title: White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning.
abstract: Fetal alcohol spectrum disorders (FASD) are characterized by a range of neurodevelopmental deficits that result from prenatal exposure to alcohol. These can include cognitive, behavioural, and neurological impairment, as well as structural and functional brain damage. Eyeblink conditioning (EBC) is among the most sensitive endpoints affected in FASD. The cerebellar peduncles, large bundles of myelinated nerve fibers that connect the cerebellum to the brainstem, constitute the principal white matter element of the EBC circuit. Diffusion tensor imaging (DTI) is used to assess white matter integrity in fibre pathways linking brain regions. DTI scans of 54 children with FASD and 23 healthy controls, mean age 10.1 ± 1.0 years, from the Cape Town Longitudinal Cohort were processed using voxelwise group comparisons. Prenatal alcohol exposure was related to lower fractional anisotropy (FA) bilaterally in the superior cerebellar peduncles and higher mean diffusivity (MD) in the left middle peduncle, effects that remained significant after controlling for potential confounding variables. Lower FA and higher MD in these regions were associated with poorer EBC performance. Moreover, effects of alcohol exposure on EBC decreased significantly after inclusion of these DTI measures in regression models, suggesting that these white matter deficits partially mediate the relation of prenatal alcohol exposure to EBC. The associations of greater alcohol consumption with these DTI measures are largely attributable to greater radial diffusivity, possibly indicating poorer myelination. Thus, these data suggest that fetal alcohol-related deficits in EBC are attributable, in part, to poorer myelination in key regions of the cerebellar peduncles.
authors.affiliation: MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa.|Department of Human Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.affiliation: MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa.|Department of Human Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Ernesta M
authors.initials: EM
authors.lastname: Meintjes
authors.affiliation: Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Molteno
authors.affiliation: Siemens Medical Solutions USA Inc., Chicago, Illinois.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Spottiswoode
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Dodge
authors.affiliation: MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa.|Department of Human Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Alkathafi A
authors.initials: AA
authors.lastname: Alhamud
authors.affiliation: Department of Psychology, University of Delaware, Delaware, Maryland.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Stanton
authors.affiliation: Institute for the Developing Mind, Children's Hospital Los Angeles and the Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Peterson
authors.affiliation: Department of Human Biology, University of Cape Town, Cape Town, South Africa.|Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.|Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Jacobson
authors.affiliation: Department of Human Biology, University of Cape Town, Cape Town, South Africa.|Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.|Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Sandra W
authors.initials: SW
authors.lastname: Jacobson
mesh_terms: D065850:Cerebral Peduncle / Q000473:pathology* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D003215:Conditioning, Eyelid / Q000502:physiology*; D056324:Diffusion Tensor Imaging; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology / Q000503:physiopathology; D065837:Middle Cerebellar Peduncle / Q000473:pathology* / Q000503:physiopathology; D011247:Pregnancy; D012720:Severity of Illness Index; D066127:White Matter
keywords: cerebellar peduncles; diffusion tensor imaging; eyeblink conditioning; fetal alcohol spectrum disorders; white matter