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This study aimed to evaluate the dose-dependent brain temperature effects of transcranial photobiomodulation (t-PBM). Thirty adult subjects with major depressive disorder were randomized to three t-PBM sessions with different doses (low: 50 mW/cm2, medium: 300 mW/cm2, high: 850 mW/cm2) and a sham treatment. The low and medium doses were administered in continuous wave mode, while the high dose was administered in pulsed wave mode. A 3T MRI scanner was used to perform proton magnetic resonance spectroscopy (1H-MRS). A voxel with a volume of 30 × 30 × 15 mm3 was placed on the left prefrontal region. Brain temperature (°C) was derived by analyzing 1H-MRS spectrum chemical shift differences between the water (~ 4.7 ppm) and N-acetyl aspartate (NAA) (~ 2.01 ppm) peaks. After quality control of the data, the following group numbers were available for both pre- and post-temperature estimations: sham (n = 10), low (n = 11), medium (n = 10), and high (n = 8). We did not detect significant temperature differences for any t-PBM-active or sham groups post-irradiation (p-value range = 0.105 and 0.781). We also tested for potential differences in the pre-post variability of brain temperature in each group. As for t-PBM active groups, the lowest fluctuation (variance) was observed for the medium dose (σ2 = 0.29), followed by the low dose (σ2 = 0.47), and the highest fluctuation was for the high dose (σ2 = 0.67). t-PBM sham condition showed the overall lowest fluctuation (σ2 = 0.11). Our 1H-MRS thermometry results showed no significant brain temperature elevations during t-PBM administration. [ABSTRACT FROM AUTHOR]

Introduction: Exploring gender differences in cognitive abilities offers vital insights into human brain functioning. Methods: Our study utilized advanced techniques like magnetic resonance thermometry, standard working memory n-back tasks, and functional MRI to investigate if gender-based variations in brain temperature correlate with distinct neuronal responses and working memory capabilities. Results: We observed a significant decrease in average brain temperature in males during working memory tasks, a phenomenon not seen in females. Although changes in female brain temperature were significantly lower than in males, we found an inverse relationship between the absolute temperature change (ATC) and cognitive performance, alongside a correlation with blood oxygen level dependent (BOLD) signal change induced by neural activity. This suggests that in females, ATC is a crucial determinant for the link between cognitive performance and BOLD responses, a linkage not evident in males. However, we also observed additional female specific BOLD responses aligned with comparable task performance to that of males. Discussion: Our results suggest that females compensate for their brain's heightened temperature sensitivity by activating additional neuronal networks to support working memory. This study not only underscores the complexity of gender differences in cognitive processing but also opens new avenues for understanding how temperature fluctuations influence brain functionality. [ABSTRACT FROM AUTHOR]

Neuronal Tau protein hyperphosphorylation (PPtau) is a hallmark of tauopathic neurodegeneration. However, a reversible brain PPtau occurs in mammals during either natural or "synthetic" torpor (ST), a transient deep hypothermic state that can be pharmacologically induced in rats. Since in both conditions a high sleep pressure builds up during the regaining of euthermia, the aim of this work was to assess the possible role of post-ST sleep in PPtau dephosphorylation. Male rats were studied at the hypothermic nadir of ST, and 3–6 h after the recovery of euthermia, after either normal sleep (NS) or total sleep deprivation (SD). The effects of SD were studied by assessing: (i) deep brain temperature (Tb); (ii) immunofluorescent staining for AT8 (phosphorylated Tau) and Tau-1 (non-phosphorylated Tau), assessed in 19 brain structures; (iii) different phosphorylated forms of Tau and the main cellular factors involved in Tau phospho-regulation, including pro- and anti-apoptotic markers, assessed through western blot in the parietal cortex and hippocampus; (iv) systemic factors which are involved in natural torpor; (v) microglia activation state, by considering morphometric variations. Unexpectedly, the reversibility of PPtau was more efficient in SD than in NS animals, and was concomitant with a higher Tb, higher melatonin plasma levels, and a higher frequency of the microglia resting phenotype. Since the reversibility of ST-induced PPtau was previously shown to be driven by a latent physiological molecular mechanism triggered by deep hypothermia, short-term SD soon after the regaining of euthermia seems to boost the possible neuroprotective effects of this mechanism. [ABSTRACT FROM AUTHOR]

Deviation from the optimal bifurcation structure causes abnormal hemodynamic stress, increasing the risk of cerebral aneurysm initiation at the arterial bifurcation apexes of the Circle of Willis. Although Murray's law describes the optimal relationship between bifurcation calibers, major arterial bifurcations within the Circle of Willis show deviations from this law. This study introduces a novel scaling law that describes the optimum relationship between bifurcation characteristics based on pulsatile flow and the internal surface of vessels. The proposed scaling law applies to major intracranial arteries, such as the basilar, internal carotid and common carotid arteries, encompassing both symmetrical and asymmetrical bifurcations. One of the merits of this scaling law is its sole dependence on the Womersley number of parent vessels to determine bifurcation characteristics. The diameter ratios suggested by these relationships are in good agreement with available clinical morphometric data. Numerical simulations of pulsatile flow for several Womersley numbers indicate that the flow resistance and temperature stability of the proposed scaling law are preferable to those of Murray's law. That might be the reason this scaling law is the optimality principle governing the major cerebral arteries, particularly those arterial blood vessels responsible for the brain's thermoregulatory, because the brain's thermoregulatory and temperature stability are the physiological and anatomical constraints of the human brain. [ABSTRACT FROM AUTHOR]

Simple Summary: Birds have an electrophysiological sleep state that resembles rapid-eye-movement (REM) sleep in mammals. Whether the regulation and function of this REM sleep state in birds is similar to that in mammals is unclear. In the current experiment, we studied sleep regulation in jackdaws (Coloeus monedula) by exposing the birds to low ambient temperature, a procedure that selectively suppresses REM sleep in mammals. Jackdaws were equipped with electrodes to record brain activity and neck muscle activity and a sensor to record brain temperature. Exposure to a low ambient temperature of 4 °C during the nighttime sleep phase caused a significant drop in brain temperature of 1.4 °C, compared to the baseline night at 21 °C. However, cold exposure did not affect the amount of NREM sleep and REM sleep. This indicates that REM sleep in jackdaws is protected against the influence of low temperature. Hence, the well-established relationship between thermoregulation and REM sleep regulation that exists in mammals may not be present in birds. Birds have an electrophysiological sleep state that resembles mammalian rapid-eye-movement (REM) sleep. However, whether its regulation and function are similar is unclear. In the current experiment, we studied REM sleep regulation in jackdaws (Coloeus monedula) by exposing the birds to low ambient temperature, a procedure that selectively suppresses REM sleep in mammals. Eight jackdaws were equipped with electrodes to record brain activity and neck muscle activity and a thermistor to record cortical brain temperature. Recordings covered a three-day period starting with a 24 h baseline day at an ambient temperature of 21 °C, followed by a 12 h cold night at 4 °C, after which the ambient temperature was restored to 21 °C for the remaining recovery period. Cold exposure at night caused a significant drop in brain temperature of 1.4 °C compared to the baseline night. However, throughout the cold night, jackdaws expressed NREM sleep and REM sleep levels that were not significantly different from the baseline. Also, EEG spectral power during NREM sleep was unaffected by cold exposure. Thus, while cold exposure had a clear effect on brain temperature in jackdaws, it did not have the same REM sleep suppressing effect reported for mammals. These findings suggest that the REM-sleep-like state in birds, unlike REM sleep in mammals, is protected against the influence of low temperature. [ABSTRACT FROM AUTHOR]

