Thalamic Microstimulation Research Articles

System identification of the nonlinear dynamics in the thalamocortical circuit in response to patterned thalamic microstimulation in vivo

Objective. Nonlinear system identification approaches were used to develop a dynamical model of the network level response to patterns of microstimulation in vivo. Approach. The thalamocortical circuit of the rodent vibrissa pathway was the model system, with voltage sensitive dye imaging capturing the cortical response to patterns of stimulation delivered from a single electrode in the ventral posteromedial thalamus. The results of simple paired stimulus experiments formed the basis for the development of a phenomenological model explicitly containing nonlinear elements observed experimentally. The phenomenological model was fit using datasets obtained with impulse train inputs, Poisson-distributed in time and uniformly varying in amplitude. Main results. The phenomenological model explained 58% of the variance in the cortical response to out of sample patterns of thalamic microstimulation. Furthermore, while fit on trial-averaged data, the phenomenological model reproduced single trial response properties when simulated with noise added into the system during stimulus presentation. The simulations indicate that the single trial response properties were dependent on the relative sensitivity of the static nonlinearities in the two stages of the model, and ultimately suggest that electrical stimulation activates local circuitry through linear recruitment, but that this activity propagates in a highly nonlinear fashion to downstream targets. Significance. The development of nonlinear dynamical models of neural circuitry will guide information delivery for sensory prosthesis applications, and more generally reveal properties of population coding within neural circuits.

Optimal space–time precoding of artificial sensory feedback through mutichannel microstimulation in bi-directional brain–machine interfaces

Brain–machine interfaces (BMIs) aim to restore lost sensorimotor and cognitive function in subjects with severe neurological deficits. In particular, lost somatosensory function may be restored by artificially evoking patterns of neural activity through microstimulation to induce perception of tactile and proprioceptive feedback to the brain about the state of the limb. Despite an early proof of concept that subjects could learn to discriminate a limited vocabulary of intracortical microstimulation (ICMS) patterns that instruct the subject about the state of the limb, the dynamics of a moving limb are unlikely to be perceived by an arbitrarily-selected, discrete set of static microstimulation patterns, raising questions about the generalization and the scalability of this approach. In this work, we propose a microstimulation protocol intended to activate optimally the ascending somatosensory pathway. The optimization is achieved through a space–time precoder that maximizes the mutual information between the sensory feedback indicating the limb state and the cortical neural response evoked by thalamic microstimulation. Using a simplified multi-input multi-output model of the thalamocortical pathway, we show that this optimal precoder can deliver information more efficiently in the presence of noise compared to suboptimal precoders that do not account for the afferent pathway structure and/or cortical states. These results are expected to enhance the way microstimulation is used to induce somatosensory perception during sensorimotor control of artificial devices or paralyzed limbs.

Voltage-sensitive dye imaging reveals improved topographic activation of cortex in response to manipulation of thalamic microstimulation parameters

Voltage-sensitive dye imaging was used to quantify in vivo, network level spatiotemporal cortical activation in response to electrical microstimulation of the thalamus in the rat vibrissa pathway. Thalamic microstimulation evoked a distinctly different cortical response than natural sensory stimulation, with response to microstimulation spreading over a larger area of cortex and being topographically misaligned with the cortical column to which the stimulated thalamic region projects. Electrical stimulation with cathode-leading asymmetric waveforms reduced this topographic misalignment while simultaneously increasing the spatial specificity of the cortical activation. Systematically increasing the asymmetry of the microstimulation pulses revealed a continuum between symmetric and asymmetric stimulation that gradually reduced the topographic bias. These data strongly support the hypothesis that manipulation of the electrical stimulation waveform can be used to selectively activate specific neural elements. Specifically, our results are consistent with the prediction that cathode-leading asymmetric waveforms preferentially stimulate cell bodies over axons, while symmetric waveforms preferentially activate axons over cell bodies. The findings here provide some initial steps toward the design and optimization of microstimulation of neural circuitry, and open the door to more sophisticated engineering tools, such as nonlinear system identification techniques, to develop technologies for more effective control of activity in the nervous system.

An Electric Field Model for Prediction of Somatosensory (S1) Cortical Field Potentials Induced by Ventral Posterior Lateral (VPL) Thalamic Microstimulation

Microstimulation (MiSt) is used experimentally and clinically to activate localized populations of neural elements. However, it is difficult to predict-and subsequently control-neural responses to simultaneous current injection through multiple electrodes in an array. This is due to the unknown locations of neuronal elements in the extracellular medium that are excited by the superposition of multiple parallel current sources. We, therefore, propose a model that maps the computed electric field in the 3-D space surrounding the stimulating electrodes in one brain region to the local field potential (LFP) fluctuations evoked in a downstream region. Our model is trained with the recorded LFP waveforms in the primary somatosensory cortex (S1) resulting from MiSt applied in multiple electrode configurations in the ventral posterolateral nucleus (VPL) of the quiet awake rat. We then predict the cortical responses to MiSt in "novel" electrode configurations, a result that suggests that this technique could aid in the design of spatially optimized MiSt patterns through a multielectrode array.

