Fostering restoration of corticospinal tract integrity in chronic stroke using a brain/neural hand exoskeleton (B/NHE) and closed-loop transcranial alternating current stimulation (cl-tACS)

• Applicant: Professor Dr. Surjo R. Soekadar
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 498115854

Despite numerous advancements in neurological rehabilit ation, there is still no established strategy to treat complete chronic muscle paralysis after stroke. Thus, many stroke survivors depend on assistance in their daily life. Over the last years, it was shown that brain/neural hand exoskeletons (B/NHE) translating electric, magnetic or metabolic brain activity into exoskeleton control signals can be operated by chronic stroke patients, e.g., to open and close their paralyzed hand and fingers. Preliminary results suggest that repeated use of such a device can trigger neural recovery, but the underlying mechanisms are not well understood. The proposed project aims at identifying these mechanisms by employing electroencephalography (EEG)-informed closed-loop transcranial alternating current stimulation (cl-tACS) during B/NHE control. cl-tACS allows to specifically target electric brain oscillations causally linked to motor preparation or motor execution and to adapt this stimulation according to the ongoing task-related brain dynamics. We hypothesize that purposeful augmentation of perilesional motor-related cortical oscillations in the mu-range (8-13 Hz) during B/NHE control that mimics physiological modulation improves ipsilesional corticospinal tract integrity of chronic stroke survivors as measured by upper limb motor-evoked potentials (MEP) and impacts functional brain network connectivity as measured by high-density EEG (HD-EEG). The proposed project comprises two phases: Phase I (M1-M12) will be devoted to setting up and testing the paradigm in healthy volunteers (n=20) and to recruiting chronic stroke survivors with severe hand and finger paralysis (n=36). To obtain valid baseline measures, corticospinal tract integrity, and motor function will be assessed across all stroke survivors. In phase II (M12-M36), stroke survivors will be assigned to one of two groups: While group I (n=18) will use a B/NHE in conjunction with cl-tACS targeting the individual mu-rhythm over 20 daily sessions, group II (n=18) will receive an unspecific direct current stimulation during B/NHE control. The B/NHE will be used to assist in activities of daily living (ADL), such as drinking from a bottle or preparing a meal, for 40 minutes per session. MEPs, HD-EEG, and motor function will be assessed before, immediately after, and 3 months after the end of the training. We expect that MEP assessments in group I will show faster recovery of ipsilesional corticospinal tract integrity and increased functional brain network connectivity as compared to group II, providing direct evidence for the causal role of perilesional mu-rhythm modulation for the restoration of motor function. Besides elucidating the functional role of motor-related brain oscillations in chronic stroke, the findings of this study will be critical to design and develop novel treatment strategies for stroke survivors with complete chronic finger paralysis for whom no other treatment strategy exists.

• DFG Programme: Research Grants