Ranganatha SitaramAndrea Sanchez-CorzoGabriela VargasAurelio CorteseEl-deredy, WaelWaelEl-deredyAndrew JacksonEberhard Fetz2025-12-072025-12-072024-10-2110.1098/rstb.2023.00932-s2.0-85206872699https://cris-uv-2.scimago.es/handle/123456789/7751WOS:001340597400007While neurofeedback represents a promising tool for neuroscience and a brain self-regulation approach to psychological rehabilitation, the field faces several problems and challenges. Current research has shown great variability and even failure among human participants in learning to self-regulate target features of brain activity with neurofeedback. A better understanding of cognitive mechanisms, psychological factors and neural substrates underlying self-regulation might help improve neurofeedback’s scientific and clinical practices. This article reviews the current understanding of the neural mechanisms of brain self-regulation by drawing on findings from human and animal studies in neurofeedback, brain–computer/machine interfaces and neuroprosthetics. In this article, we look closer at the following topics: cognitive processes and psychophysiological factors affecting self-regulation, theoretical models and neural substrates underlying self-regulation, and finally, we provide an outlook on the outstanding gaps in knowledge and technical challenges. This article is part of the theme issue ‘Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation’.enacceso abiertoBiologyreview