Nerve stimulation system

Abstract

To provide a system for electrically stimulating nerves.SOLUTION: A system 1 for electrically stimulating a nerve 3 comprises: a first stimulator 5 and a second stimulator 7 for electrically stimulating the nerve, the first stimulator and the second stimulator spaced apart from one another by a first distance; and a controller 9 arranged to: a) set a time interval as a function of the first distance and the speed of propagation of an action potential in the nerve; b) activate the first stimulator for a first stimulation period, thus inducing electrical activity in the nerve; and c) activate the second stimulator for a second stimulation period after the time interval has elapsed after the end of the first time period. Preferably, the time interval is a sum of the first time period and a buffer time period for allowing the nerve to recover from stimulation.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present disclosure relates to systems and methods for electrically stimulating nerves. [Background technology]

[0002] It is desirable to electrically stimulate a patient's nerves at a certain frequency in the treatment of disease. However, nerves are prone to fatigue when stimulated at frequencies above a certain level (also known as action potential conduction delay (APCS)). For example, C-fibers, unmyelinated fibers that make up the nerves in the splenic neurovascular bundle, are subject to fatigue, APCS, and become less responsive over time when stimulated at a certain frequency. The reduced responsiveness may be due to a prolongation of the action potential profile of polarization and repolarization across the membrane (Ringkamp et al. 2010 PLoS ONE 5(2): e9076 doi:1371 / journal.pone.0009076).

[0003] C-fibers, unmyelinated fibers, require much higher levels of electrical stimulation to activate than the larger nerve fibers of somatic nerves, which exacerbates the problem of fatigue, APCS. The high activation threshold also means that nerve activation occurs in the vicinity of the electrode contact where the current density and field curvature are highest. Axon activation occurs first in the closest vicinity of the electrode contact, and axons that are farther from the electrode contact (e.g., axons in a fascicle or within the anatomy of a neurovascular bundle) are activated later or not at all.

[0004] The activation threshold is lower for cathodic pulses (i.e., pulses emanating from the cathode) compared to anodic pulses (i.e., pulses emanating from the anode). This difference in threshold may be due to the polarized resting membrane potential of the axon. However, cathodic pulses may cause anodic block at the contact end if the nerve fiber is in close proximity to the cathodic contact surface. Anodic block may block action potential propagation along the nerve away from the contact. In contrast, anodic pulses may be more effective at activating nerves in the vicinity of the electrode because depolarization occurs at the contact end.

[0005] Conventional bipolar neural interfaces always use the electrode closest to the target organ (i.e., the distal contact) as the cathode and the electrode farther from the target organ (i.e., the proximal contact) as the anode. Fibers near the cathode surface are subject to anodic block at the contact end. Furthermore, fibers far below the anodic contact surface may not be activated due to higher threshold activation. Furthermore, higher compliance voltages are required and current is limited by the compliance voltage compared to monopolar electrodes. Conventional bipolar stimulation does not fully utilize the ability of each contact to activate nearby nerve fibers. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Ringkamp et al. 2010 PLoS ONE 5(2): e9076 doi:1371 / journal.pone.0009076 Summary of the Invention [Problem to be solved by the invention]

[0007] Therefore, there is a need for a system that more effectively electrically stimulates nerve fibers, for example, by reducing nerve fatigue, APCS, reducing anodal blockade, and allowing activation of underlying nerve fibers. New systems would produce larger and more uniform boluses of axonal firing to activate target structures, resulting in more effective therapy. [Means for solving the problem]

[0008] In one aspect of the invention, there is a system for electrically stimulating a nerve, the system including a first stimulator and a second stimulator spaced apart a first distance from each other for electrically stimulating the nerve, and a controller configured to a) set a time interval as a function of the first distance and a propagation velocity of an action potential of the nerve, b) induce electrical activity of the nerve by activating the first stimulator for a first stimulation period, and c) activate the second stimulator for a second stimulation period after the time interval has elapsed following the end of the first time period.

