Age differences in intercorrelations between regional cerebral metabolic rates for glucose

Patterns of cerebral metabolic intercorrelations were compared in the resting state in 15 healthy young men (ages 20 to 32 years) and 15 healthy elderly men (ages 64 to 83 years). Controlling for whole-brain glucose metabolism, partial correlation coefficients were determined between pairs of regional cerebral metabolic rates for glucose determined by positron emission tomography using [18F]fluorodeoxyglucose and obtained in 59 brain regions. Compared with the young men, the elderly men had fewer statistically significant correlations, with the most notable reductions observed between the parietal lobe regions, and between the parietal and frontal lobe regions. These results suggest that cerebral functional interactions are reduced in healthy elderly men.     

Cerebral metabolic pattern in obsessive-compulsive disorder: Altered intercorrelations between regional rates of glucose utilization

Correlations between normalized regional cerebral metabolic rates for glucose, determined by positron emission tomography with ¹⁸F-2-fluoro-2-deoxy- -glucose, were used to investigate functional associations between pairs of brain regions in 18 adult patients with primary obsessive-compulsive disorder (OCD) of childhood-onset, as compared with 18 age- and sex-matched control subjects. The number of correlations that differed significantly between the two groups exceeded chance, although as many of these correlations were larger in the OCD group relative to controls as were smaller. The two regions that had the largest number of correlations that differed significantly between groups were a left hemisphere superior parietal region and the left hemisphere anterior medial temporal area (which includes principally the amygdala). Correlations involving the caudate nuclei did not differ between the two groups for the most part. Anterior limbic/paralimbic regions had correlations in the OCD group that were significantly larger with frontal areas than in controls, and correlations that were significantly smaller with posterior brain regions. This pattern was especially pronounced for the left hemisphere anterior medial temporal region. These results suggest that the correlation pattern in OCD is not characterized by an overall loss of functional integration but, rather, by functional reorganization.     

Cerebral metabolic pattern in obsessive-compulsive disorder: altered intercorrelations between regional rates of glucose utilization.

Correlations between normalized regional cerebral metabolic rates for glucose, determined by positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose, were used to investigate functional associations between pairs of brain regions in 18 adult patients with primary obsessive-compulsive disorder (OCD) of childhood-onset, as compared with 18 age- and sex-matched control subjects. The number of correlations that differed significantly between the two groups exceeded chance, although as many of these correlations were larger in the OCD group relative to controls as were smaller. The two regions that had the largest number of correlations that differed significantly between groups were a left hemisphere superior parietal region and the left hemisphere anterior medial temporal area (which includes principally the amygdala). Correlations involving the caudate nuclei did not differ between the two groups for the most part. Anterior limbic/paralimbic regions had correlations in the OCD group that were significantly larger with frontal areas than in controls, and correlations that were significantly smaller with posterior brain regions. This pattern was especially pronounced for the left hemisphere anterior medial temporal region. These results suggest that the correlation pattern in OCD is not characterized by an overall loss of functional integration but, rather, by functional reorganization.     

Altered relationships between metabolic rates of glucose in brain regions of schizophrenic patients

Regional brain glucose metabolism was studied with positron emission tomography (PET) in healthy volunteers (n = 9) and schizophrenic patients (n = 15). The patients were in an acute phase of the disease and drug free. Cerebral metabolic rate with 11C-glucose as the tracer (CMRgl) was determined in both cortical and subcortical structures. In the healthy volunteers significant correlations were found between metabolic rates of some regions, but no relationships were found between CMRgl of limbic cortical areas and that of neocortical or subcortical structures. In the patients, high and significant positive correlations were found between metabolic rates in the neocortical areas, the limbic cortical areas and the subcortical areas. The results indicate differences in the neuronal interplay between regions of healthy and schizophrenic subjects. It is proposed that neuronal systems guiding the specificity and diversity in neuronal functions between different brain regions, are abnormal in schizophrenic patients. Such a disturbance may be the basis for the diversity of psychiatric symptoms in schizophrenics.     

