Neural Substrates of Motor Recovery in Severely Impaired Stroke Patients With Hand Paralysis

Abstract

In well-recovered stroke patients with preserved hand movement, motor dysfunction relates to interhemispheric and intracortical inhibition in affected hand muscles. In less fully recovered patients unable to move their hand, the neural substrates of recovered arm movements, crucial for performance of daily living tasks, are not well understood. Here, we evaluated interhemispheric and intracortical inhibition in paretic arm muscles of patients with no recovery of hand movement (n=16, upper extremity Fugl-Meyer Assessment = 27.0 ± 8.6). We recorded silent periods (contralateral and ipsilateral) induced by transcranial magnetic stimulation (TMS) during voluntary isometric contraction of the paretic biceps and triceps brachii muscles (correlates of intracortical and interhemispheric inhibition respectively), and investigated links between the silent periods and motor recovery, an issue that has not been previously explored. We report that interhemispheric inhibition, stronger in the paretic triceps than biceps brachii muscles, significantly correlated with the magnitude of residual impairment (lower Fugl-Meyer scores). In contrast, intracortical inhibition in the paretic biceps brachii, but not in the triceps, correlated positively with motor recovery (Fugl-Meyer scores) and negatively with spasticity (lower Modified Ashworth scores). Our results suggest that interhemispheric inhibition and intracortical inhibition of paretic upper arm muscles relate to motor recovery in different ways. While interhemispheric inhibition may contribute to poorer recovery, muscle-specific intracortical inhibition may relate to successful motor recovery and lesser spasticity.

Primary Motor Cortex Ipsilateral to the Paretic Arm - A Potential Neural Substrate for Compensatory Trunk Use in Chronic Stroke

“…Consistent with overwhelming evidence from fMRI [40][41][42] and movement kinematic studies [71][72][73] including ours [38] in stroke, we found before training higher iM1 activation and greater trunk use during the paretic arm movements in chronic patients relative to controls. Notably, the relationships between these two variables were different in our patients compared to controls: iM1 activation pattern was tightly related to the trunk motion and overall correlation was higher (positive and significant) than in controls.…”

“…Based on overwhelming evidence of iM1 hyperactivity in humans [40][41][42] and animal models [43,44], we predicted that patients would show increased activity in iM1 relative to healthy controls during a task executed with the paretic arm. If iM1 hyperactivity was adaptive, then patients would show a negative relationship between this variable and the trunk motion.…”

Motor compensation and its effects on neural reorganization after stroke

“…Various clinical studies suggest that the contralesional hemisphere may contribute to function of the paretic side, or may be disruptive of this function, depending on the severity of damage to the corticospinal system, the time since stroke and other factors, as reviewed elsewhere 113,155–159 . For example, in support of disruptive influences, the contralesional M1 can exert an excessive inhibitory influence over the ipsilesional hemisphere during paretic hand movements, as detected using paired-pulse protocols with TMS 155,160,161 . Manipulations such as low-frequency TMS that reduce excitability or disrupt activity in the contralesional cortex improve the performance of the paretic hand in motor tasks in some patients 155,162–164 , but there is considerable variability in this effect 165–167 .…”

“…However, the possibility that its involvement in doing so could be a source of variability in how it contributes to paretic limb function has not received very much attention. Bilateral patterns of cortical functional activation 113 and interhemispheric inhibition 176 during paretic hand movement vary with the severity of motor impairments. That behavioural experiences can influence these patterns is supported by findings that rehabilitative training of the paretic upper limb can increase the functional activation of motor regions of the ipsilesional cortex 177,178 and reduce interhemispheric inhibition from the contralesional motor cortex 179 .…”

Neurophysiological Characterization of Subacute Stroke Patients: A Longitudinal Study

“…In pre-activated muscles, TMS may also induce a transient suppression of the EMG-activity after MEP, the so-called silent period (SP) (Kukowski and Haug, 1991; Uozumi et al, 1992), as an inhibitory effect. SP is reported to be abnormally increased in the paretic hand after a stroke (Haug and Kukowski, 1994; Braune and Fritz, 1996; Harris-Love et al, 2016) and tend to decrease with motor recovery. To date, studies on the role of the SP in predicting motor recovery after severe stroke showed rather inconsistent results (van Kuijk et al, 2005, 2014).…”