Overview

The study will recruit 50 adults with stimulant use disorder currently in treatment and abstinent for at least 2 weeks. The study will also recruit up to 10 healthy controls (adults without StUD) for initial study configuration. The study will consist of five steps that are expected to be completed over two lab visits.

Step 1: The 3T MRI scan will provide accurate prefrontal cortex anatomy for using neuronavigation for TMS. In addition, the study will use an analysis of resting fMRI connectivity to determine the location in the left DLPFC that has the maximum connectivity with the incentive-salience network.

Step 2: The study will use the data collected at the MRI to select the individual TMS location. EEG will be used to collect TEPs in response to single pulse TMS at the left DLPFC. Participants will then be randomized to one of three conditions: A) TMS unsynchronized with EEG, B) TMS synchronized with EEG theta frequency trough, and C) TMS synchronized with EEG theta frequency peak. The stimulation will be applied with an intensity of up to 120% of the resting motor threshold (which is a safe and common practice; Rossi et al., 2021). The intensity can be decreased for individual participants.

Step 3: Following randomization, the study will administer a pre-iTBS assessment.

Step 4: The study will compare brain and behavioral responses before and after the iTBS session with TMS and EEG synchronization as assigned by their randomized group.

Step 5: The study will administer a post-iTBS assessment.

Eligibility

Inclusion Criteria:

• Age 18 or older
• Ability to provide consent and comply with all study procedures.
• Meets Diagnostic and Statistical Manual of Mental Disorders criteria for StUD (As assessed by MINI and self-report; Participants may have current comorbid drug use, but primary diagnosis must be StUD; does not apply to healthy control participants).
• At least 2 weeks of abstinence from substance use (other than caffeine or nicotine).
• Intention to remain in an addiction treatment program until intervention completion (does not apply to healthy control participants).
• Confident level of English language proficiency.

Exclusion Criteria:

• Any organic brain disorder (e.g. TBI, stroke).
• Head injury resulting in skull fracture or loss of consciousness exceeding 30 minutes.
• TMS contraindication (history of seizures, metallic cranial plates/screws or implanted device).
• MRI contraindications (unapproved metallic implants, pacemakers or any other implanted electrical device, shrapnel, metallic braces, non-removable body piercings, pregnancy, breathing or movement disorder, claustrophobia).
• Any psychotic disorder (Participants with other treated and stable psychiatric disorders will be included).
• Presence of a condition that would render study measures impossible to administer or interpret.
• Primary current substance use disorder diagnosis on a substance other than stimulants or cocaine, except for caffeine or nicotine.
• Greater than 9 months abstinence from substance use (does not apply to healthy control participants).
• Pregnancy or breastfeeding.