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[0] Beurrier C, Bezard E, Bioulac B, Gross C, Subthalamic stimulation elicits hemiballismus in normal monkey.Neuroreport 8:7, 1625-9 (1997 May 6)

[0] Ativanichayaphong T, He JW, Hagains CE, Peng YB, Chiao JC, A combined wireless neural stimulating and recording system for study of pain processing.J Neurosci Methods 170:1, 25-34 (2008 May 15)

[0] Jackson A, Mavoori J, Fetz EE, Long-term motor cortex plasticity induced by an electronic neural implant.Nature 444:7115, 56-60 (2006 Nov 2)

[0] Isoda M, Hikosaka O, Switching from automatic to controlled action by monkey medial frontal cortex.Nat Neurosci 10:2, 240-8 (2007 Feb)

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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: -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: carbon fiber thread spinning Pasquali Kemere nanotube stimulation date: 02-09-2017 01:09 gmt revision:0 [head]

PMID-25803728 Neural stimulation and recording with bidirectional, soft carbon nanotube fiber microelectrodes.

  • Poulin et al. demonstrated that microelectrodes made solely of CNT fibers22 show remarkable electrochemical activity, sensitivity, and resistance to biofouling compared to conventional carbon fibers when used for bioanalyte detection in vitro.23-25
  • Fibers were insulated with 3 um of block copolymer polystyrene-polybutadiene (PS-b-PBD) (polybutadiene is sythetic rubber)
    • Selected for good properties of biocompatibility, flexibility, resistance to flextural fatigue.
    • Available from Sigma-Aldrich.
    • Custom continuous dip-coating process.
  • 18um diameter, 15 - 20 x lower impedance than equivalently size PtIr.
    • 2.5 - 6x lower than W.
    • In practice, 43um dia, 1450um^2, impedance of 11.2 k; 12.6um, 151k.
  • Charge storage capacity 327 mC / cm^2; PtIr = 1.2 mC/cm^2
  • Wide water window of -1.5V - 1.5V, consistent with noble electrochemical properties of C.
  • Lasts for over 97e6 pulsing cycles beyond the water window, vs 43e6 for PEDOT.
  • Tested via 6-OHDA model of PD disease vs. standard PtIr stimulating electrodes, implanted via 100um PI shuttled attached with PEG.
  • Yes, debatable...
  • Tested out to 3 weeks durability. Appear to function as well or better than metal electrodes.

PMID-23307737 Strong, light, multifunctional fibers of carbon nanotubes with ultrahigh conductivity.

  • Full process:
    1. Dissolve high-quality, 5um long CNT in chlorosulfonic acid (the only known solvent for CNTs)
    2. Filter to remove particles
    3. Extrude liquid crystal dope through a spinneret, 65 or 130um orifice
    4. Into a coagulant, acetone or water
    5. Onto a rotating drum to put tension on the thread & align the CNTs.
    6. Wash in water and dry at 115C.
  • Properties:
    • Tensile strength 1 GPa +- 0.2 GPa.
    • Tensile modulus 120 GPa +- 50, best value 200 GPa
      • Pt: 168 GPa ; Au: 79 GPa.
    • Elongation to break 1.4 %
    • Conductivity: 0.3 MS/m, Iodine doped 5 +- 0.5 MS/m (22 +- 4 microhm cm)
      • Cu: 59.6 MS/m ; Pt: 9.4 MS/m ; Au: 41 MS/m
      • Electrical conductivity drops after annealing @ 600C
      • But does not drop after kinking and repeated mechanical cycling.
  • Theoretical modulus of MWCNT ~ 350 GPa.
  • Fibers well-aligned at ~ 90% the density (measure 1.3 g/cc) of close-packed CNT.

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ref: -0 tags: microstimulation rat cortex measurement ICMS spread date: 01-26-2017 02:52 gmt revision:0 [head]

PMID-12878710 Spatiotemporal effects of microstimulation in rat neocortex: a parametric study using multielectrode recordings.

  • Measure using extracellular ephys a spread of ~ 1.3mm from near-threshold microstimulation.
  • Study seems thorough despite limited techniques.

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ref: -0 tags: direct electrical stimulation neural mapping review date: 01-26-2017 02:28 gmt revision:0 [head]

PMID-22127300 Direct electrical stimulation of human cortex -- the gold standard for mapping brain functions?

  • Fairly straightforward review, shows the strengths and weaknesses / caveats of cortical surface stimulation.
  • Axon initial segment and nodes of Ranvier (which has a high concentration of Na channels) are the most excitable.
  • Stimulation of a site in the LGN of the thalamus increased the BOLD signal in the regions of V1 that received input from that site, but strongly suppressed it in the retinotopicaly matched regions of extrastriate cortex.
  • To test the hypothesis that the deactivation of extrastriate cortex might be due to synaptic inhibition of V1 projection neurons, GABA antagonists were microinjected into V1 in monkeys in experiments that combined fMRI, ephys, and microstim.
    • Ref 25. PMID-20818384
    • These findings suggest that the stimulation of cortical neurons disrupts the propagation of cortico-cortico signals after the first synapse.
    • Likely due to feedforward and recurrent inhibition.
  • Revisit the hypothesis of tight control of excitation and inhibition (e.g. in-vivo patch clamping + drugs). "The interactions between excitation and inhibition within cortical microcircuits as well as between inter-regional connections haper the predicability of stimulation."
  • The average size of a fMRI voxel:
    • 55ul, 55mm^2
    • 5.5e6 neurons,
    • 22 - 55e9 billion synapses,
    • 22km dendrites (??)
    • 220km axons.
  • In the 1970s, Daniel Pollen conducted a series of studies stimulating the visual cortex of cats and humans.
    • Observed long intra-stim responses, and post-stim afterdischarges.
    • Importantly, he also observed inhibitory effects of DES on cortical responses at the stimulation site.
      • The inhibitory effect depended on the state of the neuron before stimulation.
      • High spontaneous activity + low stim strengths = inhibition;
      • low spontaneous activity + high stim strengths = excitation.
  • In the author's opinion, there is an equal or greater number of inhibitory responses to electrical microstimulation as excitatory. Only, there is a reporting bias toward the positive.
  • Many locations for paresthesias:
    • postcentral sulcus (duh)
    • opercular area inferior postcentral gyrus (e.g. superior to and facing the temporal lobe)[60]
    • posterior cingulate gyrus
    • supramarginal gyrus
    • temporal lobe, limbic and isocortical structures.

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ref: -0 tags: nucleus accumbens caudate stimulation learning enhancement MIT date: 09-20-2016 23:51 gmt revision:1 [0] [head]

Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning

  • Monkeys had to learn to associate an image with one of 4 reward targets.
    • Fixation period, movement period, reward period -- more or less standard task.
    • Blocked trial structure with randomized associations + control novel images + control familiar images.
  • Timed stimulation:
    • Nucleus Accumbens during fixation period
      • Shell not core; non-hedonic in separate test.
    • Caudate (which part -- targeting?) during feedback on correct trials.
  • Performance on stimulated images improved in reaction time, learning rate, and ultimate % correct.
  • Small non-significant improvement in non-stimulated novel image.
  • Wonder how many stim protocols they had to try to get this correct?

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ref: Gradinaru-2009.04 tags: Deisseroth DBS STN optical stimulation 6-OHDA optogenetics date: 05-10-2016 23:48 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-19299587[0] Optical Deconstruction of Parkinsonian Neural Circuitry.

  • Viviana Gradinaru, Murtaza Mogri, Kimberly R. Thompson, Jaimie M. Henderson, Karl Deisseroth
  • DA depletion of the SN leads to abnormal activity in the BG ; HFS (>90Hz) of the STN has been found to be therapeutic, but the mechanism is imperfectly understood.
    • lesions of the BG can also be therapeutic.
  • Used chanelrhodopsin (light activated cation channel (+)) which are expressed by cell type specific promoters. (transgenic animals). Also used halorhodopsins, which are light activated chloride pumps (inhibition).
    • optogenetics allows simultaneous optical stimulation and electrical recording without artifact.
  • Made PD rats by 6-hydroxydopamine unilaterally into the medial forebrain bundle of rats.
  • Then they injected eNpHr (inhibitory) opsin vector targeting excitatory neurons (under control of the CaMKIIa receptor) to the STN as identified stereotaxically & by firing pattern.
    • Electrical stimulation of this area alleviated rotational behavior (they were hemiparkinsonian rats), but not optical inhibition of STN.
  • Alternately, the glia in STN may be secreting molecules that modulate local circuit activity; it has been shown that glial-derived factor adenosine accumulates during DBS & seems to help with attenuation of tremor.
    • Tested this by activating glia with ChR2, which can pass small Ca+2 currents.
    • This worked: blue light halted firing in the STN; but, again, no behavioral trace of the silencing was found.
  • PD is characterized by pathological levels of beta oscillations in the BG, and synchronizing STN with the BG at gamma frequencies may ameliorate PD symptoms; while sync. at beta will worsen -- see [1][2]
  • Therefore, they tried excitatory optical stimulation of excitatory STN neurons at the high frequencies used in DBS (90-130Hz).
    • HFS to STN failed, again, to produce any therapeutic effect!
  • Next expressed channel rhodopsin in only projection neurons Thy1::ChR2 (not excitatory cells in STN), again did optotrode (optical stim, eletrical record) recordings.
    • HFS of afferent fibers to STN shut down most of the local circuitry there, with some residual low-amplitude high frequency burstiness.
    • Observed marked effects with this treatment! Afferent HFS alleviated Parkinsonian symptoms, profoundly, with immediate reversal once the laser was turned off.
    • LFS worsened PD symptoms, in accord with electrical stimulation.
    • The Thy1::ChR2 only affected excitatory projections; GABAergic projections from GPe were absent. Dopamine projections from SNr were not affected by the virus either. However, M1 layer V projection neurons were strongly labeled by the retrovirus.
      • M1 layer V neurons could be antidromically recruited by optical stimulation in the STN.
  • Selective M1 layer V HFS also alleviated PD symptoms ; LFS had no effect; M2 (Pmd/Pmv?) LFS causes motor behavior.
  • Remind us that DBS can treat tremor, rigidity, and bradykinesia, but is ineffective at treating speech impairment, depression, and dementia.
  • Suggest that axon tract modulation could be a common theme in DBS (all the different types..), as activity in white matter represents the activity of larger regions compactly.
  • The result that the excitatory fibers of projections, mainly from the motor cortex, matter most in producing therapeutic effects of DBS is counterintuitive but important.
    • What do these neurons do normally, anyway? give a 'copy' of an action plan to the STN? What is their role in M1 / the BG? They should test with normal mice.

