Balderston Nicholas L, Vytal Katherine E, O'Connell Katherine, Torrisi Salvatore, Letkiewicz Allison, Ernst Monique, Grillon Christian
Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
Depress Anxiety. 2017 Jan;34(1):25-36. doi: 10.1002/da.22518. Epub 2016 Apr 25.
Anxiety patients exhibit deficits in cognitive tasks that require prefrontal control of attention, including those that tap working memory (WM). However, it is unclear whether these deficits reflect threat-related processes or symptoms of the disorder. Here, we distinguish between these hypotheses by determining the effect of shock threat versus safety on the neural substrates of WM performance in anxiety patients and healthy controls.
Patients, diagnosed with generalized and/or social anxiety disorder, and controls performed blocks of an N-back WM task during periods of safety and threat of shock. We recorded blood-oxygen-level dependent (BOLD) activity during the task, and investigated the effect of clinical anxiety (patients vs. controls) and threat on WM load-related BOLD activation.
Behaviorally, patients showed an overall impairment in both accuracy and reaction time compared to controls, independent of threat. At the neural level, patients showed less WM load-related activation in the dorsolateral prefrontal cortex, a region critical for cognitive control. In addition, patients showed less WM load-related deactivation in the ventromedial prefrontal cortex and posterior cingulate cortex, which are regions of the default mode network. Most importantly, these effects were not modulated by threat.
This work suggests that the cognitive deficits seen in anxiety patients may represent a key component of clinical anxiety, rather than a consequence of threat.
焦虑症患者在需要前额叶对注意力进行控制的认知任务中表现出缺陷,包括那些涉及工作记忆(WM)的任务。然而,尚不清楚这些缺陷是反映了与威胁相关的过程还是该疾病的症状。在此,我们通过确定电击威胁与安全对焦虑症患者和健康对照者工作记忆表现的神经基质的影响,来区分这些假设。
被诊断患有广泛性焦虑症和/或社交焦虑症的患者以及对照者在安全和电击威胁期间执行N-回溯工作记忆任务的组块。我们在任务期间记录了血氧水平依赖(BOLD)活动,并研究了临床焦虑(患者与对照者)和威胁对与工作记忆负荷相关的BOLD激活的影响。
在行为上,与对照者相比,患者在准确性和反应时间方面均表现出总体受损,与威胁无关。在神经层面,患者在背外侧前额叶皮层(对认知控制至关重要的区域)中与工作记忆负荷相关的激活较少。此外,患者在腹内侧前额叶皮层和后扣带回皮层(默认模式网络的区域)中与工作记忆负荷相关的失活较少。最重要的是,这些效应不受威胁的调节。
这项研究表明,焦虑症患者中出现的认知缺陷可能代表临床焦虑的一个关键组成部分,而不是威胁的结果。