Biomedical subjects

Mark A Eckert

Publications and source records attributed to Mark A Eckert.

12 recordsLinked to original sources

PubMed2006

Frontostriatal dysfunction during response inhibition in Williams syndrome.

BACKGROUND: Williams syndrome (WS) has provided researchers with an exciting opportunity to understand the complex interplay among genes, neurobiological and cognitive functions. However, despite a well-characterized cognitive and behavioral phenotype, little attention has been paid to the marked deficits in social and behavioral inhibition. Here we explore the neural systems that mediate response inhibition in WS. METHODS: We used functional MRI (fMRI) to obtain blood oxygenation level dependence (BOLD) signal maps during the performance of a Go/NoGo response inhibition task from 11 clinically and genetically diagnosed WS patients and 11 age- and gender-matched typically developing (TD) control subjects. Correlations between behavioral, neuropsychological measures, and BOLD signal were also conducted. RESULTS: Although TD control subjects showed significantly faster response times, no group differences in behavioral accuracy were observed. Compared with control subjects, WS participants demonstrated significantly reduced activity in the striatum, dorsolateral prefrontal, and dorsal anterior cingulate cortices. These findings support the hypothesis that persons with WS fail to activate critical cortical and subcortical structures involved in behavioral inhibition. CONCLUSIONS: Our results provide important evidence for reduced engagement of the frontostriatal circuits in WS and provide putative biological markers for the deficits in response inhibition and the unusual social phenotype.

Adolescent↗

PubMed2006

Anomalous sylvian fissure morphology in Williams syndrome.

The unusual sensitivity and attraction to auditory stimuli in people with Williams syndrome (WS) has been hypothesized to be the consequence of atypical development of brain regions surrounding the Sylvian fissure. Planum temporale surface area, which is determined in part by Sylvian fissure patterning, was examined in 42 WS and 40 control participants to determine if anomalous Sylvian fissure morphology is present in WS. WS participants had significantly reduced leftward asymmetry of the planum temporale compared to control participants, due to a significant expansion in the size of the right planum temporale. The increased right planum temporale size was largely due to WS participants (24%) who had a right hemisphere Sylvian fissure that coursed horizontally and failed to ascend into the parietal lobe. This sulcal pattern is unusual in the right hemisphere and is more commonly found in the left hemisphere of typically developing individuals. There were no control participants with this type of right hemisphere Sylvian fissure pattern. The right hemisphere Sylvian fissure sulcal patterns were also related to a measure of cortical complexity and the amount of right hemisphere occipital lobe volume, suggesting that intrinsic genetic influences leading to anomalous visual system development in WS have widespread influences on cortical morphology that are similar in manner to extrinsic embryonic visual system lesions.

Adult↗

PubMed2006

Selective alterations of white matter associated with visuospatial and sensorimotor dysfunction in turner syndrome.

Turner syndrome (TS) is a neurogenetic disorder characterized by impaired spatial, numerical, and motor functioning but relatively spared verbal ability. Results from previous neuroimaging studies suggest that gray matter alterations in parietal and frontal regions may contribute to atypical visuospatial and executive functioning in TS. Recent findings in TS also indicate variations in the shape of parietal gyri and white matter microstructural anomalies of the temporal lobe. Diffusion tensor imaging and structural imaging methods were used to determine whether 10 females with TS and 10 age- and gender-matched control subjects exhibited differences in fractional anisotropy, white matter density, and local brain shape. Relative to controls, females with TS had lower fractional anisotropy (FA) values in the deep white matter of the left parietal-occipital region extending anteriorly along the superior longitudinal fasciculus into the deep white matter of the frontal lobe. In addition, decreased FA values were located bilaterally in the internal capsule extending into the globus pallidus and in the right prefrontal region. Voxel-based morphometry (VBM) analysis showed corresponding white matter density differences in the internal capsules and left centrum semiovale. Tensor-based morphometry analysis indicated that the FA and VBM results were not attributable to differences in the local shape of brain structures. Compared with controls, females with TS had increases in FA values and white matter density in language-related areas of the inferior parietal and temporal lobes. These complementary analyses provide evidence for alterations in white matter pathways that subserve affected and preserved cognitive functions in TS.

