Extensive Deep Gray Matter Volume Reductions in Children and Adolescents with Fetal Alcohol Spectrum Disorders

Background: The link between the numerous cognitive, motor, and behavioral difficulties of individuals with fetal alcohol spectrum disorders (FASD) and underlying specific structural brain injuries can be investigated using high-resolution imaging. Differential sensitivity of the brain's "relay" stations, namely the deep gray matter structures, may play a key factor given their multifaceted role in brain function. The purpose of our study was to analyze differences in deep gray matter volumes of children and adolescents with FASD relative to age/sex-matched controls and to examine whether any volume differences were consistent across the age range of neurodevelopment. Methods: Children and adolescents (N = 28, 6 to 17 years) diagnosed with FASD and 56 ageand sex-matched healthy controls (i.e., 2 matched controls per FASD subject) underwent 3-dimensional T1-weighted MRI scans that were used for the automated volume measurement (FreeSurfer) of the intracranial space, total white matter, cortical gray matter, and 6 deep gray matter structures, namely the hippocampus, amygdala, thalamus, caudate, putamen, and globus pallidus, with left and right measured separately. Volumes were compared between FASD and controls, as well as changes with age. Results: Significant reductions of volume in FASD were observed for the intracranial vault (7.6%), total white matter (8.6%), total cortical gray matter (7.8%), and total deep gray matter (13.1%). All 6 deep gray matter structures showed significant volume reductions bilaterally with the caudate (approximately 16%) and globus pallidus (approximately 18%) being most affected. The hippocampus, thalamus, and globus pallidus showed reductions in all 3 age subgroups (6 to 9, 10 to 13, and 14 to 17 years) but the caudate and putamen had smaller volumes for FASD only within the 2 youngest subgroups; the amygdala was only smaller for FASD in the 2 oldest subgroups. Conclusions: Significant, but variable, volume reductions throughout the deep gray matter are observed over a wide age range of 6 to 17 years in FASD.