Characterizing the short-latency evoked response to intracortical microstimulation across a multi-electrode array.

Objective.Persons with tetraplegia can use brain-machine interfaces to make visually guided reaches with robotic arms. Without somatosensory feedback, these movements will likely be slow and imprecise, like those of persons who retain movement but have lost proprioception. Intracortical microstimulation (ICMS) has promise for providing artificial somatosensory feedback. ICMS that mimics naturally occurring neural activity, may allow afferent interfaces that are more informative and easier to learn than stimulation evoking unnaturalistic activity. To develop such biomimetic stimulation patterns, it is important to characterize the responses of neurons to ICMS.Approach.Using a Utah multi-electrode array, we recorded activity evoked by both single pulses and trains of ICMS at a wide range of amplitudes and frequencies in two rhesus macaques. As the electrical artifact caused by ICMS typically prevents recording for many milliseconds, we deployed a custom rapid-recovery amplifier with nonlinear gain to limit signal saturation on the stimulated electrode. Across all electrodes after stimulation, we removed the remaining slow return to baseline with acausal high-pass filtering of time-reversed recordings.Main results.After single pulses of stimulation, we recorded what was likely transsynaptically-evoked activity even on the stimulated electrode as early as ∼0.7 ms. This was immediately followed by suppressed neural activity lasting 10-150 ms. After trains, this long-lasting inhibition was replaced by increased firing rates for ∼100 ms. During long trains, the evoked response on the stimulated electrode decayed rapidly while the response was maintained on non-stimulated channels.Significance.The detailed description of the spatial and temporal response to ICMS can be used to better interpret results from experiments that probe circuit connectivity or function of cortical areas. These results can also contribute to the design of stimulation patterns to improve afferent interfaces for artificial sensory feedback.

Stoney vs. Histed: Quantifying the spatial effects of intracortical microstimulation.

BACKGROUND: Intracortical microstimulation (ICMS) is used to map neural circuits and restore lost sensory modalities such as vision, hearing, and somatosensation. The spatial effects of ICMS remain controversial: Stoney and colleagues proposed that the volume of somatic activation increased with stimulation intensity, while Histed et al., suggested activation density, but not somatic activation volume, increases with stimulation intensity. OBJECTIVE: We used computational modeling to quantify the spatial effects of ICMS intensity and unify the apparently paradoxical findings of Histed and Stoney. METHODS: We implemented a biophysically-based computational model of a cortical column comprising neurons with realistic morphology and representative synapses. We quantified the spatial effects of single pulses and short trains of ICMS, including the volume of activated neurons and the density of activated neurons as a function of stimulation intensity. RESULTS: At all amplitudes, the dominant mode of somatic activation was by antidromic propagation to the soma following axonal activation, rather than via transsynaptic activation. There were no occurrences of direct activation of somata or dendrites. The volume over which antidromic action potentials were initiated grew with stimulation amplitude, while the volume of somatic activation increased marginally. However, the density of somatic activation within the activated volume increased with stimulation amplitude. CONCLUSIONS: The results resolve the apparent paradox between Stoney and Histed's results by demonstrating that the volume over which action potentials are initiated grows with ICMS amplitude, consistent with Stoney. However, the volume occupied by the activated somata remains approximately constant, while the density of activated neurons within that volume increase, consistent with Histed.

A comprehensive model-based framework for optimal design of biomimetic patterns of electrical stimulation for prosthetic sensation.

OBJECTIVE: Touch and proprioception are essential to motor function as shown by the movement deficits that result from the loss of these senses, e.g. due to neuropathy of sensory nerves. To achieve a high-performance brain-controlled prosthetic arm/hand thus requires the restoration of somatosensation, perhaps through intracortical microstimulation (ICMS) of somatosensory cortex (S1). The challenge is to generate patterns of neuronal activation that evoke interpretable percepts. We present a framework to design optimal spatiotemporal patterns of ICMS (STIM) that evoke naturalistic patterns of neuronal activity and demonstrate performance superior to four previous approaches. APPROACH: We recorded multiunit activity from S1 during a center-out reach task (from proprioceptive neurons in Brodmann's area 2) and during application of skin indentations (from cutaneous neurons in Brodmann's area 1). We implemented a computational model of a cortical hypercolumn and used a genetic algorithm to design STIM that evoked patterns of model neuron activity that mimicked their experimentally-measured counterparts. Finally, from the ICMS patterns, the evoked neuronal activity, and the stimulus parameters that gave rise to it, we trained a recurrent neural network (RNN) to learn the mapping function between the physical stimulus and the biomimetic stimulation pattern, i.e. the sensory encoder to be integrated into a neuroprosthetic device. MAIN RESULTS: We identified ICMS patterns that evoked simulated responses that closely approximated the measured responses for neurons within 50 µm of the electrode tip. The RNN-based sensory encoder generalized well to untrained limb movements or skin indentations. STIM designed using the model-based optimization approach outperformed STIM designed using existing linear and nonlinear mappings. SIGNIFICANCE: The proposed framework produces an encoder that converts limb state or patterns of pressure exerted onto the prosthetic hand into STIM that evoke naturalistic patterns of neuronal activation.

