Physical activity and anodal-transcranial direct current stimulation: a synergistic approach to boost motor cortex plasticity.

The application of anodal-transcranial direct current stimulation (A-tDCS) over the primary motor cortex (M1) increases its structural and functional plasticity, as also physical exercise. Combining both interventions has a boosting effect, thus revealing a crucial role of the brain state during stimulation. Although brain slice and anesthetized animal studies support this, further investigation in awake animals is necessary. In the present study, we analyzed the effects of coupling A-tDCS with low-intensity physical activity on the mouse M1 structural and functional plasticity. C57BL/6 mice were monolaterally treated with M1 A-tDCS while walking on a rotarod or at rest. To assess the impact of our interventions, we analyzed both motor cortices for changes in neuronal activation, dendritic spine density, and functional synchronisation as measured by local field potential coherence. The combination of physical activity and M1 stimulation revealed a synergistic interhemispheric effect on cortical activation in both layers II/III and V, not present when using a single type of intervention. These data were accompanied by increased M1-M1 synchrony in the low-theta frequency, a hallmark of motor network activity in mice. Dendritic spine density revealed an effect of the combo, which was significantly higher only in layer II/III, accompanied by increased post-synaptic density protein 95 expression in the same area. Based on our findings, we propose that the efficacy of tDCS hinges on brain state rather than being merely a direct causal factor. The observed outcomes contribute to a deeper comprehension of the mechanisms governing structural and functional reorganisation within the motor cortex under physiological conditions, with potential implications for research on learning, memory, and neurological disorders such as stroke.