Deep Brain Stimulation to Understand and Treat Addiction

Alcohol use will be assessed using the Timeline Followback (TLFB), a validated self-report measure of daily alcohol consumption. Participants will report the number of days per week on which alcohol was consumed. TLFB data are collected for a 6-month pre-surgical baseline, monthly during the 6-month open-label optimization phase, and monthly during the 4-month randomized cross-over phase. Changes in drinking frequency across phases and stimulation conditions will be compared to evaluate the effect of deep brain stimulation on alcohol use.

Weekly alcohol intake will be quantified using the Timeline Followback (TLFB). The total number of standard UK alcohol units consumed per week will be calculated from participant self-report. TLFB data are collected for a 6-month pre-surgical baseline, monthly during the 6-month open-label optimization phase, and monthly during the 4-month randomized cross-over phase. Changes in total weekly consumption across phases and stimulation conditions will be compared to determine the effect of deep brain stimulation on overall drinking volume.

All adverse events related to DBS surgery, the implanted device, or stimulation are recorded and reviewed by the clinical and research teams. Events are categorized by severity (mild, moderate, severe) and relatedness (unrelated, possibly related, related). Higher severity classifications indicate more serious adverse outcomes.

Alcohol craving will be assessed using the Alcohol Urge Questionnaire (AUQ), a validated self-report measure of desire to drink, anticipated effects, and perceived control over drinking. Scores range from 8 to 56, with higher scores indicating stronger craving. Participants complete the AUQ daily during the open-label and randomized phases and monthly during laboratory sessions.

Health-related quality of life will be assessed with the Short Form Health Survey (SF-36), a 36-item self-report measure comprising eight domains of physical and mental health. Domain scores are transformed to a 0-100 scale, with higher scores indicating better health status. Physical and Mental Component Summary scores may also be calculated, with higher scores reflecting better quality of life.

Illness severity and clinical change over time will be assessed with The Clinical Global Impression (CGI) scale. The CGI-Severity (CGI-S) is a clinician-rated measure of current illness severity ranked on a 7-point scale, whereby the CGI-Improvement (CGI-I) rates change from baseline on a 7-point scale. Lower scores indicate lower severity and greater improvement.

Participants complete high-frequency ecological momentary assessments (EMAs) via a smartphone-based web application up to five times per day. Each EMA consists of composite of single-item visual analogue scale (VAS) questions assessing current depression, anxiety, and craving (e.g., "What is your craving right now?"). Responses are recorded on a continuous scale from 0 to 100, where 0 indicates none/not at all and 100 indicates the most extreme level. Higher scores indicate greater levels of the assessed state.

Cue-induced craving is assessed using a 0-100 visual analogue scale immediately after viewing personalized alcohol-related cues in laboratory sessions. Participants rate their urge to drink after each cue, with 0 representing "no urge" and 100 representing the "strongest imaginable urge." Higher scores indicate stronger cue-induced craving.

Depressive symptoms are assessed once daily using a battery comprising the nine items of the Patient Health Questionnaire-9 (PHQ-9), adapted for daily assessment. Items are administered via a smartphone-accessible Qualtrics survey and assess current depressive symptom severity. Each item is rated using a continuous visual analogue scale (VAS) ranging from 0 (not at all) to 100 (most extreme). Higher scores indicate greater depressive symptom severity.

Anxiety symptoms are assessed once daily using a battery comprising the seven items of the Generalized Anxiety Disorder-7 (GAD-7), adapted for daily assessment. Items are administered via a smartphone-accessible Qualtrics survey and assess current anxiety symptom severity. Each item is rated using a continuous visual analogue scale (VAS) ranging from 0 (not at all) to 100 (most extreme). Items are not rated using Likert-type response options. Higher scores indicate greater anxiety symptom severity.

Alcohol urge is assessed once daily using an ecological momentary assessment (EMA) battery comprising the eight items of the Alcohol Urge Questionnaire (AUQ), adapted for daily assessment. Items are administered via a smartphone-accessible survey and assess current alcohol urge. Each item is rated using a continuous visual analogue scale (VAS) ranging from 0 (no urge) to 100 (strongest urge). Items are not rated using Likert-type response options. Higher scores indicate greater alcohol urge.

Delay discounting is assessed once daily using the Monetary Choice Questionnaire (MCQ), administered via a smartphone-accessible Qualtrics survey. The MCQ comprises a series of 27 choice items in which participants select between a smaller, sooner monetary reward and a larger, later monetary reward. Each item requires a forced choice between the shorter-delay and longer-delay option. Responses are used to characterize individual differences in delay discounting, with a stronger preference for sooner rewards reflecting steeper discounting.

Risk-taking behavior is assessed once daily using a mixed gamble decision-making task administered via an online application. On each of the 80 total trials, participants are presented with gambles offering a 50% probability of monetary gain and a 50% probability of monetary loss, with the magnitudes of potential gains and losses varying across trials. Participants indicate whether they would accept or reject each gamble. Patterns of acceptance and rejection across varying gain-loss combinations are used to characterize individual differences in risk-taking behavior, with greater acceptance of gambles indicating increased risk-taking.

Compulsive alcohol-related thoughts and behaviors are assessed using the Obsessive-Compulsive Drinking Scale (OCDUS). Scores range from 0 to 56, with higher scores indicating more severe obsessive thoughts, urges, and loss of control related to drinking. Participants complete the OCDUS monthly to evaluate changes across study phases.

Local field potentials (LFPs) are recorded from implanted deep brain stimulation electrodes during resting-state periods and during computerized behavioral tasks. LFP recordings are used to characterize neural activity associated with behavioral state and task performance.

Scalp electroencephalography (EEG) is recorded during resting-state periods and during computerized behavioral tasks. EEG recordings are used to characterize cortical neural activity associated with behavioral state and task performance.

Peripheral physiological signals are recorded during laboratory sessions while participants complete resting-state assessments and computerized behavioral tasks. Measures include heart rate, heart rate variability, and galvanized skin response, and are used to characterize autonomic and physiological responses associated with task performance.

Peripheral physiological signals are continuously recorded during daily life using a wearable device. Measures include heart rate, heart rate variability, and galvanized skin response, and are used to characterize autonomic and physiological activity over time outside the laboratory setting.

Cognitive domains including executive function, impulsivity, and compulsivity are assessed during laboratory sessions using a battery of validated computerized behavioral tasks. Tasks are designed to probe components of cognitive control, decision-making, and behavioral flexibility. Performance measures derived from these tasks are used to characterize individual differences in these cognitive domains.