Spatial evolution of neural activity

Abstract

A method for identifying a candidate drug includes administering a test compound to test subjects and having the test subjects perform a sustained task. A first evolution of neural activity in the test subjects is then determined and compared with a second evolution of neural activity. This second evolution of neural activity is obtained from control subjects performing the sustained task in the absence of the test compound. The test compound is then designated to be a candidate drug when a difference between the first and second evolutions of neural activity is above a difference threshold.

1 . A method for identifying a candidate drug, the method comprising:
 administering a test compound to test subjects;   having the test subjects perform a sustained task;   determining a first evolution of neural activity in the test subjects;   comparing the first evolution of neural activity with a second evolution of neural activity, wherein the second evolution of neural activity is obtained from control subjects performing the sustained task in the absence of the test compound; and   designating the test compound to be a candidate drug when a difference between the first and second evolutions of neural activity is above a difference threshold.   
   
   
       2 . The method of  claim 1 , wherein the test subjects are selected from a population afflicted with a neurological disorder for which the candidate drug is intended to have therapeutic value, and the control subjects are free of the disorder. 
   
   
       3 . The method of  claim 2 , wherein the neurological disorder is Alzheimer's disease. 
   
   
       4 . The method of  claim 2 , wherein the neurological disorder is Parkinson's disease. 
   
   
       5 . The method of  claim 2 , wherein the neurological disorder is schizophrenia. 
   
   
       6 . The method of  claim 1 , wherein the sustained task comprises a motor task. 
   
   
       7 . The method of  claim 1 , wherein the sustained task comprises a cognitive task. 
   
   
       8 . The method of  claim 1 , wherein the sustained task comprises an N-back task. 
   
   
       9 . The method of  claim 1 , wherein the sustained task comprises a semantic reasoning task. 
   
   
       10 . The method of  claim 1 , wherein the sustained task comprises a visuospatial recognition task. 
   
   
       11 . The method of  claim 1 , wherein determining a first evolution of neural activity comprises obtaining a sequence of magnetic resonance images of each of the test subjects during performance of the sustained task. 
   
   
       12 . The method of  claim 1 , wherein determining a first evolution of neural activity comprises:
 collecting task data indicative of evolution of neural activity during performance of the sustained task; and   filtering, from the task data, a contribution to the task data arising from background neural activity.   
   
   
       13 . The method of  claim 12 , wherein the background neural activity comprises neural activity associated with performance of a reference task. 
   
   
       14 . The method of  claim 12 , wherein the background neural activity comprises neural activity associated with a selected portion of the test subject. 
   
   
       15 . The method of  claim 14 , wherein the background neural activity comprises neural activity associated with the selected portion during performance of the sustained task. 
   
   
       16 . The method of  claim 1 , wherein determining a first evolution of neural activity comprises:
 having the subjects perform the sustained task during a first plurality of task intervals, each having at least a first time segment and a second time segment;   collecting data from each of the first time segments into a first data set;   collecting data from each of the second time segments into a second data set; and   filtering, from the first and second data sets, a contribution to the first and second data sets arising from background neural activity.   
   
   
       17 . The method of  claim 16 , wherein filtering comprises performing a correlation between data representative of the background neural activity and the first and second data sets. 
   
   
       18 . The method of  claim 16 , wherein filtering comprises performing a t-test between data representative of the background neural activity and the first and second data sets. 
   
   
       19 . A drug screening system comprising:
 an imaging system, and   a data-processing system connected to the imaging system, the processor being configured to carry out the drug screening method recited in  claim 1 .   
   
   
       20 . A method for evaluating an effect of a physiologic stimulus on treatment of a neurological disorder, the method comprising:
 comparing evolution of neural activity between first and second groups, the subjects in the first group having been administered the stimulus and the subjects in the second group not having been administered the stimulus;   on the basis of a difference between the evolution of neural activity, determining an efficacy of the stimulus.   
   
   
       21 . The method of  claim 20 , further comprising selecting the stimulus to be a pharmacological agent. 
   
   
       22 . The method of  claim 20 , wherein comparing evolution of neural activity comprises obtaining functional MRI data for subjects in the first and second groups. 
   
   
       23 . The method of  claim 20 , wherein comparing evolution comprises having subjects from the first and second groups perform a sustained task. 
   
   
       24 . The method of  claim 20 , wherein comparing evolution comprises having subjects from the first and second groups alternate between performing a sustained task and not performing the sustained task. 
   
   
       25 . A system for evaluating an effect of a physiologic stimulus on treatment of a neurological disorder, the system comprising:
 an imaging system, and   a data-processing system connected to the imaging system, the processor being configured to carry out the drug screening method recited in  claim 20 .