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Review Article

Effects of Psychotherapy on Brain Activation Patterns in Anxiety Disorders

Published Online:https://doi.org/10.1027/2151-2604/a000240

Abstract. Psychotherapy is an effective treatment for most mental disorders, including anxiety disorders. Successful psychotherapy implies new learning experiences and therefore neural alterations. With the increasing availability of functional neuroimaging methods, it has become possible to investigate psychotherapeutically induced neuronal plasticity across the whole brain in controlled studies. However, the detectable effects strongly depend on neuroscientific methods, experimental paradigms, analytical strategies, and sample characteristics. This article summarizes the state of the art, discusses current theoretical and methodological issues, and suggests future directions of the research on the neurobiology of psychotherapy in anxiety disorders.

References

  • Andreescu, C., Sheu, L. K., Tudorascu, D., Gross, J. J., Walker, S., Banihashemi, L. & Aizenstein, H. (2015). Emotion reactivity and regulation in late-life generalized anxiety disorder: Functional connectivity at baseline and post-treatment. The American Journal of Geriatric Psychiatry, 23, 200–214. First citation in articleCrossrefGoogle Scholar

  • Ball, T. M., Ramsawh, H. J., Campbell-Sills, L., Paulus, M. P. & Stein, M. B. (2013). Prefrontal dysfunction during emotion regulation in generalized anxiety and panic disorders. Psychological Medicine, 43, 1475–1486. First citation in articleCrossrefGoogle Scholar

  • Barsaglini, A., Sartori, G., Benetti, S., Pettersson-Yeo, W. & Mechelli, A. (2014). The effects of psychotherapy on brain function: A systematic and critical review. Progress in Neurobiology, 114, 1–14. First citation in articleCrossrefGoogle Scholar

  • Blair, K., Shaywitz, J., Smith, B. W., Rhodes, R., Geraci, M., Jones, M., … Pine, D. S. (2008). Response to emotional expressions in generalized social phobia and generalized anxiety disorder: Evidence for separate disorders. The American Journal of Psychiatry, 165, 1193–1202. First citation in articleCrossrefGoogle Scholar

  • Blair, K. S., Geraci, M., Smith, B. W., Hollon, N., DeVido, J., Otero, M. & Pine, D. S. (2012). Reduced dorsal anterior cingulate cortical activity during emotional regulation and top-down attentional control in generalized social phobia, generalized anxiety disorder, and comorbid generalized social phobia/generalized anxiety disorder. Biological Psychiatry, 72, 476–482. First citation in articleCrossrefGoogle Scholar

  • Boehme, S., Miltner, W. H. R. & Straube, T. (2015). Neural correlates of self-focused attention in social anxiety. Social Cognitive and Affective Neuroscience, 10, 856–862. First citation in articleCrossrefGoogle Scholar

  • Boehme, S., Mohr, A., Becker, M. P., Miltner, W. H. & Straube, T. (2014). Area-dependent time courses of brain activation during video-induced symptom provocation in social anxiety disorder. Biology of Mood and Anxiety Disorders, 4, 6. First citation in articleCrossrefGoogle Scholar

  • Boehme, S., Ritter, V., Tefikow, S., Stangier, U., Strauss, B., Miltner, W. H. & Straube, T. (2014). Brain activation during anticipatory anxiety in social anxiety disorder. Social Cognitive and Affective Neuroscience, 9, 1413–1418. First citation in articleCrossrefGoogle Scholar

  • Boehme, S., Ritter, V., Tefikow, S., Stangier, U., Strauss, B., Miltner, W. H. & Straube, T. (2015). Neural correlates of emotional interference in social anxiety disorder. PLoS One, 10, e0128608. First citation in articleGoogle Scholar

  • Brühl, A. B., Delsignore, A., Komossa, K. & Weidt, S. (2014). Neuroimaging in social anxiety disorder: A meta-analytic review resulting in a new neurofunctional model. Neuroscience & Biobehavioral Reviews, 47, 260–280. First citation in articleCrossrefGoogle Scholar

  • Caseras, X., Giampietro, V., Lamas, A., Brammer, M., Vilarroya, O., Carmona, S., … Mataix-Cols, D. (2010). The functional neuroanatomy of blood-injection-injury phobia: A comparison with spider phobics and healthy controls. Psychological Medicine, 40, 125–134. First citation in articleCrossrefGoogle Scholar

