ELECTROPHYSIOLOGICAL SCREENS FOR COGNITIVE MODULATORS

• US 20090312624A1
• Filed: 02/24/2009
• Published: 12/17/2009
• Est. Priority Date: 02/25/2008
• Status: Active Grant

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Berridge, Craig W., Devilbiss, David M.
• Granted Patent: US 8,396,545 B2
• Time in Patent Office: Days
• US Class Current: 600/407
• CPC Class Codes: A61B 5/377 using evoked responses
• CPC Class Codes: A61B 5/383 Somatosensory stimuli, e.g. electric stimulation
• CPC Class Codes: A61B 5/4848 Monitoring or testing the effects of treatment, e.g. of medication

Abstract

Methods, apparatuses, and systems for analysis of electromagnetic activity of prefrontal cortex neurons in subjects are provided. The methods, apparatuses, and systems of the present invention can be used as a means to screen for cognitive modulators. They can be used to predict the effects of compounds such as psychostimulants and other drugs on prefrontal cortex-dependent cognition.

Claims

1. A method of testing a subject to predict an effect of an administered compound on the subject'"'"'s prefrontal cortex-dependent cognition, which comprises:

administering a compound;

subsequently administering a stimulus that evokes an electromagnetic response in the subject'"'"'s prefrontal cortex;

sensing at least one component of the electromagnetic response in the subject'"'"'s prefrontal cortex in response to the administered stimulus both in the presence and in the absence of the compound;

comparing the at least one component of the electromagnetic response evoked by the stimulus in the absence of the administered compound with the at least one component of the electromagnetic response evoked by the stimulus in the presence of the administered compound; and

determining the effect of the administered compound based on the comparison.

2. The method of claim 1 wherein determining the effect of the administered compound comprises correlating the at least one component of the electromagnetic response evoked by the stimulus with the effect of the administered compound on the subject'"'"'s prefrontal cortex-dependent cognition.

3. The method of claim 1 wherein the at least one component of the electromagnetic response is an electrical component.

4. The method of claim 1 wherein the stimulus is selected from the group consisting of electrical, magnetic, photic, auditory, or mechanical stimulation of the subject'"'"'s nervous system.

5. The method of claim 1 wherein the sensing of the at least one component of the electromagnetic response comprises measuring field potentials of the prefrontal cortex.

6. The method of claim 1 wherein the sensing of the at least one component of the electromagnetic response comprises electroencephalography or magnetoencephalography.

7. The method of claim 1 wherein the administering the stimulus comprises an electrical stimulation of the subject'"'"'s hippocampus.

8. The method of claim 1 wherein the administering of the stimulus comprises an electrical stimulation with a current of between about 0.01 mA and about 10.0 mA, a duration of between about 0.01 ms and about 10.0 ms, and a frequency of between about 0.1 Hz and about 10 Hz.

9. The method of claim 1 wherein the administered compound enhances the prefrontal cortex-dependent cognition.

10. The method of claim 1 wherein the administered compound impairs the prefrontal cortex-dependent cognition.

11. The method of claim 1 wherein sensing the at least one component of the electromagnetic response in the subject'"'"'s prefrontal cortex in response to the administered stimulus in the absence of the compound comprises:

administering the stimulus; and

sensing the at least one component of the electromagnetic response, the sensing being performed prior to administering the compound.

12. The method of claim 1 wherein administering the stimulus is performed during sensing the at least one component of the electromagnetic response in order to obtain the at least one component of the electromagnetic response prior to, during, and after administering the stimulus.

13. A method of testing a subject to predict an effect of an administered compound on the subject'"'"'s prefrontal cortex-dependent cognition, which comprises:

administering a compound;

subsequently administering a stimulus that evokes an electromagnetic response in the subject'"'"'s prefrontal cortex;

sensing at least one component of the electromagnetic response in the subject'"'"'s prefrontal cortex both in the presence and in the absence of the compound;

comparing the at least one component of the electromagnetic response evoked by the stimulus in the presence of the administered compound to the at least one component of the electromagnetic response evoked by the stimulus when a known cognition modulator is administered to the subject; and

predicting the effect of the administered compound on the subject'"'"'s prefrontal cortex-dependent cognition based on the comparison.

14. The method of claim 13 wherein the known cognition modulator is methylphenidate.

15. The method of claim 13 wherein the stimulus is selected from the group consisting of electrical, magnetic, photic, auditory, or mechanical stimulation of the subject'"'"'s nervous system.

16. The method of claim 13 wherein the sensing of the at least one component of the electromagnetic response comprises measuring field potentials of the prefrontal cortex.

17. The method of claim 13 wherein the sensing of the at least one component of the electromagnetic response comprises electroencephalography or magnetoencephalography.

18. The method of claim 13 wherein the administering the stimulus comprises an electrical stimulation of the subject'"'"'s hippocampus.

19. The method of claim 13 wherein the administering the stimulus comprises an electrical stimulation with a current of between about 0.01 mA and about 10.0 mA, a duration of between about 0.01 ms and about 10.0 ms, and a frequency of between about 0.1 Hz and about 10 Hz.

20. A system for determining an effect of a compound that modulates prefrontal cortex-dependent cognition, the system comprising:

a recording electrode for detecting at least one component of an electromagnetic response in the prefrontal cortex of a subject;

a stimulation electrode for evoking the at least one component of the electromagnetic response in the subject'"'"'s prefrontal cortex;

a recording module for receiving and recording the at least one component of the electromagnetic response from the recording electrode in the subject'"'"'s prefrontal cortex in response to an administered stimulus from the stimulation electrode both in the presence and in the absence of the compound; and

an analytical module for analyzing the recorded component of the electromagnetic response in the subject'"'"'s prefrontal cortex in response to the administered stimulus both in the presence and in the absence of the compound in order to determine an effect of the administered compound.

21. The system of claim 20 wherein the detection of the at least one component of the electromagnetic response comprises measuring field potentials of the prefrontal cortex.

22. The system of claim 20 wherein the detection of the at least one component of the electromagnetic response comprises electroencephalography or magnetoencephalography.

23. The system of claim 20 wherein the stimulation electrode electrically stimulates the subject'"'"'s hippocampus.

24. The system of claim 20 wherein the stimulation electrode is used for stimulation with a current of between about 0.01 mA and about 10.0 mA, a duration of between about 0.01 ms and about 10.0 ms, and a frequency of between about 0.1 Hz and about 10 Hz.

25. The system of claim 20 wherein the administered compound enhances the prefrontal cortex-dependent cognition.

26. The system of claim 20 wherein the administered compound impairs the prefrontal cortex-dependent cognition.