Effects Of Intracortical Microstimulation Research Articles

Motor cortex outputs evoked by long-duration microstimulation encode synergistic muscle activation patterns not controlled movement trajectories.

The effects of intracortical microstimulation (ICMS) parameters on the evoked electromyographic (EMG) responses and resulting limb movement were investigated. In ketamine-anesthetized cats, paw movement kinematics in 3D and EMG activity from 8 to 12 forelimb muscles evoked by ICMS applied to the forelimb area of the cat motor cortex (MCx) were recorded. The EMG responses evoked by ICMS were also compared to those evoked by focal ictal bursts induced by the iontophoretic ejection of the GABAA receptor antagonist bicuculline methochloride (BIC) at the same cortical point. The effects of different initial limb starting positions on movement trajectories resulting from long-duration ICMS were also studied. The ICMS duration did not affect the evoked muscle activation pattern (MAP). Short (50 ms) and long (500 ms) stimulus trains activated the same muscles in the same proportions. MAPs could, however, be modified by gradually increasing the stimulus intensity. MAPs evoked by focal ictal bursts were also highly correlated with those obtained by ICMS at the same cortical point. Varying the initial position of the forelimb did not change the MAPs evoked from a cortical point. Consequently, the evoked movements reached nearly the same final end point and posture, with variability. However, the movement trajectories were quite different depending on the initial limb configuration and starting position of the paw. The evoked movement trajectory was most natural when the forelimb lay pendant ~ perpendicular to the ground (i.e., in equilibrium with the gravitational force). From other starting positions, the movements did not appear natural. These observations demonstrate that while the output of the cortical point evokes a seemingly coordinated limb movement from a rest position, it does not specify a particular movement direction or a controlled trajectory from other initial positions.

Spatio-temporal characteristics of population responses evoked by microstimulation in the barrel cortex

Intra-cortical microstimulation (ICMS) is a widely used technique to artificially stimulate cortical tissue. This method revealed functional maps and provided causal links between neuronal activity and cognitive, sensory or motor functions. The effects of ICMS on neural activity depend on stimulation parameters. Past studies investigated the effects of stimulation frequency mainly at the behavioral or motor level. Therefore the direct effect of frequency stimulation on the evoked spatio-temporal patterns of cortical activity is largely unknown. To study this question we used voltage-sensitive dye imaging to measure the population response in the barrel cortex of anesthetized rats evoked by high frequency stimulation (HFS), a lower frequency stimulation (LFS) of the same duration or a single pulse stimulation. We found that single pulse and short trains of ICMS induced cortical activity extending over few mm. HFS evoked a lower population response during the sustained response and showed a smaller activation across time and space compared with LFS. Finally the evoked population response started near the electrode site and spread horizontally at a propagation velocity in accordance with horizontal connections. In summary, HFS was less effective in cortical activation compared to LFS although HFS had 5 fold more energy than LFS.

A study on the effect of multisensory stimulation in behaving rats.

This study explored the psychophysical effects of intracortical microstimulation (ICMS) coupled to auditory stimulation during a behavioral detection task in rats. ICMS directed to the sensory areas of the cortex can be instrumental in facilitating operant conditioning behavior. Moreover, multisensory stimulation promotes learning by enabling the subject to access multiple information channels. However, the extent to which multisensory information can be used as a cue to make decisions has not been fully understood. This study addressed the exploration of the parameters of multisensory stimulation delivered to behaving rats in an operant conditioning task. Preliminary data indicate that animal decisions can be shaped by online changing the stimulation parameters.

Feedback control of the spatiotemporal firing pattern of a basal ganglia microcircuit model

One of the fundamental objectives in systems neuroscience is to precisely control the spatiotemporal firing patterns of cortical neurons to elicit a desired pattern of activity. In this work, we study the effects of intracortical micro-stimulation on the dynamics of a basal ganglia microcircuit model, and explore the feasibility of controlling the spatiotemporal firing patterns of the modeled population in the presence of unobserved inputs. Results from the simulation study suggest that properly designed Multiple-Input-Multiple-Output (MIMO) feedback control paradigm can force a subpopulation of observed output neurons to follow a prescribed spatiotemporal firing pattern despite the presence of unobserved inputs. The accuracy of the spike timing of the controlled neural firing with respect to the reference spike trains is in the order of tens of milliseconds.

Input and output organization of the supplementary motor area.

