Neural Correlates of Procedural Variants in Cognitive-Behavioral Therapy: A Randomized, Controlled Multicenter fMRI Study

Abstract

Background: Cognitive behavioral therapy (CBT) is an effective treatment for panic disorder with agoraphobia (PD/AG). It is unknown, how variants of CBT differentially modulate brain networks involved in PD/AG. This study was aimed to evaluate the effects of therapist-guided (T+) versus self-guided (T-) exposure on the neural correlates of fear conditioning in PD/AG. Method: In a randomized, controlled multicenter clinical trial in medication-free patients with PD/AG who were treated with 12 sessions of manualized CBT, functional magnetic resonance imaging (fMRI) was used during fear conditioning before (t1) and after CBT (t2). Quality-controlled fMRI data from 42 patients and 42 healthy subjects (HS) were obtained. Patients were randomized to two variants of CBT (T+, n = 22, and T-, n = 20). Results: The interaction of diagnosis (PD/AG, HS), treatment group (T+, T-), time point (t1, t2) and stimulus type (conditioned stimulus: yes, no) revealed activation in the left hippocampus and the occipitotemporal cortex. The T+ group demonstrated increased activation of the hippocampus at t2 (t2 > t1), which was positively correlated with treatment outcome, and a decreased connectivity between the left inferior frontal gyrus and the left hippocampus across time (t1 > t2). Conclusion: After T+ exposure, contingency-encoding processes related to the posterior hippocampus are augmented and more decoupled from processes of the left inferior frontal gyrus, previously shown to be dysfunctionally activated in PD/AG. Linking single procedural variants to neural substrates offers the potential to inform about the optimization of targeted psychotherapeutic interventions.

The functional −1019C/G HTR1A polymorphism and mechanisms of fear

“…Importantly variation in HTR1A is not related ( P >0.2) to treatment variants (therapist vs self-guided exposure), which has been previously shown to be related to exposure behaviour 35 and the neural correlates of conditioning. 50 …”

“…For detailed information of the clinical and treatment aspects of the study, please see Gloster et al 35 , 45 and Straube et al 46 Sessions 1–3 consisted of psychoeducation and an individualized behavioural analysis of the patient's symptoms and coping behaviours. Sessions 4–5 provided the treatment rational for exposure and implemented interoceptive exposure exercises in the therapy room identically for both groups.…”

Neuroimaging of Fear-Associated Learning

“…During acquisition, greater differential activation of IFG has been seen in PD/A patients versus controls (Lueken et al, 2014), and cognitive behavioral therapy (CBT) reduced this activation in PD/A patients (Kircher et al, 2013). Further studies found that PD/A patients receiving CBT treatment also showed greater activation of the hippocampus during fear acquisition, and this was positively correlated with treatment outcome (Lueken et al, 2013;Straube et al, 2014a). These studies also found that CBT treatment is associated with lowered connectivity between the left IFG and the left hippocampus across time.…”

Angst und Panik

“…Viele dieser Studien sind innerhalb der großen Multizenterstudie Panik-Netz durchgeführt worden [43]. Veränderungen regionaler Aktivierungen und Konnektivitätsmuster in Verbindung mit Psychotherapieeffekten werden für Amygdala, Mittelhirn, Hippocampus, ACC und frontale Regionen beschrieben, was weitgehend mit dem beschriebenen Furchtnetzwerk überlappt (für Effekte einer psychodynamischen Therapie [44], für Effekte in einem Konditionierungsparadigma [33,45]; für eine Übersicht [46].…”