Adolescent engagement in dangerous behaviors is associated with increased white matter maturity of frontal cortex

Abstract

Background: Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence.

Methodology/principal findings: We tested this hypothesis in a group of healthy adolescents, age 12-18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14-18, N = 60).

Conclusions/significance: The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers.

Figure 1. Relationship of Adolescent Risk Questionnaire (ARQ) score to chronological age.

The ARQ score ranges from 0–100 and is expressed as a percentage out of the maximum possible score. Prior to age 14, there was very little variation in the ARQ. Beginning at age 14, there was a linearly increasing trend with age and also an increase in the variance. DTI analyses were subsequently performed on the >14 cohort after adjusting the ARQ for the age trend. The residuals of this linear regression (AdjARQ) were checked to make sure that they were not correlated with age (inset), which they were not (R²<0.001, P = 0.879).

Figure 2. White matter tracts with significant correlations of DTI components to chronological age (N = 83).

Using the map for transverse diffusivity (TD), we used tract-based spatial statistics to identify regions within skeletonized white matter tracts that were significantly correlated with age. The maps were fully-corrected for familywise error (FWE) and thresholded at P<0.05 (light blue). Because significance was determined using a permutation test based on 10,000 samplings of the dataset, the exact level of significance had a margin of error. The 95% confidence interval on this statistic (±0.0044) is also shown (dark blue). The scatter plots illustrate the relationship between participant age and component DTI measures for the left anterior internal capsule (arrow). Increasing chronological age was associated with increases in fractional anisotropy (FA), which was due primarily to a decrease in TD (middle bottom).

Figure 3. White matter tracts with significant correlations of DTI components to adjusted-ARQ in adolescents 14 years and older (N = 60).

The effect of age and sex was first removed from ARQ (Fig. 1), yielding a score that captures engagement in dangerous behaviors independent of sex and chronological age. Using the map for fractional anisotropy (FA), we used tract-based spatial statistics to identify regions within skeletonized white matter tracts that were significantly correlated with adjusted-ARQ. Main effects for sex and age were also included in the DTI model so that the regions identified as being correlated with adjusted-ARQ were purely ARQ-related. The maps were fully-corrected for familywise error (FWE) and thresholded at P<0.05 (yellow). Because significance was determined using a permutation test based on 10,000 samplings of the dataset, the exact level of significance had a margin of error. The 95% confidence interval on this statistic (±0.0044) is also shown (red). The scatter plots illustrate the relationship between adjusted-ARQ and component DTI measures for the right superior corona radiata (arrow), but the pattern was the same for all significant regions. Increased ARQ was associated with increased fractional anisotropy (FA, left bottom), which was due primarily to a decrease in TD (middle bottom). These results show that adolescents who engage in dangerous activities have more mature frontal white matter tracts relative to their conservative peers.

Figure 4. Probabilistic tractography from a typical participant.

The significant (P<0.05, green) TFCE-corrected regions from the FA correlation with adjusted-ARQ were used as seeds for tractography in the participant with the median adjusted-ARQ (female, age 16 years). Tractography revealed that the white matter regions that were significantly correlated with FA were located predominately in descending tracts from prefrontal cortex through the internal capsule, interhemispheric fibers connecting left and right homologous regions through the corpus collosum, and fibers connecting prefrontal regions with the temporal lobe (lower middle).

Figure 5. Correlations with FA in right superior corona radiata cluster with age and different factors of the ARQ.

Age was uncorrelated with TD in this region (A). Total ARQ was significantly correlated with TD both before (B) and after adjusting ARQ for sex and age (C). Analysis of the subfactors showed that this correlation was driven predominately by factor 2 – rebelliousness (F and G) and slightly to factor 3 – recklessness (H and I).

Figure 6. Correlations with TD in right superior corona radiata cluster with age and different factors of the ARQ.

Age was uncorrelated with TD in this region (A). Total ARQ was significantly correlated with TD after adjusting ARQ for sex and age (C) and with a trend toward signficance in the unadjusted total ARQ (B). Analysis of the subfactors showed that this correlation was driven predominately by factor 2 – rebelliousness (F and G).