A tool for monitoring cell type-specific focused ultrasound neuromodulation and control of chronic epilepsy

Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within hete...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2022-11, Vol.119 (46), p.e2206828119
Main Authors: Murphy, Keith R, Farrell, Jordan S, Gomez, Juan L, Stedman, Quintin G, Li, Ningrui, Leung, Steven A, Good, Cameron H, Qiu, Zhihai, Firouzi, Kamyar, Butts Pauly, Kim, Khuri-Yakub, Butrus Pierre T, Michaelides, Michael, Soltesz, Ivan, de Lecea, Luis
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Brain
Brain - diagnostic imaging
Brain - physiology
Epilepsy
Epilepsy - therapy
Epilepsy, Temporal Lobe
Hippocampus
Hippocampus - diagnostic imaging
Interneurons
Monitoring
Neuroimaging
Neuromodulation
Parameter identification
Parvalbumin
Photometry
Temporal lobe
Ultrasonic imaging
Ultrasonography
Ultrasound
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Summary:Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether parameters can be identified to bias these networks in the context of complex behaviors remains unknown. To address this, we developed a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simultaneously monitoring FUS effects on neural activity of subcortical genetically targeted cell types in freely behaving animals. We identified a parameter set that selectively increases activity of parvalbumin interneurons while suppressing excitatory neurons in the hippocampus. A net inhibitory effect localized to the hippocampus was further confirmed through whole brain metabolic imaging. Finally, these inhibitory selective parameters achieved significant spike suppression in the kainate model of chronic temporal lobe epilepsy, opening the door for future noninvasive therapies.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.2206828119