Biomedical subjects

A L Reiss

Publications and source records attributed to A L Reiss.

At least 37 records · Page 2Linked to original sources

PubMed2001

Dorsal forebrain anomaly in Williams syndrome.

BACKGROUND: Williams syndrome (WMS) is a rare neurogenetic condition with a behavioral phenotype that suggests a dorsal and/or ventral developmental dissociation, with deficits in dorsal but not the ventral hemispheric visual stream. A shortened extent of the dorsal central sulcus has been observed in autopsy specimens. OBJECTIVE: To compare gross anatomical features between the dorsal and ventral portions of the cerebral hemispheres by examining the dorsal extent of the central sulcus in brain magnetic resonance images from a sample of subjects with WMS and age- and sex-matched control subjects. SUBJECTS: Twenty-one subjects having clinically and genetically diagnosed WMS (mean +/- SD age, 28.9 +/- 7.9 years) were compared with 21 age- and sex-matched typically developing controls (mean +/- SD age, 28.8 +/- 7.9 years). DESIGN: High-resolution structural magnetic resonance images were acquired. The extent of the central sulcus was qualitatively assessed via surface projections of the cerebral cortex. RESULTS: The dorsal central sulcus is less likely to reach the interhemispheric fissure in subjects with WMS than in controls for both left (P< .001, chi(2) = 15.79) and right (P< .001, chi(2) = 12.95) hemispheres. No differences between the groups were found in the ventral extent of the central sulcus. CONCLUSIONS: Anomalies in the dorsal region in patients with WMS are indicative of early neurodevelopmental problems affecting the development of the dorsal forebrain and are most likely related to the deficits in visuospatial ability and behavioral timing often observed in this condition.

Adult↗

PubMed2001

Analysis of cerebral shape in Williams syndrome.

BACKGROUND: As a neurobehavioral disorder with a specific neurocognitive profile and a well-defined genetic etiology, Williams syndrome (WMS) provides an exceptional opportunity to examine associations among measures of behavior, neuroanatomy, and genetics. This study was designed to determine how cerebral shape differs between the brains of subjects with WMS and those of normal controls. SUBJECTS: Twenty adults with clinically and genetically diagnosed WMS (mean +/- SD age, 28.5 +/- 8.3 years) and 20 healthy, age- and sex-matched controls (mean +/- SD age, 28.5 +/- 8.2 years). DESIGN: High-resolution structural magnetic resonance imaging data were used for shape-based morphological analysis of the right and left cerebral hemispheres and the corpus callosum. Statistical analyses were performed to examine group differences. RESULTS: Both right and left cerebral hemispheres of subjects with WMS bend to a lesser degree in the sagittal plane than normal controls (P<.001). The corpus callosum also bends less in subjects with WMS (P =.05). In addition, subjects with WMS have decreased cerebral (P<.001) and corpus callosum (P<.001) midline lengths. CONCLUSIONS: Subjects with WMS have significantly different cerebral shape from normal controls, perhaps due to decreased parieto-occipital lobe volumes relative to frontal regions. The similar observation in the corpus callosum may be associated with a decreased size of the splenium in WMS. These findings may provide important clues to the effect of genes in the WMS-deleted region on brain development.

Adult↗

PubMed2001

Parental origin of the deletion 22q11.2 and brain development in velocardiofacial syndrome: a preliminary study.

BACKGROUND: As children with velocardiofacial syndrome (VCFS) develop, they are at increased risk for psychopathology; one third will eventually develop schizophrenia. Because VCFS and the concomitant symptomatology result from a known genetic origin, the biological and behavioral characteristics of the syndrome provide an optimal framework for conceptualizing the associations among genes, brain development, and behavior. The purpose of this study was to investigate the effect of the parental origin of the 22q11.2 microdeletion on the brain development of children and adolescents with VCFS. METHODS: Eighteen persons with VCFS and 18 normal control subjects were matched individually for age and sex. Results of DNA polymorphism analyses determined the parental origin of the deletion. Nine persons with VCFS had a deletion on the maternally derived chromosome 22; 9 persons, on the paternally derived chromosome 22. High-resolution magnetic resonance imaging scans were analyzed to provide quantitative measures of gray and white matter brain tissue. RESULTS: Total brain volume was approximately 11% smaller in the VCFS group than in controls. Comparisons between VCFS subgroups (maternal vs paternal microdeletion 22q11.2) indicated a significant 9% volumetric difference in total volume of cerebral gray matter (volume was greater in patients with paternal microdeletion) but not cerebral white matter. Significant age-related changes in gray matter were detected for subjects whose 22q11.2 deletion was on the maternal chromosome. CONCLUSIONS: Children and adolescents with VCFS experience major alterations in brain volumes. Significant reduction in gray matter development is attributable to presence of 22q11.2 microdeletion on the maternal chromosome.

