The influence of bilingualism on gray matter volume in the course of aging: a longitudinal study

BackgroundBilingualism is associated with higher gray matter volume (GMV) as a form of brain reserve in brain regions such as the inferior frontal gyrus (IFG) and the inferior parietal lobule (IPL). A recent cross-sectional study reported the age-related GMV decline in the left IFG and IPL to be steeper for bilinguals than for monolinguals. The present study aimed at supporting this finding for the first time with longitudinal data.MethodsIn the current study, 200 participants aged 19 to 79 years (87 monolinguals, 113 sequential bilinguals, mostly native German speakers with variable second language background) were included. Trajectories of GMV decline in the bilateral IFG and IPL were analyzed in mono- and bilinguals over two time points (mean time interval: 3.6 years). For four regions of interest (left/right IFG and left/right IPL), mixed Analyses of Covariance were conducted to assess (i) GMV changes over time, (ii) GMV differences for language groups (monolinguals/bilinguals), and (iii) the interaction between time point and language group. Corresponding analyses were conducted for the two factors of GMV, surface area (SA) and cortical thickness (CT).ResultsThere was higher GMV in bilinguals compared to monolinguals in the IPL, but not IFG. While the left and right IFG and the right IPL displayed a similar GMV change in mono- and bilinguals, GMV decline within the left IPL was significantly steeper in bilinguals. There was greater SA in bilinguals in the bilateral IPL and a steeper CT decline in bilinguals within in the left IPL.ConclusionThe cross-sectional observations of a steeper GMV decline in bilinguals could be confirmed for the left IPL. Additionally, the higher GMV in bilinguals in the bilateral IPL may indicate that bilingualism contributes to brain reserve especially in posterior brain regions. SA appeared to contribute to bilinguals’ higher GMV in the bilateral IPL, while CT seemed to account for the steeper structural decline in bilinguals in the left IPL. The present findings demonstrate the importance of time as an additional factor when assessing the neuroprotective effects of bilingualism on structural features of the human brain

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

Beyond the Global Brain Differences:Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and globalbrain differences compared with noncarriers. However, interpreting regional differences is challenging if a globaldifference drives the regional brain differences. Intraindividual variability measures can be used to test for regionaldifferences beyond global differences in brain structure.METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n =30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matchednoncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’sregional difference and global difference, were used to test for regional differences that diverge from the globaldifference.RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differedmore than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thicknessin regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal andsomatosensory cortex differed more than the global difference in cortical thickness.CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanismsinvolved in altered neurodevelopment

Genetic Variants For Head Size Share Genes and Pathways With Cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Structure-function relationships in elderly resting-state-networks : influence of age and cognitive performance

The aim of this work was to investigate the structure-function relationship in cognitive resting state networks in a large population-based elderly sample. The first study characterized the functional connectivity in four cognitive resting state networks with respect to age, gender and cognitive performance: Default Mode Network (DMN), executive, and left and right frontoparietal resting state networks. The second study assessed the structural correlates of the functional reorganization of the DMN during aging, using local gyrification index.Small age-related increases in functional connectivity were present for the executive, left and right frontoparietal resting state networks, but not for the DMN. Men and women were found to differ across all resting state networks of interest. Performance in working memory was negatively associated with functional connectivity within the left frontoparietal resting state network. Elderly seem to exhibit compensatory mechanisms as an attempt to maintain cognitive performance. However, the negative correlation between resting state functional connectivity and cognitive performance emphasizes limits in cognitive reserve in the elderly. Interestingly, men and women seem to show differences in cognitive strategies, which might be related to differences in performance of various cognitive domains. Thus, the current results provide a basis for further research with a particular focus on the functional organization of the elderly brain. Structurally, age-related decreases in gyrification were present for the right anterior DMN and the medial posterior DMN bilaterally. Relations of gyrification to cognitive performance were found for all right hemispheric parts of the DMN and the left medial posterior DMN. The more pronounced vulnerability of the posterior DMN as well as the right hemispheric parts of the DMN in relation to age and cognitive performance provide the structural underpinning of functional theories of aging, i.e. posterior to anterior shift in aging and the right-hemi aging theory. Thus, gyrification decreases within the DMN may functionally lead to an insufficient DMN in the current elderly sample

Resting-state networks in the course of aging—differential insights from studies across the lifespan vs. amongst the old

Resting-state functional connectivity (RSFC) has widely been used to examine reorganization of functional brain networks during normal aging. The extraction of generalizable age trends, however, is hampered by differences in methodological approaches, study designs and sample characteristics. Distinct age ranges of study samples thereby represent an important aspect between studies especially due to the increase in inter-individual variability over the lifespan. The current review focuses on comparing age-related differences in RSFC in the course of the whole adult lifespan versus later decades of life. We summarize and compare studies assessing age-related differences in within- and between-network RSFC of major resting-state brain networks. Differential effects of the factor age on resting-state networks can be identified when comparing studies focusing on younger versus older adults with studies investigating effects within the older adult population. These differential effects pertain to higher order and primary processing resting-state networks to a varying extent. Especially during later decades of life, other factors beyond age might come into play to understand the high inter-individual variability in RSFC