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Biomedical subjects

C L Grady

Publications and source records attributed to C L Grady.

At least 19 recordsLinked to original sources

Interregional correlations of resting cerebral glucose metabolism in old and young women.

A correlational analysis of normalized (regional to whole-brain) regional cerebral metabolic rates for glucose obtained in the 'resting' state (eyes covered, ears plugged) using [18F]fluorodeoxyglucose, demonstrated differences between old and young women in patterns of functional associations. Fifteen healthy young (age less than 40 years) and 17 healthy old women (age greater than 64 years) were scanned with a Scanditronix PC1024-7B tomograph. The brain was divided into 65 regions of interest. The old women had fewer and less positive correlations between pairs of metabolic ratios in the frontal and parietal cortices. The results suggest an age-related reduction in frontal and parietal functional interactions in the 'resting' state that is consistent with a prior correlation analysis using a low resolution ECAT II scanner on young and old men. Reduced functional interactions may reflect age-related cognitive changes.

Adult

Gender differences in correlations of cerebral glucose metabolic rates in young normal adults.

Correlational analysis of normalized regional cerebral metabolic data obtained by positron emission tomography, in healthy subjects in the 'resting' state (eyes covered, ears plugged) using [18F]2-fluoro-2-deoxy-D-glucose, demonstrated gender differences in patterns of functional associations. Fifteen women and 18 men (less than 40 yr) were scanned with a Scanditronix PC1024-7B tomograph. The brain was divided into 65 regions of interest (ROIs). There were no differences between men and women in global or regional metabolic rates, or in metabolic right-left asymmetries. Although the total number of significant correlations did not differ between men and women, patterns differed: female correlations rF were most positive than male correlations rM more often than rM greater than rF; and most rF greater than rM cases involved left frontal and sensorimotor ROIs, whereas most rM greater than rF cases involved right sensorimotor and occipital ROIs. The findings demonstrate gender differences in the pattern of functional neocortical interactions at the 'resting' state.

Adult

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy.

To investigate the effects of drug treatment in childhood-onset obsessive-compulsive disorder (OCD), we repeated positron emission tomographic scans in 13 adults with OCD (eight taking clomipramine, two taking fluoxetine, and three taking no drug) after at least 1 year of pharmacotherapy. As a group, the patients had a significant improvement on all OCD and anxiety ratings. Positron emission tomography revealed a significant decrease in normalized orbitofrontal regional cerebral glucose metabolism (relative to global metabolism) bilaterally. Among the treated patients, the decrease in right orbitofrontal metabolism was directly correlated with two measures of OCD improvement. These results extend previous positron emission tomographic findings of regional dysfunction in OCD and suggest involvement of the orbitofrontal regions in the pathophysiology of OCD.

Adult

Visuospatial attention in dementia of the Alzheimer type.

Cue-directed shifts of spatial attention were examined for a letter-discrimination task in 15 patients with mild to moderate dementia of the Alzheimer type (DAT) and 15 healthy, age-matched controls. Spatial cues were valid, invalid or neutral in indicating probable target location and were presented either centrally at fixation or peripherally 6.7 degrees to the left or right of fixation. Stimulus-onset asynchrony (SOA) between cue and target was varied between 200 ms and 2000 ms. Reaction time (RT) benefits conferred by valid cues did not differ between the DAT group and the controls. However, RT costs incurred by invalid cues were significantly greater in the DAT group than in the control group. Group differences in RT costs plus benefits occurred at short SOAs (less than 500 ms) for peripheral cues and at long SOAs (greater than 500 ms) for central cues. Reaction time costs plus benefits were correlated with right-left asymmetry in resting levels of cerebral glucose metabolism in the superior parietal lobe for DAT patients but not for controls. The results indicate that focusing of attention to spatial location is intact in early DAT, whereas the disengagement of visuospatial attention is impaired. Automatic attention shifts elicited by peripheral cues reveal abnormalities earlier than attention shifts initiated 'effortfully' by central cues. Intact focusing and impaired disengagement of visuospatial attention may be linked to dysfunction in early DAT of cortico-cortical networks linking the posterior parietal and frontal lobes.

