Early brain neuroinflammatory and metabolic changes identified by dual tracer microPET imaging in mice with acute liver injury.

Background: Acute liver injury (ALI) that progresses into acute liver failure (ALF) is a life-threatening condition with an increasing incidence and associated costs. Acetaminophen (N-acetyl-p-aminophenol, APAP) overdosing is among the leading causes of ALI and ALF in the Northern Hemisphere. Brain dysfunction defined as hepatic encephalopathy is one of the main diagnostic criteria for ALF. While neuroinflammation and brain metabolic alterations significantly contribute to hepatic encephalopathy, their evaluation at early stages of ALI remained challenging. To provide insights, we utilized post-mortem analysis and non-invasive brain micro positron emission tomography (microPET) imaging of mice with APAP-induced ALI. Methods: Male C57BL/6 mice were treated with vehicle or APAP (600 mg/kg, i.p.). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver damage (using H&E staining), hepatic and serum IL-6 levels, and hippocampal IBA1 (using immunolabeling) were evaluated at 24h and 48h. Vehicle and APAP treated animals also underwent microPET imaging utilizing a dual tracer approach, including [11C]-peripheral benzodiazepine receptor ([11C]PBR28) to assess microglia/astrocyte activation and [18F]-fluoro-2-deoxy-2-D-glucose ([18F]FDG) to assess energy metabolism. Brain images were pre-processed and evaluated using conjunction and individual tracer uptake analysis. Results: APAP-induced ALI and hepatic and systemic inflammation were detected at 24h and 48h by significantly elevated serum ALT and AST levels, hepatocellular damage, and increased hepatic and serum IL-6 levels. In parallel, increased microglial numbers, indicative for neuroinflammation were observed in the hippocampus of APAP-treated mice. MicroPET imaging revealed overlapping increases in [11C]PBR28 and [18F]FDG uptake in the hippocampus, thalamus, and habenular nucleus indicating microglial/astroglial activation and increased energy metabolism in APAP-treated mice (vs. vehicle-treated mice) at 24h. Similar significant increases were also found in the hypothalamus, thalamus, and cerebellum at 48h. The individual tracer uptake analyses (APAP vs vehicle) at 24h and 48h confirmed increases in these brain areas and indicated additional tracer- and region-specific effects including hippocampal alterations. Conclusion: Peripheral manifestations of APAP-induced ALI in mice are associated with brain neuroinflammatory and metabolic alterations at relatively early stages of disease progression, which can be non-invasively evaluated using microPET imaging and conjunction analysis. These findings support further PET-based investigations of brain function in ALI/ALF that may inform timely therapeutic interventions.

Relation of Insulin Resistance to Brain Glucose Metabolism in Fasting and Hyperinsulinemic States: A Systematic Review and Meta-Analysis.

CONTEXT: Abnormal brain glucose metabolism may cause cognitive disease in type 2 diabetes, yet the relation between insulin resistance and brain glucose metabolism has not been systematically described. OBJECTIVE: We evaluated the impact of metabolic condition (fasting vs insulin stimulation, e.g., from hyperinsulinemic clamp) on the association between insulin resistance of different etiologies and brain glucose metabolism. DATA SOURCES: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from inception until February 2022. STUDY SELECTION: Of 656 unique records, we deemed thirty-one eligible. Criteria were studies assessing brain glucose metabolism (uptake or metabolic rate) by 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography ([18F]-FDG-PET) in individuals characterized by measures of or clinical proxies for insulin resistance (e.g., type 2 diabetes and obesity). DATA EXTRACTION: Two independent investigators extracted data and assessed study quality. DATA SYNTHESIS: We applied random-effects models to pool Hedge's g standardized mean differences. Insulin resistance was associated with decreased brain glucose metabolism during fasting (-0.47SD, 95%CI: -0.73 to -0.22, p<0.001, I2=71%) and increased metabolism during insulin stimulation (1.44SD, 95%CI: 0.79 to 2.09, p=0.002, I2=43%). Contrary to type 2 diabetes and other insulin resistance-related conditions, obesity was not associated with brain hypometabolism in fasting states (0.29SD, 95%CI: -0.81 to 1.39). CONCLUSIONS: Metabolic conditions modify associations between insulin resistance and brain glucose metabolism, i.e. most individuals with insulin resistance display hypometabolism during fasting and hypermetabolism during insulin stimulation.

