Response inhibition deficits in children with Fetal Alcohol Spectrum Disorder: Relationship between diffusion tensor imaging of the corpus callosum and eye movement control

Abstract

Response inhibition is the ability to suppress irrelevant impulses to enable goal-directed behavior. The underlying neural mechanisms of inhibition deficits are not clearly understood, but may be related to white matter connectivity, which can be assessed using diffusion tensor imaging (DTI). The goal of this study was to investigate the relationship between response inhibition during the performance of saccadic eye movement tasks and DTI measures of the corpus callosum in children with or without Fetal Alcohol Spectrum Disorder (FASD). Participants included 43 children with an FASD diagnosis (12.3 ± 3.1 years old) and 35 typically developing children (12.5 ± 3.0 years old) both aged 7–18, assessed at three sites across Canada. Response inhibition was measured by direction errors in an antisaccade task and timing errors in a delayed memory-guided saccade task. Manual deterministic tractography was used to delineate six regions of the corpus callosum and calculate fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity, and perpendicular diffusivity. Group differences in saccade measures were assessed using t-tests, followed by partial correlations between eye movement inhibition scores and corpus callosum FA and MD, controlling for age. Children with FASD made more saccade direction errors and more timing errors, which indicates a deficit in response inhibition. The only group difference in DTI metrics was significantly higher MD of the splenium in FASD compared to controls. Notably, direction errors in the antisaccade task were correlated negatively to FA and positively to MD of the splenium in the control, but not the FASD group, which suggests that alterations in connectivity between the two hemispheres of the brain may contribute to inhibition deficits in children with FASD.

Deviant white matter structure in adults with attention-deficit/hyperactivity disorder points to aberrant myelination and affects neuropsychological performance

“…Importantly, reduced FA values in the splenium were associated with worse inhibition performance. Poorer response inhibition in healthy children has been correlated previously with decreased FA (and increased MD) in the splenium (Paolozza et al, 2014). It has been linked to decreased splenium volume in children prenatally exposed to polychlorinated biphenyls (Stewart et al, 2003) and in adults with bipolar disorder (Bearden et al, 2011), populations also characterized by insufficient inhibitory control.…”

Acute oligodendrocyte loss with persistent white matter injury in a third trimester equivalent mouse model of fetal alcohol spectrum disorder

“…Sex-separate analysis of neurophysiological data due to the variance in vulnerability between males and females to the constellation of teratogenic effects induced by perinatal EtOH is increasingly recognized as important (Paolozza et al 2014; Tesche et al 2015). Sexual dimorphism of oligodendrocytes and myelin gene expression in the corpus callosum has been consistently observed in the brains of normally developing rodents (Cerghet et al 2009), but the sex-specific effects of prenatal EtOH exposure on oligodendrocyte cells has not been comprehensively explored (Wilhelm and Guizzetti 2015).…”

“…MRI techniques that utilize diffusion tensor imaging (DTI) have further revealed changes to the organization and microstructure of callosal white matter in individuals with FASD (Moore et al 2014). Microstructural abnormalities as assessed by fractional anisotropy (FA) occur throughout the corpus callosum and are correlated with impaired cognition (Wozniak et al 2009) and oculomotor control (Green et al 2013; Paolozza et al 2014). A recent MRI study relating improved cognitive function with increasing white matter volume in the corpus callosum of adolescent FASD subjects underscores the need to elucidate the cellular underpinnings of white matter injury and plasticity for improved therapeutic targeting (Gautam et al 2014).…”

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

“…In the infants with PAE, neurobehavioral scores exhibited a positive correlation with FA and a negative correlation with MD of the right inferior cerebellar peduncle [85]. In an antisaccade test, which is designed to assess response inhibition or cognitive control, normally developing children showed a negative correlation between FA of the corpus callosum and visual stimulus detection errors and a positive correlation between MD of the splenium and visual stimulus detection errors, while children with PAE did not exhibit such correlations [81]. These data suggest deficits in information transfer due to abnormal tract formation, resulting in failure in inhibition control (discussed in 2.4.1).…”