Resting-state functional connectivity of the amygdala subregions in unmedicated patients with obsessive-compulsive disorder before and after cognitive behavioural therapy

Abstract

Background: Cognitive behavioural therapy (CBT) is considered an effective first-line treatment for obsessive-compulsive disorder (OCD). However, the neural basis of CBT for OCD has not yet been elucidated. The role of the amygdala in OCD and its functional coupling with the cerebral cortex have received increasing attention, and may provide new understanding of the neural basis of CBT for OCD.

Methods: We acquired baseline resting-state functional MRI (fMRI) scans from 45 unmedicated patients with OCD and 40 healthy controls; we then acquired another wave of resting-state fMRI scans from the patients with OCD after 12 weeks of CBT. We performed seed-based resting-state functional connectivity analyses of the amygdala subregions to examine changes in patients with OCD as a result of CBT.

Results: Compared to healthy controls, patients with OCD showed significantly increased resting-state functional connectivity at baseline between the left basolateral amygdala and the right middle frontal gyrus, and between the superficial amygdala and the right cuneus. In patients with OCD who responded to CBT, we found decreased resting-state functional connectivity after CBT between the amygdala subregions and the visual association cortices and increased resting-state functional connectivity between the amygdala subregions and the right inferior parietal lobe. Furthermore, these changes in resting-state functional connectivity were positively associated with changes in scores on the compulsion or obsession subscales of the Yale-Brown Obsessive-Compulsive Scale.

Limitations: Because of the lack of a second scan for healthy controls after 12 weeks, our results may have been confounded by other variables.

Conclusion: Our findings yield insights into the pathophysiology of OCD; they also reveal the potential neural changes elicited by CBT, and thus have implications for guiding effective treatment strategies with CBT for OCD.

Figure 1

Subregions of the amygdala. Red: left centromedial amygdala; green: left basolateral amygdala; yellow: left superficial amygdala; dark blue: right centromedial amygdala; violet: right basolateral amygdala; light blue: right superficial amygdala. Created using the SPM Anatomy toolbox and registered to Montreal Neurological Institute space.

Figure 2

Resting-state functional connectivity of the amygdala subregions that showed significant differences at baseline in patients with OCD compared to healthy controls. (A) Seed regions: left basolateral amygdala and right superficial amygdala. (B and C) Resting-state functional connectivity in (B) healthy controls and (C) patients with OCD. (D) Regions in which we found significant differences in resting-state functional connectivity with the seed region (cluster-level p_FWE < 0.05). *Survived Bonferroni correction. BLA = basolateral amygdala; FWE = family-wise error; MFG = middle frontal gyrus; OCD = obsessive–compulsive disorder; SFA = superficial amygdala.

Figure 3

Altered resting-state functional connectivity of the amygdala subregions in patients with OCD who responded to CBT, before and after treatment (cluster-level p_FWE < 0.05). The red regions are locations where functional connectivity with the amygdala subregions was increased in responders to CBT after treatment (compared to before treatment). The blue regions are locations where functional connectivity with the amygdala subregions was decreased in responders to CBT after treatment. BLA = basolateral amygdala; CBT = cognitive behavioural therapy; CMA = centromedial amygdala; FWE = family-wise error; IPL = inferior parietal lobule; ITG = inferior temporal gyrus; MOG = middle occipital gyrus; MTG = middle temporal gyrus; OCD = obsessive–compulsive disorder; SFA = superficial amygdala.

Figure 4

Correlations between changes in functional connectivity in amygdala subregions and symptom improvement in responders to CBT. (A) Positive correlation between changes in resting-state functional connectivity after CBT (right centromedial amygdala and left middle occipital gyrus) and a reduction in Y-BOCS compulsion score in responders to CBT. (B) Positive correlation between changes in resting-state functional connectivity after CBT (left basolateral amygdala and inferior temporal gyrus) and a reduction in Y-BOCS obsession score in responders to CBT. CBT = cognitive behavioural therapy; Y-BOCS, Yale–Brown Obsessive Compulsive Scale.