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

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.