Skip to main content Accessibility help

Reappraisal-related neural predictors of treatment response to cognitive behavior therapy for post-traumatic stress disorder

  • Richard A. Bryant (a1) (a2), May Erlinger (a2), Kim Felmingham (a3), Aleksandra Klimova (a2), Leanne M. Williams (a4) (a5), Gin Malhi (a6), David Forbes (a7) and Mayuresh S. Korgaonkar (a2) (a6)...



Although trauma-focused cognitive behavior therapy (TF-CBT) is the frontline treatment for post-traumatic stress disorder (PTSD), one-third of patients are treatment non-responders. To identify neural markers of treatment response to TF-CBT when participants are reappraising aversive material.


This study assessed PTSD patients (n = 37) prior to TF-CBT during functional magnetic brain resonance imaging (fMRI) when they reappraised or watched traumatic images. Patients then underwent nine sessions of TF-CBT, and were then assessed for symptom severity on the Clinician-Administered PTSD Scale. FMRI responses for cognitive reappraisal and emotional reactivity contrasts of traumatic images were correlated with the reduction of PTSD severity from pretreatment to post-treatment.


Symptom improvement was associated with decreased activation of the left amygdala during reappraisal, but increased activation of bilateral amygdala and hippocampus during emotional reactivity prior to treatment. Lower connectivity of the left amygdala to the subgenual anterior cingulate cortex, pregenual anterior cingulate cortex, and right insula, and that between the left hippocampus and right amygdala were also associated with symptom improvement.


These findings provide evidence that optimal treatment response to TF-CBT involves the capacity to engage emotional networks during emotional processing, and also to reduce the engagement of these networks when down-regulating emotions.


Corresponding author

Author for correspondence: Richard A. Bryant, E-mail:


