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Biomedical subjects

B Horwitz

Publications and source records attributed to B Horwitz.

At least 109 records · Page 6Linked to original sources
PubMed1988

The cerebral metabolic landscape in autism. Intercorrelations of regional glucose utilization.

Correlations between regional cerebral metabolic rates for glucose (rCMRglc), determined by positron emission tomography using 18F-2-deoxy-2-fluoro-D-glucose, provide a measure of the functional associations between brain regions. We compared correlations between ratios of resting rCMRglc to global brain metabolism from 14 healthy autistic men (ages, 18 to 39 years) with those from 14 matched control subjects. The autistic group showed significantly fewer large positive correlations between frontal and parietal regions, particularly those with the left inferior frontal region and its right hemispheric homologue, and significantly lower correlations of the thalamus, caudate nucleus, lenticular nucleus, and insula with frontal and parietal regions, with many correlations negative in the autistic group that were positive in the control group. These results are compatible with functionally impaired interactions between frontal/parietal regions and the neostriatum and thalamus, regions that subserve directed attention.

Adolescent↗
PubMed1988

Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type.

To examine the progression of neuropsychologic and metabolic changes in the early stages of dementia of the Alzheimer type (DAT), we studied 11 midly demented patients longitudinally. Three aspects of neuropsychological function were measured: memory, attention to complex sets and abstract reasoning, and lateralized functions, i.e., language and visuoconstruction. Regional cerebral metabolic rates for glucose were measured in frontal, parietal, and temporal association cortices. Our results show that, in general, memory deficits are the first neuropsychological impairments to occur in DAT, followed by problems with attention to complex cognitive sets and abstract reasoning, which are followed in turn by deficits in language and visuospatial abilities. In addition, neocortical metabolic abnormalities usually precede impairment of neocortically mediated attention and abstract reasoning by 8 to 16 months, and precede impairment of neocortically mediated language and visuospatial function by 12 to 37 months. These findings suggest that the first nonmnestic neuropsychological consequence of neocortical physiological dysfunction in DAT is a loss of attentional capacity. Since neocortical metabolic changes generally precede the appearance of neocortically mediated neuropsychological dysfunction, physiologic dysfunction may exist for some time before cognition is affected.

Aged↗
PubMed1988

Heterogeneous anterior-posterior metabolic patterns in dementia of the Alzheimer type.

The parietal-frontal distribution of reductions of regional cerebral metabolic rates for glucose (rCMRglc) was studied in 32 patients with mild to severe dementia of the Alzheimer type (DAT), using positron emission tomography and fluorodeoxyglucose, and was related to patterns of neuropsychological impairment. In moderate and severe DAT patients, one frontal association region, the premotor cortex, demonstrated significant metabolic reductions equivalent to reductions in the parietal association cortex, and the ratio of parietal to premotor rCMRglc had significantly greater variance than in controls. In moderately demented patients, parietal-premotor and parietal-prefrontal metabolic ratios correlated significantly with neuropsychological impairments. Disproportionate parietal hypometabolism was associated with more impairment of verbal comprehension, calculations, visuospatial construction, and immediate visuospatial memory span. Disproportionate frontal hypometabolism was associated with more impaired verbal fluency and attention. Longitudinal follow-up of 20 of the patients showed that parietal/frontal metabolic ratios and their correlated neuropsychological patterns were stable over time, as dementia severity worsened. These results indicate that in moderate to severe DAT patients, metabolic reductions in the premotor cortex are as severe as the reductions in the parietal association cortex. Moreover, the parietal-premotor distribution of metabolic reductions is variable and related to variable patterns of cognitive impairment.

Alzheimer Disease↗
PubMed1988

Meal-induced thermogenesis following exercise training in the rat.

