Tyler S. Davis

Multiple factors may influence the performance of a visual prosthesis based on intracortical microstimulation: nonhuman primate behavioural experimentation

We hypothesize that a visual prosthesis capable of evoking high-resolution visual perceptions can be produced using high-electrode-count arrays of penetrating microelectrodes implanted into the primary visual cortex of a blind human subject. To explore this hypothesis, and as a prelude to human psychophysical experiments, we have conducted a set of experiments in primary visual cortex (V1) of non-human primates using chronically implanted Utah Electrode Arrays (UEAs). The electrical and recording properties of implanted electrodes, the high-resolution visuotopic organization of V1, and the stimulation levels required to evoke behavioural responses were measured. The impedances of stimulated electrodes were found to drop significantly immediately following stimulation sessions, but these post-stimulation impedances returned to pre-stimulation values by the next experimental session. Two months of periodic microstimulation at currents of up to 96 µA did not impair the mapping of receptive fields from local field potentials or multi-unit activity, or impact behavioural visual thresholds of light stimuli that excited regions of V1 that were implanted with UEAs. These results demonstrate that microstimulation at the levels used did not cause functional impairment of the electrode array or the neural tissue. However, microstimulation with current levels ranging from 18 to 76 µA (46 ± 19 µA, mean ± std) was able to elicit behavioural responses on eight out of 82 systematically stimulated electrodes. We suggest that the ability of microstimulation to evoke phosphenes and elicit a subsequent behavioural response may depend on several factors: the location of the electrode tips within the cortical layers of V1, distance of the electrode tips to neuronal somata, and the inability of nonhuman primates to recognize and respond to a generalized set of evoked percepts.

The functional consequences of chronic, physiologically effective intracortical microstimulation.

Many studies have demonstrated the ability of chronically implanted multielectrode arrays (MEAs) to extract information from the motor cortex of both humans and nonhuman primates. Similarly, many studies have shown the ability of intracortical microstimulation to impart information to the brain via a single or a few electrodes acutely implanted in sensory cortex of nonhuman primates, but relatively few microstimulation studies characterizing chronically implanted MEAs have been performed. Additionally, device and tissue damage have been reported at the levels of microstimulation used in these studies. Whether the damage resulting from microstimulation impairs the ability of MEAs to chronically produce physiological effects, however, has not been directly tested. In this study, we examined the functional consequences of multiple months of periodic microstimulation via chronically implanted MEAs at levels capable of evoking physiological responses, that is, electromyogram (EMG) activity. The functionality of the MEA and neural tissue was determined by measuring impedances, the ability of microstimulation to evoke EMG responses, and the recording of action potentials. We found that impedances and the number of recorded action potentials followed the previously reported trend of decreasing over time in both animals that received microstimulation and those which did not receive microstimulation. Despite these trends, the ability to evoke EMG responses and record action potentials was retained throughout the study. The results of this study suggest that intracortical microstimulation via MEAs did not cause functional failure, suggesting that MEA-based microstimulation is ready to transition into subchronic (< 30 days) human trials to determine whether complex spatiotemporal sensory percepts can be evoked by patterned microstimulation.

Spatial and temporal characteristics of V1 microstimulation during chronic implantation of a microelectrode array in a behaving macaque

OBJECTIVE It has been hypothesized that a vision prosthesis capable of evoking useful visual percepts can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays. As a continuation of earlier work, we examined several spatial and temporal characteristics of V1 microstimulation. APPROACH An array of 100 penetrating microelectrodes was chronically implanted in V1 of a behaving macaque monkey. Microstimulation thresholds were measured using a two-alternative forced choice detection task. Relative locations of electrically-evoked percepts were measured using a memory saccade-to-target task. MAIN RESULTS The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes. Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked percepts using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0° ± 0.2° in visual space. Significance. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.

Using multiple high-count electrode arrays in human median and ulnar nerves to restore sensorimotor function after previous transradial amputation of the hand.

Peripheral nerve interfaces that can record from and stimulate large numbers of different nerve fibers selectively and independently may help restore intuitive and effective motor and sensory function after hand amputation. To this end, and extending previous work in two subjects, two 100-electrode Utah Slanted Electrode Arrays (USEAs) were implanted for four weeks in the residual ulnar and median nerves of a 50-year-old male whose left, dominant hand had been amputated 21 years previously. Subsequent experiments involved 1) recording from USEAs for real-time control of a virtual prosthetic hand; 2) stimulation to evoke somatosensory percepts; and 3) closed-loop sensorimotor control. Overall, partial motor control and sensation were achieved using USEAs. 1) Isolated action potentials recorded from nerve motor fibers, although sparse at these distal implant sites, were activated during fictive movements of the phantom hand. Unlike in our previous two subjects, electromyographic (EMG) activity contributed to most online recordings and decodes, but was reduced in offline analyses using common average referencing. Online and offline Kalman-filter decodes of thresholded neural or EMG spikes independently controlled different digits of the virtual hand with one or two degrees of freedom. 2) Microstimulation through individual electrodes of the two USEAs evoked up to 106 different percepts, covering much of the phantom hand. The subject discriminated among five perceived stimulus locations, and between two somatosensory submodalities at a single location. 3) USEA-evoked percepts, mimicking contact with either a near or distal virtual target, were used to terminate movements of the virtual hand controlled with USEA recordings comprised wholly or mostly of EMG. These results further indicate that USEAs can help restore sensory and motor function after hand loss.

