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Biomedical subjects

B Horwitz

Publications and source records attributed to B Horwitz.

At least 73 records · Page 4Linked to original sources
PubMed1995

Brain activity during transient sadness and happiness in healthy women.

OBJECTIVE: The specific brain regions involved in the normal emotional states of transient sadness or happiness are poorly understood. The authors therefore sought to determine if H2(15)O positron emission tomography (PET) might demonstrate changes in regional cerebral blood flow (rCBF) associated with transient sadness or happiness in healthy adult women. METHOD: Eleven healthy and never mentally ill adult women were scanned, by using PET and H2(15)O, during happy, sad, and neutral states induced by recalling affect-appropriate life events and looking at happy, sad, or neutral human faces. RESULTS: Compared to the neutral condition, transient sadness significantly activated bilateral limbic and paralimbic structures (cingulate, medial prefrontal, and mesial temporal cortex), as well as brainstem, thalamus, and caudate/putamen. In contrast, transient happiness had no areas of significantly increased activity but was associated with significant and widespread reductions in cortical rCBF, especially in the right prefrontal and bilateral temporal-parietal regions. CONCLUSIONS: Transient sadness and happiness in healthy volunteer women are accompanied by significant changes in regional brain activity in the limbic system, as well as other brain regions. Transient sadness and happiness affect different brain regions in divergent directions and are not merely opposite activity in identical brain regions. These findings have implications for understanding the neural substrates of both normal and pathological emotion.

Adult↗
PubMed1995

The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults.

OBJECTIVE: To assess the association of MRI white matter hyperintensities (WMHI) with cognitive performance, cerebral structure, and cerebral metabolism in 51 healthy individuals aged 19 to 91 years without cerebrovascular risk factors. BACKGROUND: Abnormal white matter signals have been associated with brain atrophy, reduced cerebral blood flow, focal neurologic signs, gait disorder, and poorer neuropsychological test performance. Most studies of WMHI, however, include subjects with hypertension or other identifiable causes of cerebrovascular disease that may have an independent effect on brain structure and function. To assess brain changes associated with WMHI independent of cerebrovascular risk factors, we determined WMHI volume, brain volume, cerebral metabolism, and cognitive performance for a group of subjects free of medical illness. Regional cerebral metabolism and cognitive domains were also assessed to evaluate the possible role of frontal lobe dysfunction in subjects with WMHI. DESIGN: Cross-sectional study of 51 very healthy subjects aged 19 to 91 years. METHODS: WMHI, brain, and CSF volumes were determined by MRI segmentation. Neuropsychological tests were employed to assess multiple cognitive domains. Brain metabolism was determined from 18-fluoro-2-deoxy-D-glucose PET. Multivariate relations were tested with stepwise linear regression. Models included the potential confounders of age and education where appropriate. RESULTS: The distribution of WMHI volume was bimodal, with five subjects having WMHI volumes beyond three SDs from the normally distributed population. A WMHI volume of greater than 0.5% of intracranial volume was considered abnormal. Within the multivariate models, WMHI volumes were significantly predictive of increased ventricular volume, reduced brain volume, and reduced cognitive scores. Subjects with greater than 0.5% WMHI volume also had significantly lower frontal lobe metabolism, significantly higher systolic blood pressure, significantly larger ventricular volume, and significantly lower scores on frontal lobe-mediated neuropsychological tests than age-matched controls. CONCLUSION: WMHI volume is associated with structural and functional brain changes even within a group of very healthy individuals. WMHI is associated with poorer frontal lobe cognitive function and, when severe, is accompanied by significantly reduced frontal lobe metabolism. Subjects with large WMHI volumes have significantly higher systolic blood pressure, brain atrophy, reduced cerebral metabolism, and lower scores on tests of frontal lobe function than age-matched controls. Large amounts of WMHI are, therefore, pathologic and may be related to elevated systolic blood pressure even when it is within the normal age-related range.

Adult↗
PubMed1995

Sex differences in patterns of hemispheric cerebral metabolism: a multiple regression/discriminant analysis of positron emission tomographic data.

