Functional MRI of Human Eyeblink Classical Conditioning in Children with Fetal Alcohol Spectrum Disorders.
Prenatal alcohol exposure has been linked to a broad range of developmental deficits, with eyeblink classical conditioning (EBC) among the most sensitive endpoints. This fMRI study compared EBC-related brain activity in 47 children with fetal alcohol syndrome (FAS), partial FAS (PFAS), heavily exposed (HE) non-syndromal children, and healthy controls. All of the children had previously participated in two EBC studies conducted as part of our longitudinal study of fetal alcohol spectrum disorders. Although learning-related behavioral differences were seen in all groups during the scans, controls showed more conditioned responses (CR) than the alcohol-exposed groups. Despite lower conditioning levels relative to controls, the exposed groups exhibited extensive cerebellar activations. Specifically, children with FAS/PFAS showed increased activation of cerebellar lobule VI in session 2, while HE children showed increased activation in session 1. Continuous measures of prenatal alcohol use correlated with learning-related activations in cerebellum and frontal cortices. Only controls showed significant cerebellar activation-CR correlations in the deep nuclei and lateral lobule VI, suggesting that these key regions supporting EBC may be functionally disorganized in alcohol-exposed children. These findings are the first to characterize abnormalities in brain function associated with the behavioral conditioning deficits seen in children with prenatal alcohol exposure.
Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Dominic T
DT
Cheng
University of Cape Town, Faculty of Health Sciences, Observatory, Western Cape 7925, South Africa.
Ernesta M
EM
Meintjes
University of Delaware, Newark, DE 19716, USA.
Mark E
ME
Stanton
Wayne State University, School of Medicine, Detroit, MI 48207, USA.
Neil C
NC
Dodge
University of Cape Town, Faculty of Health Sciences, Observatory, Western Cape 7925, South Africa.
Mariska
M
Pienaar
University of Cape Town, Faculty of Health Sciences, Observatory, Western Cape 7925, South Africa.
Christopher M R
CMR
Warton
Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
John E
JE
Desmond
University of Cape Town, Faculty of Health Sciences, Observatory, Western Cape 7925, South Africa.
Christopher D
CD
Molteno
Children's Hospital Los Angeles andUniversity of Southern California, Los Angeles, CA 90027, USA.
Bradley S
BS
Peterson
University of Cape Town, Faculty of Health Sciences, Observatory, Western Cape 7925, South Africa.|Wayne State University, School of Medicine, Detroit, MI 48207, USA.
Joseph L
JL
Jacobson
University of Cape Town, Faculty of Health Sciences, Observatory, Western Cape 7925, South Africa.|Wayne State University, School of Medicine, Detroit, MI 48207, USA.
Sandra W
SW
Jacobson
D000428:Alcohol Drinking / Q000503:physiopathology; D000704:Analysis of Variance; D001767:Blinking / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging*; D002648:Child; D015331:Cohort Studies; D003214:Conditioning, Classical / Q000502:physiology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008431:Maternal-Fetal Exchange; D010100:Oxygen; D010812:Physical Stimulation / Q000009:adverse effects; D011247:Pregnancy; D011296:Prenatal Diagnosis
D010100:Oxygen
cerebellar volume; cerebellum; fetal alcohol syndrome; gray matter volume; learning; prenatal alcohol exposure; white matter volume