Patent Description:
Implantable electrical stimulation systems have proven therapeutic in a variety of diseases and disorders. For example, spinal cord stimulation systems have been used as a therapeutic modality for the treatment of chronic pain syndromes. Peripheral nerve stimulation has been used to treat chronic pain syndrome and incontinence, with a number of other applications under investigation. Deep brain stimulation can be used to treat a variety of diseases and disorders.

Stimulators have been developed to provide therapy for a variety of treatments. A stimulator can include a control module (with a pulse generator) and one or more stimulator electrodes. The one or more stimulator electrodes can be disposed along one or more leads, or along the control module, or both. The stimulator electrodes are in contact with or near the nerves, muscles, or other tissue to be stimulated. The pulse generator in the control module generates electrical pulses that are delivered by the electrodes to body tissue.

<CIT> discloses a method and system of providing therapy to a patient implanted with an array of electrodes. A train of electrical stimulation pulses is conveyed within a stimulation timing channel between a group of the electrodes to stimulate neural tissue, thereby providing continuous therapy to the patient. Electrical parameter is sensed within a sensing timing channel using at least one of the electrodes, wherein the first stimulation timing channel and sensing timing channel are coordinated, such that the electrical parameter is sensed during the conveyance of the pulse train within time slots that do not temporally overlap any active phase of the stimulation pulses.

In the following any method of therapy or stimulation is not claimed and disclosed for illustrative purposes only.

The present invention relates to an electrical stimulation system that includes at least one electrical stimulation lead, each of the at least one electrical stimulation lead including a plurality of stimulation electrodes; and a processor coupled to the at least one electrical stimulation lead and configured to perform actions. The actions include directing delivery of at least one therapeutic waveform through at least one of the stimulation electrodes of the at least one electrical stimulation lead to tissue of a patient during each of a plurality of therapeutic periods; directing sensing of an electrical signal using at least one of the stimulation electrodes of the at least one electrical stimulation lead during each of a plurality of sensing periods, wherein the therapeutic periods alternate with the sensing periods; and directing delivery of at least one sensing waveform through at least one of the stimulation electrodes of the at least one electrical stimulation lead during at least one of the sensing periods, wherein the at least one sensing waveform is a biphasic waveform comprising a positive phase and a negative phase.

In at least some aspects, directing sensing includes, during at least one of the sensing periods, directing the sensing of the electrical signal without delivering a waveform through the stimulation electrodes.

In at least some aspects, directing sensing includes directing delivery of at least one sensing waveform through at least one of the stimulation electrodes of the at least one electrical stimulation lead during at least one of the sensing periods. In at least some aspects, parameters for the sensing waveform differ from parameters for the therapeutic waveform. In at least some aspects, directing delivery of at least one sensing waveform includes, for a set of consecutive sensing periods, directing delivery of the at least one sensing waveform from a different at least one electrode during each one of the sensing periods of the set. In at least some aspects, the sensing waveform is a biphasic waveform including a positive phase and a negative phase. In at least some aspects, the therapeutic waveform is a biphasic waveform comprising a positive phase and a negative phase and directing delivery of at least one therapeutic waveform and directing delivery of at least one sensing waveform comprises, for a pair of consecutive therapeutic and sensing periods, directing delivery of the therapeutic waveform during the therapeutic period with a first temporal order of the positive and negative phases of the therapeutic waveform and directing delivery of the sensing waveform during the sensing period with a second temporal order of the positive and negative phases of the sensing waveform that is opposite the first temporal order.

In at least some aspects, an amplitude of the sensing waveform is larger than an amplitude of the therapeutic waveform and a pulse width of the sensing waveform is shorter than a pulse width of the therapeutic waveform. In at least some aspects, the therapeutic periods are longer or shorter in time than the sensing periods.

Another aspect is an electrical stimulation system that includes at least one electrical stimulation lead, each of the at least one electrical stimulation lead including a plurality of stimulation electrodes; and a processor coupled to the lead and configured to perform actions, including: directing delivery of a first biphasic waveform through at least one of the stimulation electrodes of the at least one electrical stimulation lead to tissue of a patient, wherein the first biphasic waveform includes a first phase and a second phase which occurs after the first phase and is opposite in polarity to the first phase; directing sensing of a first electrical signal using at least one of the stimulation electrodes of the at least one electrical stimulation lead after delivery of the first biphasic waveform; after directing delivery of the first biphasic waveform, directing delivery of a second biphasic waveform through at least one of the stimulation electrodes of the at least one electrical stimulation lead to tissue of the patient, wherein the second biphasic waveform includes a third phase and a fourth phase which occurs after the third phase, wherein the third phase is opposite in polarity to both the first phase and the fourth phase; directing sensing of a second electrical signal using at least one of the stimulation electrodes of the at least one electrical stimulation lead after delivery of the second biphasic waveform; and combining the first and second electrical signals to reduce at least one artifact arising in the sensing of the first and second electrical signals.

In at least some aspects, the first and second biphasic waveforms are therapeutic waveforms. In at least some aspects, the first biphasic waveform is asymmetric. In at least some aspects, the first and second biphasic waveforms are the same except for temporal phase ordering. In at least some aspects, the actions further include scaling at least one of the first and second electrical signals prior to combining the first and second electrical signals. In at least some aspects, combining the first and second electrical signals includes adding or averaging the first and second electrical signals.

Yet another aspect is an electrical stimulation system that includes at least one electrical stimulation lead, each of the at least one electrical stimulation lead including a plurality of stimulation electrodes; and a processor coupled to the lead and configured to perform actions, including: a) directing delivery of a first waveform through at least one of the stimulation electrodes of the at least one electrical stimulation lead to tissue of a patient; b) directing sensing of a first electrical signal from the tissue using at least one of the stimulation electrodes of the at least one electrical stimulation lead after delivery of the first waveform; c) after directing delivery of the first waveform, directing delivery of a second waveform through at least one of the stimulation electrodes of the at least one electrical stimulation lead to tissue of the patient, wherein the first waveform differs from the second waveform in amplitude, pulse shape, pulse width, pulse period, electrode selection, or electrode fractionalization; d) directing sensing of a second electrical signal from the tissue using at least one of the stimulation electrodes of the at least one electrical stimulation lead after delivery of the second waveform; and e) using the first and second electrical signals to adjust at least one of the first waveform or the second waveform.

