Systems and methods for delivering neurostimulation to induce a state of remission in a patient

Abstract

The present technology is directed generally to electrical stimulation and associated systems and methods. For example, the present technology provides stimulation schedules / regimens that are expected to reduce the amount of power required for paresthesia-free stimulation, while maintaining the benefits of paresthesia- free stimulation. This is accomplished by reducing the dose of paresthesia-free neurostimulation provided to a patient over time. The dose can be reduced without a corresponding reduction, or significant reduction, in effectiveness.

Description

CROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] The present application claims priority to U.S. Provisional Patent Application No. 63 / 620,154, filed January 11, 2024, the disclosure of which is incorporated by reference in its entirety. TECHNICAL FIELD

[0002] The present technology is directed toward electrically modulating nervous tissue to treat a patient condition. BACKGROUND

[0003] Neurological stimulators have been developed to treat pain, movement disorders, functional disorders, spasticity, cancer, cardiac disorders, and various other medical conditions. Neurological stimulation systems generally have a signal generator and one or more implantable leads that deliver electrical pulses to neurological tissue or muscle tissue. For example, several neurological stimulation systems for spinal cord stimulation (SCS) have cylindrical leads that include a lead body with a circular crosssectional shape and one or more conductive rings (e.g., contacts) spaced apart from each other at the distal end of the lead body. The conductive rings operate as individual electrodes and, in many cases, the SCS leads are implanted percutaneously through a needle inserted into the epidural space, with or without the assistance of a stylet. In other systems, the electrodes are carried by a paddle that is implanted via a laminotomy.

[0004] The signal generator transmits electrical pulses to the electrodes, creating an electric field, which in turn modifies the function of the patient's nervous system, such as by altering the patient's responsiveness to sensory stimuli and / or altering the patient's motor-circuit output. In SCS therapy for the treatment of pain, for example, the signal generator applies electrical pulses to the spinal cord via the electrodes. BRIEF DESCRIPTION OF THE DRAWINGS

[0005] Figure 1 is a partially schematic illustration of an implantable spinal cord modulation system positioned at a patient's spine to deliver electrical signals in accordance with some embodiments of the present technology.

[0006] Figure 2A is a partially schematic, cross-sectional illustration of a patient's spine, illustrating representative locations for implanted lead bodies in accordance with some embodiments of the present technology.

[0007] Figure 2B is a partially schematic, cross-sectional illustration of a patient's brain, illustrating representative locations for implanted lead bodies in accordance with some embodiments of the present technology.

[0008] Figure 2C is a schematic illustration of a patient's peripheral nerve illustrating representative locations for implanted lead bodies in accordance with some embodiments of the present technology.

[0009] Figure 3 is a schematic illustration of a representative lead body suitable for providing modulation to a patient in accordance with some embodiments of the present technology.

[0010] Figure 4 is a flowchart of a method of treating a patient in accordance with some embodiments of the present technology.

[0011] Figure 5 is a flowchart of another method of treating a patient in accordance with some embodiments of the present technology.

[0012] Figure 6 is a flowchart of another method of treating a patient in accordance with some embodiments of the present technology.

[0013] Figure 7 is a flowchart of another method of treating a patient in accordance with some embodiments of the present technology.

[0014] Figure 8 is a table showing certain clinical data gathered from Applicant's clinical study on use of reduced stimulation schedules, in accordance with embodiments of the present technology.

[0015] Figures 9A-9F are graphs showing additional clinical data gathered from Applicant's clinical study on use of reduced stimulation schedules, in accordance with embodiments of the present technology.

[0016] Figures 10A and 10B are graphs showing additional clinical data gathered from Applicant's clinical study on use of reduced stimulation schedules, in accordance with embodiments of the present technology. DETAILED DESCRIPTION

[0017] This Detailed Description includes the following headers and sections, which are provided for convenience only and do not affect the scope or meaning of the claimed present technology: • Definitions of selected terms are provided under Heading 1.0 ("Definitions"); • General aspects of the present technology are described below under Heading 2.0 ("Overview of Present Technology"); • Representative treatment systems and their characteristics are described under Heading 3.0 ("System Characteristics") with reference to Figures 1-3; • Representative embodiments of the present technology are described under Heading 4.0 ("Representative Embodiments of the Present Technology") with reference to Figures 4-7, including reduced dosing schedules and associated methods described under subheading A, and maintenance dosing schedules and associated method described under subheading B; • Representative stimulation parameters of the present technology are described under Heading 5.0 ("Representative Stimulation Parameters"); • Representative clinical applications for the present technology are described under Heading 6.0 ("Representative Clinical Applications"); • Clinical data obtained in accordance with the present technology is described under Heading 7.0 ("Clinical Data") with reference to Figures 8-10B; and • Representative examples are described under Heading 8.0 ("Representative Examples"). 1.0 Definitions

[0018] Unless otherwise stated, the terms "generally," "about," and "approximately" refer to values within 10% of a stated value. For example, the use of the term "about 100" refers to a range of 90 to 110, inclusive. In instances in which relative terminology is used in reference to something that does not include a numerical value, the terms are given their ordinary meaning to one skilled in the art.

[0019] As used herein, and unless otherwise noted, the terms "modulate," "modulation," "stimulate," and "stimulation" refer generally to electrical signals that have an inhibitory, excitatory, and / or other effect on a target neural population. Accordingly, a spinal cord "stimulator" can have an inhibitory effect and / or an excitatory effect on certain neural populations. Moreover, the use of the terms "suppress" and "inhibit" in relation to an electrical signal's effect on a neuron refers to a reduction in the neuron's firing rate relative to the neuron's baseline firing rate in the absence of the electrical signal, and does not necessarily refer to a complete elimination of action potentials in the neuron. The "baseline" firing rate can refer to the neuron's spontaneous firing rate and / or the firing rate of the neuron in response to an external stimulus other than the therapy signal.

[0020] As used herein, the terms "neuromodulation signal", "electrical therapy signal," "electrical signal," "therapy signal," "signal," and other associated terms are used interchangeably and generally refer to an electrical signal that can be characterized by one more parameters, such as frequency, pulse width, and / or amplitude.

[0021] As used herein, the term "high frequency" when used to describe an electrical signal refers to an electrical signal having a frequency between 1.2 kHz and about 1 MHz, unless specifically stated otherwise. As used herein, the term "low frequency" when used to describe an electrical signal refers to an electrical signal having a frequency of less than 1.2 kHz, unless specifically stated otherwise.

[0022] As used herein, the term "paresthesia-free" when used to describe an electrical signal refers to an electrical signal that does not produce paresthesia when delivered to a patient. Paresthesia-free signals may have combinations of frequency, pulse widths, amplitudes, and / or pulse dosing rates that cause the signal to be below a patient's perception threshold. For example, paresthesia-free electrical signals may have a frequency of between about 0.01 Hz and about 1 MHz, or between about 1.2 kHz and 500 kHz, or between about 1.2 kHz and about 100 kHz. As another example, paresthesia-free electrical signals may be delivered in discrete bursts, separated by quiescent periods in which the electrical signal is not delivered. As yet another example, paresthesia-free electrical signals may have a "long" pulse width of between about 5 milliseconds and about 25 seconds with an amplitude below an activation threshold of a target neural population. Additional examples of paresthesia-free electrical signals, including those mentioned above, are described in U.S. Patent Application Publication Nos. US2010 / 0274314, US2021 / 0228881, and US2022 / 0401730, and U.S. Provisional Patent Application No. 63 / 501,122, each of the which is incorporated by reference herein.

[0023] As used herein, the term "pulse width" refers to the width of any phase of a repeating pulse, such as the portion of a pulse at a given polarity, unless explicitly described otherwise. For example, the use of the term pulse width with respect to a signal having bi-phasic pulses can refer to the duration of an anodic pulse phase or a cathodic pulse phase. The use of the term pulse width with respect to a signal having monophasic pulses can refer to the duration of the monophasic pulse phase.

[0024] As used herein, the term "pulse dosing" refers to repeatedly alternating between a first period in which pulses of an electrical signal are actively delivered and a second period in which the pulses are not delivered (e.g., a quiescent period). The pattern of alternating between the first (active) period and the second (quiescent) period is repeated for the "duration" the therapy is being applied for. The term "pulse dosing rate" or equivalents therefore refer to the percentage of the first period compared to the sum of the first period and the second period. For example, an electrical signal may be delivered continuously for 30 seconds (i.e., the first period equals 30 seconds), followed by a 30 second quiescent period (i.e., the second period equals 30 seconds). Such signal has a pulse dosing rate of 50%. In general, for purposes of pulse dosing, the second (quiescent) period is typically less than about 60 minutes, and more typically less than about 30 minutes, less than about 15 minutes, less than about 5 minutes, less than about 1 minute, or less than about 30 seconds. As described below, pulse dosing rates in accordance with the present technology can range from about 1 % to about 100%.

[0025] In contrast, the terms "bolus" and "stimulation session" refer to a discrete period during which neurostimulation therapy is being applied to the patient, followed by a relatively prolonged off-period during which no neurostimulation therapy is applied to the patient. Of note, the neurostimulation therapy may be "pulsed dosed" during the discrete period during which neurostimulation therapy is being applied. For example, a "bolus" or "stimulation session" of one hour may include delivering an electrical stimulation at a pulse dose rate of 50%, such as alternating between 30 second active periods and 30 second quiescent periods for the one hour bolus period. In general, a bolus or stimulation session is typically followed by an off-period of greater duration than any quiescent period associated with pulse dosing. For example, a bolus or stimulation session is typically followed by an off-period of at least 1 hour, and more typically by an off-period of at least 2 hours, at least 3 hours, or at least 4 hours.

[0026] As used herein, the term "maintenance dose" refers to a bolus or stimulation session that is separated from any preceding and / or following bolus or stimulation session by about one week or more. For example, maintenance doses can be delivered as individual boluses of electrical stimulation spaced apart by about one week or more.

[0027] As used herein, "proximate a spinal cord region" refers to the placement of a signal delivery element or device such that it can deliver electrical stimulation to a neural population located in the spinal cord and / or within the spinal canal. For example, "proximate a spinal cord region" includes, but is not limited to, the relative lead positions described and shown in Figure 2A, as well as other positions not expressly described herein.

[0028] As used herein, "proximate a target neural population" refers to the placement of a signal delivery element such that it can deliver electrical stimulation to the target neural population. For example, if the target population includes neurons in the spinal cord at a given vertebral level, "proximate the target neural population" includes, but is not limited to, the relative lead positions described and shown in Figure 2A at the given vertebral level, as well as other positions not expressly described herein. As another example, if the target population includes neurons in the patient's cortex (e.g., motor cortex), "proximate the target neural population" includes, but is not limited to, leads positioned in or on the patient's cortex or near deep brain structures. 2.0 Overview of the Present Technology

[0029] Nevro Corp., the assignee of the present application, has previously developed and commercialized paresthesia-free spinal cord stimulation for treating pain and other conditions. For many patients, the paresthesia-free stimulation therapy provides superior pain relief and / or other symptom alleviation compared to conventional paresthesia-based stimulation. The paresthesia-free stimulation also often provides fewer side effects compared to conventional paresthesia-based stimulation.

[0030] However, one drawback of some paresthesia-free therapies is that more energy / power is required to generate and deliver the therapy. For example, more energy / power is generally required to generate and deliver a high frequency, paresthesia-free electrical signal than a low frequency, paresthesia-based electrical signal for the same duration. This is because, for a single pulse cycle consisting of a pulse and an interpulse interval, a high frequency signal typically has a higher percent "on" time than a low frequency signal. That is, the ratio between the pulse width and the total duration of the pulse cycle is generally higher for a high frequency signal. This means that the amount of time a system must provide power (e.g., the sum of all the pulse widths over a given period) is higher for high frequency stimulation than low frequency stimulation. As a result, high frequency, paresthesia-free stimulation systems may require larger batteries (and thus larger implants) and / or may require the patient to recharge the system more frequently. Despite these inconveniences, paresthesia-free therapy is still preferred by many patients over paresthesia-based therapy due to its superior effectiveness and reduced side effects.

[0031] The present technology provides systems and methods that are expected to at least partially address these inconveniences associated with the higher power requirement of some paresthesia-free neurostimulation therapies, such as high frequency, paresthesia-free therapy. In particular, the present technology provides stimulation schedules / regimens that are expected to reduce the amount of power required for extended paresthesia-free stimulation therapy, while maintaining the benefits of paresthesia-free stimulation. As described below, this is accomplished by reducing the dose of paresthesia-free neurostimulation provided to a patient over an extended time. Of note, the stimulation dose can be reduced in accordance with the therapy regimens described herein without a corresponding reduction, or meaningful reduction, in effectiveness. For example, paresthesia-free stimulation can induce a prolonged "wash out" period during which symptomatic relief (e.g., pain relief) persists even after delivery of the electrical signal is stopped. Accordingly, stimulation can be periodically and repeatedly turned off without a corresponding reduction, or meaningful reduction, in effectiveness. This is in contrast with paresthesia-based therapies, which require paresthesia (and thus continuous application of the signal to induce paresthesia) to maintain pain relief. Reducing the dose of paresthesia-free neurostimulation provided to a patient over time may facilitate additional patient conveniences beyond reducing power-consumption, such as enabling smaller implants, enabling externally powered devices, negating the need for an implanted signal generator and / or an implantable rechargeable battery, enabling using a primary cell battery in the implant, among others.

