Invasive Decoding and Stimulation of Altered Reward Computations in Depression Patients

NCT05239780 | Recruiting

• 2 other identifiers: STUDY-17-002581R01MH124763-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Major Depressive Disorder

Keywords

Electrophysiology; Stereotactic encephalography; Brain stimulation

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 1

Secondary Outcomes (2)

• Beck's Depression I-II (BDI-II) score

  Day 1

• Hamilton scales for depression and anxiety (HSDA)

  Day 1

Study Arms (1)

Participants with depression

EXPERIMENTAL

Participants with depression to undergo brain stimulation

Procedure: Brain stimulation

Interventions

Brain stimulation PROCEDURE

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.

Participants with depression

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• University of California, Davis: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 100119, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Ignacio Saez, Ph.D.

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lizbeth Nunez Martinez

CONTACT

(661) 772-6200; lizbeth.nunezmartinez@mssm.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 4, 2022
• First Posted: February 15, 2022
• Study Start: October 6, 2021
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: September 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal. Any purpose. Proposals should be directed to ignacio.saez@mssm.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Link to be included in the URL field below).

Locations

US (1)