In at least some aspects, the first and second waveforms are therapeutic waveforms. In at least some aspects, the actions further include, after directing delivery of the first and second waveforms, directing delivery of a third waveform through at least one of the stimulation electrodes of the at least one electrical stimulation lead to tissue of the patient, wherein the third waveform differs from the first and second waveforms in amplitude, pulse shape, pulse width, pulse period, electrode selection, or electrode fractionalization; and directing sensing of a third electrical signal from the tissue using at least one of the stimulation electrodes of the at least one electrical stimulation lead after delivery of the third waveform.

In at least some aspects, the first and second waveforms are biphasic waveforms with a positive phase and a negative phase. In at least some aspects, the actions further include repeating steps a) to d) except reversing a temporal order of the positive phase and negative phase of the first and second waveforms.

Non-limiting and non-exhaustive embodiments of the present disclosure are described with reference to the following drawings. In the drawings, like reference numerals refer to like parts throughout the various figures unless otherwise specified.

The present disclosure is directed to the area of implantable electrical stimulation systems and methods of making and using the systems. The present disclosure is also directed to methods and systems for interleaving waveforms to provide electrical stimulation and measurement.

Suitable implantable electrical stimulation systems include, but are not limited to, a least one lead with one or more electrodes disposed on a distal portion of the lead and one or more terminals disposed on one or more proximal portions of the lead. Leads include, for example, percutaneous leads, paddle leads, cuff leads, or any other arrangement of electrodes on a lead. Examples of electrical stimulation systems with leads are found in, for example, <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>;<CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>; and <CIT>; <CIT>; <CIT>;<CIT>; <CIT>;<CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>;<CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>. In the discussion below, a percutaneous lead will be exemplified, but it will be understood that the methods and systems described herein are also applicable to paddle leads and other leads.

A percutaneous lead for electrical stimulation (for example, deep brain, spinal cord, or peripheral nerve stimulation) includes stimulation electrodes that can be ring electrodes, segmented electrodes that extend only partially around the circumference of the lead, or any other type of electrode, or any combination thereof. The segmented electrodes can be provided in sets of electrodes, with each set having electrodes circumferentially distributed about the lead at a particular longitudinal position. A set of segmented electrodes can include any suitable number of electrodes including, for example, two, three, four, or more electrodes. For illustrative purposes, the leads are described herein relative to use for spinal cord stimulation, but it will be understood that any of the leads can be used for applications other than spinal cord stimulation, including deep brain stimulation, peripheral nerve stimulation, dorsal root ganglion stimulation, sacral nerve stimulation, or stimulation of other nerves, muscles, and tissues.

Turning to <FIG>, one embodiment of an electrical stimulation system <NUM> includes one or more stimulation leads <NUM> and an implantable pulse generator (IPG) <NUM>. The system <NUM> can also include one or more of an external remote control (RC) <NUM>, a clinician's programmer (CP) <NUM>, an external trial stimulator (ETS) <NUM>, or an external charger <NUM>. The IPG and ETS are examples of control modules for the electrical stimulation system.

The IPG <NUM> is physically connected, optionally via one or more lead extensions <NUM>, to the stimulation lead(s) <NUM>. Each lead carries multiple electrodes <NUM> arranged in an array. The IPG <NUM> includes pulse generation circuitry that delivers electrical stimulation energy in the form of, for example, a pulsed electrical waveform (i.e., a temporal series of electrical pulses) to the electrode array <NUM> in accordance with a set of stimulation parameters. The implantable pulse generator can be implanted into a patient's body, for example, below the patient's clavicle area or within the patient's buttocks or abdominal cavity or at any other suitable site. The implantable pulse generator can have multiple stimulation channels which may be independently programmable to control the magnitude of the current stimulus from each channel. In some embodiments, the implantable pulse generator can have any suitable number of stimulation channels including, but not limited to, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or more stimulation channels. The implantable pulse generator can have one, two, three, four, or more connector ports, for receiving the terminals of the leads and/or lead extensions.

The ETS <NUM> may also be physically connected, optionally via the percutaneous lead extensions <NUM> and external cable <NUM>, to the stimulation leads <NUM>. The ETS <NUM>, which may have similar pulse generation circuitry as the IPG <NUM>, also delivers electrical stimulation energy in the form of, for example, a pulsed electrical waveform to the electrode array <NUM> in accordance with a set of stimulation parameters. One difference between the ETS <NUM> and the IPG <NUM> is that the ETS <NUM> is often a non-implantable device that is used on a trial basis after the neurostimulation leads <NUM> have been implanted and prior to implantation of the IPG <NUM>, to test the responsiveness of the stimulation that is to be provided. Any functions described herein with respect to the IPG <NUM> can likewise be performed with respect to the ETS <NUM>.

The RC <NUM> may be used to telemetrically communicate with or control the IPG <NUM> or ETS <NUM> via a uni- or bi-directional wireless communications link <NUM>. Once the IPG <NUM> and neurostimulation leads <NUM> are implanted, the RC <NUM> may be used to telemetrically communicate with or control the IPG <NUM> via a uni- or bi-directional communications link <NUM>. Such communication or control allows the IPG <NUM> to be turned on or off and to be programmed with different stimulation parameter sets. The IPG <NUM> may also be operated to modify the programmed stimulation parameters to actively control the characteristics of the electrical stimulation energy output by the IPG <NUM>. The CP <NUM> allows a user, such as a clinician, the ability to program stimulation parameters for the IPG <NUM> and ETS <NUM> in the operating room and in follow-up sessions. Alternately, or additionally, stimulation parameters can be programed via wireless communications (e.g., Bluetooth) between the RC <NUM> (or external device such as a hand-held electronic device) and the IPG <NUM>.

