Regional Specificity And Asymmetry Of Striatal Morphological Development In Fetuses,Young Children And Adolescents

BackgroundThe striatum is considered to be the largest structure of the basal ganglia and the main input nucleus for projections from specific cortical areas,which interacts with the cerebral cortex and other nuclei through a complex series of circuits.Meanwhile,as the brain relay structure,the striatum is susceptible to injury because it is metabolically very active in the immature brain and possesses a high concentration of excitatory receptors.Striatum dysfunction is not only associated with movement disorders such as Huntington’s disease and Parkinson’s disease,but also with cognitive dysfunction and psychiatric disorders such as autism spectrum disorder,schizophrenia and major depressive disorder.The study of the morphological development of the striatum can not only provide a more detailed anatomical reference,but also contribute to the prevention,diagnosis and treatment of related diseases.The development of the striatum spans a long period beginning in 6-8 postovulatory weeks and continuing into childhood and adolescence.The generation of all neurons in the striatum and the ingrowth of corticostriatal fibers occur in the first half of gestation and the characteristic modular structure of the human striatum develops already during the mid-fetal period.Insight into striatum development before birth may be of great importance,since the fetal period is a critical time in brain development in which seemingly small exposures or disturbances can produce lifelong changes in neurological and mental functioning.Therefore,understanding the development of the fetal striatum is very important for studying these processes in health and disease.Early childhood is a critical period for the striatal development after birth,which may have lasting effects on motion,cognition and other aspects in later life.Studies have shown that the volume of striatum is closely related to the polygenic risk score of major depression,and the volume of bilateral caudate nuclei is significantly reduced in children with major depression.The volume of caudate nucleus and putamen showed excessive growth in children with autism.In addition,motor development scores in young children are closely related to adult cognitive function and gray matter density in the striatum.Therefore,the study of striatal morphology in young children can not only provide detailed anatomical references,but also deepen the understanding of the pathogenesis of neuropsychiatric diseases.However,previous studies on striatum morphology were limited to the main diameters and volume measurements.Besides,the included samples were only limited to subjects over 5 years old.In general,there are few reports on striatum morphology in young children.Adolescence is an important period of brain development,with strong plasticity.The striatum undergoes massive remodeling during adolescence.Diseases closely related to the striatum,such as autism,schizophrenia and alcohol addiction,tend to be at high rates during this period.Describing the pattern of striatal morphological development in adolescents may provide a reference for the neural mechanism of individual behavioral changes and vulnerability to mental disorders.So far,most of the studies on pubertal striatal development mainly focus on the relationship between striatal volume and age.There are few studies on the developmental pattern of striatum and the results are controversial.Previous studies that only focused on global volume may have obscured development-related anatomical features of specific regions.Because two structures of the same volume may have completely different shapes,and local shape changes do not necessarily lead to volume changes.Shape analysis is a novel brain mapping method based on surface Laplace-Beltrami(LB)embedding.It can map the Euclidean distance from a given vertex to the central axis,and combine geometric information and anatomical features for image registration.It is more sensitive to the subtle developmental changes of local structures.Compared with volume analysis,Shape analysis can assess the regional specificity of striatal development,which can provide more information about local topological changes for functional anatomy.In this study,we explored the changes of the dynamic developmental curves and the regional specificity of the striatum before birth,after birth and adolescence,and revealed the hemispheric asymmetry and sex dimorphism of striatal development in the three key stages.These data improve our spatiotemporal understanding of striatum development and provide references for future striatum studies.Part 1:Regional Specificity and Hemispheric Asymmetry of StriatalMorphological Development in Fetuses during the Second TrimesterPurposeTo characterize the morphometric development of the human fetal striatum and investigate its regional developing patterns.Materials and methodsA total of 46 specimens from 14 to 22 gestational weeks(GW)were included in this study and scanned in situ by a 7.0T MRI with T2 weighted image.Segmentations were performed manually using ITK-SNAP software.The global development of the striatum was evaluated by volume measurement.Polynomial regression analysis was performed to determine the best-fit model using GW as independent variable and volumes as dependent variable.The R2 value was calculated.The differences in the hemispheres were compared using the paired t-test.P<0.05 was considered statistically significant.To model the local development of the fetal striatum,linear regression analysis was performed on the corresponding thicknesses with increasing GW.Correction for multiple comparisons was performed using a false discovery rate(FDR)at p value of 0.05.ResultsThe absolute volume(Vabs)and the relative volume(Vrel）of the caudate nucleus(CN)and putamen increased linearly with gestational age.The growth rates of the CN and putamen were