NEUROSTIMULATION THERAPY USING MULTIPLE LEADS POSITIONED IN
PROXIMITY TO A COMMON AREA TO BE STIMULATED
[0001] This application is a PCT application that claims priority to and the benefit of U.S. Provisional Patent Application No. 63/613,043, filed December 20, 2023, the entire contents of which is incorporated herein by reference.
TECHNICAL FIELD
[0002] Embodiments relate to neurostimulation therapy and more particularly to neurostimulation therapy that uses multiple leads positioned in proximity to a common area in order to stimulate the common area.
BACKGROUND
[0003] Patients suffering from one or more neurological conditions may benefit from neurostimulation therapy including, but not limited to, deep brain stimulation (hereinafter DBS). To provide DBS therapy, a distal end of a lead is implanted into the brain of the patient at a target location. The proximal end of the lead is coupled to a neurostimulator that produces electrical stimulation signals that are delivered by one or more electrodes of the lead to the brain and/or that senses physiological signals captured by the one or more electrodes of the lead within the brain.
[0004] The neurostimulation therapy must reach the target but the neurostimulation may have a field of activation that extends beyond the intended target area of the brain. This field of activation that is broader than desired may cause unwanted side effects and/or may have a less than adequate therapeutic effect. As a result, neurostimulation may be less effective for certain patients, brain structures, and neurological conditions.
SUMMARY
[0005] Embodiments address issues such as these and others by providing neurostimulation therapy with multiple leads in proximity to the area to be stimulated. The multiple leads being in proximity to the area within the brain to be stimulated may improve the ability to control where the stimulation occurs and confine the stimulation to the intended area through one or more of several implementations. In one implementation, a DBS lead may be implanted at one position in proximity to the desired area within the brain while an endovascular lead may be implanted through a blood vessel to a location also in proximity to the desired area. This allows stimulation to be introduced into the area from both leads to produce a field of activation through field interactions not otherwise possible due to the region being too small or surrounded by sensitive structures to implant multiple DBS leads outside of blood vessels. In another implementation, multiple leads are implanted in proximity to the area to be stimulated, and the stimulation from each lead interacts to provide a stimulation field confined within the area to be stimulated. In yet another implementation, multiple leads are implanted in proximity to the area to be stimulated and the stimulation of one lead is phase shifted relative to that of the other lead to confine the stimulation to the area to be stimulated.
[0006] Embodiments provide a method of providing neurostimulation therapy. The method involves providing a first stimulation signal at a first location in proximity to a subregion of a brain of a patient, the first stimulation signal being characterized by parameters comprising frequency, amplitude, pulse width, and electrode selection. The method involves providing a second stimulation signal at a second location in proximity to the subregion of the brain of the patient contemporaneously with providing the first stimulation signal at the first location, the second stimulation signal being characterized by parameters comprising frequency, amplitude, pulse width, and electrode selection. The method involves iteratively adjusting the frequency, amplitude, pulse width, and electrode selection of the first stimulation signal and the second stimulation signal until a combination of the first stimulation signal and the second stimulation signal creates a stimulation field that activates a desired brain network within the subregion of the brain the patient.
[0007] Embodiments provide an implantable medical system. The system includes a neurostimulator that contemporaneously generates a first stimulation signal and a second stimulation signal. The system includes a first lead coupled to the neurostimulator and having a distal end with at least one electrode positioned at a first location in proximity to a subregion of a brain of a patient to deliver the first stimulation signal to the first location. The system includes a second lead coupled to the neurostimulator and having a distal end with at least one electrode positioned at a second location in proximity to the subregion of the brain of the patient to deliver the second stimulation signal to the second location. The neurostimulator iteratively adjusts the frequency, amplitude, pulse width, and electrode selection of the first stimulation signal and the second stimulation signal until creating a stimulation field that activates a desired brain network within the subregion of the brain the patient.
[0008] Embodiments provide a method of providing neurostimulation therapy. The method involves providing an endovascular lead within a blood vessel of a brain of the patient and at a first position in proximity to a subregion of the brain. The method involves providing a non-endovascular lead outside of a blood vessel of the brain of the patient and at a second position in proximity to the subregion of the brain. The method involves providing a first stimulation signal from the endovascular lead while contemporaneously providing a second stimulation signal through the non-endovascular lead.
[0009] Embodiments provide an implantable medical system. The system includes a neurostimulator that contemporaneously generates a first stimulation signal and a second stimulation signal. The system includes an endovascular lead coupled to the neurostimulator and having a distal end with at least one electrode positioned within a blood vessel at a first location in proximity to a subregion of a brain of the patient to deliver the first stimulation signal at the first location. The system includes a non-endovascular lead coupled to the neurostimulator and having a distal end with at least one electrode positioned outside of blood vessels at a second location in proximity to the subregion of the brain of the patient to deliver the second stimulation signal at the second location.
