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The effect of external stimulation on functional networks in the aging healthy human brain.

Computational Neuroscience Group, Center for Brain and Cognition, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain. Department of Radiology (IDI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain. Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain. Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain. Institut d'Assistència Sanitària, Salt, Girona, Spain. Department of Diabetes, Endocrinology and Nutrition, IDIBGI, Hospital Universitari de Girona Dr Josep Trueta, and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Girona, Spain. Vascular Health Research Group of Girona (ISV-Girona), Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Girona, Spain. Primary Care Services, Catalan Institute of Health (ICS), Girona, Spain. Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLleida, Lleida, Spain. Cardiovascular Genetics Center, IDIBGI, CIBER-CV, Girona, Spain. Department of Neurology, Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain. CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. Biobanc, Girona Biomedical Research Institute (IDIBGI), Girona, Spain. Department of Radiology, AOU Cagliari, University of Cagliari, Italy. Centre for Eudaimonia and Human Flourishing, University of Oxford, Oxford, UK. Department of Psychiatry, University of Oxford, Oxford, UK. Center for Music in the Brain, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Institució Catalana de la Recerca i Estudis Avancats (ICREA), Barcelona, Catalonia, Spain. Department of Neuropsychology, Max Planck Institute for human Cognitive and Brain Sciences, Leipzig, Germany. Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia.

Cerebral cortex (New York, N.Y. : 1991). 2022;(1):235-245
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Abstract

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve to identify neurophysiological biomarkers differentiating between age groups through an exhaustive exploration of the global effect of all possible local perturbations. Here, we used a resting-state fMRI dataset divided into middle-aged (N =310, <65 years) and older adults (N =310, $\geq $65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space. We showed that the older group exhibited a reduced capability to access a metastable substate that overlaps with the rich club. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations in each node to force transitions from the brain states of the older- to the middle-aged group. We found that the precuneus was the best stimulation target. Overall, these findings could have important implications for designing neurostimulation interventions for reversing the effects of aging on whole-brain dynamics.