Systems for neurostimulation applications

Abstract

The system (100) for peripheral nerve stimulation comprises at least one neural stimulation device (110) having at least one stimulation means (112) and a controller configured to provide a neural stimulation (130) to a neural structure (200) via the neural stimulation device (110), the controller further configured to provide and apply a conditioning sequence (140) having at least one pulse to the neural structure (200) via the neural stimulation device (110) prior to and / or after application of the neural stimulation (130). The conditioning sequence (140) is configured to limit an onset response (162) and / or an offset response (164) and / or a neural response overshoot by the neural structure (200).

Description

[Technical field]

[0001] The invention particularly relates to a system for peripheral nerve stimulation (PNS) for shaping electric field potentials and / or second spatial derivatives of electric fields and / or potentials parallel and / or non-parallel to nerves / nerve structures / fibers. [Background technology]

[0002] In this regard, neural prosthetic devices are powerful tools for monitoring, preventing, and treating neurological diseases, disorders, and conditions by electrically interfacing with the nervous system. When implanted in neural tissue, they can record neural activity and electrically stimulate neural activity. Currently, most neural prosthetic technologies utilize electrodes that interface with neural tissue.

[0003] High frequency alternating current (HFAC) can block nerve conduction, but the block is always accompanied by an onset response preceding the block and / or an offset response following the block when the application of HFAC is turned off again, which is a period of repetitive nerve firing. HFAC can produce nerve conduction blocks.

[0004] Axons become blocked within milliseconds of application of HFAC, remain blocked as long as HFAC is sustained, and can return to their normal state of activity within seconds when HFAC is discontinued, features that make HFAC block extremely attractive for potential clinical use.

[0005] However, one major drawback of HFAC blockade for clinical use is the short but intense volley of activity that occurs within the nerve each time the HFAC is turned on or off, the so-called "onset" or "offset" response, depending on whether the HFAC is turned on or off.

[0006] Previous methods have attempted to apply amplitude ramping to overcome onsets, for example as described in JD Miles et al 2007 J. Neural Eng. 4 390, but have been unsuccessful.

[0007] Other methods apply an amplitude ramp from a non-zero amplitude, which is not successful in reducing the initial onset but has some effect on mitigating subsequent onsets (Vrabec 2019).

[0008] Yi2020 attempted to simulate an axon model in combination with particle swarm optimization (PSO) to find a stimulation waveform that would successfully reduce onset. This work is limited to simulations only and does not provide waveforms that are easily applicable for clinical use, e.g., it is not directly translatable to electronic devices and does not meet safe (charge-balanced) stimulation limits by default.

[0009] Ackerman 2009 suggests that bipolar electrodes with 1.0 mm separation minimize current transmission while producing high frequency block with minimal onset response in the rat sciatic nerve. The results presented in this study demonstrate that bipolar electrode contact SD affects both the amount of current required to achieve complete nerve conduction block and the magnitude of the onset response. However, the trends of these responses do not trend in the same direction. This suggests that different mechanisms may be responsible for the observed phenomena. Summary of the Invention

[0010] It is an object of the present invention to provide a system, particularly for neurostimulation applications, capable of providing enhanced nerve blocking / modulation, preferably high frequency and / or low frequency neuromodulation, by intrinsic conditioning of nerves / neural structures / fibers to limit onset and / or offset responses and / or neural response overshoot.

[0011] The above mentioned object is solved by the subject matter of independent claim 1. Advantageous configurations of the invention are set out in the dependent claims.

[0012] According to the invention, a system for peripheral nerve stimulation, in particular for shaping electric field potentials and / or second spatial derivatives of electric fields and / or potentials parallel and / or non-parallel to nerve structures, comprises at least one nerve stimulation device with at least one stimulation means, preferably a plurality of stimulation means forming a stimulation array, and a control device, the control device being configured to provide a nerve stimulation, in particular a nerve stimulation sequence comprising a plurality of consecutive nerve stimulation pulses, to the nerve / nerve structure / fiber via the nerve stimulation device, the control device being further configured to provide and apply a conditioning sequence comprising at least one pulse to the nerve / nerve structure / fiber via the nerve stimulation device prior to and / or after the application of the nerve stimulation, the conditioning sequence being configured to limit / reduce an onset response and / or offset response and / or nerve response overshoot by the nerve / nerve structure / fiber.

[0013] The present invention is based on the idea of ​​providing pre / post conditioning of neural structures in order to achieve a smoother response / reaction to electric field / charge changes in the neural structures.

[0014] For high frequency stimulation, particularly HFAC to induce nerve blocks, onset and / or offset responses by neural tissue may be reduced / limited. Additionally, overshoot responses of tissue during low frequency stimulation may be reduced / limited.

