A thorough investigation of the neural effects of psychotherapy is needed in order to provide a neurobiological foundation for widely used treatment protocols. This paper reviews functional neuroimaging studies on psychotherapy effects and their methodological background, including the development of symptom provocation techniques. Studies of cognitive behavioural therapy (CBT) effects in obsessive-compulsive disorder (OCD) were consistent in showing decreased metabolism in the right caudate nucleus. Cognitive behavioural therapy in phobia resulted in decreased activity in limbic and paralimbic areas. Interestingly, similar effects were observed after successful intervention with selective serotonin reuptake inhibitors (SSRI) in both diseases, indicating commonalities in the biological mechanisms of psycho- and pharmacotherapy. These findings are discussed in the context of current neurobiological models of anxiety disorders. Findings in depression, where both decreases and increases in prefrontal metabolism after treatment and considerable differences between pharmacological and psychological interventions were reported, seem still too heterogeneous to allow for an integrative account, but point to important differences between the mechanisms through which these interventions attain their clinical effects. Further studies with larger patient numbers, use of standardised imaging protocols across studies, and ideally integration with molecular imaging are needed to clarify the remaining contradictions. This effort is worthwhile because functional imaging can then be potentially used to monitor treatment effects and aid in the choice of the optimal therapy. Finally, recent advances in the functional imaging of hypnosis and the application of neurofeedback are evaluated for their potential use in the development of psychotherapy protocols that use the direct modulation of brain activity as a way of improving symptoms.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Kandel ER . Biology and the future of psychoanalysis: a new intellectual framework for psychiatry revisited. Am J Psychiatry 1999; 156: 505–524.
Linden DEJ . Cerebral mechanisms of learning revealed by functional neuroimaging in humans. In: Kühn R, Menzel R, Menzel W, Ratsch U, Richter MM, Stamatescu I-O (eds). Adaptivity and Learning – An Interdisciplinary Debate. Springer: Heidelberg, 2003 pp 49–57.
Brody AL, Saxena S, Schwartz JM, Stoessel PW, Maidment K, Phelps ME et al. FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder. Psychiatry Res 1998; 84: 1–6.
Hendler T, Goshen E, Tzila Zwas S, Sasson Y, Gal G, Zohar J . Brain reactivity to specific symptom provocation indicates prospective therapeutic outcome in OCD. Psychiatry Res 2003; 124: 87–103.
Dierks T, Linden DEJ, Jandl M, Formisano E, Goebel R, Lanfermann H et al. Activation of Heschl's Gyrus during auditory hallucinations. Neuron 1999; 22: 615–621.
Beutel ME, Stern E, Silbersweig DA . The emerging dialogue between psychoanalysis and neuroscience: neuroimaging perspectives. J Am Psychoanal Assoc 2003; 51: 773–801.
Linden DEJ, Prvulovic D, Stirn A, Maurer K . Funktionelle Bildgebung und Psychotherapie. In Walter H (ed). Funktionelle Bildgebung in Psychiatrie und Psychotherapie. Methodische Grundlagen und klinische Anwendungen. Schattauer: Stuttgart, 2005 pp 373–382.
Breiter HC, Rauch SL, Kwong KK, Baker JR, Weisskoff RM, Kennedy DN et al. Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder. Arch Gen Psychiatry 1996; 53: 595–606.
Mataix-Cols D, Cullen S, Lange K, Zelaya F, Andrew C, Amaro E et al. Neural correlates of anxiety associated with obsessive-compulsive symptom dimensions in normal volunteers. Biol Psychiatry 2003; 53: 482–493.
Shapira NA, Liu Y, He AG, Bradley MM, Lessig MC, James GA et al. Brain activation by disgust-inducing pictures in obsessive-compulsive disorder. Biol Psychiatry 2003; 54: 751–756.
Rauch SL, Jenike MA, Alpert NM, Baer L, Breiter HC, Savage CR et al. Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Arch Gen Psychiatry 1994; 51: 62–70.
McGuire PK, Bench CJ, Frith CD, Marks IM, Fackowiak RS, Dolan RJ . Functional anatomy of obsessive-compulsive phenomena. Br J Psychiatry 1994; 164: 459–468.