Sex-dependent susceptibility to brain metabolic dysfunction and memory impairment in response to pre and postnatal high-fat diet.

The developing brain is sensitive to the impacts of early-life nutritional intake. This study investigates whether maternal high fat diet (HFD) causes glucose metabolism impairment, neuroinflammation, and memory impairment in immature and adult offspring, and whether it may be affected by postweaning diets in a sex-dependent manner in adult offspring. After weaning, female rats were fed HFD (55.9% fat) or normal chow diet (NCD; 10% fat) for 8 weeks before mating, during pregnancy, and lactation. On postnatal day 21 (PND21), the male and female offspring of both groups were split into two new groups, and NCD or HFD feeding was maintained until PND180. On PND21 and PND180, brain glucose metabolism, inflammation, and Alzheimer's pathology-related markers were by qPCR. In adult offspring, peripheral insulin resistance parameters, spatial memory performance, and brain glucose metabolism (18F-FDG-PET scan and protein levels of IDE and GLUT3) were assessed. Histological analysis was also performed on PND21 and adult offspring. On PND21, we found that maternal HFD affected transcript levels of glucose metabolism markers in both sexes. In adult offspring, more profoundly in males, postweaning HFD in combination with maternal HFD induced peripheral and brain metabolic disturbances, impaired memory performance and elevated inflammation, dementia risk markers, and neuronal loss. Our results suggest that maternal HFD affects brain glucose metabolism in the early ages of both sexes. Postweaning HFD sex-dependently causes brain metabolic dysfunction and memory impairment in later-life offspring; effects that can be worsened in combination with maternal HFD.

Molecular neuroimaging in dominantly inherited versus sporadic early-onset Alzheimer's disease.

Approximately 5% of Alzheimer's disease patients develop symptoms before age 65 (early-onset Alzheimer's disease), with either sporadic (sporadic early-onset Alzheimer's disease) or dominantly inherited (dominantly inherited Alzheimer's disease) presentations. Both sporadic early-onset Alzheimer's disease and dominantly inherited Alzheimer's disease are characterized by brain amyloid-ß accumulation, tau tangles, hypometabolism and neurodegeneration, but differences in topography and magnitude of these pathological changes are not fully elucidated. In this study, we directly compared patterns of amyloid-ß plaque deposition and glucose hypometabolism in sporadic early-onset Alzheimer's disease and dominantly inherited Alzheimer's disease individuals. Our analysis included 134 symptomatic sporadic early-onset Alzheimer's disease amyloid-Positron Emission Tomography (PET)-positive cases from the University of California, San Francisco, Alzheimer's Disease Research Center (mean ± SD age 59.7 ± 5.6 years), 89 symptomatic dominantly inherited Alzheimer's disease cases (age 45.8 ± 9.3 years) and 102 cognitively unimpaired non-mutation carriers from the Dominantly Inherited Alzheimer Network study (age 44.9 ± 9.2). Each group underwent clinical and cognitive examinations, 11C-labelled Pittsburgh Compound B-PET and structural MRI. 18F-Fluorodeoxyglucose-PET was also available for most participants. Positron Emission Tomography scans from both studies were uniformly processed to obtain a standardized uptake value ratio (PIB50-70 cerebellar grey reference and FDG30-60 pons reference) images. Statistical analyses included pairwise global and voxelwise group comparisons and group-independent component analyses. Analyses were performed also adjusting for covariates including age, sex, Mini-Mental State Examination, apolipoprotein ε4 status and average composite cortical of standardized uptake value ratio. Compared with dominantly inherited Alzheimer's disease, sporadic early-onset Alzheimer's disease participants were older at age of onset (mean ± SD, 54.8 ± 8.2 versus 41.9 ± 8.2, Cohen's d = 1.91), with more years of education (16.4 ± 2.8 versus 13.5 ± 3.2, d = 1) and more likely to be apolipoprotein ε4 carriers (54.6% ε4 versus 28.1%, Cramer's V = 0.26), but similar Mini-Mental State Examination (20.6 ± 6.1 versus 21.2 ± 7.4, d = 0.08). Sporadic early-onset Alzheimer's disease had higher global cortical Pittsburgh Compound B-PET binding (mean ± SD standardized uptake value ratio, 1.92 ± 0.29 versus 1.58 ± 0.44, d = 0.96) and greater global cortical 18F-fluorodeoxyglucose-PET hypometabolism (mean ± SD standardized uptake value ratio, 1.32 ± 0.1 versus 1.39 ± 0.19, d = 0.48) compared with dominantly inherited Alzheimer's disease. Fully adjusted comparisons demonstrated relatively higher Pittsburgh Compound B-PET standardized uptake value ratio in the medial occipital, thalami, basal ganglia and medial/dorsal frontal regions in dominantly inherited Alzheimer's disease versus sporadic early-onset Alzheimer's disease. Sporadic early-onset Alzheimer's disease showed relatively greater 18F-fluorodeoxyglucose-PET hypometabolism in Alzheimer's disease signature temporoparietal regions and caudate nuclei, whereas dominantly inherited Alzheimer's disease showed relatively greater hypometabolism in frontal white matter and pericentral regions. Independent component analyses largely replicated these findings by highlighting common and unique Pittsburgh Compound B-PET and 18F-fluorodeoxyglucose-PET binding patterns. In summary, our findings suggest both common and distinct patterns of amyloid and glucose hypometabolism in sporadic and dominantly inherited early-onset Alzheimer's disease.