[0010] Embodiments provide a method of providing neurostimulation therapy. The method involves providing a first stimulation signal at a first location in proximity to a subregion of a brain of a patient. The method involves providing a second stimulation signal at a second location in proximity to the subregion of the brain of the patient contemporaneously with providing the first stimulation signal at the first location, the second stimulation signal being phase shifted relative to the first stimulation signal.
[0011] Embodiments provide an implantable medical system. The system includes a neurostimulator that contemporaneously generates a first stimulation signal and a second stimulation signal. The system includes a first lead coupled to the neurostimulator and having a distal end with at least one electrode positioned at a first location in proximity to a subregion within a brain of the patient to deliver the first stimulation signal to the first location. The system includes a second lead coupled to the neurostimulator and having a distal end with at least one electrode positioned at a second location in proximity to the subregion within the brain of the patient to deliver the second stimulation signal to the second location, wherein the first stimulation signal is phase shifted relative to the second signal. DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 shows an example of a patient having an implantable medical system including two leads in proximity to a target area for neurostimulation therapy.
[0013] FIG. 2A shows an example of a relationship between an endovascular lead and a DBS lead positioned in proximity to the target area.
[0014] FIG. 2B shows an example of a relationship between a first lead and a DBS lead positioned in proximity to the target area where interaction between the leads creates a stimulation field confined to the target area.
[0015] FIG. 3 shows an example of components of an external device that communicates with a neurostimulation device.
[0016] FIG. 4 shows an example of components of a neurostimulation device that may couple to the multiple leads in proximity to the target area to provide the neurostimulation related stimulation signals.
[0017] FIG. 5 shows an example of a workflow to provide the neurostimulation therapy to the desired area using the multiple leads positioned in proximity to the area.
[0018] FIG. 6 shows an example of a data structure representing various combination of stimulation parameters for the stimulation signals of the first and second leads that are used iteratively to determine the appropriate parameters for to produce the desired stimulation field.
[0019] FIG. 7 shows an example of stimulation signals of the first and second leads that are burst phase shifted to produce the desired stimulation interaction and confinement.
[0020] FIG. 8 shows an example of stimulation signals of the first and second leads that are pulse phase shifted to produce the desired stimulation interaction and confinement.
DETAILED DESCRIPTION
[0021] Embodiments provide an implantable medical system that uses two leads with each lead having a distal end located in proximity to a target area to be stimulated. The embodiments utilize one or more techniques to focus the stimulation so as to substantially confine the stimulation to the intended target area. These techniques include one or more of using an endovascular lead in combination with a non-endovascular lead, controlling stimulation parameters to create a stimulation field within the target area, and phase shifting the stimulation signals of the two leads.
[0022] This disclosure describes example techniques to confirm the efficacy of forms of neurostimulation therapy. The example techniques are described with respect to DBS, but the example techniques are not so limited and may be applied to other types of therapies and/or other anatomical locations. Neurostimulation therapy, and DBS in particular, may provide relief for many different patient conditions such as movement disorders, epilepsy, obsessive compulsive disorder (OCD), depression, and others. Patients afflicted with movement disorders or other neurodegenerative impairment, whether by disease or trauma, may experience muscle control and movement problems, such as rigidity, bradykinesia (i.e., slow physical movement), rhythmic hyperkinesia (e.g., tremor), nonrhythmic hyperkinesia (e.g., tics) or akinesia (i.e., a loss of physical movement). Movement disorders may be found in patients with Parkinson's disease, multiple sclerosis, and cerebral palsy, among other conditions. Delivery of electrical stimulation by a medical device to one or more sites in a patient, such as within the brain, may help alleviate, and in some cases, eliminate symptoms associated with these movement disorders and other conditions.
[0023] FIG. 1 shows a typical environment for an implantable medical system 100 being used to provide neurostimulation therapy such as DBS therapy. In this example, the implantable medical system 100 is installed onto a body 110 of a patient. The implantable medical system 100 of this example includes a neurostimulator 102 that has either been installed externally on the patient or has been implanted into a subcutaneous or subfascial pocket 112. A first medical lead 104, such as an endovascular lead which may be combined with an extension, is routed between a target stimulation site within the brain 111 of the patient and the neurostimulator 102. The first lead 104 has a distal end 103 and distal electrodes thereon positioned within the brain 111 in proximity to the target location for the stimulation and/or sensing to be applied. For implementations where the first lead 104 is an endovascular lead, the lead 104 can be implanted in a less invasive way relative to a DBS lead by being introduced into a blood vessel that travels into the brain 111 and branches into the location that is in proximity to the target area.
[0024] FIG. 1 also shows a location and related aspects of a second lead 105, such as a conventional DBS lead that is a non-endovascular lead as the DBS lead 105 is present outside of the blood vessels of the brain 111. The DBS lead 105 extends from the neurostimulator 102 in the conventional manner, beneath the skin, and to a location on the skull of the patient where a hole 113 is created to allow the DBS lead 105 to pass through the skull to enter the brain 111 in area 106 beneath the hole 113. The DBS lead 105 can then be routed in a non- endovascular way outside of any blood vessel to the target area within the brain 111 where a distal end 108 with electrodes is positioned.