Rauch SL, Savage CR, Alpert NM, Miguel EC, Baer L, Breiter HC et al. A positron emission tomographic study of simple phobic symptom provocation. Arch Gen Psychiatry 1995; 52: 20–28.
Dilger S, Straube T, Mentzel HJ, Fitzek C, Reichenbach JR, Hecht H et al. Brain activation to phobia-related pictures in spider phobic humans: an event-related functional magnetic resonance imaging study. Neurosci Lett 2003; 348: 29–32.
Rauch SL, van der Kolk BA, Fisler RE, Alpert NM, Orr SP, Savage CR et al. A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery. Arch Gen Psychiatry 1996; 53: 380–387.
Pissiota A, Frans O, Fernandez M, von Knorring L, Fischer H, Fredrikson M . Neurofunctional correlates of posttraumatic stress disorder: a PET symptom provocation study. Eur Arch Psychiatry Clin Neurosci 2002; 252: 68–75.
Driessen M, Beblo T, Mertens M, Piefke M, Rullkötter N, Silva Saavedra A et al. Different fMRI activation patterns of traumatic memory in borderline personality disorder with and without additional posttraumatic stress disorder. Biol Psychiatry 2004; 55: 603–611.
Bremner JD, Narayan M, Staib LH, Southwick SM, McGlashan T, Charney DS . Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. Am J Psychiatry 1999; 156: 1787–1795.
Shin LM, Orr SP, Carson MA, Rauch SL, Macklin ML, Lasko NB et al. Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Arch Gen Psychiatry 2004; 61: 168–176.
Beauregard M, Leroux JM, Bergman S, Arzoumanian Y, Beaudoin G, Bourgouin P et al. The functional neuroanatomy of major depression: an fMRI study using an emotional activation paradigm. NeuroReport 1998; 9: 3253–3258.
Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry 1999; 156: 675–682.
Sheline YI, Barch DM, Donnelly JM, Ollinger JM, Snyder AZ, Mintun MA . Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry 2001; 50: 651–658.
Siegle GJ, Steinhauer SR, Thase ME, Stenger VA, Carter CS . Can't shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biol Psychiatry 2002; 51: 693–707.
Baxter Jr LR, Schwartz JM, Bergman KS, Szuba MP, Guze BH, Mazziotta JC et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry 1992; 49: 681–689.
Schwartz JM, Stoessel PW, Baxter Jr LR, Martin KM, Phelps ME . Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder. Arch Gen Psychiatry 1996; 53: 109–113.
Nakatani E, Nakgawa A, Ohara Y, Goto S, Uozumi N, Iwakiri M et al. Effects of behavior therapy on regional cerebral blood flow in obsessive-compulsive disorder. Psychiatry Res 2003; 124: 113–120.
Schwartz JM . Neuroanatomical aspects of cognitive behavioural therapy response in obsessive-compulsive disorder. An evolving perspective on brain and behaviour. Br J Psychiatry 1998; 173 (Suppl. 35): 38–44.
Saxena S, Brody AL, Schwartz JM, Baxter LR . Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder. Br J Psychiatry 1998; 173 (Suppl 35): 26–37.
Nakao T, Nakagawa A, Yoshiura T, Nakatani E, Nabeyama M, Yoshizato C et al. Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: a functional magnetic resonance imaging study. Biol Psychiatry 2005; 57: 901–910.
Paquette V, Levesque J, Mensour B, Leroux JM, Beaudoin G, Bourgouin P et al. ‘Change the mind and you change the brain’: effects of cognitive-behavioral therapy on the neural correlates of spider phobia. Neuroimage 2003; 18: 401–409.
Straube T, Glauer M, Dilger S, Mentzel HJ, Miltner WHR . Effects of cognitive-behavioral therapy on brain activation in specific phobia. Neuroimage 2006; 29: 125–135.
Birbaumer N, Grodd W, Diedrich O, Klose U, Erb M, Lotze M et al. fMRI reveals amygdala activation to human faces in social phobics. NeuroReport 1998; 9: 1223–1226.
Stein MB, Goldin PR, Sareen J, Eyler LT, Brown GG . Increased amygdala activation to angry and contemptuous faces in generalized social phobia. Arch Gen Psychiatry 2002; 59: 1027–1034.
