Pre-treatment functional connectivity patterns associated with variability in cognitive-behavioral therapy response...

Specific phobia is an anxiety disorder marked by excessive fear of particular objects or situations. Although cognitive-behavioral therapy is generally effective, patient response varies. The study aimed to explore neural predictors for characterization of treatment-response variability and individualized treatment approaches. Focusing on connectivity rather than structural or functional magnetic resonance imaging features, it also explored pre-treatment functional magnetic resonance imaging differences between high and low responders based on clinically significant changes after therapy. Twenty-nine adults with specific phobia to small animals underwent baseline functional magnetic resonance while exposed to real or virtual 3D images of phobic stimuli. Following an eight-week cognitive behavioral therapy, patients were classified as high or low responders based on clinically significant change. Pre-treatment functional connectivity was analyzed via region-of-interest-to-region-of-interest correlations. Two groups were formed (14 high responders and 15 low responders) and compared by a t-test. Low responders exhibited greater connectivity across language, cognitive-control, reward, and sensorimotor networks. Differences included hyperconnectivity between the nucleus accumbens, inferior frontal gyrus, superior temporal gyrus, and caudate, and between the medial prefrontal cortex and motor/sensorimotor regions. This profile suggests stronger integration of motivational, verbal-conceptual, and motor-preparatory systems, potentially reflecting heightened internal verbalization, rigid habit-based responses, and anticipatory motor readiness. The results therefore point toward a maladaptive pre-treatment connectivity state in low responders, marked by over-recruitment of self-referential and control networks that limit the capacity for flexible emotional updating during cognitive-behavioral therapy. These findings suggest that functional connectivity patterns may contribute to the identification of neural markers associated with treatment response.