Elucidating the Neural Mechanisms of Cognitive- Behavioral Therapy: A Commentary on Treatment Changes in Neural Correlates of Subliminal and Supraliminal Threat in Individuals With Spider Phobia

Understanding how clinical interventions work is a fundamental task of clinical science. In particular, elucidating the brain and behavioral mechanisms of therapeutic change is essential to develop more refined and effective interventions and to understand why they work. One of the promises of functional neuroimaging is to provide a powerful window into the underlying psychological mechanisms instantiated in distributed brain networks that are modified with specific types of clinical interventions. In this issue of Biological Psychiatry ,L ipkaet al. (1) used functional magnetic resonance imaging to investigate the impact of brief (2 3–5 hours of) small group cognitive-behavioral therapy (CBT) versus a waitlist control group on the neurocircuitry involved in subliminal (preconscious) and supraliminal (conscious) threat processing in 28 female patients with spider phobia and 16 healthy control female participants. This study used a two-backward masking functional magnetic resonance imaging task with spider (vs. bird and mushroom) visual target stimuli to determine distinct brain responses to automatic versus conscious elaborative processing of threat cues, both of which represent mechanisms that may trigger and maintain hyperactive fear responses in individuals with spider phobia. Behaviorally, this study demonstrated that, compared with the waitlist control group, CBT resulted in significant decreases in selfreported negative valence and arousal to spider target stimuli, symptom severity, spider-related beliefs, self-related beliefs, and increases in behavioral approach. However, there was no evidence of reduction for vigilance suggesting that this may be an incontrovertible trait in individuals with spider phobia. Reductions in clinical symptoms and distorted beliefs related to CBT can occur despite no change in phobic hypervigilance in individuals with spider phobia. Neurally, pretreatment analyses focused on a priori brain regions of interest identified greater activation in participants with phobia versus healthy control participants in right amygdala and fusiform gyrus for subliminal threat processing with no detection of spiders and even more robust activations in bilateral amygdala, fusiform gyrus, anterior insula, dorsal anterior cingulate cortex (ACC), pregenual ACC, and dorsomedial prefrontal cortex (PFC) for supraliminal correct conscious detection of spiders. This finding suggests a hyperactive network implicated in affective, visual, visceral, and cognitive control mechanisms during conscious threat processing in individuals with spider phobia that may be a target of clinical interventions. With respect to the impact of clinical treatment, CBT produced no changes during subliminal threat processing. However, compared with the waitlist control group, CBT was associated with greater reduction in activation of right amygdala and dorsal ACC during supraliminal threat processing. Pre- to post-CBT and waitlist group changes across all participants with spider phobia revealed habituation-related reductions in bilateral amygdala, anterior insula, dorsal and pregenual ACC, and dorsomedial PFC. This pattern of results suggests that CBT for spider phobia may not have an impact on automatic preconscious processing of subliminal threat processing and that the impact of CBT on supraliminal threat processing may be accounted for solely by habituation processes. These findings are in contrast to models of psychopathology that emphasize an inverse relationship between exaggerated emotional reactivity–related amygdala responses and top-down emotion regulation deficits reflected in diminished recruitment of cognitive control mechanisms instantiated in PFC and resolution of such abnormalities after CBT, specifically, increased PFC and decreased amygdala responses (2). Models of CBT emphasize increases in cognitive reappraisal ability and self-efficacy based on the extensive training in implementing cognitive restructuring in the context of fear exposure. Neurally, CBT training has been shown to enhance cognitive reappraisal via increases in integrated recruitment of