Resting‐State Electroencephalogram Complexity Is Associated With Oral Ketamine Treatment Response: A Bayesian Analysis of Lempel–Ziv Complexity and Multiscale Entropy

ABSTRACT Introduction 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...

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Main Authors: Jules S. Mitchell, Toomas E. Anijärv, Adem T. Can, Megan Dutton, Daniel F. Hermens, Jim Lagopoulos
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:Brain and Behavior
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Online Access:https://doi.org/10.1002/brb3.70166
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author Jules S. Mitchell
Toomas E. Anijärv
Adem T. Can
Megan Dutton
Daniel F. Hermens
Jim Lagopoulos
author_facet Jules S. Mitchell
Toomas E. Anijärv
Adem T. Can
Megan Dutton
Daniel F. Hermens
Jim Lagopoulos
author_sort Jules S. Mitchell
collection DOAJ
description ABSTRACT Introduction 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. Methods 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. Results 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). Conclusion 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.
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spelling doaj-art-7de1eef21e3549cb92305a3c9fefd0c32024-11-28T14:22:33ZengWileyBrain and Behavior2162-32792024-11-011411n/an/a10.1002/brb3.70166Resting‐State Electroencephalogram Complexity Is Associated With Oral Ketamine Treatment Response: A Bayesian Analysis of Lempel–Ziv Complexity and Multiscale EntropyJules S. Mitchell0Toomas E. Anijärv1Adem T. Can2Megan Dutton3Daniel F. Hermens4Jim Lagopoulos5Thompson Institute University of Sunshine Coast Birtinya Queensland AustraliaThompson Institute University of Sunshine Coast Birtinya Queensland AustraliaThompson Institute University of Sunshine Coast Birtinya Queensland AustraliaThompson Institute University of Sunshine Coast Birtinya Queensland AustraliaThompson Institute University of Sunshine Coast Birtinya Queensland AustraliaThompson Brain & Mind Healthcare Birtinya Queensland AustraliaABSTRACT Introduction 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. Methods 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. Results 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). Conclusion 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.https://doi.org/10.1002/brb3.70166complexityelectroencephalogramketaminesuicidality
spellingShingle Jules S. Mitchell
Toomas E. Anijärv
Adem T. Can
Megan Dutton
Daniel F. Hermens
Jim Lagopoulos
Resting‐State Electroencephalogram Complexity Is Associated With Oral Ketamine Treatment Response: A Bayesian Analysis of Lempel–Ziv Complexity and Multiscale Entropy
Brain and Behavior
complexity
electroencephalogram
ketamine
suicidality
title Resting‐State Electroencephalogram Complexity Is Associated With Oral Ketamine Treatment Response: A Bayesian Analysis of Lempel–Ziv Complexity and Multiscale Entropy
title_full Resting‐State Electroencephalogram Complexity Is Associated With Oral Ketamine Treatment Response: A Bayesian Analysis of Lempel–Ziv Complexity and Multiscale Entropy
title_fullStr Resting‐State Electroencephalogram Complexity Is Associated With Oral Ketamine Treatment Response: A Bayesian Analysis of Lempel–Ziv Complexity and Multiscale Entropy
title_full_unstemmed Resting‐State Electroencephalogram Complexity Is Associated With Oral Ketamine Treatment Response: A Bayesian Analysis of Lempel–Ziv Complexity and Multiscale Entropy
title_short Resting‐State Electroencephalogram Complexity Is Associated With Oral Ketamine Treatment Response: A Bayesian Analysis of Lempel–Ziv Complexity and Multiscale Entropy
title_sort resting state electroencephalogram complexity is associated with oral ketamine treatment response a bayesian analysis of lempel ziv complexity and multiscale entropy
topic complexity
electroencephalogram
ketamine
suicidality
url https://doi.org/10.1002/brb3.70166
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