Background: Although brain activities in Alzheimer's disease (AD) might be evaluated MRI and PET, the relationships between brain temperature (BT), the index of diffusivity along the perivascular space (ALPS index), and amyloid deposition in the cerebral cortex are still unclear. Purpose: To investigate the relationship between metabolic imaging measurements and clinical information in patients with AD and normal controls (NCs). Study Type: Retrospective analysis of a prospective dataset. Population: 58 participants (78.3 ± 6.8 years; 30 female): 29 AD patients and 29 age‐ and sex‐matched NCs from the Open Access Series of Imaging Studies dataset. Field Strength/Sequence: 3T; T1‐weighted magnetization‐prepared rapid gradient‐echo, diffusion tensor imaging with 64 directions, and dynamic 18F‐florbetapir PET. Assessment: Imaging metrics were compared between AD and NCs. These included BT calculated by the diffusivity of the lateral ventricles, ALPS index that reflects the glymphatic system, the mean standardized uptake value ratio (SUVR) of amyloid PET in the cerebral cortex and clinical information, such as age, sex, and MMSE. Statistical Tests: Pearson's or Spearman's correlation and multiple linear regression analyses. P values <0.05 were defined as statistically significant. Results: Significant positive correlations were found between BT and ALPS index (r = 0.44 for NCs), while significant negative correlations were found between age and ALPS index (rs = −0.43 for AD and − 0.47 for NCs). The SUVR of amyloid PET was not significantly associated with BT (P = 0.81 for AD and 0.21 for NCs) or ALPS index (P = 0.10 for AD and 0.52 for NCs). In the multiple regression analysis, age was significantly associated with BT, while age, sex, and presence of AD were significantly associated with the ALPS index. Data Conclusion: Impairment of the glymphatic system measured using MRI was associated with lower BT and aging. Level of Evidence: 3 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

Subtle changes in body temperature affect the outcomes of ill newborns. However, the temperature profile of neonatal brains remains largely unknown. In open-cot care, increased cerebral perfusion is correlated with higher superficial brain temperatures. This study investigated the dependence of brain temperature (relative to rectal temperature) on ambient temperature, body size, cerebral perfusion, and metabolism in infants receiving incubator care. Rectal, scalp, and brain temperatures, superior vena cava flow, and brain oxygenation were assessed using echocardiography, thermo-compensatory temperature monitoring, and near-infrared spectroscopy in 60 newborns. These infants had a mean postconceptional age of 36.9 (2.2) weeks and weighed 2348 (609) g at the time of evaluation. The ambient temperature was maintained at 30.0 (1.0) °C. A higher rectal temperature was associated with greater postconceptional age (p = 0.002), body weight (p < 0.001), and head circumference (p < 0.001). Relative scalp, superficial brain, and deep brain temperatures were associated with smaller head circumference (p < 0.001, p = 0.030, and p = 0.015, respectively) and superior vena cava flow (p = 0.002, p = 0.003, and p = 0.003, respectively). In infants receiving incubator care, larger head sizes and increased brain perfusion were associated with lower relative scalp and brain temperatures. When considered alongside previous reports, cerebral perfusion may contribute to maintaining stable cerebral tissue temperature against ambient temperature changes. [ABSTRACT FROM AUTHOR]

IntroductionExploring gender differences in cognitive abilities offers vital insights into human brain functioning.MethodsOur study utilized advanced techniques like magnetic resonance thermometry, standard working memory n-back tasks, and functional MRI to investigate if gender-based variations in brain temperature correlate with distinct neuronal responses and working memory capabilities.ResultsWe observed a significant decrease in average brain temperature in males during working memory tasks, a phenomenon not seen in females. Although changes in female brain temperature were significantly lower than in males, we found an inverse relationship between the absolute temperature change (ATC) and cognitive performance, alongside a correlation with blood oxygen level dependent (BOLD) signal change induced by neural activity. This suggests that in females, ATC is a crucial determinant for the link between cognitive performance and BOLD responses, a linkage not evident in males. However, we also observed additional female specific BOLD responses aligned with comparable task performance to that of males.DiscussionOur results suggest that females compensate for their brain’s heightened temperature sensitivity by activating additional neuronal networks to support working memory. This study not only underscores the complexity of gender differences in cognitive processing but also opens new avenues for understanding how temperature fluctuations influence brain functionality.

IntroductionInfrared thermography (IT) is a non-invasive real-time imaging technique with potential application in different areas of neurosurgery. Despite technological advances in the field, intraoperative IT (IIT) has been an underestimated tool with scarce reports on its usefulness during intracranial tumor resection. We aimed to evaluate the usefulness of high-resolution IIT with static and dynamic thermographic maps for transdural lesion localization, and diagnosis, to assess the extent of resection, and the occurrence of perioperative acute ischemia.MethodsIn a prospective study, 15 patients affected by intracranial tumors (six gliomas, four meningiomas, and five brain metastases) were examined with a high-resolution thermographic camera after craniotomy, after dural opening, and at the end of tumor resection.ResultsTumors were transdurally located with 93.3% sensitivity and 100% specificity (p

Christina Mueller,1 Ayushe A Sharma,2 Jerzy P Szaflarski3 1Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA; 3Departments of Neurology, Neurobiology, and Neurosurgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USACorrespondence: Christina Mueller, Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, 1719 6th Ave S, Birmingham, AL, 35222, USA, Tel +1 205-975-4219, Fax +1 205-996-4802, Email cm1@uab.eduPurpose: Inflammation may link trauma to clinical symptoms in functional seizures (FS). We compared brain temperature and metabolites in FS, psychiatric (PCs) and healthy controls (HCs) and quantified their associations with serum biomarkers of inflammation and clinical symptoms.Patients and Methods: Brain temperature and metabolites were measured with whole-brain magnetic resonance spectroscopic imaging (MRSI) and compared between groups in regions of interest and the whole brain. Relationships with inflammatory biomarkers and symptoms were assessed with Pearson correlations.Results: Brain temperature was higher in FS than HCs in the orbitofrontal cortex (OFC) and anterior cingulate gyrus (ACG) and lower in the occipital cortex and frontal lobe. PCs showed lower temperatures than HCs in the frontal lobe including precentral gyrus and in the cerebellum. Myo-inositol (MINO) was higher in FS than HCs in the precentral gyrus, posterior temporal gyrus, ACG and OFC, and choline (CHO) was higher in the occipital lobe. CHO was higher in PCs than HCs in the ACG and OFC, and N-acetylaspartate (NAA) was higher in the ACG. There were no significant correlations with the serum inflammatory biomarkers. In FS, brain temperature correlated with depression, quality of life, psychological symptoms, and disability, CHO correlated with disability, and MINO correlated with hostility, disability, and quality of life.Conclusion: Some of the previously identified neuroimaging abnormalities in FS may be related to comorbid psychiatric symptoms, while others, such as abnormalities in sensorimotor cortex, occipital regions, and the temporo-parietal junction may be specific to FS. Overlapping MINO and temperature increases in the ACG and OFC in FS suggest neuroinflammation.Keywords: brain temperature, magnetic resonance spectroscopy, functional seizures, inflammatory biomarkers, metabolites

