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Updated: Oct 6, 2026

A Protocol For Uncovering Neural Mechanisms Of Neurotherapeutic Effects On Electroencephalography Using The Human Neocortical Neurosolver
Published on: May 19, 2026
Transdiagnostic patterns of electroencephalography (EEG)-derived aperiodic activity across schizophrenia-spectrum,
Gia Han Le1,2,3, Sabrina Wong2,3,4, Sara Di Luch2,4
1Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Abstract:
Aperiodic electroencephalographic activity is proposed as a scalable marker of cortical population dynamics relevant to excitation-inhibition balance. However, it remains unclear whether aperiodic parameters represent disorder-specific abnormalities or context-sensitive indices of clinically relevant brain states. Consistent with systematic-review guidelines and a prospectively registered protocol, Ovid databases and PubMed were searched from inception through February 9, 2026, with updated manual searching conducted through July 14, 2026. Peer-reviewed studies reporting electroencephalography-derived aperiodic parameters in adults with schizophrenia-spectrum disorders, major depressive disorder, treatment-resistant depression, and/or bipolar disorder were eligible. Studies lacking aperiodic outcomes or separable findings for eligible diagnoses were excluded. Two reviewers independently conducted study screening, data extraction, and risk-of-bias assessments. Findings were synthesized narratively by diagnosis, recording context, and parameter. Thirty articles (N = 2298 aggregate participants) spanning cross-sectional, longitudinal, and interventional designs were included. Findings in schizophrenia-spectrum disorders were heterogeneous, with several studies reporting steeper slopes, higher offsets, or reduced temporal flexibility relative to healthy controls. Task-related and dynamic measures often showed greater clinical relevance than static resting-state parameters. Studies of major depressive disorder and treatment-resistant depression more consistently reported flatter slopes and reduced offsets, particularly in central and posterior regions, with evidence from sleep and intracranial recordings. Aperiodic parameters were sensitive to treatment-related modulation, although the direction of change differed across interventions. Bipolar disorder evidence was limited, and methodological heterogeneity precluded quantitative synthesis. Aperiodic electroencephalographic activity may be more informative as a context-sensitive, within-subject marker of cortical state and treatment-related change than a fixed diagnostic signature. Methodological harmonization and direct physiological validation remain necessary before clinical implementation.
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