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Psychopathy is characterized by antisocial behavior, poor behavioral control and lacking empathy, and structural alterations in the corresponding neural circuits. Molecular brain basis of psychopathy remains poorly characterized. Here we studied type 2 dopamine receptor (D2R) and mu-opioid receptor (MOR) availability in convicted violent offenders with high psychopathic traits (n = 11) and healthy matched controls (n = 17) using positron emission tomography (PET). D2R were measured with radioligand [11C]raclopride and MORs with radioligand [11C]carfentanil. Psychopathic subjects had lowered D2R availability in caudate and putamen, and striatal D2R availability was also associated with degree of psychopathic traits in this prisoner sample. No group differences were found in MOR availability, although in the prisoner sample, psychopathic traits were negatively correlated with MOR availability in the amygdala and nucleus accumbens. We conclude that D2R signaling could be the putative neuromolecular pathway for psychopathy, whereas evidence for alterations in the MOR system is more limited.

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OBJECTIVE: 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) allows noninvasive assessment of glucose metabolism and radiodensity in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). We aimed to address the effects of ageing and metabolic factors on abdominal adipose tissue. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analyzed data from 435 healthy men (mean 42.8 years) who underwent a health check-up programme twice, at baseline and the 5-year follow-up. The mean standardized uptake value (SUV) was measured using SAT and VAT and divided by the liver SUV. The mean Hounsfield units (HU) of the SAT and VAT were measured from the CT scans. The effects of clinical variable clusters on SUVR were investigated using Bayesian hierarchical modelling; metabolic cluster (BMI, waist-to-hip ratio, fat percentage, muscle percentage*-1, HOMA-IR), blood pressure (systolic, diastolic), glucose (fasting plasma glucose level, HbA1c) and C-reactive protein. RESULTS: All the clinical variables changed during the 5-year follow-up period. The SUVR and HU of the VAT increased during follow-up; however, those of the SAT did not change. SUVR and HU were positively correlated with both VAT and SAT. SAT and VAT SUVR were negatively associated with metabolic clusters. CONCLUSIONS: Ageing led to increased glucose metabolism and radiodensity in VAT, but not in SAT. VAT may reflect the ageing process more directly than SAT. Glucose metabolism was higher and radiodensity was lower in VAT than in SAT, probably owing to differences in gene expression and lipid density. Both glucose metabolism and radiodensity of VAT and SAT reflect metabolic status.

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OBJECTIVE: The aim of this study was to investigate the impact of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET). RESEARCH DESIGN AND METHODS: In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Treatment effects were assessed using ANCOVA, and the results are reported as least square means and 95% CIs for the difference between groups. RESULTS: A total of 38 patients (dapagliflozin n = 21; placebo n = 17) completed the study. After 6 weeks, skeletal muscle FA uptake was increased by dapagliflozin compared with placebo (1.0 [0.07, 2.0] µmol ⋅ 100 g-1 ⋅ min-1; P = 0.032), whereas uptake was not significantly changed in the small intestine or visceral or subcutaneous adipose tissue. Dapagliflozin treatment significantly increased whole-brain FA uptake (0.10 [0.02, 0.17] µmol ⋅ 100 g-1 ⋅ min-1; P = 0.01), an effect observed in both gray and white matter regions. CONCLUSIONS: Six weeks of treatment with dapagliflozin increases skeletal muscle and brain FA uptake, partly driven by a rise in free FA availability. This finding is in accordance with previous indirect measurements showing enhanced FA metabolism in response to SGLT2 inhibition and extends the notion of a shift toward increased FA use to muscle and brain.

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PURPOSE: Brain functional and physiological plasticity is essential to combat dynamic environmental challenges. The rhythmic dopamine signaling pathway, which regulates emotion, reward and learning, shows seasonal patterns with higher capacity of dopamine synthesis and lower number of dopamine transporters during dark seasons. However, seasonal variation of the dopamine receptor signaling remains to be characterized. METHODS: Based on a historical database of healthy human brain [11C]raclopride PET scans (n = 291, 224 males and 67 females), we investigated the seasonal patterns of D2/3 dopamine receptor signaling. Daylength at the time of scanning was used as a predictor for brain regional non-displaceable binding of the radiotracer, while controlling for age and sex. RESULTS: Daylength was negatively correlated with availability of D2/3 dopamine receptors in the striatum. The largest effect was found in the left caudate, and based on the primary sample, every 4.26 h (i.e., one standard deviation) increase of daylength was associated with a mean 2.8% drop (95% CI -0.042 to -0.014) of the receptor availability. CONCLUSIONS: Seasonally varying D2/3 receptor signaling may also underlie the seasonality of mood, feeding, and motivational processes. Our finding suggests that in future studies of brain dopamine signaling, especially in high-latitude regions, the effect of seasonality should be considered.