[0015] Furthermore, the response of nerves / neural structures / fibers may also be reduced / limited due to inherent shaping of the electric field potential and / or second spatial derivative of the electric field and / or potential parallel and / or non-parallel to the nerves / neural structures / fibers. Such inherently shaped electric fields in and / or around the nerve structures may be achieved according to the present invention by appropriate design of the neurostimulation device and / or by inherent control and / or regulation of the application of neurostimulation along the length of the neurostimulation device.

[0016] In the sense of the present invention, the term neuromodulation may be understood to refer to the modulation of neural responses, either by activation / modulation, blocking, or a combination thereof.

[0017] In particular, the at least one stimulation means may be provided as an electrode or coil. For example, the neurostimulation device may be provided in the form of an electrode device, in particular as a transcutaneous electrical nerve stimulation (TENS) electrode, a spinal cord stimulation electrode such as a paddle lead or a percutaneous lead, and / or in the form of a nerve cuff for peripheral nerve stimulation.

[0018] In all embodiments of the present disclosure, the electrode device may have at least one electrode comprising graphene, in particular made of graphene or a graphene-based material, or provided with a graphene(based) coating.

[0019] Preferably, various forms of graphene (based) materials may be used in the context of the present invention, such as reduced graphene oxide (rGO), graphene oxide, chemical vapor deposited graphene (CVD graphene), or other potential forms of graphene.

[0020] In particular, such graphene-based materials can provide enhanced electrical and mechanical properties, such as beneficial flexibility of the resulting electrodes.

[0021] Such graphene electrodes, in particular, may provide higher safe charge injection capability and also improve signal-to-noise ratio / performance, thereby allowing electrode size to be reduced even if the same amount of electrode is maintained.

[0022] Thus, along the cross-section of the electrode device, the cross-sectional area of ​​at least one electrode may be reduced.

[0023] Moreover, such graphene-based electrodes can provide a safe electrical interface in aqueous environments, such as in the context of neuromodulation of neural tissue.

[0024] The controller may be provided, for example, as an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), and / or in the form of a microprocessor with pre-programmed waveform sequences.

[0025] The controller may be integrated, at least partially integrated, into the neurostimulator device and / or may be provided, at least partially, as an external controller.

[0026] A neurostimulation device may comprise one or more stimulation means. Neurostimulation may be applied via one stimulation means, via more than one of the multiple stimulation means, or via all of the multiple stimulation means. In particular, during a neurostimulation sequence, neurostimulation pulses may be provided via one or more of the stimulation means in a sequential or parallel manner. Thus, variable patterns of the provided neurostimulation pulses may be defined.

[0027] The neural stimulation may be provided by the control device via the stimulation means, for example in the form of HFAC or in the form of low frequency stimulation pulses. In particular, the neural stimulation may be provided as a sequence of multiple successively applied neural stimulation pulses that are applied to the neural structures along the length of the neural stimulation device, i.e., preferably a plurality of stimulation means forming a stimulation array.

[0028] In the context of the present invention, a sequence may be considered as at least one pulse provided to a neural structure, or multiple pulses applied sequentially, e.g. via a single stimulation means, or even in parallel, e.g. via multiple stimulation means along a neural stimulation device.

[0029] Furthermore, a sequence, in particular a plurality of pulses provided / applied successively, may comprise different types of pulses, in particular such successive pulses of a sequence may be offset from one another in various pulse parameters, such as pulse width, pulse intensity, frequency, sinusoidal, monophasic or biphasic shape, inter-pulse interval, i.e. time delay between cathodic and anodic phases, etc.

[0030] For example, in the case of sinusoidal or biphasic pulses, such pulse parameters may vary with respect to the anodic and / or cathodic phases of each pulse.

[0031] Thus, within the meaning of the present invention, a sequence, for example a neural stimulation sequence or a conditioning sequence, may comprise a highly variable combination of pulses. Alternatively, a sequence may comprise a plurality of identical or at least identical pulses provided in succession.

[0032] The conditioning sequence may be provided as a single pulse for preparation / conditioning of the neural structures. Additionally, the conditioning sequence may be provided in the form of multiple pulses applied in a specific sequence via the neurostimulator device.

[0033] It is therefore possible to apply a particular pattern of pulses to the neural structure as a conditioning sequence via multiple stimulation means. According to the invention, the pulses of the conditioning sequence can be different in terms of various pulse parameters as described above.

[0034] As a result, conditioning sequences, particularly conditioning sequences of specifically designed pulses, can be provided to neural structures via a neurostimulation device to limit / reduce onset / offset / overshoot responses of the nerve / neural structure / fiber.

