Real-Time Functional Magnetic Resonance Imaging Amygdala Neurofeedback Changes Positive Information Processing in Major Depressive Disorder

Abstract

Background: In participants with major depressive disorder who are trained to upregulate their amygdalar hemodynamic responses during positive autobiographical memory recall with real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training, depressive symptoms diminish. This study tested whether amygdalar rtfMRI-nf also changes emotional processing of positive and negative stimuli in a variety of behavioral and imaging tasks.

Methods: Patients with major depressive disorder completed two rtfMRI-nf sessions (18 received amygdalar rtfMRI-nf, 16 received control parietal rtfMRI-nf). One week before and following rtfMRI-nf training, participants performed tasks measuring responses to emotionally valenced stimuli including a backward-masking task, which measures the amygdalar hemodynamic response to emotional faces presented for traditionally subliminal duration and followed by a mask, and the Emotional Test Battery in which reaction times and performance accuracy are measured during tasks involving emotional faces and words.

Results: During the backward-masking task, amygdalar responses increased while viewing masked happy faces but decreased to masked sad faces in the experimental versus control group following rtfMRI-nf. During the Emotional Test Battery, reaction times decreased to identification of positive faces and during self-identification with positive words and vigilance scores increased to positive faces and decreased to negative faces during the faces dot-probe task in the experimental versus control group following rtfMRI-nf.

Conclusions: rtfMRI-nf training to increase the amygdalar hemodynamic response to positive memories was associated with changes in amygdalar responses to happy and sad faces and improved processing of positive stimuli during performance of the Emotional Test Battery. These results may suggest that amygdalar rtfMRI-nf training alters responses to emotional stimuli in a manner similar to antidepressant pharmacotherapy.

Keywords: Amygdala; Backward masking; Depression; Emotional processing; Neurofeedback; fMRI.

Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Design of the Backward Masking Task

(A) Two neutral target faces were shown prior to the start of each run in which participants were instructed to remember and determine whether subsequent face presentations matched the identity. (B) Two faces were shown as part of each trial presentation. Examples of the masked faces event types (SN, HN, NN) are shown with “N” placeholders to indicate the presentation of a neutral face. HN = Happy/Neutral face presentation; ISI = interstimulus interval; NN = Neutral/Neutral face presentation; SN = Sad/Neutral face presentations

Figure 2. Amygdala hemodynamic signal during the Backward Masking Task for each group and visit

Amygdala hemodynamic response was assessed using fMRI during exposure to: (A) masked sad face presentations (SN-NN condition) and (B) masked happy face presentations (HN-NN condition). Error bars indicate +/− one standard error of the mean. * indicates a significant difference from the corresponding baseline at pcorrected<0.05. # indicates a significant difference from the experimental group at pcorrected<0.05. HN = Happy/Neutral face presentation; NN = Neutral/Neutral face presentation; SN = Sad/Neutral face presentation

Figure 3. Vigilance scores for Faces Dot Probe Task for each group and visit

Vigilance Scores for (A) negative relative to neutral facial expressions and (B) happy relative to neutral facial expressions. Error bars indicate +/− one standard error of the mean. * indicates a significant difference from the corresponding baseline at pcorrected<0.05. # indicates a significant difference from the experimental group at pcorrected<0.05.

Figure 4. Correlations between clinical and neurofeedback performance and changes in performance on the BMT and ETB

(A) Correlation between the percent change in MADRS scores from baseline to follow-up and the change in amygdala activity to masked happy face presentation(HN-NN condition) during the BMT. (B) Correlation between neurofeedback success (defined as the change in amygdala activity from the baseline neurofeedback run to the final neurofeedback transfer run) and the change in amygdala activity to masked happy face presentation (HN-NN condition) while performing the BMT. (C) Correlation between the percent change in MADRS scores from baseline to follow-up and the change in reaction time to positive faces during the ECAT. (D) Correlation between neurofeedback success and the change in reaction time to positive faces during the ECAT e) Correlation between the percent change in MADRS scores from baseline to follow-up and the change in vigilance score to positive faces during the FDOT. BMT= backward masking task; ECAT = emotional categorization task; ETB = emotional test battery; FDOT = faces dot probe task; MADRS = Montgomery-Asberg depression rating scale