Measuring the Effects of Neurostimulation on Risky and Ambiguous Decision-Making Capacity in People With and Without Substance Use Disorder

Study Description:

Risky decision-making is a core feature of substance use disorders and contributes to the compulsive behaviors seen in opioid use disorder (OUD). Risky decision-making can be separated into two distinct components: tolerance for known risks; and tolerance for unknown ambiguous risks. Tolerance for ambiguity in decision-making has been associated with increased risk of relapse in OUD, however conventional treatments for OUD rarely consider and target the dissociable components of decision-making that might underlie risky behaviors. In this study, we will utilize connectivity-based transcranial magnetic stimulation to selectively modulate ambiguity tolerance in decision-making in people with an OUD. Individualized cortical targets for stimulation will be derived from a baseline measurement of decision-making capacity. The ability for transcranial magnetic stimulation (TMS) to modulate ambiguity tolerance in decision-making will be assessed (relative to placebo stimulation), as well as clinical correlates, such as craving.

Objectives:

• Primary Objectives:

• Determine neural correlates of risk and ambiguity tolerance in healthy controls and people with OUD.
• Measure the impact of a type of TMS (theta burst stimulation) on ambiguity tolerance in healthy controls and people with OUD.
• Secondary Objectives:

• Determine the impact of TMS on resting-state brain activity.
• Determine the impact TMS on outcomes that are relevant to substance use and relapse (e.g., craving).
• Tertiary/Exploratory Objectives:

• The effect of sex on the above metrics will be explored.

Endpoints:

The impact of transcranial magnetic stimulation on decision making will be assessed several ways.

• Primary Endpoints:

• Brain reactivity during decision-making task that separates tolerance for risk and tolerance for ambiguity.
• Modulation of behavior and neural activity in areas of the brain associated with ambiguity tolerance by TMS.
• Secondary Endpoints:

• The influence of TMS on the brain s resting state function will be assessed.
• The influence of TMS on substance use-related outcomes will be assessed.
• Tertiary/Exploratory Endpoints:

• Completion of baseline visit where neuromodulation is not administered.

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Both groups:

-Participants will be volunteers between the ages of 18-60.

Opioid-using group:

• Participants must meet DSM-5 criteria for an opioid use disorder (active or in remission and on maintenance therapy).
• Participants must be currently enrolled in and receiving medication-assisted treatment for opioid use disorder (MOUD; such as methadone, buprenorphine or naltrexone) and report a stable dose of their medication for at least 4 weeks prior to enrollment.*
• Participants in this group can meet DSM-5 criteria for other substance use disorders (such as alcohol, nicotine, or cocaine use disorder) currently or in the past but must also meet criteria for an OUD.

• To note, participants in the opioid-using group will not receive direct clinical care from NIDA study staff, but enrollment in a MOUD program will be required for inclusion in this study. This will be assessed by self-report of enrollment in a known MOUD program and a urine screen confirming their reported treatment. Participants will also sign a release of information (ROI) form that provides contact details for their treatment provider and allows for communication between the study team and the participants treatment provider if necessary.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

Controls:

-Participants cannot meet DSM-5 criteria for current substance use disorders other than nicotine and marijuana and cannot meet criteria for current moderate or severe alcohol use disorder.

All participants:

• Participants cannot meet DSM-5 criteria for lifetime and/or current psychotic disorders such as bipolar disorder, schizophrenia, schizoaffective disorder.
• Participants cannot have a history of major head trauma resulting in cognitive impairment, seizure, or other neurological disorders.
• Participants cannot have any history of significant neurological disorders, including seizures, epilepsy, or cognitive impairment which may impact MRI metrics. MAI will use discretion in evaluating the impact of minor events or history reported.
• Participants cannot be pregnant.
• Participants with Major Depressive Disorder (per DSM-V criteria) must be stable on medication(s) for 3 months.
• Subjects with suicidal ideation where outpatient treatment is determined unsafe.
• Subjects that cannot speak English. Justification: To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify, given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing MRI procedures. The inability to effectively communicate MRI safety procedures in a language other than English could compromise the safety of non-English speaking participants.
• Any contraindications to MRI.
• For subjects continuing to the TMS portion of the protocol, contraindications for TMS.