____References____

[0] Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K, Optical Deconstruction of Parkinsonian Neural Circuitry.Science no Volume no Issue no Pages (2009 Mar 19)
[1] Eusebio A, Brown P, Synchronisation in the beta frequency-band - The bad boy of parkinsonism or an innocent bystander?Exp Neurol no Volume no Issue no Pages (2009 Feb 20)
[2] Wingeier B, Tcheng T, Koop MM, Hill BC, Heit G, Bronte-Stewart HM, Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in Parkinson's disease.Exp Neurol 197:1, 244-51 (2006 Jan)

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ref: -0 tags: RF microstimulation cats threshold date: 09-04-2014 18:43 gmt revision:1 [0] [head]

PMID-13539663 Subcortical threshold voltages as a function of sine wave frequencies Brown and Brackett

  • 22 GA insulated stainless steel electrodes, both bipolar and monopolar.
    • This happens to be near spike recording passband, unfortunately.
  • Square wave stimulation (8) Mihailovic and Delgado 1956 "Electrical stimulation of monkey brain with various frequencies and pulse durations".
  • Hines (6)(1940) , stimulating the monkey cortex with [a] sine wave, reported jerky uncompleted movements from 1260 Hz to 1440 Hz.
    • Monopolar surface stimulation, though.

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ref: -0 tags: RF microstimulation UCSF date: 09-04-2014 18:42 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-4550167[1] Sensory responses elicited by subcortical high frequency electrical stimulation in man. -- everything innovative has already been done in the 70s!

  • "A radiofrequency current of 100 kHz sine wave was applied to therapeutic targets in the human brain and produced unpleasant sensory responses. Increasing the applied frequency to 250 kHz eliminated these responses.
  • Targets:
    • Near the junctions between the ventral lateral and the posteroventral lateral thalamic nuclei in patients with dyskinesias
    • Medial lemniscus in patients with intractable pain.
  • Frequently the patients reported that hte 100kHz radiofrequency current produced a severe unpleasant tingling or burning sensation.
    • The sensation was similar in quality and site to that elicited by 60 pps fstimulation, but tended to be much more intense and could not be tolerated by the patients.
  • The current necessary to produce sensory responses could produce a temperature change of less than 0.5 deg C as measured by our thermistor monitor.
  • Brown and Brackett {1298} have shown that motor responses are obtained when stimulating subcortical structures in the cat with frequencies as high as 100 kHz.
    • From 50 Hz to 25 kHz, they found the response to be smooth and definite.
    • Above 25 kHz the responses from most areas consisted of quick transient jerks at the onset of stimulus.
  • Other workers dealing with a variety of structures have reported stimulus responses to quite high frequencies.
    • As the frequency is raised, the current required for excitation increases.
    • Ultimately I 2R heating and tissue destruction provide the upper frequency limit for excitation.

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ref: Cosman-2005.12 tags: microstimulation RF pain neural tissue ICMS date: 09-04-2014 18:10 gmt revision:14 [13] [12] [11] [10] [9] [8] [head]

One of the goals/needs of the lab is to be able to stimluate and record nervous tissue at the same time. We do not have immediate access to optogenetic methods, but what about lower frequency EM stimulation? The idea: if you put the stimulation frequency outside the recording system bandwidth, there is no need to switch, and indeed no reason you can't stimulate and record at the same time.

Hence, I very briefly checked for the effects of RF stimulation on nervous tissue.

  • PMID-16336478[0] Electric and Thermal Field Effects in Tissue Around Radiofrequency Electrodes
    • Most clinical response to pulsed RF is heat ablation - the RF pulses can generate 'hot spots' c.f. continuous RF.
    • Secondary effect may be electroporation; this is not extensively investigation.
    • Suggests that 500kHz pulses can be 'rectified' by the membrane, and hence induce sodium influx, hence neuron activation.
    • They propose that some of the clinical effects of pulsed RF stimulation is mediated through LTD response.
  • {1297} -- original!
  • PMID-14206843[2] Electrical Stimulation of Excitable Tissue by Radio-Frequency Transmission
    • Actually not so interesting -- deals with RF powered pacemakers and bladder stimulators; both which include rectification.
  • Pulsed and Continous Radiofrequency Current Adjacent to the Cervical Dorsal Root Ganglion of the Rat Induces Late Cellular Activity in the Dorsal Horn
    • shows that neurons are activated by pulsed RF, albeit through c-Fos staining. Electrodes were much larger in this study.
    • Also see PMID-15618777[3] associated editorial which calls for more extensive clinical, controlled testing. The editorial gives some very interesting personal details - scientists from the former Soviet bloc!
  • PMID-16310722[4] Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons.
    • used 20ms pulses of 500kHz.
    • Small diameter fibers are differentially activated.
    • Pulsed RF induces activating transcription factor 3 (ATF3), which has been used as an indicator of cellular stress in a variety of tissues.
    • However, there were no particular signs of axonal damage; hence the clinically effective analgesia may be reflective of a decrease in cell activity, synaptic release (or general cell health?)
    • Implies that RF may be dangerous below levels that cause tissue heating.
  • Cellphone Radiation Increases Brain Activity
    • Implies that Rf energy - here presumably in 800-900Mhz or 1800-1900Mhz - is capable of exciting nervous tissue without electroporation.
  • Random idea: I wonder if it is possible to get a more active signal out of an electrode by stimulating with RF? (simultaneously?)
  • Human auditory perception of pulsed radiofrequency energy
    • Evicence seems to support the theory that it is local slight heating -- 6e-5 C -- that creates pressure waves which can be heard by humans, guinea pigs, etc.
    • Unlikely to be direct neural stimulation.
    • High frequency hearing is required for this
      • Perhaps because it is lower harmonics of thead resonance that are heard (??).

Conclusion: worth a shot, especially given the paper by Alberts et al 1972.

  • There should be a frequency that sodium channels react to, without inducing cellular stress.
  • Must be very careful to not heat the tissue - need a power controlled RF stimulator
    • The studies above seem to work with voltage-control (?!)

____References____

[0] Cosman ER Jr, Cosman ER Sr, Electric and thermal field effects in tissue around radiofrequency electrodes.Pain Med 6:6, 405-24 (2005 Nov-Dec)
[1] Alberts WW, Wright EW Jr, Feinstein B, Gleason CA, Sensory responses elicited by subcortical high frequency electrical stimulation in man.J Neurosurg 36:1, 80-2 (1972 Jan)
[2] GLENN WW, HAGEMAN JH, MAURO A, EISENBERG L, FLANIGAN S, HARVARD M, ELECTRICAL STIMULATION OF EXCITABLE TISSUE BY RADIO-FREQUENCY TRANSMISSION.Ann Surg 160no Issue 338-50 (1964 Sep)
[3] Richebé P, Rathmell JP, Brennan TJ, Immediate early genes after pulsed radiofrequency treatment: neurobiology in need of clinical trials.Anesthesiology 102:1, 1-3 (2005 Jan)
[4] Hamann W, Abou-Sherif S, Thompson S, Hall S, Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons.Eur J Pain 10:2, 171-6 (2006 Feb)

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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)

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ref: Fuentes-2009.03 tags: Nicoelis DCS spinal cord stimulation PD Fuentes Petersson 6-OHDA date: 03-03-2012 02:46 gmt revision:3 [2] [1] [0] [head]

PMID-19299613[0] Spinal cord stimulation restores locomotion in animal models of Parkinson's disease.

  • Motivation: different levels of cortical oscillation during movement and rest (LFO decreased, medium-high freq increased); PD associated with abnormal synchronous corticostriatal oscillations.
  • In epilepsy patients, stimulation of peripheral nerve afferents is effective in desychronizing low-frequency neural activity, reducing the frequency and duration of seizures (8,9,10) PMID-11050139[1] PMID-16886985[2] PMID-18188148[3]
  • DCS (dorsal column stimulation)
    • Epidural, longitudal electrodes, horizontal electrical field.
    • Upper thoracic, mice.
    • 300Hz.
    • simpler and safer than brain surgery.
    • [24] DCS induces no increase in arousal. (Wall, PD. Brain 1970; 93:505.
  • used the tyrosine hydroxyalse inhibitor AMPT
  • M1 LFP: Osc around 1.5-4Hz and 10-15Hz enhanced; osc > 25Hz subdued.
  • DCS increased locomotion by 29x in depleted animals, and 4.9x in normal animals.
  • Also titrated L-DOPA with DAT-KO mice. Without dopamine, there is no movement.
    • DCS increased L-DOPA effectiveness by 5x (1/5 the dose was required)
  • Verified in a 6-OHDA lesion model in rats.
    • Lesioned animals moved more, sham moved less.
  • Activation of locomotion is via striatal medium spiny neurons projecting to the output nuclei of the basal ganglia [26 PMID-8402406[4] ,27 PMID-1695404[5]].
  • In PD, with reduced striatal dopamine levels, the activation threshold of the projection neurons from the striatum is significantly increased [25] PMID-17916382[6].

____References____

[0] Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA, Spinal cord stimulation restores locomotion in animal models of Parkinson's disease.Science 323:5921, 1578-82 (2009 Mar 20)
[1] Fanselow EE, Reid AP, Nicolelis MA, Reduction of pentylenetetrazole-induced seizure activity in awake rats by seizure-triggered trigeminal nerve stimulation.J Neurosci 20:21, 8160-8 (2000 Nov 1)
[2] DeGiorgio CM, Shewmon A, Murray D, Whitehurst T, Pilot study of trigeminal nerve stimulation (TNS) for epilepsy: a proof-of-concept trial.Epilepsia 47:7, 1213-5 (2006 Jul)
[3] George MS, Nahas Z, Bohning DE, Lomarev M, Denslow S, Osenbach R, Ballenger JC, Vagus nerve stimulation: a new form of therapeutic brain stimulation.CNS Spectr 5:11, 43-52 (2000 Nov)
[4] Brudzynski SM, Wu M, Mogenson GJ, Decreases in rat locomotor activity as a result of changes in synaptic transmission to neurons within the mesencephalic locomotor region.Can J Physiol Pharmacol 71:5-6, 394-406 (1993 May-Jun)
[5] DeLong MR, Primate models of movement disorders of basal ganglia origin.Trends Neurosci 13:7, 281-5 (1990 Jul)
[6] Grillner S, Wallén P, Saitoh K, Kozlov A, Robertson B, Neural bases of goal-directed locomotion in vertebrates--an overview.Brain Res Rev 57:1, 2-12 (2008 Jan)

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ref: -0 tags: locomotion decerebrated monkeys spinal cord section STN stimulation date: 03-01-2012 23:53 gmt revision:0 [head]

PMID-7326562 Locomotor control in macaque monkeys

  • Were not able to induce walking with in monkeys with a sectioned spinal cord
  • Were able to induce walking motion by pulsed stimulation of the STN, with varying walking speed with varying currents!
  • Detailed, informative report, more than I have time to record here today.

