Depression - Major Depressive DisorderNCT07896343
Understanding the Neural Underpinnings of Risk-Taking Behavior in Psychiatric Disease
A study testing Approach-Avoidance Decision-Making Task in people with Depression - Major Depressive Disorder, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depression - Major Depressive Disorder
- What is being tested?
- Approach-Avoidance Decision-Making Task
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2026to Jun 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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)
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UCSF
San Francisco, California, 94143-2204
Clara Starkweather, MD PhD, 706-330-0885, clara.starkweather@ucsf.edu
About this study
Official title: Defining Orbitofrontal Circuit Function in Health and Depression
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.
Read more
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
- Being tested
- Approach-Avoidance Decision-Making Task
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Approach-Avoidance Decision-Making TaskBehavioural
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).
| Study group | Role | What they receive |
|---|---|---|
| Approach-Avoidance Task During sEEG Monitoring | Experimental | 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. Receives: Behavioral: Approach-Avoidance Decision-Making Task |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Orbitofrontal Cortex High-Frequency Activity (70-150 Hz) Between Approach and Avoidance Decisions
High-frequency activity (HFA; 70-150 Hz band-limited power) is extracted from sEEG electrodes in the orbitofrontal cortex (OFC) and normalized to each channel's baseline. Mean HFA is computed in a pre-specified decision epoch (300 ms preceding the button press). The outcome is the difference in mean HFA between approach and avoidance trials (HFA on approach trials minus HFA on avoidance trials), computed per electrode and reported separately for medial and lateral OFC electrodes. Analyzed in the non-depressed cohort (Aim 1). Unit of measure: percent of baseline HFA.
Measured: During task session(s) completed during inpatient sEEG monitoring, from enrollment up to 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2026
- Study startOct 2026 (estimated)
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depression - Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants complete the same computerized approach-avoidance decision-making task during inpatient stereo-EEG (sEEG) monitoring for clinical purposes. Participants are enrolled into one of two cohorts based on clinical diagnosis rather than investigator assignment: a non-depressed cohort (Aim 1) and a depressed cohort meeting DSM-5 criteria for major depressive disorder, including patients implanted as part of a separate clinical trial for treatment-resistant depression (Aim 2). Neural and behavioral outcomes are compared between cohorts. There is no randomization, and no drug, device, or stimulation is administered for research purposes.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Andrew Krystal, MD, Principal investigator, University of California, San FranciscoClara Starkweather, MD, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07896343
- Sponsor's protocol ID
- 17-23724-B
- Other IDs
- 1K99MH146164-01
- Status last verified
- Oct 2026
- First submitted
- 20 Oct 2026
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified electrophysiological and behavioral data will be made available via data repository.
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining Orbitofrontal Circuit Function in Health and Depression
- ClinicalTrials.gov ID
- NCT07896343
- Acronym / sponsor ID
- 17-23724-B
- Conditions
- Depression - Major Depressive Disorder
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Oct 2026 (estimated)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 27 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants complete the same computerized approach-avoidance decision-making task during inpatient stereo-EEG (sEEG) monitoring for clinical purposes. Participants are enrolled into one of two cohorts based on clinical diagnosis rather than investigator assignment: a non-depressed cohort (Aim 1) and a depressed cohort meeting DSM-5 criteria for major depressive disorder, including patients implanted as part of a separate clinical trial for treatment-resistant depression (Aim 2). Neural and behavioral outcomes are compared between cohorts. There is no randomization, and no drug, device, or stimulation is administered for research purposes.
| Arm | Type | Receives |
|---|---|---|
| Approach-Avoidance Task During sEEG Monitoring | Experimental | Behavioral: Approach-Avoidance Decision-Making TaskAdults 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Approach-Avoidance Decision-Making TaskA 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). | Behavioural | Approach-Avoidance Task During sEEG Monitoring |
Primary outcome
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
High-frequency activity (HFA; 70-150 Hz band-limited power) is extracted from sEEG electrodes in the orbitofrontal cortex (OFC) and normalized to each channel's baseline. Mean HFA is computed in a pre-specified decision epoch (300 ms preceding the button press). The outcome is the difference in mean HFA between approach and avoidance trials (HFA on approach trials minus HFA on avoidance trials), computed per electrode and reported separately for medial and lateral OFC electrodes. Analyzed in the non-depressed cohort (Aim 1). Unit of measure: percent of baseline HFA.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Individual participant dataSharing planned: Yes. De-identified electrophysiological and behavioral data will be made available via data repository.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andrew Krystal, MD principal investigator
University of California, San Francisco
Clara Starkweather, MD, PhD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Approach-Avoidance Decision-Making Task in people with Depression - Major Depressive Disorder, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clara K Starkweather, MD, PhD (706-330-0885, clara.starkweather@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.