Structural Brain Networks Underlying Attention And Genetic Correlation Between Brain Regions And Attention

Attention is the behavioral and cognitive process of the preparedness for and selection of certain physical environments or some mental aspects stored in memory.Although many competing theories have proposed different potential components of attention,emerging brain imaging studies have consistently supported the idea that there are three distinct key subsystems of attention,namely alerting,orienting,and executive control(EC).Briefly,alerting refers to the ability to achieve and maintain a state of high sensitivity;orienting is defined as the ability to select information from sensory stimuli;and EC is involved with resolving cognitively incongruent stimuli.Functional neuroimaging studies have demonstrated that these three attentional functions are mediated by anatomically separate neural networks.However,because of different attentional theories and multiple neuroimaging modalities,the anatomical and functional substrates of attention are still not clear.Human brain is a complex network with structural and functional connections between different brain regions.Interactions among the brain network are required to finish the advanced cognitive functions.Previous studies have shown that the brain networks showed a small-world organization,with the topological advantages of both random networks and regular networks,which suggest that the brain networks exist high clustering of connection and long connections between brain regions,responsible for local information processing and integration of information across the brain networks.This supports the optimal balance of the brain between local specialization and global integration.Thus,large-scale network analysis offers a new way to investigate the integration of structure and cognitive function and to discover the potential biological mechanism responsible for brain dynamics.We can construct the structural brain networks based on DTI tractography and parcellation of cerebral cortex.Graph theoretical approaches could reveal the basic topological characteristics of brain networks.Applying such method to neurological and psychotic disorders studies could help measure the abnormal network properties,and provide a new perspective for anatomical basis of cognitive disorders.The structure and function of human brain develops from the combined impact of genetic and environment factors.Heritability refers to the extent to which genetic factors affect a phenotype across population.Investigating the effects of genetic and environmental factors on brain structure-function can determine the association between brain morphological changes and cognitive function,and can further explore the cause of neuropsychiatric disorders.Twin method is the most commonly used method of genetic analysis.Monozygotic twins have the same genotype,with the traits difference resulted from environment factors;Dizygotic twins have half the same genotype,with the traits difference resulted from both genetic and environment factors.The neuroimaging methods measure brain structural or functional characteristics as intermediate phenotypes.These quantitative indicators can greatly improve gene discovery and improve the effects of statistical analysis in the gene detection.Moreover,this method is relatively stable and small sample size is useful.Previous studies have shown that the heritability of average cortical thickness of human brain is 81%and the heritability of overall surface area is 89%.In addition,different brain regions are coordinated to achieve advanced cognitive function.Different regions are affected by different genetic and environment factors.Exploring the genetic structure of each brain area is important to understand the normal brain development and pathological mechanism.Using cortical thickness and surface area as phenotypic objects could narrow the search range of the number of trait loci that brain structures.Moreover,cortical thickness and surface area are genetically and phenotypically independent,which means that these two traits are superior to gray matter volume and should be applied to imaging genetic studies respectively.Thus,twin study provides an efficient way to investigate the genetic and environment correlation between executive control function and cortical thickness and surface area.With T1 and DTI data,brain structural networks were constructed based on deterministic tractography.This study aimed to explore the relationships between attention and topologies of brain structural networks;to explore the associations between attention and regional cortical thickness;and to explore the genetic and environmental correlation between executive control and regional cortical thickness and surface area.This study is divided into three parts.The abstracts are as follows:Part 1:The Relationship between Attention and Global and Regional Efficiency of Structural Brain NetworksObjective:Attention is the behavioral and cognitive process for the preparedness for and selection of certain physical environments or some mental aspects stored in memory.Emerging brain imaging studies have consistently supported the idea that there are three distinct key subsystems of attention,namely alerting,orienting and executive control.Previous task-related