Techniques for neuromodulation

Abstract

The subject matter of the present disclosure generally relates to techniques for neuromodulation of a tissue that include applying energy (e.g., ultrasound energy) into the tissue to cause altered activity at a synapse between a neuron and a non-neuronal cell.

1 . A neuromodulation system comprising:
 an energy application device configured to apply energy to a region of interest in a liver tissue in a subject; and   a controller comprising a memory, wherein the memory stores instructions that, when executed by the controller, cause the controller to control the energy application device to:
 operate in a targeting mode to acquire image data to identify the region of interest using the image data, the region of interest comprising an axoextracellular synapse comprising a junction of an axon terminal and a non-neuronal cell of the liver; 
 focus the energy on the region of interest; 
 operate in a treatment mode to apply the energy according to a set of modulation parameters to the region of interest to induce neuromodulation; and 
 receive feedback indicative of a circulating glucose concentration relative to a baseline concentration. 
   
     
     
         2 . The system of  claim 1 , wherein the controller is configured to:
 determine that glucose concentration is below a threshold; and   stop application of the energy.   
     
     
         3 . The system of  claim 1 , wherein the controller is configured to:
 determine that glucose concentration is not below a threshold; and   change one or more modulation parameters of the set of modulation parameters.   
     
     
         4 . The system of  claim 3 , wherein the change of the one or more modulation parameters comprises a stepwise increase in pulse repetition frequency. 
     
     
         5 . The system of  claim 1 , wherein the controller is configured to:
 determine that glucose concentration is not below a threshold; and   change a focus of the energy application device.   
     
     
         6 . The system of  claim 1 , wherein the region of interest comprises a porta hepatis. 
     
     
         7 . The system of  claim 1 , wherein the region of interest comprises less than 5% of a total volume of the liver, and wherein the energy application device does not apply energy outside of the region of interest. 
     
     
         8 . The system of  claim 1 , wherein the feedback is from a timepoint at least 10 minutes after application of the energy. 
     
     
         9 . The system of  claim 1 , wherein a peak pressure of the applied energy is 7 MPa or less. 
     
     
         10 . The system of  claim 1 , wherein a peak pressure of the applied energy is between 2-7 MPa. 
     
     
         11 . A method of ultrasound neuromodulation, the method comprising:
 acquiring image data in a subject having a glucose regulation disorder using an ultrasound energy application device;   identifying a region of interest in a liver tissue of the subject using the image data;   operating in a treatment mode to control the ultrasound energy application device to apply ultrasound energy to the region of interest to treat the subject; and   identifying a change in a concentration of glucose in the subject after application of the ultrasound energy relative to a baseline concentration before application of the ultrasound energy.   
     
     
         12 . The method of  claim 11 , wherein the glucose regulation disorder is obesity. 
     
     
         13 . The method of  claim 11 , wherein the glucose regulation disorder is diabetes. 
     
     
         14 . The method of  claim 11 , wherein the region of interest comprises a porta hepatis. 
     
     
         15 . The method of  claim 14 , wherein the region of interest comprises glucose sensing neurons. 
     
     
         16 . A neuromodulation system comprising:
 an energy application device configured to apply energy to a region of interest in a liver tissue in a subject; and   a controller comprising a memory, wherein the memory stores instructions that, when executed by the controller, cause the controller to control the energy application device to:
 operate in a targeting mode to acquire image data to identify the region of interest using the image data, the region of interest comprising an axoextracellular synapse comprising a junction of an axon terminal and a non-neuronal cell of the liver; 
 focus the energy on the region of interest; 
 operate in a treatment mode to apply the energy according to a set of modulation parameters to the region of interest to induce neuromodulation; and 
 receive feedback indicative of a change in a hypothalamus tissue molecule relative to a baseline concentration. 
   
     
     
         17 . The system of  claim 16 , wherein the feedback is based on image data or MRI data. 
     
     
         18 . The system of  claim 16 , wherein the hypothalamus tissue molecule is 1, pAKT 1/2, norepinephrine, epinephrine, and/or NPY. 
     
     
         19 . The system of  claim 16 , wherein the region of interest comprises a porta hepatis. 
     
     
         20 . The system of  claim 16 , wherein the energy application device does not apply the energy directly to the hypothalamus tissue or other brain tissue.