Aged

Dissociation of object and spatial visual processing pathways in human extrastriate cortex.

The existence and neuroanatomical locations of separate extrastriate visual pathways for object recognition and spatial localization were investigated in healthy young men. Regional cerebral blood flow was measured by positron emission tomography and bolus injections of H2(15)O, while subjects performed face matching, dot-location matching, or sensorimotor control tasks. Both visual matching tasks activated lateral occipital cortex. Face discrimination alone activated a region of occipitotemporal cortex that was anterior and inferior to the occipital area activated by both tasks. The spatial location task alone activated a region of lateral superior parietal cortex. Perisylvian and anterior temporal cortices were not activated by either task. These results demonstrate the existence of three functionally dissociable regions of human visual extrastriate cortex. The ventral and dorsal locations of the regions specialized for object recognition and spatial localization, respectively, suggest some homology between human and nonhuman primate extrastriate cortex, with displacement in human brain, possibly related to the evolution of phylogenetically newer cortical areas.

Adult

Anatomic, metabolic, neuropsychological, and molecular genetic studies of three pairs of identical twins discordant for dementia of the Alzheimer's type.

Three pairs of twins, each with proved monozygosity, were shown to be discordant for dementia of the Alzheimer's type and to have remained discordant for periods of 8 to 11 years. Dementia of the Alzheimer's type was demonstrated by history; serial clinical examinations; serial measurements of cerebral glucose utilization using positron emission tomography and of cerebral ventricular volumes and of rates of change of volumes using quantitative computed tomography; and by serial neuropsychological tests. The results of each of these measures showed no evidence of clinical abnormality in any unaffected twin. DNA markers from the proximal long arm of chromosome 21 did not distinguish between the affected and the unaffected member of any pair of identical twins. Family pedigrees were negative for Alzheimer's disease. The results suggest that environmental or other nongenetic factors contribute to Alzheimer's disease in discordant monozygotic twins, or that some cases arise by a postzygotic somatic mutation.

Aged

Regional cerebral glucose metabolism of women with trichotillomania.

Positron emission tomography and 18-F-fluorodeoxyglucose were used to study resting cerebral glucose metabolism in 10 adult women with trichotillomania and 20 age-matched female controls. As a group, the patients with trichotillomania showed significantly increased global (mean gray matter) and normalized right and left cerebellar and right superior parietal glucose metabolic rates. Contrary to expectation, this pattern differed from that seen in our previous investigation of obsessive-compulsive disorder. Clomipramine hydrochloride-induced improvement was negatively correlated with anterior cingulate and orbital frontal metabolism, of particular interest because similar results had been obtained for obsessive-compulsive disorder.

Adult

Abnormal brain glucose metabolism in Alzheimer's disease, as measured by position emission tomography.

Resting glucose metabolism in the association neocortices, measured with positron emission tomography (PET), is disturbed early and throughout the course of Alzheimer's disease (AD), whereas resting metabolism in the primary sensory and motor neocortices is relatively spared. Neocortical metabolic asymmetries precede and predict appropriate deficits in neocortically-mediated cognitive functions in the initial course of disease, indicating that PET can be used for the early diagnosis and characterization of AD. Metabolic abnormalities of the neocortices in late-stage AD correlate with regional densities of neurofibrillary tangles but not of senile plaques post mortem, suggesting that tangle formation is important in disease pathogenesis. Despite demonstrating reduced resting glucose metabolism, visual association areas demonstrate equivalent (as percent baseline) blood flow responses in mildly-moderately demented AD patients and controls who are performing a face matching task. Thus, viability and integrity of this cortical circuitry is retained into the intermediate stages of the disease, and glucose delivery to the AD brain can be increased.

Alzheimer Disease

Mapping the functional neuroanatomy of the intact human brain with brain work imaging.

