Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use

Abstract

Background: There is growing evidence that adolescence is a key period for neuronal maturation. Despite the high prevalence of marijuana use among adolescents and young adults in the United States and internationally, very little is known about its impact on the developing brain. Based on neuroimaging literature on normal brain developmental during adolescence, we hypothesized that individuals with heavy cannabis use (HCU) would have brain structure abnormalities in similar brain regions that undergo development during late adolescence, particularly the fronto-temporal connection.

Method: Fourteen young adult males in residential treatment for cannabis dependence and 14 age-matched healthy male control subjects were recruited. Patients had a history of HCU throughout adolescence; 5 had concurrent alcohol abuse. Subjects underwent structural and diffusion tensor magnetic resonance imaging. White matter integrity was compared between subject groups using voxelwise and fiber tractography analysis.

Results: Voxelwise and tractography analyses revealed that adolescents with HCU had reduced fractional anisotropy, increased radial diffusivity, and increased trace in the homologous areas known to be involved in ongoing development during late adolescence, particularly in the fronto-temporal connection via arcuate fasciculus.

Conclusions: Our results support the hypothesis that heavy cannabis use during adolescence may affect the trajectory of normal brain maturation. Due to concurrent alcohol consumption in five HCU subjects, conclusions from this study should be considered preliminary, as the DTI findings reported here may be reflective of the combination of alcohol and marijuana use. Further research in larger samples, longitudinal in nature, and controlling for alcohol consumption is needed to better understand the pathophysiology of the effect of cannabis on the developing brain.

Figure 1

VANCOVA analysis shows decreased FA for ≥100 contiguous voxels at P<.001 superimposed on the averaged Talairach transferred images of all subjects. Reduced FA clusters are depicted along the left middle temporal lobe (First Column), the right superior temporal gyrus (Second Column), and the bilateral posterior internal capsules/thalamic radiations (Third Column).

Figure 2

VANCOVA analysis shows increased radial diffusivity (λ_⊥) in ≥200 contiguous voxels at P<.005 superimposed on the averaged Talairach transferred images of all subjects. Increased radial diffusivity is depicted along the left middle temporal gyrus (First Column), right superior temporal gyrus (Second Column) and the bilateral posterior internal capsule/thalamic radiations (Third Column).

Figure 3

VANCOVA analysis shows increased trace (D_tr) in ≥200 contiguous voxels at P<.005 superimposed on the averaged Talairach transferred images of all subjects. Increased trace is depicted along the left middle temporal gyrus (First Column), right superior temporal gyrus (Second Column) and the left posterior internal capsule/thalamic radiations (Third Column).

Figure 4

VANCOVA analysis shows decreased axial diffusivity (λ₁) in ≥200 contiguous voxels at P<.005 superimposed on the averaged Talairach transferred images of all subjects. Decreased axial diffusivity is depicted the right superior temporal gyrus (First Column), the left posterior internal capsule/thalamic radiations (Second Column).

Figure 5

Extraction of the arcuate fasciculus (AF) fiber bundle (left AF; Image A, right AF; Image C) using the DTIStudio with a FA threshold of 0.2 and tract turning angle of 41 degrees. The seed ROI locations on the color coronal slices used in conjunction with the “OR” function of the DTIStudio are depicted for the left and the right AF in Images B and D respectfully.

Figure 6

Fiber bundle extraction for the left (Image A) and the right (Image D) motor fibers using the DTIStudio with a FA threshold of 0.2 and tract turning angle of 41 degrees. Motor fibers were extracted using two ROIs, first with the “OR” function a seed ROI was placed at the posterior segment of the internal capsule (left motor; Image B, right motor; Image E). The “AND” function was used in conjunction with a second ROI (left motor; Image C, right motor; Image F) encompassing the precentral gyrus projection of the fibers created with the first ROI.