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B Horwitz

Publications and source records attributed to B Horwitz.

At least 37 records · Page 2Linked to original sources
PubMed1999

A functional lesion in developmental dyslexia: left angular gyral blood flow predicts severity.

Functional imaging studies have shown reduced regional cerebral blood flow (rCBF) in temporal and inferior parietal regions in dyslexia. To relate such abnormalities to the severity of dyslexia, correlations between reading skill and rCBF during a series of reading tasks and visual fixation were mapped for 17 right-handed dyslexic men, ages 18-40, and 14 matched controls. These correlations uniquely identified the left angular gyrus as the most probable site of a functional lesion in dyslexia: Here, higher rCBF was associated with better reading skill in controls (p <.01), but with worse reading skill in dyslexia (p <.01). This suggests that greater reliance on this region normally facilitates reading, but impairs reading in dyslexia. Thus, developmental dyslexia may share a common localization with alexia.

Adolescent↗
PubMed1999

Neural modeling, functional brain imaging, and cognition.

The richness and complexity of data sets acquired from PET or fMRI studies of human cognition have not been exploited until recently by computational neural-modeling methods. In this article, two neural-modeling approaches for use with functional brain imaging data are described. One, which uses structural equation modeling, estimates the functional strengths of the anatomical connections between various brain regions during specific cognitive tasks. The second employs large-scale neural modeling to relate functional neuroimaging signals in multiple, interconnected brain regions to the underlying neurobiological time-varying activities in each region. Delayed match-to-sample (visual working memory for form) tasks are used to illustrate these models.

Journal Article↗
PubMed1999

Network analysis in episodic encoding and retrieval of word-pair associates: a PET study.

The involvement of distributed brain regions in declarative memory has been hypothesized based on studies with verbal memory tasks. To characterize episodic declarative memory function further, 14 right-handed volunteers performed a visual verbal learning task using paired word associates. The volunteers underwent positron emission tomography. 15O-butanol was used as a tracer of regional cerebral blood flow (rCBF). Inter-regional functional interactions were assessed based on within-task, across-subject inter-regional rCBF correlations. Anatomical connections between brain areas were based on known anatomy. Structural equation modelling was used to calculate the path coefficients representing the magnitudes of the functional influences of each area on the ones to which it is connected by anatomical pathways. The encoding and the retrieval network elicit similarities in a general manner but also differences. Strong functional linkages involving visual integration areas, parahippocampal regions, left precuneus and cingulate gyrus were found in both encoding and retrieval; the functional linkages between posterior regions and prefrontal regions were more closely linked during encoding, whereas functional linkages between the left parahippocampal region and posterior cingulate as well as extrastriate areas and posterior cingulate gyrus were stronger during retrieval. In conclusion, these findings support the idea of a global bihemispheric, asymmetric encoding/retrieval network subserving episodic declarative memory. Our results further underline the role of the precuneus in episodic memory, not only during retrieval but also during encoding.

Adult↗
PubMed1999

Premutation female carriers of fragile X syndrome: a pilot study on brain anatomy and metabolism.

OBJECTIVE: It was thought that premutation carriers of fragile X syndrome (FraX) have no neurobiological abnormalities, but there have been no quantitative studies of brain morphometry and metabolism. Thus the authors investigated brain structure and metabolism in premutation carriers of FraX. METHOD: Eight normal IQ, healthy female permutation FraX carriers aged 39 +/- 9 years (mean +/- SD) and 32 age-sex-handedness-matched controls (39 +/- 10 years) were studied; in vivo brain morphometry was measured using volumetric magnetic resonances imaging, and regional cerebral metabolic rates for glucose were measured using positron emission tomography and (18F)-2-fluoro-2-deoxy-D-glucose. RESULTS: Compared with controls, FraX premutation carriers had a significant (1) decrease in volume of whole brain, and caudate and thalamic nuclei bilaterally; (2) increase in volume of hippocampus and peripheral CSF bilaterally, and third ventricle; (3) relative hypometabolism of right parietal, temporal, and occipital association areas; (4) bilateral relative hypermetabolism of hippocampus; (5) relative hypermetabolism of left cerebellum; and (6) difference in right-left asymmetry of the Wernicke and Broca language areas. CONCLUSIONS: Premutation carriers of FraX, as defined by analysis of peripheral lymphocytes, have abnormalities in brain anatomy and metabolism. The biological basis for this is unknown, but most likely it includes tissue heterogeneity for mutation status. The findings may be of relevance to people counseling families with FraX and to understanding other neuropsychiatric disorders which are associated with expansion of triplet repeats and genetic anticipation.

