Diffusion Tensor Imaging of the Cerebellum and Eyeblink Conditioning in Fetal Alcohol Spectrum Disorder

Authors

  • Bruce S. Spottiswoode,

    1. From the Department of Human Biology (BSS, EMM, JLJ, SWJ), the MRC UCT Medical Imaging Research Unit (BSS, EMM), and the Department of Psychiatry and Mental Health (CDM, JLJ, SWJ), University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Division of Radiology (BSS), University of Stellenbosch Faculty of Health Sciences, Cape Town, South Africa; Vanderbilt University Institute of Imaging Science (AWA, JCG), Department of Biomedical Engineering (AWA), and Department of Radiology and Radiological Sciences, Vanderbilt University (JCG), Vanderbilt University, Nashville, Tennessee; Department of Psychology (MES), University of Delaware, Newark, Delaware; Department of Psychiatry and Behavioral Neurosciences (NCD, JLJ, SWJ), Wayne State University School of Medicine, Detroit, Michigan; Division of Child Psychiatry (BSP), Columbia College of Physicians & Surgeons, New York, New York.
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  • Ernesta M. Meintjes,

    1. From the Department of Human Biology (BSS, EMM, JLJ, SWJ), the MRC UCT Medical Imaging Research Unit (BSS, EMM), and the Department of Psychiatry and Mental Health (CDM, JLJ, SWJ), University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Division of Radiology (BSS), University of Stellenbosch Faculty of Health Sciences, Cape Town, South Africa; Vanderbilt University Institute of Imaging Science (AWA, JCG), Department of Biomedical Engineering (AWA), and Department of Radiology and Radiological Sciences, Vanderbilt University (JCG), Vanderbilt University, Nashville, Tennessee; Department of Psychology (MES), University of Delaware, Newark, Delaware; Department of Psychiatry and Behavioral Neurosciences (NCD, JLJ, SWJ), Wayne State University School of Medicine, Detroit, Michigan; Division of Child Psychiatry (BSP), Columbia College of Physicians & Surgeons, New York, New York.
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  • Adam W. Anderson,

    1. From the Department of Human Biology (BSS, EMM, JLJ, SWJ), the MRC UCT Medical Imaging Research Unit (BSS, EMM), and the Department of Psychiatry and Mental Health (CDM, JLJ, SWJ), University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Division of Radiology (BSS), University of Stellenbosch Faculty of Health Sciences, Cape Town, South Africa; Vanderbilt University Institute of Imaging Science (AWA, JCG), Department of Biomedical Engineering (AWA), and Department of Radiology and Radiological Sciences, Vanderbilt University (JCG), Vanderbilt University, Nashville, Tennessee; Department of Psychology (MES), University of Delaware, Newark, Delaware; Department of Psychiatry and Behavioral Neurosciences (NCD, JLJ, SWJ), Wayne State University School of Medicine, Detroit, Michigan; Division of Child Psychiatry (BSP), Columbia College of Physicians & Surgeons, New York, New York.
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  • Christopher D. Molteno,

    1. From the Department of Human Biology (BSS, EMM, JLJ, SWJ), the MRC UCT Medical Imaging Research Unit (BSS, EMM), and the Department of Psychiatry and Mental Health (CDM, JLJ, SWJ), University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Division of Radiology (BSS), University of Stellenbosch Faculty of Health Sciences, Cape Town, South Africa; Vanderbilt University Institute of Imaging Science (AWA, JCG), Department of Biomedical Engineering (AWA), and Department of Radiology and Radiological Sciences, Vanderbilt University (JCG), Vanderbilt University, Nashville, Tennessee; Department of Psychology (MES), University of Delaware, Newark, Delaware; Department of Psychiatry and Behavioral Neurosciences (NCD, JLJ, SWJ), Wayne State University School of Medicine, Detroit, Michigan; Division of Child Psychiatry (BSP), Columbia College of Physicians & Surgeons, New York, New York.
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  • Mark E. Stanton,