Adolescent↗

PubMed2006

To modulate or not to modulate: differing results in uniquely shaped Williams syndrome brains.

Voxel based morphometry (VBM) studies of Williams syndrome (WS) have demonstrated remarkably consistent findings of reduced posterior parietal gray matter compared to typical controls. Other WS VBM findings have been inconsistent, however. In particular, different findings have been reported for hypothalamus and orbitofrontal gray matter regions. We examined a sample of 8 WS and 9 control adults and show that the hypothalamus and orbitofrontal cortex results depend on whether the images undergo Jacobian modulation. Deformation based morphometry (DBM) analysis demonstrated that major brain shape differences between the groups accounted for the Jacobian modulated gray matter findings. These results indicate that cautious interpretations of modulated gray matter findings are warranted when there are gross shape and size differences between experimental groups. This study demonstrates the importance of methodological choices towards understanding a disorder like WS, but also highlights the consistency of parietal lobe, orbitofrontal, and midbrain findings for this disorder across methodologies, participants, and research groups.

Adult↗

PubMed2006

Uncoupled leftward asymmetries for planum morphology and functional language processing.

Explanations for left hemisphere language laterality have often focused on hemispheric structural asymmetry of the planum temporale. We examined the association between an index of language laterality and brain morphology in 99 normal adults whose degree of laterality was established using a functional MRI single-word comprehension task. The index of language laterality was derived from the difference in volume of activation between the left and right hemispheres. Planum temporale and brain volume measures were made using structural MRI scans, blind to the functional data. Although both planum temporale asymmetry (t(1,99) = 6.86, p < .001) and language laterality (t(1,99) = 15.26, p < .001) were significantly left hemisphere biased, there was not a significant association between these variables (r(99) = .01,ns). Brain volume, a control variable for the planum temporale analyses, was related to language laterality in a multiple regression (beta = -.30, t = -2.25, p < .05). Individuals with small brains were more likely to demonstrate strong left hemisphere language laterality. These results suggest that language laterality is a multidimensional construct with complex neurological origins.

Adolescent↗

PubMed2005

Abnormal cortical complexity and thickness profiles mapped in Williams syndrome.

We identified and mapped an anatomically localized failure of cortical maturation in Williams syndrome (WS), a genetic condition associated with deletion of approximately 20 contiguous genes on chromosome 7. Detailed three-dimensional (3D) maps of cortical thickness, based on magnetic resonance imaging (MRI) scans of 164 brain hemispheres, identified a delimited zone of right hemisphere perisylvian cortex that was thicker in WS than in matched controls, despite pervasive gray and white matter deficits and reduced total cerebral volumes. 3D cortical surface models were extracted from 82 T1-weighted brain MRI scans (256 x 192 x 124 volumes) of 42 subjects with genetically confirmed WS (mean +/- SD, 29.2 +/- 9.0 years of age; 19 males, 23 females) and 40 age-matched healthy controls (27.5 +/- 7.4 years of age; 16 males, 24 females). A cortical pattern-matching technique used 72 sulcal landmarks traced on each brain as anchors to align cortical thickness maps across subjects, build group average maps, and identify regions with altered cortical thickness in WS. Cortical models were remeshed in frequency space to compute their fractal dimension (surface complexity) for each hemisphere and lobe. Surface complexity was significantly increased in WS (p < 0.0015 and p < 0.0014 for left and right hemispheres, respectively) and correlated with temporoparietal gyrification differences, classified via Steinmetz criteria. In WS, cortical thickness was increased by 5-10% in a circumscribed right hemisphere perisylvian and inferior temporal zone (p < 0.002). Spatially extended cortical regions were identified with increased complexity and thickness; cortical thickness and complexity were also positively correlated in controls (p < 0.03). These findings visualize cortical zones with altered anatomy in WS, which merit additional study with techniques to assess function and connectivity.