The brain's "dark energy" puzzle: How strongly is glucose metabolism linked to resting-state brain activity?

Brain glucose metabolism, which can be investigated at the macroscale level with [18F]FDG PET, displays significant regional variability for reasons that remain unclear. Some of the functional drivers behind this heterogeneity may be captured by resting-state functional magnetic resonance imaging (rs-fMRI). However, the full extent to which an fMRI-based description of the brain's spontaneous activity can describe local metabolism is unknown. Here, using two multimodal datasets of healthy participants, we built a multivariable multilevel model of functional-metabolic associations, assessing multiple functional features, describing the 1) rs-fMRI signal, 2) hemodynamic response, 3) static and 4) time-varying functional connectivity, as predictors of the human brain's metabolic architecture. The full model was trained on one dataset and tested on the other to assess its reproducibility. We found that functional-metabolic spatial coupling is nonlinear and heterogeneous across the brain, and that local measures of rs-fMRI activity and synchrony are more tightly coupled to local metabolism. In the testing dataset, the degree of functional-metabolic spatial coupling was also related to peripheral metabolism. Overall, although a significant proportion of regional metabolic variability can be described by measures of spontaneous activity, additional efforts are needed to explain the remaining variance in the brain's 'dark energy'.

Thermodynamic Analysis to Evaluate the Effect of Diet on Brain Glucose Metabolism: The Case of Fish Oil.

Inefficient glucose metabolism and decreased ATP production in the brain are linked to ageing, cognitive decline, and neurodegenerative diseases (NDDs). This study employed thermodynamic analysis to assess the effect of fish oil supplementation on glucose metabolism in ageing brains. Data from previous studies on glucose metabolism in the aged human brain and grey mouse lemur brains were examined. The results demonstrated that Omega-3 fish oil supplementation in grey mouse lemurs increased entropy generation and decreased Gibbs free energy across all brain regions. Specifically, there was a 47.4% increase in entropy generation and a 47.4 decrease in Gibbs free energy in the whole brain, indicating improved metabolic efficiency. In the human model, looking at the specific brain regions, supplementation with Omega-3 polyunsaturated fatty acids (n-3 PUFAs) reduced the entropy generation difference between elderly and young individuals in the cerebellum and particular parts of the brain cortex, namely the anterior cingulate and occipital lobe, with 100%, 14.29%, and 20% reductions, respectively. The Gibbs free energy difference was reduced only in the anterior cingulate by 60.64%. This research underscores that the application of thermodynamics is a comparable and powerful tool in comprehending the dynamics and metabolic intricacies within the brain.

Intermittent fasting and Alzheimer's disease-Targeting ketone bodies as a potential strategy for brain energy rescue.

Alzheimer's disease (AD) lacks effective clinical treatments. As the disease progresses, the cerebral glucose hypometabolism that appears in the preclinical phase of AD gradually worsens, leading to increasingly severe brain energy disorders. This review analyzes the brain energy deficit in AD and its etiology, brain energy rescue strategies based on ketone intervention, the effects and mechanisms of IF, the differences in efficacy between IF and ketogenic diet and the duality of IF. The evidence suggests that brain energy deficits lead to the development and progression of AD pathology. IF, which improves brain energy impairments by promoting ketone metabolism, thus has good therapeutic potential for AD.

