Exposure therapy triggers lasting reorganization of neural fear processing

A single session of exposure therapy can eliminate recalcitrant and disabling fear of phobogenic objects or situations. We studied neural mechanisms of this remarkable outcome by monitoring changes in brain activity as a result of successful 2-h treatment. Before treatment, phobogenic images excited activity in a network of regions, including amygdala, insula, and cingulate cortex, relative to neutral images. Successful therapy dampened responsiveness in this fear-sensitive network while concomitantly heightening prefrontal involvement. Six months later, dampened fear-network activity persisted but without prefrontal engagement. Additionally, individual differences in the magnitude of visual cortex activations recorded shortly after therapy predicted therapeutic outcomes 6 mo later, which involved persistently diminished visual responsiveness to phobogenic images. Successful therapy thus entailed stable reorganization of neural responses to initially feared stimuli. These effects were linked to fear-extinction mechanisms identified in animal models, thus opening new opportunities for the treatment and prevention of debilitating anxiety disorders.

[1]  M. Craske,et al.  Mental reinstatement of context and return of fear in spider-fearful participants. , 2006, Behavior therapy.

[2]  P. Lang,et al.  Psychometric description of some specific-fear questionnaires. , 1974 .

[3]  Lutz Jäncke,et al.  Modulation of anticipatory emotion and perception processing by cognitive control , 2007, NeuroImage.

[4]  Michael S. Beauchamp,et al.  A new method for improving functional-to-structural MRI alignment using local Pearson correlation , 2009, NeuroImage.

[5]  Joseph E LeDoux,et al.  Extinction Learning in Humans Role of the Amygdala and vmPFC , 2004, Neuron.

[6]  Catherine A Hartley,et al.  Changing Fear: The Neurocircuitry of Emotion Regulation , 2010, Neuropsychopharmacology.

[7]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[8]  Lars-Göran Öst,et al.  One versus five sessions of exposure in the treatment of injection phobia , 1992 .

[9]  Leslie G. Ungerleider,et al.  Mechanisms of visual attention in the human cortex. , 2000, Annual review of neuroscience.

[10]  M. Maroun,et al.  Learning-Induced Changes in mPFC–BLA Connections After Fear Conditioning, Extinction, and Reinstatement of Fear , 2011, Neuropsychopharmacology.

[11]  Joseph E LeDoux The emotional brain , 1996 .

[12]  R. Peeters,et al.  Amygdala Hyperfunction in Phobic Fear Normalizes After Exposure , 2007, Biological Psychiatry.

[13]  P. Whalen,et al.  The structural and functional connectivity of the amygdala: From normal emotion to pathological anxiety , 2011, Behavioural Brain Research.

[14]  J. Gabrieli,et al.  Rethinking Feelings: An fMRI Study of the Cognitive Regulation of Emotion , 2002, Journal of Cognitive Neuroscience.

[15]  R. McNally Mechanisms of exposure therapy: how neuroscience can improve psychological treatments for anxiety disorders. , 2007, Clinical psychology review.

[16]  Joseph E. LeDoux,et al.  Emotional memory systems in the brain , 1993, Behavioural Brain Research.

[17]  J. D. McGaugh Memory--a century of consolidation. , 2000, Science.

[18]  D. McMillan,et al.  A systematic review of behavioral experiments vs. exposure alone in the treatment of anxiety disorders: A case of exposure while wearing the emperor's new clothes? , 2010, Clinical psychology review.

[19]  Johanne Lévesque,et al.  “Change the mind and you change the brain”: effects of cognitive-behavioral therapy on the neural correlates of spider phobia , 2003, NeuroImage.

[20]  A. Arntz,et al.  Negative beliefs of spider phobics: A psychometric evaluation of the spider phobia beliefs questionnaire , 1993 .

[21]  Lars-Göran Öst,et al.  One vs five sessions of exposure and five sessions of cognitive therapy in the treatment of claustrophobia. , 2001, Behaviour research and therapy.

[22]  Axel Schäfer,et al.  Symptom provocation and reduction in patients suffering from spider phobia , 2007, European Archives of Psychiatry and Clinical Neuroscience.

[23]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[24]  R. Dolan,et al.  Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value , 2004, Nature Neuroscience.

[25]  Joseph Wolpe,et al.  The practice of behavior therapy , 1969 .

[26]  Joseph E LeDoux,et al.  Neural Circuitry Underlying the Regulation of Conditioned Fear and Its Relation to Extinction , 2008, Neuron.

[27]  Thompson E Davis,et al.  One-session treatment of specific phobias: a detailed description and review of treatment efficacy. , 2008, Behavior therapy.

[28]  M. Delgado,et al.  Extending animal models of fear conditioning to humans , 2006, Biological Psychology.

[29]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[30]  M. Craske,et al.  Exposure Therapy and Extinction: Clinical Studies. , 2006 .

[31]  Gregory J. Quirk,et al.  Prefrontal Mechanisms in Extinction of Conditioned Fear , 2006, Biological Psychiatry.

[32]  Thomas Straube,et al.  Effects of cognitive-behavioral therapy on brain activation in specific phobia , 2006, NeuroImage.

[33]  W. Tryon Possible mechanisms for why desensitization and exposure therapy work. , 2005, Clinical psychology review.

[34]  Joel L. Voss,et al.  Establishing a relationship between activity reduction in human perirhinal cortex and priming , 2009, Hippocampus.

[35]  S. Rauch,et al.  Recall of Fear Extinction in Humans Activates the Ventromedial Prefrontal Cortex and Hippocampus in Concert , 2007, Biological Psychiatry.

[36]  S. Mineka,et al.  The effects of changing contexts on return of fear following exposure therapy for spider fear. , 1999, Journal of consulting and clinical psychology.

[37]  Joseph E LeDoux The Emotional Brain, Fear, and the Amygdala , 2003, Cellular and Molecular Neurobiology.

[38]  Paul J Reber,et al.  Encoding activity in the medial temporal lobe examined with anatomically constrained fMRI analysis , 2002, Hippocampus.

[39]  Joseph E LeDoux,et al.  Brain Mechanisms of Fear Extinction: Historical Perspectives on the Contribution of Prefrontal Cortex , 2006, Biological Psychiatry.

[40]  Y. Dudai The neurobiology of consolidations, or, how stable is the engram? , 2004, Annual review of psychology.

[41]  Neurocognitive effects of phobia-related stimuli in animal-fearful individuals , 2005, Cognitive, affective & behavioral neuroscience.