[0025] FIG. 2A shows a first example of a more detailed view of the target area as a subregion 208 within the brain 111 that is distinct from an adjacent subregion 210. The distal end 103 of the endovascular lead 104 is located in proximity to the subregion 208. As can be seen, the endovascular lead 104 including the distal end 103 with electrodes 204 is present within a blood vessel 202 that passes in proximity to the target area 208 of the brain 111. Thus, the endovascular lead 104 is capable of providing neurostimulation therapy in the form of electrical neurostimulation signals from one or more electrodes 202 that propagate into the brain 111 in proximity to the target area 208 as indicated by stimulation field 212. One or more of the electrodes 204 of the lead 104 may be used for sensing electrical physiological signals from the area in proximity to the target area 208 such as to measure effects of the neurostimulation therapy.
[0026] The distal end 108 of the DBS lead 105 has a typical DBS lead position relative to the target subregion 208 that is a different position than the distal end 103 of the endovascular lead 104. Thus, the DBS lead 105 is capable of providing neurostimulation therapy in the form of electrical neurostimulation signals from one or more electrodes 206 that propagate into the brain 111 in proximity to the target area 208 as indicated by stimulation field 214. One or more of the electrodes 206 of the lead 105 may be used for sensing electrical physiological signals from the area in proximity to the target subregion 208 such as to further measure effects of the neurostimulation therapy.
[0027] It can be seen in FIG. 2Athat the field of stimulation 212 and field of stimulation 214 can together provide a relatively large volume of neural activation within the subregion 208 while remaining substantially confined to the subregion 208 and avoiding subregion 210 so as to not produce unwanted effects in subregion 210. Because the subregion 208 may be relatively small or adjacent to sensitive brain structures, only the distal end 108 of a single DBS lead 105 may be positioned at the subregion 208. The presence of the endovascular lead 104 and distal end 103 within the blood vessel 202 in the location in proximity to the subregion 208 avoids the need for the stimulation field 214 to expand to such a degree that it would encroach into the subregion 210 in order to reach the portion of the subregion 208 where the stimulation field 212 is located. Thus, the multiple leads 104, 105 with their respective distal ends 103, 108 in proximity to the subregion 208 minimize undesired stimulation leakage into the subregion 210. [0028] FIG. 2B shows an example of an implementation where a resulting stimulation field 216 that is substantially confined to the intended subregion 208 so as to activate a desired brain network within the subregion 208 is created by virtue of interaction of the stimulation field 212 of the first lead 105 and the stimulation field 214 of the second lead 104. One example of a resulting stimulation field 216 is a beamform produced by the interactions of the stimulation fields 214, 212 of the individual leads 104, 105, respectively. While FIG. 2B shows the same configuration including the endovascular lead 104 and DBS lead 105, it will be appreciated that the resulting stimulation field approach of FIG. 2B may be provided by in other lead configurations in some cases. However, where there is an issue preventing the implantation of the distal ends of two DBS leads in proximity to the subregion 208, such as the small size of the subregion 208 or the presence of sensitive brain structures, an endovascular lead 104 can be implanted as shown and the resulting stimulation field approach may be used.
[0029] The resulting stimulation field 216 may be created by virtue of controlling stimulation parameters of the stimulation signal being output by the electrode(s) 204 of the distal end 103 of the first lead 104 and by the electrode(s) 206 of the distal end 108 of the second lead 105. The parameters include frequency, amplitude, pulse width, and electrode selection. To achieve the desired resulting stimulation field 216, these parameters of the first stimulation signal of the first lead 104 and of the second stimulation signal of the second lead 105 may be adjusted by iterating through all possible combinations. A simple example where each parameter has two settings is shown in the data structure of FIG. 6 that is discussed in more detail below in relation to the discussion of a workflow example as shown in FIG. 5. [0030] FIG. 3 shows an example of the components of an external device 114 that communicates with the neurostimulator 102 to provide programming that controls the neurostimulation therapy including stimulation and/or sensing functions and to obtain information collected by the neurostimulator 102. The external device 114 may take various forms, such as a handheld tablet, a personal computer, and the like. The several components of the external device 114 include a processor 302 as well as a communication circuitry 304 and an input/output circuitry 310. The processor 302 interacts with the communication circuitry 304 and input/output circuitry 310 to provide the operations of the implantable medical device 102. A power supply, not shown in FIG. 3, such as a battery or a utility power interface may also be included to provide electrical power to the various components.
[0031] The processor 302 performs various logical operations when interacting with the other components. These operations may involve utilizing the communication circuitry 304 to exchange data with the implantable medical device 102 and to produce relevant displays of information and receive relevant input from a user, such as a clinician or patient, viewing the displays. Examples of these logical operations in combination with logical operations performed by the neurostimulator 102 are discussed below in relation to the workflow example of FIG. 5. The processor 302 may be of various forms such as a general purpose programmable processor, application specific processor, hardwired digital logic, and/or various combinations. The processor 302 may utilize operational memory that is internal, external (not shown), or a combination of the two and may also utilize a storage device to retain data and programming in a long-term, non-volatile fashion.