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ref: -0 tags: striatum microstimulation abnormal myclonus dyskinesia date: 02-24-2012 19:44 gmt revision:0 [head]

PMID-21508304 Discontinuous Long-Train Stimulation in the Anterior Striatum in Monkeys Induces Abnormal Behavioral States

  • Long-train microstimulation induces complex, abnormal behavior: finger licking and biting, dyskinesias, grooming; more anterior (associative) resulted in hyper, hypo manic or stereotyped behaviors.
  • Short-train stimulation induces myoclonic-like movements.

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ref: Salin-2002.06 tags: STN HFS DBS stimulation dopamine date: 02-22-2012 18:23 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-12077209[0][] High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat.

  • they wanted to measure the cellular/molecular effects of STN DBS - reasonable.
    • in-situ hybridization histochemistry and immunocytochemnistry.
  • HFS of the STN decreases the metabolic activity of STN neurons (cytochrome oxidase (CoI) levels decreased!),
    • However it did not affect the overexpression of enkephalin {1135} mRNA or the decrease in substance P in the ipsilateral striatum.
    • Decreased/corrects glutamate decarboxylase 67 (GAD67) in the substantia nigra following STN lesion, worsened in the entopeduncular (GPe-ish: see wiki) nucleus, no change in GPi.
    • HFS, however, increases c-fos activity, which seems to be involved in immediate early gene induction and stress response (as well as 8,000 other papers about this protein)
  • this stimulation may not simply cause interruption of STN outflow.
  • STN on the order of 300ua through a 200um teflon-coated stainless bipolar (twisted pair) electrode (important to consider)
  • unilateral HFS in STN in hemiparkinsonian rats can induce dyskinesias
    • buuut a higher intensity of stimulation was required to elicit dyskinesia in animals with the dopamine lesion as compared to the intact rats. Parkinsonian animals are more resistant to HFS of the STN.
    • Therefore they matched the stimulus intensity to the behavior correlates, not the absolute values of the currents.
  • STN HFS in animals with dopamine lesions on the same brain side may prevent the previously reported dopamine hyperactivity in the contralateral hemisphere.
  • note bene, the entopeduncular nucleus is probably not a good taget for surgical treatment PMID-14602091[1][] High frequency stimulation of the entopeduncular nucleus has no effect on striatal dopaminergic transmission.

____References____

[0] Salin P, Manrique C, Forni C, Kerkerian-Le Goff L, High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat.J Neurosci 22:12, 5137-48 (2002 Jun 15)
[1] Meissner W, Harnack D, Hoessle N, Bezard E, Winter C, Morgenstern R, Kupsch A, High frequency stimulation of the entopeduncular nucleus has no effect on striatal dopaminergic transmission.Neurochem Int 44:4, 281-6 (2004 Mar)

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ref: Gubellini-2009.09 tags: DBS PD 2009 review historical microstimulation ICMS chronaxie rheobase date: 02-22-2012 14:33 gmt revision:11 [10] [9] [8] [7] [6] [5] [head]

PMID-19559747[0] Deep brain stimulation in neurological diseases and experimental models: from molecule to complex behavior.

  • Wow, DBS has been used since the 1950s for localization of lesion targets; in the 1960's was discovered to alleviate tremor; 70s and 80s targeted at the cerebellum for treatimng movement disorders or epilepsy.
  • Extensive list of all the other studies & their stimulation protocols.
  • Large mylenated fibers have chronaxies ranging aruond 30-200 us, while cell bodies and dendrites this value is around 1-10ms. (Rank, 1975).
    • Lapique: minimum energy is a/b, where b is the rhreobase (the minimal electric current of infinite duration that results in an action potential), and chronaxie is the minimum time over which an electric current double the strength of the rheobase needs to be applied in order ti stimulate a nerve cell.
    • Q(t)t=U rh(1+t cht) where U rh is the rheobase and t ch is the chronaxie.
    • you can simplify this to: I th=I rh(1+t cht) where I rh is the rheobase current and I th is the threshold current (Irnich, 2002).
  • Measurements of chronaxie in VIM and GPi found values of 60-75us, hence DBS effects are likely mediated through the activation of afferent and efferent axons. (Holsheimer et al 2000a, 2000b)
    • In line with these findings, cortical stimulation also results in the activation of afferent and efferent axons (Nowak and Bullier, 1998a, 1998b PMID-9504844).
    • Ustim can result in cell body hyperpolarization coupled with action potential initiation in the axon (McIntyre and Grill, 1999; Nowak and Bullier 1998a b).
  • Stimulation depends on the direction of the electric field, obviously. When the axons and E are ||.
  • Acute stimulation is different from chronic DBS (as used in patients); it may be a mistake to extrapolate conclusions.
    • DBS electrodes become encapsulated, and current delivered hence decreases.
  • Strong placebo effect of just the DBS surgery.
    • Implantation of electrodes alone had therapeutic benefit in 6-mo trial. (Mann et al 2009).
  • mean lead impedance is 400-120 ohms in clinical DBS leads, PT-IR.
    • platinum is relatively non-toxic to the brain when compared to metals such as gold or rhodium.
  • If stimulation exceeds 30 uC/cm^2/phase, there is a risk of tissue damage. This equates to 30ma.
  • Stainless steel electrodes are damadged by days of in vivo stimulation -- metal ions are lost.
  • STN neurons spontaneously oscillate due to leak Ca currents and C-activated K channels.
  • STN DBS seems to disrupt abnormal synchronized activity recorded in the BG-thalamocortical loops in PD. (meta-analysis of several studies).
  • STN DBS seems to reduce FR in the SNr.
  • STN excitotoxic leasion in rats causes increased impulsivity, impaired accuracy, premature responses, and more attention to food reward location in rats.
    • There is a hyperdirect pathway from the medial prefrontal cortex to the STN; breaking this decreases attention and perseverance.
    • STN HFS sometimes induces impulsive behavior in humans, with which this is consistent. (This may be sequelae from levodopa treatment).
    • STN HFS often causes weight gain in patients. But it might be because they can eat more or are more 'motivated at life'.
    • Controlled studies in rats show that STN lesion does not effect quantity consumed, either food, ehanol, or cocaine.
      • Differential effect when the reward was food vs. cocaine -- the STN may modulate the reward system based on the nature of the reward.
  • Huh: HFS of the ZI (zona incerta) has been reported to be superior to STN HFS for improving contralateral parkinsonism in PD patients.
    • Could be current diffusion into the STN, however, as lesioning this structure in rats has less effect than lesioning STN.
    • See also {1098}.
  • Chronic GPi DBS does not allow reducing L-DOPA dosage, unlike STN stimulation, but it is a good treatment for dyskinesia.
  • VIM treatment is very effective for tremor, but it does not treat the other motor symptoms of PD. Furthermore, it wears off after a few years.
    • CM/Pf seems like an even better target (Center median / parafasicular complex of the thalamus -- see {1119}.
  • DBS in the PPN (pedunculo pontine nucleus, brainstem target of the BG) at 10 HZ induces a feeling of well-being , concomitant with a modest improvement in motor function; no effect at 80 Hz.
  • Dystonia: GPi is a efficacious target for DBS.
    • Full effect takes a year (!), suggesting that the effect is through reorganization of the BG / neuroplascticity.
  • ET : lesions of the VIM, STN, or cerebellum can reduce symptoms. DBS of the VIM, STN, or ZI all have been found effective.
  • Huntington's disease involves degeneration of the projection neurons from the caudate and putamen.
    • HD affects motor, cognitive, and psychiatric functioning.
  • Drug addiction: inactivating the Nucelus accumbens (NAc) may reduce motivation to obtain the drug, but it may also reduce the motivation to do anything (apathy).
  • GPi DBS also a target for reducing chorea.
  • STN DBS may worsen treatment-resistant-depression; this seen in an animal model, and anecdotally in humans with PD.
  • OCD can be treated with DBS through the internal capsule extending toward the NAc / ventral striatum.
    • side effects include hypomania or anxiety.
    • Alas there is no satisfactory animal model of OCD, which hampers research.

____References____

[0] Gubellini P, Salin P, Kerkerian-Le Goff L, Baunez C, Deep brain stimulation in neurological diseases and experimental models: from molecule to complex behavior.Prog Neurobiol 89:1, 79-123 (2009 Sep)

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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: Beurrier-1997.05 tags: STN stimulation hemiballismus 2007 DBS date: 01-26-2012 17:20 gmt revision:4 [3] [2] [1] [0] [head]

PMID-9189903[] Subthalamic stimulation elicits hemiballismus in normal monkey.

  • the effects of stimulation on normal waking primates has never been evaluated (doh!)
  • In the normal monkey, HFS appears reversibly to incapacitate the STN and allow the emergence of involuntary proximal displacements, due to disinhibition of the thalamo-cortical pathway
  • in MPTP-treated monkey HFS buffers STN activity and alleviates akinesia and rigitity by reducing inputs to the internal segment of the globus pallidus. (STN output is excitatory) (or so the theory at the time goes)
  • perhaps i will need to buy this article ;(

____References____

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ref: Krack-2001.09 tags: STN subthalamic nucleus stimulation PD parkinsons DBS date: 01-24-2012 05:48 gmt revision:1 [0] [head]

PMID-11746616[0] Mirthful laughter induced by subthalamic nucleus stimulation.

  • high stimulation parameters induces mirthful laughter
  • prescribed parameters induced hypomanic behavior with marked improvement in akinesia.
  • STN must be involved in psychomotor as well as motor regulation.

