John S. Pezaris

Temporal structure in neuronal activity during working memory in macaque parietal cortex.

Many cortical structures have elevated firing rates during working memory, but it is not known how the activity is maintained. To investigate whether reverberating activity is important, we studied the temporal structure of local field potential (LFP) activity and spiking from area LIP in two awake macaques during a memory-saccade task. Using spectral analysis, we found spatially tuned elevated power in the gamma band (25–90 Hz) in LFP and spiking activity during the memory period. Spiking and LFP activity were also coherent in the gamma band but not at lower frequencies. Finally, we decoded LFP activity on a single-trial basis and found that LFP activity in parietal cortex discriminated between preferred and anti-preferred direction with approximately the same accuracy as the spike rate and predicted the time of a planned movement with better accuracy than the spike rate. This finding could accelerate the development of a cortical neural prosthesis.

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.

The spatial receptive field of thalamic inputs to single cortical simple cells revealed by the interaction of visual and electrical stimulation

Electrical stimulation of the thalamus has been widely used to test for the existence of monosynaptic input to cortical neurons, typically with stimulation currents that evoke cortical spikes with high probability. We stimulated the lateral geniculate nucleus (LGN) of the thalamus and recorded monosynaptically evoked spikes from layer 4 neurons in visual cortex. We found that with moderate currents, cortical spikes were evoked with low to moderate probability and their occurrence was modulated by ongoing sensory (visual) input. Furthermore, when repeated at 8–12 Hz, electrical stimulation of the thalamic afferents caused such profound inhibition that cortical spiking activity was suppressed, aside from electrically evoked monosynaptic spikes. Visual input to layer 4 cortical cells between electrical stimuli must therefore have derived exclusively from LGN afferents. We used white-noise visual stimuli to make a 2D map of the receptive field of each cortical simple cell during repetitive electrical stimulation in the LGN. The receptive field of electrically evoked monosynaptic spikes (and thus of the thalamic input alone) was significantly elongated. Its primary subfield was comparable to that of the control receptive field, but secondary (flanking) subfields were weaker. These findings extend previous results from intracellular recordings, but also demonstrate the effectiveness of an extracellular method of measuring subthreshold afferent input to cortex.

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.

Simultaneous paired intracellular and tetrode recordings for evaluating the performance of spike sorting algorithms

Objective evaluation of spike sorting algorithms such as those used to decompose tetrode recordings into distinct spike trains requires a priori knowledge of the correct classification for a given recording. Intracellular recording can unambiguously assign spikes to a single neuron, and thus provide correct classification if signals from that neuron concurrently appear in a tetrode recording. Simultaneous single or paired intracellular and tetrode recordings are used here to evaluate a contemporary spike sorting algorithm for isolated as well as overlapped events. These data are also used to demonstrate that overlapping extracellular spikes combine additively, and to introduce a means for quantifying variability in action potential shape.

Simulations of Electrode Placement for a Thalamic Visual Prosthesis

In this paper, placement parameters for microstimulation electrodes in a visual prosthesis are evaluated based on retinotopic models of macaque and human lateral geniculate nucleus. Phosphene patterns were simulated for idealized microwire electrodes as well as for currently available clinical electrodes. For idealized microwire electrodes, spacing as large as 600 mum in three dimensions would allow for over 250 phosphenes per visual hemifield in macaques, and over 800 in humans.

Mapping the primate lateral geniculate nucleus: A review of experiments and methods