[0009] In this manner, the system introduces a delay (i.e., a time interval) between the stimuli applied by the first stimulator and the stimuli applied by the second stimulator. This delay allows time for the nerve to recover (i.e., repolarize) from the first stimulus before the second stimulus is applied. In particular, this delay is a function of the spacing between the stimulators and the propagation speed of the nerve's action potential, and can be set to be greater than the time it takes for the stimulus to travel from the first stimulator to the second stimulator. This ensures that the second stimulator does not activate the nerve (or prevents further stimulation of the nerve) while the nerve is still in an stimulated state at the location of the second stimulator as a result of the first stimulus. For example, the second stimulator does not attempt to activate the nerve while the action potential of the first stimulator is near the location of the second stimulator. Moreover, the use of two stimulators placed at different locations reduces the number of stimuli applied at a particular location, thereby reducing nerve fatigue, APCS, at that location.

[0010] The time interval may include a first period of time that is approximately equal to or greater than the first distance divided by the propagation speed of the nerve's action potential. In this manner, the delay may be greater than or equal to the time it takes for the stimulus to travel from the first stimulator to the second stimulator. This ensures that the second stimulator does not activate the nerve while the nerve is still in an stimulated state at the location of the second stimulator as a result of the first stimulus. For example, the second stimulator does not attempt to activate the nerve while the action potential of the first stimulus is near the location of the second stimulator.

[0011] In one example, the speed of the action potential of the nerve is about 0.5 mm / ms. This may be the case when the nerve is an autonomic nerve, such as the splenic nerve. In one example, the first distance between the first stimulator and the second stimulator is about equal to or greater than 3 mm. When the first distance is about equal to or greater than 3 mm, the first period is about equal to or greater than 6 ms. When the first distance between the first stimulator and the second stimulator is 5 mm or more, the first period is about equal to or greater than 10 ms. When the first distance between the first stimulator and the second stimulator is about 6 mm, the first period is about equal to or greater than 12 ms. When the first distance is about 6.4 mm, the first period is about equal to or greater than 12.8 ms. These parameters ensure that the second stimulator does not activate the nerve while the nerve is still stimulated at the location of the second stimulator as a result of the first stimulation, e.g., the parameters are such that the second stimulator does not attempt to activate the nerve while action potentials as a result of the first stimulation are near the location of the second stimulator.

[0012] The time interval may be set as the sum of the first period and a buffer period that allows the nerve to recover from the stimulation. It serves to ensure that the nerve has enough time to fully recover before the application of the second stimulation. The buffer period may be equal to or greater than the length of time required for the effect of the induced electrical activity in the nerve to drop below a predefined threshold or disappear at the location of the second stimulator. For example, the buffer period may be 10 ms or more. This allows a sufficient length of time for the autonomic nerve fibers to recover. The electrical activity of the nerve is associated with the recovery of the nerve's sodium channels in that the nerve's sodium channels can be electrically activated again. The end of the buffer period may be set after the relative refractory period of the nerve. It may be when the majority of the sodium channels have recovered to an excitable state.

[0013] The time interval is equal to or less than half the first time stimulation period. It is the preferred maximum length of time between the first and second stimulations. It is desirable to maximize the time between pulses so that the nerve has as long as possible time to recover to its most excitable state. When unmyelinated fibers, such as C fibers, are activated, they may require longer time to recover than other nerves.

[0014] Each of the first and second stimulators may include one or more electrodes. The system may further include an attachment means for electrically coupling the first and second stimulators to the nerve, the attachment means defining an opening having an inner diameter for receiving the nerve. The inner diameter may be approximately equal to 5 mm or greater than 5 mm. The inner diameter may be approximately equal to 13 mm or less than 13 mm. The inner diameter may be approximately 7.5 mm.

[0015] The system may be attached to a nerve. The system may be attached to nerve tissue, for example, a neurovascular bundle. The nerve may be an autonomic nerve, for example, the splenic nerve of the patient. The nerve may be an unmyelinated nerve.

[0016] The system may surround the nerve, for example, the system may partially or completely surround the nerve. The system surrounding the nerve may be attached to the nerve. The system surrounding the nerve may not be attached to the nerve, but may be in physical contact with the nerve. The nerve may be an autonomic nerve, for example the patient's splenic nerve. The nerve may be an unmyelinated nerve.

