Antao Chen

Emerging research challenges the prevailing notion of uniform cognitive decline in aging, instead emphasizing the brain's adaptive ability that compensates for age-related deficits. Here we examined age-related differences in brain dynamics by focusing on rest-to-task reconfiguration, a process that reflects the brain’s ability to recruit neural resources for goal-directed behavior. Using hidden Markov modeling of whole-brain fMRI data, we characterized brain state transitions from rest to a Stroop task in young and older adults. Behaviorally, older adults exhibited generalized slowing yet preserved conflict resolution. Dynamically, both age groups could reconfigure from rest-specific towards a task-efficient brain state. However, while young adults preferentially engaged this state, older adults showed attenuated recruitment, instead maintaining a high-effort state from rest to task. Crucially, the functional benefit of this pattern was conditional: it supported conflict resolution only in high-accuracy older adults but presented detrimental in low performers. These findings demonstrate that cognitive preservation in aging depends not on preserving youthful brain reconfiguration dynamics, but on the effective recruitment of compensatory brain states.

Normal aging is accompanied by declines in executive function, and regular physical exercise has been proposed as a protective factor. However, the neural correlates linking long-term habitual exercise to executive efficiency in older adults remain unclear. This study combined resting-state functional magnetic resonance imaging (rs-fMRI) with behavioral assessments to examine whether long-term habitual exercise is associated with executive performance and resting-state neural organization in older adults. A total of 105 older adults (52 long-term habitual exercisers and 53 non-habitual exercisers) completed task-switching, Stroop and N-back paradigms and underwent rs-fMRI scanning. Behavioral outcomes included accuracy, reaction time, task cost and executive efficiency index. Neural measures included amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and degree centrality (DC). Older adults with long-term habitual exercise showed higher accuracy and faster responses across tasks, with no group differences in task cost but higher executive efficiency, compared with non-habitual exercisers. They also exhibited higher ALFF, ReHo and DC in frontoparietal, motor and striatal regions, alongside lower resting-state metrics in occipito-cerebellar networks. Mediation models indicated that ALFF in the pallidum, DC in prefrontal and cingulate cortices, and ReHo in frontoparietal regions statistically accounted for the association between exercise status and executive efficiency. Long-term habitual exercise was associated with better executive performance and distinct resting-state functional organization in older adults. Frontoparietal and striatal systems emerged as candidate intrinsic correlates of executive efficiency in physically active older adults.

Working memory training (WMT) is widely used to enhance cognitive task performance, yet traditional delivery poses challenges for sustained implementation; computerised working memory training (CWMT) provides a scalable digital format with standardised delivery and integrated monitoring and feedback. We conducted the first meta-analysis integrating behavioural and neuroimaging evidence to quantify the behavioural effects and neural correlates of CWMT, drawing on 45 neuroimaging studies. Multivariate meta-analysis indicated a moderate benefit of CWMT relative to controls (Hedges’ g = 0.503, 95% CI [0.363–0.642]). Seed-based d mapping (SDM) identified training-related decreases in activation in the left angular gyrus (L-AG), bilateral superior frontal gyrus (SFG), right inferior parietal lobule (R-IPL), left cerebellum, and right middle frontal gyrus (R-MFG), a pattern compatible with reduced recruitment following training. Moderator analyses showed significant effects of task type, training compliance, total training dose, and age, but not cognitive status and sex. Moreover, CWMT-induced brain activation changes were associated with behavioural improvements, and significant co-activation was observed among the brain regions identified in the overall analysis. Together, these findings provide convergent evidence that CWMT is associated with improved cognitive task performance and reproducible modulation of task-related activation, supporting its relevance as a scalable digital approach to cognitive health.

Background: The dose-response effects of physical exercise on brain volume remain insufficiently understood, and it is yet to be established whether exercise-induced relative changes in brain volume translate into improvements in cognitive function. Furthermore, it remains unclear whether specific physical adaptations are associated with both exercise-related changes in brain volume and cognitive outcomes. Methods: To address these gaps, we conducted a pre-registered systematic review and multilevel meta-analysis of 59 randomized controlled trials comprising a total of 5,099 participants. Comprehensive literature searches were carried out in PubMed, PsycINFO, Embase, and Web of Science up to August 2024. The meta-analysis examined overall effects of physical exercise on brain volume, investigated dose-response effects across relevant moderators, and explored potential mediation pathways linking exercise-induced relative changes in brain volume to cognitive outcomes. Results: This study found that physical exercise had a significant effect on brain volume. Dose-response analyses further revealed that this effect was more pronounced among individuals of older age, with longer intervention durations and higher compliance. Exercise sessions lasting 40–60 min were associated with the most robust effects on brain volume. Post-hoc analyses suggest that these effects are more likely attributable to the preservation of brain volume rather than substantial volumetric increases. In addition, regression analysis demonstrated a significant positive association between exercise-induced relative changes in brain volume and cognitive function. Moreover, mediation analyses indicated that exercise-induced physical adaptations in muscle function, motor performance, and cardiorespiratory fitness were indirectly associated with cognitive performance through their effects on relative brain volume change. Conclusions: These findings indicate that physical exercise exerts beneficial effects on brain volume, particularly under conditions such as older age, sufficient exercise duration, and high compliance. Exercise-induced relative changes in brain volume were significantly associated with cognitive function and served as a mediator between physical adaptations and cognitive outcomes. Together, these results provide a mechanistic foundation and practical insights for designing targeted exercise interventions to promote brain health in aging populations. Trial registration: PROSPERO CRD42024525635.

With the aging of global populations, understanding the role of the cerebellum in aging is crucial. However, existing studies primarily focus on structural and functional changes, leaving the topological properties of cerebellar functional networks in aging unclear. Here, we explored the aging effects on the topological organization of cerebellar functional networks and investigated the relationship between these changes and cognitive function. The results revealed that, compared with young adults, older adults exhibited declines in the global and local network efficiency, modularity, and small-world properties of the cerebellum. Additionally, reductions were observed in the betweenness centrality within the visual network (VN), the nodal efficiency (NE) within the VN and lateral somatomotor network (SMN(Lat)). Moreover, the nodal local efficiency (NLE) decreased in the default mode network and SMN(Lat) of older adults. Notably, the gamma value of the cerebellar network was positively correlated with Stroop task accuracy in the incongruent condition among older adults. Additionally, aging impaired whole-brain (including cerebellar) network efficiency but preserved modularity and small-world properties, and at the nodal level, cerebellar regions showed selective reductions in NE and NLE, alongside degree centrality reorganization. Exploratory analyses revealed gender-specific patterns in cerebellar network topology during aging, with males experiencing relatively limited declines and females showing more extensive deterioration. The findings indicated that aging is associated with disruptions in the global and regional topology of the cerebellar functional connectome, with females exhibiting more pronounced deterioration than males. The integrity of cerebellar network topology appeared crucial for maintaining cognitive control.