NEUROMODULATION SYSTEM FOR PLANNING AND/OR ADJUSTING AND/OR PROVIDING A NEUROMODULATION THERAPY

Abstract

A neuromodulation system for planning, adjusting, and providing a neuromodulation therapy, comprising: at least one neuromodulation means configured to provide neuromodulation at least partially by means of neurostimulation; at least one neuromodulation controller configured to control the neuromodulation means, wherein the neuromodulation controller is further configured to control the neuromodulation means at the beginning of a neuromodulation action including neurostimulation that the neurostimulation comprises a starting sequence and/or at the end of a neuromodulation action including neurostimulation that the neurostimulation comprises an ending sequence.

Claims

1. A neuromodulation system for planning and/or adjusting and/or providing a neuromodulation therapy, comprising: at least one neuromodulation means configured to provide neuromodulation at least partially by means of neurostimulation; at least one neuromodulation controller configured to control the neuromodulation means, wherein the neuromodulation controller is further configured to control the neuromodulation means at the beginning of a neuromodulation action including neurostimulation that the neurostimulation comprises a starting sequence and/or at the end of a neuromodulation action including neurostimulation that the neurostimulation comprises an ending sequence.

2. The neuromodulation system according to claim 1, wherein the neurostimulation comprises stimulation parameters, wherein the stimulation parameters comprise power, amplitude, current, voltage, pulse width, frequency and/or duration.

3. The neuromodulation system according to claim 2, wherein at least one stimulation parameter of the starting sequence and/or ending sequence has a lower level compared to the at least one stimulation parameter of the normal stimulation.

4. The neuromodulation system according to claim 1, wherein at least one stimulation parameter is increased during the starting sequence and/or decreased during the ending sequence.

5. The neuromodulation system according to claim 4, wherein the increase the at least one stimulation parameter is a linear, non-linear, exponential, polynomic and/or stepwise increase and that the decrease of the at least one stimulation parameter is a linear, non-linear, exponential, polynomic and/or stepwise decrease.

6. The neuromodulation system according to claim 1, wherein the starting sequence includes a pre-pulse (PP), wherein at least one stimulation parameter of the pre-pulse (PP) is of a lower level compared to the at least one stimulation parameter of a normal stimulation pulse.

7. The neuromodulation system according to claim 1, wherein the starting sequence and/or the ending sequence includes a pulse ramping.

8. The neuromodulation system according to claim 7, wherein the pulse ramping includes a ramping up from a starting level of at least one stimulation parameter to a higher level of the at least one stimulation parameter used for the neurostimulation and/or a ramping down from a level of at least one stimulation parameter used for the neurostimulation to a lower level of the at least one stimulation parameter, below the threshold used for neurostimulation.

9. The neuromodulation system according to claim 1, wherein the level of at least one stimulation parameter of the starting sequence and ending sequence is determined manually and/or automatically based on response data.

10. The neuromodulation system according to claim 1, wherein the neuromodulation is planned to be provided and/or provided to a spatial area of a patient, wherein the spatial area during the starting sequence and/or ending sequence is limited compared to the spatial area during the stimulation after the starting sequence and/or before the ending sequence.

11. The neuromodulation system according to claim 1, wherein the starting sequence and/or ending sequence comprises a pre-warning signal and stop-warning signal.

12. The neuromodulation system according to claim 11, wherein the pre-warning signal and/or stop-warning signal is an acoustic, visual, haptic, electrical, sensory and/or temperature signal.