Abnormalities, Multiple↗

PubMed2001

Error-related brain activation during a Go/NoGo response inhibition task.

Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error-related brain activity associated with failure to inhibit response during a Go/NoGo task. Error-related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans.

Adolescent↗

PubMed2001

Functional neuroanatomy of visuo-spatial working memory in Turner syndrome.

Turner syndrome (TS), a genetic disorder characterized by the absence of an X chromosome in females, has been associated with cognitive and visuo-spatial processing impairments. We utilized functional MRI (fMRI) to investigate the neural substrates that underlie observed deficits in executive functioning and visuo-spatial processing. Eleven females with TS and 14 typically developing females (ages 7-20) underwent fMRI scanning while performing 1-back and 2-back versions of a standard visuo-spatial working memory (WM) task. On both tasks, TS subjects performed worse than control subjects. Compared with controls, TS subjects showed increased activation in the left and right supramarginal gyrus (SMG) during the 1-back task and decreased activation in these regions during the 2-back task. In addition, decreased activation in the left and right dorsolateral prefrontal cortex (DLPFC) and caudate nucleus was observed during the 2-back task in TS subjects. Activation differences localized to the SMG, in the inferior parietal lobe, may reflect deficits in visuo-spatial encoding and WM storage mechanisms in TS. In addition, deficits in the DLPFC and caudate may be related to deficits in executive function during WM performance. Together these findings point to deficits in frontal-striatal and frontal-parietal circuits subserving multiple WM functions in TS.

Adolescent↗

PubMed2001

Brain anatomy, gender and IQ in children and adolescents with fragile X syndrome.

This study utilized MRI data to describe neuroanatomical morphology in children and adolescents with fragile X syndrome, the most common inherited cause of developmental disability. The syndrome provides a model for understanding how specific genetic factors can influence both neuroanatomy and cognitive capacity. Thirty-seven children and adolescents with fragile X syndrome received an MRI scan and cognitive testing. Scanning procedures and analytical strategies were identical to those reported in an earlier study of 85 typically developing children, permitting a comparison with a previously published template of normal brain development. Regression analyses indicated that there was a normative age-related decrease in grey matter and an increase in white matter. However, caudate and ventricular CSF volumes were significantly enlarged, and caudate volumes decreased with age. Rates of reduction of cortical grey matter were different for males and females. IQ scores were not significantly correlated with volumes of cortical and subcortical grey matter, and these relationships were statistically different from the correlational patterns observed in typically developing children. Children with fragile X syndrome exhibited several typical neurodevelopmental patterns. Aberrations in volumes of subcortical nuclei, gender differences in rates of cortical grey matter reduction and an absence of correlation between grey matter and cognitive performance provided indices of the deleterious effects of the fragile X mutation on the brain's structural organization.

Adolescent↗

PubMed2001

No widespread psychological effect of the fragile X premutation in childhood: evidence from a preliminary controlled study.

This study was designed to examine the effect of the fragile X premutation (pM) on cognitive function and behavior. Participants included 14 children (7 males, 7 females) with the fragile X pM and 14 children without the fragile X pM (and without the fragile X full mutation [fM]), each of whom was matched by age and gender with one of the participants from the pM group. The children ranged in age from 3 years, 1 month, to 17 years, 11 months. Participants were individually administered measures of intellectual functioning, academic achievement, and visual motor integration. Parent rating scales of problem behaviors were completed. Group differences were examined using nonparametric statistics. No statistically significant differences were found between the premutation and nonpremutation groups. The results from this study are consistent with the hypothesis that the premutation does not, in general, have an effect on a child's development. However, this does not preclude cases where specific factors may lead to a specific phenotype.

Adolescent↗

PubMed2001

Neuroanatomy of Down's syndrome: a high-resolution MRI study.

