Abstract 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.

/pdf/a-daily-temperature-rhythm-in-the-human-brain-predicts-f01gvdmg.pdf

A daily temperature rhythm in the human brain predicts survival after brain injury

Presently, the literature describing the influence of diurnal variation on dynamic cerebral autoregulation (dCA) metrics is sparse. Additionally, there is little data with respect to dCA comparisons between anterior/posterior circulation beds and biological sexes using squat-stand maneuvers. Eight male and eight female participants (n = 16) performed 5 min of spontaneous upright rest and squat-stand maneuvers at 0.05 and 0.10 Hz across seven time points throughout the day. All testing sessions commenced at 8:00 a.m. each day and dCA parameters were quantified across the cardiac cycle (diastole, mean, and systole) using transcranial Doppler ultrasound to insonate cerebral blood velocity within the middle and posterior cerebral arteries (MCA, PCA). No cardiac cycle alternations were seen spontaneous (all p > .207) while a trend was noted in some driven (all p > .051) dCA metrics. Driven dCA produced much lower coefficient of variances (all  .096). Between vessels, PCA absolute gain was reduced within all spontaneous and driven measures (all p   .099). There appears to be little influence of diurnal variation on dCA measures across the day (8:00 a.m. to 6:00 p.m.). Absolute gain was blunted in the PCA relative to the MCA and consistent with previous literature, driven methods demonstrated vastly improved reproducibility metrics compared to spontaneous methods. Finally, no dCA differences were found between biological sexes, demonstrating that males and females regulate in a harmonious manner, when females are tested within the early follicular phase of the menstrual cycle.

Comparison of diurnal variation, anatomical location, and biological sex within spontaneous and driven dynamic cerebral autoregulation measures.

Diurnal variation of default mode network in patients with restless legs syndrome

This study aimed to explore the changes in functional connections between cerebral hemispheres and local brain regions functional activities in patients with acute ischemic stroke (AIS) treated with International Standard Scalp Acupuncture (ISSA). Thirty patients with middle cerebral artery AIS in the dominant hemisphere were selected and randomly divided into two groups such as the control group and the scalp acupuncture group, with 15 patients in each group. Patients in the control group were treated with conventional Western medicine, while patients in the scalp acupuncture group received ISSA (acupuncture at the parietal midline [MS5], acupuncture at the left anterior parietotemporal oblique line [MS6] and acupuncture at the left posterior parietotemporal oblique line [MS7]) for one course of treatment. All patients were evaluated for treatment efficacy and received whole brain resting state functional magnetic resonance imaging (Rs-fMRI) scan before and after treatment. The observational indicators included: (a) the National Institutes of Health Stroke Scale (NIHSS) scores and the simplified Fugl-Meyer Assessment (SFMA) scores; (b) analyses of the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and voxel-mirrored homotopic connectivity (VMHC). The results showed a significant difference in the NIHSS scores before and after treatment in the scalp acupuncture group compared with the control group (p < .05), indicating that patients improved better after scalp acupuncture treatment. Compared with the control group, the VMHC, ALFF and ReHo values in the scalp acupuncture group increased after treatment. The VMHC values increased in the brain regions dominated by bilateral BA6 and BA8; the ALFF values increased in the left BA39 and the adjacent superior temporal gyrus and middle temporal gyrus; and the ReHo values increased in the brain regions extending from left middle temporal gyrus (including BA21) to BA37, and the brain regions extending from the left BA40 and angular gyrus to BA7. The present study indicated that scalp acupuncture can specifically strengthen the functional activities of the brain regions related to sensory integration, language processing and motor coordination in the middle aged and elderly patients with AIS of the dominant cerebral hemisphere, and can strengthen bilateral frontal lobe motor control. This study may provide a scientific basis for the clinical application of ISSA treatment in patients with AIS, and may also provide a preliminary research basis for further animal experiments.

Scalp acupuncture enhances local brain regions functional activities and functional connections between cerebral hemispheres in acute ischemic stroke patients.

