and 4 weeks after implantation. Makes sense for stab wound, but didn't the want to see a longer term response? Or do their electrodes just not last that long?
  • What did they coat the silicon probes in?
  • Used silastic to shock-mount their floating electrodes, but this apparently made no difference compared to conventional dental cement and bone screw mounting.
  • Suggest that chronic inflammatory response may be related to the absorption of fibrogen and complement to the surface of the device (device should not be porous?), the subsequent release of pro-inflammatory and cytotoxic cytokines by activated microphages, and the persistence of activated macrophages around materials which cannot be broken down.
    • Well then, how do you make the electrodes biochemically / biologically 'invisible'?
    • Persistently activated microglia are found around insoluble plaques in AD (plaques that cannot be / are not removed from the brain via proteolysis. Microglia form 'glitter cells' when they engulf undigestible stubstances). This has been termed 'frustrated phagocytosis', which results in increased secretion of proinflamatory cytokines that directly or indirectly cause neuronal death.
  • Significant reductions in neurofiliament reactivity was seen up to 230um from the microelectrode interface; this was not seen for stab wounds. Maximum recording distance is about 130um; 100um more reasonable in normal conditions.
  • Accumulating evidence from postmortem analysis of patients implanted with DBS electrodes reveals that chronic neuroinflamation is part of the response to such (duller, larger) implants as well. They have seen cell loss up to 1mm fromt the electrode surface here.

____References____

[0] Biran R, Martin DC, Tresco PA, Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.Exp Neurol 195:1, 115-26 (2005 Sep)

{749}
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ref: Biran-2007.07 tags: tresco biocompatibility tether skull electrodes Michigan probe recording Tresco date: 01-24-2013 20:11 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-17266019[0] The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.

  • Good, convincing, figures.

____References____

[0] Biran R, Martin DC, Tresco PA, The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.J Biomed Mater Res A 82:1, 169-78 (2007 Jul)

{1199}
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ref: -0 tags: histology atryocytes immune response electrode arrays lund multiple exacerbate date: 01-24-2013 19:56 gmt revision:1 [0] [head]

PMID-23091629 Multiple implants do not aggravate the tissue reaction in rat brain.

  • After six weeks, the astrocytic scar surrounding the middle out of five implants was significantly smaller compared to the single contralateral implant, suggesting that an intrahemispheric interaction might be taking place, reducing the astrocytic response around the central implant.
  • Weak (?) staining for ED1 in this study?
  • -- after 6 weeks.
  • Thought: every paper has a different method for quantify immune response, GFAP staining in this case.

{1024}
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ref: COLLIAS-1957.05 tags: histology microelectrode vasulature date: 01-23-2013 23:56 gmt revision:4 [3] [2] [1] [0] [head]

PMID-13429398[0] Histopathological changes produced by implanted electrodes in cat brains; comparison with histopathological changes in human and experimental puncture wounds.

  • Quite a good and overcomplete / long article -- fully describes their result of implanting bundles of 0.005" varnished steel wires into the brains of cats.
    • Saw hemorrhagic necrosis, necrosis from edema, and eventual encapsulation and collapse of capilaries around the chronic implant. All things that we still have to contend with.
  • From [1]: ... For single penetrating electrodes into cat cortex, Collias and Manuelidis noted and increase in hemorrhagic damage near electrode tracks of the cortex nearest the point of electrode entry into the pia.
  • They also reported that the damage appeared to be randomly distributed among the implants, which they attributed to differences in local vasculature.
  • The toxicity of certain metals, namely, platinum, platinum-8% tungsten, platinum-10% rhodium, platinum-10% iridium, platinum-10% nickel, platinized platinum, a gold-nickel-chromium alloy, a gold-palladium-rhodium alloy, a chromium-nickel-molybdenum alloy (Vitallium), stainless steel, silver, rhenium, and gold, was evaluated histologically following chronic implantation for 2 months in the brains of cats. Of the above metals, all but silver were found to be nontoxic. Boron was also evaluated and found to be nontoxic.

____References____

[0] COLLIAS JC, MANUELIDIS EE, Histopathological changes produced by implanted electrodes in cat brains; comparison with histopathological changes in human and experimental puncture wounds.J Neurosurg 14:3, 302-28 (1957 May)
[1] Rousche PJ, Normann RA, Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.J Neurosci Methods 82:1, 1-15 (1998 Jul 1)

{1192}
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ref: -2002 tags: sea slugs flexible electrodes polymide Washington date: 01-04-2013 18:46 gmt revision:0 [head]

IEEE-1002325 (pdf) Silicon micro-needles with flexible interconnections

  • Implanted their isolated needles (see also {219}) in sea slugs Tritonia diomedea
    • Sea slug neurons are large -- up to 400um -- makes recording easier.
  • Silicon needles fabricated via reactive ion etching and SF6 sharpening.
  • 'intracellular recording!
  • Pretty advanced fabrication, I guess.

{1040}
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ref: Du-2011.01 tags: Harrison recording electrode MEA Blanche date: 01-04-2013 02:43 gmt revision:3 [2] [1] [0] [head]

PMID-22022568[0] Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

  • The number of single-units possible to record doubles every 7 years [5].
  • Electrodes must be within 100um of soma to relaibly detect extracellular action potentials.
  • Existing Michigan arrays have trace features around >=1 um; here they use E-beam lithography to decrease the probe width dramatically.
    • Their wire widths are 290 nm. Still bigger than 40nm process (?)
  • Seem to use Reid Harrison's ASIC RHA22132 design.
  • noise of electrodes progressively decreased with consecutive gold electroplating cycles. Plating makes the electrodes rough, and decreases their impedance to around 1 M.
    • Electrode contacts are around 10 x 10 um square, 108 um^2 area.
  • Intrinsic noise of the amplifier 1.7 uV RMS.
  • 290 nm wire had an impedance of 9.2 k -- corresponding to 1.0 uV rms noise.
  • able to record from the same neuron from several adjacent electrodes. Spacing ~ 28 um.
  • Detail their process extensively -- 40% of probes survived the process with <= 5 defective channels. THey propose further optimization to the e-beam lithography. Probes took 7 hours to pattern on the lithography machine (!).

____References____

[0] Du J, Blanche TJ, Harrison RR, Lester HA, Masmanidis SC, Multiplexed, high density electrophysiology with nanofabricated neural probes.PLoS One 6:10, e26204 (2011)

{1102}
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ref: Gilletti-2006.09 tags: electrode micromotion histology GFAP variable reluctance date: 01-04-2013 02:28 gmt revision:2 [1] [0] [head]

PMID-16921202[0] Brain micromotion around implants in the rodent somatosensory cortex.

  • Used a differential variable reluctance transducer (DVRT) in adult rats (n = 6) to monitor micromotion normal to the somatosensory cortex surface
    • Reluctance e.g. AC inductance varied with a floating bobbin (or so -- they do not list the details of this COTS device).
  • Pulsatile surface micromotion was observed to be in the order of 10-30 um due to pressure changes during respiration and 2-4 um due to vascular pulsatility.
  • Large inward displacements of brain tissue between 10-60 um were observed in n = 3 animals immediately following the administration of anesthesia

____References____

[0] Gilletti A, Muthuswamy J, Brain micromotion around implants in the rodent somatosensory cortex.J Neural Eng 3:3, 189-95 (2006 Sep)

{1058}
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ref: -0 tags: Purdue magnetic bullet electrode implantation date: 01-04-2013 00:51 gmt revision:3 [2] [1] [0] [head]

PMID-19596378 Magnetic insertion system for flexible electrode implantation.

  • Probes constructed from a sharp magnetic tip attached to a flexible tether.
  • Cite Polikov et al 2005. {781}.
  • Re micromotion: (Gilletti and Muthuswamy, 2006 {1102}; Lee et al., 2004; Subbaroyan et al., 2005 {1103}).
  • 0.6 mm (600 um!) diameter steel bullet, 4mm long, on the end of 38 gauge magnet wire. Mass 7.2 +- 0.4 mg.
  • Peak current 520 A froman 800V, 900uF capacitor which produces a maximum force of 10 N on the electrode, driving it at 126.25 m/s.
  • Did manage to get neural data.
  • Experimental evidence suggests that macrophages have difficulty adhering to and spreading on polymer fibers ranging between 2.1 and 5.9 um in diameter. PMID-8902241 Bernatchez et al. 1996 and {746}.
  • Shot through the dura.
  • Also reference magnetic stereotaxis for use in manipulating magnetic 'seeds' through cancers for hyperthremic destruction.
  • See also their 2011 AES abstract

{1189}
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ref: -0 tags: microelectrode array flexible PDMS via interconnect Georgia date: 01-04-2013 00:33 gmt revision:0 [head]

IEEE-6197244 (pdf) A PDMS-Based Integrated Stretchable Microelectrode Array (isMEA) for Neural and Muscular Surface Interfacing

  • Targeted at e.g. ECoG; in this paper, they look at cat muscle (epimyscial recording).
  • MEA is directly fabricated with a stretchable substrate, such as a thin PCB or ASIC, through via bonding for built-in packaging.

{1188}
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ref: -0 tags: flexible micxrowire arrays electrode recording Georgia polymide date: 01-04-2013 00:13 gmt revision:1 [0] [head]

IEEE-906517 (pdf) Flexible microelectrode arrays with integrated insertion devices

  • 2001 MEMS Conference.
  • FMA = flexible microelectrode arrays.
  • Both for nerves (pass-through needle) and cortex (removeable needle).
    • Primarily tested in tissue proxies.
  • Anticipated the utility of photolithography for patterning the electrodes + rigid insertion devices.
  • The elastic modulus of polymers like polymide are two orders of magnitude less than metals, but still six orders of magnitude higher than brain tissue (46kPa).
  • Pass-through needle very similar to the threaded wire idea.
  • removable needle simply stops the thread & drives the needle a bit further to break the attachment site.
    • Did not test removable needle technique (?)
  • Defined electroplating with a thick photoresist mask, as Michel says.
  • Tested FMAs with movement and acceleration vs. rigid arrays. FMAs faired much better, of course!

____References____

' ''' ()

{1184}
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ref: -0 tags: optical neural recording photon induced electron transfer date: 01-02-2013 04:25 gmt revision:2 [1] [0] [head]

PMID-22308458 Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires.

  • Photoinduced electron transfer.
    • About what you would think -- a photon bumps an electron into a higher orbital, and this electron can be donated to another group or drop back down & fluoresce a photon.
  • Good sensitivity: ΔF/F\Delta F/F of 20-27% per 100mV, fast kinetics.
  • Not presently genetically targetable.
  • Makes sense in terms of energy: "A 100-mV depolarization changes the PeT driving force by 0.05 eV (one electron × half of 100-mV potential, or 0.05 V). Because PeT is a thermally controlled process, the value of 0.05 eV is large relative to the value of kT at 300 K (0.026 eV), yielding a large dynamic range between the rates of PeT at resting and depolarized potentials.
  • Why electrochromic dyes have plateaued:
    • "In contrast, electrochromic dyes have smaller delta G values, 0.003 (46) to 0.02 (47) eV, and larger comparison energies. Because the interaction is a photochemically controlled process, the energy of the exciting photon is the comparison energy, which is 1.5–2 eV for dyes in the blue-to-green region of the spectrum. Therefore, PeT and FRET dyes have large changes in energy versus their comparison energy (0.05 eV vs. 0.026 eV), giving high sensitivities; electrochromic dyes have small changes compared with the excitation photon (0.003–0.02 eV vs. 2 eV), producing low voltage sensitivity."

{1165}
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ref: -0 tags: Moxon ceramic array electrode lithography date: 07-12-2012 23:05 gmt revision:3 [2] [1] [0] [head]

IEEE-1275580 (pdf) Ceramic-based Multisite Electrode array for Chronic Single-Neuron Recording

  • Their substrate is polished to 35-50um thick
  • patterned using standard lift-off lithographic techniques
  • four electrodes per shank
  • The ceramic is considerably stiffer than silicon (table) -- 372 Gpa vs. 190 Gpa.

{1164}
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ref: -0 tags: neural recording McGill Musallam electrodes date: 07-12-2012 22:53 gmt revision:0 [head]

http://www.mdpi.com/1424-8220/8/10/6704/pdf NeuroMEMS: Neuro Probe Microtechnologies

  • Good review (as of 2008) of the many different approaches for nervous system recording.

