Neuroanatomy of hemispatial neglect and its functional components: a study using voxel-based lesion-symptom mapping

Spatial neglect is a perplexing neuropsychological syndrome, in which patients fail to detect (and/or respond to) stimuli located contralaterally to their (most often right) hemispheric lesion. Neglect is characterized by a wide heterogeneity, and a role for multiple components has been suggested, but the exact nature of the critical components remains unclear. Moreover, many different lesion sites have been reported, leading to enduring controversies about the relative contribution of different cortical and/or subcortical brain regions. Here we report a systematic anatomo-functional study of 80 patients with a focal right hemisphere stroke, who were examined by a series of neuropsychological tests assessing different clinical manifestations of neglect. We first performed a statistical factorial analysis of their behavioural performance across all tests, in order to break down neglect symptoms into coherent profiles of co-varying deficits. We then examined the neural correlates of these distinct neglect profiles using a statistical voxel-based lesion-symptom mapping method that correlated the anatomical extent of brain damage with the relative severity of deficits along the different profiles in each patient. Our factorial analysis revealed three main factors explaining 82% of the total variance across all neglect tests, which suggested distinct components related to perceptive/visuo-spatial, exploratory/visuo-motor, and allocentric/object-centred aspects of spatial neglect. Our anatomical voxel-based lesion-symptom mapping analysis pointed to specific neural correlates for each of these components, including the right inferior parietal lobule for the perceptive/visuo-spatial component, the right dorsolateral prefrontal cortex for the exploratory/visuo-motor component, and deep temporal lobe regions for the allocentric/object-centred component. By contrast, standard anatomical overlap analysis indicated that subcortical damage to paraventricular white matter tracts was associated with severe neglect encompassing several tests. Taken together, our results provide new support to the view that the clinical manifestations of hemispatial neglect might reflect a combination of distinct components affecting different domains of spatial cognition, and that intra-hemispheric disconnection due to white matter lesions might produce severe neglect by impacting on more than one functional domain.