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This study examines the role of the anterior cingulate in the development of attention. Task performance relying predominantly on either automatic or controlled processes was correlated with magnetic resonance imaging based measures of the anterior cingulate in 26 normal children ages 5 to 16 years. Attentional measures were assessed with a visual discrimination paradigm. Parasagittal slices from a 3-D, T1-weighted volume data set were used to obtain area measurements of the anterior cingulate. Response latencies decreased with age for both tasks. There were significant correlations between attentional performance and right, but not left, anterior cingulate measures. Performance was faster and more accurate during trials requiring predominantly controlled processes for those children with larger right anterior cingulate measures. The results are consistent with adult neuroimaging findings of activation in the right anterior cingulate during attention tasks and with lesion studies implicating greater right hemisphere involvement in attentional processes.

LAY ABSTRACT Autism is known to be highly heritable, and has been associated with abnormalities in the development of several brain structures, including the cerebellum. Previous research has hinted that a gene controlling the development of posterior brain regions such as the cerebellum, may influence risk for autism. This gene is called Homeobox Domain A1 (HOXA1), and the variant within HOXA1 that has been most studied in relation to autism (A218G) falls within a gene region that is important for HOXA1 protein functioning. Although we know that autism appear to influence the dynamics of brain development, and that cerebellar anatomy continues to change over the lifespan – we do not know if A218G genotype influences cerebellar development over time. We studied this issue in typically developing controls who had a total of 296 repeat structural brain scans taken between ages 5 and 23 years of age. The volume of multiple cerebellar components was measures by hand in each scan, and we related developmental changes in these volumes to A218G genotype. We found that, in a part of the cerebellum implicated in autism, A218G genotype modified the rate of cerebellar growth. This suggests for the first time that the putative ASD risk gene HOXA1 has the capacity to modify the longitudinal development of cerebellar systems implicated in ASD neurobiology. SCIENTIFIC ABSTRACT Homeobox-A-1 (HOXA1) has been proposed as a candidate gene for autism spectrum disorder (ASD) as it regulates embryological patterning of hind-brain structures implicated in autism neurobiology. In line with this notion, a non-synonymous single nucleotide polymorphism within a highly conserved domain of HOXA1 - A218G (rs10951154) - has been linked to both ASD risk, and cross-sectional differences in superior posterior lobar cerebellar anatomy in late adulthood. Despite evidence for early onset and developmentally dynamic cerebellar involvement in ASD, little is known of the relationship between A218G genotype and maturation of the cerebellum over early development. We addressed this issue using 296 longitudinally acquired structural magnetic resonance imaging brain scans from 116 healthy individuals between 5 and 23 years of age. Mixed models were used to compare the relationship between age and semi-automated measures of cerebellar volume in A-homozygotes (AA) and carriers of the G allele (Gcar). Total cerebellar volume increased between ages 5 and 23 years in both groups. However, this was accelerated in the Gcar relative to the AA group (Genotype-by-age interaction term, p=0.03), and driven by genotype-dependent differences in the rate of bilateral superior posterior lobar volume change with age (p=0.002). Resultantly, although superior posterior lobar volume did not differ significantly between genotype groups at age 5 (p=0.9), by age 23 it was 12% greater in Gcar than AA (p=0.002). Our results suggest that common genetic variation within this putative ASD risk gene has the capacity to modify the development of cerebellar systems implicated in ASD...

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