Real-time FMRI neurofeedback training of amygdala activity in patients with major depressive disorder

Abstract

Background: Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD), and normalize with remission. Real-time functional MRI neurofeedback (rtfMRI-nf) offers a non-invasive method to modulate this regional activity. We examined whether depressed participants can use rtfMRI-nf to enhance amygdala responses to positive autobiographical memories, and whether this ability alters symptom severity.

Methods: Unmedicated MDD subjects were assigned to receive rtfMRI-nf from either left amygdala (LA; experimental group, n = 14) or the horizontal segment of the intraparietal sulcus (HIPS; control group, n = 7) and instructed to contemplate happy autobiographical memories (AMs) to raise the level of a bar representing the hemodynamic signal from the target region to a target level. This 40s Happy condition alternated with 40s blocks of rest and counting backwards. A final Transfer run without neurofeedback information was included.

Results: Participants in the experimental group upregulated their amygdala responses during positive AM recall. Significant pre-post scan decreases in anxiety ratings and increases in happiness ratings were evident in the experimental versus control group. A whole brain analysis showed that during the transfer run, participants in the experimental group had increased activity compared to the control group in left superior temporal gyrus and temporal polar cortex, and right thalamus.

Conclusions: Using rtfMRI-nf from the left amygdala during recall of positive AMs, depressed subjects were able to self-regulate their amygdala response, resulting in improved mood. Results from this proof-of-concept study suggest that rtfMRI-nf training with positive AM recall holds potential as a novel therapeutic approach in the treatment of depression.

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts. Wayne Drevets, M.D., is an employee of Johnson & Johnson, Inc., and has consulted for Myriad/Rules Based Medicine and for Eisai, Inc. The other authors have declared that no competing interests exist. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Design of the rtfMRI neurofeedback experiment.

A) Regions of Interest (ROI) for the rtfMRI neurofeedback procedure. Three regions of interest (spheres of 7 mm radius) were used to assess changes in BOLD activity. These regions were the left amygdala (LA, red, centered at -21, -5, -16), right amygdala (RA, yellow, centered at 21, -5, -16), and left horizontal segment of the intraparietal sulcus (HIPS, green, centered at -42, -48, 48). ROI placements are illustrated on T1-weighted coronal (upper row) and axial (lower row) human brain sections in Talairach space. Following radiological notation, the left side (L) of the brain is shown on the right, and the right side (R) of the brain on the left. B) Real-time display screen for the rtfMRI neurofeedback procedure. During the Happy condition, the word “Happy,” two color bars, and a number indicating the neurofeedback signal were displayed on the screen. Participants were instructed to recall happy autobiographical memories to make themselves feel happy while trying to increase the level of the red bar representing the feedback signal from the target ROI to a given target level indicated by the fixed height of the blue bar (but not to exceed that target level). C) Protocol for the rtfMRI neurofeedback experiment. The experimental protocol consisted of seven runs each lasting 8 min 40 sec. During the Rest runs, participants were instructed to rest with their eyes open. During the Practice run, the participants were given the opportunity to become comfortable with the procedure and test out different memories. During Runs 1–3 participants underwent rtfMRI neurofeedback training consisting of alternating blocs of Rest (R, pink block), Happy (H, red block), and Count (C, green block, instructed to count backwards from 300 by a given integer), each lasting 40 sec. During the Transfer Run, participants were instructed to perform the same task as during the neurofeedback training, but no neurofeedback information (bars, numbers) was provided.

Figure 2. Percent BOLD Signal Change for each ROI, run, and group.

Mean percent BOLD signal change for the Happy – Rest condition for each experimental run for the left amygdala (LA; panels A, B, C), right amygdala (RA; panels D, E, F), and horizontal segment of the intraparietal sulcus (HIPS; panels G, H, I) for the LA rtfMRI-nf group (panels A, D, G), HIPS rtfMRI-nf group (panels B, E, H), and for the difference between the LA and HIPS rtfMRI-nf groups (C, F, I). Error bars indicate +/− one standard error of the mean. * indicates a significant difference from 0 at p

Figure 3. Relationship between left amygdala neurofeedback training effect and individual characteristics in the experimental rtfMRI-nf group.

A) Correlation with length of the current major depressive episode. The training effect for the left amygdala (the average Happy – Rest percent signal change over the three training runs) was inversely correlated with the length of participants' current depressive episode. B) Correlation with difficulty describing feelings (TAS-20). The more difficulty a participant had describing their own feelings, the less average BOLD activation for the Happy-Rest contrast was observed in the left amygdala for the three training runs.

Figure 4. Group differences in BOLD activity during the Transfer Run.

Regions A) Left Superior Temporal Gyrus B) Left Temporal Pole C) Right Thalamus and associated percent signal change graphs, are shown where groups had differential activation during Happy AM recall vs Rest during the Transfer run in which no neurofeedback was provided. Error bars indicate +/1 one standard deviation of the mean.