{923}
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ref: Freire-2011.01 tags: Nicolelis BMI electrodes immune respones immunohistochemistry chronic arrays rats 2011 MEA histology date: 06-29-2012 01:20 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-22096594[0] Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.

  • Says what might be expected: tungsten microelectrode arrays work, though the quality gradually declines over 6 months.
  • Histological markers correlated well with recording performance.
  • Shows persistent glial activation around electrode sites + cell body hypertropy.
    • Suggest that loss in recording quality may be due to glial encapsulation.
  • References
    • Szarowski et al 2003 {1028}
    • Ward et al 2009
  • Histology:
    • NADPH-d: nicotinamide adenine dinucleotide phosphate-diaphorase, via beta-NADP
    • CO: cytochrome oxidase, via diamnibenzidine DAB, cytochrome c and catalase.
      • both good for staining cortical layers; applied in a standard buffered solution and monitored to prevent overstaining.
  • Immunohistochemistry:
    • Activated microglia with ED-1 antibody.
    • Astrocytes labeled with glial fibrillary acid protein.
    • IEG with an antibody against EGR-1, 'a well-known marker of calcium dependent neuronal activity'
    • Neurofilament revealed using a monoclonal NF-M antibody.
    • Caspace-3 with the associated antibody
    • Details the steps for immunostaining -- wash, blocknig buffer, addition of the antibody in diluted blocking solution (skim milk) overnight, wash again, incubate in biotinylated secondary antibody, wash again, incubate in avidin-biotin-peroxidase solution.
    • Flourescent immunohistochemistry had biotynlation replaced with alexa Fluor 488-conjugated horse anti-mouse and Alexa Fluor 594-conjugated goat anti-rabbit overnight.

____References____

[0] Freire MA, Morya E, Faber J, Santos JR, Guimaraes JS, Lemos NA, Sameshima K, Pereira A, Ribeiro S, Nicolelis MA, Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.PLoS One 6:11, e27554 (2011)

{307}
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ref: Rousche-1998.07 tags: BMI Utah cat Normann recording electrode MEA histology date: 06-29-2012 01:12 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-10223510 Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.

  • Focus on (surprisingly) chronic recording from the utah array: they want to demonstrate that it works.
  • Platinum coating.
  • insulated with 2-3um polymide.
  • 10 cats, 12 arrays: 2 in S1, 8 in auditory ctx, 2 V1.
  • 11 electrodes connected in each array.
  • After a 6-month implant period, 60% of implanted arrays could still record 'some type of activity'.
  • They were completely targeting neuroprostheses.
    • But acknowledge that 'the presence of fibrous encapsulation and chronic astrogliosis suggests that more research is necessary before the UIEA can be uses as a cornerstone of a neuroprosthetic device for human use.
      • And yet they went through with the human trials?
  • Electrode impedance gave no hint as to the ability of a given electrode to record neural units: many electrodes with average impedance could not record neural activity.
  • Impedances generally decreased , which is not unusual (Schmidt and Bak, 1976).
    • Likely that the polymide had become permeated with water vapor to and equilibrium point. (rather than pinhole leaks or water permeation).
  • Quiet amplifiers: 2uv pk-pk.
  • No significant trend in background activity was noted over the implant durations.
  • In nearly every cat, the dura above the electrode array adhered to the bone flap, and the electrode array adhered to the dura. Therefore, when the bone flap was removed, the UIEA was concurrently explanted from the cortex.
    • Similar to Hoogerwerf and Wise 1994 {1025}
    • The explanted UIEAs typically had become encapsulated, the encapsulation was the cause of the cortical depression.
    • Only 1 did not become encapsulated in dura.
    • This encapsulation explains the gradually varying recording properties -- the electrodes were moving out of the brain.
    • "The capsule which formed around the substrate of the UIEA was usually continuous with the dura, which was enmeshed directly to the overlying skull. The encapsulated array therefore had no freedom of movement with respect to the skull, and this may have caused local trauma which reduced the possibility of recording neural activity. This relative micromovement between the fixed array and the ‘floating’ cortical tissue may also be responsible for sustaining continued growth of the encapsulation as described above."
    • Have tried putting teflon on the top of the Utah array -- did this work?
  • Two UIEAs were not found near the cortical surface -- these two arrays were totally removed from the leptomeningeal space. although originally implanted into the cortex beneath the dura, at the time of sacrafice these arrays were found above the repaired dura, and the implanted cortex showed no evicence of cortical implant.
  • Some electrodes healthy; other showed chronic inflammation.
  • General and intense inflamation in the upper layers of cortex even on their best-performing array; no guarantee that this ctx was working properly, as it is heavily compressed with fibroblasts.
  • Regarding vascluature, see {1024}.
  • Say that the largest impediment is the formation of a capsule around the implant. (Do not mention issue of infection; I guess cats have strong immune systems as well?)
  • Rather good biological discussion and conclusion. worth a re-read. "We currently recommend that the UIEA be used for acute and short-term applications."
    • Not too many follow-ups re teflon or fixing the encapsulation problem: See {1026}
      • Indeed, {1027} doesn't even cite this! Too disastrous?

____References____

{158}
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ref: Hashimoto-2003.03 tags: DBS STN subthalamic nucleus globus pallidus electrophysiology date: 03-07-2012 21:57 gmt revision:3 [2] [1] [0] [head]

PMID-12629196[0] Stimulation of the Subthalamic Nucleus Changes the Firing Pattern of Pallidal Neurons

  • why does STN stim work? investigated the effects of STN HFS on neuronal activity of GPi and GPe.
  • monkeys were treated with MPTP
  • used a scaled-down version of human DBS stimulator (cool!)
  • high frequency stimulation resulted in stimulus-synchronized regular firing pattern, plus an overall increase in pallidal firing rate.
    • they think that this synchrony may underlie the beneficial effect of HFS in the STN
  • only behavior was, apparently, what amplitude and frequency were required to alleviate parkinsonian symptoms.
  • if i do DBS in normal monkeys, is there anything to say that the effect will be similar or comparable to treatment stimulation?
  • they remind us that HFS = lesion in terms of alleviating symptoms of parkinsons.

____References____

[0] Hashimoto T, Elder CM, Okun MS, Patrick SK, Vitek JL, Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons.J Neurosci 23:5, 1916-23 (2003 Mar 1)

{116}
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ref: Iansek-1980.04 tags: globus pallidus GPe GPi electrophysiology 1980 date: 02-29-2012 18:17 gmt revision:2 [1] [0] [head]

PMID-7411442 The monkey globus pallidus: neuronal discharge properties in relation to movement.

  • motor units are generally inactive during inactivity. the relationship to movement of the discharges of such neurons was found to be very specific
    • This is in comparison to other results, which report a sustained firing, esp in GPi.
  • the discharges (as analyzed through histograms) of many neurones were related to only a particular direction of movement about one joint in the right limb.
  • some discharges were related to multijoint movements -> probably due to control of contraction of particular muscles.
    • nonetheless, this relationship was a loose one; there is not a tight coupling between pallidal activity and muscle contraction.
  • some responded to ipsilateral as well as contralateral movements.
    • PMID-7925805 Unilateral leasions in the GP results in bilateral increase in reaction time. hence, GP is involved in initiation. RT speed eventually recovered.
  • only the posterior globus pallidus - well posterior to the maximum expansion - contained movement related cells.
    • the a-p stereotaxic coordinates were less useful than the location of the maximum mediolateral width of the structure.
    • cells occurred in clusters, separated by regoins of non-movement related.
  • cells in the internal segment had no such organization.
  • many of the non-movement related neurons were tonically active.
  • this was before there was A/D recording, apparently!

{164}
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ref: DeLong-1985.02 tags: globus pallidus subthalamic STN electrophysiology Georgopoulos DeLong DBS date: 02-24-2012 21:50 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-3981228[0] Primate globus pallidus and subthalamic nucleus: functional organization

  • cells respond to arm, leg, and orofacial movements (mostly in the arm tho)
  • ~25% of these responded to passive joint movement - the latency is in accord with proprioceptive driving.
  • arm-related neurons were found throughout the rostrocaudal extent of both globus pallidus segments
  • look @ the articles that cite this!

____References____

[0] DeLong MR, Crutcher MD, Georgopoulos AP, Primate globus pallidus and subthalamic nucleus: functional organization.J Neurophysiol 53:2, 530-43 (1985 Feb)

{161}
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ref: Bergman-1998.01 tags: basal ganglia globus pallidus electrophysiology parkinsons 2001 DBS date: 02-22-2012 18:52 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-9464684[0] Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates.

  • The firing of neurons in the globus pallidus of normal monkeys is almost always uncorrelated.
  • after MPTP treatment, the firing patterns of GP became correlated and oscillatory (see the figures!!)
  • dopamine must support normal segregation of the informational channels in the basal ganglia, and breakdown of this causes the pathology of PD.
  • has a decent diagram of the basal ganglia-thalamo-cortical circuits.
  • two different hypotheses of BG function: segregated and convergent. data support the former.

____References____

[0] Bergman H, Feingold A, Nini A, Raz A, Slovin H, Abeles M, Vaadia E, Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates.Trends Neurosci 21:1, 32-8 (1998 Jan)

{654}
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ref: Isoda-2008.07 tags: STN switching motor control scaccades monkeys electrophysiology DBS date: 02-22-2012 15:02 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-18614691[0] Role for subthalamic nucleus neurons in switching from automatic to controlled eye movement.

  • we found neurons that showed a phasic change in activity specifically before volitionally controlled saccades which were switched from automatic saccades
  • A majority of switch-related neurons were considered to inhibit no-longer-valid automatic processes, and the inhibition started early enough to enable the animal to switch.
  • We suggest that the STN mediates the control signal originated from the medial frontal cortex and implements the behavioral switching function using its connections with other basal ganglia nuclei and the superior colliculus.
  • neurons have a really high rate of spiking - what we observe in DBS surgeries.
  • nice. There may be alternate explanations, but this one is plausible.

____References____

{1122}
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ref: Gale-2009.03 tags: STN DBS monkey comparison electrophysiology date: 02-21-2012 16:34 gmt revision:2 [1] [0] [head]

PMID-19167367[0] Subthalamic nucleus discharge patterns during movement in the normal monkey and Parkinsonian patient.

  • Compared STN activity in normal monkeys and parkinsonian humans performing the same joystick target acquisition task.
  • PD neurons were much burstier, and had lower variance in responses.
  • Simultaneously recorded neurons in the human demonstrated consistent oscillatory synchronization at restricted frequency bands, whereas synchronized oscillatory neurons in the monkey were not restricted to distinct frequencies (this is possibly not meaningful).
  • the net effect of PD may be a reduction in the physiological degrees of freedom of BG neurons with diminished information carrying capacity.
  • PETHs look bad compared to our results.

____References____

[0] Gale JT, Shields DC, Jain FA, Amirnovin R, Eskandar EN, Subthalamic nucleus discharge patterns during movement in the normal monkey and Parkinsonian patient.Brain Res 1260no Issue 15-23 (2009 Mar 13)

{1116}
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ref: Snow-2006.02 tags: electrode insertion sharp recording tissue surrogate date: 02-10-2012 18:56 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-1580838 (pdf) Microfabricated cylindrical multielectrodes for neural stimulation.

  • Used optical fiber as the substrate.
  • sharpened using a Dicing saw.
  • polymide insulatino removed by placing fiber tip next to a white-hot platinum filament.
  • cylindrical lithography system using a He-Cd laser.
  • tissue surrogate: two layers of 20um Saran Wrap over tofu. (!!!) -- see also {212}

____References____

Snow, S. and Jacobsen, S.C. and Wells, D.L. and Horch, K.W. Microfabricated cylindrical multielectrodes for neural stimulation Biomedical Engineering, IEEE Transactions on 53 2 320 -326 (2006)

{1110}
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ref: -0 tags: Seymour thesis electrode lithography fabrication date: 02-05-2012 17:35 gmt revision:4 [3] [2] [1] [0] [head]

Advanced polymer-based microfabricated neural probes using biologically driven designs.

