Normal ageing is associated with characteristic changes in brain microstructure. Although in vivo neuroimaging captures spatial and temporal patterns of age-related changes of anatomy at the macroscopic scale, our knowledge of the underlying (patho)physiological processes at cellular and molecular levels is still limited. The aim of this study is to explore brain tissue properties in normal ageing using quantitative magnetic resonance imaging (MRI) alongside conventional morphological assessment. Using a whole-brain approach in a cohort of 26 adults, aged 18-85years, we performed voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) of diffusion tensor, magnetization transfer (MT), R1, and R2* relaxation parameters. We found age-related reductions in cortical and subcortical grey matter volume paralleled by changes in fractional anisotropy (FA), mean diffusivity (MD), MT and R2*. The latter were regionally specific depending on their differential sensitivity to microscopic tissue properties. VBQ of white matter revealed distinct anatomical patterns of age-related change in microstructure. Widespread and profound reduction in MT contrasted with local FA decreases paralleled by MD increases. R1 reductions and R2* increases were observed to a smaller extent in overlapping occipito-parietal white matter regions. We interpret our findings, based on current biophysical models, as a fingerprint of age-dependent brain atrophy and underlying microstructural changes in myelin, iron deposits and water. The VBQ approach we present allows for systematic unbiased exploration of the interaction between imaging parameters and extends current methods for detection of neurodegenerative processes in the brain. The demonstrated parameter-specific distribution patterns offer insights into age-related brain structure changes in vivo and provide essential baseline data for studying disease against a background of healthy ageing.

The anatomy of the corpus callosum (CC) has been advocated as a potential marker for functional lateralization because its size is supposedly proportional to the number of fibers connecting the hemispheres. Previous morphometric studies of this relationship have compared CC size in groups of subjects who are more or less likely to show differences in their lateralization (e.g., left vs right handers). The findings, however, have been inconsistent, and to our knowledge, no previous study has directly compared CC size with lateralization assessed by functional imaging data. We therefore combined anatomical measurements of CC size with left versus right hemisphere language activation in 74 normal subjects. After controlling for perceptual and motor output effects, as well as for global white-matter volume, handedness, gender and age, we found that subjects who had a larger CC showed more left lateralization for language in posterior temporal and inferior frontal regions. Examination of these effects revealed that, as CC size increased, stronger lateralization resulted from more left hemisphere activation in both regions as well as reduced right hemisphere activation in the posterior temporal region. Our observations provide the first clear evidence in normal subjects that the midsagittal surface area of the CC contributes to the degree to which language is functionally lateralized. We discuss the complex interhemispheric processes that might underlie this effect.

Previous studies have demonstrated that a region in the left ventral occipito-temporal (LvOT) cortex is highly selective to the visual forms of written words and objects relative to closely matched visual stimuli. Here, we investigated why LvOT activation is not higher for reading than picture naming even though written words and pictures of objects have grossly different visual forms. To compare neuronal responses for words and pictures within the same LvOT area, we used functional magnetic resonance imaging adaptation and instructed participants to name target stimuli that followed briefly presented masked primes that were either presented in the same stimulus type as the target (word–word, picture–picture) or a different stimulus type (picture–word, word–picture). We found that activation throughout posterior and anterior parts of LvOT was reduced when the prime had the same name/response as the target irrespective of whether the prime-target relationship was within or between stimulus type. As posterior LvOT is a visual form processing area, and there was no visual form similarity between different stimulus types, we suggest that our results indicate automatic top-down influences from pictures to words and words to pictures. This novel perspective motivates further investigation of the functional properties of this intriguing region.