Prenatal and Neonatal Brain Structure and White Matter Maturation in Children at High Risk for Schizophrenia
ABSTRACT Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia.
Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts.
Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties.
Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia.
Full-textDOI: · Available from: Jeffrey A Lieberman, Jun 01, 2015
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ABSTRACT: Diffusion-weighted imaging (DWI) is known to be prone to artifacts related to motion originating from subject movement, cardiac pulsation, and breathing, but also to mechanical issues such as table vibrations. Given the necessity for rigorous quality control and motion correction, users are often left to use simple heuristics to select correction schemes, which involves simple qualitative viewing of the set of DWI data, or the selection of transformation parameter thresholds for detection of motion outliers. The scientific community offers strong theoretical and experimental work on noise reduction and orientation distribution function (ODF) reconstruction techniques for HARDI data, where post-acquisition motion correction is widely performed, e.g., using the open-source DTIprep software (1), FSL (the FMRIB Software Library) (2), or TORTOISE (3). Nonetheless, effects and consequences of the selection of motion correction schemes on the final analysis, and the eventual risk of introducing confounding factors when comparing populations, are much less known and far beyond simple intuitive guessing. Hence, standard users lack clear guidelines and recommendations in practical settings. This paper reports a comprehensive evaluation framework to systematically assess the outcome of different motion correction choices commonly used by the scientific community on different DWI-derived measures. We make use of human brain HARDI data from a well-controlled motion experiment to simulate various degrees of motion corruption and noise contamination. Choices for correction include exclusion/scrubbing or registration of motion corrupted directions with different choices of interpolation, as well as the option of interpolation of all directions. The comparative evaluation is based on a study of the impact of motion correction using four metrics that quantify (1) similarity of fiber orientation distribution functions (fODFs), (2) deviation of local fiber orientations, (3) global brain connectivity via graph diffusion distance (GDD), and (4) the reproducibility of prominent and anatomically defined fiber tracts. Effects of various motion correction choices are systematically explored and illustrated, leading to a general conclusion of discouraging users from setting ad hoc thresholds on the estimated motion parameters beyond which volumes are claimed to be corrupted.Frontiers in Neurology 09/2014; 240(5). DOI:10.3389/fneur.2014.00240
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ABSTRACT: Functional magnetic resonance imaging (fMRI) research with infants and toddlers has increased rapidly over the past decade, and provided a unique window into early brain development. In the current report, we review the state of the literature, which has established the feasibility and utility of task-based fMRI and resting state functional connectivity MRI (rs-fcMRI) during early periods of brain maturation. These methodologies have been successfully applied beginning in the neonatal period to increase understanding of how the brain both responds to environmental stimuli, and becomes organized into large-scale functional systems that support complex behaviors. We discuss the methodological challenges posed by this promising area of research. We also highlight that despite these challenges, early work indicates a strong potential for these methods to influence multiple research domains. As an example, we focus on the study of early life stress and its influence on brain development and mental health outcomes. We illustrate the promise of these methodologies for building on, and making important contributions to, the existing literature in this field.Developmental Cognitive Neuroscience 04/2015; 12. DOI:10.1016/j.dcn.2014.09.005 · 3.71 Impact Factor
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ABSTRACT: Schizophrenia is a neurodevelopmental disorder associated with subtle abnormal cortical thickness and cortical surface area. However, it is unclear whether these abnormalities exist in neonates associated with genetic risk for schizophrenia. To this end, this preliminary study was conducted to identify possible abnormalities of cortical thickness and surface area in the high-genetic-risk neonates. Structural magnetic resonance images were acquired from offspring of mothers (N = 21) who had schizophrenia (N = 12) or schizoaffective disorder (N = 9), and also matched healthy neonates of mothers who were free of psychiatric illness (N = 26). Neonatal cortical surfaces were reconstructed and parcellated as regions of interest (ROIs), and cortical thickness for each vertex was computed as the shortest distance between the inner and outer surfaces. Comparisons were made for the average cortical thickness and total surface area in each of 68 cortical ROIs. After false discovery rate (FDR) correction, it was found that the female high-genetic-risk neonates had significantly thinner cortical thickness in the right lateral occipital cortex than the female control neonates. Before FDR correction, the high-genetic-risk neonates had significantly thinner cortex in the left transverse temporal gyrus, left banks of superior temporal sulcus, left lingual gyrus, right paracentral cortex, right posterior cingulate cortex, right temporal pole, and right lateral occipital cortex, compared with the control neonates. Before FDR correction, in comparison with control neonates, male high-risk neonates had significantly thicker cortex in the left frontal pole, left cuneus cortex, and left lateral occipital cortex; while female high-risk neonates had significantly thinner cortex in the bilateral paracentral, bilateral lateral occipital, left transverse temporal, left pars opercularis, right cuneus, and right posterior cingulate cortices. The high-risk neonates also had significantly smaller cortical surface area in the right pars triangularis (before FDR correction), compared with control neonates. This preliminary study provides the first evidence that early development of cortical thickness and surface area might be abnormal in the neonates at genetic risk for schizophrenia.Brain Structure and Function 11/2014; DOI:10.1007/s00429-014-0917-3 · 4.57 Impact Factor