The effects of treadmill exercise on the thermic effect of a meal were studied in male Sprague-Dawley rats (370 to 400 g, 4 to 5 months of age). Rats were exercised for 60 min, 5 d.wk-1 for 8 to 10 wk, at a speed of 27 m.min-1 and with a grade of 8%. Sedentary (N = 9) and exercised (N = 8) rats were given food and water ad libitum. Oxygen consumption was measured at rest and following the ingestion of a meal consisting of 81% carbohydrate, 9% protein, and 10% fat (by calories). In those animals that were exercised, oxygen consumption measurements were performed 24 h after the completion of an exercise bout. Although all animals gained weight during the experimental period, the exercised group gained significantly less than did the sedentary rats. Resting oxygen consumption [ml/(min X g body mass.67)] was not significantly different between the exercised and sedentary rats. The ingestion of the high carbohydrate meal significantly increased mass-independent oxygen consumption above resting values in both groups; the values for the exercised rats were greater than those for the sedentary rats. However, there were no differences between the exercised and sedentary rats in meal-induced oxygen consumption when the data were expressed as a function of lean body mass [ml/(min X g lean body mass)] or as mass-independent lean body mass [ml/(min X g lean body mass.67)]. These data suggest that exercise-trained rats have increased diet-induced thermogenesis and may be one factor in the loss of weight sometimes found in response to exercise.

Animals↗
PubMed1988

Neuroplasticity and the progression of Alzheimer's disease.

A neurobiological hypothesis is proposed to explain the relation between the percentage cell loss in the cholinergic basal forebrain and the density of neuritic plaques in cortex, as found by Arendt et al. (1985) in Alzheimer's disease: When cells in the cholinergic basal forebrain die, their cortical synaptic target sites can be reoccupied by axonal sprouting of other neurons from the basal forebrain. This neuroplasticity hypothesis leads to equations that are consistent with the quantitative data of Arendt et al. (1985), and it makes specific predictions that can be tested experimentally. Moreover, this hypothesis suggests that the more rapid course of the presenile form of Alzheimer's disease and its more extensive pathology can be understood as a consequence of the decline in neuroplasticity with age.

Aging↗
PubMed1988

Partial correlation coefficients approximate the real intrasubject correlation pattern in the analysis of interregional relations of cerebral metabolic activity.

Correlation coefficients between pairs of regional glucose metabolic rates have been used to assess patterns of functional associations among brain regions in humans and animals. Partial correlation coefficients (partialing out the global metabolic rate) or correlations between reference ratios (regional to global metabolic rate) have been used to remove the distorting influence of systematic intersubject differences in glucose utilization. Suggesting that partial correlations may not preserve the true (but unknown) intrasubject correlation structure within the brain, others have used a theoretical example to show how an artifactually large negative partial correlation coefficient might arise. Here, we show that such an example is highly unlikely when applied to resting cerebral metabolism, and can be identified in experimental data by testing for a bimodal distribution of partial correlation values. We then show that partial correlations or reference ratio correlations of experimental resting metabolic rates give values which closely approximate the intrasubject correlation coefficients.

Adult↗
PubMed1987

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.

Aged↗
PubMed1987

Neuropsychological and cerebral metabolic function in early vs late onset dementia of the Alzheimer type.

Differences in age at onset of dementia of the Alzheimer type (DAT) have been associated with differences in cognitive impairments and course of the disease. To investigate this, we examined cerebral metabolism and cognitive performance in early and late onset DAT patients, who had equivalent duration and severity of illness. Regional cerebral metabolic rates for glucose were measured in the resting state by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. A cross-sectional analysis showed no significant differences between the two groups in performance on neuropsychological tests, but the early onset patients showed significantly more parietal metabolic dysfunction than did the late onset patients. Longitudinal analysis showed no significant differences between early and late onset patients in rate of cognitive decline over a mean interval of 19 months. Thus, our results do not support the hypothesis of different subgroups in DAT based on age at onset, nor suggest a faster rate of cognitive decline in younger patients.

Age Factors↗
PubMed1987

Cold-induced metabolism and brown fat GDP binding in young and old rats.

The attenuated thermogenic responses observed in older animals exposed to low environmental temperatures may reflect decreased thermogenic capacity of brown adipose tissue, a major nonshivering thermogenic effector in rats, and/or decreased metabolic capacity of lean body mass. To evaluate these possibilities, the oxygen consumption of female Sprague-Dawley rats aged 5 and 26 months was recorded at rest and during 6 h of exposure to 6 degrees C. The thermogenic capacity of brown fat was estimated from the binding of guanosine-5'-diphosphate (GDP) to isolated brown fat mitochondria. Both resting and cold-induced oxygen consumption expressed on a mass independent basis [ml/(min x kg body mass.67)] and as a function of lean body mass [ml/(min x g lean body mass)] were significantly lower in the 26-month-old animals. Colonic temperatures of younger and older rats after the 6 h of cold exposure were 37.5 +/- 0.1 and 36.1 +/- 0.2 degrees C, respectively, and were significantly different. However, no significant differences in the binding of GDP to isolated brown fat mitochondria were observed. These data indicate that the thermogenic capacity of brown fat is not decreased in the aged rat, and that the metabolic capacity as well as the amount of lean body mass is altered with age.