The recent development of noninvasive methods for measuring local rates of energy metabolism or blood flow in the brain has made it possible to investigate functional neuroanatomy in healthy human subjects. The best of these methods, high resolution measurement of regional cerebral blood flow (rCBF) with positron emission tomography (PET), provides a precision of anatomical localization that far exceeds that attainable with human brain lesion studies. Moreover, the study of healthy subjects avoids possible confounding effects of brain lesions, such as compensatory reorganization of brain function. PET-rCBF studies have already identified several cortical areas involved in higher-order visual processing, indicating that functional neuroimaging may yield a map of human visual cortex analogous to maps that have been developed by vision research in nonhuman primates. PET-rCBF studies of imagery and language demonstrate the potential of functional neuroimaging to map regions of human cortex that perform functions that cannot be studied so easily in nonhuman primates or perform functions that humans do not share with other species.

Attention

Divided attention and metabolic brain dysfunction in mild dementia of the Alzheimer's type.

The relationship between reaction time (RT) measures under single-task and dual-task conditions and resting levels of brain metabolism, as measured by positron emission tomography (PET), was examined in patients with mild dementia of the Alzheimer type (DAT) and age- and educationally-matched controls. Slowing of RT in dual-task but not single-task conditions correlated with reductions in brain metabolism in right premotor and right parietal association areas only for the mild DAT patients. The results suggest a relation between divided attention deficits and metabolic dysfunction of right frontal and parietal lobes in mild DAT patients.

Aged

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.

Adult

Quantitative comparison of measurements of cerebral glucose metabolic rate made with two positron cameras.

The rapid progress in PET technology has created the dilemma of how to compare data from old and new tomographs. We examined cerebral metabolic data from two scanners, with different spatial resolutions and methods of attenuation correction, to see if metabolic values from the lower-resolution tomograph (ECAT II) could be adjusted to make them comparable to data from the higher-resolution scanner (Scanditronix PC1024-7B). Nine subjects were scanned on both tomographs after a single injection of [18F]2-fluoro-2-deoxy-D-glucose. Regional and lobar gray matter metabolic rates for glucose were obtained from comparable images from each scanner. Ratios of lobar to global gray matter metabolism also were calculated. Regression coefficients and percent differences were computed to compare ECAT II and PC1024 data. Two-thirds of the region pairs showed significant regressions, although percent differences were quite variable, with measures of glucose utilization ranging from 30 to 120% higher on the PC1024 compared to those from the ECAT II. Comparisons of lobar glucose rates between the two machines were less variable (50 to 80%), and ratios differed by only +/- 5% (except for the temporal ratios). Since there was no simple and consistent relationship between regional metabolic rates on the two tomographs, an overall adjustment of regional ECAT values for comparison to PC1024 values would be impossible. A region-by-region adjustment would be necessary. Lobar ratios are sufficiently similar that direct comparisons might be possible.

Aged

Longitudinal study of cerebral metabolic asymmetries and associated neuropsychological patterns in early dementia of the Alzheimer type.

Regional cerebral metabolic rates for glucose (rCMRglc), as measured with positron emission tomography, and neuropsychological function were studied longitudinally (range, 15 to 48 months) in 11 mildly impaired patients with dementia of the Alzheimer type (DAT) and compared with results from patients with moderate and severe DAT and from controls. At initial evaluation, association cortex metabolic asymmetries were greater in patients with DAT than in controls for all dementia severities and correlated significantly with neuropsychological discrepancies between visuospatial and language abilities in patients with moderate dementia. In mildly impaired patients, right-left metabolic asymmetries in the association cortices were directionally stable and became more pronounced over time. At initial evaluation, these patients had significant impairment, relative to controls, on tests of memory and attention to complex tasks but not on tests of language and visuospatial function. Memory, attention, language, and visuospatial impairments, however, all worsened significantly over time. In mildly impaired patients, correlations between right-left metabolic asymmetries and neuropsychological discrepancies were insignificant initially but were significant at last evaluation. These results demonstrate that heterogeneous nonmemory language and visuospatial impairments in early DAT are related to and predicted by the earlier-appearing distribution of metabolic reductions in the association neocortex.