Abnormal brain glucose metabolism patterns in patients with advanced non-small-cell lung cancer after chemotherapy：A retrospective PET study.

PURPOSE: This study was designed to investigate the acute or chronic post-chemotherapy effect and different chemotherapy cycles effect on brain glucose metabolism. METHODS: A total of seventy-three patients who received chemotherapy after being diagnosed with advanced non-small-cell lung cancer (NSCLC) and underwent 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan at Nuclear Medicine Department of the Fifth Hospital of Sun Yat-sen University between September 2017 and August 2022 were included. Seventy-two healthy control patients who underwent whole-body 18F-FDG PET/CT scans at our department, without any evidence of malignancy and confirmed by follow-up visits, were included. Advanced NSCLC patients were classified into six arms: short-to-long course (chemotherapy cycles under 4, between 5 and 8 and more than 8) in acute chemotherapy effect (AC) group (scanned 18F-FDG PET/CT within 6 months post-chemotherapy) or chronic chemotherapy effect (CC) group (the interval between scanning and the last chemotherapy session more than six months). Statistical Parametric Mapping (SPM) analysis between patients' groups and healthy controls' brain 18F-FDG PET was performed (uncorrected p ˂ 0.001 with cluster size above 20 contiguous voxels). RESULTS: There were no significant differences between patients' groups and healthy controls in age, gender and body mass index (BMI). SPM PET analyses revealed anomalous brain metabolic activity in different groups (p ˂ 0.001). Short-course + AC group exhibited hypermetabolism in the cerebellum and widespread hypometabolism in bilateral frontal lobe predominantly. Only hypometabolic brain regions were observed in middle-course + AC patients. Long-course + AC group displayed a greater number of abnormalities. Notably, these metabolic abnormalities tended to decrease in CC groups versus AC groups across all courses. CONCLUSION: Our study revealed that patients with advanced NSCLC who underwent chemotherapy exhibited persistent abnormal brain metabolism patterns during continuous chemotherapy and these abnormalities tended to recover after completion of chemotherapy over time, but without correlation to an increasing number of chemotherapy cycles. 18F-FDG PET/CT may serve as a possible modality for evaluating brain function and guiding appropriate treatment timing.

Association of dysphagia with altered brain glucose metabolism in Parkinson's disease.

AIMS: Dysphagia is a major clinical concern in Parkinson's disease (PD). However, the relationship between the development of phase-specific dysphagia and the regional brain glucose metabolism remains unclear. Our objective was to investigate the distributions of brain glucose metabolism specific to oral and pharyngeal phases of dysphagia in PD. METHODS: In this retrospective cross-sectional study, patients with PD who underwent videofluoroscopic swallowing study (VFSS) and 18 F-fluorodeoxy-glucose positron emission tomography at intervals of <1 month were included. Each swallow was assessed by the binarized Videofluoroscopic Dysphagia Scale with 14 subitems, seven each for the oral and pharyngeal phases. Metabolism mapping was performed by superimposing significant clusters of subitems belonging to each of the two phases using voxel-wise Firth's penalized binary logistic regression model, adjusting for age and PD duration at VFSS. RESULTS: Eighty-two patients with PD who met the inclusion criteria were included in the analysis. The oral phase dysphagia-specific overlap map showed hypermetabolism in the right inferior temporal gyrus, bilateral cerebellum, superior frontal gyrus, and anterior cingulate cortices. Hypometabolism in the bilateral orbital and triangular parts of the inferior to middle frontal gyrus was also correlated with the occurrence of oral phase dysphagia. The development of pharyngeal phase dysphagia was related to hypermetabolism of posterior aspects of the bilateral parietal lobes, cerebellum, and hypometabolism of the mediodorsal aspects of anterior cingulate and middle to superior frontal gyri. CONCLUSION: These findings suggest that phase-specific distribution of brain glucose metabolism may explain the dysphagia of PD.

Sex-specific effects of high-fat diet on rat brain glucose metabolism and early-onset dementia symptoms.

