Uncovering and exploiting the return of voluntary motor programs after paralysis using a bi-cortical neuroprosthesis

Abstract

Rehabilitative and neuroprosthetic approaches after spinal cord injury (SCI) aim to reestablish voluntary control of movement. Promoting recovery requires a mechanistic understanding of the return of volition over action, but the relationship between re-emerging cortical commands and the return of locomotion is not well established. We introduced a neuroprosthesis delivering targeted bi-cortical stimulation in a clinically relevant contusive SCI model. In healthy and SCI cats, we controlled hindlimb locomotor output by tuning stimulation timing, duration, amplitude, and site. In intact cats, we unveiled a large repertoire of motor programs. After SCI, the evoked hindlimb lifts were highly stereotyped, yet effective in modulating gait and alleviating bilateral foot drag. Results suggest that the neural substrate underpinning motor recovery had traded-off selectivity for efficacy. Longitudinal tests revealed that the return of locomotion after SCI was time-locked with recovery of the descending drive, which advocates for rehabilitation interventions directed at the cortical target.HighlightsA bilateral cortical implant allowed for the delivery of alternate bilateral stimulation coherently with locomotion, which modulated gait trajectories.We analyzed the effects of stimulation parameters - timing, duration, amplitude, and site of stimulation - to maximize the improvement of locomotor output after paralysis.A varied repertoire of motor programs evoked in intact cats was reduced to one stereotyped response after spinal cord injury (SCI) consisting in flexion modulation that efficiently alleviated hindlimb dragging.After SCI, the return of cortical gait control emerged in synchrony with locomotor recovery.

Cortical neuroprosthesis-mediated functional ipsilateral control of locomotion in rats with incomplete spinal cord injury

“…These findings, in addition to shedding light on the intricate ipsilateral control of movement in rats, carry promising translational implications for the future development of neuroprosthetic solutions. Our previous work has demonstrated that phase-dependent cortical stimulation applied to the contralesional motor cortex immediately ameliorates dragging deficits following SCI by specifically enhancing contralateral hindlimb flexion (Bonizzato & Martinez, 2021 ;Duguay et al, 2023 ). Given that ipsilesional cortical stimulation induces a bilateral synergy, leading to the improvement of the affected limb's extension, this approach has the potential to effectively complement contralesional cortical stimulation.…”

“…The relationship between cortical commands and locomotion has received attention in the last decades (Amboni, Barone, & Hausdorff, 2013 ). In recent studies, we have shown that, after a unilateral spinal cord injury in rats (Bonizzato & Martinez, 2021 ) and large spinal contusion injuries in cats (Duguay et al, 2023 ), microstimulation delivered to the contralesional motor cortex in phase coherence with locomotion immediately alleviated contralateral hindlimb deficits. Other studies have shown that not only the cortex proactively controls high-level and goal-oriented motor planning but it is also involved during stereotyped locomotion (Artoni et al, 2017 ;Bretzner & Drew, 2005 ;Song & Giszter, 2011 ;Song et al, 2009 ).…”

Cortical neuroprosthesis-mediated functional ipsilateral control of locomotion in rats with spinal cord hemisection

“…These findings, in addition to shedding light on the intricate ipsilateral control of movement in rats, carry promising translational implications for the future development of neuroprosthetic solutions. Our previous work has demonstrated that phasedependent cortical stimulation applied to the contralesional motor cortex immediately ameliorates dragging deficits following SCI by specifically enhancing contralateral hindlimb flexion (Bonizzato & Martinez, 2021;Duguay et al, 2023). Given that ipsilesional cortical stimulation induces a bilateral synergy, leading to the improvement of the affected limb's extension, this approach has the potential to effectively complement contralesional cortical stimulation.…”

“…The relationship between cortical commands and locomotion has received attention in the last decades (Amboni, Barone, & Hausdorff, 2013). In recent studies, we have shown that, after a unilateral spinal cord injury in rats (Bonizzato & Martinez, 2021) and large spinal contusion injuries in cats (Duguay et al, 2023), microstimulation delivered to the contralesional motor cortex in phase coherence with locomotion immediately alleviated contralateral hindlimb deficits.…”

Cortical neuroprosthesis-mediated functional ipsilateral control of locomotion in rats with incomplete spinal cord injury

“…The relationship between cortical commands and locomotion has received attention in the last decades (Amboni, Barone, & Hausdorff, 2013 ). In recent studies, we have shown that, after a unilateral spinal cord injury in rats (Bonizzato & Martinez, 2021 ) and large spinal contusion injuries in cats (Duguay et al, 2023 ), microstimulation delivered to the contralesional motor cortex in phase coherence with locomotion immediately alleviated contralateral hindlimb deficits. Other studies have shown that not only the cortex proactively controls high-level and goal-oriented motor planning but it is also involved during stereotyped locomotion (Artoni et al, 2017 ;Bretzner & Drew, 2005 ;Song & Giszter, 2011 ;Song et al, 2009 ).…”