____References____

[0] Krack P, Kumar R, Ardouin C, Dowsey PL, McVicker JM, Benabid AL, Pollak P, Mirthful laughter induced by subthalamic nucleus stimulation.Mov Disord 16:5, 867-75 (2001 Sep)

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ref: Hilker-2004.01 tags: STN subthalamic DBS stimulation cortex cerebellum PET PD parkinsons date: 01-24-2012 05:38 gmt revision:1 [0] [head]

PMID-14688612[0] Subthalamic Nucleus Stimulation Restores Glucose Metabolism in Associative and Limbic Cortices and in Cerebellum: Evidence from a FDG-PET Study in Advanced Parkinson's Disease

  • cortical depression of glucose metabolism
  • hypermetabolic state in the left rostral cerebellum (?!)
  • DBS generally remedies this imbalance, restoring glucose metabolism to the cortex associative/motor/frontal as well as to the thalamus distant from the stimulation site.

____References____

[0] Hilker R, Voges J, Weisenbach S, Kalbe E, Burghaus L, Ghaemi M, Lehrke R, Koulousakis A, Herholz K, Sturm V, Heiss WD, Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson's disease.J Cereb Blood Flow Metab 24:1, 7-16 (2004 Jan)

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ref: Romo-1998.03 tags: Romo ICMS stimulation discrimination flutter 1998 date: 01-06-2012 23:43 gmt revision:4 [3] [2] [1] [0] [head]

PMID-9537321[0] Somatosensory discrimination based on cortical microstimulation.

  • trained monkeys to discriminate flutter frequencies; showed it generalized to ICMS stimulation, in that they could compare mechanical and electrical frequencies.
  • Electrodes in area 3b of S1.
  • Showed that cortical neurons are entrained to peripheral stimulation freq.

____References____

[0] Romo R, Hernández A, Zainos A, Salinas E, Somatosensory discrimination based on cortical microstimulation.Nature 392:6674, 387-90 (1998 Mar 26)

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ref: work-2009 tags: bipolar opamp design current control microstimulation date: 01-06-2012 20:13 gmt revision:15 [14] [13] [12] [11] [10] [9] [head]

Recently I've been working on a current-controlled microstimulator for the lab, and have not been at all satisfied with the performance - hence, I decided to redesign it.

Since it is a digitally current-controlled stimulator, and the current is set with a DAC (MCP4822), we need a voltage controlled current source. Here is one design:

  • Because the output of the DAC is ground-referenced, and there is no negative supply in the design, the input buffers must be PNP transistors. These level-shift the input (0-2V, corresponding to 0-400uA) + 0.65V ( V be ), and increase the current. Both are biased with 1uA here, though 10uA would also work (lazily, through 1M resistors - I've checked that these work well too). This sets the base current at about 10nA for Q2 and Q1.
  • Q3 and Q4 are a current-mirror pair. If Q1 Vb increases, Ie for Q3 will decrease, increasing Ib for Q4 and hence its Ic. This will decrease the base current in Q6 and Q5, as desired. On the other hand, increasing Q2 Vb will decrease Q4 Ic, increasing Ib in Q6 and Q5. The current mirror effects the needed negative feedback in the circuit. This mirror could also be implemented with PNP transistors, but it doesn't work as well as then the collector (which has voltage gain) is tied to the emitter of the input PNP transistors. Voltage gain is needed to drive Q5 / Q6.
  • Q5 & Q6 are Darlington cascaded NPN transistors for current gain. If Q6 is omitted, Ib in Q5 increases -> Ib in Q1 decreases -> Ic in Q3 decreases -> Ib in Q4 increases. This results in a set-point of Ib = 100nA in Q5 -> Ic ~10uA. (unacceptable for our task).

What I really need is a high-side regulated current source; after some fiddling, here is what I came up with:

  • V2 is from the DAC; for the testing, I just simulate with a votlage ramp. This circuit, due to the 5V biasing (I have 5V available for the DAC, hence might as well use it) works well up to about 4V input voltage - exactly what the DAC can produce.
  • Q1 and Q2 are biased through 1M resistors R6 and R8; their emitters are coupled to a common-emitter amplifier Q3 and Q4.
  • As the voltage across R1 increases, Ib in Q1 decreases. This puts more current through the base of Q4, increasing the emitter voltage on both Q3 and Q4. This reduces the current in Q3, hence reducing the current in Q5 -> the voltage across R1. feedback ;-)
  • I tried using a current mirror on the high-side, but according to spice, this actually works *worse*. Q5 & Q3 / Q4 have more than enough gain as it stands.
  • Yes, that's 100V - the electrodes we use have high impedance, so need a good bit of voltage to get the desired current.
  • Now, will need to build this circuit to verify that it actually works.

  • (click for the full image)
  • This simulates OK, but shows some bad transients related to switching - I'll have to inspect this more closely, and possibly tune the differential stage (e.g. remove the fast transient response - Q6 and Q12 seem to turn off before Q5 and Q11 do, which pulls the output to +50v briefly)

  • This is the biphasic, bipolar stimulator's response to a rising ramp command voltage, as measured by the current through R17. Note how clean the signal is :-) But, I'm sure that it won't look quite this nice in real life! Will try one half out on a breadboard to see how it looks.
  • Note I switched from NMOS switching transistors to NPN - Q15 and Q16 shunt the bias current from Q3/Q2 and Q8/Q9, keeping the output PNPs (Q5 and Q11). These transistors are in saturation, so they take 100-200ns to turn off, which should be fine for this application where pulse width is typically 100us.
  • I've fed the pull-down NPN base current from the positive supply here, so that as long as Q5 and Q11 are on, Q6 and Q12 are also on. The storage time here (not that it is much, the transistors are kept out of saturation via D1-4) helps to keep the mean difference in voltage between animal or stimulee's ground and isolated stimulator ground low. In previous stimulators the high-side was a near-saturation PNP, which pulled the voltage all the way to the positive supply when stimulation started. This meant that any stray capacitance had to be charged through the brain - bad!
    • Note this means that the emitter current through Q6 and Q12 is more than the current through R17 by that passed through Q14 and Q13. By design, this is 1/50th that through Q5 and Q11. This means that the actual stimulated current will be 95% of the commanded current, something which is easily corrected in software.

  • Larger view of the schematic. Still worried about stability - perhaps will need to add something to limit slew rate.
  • V2 on the right is the command voltage from the DAC.

  • The amplifier in figure 5 suffered from low bandwidth, primarily because the large resistors effected slow timeconstants, and because there was no short path to +50V from the high-side PNP transistors. This led to very slow turn-off times. To remedy this:
    • Bias current to Q3 & Q4 was increased (R6 & R8 decreased) -> more current to charge / discharge capacitance.
    • Common emitter resistor concomitantly decreased to 22k. This increases the collector current.
    • Pull-up resistors changed to a current mirror. This allows the current through Q4 to pull up the bases of Q5 and Q6, letting them turn off more quickly. If Q1 is off (e.g. voltage across R1 is high), Q4 will be on, and Q6 will source this current. etc.
  • With this done, I tested it on the breadboard & it oscillated. bad! Hence, I put a 1nf (10nf in the schematic) capacitor from the collector of Q3 to ground - hence limiting the slew rate. This abolished oscillations and led to a very pretty linear turn-on waveform.
  • However, the turn-off waveform was an ugly exponential. Why? With Q2 or Q10 fully on, Q3 will be off. Q4 will effectively recharge C1 through R7. As the voltage across R7 goes to zero, so does the charging current. Since I don't want to add in a negative supply, I simply shifted the base voltage of Q3 and Q4 using a diode, about as simple as you can get!
  • Eventually, I replaced R7 with a current source ... but this did not change the fall waveform that much; it is still (partially) exponential. Possibly this is from the emitter resistors on the high-side.

  • As of now, the final version - tested using surface mount devices; seems to work ok!
  • Note added transistor Q11 - this discharges / removes minority carriers from the base of Q8. Even though D1 and D2 guarantee a current-starved Q8 in previous designs, they leave no path to ground from the base, so this transistor was taking forever to turn off. This was especially the case when switching (recall this is one half of a H-bridge, and Q9 would actually be on the other side of the h-bridge), since the other sides' Q9 would push current, while Q8 would continue to conduct & sink current. This current through R1 would increase Q8 emitter voltage, reverse-biasing its' base-emitter junction, making the transistor take 100us of us to turn off. Bad, since the amplifier is intended to replicate 100us pulses! Anyway, Q11 neatly solves the problem (albeit with 100ns or so of saturated-switching storage time - something that Q10 has anyway).
  • D1 and D2 are no longer really necessary, but I've left them in this diagram for illustrative purposes. (and they improve storage time a bit).

  • Update as the result of testing. Changes:
    • Added emitter resistors on the two current mirrors (Q6, Q7; Q12, Q13). This eliminated stability problems
    • Changed the anti-saturation diodes to a resistor. This is needed as it takes some time for Q9 to turn off, and to avoid unbalanced currents through the electrode pairs, this charge should be pulled to ground through Q8. In the actual circuit, Q11 is driven with a 4-8us delayed version of the control signal V4 so that Q8 remains on longer than current source Q9.
    • Decreased C1 to 100pf; because the amplifier is more stable now, the slew rate can be increased.

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ref: Fritsch-1870 tags: Fritsch Hitzig 1870 electrical stimulation date: 01-03-2012 23:31 gmt revision:2 [1] [0] [head]

PMID-19457461[0] Electric excitability of the cerebrum (Uber die elektrische Erregbarkeit des Grosshirns).

