Adaptive electric field modulation of neural systems

Abstract

The present invention relates to devices and methods of modifying the neuronal activity of a neural system comprising neurons, comprising, one or more of the following steps, measuring the neuronal activity of a neural system; and applying an oriented electric field to said neural system effective to modify the neuronal activity of the neural system, wherein the magnitude and polarity of said applied electric field is changed in response to the measured neuronal activity. The present invention also relates to devices and methods for treating brain disorders, such as epilepsy and Parkinson's disease, comprising, one or more of the following steps, applying a sub-threshold and oriented electric field in situ to the brain of a patient having such a disorder in an amount effective to reduce the abnormal activity of the brain, wherein the electric field is applied through field electrodes in contact with the brain. The present invention also relates to methods and devices for restoring or repairing a brain function, such as sensation (e.g., taste, or smell), somatic activity, auditory activity, visual activity, or motor activity. It can also be used for testing drugs, pharmacological agents, and other modulators of neuronal function.

1 . A method of modifying the neuronal activity of a neural system comprising neurons, comprising: 
 a) measuring the neuronal activity of a neural system;    b) applying an oriented electric field to said neural system effective to modify the neuronal activity of the neural system, wherein the magnitude and polarity of said applied electric field is changed in response to the measured neuronal activity.    
     
     
         2 . A method of  claim 1 , wherein the applied electric field is sub-threshold.  
     
     
         3 . A method of  claim 1 , wherein the measuring is performed simultaneously with the applying an oriented electric field.  
     
     
         4 . A method of  claim 1 , wherein the applied field is proportional to the neuronal activity.  
     
     
         5 . A method of  claim 1 , wherein the applied field is proportional to the difference between the root-mean-square of the measured activity and a predetermined threshold activity value in a predetermined frequency band.  
     
     
         6 . A method of  claim 1 , wherein the applied electric field is under full-wave control.  
     
     
         7 . A method of  claim 1 , wherein the applied electric field is half-wave rectified.  
     
     
         8 . A method of  claim 1 , further comprising, representing the measured electric activity as the root-mean-square within a frequency band of 100-500 Hz, averaged over a time y.  
     
     
         9 . A method of  claim 1 , wherein the electric field is produced using two field electrodes positioned external to the neurons in the neural system.  
     
     
         10 . A method of  claim 1 , wherein the electric field is oriented parallel to the somatic-dendritic axis of the neurons in the neural system.  
     
     
         11 . A method of  claim 1 , wherein the oriented electric field is applied adaptively in response to changes in measured neuronal activity of the neural system.  
     
     
         12 . A method of  claim 11 , wherein the neuronal activity is electrical activity.  
     
     
         13 . A method of  claim 1 , wherein the measuring electrodes are positioned on an isopotential to the applied electric field.  
     
     
         14 . A method of  claim 1 , wherein the neuronal activity is spontaneous epileptiform electrical activity and the applied electric field suppresses it.  
     
     
         15 . A method of  claim 1 , wherein the neuronal activity is spontaneous epileptiform electrical activity and the applied electric field induces or augments it.  
     
     
         16 . A method of  claim 1 , wherein the applied electric field modifies the firing rate of neurons in the neural system.  
     
     
         17 . A method of  claim 1 , wherein the applied electric field is created by injecting current into the system.  
     
     
         18 . A method of  claim 17 , wherein the current is injected until a predetermined field potential is reached.  
     
     
         19 . A method of  claim 1 , with the proviso that the applied electric field is not a continuous stationary field.  
     
     
         20 . A method of  claim 1 , wherein the neuronal activity is modified to restore sensation, somatic activity, auditory activity, visual activity, or motor activity.  
     
     
         21 . A method of treating epilepsy in a patient in need thereof, comprising: 
 applying a sub-threshold and oriented electric field in situ to the brain of a patient having epilepsy in an amount effective to reduce epileptiform activity of the brain, wherein the electric field is applied through field electrodes located in a position effective to produce a field in said brain.    
     
     
         22 . A method of  claim 21 , wherein the electric field is applied to the brain when epileptiform activity is detected through measuring electrodes.  
     
     
         23 . A method of  claim 21 , wherein the applied electric field is under full-wave control.  
     
     
         24 . A method of  claim 21 , wherein the applied electric is half-wave rectified.  
     
     
         25 . A method of treating Parkinson's disease in a patient in need thereof, comprising: 
 applying a sub-threshold and oriented electric field in situ to the brain of a patient having Parkinson's disease in an amount effective to reduce tremors, rigidity, or difficulty in initiating movement, wherein the electric field is applied through field electrodes in contact with the brain.    
     
     
         26 . A method of  claim 25 , wherein the electric field is applied to the brain adaptively.  
     
     
         27 . A method of identifying agents which modulate the neuronal activity of a neural system comprising neurons, comprising: 
 a) measuring the neuronal activity of a neural system;    b) applying an oriented electric field to said neural system effective to modify the neuronal activity of the neural system, wherein the magnitude and polarity of said applied electric field is changed in response to the measured neuronal activity; and    c) administering an agent in an effective amount which modulates the neuronal activity of the neural system.    
     
     
         28 . A field-producing device for modifying the neuronal activity of a neural system comprising neurons, comprising: 
 (a) field electrode means for applying an external electric field to a neural system;    (b) field application electronic means for generating an external field to a neural system, which is operably connected to (a) field electrode means;    (c) measuring means for monitoring the neural activity of the neural system;    (d) measurement electronics means for recording neural activity, which is operably connected to (d) measuring electronic means;    (e) feedback controller means for determining the amount of external field to apply to the neural system, which is operably connected to (b) field application means and (c) measuring means.    
     
     
         29 . A field-producing device of  claim 28 , further comprising: 
 (f) sensing means for detecting the external field produced by the field electrode means;    (g) sensing electronic means for recording the field produced by the field electrode means, which is operably connected to (f) sensing electrode means and (b) field application means.