[0035] According to one preferred embodiment, the control device comprises: - a pre-pulse sequence comprising at least one pre-pulse, preferably a combination of multiple pre-pulses with the same or different time delays as the neural stimulation; - frequency ramp, - Frequency ramp combined with amplitude ramp, - a frequency ramp in combination with said at least one pre-pulse, preferably in combination with a pre-pulse sequence; - at least one pre-pulse, preferably a pre-pulse sequence, in combination with an amplitude ramp, - at least one pre-pulse, preferably a pre-pulse sequence, in combination with an amplitude ramp and a frequency ramp; The conditioning sequence includes at least one of:

[0036] Various options are possible regarding how to properly condition / prepare neural structures.

[0037] For example, a sequence of pre-pulses can be provided that includes a time delay between each pre-pulse and / or between the cathodic and anodic phases, which may be the same as the time delay between correspondingly applied neural stimulation pulses of the HFAC.

[0038] The frequency ramp may represent a function according to which the amplitude of the neural stimulation pulse remains the same during the ramping function, while the frequency is increased / decreased over time.

[0039] In contrast, an amplitude ramp represents a ramp function according to which the frequency remains the same during the conditioning sequence, and the amplitude of the neural stimulation pulses is increased / decreased over time.

[0040] A combination of amplitude and frequency ramps may allow for a parallel increase in both the amplitude and frequency of the conditioning sequence.

[0041] Furthermore, a combination of such an amplitude / frequency ramp with at least one pre-pulse or even a pre-pulse sequence may be provided as a ramp function that is interrupted / supplemented at any point in time by an additional application of a pre-pulse.

[0042] For example, a high or low frequency (i.e., 1-100 Hz) sinusoidal ramp may be applied. In particular, during the low frequency ramp, the frequency may be increased to 20-40 kHz to prepare / condition the neural structures for the subsequent application of HFAC. If a conditioning sequence is to be applied after the application of HFAC, the frequency may be decreased again from 20-40 kHz to 1-100 Hz in such a sinusoidal frequency ramp.

[0043] According to one preferred embodiment, the conditioning sequence is configured to shape ("shape") the electric field potential and / or the second spatial derivative of the electric field and / or potential parallel and / or non-parallel to the neural structure, and the shaping by the conditioning sequence can be individualized for different spatial areas along the extension of the neural structure and / or the shaping by the conditioning sequence is provided in a time-dependent manner, preferably in a first spatial direction in a first step and in a second spatial direction in a second step.

[0044] In particular, the electric field potentials and / or second spatial derivatives of electric fields and / or potentials parallel and / or non-parallel to nerves / neural structures / fibers may be uniquely shaped to preferably reduce / limit onset / offset and / or overshoot responses by the neural structures.

[0045] Specific / individualized shaping of the electric field potentials and / or second spatial derivatives of the electric fields and / or potentials parallel and / or non-parallel to such nerves / nerve structures / fibers may be provided for an area / multiple areas along the nerve structures.

[0046] Thus, shaping may be altered / individualized for specific regions / areas along the length of the neural structure due to specific control / regulation and / or design of the neurostimulation device in that particular region / area.

[0047] This may be considered area dependent shaping in the context of the present invention.

[0048] Alternatively or additionally, shaping may be provided in terms of time-dependent modification of the field potential and / or the second spatial derivative of the field and / or potential parallel and / or non-parallel to the neural structures.

[0049] Such time-dependent shaping may, for example, be provided in two or multiple steps, in particular the stepwise shaping causes the direction of the field potentials and / or second spatial derivatives of the fields and / or potentials parallel and / or non-parallel to the neural structures to change during each step of the shaping.

[0050] For example, the second spatial derivatives of electric fields and / or potentials parallel and / or non-parallel to neural structures may be - In the first step, the first direction is perpendicular to the neural structures. In a second step, it may be shaped so that it is rotated in a second direction parallel to the neural structures.

[0051] In this manner, nerve block may be achieved during / by the first or subsequent steps, and furthermore, onset / offset and / or overshoot responses by neural structures may be limited / reduced in multiple steps by such time-dependent shaping schemes.

[0052] In another embodiment of the invention, the conditioning sequence may include at least one variable parameter, preferably for forming a ramp function, and further stimulation parameters of the conditioning sequence are at least equivalent, and preferably similar, to the neural stimulation (sequence).

[0053] Thus, the system, and in particular the controller, provides various options as to how to properly condition / prepare neural structures prior to and / or following neural stimulation (sequences / pulses).

[0054] In particular, the conditioning sequence may focus on at least one variable parameter, such as frequency, amplitude, pulse duration, inter-pulse interval, etc., to achieve graded neural structure (pre-)conditioning.