Cerebral metabolic pattern in young adult Down's syndrome subjects: altered intercorrelations between regional rates of glucose utilization

ABSTRACT. Correlations between regional cerebral metabolic rates for glucose determined by pisitron emission tomography with [¹⁸F]-2-fluoro-2-deoxy-D-glucose, have heen used to indicate functional associations between pairs of brain regions. This method was applied to data from 14 healthy adult subjects with trisomy 21 Down's syndrome tape < 34 years) and from 24 age-matched healthy controls. Correlations were obtained between ratios of regional-to-global resting glucose utilization. In comparison to age-matched controls, the Down's svndrome group had many smaller correlations for region-pairs wilhin and between the frontal and parietal lubes, some correlations were large and negative in the Down's syndrome group, but large and positive in the controls. One region so affected was the inferior frontal gyrus thai includes Broca's area. This result is consistent with ihe relatively greater language impairment in Down's syndrome subjects. The thalamus also had smaller correlations with temporal and occipital regions in the Down's syndrome group compared: to controls. These results suggest that Down's syndrome is accompanied by a functional disruption of neural circuits associated with directed attention.     

Intercorrelations of regional cerebral glucose metabolic rates in Alzheimer''s disease

Patterns of cerebral metabolic correlations were compared between 21 Alzheimer's disease patients and 21 healthy age-matched controls in the resting state. Cerebral metabolic rates for glucose were determined by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. Partial correlation coefficients, controlling for whole brain glucose metabolism, were evaluated between pairs of regional glucose metabolic rates in 59 brain regions. Reliable correlation coefficients were obtained with the 'jackknife' and 'bootstrap' statistical procedures. Compared with healthy controls, the Alzheimer patients had significantly fewer reliable partial correlation coefficients between frontal and parietal lobe regions, and more reliable correlations between the cerebellum and temporal lobe. The number of reliable correlations between many bilaterally symmetric brain regions was reduced in the Alzheimer patients, as compared with controls. These results suggest that in the early stages of Alzheimer's disease there is a breakdown of the organized functional activity between the two cerebral hemispheres, and between parietal and frontal lobe structures.     

Functional correlates of effect: the relevance of regional cerebral brain dysfunction

Schneider F. Functional correlates of effect: the relevance of regional cerebral brain dysfunction. Bipolar Disord 2002: 4(Suppl. 1): 51. © Blackwell Munksgaard, 2002     

Integrating "brain" and "body" measures: correlations between EEG and metabolic changes over the human lifespan

AIMS: This study investigated the relationship between electroencephalograph (EEG) power and basal metabolic rate (BMR) over the human lifespan, to better understand the mechanisms involved in the decline of neural activity with age. METHODS: Eyes-open EEG power was calculated in standard frequency bands and averaged across recording sites in 1831 healthy subjects aged 6 to 86 years, from the Brain Resource International Database. In a subset of 175 subjects, structural MRI scans were also undertaken to determine the role of grey matter. Cerebral metabolic rate (CMR) was estimated using two models of EEG power, based on: (1) normalization of BMR by total body mass, and (2) scaling by cortical grey matter. RESULTS: Regression analysis revealed a linear relationship between the CMR estimates and EEG power under both models. In the full sample, CMR explained 65% of the variance in delta power, and 53% of the variance in theta power over the age span. DISCUSSION: The results demonstrate that the large EEG signals in early childhood are associated with a higher BMR during that age. INTEGRATIVE SIGNIFICANCE: The use of cross-modal measurements in this study highlights the utility of capturing data in an integrative framework to reveal fundamental physiological relationships.     

