Systems and methods of precision functional mapping-guided personalized neuromodulation

Abstract

A method of performing personalized neuromodulation on a subject is provided. The method includes acquiring functional magnetic resonance imaging (fMRI) data of a brain of the subject. The method also includes calculating functional connectivity of the brain between a voxel in a subcortical region of the brain and a voxel in a cortical region of the brain, based on the fMRI data. The method also includes identifying a target location in the brain to be targeted by neuromodulation based on the calculated functional connectivity.

What is claimed is: 
     
         1 . A method of performing personalized neuromodulation on a subject, comprising:
 acquiring functional magnetic resonance imaging (fMRI) data of a brain of the subject;   calculating functional connectivity of the brain between a voxel in a subcortical region of the brain and a voxel in a cortical region of the brain, based on the fMRI data; and   identifying a target location in the brain to be targeted by neuromodulation based on the calculated functional connectivity.   
     
     
         2 . The method of  claim 1 , further comprising performing neuromodulation on the subject directed at the identified target location. 
     
     
         3 . The method of  claim 2 , wherein performing neuromodulation comprises implanting a neurostimulator for deep brain stimulation at the target location in the brain. 
     
     
         4 . The method  claim 1 , wherein calculating functional connectivity further comprises:
 calculating functional connectivity of the brain between the voxel in the subcortical region of the brain and a vertex in a cortical functional network.   
     
     
         5 . The method of  claim 4 , wherein calculating functional connectivity further comprises:
 extracting blood oxygenation level dependent (BOLD) activity timecourses from each vertex in the cortical functional network based on the fMRI data;   averaging the BOLD activity timecourses of the cortical functional network across all vertices in the cortical functional network;   extracting BOLD activity timecourses from the voxel in the subcortical region; and   calculating functional connectivity as a correlation between the BOLD activity timecourses of the voxel and the BOLD activity timecourses of the cortical functional network.   
     
     
         6 . The method of  claim 4 , wherein the identified target location is in an integrative zone, wherein calculating functional connectivity comprises calculating functional connectivity of the brain between the voxel in the subcortical region and each cortical functional network in a plurality of cortical functional networks; and
 identifying a target location further comprises:
 identifying a winning functional network among the plurality of cortical functional networks as a functional network having the highest functional connectivity with the voxel; 
 including the voxel in the integrative zone if functional connectivity between the voxel and one or more functional networks is above a threshold, wherein the one or more functional networks are among the remaining of the plurality of cortical functional networks minus the winning functional network; and 
 identifying a target location further comprising identifying the target location to include the integrative zone. 
   
     
     
         7 . The method of  claim 6 , further comprising performing neuromodulation directed at the integrative zone. 
     
     
         8 . The method of  claim 1 , wherein the subcortical region includes basal ganglia and thalamus. 
     
     
         9 . The method of  claim 1 , wherein acquiring fMRI data of the subject comprises acquiring resting state fMRI data of the subject. 
     
     
         10 . The method of  claim 9 , wherein:
 acquiring fMRI data further comprises acquiring task fMRI data of the subject,   calculating functional connectivity further comprises calculating functional connectivity based on the resting state fMRI data; and   the method further comprises:
 identifying at least one of an activation region and a deactivation region based on the acquired task fMRI data to derive a task fMRI map; and 
 validating the identified target location using the derived task fMRI map. 
   
     
     
         11 . The method of  claim 1 , wherein acquiring fMRI data of the subject comprises acquiring more than one hundred minutes of resting state fMRI data of the subject. 
     
     
         12 . The method of  claim 1 , wherein the subcortical region includes amygdala. 
     
     
         13 . The method of  claim 12 , wherein calculating functional connectivity comprising:
 calculating functional connectivity between the voxel in the subcortical region and a region of interest (ROI) in the cortical region.   
     
     
         14 . The method of  claim 13 , wherein calculating functional connectivity further comprises defining the ROI in a medial prefrontal cortex. 
     
     
         15 . The method of  claim 12 , wherein identifying a target location further includes including a region in a medial prefrontal cortex, the method further comprising performing neuromodulation directed at the identified target location. 
     
     
         16 . The method of  claim 1 , wherein calculating functional connectivity further comprises calculating timing of the functional connectivity between the voxel in a subcortical region and the voxel in the cortical region based on the fMRI data. 
     
     
         17 . The method of  claim 16 , wherein identifying a target location further comprises identifying a voxel having an abnormal timing compared to a healthy individual as the target location. 
     
     
         18 . A system for personalize neuromodulation on a subject, comprising:
 a computing device including a processor electrically coupled to a memory, the processor programmed to:
 acquire functional magnetic resonance imaging (fMRI) data of a brain of the subject; 
 calculate functional connectivity of the brain between a voxel in a subcortical region of the brain and a voxel in a cortical region of the brain, based on the fMRI data; and 
 identify a target location in the brain to be targeted by neuromodulation based on the calculated functional connectivity. 
   
     
     
         19 . The system of  claim 18 , wherein the processor is further programmed to perform neuromodulation on the subject directed at the identified target location. 
     
     
         20 . The system of  claim 18 , wherein the subcortical region includes at least one of basal ganglia, thalamus, and amygdala.