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Understanding the Neural Underpinnings of Risk-Taking Behavior in Psychiatric Disease

Defining Orbitofrontal Circuit Function in Health and Depression

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

The purpose of this study is to understand how the orbitofrontal cortex (OFC), a region at the front of the brain, guides decisions about whether to pursue a possible reward when doing so also carries a risk of loss, and how this process is altered in depression. People with depression are often less motivated by rewards and more sensitive to potential losses, leading them to avoid situations that others would approach. The OFC is thought to play a central role in these "approach or avoid" decisions, but how it normally does so, and what goes wrong in depression, is not well understood. This study asks two questions: (1) How does activity in different parts of the OFC signal the decision to approach or avoid? (2) Does this activity differ in people with depression in a way that explains a bias toward avoidance? We hypothesize that the medial OFC (toward the middle of the brain) signals approach, the lateral OFC (toward the side of the brain) signals avoidance, and that in depression the medial OFC signal is weakened, tipping decisions toward avoidance. Participants are adults who are hospitalized with stereo-EEG (sEEG) electrodes already placed in the brain by their medical team, either to locate the source of seizures in epilepsy or as part of a separate clinical trial for treatment-resistant depression. The electrodes are placed for clinical reasons only, not for this study. During their hospital stay, participants complete a short, game-like computer task (about 20 minutes per session) in which they repeatedly choose whether to approach or avoid options that offer different chances of reward and loss. Their choices and reaction times are recorded along with brain activity from the existing electrodes, and participants rate their mood before each session. The researchers will compare OFC activity during approach versus avoid decisions, use mathematical models of decision-making to measure how strongly each participant weighs rewards and losses, and compare participants with and without depression. No drugs, devices, or brain stimulation are given as part of this study. The findings are intended to guide the development of more targeted brain-stimulation treatments for treatment-resistant depression.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Official eligibility criteria

Inclusion Criteria: All participants: * 18 years of age or older * Implanted with stereo-EEG (sEEG) depth electrodes, including at least one electrode in the orbitofrontal cortex (OFC) * Able to read, write, and provide informed consent Depressed cohort: * Enrolled in the PRESIDIO trial (NCT04004169) of deep brain stimulation for treatment-resistant depression and undergoing inpatient sEEG monitoring as part of that trial * Meets DSM-5 criteria for major depressive disorder (single episode of at least 2 years' duration, or recurrent), without psychotic features, confirmed by structured clinical interview (e.g., MINI) Control (non-depressed) cohort: * Undergoing inpatient sEEG monitoring for a clinical indication other than depression (e.g., seizure localization in refractory epilepsy) * No current diagnosis of major depressive disorder, confirmed by clinical psychiatric evaluation (e.g., MINI and symptom scales) Exclusion Criteria: All participants: * Current or past DSM-5 diagnosis of a psychotic disorder or major depressive disorder with psychotic features * Current or past DSM-5 diagnosis of bipolar or related disorder * Current obsessive-compulsive disorder * Intellectual disability * Autism spectrum disorder * Borderline, antisocial, histrionic, or narcissistic personality disorder * Impaired decision-making capacity or cognitive deficits that preclude informed consent or task completion * Employee of the investigator or study site with direct involvement in the study, or family member of the investigator Control (non-depressed) cohort only: \* Epileptiform abnormalities involving the OFC, OFC dysplasia, or prior OFC resection, as determined by clinical evaluation and imaging

Study sites (1)

CA