  • References {1109}
  • Thermal noise from 280 um^2 or 170 um^2 gold recording sites much higher than PEDOT coated sites.
  • Used an interdigitated contact-free probe for measuring insulation impedance change. Very smart!
    • Water molecules will diffuse 15 um / minute in parylene (Yasuda, Yu et. al 2010).
    • In the frequency range critical for neural recording and stimulation, 500-5k, impedance moculus decline was small.
    • 1 hr soak at 60C.
  • Chapter 3 details 60-day soak of Parylene-C + reactive parylene insulation performance testing.
    • Regular parylene seems to work perfectly fine, no better than the PPX heat-treated devices.
    • Heat treatment does improve quality -- 200C in a vacuum oven for 2 days. (Li, Rodger et al 2005)
      • However -- this increases the brittleness.

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ref: -0 tags: Cogan 2008 electrodes recording stimulation date: 02-05-2012 00:21 gmt revision:0 [head]

PMID-18429704 Neural stimulation and recording electrodes.

  • Electrical stimulation of nerve tissue and recording of neural electrical activity are the basis of emerging prostheses and treatments for spinal cord injury, stroke, sensory deficits, and neurological disorders. An understanding of the electrochemical mechanisms underlying the behavior of neural stimulation and recording electrodes is important for the development of chronically implanted devices, particularly those employing large numbers of microelectrodes. For stimulation, materials that support charge injection by capacitive and faradaic mechanisms are available. These include titanium nitride, platinum, and iridium oxide, each with certain advantages and limitations. The use of charge-balanced waveforms and maximum electrochemical potential excursions as criteria for reversible charge injection with these electrode materials are described and critiqued. Techniques for characterizing electrochemical properties relevant to stimulation and recording are described with examples of differences in the in vitro and in vivo response of electrodes.

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ref: -0 tags: micromotion electrode FEA model date: 01-27-2012 19:19 gmt revision:1 [0] [head]

PMID-16317234 A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex.

  • Postulate that mechanical strains induced around the implant site may be one of the leading factors responsible for the sustained tissue response in chronic implants
  • A tangential tethering force results in 94% reduction in the strain value at the tip of the polyimide probe track in the tissue,
  • Simulated 'soft' probe induced two orders of magnitude smaller values of strain compared to a simulated silicon probe.
  • Shows some insertion forces:
  • As well as mechanical properties of the brain.

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ref: Bergman-1994.08 tags: subthalamic nucleus STN basal ganglia globus pallidus electrophysiology 1994 MPTP DBS date: 01-26-2012 17:19 gmt revision:3 [2] [1] [0] [head]

PMID-7983515[0] The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism

  • idea: record from STN and GPi before and after MPTP treatment in green monkeys.
  • recorded 4-8hz periodic activity (via autocorrelograms) in significantly more neurons from the MPTP treated animals in both the STN and GPi.
  • mean firing rate was increased in STN,
  • tremor-correlated cells found in both.
  • burst activity higher in both, too.
  • modulations in firing rate due to the application of flexion and extension torque pulses were higher in MPTP animals (duration and amplitude), in both areas.
  • spikes were longer in MPTP
  • no tyrosene hydroxylase activity in the PD mks.
  • PD tremor only frequently occurs in green mks following MPTP

____References____

[0] Bergman H, Wichmann T, Karmon B, DeLong MR, The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism.J Neurophysiol 72:2, 507-20 (1994 Aug)

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ref: -0 tags: Najafi electrode spring dissolving Michigan date: 01-16-2012 17:55 gmt revision:1 [0] [head]

IEEE-5969351 (pdf) New class of chronic recording multichannel neural probes with post-implant self-deployed satellite recording sites

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ref: -0 tags: electrode implantation spring modeling muscles sewing date: 01-16-2012 17:30 gmt revision:0 [head]

PMID-21719340 Modelization of a self-opening peripheral neural interface: a feasibility study.

  • Electrode is self-opening, and they outline the math behind it. This could be useful!

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ref: Harrison-2003.06 tags: CMOS amplifier headstage electrophysiology neural_recording low_power chopper Reid Harrison date: 01-16-2012 04:43 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

IEEE-1201998 (pdf) A low-power low-noise CMOS amplifier for neural recording applications

  • detail novel MOS-bipolar pseudoresistor element to permit amplification of low-frequency signals down to milihertz range.
  • 80 microwatt spike amplifier in 0.16mm^2 silicon with 1.5 um CMOS, 1 microwatt EEG amplifier
  • input-referred noise of 2.2uV RMS.
  • has a nice graph comparing the power vs. noise for a number of other published designs
  • i doubt the low-frequency amplification really matters for neural recording, though certainly it matters for EEG.
    • they give an equation for the noise efficiency factor (NEF), as well as much detailed background.
    • NEF better than any prev. reported. Theoretical limit is 2.9 for this topology; they measure 4.8
  • does not compare well to Medtronic amp: http://www.eetimes.com/news/design/showArticle.jhtml?articleID=197005915
    • 2 microwatt! @ 1.8V
    • chopper-stabilized
    • not sure what they are going to use it for - the battery will be killed it it has to telemeter anything!
    • need to find the report for this.
  • tutorial on chopper-stabilized amplifiers -- they have nearly constant noise v.s. frequency, and very low input/output offset.
  • References: {1056} Single unit recording capabilities of a 100 microelectrode array. Nordhausen CT, Maynard EM, Normann RA.
  • [5] see {1041}
  • [9] {1042}
  • [12] {1043}
____References____

Harrison, R.R. and Charles, C. A low-power low-noise CMOS amplifier for neural recording applications Solid-State Circuits, IEEE Journal of 38 6 958 - 965 (2003)

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ref: -0 tags: electrode capacitance date: 01-15-2012 07:00 gmt revision:1 [0] [head]

IEEE-1448388 (pdf) The Electrical Properties of Metal Microelectrodes

  • The most important element is the electrolytic capacitor formed by the metal-electrolyte interface. Its value is about 0.2 pF/um^2 at 1 kHz.

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ref: Vibert-1979.08 tags: spike sorting recording depth extracellular glass electrodes active feedback original date: 01-15-2012 06:46 gmt revision:3 [2] [1] [0] [head]

PMID-95711[0] Spike separation in multiunit records: A multivariate analysis of spike descriptive parameters

  • Glass coated tungsten microeletrodes have high capacitance; they compensate for this by spraying colloidal silver over the outside sheath of the glass, insulating that with varnish, and driving the shield in a positive-feedback way (stabillized in some way?) This negates the capacitance. 'low impedance capacitance compensated'.
    • Capacitance compensation really matters!!
  • Were able to record from single units for 40-100um range (average: 50um) with SNRs 2:1 to 7:1.
    • Some units had SNRs that could reach 15:1 (!!!), these could be recorded for 600 um of descent.
    • more than 3 units could usually be recognized at each recording point by visual inspection of the oscilloscope, and in some cases up to 6 units could be distinguished
    • Is there some clever RF way of neutralizing the capacitance of everything but the electrode tip? Hmm. Might as well try to minimize it.
  • Bandpass 300 Hz - 10 kHz.
  • When the signal crossed the threshold level, it was retained and assumed to be a spike if the duration of the first component was between 70 and 1000 us.
    • This 70 us lower limit was determined on a preliminary study as a fairly good rise time threshold for separation of fiber spikes from somatic or dendritic spikes.
    • I really need to do some single electrode recordings. Platt?
  • Would it be possible to implement this algorithm in realtime on the DSP?
  • Describe clustering based on PCA.
  • Programming this computer (PDP-12) must have been crazy!
  • They analyzed 20k spikes. Mango gives billions.
  • First principal component (F1) represented 60-65% of total information was based mostly on amplitude
  • Second principal component, 15-20% of total information represented mainly time parameters.
  • Suggested 3 parameters: Vmax, Vmin, and T3 (time from max to min).
  • Maybe they don't know what they are talking about:

____References____

[0] Vibert JF, Costa J, Spike separation in multiunit records: a multivariate analysis of spike descriptive parameters.Electroencephalogr Clin Neurophysiol 47:2, 172-82 (1979 Aug)

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ref: Kipke-2003.06 tags: Michigan rat Kipke recording electrode MEA date: 01-08-2012 03:34 gmt revision:5 [4] [3] [2] [1] [0] [head]

IEEE-1214707 (pdf) Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex.

  • 4 of the 6 implants (66%) remaining functional for more than 28 weeks (7 mo)
  • Recording sites separated by 100um; at this site separation, adjacent sites may sometimes record the same unit.
  • It is notable that in each case in this series was terminated due to reasons other than the microelectrode not recording unit activity. (SC LIn agrees, pc).
  • around 80% of sites recorded neural activity.

____References____

{1020}
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ref: Kennedy-1998.06 tags: Kennedy cone electrode ALS BMI date: 01-08-2012 00:35 gmt revision:4 [3] [2] [1] [0] [head]

PMID-9665587[0] Restoration of neural output from a paralyzed patient by a direct brain connection.

  • (abstract) Patients with severe paralysis of limbs, face and vocal apparatus may be intelligent and aware and yet, tragically, unable to communicate. We describe a communication link for such a 'locked-in' patient with amyotrophic lateral sclerosis. We recorded action potentials in her brain over several months by means of an electrode that induces growth of myelinated fibers into its recording tip. She was able to control the neural signals in an on/off fashion. This result is an important step towards providing such patients with direct control of their environment by interfacing with a computer. Additionally, it indicates that restoration of paralyzed muscles may be possible by using the signals to control muscle stimulators.
  • Repairing the PNS is hard. I wonder if a more logical, Gates-ian topic of socially worthwhile work would be to target more people. For example: curing cancer. There is a bit of vanity and scifi chasing in BMI studies mixed up with all the curiosity (science) and worthy causes.
    • That said, plenty of people are doing shit with their lives (in terms of social worth). All that realyl matters is passion. Kenny seems to have passion for his particular recording / BMI idea, which is good!

____References____

[0] Kennedy PR, Bakay RA, Restoration of neural output from a paralyzed patient by a direct brain connection.Neuroreport 9:8, 1707-11 (1998 Jun 1)

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ref: Kennedy-2000.06 tags: BMI Kennedy IEEE 1999 Bakay neurotrophic glass electrode date: 01-08-2012 00:30 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-10896186[] Direct control of a computer from the human central nervous system

  • 1999 - eight years ago!
  • Se also {1020}
  • 3 patients, one success. (one died of ALS :-( JR had a brainstem stroke.
    • Has disconjugate eye movements with nystagmus.
    • These patients are sick - ulcers, peripheral neuropathy.
  • invasive alternative to externally applied BCI.
  • one glass electrode
  • patient can type & produce synthesized speech.
  • cursor wraps off the right of the screen; only positive deflections matter. another signal or dwell used to select letters.
  • Used surface EMG to dissociate neural activity from muscle contraction, as in previous works.
  • electrode used in this study: [1] "The cone electrode: ultrastructural studies following long-term recording in rat and monkey cortex."

____References____

{966}
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ref: Olds-1967.01 tags: Olds 1967 limbic system operant conditioning recording rats electrophysiology BMI date: 01-06-2012 03:59 gmt revision:2 [1] [0] [head]

PMID-6077726[0] The limbic system and behavioral reinforcement

  • Can't seem to find Olds 1965, as was a conference proceeding .. this will have to do, despite the lack of figures. images/966_1.pdf
  • First reference I can find of chronic (several weeks) (4-9 microelectrodes, single) recording from the rat.
  • Basically modern methods: commutator + solid state preamplifiers mounted to a counterbalanced slack-relieving arm.
    • If unit responses were observed in recordings from a given probe a week after surgery they were usually recordable indefinitely. 44 years later ...
  • Used a primitive but effective analog spike discriminator based on:
    • minimum amplitude
    • maximum amplitude
    • minimum fall time
    • maximum fall time.
  • Also had a head movement artifact detector, which blanked the recordings (stopped the paper roll) for 2 sec.
  • Reinforced on 'bursting', threshold sufficiently high that it only occurred once every 5-15 minutes.
  • Food reinforcement or 1/4 second train of brain stimulation (30ua, 60Hz, sine, in hypothalamus).
  • Reinforcement was conditioned on an 'acquisition' signal, which is visual (?) Bursting is rewarded for 2 minutes, ignored for 8 minutes.
  • Also recorded control neurons.
  • (they were looking at these things as though anew!) "The most striking aspect of the records so formed [on sheets of paper] was that all discriminators at one time or another exhibited rate changes that had the appearance of waves with a period of 10 to 20 minutes. Waves between units in the same animal were to some degree synchronized." Then describes a ramp ..
  • Longer term variations: FR would vary by a factor of 2-5 over a period of several hours.
    • This would make negatively correlated neurons (on a short time scale) appear positively correlated over long time scales (have to fix this in the BMI!)
  • As this was a conditional reinforcement task, they unexpectedly found that the acquisition periods were systematically different than extinction periods
    • More like pavlovian conditioning, esp in the hippocampus, where a conditioned response was also reflected on a control neuron.
    • Even when the light was lit throughout the acquisition period was replaced by a bell at the beginning of the acq. period, there was still a sustained change in FR.
      • Then during the extinction period: it appeared from the record of responses that a definite operant behavior was tried several times and then stopped altogether."
  • In the pontine nucleus (relay from M1 to cerebellum, v. roughly), judging from the control responses, all were conditioned.
    • Pontine responses seem to correspond with movement of the eyes or head that did not set off the movement detector/blanker.
  • Saw brief and very fast bursts during the extinction periods of the kind that Evarts found to characterize pyramical neurons during sleep.
  • When units shifted from food reward to ICS reward, units became undiffarentiated, and within a day they would be reconditioned.
  • Also tried paralyzing the animal to see if it could still generate operant responses; the animal died, results inconclusive.
  • Flood lights made it hard for the rats to produce the operant behavior.

