Neurofeedback can be used to alter brain activity and is therefore an attractive tool for neuromodulation in clinical contexts. Different contexts might call for different patterns of activity modulation. For example, following stroke, alternative therapeutic strategies could involve up or down-regulation of activity in the ipsilateral motor cortex. However, effects of such strategies on activity and brain structure are unknown. In a proof of concept study in healthy individuals, we showed that fMRI neurofeedback can be used to drive activity up or down in ipsilateral motor cortex during hand movement. Given evidence for activitydependent white matter plasticity, we also tested effects of activity modulation on white matter microstructure using diffusion tensor imaging (DTI). We show rapid opposing changes in corpus callosum microstructure that depend on the direction of activity modulation. Bidirectional modulation of ipsilateral motor cortex activity is therefore possible, and results not only in online changes in activity patterns, but also in changes in microstructure detectable 24 hours later.

The white matter is a complex network of brain fibers connecting different information processing regions in the brain. In recent years, the investigation of white matter in humans and in animal models has greatly benefitted from the introduction of in vivo noninvasive magnetic resonance imaging (MRI) techniques. MRI allows for multiple in vivo time-point whole-brain acquisition in the same subject, thus it can be used longitudinally to monitor white matter brain change, intervention effects, as well as disease progression. However, MRI has low spatial resolution compared to gold standard cellular techniques and MRI measures are sensitive to a number of tissue properties resulting in a lack of specificity.The following chapter describes in simple technical terms to non-imaging experts some common MRI techniques that can be used to investigate white matter structure noninvasively, covering some of the advantages and pitfalls of each technique.