Development and aging of the healthy human brain uncinate fasciculus across the lifespan using diffusion tensor tractography

Abstract

The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject's intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7-68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left>Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.

Figure 1

Graphical summary of the fitted curves (linear and quadratic) of UF on the entire 108 healthy controls ICV normalized UF volume (UFV/ICV ×100%) on the (A) right and (B) left and corresponding fractional anisotropy on the (C) right and (D) left hemispheres.

Figure 2

Graphical summary of the fitted curves of UF on the entire 108 healthy controls of the radial diffusivity on the (A) right and (B) left and axial diffusivity on the (C) right and (D) left hemispheres.

Figure 3

Illustration of the DTI-based fiber tracking of the uncinate fasciculus (A) The two ROIs (1 rectangle, 2 circle) were placed after identifying the anterior commissure on a coronal DTI color coded map (e.g. principal eigenvector modulated by FA and fused with the mean diffusivity to identify cerebrospinal fluid (CSF) and gray matter) (B) An illustration of the same coronal plane with the two seed ROIs on an FA map showing the gray matter bordering the UF (1 caudate, 2 putamen, 3 insula, 4 amygdala/hippocampus). (C) a 3D postero-lateral view of the right and left UF on a DTI color coded (red = right-left; green = anterior-posterior, blue = inferior superior). Note the origin (temporal lobe) and termination (frontal lobe) of the UF (D) a 3D antero-lateral view of the right and left UF showing the UF position within the cortical and subcortical gray matter structures (e.g. hippocampus).