Disruption of Macroscale Functional Network Organisation in Patients with Frontotemporal Dementia

Neurodegenerative dementias have a profound impact on higher-order cognitive and behavioural functions. Investigating macroscale functional networks through cortical gradients provides valuable insights into the neurodegenerative dementia process and overall brain function. This approach allows for the exploration of unimodal-multimodal differentiation and the intricate interplay between functional brain networks. We applied cortical gradients mapping in frontotemporal dementia (FTD) patients (behavioural-bvFTD, non-fluent and semantic) and healthy controls. In healthy controls, two principal gradients maximally distinguished sensorimotor from default-mode network (DMN) and visual from salience network (SN). However, in bvFTD, this unimodal-multimodal differentiation was disrupted, impacting the interaction among all networks. Importantly, these disruptions extended beyond the observed atrophy distribution. Semantic and non-fluent variants exhibited more focal alterations in limbic and sensorimotor networks, respectively. The DMN and visual networks demonstrated contrasting correlations with social cognition performances, suggesting either early damage (DMN) or compensatory processes (visual). In conclusion, optimal brain function requires networks to operate in a segregated yet collaborative manner. In FTD, our findings indicate a collapse and loss of differentiation between networks that goes beyond the observed atrophy distribution. These specific cortical gradients’ fingerprints could serve as a novel biomarker for identifying early changes in neurodegenerative diseases or potential compensatory processes.