Resting-State Electroencephalogram Complexity Is Associated With Oral Ketamine Treatment Response: A Bayesian Analysis of Lempel-Ziv Complexity and Multiscale Entropy.
Jules S Mitchell, Toomas E Anijärv, Adem T. Can, Megan Dutton, Daniel F. Hermens, Jim Lagopoulos
Brain and Behavior November 1, 2024 DOI: 10.1002/brb3.70166 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 31 |
| Population | Participants receiving oral ketamine treatment for suicidality |
| Intervention | Oral racemic ketamine |
| Dose | 0.5-3 mg/kg |
| Duration | 6-week intervention, 4-week follow-up (Week 10) |
| Topics | Ketamine Esketamine |
| Keywords | Complexity Electroencephalogram Suicidality Ketamine therapy Brain activity monitoring Suicide prevention EEG Patterns Mental health treatment |
| Key findings | Responders to oral ketamine treatment showed elevated baseline eyes-open EEG complexity (LZC and MSE) compared to nonresponders, with decreases from baseline to post-treatment, localized to the left frontal lobe. |
Abstract
Subanesthetic doses of ketamine are a promising novel treatment for suicidality; however, the evidence for predictive biomarkers is sparse. Recently, measures of complexity, including Lempel-Ziv complexity (LZC) and multiscale entropy (MSE), have been implicated in ketamine's therapeutic action. We evaluated electroencephalogram (EEG)-derived LZC and MSE differences between responders and nonresponders to oral ketamine treatment. A total of 31 participants received six single, weekly (titrated) doses of oral racemic ketamine (0.5-3 mg/kg) and underwent EEG scans at baseline (Week 0), post-treatment (Week 6), and follow-up (Week 10). Resting-state (eyes closed and open) recordings were processed in EEGLAB, and complexity metrics were extracted using the Neurokit2 package. Participants were designated responders or nonresponders by clinical response (Beck Suicide Scale [BSS] score reduction of ≥ 50% from baseline to the respective timepoint or score ≤ 6) and then compared in terms of complexity across resting-state conditions and time. Employing a Bayesian mixed effects model, we found strong evidence that LZC was higher in the eyes-open compared to eyes-closed condition, as were MSE scales 1-3. At a global level, responders displayed elevated eyes-open baseline complexity compared to nonresponders, with these values decreasing from baseline to post-treatment (Week 6) in responders only. Exploratory analyses revealed that the elevated baseline eyes-open LZC in responders was spatially localized to the left frontal lobe (F1, AF3, FC1, and F3). EEG-complexity metrics may be sensitive biomarkers for evaluating and predicting oral ketamine treatment response, with the left prefrontal cortex bein a possible treatment response region.
Comparable studies
Other observational and cohort studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Taming the Ketamine Tiger Volunteers from a prison population | 2010 | Observational study | n = 20 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Surgical patients undergoing induction of anesthesia with intravenous ketamine | 2013 | Observational cohort | n = 30 |
| Do the dissociative side effects of ketamine mediate its antidepressant effects? Treatment-resistant inpatients with major depressive disorder or bipolar disorder | 2014 | Observational cohort | n = 108 |
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
Citations in the library
Cites 19
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Scientific Reports April 19, 2017
- GABA interneurons are the cellular trigger for ketamine's rapid antidepressant actions. Journal of Clinical Investigation November 19, 2019
and 14 more in the library