The CP <NUM> may perform this function by indirectly communicating with the IPG <NUM> or ETS <NUM>, through the RC <NUM>, via a wireless communications link <NUM>. Alternatively, the CP <NUM> may directly communicate with the IPG <NUM> or ETS <NUM> via a wireless communications link (not shown). The stimulation parameters provided by the CP <NUM> are also used to program the RC <NUM>, so that the stimulation parameters can be subsequently modified by operation of the RC <NUM> in a stand-alone mode (i.e., without the assistance of the CP <NUM>).

For purposes of brevity, the details of the RC <NUM>, CP <NUM>, ETS <NUM>, and external charger <NUM> will not be further described herein. Details of exemplary embodiments of these devices are disclosed in <CIT>. Other examples of electrical stimulation systems can be found at <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>; and <CIT>, as well as the other references cited above.

Knowledge and characterization of physiological response to stimulation, as well as the local stimulation environment around a lead or the electrodes of a lead, can provide useful information. For example, information can be determined regarding the activity, activity intensity, posture, or postural position of the patient or changes in activity, activity intensity, posture, or postural position of the patient; impedance, conductivity, or capacitance of the tissue near the lead or electrodes; a stimulation induced voltage distribution or current intensity; tissue charging or discharging characteristics; changes in the heart beat or respiration of the patient; or any other suitable electrical characteristics of the tissue. Changes in the local stimulation environment may be used to indicate, infer or determine patient posture or activity; may indicate the development, presence, or alterations in scar tissue or fluid around the lead or electrode; may indicate thickness of the fat tissue, thickness of the cerebral spinal fluid (for spinal cord stimulation systems); may indicate lead position in spinal canal, relative lead position or electrode position among multiple lead array; or the like or any combination thereof.

As described herein, electrodes of the lead(s) can be used to sense local electrical characteristics of the environment around the lead(s) and electrodes during and between electrical pulses or waveforms (which can be, for example, therapeutic stimulation pulses or waveforms, sub-perception pulses or waveforms, sensing pulses or waveforms, or other electrical pulses or waveforms). Sensing will be exemplified herein by the measurement of electrophysiological signals, such as ESG (electrospinogram) signals, received or detected at the electrode(s) used for sensing. It will be understood that electrical characteristics, such as electric field potential, current, resistance, or impedance, can be measured in addition to, or as an alternative to, the electrophysiological signals and that the description presented herein can be readily applied to these other electrical characteristics. It will also be understood that other electrophysiological signals, such as EEG (electroencephalogram), ECG (electrocardiogram), or EMG (electromyogram) signals can also be measured.

In addition to being dependent on the physical and electrical characteristics of the local tissue, the sensed signals can arise a variety of different electrical sources including, but not limited to, stimulation and other electrical pulses, evoked or spontaneous neural response, neural signals, heartbeat signals, respiration, patient activity (e.g., sleep, active, inactive, etc.), patient posture, and the like.

When sensing electrophysiological signals there may be difficulty extracting the physiological response from the sensed signals. This difficulty may arise for one or more reasons including, but not limited to, one or more of the following: <NUM>) the physiological response may not be elicited by the therapeutic stimulation parameters (for example, the stimulation may be at low sub-perception levels that may not always elicit and evoked neural response); <NUM>) the stimulation pulse width may overlap with the neural response; or <NUM>) the stimulation frequency may be sufficiently high that evoked neural responses are not always elicited or not visible. Moreover, stimulation artifacts can interfere with the sensed signals.

<FIG> illustrates an example of stimulation pulses according to a particular stimulation program and as executable by the IPG or ETS <NUM>. In this example, stimulation is provided by electrodes <NUM> and <NUM> (E4 and E5) of a lead and each stimulation waveform is biphasic, meaning that a first phase is quickly followed by an opposite polarity second phase. The pulse width (PW) can be the duration of either of the phases individually as shown, or can be the entire duration of the biphasic waveform including both phases (which may also be considered the period of the waveform). The frequency (f) and amplitude (A) of the waveform is also shown in <FIG>. Although not shown, monophasic waveforms--having only a first phase but not followed by an active-charge recovery second phase--can also be used. In addition, biphasic waveforms where the second phase is passive charge recovery are also useful. Multiphasic waveforms (e.g., triphasic and so forth) can be used.

At least some biphasic waveforms are useful because the second phase can actively recover any charge build up after the first phase residing on capacitances (such as the DC-blocking capacitors in the IPG or ETS) in the current paths between the active electrodes. In the example stimulation program shown in <FIG>, electrode E4 is selected as the anode electrode while electrode E5 is selected as the cathode electrode (during the first pulse phase). Because two electrodes <NUM> are used, this represents bipolar stimulation. The pulses as shown are pulses of constant current and the amplitude of the current at any point in time is equal but opposite such that current injected into the patient's tissue by one electrode (e.g., E4) is removed from the tissue by the other electrode (E5). The area of the first and second phases are equal, providing active charge recovery of the same amount of charge during each phase. Although not shown, more than two electrodes can be active at any given time to produce multipolar stimulation. For example, electrode E4 could comprise an anode providing a +<NUM> mA current pulse amplitude, while electrodes E3 and E5 could both comprise cathodes with -<NUM> mA and -<NUM> mA current pulse amplitudes respectively. Monopolar stimulation can utilize one electrode on the lead and a second electrode that is distant from the lead, such as the case of the IPG or an external electrode.

