A 12-step user guide for analyzing voxel-wise gray matter asymmetries

This protocol provides the scientific community with a carefully developed guide describing, in 12 distinct steps, how to take structural images from data pre-processing, via statistical analysis, to the final interpretation of the significance maps. Key adaptations compared with the standard VBM workflow involve establishing a voxel-wise hemispheric correspondence, capturing the direction and degree of asymmetry and preventing a blurring of information across hemispheres. The workflow incorporates the most recent methodological developments, including high-dimensional spatial normalization and partial volume estimations. Although the protocol is primarily designed to enable relatively inexperienced users to conduct a voxel-based asymmetry analysis on their own, it may also be useful to experienced users who wish to efficiently adapt their existing scripts or pipelines.

Time-of-day effects in brain volume (brain volumes are larger in the morning) (!)

There was a statistically significant effect of time-of-day on the BPF change in MS clinical trial datasets (− 0.180 per day, that is, 0.180% of intracranial volume, p = 0.019) as well as the ADNI dataset (− 0.438 per day, that is, 0.438% of intracranial volume, p < 0.0001), showing that the brain volume is greater in the morning. Linearly correcting the BPF values with the time-of-day reduced the required sample size to detect a 25% treatment effect (80% power and 0.05 significance level) on change in brain volume from 2 time-points over a period of 1 year by 2.6%.