Restoration of upper limb movement via artificial corticospinal and musculospinal connections in a monkey with spinal cord injury

Abstract

Functional loss of limb control in individuals with spinal cord injury or stroke can be caused by interruption of corticospinal pathways, although the neural circuits located above and below the lesion remain functional. An artificial neural connection that bridges the lost pathway and connects cortical to spinal circuits has potential to ameliorate the functional loss. We investigated the effects of introducing novel artificial neural connections in a paretic monkey that had a unilateral spinal cord lesion at the C2 level. The first application bridged the impaired spinal lesion. This allowed the monkey to drive the spinal stimulation through volitionally controlled power of high-gamma activity in either the premotor or motor cortex, and thereby to acquire a force-matching target. The second application created an artificial recurrent connection from a paretic agonist muscle to a spinal site, allowing muscle-controlled spinal stimulation to boost on-going activity in the muscle. These results suggest that artificial neural connections can compensate for interrupted descending pathways and promote volitional control of upper limb movement after damage of descending pathways such as spinal cord injury or stroke.

Keywords: artificial neural connection; brain–computer interface; hand; local field potential; monkey; muscle; spinal cord; spinal cord injury.

FIGURE 1

(A) Electrode locations in the motor areas of the lateral aspect of the frontal lobe of the left (contralesional) hemisphere. Electrodes were placed in primary motor cortex (blue dots) and in dorsal premotor cortex (red dots). (B,C) Somatotopic map shows movements evoked from each site in frontal lobe before (B) and after (C) spinal cord injury. The pre-lesion maps were established by ICMS at movement threshold (20–120 μA). The post-lesion maps were established by ICMS at 450 μA on post-lesional day 14. The maps show the region between the central sulcus (CS: diagonal line to the right of each panel) and the arcuate sulcus (ArcS: curved line to the left). Arrow indicates site used in session illustrated in Figure 3. (D) Drawing of the C2 segments showing the extent of the spinal cord lesion (hatched in black). (E) Electrode location in spinal cord. (a) Electrodes were targeted at the ventral horn and intermediate zone of the spinal cord. (b) Higher magnification view of the location of an electrode tip (black arrow).

FIGURE 2

Output effects evoked by intraspinal stimulation. (A) Electrical stimuli were delivered to a single intraspinal electrode while the monkey performed a two-dimensional wrist task, acquiring targets in wrist flexion and extension. (B) Muscle responses evoked by a single pulse at 90 μA. The vertical scale bar at right indicates mean percent increase (MPI) over baseline. EMGs were recorded from: flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), palmaris longus (PL), flexor carpi radialis (FCR), extensor carpi ulnaris (ECU), extensor digitorum 4 and 5 (ED45), extensor digitorum communis (EDC), extensor carpi radialis (ECR), brachioradialis (BR), biceps brachii (BB), pectoralis (PEC), and deltoid (DEL).

FIGURE 3

Brain-controlled intraspinal stimulation below the lesion. (A) Schematic shows local field potential (LFP) in motor cortex gating trains of electrical stimulation (300 Hz) to a spinal site below the lesion. The switch in the recurrent loop was opened for catch trials. (B) Four successful trials with the artificial corticospinal connection (ACSC, green) and one catch trial (white). During the catch trial, the monkey made several unsuccessful attempts to produce wrist torque, as seen in the EMG and torque. The blue rectangles indicate duration and force range of target. The pink vertical bars indicate duration of electrical stimulation in the spinal site. The red line in second trace represents the threshold for spinal stimulation. From top, raw LFP in motor cortex, rectified and smoothed high-gamma LFP (90–160 Hz), EMG from four muscles (abbreviations as in Figure 2), and wrist torque. Arrows indicate times of successful task completion and reward.

FIGURE 4

Task performance in the artificial corticospinal connection (ACSC). (A) Average task performance with the ACSC and during catch trials. Error bars represent standard deviation. (B) Time course of task performance. Before time zero the monkey was required to control the cursor with LFP activity. After time zero the task involved ACSC, using the same cortical electrode in digit area of M1.

FIGURE 5

Muscle-controlled spinal cord stimulation. (A) Schematic shows EMG activity gating a train of stimuli to a spinal site below the lesion. (B) Five successful trials with AMSC (green) and unsuccessful catch trials (white). During the catch trial, the monkey made several unsuccessful attempts to produce wrist torque, as seen in the EMG and torque. The blue rectangles indicate duration and force range of target. The pink bars indicate duration of electrical stimulation in the spinal site. The red line in top row represents the threshold for gating spinal stimulation. The upper and lower traces are the EMG from ECR and wrist torque generated by the monkey, during stimulation (AMSC, in green) or without stimulation (Catch, in white). Arrows indicate times of successful task completion and reward.

FIGURE 6

Task performance with the artificial musculospinal connection (AMSC). (A) Average task performance for AMSC and catch trials. Error bars represent standard deviation. (B) Time course of task performance in AMSC session. Before time zero the monkey controlled the cursor with EMG activity. After time zero the monkey controlled wrist torque via spinal stimulation triggered from the same muscle with the AMSC.