Cognitive behavioral therapy effects on frontopolar cortex function during future thinking in major depressive disorder: A randomized clinical trial

Background: Despite the importance of Beck's theoretical cognitive model of psychopathology, the neural mechanisms underlying future thinking in cognitive behavioral therapy (CBT) remain elusive. Recent neuroimaging studies have shown that the function of the frontopolar cortex (Brodmann area 10 [BA10]) is associated with future thinking. We hypothesized that, compared with unstructured psychotherapy (talking control: TC), CBT may involve different neural responses in BA10 associated with future thinking. Methods: This randomized clinical trial included 38 adult patients with moderate-to-severe major depressive disorder who underwent up to 16 weeks of CBT or TC with a 6-month follow-up period. We evaluated changes in BA10 activation during distant future thinking using functional magnetic resonance imaging with a future-thinking task. We assessed frontal neurocognitive function and clinical symptoms at baseline and post-treatment. Depression severity and automatic thoughts were assessed at the 6-month follow-up. Results: We found decreased activation in the frontopolar cortex during distant future thinking after CBT (t = 3.00, df=15, p = 0.009) and no changes after TC. Further, the reduction in BA10 activity significantly correlated with changes in frontal cognitive function after the treatment (r = 0.48, p = 0.007), and in positive automatic thought after 6 months of treatments (r = 0.39; p = 0.03). Limitations: Relatively small sample size and homogenous clinical profile could limit the generalizability. Patients received pharmacotherapy including antidepressant. Conclusions: CBT appears to improve frontopolar cortex function during future thinking in a manner distinct from TC. Larger clinical trials are necessary to provide firm evidence whether BA10 activity may serve as a neuro-marker for monitoring successful depression treatment with CBT.