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Differences in neural response to extinction recall in young adults with or without history of behavioral inhibition

  • Tomer Shechner (a1), Nathan A. Fox (a2), Jamie A. Mash (a3), Johanna M. Jarcho (a4), Gang Chen (a4), Ellen Leibenluft (a4), Daniel S. Pine (a4) and Jennifer C. Britton (a3)...


Behavioral inhibition (BI) is a temperament identified in early childhood that is associated with risk for anxiety disorders, yet only about half of behaviorally inhibited children manifest anxiety later in life. We compared brain function and behavior during extinction recall in a sample of nonanxious young adults characterized in childhood with BI (n = 22) or with no BI (n = 28). Three weeks after undergoing fear conditioning and extinction, participants completed a functional magnetic resonance imaging extinction recall task assessing memory and threat differentiation for conditioned stimuli. While self-report and psychophysiological measures of differential conditioning and extinction were similar across groups, BI-related differences in brain function emerged during extinction recall. Childhood BI was associated with greater activation in subgenual anterior cingulate cortex in response to cues signaling safety. This pattern of results may reflect neural correlates that promote resilience against anxiety in a temperamentally at-risk population.


Corresponding author

Address correspondence and reprint requests to: Tomer Shechner, Psychology Department, University of Haifa, Abu Hussi 234, Mount Carmel, Israel; E-mail:


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This research was supported in part by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. The first author (T.S.) is supported by Marie Curie Career Integration Grant PCIG13-GA-2013-618534 and Israel Science Foundation Grant 1377/14. The last author (J.C.B.) was supported by K99/R00 MH091183. All authors report no conflict of interests.