[0055] According to another embodiment, the conditioning sequence, preferably referring to a frequency ramp function and / or an amplitude ramp function, is configured to have a waveform similar to the neural stimulation, or - Sine wave, monophasic or biphasic waveforms, - Different pulse widths, - Different amplitudes, and / or - Different inter-pulse intervals The neurostimulation is configured to be offset with respect to being applied together.

[0056] In particular, providing different interpulse intervals may refer to staggered delays between the cathodic and anodic phases of each pulse.

[0057] In this manner, the conditioning sequences can be provided in a manner equivalent to or deviated from the corresponding neural stimulation (sequence) to provide appropriate preparation / conditioning of neural structures before / after the neural stimulation (sequence).

[0058] In a further embodiment, the neural stimulation sequence comprises: - High frequency alternating current provided to a neural structure to achieve high frequency block of the neural structure, or - is a low frequency stimulation delivered to neural structures, specifically for neuromodulation.

[0059] Preferably, a system according to the present invention is configured so as to be suitable for low frequency nerve stimulation applications as well as higher frequency applications such as nerve blocking by application of HFAC.

[0060] In particular, the response of neural structures to the application of neural stimulation, such as the onset / offset response or the overshoot response, can be shaped / influenced so as to ultimately be reduced / limited.

[0061] In another preferred embodiment, the neurostimulator device comprises at least one stimulation means that is configurable such that the neurostimulation provided via the at least one stimulation means is adaptable along the neural structure. According to one embodiment, the at least one stimulation means is adaptable by modifying the design of the neurostimulator device, in particular the shape, the configuration of the stimulation array, and / or the like.

[0062] In particular, field potentials and / or second spatial derivatives of electric fields and / or potentials parallel and / or non-parallel to nerves / neural structures / fibers can affect the onset modulation function, and thus altering them with respect to the neural structures of interest, for example by making them less steep (i.e. smoother), can reduce the onset / offset response.

[0063] Since nerves / neural structures / fibers within a nerve are not uniform, e.g. organized in bundles, and have different motor / sensory afferent / efferent functions, they can be targeted with dedicated electrode arrays and / or (intrinsic) electric field shaping to reduce onset / offset responses.

[0064] Thus, with this system according to the invention, the positioning and / or use of the neurostimulation device, in particular the single stimulation means, can be individually adapted to appropriately shape the electric field potential and / or the second spatial derivative of the electric field and / or potential in and / or around the neural structure.

[0065] In particular, the resulting field potential and / or second spatial derivative of the electric field and / or potential may be shaped to achieve limiting / reducing the onset / offset or overshoot response of neural structures not only at one particular point but preferably along a certain area / extension of the neurostimulation device.

[0066] Such shaping of the field potential and / or the second spatial derivative of the field and / or potential may in particular be timing / time dependent and / or area dependent.

[0067] For example, in case of a neurostimulation device comprising only one stimulation means, such stimulation means may comprise an individually shaped geometric extension along the neurostimulation device.

[0068] In the case of a neurostimulation device comprising multiple stimulation means, such stimulation means may form a particular geometric pattern representing a stimulation array, which may be adapted and / or used uniquely, preferably in a sequential, parallel, or any other combined manner to appropriately deliver neurostimulation pulses.

[0069] Furthermore, the (geometric) shape of the neurostimulation device, such as its length, diameter, outer perimeter shape, etc., may be adapted.

[0070] Furthermore, the control device can transfer appropriate stimulation signals, preferably individual stimulation signals, to a single stimulation means of the neurostimulation device in order to provide specific targeted stimulation of neural structures.

[0071] In a further embodiment of the invention, the control device is configured to provide an individual stimulation signal to each of the plurality of stimulation means such that the neural stimulation provided to the neural tissue via the plurality of stimulation means can be shaped along the length of the neurostimulation device. According to another embodiment, the control device is configured to shape the neural stimulation along the length of the neurostimulation device by applying a weighting factor to the stimulation signal in order to provide an individual stimulation signal to each of the plurality of stimulation means.

[0072] In the sense of the present invention, the control device provides stimulation signals to the stimulation means for applying / transmitting neural stimuli (sequences) to nerves / nerve structures / fibers.

[0073] Such stimulation signals may be adapted by the control device, for example by application of a weighting factor to amplify the stimulation signal for a particular stimulation means of the neurostimulation device. Preferably, the stimulation means may be individually controlled and / or adjusted such that the neurostimulation of each stimulation means may be individualized by an individual stimulation signal.

