Preliminary evidence of altered gray and white matter microstructural development in the frontal lobe of adolescents with attention-deficit hyperactivity disorder: a diffusional kurtosis imaging study

Abstract

Purpose: To investigate non-Gaussian water diffusion using diffusional kurtosis imaging (DKI) to assess age effects on gray matter (GM) and white matter (WM) microstructural changes in the prefrontal cortex (PFC) of adolescents with attention-deficit hyperactivity disorder (ADHD) compared to typically developing controls (TDC).

Materials and methods: In this preliminary cross-sectional study, T1-weighted magnetization-prepared rapid gradient echo (MPRAGE) and DKI images were acquired at 3T from TDC (n = 13) and adolescents with ADHD (n = 12). Regression analysis of the PFC region of interest (ROI) was conducted.

Results: TDC show a significant kurtosis increase of WM microstructural complexity from 12 to 18 years of age, particularly in the radial direction, whereas WM microstructure in ADHD is stagnant in both the axial and radial directions. In ADHD, GM microstructure also lacked a significant age-related increase in complexity as seen in TDC; only kurtosis measures were able to detect this difference.

Conclusion: These findings support the prevailing theory that ADHD is a disorder affecting frontostriatal WM. Our study is the first to directly quantify an aberrant age-related trajectory in ADHD within GM microstructure, suggesting that the assessment of non-Gaussian directional diffusion using DKI provides more sensitive and complementary information about tissue microstructural changes than conventional diffusion imaging methods.

Figure 1

DKI slab acquisition and PFC ROI. a: Fifteen-slice DKI slab spanning 58 mm in the z-direction (2 mm gaps) was acquired to include the majority of the PFC and cerebellum. Acquisition angle was determined by aligning the inferior end of the slab to the most inferior point of the hypothalamus and the most inferior point of the cerebellum’s posterior lobe. b: PFC ROI, displayed here on the MK map, was drawn on the B0 map on five consecutive slices, starting inferiorly from the last slice containing the superior colliculus. The posterior boundary was determined by connecting the lateral fissures and including everything anterior to it. c: The same ROI overlaid on the segmented GM MK map. d: The same ROI overlaid on the segmented WM MK map.

Figure 2

PFC kurtosis and diffusivity means with age. a: TDC individual MK means with age for GM and WM. b: ADHD individual MK means with age for GM and WM. c: TDC individual MD means with age for GM and WM. d: ADHD individual MD means with age for GM and WM. TDC first column and ADHD second column. GM means are represented by black dots, black regression line, left-side black y-axis, and black r² value. WM means are represented by white dots, gray regression line, right-side gray y-axis, and gray r² value. ***P < 0.005, **P < 0.01, *P < 0.05.

Figure 3

Linear regression slopes of age versus PFC means. TDCs are solid bars and ADHD are checkered bars. Gray bars represent GM and white bars represent WM. Linear regression slopes and their standard errors are shown. MK slope: 1/year, K_|| slope: 1/year, K_⊥ slope: 1/year, MD, D_||, D_⊥ slopes: (μm²/ms)/years, FA slope: 1/year.