[0032] In some embodiments, the power required for chronic stimulation therapy can also be reduced by identifying patients who have entered a state of remission, and reducing or even terminating the stimulation delivered to such patients. For example, after a relatively prolonged period of continuous or even non-continuous stimulation (e.g., one month or more), some patients may enter a state of remission, in which pain relief or another therapeutic effect persists for a week or more even in the absence of stimulation. Some patients may still require periodic and relatively spaced apart stimulation sessions to maintain the state or remission. Other patients, however, may remain in remission for extended periods of time (e.g., at least one month, at least two months, etc.), even in the absence of any stimulation. The present technology therefore also provides stimulation schedules / regimens for inducing and / or maintaining a patient in the state of remission.

[0033] Specific details of certain embodiments of the disclosure are described below with reference to methods for modulating one or more target neural populations (e.g., nerves) or sites of a patient, and associated implantable structures for providing the modulation. Although selected embodiments are described below with reference to modulating the dorsal column, dorsal horn, dorsal root, dorsal root entry zone, ventral column, ventral horn, and / or other particular regions of the spinal column, the modulation may in some instances be directed to other neurological structures and / or target neural populations of the spinal cord and / or other neurological tissues throughout the body. For example, some embodiments may include modulating brain tissue, including the cortex (e.g., motor cortex) and / or deep brain structures. As another example, some embodiments may include modulating peripheral nervous tissue, such as dorsal root ganglion, sacral nerves, the vagal nerve, the median nerve, the tibial nerve, or other peripheral nerves. Some embodiments can have configurations, components, or procedures different than those described in this section, and other embodiments may eliminate particular components or procedures. A person of ordinary skill in the relevant art, therefore, will understand that the present disclosure may include other embodiments with additional elements, and / or may include other embodiments without several of the features shown and described below with reference to Figures 1 -9B. 3.0 System Characteristics

[0034] Figure 1 schematically illustrates a representative patient therapy system 100 for treating a patient's motor, sensory, and / or other functioning, arranged relative to the general anatomy of the spinal column 191 of a patient 190. The system 100 can include a signal generator 101 (e.g., an implanted or implantable pulse generator or IPG), which can be implanted subcutaneously within a patient 190 and coupled to one or more signal delivery elements or devices 110. The signal delivery elements or devices 110 can be implanted within the patient 190, at or off the patient's spinal cord midline 189. The signal delivery elements 110 carry features for delivering therapy to the patient 190 after implantation. The signal generator 101 can be connected directly to the signal delivery devices 110, or it can be coupled to the signal delivery devices 110 via a signal link, e.g., a lead extension 102. In some embodiments, the signal delivery devices 110 can include one or more elongated lead(s) or lead body or bodies 111 (identified individually as a first lead 111a and a second lead 111b). As used herein, the terms signal delivery device, signal delivery element, lead, and / or lead body include any of a number of suitable substrates and / or supporting members that carry electrodes / devices for providing therapy signals to the patient 190. For example, the lead or leads 111 can include one or more electrodes or electrical contacts that deliver electrical signals into the patient's tissue, e.g., to provide for therapeutic relief. In some embodiments, the signal delivery elements 110 can include structures other than a lead body (e.g., a paddle) that also deliver electrical signals and / or other types of signals to the patient 190, e.g., as disclosed in U.S. Patent Application Publication No. 2018 / 0256892, incorporated herein by reference in its entirety. In some embodiments, paddles can be more suitable for patients with stenosis or other indications that compromise the epidural space and preclude the percutaneous delivery of cylindrical leads.

[0035] In some embodiments, one signal delivery device can be implanted on one side of the spinal cord midline 189, and a second signal delivery device can be implanted on the other side of the spinal cord midline 189. For example, the first and second leads 111a, 111b shown in Figure 1 can be positioned just off the spinal cord midline 189 (e.g., about 1 mm offset) in opposing lateral directions so that the two leads 111a, 111b are spaced apart from each other by about 2 mm. In some embodiments, the leads 111 can be implanted at a vertebral level ranging from, for example, about T1 to about T12, or from about T4 to about T12. In some embodiments, one or more signal delivery devices can be implanted at other vertebral levels, e.g., as disclosed in U.S. Patent No. 9,327,121, incorporated herein by reference in its entirety. In other embodiments, one or more leads 111 can be implanted at or proximate other target neural structures, including brain tissue, peripheral nerves, etc.

[0036] The signal generator 101 can transmit signals (e.g., electrical signals) to the signal delivery elements 110 that excite, inhibit, downregulate and / or suppress target nerves. The signal generator 101 can include a machine-readable (e.g., computer-readable or controller-readable) medium containing instructions for generating and transmitting suitable therapy signals, such as to perform the methods described below with respect to Figures 4 and 5. The signal generator 101 and / or other elements of the system 100 can include one or more processor(s) 107, memory unit(s) 108, and / or input / output device(s) 112. Accordingly, the process of providing modulation signals, providing guidance information for positioning the signal delivery devices 110, establishing battery charging and / or discharging parameters, and / or executing other associated functions can be performed by computer-executable instructions contained by, on, or in computer-readable media located at the pulse generator 101 and / or other system components. Further, the pulse generator 101 and / or other system components can include dedicated hardware, firmware, and / or software for executing computer-executable instructions that, when executed, perform any one or more methods, processes, and / or sub-processes described herein and / or in the materials incorporated herein by reference. The dedicated hardware, firmware, and / or software also serve as "means for" performing the methods, processes, and / or sub-processes described herein. The signal generator 101 can also include multiple portions, elements, and / or subsystems (e.g., for directing signals in accordance with multiple signal delivery parameters), carried in a single housing, as shown in Figure 1, or in multiple housings. For example, the signal generator can include some components that are implanted (e.g., a circuit that directs signals to the signal delivery device 110), and some that are not (e.g., a power source). The computer-executable instructions can be contained on one or more media that are implanted within the patient and / or positioned external to the patient, depending on the embodiment.

[0037] The signal generator 101 can also receive and respond to an input signal received from one or more sources. The input signals can direct or influence the manner in which the therapy, charging, and / or process instructions are selected, executed, updated, and / or otherwise performed. The input signals can be received from one or more sensors (e.g., an input device 112 shown schematically in Figure 1 for purposes of illustration) that are carried by the signal generator 101 and / or distributed outside the signal generator 101 (e.g., at other patient locations) while still communicating with the signal generator 101. The sensors and / or other input devices 112 can provide inputs that depend on or reflect patient state (e.g., patient position, patient posture, and / or patient activity level), and / or inputs that are patient-independent (e.g., time). Still further details are included in U.S. Patent No. 8,355,797, incorporated herein by reference in its entirety.

[0038] In some embodiments, the signal generator 101 and / or signal delivery devices 110 can obtain power to generate the therapy signals from an external power source 103. In some embodiments, the external power source 103 can bypass an implanted signal generator and generate a therapy signal directly at the signal delivery devices 110 (or via signal relay components). The external power source 103 can transmit power to the implanted signal generator 101 and / or directly to the signal delivery devices 110 using electromagnetic induction (e.g., RF signals). For example, the external power source 103 can include an external coil 104 that communicates with a corresponding internal coil (not shown) within the implantable signal generator 101, signal delivery devices 110, and / or a power relay component (not shown). In some embodiments, the external power source 103 can transmit power to the implanted signal generator 101 and / or directly to the signal delivery devices 110 in a generally continuous manner such that the system 100 can operate without an internal power source. The external power source 103 can be portable for ease of use.

[0039] In some embodiments, the implanted signal generator 101 can be omitted and the external power source 130 can be configured as an external signal generator that transmits power and / or electrical signals to the signal delivery devices 110 (e.g., via an implanted relay device; not shown). For example, the external power source 103 can either transmit the electrical signal itself to the signal delivery device or cause an electrical signal to be generated directly at the signal delivery devices 110 or at an implanted relay device (not shown). In such embodiments, the external power source 103 can be a wearable device that the patient wears while receiving therapy. In such embodiments, the patient only receives stimulation therapy while the wearable device is placed in an active state and is being worn by the patient. This is generally less invasive because such embodiments generally do not require an implanted signal generator 101, nor an implanted power storage device. In such embodiments, the external power source 103 may be wireless to enable patient mobility and / or accurate positioning of the external power source 103 during treatment. For example, the external power source 103 can include a rechargeable battery (not shown) that can be used to power the external power source 103 while in the active state, and recharged while in an inactive state.

[0040] In some embodiments, the signal generator 101 can obtain the power to generate therapy signals from an internal power source, in addition to or in lieu of the external power source 103. For example, the implanted signal generator 101 can include a non-rechargeable battery (e.g., a primary cell) or a rechargeable battery (e.g., a secondary cell) to provide such power. When the internal power source includes a rechargeable battery, the external power source 103 can be used to recharge the battery. The external power source 103 can in turn be recharged from a suitable power source (e.g., conventional wall power).

[0041] During at least some procedures, an external stimulator or trial modulator 105 can be coupled to the signal delivery elements 110, e.g., during an initial procedure, prior to implanting the signal generator 101. For example, a practitioner (e.g., a physician and / or a company representative) can use the trial modulator 105 to vary the modulation parameters provided to the signal delivery elements 110 in real time, and select optimal or particularly effective parameters. These parameters can include the location from which the electrical signals are emitted, as well as the characteristics of the electrical signals provided to the signal delivery devices 110. In some embodiments, input is collected via the external stimulator or trial modulator 105 and can be used by the clinician to help determine what parameters to vary. In a typical process, the practitioner uses a wireless connection or cable assembly 120 to temporarily connect the trial modulator 105 to the signal delivery device 110. The practitioner can test the effectiveness of the signal delivery devices 110 in an initial position. The practitioner can then disconnect the cable assembly 120 if needed (e.g., at a connector 122), reposition the signal delivery devices 110, and reapply the electrical signals. This process can be performed iteratively until the practitioner obtains the desired position for the signal delivery devices 110. Optionally, the practitioner can move the partially implanted signal delivery devices 110 without disconnecting the cable assembly 120. Furthermore, in some embodiments, the iterative process of repositioning the signal delivery devices 110 and / or varying the therapy parameters may not be performed.

[0042] The signal generator 101, the lead extension 102, the trial modulator 105 and / or the connector 122 can each include a receiving element 109. Accordingly, the receiving elements 109 can be patient implantable elements, or the receiving elements 109 can be integral with an external patient treatment element, device or component (e.g., the trial modulator 105 and / or the connector 122). The receiving elements 109 can be configured to facilitate a simple coupling and decoupling procedure between the signal delivery devices 110, the lead extension 102, the pulse generator 101, the trial modulator 105 and / or the connector 122. The receiving elements 109 can be at least generally similar in structure and function to those described in U.S. Patent Application Publication No. 2011 / 0071593, incorporated by reference herein in its entirety.

[0043] After the signal delivery elements 110 are implanted, the patient 190 can receive therapy via signals generated by the trial modulator 105 or via another external signal generator (e.g., the power source 103), generally for a limited period of time. During this time, the patient wears the trial modulator 105 outside the body. Assuming the trial therapy is effective or shows the promise of being effective, the practitioner then replaces the trial modulator 105 with the implanted signal generator 101, and programs the signal generator 101 with therapy programs selected based on the experience gained during the trial period. Optionally, the practitioner can also replace the signal delivery elements 110. In still further embodiments, the signal generator 101 can be implanted without first undergoing a trial period. Once the implantable signal generator 101 has been positioned within the patient 190, the therapy programs provided by the signal generator 101 can still be updated remotely via a wireless physician's programmer 117 (e.g., a physician's laptop, a physician's remote or remote device, etc.) and / or a wireless patient programmer 106 (e.g., a patient's laptop, patient's remote or remote device, etc.). Generally, the patient 190 has control over fewer parameters than does the practitioner. For example, the capability of the patient programmer 106 can be limited to starting and / or stopping the signal generator 101, selecting a pre-programmed therapy option, and / or adjusting the signal amplitude within a present amplitude range. The patient programmer 106 can be configured to accept inputs corresponding to pain relief, motor functioning and / or other variables, such as medication use. Accordingly, more generally, embodiments of the present technology include receiving patient feedback, via a sensor, that is indicative of, or otherwise corresponds to, the patient's response to the signal. Feedback includes, but is not limited to, motor, sensory, and verbal feedback. In response to the patient feedback, one or more signal parameters can be adjusted, such as frequency, pulse width, amplitude, or delivery location. In some embodiments, the patient programmer can be a network connected handheld computing device such as a smartphone, which can include a patient app that provides various functions such as remote programming, therapy selection, therapy tracking information such as current pain score or level of sensory restoration for use by the clinician and / or software in the app to optimize therapy.

