Identifying the impact of unconscious fear on adolescent anxiety: Cognitive neural mechanisms and interventions

doi:10.3724/SP.J.1042.2024.01221

Abstract

Abstract: Fear plays an important role in the development of anxiety disorders, with abnormalities in conditioned fear—specifically in the aspects of conditioning, generalization, and extinction—being central mechanisms. Neuroimaging evidence suggests that overreactivity of the amygdala and insufficient prefrontal modulation are key factors in the abnormal processing of fear among adolescents. This phenomenon is attributed to the earlier maturation of the amygdala compared to the prefrontal cortex, with the volume of the amygdala peaking during adolescence. Fear can manifest at both conscious and unconscious levels. Unconscious fear is automatic and not directly accessible to introspection. It's closely linked to anxiety-related symptoms because it can trigger physiological and psychological responses without the individual consciously recognizing the source of the threat. Adolescents are particularly sensitive to unconscious fear due to the ongoing development of their brains. Yet, current research on unconscious fear and its neural underpinnings in adolescents is limited. Thus, exploring unconscious fear could shed light on the developmental mechanisms underlying anxiety in adolescents. Traditional CBT focuses on altering maladaptive thought patterns and behaviors associated with anxiety, requiring a level of self-awareness and cognitive maturity that adolescents may not fully possess. Pharmacological treatments, on the other hand, target the biochemical aspects of anxiety but can come with side effects that may affect compliance and overall well-being. Examining the effects of neurofeedback on the unconscious fear in adolescents has the potential to significantly improve the efficacy of anxiety treatments in this age group.
This study aims to investigate the development and cognitive neural mechanisms of unconscious fear in adolescents, uncovering its role in the development of anxiety disorders, and exploring neurofeedback intervention techniques. Study 1 primarily investigates the dynamic change patterns of neural circuits related to unconscious fear processing in adolescents from a developmental perspective. It examines the cognitive neural mechanisms of unconscious fear processing in adolescents, utilizing the Pavlovian conditioning paradigm. Furthermore, it explores the role of chronic stress in the modulation of conditioned fear acquisition, extinction, and generalization. Study 1 aims to provide new insights into why anxiety susceptibility is higher in adolescence and uncover potential reasons for the increased prevalence of anxiety disorders in this age group. Study 2 aims to examine unconscious fear in adolescents with different types of anxiety disorders, highlighting potential differences in brain region activation patterns across these disorders. Together, the two studies offer a comprehensive view of adolescent anxiety, enhancing our understanding and management strategies. We anticipate that the results of Studies 1 and 2 will collectively indicate a pattern of either prefrontal underdevelopment in healthy adolescents or prefrontal underactivation in adolescents with anxiety disorders. Study 3 focuses on the prefrontal neural mechanisms, particularly targeting the vmPFC (ventromedial prefrontal cortex), to investigate the effects of neurofeedback on unconscious fear processing in adolescents. This has significant implications for the optimization of treatment methods for adolescent anxiety disorders.
Considering that the amygdala develops during adolescence, but the prefrontal cortex is still maturing, adolescents are more likely to have stronger unconscious fear responses. Therefore, the current research is expected to offer substantial insights into the psychopathological frameworks that underpin anxiety among adolescents. Furthermore, the capacity of neurofeedback to target the brain's fear circuits directly might offer a faster, more efficient means to reduce anxiety by helping adolescents learn to regulate their own brain activity associated with fear responses. This could help them manage anxiety better and for longer, giving them skills that traditional treatments may not fully realize. The current research could significantly enhance our understanding and treatment of anxiety disorders in adolescents, offering a complementary or alternative option that is both innovative and tailored to their developmental stage.

Key words: fear, anxiety disorders, adolescent, cognitive neural mechanism, fear extinction

CLC Number:

B844
B845

LEI Yi, MEI Ying, Wang Jinxia, YUAN Zixin. Identifying the impact of unconscious fear on adolescent anxiety: Cognitive neural mechanisms and interventions[J]. Advances in Psychological Science, 2024, 32(8): 1221-1232.

