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August 21, 2025Open Access

Neurophysiology of brain temperature dysregulation in humans

Key Points

Distinct patterns of brain temperature dysregulation can influence the progression of neurological diseases, such as Alzheimer's and brain tumors.
In Alzheimer's disease, an initial phase of hyperthermia often transitions to hypothermia as metabolic decline occurs during late stages.
Non-invasive measurement techniques like magnetic resonance-based thermometry are critical for observing brain temperature dynamics in clinical settings.
Rising concerns over climate impacts emphasize the urgent need for better understanding of thermal regulation in vulnerable populations.

Abstract

Brain temperature, a fundamental modulator of neural function, remains dramaticallyunderstudied despite its critical role in health and disease. This review synthesizescurrent understanding of brain thermoregulation and its disruption in neurologicalconditions, addressing a significant knowledge gap in neuroscience. We examined thephysiological mechanisms maintaining brain temperature homeostasis, including theinterplay between cerebral blood flow, metabolism, and cerebrospinal fluid dynamics.Analysis of publication trends reveals brain temperature research is underrepresentedby 12- to 50-fold compared to other brain physiological parameters, despitecomparable clinical relevance. We evaluated current non-invasive measurementtechniques, particularly magnetic resonance-based thermometry, highlightingadvances and limitations for clinical application. The review presents evidence fordistinct temperature dysregulation patterns in neurological diseases. In Alzheimer'sdisease, we propose a theoretical framework of early-stage hyperthermia driven byneuroinflammation and hypermetabolism, transitioning to late-stage hypothermia withmetabolic decline. Brain tumors exhibit contrasting thermal profiles: glioblastomasfrequently present as hypothermic due to necrotic cores acting as heat sinks, whilemetastases show hyperthermia from sustained metabolic activity. These temperaturealterations may influence disease progression through eZects on protein aggregation,cellular metabolism, and neuron-glial interactions. Looking forward, brain temperaturemonitoring could provide biomarkers for disease staging and treatment response.Additionally, understanding thermal limits becomes urgent as climate change exposesvulnerable populations with compromised thermoregulation to extreme heat. Thisreview establishes brain temperature as an overlooked but essential axis inneurophysiology, calling for increased research attention to address fundamentalquestions about thermal regulation in health and disease.

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