Early effects of exposure-based cognitive behaviour therapy on the neural correlates of anxiety

Abstract

Exposure-based cognitive-behaviour therapy (CBT) for anxiety disorders is an effective intervention, but the brain mechanisms driving recovery are largely unknown. In this experimental medicine study, we investigated to what degree CBT affects neural markers of anxiety at an early stage of treatment, to identify dynamic mechanistic changes which might be crucial in the process of recovery as opposed to those seen following full treatment completion. In a randomised controlled trial, unmedicated patients with panic disorder either received four weekly sessions of exposure-based CBT (N = 14) or were allocated to a waiting group (N = 14). Symptom severity was measured before and after the intervention. During functional magnetic resonance imaging (fMRI), patients performed an emotion regulation task, either viewing negative images naturally, or intentionally down-regulating negative affect using previously taught strategies. Four-session CBT led to marked reductions in symptoms and 71% of patients reached recovery status (versus 7% in the control group). This intervention normalised brain hyperactivation previously seen in panic disorder, particularly in areas linked to threat monitoring, fear memory, and maladaptive emotion regulation, such as amygdala, dorsomedial and dorsolateral prefrontal cortex, and temporal gyrus. Our findings suggest that optimal treatment doses for panic disorder might be much lower than previously thought. Furthermore, this is the first study to show that neural markers of anxiety change very early during CBT, highlighting potential neural mechanisms that might drive clinical recovery. Such knowledge is important for the development of more compact combination treatments targeting these mechanisms more effectively. (Neural Effects of Cognitive-behaviour Therapy in Panic Disorder; clinicaltrials.gov; NCT03251235).

Conflict of interest statement

C.H. has valueless shares in p1vital and serves on their advisory panel. She has received consultancy payments from p1vital, Servier, Eli-Lilly, Astra Zeneca, Lundbeck and is a director of Oxford Psychologists Ltd. The remaining authors declare that they have no conflict of interest.

Figures

Fig. 1. Whole-brain analysis.

a Main effect of Group: Compared to waiting list patients (WG), treated patients (TG) show reduced activation in left and right dmPFC and left dlPFC during picture blocks versus fixation baseline blocks (Maintain/Reappraisal both Maintain p < .001). b Group × task interaction: Maintaining negative affect versus Reappraisal was associated with attenuated signal response in treated compared to untreated patients in the left anterior superior-middle temporal gyrus (Maintain p < .01; Reappraisal p < .05). Images thresholded at Z > 2.3, P < 0.05, corrected. Note: Error bars show SEM

Fig. 2. Region of interest analyses in left and right amygdala clusters.

Compared to waiting list patients (WG), treated patients (TG) show reduced activation during Maintain blocks (p

Fig. 3. Whole-brain psychophysiological interaction analyses.

Using a right amygdala functional cluster (picture blocks versus baseline, acrossgroups) as the seed region, waiting list patients (WG) compared to treated patients (TG) showed reduced connectivity of the right amygdala with aleft precuneus/ posterior cingulate cortex cluster during Maintain blocks versus Reappraisal (Maintain: independent-samples t-test p thresholded at Z > 2.3, P