Does one size fit all? - Towards the optimization and personalization of non-invasive brain stimulation paradigms to enhance motor learning

The acquisition and re-acquisition of motor skills is an important aspect of daily life and in the recovery after a stroke. Non-invasive brain stimulation (NIBS) is a technique that is used to improve motor learning and enhance motor recovery in stroke survivors. Although the current results are promising, the outcomes are heterogeneous with responders and non-responders. This thesis aimed to investigate multiple, novel NIBS strategies to enhance stimulation efficacy and to develop approaches for protocol personalization. These alternative strategies include targeting other areas of the motor network than the primary motor cortex (M1), targeting the brain as a network with the use of multifocal stimulation, and using a variety of stimulation techniques (TMS, tACS, tDCS) to study underlying mechanisms. Study 1 explored the methodological implications of TMS for measuring inhibitory and excitatory neurotransmissions. With the use of TMS, short intracortical inhibition (SICI) and intracortical facilitation (ICF) were measured in healthy young adults. SICI and ICF were studied with different stimulators, waveforms, and current directions using a set of interstimulus intervals. Our findings indicated high comparability among the different stimulation paradigms, except for SICI at 3 ms, which enables data sharing across units and facilitates the conduction of multi-center studies.Study 2 measured the effect of 50 Hz tACS applied to the cerebellum on a novel motor learning task in healthy young adults. Targeting the cerebellum with NIBS is a relatively new field of research with open questions that need to be addressed. Therefore, we explored for the first time the effect of CB-tACS on a motor learning task. Our results did not show an improvement of learning with 50 Hz CB-tACS. We argue that this might have been related to the task and/or the selected stimulation frequency. Therefore, this stimulation paradigm requires further optimization to be effective for motor learning.Study 3 compared multifocal sequential stimulation to monofocal tDCS on motor learning in stroke patients. The multifocal paradigm consisted of an orchestrated M1 – CB stimulation setup, the monofocal paradigm targeted the M1. Our results indicated a significant effect of multifocal M1-CB stimulation, mainly driven by CB-tDCS during the early phase of learning. Moreover, baseline performance and neurophysiology were related to stimulation responsiveness that could potentially lead to biomarkers to predict stimulation efficacy in stroke patients.Study 4 measured the effect of personalized bifocal theta tACS applied to the FPN on motor learning in healthy older adults. Sequence learning has a cognitive component related to working memory (WM) capacity, a process mediated by the FPN. We hypothesized that targeting the FPN might be beneficial for motor learning. tACS to the FPN improved performance, when WM load was high, but not when WM-load was low. Therefore, we conclude that the FPN is a promising new target to enhance motor learning which might be most beneficial for individuals with decreased WM capacity due to age or stroke. In conclusion, this thesis demonstrates that targeting alternative motor network areas, and multifocal stimulation is promising. These results expand on the current knowledge of NIBS and identified open questions that require further examination but could ultimately lead towards enhanced efficacy and the personalization of study protocols.