13. The use of a system for planning, adjusting, and providing a neuromodulation therapy according to claim 1 in a method for the treatment of a patient suffering from at least one of a spinal cord injury, stroke, traumatic injury, Parkinson disease, cerebral palsy, multiple sclerosis, autonomic failure, autonomic neuropathy, and cancer of the neurological tissue.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0059] The drawings are not necessarily to scale or exhaustive. Instead, emphasis is generally placed upon illustrating the principles of the inventions described herein. The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments consistent with the disclosure and together with the description, serve to explain the principles of the disclosure. In the drawings:

[0060] FIG. 1 depicts a schematical illustration of a response to stimulation with a neurostimulation system as known in the prior art, without a starting sequence according to the present invention;

[0061] FIG. 2 depicts a schematical overview of an embodiment of the neuromodulation system for planning and/or adjusting and/or providing a neuromodulation therapy, according to the present invention;

[0062] FIG. 3 depicts an example of a starting sequence including a pre-pulse according to the present invention;

[0063] FIG. 4 depicts an example of a starting sequence including pulse ramping, according to the present invention;

[0064] FIG. 5 depicts an example of responses to a starting sequence including pulse ramping followed by responses to a standard stimulation pulse train at a fixed frequency and constant amplitude, according to the present invention;

[0065] FIG. 6 depicts examples of responses to pre-pulses of different amplitude, followed by responses to a standard stimulation block (pulse train) at a fixed frequency and constant amplitude, according to the present invention;

[0066] FIG. 7 depicts further examples of responses to pre-pulses of different amplitude, followed by responses to a standard stimulation block (pulse train) at a fixed frequency and constant amplitude, according to the present invention;

[0067] FIG. 8a depicts examples of responses to two subsequent pre-pulses separated by a time interval of 25 ms and of different amplitude, according to the present invention;

[0068] FIG. 8b depicts examples of responses to two subsequent pre-pulses separated by a time interval of 50 ms and of different amplitude, according to the present invention;

[0069] FIG. 9 depicts examples of responses to ramping over two pulses, followed by responses to a standard stimulation block (pulse train) at a fixed frequency and constant amplitude, according to the present invention;

[0070] FIG. 10 depicts further examples of responses to ramping over two pulses, followed by responses to a standard stimulation block (pulse train) at a fixed frequency and constant amplitude, according to the present invention;

[0071] FIG. 11 depicts examples of responses to ramping over one to six pulses, followed by responses to a standard stimulation block (pulse train) at a fixed frequency and constant amplitude, according to the present invention;

[0072] FIG. 12 depicts a further example of responses to stimulation according to the present invention that have been measured by EMG; and

[0073] FIG. 13 depicts an example of responses to a standard stimulation block (pulse train) at a fixed frequency and constant amplitude, measured by a goniometer, without and with ramping up.

DETAILED DESCRIPTION

[0074] Reference will now be made in detail to exemplary embodiments, discussed with regards to the accompanying drawings. In some instances, the same reference numbers will be used throughout the drawings and the following description to refer to the same or like parts. Unless otherwise defined, technical or scientific terms have the meaning commonly understood by one of ordinary skill in the art. The disclosed embodiments are described in sufficient detail to enable those skilled in the art to practice the disclosed embodiments. It is to be understood that other embodiments may be utilized and that changes may be made without departing from the scope of the disclosed embodiments. Thus, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0075] FIG. 1 shows schematical illustration of a response to stimulation with a neurostimulation system as known in the prior art, without a starting sequence according to the present invention. An abnormal initial response is observed, measured by e.g. EMG, after stimulation provided by a neurostimulation system.

[0076] FIG. 2 shows a schematical overview of an embodiment of the neuromodulation system 10 for planning and/or adjusting and/or providing a neuromodulation therapy, according to the present invention.

[0077] The system 10 shall reduce and/or eliminate abnormal initial responses to neuromodulation/neurostimulation e.g. as disclosed in FIG. 1. The system 10 comprises a neuromodulation means 12. In general, the system 10 could comprise more than one neuromodulation means 12. In this embodiment, the system 10 further comprises a neuromodulation controller 14. In general, the system 10 could comprise more than one neuromodulation controller 14. In this embodiment, the neuromodulation means 12 and the neuromodulation controller 14 are connected. The connection between the neuromodulation means 12 and the neuromodulation controller 14 is a direct connection. Alternatively, the connection between the neuromodulation means 12 and the neuromodulation controller 14 could be an indirect connection. In this embodiment, the connection between the neuromodulation means 12 and the neuromodulation controller 14 is a bidirectional connection.

