Laureate Institute for Brain Research Tulsa OK USA.
Department of Community Medicine University of Tulsa Tulsa OK USA.
Brain Behav. 2017 Jul 11;7(8):e00757. doi: 10.1002/brb3.757. eCollection 2017 Aug.
Mood and anxiety disorders are characterized by altered prefrontal-amygdala function and increased behavioral inhibition (BI) in response to potential threat. Whether these alterations constitute a vulnerability or a symptom of illness remains unclear. The medial orbitofrontal cortex (mOFC) is thought to play a central role in estimating probability and cost of threat, in turn informing selection of subsequent behaviors. To better understand the behavioral and neural processes that may be associated with risk for psychopathology, we used a virtual reality paradigm to examine behavioral and neural responses of psychiatrically healthy adults with familial history of affective disorders during anticipation of unpredictable threat.
Twenty psychiatrically healthy adults with high familial risk for affective disorders and 20 low-risk matched controls underwent functional magnetic resonance imaging concurrent with a paradigm in which they explored virtual contexts associated with the threat of shock or safety from shock. Subjective anxiety ratings, skin conductance, exploratory behavior, and neural responses were examined for threat versus safe conditions.
High-risk adults evidenced greater right mOFC activation, as well as greater BI, compared to low-risk adults. There were no significant group differences in subjective ratings or autonomic responses. Individuals exhibiting greater activity in the right mOFC showed greater BI and decreased skin conductance response.
These results suggest that BI and mOFC recruitment during anticipation of aversive outcomes may reflect a vulnerability for affective disorders. However, such a response may also serve as a compensatory response, protecting these high-risk individuals from negative outcomes (i.e., increased physiological arousal). These results suggest that the OFC may play a central role in driving threat-related behaviors and thus may be a target for efforts aimed at early detection or prevention.
情绪和焦虑障碍的特征是前额叶-杏仁核功能改变，以及对潜在威胁的行为抑制增加（BI）。这些改变是疾病的易感性还是症状尚不清楚。中眶额皮质（mOFC）被认为在估计威胁的概率和成本方面起着核心作用，进而影响后续行为的选择。为了更好地理解可能与精神病理学风险相关的行为和神经过程，我们使用虚拟现实范式来检查有情感障碍家族史的精神健康成年人在预期不可预测威胁时的行为和神经反应。
20 名有情感障碍家族高风险的精神健康成年人和 20 名低风险匹配对照者在进行功能磁共振成像的同时，参与了一个范式，他们在这个范式中探索与电击威胁或电击安全相关的虚拟环境。对威胁与安全条件下的主观焦虑评分、皮肤电导率、探索性行为和神经反应进行了检查。
与低风险成年人相比，高风险成年人的右侧 mOFC 活动增加，BI 也增加。两组在主观评分或自主反应方面没有显著差异。在右侧 mOFC 表现出更大活动的个体表现出更大的 BI 和减少的皮肤电导率反应。
这些结果表明，在预期不良结果时的 BI 和 mOFC 募集可能反映了情感障碍的易感性。然而，这种反应也可能是一种代偿性反应，保护这些高风险个体免受负面结果（即增加的生理唤醒）。这些结果表明，OFC 在驱动与威胁相关的行为方面起着核心作用，因此可能是旨在早期检测或预防的努力的目标。
