Real-time fMRI neurofeedback training as a neurorehabilitation approach on depressive disorders: A systematic review of randomized control trials

BACKGROUNDDepressive disorders are a group of neuropsychiatric disorders that cause significant distress and impairment in social, occupational, and other important areas of functioning. In the last decade, Brain-Computer Interfaces based-neurofeedback training appears as an innovative therapy for this condition and other neuropsychiatric disorders, allowing to volitionally self-regulate brain activity and behavior. Up to date, non-invasive neurofeedback training have been built on different techniques, including EEG, NIRS and fMRI. OBJECTIVESThis systematic review aims to evaluate the clinical application of fMRI neurofeedback training and its efficacy on treating depressive disorders. As a secondary objective, we intend to extract additional information on the neurofeedback training technique, in order to provide recommendations for future research. METHODS AND ANALYSISThe systematic review complies with the PRISMA guidelines and it was submitted to PROSPERO registration. We will only include randomized control trials assessing participants with a depressive disorder. The intervention of interest is real-time fMRI neurofeedback training, the comparison of interest will be placebo neurofeedback, another active non-neurofeedback control or no treatment. The primary outcome will be effects on behavior (symptomatology/disease severity reduction). The secondary outcomes will assess quality of life, acceptability and adverse effects. Finally, we will evaluate other outcomes regarding brain MRI metrics (BOLD activation/connectivity), cognitive tasks performance, and physiology measures. At least two reviewers will independently select studies, extract data and assess the risk of bias. If methodologically possible, for primary and secondary outcomes, a meta-analysis will be performed and the data will be presented in summary tables of results using the GRADE approach. STRENGTH AND LIMITATIONSAs the number of studies on neurofeedback is increasing every year, and better quality of evidence is available, this systematic review, will include only randomized control trials. To our knowledge, this is the first systematic review assessing randomized control trials on fMRI neurofeedback training as a neurorehabilitation approach on depressive disorders. The main limitation of this systematic review might arise from the low number of extant RCTs.