Determining whether a person with stroke has reached their full potential for recovery is difficult. While techniques such as transcranial magnetic stimulation (TMS) and MRI have some prognostic value, their role in rehabilitation is undefined. This study used TMS and MRI to determine which factors predict functional potential, defined as an individual's capacity for further functional improvement at least 6 months following stroke. We studied 21 chronic stroke patients with upper limb impairment. The functional integrity of the corticospinal tracts (CSTs) was assessed using TMS and functional MRI. The presence or absence of motor-evoked responses (MEPs) to TMS in the affected upper limb, and the lateralization of cortical activity during affected hand use were determined. The structural integrity of the CST was assessed using MRI, and diffusion tensor imaging was used to measure the asymmetry in fractional anisotropy (FA) of the internal capsules. A multiple linear regression analysis was performed, to predict both clinical score at inception and change in clinical score for 17 patients who completed a 30 day programme of motor practice with the affected upper limb. The main findings were that in patients with MEPs, meaningful gains were still possible 3 years after stroke, although the capacity for improvement declined with time. In patients without MEPs, functional potential declines with increasing CST disruption, with no meaningful gains possible if FA asymmetry exceeds a value of 0.25. This study is the first to demonstrate the complementary nature of TMS and MRI techniques in predicting functional potential in chronic stroke patients. An algorithm is proposed for the selection of individualized rehabilitation strategies, based on the prediction of functional potential. These strategies could include neuromodulation using a range of emerging techniques, to prime the motor system for a plastic response to rehabilitation.

After stroke, the function of primary motor cortex (M1) between the hemispheres may become unbalanced. Techniques that promote a re-balancing of M1 excitability may prime the brain to be more responsive to rehabilitation therapies and lead to improved functional outcomes. The present study examined the effects of Active-Passive Bilateral Therapy (APBT), a putative movement-based priming strategy designed to reduce intracortical inhibition and increase excitability within the ipsilesional M1. Thirty-two patients with upper limb weakness at least 6 months after stroke were randomized to a 1-month intervention of self-directed motor practice with their affected upper limb (control group) or to APBT for 10-15 min prior to the same motor practice (APBT group). A blinded clinical rater assessed upper limb function at baseline, and immediately and 1 month after the intervention. Transcranial magnetic stimulation was used to assess M1 excitability. Immediately after the intervention, motor function of the affected upper limb improved in both groups (P < 0.005). One month after the intervention, the APBT group had better upper limb motor function than control patients (P < 0.05). The APBT group had increased ipsilesional M1 excitability (P < 0.025), increased transcallosal inhibition from ipsilesional to contralesional M1 (P < 0.01) and increased intracortical inhibition within contralesional M1 (P < 0.005). None of these changes were found in the control group. APBT produced sustained improvements in upper limb motor function in chronic stroke patients and induced specific and sustained changes in motor cortex inhibitory function. We speculate that APBT may have facilitated plastic reorganization in the brain in response to motor therapy. The utility of APBT as an adjuvant to physical therapy warrants further consideration.

Coincident hand and foot movements are more reliably performed in the same direction than in opposite directions. Using transcranial magnetic stimulation (TMS) to assess motor cortex function, we examined the physiological basis of these movements across three novel experiments. Experiment 1 demonstrated that upper limb corticomotor excitability changed in a way that facilitated isodirectional movements of the hand and foot, during phasic and isometric muscle activation conditions. Experiment 2 demonstrated that motor cortex inhibition was modified with active, but not passive, foot movement in a manner that facilitated hand movement in the direction of foot movement. Together, these findings demonstrate that the coupling between motor representations within motor cortex is activity dependent. Because there are no known connections between hand and foot areas within primary motor cortex, experiment 3 used a dual-coil paired-pulse TMS protocol to examine functional connectivity between secondary and primary motor areas during active ankle dorsiflexion and plantarflexion. Dorsal premotor cortex (PMd) and supplementary motor area (SMA) conditioning, but not ventral premotor cortex (PMv) conditioning, produced distinct phases of task-dependent modulation of excitability of forearm representations within primary motor cortex (M1). Networks involving PMd-M1 facilitate isodirectional movements of hand and foot, whereas networks involving SMA-M1 facilitate corticomotor pathways nonspecifically, which may help to stabilize posture during interlimb coordination. These results may have implications for targeted neurorehabilitation after stroke.

The objective of this study was to investigate reliability of transcranial magnetic stimulation (TMS) parameters for three coil systems; hand-held circular and figure-of-eight and navigated figure-of-eight coils. Stimulus response curves, intracortical inhibition (SICI) and facilitation (ICF) were studied in the right first dorsal interosseus muscle of 10 healthy adults. Each coil system was tested twice per subject. Navigation was conducted by a custom built system. Cortical excitability showed moderate-to-good reliability for the hand-held and navigated figure-of-eight coils (Intraclass correlation coefficients (ICCs) 0.55-0.89). The circular coil showed poor reliability for motor evoked potential (MEP) amplitude at 120% resting motor threshold (RMT; MEP(120)) and MEP sum (ICCs 0.09 & 0.48). Reliability for SICI was good for all coil systems when an outlier was removed (ICCs 0.87-0.93), but poor for ICF (ICCs < 0.3). The circular coil had a higher MEP(120) than the navigated figure-of-eight coil (p = 0.004). Figure-of-eight coils can be used confidently to investigate cortical excitability over time. ICF should be interpreted with caution. The navigation device frees the experimenter and enables tracking of the position of the coil and subject. The results help guide the choice of coil system for longitudinal measurements of motor cortex function.

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