EEG-based Brain Health clocks linked to biophysical mechanisms in aging, dementia and neuroplasticity

Brisbane Convention & Exhibition Centre 

Brain clocks, which measure deviations between chronological age and predicted brain age (brain age gaps, or BAGs), reveal whether an individual's brain appears older or younger than expected. These models can characterize individual aging trajectories and identify pathological deviations in conditions like Alzheimer's Disease (AD) and behavioral variant frontotemporal dementia (bvFTD). However, challenges such as heterogeneous findings, limited computational methods, and a lack of diverse representation hinder progress in the field. Emerging biophysical whole-brain models offer a promising solution, enabling robust analyses with moderate sample sizes and shedding light on unexplored causal mechanisms. In parallel, creative and artistic experiences have been proposed as interventions to support brain health across the lifespan. Here we combine source space connectivity (EEG) with generative brain modeling in healthy controls (HCs) from both the global south and north, alongside Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) patients (N=1,399). Additionally, we analyzed how different types of creative experiences can protect the brain from accelerated brain aging via neural plasticity mechanisms, including a subsample of expert and matched non-expert participants in dance, music, visual arts, and video games, along with a pre/post-learning study (N=227). Using source-space EEG connectivity and Support Vector Machine (SVM) regression models, we examined how BAGs reflect disparities at both aggregate (e.g., geographic and income differences), individual levels (e.g., education and sex), and how can be used to characterize the effects of creativity on brain health (expertise and learning). The BAGs in aging were modulated by diversity-related factors inducing accelerated aging, including geography (south>north), income (GPD, low > high), sex (female>male), and education (low > high). A larger BAG was observed in patients, with sex further increasing the effects in AD (female>male). In creative experiences, we observed delayed brain age across all domains, and scalable effects (expertise>learning). The higher the level of expertise and performance, the greater the delay in brain age. Biophysical modeling shows that BAGs are related to specific mechanisms: global hyperexcitability and reduced connectivity (structural disintegration) were implicated in aging’s BAGs. Hypoexcitability and severe disintegration were related to dementia. On the other hand, creativity is associated with reduced hyperexcitability, increased network efficiency, and increased structural integrity. Our work sheds light on biophysical mechanisms of accelerated aging in diverse and underserved populations and provides domain-independent evidence of creativity’s positive impact on brain health.