[0074] The weighting factor may be "0" (value: zero) to "switch off" a single stimulation means, or less than 1.0 (value "1") to reduce the correspondingly transmitted neural stimulation pulse. If the neural stimulation pulse is to be applied without any amplification, the weighting factor may be 1.0. If an amplified neural stimulation (pulse / sequence) is to be transmitted via a particular stimulation means, the corresponding stimulation signal may be amplified, in particular increased, by a weighting factor, e.g. 1.1, 1.5, 2, etc.

[0075] Thus, the application of neural stimulation (sequences) via multiple stimulation means may be adapted and shaped by the control device, in particular by application of weighting factors to each stimulation signal, so that uniquely targeted application of neural stimulation pulses is possible.

[0076] Hence, the stimulation signal for one of the multiple stimulation means can even be reduced to zero or at least close to zero, while the other stimulation means are provided with an amplified stimulation signal by multiplying it by a weighting factor higher than 1.0.

[0077] Further, some of the plurality of stimulation means may receive the same stimulation signal to provide neural stimulation to neural tissue, while other of the plurality of stimulation means receive adapted stimulation signals, such that each stimulation means may receive a unique stimulation signal provided by the controller.

[0078] Alternatively, the control device may provide the same stimulation signal to all of the multiple stimulation means, the structure of the stimulation means, and in particular the structural implementation of the array of stimulation means, being configured to provide individualized neurostimulation by each stimulation means.

[0079] In further preferred embodiments, the neurostimulation device is an implantable pulse generator or a transcutaneous stimulation device, such as a skin patch.

[0080] As a result, a system according to the present invention may be specifically designed / configured for use in PNS applications.

[0081] In particular, the nerve blocking mechanism via application of HFAC and smooth initiation of low frequency nerve stimulation sequences may be utilized, particularly in the context of PNS.

[0082] Thus, for example, application of HFAC to initiate a nerve block allows targeted stimulation / non-stimulation of neural tissue, thereby achieving unique individual stimulation of nerves / nerve structures / fibers.

[0083] Further details and advantages of the invention are disclosed below in connection with the accompanying drawings. [Brief description of the drawings]

[0084] [Figure 1] FIG. 13 is a schematic diagram of the onset / offset response resulting from immediate application of a nerve block stimulus according to the prior art compared to application of a (pre)conditioning sequence according to one embodiment of the system. [Diagram 2] FIG. 13 is a schematic diagram of the application of a conditioning sequence according to another embodiment of the system. [Diagram 3] FIG. 13 is a schematic diagram of the application of a conditioning sequence according to another embodiment of the system. [Figure 4] FIG. 13 is a schematic diagram of the application of a conditioning sequence according to another embodiment of the system. [Diagram 5] 1 is a comparison of neurostimulator device configurations according to one embodiment of the system. [Figure 6] 11 is a comparison of neurostimulator device configurations according to another embodiment of the system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0085] FIG. 1 shows a schematic diagram of the onset / offset responses 162; 164 of a stimulated nerve / nerve structure / fiber 200 resulting from (immediate) application of a prior art nerve block stimulus 130 compared to application of a (pre)conditioning sequence 140 according to one embodiment of the system 100.

[0086] According to FIG. 1, a nerve stimulation sequence 130 is applied having a plurality of nerve stimulation pulses 132 in the form of high frequency alternating current to induce a nerve block.

[0087] In particular, the neural stimulation sequence 130 is applied in the form of a biphasic pulse 132 .

[0088] As can be inferred from the left diagram of FIG. 1 illustrating the application of HFAC according to the prior art, onset / offset responses 162; 164 from the stimulated neural structure 200 are evoked at the start / end of the application of HFAC, as can be inferred from the corresponding responses of the neural structure 160.

[0089] Simple instantaneous application of HFAC as a neural stimulation sequence 130 causes / elicits a strong volley of uncontrolled activity within the neural structure 200.

[0090] In contrast, the diagram on the right side of FIG. 1 illustrates the application of a neural stimulation sequence 130 in the form of HFAC in combination with a single pre-pulse 142 preceding the neural stimulation sequence 130 .

[0091] According to FIG. 1, the pre-pulse 142 is applied at an amplitude that is 75% of the intensity of the subsequent HFAC, ie, neural stimulation sequence 130 .

[0092] A single pre-pulse 142 is applied for between 1 μs and 1 minute, preferably between 1 μs and 1 second, between 1 μs and 100 ms, and even more preferably between 25 and 50 ms, prior to the start of the neurostimulation sequence 130.

[0093] The pre-pulse 142 is applied as a biphasic pulse sequence.

[0094] As can be inferred from a comparison of the left and right diagrams of FIG. 1, the application of a pre-pulse 142 prior to a neural stimulation sequence 130 causes a limit / reduction of the onset response 162 in the response (signal) of the neural structure 200.