With the advancement of technology in Neurosurgery, imaging guidance for surgical planning and intraoperative assessment has become relevant. Currently, two major methods of imaging guidance are generally explored in the literature, namely based on imaging and fluorescence. These techniques, however, are not without limitations. Thermal imaging has potentially broad applications in clinical practice, especially for intracranial diseases. Infrared thermography (IT) has been an underestimated tool with few reports on its usefulness during intracranial surgeries. In this article, we aim to provide a brief discussion on the limitations of current intraoperative imaging techniques for intracranial surgeries and to provide an in-depth state-of-the-art review on intraoperative IT (IIT) for intracranial lesions. High-resolution IIT is a non-invasive alternative imaging method that provides real-time estimation of regional cerebral blood flow. For brain tumors, the studies were mostly directed to diagnostic purposes and occasionally for lesion-localization. The use of IIT to address the extent of resection is a potential new application. Clinical data in this issue suggests that IIT might detect residual tumors, occasionally not assessed by other imaging technologies. Thermographic measurements during vascular and epilepsy surgeries comprise an interesting field for future research with potential clinical implications. Further experimental and clinical studies should be addressed to provide technical refinements and verify the usefulness of this noninvasive technology in neurosurgery.

Purpose: To investigate the daily fluctuations in brain temperature in healthy individuals using magnetic resonance (MR) diffusion-weighted imaging (DWI) thermometry and to clarify the associations between the brain and body temperatures and sex. Methods: Thirty-two age-matched healthy male and female volunteers (male = 16, 20–38 years) were recruited between July 2021 and January 2022. Brain MR examinations were performed in the morning and evening phases on the same day to calculate the brain temperatures using DWI thermometry. Body temperature was also measured in each MR examination. Group comparisons of body and brain temperatures between the two phases were performed using paired t-tests. A multiple linear regression model was used to predict the morning brain temperature using sex, evening brain temperature, and the interaction between sex and evening brain temperature as covariates. Results: Body temperatures were significantly higher in the evening than in the morning in all participants, male group, and female group (p < 0.001, = 0001, and < 0.001, respectively). Meanwhile, no significant difference was observed between the morning and evening brain temperatures in each analysis (p = 0.23, 0.70, and 0.16, respectively). Multiple linear regression analysis showed significant associations of morning brain temperature with sex (p = 0.038), evening brain temperature (p < 0.001), and the interaction between sex and evening brain temperature (p = 0.036). Conclusion: Unlike body temperature, brain temperature showed no significant daily fluctuations; however, daily fluctuations in brain temperature may vary depending on sex. [ABSTRACT FROM AUTHOR]

Subtle changes in body temperature affect the outcomes of ill newborns. However, the temperature profile of neonatal brains remains largely unknown. In open-cot care, increased cerebral perfusion is correlated with higher superficial brain temperatures. This study investigated the dependence of brain temperature (relative to rectal temperature) on ambient temperature, body size, cerebral perfusion, and metabolism in infants receiving incubator care. Rectal, scalp, and brain temperatures, superior vena cava flow, and brain oxygenation were assessed using echocardiography, thermo-compensatory temperature monitoring, and near-infrared spectroscopy in 60 newborns. These infants had a mean postconceptional age of 36.9 (2.2) weeks and weighed 2348 (609) g at the time of evaluation. The ambient temperature was maintained at 30.0 (1.0) °C. A higher rectal temperature was associated with greater postconceptional age (p = 0.002), body weight (p < 0.001), and head circumference (p < 0.001). Relative scalp, superficial brain, and deep brain temperatures were associated with smaller head circumference (p < 0.001, p = 0.030, and p = 0.015, respectively) and superior vena cava flow (p = 0.002, p = 0.003, and p = 0.003, respectively). In infants receiving incubator care, larger head sizes and increased brain perfusion were associated with lower relative scalp and brain temperatures. When considered alongside previous reports, cerebral perfusion may contribute to maintaining stable cerebral tissue temperature against ambient temperature changes.

Birds have an electrophysiological sleep state that resembles mammalian rapid-eye-movement (REM) sleep. However, whether its regulation and function are similar is unclear. In the current experiment, we studied REM sleep regulation in jackdaws (Coloeus monedula) by exposing the birds to low ambient temperature, a procedure that selectively suppresses REM sleep in mammals. Eight jackdaws were equipped with electrodes to record brain activity and neck muscle activity and a thermistor to record cortical brain temperature. Recordings covered a three-day period starting with a 24 h baseline day at an ambient temperature of 21 °C, followed by a 12 h cold night at 4 °C, after which the ambient temperature was restored to 21 °C for the remaining recovery period. Cold exposure at night caused a significant drop in brain temperature of 1.4 °C compared to the baseline night. However, throughout the cold night, jackdaws expressed NREM sleep and REM sleep levels that were not significantly different from the baseline. Also, EEG spectral power during NREM sleep was unaffected by cold exposure. Thus, while cold exposure had a clear effect on brain temperature in jackdaws, it did not have the same REM sleep suppressing effect reported for mammals. These findings suggest that the REM-sleep-like state in birds, unlike REM sleep in mammals, is protected against the influence of low temperature.

