White matter (dis)connections and gray matter (dys)functions in visual neglect: gaining insights into the brain networks of spatial awareness.

Seminal case reports collected during the middle part of the XX century, designated the parietal lobe as the principal area of damage in patients suffering from contralesional spatial neglect (Brain WC. Visual disorientation with special reference to lesions of the right cerebral hemisphere. Brain 1941;64:224-72; Paterson A, Zangwill O. Disorders of visual space perception associated with lesions of the right cerebral hemisphere. Brain 1944;67:331-58; McFie J, Piercy MF, Zangwill O. Visual spatial agnosia associated with lesions of the right hemisphere. Brain 1950;73:167-90). Based on this evidence, textbooks of neurology have traditionally referred to neglect as a "parietal sign". This view found complete accomplishment in the 1986 group study by Vallar and Perani, who confirmed that the inferior parietal lobe was the area most frequently involved in neglect patients with lesions confined to the cerebral cortex and lesions involving subcortical gray matter nuclei. In the same study, it was found that lesions limited to subcortical white matter were rarely associated with neglect. Here, we reconsider recent accumulating evidence, gathered from investigations in animals and human patients, supporting the partially different view that damage involvement of long-range white matter bundles connecting the parietal to the frontal lobe, importantly influence the occurrence and severity of spatial neglect. These findings do not dispute the role of the parietal and frontal cortex in spatial attention and space-related behaviour, but call for a reappraisal of the respective roles of disruption of white matter connections and damage of gray matter cortical modules in the pathophysiology of neglect. Disentangling the connectional and modular anatomical correlates of neglect may be crucial to better understand the pathophysiology of this syndrome, to explain the manifold clinical dissociations often encountered in clinical practice and to increase the impact of behavioural and pharmacological interventions. In this review, we focus on the role of within-hemisphere white-matter disconnection. The role of interhemispheric disconnection, perhaps the oldest connectionist theory of neglect (Geschwind N. Disconnexion syndromes in animals and man - part II. Brain 1965;88:585-644), was extensively treated elsewhere (Bartolomeo P, Thiebaut de Schotten M, Doricchi F. Left unilateral neglect as a disconnection syndrome, Cerebral Cortex 2007;45:3127-48). We first summarise the structure of long-range white matter connections within the cerebral hemispheres and sketch a brief historical review of the original findings suggesting the role of intrahemispheric disconnection to neglect. We then revisit some of the current functional interpretation of the neglect syndrome in the light of disconnectionist approach and review evidences favouring or disfavouring a purely disconnectionist interpretation of the syndrome. Finally, we address the issue of diagnostic criteria to be used in future anatomo-clinical studies aiming at investigating the role of white matter and gray matter dysfunctions in spatial neglect.