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Bar-Haim, Y., Fox, N. A., Benson, B., Guyer, A. E., Williams, A., Nelson, E. E., … Ernst, M. (2009). Neural correlates of reward processing in adolescents with a history of inhibited temperament. Psychological Science, 20, 10091018. doi:10.1111/j.1467-9280.2009.02401.xPSCI2401
Beesdo, K., Knappe, S., & Pine, D. S. (2009). Anxiety and anxiety disorders in children and adolescents: Developmental issues and implications for DSM-V. Psychiatry Clinics of North America, 32, 483524.
Britton, J. C., Grillon, C., Lissek, S., Norcross, M., Szuhany, K. L., Chen, G., … Pine, D. S. (2013). Response to learned threat: An fMRI study in adolescent and adult anxiety. American Journal of Psychiatry, 170, 11981204. doi:10.1176/ appi.ajp.2013.12050651
Chronis-Tuscano, A., Degnan, K. A., Pine, D. S., Perez-Edgar, K., Henderson, H. A., Diaz, Y., … Fox, N. A. (2009). Stable early maternal report of behavioral inhibition predicts lifetime social anxiety disorder in adolescence. Journal of the American Academy of Child & Adolescent Psychiatry, 48, 928935. doi:10.1097/CHI.0b013e3181ae09dfS0890-8567(09)60148-9
Clauss, J. A., & Blackford, J. U. (2012). Behavioral inhibition and risk for developing social anxiety disorder: A meta-analytic study. Journal of the American Academy of Child & Adolescent Psychiatry, 51, 10661075. doi:10.1016/j.jaac.2012.08.002S0890-8567(12)00592-8
Cole, M. W., Repovs, G., & Anticevic, A. (2014). The frontoparietal control system: A central role in mental health. Neuroscientist, 20, 652664.
Corcoran, K. A., Desmond, T. J., Frey, K. A., & Maren, S. (2005). Hippocampal inactivation disrupts the acquisition and contextual encoding of fear extinction. Journal of Neuroscience, 25, 89788987. doi:10.1523/jneurosci.2246-05.2005
Cromheeke, S., & Mueller, S. C. (2014). Probing emotional influences on cognitive control: An ALE meta-analysis of cognition emotion interactions. Brain Structure and Function, 219, 9951008.
Degnan, K. A., & Fox, N. A. (2007). Behavioral inhibition and anxiety disorders: Multiple levels of a resilience process. Development and Psychopathology, 19, 729746. doi:10.1017/S0954579407000363
Duits, P., Cath, D. C., Lissek, S., Hox, J. J., Hamm, A. O., Engelhard, I. M., … Baas, J. M. (2015). Updated meta-analysis of classical fear conditioning in the anxiety disorders. Depression and Anxiety, 32, 239253. doi:10.1002/da.22353
Dunsmoor, J. E., Prince, S. E., Murty, V. P., Kragel, P. A., & LaBar, K. S. (2011). Neurobehavioral mechanisms of human fear generalization. NeuroImage, 55, 18781888. doi:10.1016/j.neuroimage.2011.01.041S1053-8119(11)00076-0
Etkin, A. (2010). Functional neuroanatomy of anxiety: A neural circuit perspective. Current Topics in Behavioral Neurosciences, 2, 251277.
Etkin, A., Egner, T., & Kalisch, R. (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences, 15, 8593. doi:10.1016/j.tics.2010.11.004S1364-6613(10)00252-4
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (2002). Structured Clinical Interview for DSM-IV-TR Axis I Disorders—Patient edition (SCID-I/P, 11/2002 revsion) . New York: New York State Psychiatric Institute, Biometrics Research Department.
Fox, N. A., Henderson, H. A., Rubin, K. H., Calkins, S. D., & Schmidt, L. A. (2001). Continuity and discontinuity of behavioral inhibition and exuberance: Psychophysiological and behavioral influences across the first four years of life. Child Development, 72, 121.
Frenkel, T. I., Fox, N. A., Pine, D. S., Walker, O. L., Degnan, K. A., & Chronis-Tuscano, A. (2015). Early childhood behavioral inhibition, adult psychopathology and the buffering effects of adolescent social networks: A twenty-year prospective study. Journal of Child Psychology and Psychiatry, 56, 10651073.
Gold, A. L., Shechner, T., Farber, M. J., Spiro, C. N., Leibenluft, E., Pine, D. S., & Britton, J. C. (2016). Amygdala-cortical connectivity: Associations with anxiety, development, and threat. Depression and Anxiety, 33, 917926.
Graham, B. M., & Milad, M. R. (2011). The study of fear extinction: Implications for anxiety disorders. American Journal of Psychiatry, 168, 12551265. doi:0.1176/appi.ajp.2011.11040557
Greenberg, T., Carlson, J. M., Cha, J., Hajcak, G., & Mujica-Parodi, L. R. (2013). Neural reactivity tracks fear generalization gradients. Biological Psychology, 92, 28.
Grillon, C. (2002). Associative learning deficits increase symptoms of anxiety in humans. Biological Psychiatry, 51, 851858.
Guyer, A. E., Benson, B., Choate, V. R., Bar-Haim, Y., Perez-Edgar, K., Jarcho, J. M., … Nelson, E. E. (2014). Lasting associations between early-childhood temperament and late-adolescent reward-circuitry response to peer feedback. Development and Psychopathology, 26, 229243. doi:10.1017/S0954579413000941
Guyer, A. E., Nelson, E. E., Perez-Edgar, K., Hardin, M. G., Roberson-Nay, R., Monk, C. S., … Ernst, M. (2006). Striatal functional alteration in adolescents characterized by early childhood behavioral inhibition. Journal of Neuroscience, 26, 63996405. doi:10.1523/jneurosci.0666-06.2006
Hardee, J. E., Benson, B. E., Bar-Haim, Y., Mogg, K., Bradley, B. P., Chen, G., … Perez-Edgar, K. (2013). Patterns of neural connectivity during an attention bias task moderates associations between early childhood temperament and internalizing symptoms in young adulthood. Biological Psychiatry. Advance online publication. doi:10.1016/j.biopsych.2013.01.036
Helfinstein, S. M., Benson, B., Perez-Edgar, K., Bar-Haim, Y., Detloff, A., Pine, D. S., … Ernst, M. (2011). Striatal responses to negative monetary outcomes differ between temperamentally inhibited and non-inhibited adolescents. Neuropsychologia, 49, 479485. doi:10.1016/j.neuropsychologia.2010.12.015S0028-3932(10)00548-8