[0095] This can be inferred from FIG. 1 (right side image) in particular since only the onset response 162 is limited / reduced, and the subsequent offset response 164 is not reduced / restricted immediately upon the end of the neural stimulation sequence 130.

[0096] 2-4, schematic diagrams of the application of conditioning sequences according to further embodiments of the system 100 are shown.

[0097] According to FIG. 2, a frequency ramp 144 is applied as a conditioning sequence 140 .

[0098] A frequency ramp 144 is applied as a conditioning sequence 140 having multiple pulses having the same intensity / amplitude as the subsequent neural stimulation sequence 130, preferably HFAC.

[0099] A conditioning sequence 140 comprising a frequency ramp 144 is applied for a period of 25-50 ms before the neural stimulation sequence 130 begins.

[0100] In the context of the frequency ramp 144 as a conditioning sequence 140 , the frequency of the applied pulses is increased over time, preferably to a frequency that matches the frequency of the subsequent neural stimulation sequence 130 .

[0101] Additionally, in the right hand diagram of FIG. 2, a conditioning sequence 140 in the form of a frequency ramp 144 is also applied following completion of the neural stimulation sequence 130 to decrease the frequency over time, for example over a further 25-50 ms.

[0102] As can be seen from the corresponding response of the neural structures 160 , the conditioning sequence 140 prior to the neural stimulation sequence 130 limits / reduces the onset response 162 along with the response of the neural structures 160 .

[0103] Furthermore, if a further (post-) conditioning sequence 140 is applied after the end of the neural stimulation sequence 130 (right diagram in Figure 2), the offset response 164 can also be reduced / limited, as shown along with the response of the neural structure 160.

[0104] In FIG. 3, the conditioning sequence 140 is provided in the form of an amplitude ramp 146 .

[0105] The amplitude of the pulses applied to form the conditioning sequence 140 is preferably increased over time until the amplitude of the subsequent neural stimulation sequence 130 is achieved.

[0106] The amplitude ramp 146 may be provided at a constant frequency, preferably the frequency of the subsequent neural stimulation sequence 130 .

[0107] According to FIG. 3, the conditioning sequence 140 is provided prior to the neural stimulation sequence 130 for a time range of 25-50 ms.

[0108] Again, in the right-hand diagram of FIG. 3, a further conditioning sequence 140 is applied after the end of the neural stimulation sequence 130, particularly in the form of an amplitude ramp 146 constituting a decrease in amplitude / intensity over time.

[0109] As can be seen from the corresponding responses of the neural structures 160, the onset response 162 can be limited / reduced by the (pre-)conditioning sequences 140;146.

[0110] Furthermore, (post) conditioning sequences 140;146 applied after termination of the neural stimulation sequence 130 may also reduce / limit the offset response 164 along with the response of the neural structures 160.

[0111] The conditioning sequence 140 in the form of an amplitude ramp 146 may be capable of reducing the onset and offset responses 162; 164 to smooth the overall application of the neural stimulation sequence 130, such as the application of HFAC.

[0112] In FIG. 4, a combination of an amplitude ramp 146 and a frequency ramp 144 is applied as a conditioning sequence 140 before and / or after the neural stimulation sequence 130 .

[0113] In particular, prior to the neural stimulation sequence 130, both the amplitude and frequency are increased during conditioning sequences 140;144;146 over a period of 25-50 ms, preferably to the frequency and amplitude of the subsequent neural stimulation sequence 130.

[0114] As can be seen from the respective responses of the neural structures 160, the onset response 162 is limited in both embodiments as shown in Figure 4. Furthermore, if a corresponding conditioning sequence 140 is applied after the neural stimulation sequence 130, the offset response 164 may also be limited.

[0115] 5 and 6 show a comparison of configurations of the neurostimulator device 110 according to various embodiments of the system 100.

[0116] FIG. 5 shows three different embodiments (top, middle, bottom) of configurations of the neurostimulator device 110 of the system 100.

[0117] The three embodiments differ from each other with respect to the respective amounts of stimulation means 112 that can form the stimulation array 114 .

[0118] According to FIG. 5, the stimulation means 112 are arranged along the neural structure 200 .

[0119] In particular, FIG. 5 may, for example, generally illustrate the placement of a nerve cuff for the PNS.

[0120] Preferably, the stimulation means 112 of FIG. 5 may be provided in the form of a coil.

[0121] Alternatively, the stimulation means 112 may be provided in the form of an electrode, for example as a (rod-shaped) nerve stimulation electrode.

[0122] A single stimulation means 112 may be provided with different polarities in order to shape the electric field potential and / or the second spatial derivative 170 of the electric field and / or potential along the neural structure 200 parallel and / or non-parallel to the neural structure (see middle and top diagrams of FIG. 5 ).

