-
Catherine Lebel,
Sarah N Mattson,
Edward P Riley,
Kenneth L Jones,
Colleen M Adnams,
Philip A May,
Susan Y Bookheimer,
Mary J O'Connor,
Katherine L Narr, Eric Kan,
Zvart Abaryan,
Elizabeth R Sowell
[show abstract]
[hide abstract]
ABSTRACT: Exposure to alcohol in utero can cause birth defects, including face and brain abnormalities, and is the most common preventable cause of intellectual disabilities. Here we use structural magnetic resonance imaging to measure cortical volume change longitudinally in a cohort of human children and youth with prenatal alcohol exposure (PAE) and a group of unexposed control subjects, demonstrating that the normal processes of brain maturation are disrupted in individuals whose mothers drank heavily during pregnancy. Trajectories of cortical volume change within children and youth with PAE differed from those of unexposed control subjects in posterior brain regions, particularly in the parietal cortex. In these areas, control children appear to show a particularly plastic cortex with a prolonged pattern of cortical volume increases followed by equally vigorous volume loss during adolescence, while the alcohol-exposed participants showed primarily volume loss, demonstrating decreased plasticity. Furthermore, smaller volume changes between scans were associated with lower intelligence and worse facial morphology in both groups, and were related to the amount of PAE during each trimester of pregnancy in the exposed group. This demonstrates that measures of IQ and facial dysmorphology predict, to some degree, the structural brain development that occurs in subsequent years. These results are encouraging in that interventions aimed at altering "experience" over time may improve brain trajectories in individuals with heavy PAE and possibly other neurodevelopmental disorders.
Journal of Neuroscience 10/2012; 32(44):15243-15251. · 7.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Socioeconomic disparities in childhood are associated with remarkable differences in cognitive and socio-emotional development during a time when dramatic changes are occurring in the brain. Yet, the neurobiological pathways through which socioeconomic status (SES) shapes development remain poorly understood. Behavioral evidence suggests that language, memory, social-emotional processing, and cognitive control exhibit relatively large differences across SES. Here we investigated whether volumetric differences could be observed across SES in several neural regions that support these skills. In a sample of 60 socioeconomically diverse children, highly significant SES differences in regional brain volume were observed in the hippocampus and the amygdala. In addition, SES × age interactions were observed in the left superior temporal gyrus and left inferior frontal gyrus, suggesting increasing SES differences with age in these regions. These results were not explained by differences in gender, race or IQ. Likely mechanisms include differences in the home linguistic environment and exposure to stress, which may serve as targets for intervention at a time of high neural plasticity.
Developmental Science 07/2012; 15(4):516-27. · 3.89 Impact Factor
-
Yaling Yang,
Owen R Phillips, Eric Kan,
Kathleen K Sulik,
Sarah N Mattson,
Edward P Riley,
Kenneth L Jones,
Colleen M Adnams,
Philip A May,
Mary J O'Connor,
Katherine L Narr,
Elizabeth R Sowell
[show abstract]
[hide abstract]
ABSTRACT: Structural abnormalities of the corpus callosum (CC), such as reduced size and increased shape variability, have been documented in individuals with fetal alcohol spectrum disorders (FASD). However, the regional specificity of altered CC structure, which may point to the timing of neurodevelopmental disturbances and/or relate to specific functional impairments, remains unclear. Furthermore, associations between facial dysmorphology and callosal structure remain undetermined.
One hundred and fifty-three participants (age range 8 to 16) including 82 subjects with FASD and 71 nonexposed controls were included in this study. The structural magnetic resonance imaging data of these subjects was collected at 3 sites (Los Angeles and San Diego, California, and Cape Town, South Africa) and analyzed using classical parcellation schemes, as well as more refined surface-based geometrical modeling methods, to identify callosal morphological alterations in FASD at high spatial resolution.
Reductions in callosal thickness and area, specifically in the anterior third and the splenium, were observed in FASD compared with nonexposed controls. In addition, reduced CC thickness and area significantly correlated with reduced palpebral fissure length.
Consistent with previous reports, findings suggest an adverse effect of prenatal alcohol exposure on callosal growth and further indicate that fiber pathways connecting frontal and parieto-occipital regions in each hemisphere may be particularly affected. Significant associations between callosal and facial dysmorphology provide evidence for a concurrent insult to midline facial and brain structural development in FASD.