Indovina, I., Robbins, T. W., Nunez-Elizalde, A. O., Dunn, B. D., & Bishop, S. J. (2011). Fear-conditioning mechanisms associated with trait vulnerability to anxiety in humans. Neuron, 69, 563571. doi:10.1016/j.neuron.2010.12.034S0896-6273(10)01084-6
Jarcho, J. M., Fox, N. A., Pine, D. S., Etkin, A., Leibenluft, E., Shechner, T., & Ernst, M. (2013). The neural correlates of emotion-based cognitive control in adults with early childhood behavioral inhibition. Biological Psychology, 92, 306314. doi:10.1016/j.biopsycho.2012.09.008S0301-0511(12)00200-1
Jarcho, J. M., Fox, N. A., Pine, D. S., Leibenluft, E., Shechner, T., Degnan, K. A., … Ernst, M. (2014). Enduring influence of early temperament on neural mechanisms mediating attention-emotion conflict in adults. Depression and Anxiety, 31, 5362. doi:10.1002/da.22140
Kagan, J., Reznick, J. S., & Snidman, N. (1987). The physiology and psychology of behavioral inhibition in children. Child Development, 58, 14591473.
Kalisch, R., Korenfeld, E., Stephan, K. E., Weiskopf, N., Seymour, B., & Dolan, R. J. (2006). Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network. Journal of Neuroscience, 26, 95039511. doi:10.1523/jneurosci.2021-06.2006
Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C., Moreci, P., … Ryan, N. (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version (K-SADS-PL): Initial reliability and validity data. Journal of American Academy of Child & Adolescent Psychiatry, 36, 980988.
Koenigs, M., Barbey, A. K., Postle, B. R., & Grafman, J. (2009). Superior parietal cortex is critical for the manipulation of information in working memory. Journal of Neuroscience, 29, 1498014986.
Lau, J. Y., Lissek, S., Nelson, E. E., Lee, Y., Roberson-Nay, R., Poeth, K., … Pine, D. S. (2008). Fear conditioning in adolescents with anxiety disorders: Results from a novel experimental paradigm. Journal of the American Academy of Child & Adolescent Psychiatry, 47, 94102. doi:10.1097/chi.0b01e31815a5f01S0890-8567(09)62089-X
Lewis-Morrarty, E., Degnan, K. A., Chronis-Tuscano, A., Rubin, K. H., Cheah, C. S., Pine, D. S., … Fox, N. A. (2012). Maternal over-control moderates the association between early childhood behavioral inhibition and adolescent social anxiety symptoms. Journal of Abnormal Child Psychology, 40, 13631373.
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, 909915. doi:10.1016/j.biopsych.2013.07.025S0006-3223(13)00680-X
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, 13911424. doi:10.1016/j.brat.2004.10.007
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, 4755. doi:10.1176/appi.ajp.2009.09030410appi.ajp.2009.09030410
Lissek, S., Rabin, S. J., McDowell, D. J., Dvir, S., Bradford, D. E., Geraci, M., … Grillon, C. (2009). Impaired discriminative fear-conditioning resulting from elevated fear responding to learned safety cues among individuals with panic disorder. Behaviour Research and Therapy, 47, 111118. doi:10.1016/j.brat.2008.10.017S0005-7967(08)00220-9
McClure, E. B., Parrish, J. M., Nelson, E. E., Easter, J., Thorne, J. F., Rilling, J. K., … Pine, D. S. (2007). Responses to conflict and cooperation in adolescents with anxiety and mood disorders. Journal of Abnormal Child Psychology, 35, 567577.
McDermott, J. M., Perez-Edgar, K., Henderson, H. A., Chronis-Tuscano, A., Pine, D. S., & Fox, N. A. (2009). A history of childhood behavioral inhibition and enhanced response monitoring in adolescence are linked to clinical anxiety. Biological Psychiatry, 65, 445448. doi:10.1016/j.biopsych.2008.10.043S0006-3223(08)01392-9
Milad, M. R., Pitman, R. K., Ellis, C. B., Gold, A. L., Shin, L. M., Lasko, N. B., … Rauch, S. L. (2009). Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biological Psychiatry, 66, 10751082. doi:10.1016/j.biopsych.2009.06.026S0006-3223(09)00896-8
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, 446454. doi:10.1016/j.biopsych.2006.10.011
Perez-Edgar, K., Roberson-Nay, R., Hardin, M. G., Poeth, K., Guyer, A. E., Nelson, E. E., … Ernst, M. (2007). Attention alters neural responses to evocative faces in behaviorally inhibited adolescents. NeuroImage, 35, 15381546. doi:10.1016/j.neuroimage.2007.02.006
Pine, D. S., & Fox, N. A. (2015). Childhood antecedents and risk for adult mental disorders. Annual Review of Psychology, 66, 459485.
Quirk, G. J., & Mueller, D. (2008). Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology, 33, 5672.
Shechner, T., Britton, J. C., Perez-Edgar, K., Bar-Haim, Y., Ernst, M., Fox, N. A., … Pine, D. S. (2012). Attention biases, anxiety, and development: Toward or away from threats or rewards? Depression and Anxiety, 29, 282294. doi:10.1002/da.20914
Shechner, T., Britton, J. C., Ronkin, E. G., Jarcho, J. M., Mash, J. A., Michalska, K. J., … Pine, D. S. (2015). Fear conditioning and extinction in anxious and nonanxious youth and adults: Examining a novel developmentally appropriate fear-conditioning task. Depression and Anxiety, 32, 277288. doi:10.1002/da.22318
Shechner, T., Hong, M., Britton, J. C., Pine, D. S., & Fox, N. A. (2014). Fear conditioning and extinction across development: Evidence from human studies and animal models. Biological Psychology, 100, 112. doi:10.1016/j.biopsycho.2014.04.001S0301-0511(14)00071-4
Waters, A. M., Henry, J., & Neumann, D. L. (2009). Aversive Pavlovian conditioning in childhood anxiety disorders: Impaired response inhibition and resistance to extinction. Journal of Abnormal Psychology, 118, 311321. doi:10.1037/a00156352009-06385-006


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