Effects of Cognitive-Behavioral Therapy on Brain Responses to Subliminal and Supraliminal Threat and Their Functional Significance in Specific Phobia.
ABSTRACT Neurocircuitry models of anxiety disorders suggest dysregulated mechanisms encompassing both automatic and elaborate threat processing. However, the extent to which these processes might be differentially modified by psychotherapy and the neural basis of such changes are unknown. We examined the effects of cognitive-behavioral therapy (CBT) in patients with anxiety disorder on brain responses to subliminal and supraliminal threat.
3-Tesla functional magnetic resonance imaging was used to assess neural responses to disorder-related stimuli, presented during two backward-masking conditions employed to manipulate stimulus awareness. In 28 spider-phobic patients randomly assigned to a therapy group or a waiting-list control group scanning was performed before and after completing CBT or a waiting period. Scanning was performed one time in 16 healthy control subjects. Self-report and behavioral measures were used to relate CBT-mediated brain activation changes with symptom improvement.
Untreated patients demonstrated abnormal hyperactivation in the amygdala, fusiform gyrus, insula, anterior cingulate cortex, and dorsomedial prefrontal cortex. Successful CBT was reflected in an overall downregulation in these fear circuitry structures, especially in the right amygdala and anterior cingulate cortex, with reductions in amygdala responsiveness associated with self-reported symptom improvement. However, subliminal threat induced a pattern of right-lateralized hyperactivation in the amygdala and fusiform gyrus that was subject to intersession habituation across groups without showing significant sensitivity to CBT.
These results challenge prevailing models that emphasize a role for amygdala automaticity in the maintenance of anxiety. Our results suggest CBT-related changes in neural activation associated with fear responses to consciously perceived threat.
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ABSTRACT: Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT.Translational psychiatry. 01/2014; 4:e444.
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ABSTRACT: Psychiatric conditions of emotion dysregulation are often characterized by difficulties in regulating the activity of limbic regions such as the amygdala. Real-time functional magnetic resonance imaging (rt-fMRI) allows to feedback brain activation and opens the possibility to establish a neurofeedback (NF) training of amygdala activation, e.g., for subjects suffering from emotion dysregulation. As a first step, we investigated whether feedback of the amygdala response to aversive scenes can improve down-regulation of amygdala activation. One group of healthy female participants received amygdala feedback (N = 16) and a control group was presented with feedback from a control region located in the basal ganglia [N(sum) = 32]. Subjects completed a one-session rt-fMRI-NF training where they viewed aversive pictures and received continuous visual feedback on brain activation (REGULATE condition). In a control condition, subjects were advised to respond naturally to aversive pictures (VIEW), and a neutral condition served as the non-affective control (NEUTRAL). In an adjacent run, subjects were presented with aversive pictures without feedback to test for transfer effects of learning. In a region of interest (ROI) analysis, the VIEW and the REGULATE conditions were contrasted to estimate brain regulation success. The ROI analysis was complemented by an exploratory analysis of activations at the whole-brain level. Both groups showed down-regulation of the amygdala response during training. Feedback from the amygdala but not from the control region was associated with down-regulation of the right amygdala in the transfer test. The whole-brain analysis did not detect significant group interactions. Results of the group whole-brain analyses are discussed. We present a proof-of-concept study using rt-fMRI-NF for amygdala down-regulation in the presence of aversive scenes. Results are in line with a potential benefit of NF training for amygdala regulation.Frontiers in Behavioral Neuroscience 01/2014; 8:299. · 4.76 Impact Factor