Closed-loop vagus nerve stimulation

1. A method of closed-loop modulation of an inflammatory reflex, the method comprising:

sensing electrical activity on a vagus nerve of a patient during a baseline period from a microstimulator implanted around a cervical portion of the vagus nerve;

sensing electrical activity on the vagus nerve during a course of treatment at various levels of inflammation, including when accommodation is suspected of reducing an efficacy of the treatment;

determining a neural signature for each of a plurality of inflammatory states based on the sensed electrical activity from the baseline period and the sensed electrical activity at the various levels of inflammation to determine a sensed electrical activity relationship to a state of accommodation, wherein determining the neural signature for each of the plurality of inflammatory states includes characterizing a neural recording of the vagus nerve;

storing the neural signature for each of the plurality of inflammatory states;

determining an inflammatory state of the patient based on a comparison of a particular sensed electrical activity to at least one of the stored neural signatures; and

delivering a therapeutic dose to the patient by stimulating the vagus nerve while controlling one or more characteristic of stimulation of the microstimulator based on the determined inflammatory state, including the state of accommodation, wherein the one or more characteristic of stimulation is selected from the group consisting of: duration, intensity, frequency, on-time and off-time.

2. The method of claim 1 , wherein determining the neural signature for each of the plurality of inflammatory states includes:

performing a spectral analysis of the sensed electrical activity; and

identifying changes in power of the sensed electrical activity at one or more frequencies.

3. The method of claim 2 , wherein the one or more frequencies are between 0 and 100 Hz.

4. The method of claim 1 , wherein determining the neural signature for each of a plurality of inflammatory states includes counting electrical spikes.

5. The method of claim 1 , wherein determining the neural signature for each of a plurality of inflammatory states includes sensing the electrical activity before and after applying stimulation to the vagus nerve.

6. The method of claim 1 , wherein sensing electrical activity at various levels of inflammation includes measuring vagus nerve activity during periods when the microstimulator is not stimulating the vagus nerve.

7. The method of claim 1 , wherein determining the inflammatory state comprises analyzing compound action potentials (CAPs) in the neural recording.

8. The method of claim 7 , wherein controlling one or more characteristic of stimulation comprises modifying a treatment dosage based on the CAPs.

9. The method of claim 1 , wherein determining the neural signature for each of a plurality of inflammatory states further includes comparing the sensed electrical activity to one or more model neural signatures.

10. The method of claim 1 , wherein determining the inflammatory state includes receiving reported periods of pain from the patient.

11. The method of claim 1 , wherein sensing the electrical activity includes recording the electrical activity a predetermined time after application each of a plurality of stimulations.

12. An implantable microstimulator device for treating chronic inflammation, the device comprising:

a hermetically sealed capsule body;

at least two electrically conductive capsule regions, wherein each region electrically connects to an electrode, wherein the electrodes are configured for applying stimulation to a vagus nerve to modulate an inflammatory reflex and for sensing electrical activity from the vagus nerve;

a power source within the sealed capsule body; and

a controller within the sealed capsule body configured to:

sense electrical activity on the vagus nerve a patient during a baseline period from the microstimulator device implanted around the cervical portion of the vagus nerve;

sense electrical activity on the vagus nerve during a course of treatment at various levels of inflammation, including when accommodation is suspected of reducing an efficacy of the treatment;

determine a neural signature for each of a plurality of inflammatory states based on the sensed electrical activity from the baseline period and the sensed electrical activity at the various levels of inflammation to determine a sensed electrical activity relationship to a state of accommodation, wherein determining the neural signature for each of the plurality of inflammatory states includes characterizing a neural recording of the vagus nerve;

store the neural signature for each of the plurality of inflammatory states;

sense electrical activity on the vagus nerve at a first time period;

determine an inflammatory state of the patient based on a comparison of a particular sensed electrical activity to at least one of the stored neural signatures; and

deliver a therapeutic dose to the patient by stimulating the vagus nerve while controlling one or more characteristic of stimulation of the microstimulator device based on the determined inflammatory state, including the state of accommodation, wherein the one or more characteristic of stimulation is selected from the group consisting of: duration, intensity, frequency, on-time and off-time.

13. The implantable microstimulator device of claim 12 , further comprising an ASIC within the capsule body having a spike counter for counting electrical spikes of the sensed electrical activity from the vagus nerve.

14. The implantable microstimulator device of claim 13 , further comprising a memory in communication with the spike counter for storing the counts of the spike counter.

15. The implantable microstimulator device of claim 12 , wherein the electrode is a tri-polar, or a pseudotripolar, or a tetrode electrode.

16. The implantable microstimulator device of claim 12 , further comprising an ASIC within the sealed capsule body having a variable amplifier.

17. The implantable microstimulator device of claim 12 , wherein the controller is configured to cause the electrodes to apply a treatment dosage based on minimizing deviation of a respiratory signal.

18. The implantable microstimulator device of claim 12 , wherein a treatment dosage is determined based on patient specific neural signatures at various levels of inflammation before and after treatment.

19. A system for closed-loop modulation of an inflammatory reflex, the system comprising:

an implantable microstimulator adapted to be applied around a cervical portion of a vagus nerve to stimulate the vagus nerve and modulate the inflammatory reflex;

at least one sensing electrode on the implantable microstimulator configured to detect bioelectric activity on the vagus nerve; and

a controller configured to:

sense electrical activity on the vagus nerve a patient during a baseline period from the microstimulator implanted around the cervical portion of the vagus nerve;

sense electrical activity on the vagus nerve during a course of treatment at various levels of inflammation, including when accommodation is suspected of reducing an efficacy of the treatment;

determine a neural signature for each of a plurality of inflammatory states based on the sensed electrical activity from the baseline period and the sensed electrical activity at the various levels of inflammation to determine a sensed electrical activity relationship to a state of accommodation, wherein determining the neural signature for each of the plurality of inflammatory states includes characterizing a neural recording of the vagus nerve;

store the neural signature for each of the plurality of inflammatory states;

sense electrical activity on the vagus nerve at a first time period;

determine an inflammatory state of the patient based on a comparison of a particular sensed electrical activity to at least one of the stored neural signatures; and

deliver a therapeutic dose to the patient by stimulating the vagus nerve while controlling one or more characteristic of stimulation of the microstimulator based on the determined inflammatory state, including the state of accommodation, wherein the one or more characteristic of stimulation is selected from the group consisting of: duration, intensity, frequency, on-time and off-time.