[0044] Figure 2A is a cross-sectional illustration of the spinal cord 191 and an adjacent vertebra 195 (based generally on information from Crossman and Neary, "Neuroanatomy," 1995 (published by Churchill Livingstone)), along with multiple leads 111 (shown as leads 111 a-111 e) implanted at representative locations. For purposes of illustration, multiple leads 111 are shown in Figure 2A implanted in a single patient. In addition, for purposes of illustration, the leads 111 are shown as elongated leads however, leads 111 can be paddle leads. In actual use, any given patient will likely receive fewer than all the leads 111 shown in Figure 2A.

[0045] The spinal cord 191 is situated within a vertebral foramen 188, between a ventrally located ventral body 196 and a dorsally located transverse process 198 and spinous process 197. Arrows V and D identify the ventral and dorsal directions, respectively. The spinal cord 191 itself is located within the dura mater 199, which also surrounds portions of the nerves exiting the spinal cord 191, including the ventral roots 192, dorsal roots 193, and dorsal root ganglia 194. The dorsal roots 193 enter the spinal cord 191 at the dorsal root entry region 187, and communicate with dorsal horn neurons located at the dorsal horn 186. In some embodiments, the first and second leads 111a, 111b are positioned just off the spinal cord midline 189 (e.g., about 1 mm offset) in opposing lateral directions so that the two leads 111a, 111 b are spaced apart from each other by about 2 mm, as discussed above. In some embodiments, a lead or pairs of leads can be positioned at other locations, e.g., toward the outer edge of the dorsal root entry region 187 as shown by a third lead 111c, or at the dorsal root ganglia 194, as shown by a fourth lead 111 d, or approximately at the spinal cord midline 189, as shown by a fifth lead 111 e. One or more of the leads 111a-111e can deliver neurostimulation to various targets within the spinal cord spinal cord, including, but not limited to, the dorsal column, the dorsal horn, the intermediolateral nucleus, and / or other neurons within any of laminae l-X of the spinal cord.

[0046] In some embodiments, the devices and systems of the present technology include features other than those shown herein. For example, one lead 111 to six leads 111 can be positioned generally end-to-end at or near the patient's midline M and span vertebral levels from about C2 to about T12, or from about T4 to about T12. In some embodiments, two, three, or four leads 111 are positioned end-to-end at or near the patient's midline from T4 to T12. In some embodiments, the leads 111 and / or other signal delivery devices can have locations other than those expressly shown herein. For example, one or more signal delivery devices can be positioned at the dorsal side of the spinal cord 191. In addition, the devices and systems of the present technology can include more than one internal stimulator and / or more than one external stimulator that can be configured for wireless stimulation, such as by using electromagnetic waves.

[0047] In some embodiments, the signal delivery elements 110 can be positioned within the patient's head to modulate neurons at any suitable lobe or other structure of the cortex or deep brain. For example, Figure 2B is a partially schematic, crosssectional illustration of a first lead 111a placed at a first cortical location and a second lead 111b placed at a second cortical location. The first lead 111a is shown as positioned within the patient's dura D, in the subdural space DS, so as to lie along or adjacent to the gray matter GM of the patient's cortex. The second lead 111 b is shown as positioned within a sulcus S (e.g., the central sulcus Su) so as to better access neural populations within the folds of the patient's cortex. Of course, the signal delivery element(s) (e.g., leads) can be positioned at other cortical locations (e.g., epidurally). In some embodiments, the signal delivery elements 110 can be positioned within or proximate deep brain regions, in addition to or in lieu of placement at cortical regions. Representative deep brain targets include, but are not limited to, the subthalamic nucleus (STN), the globus pallidus internus (GPI), the ventral intermediate (VIM) nucleus, the pedunculopontine nucleus (PPN), the hippocampus, the amygdala, and the like.

[0048] In some embodiments, the signal delivery elements 110 can be positioned at or proximate one or more peripheral nerves of the patient to modulate peripheral neurons. For example, Figure 2C is a schematic representation of a lead 111 positioned adjacent a peripheral nerve PN. In some embodiments, the peripheral nerve PN includes a bundle of nerve fibers. Representative peripheral nerves include, but are not limited to, the vagal nerve, sacral nerves, median nerves, tibial nerves, femoral nerves, sciatic nerve, obturator nerve, pudendal nerve, saphenous nerve, fibulae nerve, sural nerve, axillary nerve, radial nerve, ulnar nerve, musculocutaneous nerve, etc. The lead 111 can be placed at various positions along the peripheral nerve PN, including adjacent the nerve fibers (e.g., along the length of the axons), adjacent nerve bodies, or adjacent both nerve fibers and nerve bodies. Although shown as a cylindrical lead, in some embodiments the lead 111 can be a cuff electrode configured to at least partially wrap around the peripheral nerve PN, and / or a penetrating electrode array.

[0049] Several aspects of the technology are embodied in computing devices, e.g., programmed / programmable pulse generators, controllers and / or other devices. The computing devices on / in which the described technology can be implemented can include one or more central processing units, memory, input devices (e.g., input ports), output devices (e.g., display devices), storage devices, and network devices (e.g., network interfaces). The memory and storage devices are computer-readable media that can store instructions that implement the technology. In some embodiments, the computer readable media are tangible media. In some embodiments, the data structures and message structures can be stored or transmitted via an intangible data transmission medium, such as a signal on a communications link. Various suitable communications links can be used, including but not limited to a local area network and / or a wide-area network.

[0050] Figure 3 is a partially schematic illustration of a representative lead body 311 that can be used to apply modulation to a patient in accordance with any of the foregoing embodiments. In general, the lead body 311 includes a multitude of electrodes or contacts 320. When the lead body 311 has a circular cross-sectional shape, as shown in Figure 3, the contacts 320 can have a generally ring-type or segmented shape and can be spaced apart axially along the length of the lead body 311. In a particular embodiment, the lead body 311 can include eight contacts 320, identified individually as first, second, third . . . eighth contacts 321, 322, 323 . . . 328, although in other embodiments the lead body 311 can include fewer or more electrodes, such as between 1 electrode and 64 electrodes. In general, one or more of the contacts 320 are used to provide signals, and another one or more of the contacts 320 provide a signal return path. Accordingly, the lead body 311 can be used to deliver monopolar modulation (e.g., if the return contact is spaced apart significantly from the delivery contact), or bipolar modulation (e.g., if the return contact is positioned close to the delivery contact and in particular, at the same target neural population as the delivery contact). In still further embodiments, the pulse generator 101 (Figure 1) can operate as a return contact for monopolar modulation. 4.0 Representative Embodiments of the Present Technology A. Reduced Dosing Schedules and Associated Methods

[0051] As set forth above, the present technology includes stimulation schedules / regimens that are expected to reduce the amount of power reguired for paresthesia-free stimulation, while maintaining the benefits of paresthesia-free stimulation. Additionally, the present technology includes stimulation schedules / regimens that are expected to reduce the burden on a patient undergoing stimulation in circumstances in which an external power source is reguired to be worn during the therapy stimulation. This is accomplished by reducing the dose of paresthesia-free neurostimulation provided to a patient overtime. Of note, the reduction in dose can occur without a corresponding reduction, or clinically meaningful reduction, in effectiveness.

[0052] In some embodiments, the patient may initially receive paresthesia-free stimulation on a continuous or generally continuous basis for a first stimulation period, such as immediately following implantation of the signal delivery device. As used herein, the term "continuous" refers to administering an electrical signal 24 hours per day without any significant off-periods (e.g., without an "off-period" of one or more consecutive hours). The signal may be pulse dosed for the 24 hour period and still be considered a "continuous" signal. As described above, suitable pulse dose rates include between 1% and 100%. As also described above, pulse dose patterns frequently operate on a timescale of minutes or less (e.g., 1 minute on, 1 minute off, 1 second on, 1 second off; 100 milliseconds on, 1 second off; etc.). Accordingly, the term continuous does not preclude a signal being delivered according to a pulse dose, but rather is used to contrast other stimulation schedules described below, in which stimulation is ceased for a consecutive off-period on the order of hours (e.g., the signal is off for greater than at least 1 consecutive hour).

[0053] In some embodiments, the patient may initially receive paresthesia-free stimulation on a noncontinuous basis for the first stimulation period. In such embodiments, the patient nevertheless receives a relatively significant dose of stimulation during the first stimulation period, such as at least 12 hours of stimulation per day. The at least 12 hours of stimulation can be consecutive / uninterrupted (e.g., 12 hours on, 12 hours off), or nonconsecutive (e.g., 4 hours on, 4 hours off, repeated over the course of 24 hours). As described above, the signal may be administered according to a pulse dose during the "on" time (e.g., the signal has a pulse dose of 50% for the 12 hour "on" period and is ceased entirely during the 12 hour "off1 period).

[0054] The first stimulation period can be between about 1 month and about 1 year, such as between about 1 month and about 9 months, between about 1 month and about 6 months, and / or between about 1 month and about 3 months. For example, the first period can be about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, or about 6 months. The first period may also be shorter. For example, in some embodiments the first period may be between about 1 day and about 30 days, such as between about 10 days and about 30 days, or about 10 days, about 15 days, about 20 days, about 25 days, or about 30 days.

[0055] After receiving continuous or generally continuous paresthesia-free stimulation for the first stimulation period, the patient may then receive a reduced dose of paresthesia-free stimulation during a second stimulation period that follows the first stimulation period. The reduced dose of stimulation can be noncontinuous (e.g., intermittent) stimulation in which stimulation is only administered during discrete therapeutic or stimulation sessions. Such discrete stimulation sessions may also be referred to herein as a "bolus" of stimulation. As described below, stimulation schedules during the second stimulation period generally include an "off-period" of at least 12 hours. In many embodiments described below, the off-period is greater than 12 hours, such as at least 18 hours or more.

[0056] In some embodiments, delivering the reduced dose of stimulation includes delivering stimulation during a single stimulation session per day (e.g., a once per day bolus). The once per day stimulation session may include a consecutive (e.g., uninterrupted) duration of between about 1 hour and about 12 hours, such as between about 1 hour and about 9 hours, or between about 1 hour and about 6 hours, or between about 1 hour and about 4 hours, or between about 2 hours and about 4 hours, or between about 1 hour and about 3 hours, or between about 1 hour and about 2 hours. For example, the stimulation session may have a duration of about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, or about 8 hours. The once per day stimulation session may also have shorter durations. For example, the stimulation session may have a duration of between about 1 minute and about 60 minutes, such as between about 5 minutes and about 60 minutes, or between about 15 minutes and about 45 minutes. Representative examples include about 2 minutes, about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, and about 55 minutes. As described above with respect to continuous stimulation, stimulation can be administered during the stimulation session according to a pulse dose. The patient does not receive clinically significant stimulation other than during the stimulation session.

[0057] In some embodiments, delivering the reduced dose of stimulation includes delivering stimulation during two, three, four, or more stimulation sessions per day (e.g., a twice per day bolus, three times per day bolus, etc.). Each stimulation session may have a duration equal to any of the durations recited above for the once per day stimulation session. However, in embodiments in which multiple stimulation sessions occur each day, the duration of each stimulation session is generally less than about 2 hours, such as between about 1 minute and about 1 hour, or about 5 minutes, about 10 minutes, about 15 minutes, about 30 minutes, about 45 minutes, or about 1 hour. Moreover, each stimulation session need not be the same length. For example, a first stimulation session may be about 45 minutes, and a second stimulation session may be about 15 minutes, or vice versa. In embodiments in which more than one stimulation session occurs per day, the stimulation sessions are generally spaced apart by at least one hour, at least two hours, at least three hours, or more, during which the patient receives no stimulation.

[0058] In some embodiments, delivering the reduced dose of stimulation includes delivering stimulation during stimulation sessions that occur less frequently than once per day. For example, the reduced dose may include one stimulation session every other day, one stimulation session every third day, one stimulation session per week, etc. Similarly, the reduced dose may include a number of stimulation session spread over a number of days, such as two stimulation session over a five-day period, three stimulation sessions over a five-day period, four stimulation sessions over a seven-day period, or the like.