[0078] Alternatively, the connection between the neuromodulation means 12 and the neuromodulation controller 14 could be a unidirectional connection (from the neuromodulation means 12 to the neuromodulation controller 14 or vice versa). In this embodiment, the connection between the neuromodulation means 12 and the neuromodulation controller 14 is a wireless connection. Alternatively, the connection between the neuromodulation means 12 and the neuromodulation controller 14 could be a cable-bound connection.

[0079] In a system 10 comprising more than one neuromodulation means 12 and/or more than one neuromodulation controller 14, several neuromodulation means 12 and/or several neuromodulation controllers 4 could be connected. In this embodiment, the neuromodulation means 12 provides neuromodulation by means of neurostimulation. In an alternative embodiment, the neuromodulation means 12 could provide neuromodulation partially by means of neurostimulation. In this embodiment, the neurostimulation means 12 provides neurostimulation to a patient. In this embodiment, the neurostimulation comprises a starting sequence.

[0080] Alternatively, and/or additionally, the neurostimulation could comprise an ending sequence. In this embodiment, the neurostimulation means 12 provides neurostimulation to a patient during a neuromodulation action. In this embodiment, the neuromodulation means 14 controls the neurostimulation means 12.

[0081] Further, the neuromodulation controller 14 controls the neuromodulation means 12 at the beginning of a neuromodulation action including neurostimulation that the neurostimulation comprises a starting sequence.

[0082] Alternatively, and/or additionally, the neuromodulation controller 14 could control the neuromodulation means 12 at the end of a neuromodulation action including neurostimulation that the neurostimulation comprises an ending sequence.

[0083] In general, the neurostimulation could comprise stimulation parameters, wherein the stimulation parameters comprise power, amplitude, current, voltage, pulse width, frequency and/or duration. Alternatively and/or additionally, the neuromodulation could be planned to be provided and/or provided to a spatial area of a patient, wherein the spatial area during the starting sequence and/or ending sequence is limited compared to the spatial area during the stimulation after the starting sequence and/or before the ending sequence. The starting sequence and/or ending sequence could comprise a pre-warning signal and/or stop-warning signal. The pre-warning signal and/or stop-warning signal could be an acoustic, visual, haptic, electrical, sensory and/or temperature signal.

[0084] In general, the level of at least one stimulation parameter of the starting sequence (and/or an ending sequence) could be determined manually and/or automatically based on response data. In this embodiment, the starting sequence includes a pre-pulse PP, cf. FIG. 3. The pre-pulse PP is delivered X ms before the stimulation block SB, comprising several pulses. In other words, one pre-pulse PP is delivered X ms before the stimulation block SB, is delivered. In general, a pre-pulse PP could be delivered X time units before the stimulation block SB.

[0085] In general, the starting sequence can include a pre-pulse PP, wherein at least one stimulation parameter of the pre-pulse PP is of a lower level compared to the at least one stimulation parameter of a normal stimulation pulse. In this embodiment, the starting sequence includes a pre-pulse PP, wherein the pre-pulse PP is less powerful (less amplitude) than a normal stimulation pulse (X percent of the amplitude of the normal stimulation pulses of the stimulation block SB).

[0086] In general, at least one stimulation parameter of the starting sequence and/or ending sequence could have a lower level compared to the at least one stimulation parameter of the normal stimulation.

[0087] Alternatively, the amplitude of the pre-pulse PP could be 100% percent of the amplitude of the pulses of the stimulation block SB. In general, the parameters of the pre-pulse PP are the time interval between the pre-pulse PP and the stimulation block SB and/or its amplitude. It could be generally possible, that the parameters of the pre-pulse comprise pulse width of the pre-pulse.

[0088] Alternatively, the starting sequence could include a pulse ramping, wherein the pulse ramping includes a ramping up from a starting pulse energy level to a higher pulse energy level being used for the neurostimulation, cf. FIG. 4. In this embodiment, the first N pulses are linearly increasing in amplitude, as a percentage of the amplitude stimulation block SB amplitude.

