Yalcinkaya, B. H. | Search bioRxiv

bioRxiv2022

The virtual aging brain: a model-driven explanation for cognitive decline in older subjects

Healthy aging is accompanied by heterogeneous decline of cognitive abilities among individuals, especially during senescence. The mechanisms of this variability are not understood, but have been associated with the reorganization of white matter fiber tracts and the functional co-activations of brain regions. Here, we built a causal inference framework to provide mechanistic insight into the link between structural connectivity and brain function, informed by brain imaging data and network modeling. By applying various degrees of interhemispheric degradation of structural connectivity, we were not only able to reproduce the age-related decline in interhemispheric functional communication and the associated dynamical flexibility, but we obtained an increase of global modulation of structural connectivity over the brain function during senescence. Notably, the increase in modulation between structural connectivity and brian function was higher in magnitude and steeper in its increase in older adults with poor cognitive performance. We independently validated the causal hypothesis of our framework via a Bayesian approach based on deep-learning. The current results might be the first mechanistic demonstration of dedifferentiation and scaffolding during aging leading to cognitive decline demonstrated in a large cohort.

neuroscience↗

bioRxiv2021

A comprehensive neural simulation of slow-wave sleep and highly responsive wakefulness dynamics

Hallmarks of neural dynamics during healthy human brain states span spatial scales from neuromodulators acting on microscopic ion channels to macroscopic changes in communication between brain regions. Developing a scale-integrated understanding of neural dynamics has therefore remained challenging. Here, we perform the integration across scales using mean-field modeling of Adaptive Exponential (AdEx) neurons, explicitly incorporating intrinsic properties of excitatory and inhibitory neurons. We report that when AdEx mean-field neural populations are connected via structural tracts defined by the human connectome, macroscopic dynamics resembling human brain activity emerge. Importantly, the model can qualitatively and quantitatively account for properties of empirical spontaneous and stimulus-evoked dynamics in the space, time, phase, and frequency domains. Remarkably, the model also reproduces brain-wide enhanced responsiveness and capacity to encode information particularly during wake-like states, as quantified using the perturbational complexity index. The model was run using The Virtual Brain (TVB) simulator, and is open-access in EBRAINS. This approach not only provides a scale-integrated understanding of brain states and their underlying mechanisms, but also open access tools to investigate brain responsiveness, toward producing a more unified, formal understanding of experimental data from conscious and unconscious states, as well as their associated pathologies.

neuroscience↗