# Amygdala rtfMRI Neurofeedback for Treatment Resistant Depression

> **NIH NIH R33** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $572,316

## Abstract

Abstract
Up to two-thirds of patients diagnosed with major depressive disorder (MDD) will not respond to standard
pharmacological and psychological interventions and will be considered treatment resistant (TR-MDD).
Decreased reactivity to positive stimuli, indexed by low amygdala reactivity to positive autobiographical
memory recall, may be a causal mechanism interfering with recovery from TR-MDD. Previous work in our lab
suggests that individuals who do respond to antidepressant medications show increased amygdala activity that
is indistinguishable from controls relative to baseline, while TR-MDD individuals fail to show this increase in
amygdala activity. Furthermore, we have found that MDD participants (more generally, not specifically TR-
MDD) are indeed 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 whether rtfMRI-nf training to increase the amygdala
response to positive memories may serve as an intervention for TR-MDD. The R61 period will involve
intervention refinement and evaluation of mechanism; N=40 TR-MDD individuals will undergo five amygdala
rtfMRI-nf training sessions and we will assess changes in amygdala activity with the goal of confirming that
patients with TR-MDD are able to increase the amygdala response to positive memories, and to determine the
minimal number of training sessions required for sufficient target engagement/amygdala asymptote to be
reached. The R33 phase will involve a mechanistic comparison to a control intervention and evaluation of
clinical change (including duration of effects). N=60 TR-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
are trained to regulate a parietal region putatively not involved in emotional processing or MDD. Success will
suggest a new non-pharmacological, non-invasive intervention for a traditionally treatment-resistant population
of MDD individuals.

## Key facts

- **NIH application ID:** 10830285
- **Project number:** 5R33MH115927-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Kym Young
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $572,316
- **Award type:** 5
- **Project period:** 2018-08-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830285

## Citation

> US National Institutes of Health, RePORTER application 10830285, Amygdala rtfMRI Neurofeedback for Treatment Resistant Depression (5R33MH115927-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10830285. Licensed CC0.

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