Major Depressive DisorderNCT05239780
Invasive Decoding and Stimulation of Altered Reward Computations in Depression Patients
A study testing Brain stimulation in people with Major Depressive Disorder, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
Novel invasive neurostimulation stimulation strategies through neurosurgical interventions are emerging as a promising therapeutical strategy for major depressive disorder. These have been applied mostly to the anterior cingulate cortex, but other limbic brain regions have shown promise as anatomical targets for new… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Brain stimulation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Oct 2021to 12 May 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The study will follow clinical criteria for epilepsy patient recruitment for invasive monitoring. As a results, individuals of adults of all ages are expected to be included in this study.
Who cannot join
- Adults over 80 years of age will be excluded as per concerns of cognitive decline.
- Children under 18 will be excluded from the study since the maturation of frontal lobes continues through adolescence and significant differences in frontal lobe functioning between children younger than 18 and adults are often observed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 100119
About this study
Official title: Invasive Decoding and Stimulation of Altered Reward Computations in Depression
Novel invasive neurostimulation stimulation strategies through neurosurgical interventions are emerging as a promising therapeutical strategy for major depressive disorder. These have been applied mostly to the anterior cingulate cortex, but other limbic brain regions have shown promise as anatomical targets for new neurostimulation strategies. The researchers seek to study neural activity in limbic brain areas implicated in decision behavior and mood regulation to identify novel targets for treatment through electrical stimulation. To do this, the study team will record local field potentials (LFPs) from the orbitofrontal cortex, hippocampus and amygdala of epilepsy participants undergoing invasive monitoring (intracranial encephalography, iEEG) during choice behavior. Leveraging the high co-morbidity of depression and intractable epilepsy (33-50%), neural responses will be compared to reward across depression status to identify abnormal responses in depression. Finally, the researchers will use these as biomarkers to guide development of neurostimulation strategies for the treatment of depression.
Read the detailed description
Participants (n=24) will complete a decision-making task in which participants will make decisions under uncertainty and seek to maximize rewards. The researchers will assess behavioral (risk attitudes) and neural (LFP) responses using a combination of intracranial recordings and computational modeling. A subset of patients will complete the game a second time under electrical stimulation of pre-identified anatomical targets in orbitofrontal cortex, hippocampus or amygdala. In addition, patients' depression status will be assessed through questionnaires (BDI-II and HDSA). Finally, the researchers will examine whether electrical stimulation results in behavioral or mood modulation.
- Conditions
- Major Depressive Disorder
- Being tested
- Brain stimulation
- Keywords
- Electrophysiology, Stereotactic encephalography, Brain stimulation
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brain stimulationProcedure or surgery
Brain stimulation will be performed after collection of clinical seizure data. Bipolar stimulation to one or several adjacent electrodes will be applied. Stimulation design will be either determined prior to testing or designed according to results from neurobehavioral assessments. Stimulation will consist of biphasic, constant-current trains of stimulation pulses at 100 Hz, with 100 ms pulse width or a sinusoidal wave of a predefined mean band frequency (i.e. 6Hz for θ, 11Hz for α, 20Hz for β, etc.). Stimulation intensity will be ≤6 mA, consistent with parameters used for clinical mapping, for the duration of the behavioral task or for short (2-3 s) periods of time at given epochs during the task (i.e. outcome evaluation). Clinical personnel will be available during stimulation to help monitor stimulation-induced after-discharges; if any are detected, stimulation intensity will be dialed down or terminated.
| Study group | Role | What they receive |
|---|---|---|
| Participants with depression | Experimental | Participants with depression to undergo brain stimulation Receives: Procedure: Brain stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gambling Task
Risk attitudes will be evaluated behaviorally. Patients' behavior will in examined in experimental task (a gambling task) to determine overall proportion of risky choices (gambles) and indifference points (expected gamble value at which the patient is equally likely to choose a gamble or a safe bet). Score from 0%-100%, with higher percent indicating choosing the risky gamble more often.
Measured: Day 1
Secondary outcomes (2)
Beck's Depression I-II (BDI-II) score
Self-reported mood questionnaire. BDI-II total scale 0-63, with higher score indicating more severe depression.
