The Imaging Genetic Study Between The Lobar-segments Of The Inferior Fronto-occipital Fasciculus And Attention

Imaging genetic study combining the multi-model neuroimaging technique and genetic analysis methods deeply explore the genetic variations of brain structures and functions related to the cognitive behavior and provide potential imaging basis for genetic polymorphism of brain function.The inferior fronto-occipital fasciculus is one of the longest associative fibers in human brain, which connects the occipital lobe and frontal lobe and provides important anatomic basis for brain function. By means of regions of interest (ROI), tract-based spatial statistics (TBSS) or probabilistic fiber tracking, previous researches were able to explore the white matter integirties. However, these methods are fixed at a certain area to describe the microstructural properties of fiber bundle and can’t exactly describe the attributes of the white matter. Deterministic fiber tracking with high tracking accuracy is a widely used method to describe the global properties of the fiber bundle.The inferior fronto-occipital fasciculus maybe participant in language system and provide anatomical connections for spatial attention, especially for the ventral attention system. Although direct fronto-parietal connection is crucial for attention, there remains an imcomplete understanding about its importance for the three subnetworks of attention, respectively. The study of visual neglect suggested that damage to the fronto-parietal connections in the right hemisphere was important for orienting of spatial attention. However, the other study proposed the idea that the parioto-frontal connections of IFOF were not involved in the orientation of attention.Likewise, abnormal microstructural integrity of IFOF had been linked with attention deficit hyperactive disorder (ADHD), autism spectrum disorder (ASD), schizophrenia, and so on. While in function, these diseases showed inefficiency in any one or two subnetworks of attention. These varieties led us to explore the direct relationships between IFOF and three subnetworks of attention, which might provide anatomical basis for the diagnosis and classification of attention deficit diseases.Segmental analysis could provide more details about the role of IFOF in attention. In patients with progressive superanuclear palsy, decreased FA, increased ADC and decreased number of tracked voxels were found in the frontal part of IFOF compared with the medial and occipital parts. Additionally, multi-model imaging analysis suggested that the asymmetry of IFOF in frontal lobe was related to executive control of attention. Therefore, the segmental analysis for IFOF may provide anatomical fixed position for therapy of attentional deficit diseases and help to solve the controversy about IFOF.The development and degeneration of brain structure and function were resulted from genetic and environmental factors. Twin study, the most popular method for heritability analysis so far, aimed to compare the differences between the monozygotic (r= 1) and dizygotic (r= 0.5) twins. However, the genetic effects on different age periods were different. The adolescence is an important developmental period for brain structures and functions. The heritability for children and young adults cannot be used as a compass for adolescence.This study aimed to describe the white matter integrity of whole IFOF using the quantitative tractography. Because of the course complexity and the interaction of the crossing fibers in different brain regions, the inferior fronto-occipital fasciculus was divided into five segments in this study. Regression analysis was then used to investigate the relationships between the segments of IFOF and three subnetworks of attention. With the advantages of twins, this study revealed the genetic effects on the white matter tract, attention, and their correlations.Part 1:The Correlations Between Attention and IFOF, As Well As Its LateralizationObjectiveAttention deficit diseases may show decreased functional efficiency in alerting, orienting, and/or executive control. In structure, these diseases present changes in the white matter integrities of IFOF. This study aimed to explore the direct correlations between IFOF and three components of attention.Materials and MethodsAttention network test (ANT) was used as paradigm in sixty healthy subjects of 15 to 20 years. The ratio scores of three distinct components of attention (alerting, orienting, and executive control) were collected.3.0T GE MRI scanning was then performed in all subjects. The DTI data was preprocessed by FSL. The quantitative tractography was performed by means of diffusion toolkit. The visualization and calculation of FA and MD were conducted by Trackvis. All statistical analyses were done by SPSS.ResultsFor FA analysis, the mean FA in the left IFOF was less than the right one, which indicated the right lateralization of FA in IFOF. According to the statistical analyses, EC function was attributed to the fractional anisotropy (FA) of left and right IFOF. In addition, the asymmetry