[0059] In some embodiments, the duration of the first stimulation period is predetermined such that the patient transitions to the reduced dose after the predetermined duration. In some embodiments, the predetermined duration can be based at least in part on durations associated with successful outcomes in reference patient data (e.g., aggregated patient data collected during clinical studies). Once the predetermined duration has elapsed, the stimulation system can automatically deliver, or be reprogrammed to deliver, the reduced dose of stimulation. In other embodiments, the transition between the first stimulation period and the second stimulation period is not automatic. For example, in embodiments in which the signal generator is a wearable device, the patient may simply be instructed after the predetermined duration of the first stimulation period to reduce their usage of the stimulation system. In such embodiments, the healthcare provider can "prescribe" the patient a specific number and duration of stimulation sessions for the second stimulation period (e.g., two 30-minute stimulation session per day; four one-hour stimulation sessions per week; etc.), similar to a healthcare provider instructing a patient to attend physical therapy a set number of days per week. By way of one example, this "prescription" can take place via remote programming of the patient smartphone application or other patient controller described herein.

[0060] In some embodiments, the duration of the first stimulation period is based on one or more measured or reported criteria meeting certain predetermined thresholds. Suitable objective criteria include, for example, spontaneous neural activity, evoked neural activity, patient activity level, etc. Suitable subjective criteria include, for example, patient-reported pain scores (e.g., VAS pain scores, NRS scores, etc.), patient-reported quality of life, patient satisfaction, patient sleep quality, physician observations, etc. Once the one or more objective or subjective criteria meet the predetermined threshold, the signal generator can automatically transition to delivering the reduced dose of stimulation. In other embodiments, the transition is not automatic. For example, in embodiments in which the signal generator is a wearable device, the patient may simply be instructed (e.g., by their healthcare provider, by a patient-controller, etc.) to reduce their usage of the stimulation system once the objective or subjective criteria meet the predetermined threshold. In such embodiments, and as described above, the healthcare provider can "prescribe" the patient a specific number and duration of stimulation sessions for the second stimulation period. In some embodiments, the objective / subjective criteria can continue to be periodically monitored during the second stimulation period to determine whether the "prescription" (i.e., the amount and duration of stimulation sessions) should be adjusted.

[0061] In some embodiments, the second stimulation period continues for an indefinite period. For example, once the patient has transitioned to receiving the reduced dose of stimulation during the second stimulation period, the patient may continue to receive stimulation according to the reduced schedule indefinitely. Of course, the patient can be periodically reevaluated to determine whether the reduced dose needs to be adjusted, and / or whether the patient would benefit from returning to continuous or generally continuous stimulation. Similarly, as described above, subjective and objective criteria can continue to be collected to determine whether the "prescription" should be adjusted.

[0062] In some embodiments, the second stimulation period has a predetermined duration, after which the patient receives a second reduced dose of stimulation during a third stimulation period. The second reduced dose can be less than the initial reduced dose delivered during the second stimulation period. For example, if the initial reduced dose delivered during the second stimulation period is 2 hours per day, the second reduced dose during the third stimulation period can be 1 hour per day. As another example, if the initial reduced dose delivered during the second stimulation period is 1 hour per day, the second reduced dose during the third stimulation period can be 30 minutes per day. Of course, the foregoing are provided by way of example only—the second reduced dose can have any value within the ranges previously described with respect to the first reduced dose. In embodiments in which the patient transitions to a second reduced dose, the transition between the second stimulation period and the third stimulation period can be based on the same criteria as transitioning between the first stimulation period and the second stimulation period. In some embodiments, the second reduced dose can be greater than the first reduced dose, e.g., if deemed appropriate by a clinician or other healthcare provider to meet a therapy objective. For example, if the initial reduced dose during the second stimulation period is 2 hours per day, the second reduced dose during the third stimulation period may be increased to 4 hours per day.

[0063] In some embodiments, the patient can further be titrated through additional reduced doses during subsequent stimulation periods. For example, a patient may be titrated through three, four, five, six, seven, eight, or more stimulation periods each having a reduced (or at least different) dose of stimulation. For example, a patient may receive 12 hours of stimulation per day during the first stimulation period, 8 hours of stimulation per day during the second stimulation period, 4 hours of stimulation per day during the third stimulation period, 2 hours of stimulation per day during a fourth stimulation period, and 30 minutes of stimulation per day during a fifth stimulation period. Additional representative schedules for titration include any combination of the following: 8 hours, 4 hours, 2 hours, 1 hour, or 30 minutes of stimulation per day for the second stimulation period; 4 hours, 2 hours, 1 hour, 30 minutes, 15 minutes, or 5 minutes of stimulation per day for the third stimulation period; and 2 hours, 1 hour, 30 minutes, 15 minutes, 5 minutes, or 1 minute of stimulation per day for the fourth stimulation period.

[0064] Without being bound by theory, applying stimulation on a continuous or generally continuous basis for a first stimulation period (e.g., immediately following implantation of the signal delivery device) is expected to induce a physiologic effect, that in turn is expected to produce a therapeutic effect. The first physiologic effect may be, for example, a quieting or other normalization of overactive or sensitized neurons, and the therapeutic effect may be a reduction in patient pain. Without being bound by theory, it is expected that less frequent stimulation (e.g., a lower dose of stimulation) is necessary to maintain the physiologic effect (and thus the therapeutic effect) once it has been induced. That is, the physiologic effect can be maintained by providing a reduced dose of stimulation, such as by providing stimulation on an intermittent basis as described above with respect to the second stimulation period. It is therefore expected that continuous or generally continuous stimulation is not necessary to maintain the physiologic effect once it has been achieved. Of course, response to stimulation varies by patient, so certain patients may require more stimulation to achieve and / or maintain the physiologic effect than others.

[0065] Although the foregoing describes administering continuous (or generally continuous) stimulation for a first stimulation period and a reduced dose of stimulation during a second stimulation period, in some embodiments the patient may begin therapy on an intermittent or noncontinuous stimulation schedule. For example, the patient may initially receive a first reduced dose of stimulation, such as described above with respect to the second stimulation period, before subsequently transitioning to a second reduced dose of stimulation, such as described above with respect to the third stimulation period. In some embodiments, therefore, the patient bypasses the first stimulation period and simply begins therapy at the second stimulation period. In such examples, the patient may begin therapy by receiving less than 12 hours of stimulation per day, such as about 8 hours of stimulation per day, 4 hours of stimulation per day, 2 hours of stimulation per day, 30 minutes of stimulation per day, or any of the other values described above with reference to the second stimulation period.

[0066] Figure 4 is a block diagram illustrating a method 400 for treating a patient in accordance with embodiments of the present technology. Some or all of the operations in the method 400 can be performed by a processor executing instructions stored on one or more elements of a patient treatment system, including the patient treatment system 100 described with reference to Figure 1.

[0067] The method 400 can begin at block 402 by delivering a first electrical signal to the patient's spinal cord region via an implanted signal delivery device, for a first stimulation period and according to a first stimulation schedule in which the first electrical signal is delivered for at least 12 hours per day. In some embodiments, delivering the first electrical signal according to the first stimulation schedule includes continuously delivering the first electrical signal during the first stimulation period, as described above. In other embodiments, delivering the first electrical signal according to the first stimulation schedule includes non-continuously delivering the first electrical signal during the first stimulation period. However, in embodiments in which the first electrical signal is delivered non-continuously, the first electrical signal is nevertheless delivered for at least 12 hours per day, such as at least 16 hours per day, or at least 20 hours per day. The first stimulation period can have any of the durations described above.

[0068] The method 400 can continue at block 404 by delivering, after the first stimulation period, a second electrical signal to the patient's spinal cord region via the implanted signal delivery device, for a second stimulation period and according to a second stimulation schedule in which the second electrical signal is delivered for less than 6 hours per day, such as less than 5 hours per day, or less than 4 hours per day, etc. This may include, for example, delivering the second electrical signal during one or more stimulation sessions per day. The stimulation session can have a duration between about 1 minute and about 6 hours, as previously described. In some embodiments, the second electrical signal is delivered at block 404 during a single stimulation session per day, although in other embodiments the second electrical signal is delivered at block 404 during multiple stimulation sessions per day. In yet other embodiments, the second electrical signal is delivered during fewer than seven stimulation sessions per week such that the patient averages less than one stimulation session per day.

[0069] In some embodiments, the second stimulation period continues indefinitely. In other embodiments, the method 400 can optionally continue at block 406 by delivering, after the second stimulation period, a third electrical signal to the patient's spinal cord region via the implanted signal delivery device for a third stimulation period and according to a third stimulation schedule in which the third electrical signal is delivered for less than 2 hours per day, such as less than 1 hour per day, or less than 30 minutes per day. This may include, for example, delivering the third electrical signal during one or more stimulation sessions per day. The stimulation session can have a duration between about 1 minutes and about 2 hours. In some embodiments, the third electrical signal is delivered at block 406 during a single stimulation session per day, although in other embodiments the third electrical signal is delivered at block 404 during multiple stimulation sessions per day. In yet other embodiments, the third electrical signal is delivered during fewer than seven stimulation sessions per week such that the patient averages less than one stimulation session per day.

[0070] Although not shown in Figure 4, the method 400 can optionally continue by titrating the patient through additional stimulation periods having different stimulation schedules after the third stimulation period. For example, after the third stimulation period, the method 400 can include delivering a fourth electrical signal to the patient's spinal cord region for a fourth stimulation period and according to a fourth stimulation schedule in which the fourth electrical signal is delivered for less than, e.g., 1 hour per day. After the fourth stimulation period, the method 400 can further include delivering a fifth electrical signal to the patient's spinal cord region for a fifth stimulation period and according to a fifth stimulation schedule in which the fifth electrical signal is delivered for less than, e.g., 30 minutes per day. In this way, the method 400 can include incrementally reducing a patient's stimulation dose over subsequent stimulation periods. Any number of incremental stimulation periods can be used, including two, three, four, five, six, seven, eight, or more.

[0071] The first, second, and third electrical signals (and any other electrical signals delivered during subsequent stimulation periods) can have the same or generally similar parameters. For example, each of the first, second, and third electrical signals can have the same or generally the same frequency, pulse width, amplitude, and / or pulse dosing rate. Thus, in some embodiments the signal parameters remain the same during the first stimulation period, the second stimulation period, and the third stimulation period, and the only change is the duration that the signal is administered to the patient. In other embodiments, at least one parameter (e.g., frequency, pulse width, amplitude, and / or pulse dose rate) can change as the patient transitions from the first electrical signal to the second electrical signal, and / or from the second electrical signal to the third electrical signal, and so on.

[0072] In some embodiments, the first, second, and third electrical signals (and any other electrical signals delivered during subsequent stimulation periods) are paresthesia-free electrical signals that do not induce a sensation of paresthesia when administered to the patient. That is, the patient generally cannot sense whether the signal is being actively applied. As described in detail under Section 5.0, the paresthesia-free signals may include different types of paresthesia-free signals, including, but not limited to, high frequency, paresthesia-free signals and / or low frequency, paresthesia-free signals. In other embodiments, the one or more of the electrical signals delivered during operation of the method 400 can be paresthesiaproducing signals.

[0073] Figure 5 is a block diagram illustrating another method 500 for treating a patient in accordance with embodiments of the present technology. Similar to the method 400 described with reference to Figure 4, some or all of the operations in the method 500 shown in Figure 5 can be performed by a processor executing instructions stored on one or more elements of a patient treatment system, including the patient treatment system 100 described with reference to Figure 1.

[0074] The method 500 can begin in block 502 by delivering a first electrical signal to the patient's spinal cord region via an implanted signal delivery device, for a first stimulation period according to a first stimulation schedule in which the first electrical signal is delivered for at least 12 hours per day, such as at least 16 hours per day or at least 20 hours per day. The operation at block 502 can the same as, or generally the same as, the operation at block 402 of the method 400 described with reference to Figure 4. The method 500 can continue in block 504 by delivering, after the first stimulation period, a second electrical signal to the patient's spinal cord region via the implanted signal delivery device, for a second stimulation period and according to a second stimulation schedule in which the second electrical signal is delivered for, e.g., less than 6 hours per day, such as less than 5 hours per day, less than 4 hours per day, etc. The operation at block 504 can be the same as, or generally the same as, the operation at block 402 of the method 400 described with reference to Figure 4.

[0075] The method 500 can continue in block 506 by determining whether a therapeutic effect obtained during the first stimulation period is maintained during the second stimulation period. For example, if patient pain is reduced relative to baseline during the first stimulation period, the operation at block 506 can include determining whether the reduction in patient pain is maintained during the second stimulation period. In such embodiments, determining whether patient pain is maintained during the second stimulation period can include comparing a VAS or NRS pain score during the first stimulation period to a VAS or NRS pain score during the second stimulation period. If the VAS or NRS pain score during the second stimulation period is no more than 20% greater than the VAS or NRS pain score during the first stimulation period, the reduction in pain is considered to be maintained. Of course, other thresholds (e.g., 0%, 10%, 30%, etc.) and / or other metrics (e.g., spontaneous neural activity, evoked potential, etc.) can be used to determine whether the therapeutic effect is maintained at block 506.

