State switching and high-order spatiotemporal organization of dynamic Functional Connectivity are disrupted by Alzheimer’s Disease

Abstract

Spontaneous activity during the resting state, tracked by BOLD fMRI imaging, or shortly rsfMRI, gives rise to brain-wide dynamic patterns of inter-regional correlations, whose structured flexibility relates to cognitive performance. Here we analyze resting state dynamic Functional Connectivity (dFC) in a cohort of older adults, including amnesic Mild Cognitive Impairment (aMCI, N = 34) and Alzheimer's Disease (AD, N = 13) patients, as well as normal control (NC, N = 16) and cognitively "super-normal" (SN, N = 10) subjects. Using complementary state-based and state-free approaches, we find that resting state fluctuations of different functional links are not independent but are constrained by high-order correlations between triplets or quadruplets of functionally connected regions. When contrasting patients with healthy subjects, we find that dFC between cingulate and other limbic regions is increasingly bursty and intermittent when ranking the four groups from SNC to NC, aMCI and AD. Furthermore, regions affected at early stages of AD pathology are less involved in higher-order interactions in patient than in control groups, while pairwise interactions are not significantly reduced. Our analyses thus suggest that the spatiotemporal complexity of dFC organization is precociously degraded in AD and provides a richer window into the underlying neurobiology than time-averaged FC connections.

Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole‐brain modeling

“…49 Metaconnectivity tackles third and fourth functional interactions between brain regions 50,51 and has been used to characterize aging processes, with a shift toward more viscous (uncoordinated) brain dynamics in older adult subjects. 51,52 Although little tested in dementia research, 53 combining high-order metaconnectivity with whole-brain mechanistic models and perturbational approaches 11 enables us to explore and predict whole-brain dynamics in neurodegeneration.…”

Dynamic multilayer functional connectivity detects preclinical and clinical Alzheimer’s disease

“…While there are several dynamic FC studies in patients with neurodegenerative disorders such as AD ( de Vos et al. 2018 ; Arbabyazd et al. 2023 ; Sendi et al.…”