[0017] The control device may further be configured to perform step b) after a time interval has elapsed after the end of the second stimulation period. The control device may further be configured to alternately stimulate the first and second stimulators by repeating steps c) and d). Thus, the first and second stimulators may be alternately and repeatedly stimulated. The first and second stimulation periods may be approximately equal to each other, which balances the stimulation between the first and second stimulators and thus evens out any fatigue, APCS effects due to the stimulators.

[0018] In another aspect of the invention, there is a system for electrically stimulating a nerve, the system including a first stimulator for electrically stimulating the nerve at a first stimulation site and a second stimulator for electrically stimulating the nerve at a second stimulation site, spaced a first distance from each other, a controller configured to induce electrical activity in the nerve at the first stimulation site and the second stimulation site by activating the first stimulator for a first stimulation period, and to activate the second stimulator only after an amount of induced electrical activity at the second stimulation site falls below an electrical activity threshold.

[0019] In another aspect of the invention, there is a method of electrically stimulating a nerve, the method including placing a first stimulator at a first stimulation site on the nerve, placing a second stimulator at a second stimulation site on the nerve, inducing electrical activity in the nerve at the first and second stimulation sites by activating the first stimulator for a first time period, and activating the second stimulator for a second time period only after an amount of induced electrical activity at the second stimulation site falls below an electrical activity threshold.

[0020] Embodiments of the invention will now be described, by way of example only, with reference to the following figures: [Brief description of the drawings]

[0021] [Figure 1] FIG. 13 shows the variation of splenic nerve reactivity as a percentage of peak response versus the number of pulses applied and the frequency of stimulation. [Diagram 2] FIG. 1 illustrates an example of a nerve stimulation system. [Diagram 3] FIG. 1 illustrates another example of a nerve stimulation system. [Figure 4] FIG. 13 is a diagram showing an example of a stimulation timing sequence. [Diagram 5] FIG. 13 shows another example of a stimulation timing sequence. [Figure 6] FIG. 13 shows a further example of a stimulation timing sequence. [Figure 7-1] FIG. 1 shows the effect of the number of pulses during stimulation of the splenic nerve (unmyelinated axon) at different frequencies on the latency (bottom) and therefore the conduction velocity, as well as the relative amplitude of the compound action potential (CAP) (top). [Figure 7-2] FIG. 1 shows the effect of the number of pulses during stimulation of the splenic nerve (unmyelinated axon) at different frequencies on the latency (bottom) and therefore the conduction velocity, as well as the relative amplitude of the compound action potential (CAP) (top). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] FIG. 1 shows the responsiveness of the splenic nerve, unmyelinated fibers, as a percentage of the peak response, as a function of the number of pulses applied. As shown in FIG. 1, stimulating the splenic nerve at a frequency of 30 Hz results in a high rate of nerve fatigue, APCS. A stimulation frequency of 10 Hz also results in nerve fatigue, APCS, but at a slower rate. In contrast, stimulating the nerve at a frequency of 1 Hz and stimulating the nerve with 5 pulses every 5 seconds at 10 Hz results in less fatigue, APCS. Stimulating the nerve at a frequency of 1 Hz results in almost no conduction delay, and stimulating the nerve with 5 pulses every 5 seconds at 10 Hz also effectively prevents conduction delay. However, it is not desirable to limit stimulation to these frequencies and stimulation patterns. Frequencies between 1 Hz and 10 Hz are desirable.

[0023] Unmyelinated fibers, when exposed to a stimulus following a conditioning stimulus, show a slowing of conduction velocity that depends on the delay between the two pulses (stimulus frequency) and also on the total number of pulses generated. When CAPs are recorded, this phenomenon is manifested as a reduction in CAP amplitude and latency, as well as a slowing of conduction velocity.

[0024] With reference to Figure 2, there is a system 1 for electrically stimulating a nerve 3. The system includes a first stimulator 5 and a second stimulator 7 operatively connected to a controller 9 that controls the stimulation applied by the stimulators 5, 7. The stimulators 5, 7 are attached to a neural interface 9, e.g., an electrode cuff. The neural interface 9 includes an opening having an inner diameter (id1) sized to receive the nerve 3. The first stimulator 5 and the second stimulator 7 are spaced apart a first distance (d1).

