Neurostimulation systems and methods

Abstract

Systems and methods are described that provide electrical stimulation to a human while also facilitating EEG recording. The EEG recording can be analyzed to identify intracerebral hemorrhage. In some examples, the EEG analysis can identify increased slow wave activity in a delta frequency range of approximately 1-4 Hz and / or decreased alpha activity in an alpha frequency range of approximately 8-13 Hz. The systems and methods can include delivering electrical stimulation in response to the EEG analysis and / or notifying the human or a healthcare provider of the intracerebral hemorrhage.

Description

[Background technology]

[0001] (Priority Claim) This patent application claims priority to U.S. Provisional Patent Application No. 63 / 371,496, filed August 15, 2022, and entitled "NEUROSTIMULATION SYSTEMS AND METHODS," which is incorporated herein by reference in its entirety.

[0002] (Incorporated by reference) All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[0003] (background) Electrical brain stimulation has been shown to be a potentially effective treatment for several brain disorders, including epilepsy, migraine, fibromyalgia, major depression, stroke rehabilitation, and Parkinson's disease. External stimulation tends to be non-focused, and direct cortical stimulation is often highly invasive, requiring craniotomy, i.e., drilling holes in the skull, to target specific cortical locations. It would be beneficial to find a brain stimulation solution that would provide targeted cortical stimulation without requiring a skull-penetrating surgical procedure.

[0004] Electrical brain stimulation can be accomplished by several means. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that uses a coil to deliver a series of high-energy magnetic pulses to the brain, thereby inducing electrical currents to flow into the cortex directly beneath the coil. rTMS has been shown to be effective in treating major depression and other psychiatric disorders. However, it involves large, expensive devices that are not easily directed to a specific location and generate high-current pulses to the coil. rTMS is not portable and requires a therapy administrator to deliver the therapy to the patient.

[0005] Transcranial direct current stimulation (tDCS) uses electrodes on the outside of the head to deliver small amounts of electrical current to the brain. Originally used for stroke recovery, tDCS has shown promise for the treatment of several psychiatric disorders and cognitive improvement. Electrodes are placed on the skin surface of the subject's head near the area of ​​interest for stimulation. Most of the current is shunted between the electrodes because the skull is a very effective electrical insulator. However, some of the current does not result in intracerebral current flow, which can increase or decrease neuronal excitability and alter brain function. The exact method of action is unclear. tDCS current strength is limited due to the excitability of nerves within the scalp, which can cause discomfort to the patient if the current is set too high.

[0006] Vagus nerve stimulation involves electrically stimulating the vagus nerve in a patient's neck. This can be done either using electrodes on the skin (which may be associated with a painful sensation in the patient) or by surgically implanting electrodes near the vagus nerve, generally with a power source implanted elsewhere in the body. This involves a significant surgical procedure and has shown effectiveness in treating epilepsy and depression.

[0007] Deep brain stimulation (DBS) uses electrodes implanted and placed bilaterally in the basal ganglia, cerebellum, anterior principal nucleus, centromedian nucleus, caudate nucleus, thalamic region, or subthalamic region. Stimulation may also be delivered subcortically. Stimulation trains are delivered for the treatment of several disorders, including epilepsy, Parkinson's disease, and major depression. DBS is a highly invasive procedure that generally requires long leads that penetrate the skull with multiple electrodes near the tip. The procedure is considered major surgery and is generally not used unless other methods have been exhausted.

[0008] Direct cortical stimulation (DCS) is similar to DBS, except that leads reside on the surface of the cortex, either subdurally or epidurally. The electrodes are secured in place using sutures. This technique often involves removing part of the skull to gain access to the cortical surface and potentially to make room for a power source. DCS has been shown to be effective in treating epilepsy and neuropathic pain. Shanechi et al. (2013) introduced a brain-machine interface that uses EEG to automatically titrate medication during a medically induced coma. Liu et al. (2006) automatically adjusted anesthesia during surgical procedures using the bispectral index (BIS) calculated from EEG. A company, Aspect Medical, Inc., was formed to develop devices for this purpose. Drager Medical, Inc. also developed Zeus for closed-circuit anesthesia ventilation. (Doufas et al. (2003)) used automated response testing to optimize propofol administration during conscious sedation. Phillips (US 9,872,996, US 10,780,286) uses a subcutaneous pulse generator and conductive pathways through the skull at multiple locations to generate current loops. The Phillips method and device still involves at least two perforations in the skull.