Sex differences in brain hemispheric structure and function have been reported, and sex-related differences in hemispheric interregional correlations were reported in a prior analysis of resting PET glucose metabolic (rCMRglc) data. To explore further the effect of sex on patterns of hemispheric brain functional interactions, we applied a multiple regression/discriminant analysis to resting rCMRglc PET data from young normal men and women to test two hypotheses: (1) women have stronger between-hemisphere functional interactions; (2) men have stronger within-hemisphere functional interactions. Two separate discriminant functions based on these hypotheses distinguished men and women: the first reflected rCMRglc interdependencies between hemispheres and correctly classified all women and 94% of the men; the second reflected rCMRglc interdependencies within the left hemisphere and correctly classified 82% of the women and 88% of the men. Because the discriminant functions successfully distinguished men and women, these results provide support for both hypotheses.

Adult↗
PubMed1994

Abnormal pattern of cerebral glucose metabolic rates involving language areas in young adults with Down syndrome.

Correlational and discriminant analyses were applied to "resting" state (eyes covered, ears plugged) regional cerebral glucose metabolic data, obtained with positron emission tomography (PET) and [18F] fluorodeoxyglucose in 14 retarded adults with Down syndrome (10 men, 4 women; age 26-38 years) and 17 age- and sex-matched controls. Down and control subjects showed no differences in the pattern of correlations. However, a discriminant function, reflecting regional interactions involving primary language areas, successfully classified the Down (100%) and control (88%) subjects. The results are consistent with a disruption of brain regional interactions involving language areas in adults with Down syndrome.

Adult↗
PubMed1994

Reduction of functional neuronal connectivity in long-term treated hypertension.

BACKGROUND AND PURPOSE: Anatomic imaging of patients with chronic well-treated hypertension has demonstrated dilatation of the lateral cerebral ventricles and left brain atrophy, whereas positron emission tomography has shown only subtle reductions in regional cerebral metabolic rates for glucose in some subcortical nuclei. To further explore the implications of the imaging changes, an analytic technique designed to determine functional neuronal connectivity between regions of interest (ROIs) was applied to the data on regional cerebral metabolic rates for glucose to determine if and where in the brain reduction of functional neuronal connectivity occurred. METHODS: Glucose metabolism was measured by positron emission tomography in 17 older men (age, 68 +/- 8 years) with well-controlled, noncomplicated hypertension of at least 10 years' duration and in 25 age- and sex-matched healthy control subjects. A significant correlation difference analysis was performed to determine which ROI pairs had reduced correlation coefficients (reduced functional neuronal connectivity). The vascular pattern of the reduction was determined after allocating the ROIs to their appropriate vascular territories. RESULTS: Compared with the control subjects, hypertensive patients had reduced correlation coefficients in cortical territories of the internal carotid arteries but not of the vertebrobasilar arteries. The border zone supplied by the middle and anterior cerebral arteries was most affected. CONCLUSIONS: The border zone between the anterior and middle cerebral arteries is vulnerable to ischemia from carotid pathology, systemic hypotension, or both. We hypothesize that although these hypertensive patients were "well controlled" and had normal neuropsychological tests, they may have experienced ischemia severe enough to cause border zone reduction of functional neuronal connectivity as a result of carotid pathology, antihypertensive medications, hypotensive episodes with a right-shifted autoregulation curve, or other factors in isolation or combination.

Aged↗
PubMed1994

The functional organization of human extrastriate cortex: a PET-rCBF study of selective attention to faces and locations.

The functional dissociation of human extrastriate cortical processing streams for the perception of face identity and location was investigated in healthy men by measuring visual task-related changes in regional cerebral blood flow (rCBF) with positron emission tomography (PET) and H2(15)O. Separate scans were obtained while subjects performed face matching, location matching, or sensorimotor control tasks. The matching tasks used identical stimuli for some scans and stimuli of equivalent visual complexity for others. Face matching was associated with selective rCBF increases in the fusiform gyrus in occipital and occipitotemporal cortex bilaterally and in a right prefrontal area in the inferior frontal gyrus. Location matching was associated with selective rCBF increases in dorsal occipital, superior parietal, and intraparietal sulcus cortex bilaterally and in dorsal right premotor cortex. Decreases in rCBF, relative to the sensorimotor control task, were observed for both matching tasks in auditory, auditory association, somatosensory, and midcingulate cortex. These results suggest that, within a sensory modality, selective attention is associated with increased activity in those cortical areas that process the attended information but is not associated with decreased activity in areas that process unattended visual information. Selective attention to one sensory modality, on the other hand, is associated with decreased activity in cortical areas dedicated to processing input from other sensory modalities. Direct comparison of our results with those from other PET-rCBF studies of extrastriate cortex demonstrates agreement in the localization of cortical areas mediating face and location perception and dissociations between these areas and those mediating the perception of color and motion.

