Structural localization of antisocial behaviors in patients with behavioral variant frontotemporal dementia

Behavioral variant frontotemporal dementia (bvFTD) is frequently associated with new-onset antisocial and criminal behaviors, occurring in up to 92% of bvFTD patients and presenting as an initial symptom in up to 14% of patients. Despite their frequency and severity, the structural brain changes underlying antisocial behavior in bvFTD remain unclear. Work in FTD and other populations suggests that antisocial behaviors can be further differentiated into aggressive and rule-breaking behaviors, which may have distinct neural mechanisms. In the current study, we tested the hypothesis that aggressive and rule-breaking antisocial behaviors would differentially relate to cortical volume in regions implicated in both antisocial behavior and bvFTD, including the orbitofrontal/ventromedial prefrontal cortex (OFC/vmPFC), anterior temporal lobe (ATL) and anterior insula (AIns). Structural MRI scans were acquired from bvFTD patients (n = 45, mean age: 63.2 ± 8.7 years, 22% female) and age-matched healthy controls (n = 31, mean age: 63.3 ± 8.4 years, 80% female). Antisocial behavior was measured using the Social Behavior Questionnaire (SBQ), which provides subscores for aggressive and rule-breaking behaviors. We examined associations between brain volume and antisocial behaviors using region-of-interest and whole-brain voxel-wise approaches, controlling for age, sex, and intracranial volume. To determine the effects of brain atrophy on connected regions, we also applied atrophy network mapping, which identifies regions functionally connected to atrophied regions using single-subject atrophy maps and a normative connectome derived from resting state functional connectivity in 1000 healthy individuals. Increased antisocial behaviors was associated with greater left (P = 0.02), and right (P = 0.01) OFC/vmPFC volume, but not with ATL or AIns volume. These anatomical associations were specific to aggressive but not rule-breaking behavior. Comparison with healthy controls demonstrated that this positive association between antisocial behavior and brain volume was due to mild atrophy, rather than normal or increased cortical volume in OFC/vmPFC. Atrophy network mapping revealed that antisocial behavior was associated with less atrophy in locations within OFC/vmPFC-centered networks and with atrophy in functionally anti-correlated networks. In contrast, atrophy within networks anti-correlated with the precuneus/posterior cingulate cortex was associated with decreased antisocial behavior. Our results suggest that antisocial and aggressive behaviors in bvFTD are associated with a complex pattern of mild OFC/vmPFC atrophy coupled with atrophy in anti-correlated networks, which may lead to functional dysregulation within OFC/vmPFC-centered networks.