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[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: 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: 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 2RI^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: -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: 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) \frac{Q(t)}{t} = U_{rh}(1 + \frac{t_ch}{t}) where U rhU_{rh} is the rheobase and t cht_{ch} is the chronaxie.
    • you can simplify this to: I th=I rh(1+t cht) I_{th} = I_{rh} (1 + \frac{t_{ch}}{t}) where I rhI_{rh} is the rheobase current and I thI_{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\vec{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: 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 beV_{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: 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: 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: 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: 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: 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: 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: 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.