Neuromodulation and Cognitive Training in Opioid Use Disorder

Cognitive flexibility, the ability to change maladaptive behavior, depends on dorsolateral
prefrontal cortex (DLPFC) input to the nucleus accumbens (NAcc; Gruber, Hussain, and
O'Donnell 2009). DLPFC stimulation may increase input to NAcc to facilitate proper selection
of goal-directed behavior and may also decrease craving in individuals with substance use
disorder (Boggio et al. 2008).

We will use transcranial direct current stimulation (tDCS) to stimulate the DLPFC. TDCS is a
non-invasive brain stimulation technique that can modulate brain connectivity. TDCS involves
applying a weak electrical current (2mA or less) to the scalp via anodal and cathodal
electrode sponges, causing either increases or decreases in cortical excitability,
respectively. Research has shown in both healthy subjects and patients (e.g. Alzheimer's
disease, Parkinson's disease, stroke, and depression) that tDCS has the potential to modulate
synaptic strengthening and neurotransmitter-dependent plasticity underlying changes in
behavior and learning (Lang et al. 2005).

We are anticipating enrollment of 30 participants. Fifteen participants will be randomly
assigned to the interventional tDCS condition, while 15 participants will be randomly
assigned to sham tDCS. Both conditions will undergo five sessions of tDCS across five days.
Participants will undergo pre- and post-tDCS MRI scans, in addition to clinical interviews
and questionnaires. Follow-up interviews will be conducted in person 1 and 2 months after
intervention completion to inquire about relapse status.

Inclusion Criteria:

- 20 abstinent individuals (18-60 years old; 1-2 weeks of abstinence) who meet DSM-V
criteria for opioid use disorder (OUD) will be recruited from the Lodging Plus
Program, part of University of Minnesota Medical Center

- This 28-day program provides a supervised environment to treat individuals with OUD in
which patients receive random drug screenings. Lodging Plus has 50 beds and admits an
average of 20 patients per week and about 50% of patients admitted have a diagnosis of
opioid use disorder.

- Ability to provide written consent and comply with study procedures, meet the
Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria for
OUD. Subjects may have current comorbid drug use, but their primary substance use
disorder diagnosis needs to be based on opioid use. Subjects must have the intention
to remain in the Lodging Plus program (4 weeks) until the end of the intervention
portion of the study. Vulnerable populations will not be included.

Exclusion Criteria:

- Any medical condition or treatment with neurological sequelae (i.e. stroke, tumor,
loss of consciousness>30 min, HIV)

- A head injury resulting in a skull fracture or a loss of consciousness exceeding 30
minutes (i.e., moderate or severe TBI)

- Any contraindications for tDCS or MRI scanning (tDCS contraindication: history of
seizures; MRI contraindications; metal implants, pacemakers or any other implanted
electrical device, injury with metal, braces, dental implants, non-removable body
piercings, pregnancy, breathing or moving disorder)

- DSM-V criteria for psychiatric disorder, may have a lifetime diagnosis of depression

- Presence of a condition that would render study measures difficult or impossible to
administer or interpret

- Age outside the range of 18 to 60

- Primary current substance use disorder diagnosis on a substance other than opioid
except for caffeine or nicotine

- Clinical evidence for Wernicke-Korsakoff syndrome

- Nicotine use will be recorded.