[0123] Furthermore, weighting factors 150 may be applied for shaping the electric field potentials and / or second spatial derivatives 170 of the electric fields and / or potentials parallel and / or non-parallel to the neural structures, preferably applied by the control device to the stimulation signals forwarded to the respective stimulation means 112 for delivering neural stimulation pulses 132 to the neural structures 200.

[0124] For example, application of weighting factors 150 can provide area-dependent shaping.

[0125] By designing the neurostimulation device 110, in particular the stimulation means 112 forming a specific stimulation array 114, and / or by the control device providing specifically adapted stimulation signals, for example by application of weighting factors 150, the electric field (lines) can be shaped and adapted to the neural structures 200.

[0126] This can be inferred in particular from the respective curves of the field potential 170 for the various embodiments according to FIG.

[0127] The top embodiment of FIG. 5 comprises a single stimulation means 112 with a positive electrical potential, thereby producing a unipolar anodal phase of the field potential.

[0128] The middle embodiment of FIG. 5 comprises two stimulation means 112 with different polarity, thereby generating a bipolar field potential with an anodal and a cathodal phase.

[0129] The bottom embodiment of FIG. 5 comprises multiple stimulators 112 of positive polarity with different weighting factors 150, thereby producing a relatively constant anodic phase along the length of the neural structure 200.

[0130] Alternatively, time-wise application of the weighting factors 150 can provide time-dependent shaping.

[0131] As a further alternative, time-dependent shaping may be achieved by producing / providing a step-by-step (re)orientation of the electric field potentials and / or second spatial derivatives of the electric fields and / or potentials parallel and / or non-parallel to the neural structures, preferably in successively different directions.

[0132] FIG. 6 shows a cross-section of one embodiment, with reference to a nerve cuff (bottom left diagram of FIG. 6) and electrode placement (bottom right diagram of FIG. 6) for such a neurostimulator device 110.

[0133] Additionally, FIG. 6 also shows the distribution of the neurostimulation device 110 along the neural structure 200 (middle image in FIG. 6) as well as the corresponding second spatial derivatives of the electrical potential parallel and / or non-parallel to the neural structure 200 (top image in FIG. 6).

[0134] The nerve stimulation device 110 of FIG. 6 surrounds a number of different nerve fibers 200 .

[0135] The nerve cuff embodiment of the nerve stimulation device 110 (left diagram in FIG. 6) shows a stimulation means 112 in the form of a coil.

[0136] The nerve stimulation means 112 has the same positive potential along its periphery.

[0137] For example, a neural electrode embodiment of the neurostimulator device 110 comprises a number of electrodes as stimulation means 112 distributed along the entire circumference of the neurostimulator device 110 .

[0138] The stimulating means 112 forms a stimulus array 114 .

[0139] The polarity of the single stimulation means 112 can be controlled / varied so that different electrical potentials can be applied along the circumference of the neurostimulator device 110 .

[0140] According to FIG. 6, the weighting factor 150 applied to each stimulus means may be one.

[0141] As can be further seen from the second spatial derivative potential plot in FIG. 6 (top plot), the two embodiments generate different potentials along the neural structure 200.

[0142] The embodiment referencing a nerve cuff having multiple coils as the stimulation means 112 (left diagram in FIG. 6) produces a biphasic potential along the neural structure 200, while the electrode configuration of the neural stimulation device 110 produces a monophasic potential along the neural structure 200, similar to the neural stimulation electrode (right diagram in FIG. 6).

[0143] In this manner, the shape and configuration of the neurostimulator device 110 and the individual shaping of the stimulation signal by the control device, e.g., by using weighting factors 150, enable the individualization of electrical potentials along the neural structure 200 in an area-dependent and / or time-dependent manner, for example to achieve limiting / reducing onset / offset responses in the context of HFAC application to provide a nerve block.

[0144] In summary, the system 100 according to the present invention can provide high variability in the application of high or low frequency neural stimulation (sequences) 130, which can limit / reduce uncontrolled neural responses in the onset response 162 and / or offset response 164 and / or overshoot response.

[0145] In particular, a conditioning sequence 140 may be applied before and / or after a nerve stimulation (sequence) 130, such as HFAC to achieve a nerve block, to reduce / limit the response of neural structures 160;200.

[0146] Such conditioning sequences 140 may be provided in a variety of ways, for example in the form of a pre-pulse 142, a frequency ramp 144, or an amplitude ramp 146. Additionally, a combination of such measures may be provided.

[0147] Furthermore, the onset / offset responses 162;164 of nerves / nerve structures / fibers 200 may also be limited / reduced by the specific design of the neurostimulation device 110, particularly with regard to the configuration of the stimulation means 112 in the form of a stimulation array 114, and / or by the control unit providing a stimulation signal that is amplified based on a weighting factor 150.