Peripheral metabolic disturbances are associated with a variety of clinical health consequences and may contribute to the development of neurocognitive disorders. This study investigates whether long-term high-fat diet (HFD) consumption changes the brain glucose metabolism and impairs memory performance in a sex-dependent manner. Male and female rats, after weaning, were fed HFD or normal chow diet (NCD) for 16 weeks. Behavioral tests for spatial memory and an 18 F-FDG-PET scan were performed. Also, the expression of brain insulin resistance markers and Alzheimer's pathology-related genes was assessed by qPCR. The Morris water maze and Y-maze results showed, respectively, that memory retrieval and spatial working memory were impaired only in HFD male rats compared to NCD controls. In addition, measuring whole brain 18 F-FDG uptake indicated a significant reduction in glucose metabolism in male but not female HFD rats. Analysis of 15 genes related to glucose metabolism and Alzheimer's pathology, in the hippocampus, showed that expression of GLUT3, IRS2, and IDE is significantly reduced in HFD male rats. Our results suggest that sex affects the HFD-induced dysregulation of brain glucose metabolism and cognitive performance.

Cortical Thickness and Brain Glucose Metabolism in Healthy Aging.

BACKGROUND AND PURPOSE: We aimed to determine the effect of demographic factors on cortical thickness and brain glucose metabolism in healthy aging subjects. METHODS: The following tests were performed on 71 subjects with normal cognition: neurological examination, 3-tesla magnetic resonance imaging, 18F-fluorodeoxyglucose positron-emission tomography, and neuropsychological tests. Cortical thickness and brain metabolism were measured using vertex- and voxelwise analyses, respectively. General linear models (GLMs) were used to determine the effects of age, sex, and education on cortical thickness and brain glucose metabolism. The effects of mean lobar cortical thickness and mean lobar metabolism on neuropsychological test scores were evaluated using GLMs after controlling for age, sex, and education. The intracranial volume (ICV) was further included as a predictor or covariate for the cortical thickness analyses. RESULTS: Age was negatively correlated with the mean cortical thickness in all lobes (frontal and parietal lobes, p=0.001; temporal and occipital lobes, p<0.001) and with the mean temporal metabolism (p=0.005). Education was not associated with cortical thickness or brain metabolism in any lobe. Male subjects had a lower mean parietal metabolism than did female subjects (p<0.001), while their mean cortical thicknesses were comparable. ICV was positively correlated with mean cortical thickness in the frontal (p=0.016), temporal (p=0.009), and occipital (p=0.007) lobes. The mean lobar cortical thickness was not associated with cognition scores, while the mean temporal metabolism was positively correlated with verbal memory test scores. CONCLUSIONS: Age and sex affect cortical thickness and brain glucose metabolism in different ways. Demographic factors must therefore be considered in analyses of cortical thickness and brain metabolism.

Lower brain glucose metabolism in normal ageing is predominantly frontal and temporal: A systematic review and pooled effect size and activation likelihood estimates meta-analyses.

This review provides a qualitative and quantitative analysis of cerebral glucose metabolism in ageing. We undertook a systematic literature review followed by pooled effect size and activation likelihood estimates (ALE) meta-analyses. Studies were retrieved from PubMed following the PRISMA guidelines. After reviewing 635 records, 21 studies with 22 independent samples (n = 911 participants) were included in the pooled effect size analyses. Eight studies with eleven separate samples (n = 713 participants) were included in the ALE analyses. Pooled effect sizes showed significantly lower cerebral metabolic rates of glucose for older versus younger adults for the whole brain, as well as for the frontal, temporal, parietal, and occipital lobes. Among the sub-cortical structures, the caudate showed a lower metabolic rate among older adults. In sub-group analyses controlling for changes in brain volume or partial volume effects, the lower glucose metabolism among older adults in the frontal lobe remained significant, whereas confidence intervals crossed zero for the other lobes and structures. The ALE identified nine clusters of lower glucose metabolism among older adults, ranging from 200 to 2640 mm3 . The two largest clusters were in the left and right inferior frontal and superior temporal gyri and the insula. Clusters were also found in the inferior temporal junction, the anterior cingulate and caudate. Taken together, the results are consistent with research showing less efficient glucose metabolism in the ageing brain. The findings are discussed in the context of theories of cognitive ageing and are compared to those found in neurodegenerative disease.