[0009] Nearly 40% of untreated aneurysms will eventually rupture. Rupture can be prevented using a technique called coiling, which blocks blood flow into the aneurysm. However, up to 5% of coiled aneurysms may still rupture. Aneurysmal subarachnoid hemorrhage (aSAH) has a 40-50% mortality rate, and most survivors are dependent on others for daily living. Delayed cerebral ischemia (DCI), the initial hemorrhagic event following a ruptured cerebral aneurysm, is one of the most important causes of mortality and poor neurological outcomes. Neurological monitoring is essential for early DCI detection and intervention. By catching DCI early, pharmacologically induced hypertension reverses the presenting deficits in 70% of patients. Clinical examination and intermittent transcranial Doppler ultrasound and CT are most commonly used to detect DCI, but they rely on patient visits and scheduling valuable resources, significantly delaying response. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] U.S. Patent No. 9,872,996 [Patent Document 2] U.S. Patent No. 10,780,286 Summary of the Invention [Means for solving the problem]

[0011] (summary) A device for electrical stimulation of a subject's brain is provided, the device comprising: a case adapted to be implanted relative to the subject's skull; a first electrode disposed on or within the case; a probe coupled to the case and configured to extend into the subject's brain through a burr hole in the skull; a second electrode disposed on the probe and configured to deliver electrical stimuli to a target region of the brain and sense electrical signals of the brain; and electronics disposed within the case and configured to generate electrical pulses, initiate EEG recording of the subject's brain, and communicate with an external device, wherein the device is configured to record EEG signals of the brain in response to an EEG recording request from the external device.

[0012] In one aspect, the probe is flexible.

[0013] In some aspects, the device includes an insulating seal configured to fill the space between the burr hole and the probe, hi one aspect, the insulating seal prevents fluid and current flow around the subcranial electrode.

[0014] In some aspects, the first electrode includes a ring electrode. In some aspects, the ring electrode is integrated into the case.

[0015] In one aspect, the electronics are configured to generate a current pulse between the first electrode and the second electrode.

[0016] In one aspect, the current pulse is configured to follow a path from the second electrode through the target region, from the burr hole through a conductive pathway at a separate location within the skull, and underneath the scalp to the first electrode.

[0017] In some aspects, the electronics are further configured to analyze the EEG signals and identify intracerebral hemorrhage within the target region.

[0018] In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

[0019] In other aspects, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

[0020] In one aspect, the device is configured to wirelessly transmit EEG signals to an external device.

[0021] In some aspects, the external device is further configured to analyze the EEG signal and identify intracerebral hemorrhage within the target region.

[0022] In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

[0023] In another aspect, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

[0024] In some aspects, the device is configured to wirelessly transmit the EEG signals to a cloud computing device.

[0025] In one aspect, the cloud computing device is further configured to analyze the EEG signal and identify intracerebral hemorrhage in the target region.

[0026] In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

[0027] In other aspects, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

[0028] A system comprising two or more of the devices of claim 1 is also provided.

[0029] In some aspects, the two or more devices are collectively configured to record EEG signals of the subject's brain in response to an EEG recording request from an external device.

[0030] A system for electrical stimulation of a subject's brain is provided, the system comprising a plurality of implantable neurostimulators configured to be implanted within the subject, each of the implantable neurostimulators including: a case adapted to be implanted relative to the subject's skull; a first electrode disposed on or within the case; a probe coupled to the case and configured to extend into the subject's brain through a burr hole in the skull; a second electrode disposed on the probe and configured to deliver electrical stimulation to a target region of the brain and sense electrical signals of the brain; and electronics disposed within the case and configured to generate electrical pulses, initiate EEG recording of the subject's brain, and communicate with an external device, the system being configured to record EEG signals of the brain using the plurality of implantable neurostimulators in response to an EEG recording request from the external device.

