Neurocognition and Emotion in Affective Disorders (NEAD) Group, Copenhagen Affective Disorders Research Center (CADIC), Psychiatric Centre Copenhagen, Rigshospitalet Dep. 6233, Blegdamsvej 9, 2100 Copenhagen, Denmark.; Department of Psychology, University of Copenhagen, Østre Farimagsgade 2A, 1353 Copenhagen, Denmark.
Neurocognition and Emotion in Affective Disorders (NEAD) Group, Copenhagen Affective Disorders Research Center (CADIC), Psychiatric Centre Copenhagen, Rigshospitalet Dep. 6233, Blegdamsvej 9, 2100 Copenhagen, Denmark.; Department of Psychology and Behavioural Sciences, Bartholins Allé 11, Aarhus University, Aarhus, Denmark.
Eur Neuropsychopharmacol. 2021 Jun;47:1-10. doi: 10.1016/j.euroneuro.2021.02.013. Epub 2021 Mar 13.
Cognitive impairments in bipolar disorder (BD) are prevalent but effective treatments with replicated and lasting pro-cognitive effects are lacking. Treatment development is hampered by a lack of neurocircuitry biomarkers to predict treatment efficacy. Action-Based Cognitive Remediation (ABCR) improves executive function in BD and this was accompanied by increased dorsal prefrontal cortex (dPFC) response during working memory (WM) after two weeks of treatment. This study investigated whether pre-treatment WM-related dPFC response, executive dysfunction and/or subjective cognitive difficulties predicted ABCR treatment response on executive functions. Forty-five patients with fully or partially remitted BD (ABCR: n = 25, control treatment: n = 20) in our ABCR trial completed a spatial N-back WM task during functional magnetic resonance imaging (fMRI) at baseline. Patients also completed neuropsychological tests and rated their cognitive functions before and after 10 weeks of ABCR or control treatment. Multiple linear regression analyses were conducted to assess whether pre-treatment dPFC response, objective executive impairment and/or subjective cognitive difficulties predicted greater ABCR-related improvements of executive function. We found that treatment-related improvement in executive function was predicted by more WM-related dPFC hypo-activity at baseline (p = 0.03) in linear regression analyses adjusted for age, gender and education. In contrast, there was only a non-significant trend towards more executive dysfunction at baseline predicting greater ABCR-related executive improvement (p = 0.08). Subjective cognitive difficulties at baseline showed no association with treatment effects (p = 0.16). In conclusion, pre-treatment dPFC hypo-activity during WM performance predicts greater effects of ABCR treatment on executive function and may represent a neurocircuitry biomarker for treatment efficacy in this cognitive domain.
双相情感障碍（BD）患者认知障碍普遍存在，但缺乏具有复制和持久认知效果的有效治疗方法。由于缺乏预测治疗效果的神经回路生物标志物，治疗的发展受到了阻碍。基于行动的认知矫正（ABCR）可改善 BD 的执行功能，并且在治疗两周后，在工作记忆（WM）期间，背外侧前额叶皮层（dPFC）的反应增加。这项研究调查了 WM 相关的 dPFC 反应、执行功能障碍和/或主观认知困难是否可以预测 ABCR 对执行功能的治疗反应。在我们的 ABCR 试验中，45 名完全或部分缓解的 BD 患者（ABCR：n=25，对照治疗：n=20）在基线时完成了功能磁共振成像（fMRI）期间的空间 N-back WM 任务。患者还在接受 ABCR 或对照治疗 10 周之前和之后完成了神经心理学测试并对其认知功能进行了评分。进行了多元线性回归分析，以评估基线时 dPFC 反应、客观执行功能障碍和/或主观认知困难是否可以预测 ABCR 相关的执行功能改善。我们发现，在调整年龄、性别和教育的线性回归分析中，基线时 WM 相关的 dPFC 活动减少与治疗相关的执行功能改善相关（p=0.03）。相比之下，基线时的执行功能障碍越大，与 ABCR 相关的执行功能改善越大，但这只是一种非显著趋势（p=0.08）。基线时的主观认知困难与治疗效果无关（p=0.16）。总之，WM 表现期间的基线 dPFC 活动减少预测了 ABCR 治疗对执行功能的更大影响，并且可能代表了该认知领域治疗效果的神经回路生物标志物。
