Paul A. House

Toward the development of a cortically based visual neuroprosthesis

Motivated by the success of cochlear implants for deaf patients, we are now facing the goal of creating a visual neuroprosthesis designed to interface with the occipital cortex as a means through which a limited but useful sense of vision could be restored in profoundly blind patients. We review the most important challenges regarding this neuroprosthetic approach and emphasize the need for basic human psychophysical research on the best way of presenting complex stimulating patterns through multiple microelectrodes. Continued research will hopefully lead to the development of and design specifications for the first generation of a cortically based visual prosthesis system.

Human neocortical electrical activity recorded on nonpenetrating microwire arrays: applicability for neuroprostheses.

OBJECT The goal of this study was to determine whether a nonpenetrating, high-density microwire array could provide sufficient information to serve as the interface for decoding motor cortical signals. METHODS Arrays of nonpenetrating microwires were implanted over the human motor cortex in 2 patients. The patients performed directed stereotypical reaching movements in 2 directions. The resulting data were used to determine whether the reach direction could be distinguished through a frequency power analysis. RESULTS Correlation analysis revealed decreasing signal correlation with distance. The gamma-band power during motor planning allowed binary classification of gross directionality in the reaching movements. The degree of power change was correlated to the underlying gyral pattern. CONCLUSIONS The nonpenetrating microwire platform showed good potential for allowing differentiated signals to be recorded with high spatial fidelity without cortical penetration.

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.

Acute human brain responses to intracortical microelectrode arrays: challenges and future prospects

The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons. As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the central nervous system (CNS). These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns). However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies. Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology.

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.

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.

Multi-scale analysis of neural activity in humans: Implications for micro-scale electrocorticography.

OBJECTIVE Electrocorticography grids have been used to study and diagnose neural pathophysiology for over 50 years, and recently have been used for various neural prosthetic applications. Here we provide evidence that micro-scale electrodes are better suited for studying cortical pathology and function, and for implementing neural prostheses. METHODS This work compares dynamics in space, time, and frequency of cortical field potentials recorded by three types of electrodes: electrocorticographic (ECoG) electrodes, non-penetrating micro-ECoG (μECoG) electrodes that use microelectrodes and have tighter interelectrode spacing; and penetrating microelectrodes (MEA) that penetrate the cortex to record single- or multiunit activity (SUA or MUA) and local field potentials (LFP). RESULTS While the finest spatial scales are found in LFPs recorded intracortically, we found that LFP recorded from μECoG electrodes demonstrate scales of linear similarity (i.e., correlation, coherence, and phase) closer to the intracortical electrodes than the clinical ECoG electrodes. CONCLUSIONS We conclude that LFPs can be recorded intracortically and epicortically at finer scales than clinical ECoG electrodes are capable of capturing. SIGNIFICANCE Recorded with appropriately scaled electrodes and grids, field potentials expose a more detailed representation of cortical network activity, enabling advanced analyses of cortical pathology and demanding applications such as brain-computer interfaces.

Functional Connectivity Targeting for Deep Brain Stimulation in Essential Tremor

BACKGROUND AND PURPOSE: Deep brain stimulation of the thalamus has become a valuable treatment for medication-refractory essential tremor, but current targeting provides only a limited ability to account for individual anatomic variability. We examined whether functional connectivity measurements among the motor cortex, superior cerebellum, and thalamus would allow discrimination of precise targets useful for image guidance of neurostimulator placement. MATERIALS AND METHODS: Resting BOLD images (8 minutes) were obtained in 58 healthy adolescent and adult volunteers. Regions of interest were identified from an anatomic atlas and a finger movement task in each subject in the primary motor cortex and motor activation region of the bilateral superior cerebellum. Correlation was measured in the time series of each thalamic voxel with the 4 seeds. An analogous procedure was performed on a single subject imaged for 10 hours to constrain the time needed for single-subject optimization of thalamic targets. RESULTS: Mean connectivity images from 58 subjects showed precisely localized targets within the expected location of the ventral intermediate nucleus of the thalamus, within a single voxel of currently used deep brain stimulation anatomic targets. These targets could be mapped with single-voxel accuracy in a single subject with 3 hours of imaging time, though targets were reproduced in different locations for the individual than for the group averages. CONCLUSIONS: Interindividual variability likely exists in optimal placement for thalamic deep brain stimulation targeting of the cerebellar thalamus for essential tremor. Individualized thalamic targets can be precisely estimated for image guidance with sufficient imaging time.

Seeding of a cavernous angioma with Mycoplasma hominis: case report.

OBJECTIVE AND IMPORTANCETo describe a unique case of hematogenous seeding of a cavernous angioma with the commensal organism Mycoplasma hominis. CLINICAL PRESENTATIONA 40-year-old female patient presented with a severe headache and acute left facial nerve palsy. Imaging studies revealed a right frontal mass lesion with characteristics of a cavernous angioma. INTERVENTIONThe patient underwent a craniotomy for cavernous angioma resection. Purulent material was noted at the time of resection, and no hemorrhage was observed. Despite antibiotic therapy, the patient required repeat craniotomies for subsequent abscess treatment. M. hominis was identified as the pathogen. CONCLUSIONM. hominis is a rare cause of brain abscesses and can be difficult to eradicate. Cavernous angiomas can be seeded hematogenously.