[0148] In this way, the present invention also enables inherent shaping of the field potential and / or the second spatial derivative 170 of the field and / or potential parallel and / or non-parallel to neural structures along the extension of the stimulation device 110 having at least one stimulation means 112. [Explanation of symbols]

[0149] 100 Systems 110 Neurostimulatory Devices 112 Stimulation means 114 Stimulus Array 130 Nerve Stimulation (Sequence) 132 Nerve Stimulation Pulse 140 (Pulse) Conditioning Sequence 142 Pre-pulse (sequence) 144 Frequency Ramp 146 Amplitude Ramp 150 Weighting Factor 160 Response of neural structures 162 Onset Response 164 Offset Reaction 170 Second spatial derivative of electric field potentials / fields / potentials parallel and / or non-parallel to neural structures 200 Neural Structure

Claims

1. A system for peripheral nerve stimulation for shaping the electric field potential and / or the electric field and / or the second spatial derivative of the potential that is parallel and / or non-parallel to the nerve structure, comprising: at least one nerve stimulation device having at least one stimulation means, preferably a plurality of stimulation means forming a stimulation array, and a control device; the control device is configured to provide a nerve stimulation, in particular a nerve stimulation sequence comprising a plurality of consecutive nerve stimulation pulses, to the nerve structure via the nerve stimulation device; the control device is further configured to provide and apply, via the nerve stimulation device, a conditioning sequence having at least one pulse to the nerve structure before and / or after the application of the nerve stimulation; the conditioning sequence is configured to be able to limit the onset response and / or the offset response and / or the nerve response overshoot by the nerve structure. A system.

2. The control device is: - a pre-pulse sequence comprising at least one pre-pulse, preferably a combination of a plurality of pre-pulses having the same or different time delays as the nerve stimulation; - a frequency ramp; - a frequency ramp combined with an amplitude ramp; - a frequency ramp combined with the at least one pre-pulse, preferably a pre-pulse sequence; - at least one pre-pulse, preferably a pre-pulse sequence, combined with an amplitude ramp; - a combination of the at least one pre-pulse, preferably a pre-pulse sequence, an amplitude ramp, and a frequency ramp The system according to claim 1, characterized in that it is configured to provide the conditioning sequence including at least one of them.

3. The conditioning sequence is configured to shape the electric field potential and / or the electric field and / or the second spatial derivative of the potential that is parallel and / or non-parallel to the nerve structure, the shaping by the conditioning sequence is individualized for different spatial areas along the extension of the nerve structure, and / or The shaping by the conditioning sequence is provided, preferably in a first step in a first spatial direction and in a second step in a second spatial direction, depending on time, for the system according to claim 1 or 2.

4. The conditioning sequence can preferably include at least one variable parameter for forming a ramp function, preferably a frequency ramp function and / or an amplitude ramp function, and further stimulation parameters of the conditioning sequence are at least equivalent to, preferably similar to, the nerve stimulation, for the system according to claim 1 or 2.

5. The conditioning sequence, preferably referring to a frequency ramp function and / or an amplitude ramp function, is configured to deviate from the nerve stimulation with respect to being applied with - a sine wave, single-phase, or biphasic waveform, - different pulse widths, - different amplitudes, and / or - different inter-pulse intervals so as to have a waveform similar to the nerve stimulation, for the system according to claim 1 or 2.

6. The nerve stimulation sequence is - high-frequency alternating current provided to the nerve structure to realize a high-frequency block of the nerve structure, or - low-frequency stimulation provided to the nerve structure, particularly for nerve modulation for the system according to claim 1 or 2.

7. The nerve stimulation device comprises at least one stimulation means configured such that the nerve stimulation provided through the at least one stimulation means can be adapted along the nerve structure, for the system according to claim 1 or 2.

8. The at least one stimulation means is adaptable by changing the design of the nerve stimulation device, particularly the shape, the configuration of the stimulation array, and / or the like, for the system according to claim 7.

9. The control device is configured to provide individual stimulation signals to each of the plurality of stimulation means such that the nerve stimulation provided to the nerve structure through the plurality of stimulation means can be shaped along the extension of the nerve stimulation device, for the system according to claim 1 or 2.

10. The control device is configured to shape the nerve stimulation along the extension of the nerve stimulation device by applying a weighting factor to the stimulation signal to provide an individual stimulation signal to each of the plurality of stimulation means, the system according to claim 9.

11. The nerve stimulation device is an implantable pulse generator or a transcutaneous stimulation device, particularly a skin patch or the like, the system according to claim 1 or 2.

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