Alcoholism Clinical and Experimental Research 12/2011; 36(5):798-806. · 3.34 Impact Factor
-
Yaling Yang,
Florence Roussotte, Eric Kan,
Kathleen K Sulik,
Sarah N Mattson,
Edward P Riley,
Kenneth L Jones,
Colleen M Adnams,
Philip A May,
Mary J O'Connor,
Katherine L Narr,
Elizabeth R Sowell
[show abstract]
[hide abstract]
ABSTRACT: Accumulating evidence from structural brain imaging studies on individuals with fetal alcohol spectrum disorder (FASD) has supported links between prenatal alcohol exposure and brain morphological deficits. Although global and regional volumetric reductions appear relatively robust, the effects of alcohol exposure on cortical thickness and relationships with facial dysmorphology are not yet known. The structural magnetic resonance imaging data from 69 children and adolescents with FASD and 58 nonexposed controls collected from 3 sites were examined using FreeSurfer to detect cortical thickness changes across the entire brain in FASD and their associations with facial dysmorphology. Controlling for brain size, subjects with FASD showed significantly thicker cortices than controls in several frontal, temporal, and parietal regions. Analyses conducted within site further revealed prominent group differences in left inferior frontal cortex within all 3 sites. In addition, increased inferior frontal thickness was significantly correlated with reduced palpebral fissure length. Consistent with previous reports, findings of this study are supportive of regional increases in cortical thickness serving as a biomarker for disrupted brain development in FASD. Furthermore, the significant associations between thickness and dysmorphic measures suggest that the severity of brain anomalies may be reflected by that of the face.
Cerebral Cortex 07/2011; 22(5):1170-9. · 6.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Development of syntactic processing was examined to evaluate maturational processes including left language lateralization functions and increased specialization of brain regions important for syntactic processing. We utilized multimodal methods, including indices of brain activity from fMRI during a syntactic processing task, cortical thickness measurements from structural MRI, and neuropsychological measures. To evaluate hypotheses about increasing lateralization and specialization with development, we examined relationships between cortical thickness and magnitude and spatial activation extent within the left inferior frontal gyrus (IFG) and its right hemisphere homologue. We predicted that increased activation in the left and decreased activation in the right IFG would be associated with increased syntactic proficiency. As predicted, a more mature pattern of increased thickness in the right pars triangularis was associated with decreased activation intensity and extent in the right IFG. These findings suggest a maturational shift towards decreased involvement of the right IFG for syntactic processing. Better syntactic skills were associated with increased activation in the left IFG independent from age, suggesting increased specialization of the left IFG with increased proficiency. Overall, our findings show relationships between structural and functional neurodevelopment that co-occur with improved syntactic processing in critical language regions of the IFG in typically developing children.
Developmental cognitive neuroscience. 07/2011; 1(3):313-23.
-
[show abstract]
[hide abstract]
ABSTRACT: Here we investigate the effects of prenatal exposure to methamphetamine (MA) on local brain volume using magnetic resonance imaging. Because many who use MA during pregnancy also use alcohol, a known teratogen, we examined whether local brain volumes differed among 61 children (ages 5-15 years), 21 with prenatal MA exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls. Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally and in right prefrontal and left occipitoparietal cortices. Striatal volume reductions were more severe in the MAA group than in the ALC group, and, within the MAA group, a negative correlation between full-scale intelligence quotient (FSIQ) scores and caudate volume was observed. Limbic structures, including the anterior and posterior cingulate, the inferior frontal gyrus (IFG), and ventral and lateral temporal lobes bilaterally, were increased in volume in both exposure groups. Furthermore, cingulate and right IFG volume increases were more pronounced in the MAA than ALC group. Discriminant function analyses using local volume measurements and FSIQ were used to predict group membership, yielding factor scores that correctly classified 72% of participants in jackknife analyses. These findings suggest that striatal and limbic structures, known to be sites of neurotoxicity in adult MA abusers, may be more vulnerable to prenatal MA exposure than alcohol exposure and that more severe striatal damage is associated with more severe cognitive deficit.
Journal of Neuroscience 03/2010; 30(11):3876-85. · 7.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Dynamic changes in brain structure, activation, and cognitive abilities co-occur during development, but little is known about how changes in brain structure relate to changes in cognitive function or brain activity. By using cortical pattern matching techniques to correlate cortical gray matter thickness and functional brain activity over the entire brain surface in 24 typically developing children, we integrated structural and functional magnetic resonance imaging data with cognitive test scores to identify correlates of mature performance during orthographic processing. Fast-naming individuals activated the right fronto-parietal attention network in response to novel fonts more than slow-naming individuals, and increased activation of this network was correlated with more mature brain morphology in the same fronto-parietal region. These relationships remained even after effects of age or general cognitive ability were statistically controlled. These results localized cortical regions where mature morphology corresponds to mature patterns of activation, and may suggest a role for experience in mediating brain structure-activation relationships.
