Ketamine-induced re-organisation of neural oscillations across health, MDD, and TRD: A systematic review of magnetoencephalography insights

Aug 29, 2025Journal of affective disorders

Ketamine’s effects on brain wave patterns in healthy people, depression, and hard-to-treat depression

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Abstract

A single ketamine infusion reduces MADRS scores by 10-12 points within 4-9 hours in major depressive disorder and treatment-resistant depression.

Magnetoencephalography recordings reveal rapid changes in brain activity associated with ketamine's antidepressant effects.
Increased gamma-band power and reduced alpha and beta activity are consistently observed after ketamine administration.
Enhanced connectivity in thalamocortical and frontoparietal networks is noted, suggesting alterations in glutamate signaling.
Preliminary markers in responders include higher anterior cingulate activity and elevated baseline gamma power compared to non-responders.
Further validation in larger studies is necessary to confirm the predictive value of observed MEG signatures.

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Sub-anesthetic ketamine (KT) has become a promising rapid-acting antidepressant candidate, yet its mechanisms have not been comprehensively defined. Magnetoencephalography (MEG) provides millisecond recordings of cortical rhythms, exposing the rapid glutamatergic dynamics underlying ketamine's action. We synthesized evidence on KT-induced oscillatory and connectivity changes in healthy volunteers (HVs), major depressive disorder (MDD) and treatment-resistant depression (TRD), relating neural signatures to symptomatic relief. Following PRISMA and a PROSPERO-registered protocol (CRD42024609670), five databases were searched to June 2025; eighteen eligible trials (605 adults: 242 HVs, 176 MDD, 172 TRD; 41.65 % female; mean Jadad = 3.3) administered intravenous KT ≤ 0.5 mg/kg and reported MEG outcomes. Exploratory trials indicate that a single ketamine infusion reduces MADRS scores by 10-12 points within 4-9 h in MDD and TRD and improves anxiety, psychosis and suicidality, although small sample sizes limit generalisability. MEG studies consistently report increased gamma-band (30-90 Hz) power, posterior alpha and beta suppression, reduced envelope connectivity and enhanced directed flow in thalamocortical and frontoparietal networks, glutamatergic disinhibition and network renormalisation. Task-evoked data show larger M100 and M170 responses, stronger NMDA-mediated feed-forward drive from somatosensory to inferior-frontal cortex and limbic gamma modulation. Preliminary markers such as higher pre-infusion anterior cingulate activity, elevated baseline gamma power and reduced pgACC beta rebound in responders versus delta and alpha coupling in non-responders require validation in larger cohorts and meta-analyses. KT appears to induce a reproducible MEG signature that may track and potentially forecast its rapid antidepressant effects, but such predictive claims remain provisional pending rigorous replication.

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Ketamine-induced re-organisation of neural oscillations across health, MDD, and TRD: A systematic review of magnetoencephalography insights

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