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Self-navigating the “Island of Reil”: a systematic review of real-time fMRI neurofeedback training of insula activity

Real-time fMRI (rtfMRI) neurofeedback (NF) is a novel noninvasive technique that permits individuals to voluntarily control brain activity or connectivity, with demonstrated feasibility in experimental and therapeutic applications. The crucial role of the insula in emotional and salience processing makes it a popular target in rtfMRI studies although there is no systematic review of their efficacy. To promote our understanding of mechanisms underlying insula regulation and thereby facilitate therapeutic translation, the present review identified 22 preclinical and clinical studies and found that rtfMRI-based NF training is efficient for modulating insula activity (> 86%) and its associated behavioral and neural changes. Based on findings, continuous feedback for multiple training sessions, specific strategies validated before application, inclusion of a practice session, and choosing appropriate localization strategies are suggested as guidelines. We also recommend standardization of training protocol design, statistical analyses and results reports for future studies. In summary, the present review informs both fundamental research and therapeutic translation of NF training as an intervention in mental disorders, particularly those with insula dysfunction.