____References____

[0] Olds J, The limbic system and behavioral reinforcement.Prog Brain Res 27no Issue 144-64 (1967)

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ref: neuro notes-0 tags: clementine thesis electrophysiology fit predictions tlh24 date: 01-06-2012 03:07 gmt revision:4 [3] [2] [1] [0] [head]

ok, so i fit all timestamps from clem022007001 & timarm_log_070220_173947_k.mat to clementine's behavior, and got relatively low SNR for almost everything - despite the fact that I am most likely overfitting. (bin size = 7802 x 1491) the offset is calibrated @ 2587 ms + 50 to center the juice artifact in the first bin. There are 10 lags. There are 21 sorted units.

same thing, but with only the sorted units. juice prediction is, of course, worse.

now, for file clem022007002 & timarm_log_070220_175636_k.mat. first the unsorted:

and the sorted:

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ref: Porada-2000.01 tags: electrodes recording oblique inverted MEA arrays Kruger date: 01-05-2012 23:07 gmt revision:3 [2] [1] [0] [head]

PMID-10776811[0] More than a year of recording with up to 64 microelectrodes

  • for more than a year action potentials of good quality were obtained from most electrodes!
  • used 60mm-long, 12.5um Ni-Cr-Al (Isaohm) wire, polyimide insulated, soldered to microconnectors. Tips purely ('primitively') cut after bonding them to a piece of photographic film substrate.
  • implanted in the rabbit and marmoset V1 cortex from afar.
  • with the 8 rabbits they used a magnetic release to prevent excessive force from removing the implant.
  • used small sections of thicker wire to individually label the electrodes for x-ray; thusly could reconstruct the electrode positions. electrodes in the white matter were silent mais or menos.
  • the autocorrelation functions of the neurons generally look good; some of them do not have a refractory period though.
  • in GFAP-stained sections a single electrode track appeared as a hole of about 28 um wide. The outer diameter of the wire insulation as 18um. electrode tracts were not visible in cresyl violet tracts. the neurones near the electrode tips appeared normal.
  • we recorded signals for up to 711 days, during which time the recording quality did not degrade. nice, nice!
  • they think that the large length of free wire, running about 5mm through the brain provides a sufficient degree of friction so that locally the tissue is prevented from moving relative to the electrodes. They did not need to use microstimulation to improve recording quality.

____References____

{1031}
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ref: Kelly-2007.01 tags: MEA single electrode comparison CMU Utah date: 01-05-2012 22:07 gmt revision:1 [0] [head]

PMID-17215384[0] Comparison of recordings from microelectrode arrays and single electrodes in the visual cortex.

  • We found that the array yields good recordings on a large number of electrodes, with qualities comparable to those from single electrode recordings. On average, the recording quality is somewhat lower than that of single electrodes, but nonetheless is sufficient for assessing tuning properties such as the spatiotemporal receptive field and orientation tuning.

____References____

[0] Kelly RC, Smith MA, Samonds JM, Kohn A, Bonds AB, Movshon JA, Lee TS, Comparison of recordings from microelectrode arrays and single electrodes in the visual cortex.J Neurosci 27:2, 261-4 (2007 Jan 10)

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ref: QingBai and Wise-2001.08 tags: Bai Wise buffered MEA recording electrodes Michigan date: 01-05-2012 04:53 gmt revision:5 [4] [3] [2] [1] [0] [head]

IEEE-936367 (pdf) Single-unit neural recording with active microelectrode arrays

  • Design neural probes with on-chip unity-gain amplifiers. Proven to not degrade recordings (indeed, it should help!)
  • 200ohm output impedance
  • 11uV RMS noise, 100Hz-10kHz.
  • Multiplexer adds 8uV rms noise. noise from clock transitions 2ppm.
  • Also built amplifiers with 40db voltage gain (100x).

____References____

Qing Bai and Wise, K.D. Single-unit neural recording with active microelectrode arrays Biomedical Engineering, IEEE Transactions on 48 8 911 -920 (2001)

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ref: Nicolelis-1997 tags: nicolelis microwire array electrophysiology rats date: 01-05-2012 03:35 gmt revision:2 [1] [0] [head]

PMID-9136763[0] Reconstructing the engram: simultaneous, multisite, many single neuron recordings.

  • descibes Miguel's microwire arrays.
  • 100 units from 48 microwires in rats.
  • 2.3 units / microwire.
  • stable for weeks -- c.f. 2011. [1]

____References____

[0] Nicolelis MA, Ghazanfar AA, Faggin BM, Votaw S, Oliveira LM, Reconstructing the engram: simultaneous, multisite, many single neuron recordings.Neuron 18:4, 529-37 (1997 Apr)
[1] Freire MA, Morya E, Faber J, Santos JR, Guimaraes JS, Lemos NA, Sameshima K, Pereira A, Ribeiro S, Nicolelis MA, Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.PLoS One 6:11, e27554 (2011)

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ref: Chorover-1972.1 tags: sweet electrode MEA Chorover date: 01-04-2012 03:00 gmt revision:2 [1] [0] [head]

PMID-4670862[0] A sweet new multiple electrode for chronic single unit recording in moving animals.

  • 7 or more 25um individually teflon coated Pt-Ir wires
  • Supported by 26ga hypodermic tubing.
  • coated in melted dextrose (no water, keep stirring it) via dipping.
  • connection via colloidal silver epoxy. we use that.
  • Units recorded within 48 hours. "Electrodes cmoe to exhibit ha high degree of shock-resistance and neurtral bouyancy with respect to immediately-adjacent brain tissue."
  • Durable to 2-3 months of 51 individual electrodes in 8 rats.
  • 1kHz impedance 500k.

____References____

[0] Chorover SL, DeLuca AM, A sweet new multiple electrode for chronic single unit recording in moving animals.Physiol Behav 9:4, 671-4 (1972 Oct)

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ref: Thomas-1972.09 tags: MEA electrodes cell culture platinum black date: 01-04-2012 02:40 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-4672477[0] A miniature microelectrode array to monitor the bioelectric activity of cultured cells

  • Designed for heart cells.
  • 30-element muilt into the cluture chambers.
  • Utilizes PCB lithography technology. Indeed, the insulation is photoresist / 'photopolymer'.
  • platinum black

____References____

[0] Thomas CA Jr, Springer PA, Loeb GE, Berwald-Netter Y, Okun LM, A miniature microelectrode array to monitor the bioelectric activity of cultured cells.Exp Cell Res 74:1, 61-6 (1972 Sep)

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ref: Nicolelis-2003.09 tags: nicolelis recording electrode monkeys MEA date: 01-04-2012 01:23 gmt revision:3 [2] [1] [0] [head]

PMID-12960378 Chronic, multisite, multielectrode recordings in macaque monkeys.

  • max 412 neurons, snr 5
  • up to 18 months, with precipitous decline
  • Miguel is the first author. well, that only makes sense.

____References____

{1011}
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ref: Goldstein-1973.07 tags: Salcman microelectrodes bucking analysis stiffness youngs modulus mechanical MEA date: 01-04-2012 01:22 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-4120642 (pdf) Mechanical Factors in the Design of Chronic Recording Intracortical Microelectrodes

____References____

Goldstein, Seth R. and Salcman, Michael Mechanical Factors in the Design of Chronic Recording Intracortical Microelectrodes Biomedical Engineering, IEEE Transactions on BME-20 4 260 -269 (1973)

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ref: Hubel-1957.03 tags: Hubel original tungsten electrode date: 01-03-2012 23:46 gmt revision:3 [2] [1] [0] [head]

PMID-17793797[0] Tungsten Microelectrode for Recording from Single Units.

  • Advancement upon the micropipette.
  • Lacquer insulation.
  • Suggest that 5um tips or smaller are the best for single unit recording.
  • Steel becomes too fragile near the tip of a very sharp point (what about steel blades?)
  • Electropolishing: immerse a few milimeters in KNO 2KNO_2 solution and apply 2-6V AC.
    • Such a result is explained by the fact that the meniscus height depends on the diameter of the wire, which decreases as the polishing proceeds.
  • 75M resistance (!!); 500k to 5M at 5-10kHz.
  • Note that he had been recording from at least 1959.

____References____

[0] Hubel DH, Tungsten Microelectrode for Recording from Single Units.Science 125:3247, 549-50 (1957 Mar 22)

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ref: Sodagar-2007.06 tags: neural recording telemetry Wise Najafi mulitichannel electrophysiology Michigan ASIC date: 01-03-2012 23:07 gmt revision:4 [3] [2] [1] [0] [head]

PMID-17554826[0] A fully integrated mixed-signal neural processor for implantable multichannel cortical recording.

  • document is rich in details! looks pretty well designed, too.
  • Michigan 3-d electrodes
  • inductively powered, 2Mbps output
  • 64 channels
  • 18b/spike for 64 channels in scan mode, continuous waveforms on 2 channels in monitor mode
  • programmable analog spike detection. resolution: 5 bits.
  • no timestamps - send them out as they come in, with a clock rate fast enough so that this does not matter.
    • temporary storage in SRAM
    • time compression and buffering is somewhat complex (?)
  • only transmit threshold crossings, positive, negative, and both.
    • they do not detail how the signal is telemetered - perhaps this is for another publication.
  • fabricated chip occupies 3.5 x 2.7 mm. 0.5um process.
  • fabricated chip has a power of 200uw @ 1.8V. that's 6.4mW altogether! I need to get down to this figure! (well..)

____References____

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ref: MolinaLuna-2007.03 tags: ICMS microstimulation cortical thin-film electrodes histology MEA date: 01-03-2012 22:54 gmt revision:2 [1] [0] [head]

PMID-17178423[0] Cortical stimulation mapping using epidurally implanted thin-film microelectrode arrays.

  • they claim that thin-film electrodes are better than microelectrode arrays, as they show less evidence of cortical damage.
    • thin-film electrodes show higher reproducability
    • more accurate spatial arrangement.
  • epidural stimulation (they were implanted between the dura and skull)

____References____

[0] Molina-Luna K, Buitrago MM, Hertler B, Schubring M, Haiss F, Nisch W, Schulz JB, Luft AR, Cortical stimulation mapping using epidurally implanted thin-film microelectrode arrays.J Neurosci Methods 161:1, 118-25 (2007 Mar 30)

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ref: Najafi-1990.05 tags: Najafi Michigan probe silicon strength electrodes recording MEA date: 01-03-2012 22:45 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-2345003[0] Strength characterization of silicon microprobes in neurophysiological tissues.

  • These active (with amplification/buffering circuitry) electrodes were around since 1990! It's been a while, and at least the devices are commercially available now.
  • Show that thin-film silicon is remarkably flexible and tough - about six times as strong as bulk silicon.
  • Have developed a silicon probe with an integrated phosphorous-doped polysilicon strain guague - nice.

