恐惧反转学习：一种新的恐惧调节手段&#x0002A;

刘欣; 梅颖; 吴奇; 雷怡

doi:10.16719/j.cnki.1671-6981.20240228

PDF(436 KB)

心理科学 ›› 2024, Vol. 47 ›› Issue (2) : 494-501. DOI: 10.16719/j.cnki.1671-6981.20240228

临床与咨询

恐惧反转学习：一种新的恐惧调节手段^*

刘欣, 梅颖, 吴奇, 雷怡^**

作者信息 +

Fear Reversal Learning: A New Method of Fear Regulation

Liu Xin, Mei Ying, Wu Qi, Lei Yi

Author information +

文章历史 +

摘要

恐惧反转学习指在安全和威胁刺激之间发生反转后,个体灵活地调整自身的恐惧反应,是一种适应性的恐惧调节手段。本文以条件性恐惧学习和反转学习为切入点,突出恐惧反转的特点,并从恐惧调节的角度厘清其与恐惧消退的关系,探讨两者神经机制的差异,继而揭示恐惧反转对焦虑障碍临床治疗方面的启示。未来研究可进行脑区发育、衰老与恐惧反转的发展性探索,扩展恐惧反转学习的神经回路以及尝试使用外源性激素干预恐惧反转学习。

Abstract

Fear reversal learning refers to the process in which fear reaction changes between safe and threatening stimuli after the reversal of reinforcement event. It is a novel learning process combining conditioned fear and reversal learning. It reflects the problem of flexibility in fear learning. It is important to flexibly readjust fear behavior when circumstances change. Failure to adapt to the changing environment may lead to anxiety-related mental disorders. Compared with normal people, patients with anxiety usually generalize safe stimuli as threatening stimuli. These irrational fear responses impede the extinction of fearful memory. Therefore, flexible and appropriate responses to threatening and safe signals play a critical role in the adaptive regulation of emotions.
Although the paradigm of fear reversal learning has been constantly developed and innovated in recent years, the basic experimental principle still involves the reversal of a safe stimulus into a threatening stimulus, and vice versa. In fact, related studies usually use physiological (such as skin electricity), behavioral (such as anxiety arousal or valence ratings), and fMRI indicators to measure the fear responses. Moreover, considering that fear reversal learning can effectively reflect the individual's cognitive flexibility, some researchers have used this paradigm to preliminarily explore the pathogenesis of anxiety-related mental disorders. The results show that not all anxiety-related mental disorders will damage the individual's ability of fear reversal learning, but the specific reasons should be discussed in detail in future research.
To date, fear extinction paradigms are the most common model to study the process of shifting from fear to safety. However, the regulation of fear in fear reversal learning requires more flexible and accurate responses. To be specific, the shift from fear and safety and from safety to fear occur simultaneously. Clarifying the relationship between fear reversal and fear extinction can provide new ideas for the diagnosis and treatment of anxiety disorders.
Studies have shown that fear reversal and fear extinction have different neural substrates. the ventromedial prefrontal cortex(vmPFC), the dorsal anterior cingulate cortex(dACC) and amygdala are their overlapping functional brain regions. However, the orbitofrontal cortex(OFC) is the unique functional brain area of fear reversal while hippocampus is that of fear extinction. In general, vmPFC, dACC, amygdala, and hippocampus play a key role in fear extinction. They affect each other and jointly regulate the extinction effect. And vmPFC, dACC, OFC, and amygdala, can be used as functional brain regions related to fear reversal. Specifically, vmPFC is sensitive to CS-. Yet dACC is sensitive to CS+. OFC, and some amygdala cells can quickly adjust emotions and behaviors according to external changes, while other amygdala cells continue to respond according to the initial reinforcement association. In other words, OFC and amygdala are activated to varying degrees in the process of fear reversal, which may be related to the mutual regulation between them.
According to the analysis of the existing research, there are three potential directions for future research. Firstly, future research should improve and innovate the research design. Secondly, it should explore whether there are other relevant brain regions based on the existing neural mechanisms of fear reversal learning. And hormone regulation affecting functional brain regions should also be discussed.

导出引用

刘欣, 梅颖, 吴奇, 雷怡. 恐惧反转学习：一种新的恐惧调节手段^*[J]. 心理科学. 2024, 47(2): 494-501 https://doi.org/10.16719/j.cnki.1671-6981.20240228

Liu Xin, Mei Ying, Wu Qi, Lei Yi. Fear Reversal Learning: A New Method of Fear Regulation[J]. Journal of Psychological Science. 2024, 47(2): 494-501 https://doi.org/10.16719/j.cnki.1671-6981.20240228

