Dopamine Compensates for Amyloid-Induced Default Mode Network Dysfunction to Support Learning

Area of Science:

• Neuroscience
• Cognitive Science
• Medical Imaging

Background:

• Preclinical Alzheimer's disease (AD) involves beta-amyloid (Aβ) accumulation in the default mode network (DMN).
• The functional and behavioral impacts of Aβ burden in the DMN are not well understood.

Purpose of the Study:

• To investigate how Aβ impacts learning and neural network function in cognitively normal older adults.
• To explore the role of dopamine in compensating for Aβ-related learning deficits.

Main Methods:

• Task-based functional magnetic resonance imaging (fMRI).
• Positron emission tomography (PET) for Aβ, tau, and dopamine.
• Computational modeling of effective connectivity.

Main Results:

• Aβ burden impaired learning independently of tau, but this was reversed by higher dorsolateral striatal dopamine synthesis.
• Individuals with Aβ showed reduced DMN activity in response to error feedback, correlating with poorer learning.
• Aβ disrupted DMN effective connectivity during error processing, which was counteracted by dopamine.

Conclusions:

• Aβ impairs learning by disrupting DMN modulation during feedback.
• Dopamine synthesis capacity can partially compensate for Aβ-related learning disruptions by rebalancing frontostriatal network connectivity.
• Dopamine-dependent network rebalancing may support cognitive resilience for learning in preclinical AD.