Neural stimulation therapy using multiple leads positioned to provide improved sensing of physiological signals

Abstract

Neural stimulation therapy is provided through the use of multiple leads that are positioned to provide improved sensing of physiological signals for a given patient. An implantable medical system uses at least two leads, with each lead having a distal end located within the brain of the patient. One or more techniques can be used in conjunction with the positioning of the distal ends of the multiple leads to provide improved sensing of physiological signals. When the first lead no longer provides adequate sensing, the second lead can be used as a replacement to provide sensing of physiological signals. The multiple leads can be the same type, such as two or more DBS leads, or the multiple leads can be different types, such as a DBS lead combined with an intravascular lead that is intravascular.

Description

[0001] This application is a PCT application claiming priority and benefit to U.S. Provisional Patent Application No. 63 / 625,837, filed January 26, 2024, the entire contents of which are incorporated herein by reference. Technical Field

[0002] The implementation scheme relates to neurostimulation therapy, and more specifically to neurostimulation therapy using multiple leads positioned to provide improved sensing of physiological signals. Background Technology

[0003] Patients with one or more neurological disorders may benefit from neurostimulation therapy, including deep brain stimulation (DBS). To deliver DBS therapy, the distal end of a lead is implanted at a target location in the patient's brain. The proximal end of the lead is coupled to an implantable medical device, such as a neurostimulator, which generates electrical stimulation signals delivered to the brain by one or more electrodes of the lead and / or senses physiological signals captured within the brain by one or more electrodes of the lead.

[0004] Neurostimulation therapy can be optimized for a given patient by sensing physiological signals within the brain. Sensing can be performed in a passive setting without applied stimulation to capture a baseline. Sensing can be combined with stimulation to capture information that can be considered in the future and / or used for near real-time stimulation control, such as in adaptive DBS. However, problems may arise regarding sensing due to various difficulties. For example, brain structure and / or conditions may cause sensing leads to be placed in less-than-ideal locations for sensing relevant physiological signals. As another example, the capability of sensing leads may decrease or become completely ineffective over time. Summary of the Invention

[0005] The implementation addresses these and other issues by providing sensing for neurostimulation therapy using multiple leads, which are positioned to provide improved sensing capabilities for a given patient's anatomy and condition. Using the multiple leads for sensing, various combinations of electrodes for sensing can be explored, and combinations that provide optimal biomarker resolution can be selected for the therapy. Furthermore, the placement of the multiple leads can be chosen to provide additional features, such as indirect monitoring of regions of interest within the brain, where one or two leads are located outside the region of interest, or to replace the sensing function of a single lead with the sensing function of an adjacent lead. Additionally, the multiple leads can be of the same type, such as DBS leads, or of different types, such as a first DBS lead located inside or outside the brain and outside blood vessels, and a second intravascular lead located within blood vessels in the brain.

[0006] The implementation provides a method for providing neurostimulation therapy. The method involves sensing physiological signals using a non-endovascular lead having at least one distal electrode at a first location outside a blood vessel within the patient's brain. The method also involves sensing physiological signals using an endovascular lead having at least one distal electrode at a second location within a blood vessel within the patient's brain.

[0007] The implementation provides a method for providing neurostimulation therapy. The method involves sensing physiological signals using a first lead having a plurality of distal electrodes at a first location within the patient's brain. The method also involves sensing physiological signals using a second lead having a plurality of distal electrodes at a second location within the patient's brain. In sensing physiological signals using the first and second leads, the method further involves traversing combinations of at least one distal electrode of the first lead with at least one distal electrode of the second lead to find a combination that provides optimal biomarker resolution.

[0008] An embodiment provides a method for providing neurostimulation therapy. The method involves sensing a physiological signal using a first lead having a distal electrode at a first location within the patient's brain. The method involves detecting whether the sensed physiological signal has signal characteristics that satisfy a threshold. If the signal characteristics do indeed satisfy the threshold, the method involves using the sensed physiological signal from the first location to provide neurostimulation therapy. If the signal characteristics do not satisfy the threshold, the method involves using a second lead having a distal electrode at a second location within the patient's brain to sense the physiological signal, and using the sensed physiological signal from the second location to provide neurostimulation therapy.

[0009] An embodiment provides an implantable medical system. The system includes a non-endovascular lead having at least one distal electrode at a first location within the patient's brain but outside a blood vessel within the brain. The system also includes an endovascular lead having at least one distal electrode at a second location within a blood vessel in the patient's brain. The system further includes an implantable medical device coupled to both the non-endovascular and endovascular leads. The implantable medical device has sensing circuitry for sensing physiological signals using both the non-endovascular lead and the endovascular lead.

[0010] An embodiment provides a system for delivering neurostimulation therapy. The system includes a first lead having at least one distal electrode at a first location within the patient's brain. The system includes a second lead having at least one distal electrode at a second location within the patient's brain. The system also includes an implantable medical device coupled to the first and second leads. The implantable medical device has sensing circuitry for sensing physiological signals using both the first and second leads. When sensing physiological signals using both leads, the implantable medical device traverses combinations of at least one distal electrode of the first lead and at least one distal electrode of the second lead to find a combination providing optimal biomarker resolution.

[0011] An embodiment provides a system for delivering neurostimulation therapy. The system includes a first lead having at least one distal electrode at a first location within a patient's brain. The system includes a second lead having at least one distal electrode at a second location within the patient's brain. The system also includes an implantable medical device coupled to the first and second leads. The implantable medical device has sensing circuitry for sensing physiological signals using the first lead and detecting whether the sensed physiological signals have signal characteristics that satisfy a threshold. If the signal characteristics do satisfy the threshold, the implantable medical device uses the sensed physiological signals from the first location to deliver neurostimulation therapy. If the signal characteristics do not satisfy the threshold, the implantable medical device uses the second lead having a distal electrode at the second location within the patient's brain to sense physiological signals and uses the sensed physiological signals from the second location to deliver neurostimulation therapy. Attached Figure Description

[0012] Figure 1 An example of a patient with an implantable medical system is shown, which includes two leads inside the patient's brain.

