“Change the mind and you change the brain”: effects of cognitive- behavioral therapy on the neural correlates of spider phobia Vincent Paquette, a,d Johanne Le ´vesque, a Boualem Mensour, b Jean-Maxime Leroux, b Gilles Beaudoin, b,c Pierre Bourgouin, b,c and Mario Beauregard a,b,c,d, * a Centre de Recherche, Institut Universitaire de Ge ´riatrie de Montre ´al, Montre ´al, Canada b De ´partement de Radiologie, Centre Hospitalier de l’Universite ´ de Montre ´al (CHUM), Ho ˆpital Notre-Dame, Montre ´al, Canada c De ´partement de Radiologie, Faculte ´ de Me ´decine, Universite ´ de Montre ´al, Montre ´al, Canada d Centre de Recherche en Sciences Neurologiques, De ´partement de Physiologie, Sciences Neurologiques, Universite ´ de Montre ´al, Montre ´al, Canada Received 29 January 2002; revised 22 August 2002; accepted 21 October 2002 Abstract Questions pertaining to the neurobiological effects of psychotherapy are now considered among the most topical in psychiatry. With respect to this issue, positron emission tomography (PET) findings indicate that cognitive and behavioral modifications, occurring in a psychotherapeutic context, can lead to regional brain metabolic changes in patients with major depression or obsessive-compulsive disorder. The goal of the present functional magnetic resonance imaging (fMRI) study, which constitutes the first neuroimaging investigation of the effects of cognitive-behavioral therapy (CBT) using an emotional activation paradigm, was to probe the effects of CBT on the neural correlates of spider phobia. In order to do so, fMRI was used in subjects suffering from spider phobia (n = 12) to measure, before and after effective CBT, regional brain activity during the viewing of film excerpts depicting spiders. Normal control subjects were also scanned (once) while they were exposed to the same film excerpts. Results showed that, in phobic subjects before CBT, the transient state of fear triggered, during the viewing of the phobogenic stimuli, was correlated with significant activation of the right dorsolateral prefrontal cortex (Brodmann area—BA 10), the parahippocampal gyrus, and the visual associative cortical areas, bilaterally. For normal control subjects (n = 13), only the left middle occipital gyrus and the right inferior temporal gyrus were significantly activated. In phobic subjects before CBT, the activation of the dorsolateral prefrontal cortex (BA 10) may reflect the use of metacognitive strategies aimed at self-regulating the fear triggered by the spider film excerpts, whereas the parahippocampal activation might be related to an automatic reactivation of the contextual fear memory that led to the development of avoidance behavior and the maintenance of spider phobia. After successful completion of CBT, no significant activation was found in the dorsolateral prefrontal cortex (BA 10) or the parahippocampal gyrus. These findings suggest that a psychotherapeutic approach, such as CBT, has the potential to modify the dysfunctional neural circuitry associated with anxiety disorders. They further indicate that the changes made at the mind level, within a psychotherapeutic context, are able to functionally “rewire” the brain. © 2003 Elsevier Science (USA). All rights reserved. Keywords: fMRI; Cognitive-behavioral therapy; Spider phobia; Prefrontal cortex; Parahippocampal gyrus; Anxiety Introduction Specific phobias are the most common psychiatric dis- orders, with an estimated lifetime prevalence of 11.3% in the United States (Magee et al., 1996). Spider phobia (SP) is one of the most widespread forms of specific phobia (Bourdon et al., 1988). People with SP experience persistent and intense fear when confronted with spiders and develop avoidance behavior of all contexts related to this animal (APA, 1994). To date, a few functional brain imaging studies have been carried out to map the neural substrate of SP. In the first two of this series of studies, subjects were scanned with positron emission tomography (PET) while they were view- ing a color videotape of a spider (Fredrikson et al., 1993, * Corresponding author. Centre de Recherche, Institut Universitaire de Ge ´riatrie de Montre ´al, 4565 Queen Mary Rd., Montre ´al (Que ´bec), Canada, H3W 1W5. Fax: +514-340-3548. E-mail address: mario.beauregard@umontreal.ca (M. Beauregard). R Available online at www.sciencedirect.com NeuroImage 18 (2003) 401– 409 www.elsevier.com/locate/ynimg 1053-8119/03/$ – see front matter © 2003 Elsevier Science (USA). All rights reserved. doi:10.1016/S1053-8119(02)00030-7