Reciprocal relationship between neural fibre span and node transmission in brain stabilizes information pathway and energy homeostasis across human life-span

AIMS: Though contemporary researches well investigate dysfunctions at extremes of age, i.e. children (neurodevelopmental disorders) or elderlies (neurodegenerative disorders), the integrative orchestration of global whole-brain connectivity across full-longevity ageing is much less studied. Accordingly, we investigate the adaptive reorganization of whole-brain connectivity along ageing spectrum. Our goal is to identify unitary processes characterizing life-span, whereby neuroprotection applications emerge.METHODS: We study lifespan transition, using 3-tesla MRI-DTI scans of 382 individuals (aged 15-90, gender-balanced). Using contour pathway analysis, we formulate a novel connectomics framework, by offsetting ageing-induced decline of fibre density. To probe ageing-dynamics of fibres, we construct a quantitative tissue-based analysis of age-varying interaction between neuron and extracellular bodies. RESULTS:While age-progression occurs, we find reciprocal behaviours between two basic parameters of neural connectivity: (1) information transmission pathway, as gauged by network node information linkage, maximizes at mid-age (55-60 years), displaying positive-quadratic behaviour; (2) basal neural fibre span inversely minimizes at mid-age, showing negative-quadratic behaviour. Furthermore, the neural fibre’s path integral of information linkage [namely, product (1)x(2)] remains constant, along lifespan. This indicates that the connectivity energy cost along fibre is conserved lifelong. CONCLUSION:Unlike mature adulthood, there is increased tortuosity of neural fibres both at young-age and old-age due to higher meandering of fibres, caused by enhanced postsynaptic dense bodies (young-age) and neurite deposition (old-age). Nevertheless, the neurophysiological system is resilient, enabling a homeostatic adaptive strategy that stabilizes the energy-cost of fibre’s functionality, across lifespan. The associated neuroprotective process, based on myelination dynamics, can be therapeutically probed.