Basic information

Investigator: Mgr. Grygoriy Tsenov, MSc., Ph.D.
Main recipient: National Institute of Mental Health (NIMH)
Co-recipient: Ludwig-Maximilians-Universität München (Germany), Krembil Research Institute - University Health Network (Canada), Fraunhofer Institute for Biomedical Engineering (Germany), Department of Electrical and Electronics Engineering (Turkish), Alvimedica Tıbbi Ürünler San. ve Dış Tic. A.Ş (Turkey)
Research period: 1/1/2021 - 31/12/2024
Total budget: 35,884,194 CZK
NIMH budget: 8,801,919 CZK
Supported by: Ministry of Education, Youth and Sports of the Czech Republic

Annotation

Deep brain stimulation (DBS) using electrode implants is a successful method of treating Parkinson's disease (PN). In this project, a non-invasive single and hybrid neuromodulation technology targeting the basal ganglia will be developed and used to restore motor function in PD using interference electric fields and ultrasound (US).

Two groups (partners 2-3) will focus on patients, while the others will focus on basic research and technology development. Noninvasive Electrical Stimulation: Partner 2 will apply temporal electrical interference fields (TIFs) induced by two high-frequency transcranial alternating current stimulators (tACS) with shifted frequency to activate the internal globus pallidus (GPi) resulting in lower (130 Hz) TIFs. Stimulation intensity will be optimized by modeling (partner 5) and verified on the basis of invasive recordings in patients during preoperative epilepsy assessment and in experimental rats (coordinator-partner 1 and 2). The clinical efficacy of TIF stimulation will be verified using UPDRS (Unified PD Rating Scale) scores and recording well-defined parameters of motor cortex excitability via transcranial magnetic stimulation (TMS) (motor evoked potentials, i.e. MEP, silent period, short-interval intracortical inhibition (SICI)) and others in PD patients and controls (Partner 2). Non-invasive high-precision US stimulation of the basal ganglia using low-intensity focused US (LIFUS) will be investigated using a new, multi-channel stimulator developed by partner 4. The effects of LIFUS will be verified using UPDRS scores and recording of local field potentials in PD patients, targeting the subthalamic nucleus (STN) or GPi. Stimulation parameters will be optimized based on clinical response, pathological β oscillations and connectivity studies using fMRI (Partner3). Partner 2 will focus primarily on pathophysiology in PD, while Partner 3 will conduct clinical efficacy studies. In exploratory, high-risk, high-gain experiments, Partner 2 will use hybrid tACS and LIFUS to test for synergistic effects. For this purpose, the US frequencies will be reduced to ~150 kHz, while the electrical stimulation frequency will be increased to ~150 kHz to achieve an electroacoustic effect. Partner 5 will investigate additive effects using a combination of different stimulation modalities (electrical, magnetic and LIFUS) together with realistic numerical models and tests on head phantoms, while Partner 6 will focus on hardware development and adaptation of new hybrid systems for experimental use. The possible applicability of alternative neurostimulation based on Lorentzian fields caused by the interaction of LIFUS and magnetic fields will also be investigated by partner 5. The main task of Partner 1 will be the mechanistic analysis of non-invasive neuromodulation in the rat brain and neurons in vitro with the aim of defining basic electrochemical processes and circuit mechanisms. Partner 1 will also define safety margins and optimal operating range using functional and histochemical tests. By targeted activation of selected neurons using LIFUS, thermo- and mechanosensitive effects will be disaggregated and assigned to specific channels expressed in neurons. Thanks to the ingenious combination of innovative technologies and the synergy of expertise, the most promising single and hybrid methods of neurostimulation will be thoroughly tested for the first time, from cultured neurons in vitro, through animal experiments to clinical trials in PD patients. It is expected that the described non-invasive technologies will allow not only better treatment and recovery of motor function in PD, but also a better understanding of the underlying mechanisms and safety for optimization and expatriation into routine medical practice.