[0013] Figure 2 An example of the relationship between the intravascular lead and the DBS lead regarding the location of the target area to be sensed is shown.

[0014] Figure 3 An example of a component of an external device that communicates with a neurostimulation device is shown.

[0015] Figure 4 An example of a component of a neurostimulation device that can be coupled to multiple leads to provide sensing of physiological signals is shown.

[0016] Figure 5An example of a workflow for providing neurostimulation therapy is shown, which uses multiple leads positioned according to the specific patient’s condition to sense desired physiological signals.

[0017] Figure 6 Examples of data structures representing various combinations of sensing electrodes with multiple leads and the resulting biomarker resolution are shown.

[0018] Figure 7 An example of a data structure representing electrodes forming an array of leads is shown.

[0019] Figure 8 An example of a workflow is shown where a second lead is implemented as an alternative to the first lead when sensing by the first lead becomes insufficient. Detailed Implementation

[0020] One implementation provides an implantable medical system using two leads, each with a distal end located within the patient's brain. Some implementations utilize one or more techniques combined with the positioning of the distal ends of the multiple leads to provide improved sensing of physiological signals. Other implementations utilize a second lead as an alternative to provide sensing of physiological signals when the first lead no longer provides sufficient sensing. In some implementations, the multiple leads may be of the same type, while in other implementations, the multiple leads may be of different types, such as DBS leads combined with intravascular leads within blood vessels.

[0021] This disclosure describes example techniques for confirming the efficacy of various forms of neurostimulation therapy. The example techniques are described in relation to DBS, but are not limited thereto and can be applied to other types of treatment and / or other anatomical locations. Neurostimulation therapy, particularly DBS, can provide relief for many different patient conditions such as movement disorders, epilepsy, obsessive-compulsive disorder (OCD), depression, etc. Patients with movement disorders or other neurodegenerative diseases, whether due to illness or injury, may experience problems with muscle control and movement, such as rigidity, bradykinesia (i.e., slow body movement), rhythmic hyperkinesia (e.g., tremor), non-rhythmic hyperkinesia (e.g., tics), or akinesia (i.e., loss of movement). Movement disorders may be found in patients with conditions such as Parkinson's disease, multiple sclerosis, and cerebral palsy. Delivery of electrical stimulation by medical devices to one or more sites within the patient's body (such as within the brain) can help relieve and, in some cases, eliminate symptoms associated with these movement disorders and other conditions.

[0022] Figure 1A typical setting for an implantable medical system 100 used to deliver neurostimulation therapy, such as DBS therapy, is shown. In this example, the implantable medical system 100 is mounted on a patient's body 110. The implantable medical system 100 of this example includes an implantable medical device, such as a neurostimulator 102, which has been externally mounted on the patient or implanted in a subcutaneous or subfascial pouch 112. A first medical lead 104 (such as an intravascular lead that can be combined with an extension) is wired between a target stimulation site within the patient's brain 111 and the neurostimulator 102. The first lead 104 has a distal end 103 and a distal electrode on the distal end, which is positioned within the brain 111 near the target location for applying stimulation and / or sensing. In the specific implementation of the first lead 104 as an intravascular lead, the lead 104 can be implanted in a less invasive manner compared to a DBS lead by being introduced into a blood vessel that travels into the brain (111) and branches into a location near the target region.

[0023] Figure 1 The location and related aspects of the second lead 105 are also shown, such as as a conventional DBS lead as a non-endovascular lead, since the DBS lead 105 is located outside the blood vessels of the brain 111. The DBS lead 105 extends in a conventional manner from the neurostimulator 102 under the skin and to a location on the patient's skull where a hole 113 is formed to allow the DBS lead 105 to pass through the skull to enter the brain 111 in region 106 below the hole 113. The DBS lead 105 can then be wired in a non-endovascular manner outside any blood vessels to a target region within the brain 111, with the distal end 108 having an electrode positioned at that target region.

[0024] Figure 2 An example of a more detailed view of a target region 208 within brain 111, distinct from adjacent subregion 210, is shown. The distal end 103 of an intravascular lead 104 is positioned adjacent to subregion 208. As can be seen, the intravascular lead 104, including the distal end 103 with electrodes 204, is present within a blood vessel 202 traversed adjacent to the target region 208 of brain 111. Thus, the intravascular lead 104 is capable of providing neurostimulation therapy in the form of electroneurogenic signals and / or sensing physiological signals from one or more electrodes 202 interacting with brain 111 adjacent to the target region 208, as indicated by the interaction area 212. One or more of the electrodes 204 of the lead 104 can be used to sense electrophysiological signals from the region adjacent to the target region 208 in order to measure the effect of neurostimulation therapy.

[0025] The distal end 108 of the DBS lead 105 has a typical DBS lead position relative to the target sub-region 208, which differs from the position of the distal end 103 of the intravascular lead 104. Therefore, the DBS lead 105 can provide neurostimulation therapy in the form of electroneurostimulation signals from one or more electrodes 206 that propagate to the brain 111 near the target region 208, as indicated by the stimulation and / or sensing area 214. One or more of the electrodes 206 of the lead 105 can be used to sense electrophysiological signals from the region near the target sub-region 208 for further measurement of the effectiveness of the neurostimulation therapy.

