Method and apparatus for objectively measuring pain, pain treatment and other related techniques

• US 20020042563A1
• Filed: 03/30/2001
• Published: 04/11/2002
• Est. Priority Date: 12/02/1999
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Borsook, David, Breiter, Hans C., Becerra, Lino R.
• Granted Patent: US 6,907,280 B2
• Time in Patent Office: Days
• US Class Current: 600/407
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/16 Devices for psychotechnics using teaching or educational appliances G09B1/00 - G09B7/00; Testing reaction times ; Devices for evaluating the psychological state
• CPC Class Codes: A61B 5/168 Evaluating attention deficit, hyperactivity
• CPC Class Codes: A61B 5/4064 Evaluating the brain A61B5/031, A61B5/369, A61B5/14553 take precedence
• CPC Class Codes: A61B 5/4824 Touch or pain perception evaluation A61B5/4821 takes precedence
• CPC Class Codes: A61B 5/7239 using differentiation including higher order derivatives

Abstract

A method and apparatus for measuring indices of brain activity includes non-invasively obtaining signals of central nervous system (CNS) activity, localizing signals to specific anatomical and functional CNS regions, correlating the signals from pain and reward brain regions, and interpreting the correlation results. The results of interpreting the correlation results can be used for objectively measuring, in individual humans or animals, their responses to motivationally salient stimuli including but not limited to stimuli which are internal or external, conscious or non-conscious, pharmacological or non-pharmacological therapies, and diseased based processes. This method for measuring brain activity in reward/aversive central nervous system regions, can further be used to determine the efficacy of compounds.

Claims

1. A method of for measuring brain activity comprising:

nonivasively obtaining signals of central nervous system (CNS) activity;

localizing signals to specific anatomical and functional CNS regions which participate in reward/aversion functions;

correlating the signals in a reward/aversion brain region; and

interpreting the correlation results.

2. The method of claim 1, wherein the reward/aversion regions are subcortical gray, brainstem, cerebellum and frontal brain regions.

3. The method of claim 2 wherein the brainstem region includes the spinal cord.

4. The method of claim 3 wherein the spinal cord includes the trigeminal nucleus and the method further includes the step of non-invasively obtaining signals from the trigeminal nucleus.

5. The method of claim 3, wherein the reward/aversion regions include at least one of the GOb, VT/PAG, NAc, SLEA, cingulate gyrus, S1, S2, thalamus, insula, cerebellum, prefrontal cortex, amygdala, hypothalamus, parahippocampal gyrus, hippocampus, entorrhinal cortex, ventral pallidum, dorsal striatum, M1, M2, SMA, FEF, RVM, and brainstem subnuclei.

6. The method of claim 1, wherein obtaining signals of CNS activity includes using a neuroimaging device wherein the signals reflect at least one of functional activation, chemical signatures, brain structure, neurotransmission, electromagnetic activity, perfusion effects and cell metabolism.

7. The method of claim 6, wherein the neuroimaging device corresponds to one or more of a PET device, an fMRI device, an MEG device, an EEG device, a SPECT device, an IR device, a MRS device, and a functional CT device.

8. The method of claim 4, further comprising:

aligning an imaging axis of an imaging device with the spinal cord of a subject such that the imaging axis is aligned in a plane parallel to a spinal cord axis and perpendicular to a cerebral mid-plane; and

obtaining images of CNS regions in the spine.

9. The method of claim 1, wherein non-invasively obtaining signals of central nervous system obtained non-invasively further comprises:

correcting the signals to reduce the effects of head motion;

transforming the signals into a uniform atomic space;

normalizing the transformed signals;

statistically mapping the normalized signal; and

locating the statistical maps over images reflecting at least one of;

a uniform atomic space, an average anatomic space, and an individual atomic space.

10. The method of claim 1, wherein non-invasively obtaining signals of central nervous system obtained non-invasively further comprises:

correcting the signals to reduce the effects of head motion;

aligning the signals with individual brain anatomy;

normalizing the transformed signals;

statistically mapping the normalized signal; and

locating the statistical maps over images reflecting at least one of;

a uniform atomic space, an average anatomic space, and an individual atomic space.

11. The method of claim 1, wherein correlating the signals from reward/aversive brain regions comprises evaluating the temporal nature of a neuroimaging signal using waveform based correlation analysis (WCA).

12. The method of claim 11, wherein data obtained from central nervous system activity is segregated temporally.

13. The method of claim 12 wherein data obtained from central nervous system activity is segregated temporally into a plurality of phases.

14. The method of claim 12, wherein the step of temporally segregating include the step of segregating into an early phase waveform and a late phase waveform.

15. The method of claim 13, wherein interpreting the results of the correlating procedure further comprises correlating a plurality of pixels from regions in the CNS to distinct waveforms.

16. The method of claim 15, wherein the distinct waveforms correspond to at least one of an early phase waveform and a late phase waveform.