Adult↗
PubMed1999

How accurate are our assumptions about our students' background knowledge?

Teachers establish prerequisites that students must meet before they are permitted to enter their courses. It is expected that having these prerequisites will provide students with the knowledge and skills they will need to successfully learn the course content. Also, the material that the students are expected to have previously learned need not be included in a course. We wanted to determine how accurate instructors' understanding of their students background knowledge actually was. To do this, we wrote a set of multiple-choice questions that could be used to test students' knowledge of concepts deemed to be essential for learning respiratory physiology. Instructors then selected 10 of these questions to be used as a prerequisite knowledge test. The instructors also predicted the performance they expected from the students on each of the questions they had selected. The resulting tests were administered in the first week of each of seven courses. The results of this study demonstrate that instructors are poor judges of what beginning students know. Instructors tended to both underestimate and overestimate students' knowledge by large margins on individual questions. Although on the average they tended to underestimate students' factual knowledge, they overestimated the students' abilities to apply this knowledge. Hence, the validity of decisions that instructors make, predicated on the basis of their students having the prerequisite knowledge that they expect, is open to question.

Educational Measurement↗
PubMed1999

Undergraduate students' misconceptions about respiratory physiology.

Approximately 700 undergraduates studying physiology at community colleges, a liberal arts college, and universities were surveyed to determine the prevalence of our misconceptions about respiratory phenomena. A misconception about the changes in breathing frequency and tidal volume (physiological variables whose changes can be directly sensed) that result in increased minute ventilation was found to be present in this population with comparable prevalence (approximately 60%) to that seen in a previous study. Three other misconceptions involving phenomena that cannot be experienced directly and therefore were most likely learned in some educational setting were found to be of varying prevalence. Nearly 90% of the students exhibited a misconception about the relationship between arterial oxygen partial pressure and hemoglobin saturation. Sixty-six percent of the students believed that increasing alveolar oxygen partial pressure leads to a decrease in alveolar carbon dioxide partial pressure. Nearly 33% of the population misunderstood the relationship between metabolism and ventilation. The possible origins of these respiratory misconceptions are discussed and suggestions for how to prevent and/or remediate them are proposed.

Adolescent↗
PubMed1998

Functional connectivity of the angular gyrus in normal reading and dyslexia.

The classic neurologic model for reading, based on studies of patients with acquired alexia, hypothesizes functional linkages between the angular gyrus in the left hemisphere and visual association areas in the occipital and temporal lobes. The angular gyrus also is thought to have functional links with posterior language areas (e.g., Wernicke's area), because it is presumed to be involved in mapping visually presented inputs onto linguistic representations. Using positron emission tomography , we demonstrate in normal men that regional cerebral blood flow in the left angular gyrus shows strong within-task, across-subjects correlations (i.e., functional connectivity) with regional cerebral blood flow in extrastriate occipital and temporal lobe regions during single word reading. In contrast, the left angular gyrus is functionally disconnected from these regions in men with persistent developmental dyslexia, suggesting that the anatomical disconnection of the left angular gyrus from other brain regions that are part of the "normal" brain reading network in many cases of acquired alexia is mirrored by its functional disconnection in developmental dyslexia.

Adolescent↗
PubMed1998

Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls).

BACKGROUND: The clinical diagnosis of Alzheimer's disease (AD) can be difficult to make in early stages of disease. Structural neuroimaging offers a potential tool in the clinical diagnosis of AD with mild cognitive impairment. Postmortem studies indicate that early neuropathology in AD occurs in medial temporal lobe limbic structures. Magnetic resonance imaging (MRI) studies that assessed these volumes in mildly impaired AD patients remain inconclusive. METHODS: Using MRI, we measured volumes of left and right hippocampus, amygdala, and anterior and posterior parahippocampal gyrus (PHG) in 13 AD patients with mild cognitive impairment, defined as > or = 20 on the Mini-Mental State Exam, and in 21 healthy age- and sex-matched controls. RESULTS: The AD patients had smaller medial temporal lobe volumes, except for the right anterior PHG. Discriminant function analysis using MRI volumes produced 94% correct group classification. CONCLUSIONS: These results show that in mildly impaired AD patients atrophy is present in medial temporal lobe structures; that MRI volumes of the anterior PHG, which contains entorhinal cortex, are reduced, but the amygdala and hippocampal volumes show greater reduction; and that discriminant function analysis using all volumes as predictors can correctly classify a high proportion of individuals.

