Amygdala real-time fMRI neurofeedback upregulation in treatment resistant depression: Proof of concept and dose determination.

Previous work has shown that adults suffering from major depressive disorder (MDD) can increase their amygdala reactivity while recalling positive memories via real-time neurofeedback (rt-fMRI-nf) training, which is associated with reduction in depressive symptoms. This study investigated if this intervention could also be considered for patients suffering from MDD who do not respond to standard psychological and pharmacological interventions, i.e., treatment resistant (TR-MDD). 15 participants received 5 neurofeedback sessions. Outcome measures were depressive symptoms assessed by BDI scores up to 12 weeks following acute intervention, and amygdala activity changes from initial baseline to final transfer run during neurofeedback sessions (neurofeedback success). Participants succeeded in increasing their amygdala activity. A main effect of visit on BDI scores indicated a significant reduction in depressive symptomatology. Percent signal change in the amygdala showed a learning curve during the first session only. Neurofeedback success computed by session was significantly positive only during the second session. When examining the baseline amygdala response, baseline activity stabilized/asymptoted by session 3. This proof-of-concept study suggests that only two neurofeedback sessions are necessary to enable those patients to upregulate their amygdala activity, warranting a future RCT. Over the course of the rtfMRI-nf intervention, participants also reported reduced depressive symptomatology. Clinical trial registration number: NCT03428828 on ClinicalTrials.gov.

Enhanced efficacy of CBT following augmentation with amygdala rtfMRI neurofeedback in depression.

BACKGROUND: Despite cognitive behavioral therapy (CBT) being a standard treatment in major depressive disorder (MDD), nearly half of patients do not respond. As one of the predictors of CBT's efficacy is amygdala reactivity to positive information, which is often decreased in MDD, we explored whether real-time fMRI neurofeedback (rtfMRI-nf) training to increase amygdala responses during positive memory recall prior CBT would enhance its efficacy. METHODS: In a double-blind, placebo controlled, randomized clinical trial, 35 adults with MDD received two sessions of rtfMRI-nf training to increase their amygdala (experimental group, n = 16) or parietal (control group, n = 19) responses during positive memory neurofeedback prior to receiving 10 CBT sessions. Depressive symptomatology was monitored between the rtfMRI sessions, the first three, 9th and 10th sessions of CBT and at 6 months and 1 year follow-up. RESULTS: Participants in the experimental group showed decreased depressive symptomatology and higher remission rates at 6 months and 1 year follow-up than the control group. Analysis of CBT content highlighted that participants in the experimental group focused more on positive thinking and behaviors than the control group. LIMITATIONS: The study was relatively small and not sufficiently powered to detect small effects. CONCLUSIONS: CBT, when combined with amygdala neurofeedback, results in sustained clinical changes and leads to long-lasting clinical improvement, potentially by increasing focus on positive memories and cognitions.