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BACKGROUND: Emotions are reflected in bodily sensations, and these reflections are abnormal in psychiatric conditions. However, emotion-related bodily sensations have not been studied in neurological disorders. OBJECTIVE: The aim of this study was to investigate whether Parkinson's disease (PD) is associated with altered bodily representations of emotions. METHODS: Symptoms and emotion-related sensations were investigated in 380 patients with PD and 79 control subjects, using a topographical self-report method, termed body sensation mapping. The bodily mapping data were analyzed with pixelwise generalized linear models and principal component analyses. RESULTS: Bodily maps of symptoms showed characteristic patterns of PD motor symptom distributions. Compared with control subjects, PD patients showed decreased parasternal sensation of anger, and longer PD symptom duration was associated with increased abdominal sensation of anger (PFWE < 0.05). The PD-related sensation patterns were abnormal across all basic emotions (P < 0.05). CONCLUSIONS: The results demonstrate altered bodily maps of emotions in PD, providing novel insight into the nonmotor effects of PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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PURPOSE: Aberrant dopaminergic function is linked with motor, psychotic, and affective symptoms, but studies have typically compared a single patient group with healthy controls. METHODS: Here, we investigated the variation in striatal (caudate nucleus, nucleus accumbens, and putamen) and thalamic type 2 dopamine receptor (D2R) availability using [11C]raclopride positron emission tomography (PET) data from a large sample of 437 humans including healthy controls, and subjects with Parkinson's disease (PD), antipsychotic-naïve schizophrenia, severe violent behavior, pathological gambling, depression, and overweight. We analyzed regional group differences in D2R availability. We also analyzed the interregional correlation in D2R availability within each group. RESULTS: Subjects with PD showed the clearest decline in D2R availability. Overall, the groups showed high interregional correlation in D2R availability, while this pattern was weaker in violent offenders. Subjects with schizophrenia, pathological gambling, depression, or overweight did not show clear changes in either the regional receptor availability or the interregional correlation. CONCLUSION: We conclude that the dopaminergic changes in neuropsychiatric conditions might not only affect the overall receptor availability but also how coupled regions are across people. The region-specific receptor availability more profoundly links to the motor symptoms, while the between-region coupling might be disrupted in violence.

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Accurate positron emission tomography (PET) data quantification relies on high-quality input plasma curves, but venous blood sampling may yield poor-quality data, jeopardizing modeling outcomes. In this study, we aimed to recover sub-optimal input functions by using information from the tail (5th-100th min) of curves obtained through the frequent sampling protocol and an input recovery (IR) model trained with reference curves of optimal shape. Initially, we included 170 plasma input curves from eight published studies with clamp [18F]-fluorodeoxyglucose PET exams. Model validation involved 78 brain PET studies for which compartmental model (CM) analysis was feasible (reference (ref) + training sets). Recovered curves were compared with original curves using area under curve (AUC), max peak standardized uptake value (maxSUV). CM parameters (ref + training sets) and fractional uptake rate (FUR) (all sets) were computed. Original and recovered curves from the ref set had comparable AUC (d = 0.02, not significant (NS)), maxSUV (d = 0.05, NS) and comparable brain CM results (NS). Recovered curves from the training set were different from the original according to maxSUV (d = 3) and biologically plausible according to the max theoretical K1 (53//56). Brain CM results were different in the training set (p < 0.05 for all CM parameters and brain regions) but not in the ref set. FUR showed reductions similarly in the recovered curves of the training and test sets compared to the original curves (p < 0.05 for all regions for both sets). The IR method successfully recovered the plasma inputs of poor quality, rescuing cases otherwise excluded from the kinetic modeling results. The validation approach proved useful and can be applied to different tracers and metabolic conditions.