Aged↗
PubMed1998

Corpus callosum atrophy is a possible indicator of region- and cell type-specific neuronal degeneration in Alzheimer disease: a magnetic resonance imaging analysis.

BACKGROUND: Pathological studies in Alzheimer disease indicate the specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long corticocortical connections within and between the cerebral hemispheres. OBJECTIVE: To evaluate the corpus callosum as an in vivo marker for cortical neuronal loss. METHOD: Using a new imaging technique, we measured region-specific corpus callosum atrophy in patients with Alzheimer disease and correlated the changes with neuropsychological functioning. Total cross-sectional area of the corpus callosum and areas of 5 callosal subregions were measured on midsagittal magnetic resonance imaging scans of 14 patients with Alzheimer disease (mean age, 64.4 years; Mini-Mental State Examination score, 11.4) and 22 healthy age- and sex-matched control subjects (mean age, 66.6 years; Mini-Mental State Examination score, 29.8). All subjects had minimal white matter changes. RESULTS: The total callosal area was significantly reduced in the patients with Alzheimer disease, with the greatest changes in the rostrum and splenium and relative sparing of the callosal body. Regional callosal atrophy correlated significantly with cognitive impairment in the patients with Alzheimer disease, but not with age or the white matter hyperintensities score. CONCLUSIONS: Callosal atrophy in patients with Alzheimer disease with only minimal white matter changes may indicate loss of callosal efferent neurons in corresponding regions of the cortex. Because these neurons are a subset of corticocortical projecting neurons, region-specific callosal atrophy may serve as a marker of progressive neocortical disconnection in Alzheimer disease.

Aged↗
PubMed1998

A double-masked, randomized, 1-year study comparing the corneal effects of dorzolamide, timolol, and betaxolol. Dorzolamide Corneal Effects Study Group.

OBJECTIVE: To compare the long-term effects of dorzolamide hydrochloride (Trusopt, Merck and Co Inc, White-house Station, NJ), timolol maleate, and betaxolol hydrochloride on corneal endothelial cell density and corneal thickness. METHODS: This 1-year multicenter study was conducted in 298 patients with ocular hypertension or open-angle glaucoma who had a baseline central corneal endothelial cell density greater than 1500 cells/mm2 and central corneal thickness less than 0.68 mm in each eye. Patients were randomized to 0.5% betaxolol twice daily, 0.5% timolol twice daily, or 2.0% dorzolamide 3 times daily. Specular microscopy and ultrasonic pachymetry of the central cornea was performed at baseline and 6 and 12 months following institution of therapy. Endothelial cell densities were determined by a single masked observer. RESULTS: The mean percent changes from baseline for both outcome measures were similar in all 3 treatment groups at both 6 and 12 months. After 1 year of treatment, the mean percent loss in endothelial cell density from baseline was 3.6%, 4.5%, and 4.2% for the dorzolamide, timolol, and betaxolol groups, respectively. The mean percent change from baseline for corneal thickness was 0.47%, -0.25%, and 0.39% for the dorzolamide, timolol, and betaxolol groups, respectively. CONCLUSIONS: Dorzolamide is equivalent to timolol and betaxolol in terms of the change in central endothelial cell density and thickness after 1 year of therapy. All 3 treatments exhibit good long-term corneal tolerability in patients with normal corneas at baseline.

Adrenergic beta-Antagonists↗
PubMed1998

Age-related changes in regional cerebral blood flow during working memory for faces.