  • Seemingly the first successful demonstration of ICMS (or just ICS). A step forward from the vivisectionists and the people who cauterized the cortex with potash.
  • Obtained contralateral movements by bipolar stimulation to the anterior half of a dogs cerebral cortex.
  • Used quite primitive technology (e.g. cardboard cell battery), but not at all primitive reasoning and care with the experiment.
  • may have been inducing small seizures with their DC stimulation: "Frequently tonic contractions of the muscle masses involved appear, which only subside in their intensity after a long time." The translator later calls this 'tetanization'.
  • On brain death: 'It is the fact that with exsanguination the excitability of the brain sinks with enormous rapidity, and is almost extinguished even before death.' meanwhile, muscles and (peripheral) nerves react fine after death.
  • Were not able to stimulate the striatum with insulated electrodes.
  • Survival surgeries -- after extirpation of forelim M1, the dogs recovered, though exhibited weakness in contralateral side. This weakness eventually went away, though "... they clearly had only a deficient consciousness of the conditions of this limb. "

____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: 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: 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: Bures-1968 tags: inferior colliculus stimulation classical conditioning plasticity hebb Bures date: 01-03-2012 07:08 gmt revision:5 [4] [3] [2] [1] [0] [head]

bibtex:Bures-1968 Plastic changes of unit activity based on reinforcing properties of extracellular stimulation of single neurons

  • images/972_1.pdf
  • Trained neurons to respond to auditory stimuli throughout the brain (though mostly the IC) to a auditory tone.
    • Hebb's rule, verified.
  • Yoshii & Ogura (22): Reticular units, originally not responding to sciatic nerve US, started to respond to the CS after a few tens of trials, however the conditioned reactions disappeared with continued training.
    • This must be regarded as response to arousal at the initial stages of classical aversive (sciatic nerve pain?) conditioning.
  • Used capilary electrodes 1um in diameter, filled with KCl or sodium glutamate
  • Stimulation current 10-50nA DC, 0.3-1 sec.
  • Were able to record and stimulate at the same time using these glass microelectrodes.
  • The majority of units (cortex, reticular formation, thalamus) showed no response, though some did. These responses tended to fade with overtraining.
  • Quote: "The rather low incidence of positive results int he above experiment might be due to the fact that many examined neurons lack even an indirect acoustic input and cannot, therefore, be activated by acoustic stimuli."
  • Neurons in the IC show the strongest plastic change.
  • Their study is more specific than Loucks (15), Olds and Milner (17) Delgaso (6) Doty(7) which used less specific ICMS.
  • That said, there is no behavior .. so we don't know if the stimuli is being reacted to or attended to (might explain the low # of responses in areas).
  • They also think that the response can be credited to nonspecific phenomena like dominant focus, reflex sensitization, or heterosynaptic facilitation.
    • That said, the IC did show strong responses.

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ref: Delgado-1964 tags: Delgado wireless stimulation record stimoceiver rhesus monkey date: 01-03-2012 07:07 gmt revision:5 [4] [3] [2] [1] [0] [head]

bibtex: delgado-1964 Personality, education, and electrical stimulation of the brain

  • images/977_1.pdf
  • "Is it conceivable that behavior or the psyche can be related to electronics? Before answering these questions, we should ask one more: what is the main difference between primitive tribesmen still living in the jungle and the civilized human beings so well represented by this audience?" Education.
  • Kinda a ramble saying how education and understanding the brain is essential to our future.
  • Against atomic deterrence, unsurprisingly.
    • We are in the precarious race between the acquisition of many megatons of destructive power and the development of intelligent human beings who will make wise use of the forces at our disposal"
  • Radio receiver on a belt.
  • Elicited very complex movements from stimulating the thalamus, including walking from one side of the cage to the other, including avoiding the boss monkey!
    • He calls this 'electrical stimulation of the will'.
  • stimulate nucleus postero-ventralis induces targeted, well-directed attacks against other males of the group.
  • Stimulation of the caudate-septal lobes, just behind the frontal lobes, causes the boss monkey to become tame / tolerant / less aggressive.
  • When this function was enabled by pressing a button in the monkeys cage, the monkey most harrassed learned to press the button to halt the boss's aggressive behavior.
  • Regarding patients: "some of these patients have undergone testing for weeks or months, and lead a nearly normal life wthile 10, 20 or even more fine wires were present, in different cerebral areas and ready for stimulation from outside the scalp."
    • For example, in one patient, who spike a mean of 8.5 words per minute, by means of stimulation to the second temporal column increased his conversation to 44 words per minute." Menwhile, the number of friendly remarks increased by a factor of 9.
  • "Knowledge of the human mind may be decisive for our pursuit of happiness and for the very existence of mankind"

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ref: Doty-1956 tags: Doty 1958 conditioned reflexes stimulation date: 01-03-2012 07:05 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-13367871[0] Conditioned reflexes established to electrical stimulation of cat cerebral cortex.

  • One sentence: used ICMS to act as a CS for a CR (shock-avoidance) in cats. Not really ICMS, as electrodes were placed on the surface.
  • They suggest ICMS is a means for probing the cortex without going through that trouble and complex transform of the sensory nerves and PNS.
    • If only. ICMS is complex enough.
  • Loucks [6,7,8] used a buried induction coil! Have things advanced all that much? (They bring this up in that magnetic stimulation of the induction coil induces vibration, which the animal can feel.)
  • Use 'vitalium' screws to fix their plexiglas encased platinum wire electrode to the scull.
    • Relatively large electrodes, not in the cortex but resting upon it -- this is why the current was relatively high.
  • Monophasic ICMS, 50Hz, 2ms, 2 sec train, 4-6V (not current controlled).
    • Fixed this by putting a 10k resistor in series and recording current across that. approx 700uA stimulation current -- high!
  • Most of the cortex worked as a CS: stimulation of points distributed throughout the marginal, postlateral, middle suprasylvian, and middle and posterior ectosylvian gyri (Fig. 2).
  • Observed a narrow threshold for conditioning responses, e.g. 0.35mA would give only 1/5 correct, 0.45 4/5 correct.
  • Dura excised in these surgeries, since any stimulation of the dura is painful.
    • To control for this, they severed the trigeminal nerve.
  • gave strength / duration curves. (remember, monopolar).
  • deinervated the animals as control -- could feel nothing but the current delivered to their head!
  • Other controls: Loucks (7) showed that CR persisted with stimulation to the motor cortex after the limb that moved upon superthreshold stimulation was paralyzed.
  • "The present experiments fully confirm the thesis that CRs to cortical stimulation are in no way dependent on detectable motor effects."
  • Animals can also discriminate one frequency from another (30Hz vs 100Hz). Verified by Romo, much later.

____References____

[0] DOTY RW, LARSEN RM, RUTHLEDGE LT Jr, Conditioned reflexes established to electrical stimulation of cat cerebral cortex.J Neurophysiol 19:5, 401-15 (1956 Sep)

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ref: DOTY-1965.07 tags: Doty 1965 stimulation herpes restraint date: 01-03-2012 06:56 gmt revision:1 [0] [head]

PMID-14347624[0] Conditioned reflexes elicited by Eletrical Stimulation of the Brain in Macaques

  • "The relation of neural to mental processes is nowhere more clearly and directly deominstrated than in the elicitation of subjective experience in human patients by electrical stimluation of their brains"
  • Difference between sensory and motor thresholds heretofore unexplained. I guess they were in S1 -- and higher current activates more axons (?)
  • Ewald (42) perfected the means, introduced by Simonoff (40) of stimulating the brain in freely moving, unanesthetized animals. Have to look this up.
    • Movement could be elicited by stimulation of any part of the cerebral cortex of dogs.
  • Loucks: any neocortical or subcortical locus could serve as a CS in rats.
  • permanent chairing due to fear of herpes B: "With ten laboratory workers dying in the past decade if virus B encephalitis following monkey bites (11), it was felt that all possible steps should be taken to protect techinall personel form this danger, and the monkeys were permanently restrained." (in a chair)
    • Several changes had to be made to the chair to fix this.
    • even the pigtail monkeys, which are more gentile, would become aggressive and recalcitrant when the task became more difficult.
  • Simple classical conditioning test in monkeys.
    • CR = lever pressing to aviod US (shock).
  • All electrical stimuli were fed through RF isolation units to prevent ground loop.
  • Beast of a study: Stimulation proved effective as SA-or FRCS in all areas of the brain assayed, covering 38 cortical (Table 1 and Fig. 2) and 31 subcortical loci. The latter included the optic tract, lateral and medial geniculate nuclei, pulvinar, lateral posterior nucleus, posterior hypothalamus, tegmentum dorsal to nucleus ruber, brachium of the superior colliculus, and the periaqueductal gray.
  • Threshold for response varied with both time (facilitation and habituation) and with the attentive & motivational state of the animal.
  • Can discriminate electrodes 1-3mm apart.
  • Quote: Judicious and limited use of punishment (electric shock) was required to mantain performance without making the monkey "neurotic". (This as they were testing various currents, and some were below threshold).
    • A fully trained monkey can respond to one pulse.
    • Hard to train monkeys on anything below 20Hz. (Recall anything in the ~6Hz range puts cats to sleep).
  • Subthreshold precentral ICMS would induce movement if activation was increased, eg. US, or a loud and unfamiliar sound, e.g. a truck horn.
  • Much lower threshold for ICMS in monkeys as compared to cats. But they were not controlling the critical parameter, e.g. current intensity or delivered charge.

____References____

[0] DOTY RW, CONDITIONED REFLEXES ELICITED BY ELECTRICAL STIMULATION OF THE BRAIN IN MACAQUES.J Neurophysiol 28no Issue 623-40 (1965 Jul)

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ref: Lim-2009.09 tags: auditory midbrain implant deaf cochlea stimulation inferior colliculus date: 01-03-2012 06:55 gmt revision:2 [1] [0] [head]

PMID-19762428[0] Auditory midbrain implant: a review.

  • Inferior to a cochlear implant -- subjects, at the best, could understand speech only with lip-reading cues.
  • But! It's safe, and offers some degree of perception.
  • Also see: PMID-21157353[1]
    • Neurofibramatosis type 2 can also lead to cochlear deafness.
    • Implanted in the dorsal and ventral cochlear nuclei in the lateral recess of the IVth ventricle of the brain stem.
    • EABRs (evoked auditory brain stem responses); even though these were associated with electrodes in the right place, they could not be used for device fitting (?)

____References____

[0] Lim HH, Lenarz M, Lenarz T, Auditory midbrain implant: a review.Trends Amplif 13:3, 149-80 (2009 Sep)
[1] O'Driscoll M, El-Deredy W, Ramsden RT, Brain stem responses evoked by stimulation of the mature cochlear nucleus with an auditory brain stem implant.Ear Hear 32:3, 286-99 (2011 May-Jun)

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ref: ODoherty-2011 tags: Odoherty Nicolelis ICMS stimulation randomly patterned gamma distribution date: 01-03-2012 06:55 gmt revision:1 [0] [head]

IEEE-6114258 (pdf) Towards a Brain-Machine-Brain Interface:Virtual Active Touch Using Randomly Patterned Intracortical Microstimulation.

  • Key result: monkeys can discriminate between constant-frequency ICMS and aperiodic pulses, hence can discriminate some fine temporal aspects of ICMS.
  • Also discussed blanking methods for stimulating and recording at the same time (on different electrodes, using the randomized stimulation patterns).