    1. From the Department of Human Biology (BSS, EMM, JLJ, SWJ), the MRC UCT Medical Imaging Research Unit (BSS, EMM), and the Department of Psychiatry and Mental Health (CDM, JLJ, SWJ), University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Division of Radiology (BSS), University of Stellenbosch Faculty of Health Sciences, Cape Town, South Africa; Vanderbilt University Institute of Imaging Science (AWA, JCG), Department of Biomedical Engineering (AWA), and Department of Radiology and Radiological Sciences, Vanderbilt University (JCG), Vanderbilt University, Nashville, Tennessee; Department of Psychology (MES), University of Delaware, Newark, Delaware; Department of Psychiatry and Behavioral Neurosciences (NCD, JLJ, SWJ), Wayne State University School of Medicine, Detroit, Michigan; Division of Child Psychiatry (BSP), Columbia College of Physicians & Surgeons, New York, New York.
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  • Neil C. Dodge,

    1. From the Department of Human Biology (BSS, EMM, JLJ, SWJ), the MRC UCT Medical Imaging Research Unit (BSS, EMM), and the Department of Psychiatry and Mental Health (CDM, JLJ, SWJ), University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Division of Radiology (BSS), University of Stellenbosch Faculty of Health Sciences, Cape Town, South Africa; Vanderbilt University Institute of Imaging Science (AWA, JCG), Department of Biomedical Engineering (AWA), and Department of Radiology and Radiological Sciences, Vanderbilt University (JCG), Vanderbilt University, Nashville, Tennessee; Department of Psychology (MES), University of Delaware, Newark, Delaware; Department of Psychiatry and Behavioral Neurosciences (NCD, JLJ, SWJ), Wayne State University School of Medicine, Detroit, Michigan; Division of Child Psychiatry (BSP), Columbia College of Physicians & Surgeons, New York, New York.
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  • John C. Gore,

    1. From the Department of Human Biology (BSS, EMM, JLJ, SWJ), the MRC UCT Medical Imaging Research Unit (BSS, EMM), and the Department of Psychiatry and Mental Health (CDM, JLJ, SWJ), University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Division of Radiology (BSS), University of Stellenbosch Faculty of Health Sciences, Cape Town, South Africa; Vanderbilt University Institute of Imaging Science (AWA, JCG), Department of Biomedical Engineering (AWA), and Department of Radiology and Radiological Sciences, Vanderbilt University (JCG), Vanderbilt University, Nashville, Tennessee; Department of Psychology (MES), University of Delaware, Newark, Delaware; Department of Psychiatry and Behavioral Neurosciences (NCD, JLJ, SWJ), Wayne State University School of Medicine, Detroit, Michigan; Division of Child Psychiatry (BSP), Columbia College of Physicians & Surgeons, New York, New York.
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  • Bradley S. Peterson,

    1. From the Department of Human Biology (BSS, EMM, JLJ, SWJ), the MRC UCT Medical Imaging Research Unit (BSS, EMM), and the Department of Psychiatry and Mental Health (CDM, JLJ, SWJ), University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Division of Radiology (BSS), University of Stellenbosch Faculty of Health Sciences, Cape Town, South Africa; Vanderbilt University Institute of Imaging Science (AWA, JCG), Department of Biomedical Engineering (AWA), and Department of Radiology and Radiological Sciences, Vanderbilt University (JCG), Vanderbilt University, Nashville, Tennessee; Department of Psychology (MES), University of Delaware, Newark, Delaware; Department of Psychiatry and Behavioral Neurosciences (NCD, JLJ, SWJ), Wayne State University School of Medicine, Detroit, Michigan; Division of Child Psychiatry (BSP), Columbia College of Physicians & Surgeons, New York, New York.
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  • Joseph L. Jacobson,

