https://doi.org/10.36866/pn.81.26

Regular exercise is known to have an impact on most physiological systems, and has been shown to improve cardiovascular health, bone mineral density, and provide a decreased risk for cancer, stroke and diabetes. More recently, epidemiological evidence has accumulated to suggest that physical activity may provide health-protective benefits for the nervous system, including improvements in several neurological diseases. In addition to these neuroprotective effects, exciting new evidence has emerged indicating that regular physical activity and exercise can increase brain plasticity (i.e. the capacity to reorganize connections in the brain), which is a process believed to be instrumental in the formation of memories and learning. These neuroplastic benefits of exercise are not only important for cognitive function, but may also extend to the neuromotor system to facilitate motor skill learning.

In humans, robust effects of exercise have been most clearly demonstrated in ageing populations during tasks that specifically assess neurocognitive function (Colcombe & Kramer, 2003). These effects have been neatly summarized in a meta-analysis of 18 intervention studies examining the effect of long-term aerobic fitness training on various measures of cognitive performance (Fig. 1). The outcome of this analysis clearly shows that participation in regular physical activity and exercise improves cognitive function in sedentary older adults, with the greatest improvement observed in complex executive-control processes involving coordination, planning and working memory. Furthermore, functional magnetic resonance imaging revealed that highly fit subjects show greater task-dependent modulation of activity in various cortical regions during attention-demanding tasks compared with untrained control subjects (Colcombe et al. 2004). These studies suggest that regular exercise provides neuroplastic benefits to the ageing brain, and may even slow the neural ageing process in humans.

While the majority of these studies have focused on plasticity associated with neurocognitive function, it is unknown whether regular exercise is beneficial for neuroplasticity within the motor cortex, which is vital for learning new motor skills. Recent advances in techniques of transcranial magnetic stimulation (TMS) have allowed us to address this question in humans (Cirillo et al. 2009). TMS is a non-invasive technique that gives an indirect assessment of motor cortex activity, and offers significant advantages in temporal resolution over other functional imaging techniques. TMS activates excitatory (and inhibitory) interneurons in the cortex, producing descending volleys in corticospinal neurons with projections to spinal motoneurons. This results in a short-latency contraction of contralateral muscles, with the amplitude of the muscle-evoked potential (MEP) from the electromyogram (Fig. 2A) reflecting the excitability of the neurons responsible for the movement of that particular muscle. At the motor systems level, plasticity is examined by using TMS to measure the change in excitability of motor cortex neurons before and after an intervention. Any long-lasting (<1 hour) increase in motor cortex excitability is interpreted as a change in one or more mechanisms responsible for neuroplasticity, with long-term potentiation (LTP) thought to play a major role.

Several experimental protocols have been devised for inducing cortical plasticity in humans (see Ziemann et al. 2008 for review). One commonly used protocol to artificially induce changes in the human motor cortex is paired associative stimulation (PAS), which has been deliberately adapted from similar protocols in brain slices and neuronal cultures that demonstrate spike timing-dependent synaptic plasticity. The conventional PAS approach in humans combines low-frequency, percutaneous electrical stimulation of the median nerve at the wrist with TMS over the contralateral motor cortex. The TMS is timed to coincide with the arrival at the cortex of the afferent volley evoked 25 ms earlier by the peripheral stimulus. This protocol results in substantial increases in the amplitude of hand muscle MEPs, which are long lasting (30–60 min), and are thought largely to occur through LTP-like mechanisms in cortical circuits (Stefan et al. 2000). Recent studies show that the effects of PAS and motor skill training interact, suggesting that they involve overlapping changes in functionally relevant neuronal circuits.

In a recent study, we used PAS to examine the capacity for motor cortex plasticity in a group of 14 highly active and 14 sedentary young subjects (Cirillo et al. 2009). Based on aerobic physical activity assessed via questionnaire, individuals in the active group performed moderate or vigorous-intensity exercise (involving running or cycling) an average of 9 times per week for at least 60 min in each session. In contrast, individuals in the sedentary group performed no more than three sessions of walking each week for 20 min each session. All other characteristics were well matched between groups, such as age, sex, handedness and cognitive state. Using TMS, we found that the input–output curve for a small hand muscle was steeper in active subjects (Fig. 2B), suggesting increased excitability in the corticospinal pathway to muscles not directly involved in the exercise. Furthermore, we found a 40% larger MEP in the active compared with the sedentary subjects after PAS (Fig. 2C), suggesting that regular physical activity involving aerobic exercise contributes to increased neuroplasticity after PAS. These findings indicate that regular exercise may offer benefits to motor cortex function that extend beyond the neural boundaries for control of the exercising limb. Although many mechanisms are possible, the beneficial effects of exercise on brain plasticity are likely to be mediated by increased vasculature, blood flow or growth factors that provide a more supportive cortical environment.

An important extension of this work is determining whether these differences in neuroplasticity are functionally important for learning new motor skills. As a first step in addressing this question, we have obtained preliminary data on motor performance and motor cortex plasticity in two sedentary and two active subjects that took part in our original investigation. The task was a brisk thumb movement to maximise acceleration in the abduction direction. These data show improved motor performance and faster learning in the physically active subjects, particularly in the early stages of training (Fig. 3). Furthermore, increased MEP amplitudes and TMS input–output curves in physically active individuals accompanied this improved learning after training. These preliminary data suggest that there is increased motor cortex plasticity in physically active individuals, and that this is accompanied by improved ability to learn new motor skills. However, we cannot yet exclude the possibility that the increased plasticity in physically active individuals is influenced by genetic or epigenetic factors, which makes these individuals more likely to participate in regular physical activity. Nonetheless, these findings offer promising new insights into the benefits of regular exercise on the motor system, which may improve motor skill learning and neurorehabilitation in physically active individuals.

References

Cirillo J, Lavender AP, Ridding MC & Semmler JG (2009). Motor cortex plasticity induced by paired associative stimulation is enhanced in physically active individuals. J Physiol 587, 5831–5842. http://jp.physoc.org/content/587/24/5831.full

Colcombe S & Kramer AF (2003). Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 14, 125–130.

Colcombe SJ, Kramer AF, Erickson KI, Scalf P, McAuley E, Cohen NJ, Webb A, Jerome GJ, Marquez DX & Elavsky S (2004). Cardiovascular fitness, cortical plasticity, and aging. Proc Natl Acad Sci U S A 101, 3316–3321.

Stefan K, Kunesch E, Cohen LG, Benecke R & Classen J (2000). Induction of plasticity in the human motor cortex by paired associative stimulation. Brain 123, 572–584.

Ziemann U, Paulus W, Nitsche MA, Pascual-Leone Pascual A, Byblow WD, Berardelli A, Siebner HR, Classen J, Cohen L & Rothwell JC (2008). Consensus: Motor cortex plasticity protocols. Brain Stimul 1, 164–182.

Acknowledgements

The work from the authors was supported by the National Health and Medical Research Council of Australia.