Motor unit firing rate modulation is more impaired during flexion synergy-driven contractions of the biceps brachii in chronic stroke.

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.

Abnormal synergies and associated reactions post-hemiparetic stroke reflect muscle activation patterns of brainstem motor pathways.

Individuals with moderate-to-severe post-stroke hemiparesis cannot control proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called flexion and extension synergies. Accumulating evidence indicates that these synergies emerge because of upregulation of diffusely projecting brainstem motor pathways following stroke-induced damage to corticofugal pathways. During our recent work on differences in synergy expression among proximal and distal joints, we serendipitously observed some notable characteristics of synergy-driven muscle activation. It seemed that: paretic wrist/finger muscles were activated maximally during contractions of muscles at a different joint; differences in the magnitude of synergy expression occurred when elicited via contraction of proximal vs. distal muscles; and associated reactions in the paretic limb occurred during maximal efforts with the non-paretic limb, the strength of which seemed to vary depending on which muscles in the non-paretic limb were contracting. Here we formally investigated these observations and interpreted them within the context of the neural mechanisms thought to underlie stereotypical movement patterns. If upregulation of brainstem motor pathways occurs following stroke-induced corticofugal tract damage, then we would expect a pattern of muscle dependency in the observed behaviors consistent with such neural reorganization. Twelve participants with moderate-to-severe hemiparetic stroke and six without stroke performed maximal isometric torque generation in eight directions: shoulder abduction/adduction and elbow, wrist, and finger flexion/extension. Isometric joint torques and surface EMG were recorded from shoulder, elbow, wrist, and finger joints and muscles. For some participants, joint torque and muscle activation generated during maximal voluntary contractions were lower than during maximal synergy-induced contractions (i.e., contractions about a different joint), particularly for wrist and fingers. Synergy-driven contractions were strongest when elicited via proximal joints and weakest when elicited via distal joints. Associated reactions in the wrist/finger flexors were stronger than those of other paretic muscles and were the only ones whose response depended on whether the non-paretic contraction was at a proximal or distal joint. Results provide indirect evidence linking the influence of brainstem motor pathways to abnormal motor behaviors post-stroke, and they demonstrate the need to examine whole-limb behavior when studying or seeking to rehabilitate the paretic upper limb.

Altered Neuromodulatory Drive May Contribute to Exaggerated Tonic Vibration Reflexes in Chronic Hemiparetic Stroke.

Exaggerated stretch-sensitive reflexes are a common finding in elbow flexors of the contralesional arm in chronic hemiparetic stroke, particularly when muscles are not voluntarily activated prior to stretch. Previous investigations have suggested that this exaggeration could arise either from an abnormal tonic ionotropic drive to motoneuron pools innervating the paretic limbs, which could bring additional motor units near firing threshold, or from an increased influence of descending monoaminergic neuromodulatory pathways, which could depolarize motoneurons and amplify their responses to synaptic inputs. However, previous investigations have been unable to differentiate between these explanations, leaving the source(s) of this excitability increase unclear. Here, we used tonic vibration reflexes (TVRs) during voluntary muscle contractions of increasing magnitude to infer the sources of spinal motor excitability in individuals with chronic hemiparetic stroke. We show that when the paretic and non-paretic elbow flexors are preactivated to the same percentage of maximum prior to vibration, TVRs remain significantly elevated in the paretic arm. We also show that the rate of vibration-induced torque development increases as a function of increasing preactivation in the paretic limb, even though the amplitude of vibration-induced torque remains conspicuously unchanged as preactivation increases. It is highly unlikely that these findings could be explained by a source that is either purely ionotropic or purely neuromodulatory, because matching preactivation should control for the effects of a potential ionotropic drive (and lead to comparable tonic vibration reflex responses between limbs), while a purely monoaminergic mechanism would increase reflex magnitude as a function of preactivation. Thus, our results suggest that increased excitability of motor pools innervating the paretic limb post-stroke is likely to arise from both ionotropic and neuromodulatory mechanisms.