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M B Schapiro

Publications and source records attributed to M B Schapiro.

At least 19 recordsLinked to original sources
PubMed2006

Functional magnetic resonance imaging reveals atypical language organization in children following perinatal left middle cerebral artery stroke.

We used verb generation and story listening tasks during fMRI to study language organization in children (7, 9 and 12 years old) with perinatal left MCA infarctions. Healthy, age-matched comparison children (n = 39) showed activation in left Broca's area during the verb generation task; in contrast, stroke subjects showed activation either bilaterally or in the right hemisphere homologue during both tasks. In Wernicke's area, comparison subjects showed left lateralization (verb generation) and bilateral activation (L > R) (story listening). Stroke subjects instead showed bilateral or right lateralization (verb generation) and bilateral activation (R > L) (story listening). Language is distributed atypically in children with perinatal left hemisphere stroke.

Brain Mapping↗
PubMed2005

Brain MRI and proton MRS findings in infants and children with respiratory chain defects.

OBJECTIVE: The aim of this study is to describe neuroimaging patterns in children with respiratory chain (RC) defects using magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) and to assess their role in the diagnostic evaluation. METHOD: Neuroimaging studies of 49 children (newborn to 15 years old) with biochemical evidence of RC defect were reviewed. Patients were divided in 3 groups ("definite" = 24, "probable" = 14, "possible" = 11) according to Modified Adult Criteria for the diagnosis of RC defect. Eighty-one MRI studies were reviewed for deep gray and white matter changes, degree of myelination, cerebral and cerebellar atrophy, and 67 proton MRS studies were assessed for the presence or absence of lactate elevation, as well as NAA/Cr ratio. The findings were compared among the 3 groups with chi-square test. RESULTS: All patients with "pure" myopathy had normal imaging studies. In patients with CNS involvement, significant differences in the frequency of imaging abnormalities among groups were found for deep gray matter (43 %/8 %/0 %; p = 0.01) and for the presence of lactate elevation on proton MRS (81 %/31 %/0 %; p = 0.001). CONCLUSION: Brain MRI and proton MRS abnormalities were observed only in association with clinical CNS involvement. Deep gray matter signal abnormalities on structural imaging and lactate elevation on proton MRS were more frequently observed in the "definite" group and represent neuroimaging markers for RC mitochondriopathy.

Aspartic Acid↗
PubMed2002

Congenital creatine transporter deficiency.

BACKGROUND: Two inborn errors of metabolism of creatine synthesis as well as the X-linked creatine transporter (SLC6A8) deficiency have been recognized. This report describes the features of five identified male patients and their female relatives who are carriers of the X-linked creatine transporter deficiency syndrome. METHODS: Proton MR spectroscopy was used to recognize creatine deficiency in the patients. Molecular analysis of the SLC6A8 gene was performed, confirming the diagnosis of homozygous males and heterozygous females. RESULTS: We describe four families from a metropolitan area in the U. S. with X-linked creatine transporter deficiency. All affected males present with developmental delay and severe developmental language impairment. Proton MR spectroscopy shows significantly depressed to essentially absent creatine and phosphocreatine in the male patients. Nonsense mutations and amino acid deletions were found in the SLC6A8 gene in the affected families. CONCLUSION: Creatine transporter deficiency may be a more common X-linked genetic disorder than originally presumed. The affected males exhibit mental retardation with severe expressive language impairment.

Adult↗
PubMed2001

Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome.

CONTEXT: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. DESIGN, SETTING, AND PATIENTS: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. MAIN OUTCOME MEASURES: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. RESULTS: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). CONCLUSION: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.

Aged↗
PubMed2001

Brain metabolite concentration and dementia severity in Alzheimer's disease: a (1)H MRS study.

OBJECTIVE: (1)H-MRS studies have shown abnormalities in brain levels of myo-inositol (mI) and N-acetyl aspartate (NAA) in AD, but the relation of these abnormalities with dementia severity was not examined. The authors sought to determine whether altered brain levels of mI and other metabolites occur in mild AD and whether they change as dementia severity worsens. METHODS: The authors used (1)H-MRS with external standards to measure absolute brain concentrations of mI, NAA, total creatine (Cr), and choline (Cho)-containing compounds in 21 subjects with AD and 17 age- and sex-matched controls in occipital and left and right parietal regions. RESULTS: Concentrations of NAA were significantly decreased, whereas mI and Cr concentrations were significantly increased in all three brain regions in subjects with AD compared with controls. Higher concentrations of mI and Cr occurred even in mild AD. A discriminant analysis of the (1)H-MRS data combined with CSF volume measurements distinguished subjects with AD, ranging from mild to severe dementia, from controls with 100% correct classification. NAA concentration, though not other metabolites, was positively correlated with Mini-Mental State Examination score. CONCLUSION: The measurements with (1)H-MRS of absolute metabolite concentrations in the neocortex showed abnormal concentrations of brain metabolites in AD; these metabolite concentrations do not necessarily correlate with disease severity. Although changes in myo-inositol and creatine occur in the early stages of AD, abnormalities of N-acetyl aspartate do not occur in mild AD but progressively change with dementia severity. Further, subjects with mild AD can be differentiated from controls with (1)H-MRS.