[0031] In one aspect, the probe is flexible.

[0032] In some aspects, each stimulator of the system includes an insulating seal configured to fill the space between the burr hole and the probe. In one aspect, the insulating seal prevents fluid and current flow around the subcranial electrodes.

[0033] In some aspects, the first electrode includes a ring electrode. In some aspects, the ring electrode is integrated into the case.

[0034] In one aspect, the electronics are configured to generate a current pulse between the first electrode and the second electrode.

[0035] In one aspect, the current pulse is configured to follow a path from the second electrode through the target region, from the burr hole through a conductive pathway at a separate location within the skull, and underneath the scalp to the first electrode.

[0036] In some aspects, the electronics are further configured to analyze the EEG signals and identify intracerebral hemorrhage within the target region.

[0037] In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

[0038] In other aspects, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

[0039] In one aspect, the system is configured to wirelessly transmit the EEG signals to an external device.

[0040] In some aspects, the external device is further configured to analyze the EEG signal and identify intracerebral hemorrhage within the target region.

[0041] In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

[0042] In another aspect, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

[0043] In some aspects, the system is configured to wirelessly transmit the EEG signals to a cloud computing device.

[0044] In one aspect, the cloud computing device is further configured to analyze the EEG signal and identify intracerebral hemorrhage in the target region.

[0045] In some aspects, analyzing the EEG signal further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

[0046] In other aspects, analyzing the EEG signal further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

[0047] A method for monitoring aneurysms in a subject's brain is provided, the method including initiating EEG recording in one or more implanted neurostimulator devices using an external device, analyzing the EEG recording to identify an intracerebral hemorrhage in the brain, and indicating to the subject or a healthcare provider that an intracerebral hemorrhage has been identified.

[0048] In some aspects, one or more neurostimulator devices are implanted in the subject's brain prior to the activating step.

[0049] In some aspects, the method includes transmitting EEG recordings from one or more implanted neurostimulator devices to a remote server.

[0050] In one aspect, the analyzing step is performed in a remote server.

[0051] In another aspect, the method includes generating a report regarding the analyzed EEG and transmitting the report to the subject's healthcare provider.

[0052] In one aspect, EEG recording is initiated using a smartphone, tablet, or PC.

[0053] In some embodiments, the analyzing step is performed locally on one or more implanted neurostimulator devices.

[0054] In one embodiment, analyzing the EEG recording further includes identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

[0055] In another embodiment, analyzing the EEG recording further includes identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

[0056] In another embodiment, the method includes providing electrical stimulation to the brain using one or more implanted neurostimulator devices. [Brief explanation of the drawings]

[0057] [Figure 1] FIG. 1 shows a neurostimulator device.

[0058] [Figure 2A] 2A-2B illustrate EEG recordings of a subject suffering from an aneurysm. [Figure 2B] 2A-2B illustrate EEG recordings of a subject suffering from an aneurysm.

[0059] [Figure 3] FIG. 3 is a schematic diagram showing one or more neurostimulation devices implanted near an aneurysm.

[0060] [Figure 4] 4A-4E illustrate a method of monitoring an aneurysm using one or more implanted neurostimulation devices.

[0061] [Figure 5A] 5A-5B illustrate a series of EEG recordings of a subject suffering from an aneurysm. [Figure 5B] 5A-5B illustrate a series of EEG recordings of a subject suffering from an aneurysm. DETAILED DESCRIPTION OF THE INVENTION

[0062] (Detailed explanation) While certain embodiments have been provided and described herein, it will be readily apparent to those skilled in the art that such embodiments are provided by way of example only. It will be understood that various alternatives to the embodiments described herein may be employed and are part of the invention described herein.

[0063] The present disclosure provides a minimally invasive solution for on-demand cortical EEG recording. Quantitative EEG (qEEG) analysis provides evidence of ischemic events, which can be detected using automated machine learning algorithms. Ischemia can cause increased slow-wave activity and decreased alpha power within the area of ​​infarction.