<FIG> illustrates one example of a neural response <NUM> or neural signal. When a neural fiber is recruited by electrical stimulation, it will issue an action potentialthat is, the neural fiber will "fire. " Should recruitment from electrical stimulation cause the neural fiber's resting state the neural fiber will depolarize, repolarize, and hyperpolarize before coming to rest again. If electrical stimulation continues, the neural fiber will fire again at some later time. <FIG> and <FIG> illustrate one examples of an evoked compound action potential (ECAP) which can be a cumulative response of neural fibers recruited and firing within a volume, as well as an artifact arising from a stimulation induced field potential. An ECAP's shape can be a function of the number and types of neural fibers that are recruited. The stimulation current was <NUM> mA in <FIG> and <NUM> mA in <FIG>.

Interleaving therapeutic and sensing periods can alleviate difficulties in sensing an electrophysiological response after the stimulation. Interleaving therapeutic and sensing periods can also be applied for sensing non-neural signals, such as artifacts arising from the applied waveform(s), or for sensing spontaneous neural signals or local field potentials.

<FIG> illustrate two examples of the temporal interleaving of therapeutic periods <NUM> and sensing periods <NUM>. As illustrated, the sensing periods <NUM> and therapeutic periods <NUM> alternate in a graph of time versus current. The length of time of the sensing periods <NUM> may be equal to, shorter than, or longer than the length of time of the therapeutic periods <NUM>. As an example, the therapeutic periods may have a length of <NUM> to <NUM> and the sensing period a length of <NUM> msec. It will be recognized that the length of the time of the sensing periods <NUM> can be uniform or can vary between sensing periods. Similarly, the length of time of the therapeutic periods <NUM> can be uniform or can vary between therapeutic periods.

The therapeutic stimulation during the therapeutic periods <NUM> can be provided using any suitable therapeutic waveform <NUM> or combination of waveforms. In <FIG>, the therapeutic waveform <NUM> is a repeated biphasic waveform with a positive phase 455a and a negative phase 455b. In the illustrated example, the therapeutic period includes four biphasic waveforms <NUM>, but it will be recognized that other embodiments can include therapeutic periods with any suitable number of waveforms and that the number of waveforms per therapeutic period can be uniform or can vary between therapeutic periods.

The therapeutic waveform <NUM> can be, for example, a tonic pulse waveform providing stimulation at any suitable frequency (for example, in range from <NUM> and <NUM>); a burst waveform with any suitable inter-burst frequency (for example, in a range from <NUM> to <NUM>) with a higher intra-burst frequency (for example in a range from <NUM> to <NUM>, <NUM>, <NUM>, or <NUM>) with two, three, four, five, six, or more pulses per burst; a sinewave; a modulated waveform; a sub-perception waveform (in which the stimulation is not perceived by the patient); or any other suitable waveform (utilizing any other suitable shape) or any combination of waveforms. Examples of some suitable waveforms are disclosed in <CIT>.

The therapeutic waveform <NUM> is delivered using one or more electrodes <NUM> of a lead <NUM> (<FIG>) or a combination of leads. The therapeutic waveform <NUM> can be bipolar (using two electrodes of the lead(s)), multipolar (using three or more electrodes of the lead(s)), or monopolar (using a single electrode of the lead(s) with a second electrode that is distant from the leads, such as the case of the IPG <NUM> or an external electrode disposed on the patient.

In <FIG>, a sensing waveform <NUM> can be used to elicit neural response during the sensing period <NUM>. The sensing waveform <NUM> can be any suitable waveform and can be delivered using monopolar, bipolar, or multipolar (using, respectively, one, two, or three or more of the electrodes <NUM> of one or more of the leads <NUM> (<FIG>). ) In the illustrated embodiment of <FIG>, the sensing waveform <NUM> is a single biphasic waveform that is temporally separated from the therapeutic waveform <NUM>. The sensing waveform <NUM> can include an active or passive recharge pulse Any other suitable waveform, or combination of waveforms, can be used as the sensing waveform <NUM> including, but not limited to, a short train of pulses with predefined fixed parameters that produce a neural response. In at least some embodiments, the sensing waveform can utilize the same parameters (for example, amplitude and pulse width) as the therapeutic waveform. In other embodiments, the sensing waveform uses one or more parameters (for example, amplitude, pulse shape, pulse width, pulse period, electrode selection, or electrode fractionalization) that are different in value from the therapeutic waveform. For example, the sensing waveform may utilize a larger amplitude, but shorter pulse width, as compared to the therapeutic waveform, as illustrated in <FIG>. In at least some embodiments, the sensing waveform can have a different shape from the therapeutic waveform (for example, a sinewave or other shape) or may be delivered using different electrode(s) or different electrode fractionalizations (i.e., the fraction of total current or voltage on each of the selected electrodes).

As another example, to enhance sensing of an artifact signal (arising, for example, from the therapeutic or sensing waveform, the sensing waveform can have a smaller amplitude than the therapeutic waveform to prevent the sensed artifact voltage from railing (i.e., saturating at the top). This artifact sensing period could also be alternated with sensing periods that utilize a sensing waveform to sensing the evoked neural response or other electrophysiological signal. In at least some embodiments, a closed loop system can utilize this arrangement to obtain information from sensed evoked signals and sensed artifact signals that can then be used to adjust the therapeutic periods or therapeutic waveform.

As illustrated in <FIG>, the sensing waveform delivered during the sensing period is interleaved with the therapeutic waveforms delivered during the therapeutic period. In at least some embodiments, the patient may not feel or perceive the sensing waveform. For example, the sensing waveform may have a relatively short pulse width with a high amplitude that is not perceptible to the patient. In at least some embodiments, the sensing waveform will not affect the therapeutic stimulation.

In other embodiments, the sensing waveform may also be a therapeutic waveform, but with properties that facilitate sensing. In at least some embodiments, the patient may perceive the sensing waveform and therefore the electrodes used in the sensing waveform may be chosen such that the perception is located in an agreeable area for the patient (e.g., within the pain topography, or other agreeable area). In at least some embodiments, because the patient perceives the sensing waveform, instances of the sensing waveform may be presented at irregular intervals in accordance with a pattern that the patient deems agreeable or particularly pleasant, or even therapeutic.