of FA in IFOF was also correlated with EC. No significant correlations between attention and mean MD of IFOF, as well as the asymmetry of MD in IFOF, were found.ConclusionsThe right hemisphere was dominant in attention function. The right lateralization of myelination was found in IFOF. EC ability increased with the myelination in the right IFOF and the extent of right lateralization in the myelination.Part 2:The Correlations Between Attention and Segments of IFOF, As Well As Their LateralizationObjectiveThe white matter integrities and functional connectivity might be affected by crossing fibers in different brain regions. By means of interpolation, IFOF was divided into five segments in this study to provide detailed anatomical basis for attention brain network. For further analysis, the correlations between the asymmetry of five segments and attention were also detected.Materials and MethodsWe collected both structural and DTI data in sixty young healthy participants (aged 15 to 20 years old) using 3.0 T GE MRI. Attention performance was assessed by ANT and the ration scores of alerting, orienting, and EC were collected. The MR images were first registered to the MNI structural template by means of advanced normalization tools (ANTs). Then the fiber tract was labeled and segmented by interpolation in Matlab. The mean FA and MD of five segments were calculated in Track Vis and correlated with the ratio scores of three components of attention in SmartPLS. According the results of SmartPLS, multi-regression analyses were performed to explore the extent of association of segments to attention.ResultsFor FA analysis, EC ratio score was negatively attributed to the left frontal part and right occipital part. Alerting was positively associated with FA in parietal and insular parts of left IFOF. No significant correlation was found between orienting and IFOF. For MD analysis, no significant associations were found between IFOF and attention.Moreover, the asymmetry of IFOF showed segmental inconsistency. The FA of occipital segment showed leftward asymmetry and the others were rightward. The MDs of frontal and insular segments were both rightward lateralization and the other three segments showed leftward tendency.ConclusionsThis study revealed the advantages of lobar-segmental analysis in structure-function correlation study and provided the anatomical basis for kinds of attention deficits. Additionally, the inconsistency in the lateralization of segments may help to solve the controversial in asymmetry of IFOF.Part 3:The Genetic Correlation Analysis Between Attention and IFOF, As Well As Its SegmentsObjectiveBoth genetic and environmental factors were contributed to the brain structures, functions, and their correlations. The heritability of IFOF and attention is still controversial in the previous studies and no evidence for the adolescence period. In addition, no study has revealed the genetic/environmental effects on the structure-function correlation so far.Materials and Methods30 pairs of twins (14 pairs MZ,16 pairs DZ) with 15-20 years of age (mean age: 16.9±1.53 years old) were recruited for the study. Heritability calculation was performed using the OpenMx package in the R statistical computing environment. A full ACE model was compared with an AE-model, a CE-model, or an E-model to estimate the heritability of attention and IFOF, as well as its segments, respectively. The bivariate genetic analysis yielded an estimate of the phenotypic correlations between attention and the IFOF, which can result from genes or environmental factors.ResultsFor the whole IFOF, the genetic effects on the mean FA and MD were at medium degree. For the segments, no significant genetic effects on the FA of left frontal and parietal parts, as well as the MD of right insular and occipital parts, were found. In addition, no heritability was found for the FA asymmetry of parietal segment and MD asymmetry of frontal, parietal, and occipital parts.According to the asymmetry analysis, the asymmetry of FA in the whole IFOF was highly heritable, while no genetic factors were contributed to that of MD. The FA lateralization of frontal and occipital parts was heritable in a medium degree. No significant genetic effects were found in the other segments, as well as the MD asymmetry of all segments.There were no genetic factors contributed to the alerting network of attention. However, the heritability of orienting and EC was 0.464 and 0.375, respectively.Bivariate genetic analysis suggested that the genetic associations of EC to the FA in left IFOF and right occipital segment were 0.916 and -0.570, respectively, and the correlations due to genes were 0.452 and -0.168. The environmental associations of EC to the right and left IFOF were -0.379 and -0.555, respectively, and the correlations due to environmental factors were -0.228 and -0.244.ConclusionsThe common genetic/environmental factors implicated in the correlations suggested the common physiological mechanism for two traits, which should promote the discovery of single-nucleotide polymorphisms affecting IFOF and attention.