[0064] FIG. 1 illustrates one embodiment in which a neurostimulator device 104 is implanted beneath a subject's scalp 101 and comprises a case 110, a probe-shaped subcranial electrode 106 inserted into a burr hole in the skull 102, and a subcutaneous ring electrode 105 disposed around or integrated with the case 110. In one embodiment, the subcranial electrode 106 can comprise a screw adapted to be threaded into the subject's skull. The system can further comprise an electrically insulating seal 111 configured to fill a space between the device and the inner wall of the burr hole, preventing fluid and current flow around the subcranial electrode. The case 110 can be configured to rest on the surface of the skull and can comprise a current or voltage pulse generator to generate current pulses between the subcranial electrode and the subcutaneous electrode. Due to the high impedance of the skull 102, the majority of the current is forced to follow path 107 from the subcranial electrode through the target region 112 of the brain 103, through the burr hole through conductive pathway 108 at a separate location within the skull, back along path 109, and proceeding just below the scalp to the subcutaneous ring electrode 105.

[0065] In one embodiment, the device 104 can include electronics, such as a voltage or current pulse generator, configured to generate a current waveform between the subcranial electrode 106 and the subcutaneous ring electrode 105. The device can further include a power source, such as a battery or capacitor, or alternatively, can be externally powered using wireless power transfer (e.g., inductive coupling). The electronics can further include one or more processors, microcontrollers, or CPUs configured to control the operation of the device and process and / or evaluate data sensed by the electrodes. In some embodiments, the electronics can further include memory configured to store recorded data and / or instructions related to the operation of the device and / or sensed (e.g., EEG) parameters of the patient. The electronics can be disposed or located, for example, within the case 110. In some embodiments, the electronics are positioned external to the device and the subject. In these embodiments, current pulses can be generated external to the body, with percutaneous leads transmitting the current pulses to the subcutaneous / subcranial electrodes. The electronics can further include wireless communication electronics to facilitate communication between the neurostimulator device and external devices. In some embodiments, the external device can include a smartphone, computer, tablet, or the like. In some embodiments, the external device can be configured to control the operation of the neurostimulator device. For example, in one embodiment, a smartphone, tablet, or PC can be configured to turn features of the neurostimulator device on or off, such as initiating EEG recording or stimulation therapy.

[0066] The device can be configured to record EEG, automatically determine the natural frequency from the EEG recording, and define the pulse frequency, pulse amplitude, pulse shape, pulse width, or pulse duty cycle, and other parameters. The recorded EEG can also be wirelessly transmitted to an external module, such as a mobile device running a software application, which determines the natural frequency, defines the pulse frequency, pulse amplitude, pulse shape, pulse width, or pulse duty cycle, and other parameters, and transmits the parameters to the device.

[0067] FIG. 2A shows EEG power distribution for a patient suffering from intracerebral hemorrhage located in the left posterior region in multiple frequency ranges, as shown. The frequency ranges may include the delta frequency range (1-4 Hz), theta frequency range (4-8 Hz), alpha frequency range (8-13 Hz), and beta frequency range (13-25 Hz). As shown, the brain's EEG shows increased slow-wave activity at the intracerebral hemorrhage location in the delta frequency range (1-4 Hz) and decreased alpha activity in the alpha frequency range (8-13 Hz), as indicated by reference numerals 214 and 216, respectively. Devices of the present disclosure can be configured to identify regions in the brain suffering from increased slow-wave activity in the delta frequency range and / or decreased alpha activity in the alpha frequency range to identify intracerebral hemorrhage and / or other traumatic brain events.

[0068] Figure 2B shows location F P1 And, F P2 and F3 and F4 and F7 and F8 and F Z And C Z and C3, C4, T3, T4, T5, T6, and P Z Figure 1 shows EEG recordings for the same patient taken at multiple locations within the brain, including P1, P2, P3, P4, O1, and O2. Again, this detailed EEG plot shows a drop in alpha power and an increase in delta / theta power within the area of ​​intracerebral hemorrhage lesions (e.g., within the left posterior region of the brain).

