Focal left prefrontal lesions and cognitive impairment: A multivariate lesion-symptom mapping approach.

Despite network studies of the human brain have brought consistent evidence of brain regions with diverse functional roles, the neuropsychological approach has mainly focused on the functional specialization of individual brain regions. Relatively few neuropsychological studies try to understand whether the severity of cognitive impairment across multiple cognitive abilities can be related to focal brain injuries. Here we approached this issue by applying a latent variable modeling of the severity of cognitive impairment in brain tumor patients, followed by multivariate lesion-symptom methods identifying brain regions critically involved in multiple cognitive abilities. We observed that lesions in confined left lateral prefrontal areas including the inferior frontal junction produced the most severe cognitive deficits, above and beyond tumor histology. Our findings support the recently suggested integrated albeit modular view of brain functional organization, according to which specific brain regions are highly involved across different sub-networks and subserve a vast range of cognitive abilities. Defining such brain regions is relevant not only theoretically but also clinically, since it may facilitate tailored tumor resections and improve cognitive surgical outcomes.