Adolescent↗

PubMed2005

Anatomical signatures of dyslexia in children: unique information from manual and voxel based morphometry brain measures.

Thirteen male control and thirteen male dyslexic children (age, 121-152 months) were studied to determine if voxel based morphometry (VBM) could identify anatomical differences in the right cerebellar anterior lobe, and right and left pars triangularis that were identified with manual measures of the same children. VBM demonstrated significant gray and white matter differences in these three brain regions. In contrast to the manual results, these differences were not significant after controlling for brain volume, suggesting the manual measures captured additional important variance that distinguished the groups. Post-hoc VBM comparisons demonstrated white matter volume differences in a left temporal-parietal region that are consistent in location with results from diffusion tensor imaging studies of dyslexia. The VBM analyses also identified, gray matter volume differences in the left and right lingual gyrus, left inferior parietal lobule and cerebellum, areas that had not been examined with manual methods. We conclude that manual and automated methods provide valuable and complementary approaches to the search for functionally significant neurobiological characteristics of dyslexia.

Brain↗

PubMed2004

An experiment of nature: brain anatomy parallels cognition and behavior in Williams syndrome.

Williams syndrome (WS) is a neurogenetic-neurodevelopmental disorder characterized by a highly variable and enigmatic profile of cognitive and behavioral features. Relative to overall intellect, affected individuals demonstrate disproportionately severe visual-spatial deficits and enhanced emotionality and face processing. In this study, high-resolution magnetic resonance imaging data were collected from 43 individuals with WS and 40 age- and gender-matched healthy controls. Given the distinct cognitive-behavioral dissociations associated with this disorder, we hypothesized that neuroanatomical integrity in WS would be diminished most in regions comprising the visual-spatial system and most "preserved" or even augmented in regions involved in emotion and face processing. Both volumetric analysis and voxel-based morphometry were used to provide convergent approaches for detecting the hypothesized WS neuroanatomical profile. After adjusting for overall brain volume, participants with WS showed reduced thalamic and occipital lobe gray matter volumes and reduced gray matter density in subcortical and cortical regions comprising the human visual-spatial system compared with controls. The WS group also showed disproportionate increases in volume and gray matter density in several areas known to participate in emotion and face processing, including the amygdala, orbital and medial prefrontal cortices, anterior cingulate, insular cortex, and superior temporal gyrus. These findings point to specific neuroanatomical correlates for the unique topography of cognitive and behavioral features associated with this disorder.

Adolescent↗

PubMed2003

Modulation of neural connectivity during tongue movement and reading.

In a functional magnetic resonance imaging (fMRI) study, a novel connectivity analysis method termed within-condition interregional covariance analysis (WICA) was introduced for investigation into brain modulation during tongue movement and reading Chinese pinyins and logographic characters. We found that performing a horizontal tongue movement task generated a specific brain module with hierarchical orders of neural computation. Such functional modularity was further examined during both overt and silent Chinese reading tasks. Our results showed that overt pinyin reading was associated with the following distributed regions involved in tongue movement: the primary motor cortex (M1), the supplementary motor area (SMA), Broca's area, and Wernicke's area. Furthermore, we have used the WICA and demonstrated task-dependent covariance patterns that are strongly associated with the M1 mouth/tongue region, in which the Broca-Wernicke pathway is implicated in a meaning access procedure based on assembled phonology, while the SMA-Broca pathway is implicated in a meaning access procedure based on addressed phonology. Our functional connectivity analysis of the neural pathway involved in language processing may provide a basis for future studies of the dynamic neural network associated with language learning and reading in both developmental and disease conditions.

Adult↗

PubMed2003

Anatomical correlates of dyslexia: frontal and cerebellar findings.