Cerebral Cortex 03/2009; 19(11):2595-604. · 6.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Sulcal and gyral landmarks on the human cerebral cortex are required for various studies of the human brain. Whether used directly to examine sulcal geometry, or indirectly to drive cortical surface registration methods, the accuracy of these landmarks is essential. While several methods have been developed to automatically identify sulci and gyri, their accuracy may be insufficient for certain neuroanatomical studies. We describe a semi-automated procedure that delineates a sulcus or gyrus given a limited number of user-selected points. The method uses a graph theory approach to identify the lowest-cost path between the points, where the cost is a combination of local curvature features and the distance between vertices on the surface representation. We implemented the algorithm in an interface that guides the user through a cortical surface delineation protocol, and we incorporated this tool into our BrainSuite software. We performed a study to compare the results produced using our method with results produced using Display, a popular tool that has been used extensively for manual delineation of sulcal landmarks. Six raters were trained on the delineation protocol. They performed delineations on 12 brains using both software packages. We performed a statistical analysis of 3 aspects of the delineation task: time required to delineate the surface, registration accuracy achieved compared to an expert-delineated gold-standard, and variation among raters. Our new method was shown to be faster to use, to provide reduced inter-rater variability, and to provide results that were at least as accurate as those produced using Display.
Journal of neuroscience methods 01/2009; 178(2):385-92. · 2.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The basal ganglia portions of cortico-striato-thalamo-cortical (CSTC) circuits have consistently been implicated in the pathogenesis of Tourette syndrome, whereas motor and sensorimotor cortices in these circuits have been relatively overlooked. Using magnetic resonance imaging, we detected cortical thinning in frontal and parietal lobes in groups of Tourette syndrome children relative to controls. This thinning was most prominent in ventral portions of the sensory and motor homunculi that control the facial, orolingual and laryngeal musculature that is commonly involved in tic symptoms. Correlations of cortical thickness in sensorimotor regions with tic symptoms suggest that these brain regions are important in the pathogenesis of Tourette syndrome.
Nature Neuroscience 07/2008; 11(6):637-9. · 15.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Brain structural abnormalities and neurocognitive dysfunction have been observed in individuals with fetal alcohol spectrum disorders (FASDs). Little is known about how white matter integrity is related to these functional and morphological deficits. We used a combination of diffusion tensor and T1-weighted magnetic resonance imaging to evaluate white matter integrity in individuals with FASDs and related these findings to neurocognitive deficits. Seventeen children and adolescents with FASDs were compared with 19 typically developing age- and gender-matched controls. Lower fractional anisotropy (FA) was observed in individuals with FASDs relative to controls in the right lateral temporal lobe and bilaterally in the lateral aspects of the splenium of the corpus callosum. White matter density was also lower in some, but not all regions in which FA was lower. FA abnormalities were confirmed to be in areas of white matter in post hoc region of interest analyses, further supporting that less myelin or disorganized fiber tracts are associated with heavy prenatal alcohol exposure. Significant correlations between performance on a test of visuomotor integration and FA in bilateral splenium, but not temporal regions were observed within the FASD group. Correlations between the visuomotor task and FA within the splenium were not significant within the control group, and were not significant for measures of reading ability. This suggests that this region of white matter is particularly susceptible to damage from prenatal alcohol exposure and that disruption of splenial fibers in this group is associated with poorer visuomotor integration.
Journal of Neuroscience 03/2008; 28(6):1313-9. · 7.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Quantitative magnetic resonance imaging (MRI) studies in children with fetal alcohol spectrum disorders (FASDs) have shown regional patterns of dysmorphology, most prominent in parietal and posterior temporal cortices. Various methods of image analysis have been employed in these studies, but abnormalities in cortical thickness have not yet been mapped over the entire cortical surface in individuals with FASD. Further, relationships between cognitive dysfunction and cortical thickness measures have not yet been explored. We applied cortical pattern matching algorithms and techniques for measuring cortical thickness in millimeters to the structural brain MRI images of 21 subjects with heavy prenatal alcohol exposure (8-22 years, mean age 12.6 years), and 21 normally developing control subjects (8-25 years, mean age 13.5 years). Dissociable cognitive measures, of verbal recall and visuospatial functioning, were correlated with cortical thickness, and group by test score interactions were evaluated for predicting cortical thickness. Significant cortical thickness excesses of up to 1.2 mm were observed in the FASD subjects in large areas of bilateral temporal, bilateral inferior parietal, and right frontal regions. Significant group by test score interactions were found in right dorsal frontal regions for the verbal recall measure and in left occipital regions for the visuospatial measure. These results are consistent with earlier analyses from our own and other research groups, but for the first time, we show that cortical thickness is also increased in right lateral frontal regions in children with prenatal alcohol exposure. Further, the significant interactions show for the first time that brain-behavior relationships are altered as a function of heavy prenatal alcohol exposure.
