Apergis-Schoute Annemieke M, Gillan Claire M, Fineberg Naomi A, Fernandez-Egea Emilio, Sahakian Barbara J, Robbins Trevor W
Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom;
Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom.
Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3216-3221. doi: 10.1073/pnas.1609194114. Epub 2017 Mar 6.
The ability to assign safety to stimuli in the environment is integral to everyday functioning. A key brain region for this evaluation is the ventromedial prefrontal cortex (vmPFC). To investigate the importance of vmPFC safety signaling, we used neuroimaging of Pavlovian fear reversal, a paradigm that involves flexible updating when the contingencies for a threatening (CS+) and safe (CS-) stimulus reverse, in a prototypical disorder of inflexible behavior influenced by anxiety, Obsessive Compulsive Disorder (OCD). Skin conductance responses in OCD patients ( = 43) failed to differentiate during reversal compared with healthy controls ( = 35), although significant differentiation did occur during early conditioning and amygdala BOLD signaling was unaffected in these patients. Increased vmPFC activation (for CS+ > CS-) during early conditioning predicted the degree of generalization in OCD patients during reversal, whereas vmPFC safety signals were absent throughout learning in these patients. Regions of the salience network (dorsal anterior cingulate, insula, and thalamus) showed early learning task-related hyperconnectivity with the vmPFC in OCD, consistent with biased processing of the CS+. Our findings reveal an absence of vmPFC safety signaling in OCD, undermining flexible threat updating and explicit contingency knowledge. Although differential threat learning can occur to some extent in the absence of vmPFC safety signals, effective CS- signaling becomes crucial during conflicting threat and safety cues. These results promote further investigation of vmPFC safety signaling in other anxiety disorders, with potential implications for the development of exposure-based therapies, in which safety signaling is likely to play a key role.
在环境中为刺激赋予安全性的能力是日常功能不可或缺的一部分。进行这种评估的一个关键脑区是腹内侧前额叶皮质(vmPFC)。为了研究vmPFC安全信号的重要性,我们对巴甫洛夫式恐惧逆转进行了神经成像研究,这是一种在受焦虑影响的刻板行为典型疾病——强迫症(OCD)中,当威胁性(CS+)和安全性(CS-)刺激的意外情况发生逆转时涉及灵活更新的范式。与健康对照组(n = 35)相比,强迫症患者(n = 43)在逆转过程中的皮肤电导反应未能区分,尽管在早期条件反射期间确实发生了显著区分,并且这些患者的杏仁核BOLD信号未受影响。早期条件反射期间vmPFC激活增加(CS+ > CS-)可预测强迫症患者在逆转过程中的泛化程度,而这些患者在整个学习过程中均不存在vmPFC安全信号。显著性网络区域(背侧前扣带回、岛叶和丘脑)在强迫症中显示出与vmPFC早期学习任务相关的过度连接,这与CS+的偏向性加工一致。我们的研究结果揭示了强迫症患者中不存在vmPFC安全信号,这破坏了灵活的威胁更新和明确的意外情况知识。尽管在没有vmPFC安全信号的情况下,某种程度的差异威胁学习可能会发生,但在冲突的威胁和安全线索期间,有效的CS-信号变得至关重要。这些结果促进了对其他焦虑症中vmPFC安全信号的进一步研究,这可能对基于暴露的疗法的发展具有潜在意义,在这种疗法中安全信号可能起着关键作用。