Research

Non-invasive access to motor unit discharge: a gateway into central nervous system function

Analysis of motor unit discharge patterns provides us with a remarkable window into how the central nervous system controls movement in the intact nervous system as well as the changes in neural control of movement that accompany motor dysfunction following neurological injury.

We measure motor unit discharge non-invasively in humans using high-density surface EMG recordings coupled with an automatic decomposition algorithm (Negro et al., 2016), which we can currently do in up to 6 muscles simultaneously.  The development of this advanced technology enables us to address scientific and clinical research questions that were previously infeasible.

Neural control of proximal and distal muscles of the arm (intact nervous system and post-hemiparetic stroke)

Purposeful movement includes an impressive range of motor tasks, from the large movements and sustained postures to exquisitely precise adjustments of small increments of force. Multi-joint movements of the arm require both stability and dexterity, and different muscle groups are specialized to complete these different components. We have several ongoing projects that investigate how the central nervous system controls these different muscle groups in terms of (e.g.) motor unit control of force generation, the distribution of neuromodulatory inputs to motoneurons, and frequency characteristics of neural drive to muscle.

Following hemiparetic stroke, proximal and distal muscles are affected differently. Presumably, this is because a stroke resulting in hemiparesis damages the corticospinal pathway, the primary pathway for skilled movement that provides the majority of innervation and neural control to distal muscles. Proximal muscles, however, receive a greater proportion of their innervation and neural control from brainstem-spinal motor pathways that are upregulated following corticospinal damage. We have several ongoing studies that compare the impact of hemiparetic stroke on voluntary control of proximal vs. distal muscles. 

Neural mechanisms underlying motor deficits in multiple sclerosis

People with multiple sclerosis experience a range of motor deficits such as weakness, abnormal muscle tone, and balance disturbances, that substantially impair walking and other functional activities.  Physical therapy is crucial for maintaining/improving motor function in multiple sclerosis, but its effectiveness is limited. In part, this is because we have only a limited understanding of how the structural lesions and resulting maladaptive plasticity that occurs in multiple sclerosis leads to specific motor deficits. We are interested in explicating neural mechanisms of common multiple sclerosis related motor deficits – and their heterogeneity across patients – by examining voluntary motor commands at the level of the motoneuron. 

Voluntary motor commands originate cortically and are shaped at all levels of the neuraxis, culminating as three types of inputs to a-motoneurons in the spinal cord: excitatory, inhibitory, and neuromodulatory. Excitatory and inhibitory synaptic inputs (via glutamate, glycine) convey specific task-related information (timing, amplitude) to motoneurons and encompass descending pathways, reflexive circuits, and afferent feedback. Neuromodulatory inputs (via serotonin, norepinephrine) do not directly cause a motoneuron to fire, but they dramatically increase the intrinsic excitability of the motoneuron, i.e., the degree to which a motoneuron amplifies its response to excitatory and inhibitory input. These three inputs must be appropriately balanced and tailored to a given task to produce skilled motor control. Disruptions in this balance have been identified in the post-stroke and spinal cord injury populations. 

Using a novel reverse engineering paradigm whereby we can characterize excitatory, inhibitory, and neuromodulatory components of the voluntary motor command from features of motor unit discharge, we are examining how voluntary motor commands are disrupted in multiple sclerosis and whether they are related to clinical motor deficits and disease heterogeneity.

Collaborations

We have ongoing collaborations with both human-subjects and animal labs that include a range of research topics (motoneuron modeling, assessment of intrafasicular nerve stimulation, stimulation to facilitate neural plasticity of brainstem-spinal circuits post-stroke).

Funding

Current

  • Washington University ICTS KL2 Career Development Award, McPherson (PI): Neural mechanisms of motor heterogeneity in multiple sclerosis
  • McDonnell Center for Systems Neuroscience Small Project Grant, McPherson (PI): Factors influencing the detection of accurate and reliable motor unit population recordings in humans
  • NIH/NINDS R01, Heckman (PI), McPherson (co-I): Supercomputer-based Models of Motoneurons for Estimating their Synaptic Inputs in Humans
  • NIH/NIBIB R01, Jung (multi-PI), Abbas (multi-PI), McPherson (co-I): CRCNS: Improving Bioelectronic Selectivity with Intrafascicular Stimulation
  • American Heart Association Innovative Project Award, McPherson J (PI), McPherson L (co-I): Restorative Neuroplasticity in Brainstem Motor Pathways to Enhance Rehabilitation Post-Stroke

Completed

  • Coulter Foundation SEED Grant, McPherson (multi-PI): Non-invasive decoding of neuromuscular activity for rehabilitation and prosthetic control
  • American Physical Therapy Association Section on Research Traveling Fellows Award
  • NIH/NICHD R01, Dewald (PI): Effect of neural constraints on movement in stroke.
  • Foundation for Physical Therapy Research, Promotion of Doctoral Studies II Scholarship
  • NIH/NIBIB T32, Dewald (PI): Interdisciplinary Graduate Education in Movement and Rehabilitation Sciences
  • NIDILRR, Dewald (PI): Overcoming gravity-induced arm and hand dysfunction to restore functional reaching following stroke