Short reaction times in response to multi-electrode intracortical microstimulation may provide a basis for rapid movement-related feedback.

OBJECTIVE: Tetraplegic patients using brain-machine interfaces can make visually guided reaches with robotic arms. However, restoring proprioceptive feedback to these patients will be critical, as evidenced by the movement deficit in patients with proprioceptive loss. Proprioception is critical in large part because it provides faster feedback than vision. Intracortical microstimulation (ICMS) is a promising approach, but the ICMS-evoked reaction time (RT) is typically slower than that to natural proprioceptive and often even visual cues, implying that ICMS feedback may not be fast enough to guide movement. APPROACH: For most sensory modalities, RT decreases with increased stimulus intensity. Thus, it may be that stimulation intensities beyond what has previously been used will result in faster RTs. To test this, we compared the RT to ICMS applied through multi-electrode arrays in area 2 of somatosensory cortex to that of mechanical and visual cues. MAIN RESULTS: We found that the RT to single-electrode ICMS decreased with increased current, frequency, and train length. For 100 µA, 330 Hz stimulation, the highest single-electrode intensity we tested routinely, most electrodes resulted in RTs slower than the mechanical cue but slightly faster than the visual cue. While increasing the current beyond 100 µA resulted in faster RTs, sustained stimulation at this level may damage tissue. Alternatively, by stimulating through multiple electrodes (mICMS), a large amount of current can be injected while keeping that through each electrode at a safe level. We found that stimulation with at least 480 µA equally distributed over 16 electrodes could produce RTs as much as 20 ms faster than the mechanical cue, roughly the conduction delay to cortex from the periphery. SIGNIFICANCE: These results suggest that mICMS may provide a means to supply rapid, movement-related feedback. Future neuroprosthetics may need spatiotemporally patterned mICMS to convey useful somatosensory information. Novelty & Significance Intracortical microstimulation (ICMS) is a promising approach for providing artificial somatosensation to patients with spinal cord injury or limb amputation, but in prior experiments, subjects have been unable to respond as quickly to it as to natural cues. We have investigated the use of multi-electrode stimulation (mICMS) and discovered that it can produce reaction times as fast or faster even than natural mechanical cues. Although our stimulus trains were not modulated in time, this result opens the door to more complex spatiotemporal patterns of mICMS that might be used to rapidly write in complex somatosensory information to the CNS.

Controlling sensation intensity for electrotactile stimulation in human-machine interfaces.

A barrier to practical use of electrotactile stimulation for haptic feedback has been large variability in perceived sensation intensity due to changes in the impedance of the electrode-skin interface, such as when electrodes peel or users sweat. Here, we show how to significantly reduce this variability by modulating stimulation parameters in response to measurements of impedance. Our method derives from three contributions. First, we created a model between stimulation parameters and impedance at constant perceived sensation intensity by looking at the peak pulse energy and phase charge. Our model fits experimental data better than previous models (mean R2 > 0.9) and holds over a larger set of conditions (subjects, sessions, magnitudes of sensation, stimulation locations, electrode sizes). Second, we implemented a controller that regulates perceived sensation intensity by using our model to derive a new current amplitude and pulse duration in response to changes in impedance. Our controller accurately predicts subject-chosen stimulation parameters at constant sensation intensity (mean R2 > 0.9). Third, we demonstrated as a proof-of-concept on two subjects with below-elbow amputations-using a prosthesis with electrotactile touch feedback-that our controller can regulate sensation intensity in response to large impedance changes that occur in activities of daily living. These results make electrotactile stimulation for human-machine interfaces more reliable during activities of daily living.

A Low-Cost, Open-Source, Compliant Hand for Enabling Sensorimotor Control for People with Transradial Amputations.

In this paper, we describe the design and implementation of a low-cost, open-source prosthetic hand that enables both motor control and sensory feedback for people with transradial amputations. We integrate electromyographic pattern recognition for motor control along with contact reflexes and sensory substitution to provide feedback to the user. Compliant joints allow for robustness to impacts. The entire hand can be built for around $550. This low cost makes research and development of sensorimotor prosthetic hands more accessible to researchers worldwide, while also being affordable for people with amputations in developing nations. We evaluate the sensorimotor capabilites of our hand with a subject with a transradial amputation. We show that using contact reflexes and sensory substitution, when compared to standard myoelectric prostheses that lack these features, improves grasping of delicate objects like an eggshell and a cup of water both with and without visual feedback. Our hand is easily integrated into standard sockets, facilitating long-term testing of sensorimotor capabilities.