Using Electrophysiology to Index Non-invasive Brain Stimulation Effects on Reward System Functioning in Depression

NCT05194098 | Recruiting DMC FDA Device

• 1 other identifier: MH127432
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Depression is a leading cause of morbidity and mortality, conferring substantial healthcare and societal costs. By studying methods to non-invasively target neural circuitry involved in reward responsivity, information generated by this project will improve understanding of the circuit alterations that underlie motivation and pleasure deficits in depression, and could also lead to the development of biologically-based markers of neurostimulation-based treatment response.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; Reward Processing; EEG; rTMS Neurostimulation; dorsal medial prefrontal cortex

Outcome Measures

Primary Outcomes (1)

• Targeted neurostimulation effects on reward feedback evaluation

  Within the MDD group, the investigators will examine whether neurostimulation of a dmPFC target induces changes in the Reward Positivity (RewP) event-related potential component by comparing RewP amplitude after iTBS to RewP amplitude after sham stimulation.

  EEG measurements are collected directly after neurostimulation (iTBS vs SHAM) sessions

Secondary Outcomes (1)

• Targeted neurostimulation effects on reward anticipation and late-stage evaluation

  EEG measurements are collected directly after neurostimulation (iTBS vs SHAM) sessions

Study Arms (3)

Major Depression Disorder Group: iTBS-EEG

EXPERIMENTAL

Device: MagVenture MagPro R30 device with a Cool-DB80 A/P coil (Farum, Denmark) Stimulation: intermittent theta stimulation (iTBS): the investigators will stimulate a dorsomedial prefrontal cortex target at the scalp location (0x 60y 60z). Standard iTBS of 50Hz triplet bursts, 5 times each second with a 2 s on / 8 s off duty cycle for 600 pulses per hemisphere (1200 pulses total) will be applied for a total stimulation time of 6:40 minutes, per session; total session length, including setup is 10-15 min.

Device: TMS: single session intermittent theta burst stimulation (iTBS) to dorsomedial prefrontal target in individuals with major depressive disorder, via MagVenture MagPro R30 device / Cool-DB80 A/P coil

Major Depression Disorder Group: SHAM-EEG

SHAM COMPARATOR

Device: MagVenture MagPro R30 device with a Cool-DB80 A/P coil (Farum, Denmark) Stimulation: sham stimulation (SHAM): Sham stimulation will entail the same procedures for the active stimulation day, but with the sham side of the DB-80 A/P placed exactly on the same anatomical target in the same position and duration, but without any active stimulation. \*Note, iTBS and SHAM stimulation sessions will occur on separate days scheduled one week apart (counterbalanced, across subjects). The two stimulation visits follow identical procedures (with the sole difference being active vs. sham rTMS stimulation), with each followed directly by post-stimulation EEG assessment with SLOT and MID tasks.

Device: SHAM (inactive) TMS stimulation

Baseline Evaluation (Major Depressive Disorder and Healthy Control Groups)

NO INTERVENTION

HC and MDD participants will have visits for clinical assessment and a baseline EEG session to complete reward processing tasks (SLOT AND MID). The SLOT task is a 288-trial EEG task developed in our laboratory. Design features mimic structural characteristics common to real-word slot machines, including sound effects and visualizations, and the display consists of 3 sequentially populated slot reels. Participants initiate each trial via button press, after which timing of the slot reels is automated, such that reward outcome is independent of task performance. The MID task is a 130-trial EEG task designed to model anticipatory and consummatory sub-stages of reward processing in the context of participants being rewarded based on their response times to a cued target detection task.

Interventions

TMS: single session intermittent theta burst stimulation (iTBS) to dorsomedial prefrontal target in individuals with major depressive disorder, via MagVenture MagPro R30 device / Cool-DB80 A/P coil DEVICE

Active Session: Single session of standard iTBS of 50Hz triplet bursts, 5 times each second with a 2 s on / 8 s off duty cycle for 600 pulses per hemisphere (1200 pulses total) will be applied for a total stimulation time of 6:40 minutes

Major Depression Disorder Group: iTBS-EEG

SHAM (inactive) TMS stimulation DEVICE

Sham neurostimulation (SHAM) entails use of the sham side of the D-B80 A/P placed over the same anatomical target, without any active stimulation.

Major Depression Disorder Group: SHAM-EEG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants
• years old
• Normal (or corrected to normal) vision
• Participants with MDD
• Meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for MDD
• Screened for TMS and MRI safety
• On a stable psychiatric medication regime for \> 1 month

You may not qualify if:

• Premorbid IQ estimate \< 70
• Past or present neurological problems (including seizures and head trauma resulting in neurological or cognitive sequelae)
• Loss of consciousness \> 30 minutes or any loss of consciousness with neurological sequelae
• Major medical conditions (e.g., seizure disorders, treatment with anticonvulsant medication, endocrine disorders, significant cardiac pathology), or other physical conditions if they preclude participation in EEG, TMS, or MRI protocols (e.g. peripheral nerve damage, limb paralysis etc.)
• Substance dependence, within the past year, current (past 3 months) substance misuse, or failed urine toxicology on the day of neuroimaging sessions
• Known claustrophobia
• Pregnancy (a pregnancy urine test will be conducted to rule-out pregnancy)
• Past or present DSM-5 (SCID-5) 'Schizophrenia Spectrum or Other Psychotic Disorder' diagnosis
• Past or present DSM-5 (SCID-5) Bipolar and Related Disorders Diagnosis
• Past or present DSM-5 (SCID-5) MDD with psychotic features (mood congruent or mood incongruent)
• Past or present DSM-5 (SCID-5) Gambling Disorder
• DSM-5 (SCID-5) criteria for any psychiatric disorder

Sponsors & Collaborators

• San Francisco Veterans Affairs Medical Center: lead

Study Sites (1)

San Francisco VA Medical Center

San Francisco, California, 94121, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Susanna L Fryer, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason B Hemmerle, MBA

CONTACT

4152214810; jason.hemmerle@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Clinical Psychologist (VA) and Assistant Professor (UCSF)

Model Details: This double-blind sham-controlled crossover study combines case-control and within-subjects design.

Study Record Dates

• First Submitted: January 3, 2022
• First Posted: January 18, 2022
• Study Start: October 1, 2021
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: August 2, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)