[0032] The communication circuitry 304 includes both a transmitter circuit 306 and a receiver circuit 308 for sending and receiving wireless signals. The communication circuitry 304 is either wirelessly tethered or tethered by wire to the intermediary device 116 over the communication link 120. The communication link may utilize a wireless protocol such as the Bluetooth® protocol. Alternatively, the communication link 120 may be wired and rely upon telemetry where the intermediary device 116 is a telemetry head held in very close proximity to the implantable medical device 102. As another alternative, any link with a sufficiently short latency to allow the clinician to react to changes in the patient may also be used, including remote/intemet connected management.
[0033] The input/output circuitry 310 allows the external device 114 to interact with users, including clinicians or the patient, or other devices. The input/output circuitry 310 may provide outputs such as a visual display on a screen, audio, and the like. The input/output circuitry 310 may provide inputs such as a keyboard or keypad, a mouse and/or touch screen, and the like. The input/output circuitry 310 allows users to enter information such as programming details, stimulation parameters, and other information to be provided from the external device 114 to the neurostimulator 102 as well as review information such as physiological data sent from the neurostimulator 102 to the external device 114.
[0034] FIG. 4 shows an example of the neurostimulator 102. The components of the neurostimulator 102 are contained within a housing that isolates and protects the components from the surrounding environment. Typically, the housing is a biocompatible material that forms a hermetically sealed container. The components of the neurostimulator 102 include a processor 402 as well as a communication circuitry 404. A stimulation circuitry 410 is also present to generate the stimulation signals for the first and second leads used to provide the stimulation therapy, and sensing circuitry 412 is present to sense the physiological signals relevant to the stimulation therapy, such as the local field potential signals. The processor 402 interacts with the communication circuitry 404, stimulation circuitry 410, and sensing circuitry 412 to provide the operations of the neurostimulator 102. Although not shown, the implantable medical device 102 also includes a power source, such as an on-board battery, to provide electrical power to these components.
[0035] The processor 402 performs various logical operations when interacting with the other components to provide the stimulation and/or sensing functions of the neurostimulation therapy. Thus, examples of the logical operations of the neurostimulator 102 and processor 402 in combination with those of the external device 114 and processor 302 are shown in the workflow example of FIG. 5. The processor 402 may be of various forms such as a general purpose programmable processor, application specific processor, hardwired digital logic, and/or various combinations.
[0036] The communication circuitry 404 includes both a transmitter circuit 406 and a receiver circuit 408 for sending and receiving wireless signals. This allows the processor 402 to receive information such as programming, stimulation parameters and the like from the external device 114. This also allows the processor 402 to send information such as sensed physiological data to the external device 114.
[0037] The stimulation circuitry 410 in the example shown allows the implantable medical device 102 to interact with the brain tissue of the patient 110. The stimulation circuitry 410 may produce stimulation signals that include stimulation pulses of a given amplitude, such as a given electrical current amplitude. In accordance with the stimulation therapy algorithm being performed by the processor 402, the stimulation circuitry 410 may alter the stimulation amplitude, frequency, and pulse width of the stimulation therapy as requested by the processor 402 to provide effective stimulation therapy, such as effective adaptive deep brain stimulation.
[0038] One manner of providing effective stimulation therapy may utilize feedback in the form of sensed physiological signals. Sensing circuitry 412 senses these physiological signals such as local field potential signals and provides the sensed signal to the processor 402. For instance, with adaptive deep brain stimulation, the sensing circuitry 412 may be used to sense local field potential signals during the ongoing application of stimulation signals. The sensed local field potential signals are analyzed by the processor 402 in order to then request stimulation amplitude changes by the stimulation circuitry 410. The processor 402 compares the sensed local field potential signal power to the physiological thresholds to determine whether to alter the stimulation amplitude. [0039] As shown in FIG. 4, a proximal end of the endovascular lead 104 including electrical connectors 404 may be coupled to the neurostimulator 102. The neurostimulator may then configure the stimulation circuitry 410 and sensing circuitry 412 so that stimulation outputs 114 may be electrically coupled to one or more of the electrical connectors 404 when providing stimulation signals while sensing inputs 413 may be electrically coupled to one or more of the electrical connectors 404 when sensing physiological signals.
[0040] FIG. 5 shows an example 500 of logical operations that may be performed between the external device 114 and the neurostimulator 102 and related actions by users such as the clinician or patient to provide the neurostimulation therapy including stimulation and/or sensing during the trial period. The operations begin at operation 502 by implanting the multiple leads in primary and secondary locations within the patient in proximity to the area to be stimulated such as the subregion 208 of FIGS. 2A and 2B. For example, the distal end 108 of DBS lead 105 is positioned in a primary location on or adjacent to the subregion 208. Examples of this primary location include but are not limited to the subthalamic nucleus (STN), globus pallidus internus (Gpi), anterior nucleus of thalamus (ANT), vemraus intermediate nucleus (VIM), ventral capsule/ventral striatum (VC/VS), or pedunculopontine nucleus (PPN). Likewise, the endovascular lead 104 is positioned in a secondary location within a blood vessel within or adjacent to the same subregion 208. Examples of this secondary location include but are not limited to the Thalamostriate vein, the internal cerebral vein, the basal vein of Rosenthal, the interior sagittal sinus, or any other vessel determined to be appropriate by patient specific anatomy.