References

[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] 雷怡, 王金霞, 陈庆飞, 张文海, 梅颖. (2017). 分类和概念对恐惧泛化的影响机制.心理科学, 40(5), 1266-1273.
[3] 刘佳宁, 吴奇, 谢涛, 俄眉, 王金霞, 雷怡. (2021). 应激激素对恐惧消退作用的神经生理机制.心理科学, (3), 559-566.
[4] 周晓, 赵一燕, 黄砾卉, 雷怡. (2022). 恐惧学习的发展认知神经机制研究回顾与展望.心理发展与教育, 38(2), 295-304.
[5] Bertini C., Cecere R., & Làdavas E. (2013). I am blind, but I "see" fear.Cortex, 49(4), 985-993.
[6] Bittner A., Egger H. L., Erkanli A., Costello E. J., Foley D. L., & Angold A. (2007). What do childhood anxiety disorders predict?Journal of Child Psychology and Psychiatry, 48(12), 1174-1183.
[7] Britton J. C., Grillon C., Lissek S., Norcross M. A., Szuhany K. L., Chen G., .. Pine D. S. (2013). Response to learned threat: An FMRI study in adolescent and adult anxiety.The American Journal of Psychiatry, 170(10), 1195-1204.
[8] Caballero A., Granberg R., & Tseng K. Y. (2016). Mechanisms contributing to prefrontal cortex maturation during adolescence. Neuroscience & Biobehavioral Reviews, 70, 4-12.
[9] Cho J. H., Deisseroth K., & Bolshakov V. Y. (2013). Synaptic encoding of fear extinction in mPFC-amygdala circuits. Neuron, 80(6), 1491-1507.
[10] Ciocchi S., Herry C., Grenier F., Wolff S. B., Letzkus J. J., Vlachos I., .. Lüthi A. (2010). Encoding of conditioned fear in central amygdala inhibitory circuits.Nature, 468(7321), 277-282.
[11] Collins, D. R., & Paré, D. (2000). Differential fear conditioning induces reciprocal changes in the sensory responses of lateral amygdala neurons to the CS (+) and CS (-).Learning & Memory, 7(2), 97-103.
[12] Craske, M. G., & Stein, M. B. (2016). Anxiety.Lancet, 388(10063), 3048-3059.
[13] Dou H., Lei Y., Cheng X., Wang J., & Leppänen P. (2020). Social exclusion influences conditioned fear acquisition and generalization: A mediating effect from the medial prefrontal cortex.NeuroImage, 218, 116735.
[14] El-Bar N., Laufer O., Yoran-Hegesh R., & Paz R. (2017). Over-generalization in youth with anxiety disorders.Social Neuroscience, 12(1), 76-85.
[15] Esteves F., Parra C., Dimberg U., & Ohman A. (1994). Nonconscious associative learning: Pavlovian conditioning of skin conductance responses to masked fear-relevant facial stimuli.Psychophysiology, 31(4), 375-385.
[16] Ganella D. E., Drummond K. D., Ganella E. P., Whittle S., & Kim J. H. (2018). Extinction of Conditioned Fear in Adolescents and Adults: A Human fMRI Study.Frontiers in Human Neuroscience, 11, 647.
[17] Ginsburg G. S., Becker E. M., Keeton C. P., Sakolsky D., Piacentini J., Albano A. M., .. Kendall P. C. (2014). Naturalistic follow-up of youths treated for pediatric anxiety disorders.JAMA Psychiatry, 71(3), 310-318.
[18] Greenberg T., Carlson J. M., Cha J., Hajcak G., & Mujica-Parodi L. R. (2013). Neural reactivity tracks fear generalization gradients.Biological Psychology, 92(1), 2-8.
[19] Hare T. A., Tottenham N., Galvan A., Voss H. U., Glover G. H., & Casey B. J. (2008). Biological substrates of emotional reactivity and regulation in adolescence during an emotional go-nogo task.Biological Psychiatry, 63(10), 927-934.
[20] Hu S., Pruessner J. C., Coupé P., & Collins D. L. (2013). Volumetric analysis of medial temporal lobe structures in brain development from childhood to adolescence. NeuroImage, 74, 276-287.
[21] James, A. C., James, G., Cowdrey, F. A., Soler, A., & Choke, A. (2013). Cognitive behavioural therapy for anxiety disorders in children and adolescents. The Cochrane Database of Systematic Reviews, (6), CD004690.
[22] Killgore W. D., Britton J. C., Schwab Z. J., Price L. M., Weiner M. R., Gold A. L., .. Rauch S. L. (2014). Cortico-limbic responses to masked affective faces across ptsd, panic disorder, and specific phobia.Depression and Anxiety, 31(2), 150-159.
[23] Killgore, W. D., & Yurgelun-Todd, D. A. (2010). Cerebral correlates of amygdala responses during non-conscious perception of facial affect in adolescent and pre- adolescent children.Cognitive Neuroscience, 1(1), 33-43.
[24] Kimmig A. S., Dresler T., Hudak J., Haeussinger F. B., Wildgruber D., Fallgatter A. J., Ehlis A. C., & Kreifelts B. (2019). Feasibility of NIRS-based neurofeedback training in social anxiety disorder: Behavioral and neural correlates.Journal of Neural Transmission, 126(9), 1175-1185.