Mapping neuronal responses in the lateral geniculate nucleus (LGN) is key to understanding how visual information is processed in the brain. This paper focuses on our current knowledge of the dynamics the receptive field (RF) as broken down into the classical receptive field (CRF) and the extra-classical receptive field (ECRF) in primate LGN. CRFs in the LGN are known to be similar to those in the retinal ganglion cell layer in terms of both spatial and temporal characteristics, leading to the standard interpretation of the LGN as a relay center from retina to primary visual cortex. ECRFs have generally been found to be large and inhibitory, with some differences in magnitude between the magno-, parvo-, and koniocellular pathways. The specific contributions of the retina, thalamus, and visual cortex to LGN ECRF properties are presently unknown. Some reports suggest a retinal origin for extra-classical suppression based on latency arguments and other reports have suggested a thalamic origin for extra-classical suppression. This issue is complicated by the use of anesthetized animals, where cortical activity is likely to be altered. Thus further study of LGN ECRFs is warranted to reconcile these discrepancies. Producing descriptions of RF properties of LGN neurons could be enhanced by employing preferred naturalistic stimuli. Although there has been significant work in cats with natural scene stimuli and noise that statistically imitates natural scenes, we highlight a need for similar data from primates. Obtaining these data may be aided by recent advancements in experimental and analytical techniques that permit the efficient study of nonlinear RF characteristics in addition to traditional linear factors. In light of the reviewed topics, we conclude by suggesting experiments to more clearly elucidate the spatial and temporal structure of ECRFs of primate LGN neurons.

Simulation of thalamic prosthetic vision: reading accuracy, speed, and acuity in sighted humans.

The psychophysics of reading with artificial sight has received increasing attention as visual prostheses are becoming a real possibility to restore useful function to the blind through the coarse, pseudo-pixelized vision they generate. Studies to date have focused on simulating retinal and cortical prostheses; here we extend that work to report on thalamic designs. This study examined the reading performance of normally sighted human subjects using a simulation of three thalamic visual prostheses that varied in phosphene count, to help understand the level of functional ability afforded by thalamic designs in a task of daily living. Reading accuracy, reading speed, and reading acuity of 20 subjects were measured as a function of letter size, using a task based on the MNREAD chart. Results showed that fluid reading was feasible with appropriate combinations of letter size and phosphene count, and performance degraded smoothly as font size was decreased, with an approximate doubling of phosphene count resulting in an increase of 0.2 logMAR in acuity. Results here were consistent with previous results from our laboratory. Results were also consistent with those from the literature, despite using naive subjects who were not trained on the simulator, in contrast to other reports.

Extracellular recording from multiple neighboring cells: a maximum-likelihood solution to the spike-separation problem

In recent years considerable attention among extracellular electrophysiologists has focused on the problem of simultaneously recording the activity of multiple neurons in behaving animals. Such recordings, it is hoped, will provide much-needed insight into the dynamics of neural ensemble computation and coding. Of particular interest are recordings from neighboring neurons, for example cells that lie within a single column of neocortex Such cells are likely to share functional roles and to possess the anatomical interConnectivity needed for ensemble coding, making them plausible participants in local computational and signaling circuits.

Visual Acuity of Simulated Thalamic Visual Prostheses in Normally Sighted Humans

Simulation in normally sighted individuals is a crucial tool to evaluate the performance of potential visual prosthesis designs prior to human implantation of a device. Here, we investigated the effects of electrode count on visual acuity, learning rate and response time in 16 normally sighted subjects using a simulated thalamic visual prosthesis, providing the first performance reports for thalamic designs. A new letter recognition paradigm using a multiple-optotype two-alternative forced choice task was adapted from the Snellen eye chart, and specifically devised to be readily communicated to both human and non-human primate subjects. Validation of the method against a standard Snellen acuity test in 21 human subjects showed no significant differences between the two tests. The novel task was then used to address three questions about simulations of the center-weighted phosphene patterns typical of thalamic designs: What are the expected Snellen acuities for devices with varying numbers of contacts, do subjects display rapid adaptation to the new visual modality, and can response time in the task provide clues to the mechanisms of perception in low-resolution artificial vision? Population performance (hit rate) was significantly above chance when viewing Snellen 20/200 optotypes (Log MAR 1.0) with 370 phosphenes in the central 10 degrees of vision, ranging to Snellen 20/800 (Log MAR 1.6) with 25 central phosphenes. Furthermore, subjects demonstrated learning within the 1–2 hours of task experience indicating the potential for an effective rehabilitation and possibly better visual performance after a longer period of training. Response time differences suggest that direct letter perception occurred when hit rate was above 75%, whereas a slower strategy like feature-based pattern matching was used in conditions of lower relative resolution. As pattern matching can substantially boost effective acuity, these results suggest post-implant therapy should specifically address feature detection skills.