Low Intensity Focused Ultrasound for Neuromodulation in Human

Low intensity transcranial focused ultrasound stimulation (TUS) is a novel non-invasive brain stimulation (NIBS) technique. Compared to commonly used NIBS techniques, TUS is much more focal and can reach deeper brain structures. The talk will focus on induction of plasticity or after-effects by TUS, since lasting effects are likely required for non-invasive treatment for neurological and psychiatric disorders. In human subjects, a theta burst TUS (tbTUS) protocol with TUS repeated at bursts at 5 Hz (theta frequency) for 80 to 120 s can increase motor cortical (M1) excitability for 30 min to 1 hour. Pharmacological studies showed that tbTUS plasticity is blocked by calcium channel and NMDA receptor blockers, and by benzodiazepine which enhances GABAergic transmission, consistent with a long-term potentiation-like mechanism. A magnetoencephalography study showed that TUS to the M1 led to widespread changes in connectivity between brain regions. The interactions between plasticity induced by transcranial magnetic stimulation and tbTUS are consistent with the concepts of metaplasticity and depotentiation. TUS targeting of deep brain structures requires accurate modeling based on individual MRI/CT scan because ultrasound is absorbed and deflected by the skull. Current studies in our laboratory includes targeting the basal ganglia in PD patients implanted with deep brain stimulation (DBS) device capable of chronic local field potential recordings to provide target validation of our ability to accurately target deep brain structures and to find stimulation parameters that can reduce beta oscillations, a reliable biomarker of PD motor symptoms. TUS has the potential to be developed into a novel non-invasive DBS treatment for neurological and psychiatric disorders.

Dr. Robert Chen received his MA and medical (MBBChir) degrees from University of Cambridge.  He undertook Neurology residency at the University of Western Ontario (Canada), and fellowship at the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, USA. He is currently Professor of Medicine (Neurology) at University of Toronto, Senior Scientist at Krembil Research Institute, Editor-in-Chief of Clinical Neurophysiology and Associate Editor of Movement Disorders.  His clinical and research interests include transcranial magnetic and ultrasound stimulation, neurophysiology of movement disorders, mapping of brain connectivity using functional magnetic imaging and electroencephalography, electromyography and neurophysiological assessment of the respiratory system.  He has published over 400 research papers, a book on Transcranial Magnetic Stimulation and edited two volumes of Handbook of Clinical Neurology on Respiratory Neurobiology.