参考文献

[1] 雷怡, 梅颖, 张文海, 李红. (2018). 基于知觉的恐惧泛化的认知神经机制. 心理科学进展, 26(8), 1391-1403.
[2] 李德明, 陈天勇. (2006). 认知年老化和老年心理健康. 心理科学进展, 14(4), 560-564.
[3] Apergis-Schoute A. M., Gillan C. M., Fineberg N. A., Fernandez-Egea E., Sahakian B. J., & Robbins T. W. (2017). Neural basis of impaired safety signaling in Obsessive Compulsive Disorder. Proceedings of the National Academy of Sciences of the United States of America, 114(12), 3216-3221.
[4] Barbas, H. (2000). Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices. Brain Research Bulletin, 52(5), 319-330.
[5] Bouton, M. E. (2004). Context and behavioral processes in extinction. Learning and Memory, 11(5), 485-494.
[6] Costa V. D., Bradley M. M., & Lang P. J. (2015a). From threat to safety: Instructed reversal of defensive reactions. Psychophysiology, 52(3), 325-332.
[7] Costa V. D., Tran V. L., Turchi J., & Averbeck B. B. (2015b). Reversal learning and dopamine: A bayesian perspective. The Journal of Neuroscience, 35(6), 2407-2416.
[8] de Carvalho Myskiw J., Benetti F., & Izquierdo I. (2013). Behavioral tagging of extinction learning. Proceedings of the National Academy of Sciences of the United States of America, 110(3), 1071-1076.
[9] Dunsmoor J. E., Kubota J. T., Li J., Coelho C. A. O., & Phelps E. A. (2016). Racial stereotypes impair flexibility of emotional learning. Social Cognitive and Affective Neuroscience, 11(9), 1363-1373.
[10] Eckstein M., Becker B., Scheele D., Scholz C., Preckel K., Schlaepfer T. E., & Hurlemann R. (2015). Oxytocin facilitates the extinction of conditioned fear in humans. Biological Psychiatry, 78(3), 194-202.
[11] Fellows, L. K., & Farah, M. J. (2003). Ventromedial frontal cortex mediates affective shifting in humans: Evidence from a reversal learning paradigm. Brain, 126(8), 1830-1837.
[12] Gruner, P., & Pittenger, C. (2017). Cognitive inflexibility in obsessive-compulsive disorder. Neuroscience, 345, 243-255.
[13] Hermans E. J., Kanen J. W., Tambini A., Fernández G., Davachi L., & Phelps E. A. (2017). Persistence of amygdala-hippocampal connectivity and multi-voxel correlation structures during awake rest after fear learning predicts long-term expression of fear. Cerebral Cortex, 27(5), 3028-3041.
[14] Hoppenbrouwers S. S., Bulten B. H., & Brazil I. A. (2016). Parsing fear: A reassessment of the evidence for fear deficits in psychopathy. Psychological Bulletin, 142(6), 573-600.
[15] Izquierdo A., Brigman J. L., Radke A. K., Rudebeck P. H., & Holmes A. (2017). The neural basis of reversal learning: An updated perspective. Neuroscience, 345, 12-26.
[16] Izquierdo, A., & Jentsch, J. D. (2012). Reversal learning as a measure of impulsive and compulsive behavior in addictions. Psychopharmacology, 219(2), 607-620.
[17] Jones, B., & Mishkin, M. (1972). Limbic lesions and the problem of stimulus—Reinforcement associations. Experimental Neurology, 36(2), 362-377.
[18] Kim J. H., Perry C. J., Ganella D. E., & Madsen H. B. (2017). Postnatal development of neurotransmitter systems and their relevance to extinction of conditioned fear. Neurobiology of Learning and Memory, 138, 252-270.
[19] Knapska, E., & Maren, S. (2009). Reciprocal patterns of c-Fos expression in the medial prefrontal cortex and amygdala after extinction and renewal of conditioned fear. Learning and Memory, 16(8), 486-493.
[20] LeDoux, J. E. (2014). Coming to terms with fear. Proceedings of the National Academy of Sciences of the United States of America, 111(8), 2871-2878.
[21] Lissek S., Bradford D. E., Alvarez R. P., Burton P., Espensen-Sturges T., Reynolds R. C., & Grillon C. (2014). Neural substrates of classically conditioned fear-generalization in humans: A parametric fMRI study. Social Cognitive and Affective Neuroscience, 9(8), 1134-1142.
[22] Lissemore J. I., Nagano-Saito A., Smart K., Gravel P., Leyton M., & Benkelfat C. (2020). Dopaminergic plasticity in the bilateral hippocampus following threat reversal in humans. Scientific Reports, 10(1), Article 7627.
[23] Lonsdorf T. B., Menz M. M., Andreatta M., Fullana M. A., Golkar A., Haaker J., & Merz C. J. (2017). Don' t fear 'fear conditioning': Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear. Neuroscience and Biobehavioral Reviews, 77, 247-285.
[24] Maier S., Szalkowski A., Kamphausen S., Perlov E., Feige B., Blechert J., & Tüscher O. (2012). Clarifying the role of the rostral dmPFC/dACC in fear/anxiety: Learning, appraisal or expression? PLoS ONE, 7(11), Article e50120.
[25] Mao Y., Meng J., Ding C., Wei D. T., Zhang J. F., & Qiu J. (2019). The important role of dACC in shyness. Brain Imaging and Behavior, 13(6), 1756-1765.