Adult↗
PubMed1994

Lack of age-related differences in temporal lobe volume of very healthy adults.

PURPOSE: To evaluate age-related differences in temporal and supratemporal brain regions in carefully selected, very healthy men 19 to 92 years of age. METHODS: MR quantification of brain regions used image segmentation into cerebrospinal fluid and brain matter based on nonlinear modeling of pixel intensity distributions. RESULTS: There was a significant age-related decrease (approximately 1% per decade) of posterior frontal lobe volume, but not of temporal lobe volume. The mean volume of the right temporal lobe was significantly greater than the left, and this relation did not change with age. CONCLUSION: In very healthy aging, the volume of the temporal lobes remains constant over the age range of human life.

Adult↗
PubMed1994

Age-related changes in cortical blood flow activation during visual processing of faces and location.

We examined age-related changes in object and spatial visual processing in two separate experiments. Regional cerebral blood flow (rCBF) was measured in young and old subjects with positron emission tomography and H2(15)O during tests of face matching, location matching, and a control task. The task demands in the two experiments were identical, but the stimuli in Experiment II were constructed to equalize stimulus complexity across all three tasks. The old subjects performed more slowly than the young subjects in both experiments, and showed significantly slower reaction times during location matching compared to face matching in Experiment II. Both young and old subjects showed occipitotemporal rCBF activation during face matching and occipitoparietal activation during location matching when these conditions were compared to the control task. However, in both experiments and in both tasks, young subjects showed greater activation of prestriate cortex (Brodmann's area 18), and old subjects had larger rCBF increases in occipitotemporal cortex (area 37). Areas in prefrontal cortex, as well as in inferior and medial parietal cortex, were more activated in the old subjects during location matching in both experiments. These results demonstrate that reliable age-related changes during visual processing can be found in rCBF patterns, suggesting more efficient use of occipital visual areas by younger subjects and more reliance by older subjects on one or more cortical networks, particularly for spatial vision, perhaps to compensate for reduced processing efficiency of occipital cortex. Both the differentially increased reaction times and the more widespread prefrontal activation in the old subjects during location matching suggest that spatial vision may be affected to a greater degree by aging than is object vision.

Adult↗
PubMed1994

Network analysis of cortical visual pathways mapped with PET.

Brain metabolic mapping techniques, such as positron emission tomography (PET), can provide information about the functional interactions within entire neural systems. With the large quantity of data that can accumulate from a mapping study, a network analysis, which makes sense of the complex interactions among neural elements, is necessary. A network analysis was performed on data obtained from a PET study that examined both the changes in regional cerebral blood flow (rCBF) and interregional correlations among human cortical areas during performance of an object vision (face matching) and spatial vision (dot-location matching) task. Brain areas for the network were selected based on regions showing significant rCBF or interregional correlations between tasks. Anterior temporal and frontal lobe regions were added to the network using a principal components analysis. Interactions among selected regions were quantified with structural equation modeling. In the structural equation models, connections between brain areas were based on known neuroanatomy and the interregional correlations were used to calculate path coefficients representing the magnitude of the influence of each directional path. The combination of the anatomical network and interregional correlations created a functional network for each task. The functional network for the right hemisphere showed that in the object vision task, dominant path influences were among occipitotemporal areas, while in the spatial vision task, occipitoparietal interactions were stronger. The network for the spatial vision task also had a strong feedback path from area 46 to occipital cortex, an effect that was absent in the object vision task. There were strong interactions between dorsal and ventral pathways in both networks. Functional networks for the left hemisphere did not differ between tasks. Networks for the interhemispheric interactions showed that the dominant pathway in the right hemisphere also had stronger effects on homologous left hemisphere areas and are consistent with a hypothesis that intrahemispheric interactions were greater in the right hemisphere in both tasks, and that these influences were transmitted callosally to the left hemisphere.

Adult↗
PubMed1993

Individual differences in cerebral metabolic patterns during pharmacotherapy in obsessive-compulsive disorder: a multiple regression/discriminant analysis of positron emission tomographic data.