[0026] exist Figure 2 As can be seen, stimulation and / or sensing areas 212 and 214 together can provide relatively large-volume neural activation and monitoring within subregion 208, while remaining substantially confined to subregion 208 and avoiding subregion 210, so as not to produce unwanted effects in subregion 210. Because subregion 208 may be relatively small or adjacent to sensitive brain structures, only the distal end 108 of a single DBS lead 105 can be positioned at subregion 208. The presence of intravascular leads 104 and distal ends 103 within the vessel 202 at locations close to subregion 208 avoids the need for stimulation and / or sensing area 214 to extend to the extent that it would intrude into subregion 210 to reach the portion of subregion 208 where stimulation and / or sensing area 212 is located. Therefore, multiple leads 104, 105 with corresponding distal ends 103, 108 close to subregion 208 minimize unwanted stimulation leakage into subregion 210.

[0027] Several examples of possible locations for the distal ends of the first lead 104 and the second lead 105 depend on the lead type. For example, non-endovascular leads (such as DBS leads) can be placed in primary locations, including but not limited to the subthalamic nucleus (STN), medial part of the globus pallidus, anterior thalamic nucleus (ANT), ventral intermediate nucleus (VIM), ventral bursa / ventral striatum (VC / VS), or peduncular pontine nucleus (PPN). Similarly, endovascular leads can be located in secondary locations within the same subregion 208 or in vessels adjacent to that subregion, or elsewhere for indirect monitoring discussed further below. Examples of secondary locations include, but are not limited to, the thalamic-striatal vein, internal cerebral vein, Rosenthal's basal vein, inferior sagittal sinus, or any other vessel appropriate as determined by the patient's specific anatomy.

[0028] The following text is about Figure 5 and Figure 8 Work process Figure 6 Data structures and Figure 7 Multi-lead arrays are discussed in more detail, and various techniques can be used to utilize them, such as Figure 2Multiple leads, as shown, are used to improve the sensing of physiological signals. For example, electrode combinations involving multiple leads can be identified to provide increased resolution of biomarkers and these combinations can be used for therapy. Furthermore, multiple leads can be placed in strategic locations to indirectly monitor inaccessible areas of the brain. Additionally, multiple leads can be used as arrays to achieve source separation of mixed signals, where multiple sources of physiological signals exist in the area being sensed. Another use of multiple leads includes using one lead as a replacement for another lead that may have deteriorated or become inoperable for sensing purposes.

[0029] Additionally, Figure 2 It can also represent a configuration for indirectly monitoring inaccessible areas of the brain 111 using a first lead 104 and a second lead 105. As with other techniques described herein, the first lead 104 and the second lead 105 for indirect monitoring can be of the same or different types, such as having intravascular leads and non-intravascular leads, such as DBS leads. One lead can be positioned such that the distal electrode is located at a subcortical location of the brain 111, while the distal electrode of the other lead is located at a cortical periphery location of the brain 111, wherein the area being indirectly monitored is separated from both the subcortical and cortical periphery locations. The signal of the target network in the inaccessible area is then extrapolated based on what is sensed at the two leads in different disconnected areas. As a specific example, direct sensing can occur via a lead having a distal end at the STN and another lead having a distal end at the PPN to indirectly identify modulation associated with movement.

[0030] Figure 3 Example of components of an external device 114 is shown, which communicates with a neurostimulator 102 to provide programming for controlling 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, etc. Several components of the external device 114 include a processor 302, communication circuitry 304, and input / output circuitry 310. The processor 302 interacts with the communication circuitry 304 and the input / output circuitry 310 to provide operation of the implantable medical device 102. It may also include... Figure 3 The power source (such as a battery or utility power interface, not shown) is used to provide power to various components.

[0031] Processor 302 performs various logical operations when interacting with other components. These operations may involve exchanging data with implantable medical device 102 using communication circuitry 304, generating relevant displays of information, and receiving relevant input from users viewing the displays (such as clinicians or patients). For example, data generated from sensed physiological signals may be shared with external device 114 at a future time or near real-time for the purpose of displaying information to a clinician. Processor 302 may take various forms, such as a general-purpose programmable processor, a dedicated processor, a hardwired digital logic unit, and / or various combinations thereof. Processor 302 may utilize operating memory as internal, external (not shown), or a combination of both, and may also utilize storage devices to retain data and programming in a long-term, non-volatile manner.

[0032] The communication circuit 304 includes both a transmitter circuit 306 and a receiver circuit 308 for transmitting and receiving wireless signals. The communication circuit 304 is wirelessly or wiredly connected to an intermediate device 116 via a communication link 120. The communication link may utilize technologies such as Bluetooth. ® The protocol is a wireless protocol. Alternatively, the communication link 120 can be wired and telemetry-dependent, where the intermediate device 116 is a telemetry head that remains very close to the implantable medical device 102. As another alternative, any link with sufficiently low latency to allow clinicians to respond to changes in the patient, including the management of remote / internet connections, can also be used.

[0033] Input / output circuitry 310 allows external device 114 to interact with a user (including a clinician or patient) or other devices. Input / output circuitry 310 can provide outputs such as visual displays on a screen, audio, etc. Input / output circuitry 310 can provide inputs such as a keyboard or keypad, mouse, and / or touchscreen. Input / output circuitry 310 allows the user to input information such as programming details, stimulation parameters, and other information to be provided from external device 114 to neurostimulator 102, as well as review information such as physiological data sent from neurostimulator 102 to external device 114.

