Regional Metabolic Rate Of Glucose Research Articles

Improved functional connectivity after a 6‐month ketogenic supplementation in mild cognitive impairment

AbstractBackgroundKetones, the brain’s alternative fuel to glucose, bypass the brain glucose deficit in mild cognitive impairment (MCI). The BENEFIC trial conducted in MCI showed improved measures of cognition in multiple domains after a 6‐month ketogenic intervention [Fortier et al. 2019]. Functional connectivity in the dorsal‐attention network (DAN) deteriorates early in MCI, and prior to changes in the ventral‐attention network [Zhang et al. 2015]. We aimed to assess whether improved cognitive outcomes in the BENEFIC Trial were linked to improved brain functional connectivity.MethodParticipants in this 6‐month intervention were randomized to a placebo (n= 15) or ketogenic medium chain triglyceride (kMCT; n= 17) drink. A neurocognitive battery and brain imaging were performed pre‐ and post‐intervention. Functional connectivity was computed from resting‐state functional magnetic resonance images. Independent component analysis (FSL Melodic) was used to segment seven major resting‐state networks (DAN, ventral‐attention, frontoparietal, limbic, somatomotor, default‐mode and visual) [Yeo et al. 2011]. Regional cortical ketone (11C‐acetoacetate) and glucose (18F‐fluorodeoxyglucose) metabolic rates were also quantified using positron emission tomography (PET).ResultChanges (post ‐ pre) in DAN functional connectivity was significantly higher in the kMCT group vs placebo (P= 0.024). After correction for age, sex, education, ApoE status and intracranial volume, the significant difference between groups was still present, with a large effect size (partial h2= 0.16; P= 0.043; Figure 1). Connectivity in no other networks was significantly different between groups. Changes in attention and processing speed composite Z‐score (r= 0.42; P= 0.021) and specific tests targeting attention (Trail Making visual scanning and number sequencing conditions) were significantly associated with the increased DAN functional connectivity. Change in ketone uptake specifically in DAN cortical regions (Figure 2C) was significantly higher in the kMCT vs placebo group (P= 0.001) and was directly associated with the improved DAN functional connectivity, with a large effect size (r= 0.69; P= 0.002; Figure 3).ConclusionWe show that a 6‐month ketogenic intervention improves DAN functional connectivity in MCI, an improvement that is directly linked to increased energy (ketone) supply to the DAN. The beneficial effect of ketones on cognition in MCI may be linked to improved DAN connectivity.

Utility of Absolute Quantification in Non-lesional Extratemporal Lobe Epilepsy Using FDG PET/MR Imaging.

The purpose of this study was to establish a non-invasive clinical PET/MR protocol using [18F]-labeled deoxyglucose (FDG) that provides physicians with regional metabolic rate of glucose (MRGlc) values and to clarify the contribution of absolute quantification to clinical management of patients with non-lesional extratemporal lobe epilepsy (ETLE). The study included a group of 15 patients with non-lesional ETLE who underwent a dynamic FDG PET study using a fully-integrated PET/MRI system (Siemens Biograph). FDG tracer uptake images were converted to MRGlc (μmol/100 g/min) maps using an image derived input function that was extracted based on the combined analysis of PET and MRI data. In addition, the same protocol was applied to a group of healthy controls, yielding a normative database. Abnormality maps for ETLE patients were created with respect to the normative database, defining significant hypo- or hyper-metabolic regions that exceeded ±2 SD of normal regional mean MRGlc values. Abnormality maps derived from MRGlc images of ETLE patients contributed to the localization of hypo-metabolic areas against visual readings in 53% and increased the confidence in the original clinical readings in 33% of all cases. Moreover, quantification allowed identification of hyper-metabolic areas that are associated with frequently spiking cortex, rarely acknowledged in clinical readings. Overall, besides providing some confirmatory information to visual readings, quantitative PET imaging demonstrated only a moderate impact on clinical management of patients with complex pathology that leads to epileptic seizures, failing to provide new decisive information that would have changed classification of patients from being rejected to being considered for surgical intervention.

Regional cerebral metabolism alterations affect resting-state functional connectivity in major depressive disorder.

