Contemporary Clinical Trials Communications (Feb 2025)
Left ventromedial prefrontal cortex inhibitory rTMS as an anti-stress intervention in opioid use disorder: Trial design
Abstract
Background: In people with substance use disorders (SUDs), stress-exposure can impair executive function, and increase craving and likelihood of drug-use recurrence. Research shows that acute stressors increase drug-seeking behavior; however, mechanisms underlying this effect are incompletely understood. The Competing Neurobehavioral Decisions System theory posits that persons with SUDs may have hyperactive limbic reward circuitry and hypoactive executive control circuitry. Objective: To investigate how inhibitory repetitive transcranial magnetic stimulation (rTMS) targeting the left ventromedial prefrontal cortex (vmPFC) may alter stress-induced executive dysfunction, emotion dysregulation, and drug-seeking in people with opioid use disorder. Methods: We will examine effects of a psychological stressor combined with inhibitory (1Hz) left vmPFC rTMS in participants (N = 24) receiving opioid agonist treatment. Participants undergo guided imagery of autobiographical stressors paired with 10 sessions of active vmPFC rTMS vs. sham (within-subject randomized crossover). Stress-induced dysfunction will be indexed with cognitive (e.g., executive function), affective (e.g., emotional arousal), and behavioral (e.g., opioid-seeking) measures pre- and post-rTMS. To confirm changes are associated with altered neural activity in targeted regions, we will measure event-related potentials during key tasks using EEG. We hypothesize that stressors will increase executive dysfunction, emotion dysregulation, and drug-seeking, and that left vmPFC inhibitory rTMS will decrease limbic activation, which could translate to reduced craving and drug-seeking. Conclusion: Our findings should offer insights into how neural networks modulate drug-seeking and associated dysfunctions in people with SUDs. The results of this and similar studies can advance theory and neuromodulation interventions for people with SUDs.
