Geometric morphometrics of corpus callosum and subcortical structures in the fetal‐alcohol‐affected brain

Bookstein, Fred L.; Sampson, Paul D.; Streissguth, Ann P.; Connor, Paul

doi:10.1002/tera.1044

Cited by 138 publications

(57 citation statements)

References 57 publications

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“…Some of the earliest studies showed smaller corpus callosum area (Riley, et al, 1995), regional white matter hypoplasia (Archibald, et al, 2001), altered regional white matter density (Sowell, Thompson, et al, 2001), and callosal shape anomalies in prenatally-exposed subjects (Bookstein et al, 2005; Bookstein et al, 2007; Bookstein, Sampson, Streissguth, & Connor, 2001; Sowell, Mattson, et al, 2001). More recently, DTI studies have reliably demonstrated alterations in the white matter microstructure in PAE (Donald, Roos, et al, 2015; Fan, et al, 2015; Fryer, et al, 2009; Lebel, et al, 2010; Lebel, et al, 2008; Li, Coles, Lynch, & Hu, 2009; Ma, et al, 2005; Malisza, et al, 2012; Sowell, et al, 2008; Spottiswoode, et al, 2011; Taylor, et al, 2015; Wozniak, et al, 2006; Wozniak, et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD)

Wozniak

Mueller

Mattson

et al. 2016

Brain Imaging and Behavior

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Objectives Consistent with well-documented structural and microstructural abnormalities in prenatal alcohol exposure (PAE), recent studies suggest that functional connectivity (FC) may also be disrupted. We evaluated whole-brain FC in a large multi-site sample, examined its cognitive correlates, and explored its potential to objectively identify neurodevelopmental abnormality in individuals without definitive dysmorphic features. Experimental Design Included were 75 children with PAE and 68 controls from four sites. All participants had documented heavy prenatal alcohol exposure. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Resting-state FC was examined using whole-brain graph theory metrics to characterize each individual's connectivity. Principal Observations Although whole-brain FC metrics did not discriminate prenatally-exposed from unexposed overall, atypical FC (> 1 standard deviation from the grand mean) was significantly more common (2.7 times) in the PAE group vs. controls. In a subset of 55 individuals (PAE and controls) whose dysmorphology examination could not definitively characterize them as either Fetal Alcohol Syndrome (FAS) or non-FAS, atypical FC was seen in 27% of the PAE group, but 0% of controls. Across participants, a 1% difference in local network efficiency was associated with a 36 point difference in global cognitive functioning. Conclusions Whole-brain FC metrics have potential to identify individuals with objective neurodevelopmental abnormalities from prenatal alcohol exposure. When applied to individuals unable to be classified as FAS or non-FAS from dysmorphology alone, these measures separate prenatally-exposed from non-exposed with high specificity.

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Section: Discussionmentioning

confidence: 99%

Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD)

Wozniak

Mueller

Mattson

et al. 2016

Brain Imaging and Behavior

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“…Structural imaging studies have detected abnormalities related to prenatal alcohol exposure in multiple brain systems, including frontal (Sowell et al 2002b) (Sowell et al 2008a), parietal (Archibald et al 2001) (Sowell et al 2001b) (Sowell et al 2002b) (Sowell et al 2008a), and temporal regions (Sowell et al 2001b) (Sowell et al 2008a), cerebellum (Sowell et al 1996) (O’Hare et al 2005), basal ganglia (Archibald et al 2001) (Cortese et al 2006) (Mattson et al 1996), and in the white matter that connects these brain regions (Riley et al 1995) (Swayze et al 1997) (Bookstein et al 2001) (Sowell et al 2001a) (Ma et al 2005) (Wozniak et al 2006) (Sowell et al 2008b) (Fryer et al 2009). Some studies have found relationships between these anatomical differences and cognitive function, suggesting clinical significance to the structural brain abnormalities (Sowell et al 2001a) (O’Hare et al 2005) (Sowell et al 2008b) (Sowell et al 2008a) (Dodge et al 2009) (Lebel et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Regional brain volume reductions relate to facial dysmorphology and neurocognitive function in fetal alcohol spectrum disorders