Intercorrelations of glucose metabolic rates between brain regions: application to healthy males in a state of reduced sensory input

We use a correlational analysis of regional metabolic rates to characterize relations among different brain regions. Starting with rates of local glucose metabolism (rCMRglc) obtained by positron emission tomography using [18F]fluorodeoxyglucose, we propose that the strength of the association is proportional to the magnitude of the correlation coefficient. Partial correlation coefficients, controlling for whole brain glucose metabolism, are used in the analysis. We also introduce a graphical technique to display simultaneously all the correlations, allowing us to examine patterns of relations among them. The method was applied to 40 very healthy males under conditions of reduced auditory and visual inputs (the "resting state"). Dividing the brain into 59 regions, and keeping only those partial correlation coefficients significant to p less than 0.01, we found the following: (a) All regions were significantly correlated with their contralateral homologues. For the most part, the largest partial correlation coefficients were between homologous brain regions. (b) Generally, the pattern of significant correlations between any two lobes in the left hemisphere did not differ statistically from the corresponding pattern in the right hemisphere. (c) Strong correlations were observed between primary somatosensory areas and premotor association areas. Correlations between these association areas and primary visual and auditory regions were not statistically significant. (d) Significant correlations between inferior occipital and temporal areas were found. Metabolic rates in the superior part of the occipital lobe were not correlated significantly with metabolic rates in regions of the temporal lobe, nor with metabolism in the parietal lobe. (e) As a whole, there were numerous correlations among frontal and parietal lobe regions, on the one hand, and among temporal and occipital lobe regions, on the other, but few statistically significant correlations between these two domains. We relate our results to various aspects of known brain anatomy, physiology, and cognitive functioning.     

Functional coupling of simultaneous electrical and metabolic activity in the human brain

The relationships between brain electrical and metabolic activity are being uncovered currently in animal models using invasive methods; however, in the human brain this relationship remains not well understood. In particular, the relationship between noninvasive measurements of electrical activity and metabolism remains largely undefined. To understand better these relations, cerebral activity was measured simultaneously with electroencephalography (EEG) and positron emission tomography using [(18)f]-fluoro-2-deoxy-D-glucose (PET-FDG) in 12 normal human subjects during rest. Intracerebral distributions of current density were estimated, yielding tomographic maps for seven standard EEG frequency bands. The PET and EEG data were registered to the same space and voxel dimensions, and correlational maps were created on a voxel-by-voxel basis across all subjects. For each band, significant positive and negative correlations were found that are generally consistent with extant understanding of EEG band power function. With increasing EEG frequency, there was an increase in the number of positively correlated voxels, whereas the lower alpha band (8.5-10.0 Hz) was associated with the highest number of negative correlations. This work presents a method for comparing EEG signals with other more traditionally tomographic functional imaging data on a 3-D basis. This method will be useful in the future when it is applied to functional imaging methods with faster time resolution, such as short half-life PET blood flow tracers and functional magnetic resonance imaging.     

Time-course and regional distribution of the metabolic effects of bromocriptine in the rat brain

Local cerebral glucose utilization (LCGU) and motor behavior were examined in awake Fischer-344 rats after administration of the dopaminergic agonist bromocriptine (BROMO). LCGU was measured using the [14C]2-deoxyglucose technique in 63 brain regions at 1,2,3 or 4 h after BROMO 20 mg/kg, and at 4 h after BROMO 100 mg/kg i.p. At 2 h, LCGU was reduced significantly in 13% of the 63 regions examined. The affected regions are related to the topographical distribution of dopaminergic innervation in the brain. At 3-4 h, LCGU remained depressed in some of the above dopaminergic regions, but was elevated significantly in regions which are involved in sensorimotor function. BROMO also produced two behavioral effects depending on time after administration. Locomotor activity was depressed at 1-2 h, and stereotyped behavior appeared at 3-4 h. The time-dependent effects of BROMO may reflect progressively increasing brain concentrations of the drug or of its active metabolites. The coincidence of locomotor depression and reduction of LCGU in dopaminergic regions suggests a role of dopamine autoreceptors in regulation of motor function. Metabolic stimulation of many non-dopaminergic regions when stereotypy is evident suggests that circuit(s) involving these areas may contribute to stereotypy.     

