Work

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

Year: 2025

Type: article

Abstract: • Executive dysfunction is a key characteristic of bvFTD. • Network de-differentiation reflects loss of specialized networks. • De-differentiation of the salience network relates to executive dysfunction in bvFTD. • Reduced network capacity for specialized processing may mediate emergence of executive dysfunction. The organization of the brain into distinct networks increases (i.e., differentiation) during development and decreases (i.e., de-differentiation) during healthy aging, changes that are associated with improvements and worsening of cognition, respectively. Given that behavioral variant frontotemporal degeneration (bvFTD) is a neurodegenerative disease associated with executive dysfunction and selective vulnerability of the salience network, we tested the hypotheses that bvFTD structural networks are de-differentiated compared to cognitively normal controls (CNC) and that network de-differentiation relates to worse executive function. In a sample of 90 patients with bvFTD and 71 age-matched CNC with diffusion MRI data we generated probabilistic tractography maps and calculated system segregation, a metric that compares within-network to between-network connectivity, to reflect the extent to which brain networks were differentiated. Patients with bvFTD also completed tests of executive function (digit span backwards, phonemic fluency, category fluency) and a control task (lexical retrieval). We assessed group differences in system segregation, reflecting network differentiation, and, within bvFTD, associations between system segregation and neuropsychological test performance. Compared to CNC, patients with bvFTD exhibited lower system segregation of the salience ( p < 0.001) and global brain network ( p = 0.008). In bvFTD, lower salience network system segregation was associated with worse executive function ( p corrected = 0.021) but not lexical retrieval. Results demonstrate associations between executive dysfunction and salience network de-differentiation in patients with bvFTD. Our findings indicate that brain network de-differentiation, reflecting reduced neural capacity for specialized processing, may contribute to the emergence of executive dysfunction in bvFTD.

Source: NeuroImage Clinical

DOI: 10.1016/j.nicl.2025.103853