Neurophysiology of brain temperature dysregulation in humans.

Brain temperature, a fundamental modulator of neural function, remains dramatically understudied despite its critical role in health and disease. This review synthesizes current understanding of brain thermoregulation and its disruption in neurological conditions, addressing a significant knowledge gap in neuroscience. We examined the physiological mechanisms maintaining brain temperature homeostasis, including the interplay between cerebral blood flow, metabolism, and cerebrospinal fluid dynamics. Analysis of publication trends reveals that brain temperature research is underrepresented by 7- to 37-fold compared with other brain physiological parameters, despite comparable clinical relevance. We evaluated current noninvasive measurement techniques, particularly magnetic resonance-based thermometry, highlighting advances and limitations for clinical application. The review presents evidence for distinct temperature dysregulation patterns in neurological diseases. In Alzheimer's disease, we propose a theoretical framework of early-stage hyperthermia driven by neuroinflammation and hypermetabolism, transitioning to late-stage hypothermia with metabolic decline. Brain tumors exhibit contrasting thermal profiles: glioblastomas frequently present as hypothermic due to necrotic cores acting as metabolic voids, whereas melanoma metastases show hyperthermia from sustained metabolic activity. These temperature alterations may influence disease progression through effects on protein aggregation, cellular metabolism, and neuron-glial interactions. Looking forward, brain temperature monitoring could provide biomarkers for disease staging and treatment response. In addition, understanding thermal limits becomes urgent as climate change exposes vulnerable populations with compromised thermoregulation to extreme heat. This review establishes brain temperature as an overlooked but essential axis in neurophysiology, calling for increased research attention to address fundamental questions about thermal regulation in health and disease.