The sensing waveform <NUM> facilitates physiological sensing such as, for example, sensing an ESG (electrospinogram) signal. The system (for example a control module, such as an implantable pulse generator (IPG) or external trial stimulation (ETS); remote control (RC); clinician programmer (CP); or other device) may use the sensed signals from the tissue to, for example, determine information about posture; determine changes in the sensed signals that the systems can use to tune or adjust a stimulation parameter; or for any other suitable purpose or combination of purposes. In at least some embodiments, the sensing waveform may be selected to reduce or minimize artifact contamination in the sensed physiological signal or ESG and may facilitate feature extraction or pattern recognition of specific attributes of the sensed signal.

In at least some embodiments, the sensing waveform <NUM> is delivered from the same electrode(s) during each sensing period <NUM>. In at least some embodiments, the sensing waveform <NUM> in each successive sensing period <NUM> can be delivered using electrodes that are proximal to, or distal to, the electrodes used to deliver the sensing waveform in the preceding period. In the case of spinal cord stimulation, the spatially interleaved sensing waveforms <NUM> can sense, for example, how the distance between the spinal cord and lead changes at different vertebral levels. In at least some embodiments, the arranged sequence of sensing waveforms can be selected and timed so that a sensing period <NUM> for each electrode or set of electrodes along the lead can occur in a time period that is shorter than the posture or activity of the patient can adjust. For example, for an eight electrode lead, the combination of a sensing period and adjacent therapeutic period can be in the range of <NUM> to <NUM>, resulting in a total period for all sensing at all eight electrodes of <NUM> to <NUM> msec.

In contrast, in <FIG>, there is no sensing waveform during the sensing period <NUM>. The absence of a sensing waveform in the sensing period <NUM> allows the sensing or measurement of the ESG in response to the previous therapeutic period <NUM>.

The embodiments in <FIG> illustrate examples of a method of stimulating and sensing using electrodes on one or more leads. <FIG> is a flowchart of one embodiment of a method of stimulating and sensing using electrodes on one or more leads. The sequences of waveforms illustrated in <FIG> are examples of the waveforms and arrangements that can be used in the method of <FIG>.

In step <NUM>, at least one therapeutic waveform is delivered using the electrodes of the lead(s) during a therapeutic period. As described above with respect to the sequences illustrated in <FIG>, the therapeutic waveform can be monophasic, biphasic, or multiphasic and can be monopolar, bipolar, or multipolar. The therapeutic period can include one or more of the therapeutic waveforms.

In step <NUM>, after the therapeutic period and, in some embodiments, after delivery of a sensing waveform <NUM> (<FIG>), an electrical signal, such as a neural response; a spontaneous neural signal; an ECAP; a ECG, ESG, EEG, or EMG signal; an electric field potential; or any other suitable signal or combination of signals, is sensed during a sensing period. <FIG> illustrates a sensing period <NUM> that includes a sensing waveform <NUM> and <FIG> illustrates a sensing period <NUM> without a sensing waveform. In at least some embodiments, the sensing is performed using two electrodes of the lead(s), but it will be understood that an electrode not on the lead can also be used in combination with an electrode on a lead.

In step <NUM>, the sensed electrical signal from step <NUM> is analyzed to produce information about the patient or tissue, extract features from the sensed electrical signal, recognize patterns in the sensed electrical signal, or the like. The analysis of the sensed electrical signal may include information about neural response, evoked or spontaneous neural signals, heartbeat signals, respiration, patient activity (e.g., sleep, active, inactive, coughing, laughing, and so forth), patient posture, and the like.

In optional step <NUM>, the analysis of step <NUM> may be used to alter the stimulation therapy. For example, stimulation parameters may be altered due to changes in patient posture or activity as indicated in the sensed electrical signal.

As indicated by the lines <NUM>, any combination of steps <NUM>, <NUM>, <NUM>, and <NUM> can be repeated with the therapeutic periods and sensing periods alternating.

The therapeutic waveform can generate artifacts in the resulting sensed signal. <FIG> illustrates one embodiment of a sequence of biphasic therapeutic waveforms that can reduce or eliminate artifacts in a sensed signal that arise from the biphasic therapeutic waveforms. As illustrated in <FIG>, a first waveform <NUM>, with a positive phase 654a followed by a negative phase 654b, is interleaved with a second waveform <NUM>, with a negative phase 655b followed by a positive phase 655a, to form a stimulation block <NUM> with a first stimulation epoch 651a containing the first waveform and a second stimulation epoch 651b containing the second waveform. This interleaving of two biphasic waveforms <NUM>, <NUM> with opposite temporal ordering of the phases can reduce or eliminate artifact contamination in the sensed signal (such as an ESG or a sensed evoked neural response to the stimulation) and may facilitate feature extraction of specific attributes.

The therapeutic waveforms in <FIG> alternate the polarity order of the waveform phases so that at least some artifacts arising from the first waveform <NUM> and the second waveform <NUM> exhibit opposite polarities. In contrast, the neural responses will have the same polarity (see, <FIG>).

In at least some embodiments, the artifacts arising from the waveforms <NUM>, <NUM> can be reduced or eliminated by adding, averaging, or otherwise combining the sensed signals from the first and second stimulation epochs 651a, 651b. In at least some embodiments, the sensed signals from the first and second stimulation epochs 651a, 651b can be scaled based on the size of the artifacts in the respective sensed signals or based on the size of the neural response in the sensed signals or based on any other suitable features in the sensed signals. In at least some of these embodiments, the scaled sensed signals can be added, averaged, or otherwise combined.

