Summary: The temperature of the human brain varies much more than previously believed, and the temperature variations could be a sign of healthy brain function.
Source: UK Research and Innovation
New research has shown that normal human brain temperature varies much more than we thought, and this could be a sign of healthy brain function. In healthy men and women, where oral temperature is typically less than 37°C, average brain temperature is 38.5°C, with deeper brain regions often exceeding 40°C, particularly in women during the daytime.
Previously, human brain temperature studies have relied upon data capture from brain-injured patients in intensive care, where direct brain monitoring is often needed. More recently, a brain scanning technique, called magnetic resonance spectroscopy (MRS), has enabled researchers to measure brain temperature non-invasively in healthy people.
Until now, however, MRS had not been used to explore how brain temperature varies throughout the day, or to consider how an individual’s ‘body clock’ influences this.
The new study, led by researchers at the Medical Research Council (MRC) Laboratory for Molecular Biology, in Cambridge, UK, has produced the first 4D map of healthy human brain temperature.
This map overturns several previous assumptions and shows the remarkable extent to which brain temperature varies by brain region, age, sex, and time of day. Importantly, these findings also challenge a widely held belief that human brain and body temperature are the same.
The research, published in the journal Brain, also included analysis of data from patients with traumatic brain injury, showing that the presence of daily brain temperature cycles strongly correlates with survival. These findings could be used to improve understanding, prognosis, and treatment of brain injury.
Striking brain temperature variation in health
To study the healthy brain, the researchers recruited 40 volunteers, aged 20-40 years, to be scanned in the morning, afternoon, and late evening over one day, at the Edinburgh Imaging Facility, Royal Infirmary of Edinburgh.
Crucially, they also gave the participants a wrist-worn activity monitor, allowing genetic and lifestyle differences in the timing of each person’s body clock, or circadian rhythm, to be taken into account. For both ‘night owls’ or ‘morning larks’, knowing the biological time-of-day that each brain temperature measurement was taken at allowed differences between each volunteer’s body clock to be factored into the analysis.
In healthy participants, the average brain temperature was 38.5°C, more than two degrees warmer than that measured under the tongue. The study also found that brain temperature varied depending on:
time of day,
sex and menstrual cycle,
While the brain surface was generally cooler, deeper brain structures were frequently warmer than 40°C; with the highest observed brain temperature being 40.9°C. Across all individuals, brain temperature showed consistent time-of-day variation by nearly 1°C, with highest brain temperatures observed in the afternoon, and the lowest at night.
On average, female brains were around 0.4°C warmer than male brains. This sex difference was most likely driven by the menstrual cycle, since most females were scanned in the post-ovulation phase of their cycle, and their brain temperature was around 0.4°C warmer than that of females scanned in their pre-ovulation phase.
The results also showed that brain temperature increased with age over the 20-year range of the participants, most notably in deep brain regions, where the average increase was 0.6°C. The researchers propose that the brain’s capacity to cool down may deteriorate with age and further work is needed to investigate whether there is linked with the development of age-related brain disorders.
Dr John O’Neill, Group Leader at the MRC Laboratory for Molecular Biology, said:
“To me, the most surprising finding from our study is that the healthy human brain can reach temperatures that would be diagnosed as fever anywhere else in the body. Such high temperatures have been measured in people with brain injuries in the past, but had been assumed to result from the injury.”
“We found that brain temperature drops at night before you go to sleep and rises during the day. There is good reason to believe this daily variation is associated with long-term brain health—something we hope to investigate next.”
Temperature rhythms in injured brains
To explore the clinical implications of data obtained from healthy volunteers, the researchers analysed temperature data collected continuously from the brain in 114 patients who had suffered from moderate to severe traumatic brain injury (TBI). The patients’ average brain temperature was 38.5°C, but it varied even more widely, from 32.6 to 42.3°C.