Hide All
Aupperle, R. L., Allard, C. B., Simmons, A. N., Flagan, T., Thorp, S. R., Norman, S. B., … Stein, M. B. (2013). Neural responses during emotional processing before and after cognitive trauma therapy for battered women. Psychiatry Research, 214, 4855.
Ball, T. M., Stein, M. B., Ramsawh, H. J., Campbell-Sills, L., & Paulus, M. P. (2014). Single-subject anxiety treatment outcome prediction using functional neuroimaging. Neuropsychopharmacology, 39, 12541261.
Banks, S. J., Eddy, K. T., Angstadt, M., Nathan, P. J., & Phan, K. L. (2007). Amygdala-frontal connectivity during emotion regulation. Social, Cognitive, and Affective Neuroscience, 2, 303312.
Blake, D. D., Weathers, F., Nagy, L. M., Kaloupek, D. G., Gusman, F. D., Charney, D. S., & Keane, T. M. (1995). The development of a clinician administered PTSD scale. Journal of Traumatic Stress, 8, 7590.
Blanchard, E. B., Hickling, E. J., Malta, L. S., Jaccard, J., Devineni, T., Veazey, C. H., & Galovski, T. E. (2003). Prediction of response to psychological treatment among motor vehicle accident survivors with PTSD. Behavior Therapy, 34, 351363.
Bradley, R., Greene, J., Russ, E., Dutra, L., & Westen, D. (2005). A multidimensional meta-analysis of psychotherapy for PTSD. American Journal of Psychiatry, 162, 214227.
Bryant, R. A., Felmingham, K., Kemp, A., Das, P., Hughes, G., Peduto, A., & Williams, L. (2008). Amygdala and ventral anterior cingulate activation predicts treatment response to cognitive behaviour therapy for post-traumatic stress disorder. Psychological Medicine, 38, 555561.
Bryant, R. A., Mastrodomenico, J., Hopwood, S., Kenny, L., Cahill, C., Kandris, K., & Taylor, K. (2013). Augmenting cognitive behavior therapy for PTSD with emotion tolerance training: A randomized controlled trial. Psychological Medicine, 43, 21532160.
Buhle, J. T., Silvers, J. A., Wager, T. D., Lopez, R., Onyemekwu, C., Kober, H., … Ochsner, K. N. (2014). Cognitive reappraisal of emotion: A meta-analysis of human neuroimaging studies. Cerebral Cortex, 24, 29812990.
Cisler, J. M., Sigel, B. A., Steele, J. S., Smitherman, S., Vanderzee, K., Pemberton, J., … Kilts, C. D. (2016). Changes in functional connectivity of the amygdala during cognitive reappraisal predict symptom reduction during trauma-focused cognitive-behavioral therapy among adolescent girls with post-traumatic stress disorder. Psychological Medicine, 46, 30133023.
Cisler, J. M., Steele, J. S., Lenow, J. K., Smitherman, S., Everett, B., Messias, E., & Kilts, C. D. (2014). Functional reorganization of neural networks during repeated exposure to the traumatic memory in posttraumatic stress disorder: An exploratory fMRI study. Journal of Psychiatric Research, 48, 4755.
Craske, M. G., Kircanski, K., Zelikowsky, M., Mystkowski, J., Chowdhury, N., & Baker, A. (2008). Optimizing inhibitory learning during exposure therapy. Behaviour Research and Therapy, 46, 527.
Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry, 164, 14761488.
Falconer, E., Allen, A., Felmingham, K. L., Williams, L. M., & Bryant, R. A. (2013). Inhibitory neural activity predicts response to cognitive-behavioral therapy for posttraumatic stress disorder. Journal of Clinical Psychiatry, 74, 895901.
Foa, E. B. (2006). Psychosocial therapy for posttraumatic stress disorder. Journal of Clinical Psychiatry, 67, 4045.
Fonzo, G. A., Goodkind, M. S., Oathes, D. J., Zaiko, Y. V., Harvey, M., Peng, K. K., … Etkin, A. (2017). PTSD psychotherapy outcome predicted by brain activation during emotional reactivity and regulation. American Journal of Psychiatry, 174, 11631174.
Goldin, P. R., Manber, T., Hakimi, S., Canli, T., & Gross, J. J. (2009). Neural bases of social anxiety disorder: Emotional reactivity and cognitive regulation during social and physical threat. Archives of General Psychiatry, 66, 170180.
Goldin, P. R., McRae, K., Ramel, W., & Gross, J. J. (2008). The neural bases of emotion regulation: Reappraisal and suppression of negative emotion. Biological Psychiatry, 63, 577586.
