By Klaus Linkenkaer-Hansen (Amsterdam, The Netherlands) et al.

The opposing forces of excitation (E) and inhibition (I) fundamentally shape activity at many levels of neuronal organization. Heuristic arguments have favored a certain “E/I balance” to be important for normal brain function, while “E/I imbalance” is considered a pathophysiological mechanism in several neurological and psychiatric disorders. The concept of E/I balance, however, is not uniquely defined at the mechanistic level because of many contributing factors, such as the size, number and cellular distribution of synapses, decay time of synaptic currents and network topology. Here, we explain a definition of E/I balance that is inspired by computational modeling of critical brain dynamics (1,2). In this framework, E/I balance is an emergent network property—a functional state characterized by high spatio-temporal complexity emerging in neuronal networks balancing between order and disorder. This definition enables measuring a functional network-level E/I ratio (fEI), which is useful for understanding basic principles of information processing in neuronal networks (3,4) and for studying brain disorders in which E/I balance may be disrupted (5,6).

  1. Poil, Hardstone et al. Critical-state dynamics of avalanches and oscillations jointly emerge from balanced excitation/inhibition in neuronal networks. Journal of Neuroscience, 2012.
  2. Bruining, Hardstone, Juarez-Martinez, Sprengers, et al. Measurement of excitation/inhibition ratio in autism spectrum disorder using critical brain dynamics. Scientific Reports, 2020.
  3. Avramiea et al. Amplitude and phase coupling optimize information transfer between brain networks that function at criticality. Journal of Neuroscience, 2022.
  4. Avramiea et al. Pre-stimulus phase and amplitude regulation of phase-locked responses is maximized in the critical state. eLife, 2020.
  5. Houtman, Lammertse, et al. STXBP1 syndrome is characterized by inhibition-dominated dynamics of resting-state EEG. Frontiers in Physiology, 2021.
  6. Juarez-Martinez, Sprengers, Cristian et al. Prediction of Behavioral Improvement Through Resting-State Electroencephalography and Clinical Severity in a Randomized Controlled Trial Testing Bumetanide in Autism Spectrum Disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2021
Additional authors

Klaus Linkenkaer-Hansen1,*, Arthur-Ervin Avramiea1, Erika L. Juarez-Martinez1, Richard Hardstone1, Simon J. Houtman1, Marina Diachenko1, Additya Sharma1, Huibert D. Mansvelder1, Hilgo Bruining2–3

1 Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, (CNCR), Amsterdam Neuroscience, VU University Amsterdam, Netherlands, Child and Adolescent Psychiatry and Psychosocial Care, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, 1105 AZ, The Netherlands, 3 N=You Neurodevelopmental Precision Center, Amsterdam Neuroscience, Amsterdam Reproduction and Development, Amsterdam UMC, Amsterdam, 1105 AZ, The Netherlands.

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