Recruiting

OFC & Depression

Sponsor:

UCLA

Code:

NCT07896343

Conditions

Depression - Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Approach-Avoidance Decision-Making Task

Study Details

Brief summary:

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.

Conditions

Depression - Major Depressive Disorder

Study ID

NCT07896343

Start date

Oct, 2026

Status verified date

Oct, 2026

Completion date

Jun, 2027

Anticipated

Primary completion date

Jun, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

10 participants

Anticipated

Intervention Model

Single group

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Approach-Avoidance Task During sEEG Monitoring

Adults undergoing inpatient stereo-EEG (sEEG) monitoring with electrodes in the orbitofrontal cortex (OFC). The primary cohort consists of patients with treatment-resistant depression enrolled under the parent IRB protocol of a deep brain stimulation trial for refractory depression (PRESIDIO; NCT04004169), who undergo sEEG with bilateral OFC electrodes during that trial's inpatient phase. The control cohort consists of non-depressed patients undergoing sEEG monitoring for other clinical indications, such as seizure localization in refractory epilepsy. All participants complete the same computerized approach-avoidance decision-making task (\~20 minutes per session), choosing on each trial to approach or avoid offers of probabilistic reward and punishment, while neural activity is recorded from the implanted electrodes. No drug, device, or stimulation is administered as part of this study; implantation and any stimulation occur solely under clinical care or the parent trial.

Interventions

Approach-Avoidance Decision-Making Task

A computerized, gamified approach-avoidance decision-making task built in the Unity game engine and presented on a laptop at the bedside during inpatient sEEG monitoring. On each trial, the participant views a virtual corridor containing a reward offer (0-7 treasure chests) and a punishment offer (0-4 bombs) and indicates by button press whether to approach the corridor, with probabilistic gain and loss outcomes, or avoid it, with a neutral outcome. Reward and punishment magnitudes are varied in pseudorandomized order across 220 trials per session (\~20 minutes). Choices and reaction times are recorded and synchronized with intracranial neural recordings at millisecond precision. The task serves as an experimental probe of the neural and behavioral mechanisms of approach-avoidance decision-making; it is not a treatment, and no therapeutic effect is expected. Task code is openly available (github.com/cstarkweather).

Primary outcome measure

  • Difference in Orbitofrontal Cortex High-Frequency Activity (70-150 Hz) Between Approach and Avoidance Decisions [ Time Frame: During task session(s) completed during inpatient sEEG monitoring, from enrollment up to 3 weeks ]

Central Contacts and Locations

Central contacts

Clara K Starkweather, MD, PhD

706-330-0885clara.starkweather@ucsf.edu

Locations

UCSF

Recruiting

San Francisco, California, United States, 94143-2204

Contacts

Clara Starkweather, MD PhD

706-330-0885clara.starkweather@ucsf.edu

More Information

Sponsor

University of California, San Francisco

Last update posted

Oct 27, 2026

Last verified

Oct, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-28. This information was provided to ClinicalTrials.gov by University of California, San Francisco on 2026-10-27. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.