Ott Caroline V, Macoveanu Julian, Bowie Christopher R, Fisher Patrick M, Knudsen Gitte M, Kessing Lars V, Miskowiak Kamilla W
Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Psychology, Queen's University, Kingston, ON, Canada.
Neuropsychopharmacology. 2021 May;46(6):1113-1121. doi: 10.1038/s41386-020-00901-7. Epub 2020 Nov 9.
Cognitive impairment is prevalent in bipolar disorder (BD) but treatments with pro-cognitive effects are lacking. Insight concerning the neurocircuitry of cognitive improvement could provide a biomarker for pro-cognitive effects to advance treatment development. The dorsal prefrontal cortex (dPFC) is a promising region for such treatment target engagement. The aim of this functional magnetic resonance imaging (fMRI) study was to examine the effects of action-based cognitive remediation (ABCR) on early change in the dPFC blood-oxygen-level-dependent response in patients with BD in remission, and whether the observed neural change predicted improved executive functions following 10 weeks of treatment. Forty-five participants with remitted BD (ABCR: n = 26, control treatment: n = 19) completed a spatial n-back working memory task during fMRI and executive function tasks outside the scanner before and after two weeks of ABCR/control treatment, and an additional assessment of executive function at treatment completion. Thirty-four healthy controls underwent a single fMRI and executive function assessment for baseline comparisons. We found an early reversal of pretreatment hypo-activity in the dorsolateral prefrontal cortex (dlPFC) following ABCR vs. control during both high-load (2-back > 1-back) working memory (WM) (F(1,43) = 5.69, p = 0.02, η = 0.12) and general WM (2-back > 0-back) (F(1,43) = 5.61, p = 0.02, η = 0.12). This dlPFC activity increase predicted improved executive functions at treatment completion (high-load WM: B = -0.45, p = 0.01, general WM: B = -0.41, p < 0.01), independent of changes in subsyndromal symptoms. In conclusion, early dPFC increase may provide a neurocircuitry-based biomarker for pro-cognitive effects. Future cognition trials should include fMRI assessments to confirm the validity of this putative biomarker model across disorders with cognitive impairment.
认知障碍在双相情感障碍（BD）中很常见，但缺乏具有促认知作用的治疗方法。对认知改善神经回路的深入了解可以为促认知作用提供生物标志物，以推动治疗方法的发展。背外侧前额叶皮质（dPFC）是实现这种治疗靶点的一个很有前景的区域。这项功能磁共振成像（fMRI）研究的目的是，研究基于行动的认知康复训练（ABCR）对缓解期BD患者dPFC血氧水平依赖反应早期变化的影响，以及观察到的神经变化是否能预测10周治疗后执行功能的改善。45名缓解期BD患者（ABCR组：n = 26，对照治疗组：n = 19）在接受ABCR/对照治疗两周前后，于fMRI期间完成了一项空间n-back工作记忆任务，并在扫描器外完成了执行功能任务，治疗结束时还进行了额外的执行功能评估。34名健康对照者接受了一次fMRI和执行功能评估，用于基线比较。我们发现，在高负荷（2-back > 1-back）工作记忆（WM）（F(1,43) = 5.69，p = 0.02，η = 0.12）和一般WM（2-back > 0-back）（F(1,43) = 5.61，p = 0.02，η = 0.12）过程中，ABCR组与对照组相比，背外侧前额叶皮质（dlPFC）治疗前的低活性出现了早期逆转。这种dlPFC活性增加预测了治疗结束时执行功能的改善（高负荷WM：B = -0.45，p = 0.01，一般WM：B = -0.41，p < 0.01），且与亚综合征症状的变化无关。总之，早期dPFC活性增加可能为促认知作用提供一种基于神经回路的生物标志物。未来的认知试验应包括fMRI评估，以确认这种假定生物标志物模型在伴有认知障碍的各种疾病中的有效性。
