Invasive Decoding and Stimulation of Altered Reward Computations in Depression

Not Applicable

Recruiting

• Conditions: Major Depressive Disorder
• Interventions: Procedure: Brain stimulation

• Registration Number: NCT05239780
• Lead Sponsor: Icahn School of Medicine at Mount Sinai

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.

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 Timeline

• Study Start: 2021-10-06
• Study First Submitted: 2022-02-04
• Study First Submitted QC: 2022-02-04
• Study First Posted: 2022-02-15
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-08
• Primary Completion: 2025-08-31
• Study Completion: 2027-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participants with depression	Brain stimulation	Participants with depression to undergo brain stimulation

Primary Outcome Measures

Name	Time	Method
Gambling Task	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.

Secondary Outcome Measures

Name	Time	Method
Hamilton scales for depression and anxiety (HSDA)	Day 1	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.
Beck's Depression I-II (BDI-II) score	Day 1	Self-reported mood questionnaire. BDI-II total scale 0-63, with higher score indicating more severe depression.

Trial Locations

Locations (1)

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States