  • Chen, A. C. & Etkin, A. (2013). Hippocampal network connectivity and activation differentiates post-traumatic stress disorder from generalized anxiety disorder. Neuropsychopharmacology, 38, 1889–1898. First citation in articleCrossrefGoogle Scholar

  • Craske, M. G., Rauch, S. L., Ursano, R., Prenoveau, J., Pine, D. S. & Zinbarg, R. E. (2009). What is an anxiety disorder? Depression and Anxiety, 26, 1066–1085. First citation in articleCrossrefGoogle Scholar

  • Cuthbert, B. N. (2014). The RDoC framework: Facilitating transition from ICD/DSM to dimensional approaches that integrate neuroscience and psychopathology. World Psychiatry, 13, 28–35. First citation in articleCrossrefGoogle Scholar

  • de Carvalho, M. R., Rozenthal, M. & Nardi, A. E. (2010). The fear circuitry in panic disorder and its modulation by cognitive-behaviour therapy interventions. The World Journal of Biological Psychiatry, 11, 188–198. First citation in articleCrossrefGoogle Scholar

  • Demenescu, L. R., Kortekaas, R., Cremers, H. R., Renken, R. J., van Tol, M. J., van der Wee, N. J. A., … Aleman, A. (2013). Amygdala activation and its functional connectivity during perception of emotional faces in social phobia and panic disorder. Journal of Psychiatric Research, 47, 1024–1031. First citation in articleCrossrefGoogle Scholar

  • Dresler, T., Guhn, A., Tupak, S., Ehlis, A.-C., Herrmann, M., Fallgatter, A., … Domschke, K. (2013). Revise the revised? New dimensions of the neuroanatomical hypothesis of panic disorder. Journal of Neural Transmission, 120, 3–29. First citation in articleCrossrefGoogle Scholar

  • Duval, E. R., Javanbakht, A. & Liberzon, I. (2015). Neural circuits in anxiety and stress disorders: A focused review. The Journal of Therapeutics and Clinical Risk Management, 11, 115–126. First citation in articleGoogle Scholar

  • Etkin, A., Prater, K. E., Hoeft, F., Menon, V. & Schatzberg, A. F. (2010). Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in generalized anxiety disorder. The American Journal of Psychiatry, 167, 545–554. First citation in articleCrossrefGoogle Scholar

  • Etkin, A. & Schatzberg, A. F. (2011). Common abnormalities and disorder-specific compensation during implicit regulation of emotional processing in generalized anxiety and major depressive disorders. The American Journal of Psychiatry, 168, 968–978. First citation in articleCrossrefGoogle Scholar

  • Etkin, A. & Wager, T. D. (2007). Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. The American Journal of Psychiatry, 164, 1476–1488. First citation in articleCrossrefGoogle Scholar

  • Fonzo, G. A., Ramsawh, H. J., Flagan, T. M., Sullivan, S. G., Letamendi, A., Simmons, A. N., … Stein, M. B. (2015). Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders. British Journal of Psychiatry, 206, 206–215. First citation in articleCrossrefGoogle Scholar

  • Fonzo, G. A., Ramsawh, H. J., Flagan, T. M., Sullivan, S. G., Simmons, A. N., Paulus, M. P. & Stein, M. B. (2014). Cognitive-behavioral therapy for generalized anxiety disorder is associated with attenuation of limbic activation to threat-related facial emotions. Journal of Affective Disorders, 169, 76–85. First citation in articleCrossrefGoogle Scholar

  • Fournier, J. C. & Price, R. B. (2014). Psychotherapy and Neuroimaging. Focus, 12, 290–298. First citation in articleCrossrefGoogle Scholar

  • Freitas-Ferrari, M. C., Hallak, J. E., Trzesniak, C., Filho, A. S., Machado-de-Sousa, J. P., Chagas, M. H., … Crippa, J. A. (2010). Neuroimaging in social anxiety disorder: a systematic review of the literature. Progress in Neuro-Psychopharmacology Biological Psychiatry, 34, 565–580. First citation in articleCrossrefGoogle Scholar

  • Furmark, T., Tillfors, M., Marteinsdottir, I., Fischer, H., Pissiota, A., Långström, B. & Fredrikson, M. (2002). Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy. Archives of General Psychiatry, 59, 425–433. First citation in articleCrossrefGoogle Scholar

