A polymorphism in the gene for brain-derived neurotrophic factor influences motor-related experience-dependent plasticity in the human brain

Cortical plasticity is an essential element of learning, memory, and recovery of function following brain injury, though the specific underlying mechanisms are still incompletely understood. One factor known to play a critical role in mediating synaptic plasticity is brain derived neurotrophic factor (BDNF), a common neurotrophin with important roles in health and disease. A polymorphism in the human gene for BDNF (val 66met) may provide insight into the role of BDNF in cortical plasticity, and potentially point to future therapeutic targets. This polymorphism allows an opportunity to examine BDNF's influence on experience-dependent plasticity in the human brain, both short and long-term. In addition, the polymorphism itself is common and may be helpful in developing personalized rehabilitation strategies and could thus benefit from further characterization. The current dissertation examined the influence of the BDNF val66met polymorphism on short- and long-term forms of plasticity using non-invasive imaging such as functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS). Presence of the val66met polymorphism was found to influence motor system organization, short-term experience-dependent plasticity throughout the brain, and motor performance in healthy young subjects. The effect of age was found to be more significant than the effect of BDNF genotype on short-term motor cortex plasticity, and age itself was associated with changes in neurophysiology that correlate with decrement of motor function. Additionally, sustained training was able to overcome the effects of the val 66met polymorphism on short-term cortical plasticity, and polymorphism effects were not present in an evaluation of long-term plasticity. These results help illuminate the role of BDNF in motor experience-dependent plasticity and have important clinical implications.