[0034] Figure 4An example of an implantable medical device, such as a neurostimulator 102, is shown. 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 forming an airtight container. The components of the neurostimulator 102 include a processor 402 and communication circuitry 404. A stimulation circuitry 410 is also present to generate stimulation signals for a first and second lead used to provide stimulation therapy, and a sensing circuitry 412 is present to sense physiological signals related to the stimulation therapy, such as local field potential signals and / or other biomarkers, using the first and second leads. The processor 402 interacts with the communication circuitry 404, the stimulation circuitry 410, and the sensing circuitry 412 to provide operation of the neurostimulator 102. Although not shown, the implantable medical device 102 also includes a power source, such as an onboard battery, to provide power to these components.

[0035] The processor 402 performs various logical operations when interacting with other components to provide stimulation and / or sensing functions for neurostimulation therapy. Therefore, in Figure 5 The workflow example illustrates an example of the combination of logical operations of neurostimulator 102 and processor 402 with logical operations of external device 114 and processor 302. Processor 402 can be of various forms, such as a general-purpose programmable processor, a special-purpose processor, a hardwired digital logic unit, and / or various combinations thereof.

[0036] The communication circuit 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 sensing configurations from the external device 114. It also allows the processor 402 to send information such as sensed physiological signal data to the external device 114.

[0037] The stimulation circuit 410 in the illustrated example allows the implantable medical device 102 to interact with the brain tissue of the patient 110. The stimulation circuit 410 can generate stimulation signals comprising stimulation pulses of a given amplitude (such as a given current amplitude). Depending on a stimulation therapy algorithm executed by the processor 402, the stimulation circuit 410 can vary 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 way to provide effective stimulation therapy is by utilizing feedback in the form of sensed physiological signals. Sensing circuitry 412 senses these physiological signals, such as local field potential signals and / or other biomarkers, and provides the sensed signals to processor 402. For example, using adaptive deep brain stimulation (DBS), sensing circuitry 412 can be used to sense local field potential signals during the continuous application of the stimulation signal. For example, the processor 402 analyzes the sensed local field potential signals so that it can then request stimulation circuitry 410 to change the stimulation amplitude when adaptive DBS is provided. Processor 402 compares the power of the sensed local field potential signals to physiological thresholds to determine whether to change the stimulation amplitude.

[0039] like Figure 4 As shown, in this example, the proximal end of the intravascular lead 104, including the electrical connector 404, can be coupled to the neurostimulator 102. The neurostimulator can then be configured with stimulation circuitry 410 and sensing circuitry 412 such that when a stimulation signal is provided, stimulation output 114 can be electrically coupled to one or more of the electrical connectors 404, and when a physiological signal is sensed, sensing input 413 can be electrically coupled to one or more of the electrical connectors 404. The proximal end of the DBS lead 105 and its electrical connector are similarly coupled to the neurostimulator 102.

[0040] Figure 5 An example 500 of logical operations that can be performed by an implantable medical device 102 to optimize the sensing of physiological signals by finding an electrode combination of a first lead 104 and a second lead 105 that provides optimal biomarker resolution is illustrated. During implantation of the implantable medical device 102 and the leads 104, 105, a waiting period can be used to address edema, achieve lead stabilization, and / or find optimal stimulation settings. At this time, it can be confirmed that the patient is not subject to signal limitations, such as device interference or occupational issues. Furthermore, the implantable medical device 102 can begin simultaneous sensing using the first lead 104 and the second lead 105 to confirm maximum activity of the signal biomarker and further confirm the presence of sufficient neural matrix to elicit an evoked response.

[0041] At an appropriate time thereafter, the implantable medical device 102 can begin to simultaneously sense physiological signals using the first lead 104 and the second lead 105. Specifically, at operation 502, the implantable medical device can begin to explore possible combinations of electrodes from the first and second leads to provide sensing of physiological signals. This sensing can occur in a passive context, where the physiological signals are inherent because no stimulation is provided to evoke them. Alternatively, the sensing at operation 502 can occur in conjunction with stimulation output from a combination of electrodes from the first lead 104 and / or the second lead 105. Furthermore, the implantable medical device 102 can also explore various combinations of stimulation parameters and electrodes at operation 504 in an effort to produce the desired therapeutic effect as determined by the sensing occurring at operation 502.

[0042] The electrode combinations used during sensing can involve any number of electrodes on the first lead 104 and any number of electrodes on the second lead 105. Furthermore, combinations can involve all combinations of electrodes sensed in a bipolar configuration and all combinations of electrodes sensed in a unipolar configuration. These possible combinations can include using at least one electrode from one lead (first or intravascular lead or second or DBS lead) with multiple electrodes from the other lead. These possible combinations can also include using only one electrode from lead 104 (such as an intravascular lead) or only one electrode from the other lead 105 (such as a DBS lead) for sensing. These possible combinations can further include using one or more electrodes in a hybrid unipolar configuration, wherein one or more electrodes from one of the leads (first or intravascular lead or second or DBS lead) serve as a common reference.

[0043] The following discussion Figure 6 Data structure 600, wherein the sensed physiological signal data for each electrode combination of operation 502 can be... Figure 5 The data is stored at operation 506, and compared at operation 508 to sort the combinations, thereby finding the combination that provides optimal biomarker resolution and / or signal quality. Then, at operation 510, a therapy can be performed that uses the combination providing optimal biomarker resolution to sense the physiological signal of interest.

[0044] The sensing threshold used to find optimal biomarker resolution (such as in terms of dynamic range and / or signal quality at operation 508) can be patient-specific, disease-type-specific, and / or symptom-specific, and is a function of what is being monitored and measured. For example, a decrease in β can be identified in response to stimulation, medication, sleep, etc. Furthermore, in such examples, subjective determination can also be made by considering patient feedback.

