Burnout and the Brain-A Mechanistic Review of Magnetic Resonance Imaging (MRI) Studies.

Occupational burnout is ubiquitous yet still debated as a disease entity. Previous reviews surveyed multiple biomarkers but left their neural substrate unclear. We therefore asked: What, if any, reproducible magnetic-resonance signature characterises burnout? Following PRISMA principles adapted for mechanistic synthesis, two reviewers searched PubMed, Scopus, Google Scholar, ResearchGate and Cochrane from January 2000 to May 2025 using "MRI/fMRI" AND "burnout". After duplicate removal and multi-stage screening, 17 clinical studies met predefined inclusion criteria (English language, MRI outcomes, validated burnout diagnosis). In total, ≈1365 participants were scanned, 880 with clinically significant burnout and 470 controls. Uniform Maslach Burnout Inventory thresholds defined cases; most studies matched age and sex, and all excluded primary neurological disease. Structural morphometry (8/17 studies) revealed consistent amygdala enlargement-predominantly in women-and grey-matter loss in dorsolateral/ventromedial prefrontal cortex and striatal caudate-putamen, while hippocampal volume remained unaffected, distinguishing burnout from PTSD or depression. Resting-state and task fMRI (9/17 studies) showed fronto-cortical hyper-activation, weakened amygdala-ACC coupling, and progressive fragmentation of rich-club networks, collectively indicating compensatory executive overdrive and global inefficiency. Two longitudinal cohorts and several intervention sub-studies demonstrated partial reversal of cortical thinning and limbic hyper-reactivity after mindfulness, exercise, cognitive-behavioural therapy, neurofeedback, or rTMS, underscoring plasticity. Across heterogeneous paradigms and populations, MRI converges on a coherent, sex-modulated but reversible brain-networkopathy that satisfies objective disease criteria. These findings justify early neuro-imaging-based triage, circuit-targeted therapy, and formal nosological recognition of burnout as a mental disorder, with policy ramifications for occupational health and insurance parity.