18F-FDG positron emission tomography (PET) is a reliable technique to quantify regional neural glucose metabolism even with major depressive disorder (MDD) heterogeneous features. Previous study proposed that in the resting-state (RS), pairs of brain regions whose regional glucose metabolic rates were significantly correlated were functionally associated. This synchronicity indicates a neuronal metabolic and functional interaction in high energy efficient brain regions. In this study, a multimode method was used to identify the RS-FC patterns based on regional metabolism changes, and to observe its relationship with the severity of depressive symptoms in MDD patients. The study enrolled 11 medication-naive MDD patients and 14 healthy subjects. All participants received a static 18F-FDG PET brain scan and a resting-state functional magnetic resonance imaging (RS-fMRI) scan. SPM5 software was used to compare brain metabolism in MDD patients with that in healthy controls, and designated regions with a change in metabolism as regions of interest (ROIs). The glucose metabolism-based regional RS-FC Z values were compared between groups. Then group independent component analysis (ICA) was used to identify the abnormal connectivity nodes in the intrinsic function networks. Finally, the correlation between abnormal RS-FC Z values and the severity of depressive symptoms was evaluated. Patients with MDD had reduced glucose metabolism in the putamen, claustrum, insular, inferior frontal gyrus, and supramarginal gyrus. The metabolic reduction regions impaired functional connectivity (FC) to key hubs, such as the Inferior frontal gyrus (pars triangular), angular gyrus, calcarine sulcus, middle frontal gyrus (MFG), located in dorsolateral prefrontal cortex (DLPFC)/parietal lobe, salience network (SN), primary visual cortex (V1), and language network respectively. There was no correlation between aberrant connectivity and the severity of clinical symptoms. This research puts forward a possibility that focal neural activity alteration may share RS-FC dysfunction and be susceptible to hubs in the functional network in MDD. In particular, the metabolism and function profiles of the Inferior frontal gyrus (pars triangularis) should be emphasized in future MDD studies.

The relationship between glucose metabolism, resting-state fMRI BOLD signal, and GABAA-binding potential: a preliminary study in healthy subjects and those with temporal lobe epilepsy.

Glucose metabolism has been associated with magnitude of blood oxygen level-dependent (BOLD) signal and connectivity across subjects within the default mode and dorsal attention networks. Similar correlations within subjects across the entire brain remain unexplored. [(18)F]-fluorodeoxyglucose positron emission tomography ([(18)F]-FDG PET), [(11)C]-flumazenil PET, and resting-state functional magnetic resonance imaging (fMRI) scans were acquired in eight healthy individuals and nine with temporal lobe epilepsy (TLE). Regional metabolic rate of glucose (rMRGlu) was correlated with amplitude of low frequency fluctuations (ALFFs) in the fMRI signal, global fMRI connectivity (GC), regional homogeneity (ReHo), and gamma-aminobutyric acid A-binding potential (GABAA BP(ND)) across the brain. Partial correlations for ALFFs, GC, and ReHo with GABAA BP(ND) were calculated, controlling for rMRGlu. In healthy subjects, significant positive correlations were observed across the brain between rMRGlu and ALFF, ReHo and GABAA BP(ND), and between ALFFs and GABAA BP(ND), controlling for rMRGlu. Brain-wide correlations between rMRGlu and ALFFs were significantly lower in TLE patients, and correlations between rMRGlu and GC were significantly greater in TLE than healthy subjects. These results indicate that the glutamatergic and GABAergic systems are coupled across the healthy human brain, and that ALFF is related to glutamate use throughout the healthy human brain. TLE may be a disorder of altered long-range connectivity in association with glutamate function.

Functional activity of brain structures and predisposition to aggression in patients with lingering diseases of the CNS

The relationships of unconscious aggression (according to the Hand Test) with regional glucose metabolic rates in the brain (estimated using positron emission tomography) have been analyzed in patients with multiple sclerosis. It has been shown that an increased proneness to open aggression (unconscious aggression) in patients with multiple sclerosis is mainly related to reduced functioning of different areas of the frontal lobes of the brain on the left and with changes in glucose metabolic rate in the structures of the limbic system of the left and right hemispheres. An enhanced unconscious aggression is accompanied by a decrease in the glucose metabolic rate in some areas of Broca’s convolution and the middle frontal gyrus on the left.

Anesthetic effects of propofol in the healthy human brain: functional imaging evidence.