[0025] The inner diameter (id1) may be approximately equal to or greater than 5 mm. The inner diameter (id1) may be approximately equal to or less than 13 mm. The inner diameter (id1) may be approximately 7.5 mm. These parameters are preferred when used with the splenic nerve of a human subject.

[0026] In the example shown in Figure 2, the first stimulator 5 includes a first electrode 11 and the second stimulator 7 includes a second electrode 13. The controller 9 is configured to stimulate the electrodes 11, 13 to provide either an anodic pulse, in which the controller 9 applies a negative current to one of the electrodes, or a cathodic pulse, in which the controller 9 applies a positive current to one of the electrodes.

[0027] The control device 9 is configured to activate the first stimulator 5 to apply a first electrical stimulus to the nerve 3 for a first stimulation period. The electrical stimulus induces electrical activity in the nerve 3, which may be an action potential in the nerve 3. The electrical activity travels along the nerve between the first stimulator 5 and the second stimulator 7.

[0028] The controller 9 is also configured to activate the second stimulator 7 to provide a second stimulus to the nerve 3 for a second stimulation period. The electrical stimulus induces electrical activity in the nerve 3, which may be a neural action potential. The electrical activity travels along the nerve between the second stimulator 7 and the first stimulator 75.

[0029] The controller 9 may be configured to operate the first electrode 11 as a cathode and the second electrode 12 as an anode during a first phase. The controller 9 may then be configured to operate the first electrode 11 as an anode and the second electrode 13 as a cathode during a second phase. The first and second phases may be within the same stimulation period.

[0030] The control device 9 is configured to set a time interval defining the delay between stimulation of the first stimulator 5 and the second stimulator 7. This may be pre-programmed and / or the control device 9 may be provided with a user interface allowing the operator to set the time interval.

[0031] With reference to Fig. 3, there is a system 1 for electrically stimulating a nerve 3, similar to the system 1 described with reference to Fig. 2. In the system 1 shown in Fig. 3, a first stimulator 5 includes a first electrode 11 and a third electrode 12. Moreover, a second stimulator 7 includes a second electrode 13 and a third electrode 12. Thus, the first stimulator 11 and the second stimulator 7 share the third electrode 12. In a further embodiment, the third electrode has a larger surface area than the first and second electrodes. The third electrode can be, for example, the IPG case.

[0032] The controller 9 is configured to stimulate the electrodes 11, 12, 13 to provide either an anodic pulse, in which the controller 9 applies a negative current to one of the electrodes, or a cathodic pulse, in which the controller 9 applies a positive current to one of the electrodes.

[0033] In a similar manner as described above, the controller 9 is configured to activate the first stimulator 5 to provide a first electrical stimulus to the nerve 3 for a first stimulation period. In one example, the electrical stimulus includes stimulation of the first electrode 11 and / or the third electrode 12 to provide either an anodic pulse or a cathodic pulse. For an anodic pulse, the controller 9 applies a negative current to either the first electrode 11 or the third electrode 12. For a cathodic pulse, the controller 9 applies a positive current to either the first electrode 11 or the third electrode 12.

[0034] The controller 9 is also configured to activate the second stimulator 7 to provide a second electrical stimulus to the nerve 3 for a second stimulation period. In one example, the electrical stimulus includes stimulation of the second electrode 13 and the third electrode 12 to provide either an anodic pulse or a cathodic pulse. For an anodic pulse, the controller 9 applies a negative current to either the second electrode 13 or the third electrode 12. For a cathodic pulse, the controller 9 applies a positive current to either the second electrode 13 or the third electrode 12.

[0035] The controller 9 may be configured to operate the first electrode 11 and / or the second electrode 13 as a cathode and the third electrode 12 as an anode during a first phase. The controller 9 may then be configured to operate the first electrode 11 and / or the second electrode 13 as an anode and the third electrode 12 as a cathode during a second phase. The first and second phases may be within the same stimulation period.

