Direct control of paralysed muscles by cortical neurons

Abstract

A potential treatment for paralysis resulting from spinal cord injury is to route control signals from the brain around the injury by artificial connections. Such signals could then control electrical stimulation of muscles, thereby restoring volitional movement to paralysed limbs. In previously separate experiments, activity of motor cortex neurons related to actual or imagined movements has been used to control computer cursors and robotic arms, and paralysed muscles have been activated by functional electrical stimulation. Here we show that Macaca nemestrina monkeys can directly control stimulation of muscles using the activity of neurons in the motor cortex, thereby restoring goal-directed movements to a transiently paralysed arm. Moreover, neurons could control functional stimulation equally well regardless of any previous association to movement, a finding that considerably expands the source of control signals for brain-machine interfaces. Monkeys learned to use these artificial connections from cortical cells to muscles to generate bidirectional wrist torques, and controlled multiple neuron-muscle pairs simultaneously. Such direct transforms from cortical activity to muscle stimulation could be implemented by autonomous electronic circuitry, creating a relatively natural neuroprosthesis. These results are the first demonstration that direct artificial connections between cortical cells and muscles can compensate for interrupted physiological pathways and restore volitional control of movement to paralysed limbs.

Figure 1. Brain-controlled functional electrical stimulation (FES) of muscle

(A) Schematic shows cortical cell activity converted to FES during peripheral nerve block. (B) Example of motor cortex cell activity controlling FES of paralyzed wrist extensors. Extensor (red shading) and center (grey shading) wrist torque targets were randomly presented. Monkeys learned to modulate smoothed cell rate to control proportional muscle stimulation. FES was delivered to muscles EDC & ED4,5 at 50/s, with current proportional to cell rate above a stimulation threshold (0.4 mA/pps × [cell rate – 16 pps]; ≤ 10 mA). (C) Histograms of cell rates while acquiring the extensor and center targets, illustrating cell activity used to successfully control FES. Shading indicates target hold period and horizontal line denotes baseline cell rate.

Figure 2. Brain-controlled FES of multiple muscles restores graded torque in two directions

(A) The monkey acquired targets at five levels of flexion-extension (F-E) torque using the activity of a single cell to grade FES delivered to both flexor (FCU) and extensor (ECU & ED4,5) muscles. Flexor FES was proportional to rate above a threshold (0.8 mA/pps × [cell rate – 24 pps]; ≤ 10 mA); extensor FES was inversely proportional to cell rate below a second threshold (0.6mA/pps × [12 pps – cell rate]; ≤ 10 mA). (B) Average torques produced to satisfy the five targets during 12 min of practice. With the stimulator off (shaded periods), the monkey could not produce torques greater than 10% of magnitudes used to acquire the targets (blue and red lines), confirming the efficacy of nerve block. (C) Histograms of cell rate used to acquire five target levels (colored boxes at left). Horizontal lines indicate FES thresholds for flexor (blue) and extensor (red) stimulation.

Figure 3. Cell directional tuning is unrelated to FES control

(A) Responses of an untuned and strongly tuned cell (solid symbols in B & C). The surrounding peri-event histograms show cell activity while acquiring each of eight peripheral torque targets in the flexion-extension (F-E) and radial-ulnar (R-U) plane during the un-paralyzed tracking task (horizontal lines denote baseline cell rates). The radial plot at center summarizes cell activity while matching each peripheral target (shading). Maximum target acquisition rates during direct brain control of cursor (B) and brain-controlled FES (C) plotted as a function of directional tuning strength for cells recorded during the torque-tracking task (n = 38). Performance controlling a cursor directly with cell activity was significantly correlated with cell tuning (B; r² = 0.33, p < 0.001). Subsequent brain-controlled FES performance was uncorrelated with cell tuning (C; r² = 0.03, p = 0.33).

Figure 4. Two neurons control FES

Monkey L simultaneously modulated activity of two neurons, each controlling proportional stimulation of a different muscle group when above threshold. L acquired randomly presented flexor (blue), extensor (red) and center (grey) targets by using Cell 1 to stimulate a flexor muscle (FCU; 0.2 mA/pps ×[cell rate–34 pps]) and Cell 2 to stimulate extensor muscles (ECU & ED4,5; 0.4 mA/pps × [cell rate–12 pps]).