[0076] If the therapeutic effect is determined as being maintained at block 506, the method 500 can optionally continue at block 508 by reducing (1) the duration of individual stimulation sessions, and / or (2) the number of stimulation sessions per week. An example of reducing the duration of individual stimulation sessions includes transitioning from 45 minute stimulation sessions to 30 minute stimulation sessions. An example of reducing the number of stimulation sessions per weeks includes transitioning from one stimulation session per day to one stimulation session every other day. Of course, the foregoing are provided by way of example only—one skilled in the art will appreciate from the disclosure herein that the duration and / or number of stimulation sessions can be reduced within any of the ranges provided herein.

[0077] If the therapeutic effect is determined as not being maintained at block 506, the method 500 can continue at block 510 by increasing (1) the duration of individual stimulation sessions, and / or (2) the number of stimulation sessions per week. An example of increasing the duration of individual stimulation sessions includes transitioning from 45 minute stimulation sessions to 1 hour stimulation sessions. An example of increasing the number of stimulation sessions per week includes transitioning from one stimulation session per day to two stimulation sessions per day. As with the disclosed embodiments above, the foregoing are provided by way of example only—one skilled in the art will appreciate from the disclosure herein that the duration and / or number of stimulation sessions can be increased within any of the ranges provided herein.

[0078] In some embodiments, the operations in blocks 506, 508, and 510 can be iteratively performed until the lowest effective stimulation dose / schedule that maintains the therapeutic effect is discovered, such that the patient steps through a plurality of stimulation schedules. That is, the stimulation schedule / dose is titrated to (i) minimize power requirements, (ii) have the shortest stimulation sessions, (iii) have the fewest number of stimulation sessions per day, and / or (iv) have the longest duration between subsequent stimulation sessions, while maintaining the therapeutic effect of the stimulation therapy. For example, in some embodiments the stimulation schedule / dose can be iteratively titrated by repeating the operations in blocks 506 and 508 until a stimulation schedule is reached in which the patient receives a single, relatively short (e.g., less than about 1 hour) stimulation session per week. In some embodiments, it is expected that the patient may be titrated through two, three, four, five, six, seven, eight, nine, ten, or more stimulation schedules during the iterative process of repeating the operations in blocks 506, 508, and 510. Once the lowest effective stimulation dose / schedule is discovered, the operations in blocks 506, 508, and 510 can be periodically repeated to ensure that the stimulation schedule remains optimized.

[0079] In some embodiments, the methods 400 and 500 described with respect to Figures 4 and 5 are performed using a neurostimulation system that includes an implanted signal delivery device and an implanted signal generator having a primary cell battery. Use of a primary cell battery is more convenient than a secondary cell battery because it eliminates the need for the patient to recharge the device. However, use of a primary cell battery in implanted signal generators for high frequency stimulation has previously been unrealistic due to the relatively high power requirements of high frequency stimulation systems. In other words, the lifespan of the implanted device with a primary cell battery would not be long enough to justify the patient conveniences associated with a primary cell battery. However, stimulation delivered in accordance with the present technology, such as in accordance with the method 400 described with respect to Figure 4, is expected to reduce power consumption (e.g., by virtue of reducing the duration that stimulation is administered for) such that it becomes reasonable to utilize an implantable signal generator with a primary cell battery, eliminating the need for the patient to recharge the device.

[0080] In some embodiments, the methods 400 and 500 described with respect to Figures 4 and 5 are performed using a neurostimulation system that includes an implanted signal delivery device and an external signal generator. In such embodiments, the external signal generator can be a wearable device (e.g., a puck) that the patient attaches to their skin or otherwise places in alignment with the implanted signal delivery device during stimulation sessions. The patient can recharge the external signal generator during periods of nonuse. Of course, the methods 400 and 500 described with respect to Figures 4 and 5 can be performed by other stimulation systems, including any variation of the system 100 described with respect to Figure 1, and other stimulation systems known in the art. B. Inducing and Maintaining a State of Remission, Including Maintenance Dosing Schedules and Associated Methods

[0081] As set forth above, stimulation in accordance with the present technology may induce certain physiological changes / effects in a patient that persist even once stimulation ceases. For example, in some patients with pain resulting from sensitized or overactive neurons, stimulation in accordance with the present technology may guiet or otherwise normalize the sensitized neurons, which may result in a therapeutic effect (e.g., reduced pain) that persists after the stimulation ceases. In some embodiments, this physiological change persists for more than one week following termination of stimulation, such as more than two weeks, more than three weeks, more than one month, more than six months, more than one year, etc., regardless of whether the patient receives additional stimulation during this period. In such embodiments, the patient may enter a state of "remission," in which patient symptoms or a patient condition continue to be suppressed or reduced, even during relatively prolonged therapy breaks.

[0082] Once a patient has entered a state of remission, the patient may no longer need freguent stimulation, including the reduced doses of stimulation described above in Section 4.0 under subheading A. Indeed, some patients may not reguire any stimulation at all once they have entered remission. Accordingly, in some embodiments the systems and methods described herein include stopping delivery of stimulation (e.g., clinically meaningful stimulation) once the patient enters a state of remission. Depending on the patient, remission may last indefinitely, or for at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, at least about 9 months, at least about 1 year, at least about 1.5 years, at least about 2 years, at least about 5 years, or longer. In some embodiments, the patient can continue to be monitored after stimulation has been stopped to determine if the patient exits remission (e.g., the patient relapses). If so, stimulation can be restarted. As one skilled in the art will appreciate, inducing remission in a patient and then subsequently ceasing stimulation can significantly reduce the power consumption of stimulation systems, increasing their lifespan, reducing patient burden, enabling the use of primary cell batteries for stimulation systems, and / or other advantages.

[0083] Figure 6 is a block diagram illustrating a method 600 of treating a patient in accordance with embodiments of the present technology. Similar to the method 400 described with reference to Figure 4 and the method 500 described with reference to Figure 5, some or all of the operations in the method 600 shown in Figure 6 can be performed by a processor executing instructions stored on one or more elements of a patient treatment system, including the patient treatment system 100 described with reference to Figure 1.

[0084] The method 600 can begin in block 602 by delivering electrical stimulation to a target neural population. The electrical stimulation can be delivered to induce a therapeutic effect in the patient. In some embodiments, the therapeutic effect includes reducing pain in the patient and / or inducing any of the other therapeutic effects described throughout this Detailed Description. In some embodiments, delivering the electrical stimulation includes delivering a paresthesia-free electrical signal that does not induce a sensation of paresthesia when administered to the patient. As described in detail under Section 5.0, the paresthesia-free signals may include high frequency, paresthesia-free signals, low frequency, paresthesia-free signals, and / or other types of paresthesia-free signals. In other embodiments, the electrical signals delivered during the method 600 can be paresthesia-producing signals.

[0085] The electrical stimulation can be delivered at block 602 in many different manners. For example, in some embodiments the electrical stimulation can be delivered continuously and / or substantially continuously at block 602. In other embodiments, the electrical stimulation can be delivered non-continuously, including in accordance with the reduced doses previously described herein. For example, in some embodiments delivering electrical stimulation at block 602 includes delivering an electrical signal according to a single stimulation schedule, e.g., that can be generally similar to the first stimulation schedule described above in connection with the method 400 of Figure 4. That is, the stimulation schedule can include continuously delivering the electrical signal, or non-continuously delivering the electrical signal for at least 12 hours per day. In other embodiments, the single stimulation schedule can be generally similar to the second stimulation schedule described above in connection with the method 400 of Figure 4. For example, the single stimulation schedule can include delivering an electrical signal for less than 6 hours per day. This may include, for example, delivering the electrical signal during one or more stimulation sessions per day, with each stimulation session having a duration between about 1 minute and about 6 hours, as previously described.

[0086] In other embodiments, delivering electrical stimulation at block 602 includes delivering the electrical stimulation according to two or more stimulation schedules. This may include, for example, delivering electrical stimulation according to the method 400 described with reference to Figure 4 and / or the method 500 described with reference to Figure 5. That is, the operation at block 602 can include a first treatment phase and a second treatment phase, and delivering electrical stimulation at the block 602 can include (1) delivering a first electrical signal according to a first stimulation schedule in which the first electrical signal is delivered for at least 12-hours per day for the first treatment stage, and then (2) delivering a second electrical signal according to a second stimulation schedule in which the second electrical signal is delivered for less than 6 hours per day for the second treatment stage. In other words, the operation at block 602 can include administering stimulation according to a plurality of different stimulation schedules such that stimulation is titrated from a first, relatively higher dose of stimulation to a second, relatively lower dose of stimulation, which may include stepping through one or more intermediate doses.

[0087] The method 600 can continue at block 604 by determining that the patient has entered a state of remission. In some embodiments, determining that the patient has entered a state of remission includes receiving an indication from a healthcare provider that the patient has entered a state of remission. For example, the patient may be examined by a healthcare provider who can determine, based on objective and / or subjective criteria, that the patient has entered a state of remission. In some embodiments, this may include simply indicating on a physician or patient controller that the patient has entered a state of remission, in response to which the stimulation system automatically proceeds to ceasing stimulation in accordance with the operation in block 606, described below.

[0088] In some embodiments, determining that the patient has entered a state of remission includes collecting and analyzing patient data. Representative patient data may include, for example, objective criteria such as spontaneous neural activity, evoked neural activity, patient activity level, etc., and / or subjective criteria such as patient-reported pain scores (e.g., VAS pain scores, NRS scores), patient-reported quality of life, patient-satisfaction, patient sleep quality, physician observations, etc. The collected data can be analyzed to determine whether the patient has entered a state of remission. For example the collected data can be compared to one or more predetermined remission criteria.

[0089] As a first example, determining that the patient has entered a state of remission includes comparing patient pain scores to a corresponding remission criterion. An example remission criterion includes maintaining at least a 50% pain reduction relative to baseline for a duration of at least three months. That is, patient pain levels can be periodically monitored and compared to a baseline patient pain level before the patient began stimulation therapy in block 602. If the patient has maintained at least 50% pain relief for a consecutive period of three months, the patient may be identified as having entered a state of remission. Of course, the foregoing values are provided by way of example only, and other suitable remission criteria can be used. Representative pain reduction targets can include, for example, at 60% pain relief, at least 70% pain relief, at least 80% pain relief, or at least 90% pain relief. Representative durations can include at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, etc.

[0090] As a second example, determining that the patient has entered a state of remission can include comparing spontaneous neural activity and / or evoked neural activity to one or more remission thresholds. For example, spontaneous neural activity may be collected and analyzed to determine whether previously overactive or sensitized neurons have been quieted or normalized. If the spontaneous neural activity has decreased below the remission threshold, then the patient can be identified as being in a state of remission. The foregoing are provided by way of example, and the operation in block 604 can be carried out using other suitable techniques.

[0091] The method 600 can continue at block 606 by ceasing delivery of the electrical stimulation in response to determining that the patient has entered a state of remission. Without intending to be bound by theory, it is expected that the therapeutic effect induced by the electrical stimulation at block 602 will persist even after stimulation is terminated at block 606 because the patient has entered a state of remission. In some embodiments, it is expected that the therapeutic effect may persist for at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least nine months, at least 12 months, at least 15 months, at least 18 months, at least 21 months, at least 24 months, at least 30 months, or at least 36 months after stimulation is terminated at block 606. Accordingly, in some embodiments ceasing stimulation at block 606 includes ceasing stimulation for one or more of the foregoing time periods (e.g., ceasing stimulation for at least one month, at least two months, etc.), while at least partially maintaining the therapeutic effect. In some embodiments, the duration for which stimulation remains off is predetermined, e.g., based on an expected duration of the patient's remission. In some embodiments, the stimulation can be restarted after the predetermined duration elapses.

[0092] In some embodiments, the patient can be periodically monitored after ceasing stimulation at block 606 to determine if the patient remains in remission. For example, the method 600 can include at block 608 monitoring the patient to determine if the patient remains in remission. This can include comparing patient data to one or more remission criteria. In some embodiments, the remission criteria can be generally similar to the remission criteria utilized at block 604 to determine whether the patient has entered a state of remission. For example, if the remission criteria at block 604 included a specific reduction in pain (e.g., a 50% reduction in a VAS pain score relative to baseline for three months), then the remission criteria at block 606 can be whether the specific reduction has been maintained (e.g., a 50% reduction in the VAS pain score). In some embodiments, the remission criteria values can differ between the operations at block 604 and 608. For example, the remission criteria value at block 604 may include a greater percent reduction in pain (e.g., 80% relative to baseline) than the remission criteria value at block 608 (e.g., 60% relative to baseline). As one skilled in the art will appreciate, other remission criteria can be used at block 608, including objective criteria such as spontaneous neural activity, evoked neural activity, patient activity level, etc., and / or subjective criteria such as patient-reported pain scores (e.g., VAS pain scores, NRS scores), patient-reported quality of life, patient-satisfaction, patient sleep quality, physician observations, etc. The patient can be periodically monitored at any suitable interval (e.g., weekly, monthly, every-other-month, quarterly, bi-annually, annually, etc.).

