Aging is associated with gradual changes in cognition, yet some individuals exhibit protection against age-related cognitive decline. The topological characteristics of brain networks that promote protection against cognitive decline in aging are unknown. Here, we investigated whether the robustness and resilience of brain networks, queried via the delineation of the brain’s core network structure, relate to age and cognitive performance in a cross-sectional dataset of healthy middle- and old-aged adults ( n = 478, ages 40 to 90 y). First, we decomposed each subject’s functional brain network using k -shell decomposition and found that age was negatively associated with robust core network structures. Next, we perturbed these networks, via attack simulations, and found that resilience of core brain network nodes also declined in relationship to age. We then partitioned our dataset into middle- (ages 40 to 65 y, n = 300) and old- (ages 65 to 90 y, n = 178) aged subjects and observed that older individuals had less robust core connectivity and resilience. Following these analyses, we found that episodic memory was positively related to robust connectivity and core resilience, particularly within the default node, limbic, and frontoparietal control networks. Importantly, we found that age-related differences in episodic memory were positively related to core resilience, which indicates a potential role for core resilience in protection against cognitive decline. Together, these findings suggest that robust core connectivity and resilience of brain networks could facilitate high cognitive performance in aging.

Progressive brain atrophy is a key neuropathological hallmark of Alzheimer's disease (AD) dementia. However, atrophy patterns along the progression of AD dementia are diffuse and variable and are often missed by univariate methods. Consequently, identifying the major regional atrophy patterns underlying AD dementia progression is challenging. In the current study, we propose a method that evaluates the degree to which specific regional atrophy patterns are predictive of AD dementia progression, while holding all other atrophy changes constant using a total sample of 334 subjects.We first trained a dense convolutional neural network model to differentiate individuals with mild cognitive impairment (MCI) who progress to AD dementia versus those with a stable MCI diagnosis. Then, we retested the model multiple times, each time occluding different regions of interest (ROIs) from the model's testing set's input. We also validated this approach by occluding ROIs based on Braak's staging scheme. We found that the hippocampus, fusiform, and inferior temporal gyri were the strongest predictors of AD dementia progression, in agreement with established staging models. We also found that occlusion of limbic ROIs defined according to Braak stage III had the largest impact on the performance of the model. Our predictive model reveals the major regional patterns of atrophy predictive of AD dementia progression.These results highlight the potential for early diagnosis and stratification of individuals with prodromal AD dementia based on patterns of cortical atrophy, prior to interventional clinical trials.

The aging brain undergoes major changes in its topology. The mechanisms by which the brain mitigates age-associated changes in topology to maintain robust control of brain networks are unknown. Here we used diffusion MRI data from cognitively intact participants (n=480, ages 40-90) to study age-associated changes in the controllability of structural brain networks, features that could mitigate these changes, and the overall effect on cognitive function. We found age-associated declines in controllability in control hubs and large-scale networks, particularly within the and frontoparietal control and default mode networks. Redundancy, quantified via the assessment of multi-step paths within networks, mitigated the effects of changes in topology on network controllability. Lastly, network controllability, redundancy, and grey matter volume each played important complementary roles in cognitive function. In sum, our results highlight the importance of redundancy for robust control of brain networks and in cognitive function in healthy-aging.

Aging is associated with gradual changes in cognition, yet some individuals exhibit protection against aging-related cognitive decline. The topological characteristics of brain networks that support protection against cognitive decline in aging are unknown. Here, we investigated whether the robustness of brain networks, queried via the delineation of the brain's core network structure, supports superior cognitive performance in healthy aging individuals (n=320, ages 60-90). First, we decomposed each subject's functional brain networks using k-shell decomposition, finding that cognitive function is associated with more robust connectivity of core nodes, primarily within the frontoparietal control network (FPCN). Next, we find that the resilience of core brain network nodes, within the FPCN in particular, relates to cognition. Finally, we show that the degree of segregation in functional networks mediates relationships between network resilience and cognition. Together, these findings suggest that brain networks balance between robust core connectivity and segregation to facilitate high cognitive performance in aging.

Distress tolerance (DT), the capability to persist under negative circumstances, underlies a range of psychopathologies. It has been proposed that DT may originate from the activity and connectivity in diverse neural networks integrated by the reward system. To test this hypothesis, we examined the link between DT and integration and segregation in the reward network as derived from resting-state functional connectivity data. DT was measured in 147 participants from a large community sample using the Behavioral Indicator of Resiliency to Distress task. Prior to DT evaluation, participants underwent a resting-state functional magnetic resonance imaging scan. For each participant, we constructed a whole-brain functional connectivity network and calculated the degree of reward network integration and segregation based on the extent to which reward network nodes showed functional connections within and outside their network. We found that distress-intolerant participants demonstrated heightened reward network integration relative to the distress-tolerant participants. In addition, these differences in integration were higher relative to the rest of the brain and, more specifically, the somatomotor network, which has been implicated in impulsive behavior. These findings support the notion that increased integration in large-scale brain networks may constitute a risk for distress intolerance and its psychopathological correlates.