Getting signals into the brain: visual prosthetics through thalamic microstimulation.

Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface.

Demonstration of artificial visual percepts generated through thalamic microstimulation.

Electrical stimulation of the visual system might serve as the foundation for a prosthetic device for the blind. We examined whether microstimulation of the dorsal lateral geniculate nucleus of the thalamus can generate localized visual percepts in alert monkeys. To assess electrically generated percepts, an eye-movement task was used with targets presented on a computer screen (optically) or through microstimulation of the lateral geniculate nucleus (electrically). Saccades (fast, direct eye movements) made to electrical targets were comparable to saccades made to optical targets. Gaze locations for electrical targets were well predicted by measured visual response maps of cells at the electrode tips. With two electrodes, two distinct targets could be independently created. A sequential saccade task verified that electrical targets were processed not in motor coordinates, but in visual spatial coordinates. Microstimulation produced predictable visual percepts, showing that this technique may be useful for a visual prosthesis.

Temporal excitation properties of paresthesias evoked by thalamic microstimulation

Objective The neuronal elements mediating the effects of deep brain stimulation (DBS) are unknown. The objective was to determine the strength-duration properties of the neuronal elements that mediate paresthesias evoked by thalamic microstimulation. Methods The strength-duration properties of the neuronal elements causing paresthesias were measured using intraoperative microstimulation of the human thalamus. The sample included both concordant (reported in the same region as the mapped sensory receptive fields) and discordant paresthesias (reported in a region different than the mapped sensory receptive fields). Results There were no significant differences between the chronaxies of concordant and discordant paresthesias. There was no significant correlation between chronaxie and rheobase for concordant paresthesias, but a strong negative correlation existed for discordant paresthesias. Conclusions Chronaxies did not distinguish the neuronal elements mediating concordant and discordant paresthesias, but correlations between chronaxie and rheobase suggest that concordant paresthesias were produced by activation of local cells while discordant paresthesias were caused by activation of axons of passage. Significance The similarity between the strength-duration properties of paresthesias evoked by thalamic stimulation, tremor reduction evoked by thalamic DBS, and EMG responses to thalamic DBS does not mean that these effects are caused by the same neural elements.

Phantom sensations generated by thalamic microstimulation.

Many amputees have a sense of their missing 'phantom' limb. Amputation can alter the representation of the body's surface in the cerebral cortex and thalamus, but it is unclear how these changes relate to such phantom sensations. One possibility is that, in amputees who experience phantom sensations, the region of the thalamus that originally represented the missing limb remains functional and can give rise to phantom sensations even when some thalamic 'limb' neurons begin to respond to stimulation of other body regions. Here we use microelectrode recording and microstimulation during functional stereotactic mapping of the ventrocaudal thalamus in amputees to determine both the responses of the neurons to stimulation of the skin and the perceptual effects of electrical activation of these neurons. Thalamic mapping revealed an unusually large thalamic stump representation, consistent with the findings from animal experiments. We also found that thalamic stimulation in amputees with a phantom limb could evoke phantom sensations, including pain, even in regions containing neurons responsive to tactile stimulation of the stump. These findings support the hypothesis that the thalamic representation of the amputated limb remains functional in amputees with phantoms.

Thalamic stimulation-evoked sensations in chronic pain patients and in nonpain (movement disorder) patients

1. Little is known about the effect of central and peripheral nervous system injury on the processing of somatosensory information at the thalamic level in humans. The role of the human thalamic ventrocaudal nucleus (Vc) in nociception is not well understood because reports of nociceptive neuronal responses and stimulation-evoked pain are rare. In this study, we have characterized effects of microstimulation in the tactile region of Vc. Specifically, we investigated the incidence of painful sensations evoked by thalamic microstimulation in patients with and without chronic pain. 2. Data were obtained during stereotactic thalamic procedures for relief of pain or motor disorders. Patients were divided into three groups, those with 1) central poststroke pain (PSP, n = 13); 2) nonstroke pain (NSP, n = 23); and 3) movement disorders (controls, n = 24). Most (15 of 23) of the NSP patients had peripheral nerve damage. Tungsten microelectrodes were used to record neuronal responses in the thalamus and to deliver stimuli. Localization of tactile Vc was determined according to stereotactic coordinates and neuronal responses to innocuous somatic stimuli. At selected sites, microstimulation (1-s trains, 300 Hz, 0.1-0.2 ms pulses, < 100 microA) was performed and the patient was requested to describe the quality of the sensation and its peripheral location (projected field, PF). 3. Microstimulation in tactile Vc commonly evoked paresthesia-type sensations. Threshold stimulation never evoked pain in the NSP patients and evoked pain at only 2% of Vc sites in the movement disorder patients. In these latter 2 groups of patients, stimulation at > 98% of Vc sites evoked paresthesia. By contrast, in the PSP patients, 28% of Vc sites stimulated evoked painful sensations at threshold. Suprathreshold stimuli evoked painful sensations at 46% of Vc sites in the PSP patients but at only 8% of Vc sites in NSP patients and 12% of Vc sites in the movement disorder patients. 4. The thresholds to evoke paresthesia in the NSP and movement disorder patients were significantly lower than the thresholds in the PSP patients. However, stimulation thresholds to elicit pain were similar in all patient groups. 5. All patients were capable of differentiating stimulation-evoked paresthesia from pain. Stimulation-evoked painful sensations in the PSP patients were often described as burning and sometimes as "sharp," "shocking," or "unpleasant." By contrast, the quality of pain evoked in the other patient groups was typically described as unpleasant or shocking. Pain could be evoked at sites throughout tactile Vc, although most sites were located in the ventral 2/3 of the nucleus. 6. In the movement disorder patients, the location of the projected sensation usually corresponded to the location of the receptive fields of the tactile neurons recorded at the same site. By contrast, in both groups of pain patients there was a high incidence of mismatches between the projected and receptive fields. 7. These results suggest that the effective thalamic output from Vc to the cortex is affected by somatosensory deafferentation in pain patients. In addition, in the PSP patients there are also changes in the thalamocortical processing of noxious information. The increased incidence of thalamic-evoked pain in PSP patients may be due to 1) loss of low-threshold mechanoreceptive thalamic neurons such that nociceptive neuronal output is now prominent, 2) reduced tonic inhibition of thalamic or cortical nociceptive neurons, and/or 3) unmasking or strengthening of nociceptive pathways.

