Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imagingderived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively. Neuroimaging has substantially advanced our understanding of the neuronal mechanisms of functional motor recovery after brain lesions, thereby, enhancing prediction of motor recovery 1. Diffusion Tensor Imaging (DTI) and tractography have proven useful for the in vivo delineation and assessment of white matter pathways 2. Different DTI-studies have associated motor function after hemispheric lesions with the microstructural integrity of the pyramidal tract (PT) or alternate motor fibers (aMF) 3-6. aMF are believed to constitute the imaging correlate of cortico-rubro-spinal or of cortico-reticulo-spinal pathways. They may be reconstructed by means of tractography as they descend from the precentral gyrus through the posterior limb of the internal capsule and the tegmentum pontis 7-10. Our understanding of aMF and their role as a compensatory corticospinal system was only recently investigated in patients and has been derived as a comparative neuroanatomical approach from numerous animal studies 11-13. Some studies have suggested that aMF could compensate for the damaged PT 6-8,14 , while other studies concluded that the portion of intact fibers of the affected PT determines the degree of motor recovery 3,4,15. A third possibility is that both systems contribute to motor recovery. Schulz and colleagues found no interaction between diffusivity parameters indexing the microstructural status of PT and aMF in patients after stroke, and thus concluded, that the manner in which they function is "synergistic, but independent" 7. Our hypothesis states that PT and aMF may operate synergistically by mediating distal and proximal motor functions

Summary Rasmussen encephalitis (RE) is an immune‐mediated brain disease with progressive unihemispheric atrophy. Although it is regarded as a strictly one‐sided pathology, volumetric magnetic resonance imaging (MRI) studies have revealed atrophy in the so‐called unaffected hemisphere. In contrast to previous studies, we hypothesized that the contralesional hemisphere would show increased gray matter volume in response to the ipsilesional atrophy. We assessed the gray matter volume differences among 21 patients with chronic, late‐stage RE and 89 age‐ and gender‐matched healthy controls using voxel‐based morphometry. In addition, 11 patients with more than one scan were tested longitudinally. Compared to controls, the contralesional hemisphere of the patients revealed a higher cortical volume but a lower subcortical gray matter volume (all P < 0.001, unpaired t test). Progressive gray matter volume losses in bilateral subcortical gray matter structures were observed (P < 0.05, paired t test). The comparatively higher cortical volume in the contralesional hemisphere can be interpreted as a result of compensatory structural remodeling in response to atrophy of the ipsilesional hemisphere. Contralesional subcortical gray matter volume loss may be due to the pathology or its treatment. Because MRI provides the best marker for determining the progression of RE, an accurate description of its MRI features is clinically relevant.

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Objective Using multimodal imaging, we tested the hypothesis that patients after hemispherotomy recruit non‐primary motor areas and non‐pyramidal descending motor fibers to restore motor function of the impaired limb. Methods Functional and structural MRI data were acquired in a group of 25 patients who had undergone hemispherotomy and in a matched group of healthy controls. Patients’ motor impairment was measured using the Fugl‐Meyer Motor Assessment. Cortical areas governing upper extremity motor‐control were identified by task‐based functional MRI. The resulting areas were used as nodes for functional and structural connectivity analyses. Results In hemispherotomy patients, movement of the impaired upper extremity was associated to widespread activation of non‐primary premotor areas, whereas movement of the unimpaired one and of the control group related to activations prevalently located in the primary motor cortex (all p ≤ 0.05, FWE‐corrected). Non‐pyramidal tracts originating in premotor/supplementary motor areas and descending through the pontine tegmentum showed relatively higher structural connectivity in patients (p < 0.001, FWE‐corrected). Significant correlations between structural connectivity and motor impairment were found for non‐pyramidal (p = 0.023, FWE‐corrected), but not for pyramidal connections. Interpretation A premotor/supplementary motor network and non‐pyramidal fibers seem to mediate motor function in patients after hemispherotomy. In case of hemispheric lesion, the homologous regions in the contralesional hemisphere may not compensate the resulting motor deficit, but the functionally redundant premotor network.

Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi-and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A post hoc t-test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the