[0041] Once the leads have been positioned, the stimulation using these leads at the primary and secondary locations for the subregion 208 may then be tested at an operation 504. This testing may be done over a period of time after implant to allow the stimulation performance of the leads to reach a more stabilized state as edema, microlesion effects, and the like are resolved. The testing may involve a monopolar review and/or brain sense survey of the leads concurrently to determine the maximum viability of the signal biomarkers. For instance, in one example, sensing of beta band activity is performed to determine at which electrode/lead/contact and at which post-op times throughout a treatment cycle the best beta band activity is found. Additionally, or alternatively, the determination of maximum viability may be based upon patient feedback and comparison to pre-op clinical scores. Additionally, this testing verifies that the patient does not have signal limiting considerations including device interferences and occupation. [0042] The sensing may be passive while the stimulation is active to determine if there is an appropriate signal response, where there is sufficient neural substrate present to elicit an expected evoked response for the location that is being stimulated. For example, when stimulating the STN/STI, an evoked resonant neural activity (ERNA) response would be expected. When stimulating the VIM, a single evoked non-resonant response is expected. When stimulating the ANT, a delayed evoked response is expected. If the leads are in the correct primary and secondary locations for the intended subregion 208, then expected signals for that subregion 208 will occur. For example, if stimulating/ sensing the STN, a beta peak that is responsive to medication being administered to the patient will be sensed.
[0043] Upon completing the testing to confirm lead placement and biomarker viability, more advanced techniques disclosed herein may then be provided to further refine and focus the stimulation to the intended area of the brain such as the subregion 208 at an operation 506. These techniques of operation 506 may be employed in situations where the two leads are any combination of endovascular and non-endovascular, i.e., DBS, leads. These techniques include the aforementioned resulting stimulation field approach, where a resulting stimulation field, such as a beamform, occurs due to interactions of the stimulation fields of the two leads at the primary and secondary locations and/or phase shifting of the stimulation fields of the two leads at the primary and secondary locations.
[0044] For the resulting stimulation approach, both leads provide stimulation contemporaneously and more specifically at the same time in some cases with at least some overlap of pulses or by interleaving pulses in other cases with no overlap, and the desired resulting stimulation field can be iteratively found by adjusting parameters of the stimulation of each lead 104, 105. The parameters to be adjusted include the pulse frequency or timing, pulse width, amplitude, and electrode selection. Burst width and/or burst frequency may also be adjusted where a burst is a set of contiguous pulses from a given lead. The shape of the resulting stimulation field 216 varies based on the values of these parameters for a given primary and secondary location of the two leads within the brain. To interactively find the desired resulting stimulation field 216, the neurostimulator 102 may work through all the various combinations of these parameters. An example 600 of a data structure showing a simplified version of the various combinations of parameter values that the neurostimulator 102 may iterate through for purposes of illustration is shown in FIG. 6. It will be appreciated that other variables may also be included such as burst frequency and burst width in addition to those shown in FIG. 6. [0045] The data structure is shown as containing columns 602, 604, 606, and 608 representing the parameters to be adjusted. In this example, another row 610 may maintain an outcome ranking used to keep track of which iterations produced the most desired resulting stimulation field. The resulting stimulation field 216 may be defined as activated neurons as a function of the two or more interacting fields, and the resulting stimulation field 216 may be determined using sensing, imaging, and/or computational modeling for the chosen parameter values for each lead. Each row of the data structure example 600 shows the parameter values being used for each lead for a particular iteration.
[0046] In this simplified example, the parameter values for each are shown as being two options for each lead. These parameter values include pulse frequency 1 (Fl), pulse frequency 2 (F2), amplitude 1 (Al), amplitude 2 (A2), pulse width 1 (Pl), pulse width 2 (P2), and electrode combination 1 (El) and electrode combination 2 (E2). Thus, iteration 1 includes lead 1 providing a stimulation signal of Fl, Al, and Pl via electrode configuration El and includes lead 2 providing a stimulation signal of F2, A2, and P2 via electrode configuration E2. In this example, iteration 2 reverses the electrode combinations. This carries on to cycle through all possibilities. It will be appreciated that additional combinations are possible that are not shown in this simplified example, such as where both leads may provide stimulation at the same pulse frequency, amplitude, pulse width, and/or electrode configuration in one or more iterations.