[0093] If at block 608 it is determined that the patient has exited remission (e.g., if the patient did not meet the remission criteria and / or the therapeutic effect has not been maintained at a suitable level), the method 600 can return to the operation at block 602 and deliver electrical signal to the target patient population until the patient reenters remission. However, if at block 608 it is determined that the patient remains in remission (e.g., if the patient continues to meet the remission criteria and / or the therapeutic effect has been maintained at a suitable level), stimulation can continue to be withheld, and the patient can continue to be periodically monitored at block 608.

[0094] Without being bound by theory, identifying patients as having entered a state of remission and ceasing stimulation is expected to provide several advantages. Many of the advantages are similar to those identified previously with respect to delivering reduced doses of stimulation. For example, ceasing stimulation in response to identifying a patient as having entered a state of remission is expected to reduce power-consumption, enabling smaller implants, enabling use of primary cell batteries, reducing charging-burdens, and other associated benefits. In some embodiments, implanted systems may even be explanted from a patient in response to determining that a patient has entered a state of remission.

[0095] Although the method 600 of Figure 6 describes terminating stimulation in response to determining that a patient has entered a state of remission, in some embodiments patients in a state of remission may require a relatively infrequent and periodic "maintenance" dose of stimulation to maintain the physiological change, and thus to remain in the state of remission. The maintenance dose can be even less than the reduced doses of stimulation described previously. For example, as used herein the term "maintenance dose" generally refers to a dose of stimulation that is administered, or prescribed to be administered, to the patient at a cadence of once per week or less. Accordingly, as described in greater detail below, the present technology further includes maintenance doses and stimulation schedules that provide even less stimulation than the reduced doses described above in Section 4.0 under subheading A for treating a patient once the patient has entered a state of remission.

[0096] In some embodiments, the maintenance dose is delivered during a single stimulation session per week or less. For example, delivering the maintenance dose can include delivering stimulation during one stimulation session per week, one stimulation session every other week, one stimulation session every three weeks, one stimulation session per month, one stimulation session every two months, one stimulation session every three months, one stimulation session every four months, one stimulation session every five months, one stimulation session every six months, one stimulation session every nine months, or one stimulation session per year. Additional representative examples include one, two, three, or four stimulation sessions per month, one, two, three, four, five, or six stimulation sessions every two months, etc. The patient generally does not receive clinically meaningful stimulation other than during the stimulation session. That is, the patient does not need stimulation between individual maintenance doses to maintain or at least substantially maintain a therapeutic effect.

[0097] The stimulation sessions for the maintenance dose generally have a duration of about 12 hours or less, similar to the durations of the stimulation sessions for the reduced doses described previously. For example, individual stimulation sessions for the maintenance dose may include a consecutive (e.g., uninterrupted) duration of between about 1 hour and about 12 hours, such as between about 1 hour and about 9 hours, or between about 1 hour and about 6 hours, or between about 1 hour and about 4 hours, or between about 2 hours and about 4 hours, or between about 1 hour and about 3 hours, or between about 1 hour and about 2 hours. For example, the stimulation session may have a duration of about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, or about 8 hours. The stimulation session may also have shorter durations. For example, the stimulation session may have a duration of between about 1 minute and 60 minutes, such as between about 5 minutes and about 60 minutes, or between about 15 minutes and about 45 minutes. Representative examples include about 2 minutes, about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, and about 55 minutes. In some embodiments, stimulation can be administered during the stimulation session according to pulse dose.

[0098] Figure 7 is a block diagram illustrating a method 700 for treating a patient in accordance with embodiments of the present technology. Similar to the methods described above, some or all of the operations in the method 700 shown in Figure 7 can be performed by a processor executing instructions stored on one or more elements of a patient treatment system, including the patient treatment system 100 described with reference to Figure 1.

[0099] The method 700 can begin in block 702 by delivering electrical stimulation to a target neural population for a first treatment phase or stage. The first treatment phase can also be referred to as an acute treatment phase, as the electrical stimulation is delivered in block 702 to induce a therapeutic effect in a patient. In some embodiments, the therapeutic effect includes reducing pain in the patient and / or inducing any of the other therapeutic effects described throughout this Detailed Description.

[0100] The electrical stimulation can be delivered in many different manners during the first treatment phase. For example, in some embodiments the electrical stimulation can be delivered continuously and / or substantially continuously during the first treatment phase. In some embodiments, the electrical stimulation can be delivered non-continuously during the first treatment phase, including in accordance with the reduced doses previously described herein.

[0101] In some embodiments, delivering electrical stimulation for the first treatment phase includes delivering an electrical signal according to a single stimulation schedule for the first treatment phase. For example, in some embodiments the single stimulation schedule can be generally similar to the first stimulation schedule described above in connection with the method 400 of Figure 4. That is, the stimulation schedule can include continuously delivering the electrical signal, or non-continuously delivering the electrical signal for at least 12 hours per day, for the first treatment phase. In other embodiments, the single stimulation schedule can be generally similar to the second stimulation schedule described above in connection with the method 400 of Figure 4. For example, the single stimulation schedule can include delivering an electrical signal for less than 6 hours per day for the first treatment phase. This may include, for example delivering the electrical signal during one or more stimulation sessions per day, with each stimulation session having a duration between about 1 minute and about 6 hours, as previously described.

[0102] In other embodiments, delivering electrical stimulation for the first treatment phase includes delivering the electrical stimulation according to two or more stimulation schedules during the first treatment phase. This may include, for example, delivering electrical stimulation according to the method 400 described with reference to Figure 4 and / or the method 500 described with reference to Figure 5. That is, the first treatment phase can include a first portion and a second portion, and delivering electrical stimulation at the block 702 can include (1) delivering a first electrical signal according to a first stimulation schedule in which the first electrical signal is delivered for at least 12-hours per day for the first portion, and then (2) delivering a second electrical signal according to a second stimulation schedule in which the second electrical signal is delivered for less than 6 hours per day for the second portion. In other words, the operation at block 702 can include administering stimulation according to a plurality of different stimulation schedules such that stimulation is titrated from a first, relatively higher dose of stimulation to a second, relatively lower dose of stimulation, which may include stepping through one or more intermediate doses.

[0103] In some embodiments, the first treatment phase has a predetermined duration. The predetermined duration can be between about 1 month and about 1 year, such as between about 1 month and about 9 months, between about 1 month and about 6 months, and / or between about 1 month and about 3 months. For example, the predetermined duration can be about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, or about 12 months. In embodiments in which the first treatment phase includes a first portion and a second portion, each of the first portion and the second portion can have predetermined durations that together comprise the predetermined duration of the first treatment phase.

[0104] In other embodiments, the first treatment phase does not have a predetermined duration, but rather continues until the patient is identified as being in a state of remission. Accordingly, the method 700 can optionally continue in block 704 by determining that the patient has entered a state of remission. If the patient is determined has having entered a state of remission, the first treatment phase ends, and the method 700 can proceed to the operation at block 706, described below.

[0105] The operation of determining whether a patient has entered a state of remission can be the same as, or generally similar to, the operation at block 604 of the method 600 of Figure 6, described above. In some embodiments, for example, determining that the patient has entered a state of remission includes receiving an indication from a healthcare provider that the patient has entered a state of remission. The healthcare provider may then reprogram a controller of the stimulation system to deliver stimulation in accordance with the operation in block 706, described below. In some embodiments, this may include simply indicating on a physician or patient controller that the patient has entered a state of remission, in response to which the stimulation system automatically proceeds to delivering stimulation in accordance with the operation in block 706. In yet other embodiments, the physician can simply prescribe a new dose of stimulation to the patient (e.g., as previously described), and the patient can be in control of administering stimulation in accordance with the operation in block 706. In some embodiments, determining that the patient has entered a state of criteria includes collecting patient data and comparing it to one or more remission criteria, as described previously.

[0106] After the first stimulation period and / or after the patient has been identified as being in a state of remission, the method 700 can continue in block 706 by delivering electrical stimulation to the target neural population for a second treatment phase or stage, which can also be referred to as a "chronic treatment stage" or a "remission stage." The stimulation delivered during the second treatment phase is delivered during discrete, spaced apart stimulation sessions, with each individual stimulation session (a) having a duration of 12 hours or less, and (b) being spaced apart from other individual stimulation sessions by at least about one week. The stimulation sessions can have any of the durations and frequencies of administration described above with respect to the maintenance dose. For example, the stimulation sessions may have a duration of between about 1 minute and about 12 hours, and may be administered at a frequency of once per week or less. In some embodiments, the stimulation administered during the second treatment phase can be referred to as a maintenance dose of stimulation because it maintains a physiologic effect induced during the first treatment phase.

[0107] Without being bound by theory, it is expected that the maintenance dose of stimulation administered during the second stimulation period will keep the patient in the state of remission for an indefinite period. Accordingly, in some embodiments, the second treatment phase continues for an indefinite period. For example, once the patient has transitioned to receiving the maintenance dose during the second treatment phase, the patient may continue to receive just the maintenance dose indefinitely. As previously described, the patient can be periodically reevaluated to determine whether the maintenance dose needs to be adjusted, and / or whether the patient would benefit from returning to more frequent stimulation. Similarly, as described above, subjective and objective criteria can continue to be collected to determine whether the maintenance dose should be adjusted, and / or if the patient should return to the first treatment phase.

[0108] The electrical stimulation delivered during the first treatment phase and the second treatment phase can have the same or generally similar parameters. For example, the electrical stimulation can include electrical signals having the same or generally the same frequency, pulse width, amplitude, and / or pulse dose rate. Thus, in some embodiments the electrical signal remains the same during the first treatment phase and the second treatment phase, and the only change is the duration and / or frequency with which the signal is administered to the patient. In other embodiments, at least one parameter (e.g., frequency, pulse width, amplitude, and / or pulse dose rate) can change as the patient transitions from the first treatment phase to the second treatment phase.

[0109] In some embodiments, the electrical stimulation during the first treatment phase and the electrical stimulation during the second treatment phase are paresthesia-free electrical signals that do not induce a sensation of paresthesia when administered to the patient. As set forth above, the patient generally cannot sense a paresthesia-free electrical signal, and therefore cannot determine whether the signal is being actively applied. As described in detail under Section 5.0, the paresthesia-free signals may include high frequency, paresthesia-free signals and / or low frequency, paresthesia-free signals. In other embodiments, the one or more of the electrical signals delivered during operation of the method 700 can be paresthesia-producing signals.

[0110] Without being bound by theory, identifying patients as having entered a state of remission and reducing stimulation to periodic and relatively spaced apart (e.g., by at least one week) maintenance doses is expected to provide several advantages. Many of the advantages are similar to those identified previously with respect to delivering reduced doses of stimulation. For example, reducing stimulation to periodic and relatively spaced apart maintenance doses is expected to reduce powerconsumption, enabling smaller implants, enabling use of primary cell batteries, reducing charging-burdens, and other associated benefits. 5.0 Representative Stimulation Parameters

[0111] The electrical signals described herein, including the first, second, and third electrical signals described with respect to the method 400, can have a frequency in a frequency range of from about 0.01 Hz to about 1 MHz. For example, the electrical signal can be a "high frequency" electrical signal and have a frequency of from about 1.2 kHz to about 1 MHz, or from about 1.2 kHz to about 500 kHz, or from about 1.2 kHz to about 100 kHz, or from about 1.5 kHz to about 100 kHz, or from about 2 kHz to about 50 kHz, or from about 3 kHz to about 20 kHz, or from about 3 kHz to about 15 kHz, or from about 5 kHz to about 15 kHz, or from about 3 kHz to about 10 kHz, or 1.5 kHz, 2 kHz, 3 kHz, 4 kHz, 5 kHz, 10 kHz, 15 kHz, 20 kHz, 50 kHz, 100 kHz, or 500 kHz, or 1 MHz. Alternatively, the electrical signal can be a "low frequency" electrical signal and have a frequency of from about 0.01 Hz to about 1 kHz, or from about 1 Hz to about 500 Hz, or from about 1 Hz to about 100 Hz. In some embodiments the electrical signals described herein can include multiple electrical signals being administered at different frequencies (e.g., a first, high frequency signal paired with a second, low frequency signal). The electrical signal may have a pulse width of from about 1 microsecond to about 25 seconds. For example, the electrical signal may have a pulse width of from about 1 microsecond to about 417 microseconds, or from about 10 microseconds to about 333 microseconds, or from about 10 microseconds to about 166 microseconds, or from about 25 microseconds to about 166 microseconds, or from about 20 microseconds to about 100 microseconds, or from about 30 microseconds to about 100 microseconds, or from about 30 microseconds to about 40 microseconds, or from about 10 microseconds to about 50 microseconds, or from about 20 microseconds to about 40 microseconds, or from about 25 microseconds to about 35 microseconds, or from about 30 microseconds to about 35 microseconds, or 30 microseconds. As additional examples, the electrical signal may have a pulse width of from about 5 milliseconds to about 2 seconds, or between about 5 milliseconds and about 1 second, or between about 100 milliseconds and about 1 second, or between about 100 milliseconds and about 500 milliseconds, or between about 200 milliseconds and about 500 milliseconds, or between about 250 milliseconds and about 400 milliseconds. In some embodiments, the electrical signal can be administered at current amplitudes of from 0.1 mA to 20 mA, or 0.5 mA to 10 mA, or 0.5 mA to 7 mA, or 0.5 mA to 5 mA. The electrical signal can also be administered according to a pulse dose rate ranging from about 10% to about 100%, such as about 10% to about 50%.

