Skip to main content

Amygdala and ventral anterior cingulate activation predicts treatment response to cognitive behaviour therapy for post-traumatic stress disorder

  • R. A. Bryant (a1) (a2), K. Felmingham (a1) (a2), A. Kemp (a1), P. Das (a1) (a3), G. Hughes (a4), A. Peduto (a4) and L. Williams (a1)...

Although cognitive behaviour therapy (CBT) is the treatment of choice for post-traumatic stress disorder (PTSD), approximately half of patients do not respond to CBT. No studies have investigated the capacity for neural responses during fear processing to predict treatment response in PTSD.


Functional magnetic resonance imaging (fMRI) responses of the brain were examined in individuals with PTSD (n=14). fMRI was examined in response to fearful and neutral facial expressions presented rapidly in a backwards masking paradigm adapted for a 1.5 T scanner. Patients then received eight sessions of CBT that comprised education, imaginal and in vivo exposure, and cognitive therapy. Treatment response was assessed 6 months after therapy completion.


Seven patients were treatment responders (defined as a reduction of 50% of pretreatment scores) and seven were non-responders. Poor improvement after treatment was associated with greater bilateral amygdala and ventral anterior cingulate activation in response to masked fearful faces.


Excessive fear responses in response to fear-eliciting stimuli may be a key factor in limiting responses to CBT for PTSD. This excessive amygdala response to fear may reflect difficulty in managing anxiety reactions elicited during CBT, and this factor may limit optimal response to therapy.

