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, 110 (52), 21177-82

Restoration of Function After Brain Damage Using a Neural Prosthesis

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Restoration of Function After Brain Damage Using a Neural Prosthesis

David J Guggenmos et al. Proc Natl Acad Sci U S A.

Abstract

Neural interface systems are becoming increasingly more feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as a communication link between distant locations in the cerebral cortex. The primary motor area in the cerebral cortex was injured in a rat model of focal brain injury, disrupting communication between motor and somatosensory areas and resulting in impaired reaching and grasping abilities. After implantation of microelectrodes in cerebral cortex, a neural prosthesis discriminated action potentials (spikes) in premotor cortex that triggered electrical stimulation in somatosensory cortex continuously over subsequent weeks. Within 1 wk, while receiving spike-triggered stimulation, rats showed substantially improved reaching and grasping functions that were indistinguishable from prelesion levels by 2 wk. Post hoc analysis of the spikes evoked by the stimulation provides compelling evidence that the neural prosthesis enhanced functional connectivity between the two target areas. This proof-of-concept study demonstrates that neural interface systems can be used effectively to bridge damaged neural pathways functionally and promote recovery after brain injury.

Keywords: brain–machine–brain interface; closed-loop; long-term potentiation; neural plasticity; traumatic brain injury.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Theoretical model of neuroprosthetic treatment approach after brain injury. (A) Normal connectivity of M1, S1, and PM. Both M1 (CFA in rat) and PM (RFA in rat) send substantial outputs to the spinal cord via the corticospinal tract. Also, extensive reciprocal connections exist between M1 and PM, as well as between M1 and S1. (B) Effects of focal M1 injury on brain connectivity and the hypothetical effect of a BMBI to restore somatosensory-motor communication. An injury to M1, as might occur in stroke or brain trauma, results in a focal area of necrosis, as well as loss of M1 outputs to the spinal cord. Corticocortical communication between M1 and S1 (and between M1 and PM) is also disrupted, further contributing to functional impairment. Because the uninjured PM also contains corticospinal neurons, it might have the ability to serve in a vicarious role. The dotted line indicates enhanced functional connection between PM and S1 that we propose is established after treatment with a BMBI. (C) Location of target areas in rat cerebral cortex. A topographic map of the somatosensory representation in S1 is superimposed on the cortex.
Fig. 2.
Fig. 2.
ADS protocol. After injury to the CFA, a recording microelectrode was placed in the RFA, whereas a stimulating microelectrode was placed in the distal forelimb field of S1. A BMBI discriminated action potentials in the RFA, and after a 7.5-ms delay, it delivered a low-level electrical current pulse to S1 (13). (A) Sketch of a rat retrieving a food pellet with a BMBI attached to the skull. (B) Sample traces of recordings from the RFA showing action potentials and stimulus artifacts from an ICMS current delivered to S1. Time-amplitude window discriminators are indicated by red boxes. A total of 100 superimposed traces are shown.
Fig. 3.
Fig. 3.
Performance of rats on a skilled reaching task after injury to M1 (ON condition). The ADS group is shown in red, the OLS group is shown in blue, and the control group is shown in black. The dotted line indicates the average prelesion performance of all animals in the study. The bounded area indicates the 95% confidence interval. Regression lines are based on an LMM (43). Error bars represent 95% confidence intervals. *P < 0.05 (pairwise difference between the ADS and OLS groups). Because the statistical analysis was an intent-to-treat model, rats were included in the analysis even if the microdevice was no longer functional. Only one rat in the ADS group had a microdevice that was functional by postlesion day 28; thus, figures are presented through postlesion day 21 (SI Results). Diamonds, squares, and triangles represent individual animal data points. #, microdevice not functional (Tables S1 and S2).
Fig. 4.
Fig. 4.
Comparison of spike activity in the RFA in the ADS and OLS groups. Data represent spikes discriminated in the RFA over a 28-ms period. In the ON condition, the trigger for the data acquisition was the S1 stimulus pulse. In the OFF condition, the trigger for the data acquisition was 7.5 ms after a spike event in the RFA. (A) Composite posttrigger spiking histograms derived from neural recordings in the RFA compiled from days 1, 5, 8, 14, and 21 (±1 d). Histograms portray the mean spike counts per trigger event within each time bin (also Fig. S4). Spike counts were based on an average of over 22,000 trigger events per animal per day. Poststimulus firing rates were substantially higher in the ADS ON condition (33.1 Hz), compared with the ADS OFF (12.5 Hz), OLS ON (6.6 Hz), or OLS OFF (10.1 Hz) condition. (B) Average spike firing rates throughout the 28-ms window for each day. Error bars represent between-subject variation on each day (plus 1 SD). LMMs detected higher firing rates in the ADS group compared with the OLS group with stimulation ON (P < 0.0001). Firing rates did not differ statistically between groups in the OFF condition (P > 0.05). Posttrigger spiking histograms for each day are shown in Fig. S4.

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