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The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders
Published on: August 5, 2017
Functional MRI of Human Eyeblink Classical Conditioning in Children with Fetal Alcohol Spectrum Disorders
Dominic T Cheng1, Ernesta M Meintjes2, Mark E Stanton3
1Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Insights
Prenatal alcohol exposure impairs eyeblink conditioning in children, affecting brain function. Alcohol-exposed children show altered cerebellar activity, impacting learning and memory.
Area of Science:
- Neuroscience
- Developmental Psychology
- Radiology
Background:
- Prenatal alcohol exposure is a leading cause of preventable birth defects.
- Fetal alcohol spectrum disorders (FASDs) encompass a range of neurodevelopmental deficits.
- Eyeblink classical conditioning (EBC) is a sensitive measure of learning and memory affected by prenatal alcohol exposure.
Purpose of the Study:
- To investigate EBC-related brain activity using fMRI in children with varying levels of prenatal alcohol exposure.
- To compare brain function between children with fetal alcohol syndrome (FAS), partial FAS (PFAS), heavily exposed (HE) non-syndromal children, and healthy controls.
- To explore the relationship between prenatal alcohol exposure, behavioral conditioning, and brain activation patterns.
Main Methods:
- fMRI scans were used to measure brain activity during EBC tasks.
- Participants included 47 children diagnosed with FAS, PFAS, HE, and healthy controls.
- Behavioral data on conditioned responses (CR) were collected alongside neuroimaging data.
Main Results:
- Alcohol-exposed groups exhibited lower conditioned response rates compared to controls.
- Despite behavioral differences, exposed groups showed widespread cerebellar activation.
- Children with FAS/PFAS and HE children displayed distinct patterns of cerebellar activation over two sessions.
- Prenatal alcohol exposure correlated with altered learning-related activations in the cerebellum and frontal cortices.
- Controls demonstrated significant correlations between cerebellar activation and CRs, suggesting functional organization not seen in exposed groups.
Conclusions:
- Prenatal alcohol exposure leads to functional disorganization in cerebellar regions critical for EBC.
- fMRI reveals distinct patterns of brain activity associated with behavioral deficits in FASDs.
- These findings highlight neurobiological underpinnings of conditioning impairments in children affected by prenatal alcohol exposure.
Abstract:
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.