____References____

[0] Najafi K, Hetke JF, Strength characterization of silicon microprobes in neurophysiological tissues.IEEE Trans Biomed Eng 37:5, 474-81 (1990 May)

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ref: Penfield-1937 tags: Penfield 1937 motor cortex stimulation ICMS human neurosurgery electrodes date: 01-03-2012 22:08 gmt revision:3 [2] [1] [0] [head]

No PMID / bibtex penfield-1937. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation

  • Fritsch and Hitzig (1870) [0] cited as the first paper in electrical excitation of the CNS.
  • Good review of the scientific experiments thereafter, including stimulation to S1 by Ferrier, work with apes etc.
  • Central sulcus called the 'Rolandic fissure'.
  • Interesting! quote:

The account of Bartholow (1874) is interesting to say the least and may be cited. His patient was a 30-year old-domestic. As an infant this unfortunate had chanced to fall into the fire, burning her scalp so badly that " hair was never reproduced." A piece of whale bone in the wig she was forced to wear irritated the scarred scalp and, by her statement, three months before she was admitted, an ulcer appeared. When she presented herself for relief, this had eroded the skull over a space 2 in. in diameter " where the pulsations of the brain are plainly seen." Although " rather feeble-minded " Bartholow observed that Mary returned replies to all questions and no sensory or motor loss could be made out in spite of the fact that brain substance apparently had been injured in the process of evacuation of pus from the infected area. The doctor believed, therefore, that fine insulated needles could be introduced without further damage.

While the electrodes were in the right side Bartholow decided to try the effect of more current. ' Her countenance exhibited great distress and she began to cry. Very soon the left hand was extended as if in the act of taking hold of some object in front of her; the arm presently was agitated with clonic spasms ; her eyes became fixed with pupils widely dilated ; the lips were blue and she frothed at the mouth ; her breathing became stertorous, she lost conscious-ness and was violently convulsed on the left side. This convulsion lasted for five minutes and was succeeded by coma. She returned to consciousness in twenty minutes from the beginning of the attack and complained of some weakness and vertigo." Three days after this stimulation, following a series of right-sided seizures, the patient died.

  • Relatively modern neurosurgical procedures.
  • They observe changes to blood circulation prior epileptic procedures. wow!
  • Very careful hand-drawn maps of what they have observed. Important, as you'll probably never get this trough an IRB. It pays to be meticulous.

____References____

[0] Fritsch G, Hitzig E, Electric excitability of the cerebrum (Uber die elektrische Erregbarkeit des Grosshirns).Epilepsy Behav 15:2, 123-30 (2009 Jun)

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ref: GULD-1964.07 tags: platinum iridium microelectrode eltrolytic etching original date: 01-03-2012 19:05 gmt revision:2 [1] [0] [head]

PMID-14199966[0] A Glass-covered platinum microelectrode

  • Details the manufacture and testing of PT-IR (70/30) etched solder glass-coated microelectrodes.
  • Melt a bead of the glass on the top and gradually draw the bead downward, surrounded by the heater of a pipette drawing machine.

____References____

[0] GULD C, A GLASS-COVERED PLATINUM MICROELECTRODE.Med Electron Biol Eng 2no Issue 317-27 (1964 Jul)

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ref: life-notes-2007 tags: electrode assay technology electrophysiology hack ad-hoc date: 01-03-2012 07:10 gmt revision:3 [2] [1] [0] [head]

properties of electrodes that are to penetrate the pia mater of a rhesus macaque:

  1. must easily go into a canned peach (in heavy or light sauce, it does not matter)
  2. does not go into pineapple cross-grain
  3. does go into the end-grain of pineapple
  4. penetrates the skin of a red grape (somewhat fresh) ~= pia
    1. The pia is a bit more tough than this, but is much less firm - if you are implanting electrodes that are any less than extremely sharp - e.g. etched - it will dimple the surface and not penetrate. Very sharp electrodes are key for getting through this tough membrane - which is even tougher in humans!
      • dimpling seems to silence cortical activity (observational evidence for this only)
      • however, once implanted lower-impedance electrodes work better. Low current microstimulation may be able to round the sharp tips of tungsten electrodes - we may want to test this.
    1. microdissection of the pia often damages the surface vasulature of the cortex, leading to localized infarctions, and hence should be avoided (unless you are really good)
    2. Bunching multiple elctrodes into one shaft - that is, making the shaft thicker and duller (albiet staggered) is not a good strategy for entering the brain (need to test the present monkeys).
  1. Cortical layer V (location of large pyramidal cells + betz cells in M1) in humans is 3-3.5mm below the surface, and ~1.6mm deep in rhesus. microwire/microwire arrays should have at least 2mm free wire length if intended for monkeys, and 4mm free wire if intended for humans.
    1. M1/S1 / central sulcus region is mostly inactive under isoflouro anesthesia, somewhat mangled/depressed with light ketamine, and silent with fentanyl. So, be careful with intraoperative recordings - the monkey/rat may be too deep, hence no cells to listen to!

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ref: Aflalo-2007.03 tags: Graziano motor cortex M1 SUA macaque monkey electrophysiology tuning date: 01-03-2012 03:37 gmt revision:1 [0] [head]

PMID-17360898[] Relationship between Unconstrained Arm Movements and Single-Neuron Firing in the Macaque Motor Cortex

  • the best explanation of neuronal firing was the final mulijoint configuration of the arm - it accounted for 36% of the SUA variance.
  • the search for the 'correct' motor parameter (that neurons are tuned to) is an ill-posed experimental question because motor parameters are very intercorrelated.
  • they knock experiments in which the animals are overtrained & the movements limited - and they are right!
  • single electrode recording with cronically implanted steel chamber - e.g. it took a damn long time!
    • imaged the central sulcus through the dura.
    • verified location with single unit responses to palpation of the contralateral hand/arm (in S1) & microstimulation-evoked movements in M1.
  • used optotrak to measure the position of the monkey.
  • occasionally, the monkey attemptted to scratch the experimenter with fast semi-ballistic arm movement. heh. :)
  • movements were seprarated based on speed analysis - that is, all the data were analyzed as discrete segments.
  • neurons were inactive during periods of hand stasis between movements.
  • tested the diversity of their training set in a clever way: they simulated neurons tuned to various parameters of the motion, and tested to see if their analysis could recover the tuning. it could.
    • however, they still used unvalidated regression analysis to test their hypothesis. regression analysis estimates how much variance is estimated by the cosine-tuning model - it returns an R^2.
  • either averaged the neuronal tuning over an entire movement or smoothed the firing rate using a 10hz upper cutoff.
  • Moran & Schwartz' old result seems to be as much a consequence of averaging across trials as it is a consequence of actual tuning...
    • whithout the averaging, only 3% of the variance could be attributed to speed tuning.
  • i think that they have a good point in all of this: when you eliminate sources of variance (e.g. starting position) from the behavior, either by mechanical restraint or simple omission of segments or even better averaging over trials, you will get a higher R^2. but it may be false, a compression of the space along an axis where they are not well correlated!
  • a model in which the final position matters little, but the velocity used to get there does, has been found to account for little of the neuronal variance.
    • instead, neurons are tuned to any of a number of movements that terminate near a preferred direction.
  • observational studies of of the normal psontaneous behavior of monkeys indicate that a high proportion of time is spent using the arm as a postural device.
    • therefore, they expect that neurons are tuned to endpoint posture.
    • modeled the neuronal firing as a gaussian surface in the 8-dimensional space of the arm posture.
  • in comparison to other studies, the offset between neural activity and behavior was not significantly different, over the entire population of recorded neurons, from zero. This may be due to the nature of the task, which was spontaneous and ongoing, not cue and reaction based, as in many other studies.
    • quote: This result suggests that the neuronal tuning to posture reflects reatively more and anticipation of the future state of the limb rather than a feedback signal about a recent state of the limb.

____References____

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ref: Moran-1999.11 tags: electrophysiology motor cortex Schwartz Moran M1 tuning date: 01-03-2012 03:36 gmt revision:2 [1] [0] [head]

PMID-10561437[0] Motor cortical representation of speed and direction during reaching

  • velocity is represented in the motor cortex.
  • they developed an equation relating firing rate to the position and velocity.
  • EMG direction had significantly different tuning from the cortical activity
    • the effect of speed on EMG was also different.
  • used single-electrode recording - 1,066 cells!!
  • introduce the square-root transformation of the firing rate (from Ashe and Georgopolous 1994)

____References____

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ref: Fu-1993.11 tags: electrophysiology Ebner premotor motor tuning M1 date: 01-03-2012 03:34 gmt revision:1 [0] [head]

PMID-8294972 Neuronal specification of direction and distance during reaching movements in the superior precentral premotor area and primary motor cortex of monkeys. 1993

  • trained monkey to do center-out task, 48 targets (8 angles, 6 distances).
  • single-electrode recording of 197 neurons in the primary motor and secondary motor / premotor (in the superior precentral sulcus).
  • cells were mostly tuned to direction, and less to distance, in both the premovement and movement periods. distance tuning was much stronger in the movement period.
    • tuning was measure by average firing rate for the premovement, movement, and total periods.
  • long, very detailed!

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ref: Lebedev-2006.09 tags: misha lebedev nicolelis BMI past present future electrodes review MEA date: 01-03-2012 03:26 gmt revision:2 [1] [0] [head]

PMID-16859758 Brain-machine interfaces: past, present and future.

  • Describes the state of the art & what needs to be done. Namely, better recording quality.
  • state that current EEG BMIs are limited to 5-25 bits/min (typo!!) [2,11]
    • [2] Wolpaw "Brain-computer interfaces for communication and control" 2002.
    • [11] Birbaumer "Brain-computer-interface research: coming of age" 2006.
  • set of references on biofeedback control of EEG in research animals.
  • EEG BCIs are either biofeedback based or classifier (P300, synchronous decoder ) based.
  • First invasive BMIs Fetz [40-45], Schmidt [46]; progress has been limited by technology. Must have been quite challenging for him to do the research!
    • [40] Fetz "Operant Conditioning of cortical unit activity" 1969
    • [41] Fetz "Are movement parameters recognizably coded in activity of single neurons?" 1992
    • [42] Fetz and Baker "Operantly conditioned patterns on precentral unit activity and correlated responses in adjacent cells and contralateral muscles." 1973
    • [43] Fetz and Finocchio "Operant Conditioning of specific patterns of neural and muscular activity" 1971
    • [44] Fetz and Finocchio "Operant conditioning of isolated activity in specific muscles and precentral cells" 1972
    • [45] Fetz and Finocchio 1975 "Correlations between activity of motor cortex cells and arm muscles during operantly conditioned response patterns." 1975
    • [46] Schmidt "single neuron recording from motor cortex as a possible source of signals for control of external devices." 1980
  • microelectrode arrays solved one of the problems.
  • talk about how more neurons are needed.
  • Principles of BMIs: Evarts [66-68], neuronal modulations are highly variable [69-72].
    • [66] Evarts, E.V. (1966) Pyramidal tract activity associated with a conditioned hand movement in the monkey.
    • [67] Evarts, E.V. (1968) Relation of pyramidal tract activity to force exerted during voluntary movement.
    • [68] Evarts, E.V. (1968) A technique for recording activity of subcortical neurons in moving animals.
    • "THus, as much as neighboring neurons might display highly disinct firing modulation patterns during the execution of a particular movement, single-neuron firing can vary substantially from one trial to the next, despite the fact that the overt movements remain virtually identical. :
    • "averaging across large populations of neurons significantly reduces the variability of signals derived from single neurons [54, 69].
    • Should i mention this in thesis?
  • Better way to assimilate the BMI into the body is to have proprioceptive feedback.
  • suggest the same standard things to be improved, excluding electronics. :
    • electrodes / recording
    • decoding
    • incorporating plasticity
    • better prosthetics.
  • "multi-unit signals can also be efficiently used in BMI control [57] {318}.
  • Some groups have strongly claimed that recordings from a small number of neurons can be sufficient for good performance in a BMI. [55,56,63]
    • This is not Miguel's approach: more neurons confers accuracy [54{317},57,70] and reliability [69].
      • [70] Wessberg, J. and Nicolelis, M.A. (2004) Optimizing a linear algorithm for real-time robotic control using chronic cortical ensemble recordings in monkeys. J. Cogn. Neurosci. 16, 1022–1035
  • Still need new microelectrodes; electrodes become encapsulated by fibrous tissue and cells die in the vicinity of electrodes [77] {781}.
    • suggest anti-inflammatory coating, though the jury is out.
  • Initial wireless telemetry systems: [93-99]. [93]{315}
    • [94] Knutti, J.W. et al. (1979) An integrated circuit approach to totally implantable telemetry systems. Biotelem. Patient Monit. 6, 95–106
    • [97] Chien, C.N. and Jaw, F.S. (2005) Miniature telemetry system for the recording of action and field potentials. J. Neurosci. Methods 147
    • [98] {930}
    • [99] Morizio Morizio, J. et al. (2005) Fifteen-channel wireless headstage system for single-unit rat recordings.
    • [100] (of broader interest) Moxon, K.A. et al. (2004) Ceramic-based multisite electrode arrays for chronic single-neuron recording. IEEE Trans. Biomed. Eng. 51, 647–656
  • nanotechnology probes that access the brain through the vasular system [101].
  • although a good number of linear and nonlinear algorithms have been proposed and tested [1,54,56,57,70,110-116], Wiener filters have proved sufficient [54,55,57,58,65,117].
  • almost 140 years ago Head and Holmes suggested that the body schema -- that is, the internal brain representation of one's body -- could extend itself to include a wielded tool.

