- Low responders showed greater pre-treatment functional connectivity across language, cognitive-control, reward and sensorimotor networks, including nucleus accumbens, IFG, STG and caudate.
- Hyperconnectivity between medial prefrontal cortex and motor/sensorimotor regions indicated heightened internal verbalisation, rigid habit-based responding and anticipatory motor readiness.
- These maladaptive connectivity patterns may limit flexible emotional updating during behavioural therapy and serve as neural markers to predict CBT response and personalise care.
Eur Arch Psychiatry Clin Neurosci. 2026 Aug 7. doi: 10.1007/s00406-026-02313-y. Online ahead of print.
ABSTRACT
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.
PMID:42565986 | DOI:10.1007/s00406-026-02313-y
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