Dopamine Compensates for Amyloid-Induced Default Mode Network Dysfunction to Support Learning
bioRxiv (Cold Spring Harbor Laboratory) July 10, 2026 Joseph Giorgio, Thomas Morin, Hsiang-Yu Chen et al.
In cognitively normal older adults, β-amyloid (Aβ) buildup in the default mode network impairs learning independently of tau, but higher dopamine synthesis capacity in the dorsolateral striatum can recover that learning performance. Aβ-positive individuals show reduced default mode network activity in response to error feedback, which relates to poorer learning. Computational modeling indicates that Aβ disinhibits the default mode network during error processing, and dopamine synthesis capacity in the dorsolateral striatum rebalances effective connectivity between the default mode network and frontostriatal network, counteracting Aβ-related disruption. These findings suggest that dopaminergic function can partially compensate for Aβ-related learning deficits through network rebalancing, offering a candidate mechanism for cognitive resilience in preclinical Alzheimer's disease.