[0089] In general, the increase of at least one stimulation parameter could be a linear, non-linear, exponential, polynomic and/or stepwise increase. In this embodiment, the starting sequence is comprised in the stimulation block SB. However, in an alternative embodiment, the starting sequence could be not comprised in the stimulation block SB. However, in an alternative embodiment, a non-linear increasing in the amplitude of the pulses of the ramping sequence could be generally possible. In this embodiment, the amplitude of the first N pulses increases from 55% to 70% to 85% of the amplitude of the stimulation block. However, in an alternative embodiment, any other increase (linear or non-linear, in percentage of the amplitude of the stimulation block) could be possible. In other words, the amplitude of pulses is progressively increased over N pulses. In general, the amplitude of pulses could progressively increase.

[0090] It could be generally possible, that the starting sequences includes both, a pre-pulse PP as disclosed in FIG. 3 and a ramping as disclosed in FIG. 4, wherein the pre-pulse PP is either provided before the ramping or after the ramping.

[0091] Additionally, and/or alternatively, there could be an ending sequence. At least one stimulation parameter could be decreased during the ending sequence. Additionally, and/or alternatively to the ramping up, a ramping down from a level of at least one stimulation parameter used for the neurostimulation to a lower level of the at least one stimulation parameter, below the threshold used for neurostimulation, could be possible.

[0092] In general, the starting sequence and/or the ending sequence can include a pulse ramping. In general, at least one stimulation parameter could be increased during the starting sequence and/or decreased during the ending sequence. There could be a linear, non-linear, exponential, polynomic and/or stepwise decrease of at least one stimulation parameter in an ending sequence. In this embodiment, the system 10 for planning and/or adjusting and/or providing a neuromodulation therapy is used in a method for the treatment of a patient. In this embodiment, the system 10 for planning and/or adjusting and/or providing a neuromodulation therapy is used in a method for the treatment of a patient suffering from spinal cord injury.

[0093] Alternatively, and/or additionally, the system 10 could be used in a method for the treatment of a patient suffering from stroke, traumatic injury, Parkinson disease, cerebral palsy, multiple sclerosis, autonomic failure, autonomic neuropathy and/or cancer of the neurological tissue.

[0094] FIG. 5 shows an example of responses to a starting sequence including pulse ramping followed by responses to a standard stimulation pulse train at a fixed frequency and constant amplitude, measured by EMG. In this embodiment, a patient is stimulated with the system 10 disclosed in FIG. 2. In this embodiment, the starting sequence includes a pulse ramping, wherein the pulse ramping includes a ramping up from a starting pulse energy level to a higher pulse energy level being used for the neurostimulation (amplitude of 1.5 mA). In general, any other amplitude(s) usually applied for neuromodulation could be possible. The amplitude, which could be understood as pulse energy level, is continuously increasing during ramping from the starting pulse to the amplitude used during stimulation.

[0095] The one skilled could understand that the initial stimulation causes a shock-like situation for the muscle targeted, as the first response to the first stimulation pulse is high compared to the following pulses.

[0096] FIG. 6 shows examples of responses to pre-pulses of different amplitude, followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude, measured by EMG. In particular, responses to a single pre-pulse PP at an amplitude of 0.0 mA, 0.8 mA, 0.9 mA, 1.0 mA, 1.1 mA, 1.2 mA, 1.3 mA, 1.4 mA, and 1.5 mA, followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude of 1.5 mA, measured by EMG, are shown. In this embodiment, the right tibialis anterior TA was targeted by neurostimulation with the system 10 according to FIG. 2. In this embodiment, the responses of stimulation were measured by EMG at the right tibialis anterior TA. In this embodiment, the pre-pulse PP was set 25 ms before the stimulation block SB (pulse train). However, any other time interval between the pre-pulse PP and the stimulation block sB could be generally possible. In this embodiment, a stimulation at 1.1 mA (corresponding to 73% of the target amplitude) shows the optimal result (maximal suppression of overshoot).

