1 Psychiatric Centre Copenhagen, Copenhagen University Hospital, Denmark.
2 Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Denmark.
J Psychopharmacol. 2018 Oct;32(10):1075-1085. doi: 10.1177/0269881118783334. Epub 2018 Jul 4.
Cognitive deficits are prevalent in bipolar disorder during remission but effective cognition treatments are lacking due to insufficient insight into the neurobiological targets of cognitive improvement. Emerging data suggest that dorsal prefrontal cortex target engagement is a key neurocircuitry biomarker of pro-cognitive treatment effects.
In this randomized controlled functional magnetic resonance imaging study, we test this hypothesis by investigating the effects of an ineffective cognitive remediation intervention on dorsal prefrontal response during strategic memory encoding and working memory engagement.
Bipolar disorder patients in partial remission with subjective cognitive difficulties were randomized to receive 12-week group-based cognitive remediation ( n = 13) or to continue their standard treatment ( n = 14). The patients performed a strategic episodic picture encoding task and a spatial n-back working memory task under functional magnetic resonance imaging at baseline and following cognitive remediation or standard treatment.
The right dorsolateral prefrontal cortex was commonly activated by both strategic memory tasks across all patients. The task-related prefrontal engagement was not altered by cognitive remediation relative to standard treatment. The dorsolateral prefrontal cortex response was not significantly associated with recall accuracy or working memory performance.
As hypothesized, no task-related change in prefrontal activity was observed in a negative cognitive remediation trial in remitted bipolar disorder patients. By complementing previous findings linking cognitive improvement with increased dorsolateral prefrontal cortex engagement, our negative findings provide additional validity evidence to the dorsal prefrontal target engagement biomarker model of cognitive improvement by strengthening the proposed causality between modulation of dorsolateral prefrontal cortex engagement and pro-cognitive effects.
尽管在缓解期双相情感障碍患者中认知缺陷很常见，但由于对认知改善的神经生物学靶点缺乏足够的了解，有效的认知治疗方法仍然缺乏。新出现的数据表明，背外侧前额叶皮层的靶点激活是认知改善治疗效果的关键神经回路生物标志物。
在这项随机对照功能磁共振成像研究中，我们通过研究无效认知矫正干预对策略性记忆编码和工作记忆参与期间背外侧前额叶反应的影响来检验这一假设。
部分缓解期且有主观认知困难的双相情感障碍患者被随机分为接受 12 周基于小组的认知矫正（n=13）或继续标准治疗（n=14）。患者在基线和认知矫正或标准治疗后进行了策略性情景图片编码任务和空间 n 回工作记忆任务的功能磁共振成像。
所有患者的右侧背外侧前额叶皮层在两个策略性记忆任务中均被共同激活。与标准治疗相比，认知矫正并没有改变与任务相关的前额叶激活。前额叶反应与回忆准确性或工作记忆表现无显著相关性。
正如假设的那样，在缓解期双相情感障碍患者的阴性认知矫正试验中，没有观察到与任务相关的前额叶活动变化。通过补充先前将认知改善与背外侧前额叶皮层参与增加联系起来的发现，我们的阴性发现通过加强背外侧前额叶皮层参与和认知改善之间的拟议因果关系，为认知改善的背外侧前额叶靶点参与生物标志物模型提供了额外的有效性证据。