A study of brain glucose metabolism in obsessive-compulsive disorder patients.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic neural psychological condition. Its pathogenesis is not yet completely understood. This current research used fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging to examine the changes in brain glucose metabolism in patients with OCD during the course of treatment, and analyzed its relationship with clinical efficacy. METHODS: A total of 23 patients with OCD were enrolled and divided into case group 1, consisting of patients who received no drug treatment or those who recently stopped drug treatment for more than five half-life periods (OCD1 group, N=10), and case group 2, consisting of patients who were receiving drug treatment before enrollment (OCD2 group, N=13). Ten healthy volunteers were selected as controls. All patients and healthy controls were subjected to head PET-computed tomography (CT) examination. Seven patients in case group 2 underwent scanning again after 3 months of drug treatment, namely, case group 3 (OCD3 group, N=7). Statistical Parametric Mapping (SPM) 8 software was used to analyze the PET-CT results. RESULTS: OCD patients had abnormally enhanced glucose metabolism in the medium orbito-frontal region of the brain, and abnormally reduced glucose metabolism in brain areas including the insula, caudate nucleus, and middle temporal gyrus. No changes in brain glucose metabolism related to curative effect was found. CONCLUSIONS: In OCD patients, abnormal brain function may not only be limited to the usual cortico-striato-thalamo-cortical (CSTC) loop model, but may involve a wide range of brain regions simultaneously.

Evaluation of the Effects of R-CHOP Chemotherapy on Brain Glucose Metabolism in Patients with Diffuse Large B Cell Lymphoma: A Baseline, Interim, and End-of-Treatment PET/CT Study.

BACKGROUND: To investigate the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy on brain glucose metabolism in patients with diffuse large B cell lymphoma (DLBCL). METHODS: Seventy-two patients with newly diagnosed DLBCL underwent FDG PET/CT brain and whole-body scans at baseline (PET0), in the interim of chemotherapy (PET2), and at the end (PET6) of chemotherapy. All three brain scans of each patient were analyzed using statistical parametric mapping software. RESULTS: Compared with the PET0 scan, the PET2 and PET6 scans revealed a significantly higher glucose metabolism throughout the whole brain, with the PET6 scan revealing a higher metabolism than the PET2 scan. Patients with a complete response (CR) displayed decreased glucose metabolism in the lingual gyrus and increased glucose metabolism in the pons after chemotherapy compared with the findings in patients with partial responses or progressive disease. CONCLUSIONS: Brain glucose metabolism was affected by R-CHOP treatment throughout the entire chemotherapy protocol.

Brain laterality evaluated by F-18 fluorodeoxyglucose positron emission computed tomography in autism spectrum disorders.

Background and rationale: Autism spectrum disorder (ASD) is a neuropsychiatric disorder that has no curative treatment. Little is known about the brain laterality in patients with ASD. F-18 fluorodeoxyglucose positron emission computed tomography (F-18 FDG PET/CT) is a neuroimaging technique that is suitable for ASD owing to its ability to detect whole brain functional abnormalities in a short time and is feasible in ASD patients. The purpose of this study was to evaluate brain laterality using F-18 FDG PET/CT in patients with high-functioning ASD. Materials and methods: This case-control study recruited eight ASD patients who met the DSM-5 criteria, the recorded data of eight controls matched for age, sex, and handedness were also enrolled. The resting state of brain glucose metabolism in the regions of interest (ROIs) was analyzed using the Q.Brain software. Brain glucose metabolism and laterality index in each ROI of ASD patients were compared with those of the controls. The pattern of brain metabolism was analyzed using visual analysis and is reported in the data description. Results: The ASD group's overall brain glucose metabolism was lower than that of the control group in both the left and right hemispheres, with mean differences of 1.54 and 1.21, respectively. We found statistically lower mean glucose metabolism for ASD patients than controls in the left prefrontal lateral (Z = 1.96, p = 0.049). The left laterality index was found in nine ROIs for ASD and 11 ROIs for the control. The left laterality index in the ASD group was significantly lower than that in the control group in the prefrontal lateral (Z = 2.52, p = 0.012), precuneus (Z = 2.10, p = 0.036), and parietal inferior (Z = 1.96, p = 0.049) regions. Conclusion: Individuals with ASD have lower brain glucose metabolism than control. In addition, the number of ROIs for left laterality index in the ASD group was lower than control. Left laterality defects may be one of the causes of ASD. This knowledge can be useful in the treatment of ASD by increasing the left-brain metabolism. This trial was registered in the Thai Clinical Trials Registry (TCTR20210705005).