[0097] FIG. 7 shows further examples of responses to pre-pulses PP of different amplitude, followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude, measured by EMG. In particular, responses to a single pre-pulse PP at an amplitude of 0.0 mA, 0.8 mA, 0.9 mA, 1.0 mA, 1.1 mA, 1.2 mA, 1.3 mA, 1.4 mA, and 1.5 mA, followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude of 1.5 mA, measured by EMG, are shown. In this embodiment, the right tibialis anterior TA was targeted by neurostimulation with the system according to FIG. 2. In this embodiment, the responses of stimulation were measured by EMG at the right medial gastrocnemius MG. In this embodiment, the pre-pulse was set 25 ms before the stimulation block SB (pulse train). However, any other time interval (seconds or milliseconds) between the pre-pulse PP and the stimulation block SB could be generally possible. In this embodiment, a stimulation at 0.9 mA (corresponding to 60% of the target amplitude) shows the optimal result (maximal suppression of overshoot). In this embodiment, this results in an almost complete suppression of the third pulse (2 pulses after pre-pulse). In this embodiment, the optimal amplitude for the target muscle (1.1 mA) already leads to a relatively large overshoot.

[0098] FIG. 8a shows examples of responses to two subsequent pre-pulses PP separated by a time interval of 25 ms and of different amplitude, measured by EMG. In particular, responses to a two subsequent pre-pulse PP with an amplitude of 0.0 mA, 0.8 mA, 0.9 mA, 1.0 mA, 1.1 mA, 1.2 mA, 1.3 mA, 1.4 mA, and 1.5 mA, measured by EMG, are shown. In this embodiment, the right tibialis anterior TA was targeted by neurostimulation with the system 10 according to FIG. 2. In this embodiment, the responses of stimulation were measured by EMG at the right tibialis anterior TA, the right soleus and the right medial gastrocnemius MG. In this embodiment, the time interval between the two pre-pulses PP was set at 25 ms. The response to the first pre-pulse PP is indicated by the dashed line. The response to the second pre-pulse PP is indicated by the solid line. However, any other time interval between the two pre-pulses PP could be generally possible. The optimum amplitude for the pre-pulse PP is at the crossing of the two lines, where response due to first pre-pulse PP is equal to the response due to the second pre-pulse PP. In this embodiment, different muscles respond best to different amplitudes and the optimal amplitude changes with the timing of the pre-pulse PP.

[0099] FIG. 8b shows examples of responses to two subsequent pre-pulses PP separated by a time interval of 50 ms and of different amplitude, measured by EMG. In particular, responses to a two subsequent pre-pulses PP with an amplitude of 0.0 mA, 0.7 mA, 0.8 mA, 0.9 mA, 1.0 mA, 1.1 mA, 1.2 mA, 1.3 mA, 1.4 mA, and 1.5 mA, measured by EMG, are shown. In this embodiment, the right tibialis anterior TA was targeted by neurostimulation with the system 10 according to FIG. 2. In this embodiment, the responses to stimulation were measured by EMG at the right tibialis anterior TA, the right soleus and the right medial gastrocnemius MG. In this embodiment, the time interval between the two pre-pulses PP was set at 50 ms. However, any other time interval (seconds or milliseconds) between the two pre-pulses could be generally possible. The response to the first pre-pulse PP is indicated by the dashed line. The response to the second pre-pulse PP is indicated by the solid line. The optimum amplitude for the pre-pulse PP is at the crossing of the two lines, where response due to first pre-pulse PP is equal to the response due to the second pre-pulse PP. In this embodiment, different muscles respond best to different amplitudes and the optimal amplitude changes with the timing of the pre-pulse PP.

[0100] FIG. 9 shows examples of responses to ramping over two pulses, followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude, measured by EMG. In this embodiment, responses to ramping over two pulses (first pulse of ramping with an amplitude of 0.7 mA, 0.8 mA, 0.9 mA, 1.0 mA, 1.1 mA, 1.2 mA, 1.3 mA, or 1.4 mA; second pulse of ramping with an amplitude of 1.3 mA), followed by responses to a standard stimulation block (SB pulse train) at a fixed frequency and constant amplitude of 1.5 mA, measured by EMG, are shown. In this embodiment, the right tibialis anterior TA was targeted by neurostimulation with the system 10 according to FIG. 2. In this embodiment, the responses of stimulation were measured by EMG at the right tibialis anterior RTA. The first pulse must be sufficiently strong to have any effect (see upper plots). In case the amplitude of the first plot is too high it induces the same muscle response as an onset without ramps (see lower plots).

