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Case Reports
. 2021 Dec 1;131(23):e151331.
doi: 10.1172/JCI151331.

Visual percepts evoked with an intracortical 96-channel microelectrode array inserted in human occipital cortex

Eduardo Fernández  1   2   3 , Arantxa Alfaro  1   2   4 , Cristina Soto-Sánchez  1   2 , Pablo Gonzalez-Lopez  1   5 , Antonio M Lozano  1 , Sebastian Peña  1 , Maria Dolores Grima  1 , Alfonso Rodil  1 , Bernardeta Gómez  1 , Xing Chen  6 , Pieter R Roelfsema  6   7 , John D Rolston  8 , Tyler S Davis  3   8 , Richard A Normann  3   8
Affiliations
Case Reports

Visual percepts evoked with an intracortical 96-channel microelectrode array inserted in human occipital cortex

Eduardo Fernández et al. J Clin Invest. .

Abstract

BACKGROUNDA long-held goal of vision therapy is to transfer information directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight. However, no clinically available cortical visual prosthesis yet exists.METHODSWe implanted an intracortical microelectrode array consisting of 96 electrodes in the visual cortex of a 57-year-old person with complete blindness for a 6-month period. We measured thresholds and the characteristics of the visual percepts elicited by intracortical microstimulation.RESULTSImplantation and subsequent explantation of intracortical microelectrodes were carried out without complications. The mean stimulation threshold for single electrodes was 66.8 ± 36.5 μA. We consistently obtained high-quality recordings from visually deprived neurons and the stimulation parameters remained stable over time. Simultaneous stimulation via multiple electrodes was associated with a significant reduction in thresholds (P < 0.001, ANOVA) and evoked discriminable phosphene percepts, allowing the blind participant to identify some letters and recognize object boundaries.CONCLUSIONSOur results demonstrate the safety and efficacy of chronic intracortical microstimulation via a large number of electrodes in human visual cortex, showing its high potential for restoring functional vision in the blind.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02983370.FUNDINGThe Spanish Ministerio de Ciencia Innovación y Universidades, the Generalitat Valenciana (Spain), the Europan Union's Horizon 2020 programme, the Bidons Egara Research Chair of the University Miguel Hernández (Spain), and the John Moran Eye Center of the University of Utah.

Keywords: Medical devices; Neuroscience; Ophthalmology.

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Conflict of interest statement

Conflict of interest: PRR and XC are cofounders and shareholders of a neurotechnology startup, Phosphoenix (Netherlands).