____References____

O'Doherty, J. and Lebedev, M. and Li, Z. and Nicolelis, M. Towards a Brain #x2013;Machine #x2013;Brain Interface:Virtual Active Touch Using Randomly Patterned Intracortical Microstimulation Neural Systems and Rehabilitation Engineering, IEEE Transactions on PP 99 1 (2011)

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ref: ODoherty-2009.01 tags: Odoherty Nicolelis ICMS stimulation BMI BMBI date: 01-03-2012 06:55 gmt revision:1 [0] [head]

PMID-19750199[0] A brain-machine interface instructed by direct intracortical microstimulation.

  • Both and and brain control, cud by ICMS to S1, Mango and Nectarine.
    • PP ineffective. Despite Doty [1].
  • pretty careful site mapping (fig 1).
  • SUA classified by less that 1 per 1000 ISI < 1.6ms.
  • pursuit & center out tasks.
  • Correlation coeficient (R^2) not so high across all sessions - 0.5 (?).
  • ICMS learning, once the monkey began to get it, was rapid.

____References____

[0] O'Doherty JE, Lebedev MA, Hanson TL, Fitzsimmons NA, Nicolelis MA, A brain-machine interface instructed by direct intracortical microstimulation.Front Integr Neurosci 3no Issue 20 (2009)
[1] Doty RW, Electrical stimulation of the brain in behavioral context.Annu Rev Psychol 20no Issue 289-320 (1969)

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ref: Butovas-2007.04 tags: Butovas Schwarts ICMS stimulation rat barrel cortex date: 01-03-2012 06:55 gmt revision:2 [1] [0] [head]

PMID-17419757[0] Detection psychophysics of intracortical microstimulation in rat primary somatosensory cortex.

  • headposted rats, ICMS to barrel cortex
  • single pulse threshold = 2 nC, around the threshold for evocation of short-latency action potentials near an electrode.
  • one pulse saturated at 80% correct.
  • multiple pulses had a higher rate, though this saturated at 15 pulses.
  • double pulse optimal in terms of power / discrimination.

____References____

[0] Butovas S, Schwarz C, Detection psychophysics of intracortical microstimulation in rat primary somatosensory cortex.Eur J Neurosci 25:7, 2161-9 (2007 Apr)

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ref: Blum-2007.12 tags: stimulation recording Blum integrated circuit ASIC date: 01-03-2012 03:26 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

IEEE-4358608 (pdf) An Integrated System for Simultaneous, Multichannel Neuronal Stimulation and Recording

  • Use capacitor-feedback amplifier with a seperate feedback amp to provide a DC path.
  • Input amplifier is disabled during stimulation (hopefully without blowing out gate oxide..)
  • Charge stored in the feedback caps acts as a S/H. clever!
  • Due to topology, noise increases with bias current of feedback amp.
  • Stimluation was a measly 9ua.
  • Use a feedback amplifier to actively discharge the electrode after stimulation.
  • Generally a well-though-out, informative paper, with insight as to the design compromises.

Blum RA, Ross JD Brown EA and DeWeerth SP (2007) An Integrated System for Simultaneous, Multichannel Neuronal Stimulation and Recording IEEE Trans. Circuits Syst. I. Regular Pap 54, 2608-2618

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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: Rolston-2009.01 tags: ICMS artifacts stimulation Rolston Potter recording BMI date: 01-03-2012 02:38 gmt revision:3 [2] [1] [0] [head]

PMID-19668698[0] A low-cost multielectrode system for data acquisition enabling real-time closed-loop processing with rapid recovery from stimulation artifacts

  • Well written, well tested, but fundamentally simple system - only two poles active high-pass, one pole low-pass.
  • With TBSI headstages the stimulation artifact is brief - figure 8 shows < 4ms.
  • Includes NeuroWriter software, generously open-sourced (but alas windows only - C#).

____References____

[0] Rolston JD, Gross RE, Potter SM, A low-cost multielectrode system for data acquisition enabling real-time closed-loop processing with rapid recovery from stimulation artifacts.Front Neuroengineering 2no Issue 12 (2009)

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ref: Ghovanloo-2005.01 tags: Najafi microstimulation Ghovanloo date: 01-02-2012 03:06 gmt revision:2 [1] [0] [head]

PMID-15651568[0] A compact large voltage-compliance high output-impedance programmable current source for implantable microstimulators.

  • from NCSU - reprazent!
  • (from abtract:) "A new CMOS current source is described for biomedical implantable microstimulator applications, which utilizes MOS transistors in deep triode region as linearized voltage controlled resistors (VCR)."

____References____

[0] Ghovanloo M, Najafi K, A compact large voltage-compliance high output-impedance programmable current source for implantable microstimulators.IEEE Trans Biomed Eng 52:1, 97-105 (2005 Jan)

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ref: ODoherty-2011.1 tags: nicolelis odoherty nicolelis 2011 active tactile BMBI stimulation ICMS unscented Kalman filter date: 01-01-2012 18:27 gmt revision:3 [2] [1] [0] [head]

PMID-21976021[0] Active tactile exploration using a brain-machine-brain interface.

  • Tricky part was the temporal interleaving. 50ms stim / 50ms record.
    • No proof a priori as S1 stim could affect M1 processing.
  • Real perception, as the stimulation resulted from motor commands (through a BMI).
  • RAT = rewarded ICMS (200Hs pulses)
  • UAT = unrewarded ICMS, 400Hs, skip every 100ms.
  • NAT = no ICMS.
  • So short. damn you, nature.

____References____

[0] O'Doherty JE, Lebedev MA, Ifft PJ, Zhuang KZ, Shokur S, Bleuler H, Nicolelis MA, Active tactile exploration using a brain-machine-brain interface.Nature 479:7372, 228-31 (2011 Oct 5)

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ref: Doty-1969.01 tags: Doty microstimulation brain behavior macaque conditioned stimulus attention motivation 1969 date: 12-29-2011 23:28 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-4888623[0] Electrical stimulation of the brain in behavioral context.

  • Excellent review.
  • Focal stimulation of macaques can induce insect-grabbing responses, after which they will carefully examine their hands to see what was caught!
    • Same thing has been observed in humans -- the patient reported that he wanted to catch 'that butterfly'.
  • Such complicated action must be the effect of downstream / upstream targets of the stimulated site, as the actual stimulation carries no information other than it's spatial locality within the brain.
  • Stimulation of the rostral thalamus in the language hemisphere can elicit phrases: "Now one goes home", "Thank you", "I see something".
    • These are muttered involuntarily and without recollection of having been spoken.
  • Doty stimulated macaques at 20ua for 500us as a CS in postcentral gyrus (S1?) for a lever press CR, which should (he says)only activate a few dozen neurons.
  • Can elicit mating behaviors in oposums with electrical stimulation of the hypothalamus, but only if another opossum or furry object is present.
  • Stimulation of the caudate nucleus in humans causes an arrest reaction: they may speak, smile, or laught inappropriately, but appropriate voluntary responses are brought to a halt.
  • Stimulation of the basolateral amygdala can cause:
    • Hungry cats to immediately stop eating
    • Stop stalking prey
    • Non-hunting animals to stalk prey, and indeed will solve problems to gain access to rats which can be attacked.
  • Prolonged stimulation of almost every place in the brain of a cat at 3-8Hz can put it to sleep, though since lab cats normally sleep 17/24hours, this result may not be significant.
  • Stimulation at most sites in the limbic system has the still mysterious ability to organize motor activity in any fashion required to produce more of the activity or to avoid it, as the case may be.
  • Rats that are stimulated in the periaqueductal gray will self-administer stimulation, but will squeal and otherwise indicate pain and fright during the stimulation. Increasing the duration of stimulation from 0.5 to 1 second makes self-administration of this apparently fearful stimulation stop in both rats and cats.
  • Certain patterns of activity within systems responsible for fearful or aggressive behavior, rather than being aversive are perversely gratifying. This is clearly recognized in the sociology of man...
  • Rats will self-stimulate with the same stimulus trains that will cause them to eat and drink, and under some conditions the self-stimulation occurs only if food or water is available.
  • On the other hand, rats will choose self-stimulation of the lateral hypothalamus instead of food, even when they are starving.
    • Electrically induced hunger is its own reward.
  • The work of Loucks (124, 125) forms the major point of origin for the concept that motivation is essential to learning. with careful and thorough training, Loucks was unable to form CRs to an auditory CS using stimulation of the motor cortex as the US. With this paradigm, the limb movements elicited by the US never appeared to the CS alone; but movements were readily established when each CS-US combination was immediately followed by the presentation of food.
    • However: Kupalov independently proved that stimulation of the motor cortex could be used as the US, at the same time using stimulation at other loci as the CS.
    • Why the difference? Attention -- failures are commonly obtained with animals that consistenly fidget or fight restraint, as most of them do.
    • Cortical stimulation itself is not rewarding or aversive; animals neither seek nor avoid stimulation of most neocortical areas.
  • On classical conditioning: [Bures and colleagues (20, 65) bibtex:Bures-1968 bibtex:Gerbrandt-1968] found that if an anticedent stimulus, which might or might not effect a neuron, were consistently followed by effective intracellular electrical stimulation of that individual neuron, in roughly 10 percent of the cells of the neocortex, hippocampus, thalamus, or mesencephalic reticular formation a change in the response of that cell to the antecedent stimulus could be observed.
  • With an apparent exception of the cerebellum it is possible to electrical excitation any place in the brain as a CS in chickens, rats, rabbits ...
  • Stimulation of group 1 proprioceptive muscle-afferent fibers in cats is ineffective as a CS.
    • Muscle spindles lack clear access to the systems subserving conditioned reflexes. (These instead go to the cerebellum)
  • Macaques can also discriminate between two stimulation sites 1-3 mm apart apparently over the entirety of the cortex, at frequencies between 2 and 100Hz, and over a 4-10fold range of currents.
  • In human cases where electrical stimulation or the cortex elicits specific memories, extirpation of the stimulated area does not effect recall of this memory (156) {973}.

