Mindfulness-based cognitive therapy neurobiology during self-referential processing in clinically complex obsessive-compulsive disorder

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Abstract
Mindfulness-based cognitive therapy (MBCT) has emerged as a promising strategy for patients with obsessive-compulsive disorder (OCD) who do not fully respond to cognitive behavioral therapy. However, the neurobiological mechanisms underlying the effects of MBCT remain unclear. Functional magnetic resonance imaging (fMRI) is a critical tool for identifying brain activity changes associated with therapeutic interventions. We aimed to identify the neurobiological underpinnings of MBCT for clinically complex OCD by evaluating task-based fMRI during self-referential processing. Thirty-one patients with OCD (i.e., 15 randomized to a 3-month MBCT program and 16 to a treatment-as-usual group) underwent task-based fMRI scanning sessions focused on self-referential processing at baseline and after 3 months. During the fMRI sessions, participants completed a self-referential processing task, where they responded "yes" or "no" to whether an adjective described themselves. A flexible factorial model and within-group paired t-tests were used to evaluate the impact of the treatment group on longitudinal changes in brain activation. Our analyses revealed a group-by-time interaction in the dorsolateral prefrontal cortex (dlPFC) activity during self-referential processing. Patients with OCD treated with MBCT showed a reduction in dlPFC activation. This study highlights that MBCT reduced dlPFC recruitment during self-referential processing in patients with OCD, implying less reliance on executive control when patients adopt a decentred and observer perspective. This dlPFC down-shift, potentially reflecting functional decoupling from the default-mode network, offers a plausible neurobiological route through which MBCT mitigates obsessive-compulsive symptoms.