Brain temperature, regulated by the balance between blood circulation and metabolic heat generation, is an important parameter related to neural activity, cerebral hemodynamics, and neuroinflammation. A key challenge for integrating brain temperature into clinical practice is the lack of reliable and non-invasive brain thermometry. The recognized importance of brain temperature and thermoregulation in both health and disease, combined with limited availability of experimental methods, has motivated the development of computational thermal models using bioheat equations to predict brain temperature. In this mini-review, we describe progress and the current state-of-the-art in brain thermal modeling in humans and discuss potential avenues for clinical applications. [ABSTRACT FROM AUTHOR]

Objective: Neuroinflammation (NI) is a pathophysiological factor in many neurological disorders, including epilepsy. Because NI causes microstructural tissue damage that worsens with increasing brain temperature, abnormally elevated brain temperatures may be a surrogate measure of the biochemical consequences of NI. This study investigated whether patients with temporal lobe epilepsy (TLE) have abnormal brain temperature elevations (TCRE) in seizure‐producing regions that show evidence of edema and/or microstructural damage. Methods: Twenty adults with TLE and 20 healthy controls (HCs) were scanned at 3‐Tesla. TCRE in each voxel was calculated (TCRE = −102.61(ΔH20−CRE) + 206.1°C) by non‐invasive volumetric magnetic resonance spectroscopic imaging and thermometry (MRSI‐t). Multi‐shell diffusion images were processed by neurite orientation and density imaging (NODDI). Voxel wise two‐sample t tests computed group differences in imaging data. Multimodal data fusion (joint independent component analysis [ICA]) determined the spatial coupling of TCRE with NODDI. Results: TCRE analyses showed that, compared to HCs, TLEs had higher TCRE (p <.001). NODDI analyses showed increased extracellular free water (pFWE < 0.05) in the medial temporal lobes, with the most pronounced increases ipsilateral to seizure onset. TLEs also had increased angular dispersion of neurites (p <.001) and decreased neurite density (pFWE <0.05) in the ictal‐onset medial temporal lobe, as well as more widespread, bilateral patterns of abnormalities. Focal increases in TCRE were spatially concordant with increased free water in the left inferior and middle temporal gyri and the associated cortex. In TLE, ICA loadings extracted from this region of overlap were associated with greater mood disturbance (r =.34, p =.02) and higher depression scores (r =.37, p =.009). Significance: The spatial concordance between focal TCRE elevations and edema in TLE supports the notion that brain thermometry visualizes the correlates of focal NI. MRSI‐t‐based TCRE elevations may, therefore, be a useful biomarker for identifying seizure‐producing tissue in patients with focal epilepsy caused by brain damage. [ABSTRACT FROM AUTHOR]

Simple Summary: The function and regulation of rapid-eye-movement (REM) sleep is a topic of ongoing debate. It is often assumed that REM sleep is a homeostatically regulated process and that a need for REM sleep builds up, either during prior wakefulness or during preceding slow wave sleep. In the current study, we tested this hypothesis in the day-active tree shrew (Tupaia belangeri), a small mammal closely related to primates. We exposed the animals to a low temperature of 4 °C during their main sleep phase, a procedure that is known to suppress REM sleep. Cold exposure caused a significant drop in brain temperature and body temperature and also resulted in a strong and selective suppression of REM sleep. However, contrary to our expectation, the loss of REM sleep was not recovered during the subsequent day and night. These findings in a day-active mammal confirm that the expression of REM sleep is highly sensitive to environmental temperature but do not support the view that REM sleep is homeostatically regulated in this species. The function and regulation of rapid-eye-movement (REM) sleep is a topic of ongoing debate. It is often assumed that REM sleep is a homeostatically regulated process and that a need for REM sleep builds up, either during prior wakefulness or during preceding slow wave sleep. In the current study, we tested this hypothesis in six diurnal tree shrews (Tupaia belangeri), small mammals closely related to primates. All animals were individually housed and kept under a 12:12 light-dark cycle with an ambient temperature of 24 °C. We recorded sleep and temperature in the tree shrews for 3 consecutive 24 h days. During the second night, we exposed the animals to a low ambient temperature of 4 °C, a procedure that is known to suppress REM sleep. Cold exposure caused a significant drop in brain temperature and body temperature and also resulted in a strong and selective suppression of REM sleep by 64.9%. However, contrary to our expectation, the loss of REM sleep was not recovered during the subsequent day and night. These findings in a diurnal mammal confirm that the expression of REM sleep is highly sensitive to environmental temperature but do not support the view that REM sleep is homeostatically regulated in this species. [ABSTRACT FROM AUTHOR]

Brain temperature determines not only an individual’s cognitive functionality but also the prognosis and mortality rates of many brain diseases. More specifically, brain temperature not only changes in response to different physiological events like yawning and stretching, but also plays a significant pathophysiological role in a number of neurological and neuropsychiatric illnesses. Here, we have outlined the function of brain hyperthermia in both diseased and healthy states, focusing particularly on the amyloid beta aggregation in Alzheimer's disease.

Background: Brain cooling therapy is one of the subjects of interest, and currently, data on direct brain cooling are lacking. Hence, the objective is to investigate the clinical outcomes and discuss the thermodynamics aspect of direct brain cooling on severely injured brain patients. Methods: This pilot study recruited the severely injured brain patients who were then randomized to either a direct brain cooling therapy group using a constant cooling temperature system or a control group. All studied patients must be subjected to an emergency neurosurgical procedure of decompressive craniectomy and were monitored with intracranial pressure, brain oxygenation, and temperature. Further, comparison was made with our historical group of patients who had direct brain cooling therapy through the old technique. Results: The results disclosed the direct brain cooling treated patients through a newer technique obtained a better Extended Glasgow Outcome Score than a control group (P < 001). In addition, there is a significant outcome difference between the combined cooling treated patients (new and old technique) with the control group (P < 0.001). Focal brain oxygenation and temperature are likely factors that correlate with better outcomes. Conclusion: Direct brain cooling is feasible, safe, and affects the clinical outcomes of the severely traumatized brain, and physics of thermodynamics may play a role in its pathophysiology. [ABSTRACT FROM AUTHOR]

Cerebral temperature is one of the key indicators of fever, trauma, and physical activity. It has been reported that the temperature of the healthy brain is up to 2°C higher than the core body temperature. The main methods to monitor brain temperature include infrared spectroscopy, radiometry, and acoustic thermometry. While these methods are useful, they are not very effective when portability is desired, the temperature needs to be monitored for a longer period, or localized monitoring is required. This paper presents a short review of invasive and non-invasive brain temperature monitoring sensors and tools. We discuss the type of temperature sensors that can be integrated with probes. Furthermore, implantable and bioresorbable sensors are briefly mentioned. Biocompatibility and invasiveness of the sensors in terms of their functional materials, encapsulation, and size are highlighted.

Peripheral vasoconstriction is a centrally mediated physiological effect known to play an important role in regulating body temperature by adjusting heat exchange with the external environment. However, peripheral vasoconstriction as a component of sympathetic activation also occurs following exposure to various salient stimuli and during motivated behavior at stable environmental temperatures. This review aims to consider available evidence suggesting a significant contribution of this peripheral effect to physiological increases in both brain temperature and entry of oxygen and glucose into the brain’s extracellular space. While these effects are triggered by neuronal activation, constriction of blood vessels in the skin and most internal organs results in redistribution of blood from the peripheral to central domains, thus dilating cerebral vessels, increasing global cerebral blood flow, and enhancing the intra-brain entry of oxygen and glucose from arterial blood. This powerful influence appears to determine the long duration of physiological increases in both brain temperature and brain levels of glucose and oxygen and their basic similarity across different brain structures. This work underscores the tight interrelationship between the brain and periphery and a significant contribution of cardiovascular effects in providing the enhanced inflow of oxygen and glucose into brain tissue to prevent metabolic deficit during functional neural activation.