The ictal wavefront is the spatiotemporal source of discharges during spontaneous human seizures

The extensive distribution and simultaneous termination of seizures across cortical areas has led to the hypothesis that seizures are caused by large-scale coordinated networks spanning these areas. This view, however, is difficult to reconcile with most proposed mechanisms of seizure spread and termination, which operate on a cellular scale. We hypothesize that seizures evolve into self-organized structures wherein a small seizing territory projects high-intensity electrical signals over a broad cortical area. Here we investigate human seizures on both small and large electrophysiological scales. We show that the migrating edge of the seizing territory is the source of travelling waves of synaptic activity into adjacent cortical areas. As the seizure progresses, slow dynamics in induced activity from these waves indicate a weakening and eventual failure of their source. These observations support a parsimonious theory for how large-scale evolution and termination of seizures are driven from a small, migrating cortical area.

Recording and Decoding for Neural Prostheses

This paper reviews technologies and signal processing algorithms for decoding peripheral nerve and electrocorticogram signals to interpret human intent and control prosthetic arms. The review includes a discussion of human motor system physiology and physiological signals that can be used to decode motor intent, electrode technology for acquiring neural data, and signal processing methods including decoders based on Kalman filtering and least-squares regressors. Representative results from human experiments demonstrate the progress that has been made in neural decoding and its potential for developing neuroprosthetic arms that act and feel like natural arms.

Seeing is believing: neural representations of visual stimuli in human auditory cortex correlate with illusory auditory perceptions.

In interpersonal communication, the listener can often see as well as hear the speaker. Visual stimuli can subtly change a listener’s auditory perception, as in the McGurk illusion, in which perception of a phoneme’s auditory identity is changed by a concurrent video of a mouth articulating a different phoneme. Studies have yet to link visual influences on the neural representation of language with subjective language perception. Here we show that vision influences the electrophysiological representation of phonemes in human auditory cortex prior to the presentation of the auditory stimulus. We used the McGurk effect to dissociate the subjective perception of phonemes from the auditory stimuli. With this paradigm we demonstrate that neural representations in auditory cortex are more closely correlated with the visual stimuli of mouth articulation, which drive the illusory subjective auditory perception, than the actual auditory stimuli. Additionally, information about visual and auditory stimuli transfer in the caudal–rostral direction along the superior temporal gyrus during phoneme perception as would be expected of visual information flowing from the occipital cortex into the ventral auditory processing stream. These results show that visual stimuli influence the neural representation in auditory cortex early in sensory processing and may override the subjective auditory perceptions normally generated by auditory stimuli. These findings depict a marked influence of vision on the neural processing of audition in tertiary auditory cortex and suggest a mechanistic underpinning for the McGurk effect.

The use of a novel carbon nanotube coated microelectrode array for chronic intracortical recording and microstimulation

Micro-electrode arrays (MEAs) have been used in a variety of intracortical neural prostheses. While intracortical MEAs have demonstrated their utility in neural prostheses, in many cases MEA performance declines after several months to years of in vivo implantation. The application of carbon nanotubes (CNTs) may increase the functional longevity of intracortical MEAs through enhanced biocompatibility and charge injection properties. An MEA metalized with platinum (Pt) on all electrodes had a CNT coating applied to the electrodes on half of the array. This Pt/Pt-CNT MEA was implanted into feline motor cortex for >;1 year. Recordings of action potentials and 1 kHz impedance measurements were made on all electrodes to evaluate device functionality. Additionally, electromyogram (EMG) responses were evoked using micro-stimulation via the MEA to measure device performance. These metrics were compared between Pt and Pt-CNT electrodes. There was no significant difference in the data acquisition or micro-stimulation performance of Pt and the Pt-CNT electrodes. However, impedances were lower on the Pt-CNT electrodes. These results demonstrate the functionality of CNT coatings during chronic in vivo implantation. The lower impedances suggest that for microstimulation applications CNT coatings may impart enhanced interface properties.

Decoding hand trajectories from micro-electrocorticography in human patients

A Kalman filter was used to decode hand trajectories from micro-electrocorticography recorded over motor cortex in human patients. In two cases, signals were recorded during stereotyped tasks, and the trajectories were decoded offline, with maximum correlation coefficients between actual and predicted trajectories of 0.51 (x-direction position) and 0.54 (y-direction position). In a third setting, a human patient with full neural control of a computer cursor acquired onscreen targets within 6.24 sec on average, with no algorithmic constraints on the output trajectory. These practical results illustrate the potential utility of signals recorded at the cortical surface with high spatial resolution, demonstrating that surface potentials contain relevant and sufficient information to drive sophisticated brain-computer interface systems.

Informative features of local field potential signals in primary visual cortex during natural image stimulation

The local field potential (LFP) is of growing importance in neurophysiology as a metric of network activity and as a readout signal for use in brain-machine interfaces. However, there are uncertainties regarding the kind and visual field extent of information carried by LFP signals, as well as the specific features of the LFP signal conveying such information, especially under naturalistic conditions. To address these questions, we recorded LFP responses to natural images in V1 of awake and anesthetized macaques using Utah multielectrode arrays. First, we have shown that it is possible to identify presented natural images from the LFP responses they evoke using trained Gabor wavelet (GW) models. Because GW models were devised to explain the spiking responses of V1 cells, this finding suggests that local spiking activity and LFPs (thought to reflect primarily local synaptic activity) carry similar visual information. Second, models trained on scalar metrics, such as the evoked LFP response range, provide robust image identification, supporting the informative nature of even simple LFP features. Third, image identification is robust only for the first 300 ms following image presentation, and image information is not restricted to any of the spectral bands. This suggests that the short-latency broadband LFP response carries most information during natural scene viewing. Finally, best image identification was achieved by GW models incorporating information at the scale of ∼ 0.5° in size and trained using four different orientations. This suggests that during natural image viewing, LFPs carry stimulus-specific information at spatial scales corresponding to few orientation columns in macaque V1.