Altered Regional Brain Glucose Metabolism in Diffuse Large B-Cell Lymphoma Patients Treated With Cyclophosphamide, Epirubicin, Vincristine, and Prednisone: An Fluorodeoxyglucose Positron Emission Tomography Study of 205 Cases.

Background: A growing number of neuroimaging studies reported that chemotherapy might impair brain functions, leading to persistent cognitive alterations in a subset of cancer patients. The present study aimed to investigate the regional brain glucose metabolism differences between diffuse large B cell lymphoma (DLBCL) patients treated with cyclophosphamide, epirubicin, vincristine, and prednisone and controls using positron emission tomography with 18F-labeled fluoro-2-deoxyglucose integrated with computed tomography (18F-FDG PET/CT) scanning. Methods: We analyzed 18F-FDG PET data from 205 right-handed subjects (for avoiding the influence of handedness factors on brain function), including 105 post-chemotherapy DLBCL patients and 100 controls. The two groups had similar average age, gender ratio, and years of education. First, we compared the regional brain glucose metabolism using a voxel-based two-sample t-test. Second, we compared the interregional correlation. Finally, we investigated the correlations between the regional brain glucose metabolism and the number of chemotherapy cycles. Results: Compared with the controls, the post-chemotherapy group showed higher metabolism in the right hippocampus and parahippocampal gyrus (region of interest (ROI) 1) and the left hippocampus (ROI 2), and lower metabolism in the left medial orbitofrontal gyrus (ROI 3), the left medial superior frontal gyrus (ROI 4), and the left superior frontal gyrus (ROI 5). The two groups had different interregional correlations between ROI 3 and ROI 5. In some brain regions-mainly located in the bilateral frontal gyrus-the number of chemotherapy cycles was positively correlated with the regional brain glucose metabolism. Meanwhile, in some bilateral hippocampus regions, these two parameters were negatively correlated. Conclusion: The present study provides solid data on the regional brain glucose metabolism differences between post-chemotherapy DLBCL patients and controls. These results should improve our understanding of human brain functions alterations in post-chemotherapy DLBCL patients and suggest that 18F-FDG PET/CT scanning is a valuable neuroimaging technology for studying chemotherapy-induced brain function changes.

Alcohol binge drinking decreases brain glucose metabolism and functional connectivity in adolescent rats.

Alcohol misuse represents a serious health concern, especially during adolescence, with approximately 18% of high school students engaging in binge drinking. Despite widespread misuse of alcohol, its effects on how the brain functions is not fully understood. This study utilized a binge drinking model in adolescent rats to examine effects on brain function as measured by brain glucose metabolism (BGluM). Following an injection of [18 FDG] fluro-2-deoxy-D-glucose, rats had voluntary access to either water or various concentrations of ethanol to obtain the following targeted doses: water (no ethanol), low dose ethanol (0.29 ± 0.03 g/kg), moderate dose ethanol (0.98 ± 0.05), and high dose ethanol (2.19 ± 0.23 g/kg). Rats were subsequently scanned using positron emission tomography. All three doses of ethanol were found to decrease BGluM in the restrosplenial cortex, visual cortex, jaw region of the somatosensory cortex, and cerebellum. For both the LD and MD ethanol dose, decreased BGluM was seen in the superior colliculi. The MD ethanol dose also decreased BGluM in the subiculum, frontal association area, as well as the primary motor cortex. Lastly, the HD ethanol dose decreased BGluM in the hippocampus, thalamus, raphe nucleus, inferior colliculus, and the primary motor cortex. Similar decreases in the hippocampus were also seen in the LD group. Taken together, these results highlight the negative consequences of acute binge drinking on BGluM in many regions of the brain involved in sensory, motor, and cognitive processes. Future studies are needed to assess the long-term effects of alcohol binge drinking on brain function as well as its cessation.

A resting-state fMRI pattern of spinocerebellar ataxia type 3 and comparison with 18F-FDG PET.