Functional imaging methods, including positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), have become important tools for studying how anesthetic drugs act in the human brain to induce the state of general anesthesia. Recent imaging studies using fMRI and PET techniques have demonstrated the regional effects of propofol on the brain. However, the pharmacological mechanism of the action of propofol in the intact human central nervous system is unclear. To explore the possible action targets of propofol in the human brain, a systematic review of the literature was performed. The literature search was performed with limiting factors of "propofol," "functional imaging," "positron emission tomography", and "functional magnetic resonance imaging" from 1966 to July 2013 (using Medline, EMBASE, CINAHL and hand searches of references). Studies meeting the inclusion criteria were reviewed and critiqued for the purpose of this literature research. Eighteen researches meeting the inclusion criteria were reviewed in terms of the appropriateness of valuation technique. In the unconscious state, propofol sharply reduces the regional glucose metabolism rate (rGMR) and regional cerebral blood flow (rCBF) in all brain regions, particularly in the thalamus. However, GMR, such as in the occipital, temporal, and frontal lobes, was obviously decreased at a sedative dosage of propofol, whereas, changes in the thalamus were not obvious. Using fMRI, several studies observed a decrease of connectivity of the thalamus versus an increase of connectivity within the pons of the brainstem during propofol-induced mild sedation. During deep sedation, propofol preserves cortical sensory reactivity, the specific thalamocortical network is moderately affected, whereas the nonspecific thalamocortical network is severely suppressed. In contrast, several recent fMRI studies are consistent on the systemic decreased effects of propofol in the frontoparietal network. Accumulating evidence suggest that propofol-induced unconsciousness is associated with a global metabolic and vascular depression in the human brain and especially with a significant reduction in the thalamocortical network and the frontoparietal network.

Positron Emission Tomography Patterns in Cognitive Impairment in Patients with Multiple Sclerosis

Neuropsychological studies were performed on 61 patients with the remitting (38 cases) and progressive (23 cases) types of multiple sclerosis (MS) to identify links between cognitive disorders with changes in the glucose metabolic rate (GMR) in the gray matter of the cerebral cortex in MS with different courses; neuroimaging was also performed. Correlation analysis revealed a relationship between cognitive impairment and regional GMR values, depending on the course of MS. Details of the dynamics of the functional activity of the gray matter of the cerebral cortex during progression of illness and increases in disability were also demonstrated.

Neural correlates of rapid antidepressant response to ketamine in bipolar disorder

Ketamine, an N-methyl d-aspartate (NMDA) antagonist, has rapid antidepressant effects in depressed subjects with bipolar disorder (BD). Evidence supports a role for the glutamatergic system in the pathophysiology of BD. This double-blind, randomized, cross-over study sought to determine cerebral metabolic correlates of antidepressant response to ketamine. Twenty-one subjects with BD currently in a depressed state underwent [(18) F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging after receiving a placebo infusion as well as after receiving a ketamine infusion. Metabolism was compared between ketamine and placebo infusions, and correlated with clinical response. Regional metabolic rate of glucose (rMRGlu) in regions of interest (ROIs) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores were the main outcome measures. The study found that change in metabolism between sessions was significantly correlated with percentage change in MADRS scores in the right ventral striatum; subjects who showed the greatest improvement had the largest metabolic increase after ketamine infusion compared to placebo. In a voxel-wise analysis, subjects with BD had significantly lower glucose metabolism in the left hippocampus following the ketamine infusion than following the placebo infusion. In addition, metabolism in the subgenual anterior cingulate cortex (ACC) following the placebo infusion was positively correlated with percentage improvement in MADRS score following the ketamine infusion. Taken together, the results suggest that higher activity in the subgenual ACC may predict antidepressant response to ketamine. Ketamine administration altered glucose metabolism in areas known to be involved in mood disorders; these alterations may partially underlie ketamine's mechanism of action.

The Role of Changes in Glucose Metabolism in the Brain in the Formation of Cognitive Impairments in Patients with Remitting and Secondary-Progressive Multiple Sclerosis

The mechanism of the development of cognitive impairments in multiple sclerosis (MS) was investigated by studying glucose metabolism at the level of the brain by positron emission tomography (PET). A total of 61 patients with different types of MS were studied. Correlation analysis identified a relationship between cognitive impairments and regional glucose metabolic rate. The authors believe that this may be evidence for an important role for metabolic abnormalities in the gray matter of the brain in the pathogenesis of cognitive impairments in MS.