[0069] Referring to FIG. 3 , one or more neurostimulator devices 104 (such as the neurostimulator device 104 of FIG. 1 ) can be positioned above or adjacent to an aneurysm 112 in a patient's brain. By precisely positioning the neurostimulator devices near the aneurysm, the devices can record the highest quality EEG possible directly above the brain's cortex. In some implementations, only a single neurostimulator device 104 is placed near the aneurysm. In other embodiments, multiple neurostimulator devices are placed near the aneurysm. The devices can each be individually configured to record EEG signals from the brain. In some embodiments, the devices can collectively or cooperatively collect and record EEG signals from the brain.

[0070] 4A-4E illustrate a general sequence of events involving the implantation and use of one or more neurostimulator devices for aneurysm monitoring. This procedure can be used for patients with a history of or risk of aneurysm or other brain events. With reference to FIG. 4A, a surgeon or other healthcare provider can implant a neurostimulator device in the patient's brain at a location appropriate for the aneurysm. The procedure can be, for example, a simple 20-minute or less surgical procedure. In some embodiments, implantation can be performed on an outpatient basis. In some embodiments, the neurostimulator can be implanted such that the probe-shaped subcranial electrode (from FIG. 1) is inserted into a borehole in the skull and the subcutaneous ring electrode and / or case are positioned relative to the skull and under the scalp.

[0071] 4B, at some point after implantation, the patient may begin to experience symptoms of aneurysm leakage or rupture. For example, the patient may begin to experience symptoms associated with a ruptured aneurysm, including neck stiffness, drowsiness, confusion, dizziness, balance problems, difficulty speaking, weakness or numbness in the arms or legs, etc.

[0072] Referring to FIG. 4C , a patient can initiate EEG recording in one or more implanted neurostimulator devices 104. In one example, EEG recording can be initiated wirelessly via an external electronic device 118, such as a smartphone, tablet, or PC. In other embodiments, the patient may initiate EEG recording by directly interacting with the neurostimulator device, such as by pushing a button on the device or hardware, or with leads extending from the device to another location on the patient's body. Once initiated, the one or more implanted neurostimulators can be configured to record the EEG of the patient's brain. The EEG can be recorded for a predetermined period of time. In some examples, the duration of the recording can be customized by a healthcare provider or by the user, such as with an external electronic device.

[0073] In FIG. 4D , the recorded EEG can be wirelessly transmitted to a remote or cloud-based server 120 or another computing system 122, either from the implanted device itself or from an external device (e.g., a smartphone, tablet, or PC). This remote server can include one or more processors configured to automatically analyze the recorded EEG using one or more algorithms (including machine learning algorithms) to detect slow waves within the affected area and generate a report. The report can be, for example, an electronic report containing the EEG recording and / or instructions or next steps for the patient or healthcare provider to implement. In some embodiments, the recorded EEG can be analyzed directly on the implanted stimulator or, alternatively, in the patient's external device.

[0074] 4E, the report can be transmitted to a medical clinic 124 or a physician associated with the patient. For example, transmission to the medical clinic 124 can include one or more computers, smartphones, or tablets at the medical clinic.

[0075] If analysis of the recorded EEG indicates that a rupture or leak is occurring, the clinic, healthcare provider, and / or patient can be alerted. The clinic and / or healthcare provider can be instructed to contact the patient for immediate evaluation and attention for a ruptured or leaking aneurysm.

[0076] In some embodiments, the implanted neurostimulator device can be adapted and configured to immediately deliver stimulation therapy to the region of a ruptured or leaking aneurysm in response to EEG analysis or electronic reporting. The implanted device is ideally positioned within the brain not only to record EEG in relation to the aneurysm, but also to potentially treat the aneurysm with stimulation therapy. Thus, in some embodiments, stimulation can be initiated manually or automatically in response to EEG recording and analysis that identifies a ruptured or leaking aneurysm. In some embodiments, the patient can initiate therapy through an external device (e.g., a smartphone, tablet, PC), etc. In other embodiments, a healthcare provider can initiate therapy remotely after reviewing the EEG report. Alternatively, the system can be configured to automatically initiate therapy in response to identifying a ruptured or leaking aneurysm.

