Stanford Hypnosis Integrated with Functional Connectivity-targeted Transcranial Stimulation (SHIFT): a preregistered randomized controlled trial

Hypnotizability, one’s ability to experience cognitive, emotional, behavioral and physical changes in response to suggestions in the context of hypnosis, is a stable neurobehavioral trait associated with improved treatment outcomes from hypnosis-based therapy. Increasing hypnotizability in people who are low-to-medium hypnotizable individuals could improve both the efficacy and effectiveness of therapeutic hypnosis as a clinical intervention. Hypnotizability is associated with dorsolateral prefrontal cortex (DLPFC) functions and connectivity with the salience network, yet there is conflicting evidence as to whether unilateral inhibition of the DLPFC changes hypnotizability. We hypothesized that using personalized neuroimaging-guided targeting to non-invasively stimulate the left DLPFC with transcranial magnetic stimulation (TMS) would temporarily increase hypnotizability. In a preregistered, double-blinded, randomized controlled trial, we recruited a sample of 80 patients with fibromyalgia syndrome, a functional pain disorder for which hypnosis has been a demonstrated beneficial non-pharmacological treatment option. All participants were TMS-naive. Participants were randomly assigned to active or sham continuous theta-burst stimulation over a personalized neuroimaging-derived left-DLPFC target, a technique termed SHIFT (Stanford Hypnosis Integrated with Functional Connectivity-targeted Transcranial Stimulation). We tested our hypothesis using the hypnotic induction profile scores, a standardized measure of hypnotizability. Pre-to-post SHIFT change in the hypnotic induction profile scores was significantly greater in the active versus sham group after 92 s of stimulation ( P = 0.046). Only the active SHIFT group showed a significant increase in hypnotizability following stimulation (active: P < 0.001; sham: P = 0.607). As such, modulation of trait hypnotizability is possible in humans using non-invasive neuromodulation. Our findings support a relationship between the inhibition of the left DLPFC and an increase in hypnotizability. Dose–response optimization of spaced SHIFT should be explored to understand the optimal dose–response relationship. ClinicalTrials.gov registration: NCT02969707 .