Awakening: Predicting external stimulation to force transitions between different brain states

Gustavo Deco, Josephine Cruzat, Joana Cabral, Enzo Tagliazucchi, Helmut Laufs, Nikos K. Logothetis, Morten L. Kringelbach

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


A fundamental problem in systems neuroscience is how to force a transition from one brain state to another by external driven stimulation in, for example, wakefulness, sleep, coma, or neuropsychiatric diseases. This requires a quantitative and robust definition of a brain state, which has so far proven elusive. Here, we provide such a definition, which, together with whole-brain modeling, permits the systematic study in silico of how simulated brain stimulation can force transitions between different brain states in humans. Specifically, we use a unique neuroimaging dataset of human sleep to systematically investigate where to stimulate the brain to force an awakening of the human sleeping brain and vice versa.We show where this is possible using a definition of a brain state as an ensemble of "metastable substates," each with a probabilistic stability and occurrence frequency fitted by a generative whole-brain model, fine-tuned on the basis of the effective connectivity. Given the biophysical limitations of direct electrical stimulation (DES) of microcircuits, this opens exciting possibilities for discovering stimulation targets and selecting connectivity patterns that can ensure propagation of DES-induced neural excitation, potentially making it possible to create awakenings from complex cases of brain injury.

Original languageEnglish
Pages (from-to)18088-18097
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number36
StatePublished - 3 Sep 2019
Externally publishedYes


  • Brain states
  • Computational neuroscience
  • Electrical stimulation
  • Metastates
  • Modeling


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