Aged↗
PubMed2001

The effect of brain atrophy on cerebral hypometabolism in the visual variant of Alzheimer disease.

BACKGROUND: Brain glucose metabolic rates measured by positron emission tomography can be more affected by partial volume effects in Alzheimer disease (AD) than in healthy aging because of disease-associated brain atrophy. OBJECTIVE: To determine whether the distinct distribution of cerebral metabolic lesions in patients with the visual variant of AD (AD + VS) represents a true index of neuronal/synaptic dysfunction or is the consequence of brain atrophy. SETTING: Government research hospital. DESIGN: Resting cerebral metabolic rate for glucose was measured with positron emission tomography in a cross-sectional study of AD and AD + VS groups and in healthy control subjects. Segmented magnetic resonance images were used to correct for brain atrophy. PATIENTS: Patients with AD + VS had prominent visual and visuospatial symptoms. There were 15 patients with AD, 10 with AD + VS, and 37 age-matched control subjects. MAIN OUTCOME MEASURE: Measurement of the rate of cerebral glucose metabolism. RESULTS: Before atrophy correction, the AD + VS group, compared with the control subjects, showed hypometabolism in primary and extrastriate visual areas and in parietal and superior temporal cortical areas. Compared with the AD group, the AD + VS group showed hypometabolism in visual association areas. After atrophy correction, hypometabolism remained significantly different between patients and controls and between the 2 AD groups. CONCLUSIONS: The reductions in cerebral hypometabolism represent a true loss of functional activity and are not simply an artifact caused by brain atrophy. The different patterns of hypometabolism indicate the differential development of the lesions between the AD and AD + VS groups.

Aged↗
PubMed2000

Phospholipid composition and levels are altered in Down syndrome brain.

Phospholipid composition (mol %) and levels (nmol/mg protein) were determined in postmortem frontal cortical and cerebellar gray matter from older Down Syndrome (DS) patients (age range 38-68 years) and from control subjects. Neither DS nor control tissue exhibited any age-dependent alteration in phospholipid composition or levels. Total phospholipid content was significantly reduced approximately 20% in DS frontal cortex and cerebellum relative to these regions in control tissue. Individual phospholipid levels were also reduced in DS frontal cortex and cerebellum, including a specific 37% decrease in phosphatidylinositol (PtdIns) and a nearly 35% decrease in ethanolamine plasmalogen. Because of the large decrease in phospholipid content in DS brain, the cholesterol/phospholipid ratio was calculated for each group. There was no significant difference in this ratio between groups, indicative of compensatory changes to keep the cholesterol/phospholipid ratio constant. Despite the large changes in DS brain phospholipid levels, significant changes in composition were limited to a 18% decrease in PtdIns mol % and a 22% increase in the mol % of sphingomyelin. These results suggest either a decrease in membrane phospholipids due to a loss of dendrites and dendritic spines, or a general defect in brain lipid metabolism in older DS subjects. The proportionally greater alterations in PtdIns and PlsEtn levels, indicate that the metabolism of these two phospholipids was affected to a greater extent than the other phospholipids. Further, because these changes are found in both the frontal cortical and cerebellar gray matter, they likely are related to the Down syndrome condition rather than to Alzheimer neuropathology.

Adult↗
PubMed2000

Brain myo-inositol level is elevated in Ts65Dn mouse and reduced after lithium treatment.

The segmental trisomy Ts65Dn mouse is a novel model of Down syndrome (DS). The purpose of this study was to measure brain levels of myo-inositol (ml), N-acetylaspartate (NAA), and other metabolites in Ts65Dn mice using in vivo 1H magnetic resonance spectroscopy (MRS), and to determine whether lithium (Li) treatment alters brain ml level. The ratio of ml over total creatine (Cr), ml/Cr, was significantly elevated (mean change +38%), while NAA/Cr was significantly decreased (mean change -18%) in Ts65Dn mice (n=5) compared with control mice (n= 7). This is consistent with 1H MRS findings in DS human adults. Brain ml/Cr of the entire sample group (n= 12) was reduced (mean change -15%) following Li treatment, supporting the Li-induced ml depletion hypothesis.

Animals↗
PubMed2000

Time course of pharmacodynamic and pharmacokinetic effects of physostigmine assessed by functional brain imaging in humans.