Figures

Figure 1
Figure 1. Utah Electrode Array (UEA) implantation and electrophysiological recordings.
(A) Scanning electron microscopy image of the UEA and numbering system used to identify specific electrodes (electrode side shown). (B) Location of the UEA implantation site on the right occipital cortex. Inset: Image of the UEA to be implanted during surgery. (C) Predicted retinotopic map organization superimposed on the 3D reconstruction of the volunteer’s cerebral cortex with the implantation site indicated (left, location of visual areas; middle, eccentricity; and right, polar angle). (D) Average electrode impedances across the 6-month study period. The mean impedances increased by 20% in the first week, and gradually decreased toward their initial values (blue line). (E) Examples of recorded waveforms on days 3, 77, and 154 with summary statistics of recorded multiunit responses. Color in the heatmap represents the number of days on which more than 50 reliable action potentials were recorded on a given electrode over the 2-minute recording period.
Figure 2
Figure 2. Relationship between phosphene thresholds and charge per phase.
(A) Probability of phosphene perception for different pulse durations (pulse width, PW). (B) Effects of the stimulation frequency. (C) Effects of the duration of the train (TD) of stimulation pulses. One hundred twenty responses were used for each psychometric curve. The dashed horizontal blue lines represent the thresholds (50% probability of detection).
Figure 3
Figure 3. Phosphene thresholds.
(A) Diagram illustrating the stimulation parameters of the biphasic pulse waveforms that were used for the quantification of the thresholds. (B) Distribution of phosphene thresholds for stimulation via single microelectrodes. Electrode tips are pointing away from the page. (C) Distribution of the thresholds for all the electrodes on week 21. (D) Distribution of phosphene thresholds evoked by simultaneous stimulation via sets of 4 contiguous (abutting) electrodes. Electrode tips are pointing away from the page. (E) Histogram of averaged thresholds for stimulation via the sets of 4 electrodes. (F) Evolution of the threshold for stimulation of single electrodes and for groups of 4 electrodes. Data presented as mean ± SEM. (G) Representative psychometric curves generated in response to stimulation (biphasic pulses, with a phase duration of 170 μs/phase and a frequency of 300 Hz) via 1 and 4 abutting electrodes.
Figure 4
Figure 4. Representative simultaneous stimulation and recording experiments.
(A) Repetitive stimulation of electrode 28 with 78 μA at 0.5 Hz (red lines, 10 times, identical parameters) induced an increased firing of the neurons surrounding this electrode. Only the last 4 stimulations were associated with the perception of a phosphene (see upper enlarged panel where “–” indicates no perception and “Y” indicates perception). (B) Repetitive stimulation of electrode 9 with 64 μA at 1 Hz induced an inhibition of the neurons surrounding the electrode that recovered after a few seconds. In each of these examples, the neural recording was obtained from the stimulated electrode. Red vertical bars indicate the stimulus times.
Figure 5
Figure 5. Phosphene map and relative brightness and size of perceived phosphenes.
(A) Location of the perceived phosphenes (blue dots) and electrode numbering view from the pad side. The cross indicates the center of the subject’s visual field (the intersection of her horizontal and vertical meridians). Yellow region: Expected location of the phosphenes based on a standard retinotopic map superimposed on the anatomy of the visual cortex of the patient using the procedures described by Benson et al. (22, 23) and the selected implantation site. Calibration bar = 1 degree. (B) Changes in the location of the perceived phosphenes for the same 4 electrodes in 5 different trials. Calibration bar = 1 degree.
Figure 6
Figure 6. Relative brightness and size of perceived phosphenes on a subjective scale ranging from 0 to 5.
(A) Averaged values of perceived brightness across 10 single electrodes. Maximum was reached for currents of approximately 90 μA. (B) Subjective brightness and (C) subjective size of perceived phosphenes as a function of the number of simultaneously stimulated electrodes. Error bars denote SEM.
Figure 7
Figure 7. Examples of perceptions evoked by simultaneous stimulation of multiple electrodes.
(A) The stimulation of the 2 electrodes shown in the inset electrode map induced the perception of 2 closely spaced phosphenes. (B) Box-and-whisker plot of subjective phosphene size for electrode pairs separated from 400 to 3600 μm. Inset: Relative location of electrodes 1 and 10 in the UEA, which are separated by 400 μm (light blue color), and electrodes 1 and 89, which are separated by 3600 μm (orange color). In the box-and-whisker plot, the boundary of the box closest to zero indicates the first quartile, and the boundary of the box farthest from zero indicates the third quartile. The horizontal line is the median. The whiskers show the maximum and minimum values, with the exception of outliers (small circles) and extremes (stars). (C) Simultaneous stimulation of 4 contiguous electrodes was perceived as 3 small dots. (D) Stimulation of 12 electrodes induced the perception of a horizontal line. (E) Simultaneous stimulation of the 2 groups of 4 blue electrodes evoked the percept of a line with a horizontal orientation, whereas the simultaneous stimulation of the 2 groups of 4 red electrodes evoked the percept of a line with a vertical orientation. (F) Stimulation of these electrodes elicited the perception of a lowercase letter i. (G) Stimulation of these 2 groups of electrodes unexpectedly induced the perception of an uppercase letter L. (H) Stimulation of these electrodes elicited the perception of an uppercase letter O.
Figure 8
Figure 8. Evolution of the performance in a task in which the subject discriminated an uppercase O from a lowercase o.
(A) Stimulated electrodes for the perception of each pattern. (B) Learning process that reached an accuracy of 100% in the last session. Error bars denote SEM.
Figure 9
Figure 9. Bio-inspired artificial retina.
(A) Schematic organization of the sight restoration concept. (B) The image acquisition system. The input images are captured by a video camera attached to a spectacle frame for subsequent bio-inspired processing. (C) Signal processing module. Input images are processed by a combination of several spatial and temporal filters that enhance specific features of captured information. The weighting module re-encodes this information into a neuromorphic stream of electrode addresses and sends it to the CereStim 96, which generates the stimulation signals applied to the intracortical microelectrodes. (D) Discrimination of the border between black and white bars using the bio-inspired artificial retina (frame extracted from Supplemental Video 1). (E) Evolution of the time required to perform the object location task (4 possible locations) over several days.
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