Xiaopei Xu1, Pek-Lan Khong1, Nichol M. L. Wong2,3, Rainbow T. H. Ho4, C. Mary Schooling5, Pui-sze Yeung6, Tatia M. C. Lee2,3,7,8, and Edward S Hui1
1Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong, Hong Kong, 2Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong, Hong Kong, 3Laboratory of Social Cognitive Affective Neuroscience, The University of Hong Kong, Hong Kong, Hong Kong, 4Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong, Hong Kong, 5School of Public Health, The University of Hong Kong, Hong Kong, Hong Kong, 6Faculty of Education, The University of Hong Kong, Hong Kong, Hong Kong, 7Institute of Clinical Neuropsychology, The University of Hong Kong, Hong Kong, Hong Kong, 8The State Key Laboratory of Brain and Cognitive Science, The University of Hong Kong, Hong Kong, Hong Kong
Synopsis
To better understand the importance of education, genetic, and environmental
influences on brain structural connectivity, we used DTI-based tractography and
brain network analysis to investigate the thereof in twin pairs. The correlation between network properties and
education was also studied in both twin and non-twin participants. We showed significant
correlations between twin pairs for the topology of brain network and the nodal
characteristics of brain hubs. Nodal characteristics of hubs were also significantly
correlated with education level. These findings suggested that brain topology
and cognitive capacity are heritable, and brain network analysis is of
potential value in intelligence assessment.Purpose
Brain is found to have a small-world network using network analysis
1, favoring both
integrated and segregated information processing. Using the classical ACE model
(
Fig. 1), twins share
100% of common environmental influences and at least 50% of their segregating genes
regardless of zygosity
2, the
effects of genes and environment on their brains can be studied using network
analysis. The objective of this study was to investigate the importance of education,
genetic and environmental influences on the brain at a global level.
Methods
Participants 23 twin pairs (age = 215 ± 14
months) and 24 non-twin term peers (216 ± 12 months) were recruited.
Image acquisition DWIs were acquired using single-shot
EPI with b values of 1000 and 2000 s/mm2 along 32 gradient
directions using a 3T scanner (Achieva TX scanner, Philips
Healthcare).
Network analysis 3D-MPRAGE images were segmented into
90 brain regions according to AAL atlas. Whole-brain white matter tractography
was obtained using Diffusion Toolkit (trackvis.org/dtk/). Fiber tracts traversing two
regions were counted, resulting in a connectivity matrix. Brain network
topology, including clustering coefficient, characteristic path length,
normalized clustering coefficient (γ), normalized characteristic path
length (λ), global and local efficiency were
computed using the Brain Connectivity Toolbox3.
Statistical
analysis
Non-twin subjects were paired according to their
age, gender and education level. Differences between twin pairs were studied using paired t-tests.
Pearson correlation was performed to determine the association between network
metrics and education for all subjects.
Results
Nodal
characteristics Consistent
amongst all subjects, precuneus, insular,
putamen, hippocampus, caudate, superior frontal cortex, thalamus, middle
cingulate cortex and globus pallidus were found as hubs. Significant correlations
between twin pairs for the local clustering coefficient of insula (r = 0.52, p =
0.011) and hippocampus (r = 0.50, p = 0.015); and for the nodal degree of
insula (r = 0.55, p = 0.007), caudate (r = 0.59, p = 0.003), putamen (r = 0.53,
p = 0.01) and thalamus (r = 0.57, p = 0.005) were found.
For
correlations between network metrics and the starting age of primary school of
all subjects, significant correlations for the nodal degree of precentral gyrus
(r = -0.32, p = 0.007); for the local clustering coefficient of caudate (r = -0.240,
p = 0.045); for the betweenness centrality
of insula (r = -0.272, p = 0.023); and for the nodal efficiency of globus
pallidus (r = -0.326, p = 0.006) were found. For correlations between network
metrics and the number of months of education of all subjects, significant
correlations for the nodal degree of precentral gyrus (r = 0.29, p = 0.016);
for the betweenness centrality of insula (r = 0.250, p = 0.037); and for the nodal
efficiency of globus pallidus (r = 0.253, p = 0.035) were found.
Global
network All
subjects demonstrated small-world structural brain network. Significant
correlations between twin pairs were found for characteristic path length (r =
0.57, p < 0.001) and (r = 0.56, p = 0.006) (Fig. 2), but not non-twin pairs.
Discussion
Previous studies have focused on the heritability
of the topology of functional
4 and structural
5 brain networks. Few have studied the effects of
genetic and common environmental influences on the hubs of the brain, which
play essential role in integrating and distributing information across the
brain for the normal functioning of cognition
6. Our current results showed significant
correlations between twin pairs for various characteristics of different hubs, suggesting
that cognitive function is heritable. Indeed, the hubs found in the current
study are consistent with the brain regions (except globus pallidus) that
showed heritability of working memory brain activation in a previous task-based
fMRI study
7, further supporting the notion that brain
hubs are associated with cognition such as working memory and that the hubs’
characteristics are subject to genetic and environmental influences.
We
also demonstrated significant correlation between nodal characteristics and months
of education as well as primary school starting age, suggesting that hubs
played a more dominant role in regulating information processing in adolescents
whom received longer years of education or started education earlier. This is
consistent with a prior study that investigated the association between structural
brain network and high cognitive ability
8.
Conclusion
We have successfully demonstrated that the
cognitive capacity and brain hubs are under the influences of shared genes and common
environment, and that the dominant roles of hubs were correlated with education
level. These results suggested that the topology of brain and cognitive
capacity is heritable.
Acknowledgements
No acknowledgement found.References
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