Adipose Tissue, Brown↗
PubMed1987

Relation of measured brain glucose utilisation and cerebral atrophy in man.

The effect of cerebral atrophy on measured cerebral metabolic rates for glucose (CMRglc), as determined with positron emission tomography (PET), was examined in 49 healthy males aged 21-83 years. Global CMRglc and regional CMRglc for 34 grey matter regions parallel to and from 30 to 80 mm above the inferior orbital meatal (IOM) line were measured under resting conditions, using [18F]-fluorodeoxyglucose and an ECAT II positron emission tomograph. Using a GE 8800 CT/T scanner, slices parallel to and from 30 to 80 mm above the IOM line were analysed for CSF volume. Cerebral atrophy, indicated by increased CSF volume, was correlated significantly with global CMRglc, but accounted for no more than 13% of the variance in the CMRglc measurements. Methods for correcting for inter-subject variation in CSF volume were proposed. Global values for CMRglc, uncorrected or corrected for CSF volume, were found to be age invariant. These findings indicate that (a) cerebral atrophy has a small, but statistically significant effect on CMRglc as measured with PET; (b) CMRglc is age invariant in healthy males.

Adult↗
PubMed1987

Biomechanics of hydrocephalus: a new theoretical model.

The finite element method (FEM), an advanced method of computer simulation, is used to examine biomechanical studies of hydrocephalus. Biot's theory of consolidation, which describes the mechanical behavior of a porous medium containing viscous fluid, is applied to represent the coupled behavior of tissue and fluid in the hydrocephalic brain. A computer simulation of the hydrocephalic process is carried out by FEM to evaluate the mathematical model. A two-dimensional finite element model is constructed using a horizontal computed tomographic (CT) slice of the brain. Specifying the material properties of the brain parenchyma, the loading characteristics, and the boundary conditions, the change of interstitial pressure, intracerebral stress distribution, and ventricular configuration are computed and graphically represented. The results of the computer simulation are compared with the findings of CT and magnetic resonance imaging of hydrocephalic patients. The progress of periventricular cerebrospinal fluid edema and ventricular enlargement is well represented by the mathematical model. The model demonstrated that stress concentration in the brain tissue and increased parenchymal hydraulic conductivity play an important role in the generation of periventricular cerebrospinal fluid edema.

Brain↗
PubMed1987

Topographical analysis of glucose metabolism, as measured with positron emission tomography, in dementia of the Alzheimer type: use of linear histograms.

A linear histogram method was employed to analyze brain images of glucose uptake obtained by positron emission tomography in patients with dementia of the Alzheimer type and in control subjects. A line was drawn by computer which traversed the image of a brain slice taken at 70 mm above and parallel to the inferior orbitomeatal line, and rCMRglc was plotted as a function of distance along this line in 3 brain areas: frontal, sensorimotor and parietal. Peak rCMRglc values were significantly decreased in moderately-to-severely demented patients relative to healthy age-matched controls, but not in mildly demented patients. Furthermore, both the mildly and the more severely demented patients differed from controls in having reduced ratios of parietal association to sensorimotor peak rCMRglc. The variances of right-left metabolic asymmetries did not differ significantly between Alzheimer patients and controls. Severity of dementia, as evaluated by scores on the Mini-Mental State Examination, correlated with ratios of peak rCMRglc in frontal and parietal cortex to that in sensorimotor cortex. These results indicate that measures of focal peak rCMRglc do not discriminate between mildly demented patients and controls, whereas focal ratios of rCMRglc, where the denominator corresponds to rCMRglc from a relatively spared region, provide useful measures of metabolic dysfunction in the early stages of Alzheimer's disease.

Aged↗
PubMed1987

Brain metabolism and blood flow during aging.