17. The method of claim 15, wherein interpreting the results of the correlating procedure further comprises producing indices by quantifying the signals using at least one of:

a spatial analysis;

a temporal analysis;

a comparison of slope analysis;

moment analysis;

laterality analysis;

synchrony analysis;

volume analysis;

power function used to generate indices;

power spectrum analysis used to generate indices;

integral analysis; and

derivative analysis.

18. The method of claim 17, wherein interpreting the results of the correlating procedure further comprises using one or more quantitative indices wherein at least one of the one or more quantitative indices corresponds to one of:

a coordinate index from a uniform anatomic space;

a subregion index;

a subnuclear index;

a first time index T_p corresponding to a first moment of a signal response;

a second time index Δ

corresponding to a second moment of a signal response;

a rate of signal change index;

an average time of response index;

a width of response index;

a tail index corresponding to a third moment of a signal response;

an R index;

an, L index;

a fractional laterally index

a correlation factor (r) index;

a volume index;

an exponent index;

an power spectrum index representing amplitudes of signal response harmonics and subharmonics computed using a power spectrum analysis;

an index corresponding to one or more amplitudes changes computed using an integral analysis of a signal response;

an index corresponding to a maximum rate of change of a signal response computed using a derivative analysis of a signal response; and

an index corresponding to a time to achieve a maximum rate of change of a signal response computed using a derivative analysis of the signal response.

19. The method of claim 1, further comprising:

providing a known first set of indices;

measuring one or more signal responses in a subject;

generating a second set of indices by computing one or more index for each of the one or more signal responses; and

comparing the second set of indices to the first set of indices.

20. The method of claim 19 wherein:

the step of providing the known first set of indices, includes the step of providing the known first set of indices to a processor; and

the step of comparing the second set of indices to the first set of indices includes the steps of;

providing the second set of indices to the processor; and

comparing the second set of indices to the first set of indices using the processor.

21. The method of claim 20 wherein the processor corresponds to a neural network processor.

22. The method of claim 1, further comprising:

selecting an experimental process which elicits a response in one or more reward/aversion regions of a subject;

applying a reward/aversive stimulus to the subject to illicit the response; and

correlating the experimental process to brain activity.

23. The method of claim 22, wherein the experimental process further comprises:

(a) administering to the subject at least one of;

a drug, a gene product, a biopharmaceutical, a virus, a gene, one or more receptors, and a neurochemical;

(b) applying a stimulus to the subject; and

(c) measuring a brain response of the subject.

24. The method of claim 23 further comprising measuring the response of the same subject over time.

25. The method of claim 24 wherein measuring the response of the same subject over time comprises the steps of waiting a period of time and repeating steps (a)-(c).

26. The method of claim 24 wherein measuring the response of the same subject over time comprises the steps of waiting a period of time and performing the steps of:

(a) administering a placebo to the subject;

(b) applying a stimulus to the subject;

(c) measuring an analgesic response of the subject.

27. The method of claim 22, wherein the experimental process comprises:

exposing a subject to at least one of a thermal, mechanical or chemical stimulus; and

measuring the response of the subject to the stimulus.

28. The method of claim 1, further comprising:

administering a treatment to the subject; and

correlating the treatment to brain activity.

29. The method of claim 26, wherein the treatment corresponds to at least one of a drug/gene product, a surgical treatment, a radiation treatment, a behavioral treatment, and an acupuncture treatment.

30. The method of claim 1 wherein the step of interpreting the correlation result comprises:

correlating the signals from pain and reward brain regions; and

comparing results of the correlation to a predetermined index.

31. A method for determining the efficacy of a treatment corresponding to one of a compound, a drug, a gene product, a virus, a gene, a receptor, a neurochemical, a biopharmaceutical, the method comprising:

non-invasively obtaining base line signals of central nervous system (CNS) activity;

administering a dose of the treatment;

localizing signals to specific anatomical and functional CNS regions corresponding to a reward/aversion region; and

correlating the signals in the reward/aversion brain region; and

interpreting the results of the correlation.

32. The method of claim 31, wherein the dose is a therapeutic dose.

33. The method of claim 31, wherein the dose is a sub-therapeutic dose.

34. The method of claim 31, further comprising producing an objective determination that the administered treatment alters the experience of pain in response to aversive stimuli or non-aversive stimuli.

36. The method of claim 35 wherein the step of measuring a response includes the step of administering a mechanical, thermal or chemical stimulus to the subject.

37. The method of claim 36 wherein the stimulus corresponds to one of a drug and a treatment.

35. A method of evaluating a stimulus comprising:

(a) measuring a plurality of indices;

(b) forming a matrix pattern with the indices;

(c) measuring a subject response to a stimulus;

(d) using the subject response to compute indices for the subject; and

(e) comparing the subject indices to the matrix patter indices to objectively determine the condition of the subject.

38. A system for measuring indices of brain activity comprising:

a central nervous system (CNS) imaging device;

a localization processor to map signals to specific anatomical and functional brain regions;

a correlation processor to correlate the signals from pain and reward brain regions;

a neural network processor.