OBJECTIVE: Down's syndrome, the most common genetic cause of mental retardation, results in characteristic physical and neuropsychological findings, including mental retardation and deficits in language and memory. This study was undertaken to confirm previously reported abnormalities of regional brain volumes in Down's syndrome by using high-resolution magnetic resonance imaging (MRI), determine whether these volumetric abnormalities are present from childhood, and consider the relationship between neuroanatomic abnormalities and the cognitive profile of Down's syndrome. METHOD: Sixteen children and young adults with Down's syndrome (age range=5-23 years) were matched for age and gender with 15 normal comparison subjects. High-resolution MRI scans were quantitatively analyzed for measures of overall and regional brain volumes and by tissue composition. RESULTS: Consistent with prior imaging studies, subjects with Down's syndrome had smaller overall brain volumes, with disproportionately smaller cerebellar volumes and relatively larger subcortical gray matter volumes. Also noted was relative preservation of parietal lobe gray and temporal lobe white matter in subjects with Down's syndrome versus comparison subjects. No abnormalities in pattern of brain asymmetry were noted in Down's syndrome subjects. CONCLUSIONS: The results largely confirm findings of previous studies with respect to overall patterns of brain volumes in Down's syndrome and also provide new evidence for abnormal volumes of specific regional tissue components. The presence of these abnormalities from an early age suggests that fetal or early postnatal developmental differences may underlie the observed pattern of neuroanatomic abnormalities and contribute to the specific cognitive and developmental deficits seen in individuals with Down's syndrome.

Adolescent↗

PubMed2001

Velocardiofacial syndrome: are structural changes in the temporal and mesial temporal regions related to schizophrenia?

OBJECTIVE: Velocardiofacial syndrome results from a microdeletion on chromosome 22 (22q11.2). Clinical studies indicate that more than 30% of children with the syndrome will develop schizophrenia. The authors sought to determine whether neuroanatomical features in velocardiofacial syndrome are similar to those reported in the literature on schizophrenia by measuring the volumes of the temporal lobe, superior temporal gyrus, and mesial temporal structures in children and adolescents with velocardiofacial syndrome. METHOD: Twenty-three children and adolescents with velocardiofacial syndrome and 23 comparison subjects, individually matched for age and gender, received brain magnetic resonance imaging (MRI) scans. Analysis of covariance models were used to compare regional brain volumes. Correlations between residualized brain volumes and age were standardized and compared with the Fisher r-to-z transformation. RESULTS: Children with velocardiofacial syndrome had significantly smaller average temporal lobe, superior temporal gyrus, and hippocampal volumes than normal comparison children, although these differences were commensurate with a lower overall brain size in the affected children. In a cross-sectional analysis, children with velocardiofacial syndrome exhibited aberrant volumetric reductions with age that were localized to the temporal lobe and left hippocampal regions. CONCLUSIONS: Abnormal temporal lobe and hippocampal development in velocardiofacial syndrome is potentially concordant with MRI findings in the schizophrenia literature. Temporal lobe and mesial temporal structures may represent a shared substrate for the effects of the 22q11.2 deletion and for the complex etiological pathways that lead to schizophrenia. Longitudinal research may help determine which children with velocardiofacial syndrome are at risk for serious psychiatric illness in adulthood.

Abnormalities, Multiple↗

PubMed2001

Functional neuroanatomy of visuospatial working memory in fragile X syndrome: relation to behavioral and molecular measures.

OBJECTIVE: Fragile X syndrome is a neurogenetic disorder that is the most common known heritable cause of neurodevelopmental disability. This study examined the neural substrates of working memory in female subjects with fragile X syndrome. Possible correlations among behavioral measures, brain activation, and the FMR1 gene product (FMRP expression), as well as between IQ and behavioral measures, were investigated. METHOD: Functional magnetic resonance imaging was used to examine visuospatial working memory in 10 female subjects with fragile X syndrome and 15 typically developing female subjects (ages 10-23 years). Subjects performed standard 1-back and 2-back visuospatial working memory tasks. Brain activation was examined in four regions of the cortex known to play a critical role in visuospatial working memory. Correlations between behavioral, neuroimaging, and molecular measures were examined. RESULTS: Relative to the comparison group, subjects with fragile X syndrome performed significantly worse on the 2-back task but not on the 1-back task. In a region-of-interest analysis focused on the inferior frontal gyrus, middle frontal gyrus, superior parietal lobule, and supramarginal gyrus, comparison subjects showed significantly increased brain activation between the 1-back and 2-back tasks, but subjects with fragile X syndrome showed no change in activation between the two tasks. Significant correlations were found in comparison subjects between activation in the frontal and parietal regions and the rate of correct responses on the 2-back task, but not on the 1-back task. In subjects with fragile X syndrome, significant correlations were found during the 2-back task between FMRP expression and activation in the right inferior and bilateral middle frontal gyri and the bilateral supramarginal gyri. CONCLUSIONS: Subjects with fragile X syndrome are unable to modulate activation in the prefrontal and parietal cortex in response to an increasing working memory load, and these deficits are related to a lower level of FMRP expression in fragile X syndrome subjects than in normal comparison subjects. The observed correlations between biological markers and brain activation provide new evidence for links between gene expression and cognition.

