Poor Mnemonic Discrimination Predicts Overgeneralization of Fear
Tóm tắt
Anxiety disorders are characterized by difficulty distinguishing safe contexts from previous or imagined threats. Conditioned fears spread beyond what is reasonable or adaptive, leading to broad and interfering anxieties when people overgeneralize their fears. Difficulties with mnemonic discrimination, a component process of memory supporting the integration of old and new experiences, may foster overgeneralization and increase risk for anxiety disorders. Individuals along a spectrum of anxiety severity (n = 117) completed a differential fear conditioning paradigm and the computerized Mnemonic Similarity Task. The task measures mnemonic discrimination by requiring individuals to differentiate between highly similar old and new entities. We predicted that low mnemonic discrimination would be associated with overgeneralization, i.e., flatter slopes of change in response to stimuli increasingly dissimilar to the conditioned stimulus. Conditional growth models showed that as expected, participants with the highest mnemonic discrimination scores also exhibited the steepest declines in fear ratings as stimuli increasingly differed from the conditioned stimulus. Results were unchanged after adjusting for recognition memory, self-reported anxiety, and clinical diagnoses and symptoms. Results support the hypothesis that memory interference (i.e., low mnemonic discrimination) could increase vulnerability for overgeneralization. Findings justify additional exploration of mnemonic discrimination and its role in anxious psychopathology.
Tài liệu tham khảo
Balderston, N. L., Mathur, A., Adu-Brimpong, J., Hale, E. A., Ernst, M., & Grillon, C. (2015). Effect of anxiety on behavioural pattern separation in humans. Cognition and Emotion, 31, 238–248.
Balderston, N. L., Hsiung, A., Ernst, M., & Grillon, C. (2017). The effect of threat on right dlPFC activity during behavioral pattern separation. The Journal of Neuroscience, 37, 9160–9171.
Bekinschtein, P., Oomen, C., & Saksida, L. (2011). Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Seminars in Cell and Developmental Biology, 22, 536–542.
Bennett, I. J., & Stark, C. E. L. (2015). Mnemonic discrimination relates to perforant path integrity: An ultra-high resolution diffusion tensor imaging study. Neurobiology of Learning and Memory, 129, 1–6.
Bernstein, E. E., Kleiman, E. M., & McNally, R. J. (2019). Mnemonic discrimination under stress and its clinical relevance for anxiety. Clinical Psychological Science, 7, 1014–1031.
Bernstein, E. E., & McNally, R. J. (2018). Exploring behavioral pattern separation and risk for emotional disorders. Journal of Anxiety Disorders, 59, 27–33.
Besnard, A., & Sahay, A. (2015). Adult hippocampal neurogenesis, fear generalization, and stress. Neuropsychopharmacology Reviews, 41, 24–44.
Doxey, C. R., & Kirwan, C. B. (2015). Structural and functional correlates of behavioral pattern separation in the hippocampus and medial temporal lobe. Hippocampus, 25, 524–533.
Dunsmoor, J. E., Mitroff, S. R., & LaBar, K. S. (2009). Generalization of conditioned fear along a dimension of increasing fear intensity. Learning & Memory, 16, 460–469.
Dymond, S., Dunsmoor, J. E., Vervliet, B., Roche, B., & Hermans, D. (2015). Fear generalization in humans: Systematic review and implications for anxiety disorder research. Behavior Therapy, 46, 561–582.
Dymond, S., Schlund, M. W., Roche, B., Whelan, R., Richards, J., & Davies, C. (2011). Inferred threat and safety: Symbolic generalization of human avoidance learning. Behaviour Research and Therapy, 49, 614–621.
Ehring, T., & Ehlers, A. (2011). Enhanced priming for trauma-related words predicts posttraumatic stress disorder. Journal of Abnormal Psychology, 120, 234–239.
Eysenck, M. W., & Derakshan, N. (2011). New perspectives in attentional control theory. Personality and Individual Differences, 50, 955–960.
First, M. B., Williams, J. B. W., Karg, R. S., & Spitzer, R. L. (2015). Structured clinical interview for DSM-5—Research version. American Psychiatric Association.
Gilbert, P. E., & Kesner, R. P. (2002). The amygdala but not the hippocampus is involved in pattern separation based on reward value. Neurobiology of Learning and Memory, 77, 338–353.
Greenberg, T., Carlson, J. M., Cha, J., Hajcak, G., & Mujica-Parodi, L. R. (2013). Ventromedial prefrontal cortex reactivity is altered in generalized anxiety disorder during fear generalization. Depression and Anxiety, 30, 242–250.
Guttman, N., & Kalish, H. I. (1956). Discriminability and stimulus generalization. Journal of Experimental Psychology, 51, 79–88.
Kheirbek, M. A., Klemenhagen, K. C., Sahay, A., & Hen, R. (2012). Neurogenesis and generalization: A new approach to stratify and treat anxiety disorders. Nature Neuroscience, 15, 1613–1620.
Kheirbek, M., & Hen, R. (2014). Add neurons, subtract anxiety. Scientific American, 311, 62–67.
Lange, I., Goossens, L., Michielse, S., Bakker, J., Lissek, S., Papalini, S., Verhagen, S., Leibold, N., Marcelis, M., Wichers, M., Lieverse, R., van Os, J., van Amelsvoort, T., & Schruers, K. (2017). Behavioral pattern separation and its link to the neural mechanisms of fear generalization. Social Cognitive and Affective Neuroscience, 12, 1720–1729.
