Evaluation of cortico-cerebellar network properties as biomarkers for the responsiveness to cortico-cerebellar brain stimulation in stroke patients

• Applicant: Dr. Robert Schulz
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 459728725

Various studies have aimed to explore the potential of non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) to promote motor recovery after stroke. After promising results from early proof-of-concept studies, particularly for the stimulation of the primary motor cortex (M1), it has become evident that the translation from scientific to clinical application is challenging. Aiming to uncover alternative stimulation targets, the cortico-cerebellar network and cerebellar brain stimulation have gained an increasing interest in the field of neurorehabilitation. However, large inter-study and inter-subject variability in behavioural responses to tDCS indicated that a one-size-fits-all approach might not lead to sufficient effect sizes in clinical populations. As structural and functional brain imaging has significantly evolved to powerful tools to assess distinct neuronal networks, such as the cortico-cerebellar network, in individual stroke patients and to infer structure-function-behaviour-relationships, the question arises whether such information might serve as imaging biomarkers to inform about the treatment responsiveness to non-invasive brain stimulation. The present project will evaluate the potential of cortico-cerebellar network properties in a group of chronic stroke patients and healthy participants to explain inter-subject variability in responsiveness to three brain stimulation approaches targeting the cortico-spinal and cortico-cerebellar network: cortical M1 tDCS, cerebellar tDCS and a combined approach of cortico-cerebellar tDCS. Participants will be examined clinically and by structural and functional MRI. Structural MRI will be used to primarily reconstruct cortico-spinal and cortico-cerebellar motor tracts. Tract-related diffusion-based parameters will be used to infer microstructural network integrity. Resting-state MRI will be acquired to assess functional network connectivity. Motor evoked potentials and recruitment curve properties will be investigated by means of TMS to assess electrophysiological properties of cortical excitability. There will be two main experiments. On one hand, we will focus on electrophysiology and evaluate the short-term effects of cortical and cerebellar brain stimulation on cortico-spinal excitability (33 patients, 33 controls). On the other hand, we will evaluate the behavioural impact of the tDCS during a multi-session structured motor training paradigm over seven days (116 patients). The present study aims to evaluate the informative role of structural and functional network properties as biomarkers for the responsiveness of individual patients to non-invasive brain stimulation in the example of cortico-cerebellar brain stimulation. As an overarching goal, this study might provide data towards studies investigating patient stratification protocols providing individual treatment strategies to individual patients.

• DFG Programme: Research Grants