Strengthening the SMA-M1 connection of human motor cortex by a novel non-invasive brain stimu-lation protocol to enhance motor performance and learning

• Applicant: Professor Dr. Ulf Ziemann
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Cognitive, Systems and Behavioural Neurobiology
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 259105706

Voluntary movements of the hand are associated with coordinated neuronal activity in a distributed large-scale cortical motor network. Task-dependent increases in effective connectivity, in particular of the connection between supplementary motor area (SMA) and primary motor cortex (M1), funnel driving activity into the voluntarily active M1. Stroke patients with hand paresis typically show im-pairments of this task-dependent increase of SMA-M1 connectivity and activation of the ipsilesional M1. The degree of these abnormalities correlates with motor clinical deficits of the paretic hand. Here we propose a novel MR-navigated paired associative transcranial magnetic stimulation (PAS) technique in combination with transcranial direct current stimulation (tDCS) to induce cooperative spike-timing dependent plasticity (STDP)-like. We will specifically target the SMA-M1 connection to strengthen task-dependent increases in effective connectivity of this pathway. We expect that strengthening of the SMA-M1 pathway will enhance motor performances and motor learning pro-cesses. In a first step, the experiments will be performed in young healthy subjects with a high po-tential for plastic change to explore the effects of combined SMA-M1 PAS and M1-tDCS on motor performance and learning. In a second step, successful protocols will be applied to elderly healthy subjects with an expected reduced potential for plastic change, with the ultimate translational aim to apply these protocols (in an extension of this project) to stroke patients with the intention to im-prove function of their paretic hand. Readouts of stimulation-induced changes in resting-state and task-dependent effective SMA-M1 connectivity will be obtained by paired-coil transcranial magnetic stimulation and MEG/EEG. In addition, changes in motor performance and motor learning will be assessed by standardized motor tests. The proposed project aims, for the first time, at modulating physiological dynamic connectivity states of a specific cortico-cortical projection (SMA-M1) of the human brain by timing- and site-specific non-invasive focal brain stimulation, by virtue of a novel combination of PAS and tDCS. The planned experiments rely on extensive preliminary work, and are based on hyperpolarization of axon terminals of the SMA-M1 projection by anodal M1-tDCS, and cooperativity of STDP, which in cellular physiology is a well-established principle to enhance induction of synaptic plasticity. We expect that, ultimately, this innovative timing- and site-specific non-invasive brain stimulation tech-nique will have significant impact in enhancing neurorehabilitation success of stroke patients.

• DFG Programme: Research Grants
• Participating Person: Christian Braun