Hochberger William C, Thomas Michael L, Joshi Yash B, Molina Juan, Treichler Emily B H, Nungaray John, Cardoso Lauren, Sprock Joyce, Swerdlow Neal, Light Gregory A
VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Colorado State University, Department of Psychology, Fort Collins, CO, USA.
Schizophr Res. 2020 Jan;215:97-104. doi: 10.1016/j.schres.2019.11.015. Epub 2019 Nov 20.
Auditory-based targeted cognitive training (TCT) is an effective and well-validated intervention for the treatment of cognitive impairment in schizophrenia patients. Improvements in higher-order cognition, reductions in symptom severity, and increases in psychosocial functioning secondary to TCT are thought to be driven by "bottom-up" enhancement of early auditory information processing (EAIP). Despite strong evidence of efficacy at the group level, there is significant variability in response to TCT, with few well-delineated biomarkers for predicting individual benefit. EEG biomarkers of EAIP are indicators of early-treatment sensitivity that predict full-course TCT outcome; however, further characterization is necessary for biomarker-guided clinical trials. The current study examined baseline and early-treatment sensitivity (i.e., change from baseline after 1 h) in theta band oscillatory activity to deviant stimuli as moderators of full course (30 h) TCT response in treatment-refractory schizophrenia patients randomly assigned to receive either treatment-as-usual (TAU; n = 22) or TAU augmented with TCT (n = 30). Theta evoked power and phase locking at baseline predicted patient improvements in global cognitive function after 30 h of TCT. Decrease in theta activity to deviant stimuli after 1 h of TCT predicted improvements in verbal learning after 30 h. Exploratory analyses using EEG composite scores had high levels of sensitivity and specificity for identifying patients most likely to benefit from TCT. The integrity of baseline neurophysiologic activity associated with EAIP, as well as the sensitivity of the underlying circuity to change, likely reflects an intermediate therapeutic process underlying the effectiveness of TCT that can be used to predict patient response to treatment.
基于听觉的靶向认知训练（TCT）是一种有效且经过充分验证的干预措施，用于治疗精神分裂症患者的认知障碍。高阶认知的改善、症状严重程度的降低以及TCT继发的社会心理功能的提高被认为是由早期听觉信息处理（EAIP）的“自下而上”增强所驱动的。尽管在群体水平上有强有力的疗效证据，但对TCT的反应存在显著差异，几乎没有明确的生物标志物来预测个体受益情况。EAIP的脑电图生物标志物是早期治疗敏感性的指标，可预测全程TCT结果；然而，为了进行生物标志物指导的临床试验，还需要进一步的特征描述。本研究在难治性精神分裂症患者中，检查了θ波段振荡活动对异常刺激的基线和早期治疗敏感性（即1小时后相对于基线的变化），作为全程（30小时）TCT反应的调节因素，这些患者被随机分配接受常规治疗（TAU；n = 22）或TAU联合TCT（n = 30）。基线时的θ诱发功率和锁相预测了TCT 30小时后患者整体认知功能的改善。TCT 1小时后对异常刺激的θ活动降低预测了30小时后言语学习的改善。使用脑电图综合评分的探索性分析在识别最可能从TCT中受益的患者方面具有较高的敏感性和特异性。与EAIP相关的基线神经生理活动的完整性，以及潜在回路对变化的敏感性，可能反映了TCT有效性背后的一个中间治疗过程，可用于预测患者对治疗的反应。