[0047] Phase shifting at the pulse or burst level may be performed as an alternative to, or in combination with, the resulting stimulation approach described above. Burst phase shifting involves starting and ending bursts at different times for each lead while pulse phase shifting involves starting and ending pulses at different times for each lead. Thus, the phase shifting can be done in the context of bursted stimulation or continuous/interleaved stimulation. Furthermore, within a given burst of pulses, the frequency or pulse rate may be different for the lead at the primary location relative to the lead at the secondary location to produce the desired phase shift and resulting confinement of the resulting stimulation field. Likewise, the pulse frequency or rate of bursts may be different for the lead at the primary location relative to the lead at the secondary location to produce the desired phase shift and confinement of the resulting stimulation field. Because the phase shifted stimulation of the two leads prevents the two leads from providing the same stimulation signal at the same time to the same group of neurons, entrainment may be avoided.
[0048] FIG. 7 shows an example 700 of burst phase shifting by offsetting bursts of the stimulation signal of the primary lead and the stimulation signal of the secondary lead. In this case, the primary lead includes a stimulation signal 702 that includes a plurality of individual bursts 706 and the secondary lead includes a stimulation signal 704 with a plurality of individual bursts 708. Each burst 706, 708 includes individual pulses not shown in FIG. 7. In this example, the bursts 706 have an amplitude (Al), a burst width (BW1), and a burst frequency (BF1) while the burst 708 have an amplitude (A2), a burst width (BW2), and a burst frequency (BF2). It can be seen that there is a phase shift between bursts of the primary lead and the secondary lead as each burst 706 of the stimulation signal 702 starts at a different time than the bursts 708 of the stimulation signal 704. In one particular example, the bursts 706, 708 may be alternated to avoid any overlap of the 706 bursts with the bursts 708 and thus avoid overlap of the pulses. However, in another example where the bursts 706, 708 do overlap, interleaving of the pulses may be done to avoid overlap of the pulses themselves as discussed below.
[0049] Pulse phase shifting, including interleaving as previously mentioned, is shown in FIG. 8. An example 800 provides pulse phase shifting by offsetting pulses of the stimulation signal of the primary lead and pulses of the stimulation signal of the secondary lead. In this example, pulses 806 of the primary lead have an amplitude (Al), a pulse width (Pl), and a pulse frequency (Fl) while the pulses 808 of the secondary lead have an amplitude (A2), a pulse width (P2), and a pulse frequency (F2). It can be seen that there is a phase shift between pulses of the primary lead and the secondary lead as each pulse 806 of the stimulation signal 802 starts at a different time than each pulse 808 of the stimulation signal 804. In the case of interleaving, this offset in time due to the pulse phase shift avoids any overlap of the pulses 806 with the pulses 808.
[0050] Returning to FIG. 5, at operation 508 the neurostimulator may iterate through electrode combinations and determine target outcomes and effects. While electrode combinations may have already been iterated when determining the resulting stimulation field, in implementations where the resulting stimulation field confinement is not occurring, such as where the two leads include at least one endovascular lead to achieve the focused stimulation within the subregion 208 without resulting stimulation field confinement and/or where phase shifting between leads is occurring, then the iterating of electrodes at operation 508 may still be helpful to focus the stimulation and achieve the desired outcomes. In any event, with or without the resulting stimulation field confinement, the therapy being provided may be assessed in view of the patient specific therapeutic threshold.
[0051] The assessment of outcomes as determined at operation 510 may involve comparing pre and post stimulation information. For instance, clinical scores may be considered to determine if at least a 30% reduction in clinical scores, an example of a target threshold, has occurred. Subjective information may be considered by obtaining patient feedback about the success of the stimulation. Additionally or alternatively, sensing may be performed to determine if brain network modulations within the subregion 208 are occurring and producing the expected physiological response that is believed to be beneficial to the patient. Examples of sensing locations include the circuit of Papez and cortico-basal ganglia- thalmo-cortical loops. This includes assessing resolution of symptoms of the neurological disorder as well as consideration of the presence and severity of indicated side effects. Indicated side effects for consideration may include but are not limited to: Paresthesias, Muscle contractions, Dysarthria, Contralateral Gaze Deviation, Diplopia, Deviation of ipsilateral eye, Dizziness, ALO, Personality/impulsivity changes, Depression, Sweating, Nausea, Extreme discomfort, Warm sensations, Possible impact on dyskinesias and/or tremor, Possible mood changes, Akinesias, Phosphenes, and Ataxia. Upon finding a combination of electrodes with a best outcome, therapy using that combination may then be implemented in a longer term manner.
[0052] From the discussion above, it can be seen that steps can be taken to help focus neurostimulation to substantially confine the stimulation signals to the desired area of the brain. These steps may include placing multiple leads in respective primary and secondary locations where at least one of those locations may be best accessed via a blood vessel using an endovascular lead. These steps may additionally or alternatively include utilizing a resulting stimulation field approach to provide a resulting stimulation field within the desired area of the brain using multiple leads that may include any combination of endovascular and non-endovascular leads. These steps may further additionally or alternatively include utilizing burst and/or pulse phase shifting, including alternating bursts and/or interleaved pulses, between the stimulation signals being provided by the leads at the primary and secondary locations within the brain.