Roussotte

Sulik

Mattson

et al. 2011

Human Brain Mapping

111

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Individuals with heavy prenatal alcohol exposure can experience significant deficits in cognitive and psychosocial functioning and alterations in brain structure that persist into adulthood. In this report, data from 99 participants collected across three sites (Los Angeles and San Diego, California, and Cape Town, South Africa) were analyzed to examine relationships between brain structure, neurocognitive function, facial morphology, and maternal reports of quantities of alcohol consumption during the first trimester. Across study sites, we found highly significant volume reductions in the FASD group for all of the brain regions evaluated. After correcting for scan location, age, and total brain volume, these differences remained significant in some regions of the basal ganglia and diencephalon. In alcohol-exposed subjects, we found that smaller palpebral fissures were significantly associated with reduced volumes in the diencephalon bilaterally, that greater dysmorphology of the philtrum predicted smaller volumes in basal ganglia and diencephalic structures, and that lower IQ scores were associated with both smaller basal ganglia volumes and greater facial dysmorphology. In subjects from South Africa, we found a significant negative correlation between intracranial volume and total number of drinks per week in the first trimester. These results corroborate previous reports that prenatal alcohol exposure is particularly toxic to basal ganglia and diencephalic structures. We extend previous findings by illustrating relationships between specific measures of facial dysmorphology and the volumes of particular subcortical structures, and for the first time show that continuous measures of maternal alcohol consumption during the first trimester relates to overall brain volume reduction.

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“…In contrast, recent neuroimaging studies using MRI (magnetic resonance imaging) on living human subjects prenatally exposed to alcohol have reported that some brain structures, specifically the caudate nucleus (Archibald, et al 2001; Astley, et al 2009), the parietal region (Archibald, et al 2001; Sowell, et al 2002), the frontal lobe (Astley, et al 2009), the temporal-parietal conjunction (Sowell, et al 2001b), and the left orbitofrontal areas (Sowell, et al 2002), were more influenced by PAE than other areas. In addition, abnormality of corpus callosum is one of the most consistently reported brain structural outcomes associated with PAE (Bookstein, et al 2002a; Bookstein, et al 2001; Bookstein, et al 2002b; Lebel, et al 2008; Li, et al 2009; Ma, et al 2005; Riley, et al 1995; Sowell, et al 2008; Sowell, et al 2001a; Wozniak, et al 2006; Wozniak, et al 2009). These results suggest that there may be specific patterns of PAE-related effects in addition to an overall change in brain size (Spadoni, et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Understanding specific effects of prenatal alcohol exposure on brain structure in young adults

Chen¹,

Coles²,

Lynch³

et al. 2011

Human Brain Mapping

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Prenatal alcohol exposure (PAE) is associated with various adverse effects on human brain and behavior. Recently, neuroimaging studies have begun to identify PAE effects on specific brain structures. Investigation of such specific PAE effects is important for understanding the teratogenic mechanism of PAE on human brain, which is critical for differentiating PAE from other disorders. In this structural MRI study with young adults, PAE effects on the volumes of automatically segmented cortical and sub-cortical regions of interest (ROIs) were evaluated both through a group difference approach and a parametric approach. In the group difference approach (comparing among two PAE and a control groups), a disproportionate PAE effect was found in several occipital and temporal regions. This result is inconsistent with previous studies with child samples. Moreover, a gender difference in PAE effect was shown in some cortical ROIs. These findings suggest that sampling and gender may be important factors for interpreting specific PAE effects on human brain. With the parametric approach, it was demonstrated that the higher the PAE level, the smaller the entire brain, the lower the IQ. Several cortical and sub-cortical ROIs also exhibited a negative correlation between the PAE level and ROI volume. Furthermore, our data showed that the PAE effect on the brain could not be interpreted by the PAE effect on general physical growth until the young adult age. This study provides valuable insight into specific effects of PAE on human brain, and suggests important implications for future studies in this field.

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Geometric morphometrics of corpus callosum and subcortical structures in the fetal‐alcohol‐affected brain

Cited by 138 publications

References 57 publications

Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD)

Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD)

Regional brain volume reductions relate to facial dysmorphology and neurocognitive function in fetal alcohol spectrum disorders

Understanding specific effects of prenatal alcohol exposure on brain structure in young adults

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