[0045] When sensing is performed in conjunction with the provided stimulus, as at operation 504, the sensing of physiological signals can involve identifying the modulated networks within the brain to the expected physiological response. For example, the sensed physiological signals can be analyzed in relation to the Babez circuit, the corticobasal ganglia-thalamus-cortical loop. The sensed physiological signals can be analyzed in relation to coupling patterns such as phase-amplitude coupling, Granger causality, transfer functions, propagation delays, and cases where the signal is induced or coupled to a network different from the directly stimulated network. A typical resolution of at least 0.8 μV / rtHz for the local field potential in the β range is an example of a value considered a meaningful biomarker for β.

[0046] Figure 6 Data structure 600 is shown, illustrating a simplified version of various combinations of sensing electrodes for first lead 104 and second lead 105. The data structure is shown as columns 602 and 604 representing the electrode combinations in use and the biomarker resolution provided by the electrode combinations. Each row provides a specific electrode combination and the resulting biomarker resolution. For example, the first row uses electrode 0 of lead 1 and electrode 0 of lead 2 in a bipolar (“B”) sensing configuration. As another example, row five uses electrode 0 of lead 1 for sensing and electrode 0 of lead 2 for a common reference in a first monopolar (“M1”) sensing configuration. As another example, row nine uses electrode 0 of lead 1 and electrode 0 of lead 2 in a second monopolar (“M2”) sensing configuration, such as where the electrode of the first lead provides a common reference. As another example, row thirteen uses electrodes 0 and 1 of lead 1 in a bipolar (“B”) sensing configuration without using electrode 2. As another example, line fourteen uses electrode 0 with lead 1 in a single-pole (“M”) sensing configuration, an electrode without lead 2, and the housing (“C”) of device 102. It will be understood that there are many possible combinations, including using more than one electrode with one lead, and more than one electrode with another lead.

[0047] Figure 7An example of a data structure 700 representing an electrode sensing array established by distal electrodes of multiple leads 104, 105 is shown. This data structure can be used when attempting to separate the sources of a sensed physiological mixture signal with contributions from multiple sources. Columns 702 and 704 of array 700 represent the first lead 104 and the second lead 105, respectively. Rows 706, 708, 710, and 712 of array 700 represent the location of each electrode on the first lead 104 and the second lead 105. Thus, columns 702 and 706 show the contribution of electrode 0 of lead one, while columns 704 and 706 show the contribution of electrode 0 of lead two, and so on. Source separation can then be performed, for example, at an external device, by acquiring data from the array and applying source separation algorithms to analyze the contributions of the elements of the sensing array. Examples of such algorithms include principal component analysis (PCA), independent component analysis (ICA), denoised source separation (DSS), singular value decomposition (SVD), etc.

[0048] Figure 8 Example 800 of logical operations is shown in a scenario where one of multiple leads can act as an alternative or backup to the primary lead. Initially, at operation 802, the implantable medical device 102 is using a first lead to sense a physiological signal. For example, a DBS lead 105 positioned within tissue but outside a blood vessel can be used for sensing. The processor of the implantable medical device 102 performs a comparison of the sensed physiological signal characteristics with a threshold. For example, in one example, the comparison may include comparing the dynamic range of the sensed signal with a dynamic range threshold. In another example, the comparison may be a comparison of the maximum sensed signal amplitude with an amplitude threshold. In yet another example, a biomarker resolution threshold may be used.

[0049] If the sensed physiological signal meets the threshold, the therapy continues at operation 806 using the sensed physiological signal from the first lead. If the sensed physiological signal does not meet the threshold, at operation 808, the implantable medical device 102 begins sensing using a second lead (such as a different DBS lead outside the blood vessel or a different intravascular lead inside the blood vessel). Then, at operation 810, the therapy continues using the sensed physiological signal from the second lead.

[0050] This invention can be further described with reference to the following numbered paragraphs: 1. A method for providing neurostimulation therapy, the method comprising: Sensing physiological signals using a non-endovascular lead, the non-endovascular lead having at least one distal electrode at a first location outside a blood vessel within the patient's brain; and Physiological signals are sensed using an intravascular lead, the intravascular lead having at least one distal electrode at a second location within the blood vessel in the patient's brain.

[0051] 2. The method according to paragraph 1, wherein the non-endovascular lead includes a plurality of distal electrodes at the first location, and wherein, when sensing the physiological signal using the non-endovascular lead and the endovascular lead, combinations of the plurality of distal electrodes of the non-endovascular lead with the at least one distal electrode of the endovascular lead are traversed to find a combination that provides optimal biomarker resolution.

[0052] 3. The method according to paragraph 1, wherein the intravascular lead includes a plurality of distal electrodes at the second location, and wherein, when sensing the physiological signal using the non-intravascular lead and the intravascular lead, combinations of at least one distal electrode of the non-intravascular lead with the plurality of distal electrodes of the intravascular lead are traversed to find a combination that provides optimal biomarker resolution.

[0053] 4. The method according to any one of paragraphs 2 and 3, further comprising: traversing the distal electrodes to provide a stimulation signal, in conjunction with traversing the distal electrodes of the non-intravascular lead and the intravascular lead to find the combination of the distal electrodes for stimulation and the distal electrodes for sensing that provide the optimal resolution of the biomarker.

[0054] 5. The method according to any one of paragraphs 2 to 4, wherein traversing the combination comprises: attempting to sense the physiological signal using electrodes consisting only of the non-intravascular leads and / or only of the intravascular leads.

[0055] 6. The method according to any one of paragraphs 2 to 5, wherein traversal of combinations includes: attempting to sense the physiological signal using the electrode of the non-endovascular lead or the endovascular lead as a single or common reference.