____References____

[0] Doty RW, Electrical stimulation of the brain in behavioral context.Annu Rev Psychol 20no Issue 289-320 (1969)

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ref: PENFIELD-1963.12 tags: Penfield memory stimulation music epilepsy awesome date: 12-29-2011 22:21 gmt revision:4 [3] [2] [1] [0] [head]

PMID-14090522[0] The Brains record of auditory and visual experience -- A final summary and discussion

  • 102 pages. basically, this is a book.
  • Electrical stimulation causes 'hallucinations of things previously seen or heard or experienced.'
    • 'Both the experience and the interpretation are produced by discharge in the temporal cortex and not in other areas'
    • Experiential responses only followed stimulation in the temporal lobe.
  • These tests were done in an effort to locate the source of a seizure.
  • Damn, references the Caliph at Cordova as the first to document epileptic hallucinations (1519!)
    • And Hughlings Jackson (1888)!
  • Extirpation of memories elicited by ustim to an area persist after removal of that area.
  • Performed 1,288 surgeries, 520 of them for seizures in the temporal lobes, 40 of these with experiential responses, and 24 of those with experiential epileptic hallucinations.
    • Many of the patients' epilepsy was caused by ischemia, perhaps developmental; others by glioma..
  • Stimulation of the white matter has never produced an experiential response. Deep stimulation in the amygdala or hippocampus (??) also failed to elicit experiential responses.
  • Talks about 'difficult birth' -- was/is this the cause of some epilepsy? Or has that been discounted?
  • Buncha stuff on human cortical anatomy / topology, which is not so interesting to me.
  • Walker on the chimpanzee (1938) showed that the temporal cortex has no direct connections to the thalamus except posteriorly, where projections are received from nucleus lateralis posterior and pulvinar (visual attention), and within the transverse temporal gyri which receive auditory afferent projections from the medial geniculate body.
    • Also receives large fiber projections from the hippocampus.
  • This is absolutely fascinating. Memories, art, songs (music, so much music -- temporal lobe!), childbirth, counting, childhood molestation, a whole host of experiences were brought forth by electrical stimulation.
    • Case 9. E. Le. This 44-year old woman began to have seizures at age 22 during a pregnancy. The attack pattern was: (1) flushing of face and neck (2) automatism; (3) occasional generalized seizure. During and automatism she was apt to say, "I am alright". Then she would walk about the room and show marked affection toward anyone who happened to be present.
    • Repeated without warning: She said, "Yes, another experience, a different experience." Then she added, "A true experience. This man, Mr. Meerburger, he, oh well, he drinks. Twice his boy has run away. I went to the store once for an ice cream cone and I saw that he was back, and I said 'Hmm, he is back,' and the lady asked me 'What is the matter,' and I didn't know how to explain so I said, 'Well you know Mr. Meerburger drinks.' I thought that was the easiest way but later mother told me, no, and it made it a lot worse."
    • What surprises me is the relative lack of breadth in these --many of the responses to stimulation are quite similar, over a wide range of cortex, many of them very dream-like in features and recall.
      • Their impression: It is often evident that ''each stimulation leaves behind a facilitating influence so that the same response follows each stimulation and this facilitation may cause a given response to follow stimulation at one to three centimeters distance. Illustrated by the case 5, D.F
      • This deserves far more experimentation! E.g. ask the patient to think about something, and see if the same stimulation elicits different memories.
    • Another patient had a series of experiential hallucinations which all involved some aspect of 'grabbing' -- a man grabbing a rifle from a cadet during a parade, a man snatching his hat from the hat-check girl, grabbing a stick from a dog's mouth. In this epileptic, an instance of 'grabbing' was the ictal focus. Amazing.
  • Points out that stimulation must activate a great number of neural circuits, only one specific memory is recalled -- indicating that there is strong inhibition for mutual-exclusion.
  • Non-dominant, non-speech temporal cortex is almost always involved in interpretation: stimulation produces visual experiences, or visual interpretive illusions (change in distance or speed).
    • Stimluation also produces changes in the state-of-mind.
  • Certain sorts of experiences seem absent:
    • The times of making up ones mind
    • Times of carrying out skilled acts, writing messages or adding figures,
    • Eating food
    • Sexual excitement and experience (unless the patients may have self-censored this?)
    • Intense pain or suffering.
    • These things do not involve interpretation, and the focus of attention is not on the way that things are heard or seen.
  • They would remove quite large sections of the temporal lobe!
    • Still, the excision of these areas does not abolish memory: it does not contain a record of the past.
    • Yet stimulation in the temporal lobe recalls memories as nowhere else does.
  • There is a sharp frontier / boundary between auditory and visual temporal cortices and interpretive -- millimeters movement may change phosphenes into recall of a familiar person.
  • Note the comparison between speech cortex (dominant) and interpretive -- stimulation of speech cortex produces no speech, only aphasia, whereas stimulation of non-dominant termporal cortex forces recall.
  • "He who is faithfully analysing many cases of epilepsy is doing far more than studying epilepsy"

____References____

[0] PENFIELD W, PEROT P, THE BRAIN'S RECORD OF AUDITORY AND VISUAL EXPERIENCE. A FINAL SUMMARY AND DISCUSSION.Brain 86no Issue 595-696 (1963 Dec)

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ref: Harris-2009.06 tags: Bartholow 1874 Mary experiment stimulation ICMS date: 12-29-2011 05:13 gmt revision:2 [1] [0] [head]

PMID-19286295[0] Probing the human brain with stimulating electrodes: The story of Roberts Bartholow’s (1874) experiment on Mary Rafferty

  • Excellent review / history.
  • Actual citation: Experimental investigations into the functions of the human brain" The American Journal of the medical Sciences 1874
  • Actual subject: Marry Rafferty
  • Around his time people were shifting from using intuition and observation to direct treatment to using empiricism & science, especially from work on laboratory animals.
  • One of the innovations that could not be tolerated by his colleagues was the "physiological investigations of drugs by the destruction of animal life." He was a bit of an outsider, and not terribly well liked.
  • Before then the cortex was seen to be insensitive to stimulation of any kind.
  • Ferrier 1974b: in the striatum all movements are integrated which are differentiated in the cortex" -- striatal stimulation produces general contraction, not specific contraction.
  • Ferrier 1873 was the first to discover that AC stimulation yielded more prolonged and natural movements than DC.
  • The Dura mater is extremely sensitive to pain.
  • Mary Rafferty seems to have had a tumor (he calls it an ulcer) in the meninges (epithelioma).
  • He probably spread infection into her brain through the stimulating needles.

____References____

[0] Harris LJ, Almerigi JB, Probing the human brain with stimulating electrodes: the story of Roberts Bartholow's (1874) experiment on Mary Rafferty.Brain Cogn 70:1, 92-115 (2009 Jun)

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ref: Shinkman-1974.06 tags: Shinkman Bruce Pfingst operant conditioning visual cortex cat ICMS 1974 stimulation date: 12-29-2011 05:13 gmt revision:4 [3] [2] [1] [0] [head]

PMID-4598035[0] Operant conditioning of single-unit response patterns in visual cortex.

  • In cat V1 -- suprising, this is usually considered to be sensory.
  • implanted bilater tripolar stimulating electrodes aimed at the lateral hypothalamus. These were tested for self-stimulation, and preferred locations/currents were selected for optimal ICS reinforcement.
    • 200 bar presses in 8 minute test.
  • Anesthetized, immobilized, head-restrained, contact-lens focused cats.
  • Back projected stimuli onto a screen 50 cm from eye ; dot, bar, or small spot was effective in triggering patterned response, as with many of these studies.
  • For conditioning: set a threshold at the third quartile (1/4 of trials exceeded threshold); comparator circuit counted the number of spikes during stimulus presentation, and if threshold was exceeded, reinforcing ICS was delivered.
    • Reinforcing ICS started 300ms after visual stimulus and lasted 500ms.
  • Conditioning was deemed successful if the mean trial firing rate for the last 50 conditioned trials had a mean firing rate > 30% larger than the first 50 control trials.
    • While recording some cells, ICS reinforcement was delivered at random as control.
  • Conditioning produced changes within stimulus presentation but not outside.
  • They consider the use of an immobilized subject is a pro -- better control, rules out alternative explanations based on motor feedback.

____References____

[0] Shinkman PG, Bruce CJ, Pfingst BE, Operant conditioning of single-unit response patterns in visual cortex.Science 184:4142, 1194-6 (1974 Jun 14)

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ref: Douglas-1991.01 tags: functional microcircuit cat visual cortex microstimulation date: 12-29-2011 05:12 gmt revision:3 [2] [1] [0] [head]

PMID-1666655[0] A functional microcircuit for cat visual cortex

  • Using in vivo stim and record, They describe what may be a 'cannonical' circuit for the cortex.
  • Not dominated by excitation / inhibition, but rather cell dynamics.
  • Thalamus weaker than poysynaptic inupt from the cortex for excitation.
  • Focuses on Hubel and Wiesel style stuffs. Cats, SUA.
  • Stimulated the geniculate body & observed the response using intracellular electrodes from 102 neurons.
  • Their traces show lots of long-duration inhibition.
  • Probably not relevant to my purposes.

____References____

[0] Douglas RJ, Martin KA, A functional microcircuit for cat visual cortex.J Physiol 440no Issue 735-69 (1991)

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ref: Tehovnik-1996.03 tags: ICMS technique Tehovnik MIT 1996 current density microstimulation date: 12-29-2011 05:11 gmt revision:2 [1] [0] [head]

PMID-8815302[0] Electrical stimulation of neural tissue to evoke behavioral responses

  • reference to justify our current levels.
  • radial dispersion of current, inverse square falloff of excitability.
  • low currents (10 ua) can activate 10-1000 of neurons in cat M1 (allegedly).

____References____

[0] Tehovnik EJ, Electrical stimulation of neural tissue to evoke behavioral responses.J Neurosci Methods 65:1, 1-17 (1996 Mar)

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ref: Ativanichayaphong-2008.05 tags: wireless neural recording stimulation date: 12-28-2011 21:15 gmt revision:3 [2] [1] [0] [head]

PMID-18262282[0] A combined wireless neural stimulating and recording system for study of pain processing

  • used rather simple unidirectional radio links.
  • provide schematics in the document!
  • one channel record; one-channel stim.
  • VHF bands are presntly open (?) -- perhaps use them?
  • 914 MHz transmit neural, 433Mhz RX stimulus commands.

____References____

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ref: Wyrwicka-1966.01 tags: ICMS brainstem stimulation feeding prey chasing VTA date: 12-28-2011 20:44 gmt revision:2 [1] [0] [head]

PMID-5941514[0] Feeding induced in cats by electrical stimulation of the brain stem.

