E/I ratio and net E+I strength are differentially affected across brain disorders
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Neuronal oscillations wax and wane near criticality, switching between high- and low-power states. However, the link between this bistability and excitation–inhibition balance is not well understood. Using a computational model, we demonstrate that bistability is influenced by two key factors: the excitatory-inhibitory (E/I) ratio and the combined strength of excitatory and inhibitory activity (E+I). We developed algorithms to infer both metrics from electrophysiological data and validated them in vivo. In intracranial recordings from epilepsy patients, both E/I and E+I increased during seizures, while interictally, E+I remained elevated in seizure zones as E/I decreased—consistent with compensatory inhibition. Extending the framework to scalp EEG from eight disorders, we found that Alzheimer’s disease is better classified by E/I changes, whereas autism spectrum disorder and ADHD are distinguished by E+I alterations. Our findings highlight the importance of bistability in understanding EI regulation and offer handles for diagnostic and treatment decision support.
Authors 7
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Emma Kinderziekenhuis · Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam
Affiliation as printed
Child and Adolescent Psychiatry and Psychosocial Care, Emma Children’s Hospital, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, 1081 HV, Amsterdam, The Netherlands
Child and Adolescent Psychiatry and Psychosocial Care, Emma Children's Hospital, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, 08 HV, Amsterdam, The Netherlands
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Amsterdam Neuroscience · Vrije Universiteit Amsterdam
Affiliation as printed
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, 1081 HV, Amsterdam, The Netherlands
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, 08 HV, Amsterdam, The Netherlands
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Rutgers, The State University of New Jersey
Affiliation as printed
Center for Advanced Human Brain Imaging Research, Rutgers University, Piscataway, NJ, USA
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Harvard University · Massachusetts General Hospital
Affiliation as printed
Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Amsterdam Neuroscience · Universitätsklinikum Aachen · Vrije Universiteit Amsterdam · RWTH Aachen University
Affiliation as printed
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, 1081 HV, Amsterdam, The Netherlands
Department of Neurology, Epileptology, Uniklinik RWTH Aachen, Germany
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, 08 HV, Amsterdam, The Netherlands
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Hilgo Bruining Aachen Department Education and Child Studies Faculty of Social and Behavioral Sciences
Leiden University · Emma Kinderziekenhuis · Amsterdam University Medical Centers · Levvel · Vrije Universiteit Amsterdam
Affiliation as printed
Child and Adolescent Psychiatry and Psychosocial Care, Emma Children’s Hospital, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
Department Education and Child Studies, Faculty of Social and Behavioral Sciences, Leiden University, Leiden, The Netherlands
Department of Paediatrics, Emma Neuroscience Group, Amsterdam UMC Emma Children’s Hospital, Amsterdam, The Netherlands
Levvel, Center for Child and Adolescent Psychiatry, Amsterdam, The Netherlands
Child and Adolescent Psychiatry and Psychosocial Care, Emma Children's Hospital, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, Netherlands
Department of Paediatrics, Emma Neuroscience Group, Amsterdam UMC Emma Children's Hospital, Amsterdam, The Netherlands
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Klaus Linkenkaer‐Hansen corresponding
Amsterdam Neuroscience · Vrije Universiteit Amsterdam
Affiliation as printed
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, 1081 HV, Amsterdam, The Netherlands
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, 08 HV, Amsterdam, The Netherlands
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