[0077] Figure 5A shows a series of EEGs recorded over a period of time using an implanted neurostimulator in a patient suffering from an intracerebral hemorrhage located in the left posterior region (as in Figure 2A). In this example, three EEG recordings occur over the course of approximately six weeks. Stimulation therapy was provided to the patient over this period using an implanted neurostimulator described herein, and follow-up and EEG recordings revealed improved speech, motivation, sleep, and sensory improvement. Figure 5B is a detailed EEG plot showing improved alpha activity across the entire region. Slow-wave activity is significantly reduced compared to normal rhythmic alpha waves.

[0078] When a feature or element is referred to herein as being "on" another feature or element, it may be directly on the other feature or element, or intervening features and / or elements may also be present. In contrast, when a feature or element is referred to as being "directly on" another feature or element, no intervening features or elements are present. Also, when a feature or element is referred to as being "connected," "attached," or "coupled" to another feature or element, it should be understood that it may be directly connected, attached, or coupled to the other feature or element, or intervening features or elements may be present. In contrast, when a feature or element is referred to as being "directly connected," "directly attached," or "directly coupled" to another feature or element, no intervening features or elements are present. Although described or illustrated with respect to one embodiment, features and elements so described or illustrated may be applied to other embodiments. It will also be understood by those skilled in the art that a reference to a structure or feature being located "adjacent" to another feature may have portions that overlap or underlie the adjacent feature.

[0079] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. It should be further understood that the terms "comprises" and / or "comprising," when used herein, specify the presence of stated features, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ."

[0080] Spatially relative terms such as "under," "below," "lower," "over," "upper," and the like may be used herein for ease of description to describe the relationship of one element or feature to another element or feature as illustrated in the figures. It should be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in a figure were inverted, an element described as being "under" or "beneath" the other element or feature would then be oriented "over" the other element or feature. Thus, the exemplary term "under" can encompass both an orientation of above and below. The device may be oriented differently (rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein may be interpreted accordingly. Similarly, the terms "upwardly," "downwardly," "vertical," "horizontal," and the like are used herein for illustrative purposes only, unless specifically indicated otherwise.

[0081] Although the terms "first" and "second" may be used herein to describe various features / elements (including steps), these features / elements should not be limited by these terms unless the context indicates otherwise. These terms may be used to distinguish one feature / element from another. Thus, a first feature / element discussed below could be referred to as a second feature / element, and similarly, a second feature / element discussed below could be referred to as a first feature / element, without departing from the teachings of the present invention.

[0082] Throughout this specification and the claims that follow, unless the context requires otherwise, the words "comprise" and variations such as "comprises" and "comprising" mean that various components may be employed jointly in methods and articles (e.g., apparatus, including compositions and devices, as well as methods). For example, the term "comprising" should be understood to imply the inclusion of any recited elements or steps, but not the exclusion of any other elements or steps.

[0083] As used herein in the specification and claims, including as used in the examples, unless expressly specified otherwise, all numbers may be read as if preceded by the word "about" or "approximately," even if that term does not explicitly appear. The phrase "about" or "approximately," when describing a size and / or location, may be used to indicate that the described value and / or location is within a reasonably expected range of values ​​and / or locations. For example, a numerical value may have a value that is ±0.1% of the stated value (or range of values), ±1% of the stated value (or range of values), ±2% of the stated value (or range of values), ±5% of the stated value (or range of values), ±10% of the stated value (or range of values), etc. Any numerical value given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value "10" is disclosed, then "about 10" is also disclosed. Any numerical range recited herein is intended to include all subranges subsumed therein. It is also understood that when a value is disclosed, "less than or equal to the value," "greater than or equal to the value," and possible ranges between values ​​are also disclosed, as would be well understood by one of ordinary skill in the art. For example, if a value "X" is disclosed, then "less than or equal to X" and "greater than or equal to X" (e.g., where X is a numeric value) are also disclosed. It is also understood that throughout this application, data is provided in several different formats, and that the data represents endpoints and starting points, and ranges for any combination of the data points.For example, if a particular data point "10" and a particular data point "15" are disclosed, it is understood that "between 10 and 15," as well as "greater than 10 and 15," "greater than or equal to 10 and 15," "less than 10 and 15," "less than or equal to 10 and 15," and "equal to 10 and 15" are considered disclosed. It is also understood that each number between two specific numbers is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0084] While various illustrative embodiments are described above, any of several modifications may be made to the various embodiments without departing from the scope of the invention as described by the claims. For example, the order in which various described method steps are performed may often be changed in alternative embodiments, and in other alternative embodiments, one or more method steps may be omitted entirely. Optional features of various device and system embodiments may be included in some embodiments and not included in other embodiments. Therefore, the foregoing description is provided primarily for illustrative purposes and should not be construed as limiting the scope of the invention, as set forth in the claims.

