Executive dysfunction relates to salience network desegregation in behavioral variant frontotemporal dementia

Network segregation, which facilitates functional specialization of cognition in healthy brains, breaks down with neurodegeneration and therefore is a candidate biomarker of disease. However, limited evidence exists evaluating the role of network desegregation in behavioral variant frontotemporal degeneration (bvFTD), especially the breakdown of structural networks and the impact of this process on cognition. We collected neuropsychological tests of executive function (digit span backwards, letter fluency, category fluency) and a control task (confrontation naming), and diffusion MRI data in a sample of 95 bvFTD patients without evidence of primary progressive aphasia and 72 age-matched cognitively normal controls (CNC). We evaluated the hypotheses that bvFTD would have desegregation in structural networks compared to CNC and that, in bvFTD, executive dysfunction would relate to desegregation of the salience network. Probabilistic tractography maps were generated from diffusion MRI, and network segregation was defined as greater within-network connectivity than between-network connectivity. One-way ANCOVAs tested for group differences in network desegregation. Then linear regressions examined associations between network desegregation and neuropsychological test performance. Analyses controlled for age, sex, education, mean cortical atrophy, motion during diffusion MRI scan, imaging protocol, and disease duration. Compared to CNC, patients with bvFTD exhibited desegregation of the salience ( p < .001) and global brain network ( p = .006). In bvFTD, desegregation of salience network was associated with worse executive function ( p _corrected = .039) but not confrontation naming. Results demonstrate associations between executive dysfunction and salience network desegregation in patients with bvFTD. Our findings indicate that brain network desegregation, reflecting reduced neural capacity for specialized processing, may contribute to the emergence of executive dysfunction in bvFTD.