Untersuchung der Effekte tiefer Hirnstimulation auf neuronale Plastizität bei Parkinsonsyndrom mittels kombinierter transkranieller Magnetstimulation (TMS) und Elektroenzephalographie (EEG)
Zusammenfassung der Projektergebnisse
Initially, my aim was to investigate deep brain stimulation (DBS)-induced plasticity in Parkinson’s disease (PD) using concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG). However, due to the COVID-19 pandemic, all EEG experiments on patients were canceled at Toronto Western Hospital, and only essential procedures such as DBS were permitted. Consequently, instead of EEG recordings, I shifted my focus to studying the long-term effects of DBS in PD using intracranial recordings, and developing transcranial ultrasound stimulation (TUS) as a non-invasive form of DBS which can induce plasticity in PD. In a longitudinal study, I explored the impact of DBS and dopaminergic medications on local field potentials (LFPs) recorded from the subthalamic nucleus (STN) in PD patients. LFPs have two components: aperiodic signals and oscillations. Previous studies have shown beta oscillations are exaggerated in PD and often manifest as bursts of activity. Our results revealed a systematic increase of aperiodic activities over 18 months following the DBS implantation, independent of the dopaminergic medication state of patients with PD. In contrast, beta bursts were stable over time and were suppressed by dopaminergic medications. These findings indicate that oscillations and aperiodic activities reflect at least partially distinct yet complementary neural mechanisms, which should be considered in the design of robust biomarkers to optimize adaptive DBS. Given the link between increased gamma-aminobutyric acidergic (GABAergic) transmission and higher aperiodic activity, our findings suggest that long-term STN-DBS may relate to increased inhibition in the basal ganglia. I also expanded my research to explore TUS as a non-invasive alternative to DBS. I first led a team of experts in authoring a comprehensive review paper on TUS for neuromodulation, providing guidelines for researchers and clinicians in designing experiments and clinical protocols. Following this, our team conducted a study demonstrating the potential of TUS to induce longlasting changes in brain plasticity, specifically within the motor cortex. Our findings, which highlight the use of theta burst patterned ultrasound to non-invasively modulate cortical excitability, represent a significant advancement in both basic neuroscience and clinical neuromodulation therapies.
Projektbezogene Publikationen (Auswahl)
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Induction of Human Motor Cortex Plasticity by Theta Burst Transcranial Ultrasound Stimulation. Annals of Neurology, 91(2), 238-252.
Zeng, Ke; Darmani, Ghazaleh; Fomenko, Anton; Xia, Xue; Tran, Stephanie; Nankoo, Jean‐François; Shamli, Oghli Yazan; Wang, Yanqiu; Lozano, Andres M. & Chen, Robert
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Long‐Term Recording of Subthalamic Aperiodic Activities and Beta Bursts in Parkinson's Disease. Movement Disorders, 38(2), 232-243.
Darmani, Ghazaleh; Drummond, Neil M.; Ramezanpour, Hamidreza; Saha, Utpal; Hoque, Tasnuva; Udupa, Kaviraja; Sarica, Can; Zeng, Ke; Cortez, Grippe Talyta; Nankoo, Jean‐Francois; Bergmann, Til Ole; Hodaie, Mojgan; Kalia, Suneil K.; Lozano, Andres M.; Hutchison, William D.; Fasano, Alfonso & Chen, Robert
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Non-invasive transcranial ultrasound stimulation for neuromodulation. Clinical Neurophysiology, 135, 51-73.
Darmani, G.; Bergmann, T.O.; Butts, Pauly K.; Caskey, C.F.; de Lecea, L.; Fomenko, A.; Fouragnan, E.; Legon, W.; Murphy, K.R.; Nandi, T.; Phipps, M.A.; Pinton, G.; Ramezanpour, H.; Sallet, J.; Yaakub, S.N.; Yoo, S.S. & Chen, R.
