Abstract

Introduction Neuroimaging studies in stroke patients with hemiparesis have shown altered brain activation in the contralesional hemisphere including the primary motor cortex (M1), dorsal premotor cortex (dPMC) and anterior intraparietal sulcus (aIPS) already in the first week after stroke ( Rehme et al., 2011 ). The role of these regions for motor recovery is still under debate, with some studies suggesting a supportive influence ( Lotze et al., 2006 ) while other point to a maladaptive role ( Nowak et al., 2008 ). Especially functional reorganization in the early phase after stroke is not well understood, although this phase might be critical for non-invasive interventions aiming at supporting recovery of function ( Grefkes and Fink, 2016 ). We here used fMRI-guided online TMS applied over the contralesional M1, dPMC and aIPS of first-ever stroke patients with hand motor deficits in order to probe their role for movements of the paretic hand. Methods FMRI data were recorded from 13 patients 1–8 days after first-ever ischemic stroke and 14 age-matched healthy volunteers during index finger tapping in order to localize task-related activation in the contralesional hemisphere. Each subjects’ individual maxima in the contralesional M1, dPMC and aIPS were then used as targets to apply short trains of rTMS (10 Hz trains, 90% of rMT) time locked to task execution (online-TMS). Sham stimulation served as a control condition and was conducted at 90% of rMT, tilted over the parieto-occipital vertex in order to minimize interference with the motor system. Task performance was measured using a 3D motion analysis system. Imaging data were preprocessed and analyzed using SPM8 and the MarsBar toolbox. Results The severity of stroke as assessed by the NIHSS showed a positive correlation with the partients’ activation peaks in contralesional M1, indicating higher levels of activity in more affected patients. TMS application over the individual fMRI maxima led to differential effects on motor performance. In contralesional M1 and dPMC, TMS interference with local activity led to a normalization of kinematics in patients showing higher activation during paretic hand movements. This finding implies that early increases of neural activity in these regions after stroke rather represent a maladaptive process interfering with motor performance of the stroke-affected hand. In contrast, TMS-Effects with aIPS led to an increase of tapping amplitude and peak velocity across the patient group, thus normalizing performance. Conclusion The present study examined the role of contralesional M1, dPMC and aIPS activity for motor performance in early subacute stroke patients. While higher activation of M1 and dPMC in the first week after stroke were related to an improvement of motor fluency during online TMS interference, stimulation also of lower activation in contralesional aIPS led to a normalization of spatial aspects of motor performance. These findings suggest a disturbing influence of all examined regions on different features of movement kinematics already during the first days after stroke in mildly to moderately affected patients.

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