Amygdala Neurofeedback for Depression - Large Scale Clinical Trial

Not Applicable

Recruiting

• Conditions: Major Depressive Disorder
• Interventions: Behavioral: Sham feedback; Behavioral: Amygdala real-time fMRI neurofeedback

• Registration Number: NCT05703256
• Lead Sponsor: Kymberly Young

Brief Summary

The goal of this study is to evaluate whether rtfMRI-nf training to increase the amygdala response to positive memories may serve as a stand-alone intervention for major depressive disorder

Detailed Description

Previous research has shown that real-time fMRI neurofeedback (rtfMRI-nf) training aimed at increasing the amygdala's response to positive autobiographical memory recall holds therapeutic potential for treating patients with major depressive disorder (MDD), as clinically significant decreases in clinician administered and self-report measures of depression severity were observed following two rtfMRI amygdala neurofeedback sessions. Furthermore, rtfMRI amygdala neurofeedback changed emotional processing towards a positive bias. The goal of the current study is to confirm the clinical efficacy of this intervention in a new sample of depressed participants. Thus, over the course of four years, we will conduct a randomized double-blind clinical trial examining the clinical and cognitive effects of amygdala rtfMRI-nf compared to yoked sham rtfMRI-nf (seeing the amygdala activity of another participant during training) in 200 participants with MDD from the Pittsburgh metropolitan area. Participants will undergo two rtfMRI-nf sessions. Half of the participants will receive amygdala neurofeedback and half will receive yoked sham neurofeedback. Participants will complete the BDI-II monthly for one year following completion of the neurofeedback intervention. The rationale for the proposed research is to provide new insights into possible mechanistic solutions for MDD, and to further guide development of this rtfMRI-nf intervention into a treatment for MDD.

Study Timeline

• Study First Submitted: 2023-01-18
• Study First Submitted QC: 2023-01-18
• Study First Posted: 2023-01-30
• Study Start: 2023-06-01
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-06
• Primary Completion: 2027-04-30
• Study Completion: 2028-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• ages 18 - 55
• primary diagnosis of MDD and are currently depressed
• able to give written informed consent prior to participation
• unmedicated OR are stable on an antidepressant regime (at least 4 weeks to ensure symptoms are stable). Effective medications will not be discontinued for the purposes of the study.

Exclusion Criteria

• clinically significant or unstable cardiovascular, pulmonary, endocrine, neurological, gastrointestinal illness or unstable medical disorder
• Current severe DSM-V alcohol or substance use disorder, with the exception of nicotine or caffeine. Clinician will access subjects' alcohol and substance use on a case-by-case to determine whether specific cases of mild or moderate alcohol or substance use would also interfere with the effects of the intervention.
• history of traumatic brain injury
• unable to complete MRI scan due to claustrophobia or general MRI exclusions (e.g., shrapnel inside body)
• currently pregnant or breast feeding
• unable to complete questionnaires written in English
• current (within 3 weeks of testing) use of any antipsychotics, anticonvulsants, stimulants, benzodiazepines, beta-blockers, or other medications (except antidepressants) likely to influence cerebral blood flow. Effective medications will not be discontinued for the purposes of the study.
• diagnosis of psychotic or organic mental disorder, bipolar I or II disorder.
• eye problems or difficulties in corrected vision.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham feedback	Sham feedback	Yoked sham - participants will see the amygdala activity of another subject who completed the intervention. Two sessions will be performed one week apart.
Amygdala real-time fMRI neurofeedback	Amygdala real-time fMRI neurofeedback	Amygdala neurofeedback - attempt to upregulate the left amygdala during positive autobiographical memory recall via real time fMRI neurofeedback from the amygdala. Two sessions will be performed one week apart.

Primary Outcome Measures

Name	Time	Method
Beck Depression Inventory (BDI-II)	baseline vs up to one year	measures depressive symptoms. The total score will be used, which ranges from 0-63. A total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. Lower values represent better outcomes.

Secondary Outcome Measures

Name	Time	Method
Life Functioning Questionnaire (LFQ)	baseline vs up to one year	measures ability to function in daily life. The total score will be used, which ranges from 14-56. A total score of 14-27 indicates no problems, and a score of 28+ indicates some impairment. Lower values represent better outcomes.

Trial Locations

Locations (1)

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States