A multiple regression/discriminant analysis of positron emission tomographic cerebral metabolic (rCMRglc) data in 10 obsessive-compulsive disorder (OCD) patients before and during pharmacotherapy was carried out to see if rCMRglc interdependencies distinguished OCD patients from controls. Before therapy, a discriminant function reflecting parietal, sensorimotor, and midbrain rCMRglc interdependencies correctly classified eight (80%) of the 10 patients as OCD; after therapy, six (70%) were classified as controls, most of whom were responders. Before therapy, rCMRglc interdependencies involving basal ganglia, thalamus, limbic, and sensory and association cortical regions distinguished 67% of patients who clinically responded to drug (RESP, n = 6) and 75% of patients who did not (NRESP, n = 4) from controls. After therapy, all RESP were classified as controls; classification of NRESP remained unchanged. The results suggest the conjunctive utility of this method to assess individual differences in rCMRglc during pharmacotherapy, and to explore the neurobiology of OCD.

Adult↗
PubMed1993

X-chromosome effects on female brain: a magnetic resonance imaging study of Turner's syndrome.

Many neuropsychiatric disorders differ between the sexes in incidence, symptoms, and age at onset. To investigate the effects of X-chromosome aneuploidy and of sex steroid deficiency during childhood on brain structure and function, we used neuropsychological tests and quantitative magnetic resonance imaging (MRI) to study the brains of eighteen women with Turner's syndrome (TS) and nineteen healthy control women of similar age. Nine TS subjects had mosaic 45,X karyotypes, and 9 had non-mosaic 45,X. The TS group had significantly lower scores than the controls for all the Wechsler adult intelligence scale tests, except verbal comprehension and reading level. The greatest difference was in visuospatial construction (mean 90 [SD12] vs 118 [13], p < 0.0001). The TS subjects also had a greater discrepancy than controls between verbal and performance intelligence quotients (9 [8] vs -5 [9], p < 0.001). We found that TS subjects had significantly smaller values than controls in MRI-measured volumes of hippocampus, caudate, lenticular, and thalamic nuclei, and parieto-occipital brain matter, on both sides. Women with mosaic TS had values between the full TS and control groups for cerebral hemisphere and lenticular and thalamic nuclei volume and for verbal ability. Within the mosaic TS group, visuospatial ability was significantly correlated with the percentage of lymphocytes that had the 45,X karyotype. Hippocampal volume and memory test scores were significantly lower in mosaic and non-mosaic 45,X TS subjects than in controls. We postulate that in human beings the X chromosome plays an important part in the development and ageing of grey matter in striatum, diencephalon, and cerebral hemispheres.

Adult↗
PubMed1993

Volumetric magnetic resonance imaging in men with dementia of the Alzheimer type: correlations with disease severity.

Using magnetic resonance imaging (MRI), we measured the volumes of various brain structures and cerebrospinal fluid (CSF) in 19 men with dementia of the Alzheimer type (DAT) and 18 healthy age-matched control men. The mean (+/- S.D) Mini-Mental State exam score (MMSE) of the DAT men was 16 +/- 7; 9 were mildly (MMSE > 20), 5 moderately (MMSE 10-20), and 5 severely (MMSE < 10) demented. Brain and CSF volumes were normalized as a percent of the traced intracranial volume to control for the relation of volumes of cerebral structures to head size, and analyzed statistically. The whole group of DAT subjects had significantly smaller mean cerebral brain matter and temporal lobe volumes (p < 0.05), and significantly larger mean ventricular and temporal lobe peripheral CSF volumes than did controls. Mean volumes of the subcortical nuclei did not differ significantly between groups, and mean volume of temporal lobe brain matter decreased significantly more than whole brain, suggesting regional loss of brain matter in DAT. Mildly demented DAT patients had significantly smaller mean cerebral brain matter and temporal lobe volumes and significantly larger volumes of lateral ventricles, and of temporal lobe peripheral CSF, than did controls. Neuropsychological measures of disease severity in DAT patients were significantly (p < 0.05) and appropriately correlated to volumes of cerebral brain matter and right lateral ventricle. These results suggest that in DAT: (i) significant brain atrophy is present early in the disease process, (ii) brain atrophy correlates with severity of cognitive impairment, and (iii) there is greater involvement of the telencephalic association system than whole brain, and there is relative sparing of the caudate, lenticular and thalamic nuclei.

Aged↗
PubMed1993

Early detection of Alzheimer's disease: a statistical approach using positron emission tomographic data.