Thermal and pain sensations evoked by microstimulation in the area of human ventrocaudal nucleus.

1. We have studied the sensations evoked by threshold microstimulation (TMS) in the area of the human principal sensory nucleus of the thalamus [ventralis caudalis (Vc)] in patients (n = 11) undergoing stereotactic surgery for the treatment of movement disorders and pain. Preoperatively, patients were trained to describe somatic sensory stimuli using a standard list of descriptors. This same list was used to describe sensations evoked intraoperatively by thalamic microstimulation. Stimulation sites (n = 216) were defined by location within the area where the majority of cells had a reproducible response to innocuous cutaneous stimulation (core region) or in the cellular area posterior and inferior to the core region (posteroinferior region). 2. TMS-evoked sensations were categorized as paresthetic if the descriptors "tingle," "vibration," or "electric current" were chosen by the patient to describe the sensation and as thermal/pain if the descriptors "cool," "warm," "warm and cool," or "pain" were chosen. Thermal/pain sensations were evoked by stimulation in 82% (9/11) of patients and at 19% of sites studied. These results suggest that thalamic microstimulation can evoke thermal/pain sensations reproducibly across patients. 3. Thermal/pain sensations were evoked more frequently by stimulation at sites in the posteroinferior region (30%) than by stimulation at sites in the core region (5%). Nonpainful thermal sensations composed the majority of thermal/pain sensations evoked by stimulation in both the core (80%) and posteroinferior regions (86%). Sites where stimulation evoked pain and nonpainful cool sensations were found anterior to the area where nonpainful warm sensations were evoked. Thermal/pain sensations were evoked at sites located medially near the border between the core and posteroinferior regions. 4. Radiologic techniques were used to determine the presumed nuclear location of stimulation sites. Thermal/pain sensations were evoked less frequently by stimulation in the part of Vc included in the core region than by stimulation in any of the following: the part of Vc included in the posteroinferior region, ventralis caudalis portae nucleus, ventralis caudalis parvocellularis nucleus, or the white matter underlying the ventral nuclear group. 5. The location of the sensation evoked by stimulation [projected field (PF)] varied widely in size. PFs were categorized as large if they involved more than one part of the body (e.g., face and arm) or if they crossed at least one joint proximal to the metacarpophalangeal joint or to the metatarsophalangeal joint. PFs were more frequently large at sites where thermal/pain sensations were evoked by TMS (33%) than at those where paresthesia were evoked (6%).(ABSTRACT TRUNCATED AT 400 WORDS)

Types of eye movements evoked by thalamic microstimulation in the alert cat

We characterized the type of eye movements evoked by electrical stimulation of the thalamic internal medullary lamina in alert cats. For comparison, other thalamic nuclei were studied: the lateral posterior, lateral dorsal, pulvinar complex, and ventral lateral nuclei. Three types of eye movements were distinguished: (i) Direction and amplitude-specific saccades were the most common type of eye movements evoked by electrical stimulation of the majority of the explored nuclei with the exception of the ventral lateral nucleus. Mean latency and threshold were 45 ms and 50 to 100 μA, compared with 60 ms and 200 to 300 μA for the same type of saccades evoked by electrical stimulation of the posterior thalamus. (ii) Saccades which appeared goal directed were evoked in 25% of the stimulations in the region of the internal medullary lamina. Their latency and threshold depended on the initial position of the eyes: The more deviated the eyes were from the “goal area,” the shorter the latency (minimum, 35 ms) and the lower the threshold (minimum, 16 μA). (iii) Centering saccades were evoked by stimulation of the ventral lateral nucleus. They were always accompanied by other movements. The minimum latency and threshold were, respectively, 90 ms and 200 μA. The finding that goal-directed saccades were selectively produced from certain internal medullary lamina sites is consistent with the view that a translation of spatial coordinates occurs at this level in the programming of eye movements.