Of 100 patients for whom there was enough data to test for daily rhythms, only a quarter had a daily rhythm in brain temperature. Focusing on predictors of survival in intensive care, the researchers found that absolute brain temperature measurements were of limited use, but daily brain temperature variation was strongly linked with survival—indeed, of TBI patients with a daily brain temperature rhythm only 4% died in intensive care, versus 27% who had no such rhythm.
The researchers caution that larger studies are needed to validate this association, and that the link between brain temperature and survival is correlative only, meaning that daily brain temperature rhythms cannot be assumed to directly increase survival. However, the observed link means that monitoring daily brain temperature cycles in TBI patients might be a promising tool to predict survival and would benefit from further research.
Together with the data from healthy people, the findings of this work raise important questions about the use of interventions to modify or control patient temperature in the clinic.
Dr Nina Rzechorzek, MRC Clinician Scientist Fellow from the MRC Laboratory for Molecular Biology who led the study, said:
“Using the most comprehensive exploration to date of normal human brain temperature, we’ve established ‘HEATWAVE’ – a 4D temperature map of the brain. This map provides an urgently-needed reference resource against which patient data can be compared, and could transform our understanding of how the brain works. That a daily brain temperature rhythm correlates so strongly with survival after TBI suggests that round-the-clock brain temperature measurement holds great clinical value.”
A daily temperature rhythm in the human brain predicts survival after brain injury
Patients undergo interventions to achieve a ‘normal’ brain temperature; a parameter that remains undefined for humans. The profound sensitivity of neuronal function to temperature implies the brain should be isothermal, but observations from patients and non-human primates suggest significant spatiotemporal variation.
We aimed to determine the clinical relevance of brain temperature in patients by establishing how much it varies in healthy adults.
We retrospectively screened data for all patients recruited to the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High Resolution Intensive Care Unit Sub-Study. Only patients with direct brain temperature measurements and without targeted temperature management were included.
To interpret patient analyses, we prospectively recruited 40 healthy adults (20 males, 20 females, 20–40 years) for brain thermometry using magnetic resonance spectroscopy. Participants were scanned in the morning, afternoon, and late evening of a single day.
In patients (n = 114), brain temperature ranged from 32.6 to 42.3°C and mean brain temperature (38.5 ± 0.8°C) exceeded body temperature (37.5 ± 0.5°C, P < 0.0001). Of 100 patients eligible for brain temperature rhythm analysis, 25 displayed a daily rhythm, and the brain temperature range decreased in older patients (P = 0.018). In healthy participants, brain temperature ranged from 36.1 to 40.9°C; mean brain temperature (38.5 ± 0.4°C) exceeded oral temperature (36.0 ± 0.5°C) and was 0.36°C higher in luteal females relative to follicular females and males (P = 0.0006 and P < 0.0001, respectively). Temperature increased with age, most notably in deep brain regions (0.6°C over 20 years, P = 0.0002), and varied spatially by 2.41 ± 0.46°C with highest temperatures in the thalamus. Brain temperature varied by time of day, especially in deep regions (0.86°C, P = 0.0001), and was lowest at night. From the healthy data we built HEATWAVE—a 4D map of human brain temperature.
Testing the clinical relevance of HEATWAVE in patients, we found that lack of a daily brain temperature rhythm increased the odds of death in intensive care 21-fold (P = 0.016), whilst absolute temperature maxima or minima did not predict outcome. A warmer mean brain temperature was associated with survival (P = 0.035), however, and ageing by 10 years increased the odds of death 11-fold (P = 0.0002).
Human brain temperature is higher and varies more than previously assumed—by age, sex, menstrual cycle, brain region, and time of day. This has major implications for temperature monitoring and management, with daily brain temperature rhythmicity emerging as one of the strongest single predictors of survival after brain injury.
We conclude that daily rhythmic brain temperature variation—not absolute brain temperature—is one way in which human brain physiology may be distinguished from pathophysiology.