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Emotions, bodily sensations and movement are integral parts of musical experiences. Yet, it remains unknown i) whether emotional connotations and structural features of music elicit discrete bodily sensations and ii) whether these sensations are culturally consistent. We addressed these questions in a cross-cultural study with Western (European and North American, n = 903) and East Asian (Chinese, n = 1035). We precented participants with silhouettes of human bodies and asked them to indicate the bodily regions whose activity they felt changing while listening to Western and Asian musical pieces with varying emotional and acoustic qualities. The resulting bodily sensation maps (BSMs) varied as a function of the emotional qualities of the songs, particularly in the limb, chest, and head regions. Music-induced emotions and corresponding BSMs were replicable across Western and East Asian subjects. The BSMs clustered similarly across cultures, and cluster structures were similar for BSMs and self-reports of emotional experience. The acoustic and structural features of music were consistently associated with the emotion ratings and music-induced bodily sensations across cultures. These results highlight the importance of subjective bodily experience in music-induced emotions and demonstrate consistent associations between musical features, music-induced emotions, and bodily sensations across distant cultures.

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The COVID-19 pandemic presents challenges to psychological well-being, but how can we predict when people suffer or cope during sustained stress? Here, we test the prediction that specific types of momentary emotional experiences are differently linked to psychological well-being during the pandemic. Study 1 used survey data collected from 24,221 participants in 51 countries during the COVID-19 outbreak. We show that, across countries, well-being is linked to individuals' recent emotional experiences, including calm, hope, anxiety, loneliness, and sadness. Consistent results are found in two age, sex, and ethnicity-representative samples in the United Kingdom (n = 971) and the United States (n = 961) with preregistered analyses (Study 2). A prospective 30-day daily diary study conducted in the United Kingdom (n = 110) confirms the key role of these five emotions and demonstrates that emotional experiences precede changes in well-being (Study 3). Our findings highlight differential relationships between specific types of momentary emotional experiences and well-being and point to the cultivation of calm and hope as candidate routes for well-being interventions during periods of sustained stress. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy (1H-MRS, 3 T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)) was also performed in a subset of subjects during clamp. In dataset A, 48 participants were studied during fasting with brain 1H-MRS, while in dataset B 21 participants underwent paired brain 1H-MRS acquisitions under fasting and clamp conditions. In dataset C 16 subjects underwent brain 18F-FDG-PET and 1H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity.

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Recently, PET systems with a long axial field of view have become the current state of the art. Total-body PET scanners enable unique possibilities for scientific research and clinical diagnostics, but this new technology also raises numerous challenges. A key advantage of total-body imaging is that having all the organs in the field of view allows studying biologic interaction of all organs simultaneously. One of the new, promising imaging techniques is total-body quantitative perfusion imaging. Currently, 15O-labeled water provides a feasible option for quantitation of tissue perfusion at the total-body level. This review summarizes the status of the methodology and the analysis and provides examples of preliminary findings on applications of quantitative parametric perfusion images for research and clinical work. We also describe the opportunities and challenges arising from moving from single-organ studies to modeling of a multisystem approach with total-body PET, and we discuss future directions for total-body imaging.

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Feeding induces dopamine release in the striatum, and a dysfunction of the dopaminergic reward system can lead to overeating, and obesity. Studies have reported inconsistent findings of dopamine receptor (DR) positron emission tomography scans in obesity. Here we investigated the association between DR availability and overweight/obesity using Bayesian and frequentist meta-analysis. We performed a systematic search of Embase, Medline, Scopus and Web of Science for studies that compared striatal DR availability between lean subjects and overweight/obese subjects. The standardized mean difference (Hedge's g) of DR availability was calculated after extraction of data from each study. Studies were divided into two groups according to the definition of overweight/obese subjects (body mass index [BMI] cutoff of 25 and 30 kg/m2 ). Both Bayesian and frequentist meta-analysis was done in R Statistical Software version 4.2.2 (The R Foundation for Statistical Computing). Nine studies were eligible for inclusion in this study. Three studies with C11-raclopride, one with C11-PNHO, two with F18-fallypride, one with I123-IBZM, one with C11-NMB and one with both C11-raclopride and C11-PNHO were included. In Bayesian meta-analysis, the standardized mean difference of DR availability between lean and overweight/obese subjects markedly overlapped with zero regardless of BMI cutoff for obesity. In frequentist meta-analysis, the pooled standardized mean difference of DR availability did not show the significant difference between lean and overweight/obese subjects. There was an effect of the radiopharmaceutical on the standardized mean difference of DR availability in meta-analysis of BMI cutoff of 25 kg/m2 . In conclusion, brain DR availability is not different between lean and overweight/obese subjects. However, the effect is dependent on the radiopharmaceutical and the degree of obesity. Further studies with multi-radiopharmaceutical in the same individuals are needed to understand the association between DR and obesity.