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ref: WISE-2004.01 tags: wireless electrodes silicon Michigan Kipke Najafi recording MEA date: 01-03-2012 03:23 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

IEEE-01258173 (pdf) Wireless implantable microsystems: high-density electronic interfaces to the nervous system - January 2004.

  • very impressive!
  • based on the old / well established beam-lead technology (see the image of the paper at the bottom of that page).
    • required 20 years of development to create an etching process with sufficient yield, though. Microprobes have been in development since 1966.
    • Silicon is slowly attacked by saline; however, the use of a boron etch-stop to define the substrate virtually eliminates such erosion.
    • Silicon dioxide is known to slowly hydrate in water, but this can be mitigated by CVD of silicon nitride / silicon oxide stacks. Polysilicon can be used too, since it forms a tight bond with silicon oxide, keeping water out.
      • Why don't they just seal it with a known impermeable plastic/epoxy/whatever? (They do, later) Utah probe is sealed in parylene.
    • Shunt capacitance is negligible compared to site capacitance; heavy substrate doping minimizes electrical or optically induced noise & virtually eliminates crosstalk.
    • (Of course) Silicon allows amplifiers and circuitry to be formed at/near the electrode, eliminating the need for (some) interconnects.
    • Silicon ribbon connectors cannot be made much longer than a few centimeters. 4um thick silicon cables are 100x more flexible than a 25um gold wire (!!) - but that is out-of-plane; they are relatively weak for in-plane stress.
  • Gold has a maximum charge delivery of 20uC/cm^2 ; platinum, 75 uC/cm^2 ; iridium oxide, 3000 uC/cm^2.
  • Glass can be hermetically bonded to silicon if both flat clean surfaces are put in opposition with a high voltage (1500V) placed across the interface at an elevated temperature (400C). These packages have been shown to be stable and inert in guinea pigs.
    • Silicon nitride, thin metal films, and metal films over polymers are all attractive coatings for probes (with no mention of biocompatibility); they last decades in salt water, and eventually succumb to pinholes.
  • Silicon probes outperform microwire arrays by a factor of (up to) 50 in terms of volume of tissue displaced / recording site. Michigan probes are typically 15um thick x 60um in cross section.
  • they tend to use many more recording sites than recording channels, hence, have a low expected yield. e.g. they have a 1024 site electrode (see the cool figures!), and can record from the best 128 of those. good idea, reasonable strategy, I guess.
    • they demonstrate that it is not too hard to remove the artifact of multiplexing on their systems - the multiplexing noise is below electrode noise.
  • talk about spongifying their iridium electrodes using current pulses in a PBS solution to (apparently) lower electrode impedance.
  • talk about drug delivery too
  • describe the exact manufacturing procedures that the Michigan arrays are created, including the critical back-etch (which i don't exactly understand).
  • describe the circuits used to amplify low-level neural signals.
  • Their charge-redistribution ADC is okay - 250ksps, 9b resolution, 1.4mW from a 3v source. Commercial ADCS are better - AD7467 is 0.6mw, 200ksps, 10bits. (though it scales up to 1.3mW @ 3V, 200ksps ; 0.36mW @1.8V - so the devices are comparable.)
  • some of the (very tiny) electrodes have 'holes' (!)
  • also have wireless microstimulators.
  • demonstrate long-term recording: 383days post implant in a rat & there are still many cells (though the figure is not that great, it is easy to understand) (this might be an exemplar)
  • associated website?
  • (quote:) "For ranges of a few centimeters, the high attenuation of RF signals in biological tissue dictates carrier frequencies below 10Mhz." Their solution is to use FSK with octave jumps in freqency & modulation rates up to 60% that of the carrier frequency.

____References____

WISE, K.D. and ANDERSON, D.J. and HETKE, J.F. and KIPKE, D.R. and NAJAFI, K. Wireless implantable microsystems: high-density electronic interfaces to the nervous system Proceedings of the IEEE 92 1 76 - 97 (2004)

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ref: Csicsvari-2003.08 tags: recording michigan silicon electrodes Buzsaki MEA date: 01-03-2012 03:23 gmt revision:4 [3] [2] [1] [0] [head]

PMID-12904510[0] Csicsvari 2003 Massively parallel recording of unit and local field potentials with silicon-based electrodes

  • What's so massive? 64 or 96 channel Michigan probes.
  • Motivation: recording local connections and interactions requires precise knoledge of the location of your recording sites.
  • Some classic refs on cortical building blocks.
  • Optical recording: Mao et al 2001 PMID-11738033.
  • Wired recording:, Chicurel 2001; Deadwyler and Hampson 1995 PMID-7481817; Evarts 1968; {994}
  • Tetrodes: Drake 1988, Gray 1995, McNaughton et al 1983; Recce and O'Keefe 1989.
  • on-chip active circuitry (simple voltage feedback op-amp - without reference electrodes!) reduces microphone artifact. 6mm 'antenna'.
    • refs: Bai and Wise 2001 {995}; Olsson et al. 2002
    • also Najafi and Wise 1986 {996}; Wise and Najafi 1991 .
  • Stored wideband data; sorted via KlustaKwik.
  • Total recording area 1.6mm deep by 1.8mm wide. Shanks separated by 300um ; recordings sites separated by 100um; shanks 12um thick.
    • Made via double-sided deep reactive reactive ion etching (DRIE).
  • stimulated the entorhinal cortex & recorded in the hippocampus; used the precise spatial layout of the micromachined silicon electrodes to map out the evoked potentials.
  • figure 3 shows that they can record the 'same' neuron from multiple 100um-spaced sites on a given shank. Some of this is due to the physically large extent of the hippocampal cells which they recorded; spike propagate both down the axon and back into the soma, and by using Current Source Density maps, they could estimate some of spatio-temporal characterisics of the AP.
    • CSD is the second spatial derivtive of the local field potentials.
    • Could measure forward and back-propagation of APs to the dendrites (!)
  • quote: in contrast to wire tetrodes with blunt cute ends, it was possible to record from the same cell layer numerous times after moving the probe up and subsequently back to the previous recording location.
    • size of the electrode shanks: 62um wide x 12um thick at top of recording site of 12 site shank; 82um wide at top of 16 site shank.
    • Top 4 recording sites' recording quality deteriorated with multiple penetrations.
  • good place-cell map; cells were discriminated based on a PCA across both time and electrode.

____References____

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ref: Delgado-1968.1 tags: Delgado wireless stimulation recording electrode date: 01-03-2012 03:22 gmt revision:3 [2] [1] [0] [head]

PMID-5683678[0] Intracerebral radio stimulation and recording in completely free patients.

  • images/978_1.pdf
  • See: The cordoba bull ranch experiment (youtube).
  • "This paper reports instrumentation used and clinical application in four patients with psychomotor epilepsy in whom electrodes had been implanted in the temporal lobes. To our knowledge, this is the first clinical use of intracerebral radio stimulation and recording in man. "
  • Electrode: 1.2mm plastic stylus, 15 stainless steel 3mm wide contacts attached at 3mm intervals.
  • Implanted in the anterior medial amygdala.
  • The receiver-stimulator which is carried by the subject, measures 3.7cm x 3.0cm x 1.4cm, and weighs 20g. The solid-state circuitry is encapsulated in epoxy resin which provides it with very good mechanical strength and makes it waterproof. Space for the 7-volt Mercury battery is included in the size mentioned above.
  • 3 channels stim, individual pulse intensity, same pulse duration and repetition for all 3 channels.
    • Operating range 100ft.
    • max current 2uA.
  • 216Mhz IRIG EEG transimtter, FM modulated.
    • The size of the three-channel unit, including the battery, is 4.5cm x 4.5cm x 1.5cm, and it weighs 50g.
    • Input-referred noise: 5uV.
  • Remarkable: one cerebral contact could be shared by recording and stimulating units. (2MOhm input impedance in the EEG amps)
  • Radio stimulation of different points in the amygdala and hippocampus in the four patients produced a variety of effects including pleasant sensations, elation, deep, thoughtful, concentration, odd feelings , super relaxation, colored visions, and other responses.
  • Extensive information has been published about different systems for radio telemetry in biological studies (Barwick & Fullagar, 1967; Caceres, 1965; Geddes, 1962; Slater, 1963). The disparity between the large number of technical papers and the few reports of results indicates the existence of methodological problems.
    • Recall that cardiac pacemakers were by this time in common use.

____References____

[0] Delgado JM, Mark V, Sweet W, Ervin F, Weiss G, Bach-Y-Rita G, Hagiwara R, Intracerebral radio stimulation and recording in completely free patients.J Nerv Ment Dis 147:4, 329-40 (1968 Oct)

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ref: Otto-2006.02 tags: electrophysiology recording rejuvenation stimulation MEA date: 01-03-2012 03:21 gmt revision:3 [2] [1] [0] [head]

PMID-16485763[0] Voltage pulses change neural interface properties and improve unit recordings with chronically implanted microelectrodes.

  • stimulation protocol: 1.5 volts, cortical electrode positive, 4 seconds, DC, current measured.
  • results: 10% mean improvement in SNR (not that great, oh well)
    • however, some effects were really profound: complete rejuvenation of the recordings!
  • result: 67% lower impedance.

____References____

[0] Otto KJ, Johnson MD, Kipke DR, Voltage pulses change neural interface properties and improve unit recordings with chronically implanted microelectrodes.IEEE Trans Biomed Eng 53:2, 333-40 (2006 Feb)

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ref: Kennedy-1989.09 tags: Kennedy neurotrophic electrode recording fabrication 1989 electrophysiology date: 01-03-2012 03:21 gmt revision:2 [1] [0] [head]

PMID-2796391[0] The cone electrode: a long-term electrode that records from neurites grown onto its recording surface.

  • A piece of the sciatic nerve is placed in the glass cone before implantation in the cortex of a rat.
  • A neurite can be an axon or dendrite.

____References____

[0] Kennedy PR, The cone electrode: a long-term electrode that records from neurites grown onto its recording surface.J Neurosci Methods 29:3, 181-93 (1989 Sep)

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ref: Merletti-2009.02 tags: surface EMG multielectrode recording technology italy date: 01-03-2012 01:07 gmt revision:2 [1] [0] [head]

PMID-19042063[0] Technology and instrumentation for detection and conditioning of the surface electromyographic signal: state of the art

  • good background & review of surface EMG (sEMG) - noise levels, electrodes, electronics. eg. Instrumentation amplifiers with an input resistance < 100MOhm are not recommended, and the lower the input capacitance, the better: the impedance of a 10pf capacitor at 100hz is 160MOhm.
  • Low and balanced input impedances are required to reduce asymmetric filtering of common-mode power-line noise.

____References____

[0] Merletti R, Botter A, Troiano A, Merlo E, Minetto MA, Technology and instrumentation for detection and conditioning of the surface electromyographic signal: state of the art.Clin Biomech (Bristol, Avon) 24:2, 122-34 (2009 Feb)

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ref: Verloop-1984.08 tags: recording electrode arrays MEA epoxy teflon simple mold slice cultures date: 01-03-2012 00:57 gmt revision:2 [1] [0] [head]

PMID-6492861[0] A simple method for the construction of electrode arrays.

  • It is simple!
  • of note: "Therefore arrays of equidistant electrodes have been developed for superficial and depth recording. During the last decade the construction of many of these multiple electrodes for in vivo and in vitro measurements is based o n thin film techniques (Wise a n d Angell, 1975; Pickard, 1979; Pochay et al., 1979; Prohaska et al., 1979; Kuperstein and Whittington, 1981).
    • Have to go back and check these thin-film attempts.
  • See also: PMID-7248818[1] A flexible high density multi-channel electrode array for long-term chronic implantation. (surface recording).