Brain tissue temperature is a dynamic balance between heat generation from metabolism, passive loss of energy to the environment, and thermoregulatory processes such as perfusion. Perinatal brain injuries, particularly neonatal encephalopathy, and seizures, have a significant impact on the metabolic and haemodynamic state of the developing brain, and thereby likely induce changes in brain temperature. In healthy newborn brains, brain temperature is higher than the core temperature. Magnetic resonance spectroscopy (MRS) has been used as a viable, non-invasive tool to measure temperature in the newborn brain with a reported accuracy of up to 0.2 degrees Celcius and a precision of 0.3 degrees Celcius. This measurement is based on the separation of chemical shifts between the temperature-sensitive water peaks and temperature-insensitive singlet metabolite peaks. MRS thermometry requires transport to an MRI scanner and a lengthy single-point measurement. Optical monitoring, using near infrared spectroscopy (NIRS), offers an alternative which overcomes this limitation in its ability to monitor newborn brain tissue temperature continuously at the cot side in real-time. Near infrared spectroscopy uses linear temperature-dependent changes in water absorption spectra in the near infrared range to estimate the tissue temperature. This review focuses on the currently available methodologies and their viability for accurate measurement, the potential benefits of monitoring newborn brain temperature in the neonatal intensive care unit, and the important challenges that still need to be addressed.

We studied the possibility of using microwave radiothermometry of the brain in biorhythmology. It was found that the temperature variability of the frontal lobes of the right and left hemispheres strictly corresponded to the 24-h cycle was characterized by the oscillation amplitude of 1.2-1.4°C, which significantly exceeded the amplitude of the basal temperature. A conclusion was made about the informative value of the method of noninvasive registration of the 24-h dynamics of the brain temperature. [ABSTRACT FROM AUTHOR]

Therapeutic hypothermia (TH), which prevents irreversible neuronal necrosis and ischemic brain damage, has been proven effective for preventing ischemia-reperfusion injury in post-cardiac arrest syndrome and neonatal encephalopathy in both animal studies and clinical trials. However, lowering the whole-body temperature below 34°C can lead to severe systemic complications such as cardiac, hematologic, immunologic, and metabolic side effects. Although the brain accounts for only 2% of the total body weight, it consumes 20% of the body's total energy at rest and requires a continuous supply of glucose and oxygen to maintain function and structural integrity. As such, theoretically, temperature-controlled selective brain cooling (SBC) may be more beneficial for brain ischemia than systemic pan-ischemia. Various SBC methods have been introduced to selectively cool the brain while minimizing systemic TH-related complications. However, technical setbacks of conventional SBCs, such as insufficient cooling power and relatively expensive coolant and/or irritating effects on skin or mucosal interfaces, limit its application to various clinical settings. This review aimed to integrate current literature on SBC modalities with promising therapeutic potential. Further, future directions were discussed by exploring studies on interesting coping skills in response to environmental or stress-induced hyperthermia among wild animals, including mammals and birds. [ABSTRACT FROM AUTHOR]

The core body temperature tends to decrease under general anesthesia. Consequently, monitoring the core body temperature during procedures involving general anesthesia is essential to ensure patient safety. In veterinary medicine, rectal temperature is used as an indicator of the core body temperature, owing to the accuracy and convenience of this approach. Some previous studies involving craniotomy reported differences between the brain and core temperatures under general anesthesia. However, noninvasive imaging techniques are required to ascertain this because invasive brain temperature measurements can cause unintended temperature changes by inserting the temperature sensors into the brain or by performing the surgical operations. In this study, we employed in vivo magnetic resonance thermometry to observe the brain temperatures of patients under general anesthesia using the proton resonance frequency shift method. The rectal temperature was also recorded using a fiber optic thermometer during the MR thermometry to compare with the brain temperature changes. When the rectal temperature decreased by 1.4 ± 0.5 °C (mean ± standard deviation), the brain temperature (white matter) decreased by 4.8 ± 0.5 °C. Furthermore, a difference in the temperature reduction of the different types of brain tissue was observed; the reduction in the temperature of white matter exceeded that of gray matter mainly due to the distribution of blood vessels in the gray matter. We also analyzed and interpreted the core temperature changes with the body conditioning scores of subjects to see how the body weight affected the temperature changes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Therapeutic hypothermia (TH), which prevents irreversible neuronal necrosis and ischemic brain damage, has been proven effective for preventing ischemia-reperfusion injury in post-cardiac arrest syndrome and neonatal encephalopathy in both animal studies and clinical trials. However, lowering the whole-body temperature below 34°C can lead to severe systemic complications such as cardiac, hematologic, immunologic, and metabolic side effects. Although the brain accounts for only 2% of the total body weight, it consumes 20% of the body's total energy at rest and requires a continuous supply of glucose and oxygen to maintain function and structural integrity. As such, theoretically, temperature-controlled selective brain cooling (SBC) may be more beneficial for brain ischemia than systemic pan-ischemia. Various SBC methods have been introduced to selectively cool the brain while minimizing systemic TH-related complications. However, technical setbacks of conventional SBCs, such as insufficient cooling power and relatively expensive coolant and/or irritating effects on skin or mucosal interfaces, limit its application to various clinical settings. This review aimed to integrate current literature on SBC modalities with promising therapeutic potential. Further, future directions were discussed by exploring studies on interesting coping skills in response to environmental or stress-induced hyperthermia among wild animals, including mammals and birds.

In this work, actual temperature measurements taken during the hypothermia treatment of the hypoxic-ischemic encephalopathy of a newborn are used for the solution of a state estimation problem. The objective is to sequentially estimate the newborn brain temperature during the local cooling treatment, by the application of the Sampling Importance Resampling (SIR) algorithm of the particle filter. A procedure is also proposed in this work to obtain individual geometric models for each patient, by using the mass, length and perimeter of the head measured after birth. The heat transfer model considered the body divided into spherical or cylindrical elements, representing the head, thorax, abdomen, arms, and legs. The results revealed that the SIR algorithm was accurate for the estimation of the body temperature, not only at locations where measurements were available, but also in internal regions of great interest for the hypothermia treatment, such as the brain. • A geometric model is built for each individual newborn patient. • An inverse problem is solved with the SIR algorithm of the particle filter. • The inverse problem methodology is verified with simulated data. • The inverse problem methodology is validated with actual temperature measurements. • A robust and stable tool for the estimation of the brain temperature is presented. [ABSTRACT FROM AUTHOR]

The function and regulation of rapid-eye-movement (REM) sleep is a topic of ongoing debate. It is often assumed that REM sleep is a homeostatically regulated process and that a need for REM sleep builds up, either during prior wakefulness or during preceding slow wave sleep. In the current study, we tested this hypothesis in six diurnal tree shrews (Tupaia belangeri), small mammals closely related to primates. All animals were individually housed and kept under a 12:12 light-dark cycle with an ambient temperature of 24 °C. We recorded sleep and temperature in the tree shrews for 3 consecutive 24 h days. During the second night, we exposed the animals to a low ambient temperature of 4 °C, a procedure that is known to suppress REM sleep. Cold exposure caused a significant drop in brain temperature and body temperature and also resulted in a strong and selective suppression of REM sleep by 64.9%. However, contrary to our expectation, the loss of REM sleep was not recovered during the subsequent day and night. These findings in a diurnal mammal confirm that the expression of REM sleep is highly sensitive to environmental temperature but do not support the view that REM sleep is homeostatically regulated in this species.

