Global and Regional Development of the Human Cerebral Cortex: Molecular Architecture and Occupational Aptitudes.

We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade-albeit in a very limited manner-to behaviors as complex as the choice of one's occupation.

Heritability of human visual contour integration-an integrated genomic study.

Contour integration, a key visual function to deal with occlusion and discontinuity in natural scenes, is essential to human survival. However, individuals are not equally well equipped with this ability. In particular, contour integration deficiencies are commonly detected in patients with mental disorders, especially schizophrenia. To understand the underlying sources of these individual differences, the current study investigated the genetic basis of contour integration in humans. A total of 2619 normal participants were tested on their ability to detect continuous contours embedded in a cluttered background. Quantitative genomic analysis was performed, involving heritability estimation based on single nucleotide polymorphisms (SNPs) and association testing at SNP, gene, and pathway levels. Heritability estimation showed that common SNPs contributed 49.5% (standard error of the mean = 15.6%) of overall phenotypic variation, indicating moderate heritability of contour integration. Two-stage genome-wide association analysis (GWAS) detected four SNPs reaching genome-wide significance in the discovery test (N = 1931) but not passing the replication test (N = 688). Gene-level analysis further revealed a significant genome-wide association of a microRNA-encoding gene MIR1178 in both the discovery and replication cohorts. Another gene poly(A)-binding protein nuclear 1 like, cytoplasmic (PABPN1L) showed suggestive significance in the discovery cohort (p < 1 × 10-4) and was replicated in the replication cohort (p = 0.009). The pathway analysis did not detect any significant pathway. Taken together, this study identified significant gene associations with contour integration and provided support for a genetic transmission of the ability to perceive continuous contours in the environment.

Apolipoprotein E epsilon4 genotype and gender: effects on memory.

OBJECTIVE: Episodic recognition memory for odors and visual was assessed in apolipoprotein E (ApoE) epsilon4-positive and epsilon4-negative men and women diagnosed with Alzheimer disease (AD) and a healthy age- and gender-matched comparison group. METHODS: A total of 38 AD patients and 38 age- and gender-matched healthy older adults completed a recognition memory task involving three categories of stimuli: odors, faces, and symbols. RESULTS: In the healthy comparison group, men who were epsilon4 negative outperformed epsilon4-positive men in recognition memory for odors and committed fewer false-positive errors. However, there were no significant differences between epsilon4-negative and epsilon4-positive women in the comparison group. No significant gender or ApoE status differences were detected in recognition memory for faces or symbols in the comparison group. In patients with AD, epsilon4-negative women outperformed epsilon4-positive women in recognition memory for odors and committed significantly fewer false-positive errors. However, there were no significant differences between epsilon4-positive and epsilon4-negative men. There were no significant gender or ApoE status differences in recognition memory for faces or symbols in AD patients. CONCLUSION: The results demonstrate that recognition memory for olfactory stimuli may be particularly impaired in healthy older men with the epsilon4 allele. In patients with AD, odor memory impairments may be less severe in women who are negative for the epsilon4 allele. The results offer new insight into how recognition memory is affected by gender, the epsilon4 allele, and the modality of the stimulus to be remembered in healthy older adults and patients with AD.

DNA fragmentation factor 45 knockout mice exhibit longer memory retention in the novel object recognition task compared to wild-type mice.

Apoptosis is an important process in the development and function of the central nervous system (CNS). To study the role of DNA fragmentation factor 45 (DFF45/ICAD) in CNS function, we previously generated DFF45 knockout mice. We found that whereas they exhibit apparently normal CNS development, DFF45 knockout mice exhibit an increased number of granule cells in the dentate gyrus and enhanced spatial learning and memory compared to wild-type mice in a Morris water maze test. In this study, we examined the performance of the DFF45 knockout mice in a novel object recognition task to measure short-term nonspatial memory that is believed to depend on the hippocampal formation. Both wild-type and DFF45 knockout mice exhibited novel object recognition 1 h posttraining. However, whereas wild-type mice no longer did so, DFF45 knockout mice were still able to differentiate the novel versus the familiar object 3 h posttraining. The longer memory retention in DFF45 knockout mice did not last up to 24 h as neither wild-type nor DFF45 knockout mice demonstrated novel object recognition 24 h posttraining. These results suggest that a lack of DFF45 facilitates hippocampus-dependent nonspatial memory, as well as hippocampus-dependent spatial memory.

Kinetic form discrimination in Prader-Willi syndrome.

Discrimination of the shape of motion-produced forms generated by random elements (i.e. second-order stimuli varying in element density and temporal correlation) was tested in four groups: (1) subjects with Prader-Willi syndrome (PWS), chromosome 15q deletion subtype; (2) subjects with PWS, uniparental maternal disomy (UPD) subtype; (3) equivalent non-PWS controls; and (4) normal controls. The performance of the normal controls exceeded that of all other groups (78% correct, P < 0.009). The PWS deletion (66%) and the equivalent control groups (59%) did not differ (P < 0.95). The UPD group performed significantly less well (38%, P < 0.04) than all the other groups. The performance of the PWS deletion and equivalent control groups is consistent with other data indicating that these populations encounter difficulty meeting the processing demands posed by second-order stimuli. The inferior performance of the UPD group may be attributed to receiving two active alleles of a maternally expressed gene influencing neural development. One candidate is the ubiquitin protein ligase gene (UBE3A), which is maternally expressed only and localized to the 15q region. Other possibilities include the requirement of a paternally expressed gene, residual mosaic trisomy 15 in the brain tissue or complex interactions including specific ratios of differentially spliced gene products.

Cross-modal correlation of dichotic and tachistoscopic language laterality tasks: the importance of familial sinistrality.

Previous studies have found little if any correlation between dichotic and tachistoscopic language laterality task performance asymmetries. Problems with these studies have been that quite dissimilar auditory and visual tasks have often been used, and the reliability of the asymmetry measures has generally been unknown or, when known, relatively poor. We assessed the cross-modal correlation for two tasks, the Bilateral Object Naming Latency Task (BONLT) and the Dichotic Object Naming Latency Task (DONLT). These tasks are highly similar and have demonstrated high reliabilities. A significant, though rather small, cross-modal correlation was found (r = +.28). When cross-modal correlations were computed for FS- and FS+ subjects separately, no correlation was found for FS+ subjects (r = +.02), but the correlation for FS- subjects was highly significant (r = +.54, p less than .004). This led us to reexamine some previously collected data (P.L. Van Eys and W. F. McKeever, 1988, Brain and Cognition, 4, 413-429) which had administered two highly reliable language laterality tasks (the BONLT and the Dichotic Consonant Vowel Task), but had not assessed cross-modal correlation. A significant cross-modal correlation was found for FS- but not for FS+ subjects. The results are consistent with the hypothesis of H. Hecaen, M. De Agnostini, and A. Monzon-Montes (1981, Brain and Language, 12, 261-284) which suggests that one effect of FS+ is to induce a greater heterogeneity of localizations of different language processes.