Recent work on the supplementary motor area (SMA) in Macaca fascicularis led to the conclusion that this area is involved mainly in the preparation of self-paced movements. Results are presented indicating that the posterior portion of the SMA is also directly involved in movement execution and that it receives various sensory inputs. The main results are as follows: (1) The SMA has direct access to the spinal cord by way of corticospinal neurons, but the density of these neurons is lower than in the primary motor cortex (MI). (2) Intracortical microstimulation effects can be elicited in the SMA. Facilitatory effects on ongoing EMG activity can even be produced by single micropulses (8/s). The shortest latencies are compatible with an oligosynaptic or monosynaptic transmission. (3) SMA neurons respond (as do MI neurons) to external perturbations. (4) Anatomical tracing studies revealed that basal ganglia outflow to the SMA via the thalamus is important; our results suggest that dentate outflow contributes as well. (5) Many cells of the SMA may covary with conditioned movements in the same way as MI neurons do. It is argued that it is difficult to compare the lead-time of MI and SMA neurons since 'early' discharges may be coupled with anticipatory postural events.

A repetitive intracortical microstimulation pattern induces long-lasting synaptic depression in brain slices of the rat primary somatosensory cortex.

Repetitive intracortical microstimulation (ICMS) applied to the rat primary somatosensory cortex (SI) in vivo was reported to induce reorganization of receptive fields and cortical maps. The present study was designed to examine the effect of such an ICMS pattern applied to layer IV of brain slices containing SI on the efficacy of synaptic input to layer II/III. Effects of ICMS on the synaptic strength was quantified for the first synaptic component (s1) of cortical field potentials (FPs) recorded from layer II/III of SI. FPs were evoked by stimulation in layer IV. The pattern of ICMS was identical to that used in vivo. However, stimulation intensity had to be raised to induce an alteration of synaptic strength. In brain slices superfused with standard ACSF, repetitive ICMS induced a short-lasting (60 min) reduction of the amplitude (-37%) and the slope (-61%) of s1 evoked from the ICMS site, while the amplitude and the slope of s1 evoked from a control stimulation site in cortical layer IV underwent a slow onset increase (13% and 50%, respectively). In brain slices superfused with ACSF containing 1.25 microM bicuculline, ICMS induced an initial strong reduction of the amplitude (-50%) and the slope (-79%) of s1 evoked from the ICMS site. These effects decayed to a sustained level of depression by -30% (amplitude) and -60% (slope). In contrast to experiments using standard ACSF, s1 evoked from the control site was not affected by ICMS. The presynaptic volley was not affected in either of the two groups of experiments. A conventional high frequency stimulation (HFS) protocol induced input-specific long-term potentiation (LTP) of the amplitude and slope of s1 (25% and 76%, respectively). Low frequency stimulation (LFS) induced input-specific long-term depression (LTD) of the amplitude and slope of s1 (24% and 30%, respectively). Application of common forms of conditioning stimulation (HFS and LFS) resulted in LTP or LTD of s1, indicating normal susceptibility of the brain slices studied to the induction of common forms of synaptic plasticity. Therefore, the effects of repetitive ICMS on synaptic FP components were considered ICMS-specific forms of short-lasting (standard ACSF) or long-lasting synaptic depression (ACSF containing bicuculline), the latter resembling neocortical LTD. Results of this study suggest that synaptic depression of excitatory mechanisms are involved in the cortical reorganization induced by repetitive ICMS in vivo. An additional contribution of an ICMS-induced modification of inhibitory mechanisms to cortical reorganization is discussed.

Effects of Intracortical Microstimulation and Vestibular Stimulation on Pelvic Floor Muscles in the Cat

Experimental anatomical data in primates and transcranial stimulation of the motor cortex in humans indicate that this region projects to pelvic floor musculature. We investigated this problem in intact, anesthetized cats with intracortical microstimulation (ICMS). Further, we explored the characteristics of projection to pelvic floor muscles from the lateral vestibular nucleus of the brainstem. ICMS reliably produced responses from both recorded muscles, levator ani (LA) and external ani sphincter (EAS). Responses could be obtained both from ipsi and contralateral sides, being shorter for the contralateral ones. In contrast, vestibular stimulation activates only the EAS. It is proposed that these high level inputs to pelvic floor musculature are important for appropriate coordination of defecation and micturition.

The effects upon the activity of hand and forearm muscles of intracortical stimulation in the vicinity of corticomotor neurones in the conscious monkey.

Corticomotor (CM) neurones were identified in three conscious macaque monkeys by the presence of post-spike facilitation (PSF) in spike-triggered averages of e.m.g. recorded from intrinsic hand and forearm muscles during performance of a precision grip task. Post-spike effects were compared with those produced by single-pulse intracortical microstimulation (ICMS), with strengths of 4-20 microA, delivered at the site of 47 CM cells. Most muscles facilitated by a CM cell were also facilitated by ICMS at the site of the cell. ICMS effects were stronger: at 10 microA, the amplitude of ICMS-evoked facilitation was on average 2.8 times greater than PSF, and 6.9 times greater at 20 microA. Onset latency of ICMS-evoked facilitation was consistently longer (by 1.7 and 1.3 ms at 10 and 20 microA respectively) than PSF, and it is suggested that this results from the indirect, trans-synaptic excitation of CM cells by ICMS. Post-spike suppression was rarely seen (7/421 compared to 105/421 cases of PSF). In contrast, suppression and facilitation were equally common in response to ICMS. The synaptic mechanisms underlying these effects were explored in 5 anaesthetised macaque monkeys. ICMS facilitated a greater proportion of the tested muscles than did the CM cell recorded at the stimulus site. The results suggest the juxtaposition in the motor cortex of CM neurones with different 'muscle fields'. The merits of STA and ICMS for exploring cortical organisation are discussed.

