Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation

Victoria Cotero, Ying Fan, Tea Tsaava, Adam M. Kressel, Ileana Hancu, Paul Fitzgerald, Kirk Wallace, Sireesha Kaanumalle, John Graf, Wayne Rigby, Tzu-Jen Kao, Jeanette Roberts, Chitresh Bhushan, Suresh Joel, Thomas R. Coleman, Stavros Zanos, Kevin J. Tracey, Jeffrey Ashe, Sangeeta S. Chavan and Christopher Puleo ()
Additional contact information
Victoria Cotero: GE Global Research Center
Ying Fan: GE Global Research Center
Tea Tsaava: Feinstein Institute for Medical Research
Adam M. Kressel: Feinstein Institute for Medical Research
Ileana Hancu: GE Global Research Center
Paul Fitzgerald: GE Global Research Center
Kirk Wallace: GE Global Research Center
Sireesha Kaanumalle: GE Global Research Center
John Graf: GE Global Research Center
Wayne Rigby: GE Global Research Center
Tzu-Jen Kao: GE Global Research Center
Jeanette Roberts: GE Global Research Center
Chitresh Bhushan: GE Global Research Center
Suresh Joel: GE Global Research Center
Thomas R. Coleman: Feinstein Institute for Medical Research
Stavros Zanos: Feinstein Institute for Medical Research
Kevin J. Tracey: Feinstein Institute for Medical Research
Jeffrey Ashe: GE Global Research Center
Sangeeta S. Chavan: Feinstein Institute for Medical Research
Christopher Puleo: GE Global Research Center

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Tools for noninvasively modulating neural signaling in peripheral organs will advance the study of nerves and their effect on homeostasis and disease. Herein, we demonstrate a noninvasive method to modulate specific signaling pathways within organs using ultrasound (U/S). U/S is first applied to spleen to modulate the cholinergic anti-inflammatory pathway (CAP), and US stimulation is shown to reduce cytokine response to endotoxin to the same levels as implant-based vagus nerve stimulation (VNS). Next, hepatic U/S stimulation is shown to modulate pathways that regulate blood glucose and is as effective as VNS in suppressing the hyperglycemic effect of endotoxin exposure. This response to hepatic U/S is only found when targeting specific sub-organ locations known to contain glucose sensory neurons, and both molecular (i.e. neurotransmitter concentration and cFOS expression) and neuroimaging results indicate US induced signaling to metabolism-related hypothalamic sub-nuclei. These data demonstrate that U/S stimulation within organs provides a new method for site-selective neuromodulation to regulate specific physiological functions.

Date: 2019
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DOI: 10.1038/s41467-019-08750-9

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