Goldin, P. R., Ziv, M., Jazaieri, H., Hahn, K., Heimberg, R., & Gross, J. J. (2013). Impact of cognitive behavioral therapy for social anxiety disorder on the neural dynamics of cognitive reappraisal of negative self-beliefs: Randomized clinical trial. JAMA Psychiatry, 70, 10481056.
Greco, J. A., & Liberzon, I. (2016). Neuroimaging of fear-associated learning. Neuropsychopharmacology, 41, 320334.
Gross, J. J. (1998). Antecedent- and response-focused emotion regulation: Divergent consequences for experience, expression, and physiology. Journal of Personality and Social Psychology, 74, 224237.
Institute of Medicine. (2008). Treatment of posttraumatic stress disorder: An assessment of the evidence. Washington, DC: Institute of Medicine.
Klumpp, H., Fitzgerald, D. A., & Phan, K. L. (2013). Neural predictors and mechanisms of cognitive behavioral therapy on threat processing in social anxiety disorder. Progress in Neuropsychopharmacology and Biological Psychiatry, 45, 8391.
Kober, H., Barrett, L. F., Joseph, J., Bliss-Moreau, E., Lindquist, K., & Wager, T. D. (2008). Functional grouping and cortical-subcortical interactions in emotion: A meta-analysis of neuroimaging studies. Neuroimage, 42, 9981031.
Kozel, F.A., Motes, M.A., Didehbani, N., DeLaRosa, B., Bass, C., Schraufnagel, C.D., … Hart, J. Jr. (2018). Repetitive TMS to augment cognitive processing therapy in combat veterans of recent conflicts with PTSD: A randomized clinical trial. Journal of Affective Disorders, 229, 506514.
Lang, P. J., Bradley, M. M., & Cuthbert, B. N. (2005). International affective picture system (IAPS): Affective ratings of pictures and instruction manual. Gainesville, FL: University of Florida.
Lanius, R. A., Vermetten, E., Loewenstein, R. J., Brand, B., Schmahl, C., Bremner, J. D., & Spiegel, D. (2010). A dissociative subtype of PTSD: Clinical and neurobiological evidence. American Journal of Psychiatry, 167, 640647.
McLaren, D. G., Ries, M. L., Xu, G., & Johnson, S. C. (2012). A generalized form of context-dependent psychophysiological interactions (gPPI): A comparison to standard approaches. Neuroimage, 61, 12771286.
McLean, C.P., Asnaani, A., & Foa, E.B. (2015). Prolonged exposure therapy. In Schnyder, U. & Cloitre, M. (Eds.), Evidence based treatments for trauma-related psychological disorders (pp. 143159). Heidelberg: Springer.
National Institute of Clinical Excellence. (2005). The management of PTSD in adults and children in primary and secondary care. Wiltshire: National Institute of Clinical Excellence.
New, A. S., Fan, J., Murrough, J. W., Liu, X., Liebman, R. E., Guise, K. G., … Charney, D. S. (2009). A functional magnetic resonance imaging study of deliberate emotion regulation in resilience and posttraumatic stress disorder. Biological Psychiatry, 66, 656664.
Nitschke, J. B., Sarinopoulos, I., Oathes, D. J., Johnstone, T., Whalen, P. J., Davidson, R. J., & Kalin, N. H. (2009). Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response. American Journal of Psychiatry, 166, 302310.
Ochsner, K. N., Bunge, S. A., Gross, J. J., & Gabrieli, J. D. (2002). Rethinking feelings: An FMRI study of the cognitive regulation of emotion. Journal of Cognitive Neuroscience, 14, 12151229.
Ochsner, K. N., Silvers, J. A., & Buhle, J. T. (2012). Functional imaging studies of emotion regulation: A synthetic review and evolving model of the cognitive control of emotion. Annals of the New York Academy of Sciences, 1251, E124.
Paquette, V., Levesque, J., Mensour, B., Leroux, J. M., Beaudoin, G., Bourgouin, P., & Beauregard, M. (2003). ‘Change the mind and you change the brain’: Effects of cognitive-behavioral therapy on the neural correlates of spider phobia. Neuroimage, 18, 401409.
Parsons, R. G., & Ressler, K. J. (2013). Implications of memory modulation for post-traumatic stress and fear disorders. Nature Neuroscience, 16, 146153.
Paschke, L. M., Dorfel, D., Steimke, R., Trempler, I., Magrabi, A., Ludwig, V. U., … Walter, H. (2016). Individual differences in self-reported self-control predict successful emotion regulation. Social, Cognitive, and Affective Neuroscience, 11, 11931204.
