Spatial neglect after subcortical stroke may reflect cortico-cortical disconnection

Spatial neglect is commonly attributed to lesions of a predominantly right-hemispheric cortical network. Although spatial neglect was also repeatedly observed after lesions to the basal ganglia and the thalamus, many anatomical network models omit these structures. We investigated if disruption of functional or structural connectivity can explain spatial neglect in subcortical stroke. We retrospectively investigated data of first-ever, acute stroke patients with right-sided lesions of the basal ganglia (n = 27) or the thalamus (n = 16). Based on lesion location, we estimated (i) functional connectivity via lesion-network mapping with normative resting state fMRI data, (ii) structural white matter disconnection using a white matter atlas and (iii) tract-wise disconnection of association fibres based on normative tractography data to investigate the association of spatial neglect and disconnection measures. Apart from very small clusters of functional disconnection observed in inferior/middle frontal regions in lesion-network symptom mapping for basal ganglia lesions, our analyses found no evidence of functional or structural subcortico-cortical disconnection. Instead, the multivariate consideration of lesion load to several association fibres predicted the occurrence of spatial neglect (p = 0.0048; AUC = 0.76), which were the superior longitudinal fasciculus, inferior occipitofrontal fasciculus, superior occipitofrontal fasciculus, and the uncinate fasciculus. Disconnection of long (cortico-cortical) association fibres can explain spatial neglect in subcortical stroke. Like the competing theory of remote cortical hypoperfusion, our finding does not support a genuine role for subcortical grey matter structures in spatial neglect.