Antisocial Behavior in Frontotemporal Dementia: Behavioral Phenotypes, Neural Markers, and Decision-Making Mechanisms

Project Summary: Antisocial behaviors like lying, stealing, reactive aggression, and sexually inappropriate behaviors are common in behavioral variant frontotemporal dementia (bvFTD), and can be severe, leading some patients to be charged with crimes, lose substantial amounts of money, or irrevocably damage social

relationships. Despite how problematic these symptoms are, the behavioral phenotype for antisocial behaviors in bvFTD has yet to be clearly defined and the underlying mechanisms remain poorly understood. Work in non- diseased and psychiatric populations suggests that antisocial behaviors might be differentiated into factors for

aggressive vs. rule-breaking behaviors with different underlying mechanisms. In preliminary data, we developed a novel informant-based questionnaire called the social behavior questionnaire (SBQ) to measure antisocial behavior in bvFTD and also found distinct factors for aggressive vs. rule breaking behaviors. In Aim

1 we will provide further evidence to support distinct antisocial behavioral phenotypes for aggressive vs. rule- breaking behaviors in bvFTD by administering an established measure of aggression and rule-breaking validated in non-patient populations and showing convergent validity between this established measure and

our novel, bvFTD-specific measure. In Aim 2 we will investigate the neural correlates for aggression and rule- breaking in bvFTD. Patterns of brain atrophy in bvFTD are heterogeneous between patients but preferentially affect two intrinsic functional connectivity networks within the brain: the salience network (SN) and the

semantic appraisal network (SAN). We have developed a novel method called atrophy network mapping to localize neurological symptoms to a brain network rather than to a specific brain region. In preliminary data using atrophy network mapping we found that aggressive behaviors in bvFTD localized to the SAN and rule-

breaking behaviors localized to the SN, hypotheses we will test in Aim 2. bvFTD is characterized by early and prominent changes to socioemotional processes, a neuropsychological pattern of impairment that is also seen in other patients with antisocial behavior even without executive dysfunction. Our preliminary data suggests

that different socioemotional impairments relate to different types of antisocial behaviors in bvFTD, with aggressive behaviors relating to impaired empathic concern and rule-breaking behaviors relating to impaired perspective taking, hypotheses we will test in aim 3. Determining whether aggressive and nonaggressive

behaviors are dissociable at the behavioral, neural, or decision-making levels would have a potential impact on clinical care, helping in early diagnosis, prognosis, and counseling. Study results would also have an impact on guiding future research efforts to prevent or treat antisocial behaviors in bvFTD.