[0101] FIG. 10 shows further examples of responses to ramping over two pulses, followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude, measured by EMG. In this embodiment, responses to ramping over two pulses (first pulse of ramping with an amplitude of 0.9 mA, second pulse of ramping with an amplitude of 0.9 mA, 1.0 mA, 1.1 mA, 1.2 mA, 1.3 mA, 1.4 mA, or 1.5 mA), followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude of 1.5 mA, measured by EMG, are shown. In this embodiment, the right tibialis anterior TA was targeted by neurostimulation with the system 10 according to FIG. 2. In this embodiment, the responses of stimulation were measured by EMG at the right tibialis anterior RTA. The first pulse must be sufficiently strong to have any effect (see upper plots). If ramping pulses are chosen too close to each other (in amplitude), the first ramp pulse could lead to a suppression of the response to the 2nd ramp pulse and therefore cancel out the ramping effect (e.g. 3rd plot from the top). If the ramping pulses too far apart (in amplitude), the effect of the second pulse could be too strong (bottom plot).

[0102] FIG. 11 shows examples of responses to ramping over one to six pulses, followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude, measured by EMG. In this embodiment, responses to ramping over one two six pulses (first pulse of ramping with an amplitude of 0.9 mA, 1.0 mA, 1.1 mA, 1.2 mA, 1.3 mA, or 1.4 mA; second pulse of ramping with an amplitude of 1.0 mA, 1.1 mA, 1.2 mA, 1.3 mA, or 1.4 mA; third pulse of ramping with an amplitude 1.1 mA, 1.2 mA, 1.3 mA, or 1.4 mA, fourth pulse of ramping with an amplitude of 1.2 mA, 1.3 mA, or 1.4 mA; fifth pulse of ramping with an amplitude of 1.3 mA, or 1.4 mA; six pulse of ramping with an amplitude of 1.4 mA), followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude of 1.5 mA, measured by EMG, are shown. In this embodiment, the right tibialis anterior TA was targeted by neurostimulation with the system 10 according to FIG. 2. In this embodiment, the responses of stimulation were measured by EMG at the right tibialis anterior RTA. In this embodiment, it is started with six pulses of ramping (top) and then consequently one pulse is removed from the ramping sequence. Also, for multiple pulses, the correct choice of amplitude for the first pulse is essential to benefit from the ramps.

[0103] FIG. 12 shows a further example of responses to stimulation according to the present invention that have been measured by EMG. In this embodiment, the right tibialis anterior TA was targeted by neurostimulation with the system 10 according to FIG. 2. In this embodiment, the responses of stimulation were measured by EMG at the right tibialis anterior TA. On top of FIG. 12, responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude, measured by EMG, are shown, without ramping up. On the bottom of FIG. 12, responses to up-ramping with three pulses, followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude, measured by EMG, are shown. In particular, up-ramping with pulses of 55%, 70% and 85% of the amplitude of the pulses of the stimulation block are shown. Alternatively, up-ramping with three pulses of 40-60%, 60-80% and 80-100% of the amplitude of the pulses of the stimulation block SB could be generally possible. In this embodiment, the amplitude of the pulses of the stimulation block SB is 6.0 mA. However, in an alternative embodiment, the amplitude of the pulses of the stimulation block could be 0.2 mA to 200 mA. In this embodiment, the up-ramping sequence causes significant reduction of the initial response peak. In general, the up-ramping sequence may comprise two or more pulses.

[0104] The amplitude of the pulses of up-ramping (independent of the number of pulses of the up-ramping) may be of any amplitude lower or equal to the amplitude of the pulses of the stimulation block SB.

