Scientists know that children with Fetal Alcohol Spectrum Disorder (FASD) often have structural brain damage. Yet little is known about how white matter connections, and deep gray matter structures that act as relay stations, are affected in children with FASD. A new study has used diffusion tensor imaging (DTI) to identify several specific white matter regions as well as deep gray matter areas of the brain that appear sensitive to prenatal alcohol exposure.
Results will be published in the October issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
"White matter tracts are bundles of axons that form connections between different parts of the brain," said Christian Beaulieu, associate professor in the department of biomedical engineering at the University of Alberta and corresponding author for the study. "Highly interconnected deep gray matter structures, such as the basal ganglia and the thalamus, act as relay stations to integrate incoming sensory and motor input before it passes to the cortex; they also play a role in relaying cortical output. Both white matter tracts and deep gray matter structures are essential to the rapid communication and integration of information within the brain."
Carmen Rasmussen, assistant professor in the department of pediatrics at the University of Alberta added that researchers already knew that the corpus callosum, a major white matter tract connecting the left and right hemispheres of the brain, is affected in FASD.
"Abnormalities can vary from complete to more subtle malformations but, overall, brain white-matter volume is reduced in FASD, especially in the temporal and parietal lobes," she said. "Deep gray matter structures are also known to be smaller in individuals with FASD, and have decreased metabolic rates and abnormal metabolite ratios compared to those in children without FASD."
The researchers examined two groups: 24 children (13 boys, 11 girls), ages five to 13 years, previously diagnosed with FASD; and 95 healthy children (50 boys, 45 girls) from the same age range. Diffusion tractography was used to delineate 10 major white matter tracts in each individual, and region-of-interest analysis was used to assess four deep gray matter structures. Furthermore, an indicator of white matter integrity called "fractional anisotropy," and a measure of average water diffusion called "mean diffusivity," were assessed in all 14 brain structures.
"DTI is an advanced MRI technique that uses the properties of water diffusion within the brain to obtain information about fine brain structure," explained Catherine Lebel, a doctoral student in the department of biomedical engineering working on the project. "If cell membranes and other tissue structures are degraded or malformed for some reason, then the water runs into less obstructions and the water travels further in the tissue, which can be measured with DTI. Tractography uses DTI data to virtually reconstruct white matter pathways through the brain, allowing for visualization and analysis of specific white matter tracts that are critical for various cognitive functions. Previous DTI did not use tractography to delineate individual white matter tracts, and none looked at deep gray matter structures."
Results showed that diffusion abnormalities in FASD go far beyond the corpus callosum region of the brain.
"We found widespread diffusion abnormalities in the brains of children with FASD," said Lebel. "We showed diffusion differences in the corpus callosum, which is in agreement with previous studies, but we also showed changes in many other white and deep gray matter structures that have not been previously reported. The white matter connections that seemed to be particularly affected were the corpus callosum and tracts connecting to the temporal lobe. Our study supports the notion that widespread abnormalities exist in the brain due to alcohol exposure while the child is in the womb."
Lebel added that brain-diffusion abnormalities not previously found or reported may, in fact, be widespread.
"Our results suggest that damage caused by prenatal alcohol exposure is very widespread and affects many regions of the brain," Lebel said. "Furthermore, the differences between children with FASD and controls were present across our age range, from five to 13 years of age. Finally, our findings on volume reductions and differences in the corpus callosum confirm previously reported differences, thereby supporting prior research on brain abnormalities amongst FASD populations."
Ideally, said Beaulieu, these findings will lead to a greater understanding of the relationship between the structural abnormalities and functional deficits that are associated with FASD, consequently helping to identify earlier and effectively treat and manage the condition.
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Brain Diffusion Abnormalities in Children with Fetal Alcohol Spectrum Disorder," were: Catherine Lebel and Lindsay Walker of the Department of Biomedical Engineering at the University of Alberta; Katy Wyper and Jerome Yager of the Department of Pediatrics at the University of Alberta; and Gail Andrew of the FASD Clinic at Glenrose Hospital in Edmonton, Alberta. The study was funded by the Networks of Centres of Excellence - Canadian Language and Literacy Research Network, Canada Foundation for Innovation, Alberta Science and Research Authority, Alberta Heritage Foundation for Medical Research, and the University Hospital Foundation.