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ABSTRACT: Pain is an unpleasant sensory and emotional experience. Both pain and emotions are warning signals against outside harm. Interoception, bodily sensations of emotions can be assessed with the emBODY tool where participants colour the body parts where they feel different emotions. Bodily maps of emotions (BMoE) have been shown to be similar between healthy individuals independent of age, sex, cultural background, and language. We used this tool to analyze how these body maps may differ between healthy controls and patients with persistent pain. We recruited 118 patients with chronic pain. An algorithm-selected matched controls from 2348 individuals who were recruited through social media, message boards, and student mailing lists. After providing background information, the participants completed the bodily topography colouring tasks with the emBODY tool using tablets (patients) and online using their own devices (controls), for pain, sensitivity for tactile, nociceptive and hedonic stimuli, and for the 6 basic emotions and a neutral state. Patients with pain coloured significantly larger areas for pain and more negative emotions. On the whole, their BMoEs were dampened compared with healthy controls. They also coloured more areas for nociceptive but not for tactile or hedonic sensitivity. Patients and controls marked different body areas as sensitive to nociceptive and tactile stimulation, but there was no difference in sensitivity to hedonic touch. Our findings suggest that emotional processing changes when pain persists, and this can be assessed with these colouring tasks. BMoEs may offer a new approach to assessing pain.

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The endogenous µ-opioid receptor (MOR) system plays a key role in the mammalian reward circuit. Human and animal experiments suggest the involvement of MORs in human sexual pleasure, yet this hypothesis currently lacks in vivo support. Methods: We used PET with the radioligand [11C]carfentanil, which has high affinity for MORs, to quantify endogenous opioid release after orgasm in man. Participants were scanned once immediately after orgasm and once in a baseline state. Hemodynamic activity was measured with functional MRI during penile stimulation. Results: The PET data revealed significant opioid release in the hippocampus. Hemodynamic activity in the somatosensory and motor cortices and in the hippocampus and thalamus increased during penile stimulation, and thalamic activation was linearly dependent on self-reported sexual arousal. Conclusion: Our data show that endogenous opioidergic activation in the medial temporal lobe is centrally involved in sexual arousal, and this circuit may be implicated in orgasmic disorders.

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Importance: It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions. Objective: To assess whether lesion locations associated with epilepsy map to specific brain regions and networks. Design, Setting, and Participants: This case-control study used lesion location and lesion network mapping to identify the brain regions and networks associated with epilepsy in a discovery data set of patients with poststroke epilepsy and control patients with stroke. Patients with stroke lesions and epilepsy (n = 76) or no epilepsy (n = 625) were included. Generalizability to other lesion types was assessed using 4 independent cohorts as validation data sets. The total numbers of patients across all datasets (both discovery and validation datasets) were 347 with epilepsy and 1126 without. Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data were analyzed from September 2018 through December 2022. All shared patient data were analyzed and included; no patients were excluded. Main Outcomes and Measures: Epilepsy or no epilepsy. Results: Lesion locations from 76 patients with poststroke epilepsy (39 [51%] male; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2.0] years) and 625 control patients with stroke (366 [59%] male; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the discovery data set. Lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity to the basal ganglia and cerebellum. Findings were validated in 4 independent cohorts including 772 patients with brain lesions (271 [35%] with epilepsy; 515 [67%] male; median [IQR] age, 60 [50-70] years; follow-up range, 3-35 years). Lesion connectivity to this brain network was associated with increased risk of epilepsy after stroke (odds ratio [OR], 2.82; 95% CI, 2.02-4.10; P < .001) and across different lesion types (OR, 2.85; 95% CI, 2.23-3.69; P < .001). Deep brain stimulation site connectivity to this same network was associated with improved seizure control (r, 0.63; P < .001) in 30 patients with drug-resistant epilepsy (21 [70%] male; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months). Conclusions and Relevance: The findings in this study indicate that lesion-related epilepsy mapped to a human brain network, which could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies.

