Brain metabolites are associated with sleep architecture and cognitive functioning in older adults.

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.

Model-predicted brain temperature computational imaging by multimodal noninvasive functional neuromonitoring of cerebral oxygen metabolism and hemodynamics: MRI-derived and clinical validation.

Brain temperature, a crucial yet under-researched neurophysiological parameter, is governed by the equilibrium between cerebral oxygen metabolism and hemodynamics. Therapeutic hypothermia has been demonstrated as an effective intervention for acute brain injuries, enhancing survival rates and prognosis. The success of this treatment hinges on the precise regulation of brain temperature. However, the absence of comprehensive brain temperature monitoring methods during therapy, combined with a limited understanding of human brain heat transmission mechanisms, significantly hampers the advancement of hypothermia-based neuroprotective therapies. Leveraging the principles of bioheat transfer and MRI technology, this study conducted quantitative analyses of brain heat transfer during mild hypothermia therapy. Utilizing MRI, we reconstructed brain structures, estimated cerebral blood flow and oxygen consumption parameters, and developed a brain temperature calculation model founded on bioheat transfer theory. Employing computational cerebral hemodynamic simulation analysis, we established an intracranial arterial fluid dynamics model to predict brain temperature variations across different therapeutic hypothermia modalities. We introduce a noninvasive, spatially resolved, and optimized mathematical bio-heat model that synergizes model-predicted and MRI-derived data for brain temperature prediction and imaging. Our findings reveal that the brain temperature images generated by our model reflect distinct spatial variations across individual participants, aligning with experimentally observed temperatures.

Local variation in brain temperature explains gender-specificity of working memory performance.

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.

A prospective study on the usefulness of high-resolution intraoperative infrared thermography in intracranial tumors.

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.

Sleep and Thermoregulation in Birds: Cold Exposure Reduces Brain Temperature but Has Little Influence on Sleep Time and Sleep Architecture in Jackdaws (Coloeus monedula).

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.

Body Size, Cerebral Blood Flow, Ambient Temperature, and Relative Brain Temperatures in Newborn Infants under Incubator Care.

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.

The Association of Metabolic Brain MRI, Amyloid PET, and Clinical Factors: A Study of Alzheimer's Disease and Normal Controls From the Open Access Series of Imaging Studies Dataset.

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 18 F-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.

Peripheral and Central Nervous System Biomarkers of Inflammation in Functional Seizures: Assessment with Magnetic Resonance Spectroscopy.

Purpose: 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.

Neonatal Brain Temperature Monitoring Based on Broadband Near-Infrared Spectroscopy.

We present here the initial development of a novel algorithm based on broadband near-infrared spectroscopy (bNIRS) data to estimate the changes in brain temperature (BT) in neonates. We first explored the validity of the methodology on a simple numerical phantom and reported good agreements between the theoretical and retrieved values of BT and hemodynamic parameters changes, which are the parameters usually targeted by bNIRS. However, we noted an underestimation of the absolute values of temperature and haemoglobins' concentration changes when large variations of tissue saturation were induced, probably due to a crosstalk between the species in this specific case. We then tested this methodology on data acquired on 2 piglets during a protocol that induces seizures. We showed that despite a decrease in rectal temperature (RT) over time (-0.1048 °C 1.5 h after seizure induction, 95% CI: -0.1035 to -0.1061 °C), BT was raising (0.3122 °C 1.5 h after seizure induction, 95% CI: 0.3207 to 0.3237 °C). We also noted that the piglet displaying the largest decrease in RT also displays the highest increase in BT, which could be a marker of the severity of the seizure induced brain injury. These initial results are encouraging and show that having access to the changes in BT non-invasively could help to better understand the impact of BT on injury severity and to improve the current cooling methodologies in the neonatal neurocritical care following neonatal encephalopathy.

Sleep deprivation soon after recovery from synthetic torpor enhances tau protein dephosphorylation in the rat brain.

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.

Near Infrared Emissive Lanthanide Luminescence Nanoparticle Used in Early Diagnosis and Brain Temperature Detection for Ischemic Stroke.

