Longitudinal MRI Reveals Altered Trajectory of Brain Development during Childhood and Adolescence in Fetal Alcohol Spectrum Disorders

Abstract

Diffusion tensor imaging (DTI) of brain development in fetal alcohol spectrum disorders (FASD) has revealed structural abnormalities, but studies have been limited by the use of cross-sectional designs. Longitudinal scans can provide key insights into trajectories of neurodevelopment within individuals with this common developmental disorder. Here we evaluate serial DTI and T1-weighted volumetric MRI in a human sample of 17 participants with FASD and 27 controls aged 5-15 years who underwent 2-3 scans each, ϳ2-4 years apart (92 scans total). Increases of fractional anisotropy and decreases of mean diffusivity (MD) were observed between scans for both groups, in keeping with changes expected of typical development, but mixed-models analysis revealed significant age-by-group interactions for three major white matter tracts: superior longitudinal fasciculus and superior and inferior fronto-occipital fasciculus. These findings indicate altered developmental progression in these frontal-association tracts, with the FASD group notably showing greater reduction of MD between scans. ⌬MD is shown to correlate with reading and receptive vocabulary in the FASD group, with steeper decreases of MD in the superior fronto-occipital fasciculus and superior longitudinal fasciculus between scans correlating with greater improvement in language scores. Volumetric analysis revealed reduced total brain, white, cortical gray, and deep gray matter volumes and fewer significant age-related volume increases in the FASD group, although age-by-group interactions were not significant. Longitudinal DTI indicates delayed white matter development during childhood and adolescence in FASD, which may underlie persistent or worsening behavioral and cognitive deficits during this critical period.

Neuroimaging effects of prenatal alcohol exposure on the developing human brain: a magnetic resonance imaging review

“…Frontal, parietal and temporal cortices have been implicated, although the direction of effect is not consistent between studies (37,51,52,57,58). In particular, the relationships between the abnormalities of the cortical structure have been related to cognitive functional outcomes, and the differences in cortical development over time in alcohol versus control groups have been reported by Sowell and colleagues (37,52,54). This argues for the clinical importance of damage to these areas after alcohol exposure.…”

“…Areas where findings have showed greater discrepancy include the thalamus, which has been reported to have smaller volumes even when correcting for brain volume by some groups (39,42,54) and changes only in proportion to overall brain volume by others (26,48). The diencephalon, overall, has also been reported as displaying reduced volume (40) or area (28) or no significant structural changes at all (16).…”

Developmental stage affects cognition in children with recently-diagnosed symptomatic focal epilepsy

“…The range of potential outcomes proposed by Dennis et al [41] is consistent with the view that developmental trajectories may differ for specific skills. At a structural level, a recent DTI study in children with fetal alcohol syndrome correlated abnormal white matter trajectories with specific cognitive functions, including receptive vocabulary, in children between 5 and 15 years of age [78]. While comparable research has not been undertaken in children with epilepsy, disruption to white matter trajectories is one possible mechanism underlying the vulnerability of rapidly developing skills.…”

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

“…Imaging studies reveal gray matter volume in the left cingulate gyrus, bilateral middle frontal gyri, right middle temporal gyrus, and right caudate nucleus following low-to-moderate exposure (De Guio et al, 2014;Eckstrand et al, 2012;Treit et al, 2013). Fetal alcohol has also been associated with a host of cognitive and behavioral impairments, including deficits in attention, memory, verbal fluency, executive functioning, reaction time, and motor learning (Coles et al, 2002;Howell et al, 2006;Mattson et al, 1998;Richardson et al, 2002;Riley and McGee, 2005;Willford et al, 2004).…”