In imaging studies of brain functions using pharmacological probes, identification of the time point at which central effects of intravenously infused drugs become stable is crucial to separate the effects of experimental variables from the concomitant changes in drug effects over time. We evaluated the time courses of the pharmacokinetics and pharmacodynamics, including butyrylcholinesterase inhibition and central neural responses, of physostigmine in healthy young subjects. Ten positron emission tomography (PET) scans that alternated between a rest condition (eyes open, ears unplugged) and a working memory for faces (WM) task were acquired in healthy subjects. Subjects in the drug group received a saline infusion for the first two scans, providing a baseline measure, then received an infusion of physostigmine for all subsequent scans. Subjects in the control group received a placebo infusion of saline for all scans. Physostigmine plasma levels and percent butyrylcholinesterase inhibition increased over time (p < 0. 0001), and both became stable by 40 min. Physostigmine decreased reaction time (RT) (p = 0.0005), and this effect was detected after 20 min of infusion and stable thereafter. Physostigmine also decreased regional cerebral blood flow (rCBF) in right prefrontal cortex during task (p = 0.0002), and this effect was detected after 40 min of infusion and stable thereafter. No change in RT or rCBF was observed in the control group. These results indicate that a 40-min infusion of physostigmine was necessary to obtain stable central effects. More generally, we have demonstrated that experimental effects can vary with time, especially during the initial phases of a drug infusion, indicating that it is critical that these changes are controlled.

Adult↗
PubMed2000

Cholinergic enhancement improves performance on working memory by modulating the functional activity in distinct brain regions: a positron emission tomography regional cerebral blood flow study in healthy humans.

Previously, we have shown that physostigmine, an acetylcholinesterase inhibitor, improved performance on a working memory for faces task, as reflected by reduced reaction time (RT), and reduced task-specific regional cerebral blood flow (rCBF) in right prefrontal cortex and, further, that these reductions in RT and right frontal rCBF were significantly correlated. Here we investigated the relation between the effects of physostigmine on task performance and task-specific functional brain response throughout the cortex by examining correlations between physostigmine-related changes in rCBF in all brain areas and changes in RT. In subjects who received an infusion of physostigmine, reduced RT correlated (p<0.001) positively with reduced rCBF in right frontal cortex, left temporal cortex, anterior cingulate, and left hippocampus; and correlated with increased rCBF in medial occipital visual cortex. In subjects who received a placebo infusion of saline, no significant correlations between changes in RT and cortical rCBF were observed. The results show that cholinergically induced improvements in working memory performance are related to alterations in neural activity in multiple cortical regions, including increased neural activity in regions associated with early perceptual processing and decreased neural activity in regions associated with attention, memory encoding, and memory maintenance.

Adult↗
PubMed1999

Individual differences in PET activation of object perception and attention systems predict face matching accuracy.

We sought to investigate how individual differences in the regional patterns of cerebral blood flow (rCBF) relate to task performance during the perceptual matching of faces. We analyzed rCBF data obtained by PET and H2150 from nine young healthy, right-handed, adult males (mean age 29i3 years) using a statistical model of regional covariance, the Scaled Subprofile Model (SSM). SSM analysis performed on a voxel-basis for scan subtractions comparing face-matching and control tasks extracted two patterns whose subject expression in a multiple regression analysis was highly predictive of task accuracy (R2 = 0.87, p < 0.002). The pattern reflecting this linear combination was principally characterized by higher rCBF in regions of bilateral occipital and occipitotemporal cortex, right orbitofrontal cortex, left thalamus, basal ganglia, midbrain, and cerebellum with relatively lower rCBF in anterior cingulate, regions in bilateral prefrontal and temporal cortex, right thalamus, and right inferior parietal cortex. The results indicate that individual subject differences in face matching performance are specifically associated with the functional interaction of cortical and subcortical brain regions previously implicated in aspects of object perception and visual attentional processing.

Adult↗
PubMed1999

Regional cerebral blood flow in Down syndrome adults during the Wisconsin Card Sorting Test: exploring cognitive activation in the context of poor performance.

BACKGROUND: Prior studies have indicated abnormal frontal lobes in Down syndrome (DS). The Wisconsin Card Sorting Test (WCST) has been used during functional brain imaging studies to activate the prefrontal cortex. Whether this activation is dependent on successful performance remains unclear. To determine frontal lobe regional cerebral blood flow (rCBF) response in DS and to further understand the effect of performance on rCBF during the WCST, we studied DS adults who perform poorly on this task. METHODS: Initial slope (IS), an rCBF index, was measured with the 133Xe inhalation technique during a Numbers Matching Control Task and the WCST. Ten healthy DS subjects (mean age 28.3 years) and 20 sex-matched healthy volunteers (mean age 28.7 years) were examined. RESULTS: Performance of DS subjects was markedly impaired compared to controls. Both DS and control subjects significantly increased prefrontal IS indices compared to the control task during the WCST. CONCLUSIONS: Prefrontal activation in DS during the WCST was not related to performance of that task, but may reflect engagement of some components involved in the task, such as effort. Further, these results show that failure to activate prefrontal cortex during WCST in schizophrenia is unlikely to be due to poor performance alone.

