Abstract
Using diffusion tensor imaging, we conducted an exploratory investigation of the relationship between white matter tract microstructure and age in 200 healthy adult subjects using tract-based spatial statistics (TBSS). Though most tracts showed the slight decline in microstructural organization with age widely noted, in both superior cerebellar peduncles (SCP) it correlated positively with age, a result not previously reported. We confirmed this by using an alternative method, and by repeating our TBSS analysis in an additional sample of 133 healthy adults. In exploring this surprising result we considered the possibility that this might arise from the continual cognitive and motor refinement that is enacted in the cerebellum: we found that tract microstructure in both SCPs was also strongly correlated with IQ, again in contrast with all other tracts, and its relationship with age mediated by IQ, as a training model would predict.
Highlights
The brain’s white matter undergoes marked change over the lifespan
Repeated-measures ANOVA of the tract-based spatial statistics (TBSS) tract-averages from our initial sample found a main effect of age (F = 2.25, df = 47; p < 0.001, Greenhouse–Geisser corrected for non-sphericity), an effect of tract (F = 878.6, df = 15.13; p < 0.001), and a significant tract-by-age interaction (F = 1.4, df = 711.5; p < 0.001)
Post hoc tract-age Pearson correlations were examined, revealing a strong correlation of bilateral superior cerebellar peduncles (SCP) Fractional Anisotropy (FA) with age, which was both the strongest of all tracts bar the fornix and, remarkably, was positive, bilaterally (0.39 left, 0.364 right, both at p < 0.001, Benjamini– Hochberg corrected for multiple comparisons; Hochberg and Benjamini, 1990), when every other significant tract correlation was negative (Supplementary Table S1)
Summary
The brain’s white matter undergoes marked change over the lifespan. It is progressively myelinated during childhood and adolescence (Chiang et al, 2011; Lebel and Beaulieu, 2011), dramatically improving its signal conduction; in old age there appears to be a more gradual deterioration in structure and corresponding function (Kochunov et al, 2009b; Glahn et al, 2013), perhaps due to decline in myelination (Kochunov et al, 2009a), though this is less well understood. One way of measuring these structural changes is with Diffusion Tensor Imaging (DTI), a neuroimaging modality that estimates the speed and direction of the diffusion of water in the brain using an MRI scanner (Basser et al, 1994). Scalar measures such as Fractional Anisotropy (FA) and Mean Diffusivity (MD) can be derived from the diffusion tensor, and microstructural features of the underlying brain white matter inferred from these (Basser and Pierpaoli, 1996). A moderately consistent picture of FA decline and MD increase with age has been observed in both cross sectional and longitudinal studies, and associations with the subtle decline in cognition in the healthy
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