[0056] 7. The method according to paragraph 1, wherein the plurality of sources of the physiological signal are present within the brain, wherein the non-vascular lead includes a plurality of distal electrodes at the first location, and wherein when sensing the physiological signal using the plurality of distal electrodes of the non-vascular lead and the at least one distal electrode of the vascular lead, wherein the plurality of distal electrodes of the non-vascular lead and the at least one distal electrode of the vascular lead are combined to form a sensing array, the method further comprising separating the plurality of sources contributing to the sensed physiological signal by analyzing the contribution of the sensing array.

[0057] 8. The method according to paragraph 1, wherein the plurality of sources of the physiological signal are present within the brain, wherein the intravascular lead includes a plurality of distal electrodes at the second location, and wherein when sensing the physiological signal using the at least one distal electrode of the non-intravascular lead and the plurality of distal electrodes of the intravascular lead, wherein the at least one distal electrode of the non-intravascular lead and the plurality of distal electrodes of the intravascular lead are combined to form a sensing array, the method further comprising separating the plurality of sources contributing to the sensed physiological signal by analyzing the contribution of the sensing array.

[0058] 9. A method of providing neurostimulation therapy, the method comprising: Physiological signals are sensed using a first lead, which has multiple distal electrodes at a first location within the patient's brain. A second lead is used to sense physiological signals, the second lead having multiple distal electrodes at a second location within the patient's brain; and When using the first lead and the second lead to sense the physiological signal, combinations of at least one distal electrode of the first lead and at least one distal electrode of the second lead are explored to find a combination that provides optimal biomarker resolution.

[0059] 10. The method according to paragraph 9, wherein the plurality of distal electrodes of the first lead are located at a subcortical location within the patient's brain, wherein the plurality of distal electrodes of the second lead are located at a cortical periphery location within the patient's brain, and wherein the method further comprises indirectly monitoring areas of the brain separated from the subcortical location and the cortical periphery location by sensing physiological signals from the first lead and the second lead.

[0060] 11. The method according to any one of paragraphs 9 and 10, wherein the first lead is a non-intravascular lead and the first location is outside the blood vessel in the brain, and the second lead is an intravascular lead and the second location is inside the blood vessel in the brain.

[0061] 12. The method according to any one of paragraphs 9 to 11, wherein the method further comprises traversing the distal electrodes to provide a stimulation signal, in conjunction with traversing the distal electrodes of the first lead and the second lead to find the combination of the distal electrodes for stimulation and the distal electrodes for sensing that provide the optimal resolution of the biomarker.

[0062] 13. The method according to any one of paragraphs 9 to 12, wherein traversing the combination comprises: attempting to sense the physiological signal using an electrode with only the first lead and / or only the second lead.

[0063] 14. The method according to any one of paragraphs 9 to 13, wherein traversing the combination comprises: attempting to sense the physiological signal using the electrode of the first lead or the second lead as a single or common reference.

[0064] 15. The method according to paragraph 9, wherein the plurality of sources of the physiological signal are present in the brain, wherein when sensing the physiological signal using the plurality of distal electrodes of the first lead and the plurality of distal electrodes of the second lead, wherein the plurality of distal electrodes of the first lead and the plurality of distal electrodes of the second lead are combined to form a sensing array, the method further comprising separating the plurality of sources contributing to the sensed physiological signal by analyzing the contribution of the sensing array.

[0065] 16. A method of providing neurostimulation therapy, the method comprising: Physiological signals are sensed using a first lead, the first lead having a distal electrode at a first location within the patient's brain; Detect whether the sensed physiological signal has signal characteristics that meet the threshold; If the signal characteristics do indeed meet the threshold, the sensed physiological signal from the first location is used to provide the neurostimulation therapy. If the signal characteristics do not meet the threshold, a second lead with a distal electrode at a second location within the patient's brain is used to sense a physiological signal, and the sensed physiological signal from the second location is used to provide the neurostimulation therapy.

[0066] 17. The method according to paragraph 16, wherein the first lead is a non-intravascular lead and the first location is outside the blood vessel in the brain, and the second lead is an intravascular lead and the second location is inside the blood vessel in the brain.

[0067] 18. A system for delivering neurostimulation therapy, the system comprising: A non-intravascular lead having at least one distal electrode at a first location inside the patient's brain but outside a blood vessel within the patient's brain; An intravascular lead having at least one distal electrode at a second location within the blood vessel in the patient's brain; and An implantable medical device coupled to the non-endovascular lead and the endovascular lead, the implantable medical device having a sensing circuit for: Using the aforementioned non-vascular leads to sense physiological signals; and Using intravascular leads to sense physiological signals.

[0068] 19. The system according to paragraph 18, wherein the non-endovascular lead includes a plurality of distal electrodes at the first location, and wherein, when the implantable medical device uses the non-endovascular lead and the endovascular lead to sense the physiological signal, the implantable medical device traverses combinations of the plurality of distal electrodes of the non-endovascular lead with the at least one distal electrode of the endovascular lead to find a combination that provides optimal biomarker resolution.

[0069] 20. The system according to paragraph 18, wherein the intravascular lead includes a plurality of distal electrodes at the second location, and wherein, when the implantable medical device uses the non-intravascular lead and the intravascular lead to sense the physiological signal, the implantable medical device traverses combinations of the at least one distal electrode of the non-intravascular lead with the plurality of distal electrodes of the intravascular lead to find a combination that provides optimal biomarker resolution.

[0070] 21. The system according to any one of paragraphs 19 and 20, wherein the implantable medical device traverses distal electrodes to provide stimulation signals, in conjunction with traversing distal electrodes of the non-endovascular lead and the endovascular lead to find the combination of distal electrodes for stimulation and distal electrodes for sensing that provide the optimal resolution of the biomarker.