Cerebral Cortex 02/2008; 18(1):136-44. · 6.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Findings from previous magnetic resonance imaging studies of sex differences in gray matter have been inconsistent, with some showing proportionally increased gray matter in women and some showing no differences between the sexes. Regional sex differences in gray matter thickness have not yet been mapped over the entire cortical surface in a large sample of subjects spanning the age range from early childhood to old age. We applied algorithms for cortical pattern matching and techniques for measuring cortical thickness to the structural magnetic resonance images of 176 healthy individuals between the ages of 7 and 87 years. We also mapped localized differences in brain size. Maps of sex differences in cortical thickness revealed thicker cortices in women in right inferior parietal and posterior temporal regions even without correcting for total brain volume. In these regions, the cortical mantle is up to 0.45 mm thicker, on average, in women than in men. Analysis of a subset of 18 female and 18 male subjects matched for age and brain volume confirmed the significance of thicker gray matter in temporal and parietal cortices in females, independent of brain size differences. Further analyses were conducted in the adult subjects where gender differences were evaluated using height as a covariate, and similar sex differences were observed even when body size differences between the sexes were controlled. Together, these results suggest that greater cortical thickness in posterior temporal inferior parietal regions in females relative to males are independent of differences in brain or body size. Age-by-sex interactions were not significant in the temporoparietal region, suggesting that sex differences in these regions are present from at least late childhood and then are maintained throughout life. Male brains were larger than female brains in all locations, though male enlargement was most prominent in the frontal and occipital poles, bilaterally. Given the large sample and the large range of ages studied, these results help to address controversies in the study of central nervous system sexual dimorphisms.
Cerebral Cortex 08/2007; 17(7):1550-60. · 6.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Prenatal exposure to alcohol can result in neuroanatomical and neurocognitive deficits. High-resolution magnetic resonance imaging, surface-based image analytic methods, and neuropsychological measures were used to characterize the cerebellar vermis and to evaluate potential cognitive correlates of vermal morphology in 21 children and adolescents with prenatal alcohol exposure and 21 normally developing individuals. Alcohol-exposed individuals showed statistically significant reductions in the midline sagittal areas of the anterior vermis and posterior-inferior vermis, and significant displacement of the anterior and posterior-inferior vermal regions. Anterior vermal dysmorphology was negatively correlated with verbal learning and memory performance within the alcohol-exposed group. These observations expand on previous reports of cerebellar abnormalities in prenatal alcohol exposure, in that they localize the specific pattern of cerebellar vermal dysmorphology.
Neuroreport 09/2005; 16(12):1285-90. · 1.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent advances in magnetic resonance imaging (MRI) technology now allow the tracing of developmental changes in the brains of children. We applied computer-matching algorithms and new techniques for measuring cortical thickness (in millimeters) to the structural MRI images of 45 children scanned twice (2 yr apart) between the ages 5 and 11. Changes in brain size were also assessed, showing local brain growth progressing at a rate of approximately 0.4-1.5 mm per year, most prominently in frontal and occipital regions. Estimated cortical thickness ranged from 1.5 mm in occipital regions to 5.5 mm in dorsomedial frontal cortex. Gray matter thinning coupled with cortical expansion was highly significant in right frontal and bilateral parieto-occipital regions. Significant thickening was restricted to left inferior frontal (Broca's area) and bilateral posterior perisylvian (Wernicke's area on the left) regions. In the left hemisphere, gray matter thickness was correlated with changing cognitive abilities. For the first time, developmental changes in gray matter thickness, brain size, and structure-function relationships have been traced within the same individuals studied longitudinally during a time of rapid cognitive development.
Journal of Neuroscience 10/2004; 24(38):8223-31. · 7.11 Impact Factor