Young and old adults underwent positron emission tomography during the performance of a working memory task for faces (delayed match-to-sample), in which the delay between the sample and choice faces was varied from 1 to 21 s. Reaction time was slower and accuracy lower in the old group, but not markedly so. Values of regional cerebral blood flow (rCBF) were analyzed for sustained activity across delay conditions, as well as for changes as delay increased. Many brain regions showed similar activity during these tasks in both young and old adults, including left anterior prefrontal cortex, which had increased rCBF with delay, and ventral extrastriate cortex, which showed decreased rCBF with delay. However, old adults had less activation overall and less modulation of rCBF across delay in right ventrolateral prefrontal cortex than did the young adults. Old adults also showed greater rCBF activation in left dorsolateral prefrontal cortex across all WM delays and increased rCBF at short delays in left occipitoparietal cortex compared to young adults. Activity in many of these regions was differentially related to performance in that it was associated with decreasing response times in the young group and increasing response times in the older individuals. Thus despite the finding that performance on these memory tasks and associated activity in a number of brain areas are relatively preserved in old adults, differences elsewhere in the brain suggest that different strategies or cognitive processes are used by the elderly to maintain memory representations over short periods of time.

Adult↗
PubMed1998

Single mating type-specific genes and their 3' UTRs control mating and fertility in Cochliobolus heterostrophus.

To determine the number of proteins required for mating type (MAT) locus-regulated control of mating in Cochliobolus heterostrophus, MAT fragments of various sizes were expressed in MAT deletion strains. As little as 1.5 kb of MAT sequence, encoding a single unique protein in each mating type (MAT-1 and MAT-2), conferred mating ability, although an additional 160 bp of 3' UTR was needed for production of ascospores. No other mating type-specific genes involved in mating identity or fertility were found. Thus, although homologs of the C. heterostrophus MAT-1 and MAT-2 genes exist in the filamentous ascomycetes Neurospora crassa and Podospora anserina, C. heterostrophus does not appear to have mating type-specific homologs of two additional genes required by both N. crassa and P. anserina for successful sexual reproduction. Three genes were identified in the common DNA flanking the MAT locus: a gene encoding a GTPase-activating protein and an ORF of unknown function lie 5' while a beta-glucosidase encoding gene lies found 3'. None of these genes appears to be involving in the mating process.

Ascomycota↗
PubMed1998

Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for postoperative inflammation. Loteprednol Etabonate Post-operative Inflammation Study Group 1.

PURPOSE: To compare the efficacy and safety of loteprednol etabonate 0.5% with those of a placebo (vehicle) in controlling anterior chamber cell and flare reaction in patients having cataract surgery with intraocular lens (IOL) implantation. METHODS: This randomized, double-masked, placebo-controlled, parallel-group multicenter study comprised patients who exhibited a minimum anterior chamber inflammation (ACI) score (sum of cell and flare reaction) of 3 (0 to 9 scale) on the day after cataract removal with posterior chamber IOL implantation. All 227 patients received loteprednol etabonate 0.5% or the placebo 4 times a day in the operated eye for up to 14 days after surgery. Five patients without valid on-treatment follow-up visits were not evaluated for efficacy. RESULTS: By the final visit, the ACI had resolved in 64% (70/109) of patients in the loteprednol etabonate group and 29% (33/113) of those in the placebo group (P < .001). The resolution rate and mean change from baseline of the individual components of ACI (cell and flare), as well as other signs and symptoms, was better in the loteprednol etabonate group. Both treatments were well tolerated. Among the 53 patients who did not complete the study, 34 (29%) were placebo patients discontinued for inadequate anti-inflammatory effect. The treatment failure rate and the time course of failures were lower in the loteprednol etabonate group; the differences were clinically meaningful and statistically significant (P < .001). Three patients in the loteprednol etabonate group had an intraocular pressure elevation of 10 mm Hg or more over the preoperative screening value. CONCLUSION: Loteprednol etabonate 0.5% led to a clinically meaningful reduction in the signs and symptoms of postoperative ACI and had an acceptable safety profile when compared with a placebo.

Adult↗
PubMed1998

Integrating electrophysiological and anatomical experimental data to create a large-scale model that simulates a delayed match-to-sample human brain imaging study.

