Introduction: Multiple sclerosis (MS) causes central nervous system lesions that alter neural communication between the brain and the spinal motoneurons that activate muscles. These voluntary motor commands consist of three components that must be appropriately balanced for skilled motor control: excitation, inhibition, and neuromodulation. Disruption of this balance has harmful effects, evidenced by work in spinal cord injury, stroke, and aging. In MS, we have no knowledge about voluntary motor commands or how they relate to common motor deficits (weakness, spasms, gait difficulty). The heterogeneity of MS across patients makes systematic research of neurophysiological correlates of motor deficits difficult. Here, we use a novel paradigm for reverse engineering of motor unit population discharge to characterize excitatory, inhibitory, and neuromodulatory components of the voluntary motor command in MS on a person-specific basis.
Methods: We tested 24 MS patients with a variety of motor deficits and disability levels. Eight reverse engineering variables were calculated from motor unit spike trains decomposed from high-density surface EMG of the tibialis anterior and soleus during plantarflexion and dorsiflexion.
Results: Three variables reflecting the pattern of inhibition were significantly lower in MS than controls, indicating inhibition that scales proportionally with excitation and contributes to weakness in hemiparetic stroke. The MS group was significantly more variable, with values higher and lower than controls. Some abnormalities were seen in patients without disability, indicating our measures may be sensitive to subclinical changes in voluntary motor commands.
Impact: Little is known about neural mechanisms underlying motor impairments in MS, limiting the development of targeted neuroplasticity-inducing therapies that are emerging in other neurological populations. Our study identifies how voluntary motor commands are pathological in MS on a group basis and provides insight into their variability. Future work will examine whether there are subgroups in the MS population whose different voluntary motor command pathologies could be targeted with novel neurorehabilitation interventions.
Organization: Washington University in St. Louis
McPherson LM, Reece TM, Simon S, Lohse K, Negro F, Lang C, Naismith R, Cross AH