Pico-Perez, M., Alonso, P., Contreras-Rodriguez, O., Martinez-Zalacain, I., Lopez-Sola, C., Jiminez-Murcia, S., … Soriano-Mas, C. (2018). Dispositional use of emotion regulation strategies and resting-state cortico-limbic functional connectivity. Brain Imaging and Behavior, 12, 10221031.
Rabinak, C. A., MacNamara, A., Kennedy, A. E., Angstadt, M., Stein, M. B., Liberzon, I., & Phan, K. L. (2014). Focal and aberrant prefrontal engagement during emotion regulation in veterans with posttraumatic stress disorder. Depression and Anxiety, 31, 851861.
Reinecke, A., Thilo, K., Filippini, N., Croft, A., & Harmer, C. J. (2014). Predicting rapid response to cognitive-behavioural treatment for panic disorder: The role of hippocampus, insula, and dorsolateral prefrontal cortex. Behaviour Research and Therapy, 62, 120128.
Reinhardt, I., Jansen, A., Kellerman, T., Schuppen, A., Kohn, N., Gerlach, A. L., & Kircher, T. (2010). Neural correlates of aversive conditioning: Development of a functional imaging paradigm for the investigation of anxiety disorders. European Archives of Psychiatry and Clinical Neuroscience, 260, 443453.
Seligowski, A. V., Lee, D. J., Bardeen, J. R., & Orcutt, H. K. (2015). Emotion regulation and posttraumatic stress symptoms: A meta-analysis. Cognitive Behavior Therapy, 44, 87102.
Sheehan, D.V., Lecrubier, Y., Harnett-Sheehan, K., Amorim, P., Janavs, J., Weiller, E., … Dunbar, G. (1998). The Mini International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview. Journal of Clinical Psychiatry, 59(Suppl 20), 2233.
Shiba, Y., Oikonomidis, L., Sawiak, S., Fryer, T. D., Hong, Y. T., Cockcroft, G., … Roberts, A. C. (2017). Converging prefronto-insula-amygdala pathways in negative emotion regulation in marmoset monkeys. Biological Psychiatry, 82, 895903.
Siegle, G. J., Carter, C. S., & Thase, M. E. (2006). Use of FMRI to predict recovery from unipolar depression with cognitive behavior therapy. American Journal of Psychiatry, 163, 735738.
Straube, T., Glauer, M., Dilger, S., Mentzel, H. J., & Miltner, W. H. (2006). Effects of cognitive behavioral therapy on brain activation in specific phobia. Neuroimage, 29, 125135.
Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N., … Joliot, M. (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage, 15, 273289.
Uchida, M., Biederman, J., Gabrieli, J. D., Micco, J., de Los Angeles, C., Brown, A., … Whitfield-Gabrieli, S. (2015). Emotion regulation ability varies in relation to intrinsic functional brain architecture. Social, Cognitive, and Affective Neuroscience, 10, 17381748.
Urry, H. L., van Reekum, C. M., Johnstone, T., Kalin, N. H., Thurow, M. E., Schaefer, H. S., … Davidson, R. J. (2006). Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults. Journal of Neuroscience, 26, 44154425.
Whalen, P. J., Johnstone, T., Somerville, L. H., Nitschke, J. B., Polis, S., Alexander, A. L., … Kalin, N. H. (2008). A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder. Biological Psychiatry, 63, 858863.
Williams, L. M. (2016). Precision psychiatry: A neural circuit taxonomy for depression and anxiety. The Lancet. Psychiatry, 3, 472480.
Wolf, E. J., Lunny, C. A., & Schnurr, P. P. (2016). The influence of the dissociative subtype of posttraumatic stress disorder on treatment efficacy in female veterans and active duty service members. Journal of Consulting and Clinical Psychology, 84, 95100.
Zilverstand, A., Parvaz, M. A., & Goldstein, R. Z. (2017). Neuroimaging cognitive reappraisal in clinical populations to define neural targets for enhancing emotion regulation. A systematic review. Neuroimage, 151, 105116.


Type Description Title
Supplementary materials

Bryant et al. supplementary material
Bryant et al. supplementary material

 Word (87 KB)
87 KB

Reappraisal-related neural predictors of treatment response to cognitive behavior therapy for post-traumatic stress disorder

  • Richard A. Bryant (a1) (a2), May Erlinger (a2), Kim Felmingham (a3), Aleksandra Klimova (a2), Leanne M. Williams (a4) (a5), Gin Malhi (a6), David Forbes (a7) and Mayuresh S. Korgaonkar (a2) (a6)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.