New avenues to facilitate neuroplasticity in the healthy brain: The effect of transcranial direct current stimulation on motor learning and the impact of acute physical exercise on brain derived neurotrophic factor up-regulation

The brain is a fascinating organ that controls every single movement of the human body. More importantly, it has the ability to change and adapt to its own environment. This ability is known as neuroplasticity and it is the key to learning and memory. Therefore, the idea behind this doctoral project is to take advantage of this human plastic brain and manipulate the environment by using innovative non-invasive brain stimulation techniques to boost neuroplasticity in the healthy brain.

There are different non-invasive brain stimulation techniques, however, in this dissertation we focus on two of them exclusively: transcranial direct current stimulation (tDCS) and physical exercise. We investigated each of these techniques to explore and learn more about them individually with the purpose of designing an innovative protocol to combine them.

The first technique we investigated was tDCS. TDCS is a simple technique that has been shown to effectively stimulate the brain as measured by imaging techniques as well as by neurophysiological and behavioral measurements. In the present work, we found that the effect of tDCS is task-specific and that the behavioral response to this technique is highly variable, with only 43% of subjects showing the expected benefits. These results thus highlight that the effect of tDCS is specific not only to the task being acquired, but also to the individual receiving the stimulation. Notably, we observed an overall small to moderate effect of tDCS on motor learning, which based on our findings, could result, at least partly, from the large inter-subject variability. Importantly, however, our data was acquired in young healthy subjects while it is likely that effectiveness of tDCS would generally be higher in neurological patients, providing an optimistic view on the implementation of this technique in patient’s populations.

The second technique used in this project was physical exercise. Exercise is not only easy to perform and cost-effective but has also additional secondary beneficial effects such as improvements in metabolic and cardiovascular risk profiles. Moreover, exercise could have a positive effect on the brain by activating brain derived neurotrophic factor (BDNF) related processes. We confirmed that intense exercise can increase BDNF levels. Further, it is important to mention that our findings show a slightly higher BDNF serum concentration after the high intensity interval training protocol (HIT) than after the continuous high intensity exercise protocol (CON). Thus, we argue that the HIT protocol could be a potential intervention to promote neuroplasticity and in turn brain health.

To conclude, tDCS and exercise are both promising methods to enhance neuroplasticity. However, the effectiveness of these interventions on neuroplasticity in healthy humans has proven challenging with only few studies reporting a beneficial effect of exercise on cognition and with small to moderate effect sizes found in our and many other tDCS studies. We therefore propose that combining both interventions might boost neuroplasticity in a manner that exceeds their sum. Ultimately, these findings may contribute indirectly to the improvement and design of new motor rehabilitation approaches in patients with brain damage or neurological conditions.