Aged

Plasticity in the aging brain. Reversibility of anatomic, metabolic, and cognitive deficits in normal-pressure hydrocephalus following shunt surgery.

The course of idiopathic normal-pressure hydrocephalus was studied in a 78-year-old woman with a 4-year history of progressive dementia who underwent neuropsychologic testing, quantitative x-ray computed tomography, magnetic resonance imaging, and positron emission tomography with fludeoxyglucose F 18 to measure rates of regional cerebral glucose utilization. Preshunt cognitive testing demonstrated progressive deterioration during 2 years, and positron emission tomography showed significant reductions in regional cerebral glucose utilization of 34% to 49% as compared with age- and sex-matched control subjects in frontal, temporal, parietal, and whole brain regions. Periodic testing, carried out during a 2-year period after shunt surgery, showed steady improvement in clinical status. Parallel to the clinical changes, there was a significant reversal in neuropsychologic test scores with increased brain volume and increased regional cerebral glucose utilization in several brain regions. These results documented the considerable potential for recovery of compromised brain function in older subjects even after 4 years of progressive brain disease.

Aged

Effect of gender on glucose utilization rates in healthy humans: a positron emission tomography study.

Positron emission tomography (PET) was used with 18fluorodeoxyglucose to see if gender differences in resting cerebral glucose utilization could be detected. Thirty-two healthy subjects (15 women and 17 men; age range: 21-38 yr) were examined using a high-resolution PET scanner to determine the regional cerebral metabolic rate for glucose (CMRglc) in 65 gray matter regions of interest. Whole brain CMRglc did not differ significantly between the two genders, nor did any of the regional CMRglc values. Only 1 of 65 ratios of regional-to-whole brain CMRglc differed significantly between men and women, which is consistent with chance. These results indicate that there are no differences in resting regional cerebral glucose utilization between young men and women.

Adult

Cerebral metabolic and cognitive studies in dementia with frontal lobe behavioral features.

Three subjects with dementia of the Alzheimer type (DAT) with frontal lobe features of behavioral disinhibition were studied using positron emission tomography with [18F]2-fluoro-2-deoxy-D-glucose (18 FDG) and standardized neuropsychological tests. The three subjects showed significant decrements (p less than .05) in relative glucose metabolism (regional/mean gray metabolism) in the orbitofrontal, prefrontal and anterior cingulate regions when compared to healthy controls. Severity-matched subjects with DAT without the associated frontal lobe features did not show the relative reductions in glucose metabolism in these regions when compared to controls. However, on neuropsychological testing of frontal lobe cognitive functions the three subjects did not show decrements that were more severe than those shown by severity-matched DAT patients without the behavioral features. These data demonstrate physiologic dysfunction in specific cortical regions in subjects with behavioral aberrations attributed to these regions and an apparent dissociation between behavioral and cognitive functions of the frontal lobe.

Aged

Regional cerebral glucose metabolism is normal in young adults with Down syndrome.

Regional CMRglc (rCMRglc) values were measured with [18F]2-fluoro-2-deoxy-D-glucose (18FDG) and positron emission tomography (PET), using a Scanditronix PC-1024-7B scanner, in 14 healthy, noninstitutionalized subjects with trisomy 21 (Down syndrome; DS) (mean age 30.0 years, range 25-38 years) and in 13 sex-matched, healthy volunteers (mean age 29.5 years, range 22-38 years). In the DS group, mean mental age on the Peabody Picture Vocabulary Test was 7.8 years and dementia was not present. Resting rCMRglc was determined with eyes covered and ears occluded in a quiet, darkened room. Global gray CMRglc equaled 8.76 +/- 0.76 mg/100 g/min (mean +/- SD) in the DS group as compared with 8.74 +/- 1.19 mg/100 g/min in the control group (p greater than 0.05). Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRglc, calculated to reduce the variance associated with absolute rCMRglc, and right/left ratios did not show any consistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with 18FDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur.

Adult