In at least some embodiments, the phases 654a, 654b, 655a, 655b of each of the waveforms <NUM>, <NUM> can be symmetric except for polarity (for example, having the same amplitude and width), as illustrated in <FIG>, or can be asymmetric with different amplitude, width, or other parameter or any combination of parameters. In at least some embodiments the first and second waveforms <NUM>, <NUM> can be symmetric except for the temporal arrangement of the two phases, as illustrated in <FIG>, or can be asymmetric with different amplitudes, widths, or other parameters or any combination of parameters.

In at least some embodiments, the arrangements of <FIG> and <FIG> can be combined to provide in sequence: <NUM>) a first therapeutic period (similar to period <NUM> of <FIG>) during which one or more of the first waveforms <NUM> are delivered, <NUM>) a first sensing period (similar to period <NUM> of <FIG>), <NUM>) a second therapeutic period (similar to period <NUM> of <FIG>) during which one or more of the second waveforms <NUM> are delivered, and <NUM>) a second sensing period (similar to period <NUM> of <FIG>). The sensed signals from the first and second sensing periods can be scaled, added, averaged, or otherwise combined as discussed above with respect to the first and second stimulation epochs 651a, 651b. In at least some embodiments, the entire period of time for the two therapeutic periods and two sensing periods can be arranged so that there is little or no change in patient status during that time period so that the signals between the two sensing periods represent the same patient state. For example, either period of time may be no more than <NUM> second or <NUM>, <NUM>, <NUM>, or <NUM> milliseconds or less.

In another combination of the arrangements of <FIG> and <FIG>, the waveforms <NUM>, <NUM> of <FIG> can be used during the sensing periods <NUM> of <FIG> instead of the waveform <NUM>.

<FIG> is a flowchart illustrating one embodiment of a method of stimulating and sensing using electrodes on one or more leads and alternating the temporal order of phases of biphasic therapeutic waveforms. In step <NUM>, at least one first therapeutic waveform is delivered using the electrodes of the lead(s). The therapeutic waveform is biphasic with a first phase and a second phase where the second phase is opposite in polarity to the first phase.

In step <NUM>, an electrical signal, such as an electrospinogram signal or an electric field potential, is sensed after (and, optionally, before or during) delivery of the at least one first therapeutic waveform. In many instances, the sensing will be performed using two electrodes of the lead(s), but it will be understood that an electrode not on the lead can also be used in combination with an electrode on the lead.

In step <NUM>, at least one second therapeutic waveform is delivered using the electrodes of the lead(s). The therapeutic waveform is biphasic with a third phase and a fourth phase where the third phase is opposite in polarity to the fourth phase and also opposite in polarity to the first phase of the at least one first therapeutic waveform.

In step <NUM>, an electrical signal, such as an electrospinogram signal or an electric field potential, is sensed after (and, optionally, before or during) delivery of the at least one second therapeutic waveform. In many instances, the sensing will be performed using two electrodes of the lead(s), but it will be understood that an electrode not on the lead can also be used in combination with an electrode on the lead.

In step <NUM>, the sensed electrical signals from steps <NUM> and <NUM> are analyzed. In at least some embodiments, the sensed electrical signals are scaled, added, averaged, or otherwise combined as described above in order to reduce or eliminate artifacts in the sensed electrical signals. The analysis of the sensed electrical signals can produce information, extract features from the sensed electrical signal, recognize patterns in the sensed electrical signals, or the like. The analysis of the sensed electrical signals may include information about neural response, neural signals, heartbeat signals, respiration, patient activity (e.g., sleep, active, inactive, etc.), patient posture, and the like.

In optional step <NUM>, the analysis of step <NUM> may be used to alter the stimulation therapy. For example, stimulation parameters may be altered due to changes in patient posture or activity as indicated in the sensed electrical signals.

As indicated by arrow <NUM>, any combination of steps <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> can be repeated with delivery of the first and second therapeutic waveforms alternating.

The adjustment of stimulation parameters based on sensing of signals can be enhanced by increasing the amount of information available from the sensing. This can be accomplished by, for example, using therapeutic waveforms or sensing waveforms with different parameters such as different amplitude, pulse shape, pulse width, pulse period, electrode selection, or electrode fractionalization. For example, the sensed responses to each of two consecutive therapeutic waveforms with different amplitudes, for example, <NUM> mA and <NUM> mA, can provide additional information, particularly when the therapeutic waveforms are delivered close in time so that there are no patient posture or activity changes during that period. The physiological response to two different therapeutic waveforms can provide more information, such as, for example, the current activity or posture, and may result in better adjustment of stimulation parameters to be delivered.

<FIG> illustrate three embodiments of a sequence of biphasic therapeutic waveforms with two (<FIG>) or three (<FIG>) waveforms with different amplitudes. In the illustrated embodiments, the amplitudes of the waveforms are different. It will be recognized that other waveform parameters, such as pulse width, can be selected instead of, or in addition to, amplitude for differing between waveforms.

As illustrated in <FIG>, a first waveform <NUM> having a first amplitude and a positive phase 854a followed by a negative phase 854b is interleaved with a second waveform <NUM> having a second, lower amplitude with a positive phase 855a followed by a negative phase 855b to form a stimulation block <NUM>. This stimulation block <NUM> is repeated.

<FIG> illustrates a sequence that combines the concepts in <FIG> and <FIG> so that the first stimulation epoch 851a is the sequence of first and second waveforms <NUM>, <NUM> illustrated in <FIG> and the second stimulation epoch 851b is the same sequence of waveforms except that the temporal order of the phases of the first and second waveforms <NUM>', <NUM>' is reversed. The two stimulation epochs 851a, 851b form a stimulation block <NUM> which is repeated. As described above, reversing the temporal order of the phases of the waveforms and combining the respective sensed signals can reduce or eliminate artifacts arising from the therapeutic waveforms.