Correlational analysis of regional cerebral glucose metabolism (rCMRglc) obtained by high-resolution positron emission tomography (PET) has demonstrated reduced neocortical rCMRglc interactions in mildly/moderately demented patients with probable Alzheimer's disease (AD). Thus, identification of individual differences in patterns of rCMRglc interactions may be important for the early detection of AD, particularly among individuals at greater risk for developing AD (e.g., those with a family history of AD). Recently, a statistical procedure, using multiple regression and discriminant analysis, was developed to assess individual differences in patterns of rCMRglc interdependencies. We applied this new statistical procedure to resting rCMRglc PET data from mildly/moderately demented patients with probable AD and age/sex-matched controls. The aims of the study were to identify a discriminant function that would (a) distinguish patients from controls and (b) identify an AD pattern in an individual at risk for AD with isolated memory impairment whose initial PET scan showed minor abnormalities, but whose second scan showed parietal hypometabolism, coincident with further cognitive decline. Two discriminant functions, reflecting interactions involving regions most involved in reduced correlations in probable AD, correctly classified 87% of the patients and controls, and successfully identified the first scan of the at-risk individual as AD (probability > 0.70). The results suggest that this statistical approach may be useful for the early detection of AD.

Aged↗
PubMed1993

Intraocular pressure response to loteprednol etabonate in known steroid responders.

The continuing development of ophthalmic steroids has resulted in compounds that have a low tendency to raise intraocular pressure (IOP). Preliminary clinical data have suggested that loteprednol etabonate (LE) 0.5% suspension may not elevate IOP while having promise as a potent topical ophthalmic steroid. This study was designed to evaluate the comparative potential of topical LE and prednisolone acetate (PA) to raise IOP in a population of individuals known to be steroid responders. The study used a double-masked, randomized, single eye, crossover design comparing LE 0.5% and PA 1.0%. Subjects instilled 1 drop of the assigned medication 4 times daily while awake, and follow-up examinations occurred on days 14, 28, and 42. Following a washout period of at least 14 days, subjects entered the second phase of the study, which was identical to the first phase, except that subjects received the alternate study medication. The mean IOP in the LE group increased from 17.4mm Hg at baseline to 21.5mm Hg at day 42 (p > 0.05), while in the PA group the mean IOP increased from 18.1mm Hg at baseline to 27.1mm Hg at day 42 (p < 0.05). There were no serious, severe, or clinically significant events in either group, and LE's effect on IOP was differentiable from that of PA. LE has less effect on IOP when compared to the IOP response induced by PA. LE may become a clinically useful ocular steroid with a favorable IOP-safety profile.

Adolescent↗
PubMed1993

Safety and efficacy of loteprednol etabonate for treatment of papillae in contact lens-associated giant papillary conjunctivitis.

Loteprednol etabonate (LE) is a new corticosteroid based on the "soft drug" concept. Contact lens-associated giant papillary conjunctivitis (GPC) was studied as a model for the anti-inflammatory effect of LE. Patients with bilateral GPC were enrolled in a multicenter, randomized, double-masked, placebo-controlled, parallel group comparison of loteprednol etabonate 0.5% ophthalmic suspension and the LE vehicle (placebo). Patients were instructed to instill 1 drop of the test medication into each eye 4 times daily for 4 weeks, and follow-up examinations occurred on Days 2 or 3, 7, 14, 21, and 28 of masked therapy. Of 113 patients enrolled, 110 patients (LE = 55; placebo = 55) completed the study as planned. Patients receiving LE demonstrated significant reduction in the primary ocular signs of GPC (papillae, p < 0.001) and were rated better in the Investigator's Global Assessment (p = 0.017). LE did not elevate intraocular pressure during the study, and ratings for bulbar conjunctival injection and the Patient Opinion Assessment demonstrated statistical trends that favored treatment with LE. LE was well tolerated and was clinically effective for the treatment of GPC.

Adolescent↗
PubMed1993

Endoscopic evaluation of penetrating esophageal injuries.

There are few objective data evaluating the role of flexible endoscopy in the management of penetrating esophageal and neck injuries. A retrospective analysis was performed on 13 trauma patients who had undergone emergent esophagogastroduodenoscopy for the evaluation of potential esophageal injuries. Endoscopy resulted in one true positive (esophageal injury detected), 10 true negatives (normal esophagus), two false positives, and no false negatives. This yielded a sensitivity of 100% and specificity of 83%. There were no complications of endoscopy. We conclude that urgent flexible esophagogastroduodenoscopy is a useful diagnostic procedure in the evaluation of penetrating wounds possibly involving the esophagus.

Adult↗
PubMed1992

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↗