Furmark T, Tillfors M, Marteinsdottir I, Fischer H, Pissiota A, Langstrom B et al. Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy. Arch Gen Psychiatry 2002; 59: 425–433.
Mayberg HS, Silva JA, Brannan SK, Tekell JL, Mahurin RK, McGinnis S et al. The functional neuroanatomy of the placebo effect. Am J Psychiatry 2002; 159: 728–737.
Navarro V, Gasto C, Lomena F, Mateos JJ, Marcos T, Portella MJ . Normalization of frontal cerebral perfusion in remitted elderly major depression: a 12-month follow-up SPECT study. Neuroimage 2002; 16: 781–787.
Brody AL, Saxena S, Stoessel P, Gillies LA, Fairbanks LA, Alborzian S et al. Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. Arch Gen Psychiatry 2001; 58: 631–640.
Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S et al. Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry 2004; 61: 34–41.
Martin SD, Martin E, Rai SS, Richardson MA, Royall R . Brain blood flow changes in depressed patients treated with interpersonal psychotherapy or venlafaxine hydrochloride: preliminary findings. Arch Gen Psychiatry 2001; 58: 641–648.
American Psychiatric Association Force or DSM-IV. Diagnostic and Statistical Manual of Mental Disorders, 4th edn, Text Revision (DSM-IV-TR®). American Psychiatric Association, 2000.
Thase ME . Neuroimaging profiles and the differential therapies of depression. Arch Gen Psychiatry 2001; 58: 651–653.
Cherry SR, Phelps ME . Imaging brain function with positron emission tomography. In: Toga AW, Mazziotta JC (eds). Brain Mapping. The Methods. Academic Press: San Diego, 1995 pp 191–221.
Drevets WC, Price JL, Simpson Jr JR, Todd RD, Reich T, Vannier M et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997; 386: 824–827.
Drevets WC . Neuroimaging studies of mood disorders. Biol Psychiatry 2000; 48: 813–829.
Sheline Y . Neuroimaging studies of mood disorder effects on the brain. Biol Psychiatry 2003; 54: 338–352.
Szeszko PR, MacMillan S, McMeniman M, Lorch E, Madden R, Ivey J et al. Amygdala volume reductions in pediatric patients with obsessive-compulsive disorder treated with paroxetine: preliminary findings. Neuropsychopharmacology 2004; 29: 826–832.
Gilbert AR, Moore GJ, Keshavan MS, Paulson LA, Narula V, Mac Master FP et al. Decrease in thalamic volumes of pediatric patients with obsessive-compulsive disorder who are taking paroxetine. Arch Gen Psychiatry 2000; 57: 449–456.
Laakso A, Hietala J . PET studies of brain monoamine transporters. Curr Pharmaceut Des 2000; 6: 1611–1623.
Talbot PS, Laruelle M . The role of in vivo molecular imaging with PET and SPECT in the elucidation of psychiatric drug action and new drug development. Eur Neuropsychopharmacol 2002; 12: 503–511.
Meyer JH, Wilson AA, Sagrati S, Hussey D, Carella A, Potter WZ et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB Positron Emission Tomography Study. Am J Psychiatry 2004; 161: 826–835.
Meyer JH, Wilson AA, Ginovart N, Goulding V, Hussey D, Hood K et al. Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [11C]DASB PET Imaging Study. Am J Psychiatry 2001; 158: 1843–1849.
Pirker W, Asenbaum S, Kasper S, Walter H, Angelberger P, Koch G et al. beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo. J Neural Transm Gen Sect 1995; 100: 247–256.
Kent JM, Coplan JD, Lombardo I, Hwang DR, Huang Y, Mawlawi O et al. Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with [11C]McN 5652. Psychopharmacology 2002; 164: 341–348.
Pogarell O, Poepperl G, Mulert C, Hamann C, Sadowsky N, Riedel M et al. SERT and DAT availabilities under citalopram treatment in obsessive-compulsive disorder (OCD). Eur Neuropsychopharmacol 2005; 15: 521–524.
Baer L . Behavior therapy: endogenous serotonin therapy? J Clin Psychiatry 1996; 57 (Suppl): 33–35.
Ebert D, Feistel H, Kaschka W, Barocka A, Pirner A . Single photon emission computerized tomographic assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation – Preliminary results. Biol Psychiatry 1994; 35: 880–885.
