Microstructure, length, and connection of limbic tracts in normal human brain development.

Qiaowen Yu,Virendra Mishra,Hang Li,Hao Huang,Hong Zhang,Austin Ouyang,Shuwei Liu,Yun Peng,Min Chen

doi:10.3389/fnagi.2014.00228

Abstract

The cingulum and fornix play an important role in memory, attention, spatial orientation, and feeling functions. Both microstructure and length of these limbic tracts can be affected by mental disorders such as Alzheimer’s disease, depression, autism, anxiety, and schizophrenia. To date, there has been little systematic characterization of their microstructure, length, and functional connectivity in normally developing brains. In this study, diffusion tensor imaging (DTI) and resting state functional MRI (rs-fMRI) data from 65 normally developing right-handed subjects from birth to young adulthood was acquired. After cingulate gyrus part of the cingulum (cgc), hippocampal part of the cingulum (cgh) and fornix (fx) were traced with DTI tractography, absolute and normalized tract lengths and DTI-derived metrics including fractional anisotropy, mean, axial, and radial diffusivity were measured for traced limbic tracts. Free water elimination (FWE) algorithm was adopted to improve accuracy of the measurements of DTI-derived metrics. The role of these limbic tracts in the functional network at birth and adulthood was explored. We found a logarithmic age-dependent trajectory for FWE-corrected DTI metric changes with fast increase of microstructural integrity from birth to 2 years old followed by a slow increase to 25 years old. Normalized tract length of cgc increases with age, while no significant relationship with age was found for normalized tract lengths of cgh and fx. Stronger microstructural integrity on the left side compared to that of the right side was found. With integrated DTI and rs-fMRI, the key connectional role of cgc and cgh in the default mode network was confirmed as early as birth. Systematic characterization of length and DTI metrics after FWE correction of limbic tracts offers insight into their morphological and microstructural developmental trajectories. These trajectories may serve as a normal reference for pediatric patients with mental disorders.

Highlights

The limbic system is a group of interconnected cortical and subcortical structures dedicated to linking visceral states and emotion to cognition and behavior (Mesulam, 2000)
We found a logarithmic age-dependent trajectory for Free water elimination (FWE)-corrected diffusion tensor imaging (DTI) metric changes with fast increase of microstructural integrity from birth to 2 years old followed by a slow increase to 25 years old
DEVELOPMENT OF MICROSTRUCTURES OF LIMBIC TRACTS The plots of uncorrected and corrected DTI metrics, namely, Fractional anisotropy (FA), Mean diffusivity (MD), axial diffusivity (AD), and Radial diffusivity (RD), of all limbic tracts at different ages are shown in Figures 3–6, respectively

Summary

Introduction

The limbic system is a group of interconnected cortical and subcortical structures dedicated to linking visceral states and emotion to cognition and behavior (Mesulam, 2000). Microstructural changes of fx, a major fiber bundle connecting to hippocampus, was found in subjects of mild cognitive impairment (MCI), a disorder that has been associated with risk for dementia (e.g., Oishi et al, 2011, 2012; Huang et al, 2012). Besides their important role in aging-related diseases such as dementia, disruption of limbic tracts was found to be associated with psychiatric disorders of developing brain, such as schizophrenia (e.g., White et al, 2007) and autism (e.g., Weinstein et al, 2011). Understanding maturation of the limbic tracts may provide insights on vulnerability of these

Methods

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Conclusion