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

Anira Escrichs*, Yonatan Sanz Perl, Noelia Martínez-Molina, Carles Biarnes, Josep Garre-Olmo, José Manuel Fernández-Real, Rafel Ramos, Ruth Martí, Reinald Pamplona, Ramon Brugada, Joaquin Serena, Lluís Ramió-Torrentà, Gabriel Coll-De-Tuero, Luís Gallart, Jordi Barretina, Joan C. Vilanova, Jordi Mayneris-Perxachs, Luca Saba, Salvador Pedraza, Morten L. KringelbachJosep Puig, Gustavo Deco

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

2 Citations (Scopus)


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.

Original languageEnglish
JournalCerebral Cortex
Pages (from-to)235-245
Number of pages11
Publication statusPublished - Jan 2023


  • in silico perturbations
  • aging
  • brain states
  • computational modeling
  • resting-state fMRI
  • Middle Aged
  • Humans
  • Brain/physiology
  • Parietal Lobe
  • Aging/physiology
  • Magnetic Resonance Imaging
  • Brain Mapping
  • Aged
  • Cognition/physiology


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