• We review Medical Microwave Radiometry (MWR) usage for brain internal temperature measurements and diagnostics. Brain temperature (BT) is a crucial physiological parameter used to monitor cerebral status. Physical activities and traumatic brain injuries (TBI) can affect BT; therefore, non-invasive BT monitoring is an important way to gain insight into TBI, stroke, and wellbeing. The effects of BT on physical performance have been studied at length. When humans are under extreme conditions, most of the energy consumed is used to maintain the BT. In addition, measuring the BT is useful for early brain diagnostics. Passive microwave radiometry (MWR) measures the intrinsic radiation of tissues in the 1–4 GHz range. It was shown that non-invasive passive MWR technology can successfully measure BT and identify even small TBIs. Here, we review the potential applications of MWR for assessing BT. [ABSTRACT FROM AUTHOR]

Background: After traumatic brain injury (TBI), fever is frequent. Brain temperature (BT), which is directly linked to body temperature, may influence brain physiology. Increased body and/or BT may cause secondary brain damage, with deleterious effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome. Methods: Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a prospective multicenter longitudinal study on TBI in Europe and Israel, includes a high resolution cohort of patients with data sampled at a high frequency (from 100 to 500 Hz). In this study, simultaneous BT, ICP, and CPP recordings were investigated. A mixed-effects linear model was used to examine the association between different BT levels and ICP. We additionally focused on changes in ICP and CPP during the episodes of BT changes (Δ BT ≥ 0.5 °C lasting from 15 min to 3 h) up or downward. The significance of ICP and CPP variations was estimated with the paired samples Wilcoxon test (also known as Wilcoxon signed-rank test). Results: Twenty-one patients with 2,435 h of simultaneous BT and ICP monitoring were studied. All patients reached a BT of 38 °C and experienced at least one episode of ICP above 20 mm Hg. The linear mixed-effects model revealed an association between BT above 37.5 °C and higher ICP levels that was not confirmed for lower BT. We identified 149 episodes of BT changes. During BT elevations (n = 79) ICP increased, whereas CPP was reduced; opposite ICP and CPP variations occurred during episodes of BT reduction (n = 70). All these changes were of moderate clinical relevance (increase of ICP of 4.5 and CPP decrease of 7.5 mm Hg for BT rise, and ICP reduction of 1.7 and CPP elevation of 3.7 mm Hg during BT defervescence), even if statistically significant (p < 0.0001). It has to be noted, however, that a number of therapeutic interventions against intracranial hypertension was documented during those episodes. Conclusions: Patients after TBI usually develop BT > 38 °C soon after the injury. BT may influence brain physiology, as reflected by ICP and CPP. An association between BT exceeding 37.5 °C and a higher ICP was identified but not confirmed for lower BT ranges. The relationship between BT, ICP, and CPP become clearer during rapid temperature changes. During episodes of temperature elevation, BT seems to have a significant impact on ICP and CPP. [ABSTRACT FROM AUTHOR]

Prior studies indicate a pathogenic role of neuroinflammation in psychiatric disorders; however, there are no accepted methods that can reliably measure low-level neuroinflammation non-invasively in these individuals. Magnetic resonance spectroscopic imaging (MRSI) is a versatile, non-invasive neuroimaging technique that demonstrates sensitivity to brain inflammation. MRSI in conjunction with echo-planar spectroscopic imaging (EPSI) measures brain metabolites to derive whole-brain and regional brain temperatures, which may increase in neuroinflammation. The validity of MRSI/EPSI for measurement of low level neuroinflammation was tested using a safe experimental model of human brain inflammation – intramuscular administration of typhoid vaccine. Twenty healthy volunteers participated in a double-blind, placebo-controlled crossover study including MRSI/EPSI scans before and 3 h after vaccine/placebo administration. Body temperature and mood, assessed using the Profile of Mood States, were measured every hour up to four hours post-treatment administration. A mixed model analysis of variance was used to test for treatment effects. A significant proportion of brain regions (44/47) increased in temperature post-vaccine compared to post-placebo (p

Sleep deficits are a possible risk factor for development of cognitive decline and dementia in older age. Research suggests that neuroinflammation may be a link between the two. This observational, cross-sectional study evaluated relationships between sleep architecture, neuroinflammation and cognitive functioning in healthy older adults. Twenty-two adults aged ≥60 years underwent whole-brain magnetic resonance spectroscopic imaging ( in vivo method of visualizing increased brain temperatures as a proxy for neuroinflammation), supervised laboratory-based polysomnography, and comprehensive neurocognitive testing. Multiple regressions were used to assess relationships between magnetic resonance spectroscopic imaging-derived brain temperature and metabolites related to inflammation (choline; myo -inositol; N -acetylaspartate), sleep efficiency, time and % N3 sleep and cognitive performance. Choline, myo -inositol and N -acetylaspartate were associated with sleep efficiency and cognitive performance. Higher choline and myo -inositol in the bilateral frontal lobes were associated with slower processing speed and lower sleep efficiency. Higher choline and myo -inositol in bilateral frontoparietal regions were associated with better cognitive performance. Higher N -acetylaspartate around the temporoparietal junction and adjacent white matter was associated with better visuospatial function. Brain temperature was not related to cognitive or sleep outcomes. Our findings are consistent with the limited literature regarding neuroinflammation and its relationships with sleep and cognition in older age, which has implicated ageing microglia and astrocytes in circadian dysregulation, impaired glymphatic clearance and increased blood-brain barrier integrity, with downstream effects of neurodegeneration and cognitive decline. Inflammatory processes remain difficult to measure in the clinical setting, but magnetic resonance spectroscopic imaging may serve as a marker of the relationship between neuroinflammation, sleep and cognitive decline in older adults., Competing Interests: A.W.A. received grant funding from the NIH NICHD and serves as an investigator for studies sponsored by the Michael J Fox Foundation for Parkinson’s Research, Aligning Science Across Parkinson’s (ASAP) Initiative, NIH NINDS, Eli Lilly and Company, Bial R&D Investments, S.A. She is a consultant for PhotoPharmics, Inc., and Grey Matter Technologies, a subsidiary of Modality.ai. J.P.S. was funded by the National Institutes of Health, National Science Foundation, Department of Defense, the State of Alabama, Shor Foundation for Epilepsy Research, UCB Pharma Inc., NeuroPace Inc., Greenwich Biosciences Inc., Biogen Inc., Xenon Pharmaceuticals, Serina Therapeutics Inc. and Eisai, Inc. He participates in the following consulting activities/advisory Boards: Greenwich Biosciences Inc., Pure Tech Health Inc., NeuroPace, Inc., Serina Therapeutics Inc., AdCel Biopharma Inc., iFovea Inc., LivaNova Inc., UCB Pharma Inc., SK Lifesciences Inc. and medico-legal services. He receives remuneration for editorial work as Editor-in-Chief for Epilepsy and Behavior Reports. He served as a member on the Alabama State Medical Cannabis Study Commission (nominated by Gov. Kay Ivey). He also serves on the Alabama Medical Cannabis Commission (2021–25; nominated by Dr. Scott Harris, State Health Officer). The remaining authors declare no conflicts of interest with this study., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: Infrared thermography (IT) is a non-invasive real-time imaging technique with potential application in different areas of neurosurgery. Despite technological advances in the field, intraoperative IT (IIT) has been an underestimated tool with scarce reports on its usefulness during intracranial tumor resection. We aimed to evaluate the usefulness of high-resolution IIT with static and dynamic thermographic maps for transdural lesion localization, and diagnosis, to assess the extent of resection, and the occurrence of perioperative acute ischemia., Methods: In a prospective study, 15 patients affected by intracranial tumors (six gliomas, four meningiomas, and five brain metastases) were examined with a high-resolution thermographic camera after craniotomy, after dural opening, and at the end of tumor resection., Results: Tumors were transdurally located with 93.3% sensitivity and 100% specificity ( p  < 0.00001), as well as cortical arteries and veins. Gliomas were consistently hypothermic, while metastases and meningiomas exhibited highly variable thermographic maps on static ( p  = 0.055) and dynamic ( p  = 0.015) imaging. Residual tumors revealed non-specific static but characteristic dynamic thermographic maps. Ischemic injuries were significantly hypothermic ( p  < 0.001)., Conclusions: High-resolution IIT is a non-invasive alternative intraoperative imaging method for lesion localization, diagnosis, assessing the extent of tumor resection, and identifying acute ischemia changes with static and dynamic thermographic maps., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Menezes, de Lima, Mansilla, Conci, Rueda, Velarde, Landeiro and Acioly.)