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OBJECTIVE: Cannabinoid type 1 receptors (CB1R) modulate feeding behavior and energy homeostasis, and the CB1R tone is dysgulated in obesity. This study aimed to investigate CB1R availability in peripheral tissue and brain in young men with overweight versus lean men. METHODS: Healthy males with high (HR, n = 16) or low (LR, n = 20) obesity risk were studied with fluoride 18-labeled FMPEP-d2 positron emission tomography to quantify CB1R availability in abdominal adipose tissue, brown adipose tissue, muscle, and brain. Obesity risk was assessed by BMI, physical exercise habits, and familial obesity risk, including parental overweight, obesity, and type 2 diabetes. To assess insulin sensitivity, fluoro-[18 F]-deoxy-2-D-glucose positron emission tomography during hyperinsulinemic-euglycemic clamp was performed. Serum endocannabinoids were analyzed. RESULTS: CB1R availability in abdominal adipose tissue was lower in the HR than in the LR group, whereas no difference was found in other tissues. CB1R availability of abdominal adipose tissue and brain correlated positively with insulin sensitivity and negatively with unfavorable lipid profile, BMI, body adiposity, and inflammatory markers. Serum arachidonoyl glycerol concentration was associated with lower CB1R availability of the whole brain, unfavorable lipid profile, and higher serum inflammatory markers. CONCLUSIONS: The results suggest endocannabinoid dysregulation already in the preobesity state.

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We aimed to investigate the effects of maternal obesity on brain structure and metabolism in frail women, and their reversibility in response to exercise. We recruited 37 frail elderly women (20 offspring of lean/normal-weight mothers (OLM) and 17 offspring of obese/overweight mothers (OOM)) and nine non-frail controls to undergo magnetic resonance and diffusion tensor imaging (DTI), positron emission tomography with Fluorine-18-fluorodeoxyglucose (PET), and cognitive function tests (CERAD). Frail women were studied before and after a 4-month resistance training, and controls were studied once. White matter (WM) density (voxel-based morphometry) was higher in OLM than in OOM subjects. Exercise increased WM density in both OLM and OOM in the cerebellum in superior parietal regions in OLM and in cuneal and precuneal regions in OOM. OLM gained more WM density than OOM in response to intervention. No significant results were found from the Freesurfer analysis, nor from PET or DTI images. Exercise has an impact on brain morphology and cognition in elderly frail women.

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Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 min of a full-length feature film, and iii) listened to 13.5 min of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66-77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others' bonding and distress signals.

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Humans all around the world are drawn to creating and consuming art due to its capability to evoke emotions, but the mechanisms underlying art-evoked feelings remain poorly characterised. Here we show how embodiement contributes to emotions evoked by a large database of visual art pieces (n = 336). In four experiments, we mapped the subjective feeling space of art-evoked emotions (n = 244), quantified "bodily fingerprints" of these emotions (n = 615), and recorded the subjects' interest annotations (n = 306) and eye movements (n = 21) while viewing the art. We show that art evokes a wide spectrum of feelings, and that the bodily fingerprints triggered by art are central to these feelings, especially in artworks where human figures are salient. Altogether these results support the model that bodily sensations are central to the aesthetic experience.

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Human brain metabolism is susceptible to temperature changes. It has been suggested that the supraclavicular brown adipose tissue (BAT) protects the brain from these fluctuations by regulating heat production through the presence of uncoupling protein 1 (UCP-1). It remains unsolved whether inter-individual variation in the expression of UCP-1, which represents the thermogenic capacity of the supraclavicular BAT, is linked with brain metabolism during cold stress. Ten healthy human participants underwent 18F-FDG PET scanning of the brain under cold stimulus to determine brain glucose uptake (BGU). On a separate day, an excision biopsy of the supraclavicular fat-the fat proximal to the carotid arteries supplying the brain with warm blood-was performed to determine the mRNA expression of the thermogenic protein UCP-1. Expression of UCP-1 in supraclavicular BAT was directly related to the whole brain glucose uptake rate determined under cold stimulation (rho = 0.71, p = 0.03). In sub-compartmental brain analysis, UCP-1 expression in supraclavicular BAT was directly related to cold-stimulated glucose uptake rates in the hypothalamus, medulla, midbrain, limbic system, frontal lobe, occipital lobe, and parietal lobe (all rho ≥ 0.67, p < 0.05). These relationships were independent of body mass index and age. When analysing gene expressions of BAT secretome, we found a positive correlation between cold-stimulated BGU and DIO2. These findings provide evidence of functional links between brain metabolism under cold stimulation and UCP-1 and DIO2 expressions in BAT in humans. More research is needed to evaluate the importance of these findings in clinical outcomes, for instance, in examining the supporting role of BAT in cognitive functions under cold stress.