In this study, we examined the neuroanatomy of dyslexic (14 males, four females) and control (19 males, 13 females) children in grades 4-6 from a family genetics study. The dyslexics had specific deficits in word reading relative to the population mean and verbal IQ, but did not have primary language or motor deficits. Measurements of the posterior temporal lobe, inferior frontal gyrus, cerebellum and whole brain were collected from MRI scans. The dyslexics exhibited significantly smaller right anterior lobes of the cerebellum, pars triangularis bilaterally, and brain volume. Measures of the right cerebellar anterior lobe and the left and right pars triangularis correctly classified 72% of the dyslexic subjects (94% of whom had a rapid automatic naming deficit) and 88% of the controls. The cerebellar anterior lobe and pars triangularis made significant contributions to the classification of subjects after controlling for brain volume. Correlational analyses showed that these neuroanatomical measurements were also significantly correlated with reading, spelling and language measures related to dyslexia. Age was not related to any anatomical variable. Results for the dyslexic children from the family genetics study are discussed with reference to dyslexic adults from a prior study, who were ascertained on the basis of a discrepancy between phonological coding and reading comprehension. The volume of the right anterior lobe of the cerebellum distinguished dyslexic from control participants in both studies. The cerebellum is one of the most consistent locations for structural differences between dyslexic and control participants in imaging studies. This study may be the first to show that anomalies in a cerebellar-frontal circuit are associated with rapid automatic naming and the double-deficit subtype of dyslexia.

Adolescent↗

PubMed2002

The epigenesis of planum temporale asymmetry in twins.

Variation in hemispheric asymmetry of the planum temporale (PT) has been related to verbal ability. The degree to which genetic and environmental factors mediate PT asymmetry is not known. This study examined the heritability for planar asymmetry in 12 dizygotic (DZ) and 27 monozygotic (MZ) male twin pairs who were between 6 and 16 years of age. There was weak but positive evidence for heritability of planar asymmetry. Co-twin similarity for planar asymmetry and Sylvian fissure morphology increased when excluding twins discordant for writing hand and when excluding twins exhibiting birth weight differences >20% from the analyses. Birth weight differences were also related to twin differences in total cerebral volume, but not central sulcus asymmetry. These results suggest that exogenous perinatal factors affect the epigenesis of planar asymmetry development.

Adolescent↗

PubMedDate not supplied

Anatomical risk factors that distinguish dyslexia from SLI predict reading skill in normal children.

UNLABELLED: These studies investigated whether anatomical measures could separate phonologically-based reading disability (PD) from nonphonologically-based learning disabilities such as specific language impairment (SLI). In a previous study. four brain measures (cerebral asymmetry. summed planum temporale and parietale asymmetry, anterior cerebellar asymmetry, and a duplicated left Heschl's gyrus) distinguished a group of PD adults from reading disabled adults without specific phonological deficits (URD). Study 1 found that these measures did not distinguish 14 reading disabled children from 21 children with SLI. Instead, differences were found in cerebral volume, planum temporale asymmetry, and the size of a single left Heschl's gyrus. Study 2 demonstrated that including all seven measures in a discriminant analysis separated the adults and children into two groups: one with 100% of the PD adults and 75% of the reading disabled children and the other with 72% of the SLI children and 75% of the URD adults. Study 3 demonstrated that an anatomical risk factor index (ARF7) generated from the discriminant function with seven brain measures predicted reading in normal children. Children with ARF7 near 0 (normal anatomy) had superior verbal ability and phonological decoding scores that improved with age. Normal children with negative ARF7 the relatively s mall symmetrical structures that characterize SLI)had deficits in verbal ability. Children with positive ARF7 (the asymmetrical structures that characterize PD) had phonological decoding scores that decreased with age. These results suggest that PD and SLI are qualitatively different disorders associated with anatomical deviations in opposite directions from the population mean. LEARNING OUTCOMES: As a result of this activity, the participant will be able to: (1) distinguish the neuroanatomical features that characterize PD and SLI; (2) recognize that PD is associated with large asymmetrical brain structures while SLI is associated with smaller symmetrical brain structures; (3) understand that children with moderate sized brains and whose anatomy is intermediate between symmetry and extreme asymmetry have an enhanced probability of developing good verbal ability; (4) understand that reading disabilities depend on the interaction of neurodevelopment and the environment.

Brain↗