[0085] The examples and illustrations contained herein show, by way of illustration, not limitation, specific embodiments in which the subject matter may be practiced. As noted, other embodiments may be utilized and derived therefrom, such that structural and logical substitutions and changes may be made without departing from the scope of the present disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term "invention" merely for convenience, and without intending to intentionally limit the scope of this application to any single invention or inventive concept if more than one is actually disclosed. Thus, while specific embodiments are illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. The present disclosure is intended to cover any and all adaptations or variations of the various embodiments. Combinations of the above embodiments, as well as other embodiments not specifically described herein, will be apparent to those skilled in the art upon reviewing the above description.

Claims

1. 1. A device for electrical stimulation of the brain of a subject, said device comprising: a case adapted to be implanted relative to the subject's skull; and a first electrode disposed on or within the case; a probe coupled to the case and configured to extend through a burr hole in the skull and into the brain of the subject; a second electrode disposed on the probe and configured to deliver electrical stimulation to a target region of the brain and to sense electrical signals in the brain; an electronic device disposed within the case and configured to generate electrical pulses, initiate EEG recording of the subject's brain, and communicate with an external device; Equipped with The device is configured to record EEG signals of the brain in response to an EEG recording request from the external device.

2. The device of claim 1 , wherein the probe is flexible.

3. The device of claim 1 , further comprising an insulating seal configured to fill a space between the burr hole and the probe.

4. The device of claim 3 , wherein the insulating seal prevents fluid and current flow around the subcranial electrode.

5. The device of claim 1 , wherein the first electrode comprises a ring electrode.

6. The device of claim 1 , wherein the ring electrode is integrated into the case.

7. The device of claim 1 , wherein the electronics are configured to generate a current pulse between the first electrode and the second electrode.

8. 10. The device of claim 1, wherein the current pulse is configured to follow a path that travels from the second electrode through the target region, from the burr hole through a conductive pathway at a separate location within the skull, and underneath the scalp to the first electrode.

9. The device of claim 1 , wherein the probe comprises a screw.

10. The device of claim 1 , further comprising a power source disposed within the case.

11. 10. The device of claim 1, wherein the electronics are further configured to analyze the EEG signals and identify intracerebral hemorrhage within the target region.

12. 12. The device of claim 11, wherein analyzing the EEG signal further comprises identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

13. 12. The device of claim 11, wherein analyzing the EEG signal further comprises identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

14. The device of claim 1 , wherein the device is configured to wirelessly transmit the EEG signals to the external device.

15. 15. The device of claim 14, wherein the external device is further configured to analyze the EEG signals and identify intracerebral hemorrhage within the target region.

16. 16. The device of claim 15, wherein analyzing the EEG signal further comprises identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

17. 16. The device of claim 15, wherein analyzing the EEG signal further comprises identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

18. The device of claim 1 , wherein the device is configured to wirelessly transmit the EEG signals to a cloud computing device.

19. 20. The device of claim 18, wherein the cloud computing device is further configured to analyze the EEG signals and identify intracerebral hemorrhage in the target region.

20. 20. The device of claim 19, wherein analyzing the EEG signal further comprises identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

21. 20. The device of claim 19, wherein analyzing the EEG signal further comprises identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

22. A system comprising two or more of the devices of claim 1.

23. 23. The system of claim 22, wherein the two or more devices are collectively configured to record EEG signals of a subject's brain in response to an EEG recording request from an external device.

