Evaluating Neuromuscular Function of the Biceps Brachii after Spinal Cord Injury: Assessment of Voluntary Activation and Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation

Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) or peripherally (VAPNS) to reveal what levels of the nervous system are disrupting the innervation of muscle fibers. Voluntary activation measured with TMS (VATMS) can indicate deficits in voluntary cortical drive to innervate muscle. However, measurement of VATMS is limited by technical challenges, including the difficulty in preferential stimulation of cortical neurons projecting to the target muscle and minimal stimulation of antagonists. Thus, the motor evoked potential (MEP) response to TMS in the target muscle compared to its antagonist (i.e. MEP ratio) may be an important parameter in the assessment of VATMS. Using current methodology, VATMS cannot be reliably assessed in patient populations including individuals with tetraplegia. The overall purpose of this work was to investigate novel TMS-based methods to evaluate neuromuscular function after spinal cord injury. First, we developed and evaluated new methodology to assess VATMS in individuals with tetraplegia. The objective of the first study was to optimize the biceps/triceps MEP ratio using modulation of isometric elbow flexion angle in nonimpaired participants and participants with tetraplegia following cervical SCI (C5-C6). We hypothesized that the more flexed elbow angle would increase the MEP ratio. The MEP ratio was only modulated in the nonimpaired group but not across the entire range of voluntary efforts used to estimate VATMS. However, we established that VATMS and VAPNS in individuals with tetraplegia were repeatable across days. In a second study, we aimed to optimize MEPs during the assessment of VATMS using paired pulse TMS to elicit intracortical facilitation and short-interval intracortical inhibition. We hypothesized that intracortical facilitation would lead to an increased MEP ratio compared to single pulse and that short-interval intracortical inhibition would lead to a lower MEP ratio. The MEP ratio was modulated in both groups but not across the entire range of voluntary efforts, and did not affect VATMS estimation compared to single pulse TMS. Paired pulse TMS outcomes revealed abnormal patterns of intracortical inhibition in individuals with tetraplegia. Further, VATMS was sensitive to the linearity of the voluntary moment and superimposed twitch relationship. Linearity was lower in SCI relative to nonimpaired participants. We discuss the limitations of VATMS in assessing neuromuscular impairments in tetraplegia. In a third study, we aimed to collect MEP input-output curves of the biceps in SCI and nonimpaired and evaluate curve-fitting methodology as well as their repeatability across sessions. We hypothesized that slopes would be greater in the SCI group compared to nonimpaired. Slopes obtained with linear regression were greater in tetraplegia compared to nonimpaired participants, suggesting compensatory reorganization of corticomotor pathways after SCI. Linear regression accurately represented the slope of the modeled data compared to sigmoidal function curve-fitting method. Slopes were also found to be repeatable across days in both groups. In a fourth study, we aimed to implement a low-cost navigated TMS system (\u3c $3000) that uses motion tracking, 3D printed parts and open-source software to monitor coil placement during stimulation. We hypothesized that using this system would improve coil position and orientation consistency and decrease MEP variability compared to the conventional method when targeting the biceps at rest and during voluntary contractions across two sessions in nonimpaired participants. Coil orientation error was reduced but the improvement did not translate to lower MEP variability. This low-cost approach is an alternative to expensive systems in tracking the motor hotspot between sessions and quantifying the error in coil placement when delivering TMS. Finally, we conclude and recommend future research directions to address the challenges that we identified during this work to improve our ability to monitor neuromuscular impairments and contribute to the development of more effective neurorehabilitation strategies