Amygdala Neurofeedback for Depression - Large Scale Clinical Trial

Study Overview
=================
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.

Official Title
-----------------
Confirmatory Efficacy Randomized Clinical Trial of Amygdala Neurofeedback for Major Depressive Disorder

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Behavioral: Amygdala real-time fMRI neurofeedback
* Behavioral: Sham feedback


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly assigned to receive amygdala neurofeedback or yoked sham neurofeedback (seeing the amygdala activity of another participant)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amygdala real-time fMRI neurofeedback<br>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. | Behavioral: Amygdala real-time fMRI neurofeedback<br>* Participants are shown activity from their left amygdala in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories<br>|
| Sham Comparator: Sham feedback<br>Yoked sham - participants will see the amygdala activity of another subject who completed the intervention. Two sessions will be performed one week apart. | Behavioral: Sham feedback<br>* Participants are shown activity from another participant's left amygdala who previously completed the task and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck Depression Inventory (BDI-II) | 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. | baseline vs up to one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Life Functioning Questionnaire (LFQ) | 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. | baseline vs up to one year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
amygdala, neurofeedback, depression, major depressive disorder