[0112] In many of the embodiments described herein, the electrical signals generally do not produce paresthesia when delivered to the patient, and can therefore be referred to as "non-paresthesia producing electrical signals," or "paresthesia-free signals." As set forth previously, such signals have combinations of frequency, pulse widths, amplitudes, and / or pulse dose rates that cause the signal to be below a patient's perception threshold. For example, some paresthesia-free electrical signals may have a frequency of between about 0.01 Hz and about 1 MHz, or between about 1.2 kHz and 500 kHz, or between about 1.2 kHz and about 100 kHz. As another example, some paresthesia-free electrical signals may be delivered in discrete bursts, separated by quiescent periods in which the electrical signal is not delivered. As yet another example, some paresthesia-free electrical signals may have a "long" pulse width of between about 5 milliseconds and about 25 seconds with an amplitude below an activation threshold of a target neural population. Additional examples of paresthesia-free electrical signals, including those mentioned above, are described in U.S. Patent Application Publication Nos. US2010 / 0274314,   US2021 / 0228881, and US2022 / 0401730, and U.S. Provisional Patent Application No. 63 / 501,122, each of the which is incorporated by reference herein.

[0113] In yet other embodiments, the electrical signals described herein may produce paresthesia when delivered to the patient, and can therefore be referred to as "paresthesia-producing" signals. Such signals have combinations of frequency, pulse widths, amplitudes, and / or pulse dosing rates that cause the signal to be above a patient's perception threshold. 6.0 Representative Clinical Applications

[0114] The present technology has generally been described in the context of treating pain. For example, stimulation delivered during the first stimulation period reduces patient pain, and stimulation delivered during the second stimulation period maintains the reduction in patient pain. Without being bound by theory, it is expected that many different types of pain can be treated using the stimulation schedules described herein. For example, the stimulation schedules described herein can be applied to treat pain at various locations, including neck pain, back pain, and / or leg pain. Similarly, the stimulation schedules described herein can be applied to treat pain associated with various neuropathies, such as diabetic neuropathy, peripheral neuropathy, peripheral polyneuropathy, chemotherapy-induced neuropathy, among others. Such pain is typically (but not always) located in a patient's arms, hands, legs, and / or feet. The stimulation schedules described herein can also be applied to treat other types of pain, including headache pain, facial pain, cancer pain, shoulder pain, elbow pain, hand pain, other upper extremity pain, abdominal pain, visceral pain, pelvic pain, hip pain, knee pain, foot pain, other lower extremity pain, whole body pain, phantom limb pain, among others. The stimulation schedules described herein can also be applied to treat different types of pain, including neuropathic pain and nociceptive pain.

[0115] The stimulation schedules described herein can also be used to treat indications or symptoms other than pain. For example, the stimulation schedules described herein can be used to treat sensory loss or numbness (e.g., sensation loss associated with diabetic neuropathy or other neuropathies, spinal cord injury, etc.). In such embodiments, stimulation delivered during the first stimulation period improves patient sensation / reduces patient numbness, and stimulation delivered during the second stimulation period maintains the improvement in patient sensation / reduction in patient numbness. The stimulation schedules described herein can also be used to treat abnormal sensations, such as naturally occurring tingling or paresthesia (e.g., paresthesia associated with diabetic neuropathy or other neuropathies).

[0116] In further embodiments, the stimulation schedules described herein can be used to treat neurodegenerative diseases, including Parkinson's diseases and related disorders, Alzheimer's diseases and related disorders, Prion disease, Motor neuron diseases, Huntington's disease, Spinocerebellar ataxia, Spinal muscular atrophy, Amyotrophic lateral sclerosis, Friedreich's ataxia, and Lewy body disease. The stimulation schedules can also be used to treat various other motor or movement disorders, such as tremor, epilepsy, or the like. In some embodiments, the stimulation schedules described herein can be used to treat blood glucose abnormalities, such as metabolic syndrome, diabetes (e.g., type 2 diabetes and / or type 1 diabetes), among others. In yet other embodiments, the stimulation schedules described herein can be used to treat cardiovascular disorders, such as heart failure (e.g., congestive heart failure, decompensated heart failure, etc.). Of course, the stimulation schedules described herein may be applied to treat indications and / or symptoms beyond those expressly recited herein. 7.0 Clinical Data

[0117] Nevro Corp., the applicant of the present application, is conducting clinical studies of certain reduced stimulation schedules described herein. One study included cohorts of both "already implanted patients" (e.g., patients who already had a stimulator implanted, and thus were already receiving continuous spinal cord stimulation for a prolonged duration, such as three months or more), and "naive patients" (e.g., patients who had the stimulator implanted to participate in the study, and thus were not previously receiving prolonged continuous stimulation). The already implanted patients and the naive patients were assigned to one of three groups: (1) group 1, which received 8 hours of daily stimulation, followed by 16 hours of no stimulation, (2) group 2, which received 4 hours of daily stimulation, followed by 20 hours of no stimulation, and (3) group 3, which received 2 hours of daily stimulation, followed by 22 hours of no stimulation. For all groups, the stimulation had a frequency of 10 kHz and was applied to the patient's spinal cord.

[0118] Figure 8 is a chart 800 showing the initial responder rate of already implanted patients and naive patients assigned to each group. A patient was considered a responder if the patient had greater than or equal to 50% reduction in pain relative to their baseline pain level within 7-14 days of receiving the reduced dose of stimulation. For both already implanted patients and naive patients, the baseline pain level was the patient's pain level (measured by VAS pain score) before receiving any stimulation therapy (or, for some already implanted patients, after an extended break from stimulation such that the patient's pain levels returned to pre-stimulation levels and an effective baseline state). Thus, for the already implanted patients, the baseline represented the patients' pain levels before the patient received continuous stimulation. As shown in Figure 8, already implanted patients had a high responder rate in each group: 100% of already implanted patients receiving 8 hours of stimulation per day, 88% of already implanted patients receiving 4 hours of stimulation per day, and 93% of already implanted patients receiving 2 hours of stimulation per day experienced greater than or equal to a 50% reduction in pain relative to their baseline pain level. Naive patients also had relatively high responder rates, although generally lower than already implanted patients. For example, 86% of naive patients who received 8 hours of stimulation per day, 93% of naive patients who received 4 hours of stimulation per day, and 75% of naive patients who received 2 hours of stimulation per day experienced greater than or equal to a 50% reduction in pain relative to their baseline pain level.

[0119] Figures 9A-9F are graphs showing the average reduction in pain levels for the patients included in the chart 800. Figure 9A is a graph 900 illustrating average back pain scores (line 902) and average leg pain scores (line 904) at various intervals for the cohort of already implanted patients assigned to group 1 (8 hours of stimulation per day). As shown on the x-axis, pain scores were measured at baseline, at enrollment, at 1 month post enrollment, at 2 months post enrollment, at 3 months post enrollment, at 6 months post enrollment, at 9 months post enrollment, and at 12 months post enrollment. As set forth above, baseline refers to patient pain level before the patient received stimulation therapy. Enrollment refers to when the patients began the trial— that is, when the patient transitioned from receiving continuous stimulation to 8 hours of stimulation per day. 3 months post enrollment represents the patient's pain level after being subjected to 8 hours of stimulation per day for 3 months, 6 months post enrollment represents the patient's pain level after being subjected to 8 hours of stimulation per day for 6 months, and so on. As shown in Figure 9A, continuous stimulation reduced both back and leg pain scores (e.g., comparing average pain scores reported at baseline to average pain scores reported at enrollment). Moreover, the 8 hours of daily stimulation substantially maintained back and leg pain scores at the 3 month, 6 month, 9 month, and 12 month endpoints.

[0120] Figure 9B is a graph 910 comparing average back pain scores (line 912) and average leg pain scores (line 914) at various intervals for the cohort of naive patients assigned to group 1 (8 hours of stimulation per day). Unlike the graph 900, the graph 910 does not include an "enrollment" data set. Naive patients' pain scores at baseline are the same as their pain scores at enrollment because they did not previously receive continuous stimulation. As shown in Figure 9B, 8 hours of stimulation per day reduced both back and leg pain scores in naive patients. Without intending to be bound by theory, this means that, in at least some patients, it is not necessary to have an initial period of continuous stimulation that precedes the reduced dose, as described above in Section 4.0. However, some patients may respond better, may have a greater degree of pain relief, and / or may ultimately be able to be titrated to a lower level of therapy if they initially receive continuous stimulation, as also described above in Section 4.0.

[0121] Figures 9C-9F show that back and leg pain was also substantially reduced relative to baseline pain levels in the patients assigned to group 2 (4 hours of stimulation per day) and group 3 (2 hours of stimulation per day). Figure 9C is a graph 920 comparing average back pain scores (line 922) and average leg pain scores (line 924) at baseline, at enrollment, and at various stages post-enrollment for the cohort of already implanted subjects assigned to group 2 (4 hours of stimulation per day). As shown in Figure 9C, 4 hours of stimulation per day reduced both back and leg pain scores in already implanted patients. Figure 9D is a graph 930 comparing average back pain scores (line 932) and average leg pain scores (line 934) at baseline / enrollment and at various stages post-enrollment for the cohort of naive subjects assigned to group 2 (4 hours of stimulation per day). As shown in Figure 9D, 4 hours of stimulation per day reduced both back and leg pain scores in naive patients. Figure 9E is a graph 940 comparing average back pain scores (line 942) and average leg pain scores (line 944) at baseline, at enrollment, and at various stages post-enrollment for the cohort of already implanted subjects assigned to group 3 (2 hours of stimulation per day). As shown in Figure 9E, 2 hours of stimulation per day reduced both back and leg pain scores in already implanted subjects. Finally, Figure 9F is a graph 950 comparing average back pain scores (line 952) and average leg pain scores (line 954) at baseline / enrollment and at various stages post-enrollment for the cohort of naive subjects assigned to group 3 (2 hours of stimulation per day). As shown in Figure 9F, 2 hours of stimulation per day also reduced both back and leg pain scores in naive patients.

[0122] Figures 10A and 10B illustrate individualized patient results from the same trials that produced the aggregated data reported above. In particular, Figure 10A is a tornado chart illustrating the magnitude of pain reduction relative to baseline (as a percent reduction from baseline) for each naive patient in groups 1-3, and Figure 10B is a tornado chart illustrating the magnitude of pain reduction relative to baseline (as a percent reduction from baseline) for each already implanted patient in groups 1-3. Referring collectively to Figures 10A and 10B, the x axis measures the percent reduction in pain from baseline, with 50% reduction the mid-point of the graph. Each horizontal bar represents an individual patient's reduction in pain, measured at 3- months post enrollment (for responders who continued with the trial) or at the failure point (for non-responders having less than 50% pain reduction). Because the trial was set to identify responders as patients with at least a 50% pain reduction relative to baseline, individual patients identified by horizontal bars that extend past the 50% mark were responders. Of note, in both the already implanted groups and naive groups, at least some patients reported a 100% reduction in pain relative to baseline.

[0123] Taken together, the data in Figures 8-10B support that a reduced dose of stimulation can provide effective therapy. For example, Figures 8-10B demonstrate that 8 hours of daily stimulation, 4 hours of daily stimulation, and 2 hours of daily stimulation reduced, or at least maintained a reduction in, both back pain and leg pain. Although data is only reported for three particular stimulation schedules (i.e., 8 hours per day, 4 hours per day, and 2 hours per day), it is expected that other reduced stimulation schedules described herein will similarly provide effective therapy.