[25] Knight D. C., Nguyen H. T., & Bandettini P. A. (2005). The role of the human amygdala in the production of conditioned fear responses.NeuroImage, 26(4), 1193-1200.
[26] Kumaran, D., & McClelland, J. L. (2012). Generalization through the recurrent interaction of episodic memories: A model of the hippocampal system.Psychological Review, 119(3), 573-616.
[27] Lau J. Y., Britton J. C., Nelson E. E., Angold A., Ernst M., Goldwin M., .. Pine D. S. (2011). Distinct neural signatures of threat learning in adolescents and adults.Proceedings of the National Academy of Sciences of the United States of America, 108(11), 4500-4505.
[28] LeDoux, J. E. (2000). Emotion circuits in the brain.Annual Review of Neuroscience, 23, 155-184.
[29] LeDoux, J. E., & Pine, D. S. (2016). Using neuroscience to help understand fear and anxiety: A two-system framework.American Journal of Psychiatry, 173(11), 1083-1093.
[30] Lei Y., Mei Y., Dai Y., & Peng W. (2019). Taxonomic relations evoke more fear than thematic relations after fear conditioning: An EEG study.Neurobiology of Learning and Memory, 167, 107099.
[31] Lissek, S. (2012). Toward an account of clinical anxiety predicated on basic, neurally mapped mechanisms of Pavlovian fear-learning: The case for conditioned overgeneralization.Depression and Anxiety, 29(4), 257-263.
[32] Lissek S., Kaczkurkin A. N., Rabin S., Geraci M., Pine D. S., & Grillon C. (2014). Generalized anxiety disorder is associated with overgeneralization of classically conditioned fear.Biological Psychiatry, 75(11), 909-915.
[33] Lopresto D., Schipper P., & Homberg J. R. (2016). Neural circuits and mechanisms involved in fear generalization: Implications for the pathophysiology and treatment of posttraumatic stress disorder.Neuroscience and Biobehavioral Reviews, 60, 31-42.
[34] Martz M. E., Hart T., Heitzeg M. M., & Peltier S. J. (2020). Neuromodulation of brain activation associated with addiction: A review of real-time fMRI neurofeedback studies.NeuroImage: Clinical, 27, 102350.
[35] McCrory E. J., De Brito S. A., Kelly P. A., Bird G., Sebastian C. L., Mechelli A., Samuel S., & Viding E. (2013). Amygdala activation in maltreated children during pre-attentive emotional processing.The British Journal of Psychiatry : the Journal of Mental Science, 202(4), 269-276.
[36] McNally, R. J. (2007). Mechanisms of exposure therapy: How neuroscience can improve psychological treatments for anxiety disorders.Clinical Psychology Review, 27(6), 750-759.
[37] Mennella R., Patron E., & Palomba D. (2017). Frontal alpha asymmetry neurofeedback for the reduction of negative affect and anxiety.Behaviour Research and Therapy, 92, 32-40.
[38] Mertens, G., & Engelhard, I. M. (2020). A systematic review and meta-analysis of the evidence for unaware fear conditioning.Neuroscience & Biobehavioral Reviews, 108, 254-268.
[39] Michalska K. J., Machlin L., Moroney E., Lowet D. S., Hettema J. M., Roberson-Nay R., .. Pine D. S. (2017). Anxiety symptoms and children's eye gaze during fear learning.Journal of Child Psychology and Psychiatry, and Allied Disciplines, 58(11), 1276-1286.
[40] Öhman, A., & Soares, J. J. (1994). "Unconscious anxiety": Phobic responses to masked stimuli.Journal of Abnormal Psychology, 103(2), 231-240.
[41] Öhman, A., & Soares, J. J. (1998). Emotional conditioning to masked stimuli: Expectancies for aversive outcomes following nonrecognized fear-relevant stimuli.Journal of experimental psychology: General, 127(1), 69-82.
[42] Orsini, C. A., & Maren, S. (2012). Neural and cellular mechanisms of fear and extinction memory formation. Neuroscience & Biobehavioral Reviews, 36(7), 1773-1802.
[43] Pagliaccio D., Luby J. L., Luking K. R., Belden A. C., & Barch D. M. (2014). Brain-behavior relationships in the experience and regulation of negative emotion in healthy children: Implications for risk for childhood depression.Development and Psychopathology, 26(4 Pt 2), 1289-1303.
