Differences in cortico‐striatal‐cerebellar activation during working memory in syndromal and nonsyndromal children with prenatal alcohol exposure

Abstract

Although children with heavy prenatal alcohol exposure may exhibit the distinctive facial dysmorphology seen in full or partial fetal alcohol syndrome (FAS/PFAS), many lack that dysmorphology. This study examined the functional organization of working memory in the brain in three groups of children-those meeting diagnostic criteria for FAS or PFAS, heavily exposed (HE) nonsyndromal children, and healthy controls. A verbal n-back task (1-back and 0-back) was administered to 47 children (17 with FAS/PFAS, 13 HE, and 17 controls) during fMRI. Intra-group one-sample t-tests were used to identify activity regions of interest central to verbal working memory including the dorsal prefrontal cortex (dPFC), inferior frontal gyrus, caudate/putamen, parietal cortex, and cerebellar Crus I/lobule VI and lobule VIIB-IX. Whereas groups did not differ in task sensitivity, fMRI analyses suggested different patterns of sub-network recruitment across groups. Controls primarily recruited left inferior frontal gyrus (Broca's area). By contrast, HE primarily recruited an extensive set of fronto-striatal regions, including left dPFC and left caudate, and the FAS/PFAS group relied primarily on two cerebellar subregions and parietal cortex. This study is, to our knowledge, the first to demonstrate differential recruitment of critical brain regions that subserve basic function in children with different fetal alcohol spectrum disorders compared to controls. The distinct activation patterns seen in the two exposed groups may be related to substantial differences in alcohol dose/occasion to which these groups were exposed in utero.

Radiological studies of fetal alcohol spectrum disorders in humans and animal models: An updated comprehensive review

“…The activation increases from 0-back to 1-back task were significantly different between controls and PAE subjects in the inferior frontal region (higher in controls), and in the basal ganglia and dorsal prefrontal cortex (higher in PAE subjects) [109].…”

“…Relative to the 0-back task, increased activations in the 1-back task were observed in the left inferior frontal gyrus in controls, and in the dorsal prefrontal cortex, caudate and putamen in nonsyndromal heavily-exposed children, while children with FAS/PFAS showed increased activity in two Crus I/lobule VI and lobule VIIB/VIIIA of the cerebellum and the inferior parietal cortex [109]. The activation increases from 0-back to 1-back task were significantly different between controls and PAE subjects in the inferior frontal region (higher in controls), and in the basal ganglia and dorsal prefrontal cortex (higher in PAE subjects) [109].…”

“…Subjects with FAS/PFAS also relied on a distinctly different subnetwork compared to normally developing peers and also to nonsyndromal heavily-exposed children [109].…”

Executive Functioning in Children and Adolescents Prenatally Exposed to Alcohol: A Meta-Analytic Review

“…In fact sex of the non-FASD group only moderated the inhibition standard score results. Sex is rarely explored as a moderator of EF deficits in FASD samples, mainly because sex distributions are similar across FASD and comparison groups (e.g., Aragon et al 2008;Diwadkar et al 2013). Astley et al (2009) directly examined this association and showed that sex does not significantly moderate EF findings (e.g., Astley et al 2009).…”

Cerebral Magnetic Resonance Imaging in Children With Prenatal Drug Exposure

“…143 Image processing and analysis using the SPM12 software package (or earlier versions) has been widely used in previous pediatric samples. 127,[144][145][146] Typical whole brain fMRI analyses using voxel-based methods, like the present study, include more than 50.000 voxels, resulting in numerous statistical tests. Consequently, corrections for multiple comparisons are important in all statistical analyses of fMRI data.…”