[0036] Figure 4 shows an example of timing sequences of stimuli provided by the system 1 described with reference to Figures 2 and 3. There is a first timing sequence 101 showing stimuli provided by a first stimulator 5, a second timing sequence 102 showing stimuli provided by a second stimulator 7, and a combined timing sequence 103 showing the combined effect on the nerve 3 of the stimuli provided by the first and second stimulators 5, 7.

[0037] 2 to 4, first the first stimulator 5 stimulates the nerve 3 with a first electrical stimulus 111 for a first stimulation period (t1). Next, the second stimulator 7 stimulates the nerve 3 with a second electrical stimulus 121 for a second stimulation period (t2). The first stimulator 5 then stimulates the nerve 3 with a third electrical stimulus 112 for the first stimulation period, after which the second stimulator 7 stimulates the nerve 3 with a fourth stimulus 122 for the second stimulation period. This process can be repeated, so that the first and second stimulators 5, 7 are alternately activated.

[0038] In FIG. 4, the stimuli 111, 121, 112, 122 are square wave pulses, however this is only one example and different stimulation patterns can be used, for example pulse bursts and / or biphasic pulses.

[0039] As can be seen in FIG. 4, there is a time interval (t i ) is the delay between the end of the first stimulus 112 and the start of the second stimulus 121.

[0040] Time interval (t i ) is set to ensure that the electrical activity induced by the first stimulus has subsided in the vicinity of the second stimulator before the second stimulus is activated. This delay is set as a function of the spacing between the stimulators 5, 7 (i.e., the first distance d1) and the propagation speed of the nerve action potential.

[0041] In this example, the time interval (t i ) is defined by a function of the first distance (d1) and the propagation speed, c ) (i.e., a first period). This function defines that the first period is approximately equal to or greater than a first distance (d1) divided by the propagation velocity (v) of the nerve action potential. The propagation velocity is the speed at which the electrical signal travels between the stimulators 5, 7. The function can be expressed as:

[0042]

number

[0043] For example, the propagation velocity of unmyelinated C-fibers of an autonomic nerve, such as the splenic nerve, is 0.5 mm / ms. The stimulation periods t1 and t2 may each be equal to 1 ms.

[0044] Therefore, the function may define a first period as shown in the table below, resulting in a combined effective stimulation frequency rate as shown in Table 1.

[0045] [Table 1]

[0046] With reference to Table 1, the system can be evaluated as allowing higher stimulation frequencies while reducing neural fatigue, an issue with APCS.

[0047] In this other example, the time interval (ti ) is at least the first period (t c ) and the buffer period (t b ) and the time interval (t i ) is the first period (t c ) and the buffer period (t b ), this function can be shown as:

[0048]

number

[0049] Buffer period (t b ) may be 10 ms or more, which allows a sufficient amount of time for autonomic nerve fiber recovery. However, other periods can be used depending on the nerve type. For example, different fiber types and diameters will have different refractory periods. Myelinated fibers have very short recovery times, on the order of a few milliseconds. Unmyelinated fibers, such as C fibers, require recovery times on the order of 10 ms. Recovery times within a fiber type will be shorter for larger diameters and longer for smaller diameters. Similarly, the buffer period (t b Increasing the length of the buffer period (t ) increases the likelihood, but decreases the frequency, of complete nerve recovery before the next stimulation is applied. b Decreasing the length of the buffer period (t) decreases the likelihood that the nerve will fully recover before the next stimulus is applied, but increases its frequency. b ) can be adjusted to find the optimum tradeoff between frequency and recovery. The operator can select the buffer period (t b ) can be adjusted.

[0050] Table 2 shows the time interval (t i ) values ​​and resulting frequency rates are shown.

[0051] [Table 2]

[0052] Referring to Table 2, the system can be evaluated as allowing high stimulation frequencies while reducing neural fatigue, an issue with APCS.

[0053] Figures 5 and 6 show specific examples of stimulation patterns provided by system 1. Referring to Figure 5, system 1 alternates the waveform polarity on each stimulator 5, 7 to allow anodal and cathodal activation. As already explained, anodal stimulation can activate nerve fibers very close to the interface, whereas cathodal stimulation can activate underlying fibers. Therefore, by using the waveforms shown in Figure 5, it is possible to activate fibers close to the electrode as well as fibers far from the electrode.