A Pilot Study of Fluorodeoxyglucose Positron Emission Tomography Findings in Patients with Phenylketonuria before and during Sapropterin Supplementation

Background and PurposePET scanning with fluorodeoxyglucose (FDG-PET) is a non-invasive method that measures regional glucose metabolic rate. Phenylalanine (Phe) and its metabolites appear to impair several aspects of brain energy metabolism. 1) To evaluate brain glucose metabolism with FDG-PET imaging in phenylketonuria (PKU) patients before and 4 months after sapropterin therapy; 2) to evaluate neurodevelopmental changes, blood Phe levels and dietary Phe tolerance before and after sapropterin therapy; 3) to generate pilot data to assess the feasibility of evaluating brain glucose metabolism with FDG-PET imaging and to explore potential trends resulting from the administration of sapropterin therapy.MethodsWe enrolled 5 subjects, ranged in age from 22 years to 51 years, with PKU. Subjects underwent FDG-PET brain imaging, blood tests for Phe and tyrosine levels, and neurocognitive evaluations before and 4 months after sapropterin therapy (20 mg/kg/day). All subjects' Phe and tyrosine levels were monitored once a week during the study. Subjects kept 3 day diet records that allow calculation of Phe intake.ResultsNone of the subjects responded to sapropterin therapy based on 30% decrease in blood Phe level. The data show that glucose metabolism appeared depressed in the cerebellum and left parietal cortex while it was increased in the frontal and anterior cingulate cortices in all five subjects. In response to sapropterin therapy, relative glucose metabolism showed significant increases in left Broca's and right superior lateral temporal cortices. Interestingly, there was corresponding enhanced performance in a phonemic fluency test performed during pre- and postneurocognitive evaluation.ConclusionsFurther studies with a larger sample size are needed to confirm the above changes in both sapropterin non-responsive and responsive PKU patients.

Measurement of glucose metabolism in rat spinal cord slices with dynamic positron autoradiography

We attempted to measure the regional metabolic rate of glucose (MRglc) in sliced spinal cords in vitro. The thoracic spinal cord of a mature Wister rat was cut into 400-mum slices in oxygenated and cooled (1-4 degrees C) Krebs-Ringer solution. After at least 60 min of preincubation, the spinal cord slices were transferred into double polystyrene chambers and incubated in Krebs-Ringer solution at 36 degrees C, bubbled with 5% O(2)/5% CO(2) gas. To measure MRglc, we used the dynamic positron autoradiography technique (dPAT) with F-18-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) and the net influx constant of [(18)F]FDG as an index. Uptake curves of [(18)F]FDG were well fitted by straight lines for more than 7 h after the slicing of the spinal cord (linear regression coefficient, r=0.99), indicating a constant uptake of glucose by the spinal cord tissue. The slope (K), which denotes MRglc, is affected by tetrodotoxin, and high K(+) (50 mM) or Ca(2+)-free, high Mg(2+) solution. After 10 min of hypoxia, the K value following reoxygenation was similar to the unloaded control value, but after 45 min of hypoxia, the K value was markedly lower than the unloaded control value, and after >90 min of reoxygenation it was nearly 0. Our results indicate that the living spinal cord slices used retained an activity-dependent metabolism to some extent. This technique may provide a new approach for measuring MRglc in sliced living spinal cord tissue in vitro and for quantifying the dynamic changes in MRglc in response to various interventions such as hypoxia.

Redistribution of whole-body energy metabolism by exercise: a positron emission tomography study

Our aim was to evaluate changes in glucose metabolism of skeletal muscles and viscera induced by different workloads using (18)F-2-fluoro-2-deoxyglucose ([(18)F]FDG) and three-dimensional positron emission tomography (3-D PET). Five male volunteers performed ergometer bicycle exercise for 40 min at 40% and 70% of the maximal O(2) consumption (VO(2max)). [(18)F]FDG was injected 10 min later following the exercise task. Wholebody 3-D PET was performed. Five other male volunteers were studied as a control to compare with the exercise group. The PET image data were analyzed using manually defined regions of interest to quantify the regional metabolic rate of glucose (rMRGlc). Group comparisons were made using analysis of variance, and significant differences (P < 0.05) were determined using Scheffe's test (post hoc analysis). Quantitative analysis demonstrated that rMRGlc increased (P < 0.05) in the skeletal muscles of the thigh at mild or moderate workloads when compared with the resting controls. For visceral organs such as the liver and brain, metabolic reduction was significant (P < 0.05) at mild and/or moderate exercise workload. The present study demonstrated linear increases or decreases in glucose uptake by skeletal muscles and viscera with mild and moderate exercise workloads, suggesting the presence of homeostatic energy metabolism. This result supports the finding that [(18)F]FDG-PET can be used as an index of organ energy metabolism for moderate exercise workloads (70% VO(2max)). The results of this investigation may contribute to sports medicine and rehabilitation science.

