Using Combined EEG and Non-invasive Brain Stimulation to Examine and Improve Reward Functioning in Opioid Use Disorder

Not Applicable

Completed

Interventions: Device: Sham repetitive transcranial magnetic stimulation (rTMS)
Device: Active repetitive transcranial magnetic stimulation (rTMS)

Brief Summary: The primary aims of this study are to identify impaired cognitive control in opioid use disorder (OUD) and subsequently to examine the effects of transcranial magnetic stimulation (TMS) on reward processing, as measured by the reward positivity (an electrophysiological signal) in people with OUD. To this end, the investigators will adopt a randomized sham-controlled trial to evaluate the efficacy of Ri-TMS on cognitive control in OUD.

The investigators hypothesize that Ri-TMS will be successful in modulating the reward positivity in opioid users in the active TMS condition.

Detailed Description: The design is primarily a randomized control-trial design, comparing the effects of placebo (sham) and active TMS stimulation on reward processing across two groups of participants - healthy controls and opioid users.

Participants will be asked to engage in a virtual T-maze task, a reward-based choice task that elicits robust reward positivities. During this task participants will receive simultaneous EEG/TMS, while they engage in the virtual T-maze decision making task, used in our previous reward positivity studies on SUDs. ERPs will be recorded throughout the T-Maze task, and the reward positivity will be measured as the difference in maximum amplitude between reward and no-reward feedback conditions.

The TMS coil will be positioned using a an Adept Viper s850 robotic arm (SmartMove, ANT Neuro, Enschede, The Netherlands), providing precise targeting of the predetermined left dorsolateral prefrontal (DLPFC) coordinate (\< 10 mm from the scalp, orientated at a 45º angle). Participants in the active TMS condition will receive rTMS pulses throughout the duration of the T-Maze task, with a maximum of 2000 pulses delivered to each participant. Identical parameters will be applied to the SHAM group with the exception that the TMS coil will be flipped 180º to mimic auditory stimulation.

Recruitment & Eligibility

Inclusion Criteria

Native English speakers
Males and Females aged 18-55 years old
Ability to provide informed written or verbal consent
Opioid dependent individuals (according to the Alcohol, Smoking and Substance Involvement Screening Test opioid dependence score), or
Healthy controls with no history of significant substance use

Exclusion Criteria

Un-correctable visual impairment
Uninterruptable central nervous system medication
TMS contraindications (e.g., pregnancy, braces, history of seizures, metal implants).
History of neurological or psychiatric illness
Diagnosed learning disability
History of significant head injury (loss of consciousness for more than five minutes)
Substance abuse (Participants who score above 39.5 on the Global Continuum of Substance Risk scale of the Alcohol, Smoking and Substance Involvement Screening Test - controls only)
Use of psychoactive or vasoactive medications

Arm && Interventions

Group	Intervention	Description
Sham TMS - OUD	Sham repetitive transcranial magnetic stimulation (rTMS)	Identical parameters will be applied to the opioid used disorder (OUD) SHAM group with the exception that the TMS coil will be flipped 180º to mimic auditory stimulation
Active TMS - OUD	Active repetitive transcranial magnetic stimulation (rTMS)	Participants in the opioid used disorder group (OUD) in the active condition will receive repetitive TMS (rTMS), delivered at 110% of participants' resting motor threshold at 10 Hz continuously over the predefined DLFPC target for a total of 2000 pulses
Active TMS - HC	Active repetitive transcranial magnetic stimulation (rTMS)	Healthy Control (HC) participants in the active condition will receive repetitive TMS (rTMS), delivered at 110% of participants' resting motor threshold at 10 Hz continuously over the predefined DLFPC target for a total of 2000 pulses
Sham TMS - HC	Sham repetitive transcranial magnetic stimulation (rTMS)	Identical parameters will be applied to the healthy control (HC) SHAM group with the exception that the TMS coil will be flipped 180º to mimic auditory stimulation

Primary Outcome Measures

Name	Time	Method
Reward Positivity	Day 0 (day of testing)	The reward positivity is an event-related brain potential, sensitive to reward feedback. The reward positivity will be measured during the t-maze task, where participants will receive feedback on choices (Reward, No-reward). Reward positivity amplitude will be determined by identifying the maximum absolute amplitude of the difference wave within a 200- to 400-ms window following feedback onset. The reward positivity will be evaluated along front-central electrodes (Fz, FCz, Cz).

Secondary Outcome Measures