Adult↗
PubMed1999

Region-specific corpus callosum atrophy correlates with the regional pattern of cortical glucose metabolism in Alzheimer disease.

BACKGROUND: Positron emission tomographic studies of patients with Alzheimer disease (AD) suggest a loss of metabolic functional interactions between different cortical regions. Atrophy of the corpus callosum as the major tract of intracortical connective fibers may reflect decreased cortical functional integration in AD. OBJECTIVES: To investigate whether regional atrophy of the corpus callosum is correlated with regional reductions of cortical glucose metabolism, as shown by positron emission tomography, and whether primary white matter degeneration is a possible cofactor of corpus callosum atrophy in AD. PATIENTS AND METHODS: We measured total and regional cross-sectional areas of the corpus callosum on midsagittal magnetic resonance imaging scans from 12 patients with AD and 15 age-matched control subjects. Regional cerebral metabolic rates for glucose in cortical lobes were measured by positron emission tomography using fludeoxyglucose F 18. White matter hyperintensities were rated in T2-weighted magnetic resonance imaging scans. RESULTS: The total cross-sectional area of corpus callosum was significantly reduced in patients with AD, with the most prominent changes in the rostrum and splenium and relative sparing of the body of the corpus callosum. Frontal and parietal lobe metabolism was correlated with the truncal area of the corpus callosum in AD. The ratios of frontal to parietal and of frontal to occipital metabolism were correlated with the ratio of anterior to posterior corpus callosum area in the group with AD. White matter hyperintensities did not correlate with corpus callosum atrophy in the patients with AD. CONCLUSION: The regional pattern of corpus callosum atrophy correlated with reduced regional glucose metabolism independently of primary white matter degeneration in the patients with AD.

Aged↗
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

High brain myo-inositol levels in the predementia phase of Alzheimer's disease in adults with Down's syndrome: a 1H MRS study.

OBJECTIVE: An extra portion of chromosome 21 in Down's syndrome leads to a dementia in later life that is phenotypically similar to Alzheimer's disease. Down's syndrome therefore represents a model for studying preclinical stages of Alzheimer's disease. Markers that have been investigated in symptomatic Alzheimer's disease are myoinositol and N-acetyl-aspartate. The authors investigated whether abnormal brain levels of myo-inositol and other metabolites occur in the preclinical stages of Alzheimer's disease associated with Down's syndrome. METHOD: The authors used 1H magnetic resonance spectroscopy (MRS) with external standards to measure absolute brain metabolite concentrations in 19 nondemented adults with Down's syndrome and 17 age- and sex-matched healthy comparison subjects. RESULTS: Concentrations of myoinositol and choline-containing compounds were significantly higher in the occipital and parietal regions of the adults with Down's syndrome than in the comparison subjects. Within the Down's syndrome group, older subjects (42-62 years, N = 11) had higher myo-inositol levels than younger subjects (28-39 years, N = 8). Older subjects in both groups had lower N-acetylaspartate levels than the respective younger subjects, although this old-young difference was not greater in the Down's syndrome group. CONCLUSIONS: The approximately 50% higher level of myo-inositol in Down's syndrome suggests a gene dose effect of the extra chromosome 21, where the human osmoregulatory sodium/myo-inositol cotransporter gene is located. The even higher myoinositol level in older adults with Down's syndrome extends to the predementia phase earlier findings of high myoinositol levels in symptomatic Alzheimer's disease.

Adult↗
PubMed1999

Association between brain functional failure and dementia severity in Alzheimer's disease: resting versus stimulation PET study.

OBJECTIVE: This study tested the hypothesis that regional cerebral glucose metabolism during neuronal activation is a more sensitive index of neuronal dysfunction and clinical severity in Alzheimer's disease than is glucose metabolism at rest. METHOD: The subjects were 15 Alzheimer's disease patients with a wide range of Mattis Dementia Rating Scale scores (23-128). By using positron emission tomography, absolute glucose metabolism was measured in the parietal, occipital (visual areas), and temporal (auditory areas) cortical regions during rest (eyes/ears covered) and audiovisual stimulation. RESULTS: In the parietal cortex, glucose metabolism correlated with dementia severity in both conditions. In contrast, in the relatively preserved visual and auditory cortical regions, glucose metabolism predicted dementia severity during stimulation but not at rest. CONCLUSIONS: These findings suggest that regional cerebral glucose metabolism during stimulation is a more sensitive index of the functional/metabolic failure of neuronal systems than is metabolism at rest.

Acoustic Stimulation↗
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↗