Management of vestibular dysfunction may include treatment with medications that are thought to act to suppress vestibular function and reduce or eliminate abnormal sensitivity to head motions. The extent to which vestibular medications act centrally or peripherally is still debated. In this study, two commonly prescribed medications, meclizine and diazepam, and a candidate for future clinical use, JNJ7777120, were evaluated for their effects on short latency compound action potentials generated by the peripheral vestibular system and corresponding central neural relays (i.e., vestibular sensory-evoked potentials, VsEPs). The effects of the selected drugs developed slowly over the course of two hours in the mouse. Findings indicate that meclizine (600 mg/kg) and diazepam (> 60 mg/kg) can act on peripheral elements of the vestibular maculae whereas diazepam also acts most effectively on central gravity receptor circuits to exert its suppressive effects. The novel pharmacological agent JNJ7777120 (160 mg/kg) acts in the vestibular periphery to enhance macular responses to transient stimuli (VsEPs) while, hypothetically, suppressing macular responses to sustained or slowly changing stimuli. [ABSTRACT FROM AUTHOR]

The stress-inducible 70 kDa heat shock protein (Hsp70) can exert a protective effect on endotoxemia and sepsis due to its ability to interact with immune cells and modulate the immune response. However, it remains unknown whether Hsp70 is able to relieve endotoxemia-induced fever. We carried out a comparative study of the effects of preventive administration of the human recombinant Hsp70 (HSPA1A) on lipopolysaccharide (LPS)-induced endotoxemia in pigeons and rats with preimplanted electrodes and thermistors for recording the thermoregulation parameters (brain temperature, peripheral vasomotor reaction, muscular contractile activity). Additionally, we analyzed the dynamics of the white blood cell (WBC) count in rats under the same conditions. It was found that preventive administration of Hsp70 relieves the LPS-induced febrile reaction in pigeons and rats and accelerates the restoration of the WBC count in rats. The data obtained suggest that these warm-blooded animals share a common physiological mechanism that underlies the protective effect of Hsp70. [ABSTRACT FROM AUTHOR]

Peripheral vasoconstriction is a centrally mediated physiological effect known to play an important role in regulating body temperature by adjusting heat exchange with the external environment. However, peripheral vasoconstriction as a component of sympathetic activation also occurs following exposure to various salient stimuli and during motivated behavior at stable environmental temperatures. This review aims to consider available evidence suggesting a significant contribution of this peripheral effect to physiological increases in both brain temperature and entry of oxygen and glucose into the brain's extracellular space. While these effects are triggered by neuronal activation, constriction of blood vessels in the skin and most internal organs results in redistribution of blood from the peripheral to central domains, thus dilating cerebral vessels, increasing global cerebral blood flow, and enhancing the intra-brain entry of oxygen and glucose from arterial blood. This powerful influence appears to determine the long duration of physiological increases in both brain temperature and brain levels of glucose and oxygen and their basic similarity across different brain structures. This work underscores the tight interrelationship between the brain and periphery and a significant contribution of cardiovascular effects in providing the enhanced inflow of oxygen and glucose into brain tissue to prevent metabolic deficit during functional neural activation. [ABSTRACT FROM AUTHOR]

We aimed to investigate whether selective head–neck cooling could shorten recovery after sports-related concussions (SRCs). In a nonrandomized study of 15 Swedish professional ice hockey teams, 29 concussed players received immediate head and neck cooling for ≥30 min (initiated at 12.3 ± 9.2 min post-SRC by a portable cooling system), and 52 SRC controls received standard management. Players receiving head–neck cooling had shorter time to return-to-play than controls (7 vs 12.5 days, p

Introduction: Selective brain cooling can minimize systemic complications associated with whole body cooling but maximize neuroprotection. Recently, we developed a non-invasive, portable and inexpensive system for selectively cooling the brain rapidly and demonstrated its safety and efficacy in porcine models. However, the widespread application of this technique in the clinical setting requires a reliable, non-invasive and accurate method for measuring local brain temperature so that cooling and rewarming rates can be controlled during targeted temperature management. In this study, we evaluate the ability of a zero-heat-flux SpotOn sensor, mounted on three different locations, to measure brain temperature during selective brain cooling in a pig model. Computed Tomography (CT) was used to determine the position of the SpotOn patches relative to the brain at different placement locations. Methods and Results: Experiments were conducted on two juvenile pigs. Body temperature was measured using a rectal temperature probe while brain temperature with an intraparenchymal thermocouple probe. A SpotOn patch was taped to the pig’s head at three different locations: 1-2 cm posterior (Location #1, n=1), central forehead (Location #2, n=1); and 1-2 cm anterior and lateral to the bregma i.e., above the eye on the forehead (Location #3, n=1). This cooling system was able to rapidly cool the brain temperature to 33.7 ± 0.2°C within 15 minutes, and maintain the brain temperature within 33-34°C for 4-6 hours before slowly rewarming to 34.8 ± 1.1°C from 33.7 ± 0.2°C, while maintaining the core body temperature (as per rectal temperature probe) above 36°C. We measured a mean bias of -1.1°C, -0.2°C and 0.7°C during rapid cooling in induction phase, maintenance and rewarming phase, respectively. Amongst the three locations, location #2 had the highest correlation (R2 = 0.8) between the SpotOn sensor and the thermocouple probe. Conclusions: This SBC method is able to tightly control the rewarming rate within 0.52 ± 0.20°C/h. The SpotOn sensor placed on the center of the forehead provides a good measurement of brain temperature in comparison to the invasive needle probe.