[44] Pattwell S. S., Lee F. S., & Casey B. (2013). Fear learning and memory across adolescent development: Hormones and Behavior Special Issue: Puberty and Adolescence.Hormones and Behavior, 64(2), 380-389.
[45] Peng W., Zhan Y., Jiang Y., Nan W., Kadosh R. C., & Wan F. (2020). Individual variation in alpha neurofeedback training efficacy predicts pain modulation.NeuroImage: Clinical, 28, 102454.
[46] Pfeifer J. H., Masten C. L., Moore W. E., 3rd, Oswald T. M., Mazziotta J. C., Iacoboni M., & Dapretto M. (2011). Entering adolescence: Resistance to peer influence, risky behavior, and neural changes in emotion reactivity.Neuron, 69(5), 1029-1036.
[47] Reinhard J., Slyschak A., Schiele M. A., Andreatta M., Kneer K., Reif A., .. Romanos M. (2022). Fear conditioning and stimulus generalization in association with age in children and adolescents.European Child & Adolescent Psychiatry, 31(10), 1581-1590.
[48] Scherf K. S., Smyth J. M., & Delgado M. R. (2013). The amygdala: An agent of change in adolescent neural networks.Hormones and Behavior, 64(2), 298-313.
[49] Sevenster D., Visser R. M., & D'Hooge R. (2018). A translational perspective on neural circuits of fear extinction: Current promises and challenges.Neurobiology of Learning and Memory, 155, 113-126.
[50] Siegel P., Warren R., Jacobson G., & Merritt E. (2018). Masking exposure to phobic stimuli reduces fear without inducing electrodermal activity.Psychophysiology, 55(5), e13045.
[51] Strobel C., Marek R., Gooch H. M., Sullivan R., & Sah P. (2015). Prefrontal and auditory input to intercalated neurons of the amygdala.Cell Reports, 10(9), 1435-1442.
[52] Suslow T., Ohrmann P., Bauer J., Rauch A. V., Schwindt W., Arolt V., Heindel W., & Kugel H. (2006). Amygdala activation during masked presentation of emotional faces predicts conscious detection of threat-related faces.Brain and Cognition, 61(3), 243-248.
[53] Tamietto, M., & de Gelder, B. (2010). Neural bases of the non-conscious perception of emotional signals.Nature reviews. Neuroscience, 11(10), 697-709.
[54] Taschereau-Dumouchel V., Cortese A., Chiba T., Knotts J. D., Kawato M., & Lau H. (2018). Towards an unconscious neural reinforcement intervention for common fears.Proceedings of the National Academy of Sciences of the United States of America, 115(13), 3470-3475.
[55] Treanor M., Rosenberg B. M., & Craske M. G. (2021). Pavlovian learning processes in pediatric anxiety disorders: A critical review.Biological Psychiatry, 89(7), 690-696.
[56] Vizueta N., Patrick C. J., Jiang Y., Thomas K. M., & He S. (2012). Dispositional fear, negative affectivity, and neuroimaging response to visually suppressed emotional faces.NeuroImage, 59(1), 761-771.
[57] Wang J., Mei E., Wu Q., Xie T., Dou H., & Lei Y. (2021). Influence of perceptual and conceptual information on fear generalization: A behavioral and event-related potential study.Cognitive, Affective & Behavioral Neuroscience, 21(5), 1054-1065.
[58] Wang J., Wang Y., Liao M., Zou Y., Lei Y., & Zhu Y. (2021). Conditioned generalisation in generalised anxiety disorder: The role of concurrent perceptual and conceptual cues.Cognition & Emotion, 35(8), 1516-1526.
[59] Weems, C. F., & Pina, A. A. (2010). The assessment of emotion regulation: Improving construct validity in research on psychopathology in youth—An introduction to the special section.Journal of Psychopathology and Behavioral Assessment, 32, 1-7.
[60] Xie S., Zhang X., Cheng W., & Yang Z. (2021). Adolescent anxiety disorders and the developing brain: Comparing neuroimaging findings in adolescents and adults.General Psychiatry, 34(4), e100411.
[61] Yehuda, R., & LeDoux, J. (2007). Response variation following trauma: A translational neuroscience approach to understanding PTSD.Neuron, 56(1), 19-32.
[62] Zilverstand A., Sorger B., Sarkheil P., & Goebel R. (2015). fMRI neurofeedback facilitates anxiety regulation in females with spider phobia.Frontiers in Behavioral Neuroscience, 9, 148.
[63] Zimmermann K. S., Richardson R., & Baker K. D. (2019). Maturational changes in prefrontal and amygdala circuits in adolescence: Implications for understanding fear inhibition during a vulnerable period of development. Brain Sciences, 9(3), 65.