TY - JOUR T1 - Cognitive and Neuroanatomic Accounts of Referential Communication in Focal Dementia JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0488-18.2019 SP - ENEURO.0488-18.2019 AU - Meghan Healey AU - Nicola Spotorno AU - Christopher Olm AU - David J. Irwin AU - Murray Grossman Y1 - 2019/08/26 UR - http://www.eneuro.org/content/early/2019/08/26/ENEURO.0488-18.2019.abstract N2 - The primary function of language is to communicate– that is, to make individuals reach a state of mutual understanding about a particular thought or idea. Accordingly, daily communication is truly a task of social coordination. Indeed, successful interactions require individuals to 1) track and adopt a partner's perspective, and 2) continuously shift between the numerous elements relevant to the exchange. Here, we use a referential communication task to study the contributions of perspective-taking and executive function to effective communication in non-aphasic human patients with behavioral variant frontotemporal dementia (bvFTD). Similar to previous work, the task was to identify a target object, embedded amongst an array of competitors, for an interlocutor. Results indicate that bvFTD patients are impaired relative to controls in selecting the optimal, precise response. Neuropsychological testing related this performance to mental set-shifting, but not to working memory or inhibition. Follow-up analyses indicated that some bvFTD patients perform equally well as controls, while a second, clinically-matched patient group performs significantly worse. Importantly, the neuropsychological profiles of these subgroups differed only in set-shifting. Finally, structural MRI imaging analyses related patient impairment to gray matter disease in orbitofrontal, medial prefrontal, and dorsolateral prefrontal cortex, all regions previously implicated in social cognition and overlapping those related to set-shifting. Complementary white matter analyses implicated uncinate fasciculus, which carries projections between orbitofrontal and temporal cortices. Taken together, these findings demonstrate that impaired referential communication in bvFTD is cognitively related to set-shifting, and anatomically related to a social-executive network including prefrontal cortices and uncinate fasciculus.Significance Statement While traditional models of language processing focus on single word and sentence comprehension, successful communication during conversational exchanges may involve additional executive resources and social perspective-taking. Here, we report a novel study of non-aphasic patients with behavioral variant frontotemporal dementia (bvFTD), who have documented deficits in social and executive function but relatively preserved language. Our findings demonstrate that patients with bvFTD have difficulty coordinating perspectives with a conversational partner in a referential communication task. Patient impairment was related to disease in a network of prefrontal regions associated with social functioning and mental set-shifting, highlighting the essential contribution of non-language brain regions to daily communication. ER -