neuroimaging studies mainly focused on the roles played by each brain region of the three attentional effects.With such univariate approach,interactions among brain regions within the networks were not evaluated.This study aimed to utilize graph theoretical measures to establish the neuro anatomical correlates of the three ANT networks.Materials and Methods:65 healthy subjects were recruited in this study.Attention network test(ANT)was used to obtain the behavioral performance of alerting,orienting and EC.DTI and T1 images were acquired using a 3.0 Tesla GE Signa Scanner.We used FSL to pre-process the DTI data.With DTI deterministic tractography and graph theory,PANDA was used to construct the structural brain networks and Brainnetome fMRI Toolkit was used to calculate the topological properties of these networks.SPSS was used to do the statistical analysis.Results:The constructed structural brain networks showed small-world characteristics.A significantly positive correlation between EC function and global efficiency of structural brain networks were discovered.Furthermore,nodal efficiencies of specific regions,including left dorsolateral superior frontal gyrus,left parahippocampal gyrus,bilateral thalamus and bilateral pallidum were found significantly correlated with EC.We also observed alerting effect was correlated with nodal efficiency of left thalamus and right inferior parietal gyrus.Orienting component was found correlated with right paracentral lobule and right inferior occipital.Conclusion:Our results provided useful information of fundamental architecture of interregional structural connectivity involved in attention.Large scale brain network analysis based on graph theory could help explore the integration of function and substrates underlying cognitive function and provided new sights into the anatomical basis underlying attentional deficits in both neuropsychiatric and neurological disorders.Part 2:The Relationship between Attention and Regional Cortical ThicknessObjective:The cerebral cortex is a complex structure that neurons are highly folded.Cortical thickness reflects the cytoarchitecture.However,the fundamental architecture of the three attentional components is not established.This study aimed to discover correlation between regional cortical thickness and alerting,orienting and EC,respectively.Materials and Methods:A total of 84 healthy subjects were recruited for this study.Attention Network Test(ANT)was used to examine the efficiency of the alerting,orienting and EC.T1-weighted images were obtained on a 3.0 Tesla GE Signa scanner.The study applied CIVET software on CBRAIN platform to calculate the cortical thickness across the whole brain.Then multiple linear regression was done in SPSS.Results:Significant correlation between alerting effect and cortical thickness of left superior frontal gyrus and right paracentral lobule were found.We also discovered significant correlations between orienting and cortical thickness of right fusiform gyrus,right parahippocampal gyrus and right medial superior frontal gyrus.For EC component,significant correlations with cortical thickness were observed in left anterior cingulate gyrus and right inferior parietal gyrus.Conclusion:Significant correlations between cortical thickness and attention were found.Our results help establish the neuroanatomy of attentional function and provide evidence for structural correlates involved in behavior.Part 3:The Genetic Correlation Analysis between Executive control and Cortical Thickness and Surface AreaObjective:Brain structure and function were affected by both genetic and environmental factors.However,few studies focused on the genetic correlation between executive control and cortical thickness.This study aimed to use MRI data from twins to investigate the genetic correlation between these two traits.Materials and Methods:37 pairs of twins were recruited for this study.Attention network test was used as the cognitive task to test the performance of executive control function.T1 images were obtained with a 3.0 T GE scanner.This study used CIVET software to obtain the cortical thickness of the brain and used Solar software to calculate heritability of both cortical thickness and EC effect,and genetic correlation between these two traits.Results:The heritability of EC function is 0.356.There are significant genetic associations between executive control and cortical thickness of posterior cingulate gyrus and temporal pole;environment associations between EC and cortical thickness of supplementary motor area and inferior temporal gyrus.EC and cortical thickness of dorsolateral superior frontal gyrus and superior parietal gyrus trend to be environment correlated.In addition,genetic correlations between EC and surface area of gyrus rectus and calcarine cortex were observed.There are also environmental correlations between EC and surface area of superior frontal gyrus(orbital part),medial superior frontal gyrus,middle frontal gyrus(orbital part)and parahippocampal gyrus.Conclusion:The common genetic factors involved in both EC and cortical thickness or surface area of specific regions could provide the foundation of genome-wide association analysis.Exploring the genetic model of brain structure could help understand the human brain development and pathological mechanism.