Post-stroke brain excitability of contralesional motor representations depends on lesion location

Introduction: Transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) elicits motor evoked potentials (MEPs) in contralateral muscles and can be used to gather information about local excitability and the extent of motor representations in the human cortex1 . Such information provides useful insights to cortical physiology in the intact brain and its changes in pathologic brain states or after CNS lesions, e.g. after neurotrauma or stroke1 . Recent animal and human studies showed that a severe cortical lesion has significant metabolic and neurophysiologic effects on the non-affected (contralesional) brain hemisphere2-5 , associated e.g. with a decrease of intra-cortical inhibition2,3, down-regulation of GABAA receptors4,5 and up-regulation of NMDA receptors5 . Such changes were explained by the disruption of transcallosal fibers conveying transcallosal inhibition (TCI) from the affected to the non-affected brain hemisphere6 . However, it is unknown how the local disinhibition influences the extent of cortical motor maps in the unaffected hemisphere and how lesion location and changes of motor representations in the unaffected brain hemisphere interrelate. In the present study, we aim to elucidate the relationship between stimulation intensity, motor map extent and MEP amplitudes in cortical (CL) and sub-cortical (SL) stroke patients. Methods: Severely affected stroke patients (n=24) with no capacity for active finger extension were categorized according to their lesion site (CL, n=12; SL, n=12) and underwent evaluation of functional anisotropy (FA) in the corpus callosum reflecting integrity of inter-hemispheric fiber tracts, resting motor threshold (rMT), recruitment curves and cortical mapping of the first dorsal interosseous (FDI) muscle in the nonaffected hemisphere using single pulse TMS. Age-matched volunteers were used as controls (n=7).Results: FA values significantly differed between the CL (n=10, median=452.0) and SL group (n=10, CC=535.5; p<0.001). The CL group shows a positive correlation of contralesional rMT and cortical map size (r=0.71, p=0.01, Figure 1a) indicating that stronger stimulation intensities applied over M1 activates motor neurons in broader areas, a possible consequence of the reduced intra- and inter-hemispheric inhibition. In SL patients, on the other hand, these parameters showed a negative correlation (r=0.6, p=0.03, Fig. 1b). Healthy subjects and stroke patients if pooled disregarding their lesion location showed no correlation between rMT and motor map size (r=0.199, p=0.66 and r=0.084, p=0.69, respectively) (Fig. 1c,d). Conclusions: Changes of motor cortex excitability on the non-affected hemisphere depend on lesion location, a finding with important implications for the understanding of neuroplastic changes and homeostasis following brain lesions. References: 1. Terao Y, Ugawa Y. (2002) Basic Mechanisms of TMS. Journal of Clinical Neurophysiology, vol. 19, no. 4, pp. 322-343. 2. Shimizu T. et al. (2002) Motor cortical disinhibition in the unaffected hemisphere after unilateral cortical stroke. Brain, vol. 125, pp. 1896-1907. 3. Manganotti P. et al. (2008) Motor cortical disinhibition during early and late recovery after stroke. Neurorehabili Neural Repair, vol. 22, no. 4, pp. 396-403. 4. Qu M. et al. (1998) Bihemispheric reduction of GABAA receptor binding following focal cortical photothrombotic lesions in the rat brain. Brain Research, vol. 813, no. 2, pp. 374- 380. 5. Qu M. et al. (1998) Long-term changes of ionotropic glutamate and GABA receptors after unilateral permanent focal cerebral ischemia in the mouse brain. Neuroscience, vol. 85, no. 1, pp. 29-43. 6. Boroojerdi B. et al. (1996) Transcallosal inhibition in cortical and subcortical cerebral vascular lesions. Journal of Neurological Sciences, vol. 144, pp. 160-170