The main objective of the proposed research is to develop a focused ultrasound (FUS) method to reversibly modulate (either elicit or suppress) neural activities of specific brain regions. We will develop a magnetic resonance imaging (MRI)-guided sonication environment, capable of evaluating local brain function using electrophysiological recordings (electroencephalography and electromyography) and real- time functional magnetic resonance imaging (rtfMRI). We will examine sonication parameters and their corresponding modulatory effects based on closed-loop monitoring of the electrophysiological data (EEG and EMG signal magnitude), supported by the level of the blood-oxygenation-level-dependent (BOLD) fMRI signal originating from the targeted brain tissue. Consequently, we will examine the range of sonication parameters which induce reversible suppression of regional cortical activity in the primary visual cortex and elicit excitation of activity in the sensorimotor cortex. The dose (duration)-dependent modulatory effects of FUS and their temporal dynamics will be probed via interleaved acquisition of fMRI and EEG/EMG using a trial-based paradigm design. To probe the safety of the method, immunohistological analysis examining biological effects of the sonication in terms of tissue or vascular damage will be performed at variable time points, covering acute, delayed, and long-term periods after the initial sonication. The ability to non-invasively modulate a specific brain area would enable the study of causal relations between brain activity and behavior, including the investigation of functional connectivity between brain regions. The success of this study will result in the exploration of novel potential therapeutic applications of FUS for numerous neurological and psychiatric disorders.

Public Health Relevance

This study will explore the use of focused ultrasound sound waves to temporarily modulate the function of region-specific brain tissue in a non-invasive manner. The success of the proposed method will offer a diagnostic assessment of how well the different parts of the brain are functionally operated and connected to each other. Apart from its potential utility as a diagnostic tool, the ability to suppress or excite local brain tissue in a controlled manner also offers therapeutic potential in the treatment of various neurological and psychiatric disorders.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-NT-B (08))
Program Officer
Babcock, Debra J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brigham and Women's Hospital
United States
Zip Code
Lee, Wonhye; Lee, Stephanie D; Park, Michael Y et al. (2016) Image-Guided Focused Ultrasound-Mediated Regional Brain Stimulation in Sheep. Ultrasound Med Biol 42:459-70
Lee, Wonhye; Lee, Stephanie D; Park, Michael Y et al. (2015) Functional and diffusion tensor magnetic resonance imaging of the sheep brain. BMC Vet Res 11:262
Kim, Hyungmin; Park, Michael Y; Lee, Stephanie D et al. (2015) Suppression of EEG visual-evoked potentials in rats through neuromodulatory focused ultrasound. Neuroreport 26:211-5
Kim, Hyungmin; Chiu, Alan; Lee, Stephanie D et al. (2014) Focused ultrasound-mediated non-invasive brain stimulation: examination of sonication parameters. Brain Stimul 7:748-56
Kim, Hyungmin; Lee, Stephanie D; Chiu, Alan et al. (2014) Estimation of the spatial profile of neuromodulation and the temporal latency in motor responses induced by focused ultrasound brain stimulation. Neuroreport 25:475-9
Yoo, Seung-Schik; Kim, Hyungmin; Filandrianos, Emmanuel et al. (2013) Non-invasive brain-to-brain interface (BBI): establishing functional links between two brains. PLoS One 8:e60410
Kim, Hyungmin; Park, Mi-Ae; Wang, Shuyan et al. (2013) PET?CT imaging evidence of FUS-mediated (18)F-FDG uptake changes in rat brain. Med Phys 40:033501
Kim, Hyungmin; Taghados, Seyed Javid; Fischer, Krisztina et al. (2012) Noninvasive transcranial stimulation of rat abducens nerve by focused ultrasound. Ultrasound Med Biol 38:1568-75
Kim, Hyungmin; Chiu, Alan; Park, Shinsuk et al. (2012) Image-guided Navigation of Single-element Focused Ultrasound Transducer. Int J Imaging Syst Technol 22:177-184
Yoo, Seung-Schik; Kim, Hyungmin; Min, Byoung-Kyong et al. (2011) Transcranial focused ultrasound to the thalamus alters anesthesia time in rats. Neuroreport 22:783-7