<FIG> illustrates a sequence that includes the first and second waveforms <NUM>, <NUM> of <FIG> and interleaves a third waveform <NUM> having a third amplitude and a positive phase 856a followed by a negative phase 856b to form the stimulation block <NUM>. This stimulation block <NUM> is repeated. In one example, the first waveform has an amplitude of <NUM> mA, the second waveform has an amplitude of <NUM> mA, and the third waveform has an amplitude of <NUM> mA. It will be recognized that additional embodiments can include four, five, or more waveforms with each waveform having a different amplitude.

In at least some embodiments, the phases of each of the individual waveforms <NUM>, <NUM>, <NUM> can be symmetric except for polarity (for example, having the same amplitude and width), as illustrated in <FIG>, or can be asymmetric with different amplitude, pulse shape, pulse width, pulse period, electrode selection, or electrode fractionalization, or other parameter or any combination of parameters.

In a combination of the arrangements of <FIG> and any one of <FIG>, the waveforms <NUM>, <NUM>, <NUM> of any one of <FIG> can be used during the sensing periods <NUM> of <FIG> instead of the waveform <NUM>.

Instead of variation in amplitude, the different therapeutic waveforms can differ in electrode selection for delivery of the waveform to produce a spatial interleaving of the waveforms. For example, each successive waveform can be delivered using electrodes that are proximal to, or distal to, the electrodes used to deliver the preceding waveform. In the case of spinal cord stimulation, the spatially interleaved waveforms can sense, for example, how the distance between the spinal cord and lead changes at different vertebral levels. This spatial interleaving can also be combined with the arrangement of <FIG> so that each sensing period <NUM> includes one or more waveforms delivered from a different set of electrodes.

The therapeutic and sensing waveforms can differ in any of the following parameters: amplitude, pulse shape, pulse width, pulse period, electrode selection, or electrode fractionalization.

<FIG> is a flowchart illustrating one embodiment of a method of stimulating and sensing using electrodes on one or more leads and alternating the temporal order of phases of biphasic therapeutic waveforms. In step <NUM>, at least one first therapeutic waveform is delivered using the electrodes of the lead. In step <NUM>, an electrical signal, such as an electrospinogram signal or an electric field potential, is sensed after (and, optionally, before or during) delivery of the at least one first therapeutic waveform. In at least some embodiments, the sensing will be performed using two electrodes of the lead(s), but it will be understood that an electrode not on the lead can also be used in combination with an electrode on the lead.

In step <NUM>, at least one second therapeutic waveform is delivered using the electrodes of the lead(s). The first and second therapeutic waveforms differ in at least one stimulation parameter, such as amplitude, pulse shape, pulse width, pulse period, electrode selection, or electrode fractionalization. In step <NUM>, an electrical signal, such as an electrospinogram signal or an electric field potential, is sensed after (and, optionally, before or during) delivery of the at least one second therapeutic waveform. In at least some embodiments, the sensing will be performed using two electrodes of the lead(s), but it will be understood that an electrode not on the lead can also be used in combination with an electrode on the lead.

In optional step <NUM>, at least one third therapeutic waveform is delivered using the electrodes of the lead(s). The first, second, and third therapeutic waveforms differ in at least one stimulation parameter, such as amplitude, pulse shape, pulse width, pulse period, electrode selection, or electrode fractionalization. In optional step <NUM>, an electrical signal, such as an electrospinogram signal or an electric field potential, is sensed after (and, optionally, before or during) delivery of the at least one third therapeutic waveform. In at least some embodiments, the sensing will be performed using two electrodes of the lead(s), but it will be understood that an electrode not on the lead can also be used in combination with an electrode on the lead.

In step <NUM>, the sensed electrical signals from steps <NUM>, step <NUM>, and optionally step <NUM> are analyzed. In at least some embodiments, the sensed electrical signals are scaled, added, averaged, or otherwise combined. The analysis of the sensed electrical signals can produce information, extract features from the sensed electrical signal, recognize patterns in the sensed electrical signals, or the like. The analysis of the sensed electrical signals may include information about neural response, neural signals, heartbeat signals, respiration, patient activity (e.g., sleep, active, inactive, etc.), patient posture, and the like.

As indicated by arrow <NUM>, any combination of steps <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> can be repeated with delivery of the first and second therapeutic waveforms alternating.

In at least some embodiments, the methods presented in the flowcharts of <FIG>, <FIG>, and <FIG> (or any subset of the steps in those flowcharts) can be performed by a stimulation engine <NUM> (or a stimulation module or stimulation algorithm) and a sensing engine <NUM> (or a sensing module or sensing algorithm) residing in a memory <NUM> and operating in a processor <NUM> of a device <NUM> as illustrated in <FIG>. (In some embodiments, the stimulation engine <NUM> and sensing engine <NUM> can be combined into a stimulation/sensing engine. ) The device <NUM> can be, for example, devices illustrated in <FIG>, such as an IPG <NUM>, RC <NUM>, CP <NUM>, or ETS <NUM>, or any other suitable device.

It will be understood that each block of the flowchart illustration, and combinations of blocks in the flowchart illustration and methods disclosed herein, can be implemented by computer program instructions. These program instructions may be provided to a processor to produce a machine, such that the instructions, which execute on the processor, create means for implementing the actions specified in the flowchart block or blocks disclosed herein. The computer program instructions may be executed by a processor to cause a series of operational steps to be performed by the processor to produce a computer implemented process. The computer program instructions may also cause at least some of the operational steps to be performed in parallel. Moreover, some of the steps may also be performed across more than one processor, such as might arise in a multi-processor computing device. In addition, one or more processes may also be performed concurrently with other processes, or even in a different sequence than illustrated.

The computer program instructions can be stored on any suitable computer-readable medium including, but not limited to, RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, digital versatile disks ("DVD") or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store the desired information and which can be accessed by a computing device.