    1. From the Department of Human Biology (BSS, EMM, JLJ, SWJ), the MRC UCT Medical Imaging Research Unit (BSS, EMM), and the Department of Psychiatry and Mental Health (CDM, JLJ, SWJ), University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Division of Radiology (BSS), University of Stellenbosch Faculty of Health Sciences, Cape Town, South Africa; Vanderbilt University Institute of Imaging Science (AWA, JCG), Department of Biomedical Engineering (AWA), and Department of Radiology and Radiological Sciences, Vanderbilt University (JCG), Vanderbilt University, Nashville, Tennessee; Department of Psychology (MES), University of Delaware, Newark, Delaware; Department of Psychiatry and Behavioral Neurosciences (NCD, JLJ, SWJ), Wayne State University School of Medicine, Detroit, Michigan; Division of Child Psychiatry (BSP), Columbia College of Physicians & Surgeons, New York, New York.
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  • Sandra W. Jacobson

    1. From the Department of Human Biology (BSS, EMM, JLJ, SWJ), the MRC UCT Medical Imaging Research Unit (BSS, EMM), and the Department of Psychiatry and Mental Health (CDM, JLJ, SWJ), University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Division of Radiology (BSS), University of Stellenbosch Faculty of Health Sciences, Cape Town, South Africa; Vanderbilt University Institute of Imaging Science (AWA, JCG), Department of Biomedical Engineering (AWA), and Department of Radiology and Radiological Sciences, Vanderbilt University (JCG), Vanderbilt University, Nashville, Tennessee; Department of Psychology (MES), University of Delaware, Newark, Delaware; Department of Psychiatry and Behavioral Neurosciences (NCD, JLJ, SWJ), Wayne State University School of Medicine, Detroit, Michigan; Division of Child Psychiatry (BSP), Columbia College of Physicians & Surgeons, New York, New York.
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Reprints requests: B. S. Spottiswoode, PhD, Department of Human Biology, University of Cape Town, Faculty of Health Sciences, Anatomy Building 7th Floor, Anzio Road, Cape Town, South Africa; Tel.: +27-21-938-9652; Fax: +27-21-938-9728; E-mail: bspotty@gmail.comor Sandra W. Jacobson, PhD, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 2751 E. Jefferson, Room 460, Detroit, MI 48207; Tel.: 313-993-5454; Fax: 313-993-3427; E-mail: sandra.jacobson@wayne.edu

Abstract

Background:  Prenatal alcohol exposure is related to a wide range of neurocognitive effects. Eyeblink conditioning (EBC), which involves temporal pairing of a conditioned with an unconditioned stimulus, has been shown to be a potential biomarker of fetal alcohol exposure. A growing body of evidence suggests that white matter may be a specific target of alcohol teratogenesis, and the neural circuitry underlying EBC is known to involve the cerebellar peduncles. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that has proven useful for assessing central nervous system white matter integrity. This study used DTI to examine the degree to which the fetal alcohol-related deficit in EBC may be mediated by structural impairment in the cerebellar peduncles.

Methods:  Thirteen children with fetal alcohol spectrum disorder (FASD) and 12 matched controls were scanned using DTI and structural MRI sequences. The DTI data were processed using a voxelwise technique, and the structural data were used for volumetric analyses. Prenatal alcohol exposure group and EBC performance were examined in relation to brain volumes and outputs from the DTI analysis.

Results:  Fractional anisotropy (FA) and perpendicular diffusivity group differences between alcohol-exposed and nonexposed children were identified in the left middle cerebellar peduncle. Alcohol exposure correlated with lower FA and greater perpendicular diffusivity in this region, and these correlations remained significant even after controlling for total brain and cerebellar volumes. Conversely, trace conditioning performance was related to higher FA and lower perpendicular diffusivity in the left middle peduncle. The effect of prenatal alcohol exposure on trace conditioning was partially mediated by lower FA in this region.

Conclusions:  This study extends recent findings that have used DTI to reveal microstructural deficits in white matter in children with FASD. This is the first DTI study to demonstrate mediation of a fetal alcohol-related effect on neuropsychological function by deficits in white matter integrity.

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