Inducing and disrupting white matter plasticity (360G-Wellcome-109062_Z_15_A)

Recent evidence has shown that dynamical changes in white matter underlie the learning of motor skills. This has been observed both in humans with Diffusion Tensor Imaging (DTI, Schulz et al., 2009) and in rodents with histology (Sampaio-Baptista et al., 2013). These findings raise questions on which conditions are necessary for WM plasticity induction and how the plasticity they induce is modulated by genetic factors. Can an artificial induction of white matter plasticity in humans lead to behavioural changes, even without actual motor experience? To answer this question, the first aim of my DPhil will be to induce white matter plasticity at rest; more specifically, I will attempt to do so through fMRI neurofeedback, and will monitor the outcome with DTI and other myelin-specific MRI modalities. Given that white matter is often implicated in psychiatric disorders, a second question regards whether genes related to mental health conditions (in this case, NR1), can influence how white matter responds to learning, and possibly underlie a deficient or maladaptive response. Therefore, the second aim of my DPhil will be to investigate whether WM plasticity is affected in a mouse model of white matter-specific knockout of NMDA receptors.