Brain-derived neurotrophic factor (BDNF) is important to brain functions such as plasticity and repair. A single nucleotide polymorphism for this growth factor, val(66)met, is common and associated with decreased activity-dependent BDNF release. The current study evaluated the effects of this polymorphism in relation to human brain motor system function, short-term plasticity, and learning. Functional magnetic resonance imaging (fMRI) scanning during right index finger movement (n = 24) identified activation in a broad sensorimotor network. However, subjects with the polymorphism showed smaller activation volume within several brain regions as compared with subjects without the polymorphism. Repeat fMRI after 25 min of right index finger training found that the 2 genotype groups modulated brain activation differently. In several brain regions, subjects with the polymorphism showed greater activation volume reduction, whereas subjects without the polymorphism showed greater activation volume expansion. On a driving-based motor learning task (independent cohort, n = 29), subjects with the polymorphism showed greater error during short-term learning and poorer retention over 4 days, relative to subjects without the polymorphism. The presence of this BDNF polymorphism is associated with differences in brain motor system function, altered short-term plasticity, and greater error in short-term motor learning. The broader implications of these findings are considered.

In a previous study, we found that haptic guidance from a robotic steering wheel can improve short-term learning of steering of a simulated vehicle, in contrast to several studies of other tasks that had found that the guidance either impairs or does not aid motor learning. In this study, we examined whether haptic guidance-as-needed can improve long-term retention (across 1 week) of the steering task, with age and initial skill level as independent variables. Training with guidance-as-needed allowed all participants to learn to steer without experiencing large errors. For young participants (age 18–30), training with guidance-as-needed produced better long-term retention of driving skill than did training without guidance. For older participants (age 65–92), training with guidance-as-needed improved long-term retention in tracking error, but not significantly. However, for a subset of less skilled, older subjects, training with guidance-as-needed significantly improved long-term retention. The benefits of guidance-based training were most evident as an improved ability to straighten the vehicle direction when coming out of turns. In general, older participants not only systematically performed worse at the task than younger subjects (errors ∼3 times greater), but also apparently learned more slowly, forgetting a greater percentage of the learned task during the 1 week layoffs between the experimental sessions. This study demonstrates that training with haptic guidance can benefit long-term retention of a driving skill for young and for some old drivers. Training with haptic guidance is more useful for people with less initial skill.

The val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene impacts activity-dependent secretion of BDNF and modifies short-term cortical plasticity. The current study examined whether sustained training overcomes polymorphism effects on short-term plasticity and also examined polymorphism effects on long-term plasticity. Twenty-four subjects completed a 12-day protocol of daily training on a marble navigation task that required intense use of the first dorsal interosseus (FDI) muscle. In parallel, transcranial magnetic stimulation (TMS) mapping was used to assess serial measures of short-term cortical motor map plasticity, plus long-term cortical motor map plasticity, of the cortical FDI map. On Day 1, subjects with the polymorphism did not show significant short-term cortical motor map plasticity over 30 min of FDI activity, but subjects without the polymorphism did. After 5 days of intense training, a genotype-based difference in short-term cortical motor map plasticity was no longer found, as both groups showed short-term plasticity across the 30 min of FDI activity. Also, across 12 days of training, map area decreased significantly, in a manner that did not vary in relation to genotype. Training of sufficient intensity and duration overcomes effects that the val(66)met polymorphism has on short-term cortical motor map plasticity. The polymorphism-related differences seen with short-term plasticity are not found with long-term cortical motor map plasticity.

The brain derived neurotrophic factor (BDNF) val66 met polymorphism affects function of the motor system in young subjects, but little is known about motor system effects in the elderly. The current study assessed motor system physiology and behavior, plus a measure of short-term motor cortex plasticity using transcranial magnetic stimulation, in 38 elderly subjects, then examined whether findings varied in relation to BDNF genotype. Baseline data were also collected from 14 young subjects. At baseline, elderly subjects had poorer motor performances, larger motor cortex maps, and smaller motor evoked potentials compared to young subjects. Degree of age-related differences in neurophysiology correlated inversely with motor performance, for example, larger map area correlated with weaker pinch grip force (r= −0.42, P=0.01). In elderly subjects, baseline behavior and neurophysiology did not differ in relation to BDNF genotype. In addition, although map area increased significantly (P=0.03) across 30 minutes of exercise, this change did not vary according to BDNF genotype. Aging is associated with changes in neurophysiology that might represent a compensatory response. The data do not support an association between BDNF genotype and behavior, neurophysiology, or short-term cortical plasticity in the motor system of healthy elderly subjects.