Ischemic stroke (IS) is one of the most dangerous medical conditions resulting in high mortality and morbidity. The increased brain temperature after IS is closely related to prognosis, making it highly significant for the early diagnosis and the progression evaluation of IS. Herein, a temperature-responsive near infrared (NIR) emissive lanthanide luminescence nanoparticle is developed for the early diagnosis and brain temperature detection of IS. After intravenous injection, the nanoparticles can pass through the damaged blood-brain barrier of the ischemic region, allowing the extravasation and enrichment of nanoparticles into the ischemic brain tissue. The NIR luminescence signals of the nanoparticles are used not only to judge the location and severity of the cerebral ischemic injury but also to report the brain temperature variation in the ischemic area through a visualized way. The results show that the designed nanoparticles can be used for the early diagnosis of ischemic stroke and minimally invasive temperature detection of cerebral ischemic tissues in transient middle cerebral artery occlusion mice model, which is expected to make the clinical diagnosis of ischemic stroke more rapid and convenient, more accurately evaluate the state of brain injury in stroke patients and also guide stroke hypothermia treatment.

Prediction of Intracranial Temperature Through Invasive and Noninvasive Measurements on Patients with Severe Traumatic Brain Injury.

The brain's temperature measurements (TB) in patients with severe brain damage are important, in order to offer the optimal treatment. The purpose of this research is the creation of mathematical models for the TB's prediction, based on the temperatures in the bladder (TBL), femoral artery (TFA), ear canal (TΕC), and axilla (TA), without the need for placement of intracranial catheter, contributing significantly to the research of the human thermoregulatory system.The research involved 18 patients (13 men and 5 women), who were hospitalized in the adult intensive care units (ICU) of Larissa's two hospitals, with severe brain injury. An intracranial catheter with a thermistor was used to continuously measure TB and other parameters. The TB's measurements, and simultaneously one or more of TBL, TFA, TEC, and TA, were recorded every 1 h.To create TB predicting models, the data of each measurement was separated into (a) model sample (measurements' 80%) and (b) validation sample (measurements' 20%). Multivariate linear regression analysis demonstrated that it is possible to predict brain's temperature (PrTB), using independent variables (R2 was TBL = 0.73, TFA = 0.80, TEC = 0.27, and TA = 0.17, p < 0.05). Significant linear associations were found, statistically, and no difference in means between TB and PrTB of each prediction model. Also, the 95% limits of agreement and the percent coefficient of variation showed sufficient agreement between the TB and PrTB in each prediction model.In conclusion, brain's temperature prediction models based on TBL, TFA, TEC, and TA were successful. Its determination contributes to the improvement of clinical decision-making.

Investigation of post mortem brain, rectal and forehead temperature relations.

It is well known that magnetic resonance (MR) imaging is temperature sensitive, which is highly relevant for post mortem examinations. Therefore, the determination of the exact temperature of the investigated body site, e.g. the brain, is crucial. However, direct temperature measurements are invasive and inconvenient. Thus, in view of post mortem MR imaging of the brain, this study aims at investigating the relation between the brain and the forehead temperature for modelling the brain temperature based on the non-invasive forehead temperature. In addition, the brain temperature will be compared to the rectal temperature. Brain temperature profiles measured in the longitudinal fissure between the brain hemispheres, as well as rectal and forehead temperature profiles of 16 deceased were acquired continuously. Linear mixed, linear, quadratic and cubic models were fitted to the relation between the longitudinal fissure and the forehead and between the longitudinal fissure and the rectal temperature, respectively. Highest adjusted R2 values were found between the longitudinal fissure and the forehead temperature, as well as between the longitudinal fissure and the rectal temperature using a linear mixed model including the sex, environmental temperature and humidity as fixed effects. The results indicate that the forehead, as well as the rectal temperature, can be used to model the brain temperature measured in the longitudinal fissure. Comparable fit results were observed for the longitudinal fissure-forehead temperature relation and for the longitudinal fissure-rectal temperature relation. Combined with the fact that the forehead temperature overcomes the problem of measurement invasiveness, the results suggest using the forehead temperature for modelling the brain temperature in the longitudinal fissure.