Recent studies of cerebral metabolism have suggested that although cerebral blood flow is reduced during rest in the healthy aged brain, there is little or no decline in resting glucose consumption. Intercorrelations between resting regional cerebral rates for glucose (rCMRglc), as determined by positron emission tomography using [18F]fluorodeoxyglucose, were shown to provide a measure of the functional associativity of brain regions. Partial correlation coefficients, controlling for whole brain glucose metabolism, were used in the analysis. Dividing the brain into 59 regions, we found, for 40 healthy males (21-83 years in age) in a state of reduced sensory input, that the strongest correlations generally were between bilaterally symmetric brain regions, and that there were many statistically significant correlations (P less than 0.01) among frontal and parietal lobe regions and also among temporal and occipital lobe areas, but few significant correlations between these two domains. The correlation analysis then was applied to two groups (15 healthy males each) of young (20-32 years old) and elderly (64-83 years old) subjects in the same resting state. Compared with the young group, we found that the elderly subjects have fewer statistically significant (P less than 0.01) correlations, with the most noteworthy reductions being between parietal and frontal lobe regions, and among parietal lobe areas. These findings indicated that cerebral functional interactions were reduced in the healthy elderly. The same analysis, applied to 21 mainly mildly-to-moderately impaired presumed Alzheimer subjects (and 21 age-matched controls), revealed fewer significant correlations between homologous brain regions which correspond to metabolic asymmetries linked to neuropsychological deficiencies.

Adult↗
PubMed1986

The pattern of functional coupling of brain regions in the awake rat.

The functional interactions among many regions of the rat brain were characterized simultaneously by using a new method for analyzing regional cerebral metabolic rates for glucose (rCMRglc). Regional CMRglc, a measure of regional functional activity, was determined in 68 brain regions of 24 awake, male, 3-month-old Fischer rats by the quantitative autoradiographic [14C]deoxyglucose technique. Because rCMRglc for each region varies among subjects, the functional coupling of two regions can be assessed by determining whether their metabolic rate change in a coordinated manner from rat to rat. Positive coupling arises if, for each rat, higher rCMRglc in one region is accompanied by a higher metabolic rate in another area; likewise, regions whose metabolic rates vary inversely are negatively coupled. A pairwise coupling can be quantified by calculating the linear correlation coefficient for points whose coordinates represent rCMRglc values for the two regions in each of the 24 rats. Correlation coefficients were calculated for each possible region pair among the 68 areas studied. The technique of partial correlation was used to weight equally the contribution of each rat to the correlation coefficient, regardless of its overall mean CMRglc. In general, highly positive couplings (R greater than 0.5) were found between adjacent or nearby regions, whereas distant region pairs often were coupled negatively (R less than -0.5). A large number of positive couplings were found between left-right homologous regions and between neocortical areas. Similar findings in humans, obtained by positron emission tomography, have been reported. This technique uses inter-animal variation in rCMRglc to demonstrate functional interactions among brain areas, thus providing a method to explore anatomical-functional linkages in a given experimental state.

Animals↗
PubMed1986

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.

Adult↗
PubMed1986

Alzheimer's disease: metabolic uncoupling of associative brain regions.

Evidence indicates that Alzheimer's disease (AD) causes functional disconnection of neocortical association areas. In midly demented AD patients without measurable neocortically-mediated cognitive abnormalities, positron emission tomography demonstrates reduced parietal lobe glucose metabolism and left/right metabolic asymmetries in neocortical association areas. Similar metabolic abnormalities occur in moderately demented patients, but are accompanied by appropriate language and visuospatial discrepancies. Left/right metabolic asymmetries correspond with reduced numbers of partial correlations between metabolic rates in homologous right and left regions, and in the frontal and parietal cortices, indicating metabolic uncoupling among these regions. The affected association regions are those which demonstrate Alzheimer-type neuropathology post-mortem.

Alzheimer Disease↗
PubMed1985

Differential effect of subtype of parental major affective disorder on children.

Fifty offspring of patients with major affective disorder (MAD) were studied. The children and their parents were interviewed using a structured diagnostic instrument. The results supported previous studies that the children of patients with MAD endorse a variety of symptoms of psychopathology. In addition, when the sample was separated by subtype of parental MAD, few differences in the types of symptoms were reported, and the differences that were found may be spurious. The differences, as well as indications for future research, are discussed.

Adolescent↗