[0071] 22. The system according to any one of paragraphs 19 to 21, wherein the implantable medical device traverses the combination by attempting to sense the physiological signals using electrodes that are only the non-intravascular leads and / or only the intravascular leads.

[0072] 23. The system according to any one of paragraphs 19 to 22, wherein the implantable medical device traverses the combination by attempting to sense the physiological signals using the electrodes of the non-endovascular lead or the endovascular lead as a single or common reference.

[0073] 24. The system according to paragraph 18, wherein the plurality of sources of the physiological signal are present within the brain, wherein the non-vascular lead includes a plurality of distal electrodes at the first location, and wherein when the implantable medical device senses the physiological signal using the plurality of distal electrodes of the non-vascular lead and the at least one distal electrode of the vascular lead, wherein the plurality of distal electrodes of the non-vascular lead and the at least one distal electrode of the vascular lead are combined to form a sensing array, and the implantable medical device separates the plurality of sources contributing to the sensed physiological signal by analyzing the contribution of the sensing array.

[0074] 25. The system according to paragraph 18, wherein the plurality of sources of the physiological signal are present within the brain, wherein the intravascular lead includes a plurality of distal electrodes at the second location, and wherein when the implantable medical device senses the physiological signal using the at least one distal electrode of the non-intravascular lead and the plurality of distal electrodes of the intravascular lead, wherein the at least one distal electrode of the non-intravascular lead and the plurality of distal electrodes of the intravascular lead are combined to form a sensing array, and the implantable medical device separates the plurality of sources contributing to the sensed physiological signal by analyzing the contribution of the sensing array.

[0075] 26. A system for delivering neurostimulation therapy, the system comprising: A first lead, the first lead having at least one distal electrode at a first location within the patient's brain; A second lead, the second lead having at least one distal electrode at a second location within the patient's brain; and An implantable medical device coupled to a first lead and a second lead, the implantable medical device having a sensing circuit for: Physiological signals are sensed using the first lead; Using the second lead to sense physiological signals; and When using the first lead and the second lead to sense the physiological signal, combinations of at least one distal electrode of the first lead and at least one distal electrode of the second lead are explored to find a combination that provides optimal biomarker resolution.

[0076] 27. The system according to paragraph 26, wherein the plurality of distal electrodes of the first lead are located at a subcortical location within the patient's brain, wherein the plurality of distal electrodes of the second lead are located at a cortical periphery location within the patient's brain, and wherein the implantable medical device indirectly monitors areas of the brain separated from the subcortical location and the cortical periphery location by sensing physiological signals from the first lead and the second lead.

[0077] 28. The system according to any one of paragraphs 26 and 27, wherein the first lead is a non-intravascular lead and the first location is outside the blood vessel in the brain, and the second lead is an intravascular lead and the second location is inside the blood vessel in the brain.

[0078] 29. The system according to any one of paragraphs 26 to 28, wherein the implantable medical device traverses distal electrodes to provide a stimulation signal, and the implantable medical device senses by traversing distal electrodes of the first lead and the second lead to find the combination of distal electrodes for stimulation and distal electrodes for sensing that provide the optimal resolution of the biomarker.

[0079] 30. The system according to any one of paragraphs 26 to 29, wherein the implantable medical device traverses the combination by attempting to sense the physiological signal using electrodes of only the first lead and / or only the second lead.

[0080] 31. The system according to any one of paragraphs 26 to 30, wherein the implantable medical device traverses the combination by attempting to sense the physiological signals using the electrodes of the first lead or the second lead as a single or common reference.

[0081] 32. The system according to paragraph 26, wherein the plurality of sources of the physiological signal are present in the brain, wherein when the implantable medical device senses the physiological signal using the plurality of distal electrodes of the first lead and the plurality of distal electrodes of the second lead, wherein the plurality of distal electrodes of the first lead and the plurality of distal electrodes of the second lead are combined to form a sensing array, and the implantable medical device separates the plurality of sources that contribute to the sensed physiological signal by analyzing the contribution of the sensing array.

[0082] 33. A system for delivering neurostimulation therapy, the system comprising: A first lead, the first lead having at least one distal electrode at a first location within the patient's brain; A second lead, the second lead having at least one distal electrode at a second location within the patient's brain; and An implantable medical device coupled to a first lead and a second lead, the implantable medical device having a sensing circuit for: Physiological signals are sensed using the first lead; Detect whether the sensed physiological signal has signal characteristics that meet the threshold; If the signal characteristics do indeed meet the threshold, then the sensed physiological signal from the first location is used to provide the neurostimulation therapy; and If the signal characteristics do not meet the threshold, a physiological signal is sensed using the second lead, which has a distal electrode at a second location within the patient's brain, and the sensed physiological signal from the second location is used to provide the neurostimulation therapy.

[0083] 34. The system according to paragraph 33, wherein the first lead is a non-intravascular lead and the first location is outside the blood vessel in the brain, and the second lead is an intravascular lead and the second location is inside the blood vessel in the brain.

[0084] Although embodiments have been specifically shown and described, those skilled in the art will understand that various other changes in form and detail may be made without departing from the spirit and scope of the invention.

Claims

1. A system (100) for providing neurostimulation therapy, the system comprising: A non-vascular lead (105) having at least one distal electrode (206) at a first location inside the patient’s brain but outside a blood vessel (202) inside the patient’s brain. An intravascular lead (104) having at least one distal electrode (204) at a second location within the blood vessel (202) in the patient's brain; and An implantable medical device (102) coupled to the non-intravascular lead and the intravascular lead, the implantable medical device having a sensing circuit (412) for: Using the aforementioned non-vascular leads to sense physiological signals; and Using intravascular leads to sense physiological signals.