Adolescent↗

PubMed2001

The influence of environmental and genetic factors on behavior problems and autistic symptoms in boys and girls with fragile X syndrome.

OBJECTIVE: Fragile X syndrome, caused by mutations in a single gene of the X chromosome (FMR1), is associated with neurobehavioral characteristics including social deficits with peers, social withdrawal, gaze aversion, inattention, hyperactivity, anxiety, depression, and autistic behavior. However, there is considerable variability in the behavioral and psychiatric problems among children with this condition. The purpose of this study was to measure genetic and environmental factors influencing behavior problems and autistic symptoms in children with fragile X syndrome. DESIGN: We conducted an in-home evaluation of 120 children (80 boys and 40 girls) with the fragile X full mutation and their unaffected siblings, including measurements of the FMR1 protein (FMRP), quality of the home environment, maternal and paternal psychopathology, effectiveness of educational and therapeutic services, and child behavior problems. RESULTS: Results of multiple regression analyses showed that for boys with fragile X, effectiveness of educational and therapeutic services and parental psychological problems predicted internalizing and externalizing types of problems, while the quality of the home environment predicted autistic behavior. For girls with fragile X, the results emphasized significant effects of FMRP on behavior, in particular social withdrawal and anxious/depressed behavior. CONCLUSIONS: These findings are among the first to link FMRP expression to behavior. They also emphasize the significance of home- and school-based environmental variables in the neurobehavioral phenotype and help to lay the foundation for studies designed to identify specific interventions for reducing problem behavior in children with fragile X syndrome.

Adolescent↗

PubMed2001

Corpus callosum morphology of Williams syndrome: relation to genetics and behavior.

As the largest interhemispheric commissure in the brain, the corpus callosum is of particular interest in disorders that may preferentially affect white matter development such as Williams syndrome (WS). Individuals with WS possess a remarkable array of neurobehavioral peaks and valleys, including deficits in visuospatial ability, mathematics, and attention, but with relative preservation of language and affect. Our study measured the corpus callosum and its primary subdivisions using high-resolution MRI in 20 individuals with WS (13 females and seven males; mean age 28.5, SD 8.3 years; range 19 to 44 years) and 20 age- and sex-matched control participants (mean age 28.5, SD 8.2 years; range 19 to 48 years). Total midsagittal corpus callosum area was reduced (F=4.5, p=0.04, df=36) in the WS population. The area of the splenium (F=12.4, p=0.001, df=36) and isthmus (F=9.4, p=0.004, df=36) were disproportionately reduced in WS beyond the absolute reduction of the entire corpus callosum. These reductions are in concordance with other neuroanatomical findings of decreased parietooccipital volumes as well as the observed visuospatial problems associated with WS.

Adult↗

PubMed2000

Functional brain activation during cognition is related to FMR1 gene expression.

Fragile X syndrome, the most common known cause of inherited mental retardation, is caused by alterations of the FMR1 gene encoding the FMRP protein. We investigated the relation between FMRP protein levels and functional brain activation during a working memory task. Our study provides the first evidence for a relation between FMR1 gene expression and neural activity during higher-order cognition. More broadly, our findings provide the first demonstration of how gene-brain-behavior investigations can help to bridge the gap between molecular and systems neuroscience.

Adolescent↗

PubMed2000

Brain morphology in Klinefelter syndrome: extra X chromosome and testosterone supplementation.

OBJECTIVE: This study focuses on variation in brain morphology associated with supernumerary X chromosome and Klinefelter syndrome (KS). Using an unselected birth cohort of KS subjects and high-resolution MRI, the authors investigated the neuroanatomic consequences of the 47,XXY karyotype in the presence and absence of exogenous testosterone supplementation. METHODS: Regional brain volumes were measured in 10 subjects with KS and 10 age-matched control men. Five of the KS subjects had received testosterone supplementation since puberty (KS+T) and five had not (KS-T). RESULTS: KS subjects showed significant (p < 0.01) reduction in left temporal lobe gray matter volumes compared with normal control subjects. Differences in left temporal gray volumes were also significant between the KS+T and KS-T groups (p < 0.01). Verbal fluency scores were significantly different between the KS+T and KS-T groups as well. CONCLUSION: Supernumerary X chromosome material in men is associated with a reduction in left temporal lobe gray matter, a finding that is consistent with the verbal and language deficits associated with KS. Also, relative preservation of gray matter in the left temporal region is associated with exposure to exogenous androgen during development. A history of testosterone supplementation also appears to be associated with increased verbal fluency scores in KS patients.