24. 1. A system for electrical stimulation of the brain of a subject, comprising: a plurality of implantable neurostimulators configured to be implanted within a subject; Each of the implantable neurostimulation devices comprises: a case adapted to be implanted relative to the subject's skull; and a first electrode disposed on or within the case; a probe coupled to the case and configured to extend through a burr hole in the skull and into the brain of the subject; a second electrode disposed on the probe and configured to deliver electrical stimulation to a target region of the brain and to sense electrical signals in the brain; an electronic device disposed within the case and configured to generate electrical pulses, initiate EEG recording of the subject's brain, and communicate with an external device; Including, The system is configured to record EEG signals of the brain using the plurality of implanted neurostimulators in response to an EEG recording request from the external device.

25. 25. The system of claim 24, wherein each of the probes is flexible.

26. 25. The system of claim 24, wherein each implantable neurostimulator device further comprises an insulating seal configured to fill a space between the burr hole and the probe.

27. 27. The system of claim 26, wherein the insulating seal prevents fluid and current flow around the subcranial electrodes.

28. 25. The system of claim 24, wherein each first electrode comprises a ring electrode.

29. 25. The system of claim 24, wherein each ring electrode is integrated into the case.

30. 25. The system of claim 24, wherein the electronics are configured to generate a current pulse between the first electrode and the second electrode.

31. 25. The system of claim 24, wherein the current pulse of each implanted neurostimulator is configured to follow a path that travels from the second electrode through the target region, from the burr hole through a conductive pathway at a separate location within the skull, and underneath the scalp to the first electrode.

32. 25. The system of claim 24, wherein the electronics of each implanted neurostimulator device are further configured to analyze the EEG signals and identify intracerebral hemorrhage within the target region.

33. 33. The system of claim 32, wherein analyzing the EEG signal further comprises identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

34. 33. The system of claim 32, wherein analyzing the EEG signal further comprises identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

35. 25. The system of claim 24, wherein the system is configured to transmit the EEG signals to the external device wirelessly.

36. 36. The system of claim 35, wherein the external device is further configured to analyze the EEG signals and identify intracerebral hemorrhage within the target region.

37. 37. The system of claim 36, wherein analyzing the EEG signal further comprises identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

38. 37. The system of claim 36, wherein analyzing the EEG signal further comprises identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

39. 25. The system of claim 24, wherein the system is configured to wirelessly transmit the EEG signals to a cloud computing device.

40. 40. The system of claim 39, wherein the cloud computing device is further configured to analyze the EEG signals and identify intracerebral hemorrhage in the target region.

41. 41. The system of claim 40, wherein analyzing the EEG signal further comprises identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

42. 41. The system of claim 40, wherein analyzing the EEG signal further comprises identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

43. 1. A method for monitoring an aneurysm in the brain of a subject, comprising: initiating EEG recording in one or more implanted neurostimulator devices using an external device; analyzing the EEG recording to identify intracerebral hemorrhage in the brain; indicating to said subject or a health care provider that said intracerebral hemorrhage has been identified; A method comprising:

44. 44. The method of claim 43, wherein one or more neurostimulator devices are implanted in the brain of the subject prior to the initiating step.

45. 44. The method of claim 43, further comprising transmitting the EEG recordings from the one or more implanted neurostimulator devices to a remote server.

46. 46. ​​The method of claim 45, wherein the analyzing step is performed within the remote server.

47. 44. The method of claim 43, further comprising generating a report regarding the analyzed EEG and transmitting the report to the subject's healthcare provider.

48. 44. The method of claim 43, wherein the EEG recording is initiated using a smartphone, tablet, or PC.

49. 44. The method of claim 43, wherein the analyzing step is performed locally on the one or more implanted neurostimulator devices.

50. 44. The method of claim 43, wherein analyzing the EEG recording further comprises identifying increased slow wave activity in a delta frequency range of approximately 1-4 Hz.

51. 44. The method of claim 43, wherein analyzing the EEG recording further comprises identifying reduced alpha activity in an alpha frequency range of approximately 8-13 Hz.

52. 44. The method of claim 43, further comprising providing electrical stimulation to the brain using the one or more implanted neurostimulator devices.

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