Effects of intracortical microstimulation on the activity of limb muscles in alert rabbits.

Motor and EMG responses of the limbs to intracortical microstimulation (IM) were studied in 14 rabbits. The motor representations (MR) of contralateral limbs are separately located in the neocortex. The zone of wrist control lies in the center the MR of the forepaw, surrounded by the zones of the forearm and shoulder. Efforts to obtain isolated responses of the digits to IM were not successful. We did not observe a geometrical pattern of organization in the more caudally placed MR of the hindleg, where IM elicited isolated responses in the muscles of the lower leg and the haunch. Minimal thresholds of IM reached 3-10 microA for the MR of the shoulder and forearm, but were as high as 30-200 microA in the MR of the haunch and lower leg. The latent periods of the EMG responses lasted 25-52 msec for the shoulder, 24-73 msec for the forearm, 32-54 msec for the haunch, and 36-71 msec for the lower leg. We conclude that the organization involved in the cortical regulation of limb movement in rabbits is primitive, especially where movement of the hindlimb is involved.

Sequential activation of neurons in primate motor cortex during unrestrained forelimb movement.

We trained monkeys to perform an unrestrained, reaching movement of the arm. Electromyogram (EMG) recordings of forelimb muscles revealed sequential activation, proximal to distal, of muscle groups involved in the task. The delay in onset of EMG activity between proximal (shoulder and elbow) and distal (wrist and finger) muscles was approximately 60 ms. We identified the neurons in the forelimb area of the contralateral motor cortex as controlling particular joints by previously defined criteria involving responses to somatosensory stimulation and effects of intracortical microstimulation. Many cells discharged prior to the onset of EMG activity acting on the appropriate joint, whereas others began firing at a later phase of the movement. The population of all proximal cells altered discharge patterns approximately 60 ms earlier than the population of distal cells. A small percentage of cells showed an initial inhibitory change in discharge frequency, and this inhibition typically occurred prior to the excitatory changes seen in the majority of cells. The results are discussed in terms of the "nested-zone" model of the forelimb motor cortex. The data support one of the predictions of this model, namely that discharges of identified cells within the cortical zones are causally related to voluntary movement at appropriate forelimb joints.

Microstimulation of the supplementary motor area (SMA) in the awake monkey.

The supplementary motor area of three Macaca fascicularis was mapped using intracortical microstimulation (ICMS). Both forelimb and hindlimb movements were evoked using currents of 30 microA or less. However, thresholds for evoking movements were higher than those in the primary motor cortex. Proximal motor effects predominated, but distal joint movements were also elicited. Forelimb points were clustered in mesial cortex of area 6, anterior to the precentral hindlimb and tail region. Distal joint effects were located deep in the cortex, intermingled with proximal effects. Hindlimb response which were less spatially localized, were found both ventral to the forelimb area, in the dorsal bank of the cingulate sulcus, and in mesial cortex, well anterior to area 4. No movements of facial muscles were elicited. Injections of HRP were made into the spinal cord at the cervical level in two animals and the lumbar level in the third one. An area of labelled cells was seen in mesial area 6 which corresponded closely to the region from which ICMS effects were elicited. No movements were evoked from the anterior portions of the fundal region of the cingulate sulcus which were also labelled.

Spread of mono- and polysynaptic connections within cat's motor cortex.

1. Spread of synaptic effects within the gray substance of the motor cortex was examined in cats by delivering intracortical microstimulation (ICMS) through a tungsten electrode and recording postsynaptic potentials (p.s.p.'s) intracellularly from neighbouring cells. 2. ICMS of 4 μa within layer I did not produce any p.s.p.'s in the surrounding neurons. 3. ICMS of 4 μa at layers II, III and IV produced monosynaptic p.s.p.'s only in adjacent neurons. Their horizontal and vertical spread was limited to within 0.5 mm of the stimulating site. Ascending spread from the stimulating sites was not observed in these layers. 4. Polysynaptic effects from layers II, III and IV were found at a distance up to 1.0 mm from the stimulating site both in horizontal and vertical directions. Inhibitory spread was wider than excitatory. 5. ICMS of 4 μa in the deep layers (V and VI) produced both mono and poly synaptic activation of cells in these same layers as well as in the superficial layers (II–III). The effects of ICMS were mixed, but were predominantly inhibitory. 6. The possible synaptic organization within the cortex is discussed and it is concluded that these neuronal connections as a whole constitute a columnar organization within the cortex with feedback circuits built into the system.