____References____

[0] Verloop AJ, Holsheimer J, A simple method for the construction of electrode arrays.J Neurosci Methods 11:3, 173-8 (1984 Aug)
[1] Weissman AD, Schwartz EL, A flexible high density multi-channel electrode array for long-term chronic implantation.Brain Res Bull 6:6, 543-6 (1981 Jun)

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ref: Nicolelis-2002.1 tags: Nicolelis MEA electrodes recording date: 01-03-2012 00:57 gmt revision:1 [0] [head]

PMID-12367642[0] Multielectrode recordings: the next steps.

  • Ensemble recordings have actually been around for a long time -- Schmidt, at least.
    • 100s of electrodes, however, have not.
  • Predicted the death of single unit recordings and the emergence of 1000s of channels with indefinite longevity.
  • Also talk about gene arrays & antisense RNA & cre/loxP. Oldish.

____References____

[0] Nicolelis MA, Ribeiro S, Multielectrode recordings: the next steps.Curr Opin Neurobiol 12:5, 602-6 (2002 Oct)

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ref: Obeid-2004.02 tags: Wolf BMI recording electronics telemetry Obeid date: 12-31-2011 18:27 gmt revision:4 [3] [2] [1] [0] [head]

PMID-14757341[1] A low power multichannel analog front end for portable neural signal recordings.

  • have an interesting section on CMRR, quote: Although we use a precision differential amplifier with a CMRR of 110 dB, we were unable, in practice, to measure CMRRs greater than not, vert, similar42 dB. This can be accounted for by the device tolerances in the preamplifier stage; using ±0.1% resistors and ±5% capacitors in the preamplifier, the expected worst case CMRR at 1 kHz is 39.2 dB

____References____

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ref: -0 tags: M1 Evarts PTN conduction velocity monkey electrophysiology spinal cord date: 12-25-2011 04:25 gmt revision:0 [head]

PMID-14283057 Relation of Discharge Frequency to conduction velocity in pyramidal tract neurons

  • Not all PTN arise from the giant Betz cells -- there are too many pyramical tract axons, and not enough betz cells.
  • Most axons come from smaller cortical neurons [8,11,12].
  • Large cells have large axons hence the highest conduction velocity. (cite the squid studies...)
  • Estimate conduction velocity my stimulating in the medullary pyramid (e.g. the pyramidal tract at the level of the medulla)
  • Conduction velocity, in m/s, is six times diameter in microns (roughly; he lists no source here)
  • Mean frequency for 28 rapidly conductin units was 4.1 Hz;
    • These had a non-moving FR of fractional Hz.
    • Showed bursts with sleep, a few spikes when drowsy, very quiet when not moving.
  • MFR for 34 slower cells was 15.6 Hz.
    • Resting rate was higher in these cells.
    • Also showed bursts / more irregular firing with sleep.
  • Amazingly clean recordings. envy.
  • Some cells have much more irregular / more
  • Brookhart [2] concluded that large, rapidly conducting pyramidal fibers are probably responsible for the phasic element of movement control, whereas the smaller slower neurons are responsible for the tonic element.
  • Also true in the spinal cord: large afferents of the nuclear bag fibers in the muscle spindle carry transient info; group II are smaller and carry steady-state info.
  • ref Mountcastle [14] regarding reciprocal pairs of neurons being (surprise) reciprocally activated during joint movements.

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ref: Guenther-2009.12 tags: Guenther Kennedy 2009 neurotrophic electrode speech synthesize formant BMI date: 12-17-2011 02:12 gmt revision:2 [1] [0] [head]

PMID-20011034[0] A Wireless Brain-Machine Interface for Real-Time Speech Synthesis

  • Neurites grow into the glass electrode over the course of 3-4 months; the signals and neurons are henceforth stable, at least for the period prior publication (>4 years).
  • Used an FM modulator to send out the broadband neural signal; powered the implanted electronics inductively.
  • Sorted 56 spike clusters (!!)
    • quote: "We chose to err on the side of overestimating the number of clusters in our BMI since our Kalman filter decoding technique is somewhat robust to noisy inputs, whereas a stricter criterion for cluster definition might leave out information-carrying spike clusters."
    • 27 units on one wire and 29 on the other.
  • Quote: "neurons in the implanted region of left ventral premotor cortex represent intended speech sounds in terms of formant frequency trajectories, and projections from these neurons to primary motor cortex transform the intended formant trajectories into motor commands to the speech articulators."
    • Thus speech can be represented as a trajectory through formant space.
    • plus there are many simple low-load formant-based sw synthesizers
  • Used supervised methods (ridge regression), where the user was asked to imagine making vowel sounds mimicking what he heard.
    • only used the first 2 vowel formants; hence 2D task.
    • Supervised from 8 ~1-minute recording sessions.
  • 25 real-time feedback sessions over 5 months -- not much training time, why?
  • Video looks alright.

____References____

[0] Guenther FH, Brumberg JS, Wright EJ, Nieto-Castanon A, Tourville JA, Panko M, Law R, Siebert SA, Bartels JL, Andreasen DS, Ehirim P, Mao H, Kennedy PR, A wireless brain-machine interface for real-time speech synthesis.PLoS One 4:12, e8218 (2009 Dec 9)

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ref: Nicolelis-1997.04 tags: nicolelis kralik electrodes electrophysiology 1997 date: 12-17-2011 01:41 gmt revision:3 [2] [1] [0] [head]

PMID-11812202[0] Techniques for long-term multisite neuronal ensemble recordings in behaving animals.

  • talk about moveable bundles.
  • human-level surgical techniques and anesthesia.
  • new methods of data analysis.

____References____

[0] Kralik JD, Dimitrov DF, Krupa DJ, Katz DB, Cohen D, Nicolelis MA, Techniques for long-term multisite neuronal ensemble recordings in behaving animals.Methods 25:2, 121-50 (2001 Oct)

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ref: Kennedy-1992.08 tags: BMI Kennedy cone electrode electrophysiology recording neurotrophic date: 12-17-2011 01:00 gmt revision:1 [0] [head]

PMID-1407726[] The cone electrode: ultrastructural studies following long-term recording in rat and monkey cortex

  • they placed sciatic nerve inside the glass cone electrode to encourage regrowth.
    • alternatively, they filled the cone electrode with 'matrigel' whatever that 'neurotrophic substance' is.
  • good recordings at 6 months post impantation.
  • virtually no neurons were found in the tissue in any cone
    • however, they saw plenty of mylenated axons. (the mylenation assuredly is good for the quality of recordings hah)
    • in no case was the tissue absent from the glass.

____References____

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ref: notes-0 tags: EWH electrosurgery comments date: 03-26-2009 17:18 gmt revision:2 [1] [0] [head]

For the Instructions for use:

  • Section 1.0 -- "... instructions for use of the Electro Surgery ..."
    • Why do we need the decimal point? "Section 1"
  • Section 2.0 -- the figures are labeled 1.1, 1.2, 1.3. Should be 2.1, 2.2, 2.3? Good figures though.
    • Is there some way of cleaning up the figure labeling & numbering in section 5 (and indeed the assembly instructions). It's not bad, but...
  • Section 3.0 -- Maybe make "3.x.x" into bullet points. Numbers are a bit much.
  • Section 4.0 -- The 4.1 is extraneous...
  • Section 5.4 -- Why is the second paragraph text gray?
  • Section 5.5 -- "Wait two minutes for the power resistor to cool before repeating step 5.4". (Might as well tell them why they are waiting, gives them more reason to do so).
  • Section 5.7 -- Remind the user to wait some time for the power resistors to cool before trying different power settings. At lower powers, they will not have to wait too long; higher power will require longer wait time. In the future might want to put a thermsistor/resettable poly fuse or the like in there to thermally protect the device. Or one of the bimetal heat switches that they use in hair dryers; I'd imagine that they are cheap.
  • I'm not very familiar with ESU devices, but is there a possibility to see varying power levels within the 4-second evaluation period? Would this be important to note?

For the assembly instructions:

  • Section 2.0 -- You can probably get some images of the resistors off digikey :-)
    • Also, don't need to number "2.x" all of the components. One number in that table should be enough.
    • Separate column for device quantity would aid clarity.
  • Section 3.0 -- Are numbers needed for this short list?
  • Section 4.0 -- Ditto. Maybe bullets would be clearer. As for the grounded bench, perhaps should explain that static electricity can damage the diodes.
  • Section 5.0 --
    • Why make the user refer to the appendix for the resistor color codes? Just take a picture of the finished board, with all but the resistors masked out or lightened in photoshop, so the assembler can see what goes where. Or some other clear figure.
    • Tools and materials should not get its own column; put that in a row or bullet before the table. Maybe have a bullet point: "Components needed: R8, R7, R6..." This lets you make the pictures larger.
  • Section 5.2 -- Figure 3 - exactly! good figure.
    • Might as well put the diode numbers and values in the table. There is enough space below the first instruction bullet point.
  • Section 5.3 - 5.6 -- looks good.
  • Section 5.7 -- I would have to try this; it seems that most of the creases are intuitively obvious. Again, don't see the need for the gray text, though. The figures are good & illustrative.
  • Section 5.9 -- Would it be easier to apply the labels before folding, that way it is easy to apply even and firm pressure? I'm extrapolating here, don't know.
  • Appendix A -- You can hold LEDs or other components flush by bending the leads out after insertion. Re-melting & pushing the leads in sometimes results in bad solder joints. Otherwise good.

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ref: Kimura-1996.12 tags: putamen globus pallidus learning basal ganglia electrophysiology projection date: 10-03-2008 17:05 gmt revision:1 [0] [head]

PMID-8985875 Neural information transferred from the putamen to the globus pallidus during learned movement in the monkey.

  • study of the physiology of the projection from the striatum to the external and internal segments of the globus pallidus.
  • Identified neurons which project from the striatum to pallidus via antridromic activation after stim to the GPe / GPi.
  • there were two classes of striatal neurons:
    • tonically active neurons (TANs, rate: 4-8hz)
      • TANs were never activated by antidromic stimulation. therefore, they probably do not project to the pallidus.
    • phasically active neurons (very low basal rate, high frequency discharge in relation to behavioral tasks
      • All PANs found projected to the globus pallidus.
      • PANs were responsive to movement or movement preparation. (or not responsive to the particular behaviors investigated)
        • the PANns that showed activity before movement initiation more frequently projected to GPi and not GPE (or both - need to look at the anatomy more).
      • PANs also show bursts of activity time-locked to the initiation of movement (e.g. time locked to a particular part of the movement).
      • no neurons with sensory response!
  • when they microstimulated in the putamen, a few pallidal neurons showed exitatory response; most showed inhibitory/supressive response.

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ref: bookmark-0 tags: neural recording companies electrodes wireless bioamplifier germany date: 10-22-2007 01:39 gmt revision:2 [1] [0] [head]

http://www.neuroconnex.com/ -- looks like they have some excellent products, but not sure how to purchase them.

  • links to specification sheets are broken.
  • they have a closed-loop stimulator for treatment of Parkinsons etc. cool!
also see Mega biomonitor. (14 bit resolution)

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ref: notes-0 tags: nordic pinout nRF24L01 spark fun electronics date: 10-09-2007 19:59 gmt revision:5 [4] [3] [2] [1] [0] [head]

nordic semi links:

here is the connection list for the nRF24L01 module made by sparkfunelectronics
  1. VCC
  2. CE
  3. CSN
  4. SCK
  5. MOSI
  6. MISO
  7. IRQ
  8. GND
(1 is by the voltage regulator, obviously.) reversed:
  1. GND
  2. IRQ
  3. MISO
  4. MOSI
  5. SCK
  6. CSN
  7. CE
  8. VCC

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ref: Boline-2005.11 tags: electrophysiology motor cortex force isometric Ashe 2005 date: 04-09-2007 22:39 gmt revision:3 [2] [1] [0] [head]

this seems to be the same as {339}, with a different pubmed id & different author list. bug in the system!

PMID-16193273[0] On the relations between single cell activity in the motor cortex and the direction and magnitude of three-dimensional dynamic isometric force* the majority of cells responded to direction

  • few to the magnitude,
  • and ~10% to the direction & magnitude
  • control of static and dynamic motor systems is based on a common control process!
  • 2d task, monkeys, single-unit recording, regression analysis.