2. The system of claim 1, wherein the non-vascular lead (105) includes a plurality of distal electrodes (206) at the first location, and wherein, when the implantable medical device (102) senses the physiological signal using the non-vascular lead and the vascular lead (104), the implantable medical device traverses combinations of the plurality of distal electrodes of the non-vascular lead and the at least one distal electrode (204) of the vascular lead to find a combination that provides optimal biomarker resolution.

3. The system of claim 1, wherein the intravascular lead (104) includes a plurality of distal electrodes (204) at the second location, and wherein, when the implantable medical device (102) senses the physiological signal using the non-intravascular lead (105) and the intravascular lead, the implantable medical device traverses combinations of the at least one distal electrode (105) of the non-intravascular lead with the plurality of distal electrodes of the intravascular lead to find a combination that provides optimal biomarker resolution.

4. The system according to any one of claims 2 and 3, wherein the implantable medical device (102) traverses the distal electrodes to provide stimulation signals, in conjunction with traversing the distal electrodes of the non-vascular lead (105) and the vascular lead (104) to find the combination of the distal electrodes for stimulation and the distal electrodes for sensing that provide the optimal resolution of the biomarker.

5. The system according to any one of claims 2 to 4, wherein the implantable medical device (102) traverses the combination by attempting to sense the physiological signals using only the electrodes of the non-intravascular lead (105) and / or only the intravascular lead (104).

6. The system according to any one of claims 2 to 5, wherein the implantable medical device (102) traverses the combination by attempting to sense the physiological signal using the electrodes of the non-endovascular lead (105) or the endovascular lead (104) as a single or common reference.

7. The system of claim 1, wherein the plurality of sources of the physiological signal are present within the brain, wherein the non-vascular lead (105) includes a plurality of distal electrodes (206) at the first location, and wherein when the implantable medical device senses the physiological signal using the plurality of distal electrodes of the non-vascular lead and the at least one distal electrode (204) of the vascular lead (104), wherein the plurality of distal electrodes of the non-vascular lead and the at least one distal electrode of the vascular lead are combined to form a sensing array, and the implantable medical device separates the plurality of sources contributing to the sensed physiological signal by analyzing the contribution of the sensing array.

8. The system of claim 1, wherein the plurality of sources of the physiological signal are present within the brain, wherein the intravascular lead (104) includes a plurality of distal electrodes (204) at the second location, and wherein when the implantable medical device senses the physiological signal using the at least one distal electrode (206) of the non-intravascular lead (105) and the plurality of distal electrodes of the intravascular lead, wherein the at least one distal electrode of the non-intravascular lead and the plurality of distal electrodes of the intravascular lead are combined to form a sensing array, and the implantable medical device separates the plurality of sources contributing to the sensed physiological signal by analyzing the contribution of the sensing array.

9. A system (100) for providing neurostimulation therapy, said system comprising: A first lead (105) has at least one distal electrode (206) at a first location within the patient’s brain. A second lead (104) having at least one distal electrode (204) at a second location within the patient's brain; and An implantable medical device (102) coupled to a first lead (105) and a second lead (104), the implantable medical device having a sensing circuit (412) for: Physiological signals are sensed using the first lead; Using the second lead to sense physiological signals; and When using the first lead and the second lead to sense the physiological signal, combinations of at least one distal electrode of the first lead and at least one distal electrode of the second lead are explored to find a combination that provides optimal biomarker resolution.

10. The system of claim 9, wherein a plurality of distal electrodes (206) of the first lead (105) are located at a subcortical location within the patient's brain, wherein a plurality of distal electrodes (204) of the second lead (104) are located at a cortical periphery location within the patient's brain, and wherein the implantable medical device (102) indirectly monitors areas of the brain separated from the subcortical location and the cortical periphery location by sensing physiological signals from the first lead and the second lead.

11. The system according to any one of claims 9 and 10, wherein the first lead (105) is a non-intravascular lead and the first location is outside the blood vessel (202) in the brain, and the second lead (104) is an intravascular lead and the second location is inside the blood vessel (202) in the brain.

12. The system according to any one of claims 9 to 11, wherein the implantable medical device (102) traverses the distal electrodes to provide a stimulation signal, and the implantable medical device senses by traversing the distal electrodes of the first lead (105) and the second lead (104) to find the combination of the distal electrodes for stimulation and the distal electrodes for sensing that provide the optimal resolution of the biomarker.

13. The system according to any one of claims 9 to 12, wherein the implantable medical device (102) traverses the combination by attempting to sense the physiological signal using electrodes of only the first lead (105) and / or only the second lead (104).

14. A system (100) for providing neurostimulation therapy, the system comprising: A first lead (105) has at least one distal electrode (206) at a first location within the patient’s brain. A second lead (104) having at least one distal electrode (204) at a second location within the patient's brain; and An implantable medical device (102) coupled to the first lead and the second lead, the implantable medical device having a sensing circuit (412) for: Physiological signals are sensed using the first lead; Detect whether the sensed physiological signal has signal characteristics that meet the threshold; If the signal characteristics do indeed meet the threshold, the sensed physiological signal from the first location is used to provide the neurostimulation therapy. as well as If the signal characteristics do not meet the threshold, a physiological signal is sensed using the second lead, which has a distal electrode at a second location within the patient's brain, and the sensed physiological signal from the second location is used to provide the neurostimulation therapy.

15. The system of claim 14, wherein the first lead (105) is a non-intravascular lead and the first location is outside the blood vessel (202) in the brain, and the second lead (104) is an intravascular lead and the second location is inside the blood vessel (202) in the brain.

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