significantly faster than that of the intracranial volume(ICV).The right CN was larger than the left,whereas there was no significant hemispheric asymmetry in the putamen.Except for the CN tail,the lateral and medial parts of the CN grew faster than the middle regions,with a clear rostral-caudal growth gradient as well as a distinct ’outside-in’ growth gradient.For putamen,the dorsal and ventral regions grew obviously faster than the other regions,with a dorsal-ventral bidirectional developmental pattern.ConclusionsThis study used 7.0T MRI data of human fetal specimens to construct a developmental model of fetal striatum at 14-22GW.The volume of the striatum increased linearly in the second trimester,and the caudate nucleus showed a right dominance during this period.The CN exhibited a rostral-caudal growth gradient and a distinct ’outside-in’ growth gradient,while the putamen showed a dorsal-ventral bidirectional developmental pattern,which has not been reported before.The regional developmental differences may be driven by functional differences,possibly suggesting that regions of the CN involved in cognitive and associative processing grow preferentially,while regions of the putamen involved in motor function preferentially grow.These data bring new insight into the fetal striatum development and provide detailed anatomical references for future striatal studies.Part 2:Regional Specificity,Hemispheric Asymmetry and Sexual Dimorphism of Striatal Morphological Development in Young ChildrenPurposeTo explore the regional development pattern,hemispheric asymmetry and sex differences in the striatum of young children.Materials and MethodsA total of 51 healthy young children aged 16-45 months were collected and then performed by 3.0T MR scanner.The CN and putamen were segmented automatically by Freesurfer software for 3D-T1 weighted image.The global development of the striatum was assessed by volume measurement.Shape analysis was used to demonstrate the region specificity during striatum development.Polynomial regression analysis was used to determine the optimal fitting model and calculate R2 values.Paired t test was used to analyze the morphological data of left and right hemispheres,and independent-samples t test was used to test the sex difference of striatal volume.The thickness at each vertex of caudate nucleus and putamen was analyzed by linear regression with month,and multiple comparison correction was performed using FDR.ResultsThe absolute volumes of the CN and putamen increased linearly with month in young children.The growth rates of the CN and putamen were consistent with ICV.The volume of the right C N was significantly larger than that of the left,and there was no significant difference between the left and right putamen.There was no significant sex difference in the volume of CN and p utamen.Shape analysis showed that different regions of CN and putamen had different growth rates,showing an "inside-out" growth gradient.ConclusionsThe volume of the striatum in young children increased linearly with the increase of months,which was consistent with the growth rate of the ICV.There was no significant difference in th e volume of the striatum between males and females.In particular,this study innovatively des cribed the "inside-out" regional specificity during this period.Such regional differences in stri atal development in young children may be related to developmental changes in behavioral an d cognitive functions during this period.Part 3:Regional Specificity,Hemispheric Asymmetry and SexualDimorphism of Striatal Morphological Development in Adolescents Purpose To explore the regional development pattern,hemispheric asymmetry and sex differences in striatum of adolescents.Materials and methodsA total of 100 healthy adolescents aged 14-20 years were collected and 3.0T MR scans were performed.The CN and putamen were segmented automatically by Freesurfer software for 3DT1 weighted image.The global development of the striatum was assessed by volume measurement.Shape analysis was used to demonstrate the region specificity during striatum development.Polynomial regression analysis was used to determine the optimal fitting model and calculate R2 values.Paired t-test was used to analyze the morphological data of left and right hemispheres,and independent-samples t test was used to test the sex difference of striatal volume.The thickness at each vertex of caudate nucleus and putamen was analyzed by linear regression with age,and multiple comparison correction was performed using FDR.ResultsThe absolute volume of bilateral CN decreased with the increase of age(P<0.05),while there was no significant correlation between relative volume and age(P>0.05).There was no significant difference in the absolute volume of CN on both sides(t=0.481,P=0.632).The absolute volume and relative volume of putamen were not significantly correlated with age(P>0.05).The absolute volume of putamen on the left was significantly smaller than that on the right(t=-5.189,P<0.001),the relative volume of left and right putamen was still statistically different(t=-5.555,P<0.001).Independent-samples t test showed that the absolute volumes of CN and putamen were larger in males than in females.Regression coefficients map indicated that different regions of the CN had different developmental rates.Expansion of the CN head accompanied by contraction of the CN body and tail.The regional specificity of putamen development during this period was not obvious.ConclusionsThe volume of the CN gradually decreased in 14-20 year old adolescents,with a region-specific pattern of head expansion and body-tail contraction.During this period,the development of the putamen was basically stable,and the region specificity was not significant.This study contributed to spatiotemporal understand of adolescent striatum development,and may provide insights into the neural mechanisms underlying behavioral changes and vulnerability to mental disorders in individuals.