<FIG> is a schematic overview of one embodiment of components of an electrical stimulation system <NUM> including an electronic subassembly <NUM> disposed within a control module. The electronic subassembly <NUM> may include one or more components of the IPG. It will be understood that the electrical stimulation system can include more, fewer, or different components and can have a variety of different configurations including those configurations disclosed in the stimulator references cited herein.

Some of the components (for example, a power source <NUM>, an antenna <NUM>, a receiver <NUM>, and a processor <NUM>) of the electrical stimulation system can be positioned on one or more circuit boards or similar carriers within a sealed housing of an implantable pulse generator (see e.g., <NUM> in <FIG>), if desired. Any power source <NUM> can be used including, for example, a battery such as a primary battery or a rechargeable battery. Examples of other power sources include super capacitors, nuclear or atomic batteries, mechanical resonators, infrared collectors, thermally-powered energy sources, flexural powered energy sources, bioenergy power sources, fuel cells, bioelectric cells, osmotic pressure pumps, and the like including the power sources described in <CIT>.

As another alternative, power can be supplied by an external power source through inductive coupling via the optional antenna <NUM> or a secondary antenna. In at least some embodiments, the antenna <NUM> (or the secondary antenna) is implemented using the auxiliary electrically-conductive conductor. The external power source can be in a device that is mounted on the skin of the user or in a unit that is provided near the user on a permanent or periodic basis.

If the power source <NUM> is a rechargeable battery, the battery may be recharged using the optional antenna <NUM>, if desired. Power can be provided to the battery for recharging by inductively coupling the battery through the antenna to a recharging unit <NUM> external to the user. Examples of such arrangements can be found in the references identified above. The electronic subassembly <NUM> and, optionally, the power source <NUM> can be disposed within a control module (e.g., the IPG <NUM> or the ETS <NUM> of <FIG>).

In one embodiment, electrical stimulation signals are emitted by the electrodes <NUM> to stimulate nerve fibers, muscle fibers, or other body tissues near the electrical stimulation system. The processor <NUM> is generally included to control the timing and electrical characteristics of the electrical stimulation system. For example, the processor <NUM> can, if desired, control one or more of the timing, frequency, strength, duration, and waveform of the pulses. In addition, the processor <NUM> can select which electrodes can be used to provide stimulation, if desired. In some embodiments, the processor <NUM> selects which electrode(s) are cathodes and which electrode(s) are anodes. In some embodiments, the processor <NUM> is used to identify which electrodes provide the most useful stimulation of the desired tissue.

Any processor can be used and can be as simple as an electronic device that, for example, produces pulses at a regular interval or the processor can be capable of receiving and interpreting instructions from an external programming unit <NUM> that, for example, allows modification of pulse characteristics. In the illustrated embodiment, the processor <NUM> is coupled to a receiver <NUM> which, in turn, is coupled to the optional antenna <NUM>. This allows the processor <NUM> to receive instructions from an external source to, for example, direct the pulse characteristics and the selection of electrodes, if desired.

In one embodiment, the antenna <NUM> is capable of receiving signals (e.g., RF signals) from an external telemetry unit <NUM> which is programmed by the programming unit <NUM>. The programming unit <NUM> can be external to, or part of, the telemetry unit <NUM>. The telemetry unit <NUM> can be a device that is worn on the skin of the user or can be carried by the user and can have a form similar to a pager, cellular phone, or remote control, if desired. As another alternative, the telemetry unit <NUM> may not be worn or carried by the user but may only be available at a home station or at a clinician's office. The programming unit <NUM> can be any unit that can provide information to the telemetry unit <NUM> for transmission to the electrical stimulation system <NUM>. The programming unit <NUM> can be part of the telemetry unit <NUM> or can provide signals or information to the telemetry unit <NUM> via a wireless or wired connection. One example of a suitable programming unit is a computer operated by the user or clinician to send signals to the telemetry unit <NUM>.

The signals sent to the processor <NUM> via the antenna <NUM> and the receiver <NUM> can be used to modify or otherwise direct the operation of the electrical stimulation system. For example, the signals may be used to modify the pulses of the electrical stimulation system such as modifying one or more of pulse duration, pulse frequency, pulse waveform, and pulse strength. The signals may also direct the electrical stimulation system <NUM> to cease operation, to start operation, to start charging the battery, or to stop charging the battery. In other embodiments, the stimulation system does not include the antenna <NUM> or receiver <NUM> and the processor <NUM> operates as programmed.

Optionally, the electrical stimulation system <NUM> may include a transmitter (not shown) coupled to the processor <NUM> and the antenna <NUM> for transmitting signals back to the telemetry unit <NUM> or another unit capable of receiving the signals. For example, the electrical stimulation system <NUM> may transmit signals indicating whether the electrical stimulation system <NUM> is operating properly or not or indicating when the battery needs to be charged or the level of charge remaining in the battery. The processor <NUM> may also be capable of transmitting information about the pulse characteristics so that a user or clinician can determine or verify the characteristics.

Claim 1:
An electrical stimulation system, comprising:
at least one electrical stimulation lead (<NUM>), each of the at least one electrical stimulation lead comprising a plurality of stimulation electrodes (<NUM>); and
a processor (<NUM>, <NUM>) coupled to the at least one electrical stimulation lead and configured to perform actions, comprising:
directing delivery of at least one therapeutic waveform (<NUM>) through at least one of the stimulation electrodes of the at least one electrical stimulation lead to tissue of a patient during each of a plurality of therapeutic periods (<NUM>);
directing sensing of an electrical signal using at least one of the stimulation electrodes of the at least one electrical stimulation lead during each of a plurality of sensing periods (<NUM>), wherein the therapeutic periods alternate with the sensing periods; and
directing delivery of at least one sensing waveform (<NUM>) through at least one of the stimulation electrodes of the at least one electrical stimulation lead during at least one of the sensing periods, wherein the at least one sensing waveform is a biphasic waveform comprising a positive phase and a negative phase.