Atypical intrinsic neural timescale in the left angular gyrus in Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is characterised by cognitive impairment and progressive brain atrophy. Recent human neuroimaging studies showed that such AD symptoms are linked with anatomical and functional changes seen in the default mode network (DMN), but the key brain region whose atrophy disturbs the neural activity of the DMN and consequently contributes to the symptoms of AD remains unclear. Here, we examined the intrinsic neural timescales (INT) of the regions in the DMN aiming to identify such a crucial brain area. We investigated INT since prior work demonstrated its utility in quantifying local neural dynamics and bridging knowledge gaps between atypical local neuroanatomical features and symptoms in neuropsychiatric disorders. We used resting-state functional MRI data and compared INT between individuals diagnosed with AD and age-/sex-/handedness-matched cognitively normal individuals. To exclude the possibility that a region outside of the DMN has such a critical role, we first performed an exploratory whole-brain analysis and found that only the left angular gyrus, a region within the DMN, exhibited a shorter INT in the AD group compared to those with normal cognition. We also identified an AD-specific decrease in the grey matter volume in the left angular gyrus and revealed that such regional atrophy shortened the INT of the angular gyrus and consequently reduced the overall INT of the DMN. Moreover, we found that the overall shorter DMN INT led to the symptoms of AD, particularly, its impairments of attention control. Taken together, our findings indicate that the left angular gyrus serves as a key brain region whose structural atrophy and resultantly shorter INT destabilise DMN neural dynamics and contribute substantially to AD cognitive decline. Clinically, the outcome of this study indicates that INT of the left angular gyrus could serve as a convenient biomarker for the cognitive symptoms of AD.