The dark matter of the brain

  • Saak V. OvsepianEmail author


The bulk of brain energy expenditure is allocated for maintenance of perpetual intrinsic activity of neurons and neural circuits. Long-term electrophysiological and neuroimaging studies in anesthetized and behaving animals show, however, that the great majority of nerve cells in the intact brain do not fire action potentials, i.e., are permanently silent. Herein, I review emerging data suggesting massive redundancy of nerve cells in mammalian nervous system, maintained in inhibited state at high energetic costs. Acquired in the course of evolution, these collections of dormant neurons and circuits evade routine functional undertakings, and hence, keep out of the reach of natural selection. Under penetrating stress and disease, however, they occasionally switch in active state and drive a variety of neuro-psychiatric symptoms and behavioral abnormalities. The increasing evidence for widespread occurrence of silent neurons warrants careful revision of functional models of the brain and entails unforeseen reserves for rehabilitation and plasticity.


Silent neurons Brain evolution fMRI Synchronous activity Schizophrenia; disinhibition; neuronal plasticity 



This review is dedicated to the memory of Dr. Oliver Sacks. The author would like to thank Drs. R. Llinas, G. Buzsaki, M. Raichle, N. Logothetis and other leaders in the field of neuroscience and neuroimaging for their excellent research and inspiring articles and books. Special thanks go to Dr. V. O’Leary for insightful discussions and for proofreading the manuscript. The author would like to thank the National Sustainability Program 1 of the Czech Republic for supporting ongoing research projects (nr. LO1611) within the Department of Experimental Neurobiology at the National Institute of Mental Health, Czech Republic.

Compliance with ethical standards

Conflict of interest

This manuscript describes original research and is not under consideration in any other journal. The author reports no potential conflict of interest.

Ethical approval

This is a review paper and does not involve human or animal tissue. The original sources of presented and discussed material are fully acknowledged in compliance with journal’s policies.


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Authors and Affiliations

  1. 1.National Institute of Mental HealthKlecanyCzech Republic
  2. 2.Faculty of Medicine at Charles UniversityPragueCzech Republic
  3. 3.Institute for Biological and Medical ImagingHelmholtz Zentrum MunichNeuherbergGermany
  4. 4.Munich School of BioengineeringTechnical University MunichMunichGermany
  5. 5.International Centre for NeurotherapeuticsDublin City UniversityDublinRepublic of Ireland

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