Reduced network switching in aging correlates with atrophy of the cholinergic basal forebrain

Elderly subjects demonstrate a dysfunctional attenuation of task-induced deactivation of the default mode network (DMN) in cognitively demanding tasks¹. Based on findings from animal studies, it has been suggested that the basal forebrain cholinergic system (BFCS) may play a critical role in mediating the switch from DMN activity to task-associated activity in attention-demanding situations². We hypothesized that the reduced capability of older adults to disengage from DMN activity in cognitively demanding tasks would also be reflected in a reduced anticorrelated behavior of the spontaneous fMRI signal fluctuations of the DMN and the dorsal attention network (DAN) at rest^3,4. Furthermore, we sought to examine if this reduced reciprocal network behavior at rest is associated to atrophy of the BFCS^5,6.

Structural MRI and resting-state fMRI scans were retrieved for 29 healthy older adults (61–85 y) and 30 young adults (20–40 y) from the NKI/Rockland-sample of the International Neuroimaging Data-sharing Initiative (INDI). Standardized network masks⁷ were used to calculate correlations between fMRI signal fluctuations of the DAN and the DMN. Associations between decreased anticorrelation and BF atrophy in the elderly were assessed using automated morphometry techniques in combination with a cytoarchitectonic map of the BFCS^6,8.

Fisher z-transformed correlation coefficients between DAN and DMN signal fluctuations were significantly less anticorrelated in the elderly subjects (z=–0.47±0.26) compared to young adults (z=–0.72±0.24; p<0.0001). Furthermore, less negative correlation coefficients were associated with reduced volume of the BFCS in the elderly (r=–0.41, p<0.05).

The anticorrelated character of spontaneous fMRI signal fluctuations in the DMN and the DAN is less marked in elderly subjects compared to young adults, possibly reflecting a decreased capacity for network switching in attention-demanding tasks, which may be related to a dysfunctional BFCS.

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