Measured: Day 1
Hamilton scales for depression and anxiety (HSDA)
HSDA comprise the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HAM-A). These are clinician-administered mood and anxiety reports. HDRS total score range from 0-81 with higher scores indicating greater depression severity. HAM-A total score range from 0-56, with higher score indicating higher severity. HRDS full scale from 0-137 where scores of 0-7 indicate normal range, whereas a score of 20 or higher indicates at least moderate severity.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2022
- Study start6 Oct 2021
- Primary completion12 May 2026
- Study completion12 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Davis, National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Ignacio Saez, Icahn School of Medicine at Mount Sinai
- Investigators
- Ignacio Saez, Ph.D., Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05239780
- Sponsor's protocol ID
- STUDY-17-00258
- Other IDs
- 1R01MH124763-01
- Status last verified
- Oct 2026
- First submitted
- 4 Feb 2022
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Invasive Decoding and Stimulation of Altered Reward Computations in Depression
- ClinicalTrials.gov ID
- NCT05239780
- Acronym / sponsor ID
- STUDY-17-00258
- Conditions
- Major Depressive Disorder
- Keywords
- Electrophysiology, Stereotactic encephalography, Brain stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- University of California, Davis, National Institute of Mental Health (NIMH)
- Study start
- 6 Oct 2021 (actual)
- Primary completion
- 12 May 2026 (actual)
- Study completion
- 12 May 2026 (actual)
- First posted
- 15 Feb 2022 (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.
Novel invasive neurostimulation stimulation strategies through neurosurgical interventions are emerging as a promising therapeutical strategy for major depressive disorder. These have been applied mostly to the anterior cingulate cortex, but other limbic brain regions have shown promise as anatomical targets for new neurostimulation strategies. The researchers seek to study neural activity in limbic brain areas implicated in decision behavior and mood regulation to identify novel targets for treatment through electrical stimulation. To do this, the study team will record local field potentials (LFPs) from the orbitofrontal cortex, hippocampus and amygdala of epilepsy participants undergoing invasive monitoring (intracranial encephalography, iEEG) during choice behavior. Leveraging the high co-morbidity of depression and intractable epilepsy (33-50%), neural responses will be compared to reward across depression status to identify abnormal responses in depression. Finally, the researchers will use these as biomarkers to guide development of neurostimulation strategies for the treatment of depression.
Detailed description
Participants (n=24) will complete a decision-making task in which participants will make decisions under uncertainty and seek to maximize rewards. The researchers will assess behavioral (risk attitudes) and neural (LFP) responses using a combination of intracranial recordings and computational modeling. A subset of patients will complete the game a second time under electrical stimulation of pre-identified anatomical targets in orbitofrontal cortex, hippocampus or amygdala. In addition, patients' depression status will be assessed through questionnaires (BDI-II and HDSA). Finally, the researchers will examine whether electrical stimulation results in behavioral or mood modulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with depression | Experimental | Procedure: Brain stimulationParticipants with depression to undergo brain stimulation |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- The study will follow clinical criteria for epilepsy patient recruitment for invasive monitoring. As a results, individuals of adults of all ages are expected to be included in this study.
Key exclusion criteria (2 listed)
- Adults over 80 years of age will be excluded as per concerns of cognitive decline.
- Children under 18 will be excluded from the study since the maturation of frontal lobes continues through adolescence and significant differences in frontal lobe functioning between children younger than 18 and adults are often observed.
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 |
|---|---|---|
| Brain stimulationBrain stimulation will be performed after collection of clinical seizure data. Bipolar stimulation to one or several adjacent electrodes will be applied. Stimulation design will be either determined prior to testing or designed according to results from neurobehavioral assessments. Stimulation will consist of biphasic, constant-current trains of stimulation pulses at 100 Hz, with 100 ms pulse width or a sinusoidal wave of a predefined mean band frequency (i.e. 6Hz for θ, 11Hz for α, 20Hz for β, etc.). Stimulation intensity will be ≤6 mA, consistent with parameters used for clinical mapping, for the duration of the behavioral task or for short (2-3 s) periods of time at given epochs during the task (i.e. outcome evaluation). Clinical personnel will be available during stimulation to help monitor stimulation-induced after-discharges; if any are detected, stimulation intensity will be dialed down or terminated. | Procedure or surgery | Participants with depression |
Primary outcome
Gambling Task
Time frame: Day 1
Risk attitudes will be evaluated behaviorally. Patients' behavior will in examined in experimental task (a gambling task) to determine overall proportion of risky choices (gambles) and indifference points (expected gamble value at which the patient is equally likely to choose a gamble or a safe bet). Score from 0%-100%, with higher percent indicating choosing the risky gamble more often.
2 secondary outcomes
Beck's Depression I-II (BDI-II) score
Time frame: Day 1
Hamilton scales for depression and anxiety (HSDA)
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
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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. This study is not recruiting at the moment.
Ignacio Saez, Ph.D. principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Brain stimulation in people with Major Depressive Disorder, run by Icahn School of Medicine at Mount Sinai 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 1 inclusion and 2 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: finished, as of the sponsor's last update on 20 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gambling Task (time frame: Day 1). 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 20 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.