  • tested in cats.
  • stimulation points in the lateral hypothalamus (makes sense, controlls hunger)
  • half in ventral tegmental area (VTA)
  • aphygia is induced by lesions of the lateral hypothalamus.
  • in one experiment, the meat in the bowl was replaced with a banana. "Upon stimulation the cat quickly approached the bowl, sniffed the banana, turned away (in some disgust and frustration!?), searched the chamber, returned to the banana etc, but would not eat the banana."

____References____

[0] Wyrwicka W, Doty RW, Feeding induced in cats by electrical stimulation of the brain stem.Exp Brain Res 1:2, 152-60 (1966)

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ref: Brown-2008.03 tags: microstimulation recording artifact supression MEA ICMS date: 12-28-2011 20:43 gmt revision:3 [2] [1] [0] [head]

IEEE-4464125 (pdf) Stimulus-Artifact Elimination in a Multi-Electrode System

  • Stimulate and record on the same electrode within 3ms; record on adjacent electrodes within 500us.
  • Target at MEAs, again.
  • Notes that very small charge mismatches of 1% or less, which is common and acceptable in traditional analog circuit designs, generates an artifact that saturates the neural amp signal chain.
  • for stimulating & recording on the same electrode, the the residual charge must be brought down to 1/1e5 the stimulating charge (or less).
  • paper follows upon {833} -- shared author, Blum -- especially in the idea of using active feedback to cancel artifact charge & associated voltage.
  • target the active feedback for keeping all amplifier out of saturation.
  • vary highpass filter poles during artifact supression (!)
  • bias currents of 1fA on the feedback highpass stage. yikes.

Brown EA, Ross JD, Blum RA, Yoonkey N, Wheeler BC, and DeWeerth SP (2008) Stimulus-Artifact Elimination in a Multi-Electrode System. IEEE TRans. Biomed. Circuit Sys. 2. 10-21

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ref: Thevathasan-2010.04 tags: DCS DBS spinal cord stimulation PD date: 12-28-2011 20:43 gmt revision:4 [3] [2] [1] [0] [head]

PMID-20404313[0] Spinal cord stimulation failed to relieve akinesia or restore locomotion in Parkinson disease.

  • motivated by [1]
  • Implanted two PD patients with commercial DBS stimulators and electrodes; observed no therapeutic effect.
  • Electric field was axial rather than transverse, hence likely did not activate the same way or same ammount as in the Nicolelis study.
  • Not sure if anyone has tried with other eletrodes... spinal cord stimulation would be great for inductive powering.

____References____

[0] Thevathasan W, Mazzone P, Jha A, Djamshidian A, Dileone M, Di Lazzaro V, Brown P, Spinal cord stimulation failed to relieve akinesia or restore locomotion in Parkinson disease.Neurology 74:16, 1325-7 (2010 Apr 20)
[1] Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA, Spinal cord stimulation restores locomotion in animal models of Parkinson's disease.Science 323:5921, 1578-82 (2009 Mar 20)

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ref: Tehovnik-2006.08 tags: ICMS cortical microstimulation pyramidal neurons date: 12-20-2011 06:08 gmt revision:1 [0] [head]

PMID-16835359[0] Direct and indirect activation of cortical neurons by electrical microstimulation.

  • looked at ICMS via single-cell recording, behavior, and fMRI.
  • These properties suggested that microstimulation activates the most excitable elements in cortex, that is, by and large the fibers of the pyramidal cells.
    • this is a useful result to perhaps reference..

____References____

[0] Tehovnik EJ, Tolias AS, Sultan F, Slocum WM, Logothetis NK, Direct and indirect activation of cortical neurons by electrical microstimulation.J Neurophysiol 96:2, 512-21 (2006 Aug)

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ref: Jimbo-2003.02 tags: MEA microstimulation artifact supression date: 12-17-2011 01:41 gmt revision:2 [1] [0] [head]

PMID-12665038[0] A system for MEA-based multisite stimulation.

  • stimulate and record the same MEA channel.
  • used voltage-control stimulation.
  • very low leakage current switches, DG202CSE, 100Gohm, Maxim, above. non-mechanical = low vibration.
  • switches switch between stimulator and preamp. obvious.
  • uses active shorting post-stimulation to remove residual charge,
  • uses active sample/hold of the preamplifier while the stimulator is connected to the electrodes.
  • adds stimulation pulse to the initial electrode offset (interesting!)

____References____

[0] Jimbo Y, Kasai N, Torimitsu K, Tateno T, Robinson HP, A system for MEA-based multisite stimulation.IEEE Trans Biomed Eng 50:2, 241-8 (2003 Feb)

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ref: Laubach-2003.03 tags: cluster matlab linux neurophysiology recording on-line data_analysis microstimulation nicolelis laubach date: 12-17-2011 00:38 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-1215970 (pdf)

  • 2003
  • M. Laubach
  • Random Forests - what are these?
  • was this ever used??

follow up paper: http://spikelab.jbpierce.org/Publications/LaubachEMBS2003.pdf

  • discriminant pusuit algorithm & local regression basis (again what are these? lead me to find the lazy learning package: http://iridia.ulb.ac.be/~lazy/

____References____

Laubach, M. and Arieh, Y. and Luczak, A. and Oh, J. and Xu, Y. Bioengineering Conference, 2003 IEEE 29th Annual, Proceedings of 17 - 18 (2003.03)

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ref: delgado-0 tags: Delgado roborat ICMS stimulation control date: 12-16-2011 06:41 gmt revision:2 [1] [0] [head]

quote:

All the loose speculation provoked by roborats is ironic considering that the experiment is just a small-scale replay of a major media event that is 40 years old. In 1964, José Delgado, a neuroscientist from Yale University, stood in a Spanish bullring as a bull with a radio-equipped array of electrodes, or "stimoceiver," implanted in its brain charged toward him. When Delgado pushed a button on a radio transmitter he was holding, the bull stopped in its tracks. Delgado pushed another button, and the bull obediently turned to the right and trotted away. The New York Times hailed the event as "probably the most spectacular demonstration ever performed of the deliberate modification of animal behavior through external control of the brain."

from: http://discovermagazine.com/2004/oct/cover

from: http://www.angelfire.com/or/mctrl/chap16.htm

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ref: Arfin-2009.07 tags: ICMS birdsong wireless stimulation ARfin 2009 MIT date: 12-16-2011 04:21 gmt revision:1 [0] [head]

PMID-19386759[0] Wireless neural stimulation in freely behaving small animals.

  • Made a custom ASIC for delivering bipolar, biphasic current pulses.
  • 32 output channels.
  • Powered by small batteries
  • device in sleep state when not in use
  • controlled by inductive radio transfer with PWM modulation scheme.
  • Tested in Zebra finches, HVC: terminates song in all birds tested.
  • Impressive bit of engineering!

____References____

[0] Arfin SK, Long MA, Fee MS, Sarpeshkar R, Wireless neural stimulation in freely behaving small animals.J Neurophysiol 102:1, 598-605 (2009 Jul)

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ref: Jackson-2006.11 tags: Fetz Andrew Jackson BMI motor learning microstimulation date: 12-16-2011 04:20 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-17057705 Long-term motor cortex plasticity induced by an electronic neural implant.

  • used an implanted neurochip.
  • record from site A in motor cortex (encodes movement A)
  • stimulate site B of motor cortex (encodes movement B)
  • after a few days of learning, stimulate A and generate mixure of AB then B-type movements.
  • changes only occurred when stimuli were delivered within 50ms of recorded spikes.
  • quantified with measurement of (to) radial/ulnar deviation and flexion/extension of the wrist.
  • stimulation in target (site B) was completely sub-threshold (40ua)
  • distance between recording and stimulation site did not matter.
  • they claim this is from Hebb's rule: if one neuron fires just before another (e.g. it contributes to the second's firing), then the connection between the two is strengthened. However, i originally thought this was because site A was controlling the betz cells in B, therefore for consistency A's map was modified to agree with its /function/.
  • repetitive high-frequency stimulation has been shown to expand movement representations in the motor cortex of rats (hmm.. interesting)
  • motor cortex is highly active in REM

____References____

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ref: Isoda-2007.02 tags: SMA saccade basal_forebrain executive function 2007 microstimulation SUA cortex sclin date: 10-03-2008 17:12 gmt revision:2 [1] [0] [head]

PMID-17237780[0] Switching from automatic to controlled action by monkey medial frontal cortex.

  • SCLIN's blog entry
  • task: two monkeys were trained to saccade to one of two targets, left/right pink/yellow. the choice was cued by the color of the central fixation target; when it changed, they should saccade to the same-colored target.
    • usually, the saccade direction remained the same; sometimes, it switched.
    • the switch could either occur to the same side as the SUA recording (ipsilateral) or to the opposite (contralateral).
  • found cells in the pre-SMA that would fire when the monkey had to change his adapted behavior
    • both cells that increased firing upon an ipsi-switch and contra-switch
  • microstimulated in SMA, and increased the number of correct trials!
    • 60ua, 0.2ms, cathodal only,
    • design: stimulation simulated adaptive-response related activity in a slightly advanced manner
    • don't actually have that many trials of this. humm?
  • they also did some go-nogo (no saccade) work, in which there were neurons responsive to inhibiting as well as facilitating saccades on both sides.
    • not a hell of a lot of neurons here nor trials, either - but i guess proper statistical design obviates the need for this.
  • I think if you recast this in tems of reward expectation it will make more sense and be less magical.
  • would like to do shadlen-similar type stuff in the STN
questions
  1. how long did it take to train the monkeys to do this?
  2. what part of the nervous system looked at the planned action with visual context, and realized that the normal habitual basal-ganglia output would be wrong?
    1. probably the whole brain is involved in this.
    2. hypothetical path of error trials: visual system -> cortico-cortico projections + context activation -> preparatory motor activity -> basal ganglia + visual context (is there anatomical basis for this?) -> activation of some region that detects the motor plan is unlikely to result in reward -> SMA?

____References____

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ref: bookmark-0 tags: Delgado Bulls microstimulation ICMS control implant date: 01-06-2008 18:05 gmt revision:2 [1] [0] [head]

http://www.biotele.com/Delgado.htm

  • stimulated the caudate to stop the charging bull.
  • interesting account of the later part of his life spent in Spain, when his popularity wained
  • Delgado still appears to have some quite radical tendencies, such as belief in the inexorable advance of technology, even if it is immoral/unethical.