It is critical that the regulatory system functions well in space’s microgravity. However, the “intrinsic” cardiovascular regulatory system (β), estimated by the fractal scaling of heart rate variability (HRV) (0.0001–0.01 Hz), does not adapt to the space environment during long-duration (6-month) space flights. Neuroimaging studies suggest that the default mode network (DMN) serves a broad adaptive purpose, its topology changing over time in association with different brain states of adaptive behavior. Hypothesizing that HRV varies in concert with changes in brain’s functional connectivity, we analyzed 24-hour HRV records from 8 healthy astronauts (51.8 ± 3.7 years; 6 men) on long (174.5 ± 13.8 days) space missions, obtained before launch, after about 21 (ISS01), 73 (ISS02), and 156 (ISS03) days in space, and after return to Earth. Spectral power in 8 frequency regions reflecting activity in different brain regions was computed by maximal entropy. Improved β (p < 0.05) found in 4 astronauts with a positive activation in the “HRV slow-frequency oscillation” (0.10–0.20 Hz) occurred even in the absence of consciousness. The adaptive response was stronger in the evening and early sleep compared to morning (p = 0.039). Brain functional networks, the DMN in particular, can help adapt to microgravity in space with help from the circadian clock.

/pdf/circadian-challenge-of-astronauts-unconscious-mind-adapting-b4bpnphg7d.pdf

Circadian challenge of astronauts' unconscious mind adapting to microgravity in space, estimated by heart rate variability.

It remains an ongoing investigation about how the neural activity alters with the diurnal rhythms in human brain. Resting-state functional magnetic resonance imaging (RS-fMRI) reflects spontaneous activities and/or the endogenous neurophysiological process of the human brain. In the present study, we applied the ReHo (regional homogeneity) and ALFF (amplitude of low frequency fluctuation) based on RS-fMRI to explore the regional differences in the spontaneous cerebral activities throughout the entire brain between the morning and evening sessions within a 24-hour time cycle. Wide spread brain areas were found to exhibit diurnal variations, which may be attributed to the internal molecular systems regulated by clock genes, and the environmental factors including light-dark cycle, daily activities and homeostatic sleep drive. Notably, the diurnal variation of default mode network (DMN) suggests that there is an adaptation or compensation response within the subregions of DMN, implying a balance or a decoupling of regulation between these regions.

/pdf/diurnal-variations-in-neural-activity-of-healthy-human-brain-4767sfxrca.pdf

Diurnal Variations in Neural Activity of Healthy Human Brain Decoded with Resting-State Blood Oxygen Level Dependent fMRI.

Objective: This study aims to investigate location-specific functional remodeling following ischemic stroke in pons and corona radiata. Methods: This study was approved by the local Institutional Review Board. Written consent was obtained from each of the participants prior to the MRI examination. Thirty six subjects with first ever acute ischemic stroke in pons (PS, n = 15, aged 62.8 ± 11.01 years) or corona radiata (CRS, n = 21, aged 59.33 ± 13.84 years) as well as 30 age and sex matched healthy controls (HC, n = 30, aged 60 ± 6.43 years) were examined with resting state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) and degree centrality (DC) were calculated using a voxel-based approach. Intergroup differences in ReHo and DC were explored using a permutation test with a threshold-free cluster enhancement (PT TFCE, number of permutations = 1,000, family-wise error rate (FWER) 0.05). Conclusions: Focal ischemic stroke in pons or corona radiata leads to extensive alterations in the functional network centrality. IS-induced network remodeling is more anatomy-specific than pathway-specific, which may underpin the clinicotopographical profiles during the disease dynamic. Approaches targeting neural pathway and functional connectivity may shed light on a better characterization and management innovation of ischemic stroke.

/pdf/ischemic-stroke-in-pontine-and-corona-radiata-location-1s9lhjkukb.pdf

Ischemic Stroke in Pontine and Corona Radiata: Location Specific Impairment of Neural Network Investigated With Resting State fMRI.

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Diurnal Variations in Neural Activity of Healthy Human Brain Decoded with Resting-State Blood Oxygen Level Dependent fMRI.

Ischemic Stroke in Pontine and Corona Radiata: Location Specific Impairment of Neural Network Investigated With Resting State fMRI.