We propose that the preservation of functional integration, estimated from measures of neural synchrony, is a key objective of neurocompensatory mechanisms associated with healthy human ageing. To support this proposal, we demonstrate how phase-locking at the peak alpha frequency in Magnetoencephalography recordings remains invariant over the lifespan in a large cohort of human participants, aged 18-88 years. Using empirically derived connection topologies from diffusion tensor imaging data, we create an in-silico model of whole-brain alpha dynamics. We show that enhancing inter-areal coupling can cancel the effect of increased axonal transmission delays associated with age-related degeneration of white matter tracts, albeit at slower network frequencies. By deriving analytical solutions for simplified connection topologies, we further establish the theoretical principles underlying compensatory network re-organization. Our findings suggest that frequency slowing with age- frequently observed in the alpha band in diverse populations- may be viewed as an epiphenomenon of the underlying compensatory mechanism.
Computational neuroscience has come a long way from its humble origins in the pioneering work of Hodgkin and Huxley. Contemporary computational models of the brain span multiple spatiotemporal scales, from single neuronal compartments to models of social cognition. Each spatial scale comes with its own unique set of promises and challenges. Here, we review models of large-scale neural communication facilitated by white matter tracts, also known as whole-brain models (WBMs). Whole-brain approaches employ inputs from neuroimaging data and insights from graph theory and non-linear systems theory to model brain-wide dynamics. Over the years, WBM models have shown promise in providing predictive insights into various facets of neuropathologies such as Alzheimer's disease, Schizophrenia, Epilepsy, Traumatic brain injury, while also offering mechanistic insights into large-scale cortical communication. First, we briefly trace the history of WBMs, leading up to the state-of-the-art. We discuss various methodological considerations for implementing a whole-brain modeling pipeline, such as choice of node dynamics, model fitting and appropriate parcellations. We then demonstrate the applicability of WBMs toward understanding various neuropathologies. We conclude by discussing ways of augmenting the biological and clinical validity of whole-brain models.
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