Thompson Institute, University of Sunshine Coast, Birtinya, Queensland, Australia.
Department of Clinical Sciences Malmö, Faculty of Medicine, Clinical Memory Research Unit, Lund University, Lund, Sweden.
Brain Behav. 2024 Nov;14(11):e70166. doi: 10.1002/brb3.70166.
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.
亚麻醉剂量的氯胺酮是一种有前途的新型自杀治疗方法；然而，预测生物标志物的证据很少。最近，复杂性的度量，包括莱姆尔-泽维复杂度（LZC）和多尺度熵（MSE），与氯胺酮的治疗作用有关。我们评估了口服氯胺酮治疗的反应者和非反应者之间脑电图（EEG）衍生的 LZC 和 MSE 差异。
共有 31 名参与者接受了六次单次、每周（滴定）口服外消旋氯胺酮（0.5-3mg/kg）治疗，并在基线（第 0 周）、治疗后（第 6 周）和随访（第 10 周）进行 EEG 扫描。静息状态（闭眼和睁眼）记录在 EEGLAB 中进行处理，并使用 Neurokit2 包提取复杂性指标。根据临床反应（贝克自杀量表[BSS]评分从基线到相应时间点降低≥50%或评分≤6）将参与者指定为反应者或非反应者，然后比较静息状态条件和时间的复杂性。
采用贝叶斯混合效应模型，我们发现有力证据表明，与闭眼相比，睁眼时 LZC 更高，MSE 尺度 1-3 也是如此。在全局水平上，与非反应者相比，反应者的睁眼基线复杂性更高，只有反应者的这些值从基线到治疗后（第 6 周）下降。探索性分析表明，反应者睁眼基线 LZC 升高的部位局限于左额叶（F1、AF3、FC1 和 F3）。
EEG 复杂性指标可能是评估和预测口服氯胺酮治疗反应的敏感生物标志物，左前额叶皮层可能是治疗反应的区域。