[0105] FIG. 13 shows responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude, measured by a goniometer, without and with ramping up. In FIG. 13, responses to stimulation according to the present invention are shown that have been measured by a goniometer. In this embodiment, the right tibialis anterior TA was targeted by neurostimulation with the system 10 according to FIG. 2. On top of FIG. 13, responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude are shown, without ramping up (no starting sequence). On the bottom of FIG. 13, responses to up-ramping with three pulses of, followed by responses to a standard stimulation block SB (pulse train) at a fixed frequency and constant amplitude, measured by EMG, are shown. In particular, up-ramping with pulses of 55%, 70% and 85% of the amplitude of the pulses of the respective stimulation block SB are shown. In general, the amplitude of the pulses of up-ramping may be of any amplitude lower or equal to the amplitude of the pulses of the stimulation block SB. In this embodiment, the up-ramping sequence causes significant reduction/elimination of the initial response peak (as illustrated in the bottom graph).

[0106] The foregoing descriptions have been presented for purposes of illustration. They are not exhaustive and are not limited to precise forms or embodiments disclosed. Modifications and adaptations of the embodiments will be apparent from consideration of the specification and practice of the disclosed embodiments. For example, the described implementations include hardware, but systems and methods consistent with the present disclosure can be implemented with hardware and software. In addition, while certain components have been described as being coupled to one another, such components may be integrated with one another or distributed in any suitable fashion.

[0107] Moreover, while illustrative embodiments have been described herein, the scope includes any and all embodiments having equivalent elements, modifications, omissions, combinations (e.g., of aspects across various embodiments), adaptations or alterations based on the present disclosure. The elements in the claims are to be interpreted broadly based on the language employed in the claims and not limited to examples described in the present specification or during the prosecution of the application, which examples are to be construed as nonexclusive. Further, the steps of the disclosed methods can be modified in any manner, including reordering steps or inserting or deleting steps.

[0108] It should be noted that, the relational terms herein such as “first” and “second” are used only to differentiate an entity or operation from another entity or operation, and do not require or imply any actual relationship or sequence between these entities or operations. Moreover, the words “comprising,” “having,” “containing,” and “including,” and other similar forms are intended to be equivalent in meaning and be open ended in that an item or items following any one of these words is not meant to be an exhaustive listing of such item or items, or meant to be limited to only the listed item or items.

[0109] The features and advantages of the disclosure are apparent from the detailed specification, and thus, it is intended that the appended claims cover all systems and methods falling within the true spirit and scope of the disclosure. As used herein, the indefinite articles “a” and “an” mean “one or more.” Similarly, the use of a plural term does not necessarily denote a plurality unless it is unambiguous in the given context. Further, since numerous modifications and variations will readily occur from studying the present disclosure, it is not desired to limit the disclosure to the exact construction and operation illustrated and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the disclosure.

[0110] As used herein, unless specifically stated otherwise, the terms “and/or” and “or” encompass all possible combinations, except where infeasible. For example, if it is stated that a database may include A or B, then, unless specifically stated otherwise or infeasible, the database may include A, or B, or A and B. As a second example, if it is stated that a database may include A, B, or C, then, unless specifically stated otherwise or infeasible, the database may include A, or B, or C, or A and B, or A and C, or B and C, or A and B and C.

[0111] It is appreciated that the above-described embodiments can be implemented by hardware, or software (program codes), or a combination of hardware and software. If implemented by software, it may be stored in the above-described computer-readable media. The software, when executed by the processor can perform the disclosed methods. The computing units and other functional units described in this disclosure can be implemented by hardware, or software, or a combination of hardware and software. One of ordinary skill in the art will also understand that multiple ones of the above-described modules/units may be combined as one module/unit, and each of the above-described modules/units may be further divided into a plurality of sub-modules/sub-units.

[0112] In the foregoing specification, embodiments have been described with reference to numerous specific details that can vary from implementation to implementation. Certain adaptations and modifications of the described embodiments can be made. Other embodiments can be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims. It is also intended that the sequence of steps shown in figures are only for illustrative purposes and are not intended to be limited to any particular sequence of steps. As such, those skilled in the art can appreciate that these steps can be performed in a different order while implementing the same method.