Corresponding author
*Address for correspondence: Dr R. A. Bryant, School of Psychology, University of New South Wales, Sydney, NSW 2052, Australia. (Email:
Hide All
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.
Armony A, Corbo V, Clément M-H, Brunet A (2005). Amygdala response in patients with acute PTSD to masked and unmasked emotional facial expressions. American Journal of Psychiatry 162, 19611963.
Beck AT, Steer AJ, Brown GK (1996). Manual for Beck Depression Inventory, 2nd edn. Psychological Corporation: San Antonio, TX.
Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Klauminzer G, Charney DS, Keane TM (1990). A clinician rating scale for assessing current and lifetime PTSD: the CAPS-1. Behavior Therapist 13, 187188.
Blanchard EB, Hickling EJ, Malta LS, Jaccard J, Devineni T, Veazey CH, Galovski TE (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.
Bremner JD, Staib LH, Kaloupek D, Southwick SM, Soufer R, Charney DS (1999). Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study. Biological Psychiatry 45, 806816.
Brody AL, Saxena S, Schwartz JM, Stoessel PW, Maidment R, Phelps ME, Baxter LR (1998). FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive-compulsive disorder. Psychiatry Research: Neuroimaging 84, 16.
Bryant RA (2006). Cognitive behavior therapy: implications from advances in neuroscience. In PTSD: Brain Mechanisms and Clinical Implications (ed. Kato N., Kawata M. and Pitman R.K.), pp. 255270. Springer-Verlag: Tokyo.
Bryant RA, Moulds ML, Guthrie RM, Dang ST, Nixon RDV (2003). Imaginal exposure alone and imaginal exposure with cognitive restructuring in treatment of posttraumatic stress disorder. Journal of Consulting and Clinical Psychology 71, 706712.
Charney DS, Deutch AY, Krystal JH, Southwick SM, Davis M (1993). Psychobiologic mechanisms of posttraumatic stress disorder. Archives of General Psychiatry 50, 294305.
Chen C-H, Ridler K, Suckling J, Williams S, Fu CHY, Merlo-Pich E, Bullmore E (2007). Brain imaging correlates of depressive symptom severity and predictors of symptom improvement after antidepressant treatment. Biological Psychiatry 62, 407414.
Davidson RJ, Irwin W, Anderle MJ, Kalin NH (2003). The neural substrates of affective processing in depressed patients treated with venlafaxine. American Journal of Psychiatry 160, 6475.
Davis M (1992). The role of the amygdala in fear and anxiety. Annual Review of Neuroscience 15, 353375.
Davis M (2000). The role of the amygdala in conditioned and unconditioned fear and anxiety. In The Amygdala (ed. Aggleton J.P), pp. 213287. Oxford University Press: New York.
Davis M, Myers KM (2002). The role of glutamate and gamma-aminobutyric acid in fear extinction: clinical implications for exposure therapy. Biological Psychiatry 52, 9981007.
Etkin A, Pittenger C, Polan HJ, Kandel ER (2005). Toward a neurobiology of psychotherapy: basic science and clinical applications. Journal of Neuropsychiatry and Clinical Neuroscience 17, 145158.
Evans KC, Dougherty DD, Pollak MH, Rauch SL (2006). Using neuroimaging to predict treatment response in mood and anxiety disorders. Annals of Clinical Psychiatry 18, 3342.
First MB, Spitzer RL, Gibbon M, Williams JBW (1997). Structured Clinical Interview for DSM-IV Axis 1 Disorders – Clinician Version (SCID-CV). American Psychiatric Press: Washington, DC.
Foa EB, Meadows EA (1997). Psychosocial treatments for posttraumatic stress disorder: a critical review. Annual Review of Psychology 48, 449480.
Furmark T, Tillfors M, Marteinsdottir I, Fischer H, Pissiota A, Långstrõm B, Fredrikson M (2002). Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive behavior therapy. Archives of General Psychiatry 59, 425433.
Garcia R, Voulmba RM, Baudry M, Thompson RF (1999). The amygdala modulates prefrontal cortex activity relative to conditioned fear. Nature 402, 294296.
Gilboa A, Shalev AY, Laor L, Lester H, Louzoun Y, Chisin R, Bonne O (2004). Functional connectivity of the prefrontal cortex and the amygdala in posttraumatic stress disorder. Biological Psychiatry 55, 263272.
Gur RC, Sara R, Hagendoorn M, Marom O, Hughett P, Macy L, Turner T, Bajcsy R, Posner A, Gur RE (2002). A method for obtaining 3-dimensional facial expressions and its standardization for use in neurocognitive studies. Journal of Neuroscience Methods 115, 137143.
Harvey AG, Bryant RA, Tarrier N (2003). Cognitive behaviour therapy of posttraumatic stress disorder. Clinical Psychology Review 23, 501522.
Lanius RA, Williamson PC, Densmore M, Boksman K, Gupta MA, Neufeld R (2001). Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. American Journal of Psychiatry 158, 19201922.
LeDoux J (1998). Fear and the brain: where have we been, and where are we going? Biological Psychiatry 44, 12291238.
Liberzon I, Taylor SF, Amdur R, Jung TD, Chamberlain KR, Minoshima S (1999). Brain activation in PTSD in response to trauma-related stimuli. Biological Psychiatry 45, 817826.
Liddell BJ, Brown KJ, Kemp AH, Barton MJ, Das P, Peduto A, Gordon E, Williams LM (2005). A direct brainstem-amygdala-cortical ‘alarm’ system for subliminal signals of fear. Neuroimage 24, 235243.
Linden DEJ (2006). How psychotherapy changes the brain – the contribution of functional neuroimaging. Molecular Psychiatry 11, 528538.
Macmillan N (1986). The psychophysics of nonconscious perception. Behavioral Brain Sciences 9, 3839.
Maren S, Chang C (2006). Recent fear is resistant to extinction. Proceedings of the National Academy of Sciences of the United States of America 103, 1802018025.
Mayberg HS, Brannan SK, Mahurin RK, Jerabek PA, Brickman JS, Tekell JL, Silva JA, McGinnis S, Glass TG, Martin CC, Fox PT (1997). Cingulate function in depression: a potential predictor of treatment response. Neuroreport 8, 10571061.
Milad MR, Rauch SL, Pitman RK, Quirk GJ (2006). Fear extinction in rats: implications for human brain imaging and anxiety disorders. Biological Psychology 73, 6171.
Phan KL, Britton JC, Taylor SF, Fig LM, Liberzon I (2006). Corticolimbic blood flow during nontraumatic emotional processing in posttraumatic stress disorder. Archives of General Psychiatry 63, 184192.
Rauch SL, Whalen PJ, Shin LM, McInerney SC, Macklin ML, Lasko NB, Orr SP, Pitman RK (2000). Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study. Biological Psychiatry 47, 769776.
Saxena S, Brody AL, Ho ML, Zohrabi N, Maidment KM, Baxter LR (2003). Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression. American Journal of Psychiatry 160, 522532.
Shin LM, Wright CI, Cannistraro PA, Wedig MM, McMullin K, Martis B, Macklin ML, Lasko M, Cavanagh SR, Krangek TS, Orr SP, Pitman RK, Whalen PJ, Rauch SL (2005). A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Archives of General Psychiatry 62, 273281.
Siegle GJ, Carter CS, Thase ME (2006). Use of fMRI to predict recovery: from unipolar depression with cognitive behavior therapy. American Journal of Psychiatry 163, 735738.
Tzourio-Mazoyer N, Landaeau B, Papthanasciou D, Crivello F, Etard O, Delcroix N, Mazoyer B, 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.
Williams LM, Kemp AH, Felmingham KL, Barton M, Olivieri G, Peduto AS, Gordon E, Bryant RA (2006). Trauma modulates amygdale and medial prefrontal responses to consciously attended fear. Neuroimage 29, 347357.
Williams LM, Liddell BJ, Rathjen J, Brown KJ, Gray J, Phillips M, Young A, Gordon E (2004). Mapping the time course of nonconscious and conscious perception of fear: an integration of central and peripheral measures. Human Brain Mapping 21, 6474.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 61
Total number of PDF views: 244 *
Loading metrics...

Abstract views

Total abstract views: 852 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 23rd January 2018. This data will be updated every 24 hours.