Clinical outcomes and thermodynamics aspect of direct brain cooling in severe head injury.

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.

A Study on REM Sleep Homeostasis in the Day-Active Tree Shrew (Tupaia belangeri): Cold-Induced Suppression of REM Sleep Is Not Followed by a Rebound.

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.

Measuring Brain Temperature in Youth Bipolar Disorder Using a Novel Magnetic Resonance Imaging Approach: A Proof-of-concept Study.

BACKGROUND: There is evidence of alterations in mitochondrial energy metabolism and cerebral blood flow (CBF) in adults and youth with bipolar disorder (BD). Brain thermoregulation is based on the balance of heat-producing metabolism and heat-dissipating mechanisms, including CBF. OBJECTIVE: To examine brain temperature, and its relation to CBF, in relation to BD and mood symptom severity in youth. METHODS: This study included 25 youth participants (age 17.4 ± 1.7 years; 13 BD, 12 control group (CG)). Magnetic resonance spectroscopy data were acquired to obtain brain temperature in the left anterior cingulate cortex (ACC) and the left precuneus. Regional estimates of CBF were provided by arterial spin labeling imaging. Analyses used general linear regression models, covarying for age, sex, and psychiatric medications. RESULTS: Brain temperature was significantly higher in BD compared to CG in the precuneus. A higher ratio of brain temperature to CBF was significantly associated with greater depression symptom severity in both the ACC and precuneus within BD. Analyses examining the relationship of brain temperature or CBF with depression severity score did not reveal any significant finding in the ACC or the precuneus. CONCLUSION: The current study provides preliminary evidence of increased brain temperature in youth with BD, in whom reduced thermoregulatory capacity is putatively associated with depression symptom severity. Evaluation of brain temperature and CBF in conjunction may provide valuable insight beyond what can be gleaned by either metric alone. Larger prospective studies are warranted to further evaluate brain temperature and its association with CBF concerning BD.

Predicting brain temperature in humans using bioheat models: Progress and outlook.

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.

Brain temperature remains stable during the day: a study of diffusion-weighted imaging thermometry in healthy individuals.

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.

Concordance between focal brain temperature elevations and focal edema in temporal lobe epilepsy.

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.

Basic metabolic and vascular effects of ketamine and its interaction with fentanyl.

Ketamine is a short-acting general anesthetic with hallucinogenic, analgesic, and amnestic properties. In addition to its anesthetic use, ketamine is commonly abused in rave settings. While safe when used by medical professionals, uncontrolled recreational use of ketamine is dangerous, especially when mixed with other sedative drugs, including alcohol, benzodiazepines, and opioid drugs. Since synergistic antinociceptive interactions between opioids and ketamine were demonstrated in both preclinical and clinical studies, such an interaction could exist for the hypoxic effects of opioid drugs. Here, we focused on the basic physiological effects of ketamine as a recreational drug and its possible interactions with fentanyl-a highly potent opioid that induces strong respiratory depression and robust brain hypoxia. By using multi-site thermorecording in freely-moving rats, we showed that intravenous ketamine at a range of human relevant doses (3, 9, 27 mg/kg) dose-dependently increases locomotor activity and brain temperature, as assessed in the nucleus accumbens (NAc). By determining temperature differentials between the brain, temporal muscle, and skin, we showed that the brain hyperthermic effect of ketamine results from increased intracerebral heat production, an index of metabolic neural activation, and decreased heat loss due to peripheral vasoconstriction. By using oxygen sensors coupled with high-speed amperometry we showed that ketamine at the same doses increases NAc oxygen levels. Finally, co-administration of ketamine with intravenous fentanyl results in modest enhancement of fentanyl-induced brain hypoxia also enhancing the post-hypoxic oxygen increase. Therefore, in contrast to fentanyl, ketamine increases brain oxygenation but potentiates brain hypoxia induced by fentanyl.