  • Goldin, P. R., Ziv, M., Jazaieri, H., Weeks, J., Heimberg, R. G. & Gross, J. J. (2014). Impact of cognitive-behavioral therapy for social anxiety disorder on the neural bases of emotional reactivity to and regulation of social evaluation. Behaviour Research and Therapy, 62, 97–106. First citation in articleCrossrefGoogle Scholar

  • 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, 1048–1056. First citation in articleCrossrefGoogle Scholar

  • Heitmann, C. Y., Feldker, K., Neumeister, P., Zepp, B. M., Peterburs, J., Zwitserlood, P. & Straube, T. (2016). Abnormal brain activation and connectivity to standardized disorder-related visual scenes in social anxiety disorder. Human Brain Mapping, Advance online publication. doi: 10.1002/hbm.23120 First citation in articleCrossrefGoogle Scholar

  • Herrmann, M. J., Boehme, S., Becker, M. P. I., Tupak, S., Schmidt, B., Guhn, A., … Straube, T. (2016). Phasic and sustained brain responses in the amygdala and the bed nucleus of the stria terminalis during threat anticipation. Human Brain Mapping, 37, 1091–1102. First citation in articleCrossrefGoogle Scholar

  • Ipser, J. C., Singh, L. & Stein, D. J. (2013). Meta-analysis of functional brain imaging in specific phobia. Psychiatry & Clinical Neurosciences, 67, 311–322. First citation in articleCrossrefGoogle Scholar

  • Kandel, E. R. (1979). Psychotherapy and the single synapse: the impact of psychiatric thought on neurobiological research. New England Journal of Medicine, 301, 1028–1037. First citation in articleCrossrefGoogle Scholar

  • Kircher, T., Arolt, V., Jansen, A., Pyka, M., Reinhardt, I., Kellermann, T., … Straube, B. (2013). Effect of cognitive-behavioral therapy on neural correlates of fear conditioning in panic disorder. Biological Psychiatry, 73, 93–101. First citation in articleCrossrefGoogle Scholar

  • Lipka, J., Hoffmann, M., Miltner, W. H. R. & Straube, T. (2014). Effects of cognitive-behavioral therapy on brain responses to subliminal and supraliminal threat and their functional significance in specific phobia. Biological Psychiatry, 76, 869–877. First citation in articleCrossrefGoogle Scholar

  • Lipka, J., Miltner, W. H. R. & Straube, T. (2011). Vigilance for threat interacts with amygdala responses to subliminal threat cues in specific phobia. Biological Psychiatry, 70, 472–478. First citation in articleCrossrefGoogle Scholar

  • Lueken, U., Kruschwitz, J. D., Muehlhan, M., Siegert, J., Hoyer, J. & Wittchen, H.-U. (2011). How specific is specific phobia? Different neural response patterns in two subtypes of specific phobia. NeuroImage, 56, 363–372. First citation in articleCrossrefGoogle Scholar

  • Lueken, U., Straube, B., Konrad, C., Wittchen, H. U., Ströhle, A., Wittmann, A., … Kircher, T. (2013). Neural substrates of treatment response to cognitive-behavioral therapy in panic disorder with agoraphobia. The American Journal of Psychiatry, 170, 1345–1355. First citation in articleCrossrefGoogle Scholar

  • Makovac, E., Meeten, F., Watson, D. R., Herman, A., Garfinkel, S. N., Critchley, H. D. & Ottaviani, C. (2015). Alterations in Amygdala-prefrontal functional connectivity account for excessive worry and autonomic dysregulation in generalized anxiety disorder. Biological Psychiatry, Advance online publication. doi: 10.1016/j.biopsych.2015.10.013 First citation in articleCrossrefGoogle Scholar

  • Månsson, K. N., Carlbring, P., Frick, A., Engman, J., Olsson, C. J., Bodlund, O., … Andersson, G. (2013). Altered neural correlates of affective processing after Internet-delivered cognitive behavior therapy for social anxiety disorder. Psychiatry Research, 214, 229–237. First citation in articleCrossrefGoogle Scholar

  • Månsson, K. N., Frick, A., Boraxbekk, C. J., Marquand, A. F., Williams, S. C., Carlbring, P., … Furmark, T. (2015). Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning. Translational Psychiatry, 5, e530. First citation in articleCrossrefGoogle Scholar

  • Maren, S., Phan, K. L. & Liberzon, I. (2013). The contextual brain: Implications for fear conditioning, extinction and psychopathology. Nature Reviews Neuroscience, 14, 417–428. First citation in articleCrossrefGoogle Scholar

