Despite the importance of memories in everyday life and the progress made in understanding how they are encoded and retrieved, the neural processes by which declarative memories are maintained or forgotten remain elusive. Part of the problem is that it is empirically difficult to measure the rate at which memories fade, even between repeated presentations of the source of the memory. Without such a ground-truth measure, it is hard to identify the corresponding neural correlates. This study addresses this problem by comparing individual patterns of functional connectivity against behavioral differences in forgetting speed derived from computational phenotyping. Specifically, the individual-specific values of the speed of forgetting in long-term memory (LTM) were estimated for 33 participants using a formal model fit to accuracy and response time data from an adaptive paired-associate learning task. Individual speeds of forgetting were then used to examine participant-specific patterns of resting-state fMRI connectivity, using machine learning techniques to identify the most predictive and generalizable features. Our results show that individual speeds of forgetting are associated with resting-state connectivity within the default mode network (DMN) as well as between the DMN and cortical sensory areas. Cross-validation showed that individual speeds of forgetting were predicted with high accuracy (r = .78) from these connectivity patterns alone. These results support the view that DMN activity and the associated sensory regions are actively involved in maintaining memories and preventing their decline, a view that can be seen as evidence for the hypothesis that forgetting is a result of storage degradation, rather than of retrieval failure.

Alzheimer's disease (AD) progressively alters brain structure and function, yet the associated changes in large-scale brain network dynamics remain poorly understood. We applied the intrinsic ignition framework to resting-state functional MRI (rs-fMRI) data from AD patients, individuals with mild cognitive impairment (MCI), and cognitively healthy controls (HC) to elucidate how AD shapes intrinsic brain activity. We assessed node-metastability at the whole-brain level and in 7 canonical resting-state networks (RSNs). Our results revealed a progressive decline in dynamical complexity across the disease continuum. HC exhibited the highest node-metastability, whereas it was substantially reduced in MCI and AD patients. The cortical hierarchy of information processing was also disrupted, indicating that rich-club hubs may be selectively affected in AD progression. Furthermore, we used linear mixed-effects models to evaluate the influence of Amyloid-{beta} (A{beta}) and tau pathology on brain dynamics at both regional and whole-brain levels. We found significant associations between both protein burdens and alterations in node metastability. Lastly, a machine learning classifier trained on brain dynamics, A{beta}, and tau burden features achieved high accuracy in discriminating between disease stages. Together, our findings highlight the progressive disruption of intrinsic ignition across whole-brain and RSNs in AD and support the use of node-metastability in conjunction with proteinopathy as a novel framework for tracking disease progression.