[26] Maren, S., & Holmes, A. (2016). Stress and fear extinction. Neuropsychopharmacology, 41(1), 58-79.
[27] Maren S., Phan K. L., & Liberzon I. (2013). The contextual brain: Implications for fear conditioning, extinction and psychopathology. Nature Reviews Neuroscience, 14(6), 417-428.
[28] Marin M. F., Zsido R. G., Song H. J., Lasko N. B., Killgore W. D. S., Rauch S. L., & Milad M. R. (2017). Skin conductance responses and neural activations during fear conditioning and extinction recall across anxiety disorders. JAMA Psychiatry, 74(6), 622-631.
[29] Milad M. R., Orr S. P., Lasko N. B., Chang Y., Rauch S. L., & Pitman R. K. (2008). Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study. Journal of Psychiatric Research, 42(7), 515-520.
[30] Milad, M. R., & Quirk, G. J. (2012). Fear extinction as a model for translational neuroscience: Ten years of progress. Annual Review of Psychology, 63, 129-151.
[31] Milad M. R., Wright C. I., Orr S. P., Pitman R. K., Quirk G. J., & Rauch S. L. (2007). Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biological Psychiatry, 62(5), 446-454.
[32] Morgan M. A., Romanski L. M., & LeDoux J. E. (1993). Extinction of emotional learning: Contribution of medial prefrontal cortex. Neuroscience Letters, 163(1), 109-113.
[33] Morris, J. S., & Dolan, R. J. (2004). Dissociable amygdala and orbitofrontal responses during reversal fear conditioning. NeuroImage, 22(1), 372-380.
[34] Morriss J., Saldarini F., Chapman C., Pollard M., & van Reekum, C. M. (2019, in press). Out with the old and in with the new: The role of intolerance of uncertainty in reversal of threat and safety. Journal of Experimental Psychopathology.
[35] Pervanidou, P., & Chrousos, G. P. (2010). Neuroendocrinology of post-traumatic stress disorder. Progress in Brain Research, 182, 149-160.
[36] Phelps E. A., Delgado M. R., Nearing K. I., & LeDoux J. E. (2004). Extinction learning in humans: Role of the amygdala and vmPFC. Neuron, 43(6), 897-905.
[37] Quirk G. J., Likhtik E., Pelletier J. G., & Paré D. (2003). Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. The Journal of Neuroscience, 23(25), 8800-8807.
[38] Quirk G. J., Russo G. K., Barron J. L., & Lebron K. (2000). The role of ventromedial prefrontal cortex in the recovery of extinguished fear. The Journal of Neuroscience, 20(16), 6225-6231.
[39] Rolls E. T., Critchley H. D., Mason R., & Wakeman E. A. (1996). Orbitofrontal cortex neurons: Role in olfactory and visual association learning. Journal of Neurophysiology, 75(5), 1970-1981.
[40] Savage H. S., Davey C. G., Fullana M. A., & Harrison B. J. (2020a). Clarifying the neural substrates of threat and safety reversal learning in humans. NeuroImage, 207, Article 116427.
[41] Savage H. S., Davey C. G., Fullana M. A., & Harrison B. J. (2020b). Threat and safety reversal learning in social anxiety disorder—an fMRI study. Journal of Anxiety Disorders, 76, Article 102321.
[42] Schiller, D., & Delgado, M. R. (2010). Overlapping neural systems mediating extinction, reversal and regulation of fear. Trends in Cognitive Sciences, 14(6), 268-276.
[43] Schiller D., Levy I., Niv Y., LeDoux J. E., & Phelps E. A. (2008). From fear to safety and back: Reversal of fear in the human brain. The Journal of Neuroscience, 28(45), 11517-11525.
[44] Schoenbaum G., Chiba A. A., & Gallagher M. (2000). Changes in functional connectivity in orbitofrontal cortex and basolateral amygdala during learning and reversal training. The Journal of Neuroscience, 20(13), 5179-5189.
[45] Sehlmeyer C., Dannlowski U., Schöning S., Kugel H., Pyka M., Pfleiderer B., & Konrad C. (2011). Neural correlates of trait anxiety in fear extinction. Psychological Medicine, 41(4), 789-798.
[46] Sierra-Mercado D., Padilla-Coreano N., & Quirk G. J. (2011). Dissociable roles of prelimbic and infralimbic cortices, ventral hippocampus, and basolateral amygdala in the expression and extinction of conditioned fear. Neuropsychopharmacology, 36(2), 529-538.
[47] South M., Newton T., & Chamberlain P. D. (2012). Delayed reversal learning and association with repetitive behavior in autism spectrum disorders. Autism Research, 5(6), 398-406.
[48] Vertes, R. P. (2004). Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse, 51(1), 32-58.
[49] Volkmar F. R., Lord C., Bailey A., Schultz R. T., & Klin A. (2004). Autism and pervasive developmental disorders. Journal of Child Psychology and Psychiatry, 45(1), 135-170.

基金

*本研究得到国家自然科学基金面上项目(32271142,31871130)、广东省“脑科学与类脑研究”重大科技专项：自闭症诊疗方法研究(2018B030335001)、教育部哲学社会科学研究重大课题攻关项目(21JZD063）和深圳科学与技术研究项目（JCYJ20200109144801736）的资助