  • Messina, I., Sambin, M., Palmieri, A. & Viviani, R. (2013). Neural correlates of psychotherapy in anxiety and depression: A meta-analysis. PLoS One, 8, e74657. First citation in articleGoogle Scholar

  • Mochcovitch, M. D., da Rocha Freire, R. C., Garcia, R. F. & Nardi, A. E. (2014). A systematic review of fMRI studies in generalized anxiety disorder: Evaluating its neural and cognitive basis. Journal of Affective Disorders, 167, 336–342. First citation in articleCrossrefGoogle Scholar

  • Otte, C. (2011). Cognitive behavioral therapy in anxiety disorders: Current state of the evidence. Dialogues in Clinical Neuroscience, 13, 413–421. First citation in articleGoogle Scholar

  • Pannekoek, J. N., Veer, I. M., van Tol, M.-J., van der Werff, S. J. A., Demenescu, L. R., Aleman, A., … van der Wee, N. J. A. (2013). Aberrant limbic and salience network resting- state functional connectivity in panic disorder without comorbidity. Journal of Affective Disorders, 145, 29–35. First citation in articleCrossrefGoogle Scholar

  • Quirk, G. J., Martinez, K. G. & Nazario Rodriguez, L. L. (2007). Translating findings from basic fear research to clinical psychiatry in Puerto Rico. Puerto Rico Health Sciences Journal, 26, 321–328. First citation in articleGoogle Scholar

  • Schienle, A., Schäfer, A., Hermann, A., Rohrmann, S. & Vaitl, D. (2007). Symptom provocation and reduction in patients suffering from spider phobia: An fMRI study on exposure therapy. European Archives of Psychiatry and Clinical Neuroscience, 257, 486–493. First citation in articleCrossrefGoogle Scholar

  • Schulz, C., Mothes-Lasch, M. & Straube, T. (2013). Automatic neural processing of disorder-related stimuli in social anxiety disorder: Faces and more. Frontiers in Psychology, 4, 282. First citation in articleCrossrefGoogle Scholar

  • Shin, L. M. & Liberzon, I. (2010). The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology, 35, 169–191. First citation in articleCrossrefGoogle Scholar

  • Straube, B., Lueken, U., Jansen, A., Konrad, C., Gloster, A. T., Gerlach, A. L., … Kircher, T. (2014). Neural correlates of procedural variants in cognitive-behavioral therapy: A randomized, controlled multicenter fMRI study. Psychotherapy and Psychosomatics, 83, 222–233. First citation in articleCrossrefGoogle Scholar

  • Straube, T., Glauer, M., Dilger, S., Mentzel, H. J. & Miltner, W. H. R. (2006). Effects of cognitive-behavioral therapy on brain activation in specific phobia. Neuroimage, 29, 125–135. First citation in articleCrossrefGoogle Scholar

  • Straube, T., Kolassa, I. T., Glauer, M., Mentzel, H. J. & Miltner, W. H. R. (2004). Effect of task conditions on brain responses to threatening faces in social phobics: an event-related functional magnetic resonance imaging study. Biological Psychiatry, 56, 921–930. First citation in articleCrossrefGoogle Scholar

  • Straube, T., Mentzel, H. J. & Miltner, W. H. R. (2007). Waiting for spiders: brain activation during anticipatory anxiety in spider phobics. Neuroimage, 7(4), 1427–1436. First citation in articleCrossrefGoogle Scholar

  • Straube, T. & Miltner, W. H. R. (2011). Ängste und Phobien. In G. SchiepekEd., Neurobiologie der Psychotherapie [Neurobiology of psychotherapy] (pp. 385–397). Stuttgart, Germany: Schattauer. First citation in articleGoogle Scholar

  • Tupak, S. V. & Straube, T. (2014a). Imaging methods in psychotherapy. In J. D. WrightEd., International encyclopedia of the social and behavioral sciences (pp. 612–620). Amsterdam, The Netherlands: Elsevier. First citation in articleGoogle Scholar

  • Tupak, S. V. & Straube, T. (2014b). Imaging methods in clinical psychology. In J. D. WrightEd., International encyclopedia of the social and behavioral sciences (pp. 603–611). Amsterdam, The Netherlands: Elsevier. First citation in articleGoogle Scholar

  • Weingarten, C. P. & Strauman, T. J. (2015). Neuroimaging for psychotherapy research: Current trends. Psychotherapy Research, 25, 185–213. First citation in articleCrossrefGoogle Scholar