Developmental cortical thinning in fetal alcohol spectrum disorders
Graphical abstract
Research highlights
► Prenatal alcohol exposure can result in brain injury and a diagnosis of FASD. ► Brain cortical thickness measured over developmental age span of 6–30 years. ► Regional bilateral decreases of cortical thickness were observed in FASD. ► Thinner cortex was observed in FASD over the entire age span. ► Cortical thinning with age was evident in both FASD and controls.
Introduction
Maternal alcohol consumption during pregnancy can lead to a variety of developmental disorders (Jones and Smith, 1973, Lemoine et al., 1968). Fetal alcohol syndrome (FAS) refers to a specific set of abnormalities associated with prenatal alcohol exposure (PAE), including facial dysmorphology, growth deficiency and cognitive disabilities (Bertrand et al., 2005), but frequently, children with prenatal exposure to alcohol who do not have the facial characteristics of FAS also suffer severe cognitive and neurological deficits. These children may be diagnosed with a variety of disorders falling under the umbrella term fetal alcohol spectrum disorders (FASD) (Astley, 2004, Chudley et al., 2005). Individuals with FASD may experience cognitive difficulties, which include lower overall intelligence, hyperactivity, behavioral and adaptive difficulties, and deficits in motor function, attention and executive function, learning and memory, expressive and receptive language, executive function and visuospatial skills (for a review, see Kodituwakku, 2007, Mattson et al., 1998, Niccols, 2007).
Brain morphological abnormalities in individuals with FASD have been observed in autopsy (Clarren et al., 1978, Jones and Smith, 1975), but also have been identified by a variety of in vivo quantitative neuroimaging techniques (for a review, see Norman et al., 2009). For example, overall brain volume is reduced in FASD, as are gray and white matter volumes (Lebel et al., 2008a). Whether the volume changes are more severe in certain cortical regions than others has been investigated by voxel based morphometry (VBM) of gray matter density and surface based shape analysis (Sowell et al., 2001a, Sowell et al., 2001b, Sowell et al., 2002). In 21 participants with FASD, bilateral inferior parietal/perisylvian regions (more prominent in the left) and left ventral frontal cortex were shown to have increased gray matter density and smaller brain growth (as measured by radial distance from the center of the brain) (Sowell et al., 2001a, Sowell et al., 2001b, Sowell et al., 2002).
Algorithms have been developed in order to measure regional cortical thickness as the distance between two surfaces (pial–cortical surface and gray–white interface), usually on 3D, isotropic T1-weighted images (Fischl and Dale, 2000, MacDonald et al., 2000, Sowell et al., 2004). From typically developing children to young adults, the cortex generally has been shown to thin across development (Shaw et al., 2008, Tamnes et al., 2010).
There has only been one study reporting cortical thickness measurements in individuals with prenatal exposure to alcohol (Sowell et al., 2008) where thicker cortices in the bilateral temporal, bilateral inferior parietal, and right frontal regions were observed in 21 FASD participants (14 of these with FAS) aged 8–22 years relative to healthy controls. It was proposed that the thicker cortices may be explained by an absence of the cortical thinning that usually occurs in healthy development. Notably, cortical thickness in the right dorsal frontal and left occipital regions was related to verbal recall and visuospatial measures, respectively; however, these were positive correlations where thinner cortex was associated with worse performances in the FASD group. This latter observation is more in line with animal models of PAE showing thinner cortices in rat (Aronne et al., 2008) and fewer neurons in the somatosensory cortex of the macaque brain (Miller, 2007). There is a need to further study cortical thickness in human FASD participants to evaluate the consistency of findings, and to explore their relationship with cognitive abilities. Furthermore, age-related changes of cortical thickness have not previously been evaluated in participants with FASD.
Therefore, the purpose of the current research was to assess 1) the regional variation in cortical thickness in a cohort of 33 FASD participants versus age/sex/handedness matched healthy controls, 2) cortical thickness differences with age from childhood to young adulthood (6 to 30 years) in both FASD and controls, and 3) correlations between cortical thickness and cognitive functioning in FASD.
Section snippets
Participants
Thirty eight FASD participants were recruited through medical FASD clinics and FASD community agencies and 5 were left out of this research due to poor MRI quality. The rest of the 33 FASD participants were aged 6–30 years (mean ± SD: 12.3 ± 6.0 years, 19 males/14 females, 29 right handed/4 left handed) and all had a confirmed medical diagnosis of a disorder falling under the umbrella term FASD: fetal alcohol syndrome (FAS, 3 males, mean age 8.4), partial FAS (pFAS, 2 females, mean age 8.0), static
Participants
The 33 participants diagnosed with FASD overall had below average standard scores on various memory tasks, visuomotor, receptive and expressive vocabulary, math, and reading skills (Table 1), demonstrating that their cognitive performance was indeed impaired. The 23 younger control participants aged 5–13 years had overall cognitive scores greater than the mean standard score of 100 (or 10 for phonological processing) for reading, vocabulary and non-verbal intelligence (Table 2). The Word
Thinner cortex in FASD participants
In the current paper, widespread bilateral cortical thinning was observed in FASD participants over 6–30 years of age in the frontal, parietal, temporal, and occipital areas (Fig. 2d). Although correlative analysis between standardized cognitive scores and vertex-wise cortical thickness yielded no significant findings, thinning in inferior and middle frontal, middle and inferior temporal, parahippocampal, motor, premotor, supplementary motor area, and occipital cortex could be associated with
Acknowledgments
Canadian Institutes of Health Research and Networks of Centres of Excellence (CLLRNet) funding for operation and Alberta Innovates — Health Solutions (CB) and Natural Sciences and Engineering Research Council (CL) for salary.
We thank the CLUMEQ supercomputing center (www.clumeq.mcgill.ca) for the usage of the computing facilities for the development of this work.
We thank Dr. Valerie Massey for some patient recruitment, Mr. Boris Bernhardt's advice on data processing with SurfStat, J-Sebastian
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2018, Developmental Cognitive NeuroscienceCitation Excerpt :Neuroimaging has helped highlight the neurodevelopmental effects, reliably demonstrating both macrostructural and microstructural brain abnormalities (Archibald et al., 2001; Nardelli et al., 2011; Roussotte et al., 2012; Sowell et al., 2008, 2002; Swayze et al., 1997; Wozniak et al., 2009) for reviews, see (Lebel et al., 2011; Moore et al., 2014). More subtle disruptions in functional connectivity have also been observed (Roussotte et al., 2011; Santhanam et al., 2011; Wozniak et al., 2013, 2011) and a few studies have begun to show atypical cortical development including abnormal gyrification (De Guio et al., 2014; Hendrickson et al., 2017; Infante et al., 2015), cortical thickness (Fernández-Jaén et al., 2011; Robertson et al., 2016; Sowell et al., 2008; Treit et al., 2014; Yang et al., 2012; Zhou et al., 2011), and cortical surface area and volume (Lebel et al., 2012; Leigland et al., 2013; Migliorini et al., 2015; Rajaprakash et al., 2014; Roussotte et al., 2012; Treit et al., 2013). Much of what is known about cortical development in PAE has come from cross-sectional studies.
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