[0054] Figure 5 shows the distal contact (E d ), proximal contact (E p ) and the case. As shown, the neural interface stimulates the nerve with a symmetric biphasic waveform. In this example, the case is always utilized as the anode, and the proximal and distal contacts are always cathodes with two different timing channels operating at the same speed, 180 degrees out of phase. 180 degrees out of phase means that the sequence interval is half the interval of the timing channels to maximize recovery time in the event that a fiber is activated by both contacts.

[0055] For a bipolar nerve interface with proximal and distal contacts spaced approximately 6 mm apart along the length of the splenic nerve, an action potential with a conduction velocity of 0.5 m / s would take approximately 12 ms to propagate between the contacts. The recovery time available to the nerve is approximately half the interval minus 12 ms, or 38 ms for a 10 pps stimulation (i.e., 50 ms sequence interval). In other words, if it takes 12 ms for an action potential to propagate to the second contact, the fiber has 38 ms at that second contact to recover from activation by the action potential in transit. Since the pulse rate at each contact is 10 pps, there will be 50 ms from the first contact fire to the second (50 ms-12 ms=38 ms recovery time at the second contact). The recovery time (refractory time) of a first stimulated unmyelinated fiber, e.g., C fiber, is less than 10 ms. This suggests that if the average pulse rate is approximately 1 pps, the burst rate will be up to 30 pps without fatigue, APCS, or exit block. To lower the activation threshold by avoiding membrane repolarization at the activation site prior to sodium channel activation, the charge recovery phase of each pulse is delayed by at least 0.1 ms.

[0056] AC monopolar stimulation, as shown in FIG. 5, concentrates the entire output current of the stimulator onto a portion of the contacts that uses a larger surface area of ​​the implantable pulse generator (IPG) case, lowering the required compliance voltage and allowing for a lower current density to avoid IPG pocket stimulation.

[0057] Figure 6 shows a stimulation pattern that requires four timing channels to sequence the proximal and distal contacts as anodes and cathodes. This allows fibers very close to the contact surface to be activated by anodal pulses, while underlying fibers are activated by cathodal pulses. If limited to two timing channels, an AC bipolar waveform may be used to achieve the same effect as the AC monopolar stimulation shown in Figure 5.

[0058] Passive charge recovery is used in this example as a way to avoid any possible activation by the recharge phase. Even with symmetric biphasic pulses, there is likely no activation of the recharge phase, because the reversal of membrane polarization after the initial subthreshold phase is generally non-excitatory.

[0059] The term "comprising" includes "including" as well as "consisting of," e.g., a composition "comprising" X may consist only of X or may include additional, e.g., X+Y. Unless otherwise specified, each embodiment described herein may be combined with another embodiment described herein.

[0060] The methods described herein may be performed by software in machine-readable form on a tangible storage medium, for example in the form of a computer program including computer program code means adapted to perform all steps of any of the methods described herein, when the program is executed on a computer and the computer program may be embodied on a computer readable medium. Examples of tangible (or non-transitory) storage media include disks, thumb drives, memory cards, etc., but not propagated signals. The software may be suitable for execution on parallel or sequential processing devices, such that the method steps may be performed in any suitable order or simultaneously. This recognizes that firmware and software may be valuable commodities that can be traded separately. It is intended to encompass software that runs on or controls "dumb terminals" or standard hardware to perform a desired function. It is also intended to encompass software that "describes" or defines hardware configurations, such as those used to design silicon chips or configure universal programmable chips, for example, hardware description language (HDL) software, to perform a desired function.

[0061] The modules described herein, e.g., controllers, may conveniently be implemented in hardware or software. Furthermore, the modules may be implemented in different parts of the system.

[0062] Those skilled in the art will appreciate that storage devices used to store program instructions can be distributed across a network. For example, a remote computer may store an example of a process described as software. A local or terminal computer may access a remote computer and download some or all of the software to execute the program. Alternatively, a local computer may download multiple pieces of software as needed, or execute some software instructions on a local terminal and some on a remote computer (or computer network). Those skilled in the art will also appreciate that all or some of the software instructions can be performed by dedicated circuitry, e.g., DSPs, programmable logic arrays, etc., using conventional techniques known to those skilled in the art.