Brain-Mapping Techniques for Evaluating Poststroke Recovery and Rehabilitation: A Review

Brain-mapping techniques have proven to be vital in understanding the molecular, cellular, and functional mechanisms of recovery after stroke. This article briefly summarizes the current molecular and functional concepts of stroke recovery and addresses how various neuroimaging techniques can be used to observe these changes. The authors provide an overview of various techniques including diffusion-tensor imaging (DTI), magnetic resonance spectroscopy (MRS), ligand-based positron emission tomography (PET), single-photon emission computed tomography (SPECT), regional cerebral blood flow (rCBF) and regional metabolic rate of glucose (rCMRglc) PET and SPECT, functional magnetic resonance imaging (fMRI), near infrared spectroscopy (NIRS), electroencephalography (EEG), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS). Discussion in the context of poststroke recovery research informs about the applications and limitations of the techniques in the area of rehabilitation research. The authors also provide suggestions on using these techniques in tandem to more thoroughly address the outstanding questions in the field.

Positron emission tomography study of regional brain metabolic responses to a serotonergic challenge in major depressive disorder with and without comorbid lifetime alcohol dependence

This is the first study contrasting regional glucose metabolic rate (rCMRglu) responses to a serotonergic challenge in major depressive disorder (MDD) with and without comorbid alcohol dependence. In a university hospital, patients with MDD without a history of alcohol dependence (MDD only) and patients with MDD and comorbid alcohol dependence (MDD/ALC) were enrolled in this study. Subjects with comorbid borderline personality disorder were excluded. A bolus injection of approximately 5 mCi of 18fluorodeoxyglucose was administered 3 h after the administration of placebo or fenfluramine. We found an anterior medial prefrontal cortical area where MDD/ALC subjects had more severe hypofrontality than MDD only patients. This area encompassed the left medial frontal and left and right anterior cingulate gyri. This group difference disappeared after fenfluramine administration. The fact that the observed group difference disappeared after the fenfluramine challenge suggests that serotonergic mechanisms play a role in the observed differences between the groups.

Differences in glucose metabolism between dementia with Lewy bodies and dementia associated with Parkinson's disease

Objectives: Post-mortem studies of patients with Parkinson's disease with dementia (PDD) and patients with Lewy body dementia (DLB) have shown both cortical Lewy bodies and Alzheimer-type pathology; however, the associated metabolic changes are not well characterized in this population. We performed 3D positron emission tomography (PET) with 18F-2-fluoro-2-desoxyglucose (18F-FDG) to determine the impact of PDD and DLB upon the regional metabolic rate of glucose (CMRglc).

High intensity exercise decreases global brain glucose uptake in humans.

Physiological activation increases glucose uptake locally in the brain. However, it is not known how high intensity exercise affects regional and global brain glucose uptake. The effect of exercise intensity and exercise capacity on brain glucose uptake was directly measured using positron emission tomography (PET) and [18F]fluoro-deoxy-glucose ([18F]FDG). Fourteen healthy, right-handed men were studied after 35 min of bicycle exercise at exercise intensities corresponding to 30, 55 and 75% of on three separate days. [18F]FDG was injected 10 min after the start of the exercise. Thereafter exercise was continued for another 25 min. PET scanning of the brain was conducted after completion of the exercise. Regional glucose metabolic rate (rGMR) decreased in all measured cortical regions as exercise intensity increased. The mean decrease between the highest and lowest exercise intensity was 32% globally in the brain (38.6+/-4.6 versus 26.1+/-5.0 micromol (100 g)-1 min-1, P<0.001). Lactate availability during exercise tended to correlate negatively with the observed brain glucose uptake. In addition, the decrease in glucose uptake in the dorsal part of the anterior cingulate cortex (37% versus 20%, P<0.05 between 30% and 75% of VO2max) was significantly more pronounced in subjects with higher exercise capacity. These results demonstrate that brain glucose uptake decreases with increase in exercise intensity. Therefore substrates other than glucose, most likely lactate, are utilized by the brain in order to compensate the increased energy needed to maintain neuronal activity during high intensity exercise. Moreover, it seems that exercise training could be related to adaptive metabolic changes locally in the frontal cortical regions.

