Luigi Borda

Whether proprioception is necessary for upper-limb motor control has been debated for decades. Classic studies in deafferented animals and humans suggested that proprioception may be dispensable for rapid, goal-directed movements. However, chronic sensory loss conflates the absence of proprioceptive input with years of compensatory adaptation. As a result, the field has lacked a strong causal test of proprioception's contribution to motor control. Here, we leveraged a clinical trial of cervical spinal cord stimulation (SCS) in individuals with chronic post-stroke hemiparesis to study if electrical stimulation of sensory afferents causally perturbs proprioception and affects arm reaching. We found that turning SCS ON causally impaired proprioceptive perception and postural stabilization in response to force perturbations, and enhanced adaptation to visual errors during implicit learning. Yet visually and non-visually rapid, goal-directed reaching improved in smoothness, straightness and spatial accuracy. These findings provide strong causal evidence that proprioception is not required for rapid, goal-directed action, helping resolve a decades-long debate regarding its necessity for effective movement.

Chronic arm and hand hemiparesis is a major cause of disability after stroke. Unfortunately, standard-of-care rehabilitation falls well short of the high doses required to experience improvements. In this feasibility study, we explored the use of cervical epidural spinal cord stimulation (SCS) to assist motor function and provide meaningful functional improvements without the need of a high-dose rehabilitation program. Here we report the final outcomes of this study testing safety, feasibility and preliminary efficacy of cervical SCS as a neuroprosthetic approach for chronic post-stroke upper limb hemiparesis. We implanted seven participants with profound motor deficits (Fugl-Meyer Assessment (FMA) scores 15–35) using two leads implanted unilaterally in the cervical spinal cord for 4 weeks. No serious adverse events occurred. Under SCS ON, motor function immediately improved regardless of impairment severity (average +32% strength and +5.6 FMA points). Notably, three of seven participants with residual corticospinal connectivity to finger muscles improved hand/finger movement with SCS. Despite performing only 8.6 hours of motor activity (5.5 hours with SCS ON), participants improved by an average of +6.6 FMA points at the end of the study compared to baseline, and spasticity decreased in all participants. Although all benefited, our preliminary analysis indicates that spared sensory function may be a determinant of responsiveness to SCS. These findings provide preliminary evidence of the safety, feasibility and efficacy of cervical SCS for chronic post-stroke hemiparesis, suggesting its potential as a fully implantable neuroprosthetic solution for assisting upper limb function in daily living. ClinicalTrials.gov identifier: NCT04512690.

SUMMARY: Fine motor control of the human arm is assumed to depend on monosynaptic connections between the motor cortex and spinal motoneurons. We report that people with post-stroke hemiparesis could regain dexterous control using non-monosynaptic corticospinal tract (CST) projections during epidural cervical spinal cord stimulation (SCS). Participants in our pilot clinical study demonstrated the ability to improve strength, reaching smoothness, and fine force control of the arm and hand while receiving continuous stimulation. Detailed electrophysiology of corticospinal connectivity with transcranial magnetic stimulation, electromyography spectral analysis, and single motor-unit firing showed that SCS did not reliably strengthen CST-activation of motoneurons. Instead, residual CST axons sculpted the strength of spinal reflexes produced by each pulse of SCS via polysynaptic mechanisms, including presynaptic gating of sensory afferent excitability, to promote functionally relevant muscle activation patterns. Our findings reveal the ability of non-monosynaptic CST pathways to finely tune spinal motor output in humans after stroke.

Most individuals with tetraplegia retain some myoelectric function in their forearms, which offers the possibility of using surface electromyographic (sEMG) control for human-computer interaction (HCI). We demonstrate the potential of this approach by showing that people with motor-complete (n=5) and motor-incomplete (n=2) tetraplegia can accurately control myoelectric activity in their forearm to perform discrete button-click and continuous positioning tasks. These control inputs were mapped to the firing rate of motor units detected by a wireless wristband sensor designed for everyday use. Participants completed four testing sessions to assess their speed and accuracy. Motor units that displayed a wide dynamic range in their firing rate performed best during tasks requiring continuous, single-axis control. Interestingly, the level of impairment did not affect performance on the clicking and 1D cursor control tasks. However, those with motor-incomplete injuries showed greater independent control over two motor units than participants with motor-complete injuries, who exhibited stronger coupling between units. Participants also confirmed the practical utility of the device, successfully placing and removing the sEMG wristband on their own and consistently rating it as comfortable and easy to manage. These findings are significant because they offer the first demonstration of motor unit-based control in individuals with cervical spinal cord injury (SCI) using a fully wearable wristband interface, highlighting the feasibility of moving these systems out of the lab and into daily life.

