Methods of neuromodulation using infraslow stimulation

Abstract

Methods are provided to treat a neurological disorder in a patient by adjusting connectivity between network nodes in a brain of patient using electrical stimulation. Electrical stimulation including a carrier wave component is employed to adjust connectivity using infraslow frequencies of less than 1 Hz.

What is claimed is: 
     
         1 . A method to deliver nested stimulation to nerve tissue of interest, the method comprising:
 setting first parameters that define a carrier waveform, wherein the carrier waveform exhibits a waveform frequency of less than 1 Hz;   setting second parameters that define a high frequency waveform, wherein at least one of the carrier waveform and high frequency waveform are defined to correspond to physiologic neural oscillations associated with the nerve tissue of interest;   operating a pulse generator to generate a nested stimulation waveform that combines the carrier waveform and high frequency waveform, the nested stimulation waveform having a plurality of pulse bursts; and   delivering the nested stimulation waveform through one or more electrodes to the nerve tissue of interest.   
     
     
         2 . The method of  claim 1 , wherein the nerve tissue of interest includes brain tissue of interest, and wherein the high frequency waveform corresponding to high-frequency physiologic neural oscillations associated with brain tissue of interest, and herein the pulse bursts including pulses having a frequency corresponding to the high frequency neural oscillations. 
     
     
         3 . The method of  claim 1 , wherein the carrier waveform exhibits an frequency of 0.01 Hz. 
     
     
         4 . The method of  claim 3 , wherein the pulse bursts are separated from one another with a burst to burst period that corresponds to a frequency of the low-frequency neural oscillations. 
     
     
         5 . The method of  claim 1 , wherein the first and second parameters define at least one of an amplitude, burst to burst frequency, pulse frequency, pulse width, burst length and burst period for the plurality of pulse bursts. 
     
     
         6 . The method of  claim 1 , further comprising combining the carrier and high-frequency waveforms utilizing one of the following types of cross frequency coupling: power to power; phase to power; phase to phase; phase to frequency; power to frequency and frequency to frequency. 
     
     
         7 . The method of  claim 1 , wherein the carrier and high-frequency waveforms are combined through phase to power cross frequency coupling, in which the phase of the carrier waveform modulates the power of the high-frequency waveform. 
     
     
         8 . The method of  claim 1 , wherein the first parameters are set to define the carrier waveform to correspond to the theta wave frequency band, while the second parameters are set to define the high-frequency waveform to correspond to the gamma wave frequency band, the method further comprising managing the nested stimulation waveform modulating the neural oscillations in the gamma wave frequency band in connection with at least one of sensory, motor, and cognitive events. 
     
     
         9 . The method of  claim 1 , wherein the nerve tissue of interest includes brain tissue of interest, and further comprising managing the nested stimulation waveform in connection with an event of interest through cross frequency coupling between theta and gamma waves associated with brain tissue of interest. 
     
     
         10 . The method of  claim 1 , wherein the nerve tissue of interest includes brain tissue of interest, and wherein the brain tissue of interest comprises distributed neural modules located in separate regions of the brain, the method further comprising managing the nested stimulation waveform in connection with cross frequency coupling between neural oscillations associated with the distributed neural modules that exhibit long-distance communication over neural oscillations within at least one of delta, theta and alpha wave frequency bands 
     
     
         11 . A method of treating a neurological disorder in a patient, comprising:
 identifying a neural network in the brain of the patient related to the neurological disorder;   identifying at least two separate target sites in the neural network for stimulation, wherein the at least two separate target sites include a hub site within the neural network;   providing one or more stimulation leads with electrodes positioned relative to the at least two separate target sites;   providing electrical stimulation to the at least two separate target sites to adjust functional connectivity between the at least two separate target sites to treat the neurological disorder, wherein the electrical stimulation exhibits a carrier wave frequency of less than 1 Hz.   
     
     
         12 . The method of  claim 11  wherein the providing electrical stimulation comprises: repeatedly providing respective electrical pulses to the at least two separate target sites in a synchronized manner to strengthen functional connectivity between the at least two separate target sites. 
     
     
         13 . The method of  claim 11  wherein the providing electrical stimulation comprises: providing electrical stimulation to the at least two separate target sites in a pseudo-random manner to weaken functional connectivity between the at least two separate target sites. 
     
     
         14 . The method of  claim 11 , wherein the electrical stimulation exhibits a carrier wave frequency of 0.01 Hz.