Global and regional annual brain volume loss rates in physiological aging

The objective is to estimate average global and regional percentage brain volume loss per year (BVL/year) of the physiologically ageing brain. Two independent, cross-sectional single scanner cohorts of healthy subjects were included. The first cohort (n = 248) was acquired at the Medical Prevention Center (MPCH) in Hamburg, Germany. The second cohort (n = 316) was taken from the Open Access Series of Imaging Studies (OASIS). Brain parenchyma (BP), grey matter (GM), white matter (WM), corpus callosum (CC), and thalamus volumes were calculated. A non-parametric technique was applied to fit the resulting age–volume data. For each age, the BVL/year was derived from the age–volume curves. The resulting BVL/year curves were compared between the two cohorts. For the MPCH cohort, the BVL/year curve of the BP was an increasing function starting from 0.20% at the age of 35 years increasing to 0.52% at 70 years (corresponding values for GM ranged from 0.32 to 0.55%, WM from 0.02 to 0.47%, CC from 0.07 to 0.48%, and thalamus from 0.25 to 0.54%). Mean absolute difference between BVL/year trajectories across the age range of 35–70 years was 0.02% for BP, 0.04% for GM, 0.04% for WM, 0.11% for CC, and 0.02% for the thalamus. Physiological BVL/year rates were remarkably consistent between the two cohorts and independent from the scanner applied. Average BVL/year was clearly age and compartment dependent. These results need to be taken into account when defining cut-off values for pathological annual brain volume loss in disease models, such as multiple sclerosis.     

Father-infant interactions and infant regional brain volumes: A cross-sectional MRI study

Fathers play a crucial role in their children’s socio-emotional and cognitive development. A plausible intermediate phenotype underlying this association is father’s impact on infant brain. However, research on the association between paternal caregiving and child brain biology is scarce, particularly during infancy. Thus, we used magnetic resonance imaging (MRI) to investigate the relationship between observed father–infant interactions, specifically paternal sensitivity, and regional brain volumes in a community sample of 3-to-6-month-old infants (N = 28). We controlled for maternal sensitivity and examined the moderating role of infant communication on this relationship. T2-weighted MR images were acquired from infants during natural sleep. Higher levels of paternal sensitivity were associated with smaller cerebellar volumes in infants with high communication levels. In contrast, paternal sensitivity was not associated with subcortical grey matter volumes in the whole sample, and this was similar in infants with both high and low communication levels. This preliminary study provides the first evidence for an association between father-child interactions and variation in infant brain anatomy.     

Enhanced regional cerebral metabolic interactions in thalamic circuitry predicts motor recovery in hemiparetic stroke

We applied a multiple regression/discriminant analysis to resting metabolic data from patients with first hemiparetic suprathalamic infarctions to determine if metabolic interdependencies, which may separate recovered (N = 12) from nonrecovered (N = 9) patients, suggest important motor-recovery pathways. Recovered, vs. nonrecovered, patients showed an enhanced ipsilesional thalamic-contralesional cerebellar metabolic interdependency. This pattern correctly classified 91% of recovered and 88% of nonrecovered patients. Metabolic interactions involving bilateral supplementary motor area, ipsilesional thalamus, and contralesional cerebellum distinguished all recovered patients from age/sex-matched controls (N = 12). These results suggest that altered functional interactions in thalamic circuitry may reflect plastic reorganization associated with motor recovery from hemiparesis. © 1997 Wiley-Liss, Inc.     

Functional brain imaging of tobacco use and dependence

While most cigarette smokers endorse a desire to quit smoking, only about 14% to 49% will achieve abstinence after 6 months or more of treatment. A greater understanding of the effects of smoking on brain function may (in conjunction with other lines of research) result in improved pharmacological (and behavioral) interventions. Many research groups have examined the effects of acute and chronic nicotine/cigarette exposure on brain activity using functional imaging; the purpose of this paper is to synthesize findings from such studies and present a coherent model of brain function in smokers. Responses to acute administration of nicotine/smoking include: a reduction in global brain activity; activation of the prefrontal cortex, thalamus, and visual system; activation of the thalamus and visual cortex during visual cognitive tasks; and increased dopamine (DA) concentration in the ventral striatum/nucleus accumbens. Responses to chronic nicotine/cigarette exposure include decreased monoamine oxidase (MAO) A and B activity in the basal ganglia and a reduction in alpha4beta2 nicotinic acetylcholine receptor (nAChR) availability in the thalamus and putamen. Taken together, these findings indicate that smoking enhances neurotransmission through cortico-basal ganglia-thalamic circuits either by direct stimulation of nAChRs, indirect stimulation via DA release or MAO inhibition, or a combination of these factors. Activation of this circuitry may be responsible for the effects of smoking seen in tobacco dependent subjects, such as improvements in attentional performance, mood, anxiety, and irritability.     

