Characterizing the Developmental Trajectories for Cerebellar Volumes via Penalized Splines and Derivative Analysis Público
Li, Yiheng (Summer 2021)
Published
Abstract
The human cerebellum has been established an important role in both motor and cognitive functions. Many of these functions change across age, especially during childhood and adolescence. A representation of cerebellar development is the volume of the cerebellum and of various regions of the cerebellum. Past literature has spotted a non-linear trajectory as well as a gender dimorphism of how the cerebellar volumes develop across age. Specifically in this paper, the focus is on how total cerebellum volume (TCV), cerebellar cortex volume (CCV), cerebellum white-matter volume (CWM) and the total intracranial volume (TICV) changes during childhood, adolescence and adulthood in different gender groups. Cross-sectional volumetric data both with and without TICV adjustment from 1608 healthy subjects ranging from 5 to 37 years old is analyzed stratified on sex. To characterize the developmental trajectories of the cerebellar volumes, a flexible penalized cubic spline modeling framework is adopted, which combines the reduced knots of a regression spline (computational efficiency) and the roughness penalty of a smoothing spline (smoothness control of the fitted splines). Derivatives of the fitted trajectories are then approximated by difference quotients and their variances are estimated based on the posterior Bayesian covariance matrix of the smoothing coefficients. Hypothesis tests of whether the non-zero derivatives are significantly different from 0 are derived, through which the age periods of significant increase/decrease of the cerebellar volumes of interest are identified. The TCV of males experiences an increase in childhood and adolescence and reaches its peak at14 years old with minimal change afterward. The CCV of males follows an inverse-U-shaped curve peaking at 13 years. For both female and male CWM, a steady increase is fitted in the studied age range. The TICV adjustment does not affect the general trend of the development of male TCV and male CCV. For TCV and CCV of females, the predicted trajectory is in the shape of 2 inverse-U connected together with 2 peaks around age 12 and at age 28. However, after adjusting for TICV, age is no longer a significant factor affecting TCV and CCV is predicted to show a sustained volume loss.
Table of Contents
1 Introduction 1
2 Dataset and Preliminary Analysis 3
3 Statistical Methods 5
3.1 Building Developmental Trajectories of the Cerebellar Volumes . . . . . . . . . . . . . . . 5
3.2 Estimating Rate of Volume Change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.3 Detection of Significantly Changing Periods and Peaks . . . . . . . . . . . . . . . . . . . . 10
4 Results 12
4.1 Developmental Trajectories of the Cerebellar Volumes and Trend Assessment . . . . . . . . 12
4.2 Resampling Results: Robustness Check . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
5 Conclusions and Discussion 23
A Appendix 26
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