[0124] Moreover, the data in Figures 8-10B support that, for at least some patients, the reduced dose of stimulation can be effective regardless of whether it is preceded by a period of continuous stimulation. Without being bound by theory, it is expected that, in some patients, the reduced dose of therapy may be substantially as effective if the patient begins with the reduced dose, as opposed to starting with continuous therapy and transitioning to a reduced dose. In other patients, however, it is expected that the reduced dose of therapy may be more effective if it is preceded by a period of continuous stimulation. Accordingly, as described in detail in Section 4.0 above, the present technology includes (1) embodiments in which patients receive continuous or generally continuous stimulation for a first stimulation period before transitioning to a reduced dose of stimulation during a second stimulation period, and (2) embodiments in which the patients start therapy at a reduced dose of stimulation. In either embodiment, the dose can be further titrated down to reduce the number of stimulation sessions per day or per week, and / or to reduce the duration of stimulation sessions. Moreover, the foregoing data shows that a reduced dose of stimulation can maintain consistent pain relief over at least 12 months, which is expected to translate into substantially reduced power consumption and associated patient advantages. 8.0 Representative Examples

[0125] The following examples are provided to further illustrate embodiments of the present technology and are not to be interpreted as limiting the scope of the present technology. To the extent that certain embodiments or features thereof are mentioned, it is merely for purposes of illustration and, unless otherwise specified, is not intended to limit the present technology. It will be understood that many variations can be made in the procedures described herein while still remaining within the bounds of the present technology. Such variations are intended to be included within the scope of the presently disclosed technology. 1. A method of treating pain in a patient, the method comprising: delivering electrical stimulation to a target neural population of the patient, wherein the electrical stimulation reduces the patient's pain; determining that the patient has entered a state of remission induced at least in part by the electrical stimulation; and in response to determining that the patient has entered the state of remission, ceasing delivery of the electrical stimulation, wherein the reduction in patient pain is at least partially maintained for at least one month following the cessation of stimulation. 2. The method of example 1 wherein the reduction in patient pain is at least partially maintained for at least six months following the cessation of stimulation. 3. The method of example 1 wherein the reduction in patient pain is at least partially maintained for at least one year following the cessation of stimulation. 4. The method of any of examples 1-3 wherein determining that the patient has entered a state of remission includes comparing patient data to one or more remission criteria. 5. The method of example 4 wherein the patient data includes one or more of spontaneous neural activity, evoked neural activity, patient activity level, and / or patient VAS scores. 6. The method of any of examples 1 -5, further comprising: periodically monitoring the patient after ceasing delivery of the electrical stimulation to determine if the patient remains in remission; and if the patient is no longer in remission, restarting delivery of electrical stimulation; and if the patient remains in remission, continuing to not deliver the electrical stimulation. 7. The method of any of examples 1-5 wherein ceasing delivery of the electrical stimulation includes ceasing delivery of the electrical stimulation for a predetermined duration. 8. The method of example 7 wherein the predetermined duration is based at least in part on an expected duration of the patient's remission. 9. The method of example 7 or example 8 wherein the predetermined duration is between about 1 month and about 36 months. 10. The method of example 7 or example 8 wherein the predetermined duration is between about 6 months and about 24 months. 11. The method of any of examples 7-10, further comprising restarting the delivery of electrical stimulation after the predetermined duration elapses. 12. The method of any of examples 1-11 wherein delivering the electrical stimulation includes delivering a paresthesia-free electrical signal to the patient. 13. A system for treating pain in a patient, the system comprising: an implantable signal delivery device positionable proximate a target neural population in the patient; and a signal generator configured to generate and deliver electrical stimulation to the target neural population, via the implantable signal delivery device, to reduce the pain in the patient; and a controller configured to— control the signal generator to generate and deliver the electrical stimulation to reduce the patient’s pain, determine that the patient has entered a state of remission induced at least in part by the electrical stimulation, and in response to determining that the patient has entered the state of remission, control the signal generator to cease delivery of the electrical stimulation, wherein the reduction in patient pain is at least partially maintained for at least one month following the cessation of stimulation. 14. The system of example 13 wherein the signal generator includes the controller. 15. The system of example 13, further comprising an external programmer, wherein the external programmer includes the controller. 16. The system of any of examples 13-15 wherein the operation of determining that the patient has entered the state of remission includes receiving an indication that the patient has entered the state of remission. 17. The system of any of examples 13-15 wherein the operation of determining that the patient has entered the state of remission includes: receiving patient data associated with the reduction in patient pain, and comparing the received patient data to one or more remission criteria. 18. The system of example 17 wherein: the patient data includes one or more of spontaneous neural activity, evoked neural activity, patient activity level, and / or patient VAS scores, and the one or more remission criteria include predetermined values or metrics associated with one or more of spontaneous neural activity, evoked neural activity, patient activity level, and / or patient VAS scores. 19. The system of any of examples 13-19 wherein the controller is configured to cease delivery of the electrical stimulation for a predetermined duration. 20. The system of example 19 wherein the predetermined duration is between about 1 month and about 36 months. 21. The system of example 19 or example 20 wherein the controller is further configured to restart the delivery of electrical stimulation after the predetermined duration elapses. 22. The system of any of examples 13-21 wherein the operation of controlling the signal generator to cease delivery of the electrical stimulation in response to determining that the patient has entered the state of remission is automatic. 23. The system of any of examples 13-22 wherein the electrical stimulation includes paresthesia-free electrical stimulation. 24. A method of treating a patient, the method comprising: delivering electrical stimulation to a target neural population of the patient, wherein the electrical stimulation induces a therapeutic effect in the patient; determining that the patient has entered a state of remission induced at least in part by the electrical stimulation; and in response to determining that the patient has entered the state of remission, ceasing delivery of the electrical stimulation, wherein the therapeutic effect is at least partially maintained for at least one month following the cessation of stimulation. 25. The method of claim 24 wherein determining that the patient has entered a state of remission includes: collecting patient data associated with the reduction in patient pain, and comparing the collected patient data to one or more remission criteria. 26. The method of claim 25 wherein: the patient data includes one or more of spontaneous neural activity, evoked neural activity, patient activity level, and / or patient VAS scores, and the one or more remission criteria include predetermined values or metrics associated with one or more of spontaneous neural activity, evoked neural activity, patient activity level, and / or patient VAS scores. 27.   The method of any of examples 24-26, further comprising: periodically monitoring the patient after ceasing delivery of the electrical stimulation to determine if the patient remains in remission; and if the patient is no longer in remission, restarting delivery of electrical stimulation; and if the patient remains in remission, continuing to not deliver the electrical stimulation. 28. The method of any of examples 24-27 wherein ceasing delivery of the electrical stimulation includes ceasing delivery of the electrical stimulation for a predetermined duration. 29. The method of example 28 wherein the predetermined duration is between about 1 month and about 36 months. 30. The method of example 28 or example 29, further comprising restarting the delivery of electrical stimulation after the predetermined duration elapses. 31. The method of any of examples 24-31 wherein the electrical stimulation is paresthesia-free electrical stimulation. 9.0 Conclusion

[0126] From the foregoing, it will be appreciated that specific embodiments of the disclosed technology have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. For example, therapy signals described herein can be delivered at combinations of parameter values within the foregoing ranges at values that are not expressly disclosed herein. Certain aspects of the technology described in the context of particular embodiments may be combined or eliminated in other embodiments. For example, the therapy signal can be monophasic with a passive charge elimination phase. In some embodiments, the foregoing techniques can be used to address patient deficits than pain. Further, while advantages associated with certain embodiments of the disclosed technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the present technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.

[0127] The use of "and / or," as in "A and / or B" refers to A alone, B alone, and both A and B. Additionally, the term "comprising" is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and / or additional types of other features are not precluded. It will also be appreciated that specific embodiments have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. Further, while advantages associated with certain embodiments of the technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.

[0128] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, to between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.

[0129] Each of the patents and patent application publications referenced herein are incorporated by reference in their entireties and for all purposes. However, to the extent any patent or patent application publication conflicts with the present disclosure, the present disclosure controls.

Claims

l / we claim:

1. A method of treating pain in a patient, the method comprising: delivering electrical stimulation to a target neural population of the patient, wherein the electrical stimulation reduces the patient's pain;determining that the patient has entered a state of remission induced at least in part by the electrical stimulation; andin response to determining that the patient has entered the state of remission, ceasing delivery of the electrical stimulation,wherein the reduction in patient pain is at least partially maintained for at least one month following the cessation of stimulation.

2. The method of claim 1 wherein the reduction in patient pain is at least partially maintained for at least six months following the cessation of stimulation.

3. The method of claim 1 wherein the reduction in patient pain is at least partially maintained for at least one year following the cessation of stimulation.

4. The method of claim 1 wherein determining that the patient has entered a state of remission includes comparing patient data to one or more remission criteria.

5. The method of claim 4 wherein the patient data includes one or more of spontaneous neural activity, evoked neural activity, patient activity level, and / or patient VAS scores.

6. The method of claim 1, further comprising:periodically monitoring the patient after ceasing delivery of the electrical stimulation to determine if the patient remains in remission; andif the patient is no longer in remission, restarting delivery of electrical stimulation; andif the patient remains in remission, continuing to not deliver the electrical stimulation.

7. The method of claim 1 wherein ceasing delivery of the electrical stimulation includes ceasing delivery of the electrical stimulation for a predetermined duration.

8. The method of claim 7 wherein the predetermined duration is based at least in part on an expected duration of the patient's remission.

9. The method of claim 7 wherein the predetermined duration is between about 1 month and about 36 months.

10. The method of claim 7 wherein the predetermined duration is between about 6 months and about 24 months.

11. The method of claim 7, further comprising restarting the delivery of electrical stimulation after the predetermined duration elapses.

12. The method of claim 1 wherein delivering the electrical stimulation includes delivering a paresthesia-free electrical signal to the patient.

13. A system for treating pain in a patient, the system comprising:an implantable signal delivery device positionable proximate a target neural population in the patient; anda signal generator configured to generate and deliver electrical stimulation to the target neural population, via the implantable signal delivery device, to reduce the pain in the patient; anda controller configured to—control the signal generator to generate and deliver the electrical stimulation to reduce the patient’s pain,determine that the patient has entered a state of remission induced at least in part by the electrical stimulation, andin response to determining that the patient has entered the state of remission, control the signal generator to cease delivery of the electrical stimulation,wherein the reduction in patient pain is at least partially maintained for at least one month following the cessation of stimulation.

14. The system of claim 13 wherein the signal generator includes the controller.

15. The system of claim 13, further comprising an external programmer, wherein the external programmer includes the controller.

16. The system of claim 13 wherein the operation of determining that the patient has entered the state of remission includes receiving an indication that the patient has entered the state of remission.

17. The system of claim 13 wherein the operation of determining that the patient has entered the state of remission includes:receiving patient data associated with the reduction in patient pain, and comparing the received patient data to one or more remission criteria.

18. The system of claim 17 wherein:the patient data includes one or more of spontaneous neural activity, evoked neural activity, patient activity level, and / or patient VAS scores, andthe one or more remission criteria include predetermined values or metrics associated with one or more of spontaneous neural activity, evoked neural activity, patient activity level, and / or patient VAS scores.

19. The system of claim 13 wherein the controller is configured to cease delivery of the electrical stimulation for a predetermined duration.

20. The system of claim 19 wherein the predetermined duration is between about 1 month and about 36 months.

21. The system of claim 19 wherein the controller is further configured to restart the delivery of electrical stimulation after the predetermined duration elapses.

22. The system of claim 13 wherein the operation of controlling the signal generator to cease delivery of the electrical stimulation in response to determining that the patient has entered the state of remission is automatic.

23. The system of claim 13 wherein the electrical stimulation includes paresthesia-free electrical stimulation.

24. A method of treating a patient, the method comprising:delivering electrical stimulation to a target neural population of the patient, wherein the electrical stimulation induces a therapeutic effect in the patient;determining that the patient has entered a state of remission induced at least in part by the electrical stimulation; andin response to determining that the patient has entered the state of remission, ceasing delivery of the electrical stimulation,wherein the therapeutic effect is at least partially maintained for at least one month following the cessation of stimulation.

25. The method of claim 24 wherein determining that the patient has entered a state of remission includes:collecting patient data associated with the reduction in patient pain, and comparing the collected patient data to one or more remission criteria.

26. The method of claim 25 wherein:the patient data includes one or more of spontaneous neural activity, evoked neural activity, patient activity level, and / or patient VAS scores, andthe one or more remission criteria include predetermined values or metrics associated with one or more of spontaneous neural activity, evoked neural activity, patient activity level, and / or patient VAS scores.

27. The method of claim 24, further comprising:periodically monitoring the patient after ceasing delivery of the electrical stimulation to determine if the patient remains in remission; andif the patient is no longer in remission, restarting delivery of electrical stimulation; andif the patient remains in remission, continuing to not deliver the electrical stimulation.

28. The method of claim 24 wherein ceasing delivery of the electrical stimulation includes ceasing delivery of the electrical stimulation for a predetermined duration.

29. The method of claim 28 wherein the predetermined duration is between about 1 month and about 36 months.

30. The method of claim 28, further comprising restarting the delivery of electrical stimulation after the predetermined duration elapses.

31. The method of claim 24 wherein the electrical stimulation is paresthesia-free electrical stimulation.

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