The core body temperature tends to decrease under general anesthesia. Consequently, monitoring the core body temperature during procedures involving general anesthesia is essential to ensure patient safety. In veterinary medicine, rectal temperature is used as an indicator of the core body temperature, owing to the accuracy and convenience of this approach. Some previous studies involving craniotomy reported differences between the brain and core temperatures under general anesthesia. However, noninvasive imaging techniques are required to ascertain this because invasive brain temperature measurements can cause unintended temperature changes by inserting the temperature sensors into the brain or by performing the surgical operations. In this study, we employed in vivo magnetic resonance thermometry to observe the brain temperatures of patients under general anesthesia using the proton resonance frequency shift method. The rectal temperature was also recorded using a fiber optic thermometer during the MR thermometry to compare with the brain temperature changes. When the rectal temperature decreased by 1.4 ± 0.5 °C (mean ± standard deviation), the brain temperature (white matter) decreased by 4.8 ± 0.5 °C. Furthermore, a difference in the temperature reduction of the different types of brain tissue was observed; the reduction in the temperature of white matter exceeded that of gray matter mainly due to the distribution of blood vessels in the gray matter. We also analyzed and interpreted the core temperature changes with the body conditioning scores of subjects to see how the body weight affected the temperature changes.

Abstract Background Selective brain cooling (SBC) methods could alleviate the complications associated with systemic hypothermia. The authors (MFB, LK, and T-YL) have developed a simple and an effective nasopharyngeal SBC method using a vortex tube. The primary focus of the study is to evaluate the effectiveness of this approach on rabbits and compare it with our previous published finding on piglets, which are mammals without and with a carotid rete, respectively. Methods Experiments were conducted on six rabbits. Body temperature was measured continuously using an esophageal temperature probe while brain temperature was measured with an implanted thermometer. Two successive experiments were performed on each animal. In the first experiment, brain cooling was initiated by blowing room temperature air from the hospital medical air outlet, at a flow rate of 14–15 L/min into both nostrils for 60 min. The second series of measurements and brain cooling was performed in the same manner as the first one but blowing cold air (− 7 °C) at the same flow rate. Results One hour post cooling with room temperature air at a flow rate of 14–15 L/min, the brain temperature was 34.2 ± 1.2 °C which resulted in mean brain cooling rates of 3.7 ± 0.9 °C/h. Brain temperature could be reduced more rapidly at mean rates of 5.2 ± 1.9 °C/h, while the body temperature as measured by the esophageal temperature probe was maintained above 36 °C during cooling and maintaining period. Conclusions We have demonstrated that using the vortex tube allows initial rapid and SBC in rabbits. Moreover, comparing results between piglets and rabbits demonstrates clearly that the lack of a carotid rete does not prevent specific cooling of the brain by means of the nasopharyngeal method.

Critical studies that form the foundation of the glymphatic system and the clearance of metabolic by-products of unwanted proteins from the brain are reviewed. Concerns are raised about studying glymphatic flow in anesthetized animals and making assumptions about the whole brain based upon data collected from a cranial window on the cortex. A new model is proposed arguing that the flow of cerebral spinal fluid and parenchymal clearance in the perivascular system of unwanted proteins is regulated by circadian changes in brain temperature and blood flow at the level of the microvasculature.

Although brain temperature has neurobiological and clinical importance, it remains unclear which factors contribute to its daily dynamics and to what extent. Using a statistical approach, we previously demonstrated that hourly brain temperature values co-varied strongly with time spent awake (Hoekstra et al., 2019). Here we develop and make available a mathematical tool to simulate and predict cortical temperature in mice based on a 4-s sleep–wake sequence. Our model estimated cortical temperature with remarkable precision and accounted for 91% of the variance based on three factors: sleep–wake sequence, time-of-day (‘circadian’), and a novel ‘prior wake prevalence’ factor, contributing with 74%, 9%, and 43%, respectively (including shared variance). We applied these optimized parameters to an independent cohort of mice and predicted cortical temperature with similar accuracy. This model confirms the profound influence of sleep–wake state on brain temperature, and can be harnessed to differentiate between thermoregulatory and sleep–wake-driven effects in experiments affecting both.

Critical studies that form the foundation of the glymphatic system and the clearance of metabolic by-products of unwanted proteins from the brain are reviewed. Concerns are raised about studying glymphatic flow in anesthetized animals and making assumptions about the whole brain based upon data collected from a cranial window on the cortex. A new model is proposed arguing that the flow of cerebral spinal fluid and parenchymal clearance in the perivascular system of unwanted proteins is regulated by circadian changes in brain temperature and blood flow at the level of the microvasculature. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance spectroscopic imaging (MRSI) is a neuroimaging technique that may be useful for non-invasive mapping of brain temperature (i.e., thermometry) over a large brain volume. To date, intra-subject reproducibility of MRSI-based brain temperature (MRSI-t) has not been investigated. The objective of this repeated measures MRSI-t study was to establish intra-subject reproducibility and repeatability of brain temperature, as well as typical brain temperature range.Methods: Healthy participants aged 23–46 years (N = 18; 7 females) were scanned at two time points ~12-weeks apart. Volumetric MRSI data were processed by reconstructing metabolite and water images using parametric spectral analysis. Brain temperature was derived using the frequency difference between water and creatine (TCRE) for 47 regions of interest (ROIs) delineated by the modified Automated Anatomical Labeling (AAL) atlas. Reproducibility was measured using the coefficient of variation for repeated measures (COVrep), and repeatability was determined using the standard error of measurement (SEM). For each region, the upper and lower bounds of Minimal Detectable Change (MDC) were established to characterize the typical range of TCRE values.Results: The mean global brain temperature over all subjects was 37.2°C with spatial variations across ROIs. There was a significant main effect for time [F(1, 1,591) = 37.0, p < 0.0001] and for brain region [F(46, 1,591) = 2.66, p < 0.0001]. The time*brain region interaction was not significant [F(46, 1,591) = 0.80, p = 0.83]. Participants' TCRE was stable for each ROI across both time points, with ROIs' COVrep ranging from 0.81 to 3.08% (mean COVrep = 1.92%); majority of ROIs had a COVrep