# Confirmatory Efficacy Clinical Trial of Amygdala Neurofeedback for Depression

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $725,042

## Abstract

Abstract
Up to two-thirds of patients diagnosed with major depressive disorder (MDD) will not respond to standard
pharmacological and psychological interventions, suggesting a need to develop novel therapeutics. Decreased
reactivity to positive stimuli, indexed by low amygdala reactivity to positive autobiographical memory recall,
may be a causal mechanism interfering with recovery from MDD. Previous work suggests that individuals who
do respond to antidepressant medications show increased amygdala activity to positive stimuli that is
indistinguishable from controls, while those who do not respond fail to show this increase in amygdala activity.
In several small studies we have shown that MDD participants are able to increase their amygdala response
during positive memory recall via real-time fMRI neurofeedback (rtfMRI-nf) training, and that this increase is
associated with large and rapid reductions in depressive symptoms. Here, we propose to evaluate the efficacy
of this intervention in a large-scale confirmatory R01 clinical trial. N=200 MDD individuals will be randomly
assigned under double-blind conditions to the amygdala rtfMRI-nf intervention or to a control rtfMRI-nf
intervention where they receive yoked sham neurofeedback (instead of their own brain activity they see the
signal from another participant who underwent amygdala rtfMRI-nf). We propose to use the same
neurofeedback paradigm as our prior studies, with one critical difference. Rather than using a control condition
that involves training another brain region, we will adopt a yoked sham control group in order to demonstrate
that our findings are robust to the type of control condition used. We additionally aim to determine whether we
can use self-report mechanisms to assess who might need the proposed neurofeedback intervention and
whether they are likely to be successful in using it. Finally, we will work with implementation scientists to obtain
feedback from end-users and clinicians to understand contextual influences on outcomes and increase
intervention acceptability. Success will confirm a new non-pharmacological, non-invasive intervention for MDD
individuals.

## Key facts

- **NIH application ID:** 10847369
- **Project number:** 5R01MH130337-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Kym Young
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $725,042
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847369

## Citation

> US National Institutes of Health, RePORTER application 10847369, Confirmatory Efficacy Clinical Trial of Amygdala Neurofeedback for Depression (5R01MH130337-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10847369. Licensed CC0.

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