Impact of cognitive behavioral therapy for social anxiety disorder on the neural dynamics of cognitive reappraisal of negative self-beliefs: randomized clinical trial

Abstract

Importance: Cognitive behavioral therapy (CBT) for social anxiety disorder (SAD) is thought to enhance cognitive reappraisal in patients with SAD. Such improvements should be evident in cognitive reappraisal-related prefrontal cortex responses.

Objective: To determine whether CBT for SAD modifies cognitive reappraisal-related prefrontal cortex neural signal magnitude and timing when implementing cognitive reappraisal with negative self-beliefs. DESIGN Randomized clinical trial of CBT for SAD vs wait-list control group during a study that enrolled patients from 2007 to 2010.

Setting: University psychology department.

Participants: Seventy-five patients with generalized SAD randomly assigned to CBT or wait list.

Intervention: Sixteen sessions of individual CBT for SAD.

Main outcome measures: Negative emotion ratings and functional magnetic resonance imaging blood oxygen-level dependent signal when reacting to and cognitively reappraising negative self-beliefs embedded in autobiographical social anxiety situations. RESULTS During reactivity trials, compared with wait list, CBT produced (1) greater reduction in negative emotion ratings and (2) greater blood oxygen-level dependent signal magnitude in the medial prefrontal cortex. During cognitive reappraisal trials, compared with wait list, CBT produced (3) greater reduction in negative emotion ratings, (4) greater blood oxygen level-dependent signal magnitude in the dorsolateral and dorsomedial prefrontal cortex, (5) earlier temporal onset of dorsomedial prefrontal cortex activity, and (6) greater dorsomedial prefrontal cortex-amygdala inverse functional connectivity.

Conclusions and relevance: Modulation of cognitive reappraisal-related brain responses, timing, and functional connectivity may be important brain changes that contribute to the effectiveness of CBT for social anxiety. This study demonstrates that clinically applied neuroscience investigations can elucidate neurobiological mechanisms of change in psychiatric conditions.

Trial registration: clinicaltrials.gov Identifier: NCT00380731.

Conflict of interest statement

None of the authors of this manuscript have any biomedical financial interests or potential conflicts of interest.

Figures

Figure 1

Consolidated Standards of Reporting Trials Diagram for a Randomized Controlled Trial of Individual Cognitive-Behavioral Therapy (I-CBT) vs. Waitlist (WL) Groups.

Figure 2

Experimental Design. Components and structure of one autobiographical social situation trial. After each negative self-belief (NSB), participants provide a negative emotion rating from 1=not negative to 5=extremely negative.

Figure 3

Changes in Negative Emotion Intensity Ratings for React Negative Self-Beliefs and Cognitive Reappraisal of Negative Self-Beliefs in Patients with Social Anxiety Disorder (SAD) Before and After Individual Cognitive-Behavioral Therapy (I-CBT) vs. Waitlist (WL) Groups. Negative emotion ratings after the offset of each stimulus were provided by participants in response to “How negative do you feel?” (1=not at all, 2=slightly, 3=moderately, and 4=very much, 5=extreme). * p<.001 error bars="standard" of the mean.>

Figure 4

Changes in Brain Responses in Dorsomedial Prefrontal Cortex (DMPFC) and Left Dorsolateral Prefrontal Cortex (DLPFC) A Priori Cognitive Reappraisal-related Prefrontal Cortical Brain Regions of Interest in Patients with Social Anxiety Disorder (SAD) Before and After Individual Cognitive-Behavioral Therapy (I-CBT) vs. Waitlist (WL) Groups. The red dot represents the spherical region of interest mask used in the analysis. BOLD signal represents pre-to-post change scores in BOLD signal responses.

Figure 5

Blood Oxygen Level Dependent (BOLD) Signal Time Series in Dorsomedial Prefrontal Cortex (DMPFC) and Left Dorsolateral Prefrontal Cortex (DLPFC) During Reappraise Negative Self-Beliefs (NSBs) vs. Read Neutral Statements.

Figure 6

Differential Between-Group Pre-to-Post Change in Dorsomedial Prefrontal Cortex-Seeded Context-Dependent Functional Connectivity of Cognitive Reappraisal vs. React Negative Self-Beliefs 1=MPFC, 2=right DLPFC, 3=right MFG, 4=DMPFC seed, 5=left hippocampus, 6=left amygdala. For the whole-brain, thresholding consisted of per voxel p<.005 and cluster volume threshold mm3. within the amygdala search region thresholding consisted of per voxel p>