Clinical translation of a high-performance neural prosthesis

Abstract

Neural prostheses have the potential to improve the quality of life of individuals with paralysis by directly mapping neural activity to limb- and computer-control signals. We translated a neural prosthetic system previously developed in animal model studies for use by two individuals with amyotrophic lateral sclerosis who had intracortical microelectrode arrays placed in motor cortex. Measured more than 1 year after implant, the neural cursor-control system showed the highest published performance achieved by a person to date, more than double that of previous pilot clinical trial participants.

Figure 1. Comparison of neural control performance for participants S3, T6 and T7

(a) Neural control paradigm. Broadband neural signals are recorded from an implanted microelectrode array. Signal conditioning extracts neural features, multi-unit spike counts and high-frequency local field potential power (HF-LFP), which are decoded to estimate intended cursor velocity. (b) “Radial-8” cursor trajectories: (top) mean trajectories of fifteen randomly selected trials per target and (bottom) ten randomly selected example trajectories per target. (c) Target acquisition time (mean ± 95% bootstrap confidence intervals) for “Radial-8” (S3: 278 trials, T6: 665 trials, T7: 358 trials). T6 and T7 acquisition times are significantly lower than S3 acquisition times (p < 10^-100, unpaired t-test). (d) “mFitts1” performance summary (S3: 248 trials, T6: 1072 trials, T7: 241 trials): index of difficulty was binned at 0.5 bit intervals and mean target acquisition times (mean ± 95% confidence intervals) were calculated. (e) Slope and (f) intercept for linear regression of index of difficulty vs. acquire time for “mFitts1” (95% bootstrap confidence intervals). T6 and T7 acquisition times are significantly lower than S3 acquisition times (p < 1×10^-5, analysis of covariance). T6 and T7 acquisition time includes the 500 dwell time used by these participants to select targets. Sessions shown are 224-256 and 349-387 days post-implantation for T6 and T7, respectively (T6 achieved comparable performance when tested 628, 791, and 798 days post-implantation (Supplementary Table 2)). S3 data in panels b-e re-plotted with permission from . Values plotted in this figure are summarized in Supplementary Table 3.

Figure 2. Comparison of VKF and ReFIT neural control performance for T6 and T7

(a) Target acquisition time, including the 500ms dwell time (performance for individual blocks shown in Supplementary Fig. 8a–b). (b–c) Two additional performance measures rely on the task movement axis, defined by the direct line path from the cursor position at the start of the trial to the target position. (b) Task direction change count is the number of times the cursor velocity in the task movement axis reversed signs. (c) Orthogonal direction change count is the number of times the cursor velocity orthogonal to the task movement axis reversed signs. Data in panels a–c represent 418 (VKF) and 377 (ReFIT) trials for T6, and 418 (VKF) and 555 (ReFIT) trials from T7. (d) Participant-reported difficulty scores within a range of 0 (effortless control) to 10 (impossible control). Data represent 4 comparison blocks (T6) and 5 comparison blocks (T7) for each decoder (individual ratings shown in Supplementary Fig. 8c). For all bar graphs the mean ± 95% bootstrap confidence intervals are shown and * indicates a significant difference between VKF and ReFIT (p<0.01, unpaired t-test). Values plotted in this figure are summarized in Supplementary Table 4. Channel counts used by each decoder are summarized in Supplementary Table 5.