Thalamic and Prefrontal FDG Uptake in Never Medicated Patients With Schizophrenia

Because neuroleptic treatment may cause long-lasting changes in brain structure and function, a group of patients with schizophrenia who had never been medicated was recruited to examine regional glucose metabolic rates in the frontal-striato-thalamic circuit. Twelve never medicated patients with schizophrenia (seven men, five women; mean age=29 years) and 13 normal volunteers (eight men and five women; mean age=28.5 years) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography, and coregistered anatomical magnetic resonance imaging scans were also obtained. During FDG uptake, subjects performed a spatial attention task previously shown to activate the pulvinar region of the thalamus. Diminished regional glucose metabolism was found in the medial dorsal nucleus, posterior thalamus, and prefrontal cortex of patients with schizophrenia relative to normal volunteers, extending earlier results from studies of medicated and previously medicated patients. The finding of lower relative metabolic rates in the frontothalamic circuits of patients with schizophrenia is consistent with extended circuit deficits involving interactions of frontal executive areas with thalamic sensory and association processes.

MCI conversion to dementia and the APOE genotype

To investigate whether the combination of fluoro-2-deoxy-d-glucose (FDG) PET measures with the APOE genotype would improve prediction of the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). After 1 year, 8 of 37 patients with MCI converted to AD (22%). Differences in baseline regional glucose metabolic rate (rCMRglc) across groups were assessed on a voxel-based basis using a two-factor analysis of variance with outcome (converters [n = 8] vs nonconverters [n = 29]) and APOE genotype (E4 carriers [E4+] [n = 16] vs noncarriers [E4-] [n = 21]) as grouping factors. Results were considered significant at p < 0.05, corrected for multiple comparisons. All converters showed reduced rCMRglc in the inferior parietal cortex (IPC) as compared with the nonconverters. Hypometabolism in AD-typical regions, that is, temporoparietal and posterior cingulate cortex, was found for the E4+ as compared with the E4- patients, with the E4+/converters (n = 5) having additional rCMRglc reductions within frontal areas, such as the anterior cingulate (ACC) and inferior frontal (IFC) cortex. For the whole MCI sample, IPC rCMRglc predicted conversion to AD with 84% overall diagnostic accuracy (p = 0.003). Moreover, ACC and IFC rCMRglc improved prediction for the E4+ group, yielding 100% sensitivity, 90% specificity, and 94% accuracy (p < 0.0005), thus leading to an excellent discrimination. Fluoro-2-deoxy-d-glucose-PET measures may improve prediction of the conversion to Alzheimer disease, especially in combination with the APOE genotype.

Regional brain responses to serotonin in major depressive disorder

Background: Positron Emission Tomography (PET) studies have reported altered resting regional brain glucose metabolism in mood disorders. This study examines the relationship of such changes to serotonin system abnormalities associated with depression. Methods: Thirteen male medication free subjects who were inpatients with a DSM-IIIR major depressive disorder and seven healthy male subjects underwent an [ 18F]-fluorodeoxyglucose ( 18FDG) PET scan on consecutive days. Three hours prior to 18FDG subjects received single blind placebo or fenfluramine. Comparisons of voxel level regional glucose metabolic rate responses (rCMRglu) between groups in the two states were performed with SPM99. Results: Unlike healthy male subjects who have significant increases in rCMRglu in prefrontal and parietal cortical regions after receiving fenfluramine, depressed male subjects have no significant increases in rCMRglu. Conclusions: Blunted increases in rCMRglu in response to fenfluramine in prefrontal and parietal cortex are consistent with our previous pilot study and the indoleamine hypothesis of depression. Differences in specific brain regions affected between this study and previous studies may be attributable to gender differences.

Hemispherical dominance of glucose metabolic rate in the brain of the 'normal' ageing population

In the 'normal' ageing brain a decrease in the cerebral metabolic rate has been determined across many brain regions. This study determines whether age differences would affect metabolic rates in regions and different hemispheres of the brain. The regional metabolic rate of glucose (rCMRGlu) was examined in a group of 72 subjects, ages 22 to 82 years, with 36 regions of interest chosen from both hemispheres of the cortex, midbrain and cerebellum. To determine metabolic rates the in-vivo technique of positron emission tomography (PET) was employed. Three age groups were chosen to compare hemispherical differences. In both young and intermediate age groups the left hemisphere had higher rCMRGlu values than those of the right for the majority of regions with, although less pronounced in the intermediate group. Importantly, the older age group displayed little difference between hemispheres.