Cervical spinal cord stimulation (SCS) improves arm function in people with chronic post-stroke hemiparesis, yet its mechanism remains unclear. The leading hypothesis is that SCS enhances motor drive to agonist muscles. To test this, we developed a proportional-derivative (PD) control model of agonist–antagonist interactions and estimated feedback control gains in 12 healthy and 5 stroke participants. In healthy individuals, gains followed a stereotypical structure that we showed was optimal for generating smooth, stable movements. In stroke participants, this structure was disrupted but shifted toward neurotypical (optimal) values with SCS. Contrary to the prevailing hypothesis, the most consistent effect of SCS was a reduction in stabilization (derivative) gains rather than an increase in motor drive (proportional) gains, suggesting engagement of inhibitory control mechanisms of antagonist (and agonist) muscles. SCS also tuned feedback gains in a frequency-dependent manner, indicating that controller gains could guide stimulation parameter selection. This model-based framework offers an objective means to quantify neuromodulation effects on motor control and identify mechanisms of functional recovery after stroke.

Epidural spinal cord stimulation has been shown to be a promising neurotechnology to improve upper limb function in people affected by stroke. It is well established that SCS targeting the dorsal root entry zone increases excitatory drive to α-motoneurons via the monosynaptic reflex pathway. However, the effects of SCS on inhibitory neural pathways remain unexplored. We hypothesized that SCS improves the neuromotor control of arm movement by strengthening both excitatory and inhibitory circuit function. We show in three individuals with post-stroke motor symptoms that SCS enhances postsynaptic Ia reciprocal inhibition. These changes correlate with enhanced muscle coordination and arm kinematics resulting in smoother and faster trajectories. Our study provides further insights into the neural targets of spinal cord stimulation and the use of this technology to treat post-stroke motor deficits.

Here, we report the final outcomes of a pilot clinical trial testing preliminary efficacy and safety of cervical epidural spinal cord stimulation (SCS) for chronic post-stroke upper-limb hemiparesis (NCT04512690). We implanted seven participants with profound motor deficits (Fugl-Meyer Assessment [FMA] scores 15–35) using two leads implanted unilaterally in the cervical spinal cord for 4 weeks. Under SCS ON, motor function immediately improved regardless of impairment severity (average +32% strength and +5.6 FMA-points). Notably, 3/7 participants with residual corticospinal connectivity to finger muscles regained hand/finger function with SCS. Despite performing only 8.6hrs of motor activity (5.5hrs with SCS ON), participants improved by average +6.6 FMA-points at the end of the study compared to baseline and spasticity decreased in all participants. While all benefited, our preliminary analysis indicates that spared sensory function may be a determinant of responsiveness to SCS. No serious adverse events occurred.

Here, we report the final outcomes of a pilot clinical trial testing preliminary efficacy and safety of cervical epidural spinal cord stimulation (SCS) for chronic post-stroke upper-limb hemiparesis ( NCT04512690 ). We implanted seven participants with profound motor deficits (Fugl-Meyer Assessment [FMA] scores 15–35) using two leads implanted unilaterally in the cervical spinal cord for 4 weeks. Under SCS ON, motor function immediately improved regardless of impairment severity (average +32% strength and +5.6 FMA-points). Notably, 3/7 participants with residual corticospinal connectivity to finger muscles regained hand/finger function with SCS. Despite performing only 8.6hrs of motor activity (5.5hrs with SCS ON), participants improved by average +6.6 FMA-points at the end of the study compared to baseline and spasticity decreased in all participants. While all benefited, our preliminary analysis indicates that spared sensory function may be a determinant of responsiveness to SCS. No serious adverse events occurred.

Spinal muscular atrophy (SMA) is an inherited neurodegenerative disease causing motoneuron dysfunction, muscle weakness, fatigue and early mortality. Three new therapies can slow disease progression, enabling people to survive albeit with lingering motor impairments. Indeed, weakness and fatigue are still among patients’ main concerns. Here we show that epidural spinal cord stimulation (SCS) improved motoneuron function, thereby increasing strength, endurance and gait quality, in three adults with type 3 SMA. Preclinical works demonstrated that SMA motoneurons show low firing rates because of a loss of excitatory input from primary sensory afferents. In the present study, we hypothesized that correcting this loss with electrical stimulation of the sensory afferents could improve motoneuron function. To test this hypothesis, we implanted three adults with SMA with epidural electrodes over the lumbosacral spinal cord, targeting sensory axons of the legs. We delivered SCS for 4 weeks, 2 h per day during motor tasks. Our intervention led to improvements in strength (up to +180%), gait quality (mean step length: +40%) and endurance (mean change in 6-minute walk test: +26 m), paralleled by increased motoneuron firing rates. These changes persisted even when SCS was turned OFF. Notably, no adverse events related to the stimulation were reported. ClinicalTrials.gov identifier: NCT05430113.