Correlations of regional postmortem enzyme activities with premortem local glucose metabolic rates in Alzheimer's disease

Correlations were sought between local cerebral metabolic rates (LCMRs) for glucose in various regions of the cortex, determined in premortem PET scans, with the regional activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), beta-glucuronidase (Gluc, a probable index of reactive gliosis), and phosphate-activated glutaminase (PAG, a possible indice of the large pyramidal neurons) measured on postmortem tissue. Significant negative correlations between LCMRs and Gluc activities were found in 6 PET-scanned cases of Alzheimer disease (AD), and positive correlations of LCMRs with PAG were found in 5. By contrast, a positive correlation with ChAT and AChE was found in only 1. The results are consistent with the metabolic deficits in AD being primarily a reflection of local neuronal loss and gliosis. Similar data on two cases of Huntington's disease showed no significant correlations, while 1 patient with Parkinson dementia showed a significant (negative) correlation only with Gluc.     

Functional integration changes in regional brain glucose metabolism from childhood to adulthood

The aim of this study was to investigate the age‐related changes in resting‐state neurometabolic connectivity from childhood to adulthood (6–50 years old). Fifty‐four healthy adult subjects and twenty‐three pseudo‐healthy children underwent [¹⁸F]‐fluorodeoxyglucose positron emission tomography at rest. Using statistical parametric mapping (SPM8), age and age squared were first used as covariate of interest to identify linear and non‐linear age effects on the regional distribution of glucose metabolism throughout the brain. Then, by selecting voxels of interest (VOI) within the regions showing significant age‐related metabolic changes, a psychophysiological interaction (PPI) analysis was used to search for age‐induced changes in the contribution of VOIs to the metabolic activity in other brain areas. Significant linear or non‐linear age‐related changes in regional glucose metabolism were found in prefrontal cortices (DMPFC/ACC), cerebellar lobules, and thalamo‐hippocampal areas bilaterally. Decreases were found in the contribution of thalamic, hippocampal, and cerebellar regions to DMPFC/ACC metabolic activity as well as in the contribution of hippocampi to preSMA and right IFG metabolic activities. Increases were found in the contribution of the right hippocampus to insular cortex and of the cerebellar lobule IX to superior parietal cortex metabolic activities. This study evidences significant linear or non‐linear age‐related changes in regional glucose metabolism of mesial prefrontal, thalamic, mesiotemporal, and cerebellar areas, associated with significant modifications in neurometabolic connectivity involving fronto‐thalamic, fronto‐hippocampal, and fronto‐cerebellar networks. These changes in functional brain integration likely represent a metabolic correlate of age‐dependent effects on sensory, motor, and high‐level cognitive functional networks. Hum Brain Mapp 37:3017–3030, 2016. © 2016 Wiley Periodicals, Inc .     

Functional heterotypic interactions between astrocyte and oligodendrocyte connexins

Human genetic diseases and mouse knockouts illustrate that the maintenance of central nervous system myelin requires connexin expression by both astrocytes and oligodendrocytes. Because these cell types express nonoverlapping sets of connexins, the intercellular channels formed between them must be asymmetric with regard to connexin content, defined as heterotypic. Here, we show that oligodendrocyte Cx47 can form heterotypic channels with astrocyte Cx43 or Cx30 but not Cx26, whereas oligodendrocyte Cx32 can functionally interact with astrocyte Cx30 or Cx26 but not Cx43. Thus, as many as four types of intercellular channels could be formed between astrocytes and oligodendrocytes.     

Brief report: Attention performance in autism and regional brain metabolic rate assessed by positron emission tomography

The Stallone Foundation and the MacArthur Foundation provided partial support for this research. Andrew Russell, Linda Bott, and Cathy Sammons did the diagnostic interviews.