Abstract

A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P