[0063] Any range or device values ​​given herein may be expanded or modified, as will be obvious to those skilled in the art, without losing the effect found.

[0064] It is understood that the benefits and advantages described above may relate to one embodiment or to several embodiments, and the embodiments are not limited to embodiments that solve some or all of the problems described or that have some or all of the benefits and advantages described above.

[0065] Any reference to "a" or "an" item refers to one or more of those items. The term "comprising" is used herein to mean including the identified method blocks or elements, but that such blocks or elements do not include an exclusive list, and that the method or apparatus may include additional blocks or elements.

[0066] The steps of the methods described herein may be performed in any suitable order, or simultaneously as appropriate. Moreover, individual blocks may be deleted from any of the methods without departing from the spirit and scope of the subject matter described herein. Aspects of any of the above examples may be combined with aspects of any of the above other examples to form further examples without loss of effect. Any of the above modules may be implemented in hardware or software.

[0067] It will be understood that the above description of preferred embodiments is given by way of example only and may be variously modified by those skilled in the art. Although various embodiments have been described above in some detail, or with reference to one or more individual embodiments, those skilled in the art will be able to make numerous modifications to the disclosed embodiments without departing from the scope of the claims. [Explanation of symbols]

[0068] 1 System 3. Nerves 5. First Stimulator 7 Second Stimulator 9. Control Device 11 First electrode 12 Third electrode 13 Second electrode 101 First Timing Sequence 102 Second Timing Sequence 103 Complex Timing Sequence 111 First Electrical Stimulation 112 The Third Electrical Stimulation 121 Second Electrical Stimulation 122 The Fourth Electrical Stimulation

Claims

1. A system for electrically stimulating a nerve, comprising: a first stimulator for electrically stimulating the nerve at a first stimulation location and a second stimulator for electrically stimulating the nerve at a second stimulation location, the first stimulator and the second stimulator being spaced apart a first distance from each other; inducing neural electrical activity at the first stimulation site and the second stimulation site by activating a first stimulator for a first stimulation period; Activating the second stimulator only after the amount of induced electrical activity at the second stimulation site falls below an electrical activity threshold. A control device configured as follows: A system including:

2. The system described in claim 1, wherein a first distance between the first stimulator and the second stimulator is approximately equal to or greater than 3 mm.

3. A system as described in claim 1 or 2, wherein the first distance between the first stimulation device and the second stimulation device is 5 mm or more.

4. A system described in any one of claims 1 to 3, wherein the first distance between the first stimulator and the second stimulator is approximately 6 mm.

5. The system of claim 1, wherein the first distance is approximately 6.4 mm.

6. A system described in any one of claims 1 to 5, wherein each of the first stimulator and the second stimulator includes one or more electrodes.

7. A system as described in any one of claims 1 to 6, further comprising an attachment means for electrically coupling the first stimulator and the second stimulator to the nerve, the attachment means defining an opening having an inner diameter for receiving the nerve.

8. The system of claim 7, wherein the inner diameter is approximately equal to or greater than 5 mm.

9. The system of claim 7 or 8, wherein the inner diameter is approximately equal to or less than 13 mm.

10. A system as claimed in any one of claims 7 to 9, having an inner diameter of approximately 7.5 mm.

11. A system described in any one of claims 1 to 10, wherein the system is attached to a nerve.

12. A system described in any one of claims 1 to 11, wherein the system surrounds a nerve.

13. A system described in claim 11 or 12, wherein the nerve is an autonomic nerve.

14. A system described in any one of claims 11 to 13, wherein the nerve is the splenic nerve.

15. The system of claim 11 or 12, wherein the nerve is unmyelinated.

16. A system as described in any one of claims 6 to 15, comprising a third electrode.

17. The system of claim 16, wherein the third electrode has a larger surface area than the first electrode and the second electrode.

18. A system as described in claim 16 or 17, wherein the third electrode is an IPG case.

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