Following a hemiparetic stroke, individuals exhibit altered motor unit firing patterns during voluntary muscle contractions, including impairments in firing rate modulation and recruitment. These individuals also exhibit abnormal muscle coactivation through multi-joint synergies (e.g., flexion synergy). Here, we investigate whether motor unit firing activity during flexion synergy-driven contractions of the paretic biceps brachii differs from that of voluntary contractions and use these differences to predict changes in descending motor commands. To accomplish this, we characterized motor unit firing patterns of the biceps brachii in individuals with chronic hemiparetic stroke during voluntary isometric elbow flexion contractions in the paretic and non-paretic limbs, as well as during contractions driven by voluntary effort and by flexion synergy expression in the paretic limb. We observed significant reductions in motor unit firing rate modulation from the non-paretic to paretic limb (non-paretic – paretic: 0.14 pps/%MVT, 95% CI: [0.09 0.19]) that were further reduced during synergy-driven contractions (voluntary paretic – synergy driven: 0.19 pps/%MVT, 95% CI: [0.14 0.25]). Moreover, using recently developed metrics, we evaluated how a stroke-induced reliance on indirect motor pathways alters the inputs that motor units receive and revealed progressive increases in neuromodulatory and inhibitory drive to the motor pool in the paretic limb, with the changes greatest during synergy-driven contractions. These findings suggest that an interplay between heightened neuromodulatory drive and alterations in inhibitory command structure may account for the observed motor unit impairments, further illuminating underlying neural mechanisms involved in the flexion synergy and its impact on motor unit firing patterns post-stroke.

Cerebrovascular accident (CVA) or stroke is a devastating neurological condition with dismal prognosis associated with recurrent episodes that further damage the neuronal networks, thus disabling neuronal plasticity. Vagus nerve stimulation (VNS) has been used in clinical practice to treat epilepsy for several decades and is well accepted as a safe procedure devoid of serious adverse events. Bailey and Bremer demonstrated that VNS has the capabilities to stimulate neuronal pathways that enhance the recovery of damaged cerebral function. Further studies have strengthened these observations, while technology has improved the tolerability of implants, resulting in VNS applications for epilepsy. Several animal models on neural plasticity have improved our understanding of VNS and its ability to provide neuromodulation to improve recovery in stroke patients. The closed-loop stimulation of the vagus nerve with individualized stimulation parameters combined with physical therapy appears to be an attractive option today. VNS is also being tested as a noninvasive trans-cutaneous modality to further improve patient acceptance and tolerability. However, the implantation of VNS is yielding desirable outcomes and appears to be a more reliable treatment for stroke rehabilitation in clinical trials.