[0053] The invention may further be described by reference to the following numbered paragraphs:
1. A method of providing neurostimulation therapy, comprising: providing a first stimulation signal at a first location in proximity to a subregion of a brain of a patient, the first stimulation signal being characterized by parameters comprising frequency, amplitude, pulse width, and electrode selection; providing a second stimulation signal at a second location in proximity to the subregion of the brain of the patient contemporaneously with providing the first stimulation signal at the first location, the second stimulation signal being characterized by parameters comprising frequency, amplitude, pulse width, and electrode selection; and iteratively adjusting the frequency, amplitude, pulse width, and electrode selection of the first stimulation signal and the second stimulation signal until a combination of the first stimulation signal and the second stimulation signal creates a resulting stimulation field that activates a desired brain network within the subregion of the brain of the patient.
2. The method of paragraph 1, further comprising: providing an endovascular lead within a blood vessel of a brain of the patient and at the first location in proximity to a subregion of the brain and wherein providing the first stimulation signal comprises providing the first stimulation signal from the endovascular lead; and providing a non-endovascular lead outside of a blood vessel of the brain of the patient and at the second location in proximity to the subregion of the brain and wherein providing the second stimulation signal comprises providing the second stimulation signal from the non-endovascular lead.
3. The method of paragraph 1 or 2, wherein the second stimulation signal is phase shifted relative to the first stimulation signal.
4. The method of paragraph 3, wherein bursts of the second stimulation signal are burst phase shifted to alternate with bursts of the first stimulation signal and/or pulses of the second stimulation signal are pulse phase shifted to be interleaved with pulses of the first stimulation signal.
5. The method of any of paragraphs 1-4, further comprising determining that the resulting stimulation field activates a desired brain network by at least one of sensing, imaging, or computational modeling.
6. The method of any of paragraphs 1-5, further comprising determining an efficacy of the neurostimulation therapy by at least one of an at least 30% reduction in clinical scores, patient feedback, and sensed physiological response. 7. An implantable medical system, comprising: a neurostimulator that contemporaneously generates a first stimulation signal and a second stimulation signal; a first lead coupled to the neurostimulator and having a distal end with at least one electrode positioned at a first location in proximity to a subregion of a brain of a patient to deliver the first stimulation signal to the first location; a second lead coupled to the neurostimulator and having a distal end with at least one electrode positioned at a second location in proximity to the subregion of the brain of the patient to deliver the second stimulation signal to the second location, wherein the neurostimulator iteratively adjusts the frequency, amplitude, pulse width, and electrode selection of the first stimulation signal and the second stimulation signal until creating a resulting stimulation field that activates a desired brain network within the subregion of the brain the patient.
8. The system of paragraph 7, wherein the first lead is an endovascular lead within a blood vessel of a brain of the patient wherein the second lead is a non-endovascular lead outside of a blood vessel of the brain of the patient.
9. The system of paragraph 7 or 8, wherein the second stimulation signal is phase shifted relative to the first stimulation signal.
10. The system of paragraph 9, wherein bursts of the second stimulation signal are burst phase shifted to alternate with bursts of the first stimulation signal and/or pulses of the second stimulation signal are pulse phase shifted to be interleaved with pulses of the first stimulation signal.
11. The system of any of paragraphs 8-10, wherein the neurostimulator determines that the resulting stimulation field activates a desired brain network by sensing.
12. The system of any of paragraphs 8-11, wherein the neurostimulator determines an efficacy of the neurostimulation therapy by sensing a physiological response.
13. A method of providing neurostimulation therapy, comprising: providing an endovascular lead within a blood vessel of a brain of the patient and at a first position in proximity to a subregion of the brain; providing a non-endovascular lead outside of a blood vessel of the brain of the patient and at a second position in proximity to the subregion of the brain; and providing a first stimulation signal from the endovascular lead while contemporaneously providing a second stimulation signal through the non-endovascular lead.
14. The method of paragraph 13, wherein a combination of the first stimulation signal and the second stimulation signal activates a brain network within the subregion of the brain.
15. The method of paragraph 13 or 14, wherein the first stimulation signal and the second stimulation signal are characterized by parameters comprising frequency, amplitude, pulse width, and electrode selection, and wherein the method further comprises iteratively adjusting the frequency, amplitude, pulse width, and electrode selection of the first stimulation signal and the second stimulation signal until a combination of the first stimulation signal and the second stimulation signal creates a resulting stimulation field that activates a desired brain network within the subregion of the brain the patient.
16. The method of any of paragraphs 12-15, wherein the second stimulation signal is phase shifted relative to the first stimulation signal.
17. The method of any of paragraphs 15-16, further comprising determining that the resulting stimulation field activates a desired brain network by at least one of sensing, imaging, or computational modeling.
18. The method of any of paragraphs 13-17, further comprising determining an efficacy of the neurostimulation therapy by at least one of an at least 30% reduction in clinical scores, patient feedback, and sensed physiological response.
