Severity-dependent interhemispheric white matter connectivity predicts post-stroke neglect recovery

Left-sided spatial neglect is a very common and challenging issue after right-hemispheric stroke, which strongly and negatively affects daily living behaviour and recovery of stroke survivors. The mechanisms underlying recovery of spatial neglect remain controversial, particularly regarding the involvement of the intact, contralesional hemisphere, with potential contributions ranging from maladaptive to compensatory. In the present prospective, observational study, we assessed neglect severity in 54 right-hemispheric stroke patients (32 male; 22 female) at admission to and discharge from inpatient neurorehabilitation. We demonstrate that the interaction of initial neglect severity, and spared white matter (dis) connectivity resulting from individual lesions (as assessed by diffusion tensor imaging, DTI) explains a significant portion of the variability of post-stroke neglect recovery. In mildly impaired patients, spared structural connectivity within the lesioned hemisphere is sufficient to attain good recovery. Conversely, in patients with severe impairment, successful recovery critically depends on structural connectivity within the intact hemisphere and between hemispheres. These distinct patterns, mediated by their respective white matter connections, may help to reconcile the dichotomous perspectives regarding the role of the contralesional hemisphere as exclusively compensatory or not. Instead, they suggest a unified viewpoint wherein the contralesional hemisphere can - but must not necessarily - assume a compensatory role. This would depend on initial impairment severity and on the available, spared structural connectivity. In the future, our findings could serve as a prognostic biomarker for neglect recovery and guide patient-tailored therapeutic approaches.Significance Statement Visuospatial neglect is a common and challenging issue affecting the daily living of stroke survivors. Mechanisms underlying the recovery of neglect, especially the contribution of the intact hemisphere, remain controversial, ranging from maladaptive to compensatory. In 54 neglect patients, we show that a tight interaction of initial neglect severity and structural (dis)connectivity profiles relate to good recovery: in mild neglect, spared ipsilesional structural connectivity is sufficient for good recovery; conversely, in more severe neglect, structural connectivity within the contralesional hemisphere and between hemispheres plays a central role. These findings may help to reconcile rival models concerning the role of the contralesional hemisphere in neglect recovery after stroke. Furthermore, they could serve as a prognostic biomarker and guide patient-tailored therapeutic approaches.