Adult↗

PubMed2000

Brain imaging in neurogenetic conditions: realizing the potential of behavioral neurogenetics research.

Behavioral neurogenetics research is a new method of scientific inquiry that focuses on investigation of neurodevelopmental dysfunction associated with specific genetic conditions. This research method provides a powerful tool for scientific inquiry into human gene-brain-behavior linkages that complements more traditional research approaches. In particular, the use of specific genetic conditions as models of common behavioral and cognitive disorders occurring in the general population can reveal insights into neurodevelopmental pathways that might otherwise be obscured or diluted when investigating more heterogeneous, behaviorally defined subject groups. In this paper, we review five genetic conditions that commonly give rise to identifiable neurodevelopmental and neuropsychiatric disability in children: fragile X syndrome, velo-cardio-facial syndrome, Williams syndrome, Turner syndrome, and Klinefelter syndrome. While emphasis is placed on describing the brain morphology associated with these conditions as revealed by neuroimaging studies, we also include information pertaining to molecular genetic, postmortem, and neurobehavioral investigations to illustrate how behavioral neurogenetics research can contribute to an improved understanding of brain disorders in childhood.

Diagnostic Imaging↗

PubMed2000

Dissociating prefrontal and parietal cortex activation during arithmetic processing.

Lesion and brain-imaging studies have implicated the prefrontal and parietal cortices in arithmetic processing, but do not exclude the possibility that these brain areas are also involved in nonarithmetic operations. In the present study, we used functional magnetic resonance imaging to explore which brain areas contribute uniquely to numeric computation. Task difficulty was manipulated in a factorial design by varying the number of operands and the rate of stimulus presentation. Both manipulations increased the number of operations to be performed in unit time. Manipulating the number of operands allowed us to investigate the specific effect of calculation, while manipulating the rate of presentation allowed us to increase task difficulty independent of calculation. We found quantitative changes in activation patterns in the prefrontal and parietal cortices as well as the recruitment of additional brain regions, including the caudate and midcerebellar cortex, with increasing task difficulty. More importantly, the main effect of arithmetic complexity was observed in the left and right angular gyrus, while the main effect of rate of stimulus presentation was observed in the left insular/orbitofrontal cortex. Our findings indicate a dissociation in prefrontal and parietal cortex function during arithmetic processing and further provide the first evidence for a specific role for the angular gyrus in arithmetic computation independent of other processing demands.

Adolescent↗

PubMed2000

Functional optimization of arithmetic processing in perfect performers.

Lesion and imaging studies to date have not clarified which sub-regions of the parietal lobe are specialized for arithmetic processing, and which perform supporting functions. We used functional magnetic resonance imaging to investigate parietal lobe function during arithmetic processing. Functional optimization was examined by analyzing regional differences in brain activation between perfect (100% accuracy) and imperfect performers. Perfect performers had significantly less activation only in the left angular gyrus, a finding that may be associated with skill mastery and long-term practice effects. The present results provide the first direct evidence of localized functional optimization for arithmetic processing in the human brain.

Adolescent↗

PubMed2000

Survey of the fragile X syndrome CGG repeat and the short-tandem-repeat and single-nucleotide-polymorphism haplotypes in an African American population.

Previous studies have shown that specific short-tandem-repeat (STR) and single-nucleotide-polymorphism (SNP)-based haplotypes within and among unaffected and fragile X white populations are found to be associated with specific CGG-repeat patterns. It has been hypothesized that these associations result from different mutational mechanisms, possibly influenced by the CGG structure and/or cis-acting factors. Alternatively, haplotype associations may result from the long mutational history of increasing instability. To understand the basis of the mutational process, we examined the CGG-repeat size, three flanking STR markers (DXS548-FRAXAC1-FRAXAC2), and one SNP (ATL1) spanning 150 kb around the CGG repeat in unaffected (n=637) and fragile X (n=63) African American populations and compared them with unaffected (n=721) and fragile X (n=102) white populations. Several important differences were found between the two ethnic groups. First, in contrast to that seen in the white population, no associations were observed among the African American intermediate or "predisposed" alleles (41-60 repeats). Second, two previously undescribed haplotypes accounted for the majority of the African American fragile X population. Third, a putative "protective" haplotype was not found among African Americans, whereas it was found among whites. Fourth, in contrast to that seen in whites, the SNP ATL1 was in linkage equilibrium among African Americans, and it did not add new information to the STR haplotypes. These data indicate that the STR- and SNP-based haplotype associations identified in whites probably reflect the mutational history of the expansion, rather than a mutational mechanism or pathway.

Black or African American↗