Laufer, O., Israeli, D., & Paz, R. (2016). Behavioral and neural mechanisms of overgeneralization in anxiety. Current Biology, 26, 713–722.
Lenaert, B., Boddez, Y., Griffith, J. W., Vervliet, B., Schruers, K., & Hermans, D. (2014). Aversive learning and generalization predict subclinical levels of anxiety: A six-month longitudinal study. Journal of Anxiety Disorders, 28, 747–753.
Lissek, S., Powers, A. S., McClure, E. B., Phelps, E. A., Woldehawariat, G., Grillon, C., & Pine, D. S. (2005). Classical fear conditioning in the anxiety disorders: A meta-analysis. Behaviour Research and Therapy, 43, 1391–1424.
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, 257–263.
Lissek, S., Biggs, A. L., Rabin, S. J., Cornwell, B. R., Alvarez, R. P., Pine, D. S., & Grillon, C. (2008). Generalization of conditioned fear-potentiated startle in humans: Experimental validation and clinical relevance. Behaviour Research and Therapy, 46, 678–687.
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, 909–915.
Lissek, S., Rabin, S., Heller, R. E., Lukenbaugh, D., Geraci, M., Pine, D. S., & Grillon, C. (2010). Overgeneralization of conditioned fear as a pathogenic marker of panic disorder. American Journal of Psychiatry, 167, 47–55.
Mattson, M. P. (2014). Superior pattern processing is the essence of the evolved human brain. Frontiers in Neuroscience, 8, 265.
McGaugh, J. L. (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience, 27, 1–28.
McHugh, T. J., Jones, M. W., Quinn, J. J., Balthasar, N., Coppari, R., Elmquist, J. K., Lowell, B. B., Fanselow, M. S., Wilson, M. A., & Tonegawa, S. (2007). Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science, 317, 94–99.
Mineka, S., & Zinbarg, R. (2006). A contemporary learning theory perspective on the etiology of anxiety disorders: it’s not what you thought it was. The American Psychologist, 61, 10–26.
Nave, C., & Nave, B. (1985). Physics For the Health Sciences (3rd ed.; W. Saunders, Ed.). Philadelphia.
Orr, S. P., Metzger, L. J., Lasko, N. B., Macklin, M. L., Peri, T., & Pitman, R. K. (2000). De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder. Journal of Abnormal Psychology, 109, 290–298.
Rolls, E. T. (2016). Pattern separation, completion, and categorisation in the hippocampus and neocortex. Neurobiology of Learning and Memory, 129, 4–28.
Rosebrock, L. E., Hoxha, D., Norris, C., Cacioppo, J. T., & Gollan, J. K. (2017). Skin conductance and subjective arousal in anxiety, depression, and comorbidity: Implications for affective reactivity. Journal of Psychophysiology, 31, 145–157.
Sahay, A., Scobie, K. N., Hill, A. S., O’Carroll, C. M., Kheirbek, M. A., Burghardt, N. S., et al. (2011). Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature, 472, 466–470.
Schwabe, L., & Wolf, O. T. (2013). Stress and multiple memory systems: From “thinking” to “doing”. Trends in Cognitive Sciences, 17, 60–68.
Starita, F., Kroes, M. C. W., Davachi, L., Phelps, E. A., & Dunsmoor, J. E. (2019). Threat learning promotes generalization of episodic memory. Journal of Experimental Psychology: General, 148, 1426–1434.
Stark, S. M., Stevenson, R., Wu, C., Rutledge, S., & Stark, C. E. L. (2015). Stability of age-related deficits in the mnemonic similarity task across task variations. Behavioral Neuroscience, 129, 257–268.
Stark, S. M., Yassa, M. A., Lacy, J. W., & Stark, C. E. L. (2013). A task to assess behavioral pattern separation (BPS) in humans: Data from healthy aging and mild cognitive impairment. Neuropsychologia, 51(12), 2442–2449.
Struyf, D., Zaman, J., Hermans, D., & Vervliet, B. (2017). Gradients of fear: How perception influences fear generalization. Behaviour Research and Therapy, 93, 116–122.
Tanti, A., & Belzung, C. (2013). Hippocampal neurogenesis: A biomarker for depression or antidepressant effects? Methodological considerations and perspectives for future research. Cell and Tissue Research, 354, 203–219.
Taylor, C. T., Cross, K., & Amir, N. (2016). Attentional control moderates the relationship between social anxiety symptoms and attentional disengagement from threatening information. Journal of Behavior Therapy and Experimental Psychiatry, 50, 68–76.
Witthoft, M., Kerstner, T., Ofer, J., Mier, D., Rist, F., Diener, C., et al. (2015). Cognitive biases in pathological health anxiety: The contribution of attention, memory, and evaluation processes. Clinical Psychological Science, 4, 464–479.
Yassa, M. A., Lacy, J. W., Stark, S. M., Albert, M. S., Gallagher, M., & Stark, C. E. L. (2011). Pattern separation deficits associated with increased hippocampal CA3 and dentate gyrus activity in nondemented older adults. Hippocampus, 21, 968–979.
Yiend, J., Mathews, A., Burns, T., Dutton, K., Fernández-Martín, A., Georgiou, G. A., Luckie, M., Rose, A., Russo, R., & Fox, E. (2015). Mechanisms of selective attention in generalized anxiety disorder. Clinical Psychological Science, 3, 758–771.