19. An implantable medical system, comprising: a neurostimulator that contemporaneously generates a first stimulation signal and a second stimulation signal; an endovascular lead coupled to the neurostimulator and having a distal end with at least one electrode positioned within a blood vessel at a first location in proximity to a subregion of a brain of the patient to deliver the first stimulation signal at the first location; a non-endovascular lead coupled to the neurostimulator and having a distal end with at least one electrode positioned outside of blood vessels at a second location in proximity to the subregion of the brain of the patient to deliver the second stimulation signal at the second location.
20. The system of paragraph 19, wherein a combination of the first stimulation signal and the second stimulation signal activates a brain network within the subregion of the brain.
21. The system of paragraph 19 or 20, wherein the first stimulation signal and the second stimulation signal are characterized by parameters comprising frequency, amplitude, pulse width, and electrode selection, and wherein the neurostimulator iteratively adjusts the frequency, amplitude, pulse width, and electrode selection of the first stimulation signal and the second stimulation signal until a combination of the first stimulation signal and the second stimulation signal creates a resulting stimulation field that activates a desired brain network within the subregion of the brain the patient.
22. The system of any of paragraphs 19-21, wherein the second stimulation signal is phase shifted relative to the first stimulation signal.
23. The system of any of paragraphs 21-22, wherein the neurostimulator determines that the resulting stimulation field activates a desired brain network by sensing.
24. The system of any of paragraphs 19-23, wherein the neurostimulator determines an efficacy of the neurostimulation therapy by sensing a physiological response.
25. A method of providing neurostimulation therapy, comprising: providing a first stimulation signal at a first location in proximity to a subregion of a brain of a patient; and providing a second stimulation signal at a second location in proximity to the subregion of the brain of the patient contemporaneously with providing the first stimulation signal at the first location, the second stimulation signal being phase shifted relative to the first stimulation signal.
26. The method of paragraph 25, wherein a combination of the first stimulation signal and the second stimulation signal activates a brain network within the subregion of the brain.
27. The method of paragraph 25 or 26, further comprising: providing an endovascular lead within a blood vessel of a brain of the patient and at the first location in proximity to a subregion of the brain and wherein providing the first stimulation signal comprises providing the first stimulation signal from the endovascular lead; and providing a non-endovascular lead outside of a blood vessel of the brain of the patient and at the second location in proximity to the subregion of the brain and wherein providing the second stimulation signal comprises providing the second stimulation signal from the non-endovascular lead.
28. The method of any of paragraphs 25-27, wherein the first stimulation signal and the second stimulation signal are characterized by parameters comprising frequency, amplitude, pulse width, and electrode selection, and wherein the method further comprises iteratively adjusting the frequency, amplitude, pulse width, and electrode selection of the first stimulation signal and the second stimulation signal until a combination of the first stimulation signal and the second stimulation signal creates a resulting stimulation field that activates a desired brain network within the subregion of the brain the patient.
29. The method of any of paragraph 28, further comprising determining that the resulting stimulation field activates a desired brain network by at least one of sensing, imaging, or computational modeling.
30. The method of any of paragraphs 25-29, further comprising determining an efficacy of the neurostimulation therapy by at least one of an at least 30% reduction in clinical scores, patient feedback, and sensed physiological response. 31. An implantable medical system, comprising: a neurostimulator that contemporaneously generates a first stimulation signal and a second stimulation signal; a first lead coupled to the neurostimulator and having a distal end with at least one electrode positioned at a first location in proximity to a subregion within a brain of the patient to deliver the first stimulation signal to the first location; a second lead coupled to the neurostimulator and having a distal end with at least one electrode positioned at a second location in proximity to the subregion within the brain of the patient to deliver the second stimulation signal to the second location, wherein the first stimulation signal is phase shifted relative to the second signal.
32. The system of paragraph 31, wherein a combination of the first stimulation signal and the second stimulation signal activates a brain network within the subregion of the brain.
33. The system of paragraph 31 or 32, wherein the first lead is an endovascular lead within a blood vessel of a brain of the patient wherein the second lead is a non- endovascular lead outside of a blood vessel of the brain of the patient.
34. The system of any of paragraphs 31-33, wherein the first stimulation signal and the second stimulation signal are characterized by parameters comprising frequency, amplitude, pulse width, and electrode selection, and wherein the neurostimulator iteratively adjusts the frequency, amplitude, pulse width, and electrode selection of the first stimulation signal and the second stimulation signal until a combination of the first stimulation signal and the second stimulation signal creates a resulting stimulation field that activates a desired brain network within the subregion of the brain the patient.
35. The system of paragraph 34, wherein the neurostimulator determines that the resulting stimulation field activates a desired brain network by sensing.
36. The system of any of paragraphs 31-35, wherein the neurostimulator determines an efficacy of the neurostimulation therapy by sensing a physiological response. [0054] While embodiments have been particularly shown and described, it will be understood by those skilled in the art that various other changes in the form and details may be made therein without departing from the spirit and scope of the invention.