Ebert D, Ebmeier K . The role of the cingulate gyrus in depression: from functional anatomy to neurochemistry. Biol Psychiatry 1996; 39: 1044–1050.
Rainville P, Carrier B, Hofbauer RK, Bushnell MC, Duncan GH . Dissociation of sensory and affective dimensions of pain using hypnotic modulation. Pain 1999; 82: 159–171.
Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC . Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 1997; 277: 968–971.
Hofbauer RK, Rainville P, Duncan GH, Bushnell MC . Cortical representation of the sensory dimension of pain. J Neurophysiol 2001; 86: 402–411.
Röder CH, Michal M, Overbeck G, van de Ven V, Linden DEJ . Pain response in depersonalization – a functional imaging study using hypnosis in healthy subjects. Psychother Psychosomatics, in press.
Rainville P, Hofbauer RK, Paus T, Duncan GH, Bushnell MC, Price DD . Cerebral mechanisms of hypnotic induction and suggestion. J Cogn Neurosci 1999; 11: 110–125.
Birbaumer N, Ghanayim N, Hinterberger T, Iversen I, Kotchoubey B, Kuebler A et al. A spelling device for the paralysed. Nature 1999; 398: 297–298.
Weiskopf N, Veit R, Erb M, Mathiak K, Grodd W, Goebel R et al. Physiological self-regulation of regional brain activity using real-time functional magnetic resonance imaging (fMRI): methodology and exemplary data. Neuroimage 2003; 19: 577–586.
deCharms RC, Christoff K, Glover GH, Pauly JM, Whitfield S, Gabrieli JDE . Learned regulation of spatially localized brain activation using real-time fMRI. Neuroimage 2004; 21: 436–443.
deCharms RC, Maeda F, Glover GH, Ludlow D, Pauly JM, Soneji D et al. Control over brain activation and pain learned by using real-time functional MRI. Proc Natl Acad Sci USA 2005; 102: 18626–18631.
van de Ven VG, Formisano E, Prvulovic D, Roeder CH, Linden DEJ . Functional connectivity as revealed by spatial independent component analysis of fMRI measurements during rest. Hum Brain Mapp 2004; 22: 165–178.
Kent JM, Rauch SL . Neuroimaging studies of anxiety disorders. In: Charney DS, Nestler EJ (eds). Neurobiology of Mental Illness, 2nd edn. Oxford University Press: Oxford, UK, 2004 pp 639–660.
Rauch SL, Whalen PJ, Curran T, Shin LM, Coffey BJ, Savage CR et al. Probing striato-thalamic function in obsessive-compulsive disorder and Tourette syndrome using neuroimaging methods. Adv Neurol 2001; 85: 207–224.
Pasupathy A, Miller EK . Different time courses of learning-related activity in the prefrontal cortex and striatum. Nature 2005; 433: 873–876.
Davis M . Functional neuroanatomy of anxiety and fear. In: Charney DS, Nestler EJ (eds). Neurobiology of Mental Illness, 2nd edn. Oxford University Press: Oxford, UK, 2004 pp 584–604.
Goebel R, Roebroeck A, Kim D-S, Formisano E . Investigating directed cortical interactions in time-resolved fMRI data using vector autoregressive modeling and Granger causality mapping. Magn Res Imaging 2003; 21: 1251–1261.
Saxena S, Brody AL, Ho ML, Zohrabi N, Maidment KM, Baxter Jr LR . Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression. Am J Psychiatry 2003; 160: 522–532.
D'Esposito M, Deouell LY, Gazzaley A . Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nat Rev Neurosci 2003; 4: 863–872.
Prasko J, Horacek J, Zalesky R, Kopecek M, Novak T, Paskova B et al. The change of regional brain metabolism (18FDG PET) in panic disorder during the treatment with cognitive behavioural therapy or antidepressants. Neuroendocrinol Lett 2004; 25: 340–348.
About this article
Cite this article
Linden, D. How psychotherapy changes the brain – the contribution of functional neuroimaging. Mol Psychiatry 11, 528–538 (2006). https://doi.org/10.1038/sj.mp.4001816
- anxiety disorders
- functional magnetic resonance imaging
- positron emission tomography
- selective serotonin reuptake inhibitors
Current Neurology and Neuroscience Reports (2018)