We propose a model that draws together experimental evidence from anatomical, electrophysiological and imaging experiments in order to understand better the neural substrate of human imaging studies using positron electron tomography (PET) and functional magnetic resonance imaging (fMRI). First, we define a simple local circuit that reflects the major role that local connectivity plays in producing PET and fMRI data, which are thought to mainly reflect synaptic activity. Second, in order to account for the role of varying behaviors during the course of a typical imaging experiment, we propose a local circuit that can perform a delayed match-to-sample task. The elements of this circuit behave very much like neurons that have been found in the prefrontal cortex during similar tasks in monkeys. One subpopulation responds selectively only when stimuli are present. Two different populations show the two types of delay-period activity that have been identified, one with high activity both during the cue and the delay period, the other with a rise during the delay period only. Last, a subpopulation shows a brief response only if the second stimulus matches the first, thus mediating the decision about whether the stimuli match. We show that in addition to performing the task, the integrated summed synaptic activities of the model are similar to experimental PET data.

Behavior↗
PubMed1998

Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease.

OBJECTIVE: To determine whether the hypometabolism observed in PET images of patients with Alzheimer's disease (AD) is due entirely to brain atrophy. BACKGROUND: Reduced brain glucose metabolism in AD patients measured using PET has been reported by numerous authors. Actual glucose metabolic values in AD may be reduced artificially because of brain atrophy, which accentuates the partial volume effect (PVE) on data collected by PET. METHODS: Using segmented MR images, we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate the effect of atrophy on uncorrected values for brain metabolism in AD patients and healthy control subjects. RESULTS: Global glucose metabolism was reduced significantly before and after correction in AD patients compared with controls. Before PVE correction, glucose metabolic values in patients were lower than in control subjects in the inferior parietal, frontal, and lateral temporal cortex; in the posterior cingulate; and in the precuneus. These reductions remained significantly lower after PVE correction, although in the posterior cingulate the difference in metabolism between AD patients and control subjects lessened. Regional glucose metabolism of these areas with PVE correction was lower in moderately-severely demented patients than in mildly demented patients. CONCLUSION: Reduced glucose metabolism measured by PET in AD is not simply an artifact due to an increase in CSF space induced by atrophy, but reflects a true metabolic reduction per gram of tissue.

Aged↗
PubMed1998

Dissociation between corpus callosum atrophy and white matter pathology in Alzheimer's disease.

OBJECTIVE: To determine whether the size of the corpus callosum is related to the extent of white matter pathology in patients with AD and age-matched healthy control subjects. METHODS: White matter hyperintensity load and corpus callosum size were compared between 20 clinically diagnosed AD patients and 21 age-matched healthy control subjects. We investigated the effect of age and disease severity on corpus callosum size and white matter hyperintensity, in addition to the relation between corpus callosum areas and white matter hyperintensity load. RESULTS: We found significant regional atrophy of the corpus callosum in AD when compared with control subjects, although the groups did not differ in their white matter hyperintensity load. We further showed a region-specific correlation between corpus callosum size and white matter hyperintensity in the control group but not in AD patients. In the AD group, corpus callosum size correlated with age and dementia severity, whereas white matter hyperintensity correlated only with age. CONCLUSION: Corpus callosum atrophy in AD can occur independent of white matter degeneration, likely reflecting specific AD pathology in projecting neurons.

Aged↗
PubMed1997

A PET study of Turner's syndrome: effects of sex steroids and the X chromosome on brain.

Women with Turner's syndrome (TS) allow us to study the neurobiological associates of cognitive and behavioral abnormalities because they lack one/part of one X chromosome, and endogenous estrogen. We studied 13 healthy controls (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6 years). We measured cognitive abilities using neuropsychological tests, and cerebral metabolic rates for glucose with positron emission tomography. Compared to controls, TS subjects had significant absolute hypermetabolism in most brain areas; however, normalized metabolism was significantly lower in TS subjects than controls in the insula and association neocortices bilaterally, and there were significant differences in functional metabolic associations of brain region pairs originating in occipital cortex bilaterally, and within the right hemisphere. There were significant correlations between right-left cognitive and metabolic asymmetries in the TS group. Also, within TS a preliminary analysis demonstrated "X chromosome dosage" effects in language ability and left temporal metabolism, asymmetry of right-left test scores, and parietal metabolism. We hypothesize that within TS: i) generalized brain hypermetabolism reflects global abnormalities in neuron packing; ii) neuronal abnormalities occur in association neocortex that differ in nature or extent from whole brain and are associated with significant differences in normalized metabolism; iii) cognitive deficits are related to brain metabolic abnormalities; and iv) social-behavioral problems may be related to abnormalities of brain metabolism. Moreover, in human brain the X chromosome involved in development of the association neocortices.

Adult↗