Spinocerebellar ataxia type 3 (SCA3) is a rare genetic neurodegenerative disease. The neurobiological basis of SCA3 is still poorly understood, and up until now resting-state fMRI (rs-fMRI) has not been used to study this disease. In the current study we investigated (multi-echo) rs-fMRI data from patients with genetically confirmed SCA3 (n = 17) and matched healthy subjects (n = 16). Using independent component analysis (ICA) and subsequent regression with bootstrap resampling, we identified a pattern of differences between patients and healthy subjects, which we coined the fMRI SCA3 related pattern (fSCA3-RP) comprising cerebellum, anterior striatum and various cortical regions. Individual fSCA3-RP scores were highly correlated with a previously published 18F-FDG PET pattern found in the same sample (rho = 0.78, P = 0.0003). Also, a high correlation was found with the Scale for Assessment and Rating of Ataxia scores (r = 0.63, P = 0.007). No correlations were found with neuropsychological test scores, nor with levels of grey matter atrophy. Compared with the 18F-FDG PET pattern, the fSCA3-RP included a more extensive contribution of the mediofrontal cortex, putatively representing changes in default network activity. This rs-fMRI identification of additional regions is proposed to reflect a consequence of the nature of the BOLD technique, enabling measurement of dynamic network activity, compared to the more static 18F-FDG PET methodology. Altogether, our findings shed new light on the neural substrate of SCA3, and encourage further validation of the fSCA3-RP to assess its potential contribution as imaging biomarker for future research and clinical use.

Impact of medium-chain triglycerides on gait performance and brain metabolic network in healthy older adults: a double-blind, randomized controlled study.

Nutritional supplementation with medium-chain triglycerides (MCTs) has the potential to increase memory function in elderly patients with frailty and dementia. Our aim was to investigate the effects of MCT on cognitive and gait functions and their relationships with focal brain metabolism and functional connectivity even in healthy older adults. Participants were blindly randomized and allocated to two groups: 18 g/day of MCT oil and matching placebo formula (control) administered as a jelly stick (6 g/pack, ingested three times a day). Gait analysis during the 6-m walk test, cognition, brain focal glucose metabolism quantified by 18F-fluorodeocyglucose positron emission tomography, and magnetic resonance imaging-based functional connectivity were assessed before and after a 3-month intervention. Sixty-three healthy, normal adults (females and males) were included. Compared with the control group, the MCT group showed better balance ability, as represented by the lower Lissajous index (23.1 ± 14.4 vs. 31.3 ± 18.9; P < 0.01), although no time × group interaction was observed in cognitive and other gait parameters. Moreover, MCT led to suppressed glucose metabolism in the right sensorimotor cortex compared with the control (P < 0.001), which was related to improved balance (r = 0.37; P = 0.04) along with increased functional connectivity from the ipsilateral cerebellar hemisphere. In conclusion, a 3-month MCT supplementation improves walking balance by suppressing glucose metabolism, which suggests the involvement of the cerebro-cerebellar network. This may reflect, at least in part, the inverse reaction of the ketogenic switch as a beneficial effect of long-term MCT dietary treatment.

Chronic treatment and abstinence from methylphenidate exposure dose-dependently changes glucose metabolism in the rat brain.

Methylphenidate (MP) is extensively prescribed for attention deficit hyperactivity disorder (ADHD). While MP is effective in ameliorating symptoms of ADHD, MP is also used illicitly among healthy subjects without ADHD for cognitive-enhancing purposes. The deleterious consequences associated with long-term MP use as well as its cessation on brain activity remains to be understood. To address this, we administered either water, low dose MP (LD MP), or high dose MP (HD MP) to healthy adolescent Sprague Dawley rats, with five days on the treatment and two days off for thirteen consecutive weeks. Rats were then abstinent from their respective treatments for four weeks. Using positron emission tomography (PET) and fluorodeoxyglucose [18F] (FDG), we scanned rats at three time points: after thirteen weeks of treatment, after one week of abstinence, and after four weeks of abstinence. After thirteen weeks of LD and HD MP treatment, increases in brain glucose metabolism (BGluM) were seen in several cortical and subcortical regions associated with sensory and motor functions as well as learning and memory. One-week abstinence from LD MP treatment promoted increased BGluM compared to both water treated and HP MP treated groups. After four weeks of abstinence, little group differences were seen. Longitudinally, we observed contrasting differences on BGluM depending on whether a LD or HD of MP was administered. Our results demonstrate that MP treatment during adolescence can significantly alter BGluM. Moreover, these changes in brain activity do not subside in many areas of the brain after both one and four-week drug abstinence.