Randomized Clinical Trial of Real-Time fMRI Amygdala Neurofeedback for Major Depressive Disorder: Effects on Symptoms and Autobiographical Memory Recall

Abstract

Objective: Patients with depression show blunted amygdala hemodynamic activity to positive stimuli, including autobiographical memories. The authors examined the therapeutic efficacy of real-time functional MRI neurofeedback (rtfMRI-nf) training aimed at increasing the amygdala's hemodynamic response to positive memories in patients with depression.

Method: In a double-blind, placebo-controlled, randomized clinical trial, unmedicated adults with depression (N=36) were randomly assigned to receive two sessions of rtfMRI-nf either from the amygdala (N=19) or from a parietal control region not involved in emotional processing (N=17). Clinical scores and autobiographical memory performance were assessed at baseline and 1 week after the final rtfMRI-nf session. The primary outcome measure was change in score on the Montgomery-Åsberg Depression Rating Scale (MADRS), and the main analytic approach consisted of a linear mixed-model analysis.

Results: In participants in the experimental group, the hemodynamic response in the amygdala increased relative to their own baseline and to the control group. Twelve participants in the amygdala rtfMRI-nf group, compared with only two in the control group, had a >50% decrease in MADRS score. Six participants in the experimental group, compared with one in the control group, met conventional criteria for remission at study end, resulting in a number needed to treat of 4. In participants receiving amygdala rtfMRI-nf, the percent of positive specific memories recalled increased relative to baseline and to the control group.

Conclusions: rtfMRI-nf training to increase the amygdala hemodynamic response to positive memories significantly decreased depressive symptoms and increased the percent of specific memories recalled on an autobiographical memory test. These data support a role of the amygdala in recovery from depression.

Trial registration: ClinicalTrials.gov NCT02079610.

Keywords: Brain Imaging Techniques; Emotion; Memory; Mood Disorders-Unipolar; Other Psychosocial Techniques/Treatments; fMRI neurofeedback.

FIGURE 1. Regional Percent Signal Change for Each Region of Interest, Run, and Group in a Trial of Real-Time fMRI Amygdala Neurofeedback for Major Depressive Disorder^a

^aIn each group, the average percent signal change for the happy-rest condition for each run in the left amygdala (panel A) and in the left horizontal segment of the intraparietal sulcus (panel B). ^b Significant difference from the initial pre-neurofeedback baseline run, p<0.05. ^c Significant difference from the corresponding run in the experimental group, p<0.05.

FIGURE 2. Overall Mediation Model in a Trial of Real-Time fMRI Amygdala Neurofeedback for Major Depressive Disorder^a

MADRS=Montgomery-Åsberg Depression Rating Scale. In A, the predictor is residualized positive specific autobiographical memory recall at follow-up. In B, the mediator is residual amygdala activity during the final transfer run. In C, outcome is residual depressive symptoms. C denotes the relationship between predictor and outcome, and C′ denotes the same relationship after controlling for the effect of the mediator.