____References____

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ref: Ashe-1994.12 tags: Georgoplous motor control M1 S1 SUA electrophysiology 2D date: 04-09-2007 20:27 gmt revision:2 [1] [0] [head]

PMID-7703686[0] Movement parameters and neural activity in motor cortex and area 5

  • 290 cells in the motor cortex and 207 cells in area 5 (S1)
  • median R^2 = 0.581 & 0.530 in motor cortex
  • most prominent representation of target direction; least prominent representation of acceleration. (though statistically significant correlations were observed for all behavioral parameters)

Duke does not have online access to the article :(

____References____

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ref: Maier-1993.03 tags: force motor control grip electrophysiology date: 04-09-2007 20:20 gmt revision:4 [3] [2] [1] [0] [head]

PMID-8463818[0] Contribution of the monkey corticomotoneuronal system to the control of force in precision grip

  • recorded 33 corticomotoneronal cells
  • used spike-triggered averaging to find putative pyramidal tract neurons.
  • considerable trail-by-trial variability in the cells activity-force relationship
  • and, in an earlier work: PMID-810360[1] Relation of activity in precentral cortical neurons to force and rate of force change during isometric contractions of finger muscles.

____References____

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ref: HeppReymond-1999.09 tags: force motor control grip electrophysiology date: 04-09-2007 20:20 gmt revision:0 [head]

PMID-10473750[0] Context-dependent force coding in motor and premotor cortical areas.

  • here they found neurons related to dF/dt during another isometric precision grip task.

____References____

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ref: Thach-1978.05 tags: monkeys motor control M1 cerebellum electropysiology date: 04-09-2007 19:53 gmt revision:3 [2] [1] [0] [head]

PMID-96223[0] Correlation of neural discharge with pattern and force of muscular activity, joint position, and direction of intended next movement in motor cortex and cerebellum.

  • recorded from M1 and interpositus/dentate nucleus of the cerebellum.
  • three classes of response in the interpositus/dentate and M1
    1. some in relation to the pattern of muscle activity
    2. some in relation to the position of the wrist
    3. some in relation to the next intended movement.

____References____

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ref: Amirikian-2000.01 tags: Georgopulos directional tuning motor cortex SUA electrophysiology date: 04-05-2007 16:34 gmt revision:2 [1] [0] [head]

PMID-10678534[0] Directional tuning profiles of motor cortical cells

  • trained the monkeys to move to 20 targets in a horizontal plane
    • the larger number of targets allowed a more accurate estimation of the tuning properties of the cells
    • measured tuning based on the spike count during movement.
  • typical r^2 = 0.7 for a modified cosine fit

____References____

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ref: bookmark-0 tags: DARPA projects quantum electron spin date: 04-04-2007 20:39 gmt revision:0 [head]

http://www.darpa.mil/DSO/trans/transit.htm

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ref: physics notes-0 tags: plasma mercury vapor lamp electron ozone date: 04-03-2007 15:23 gmt revision:3 [2] [1] [0] [head]

ok, so i just (19 Feb 2007) did some simple experiments with the small (100W) mercury vapor lamp that i have + a hard-drive magnet + a solenoid.

  1. magnet splits the plasma into two paths, depending on the direction of the AC plasma current. The split is strongest when at the transition between north and south poles on the HD rare-earth magnet, as here the field lines are going in short loops with the vertical part approximately intersecting the plasma, and hence exerting the lorentz force towards or away from the magnet.
    1. it is possible to extinguish the bulb by moving the plasma too close! I think that this forces the electrons to collide with the quartz tube, cooling them too much.
  2. I also built a solenoid out of a small spool of 14 gauge magnet wire attached to my buzz box arc welder. The current was set at ~50 amps, (not sure how accurate that setting was) - enough to get the small coil pretty hot rather quickly. When placed inside the AC-energized coil, the plasma arc was forced to spiral around the walls of the quartz tube.
    1. This is most likely because the mean velocity of the electrons is pretty low, hence the lamour radius is high in the relatively-weak magnetic field. I notice that at the beginning of igniting the mercury-vapor lamp, far more ozone is produced (as gauged by smell) than is produced when it is hot and the plasma current is high. This accompanies a shift from a very blue emission spectra to a whiter emission, I think this is because the pressure becomes higher inside the tube, hence the mean free path of the electrons is lower, hence they have less energy to excite the hard-UV bands of mercury ions once the lamp is hot. http://en.wikipedia.org/wiki/Planck's_constant --> E=hv, where v is the frequency --> 250nm approximately equals 5 eV. lamour radius: mv/qB. 5ev ~= 1.33e6 m/s. @ B= 0.1T, lamour radius = 7.5e-5m = 0.07mm (what?) ok, more reasonable: B = 0.005T, r = 1mm - still smaller than observed! Need to check this magnetic field. B=mu n I. I = 50A, n = 3 * 2/0.064) = 93 turns, mu (air) = 4*pi*10^-7 --> B ~= 0.005T. (as a first approximation). If the electron velocity is lower, then the radius will be smaller; it is the opposite for the magnetic field strength.
    2. of course, we are disregarding thermal interactions, as well as drift - will have to look at the textbook for this.
  3. Feb 23 2007 - I made a larger-diameter solenoid out of the 14 gauge copper wire & turned the buzz-box welder current up to 100A (or so it says, don't know how much in practice) - enough to get the coil very hot very quickly. I put this current loop around the broken 400W metal-halide lamp - the one originally from the blacklight cannon. As it is still being driven from the same low-wattage power supply, it remains cool, the bulb voltage is low (21V) and much UV (and ozone) is produced - generally indicating that the pressure in the bulb is low and the electron velocity/mean free path is higher.
    1. well, actually: when the blub pressure is low, much energy below 240nm is produced. Apparently this is what is required for ozone production:
    2. HBO lamps do not generate ozone, because owing to the self-absorption in the cooler outer arc regions, all radiation below 240nm is trapped within the discharge. However during run-up before pressure increases, some ozone is produced.
    3. When I turned the solenoid on around the ignited bulb, the concentration of plasma in the center noticably increased, and the luminous intensity increased also. I'm not sure if this was due to AC pumping of plasma current; I doubt it, as most of the magnetic flux should have went around the plasma.
    4. The bulb voltage went to 23 - 24V; I do not know the current, I will have to measure it (perhaps with an oscilloscope?)
    5. The plasma became less uniform, too, perhaps because the solenoid was not aligned to the E-field with any accuracy.

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ref: physics notes-0 tags: plasma physics electromagnet tesla coil copper capillary tubing calculations date: 02-23-2007 16:01 gmt revision:0 [head]

calculations for a strong DC loop magnet using 1/8" copper capillary tubing:

  1. OD .125" = 3.1.7mm^2; ID 0.065 -> copper area = 23.2mm^2 ~= AWG 4
  2. AWG 4 = 0.8 ohms/km
  3. length of tubing: 30' ~= 40 turns @ 9" each (windings packed into a torus of major radius 1.5"; minor radius 0.5")
  4. water flow rate through copper capillary tubing: 1 liter/min; assuming we can heat it up from 30C -> 100C, this is 70KCal = 292 KJ/min = 4881 W total. (better pipe it into our hot water heater!)
  5. 4.8kw / 9m of tubing = 540 W/m
  6. 540W/m / 8e-4 = 821 A ; V = 821 * 9 * 8e-4 = 5.9V (!!! where the hall am i going to get that kind of power?)
  7. 821A * 40 turns = 32.8KA in a loop major radius 1.5" = 3.8cm
  8. magnetic field of a current loop -> B = 0.54T
  9. lamour radius: 5eV electrons @B = 0.54T : 15um; proton: 2.7cm; electrons @1KeV ~= 2.66e8 (this is close to the speed of light?) r = 3mm.

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ref: Teich-1997.03 tags: fractal LGN RGC electrophysiology SUA fano_factor date: 02-05-2007 19:00 gmt revision:0 [head]

PMID-9058948[0] Fractal character of the neural spike train in the visual system of the cat

  • excellent description of several analyses of point-process spike trains (here RGC and LGN cells): interevent-interval histogram, rescaled range analysis, the event-number histogram, the Fano factor, the Allan factor, and the periodogram.

http://hardcarve.com/wikipic/Teich1997_fanofactor.gif

____References____

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ref: Afanasev-2004.03 tags: striatum learning reinforcement electrophysiology putamen russians date: 02-05-2007 17:33 gmt revision:3 [2] [1] [0] [head]

PMID-15151178[0] Sequential Rearrangements of the Ensemble Activity of Putamen Neurons in the Monkey Brain as a Correlate of Continuous Behavior

  • recorded 6-7 neurons in the putamen during alternative spatial selection
  • used discriminant analysis (whats that?) to analyze re-arrangements in spike activity
  • dynamics of re-arrangnement were dependent on reinforcement, and mostly contralateral striatum

____References____

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ref: Gdowski-2001.02 tags: globus pallidus reward electrophysiology 2001 date: 0-0-2007 0:0 revision:0 [head]

PMID-11160530 Context Dependency in the Globus Pallidus Internal Segment During Targeted Arm Movements

  • most of the movement-responsive neurons had modulations in the cued segment of the task, not in the subsequent relaxed, self-paced phase.
  • this constitutes a reward or context-dependence.
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ref: Cooper-2000.09 tags: globus pallidus electrophysiology current clamp channel date: 0-0-2007 0:0 revision:0 [head]

PMID-10970430 Electrophysiological and morphological characteristics of three subtypes of rat globus pallidus neurone in vitro

  • there are 3 morphological types of neurons.
    • A: inward rectfier + low-threshold calcium current = anode break depolarizations.
    • B: no inward rectifier, just fast monophasic AHP. small.
    • C: big! (...)

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ref: Stefani-1995.09 tags: electrophysiology dopamine basal_ganglia motor learning date: 0-0-2007 0:0 revision:0 [head]

PMID-8539419 Electrophysiology of dopamine D-1 receptors in the basal ganglia: old facts and new perspectives.

  • D1 is inhibitory (modulatory) on striatal neurons.
  • D1 cloned in 1990
  • D1 stimulates adenyl cyclase. (cAMP)
  • D1 activity shown to be necessary, but not sufficient, to generate long-term depression in striatal slices.
  • SKF 38393 was designed as a selective D1 receptor agonist; it has been available since the late 70's; it has nanomolar affinity for D1-R. SKF 38393 inhibits action potential discharge in striatal neurons as measued through response to intracellular current depolarizations.
  • striatal cells project to the substantia nigra.
  • alternate hypothesis: D1 activation on the striatonigral afferents to the ventral tegmental area (VTA) promotes GABA release.
    • recall that the VTA projects to the frontal/prefrontal cortex (PFC) via the mesocortical dopiminergic pathway. http://grad.uchc.edu/phdfaculty/antic.html There, DA synapese on spines of distal dendrites in juxtaposition with glutamergic synapses. this guy posits that these DA synapses are involved in the pathology of schizophrenia, and he uses optical techniques to measure the DA/Glu synapses.
    • VTA is just below the red nucleus in rats.
  • some people report that SKF 38393 potentiated depolarizing membrane responses to exogenous NMDA (agonist, excitotoxin).
  • they prefer the magnesium-dependent LTD pathway.
    • D1 receptor antagonist SCH 23390 prevented the generation of LTD in striatum. (Calabresi et al 1992).
    • in DA-depleted slices, LTD could be restored by the co-administration of D1 and D2 agonists.

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ref: Wannier-2002.01 tags: globus_pallidus electrophysiology caudate putamen basal_ganglia date: 0-0-2007 0:0 revision:0 [head]

PMID-11924876 Neuronal activity in primate striatum and pallidum related to bimanual motor actions

  • monkeys had to pull on a spring-loaded drawer and grab food with other hand.
  • half the recorded neurons were responsive to this task.
  • targeted: 20.1 to 14.v mm anterior to the interaural plane of the rhesus monkey brain.
    • 19.2 mm looks good for GPe
    • 17.4 for putamen and caudate (right below area 24 in the cortex - Ventral cingulate cortex)
    • 15.6 for putamen, GPe, and GPi.
  • can these be modulated by imagined movement? e.g. in a BMI?

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ref: Ito-2003.1 tags: anterior cingulate cortex ACC electrophysiology date: 0-0-2007 0:0 revision:0 [head]

PMID-14526085 Performance Monitoring by the Anterior Cingulate Cortex During Saccade Countermanding

locations of neurons http://www.sciencemag.org/content/vol302/issue5642/images/large/se3831902004.jpeg