CN118055791A - Stimulation pattern for deep brain stimulation - Google Patents

Abstract

The present disclosure relates to devices, systems, and techniques for delivering electrical stimulation. In some examples, a system includes a processing circuit configured to: receive information representing a bioelectrical brain signal recorded from a patient's brain; and determine at least one pathological frequency of the bioelectrical brain signal based on the information. Additionally, the processing circuit is configured to: select a pulse burst sequence at a pulse burst frequency based on the at least one pathological frequency, the pulse burst sequence at least partially defining electrical stimulation that can be delivered to a region of the patient's brain, wherein adjacent pulse bursts within the sequence include different intra-burst pulse frequencies; and control a medical device to deliver the electrical stimulation including the pulse burst sequence to the region of the patient's brain.

Description

Stimulation Modes for Deep Brain Stimulation

Technical Field

The present disclosure relates generally to electrical stimulation therapy, and more particularly to the control of electrical stimulation therapy.

Background technique

The medical device may be external or implanted and may be used to deliver electrical stimulation therapy to a patient via various tissue sites to treat a variety of symptoms or conditions, such as chronic pain, tremor, Parkinson's disease, epilepsy, urinary or fecal incontinence, sexual dysfunction, obesity, or gastroparesis. The medical device may deliver electrical stimulation therapy via one or more leads comprising electrodes located near a target location associated with the patient's brain, spinal cord, pelvic nerves, peripheral nerves, or gastrointestinal tract. Stimulation near the spinal cord, near the sacral nerves, within the brain, and near the peripheral nerves is commonly referred to as spinal cord stimulation (SCS), sacral neuromodulation (SNM), deep brain stimulation (DBS), and peripheral nerve stimulation (PNS), respectively.

Patients with movement disorders or other neurodegenerative diseases, whether due to disease or injury, may experience muscle control and movement problems such as rigidity, bradykinesia (i.e., slow body movements), rhythmic hyperkinesia (e.g., tremors), non-rhythmic hyperkinesia (e.g., tics), or akinesia (i.e., loss of body movement). Movement disorders may be found in patients with diseases such as Parkinson's disease, multiple sclerosis, and cerebral palsy. The delivery of electrical stimulation and/or fluids (e.g., drugs) to one or more areas of a patient, such as the patient's brain, spinal cord, leg muscles, or arm muscles, via a medical device may help alleviate, and in some cases, eliminate, the symptoms associated with movement disorders.

Summary of the invention

In general, the present disclosure relates to devices, systems, and techniques for delivering electrical stimulation to a patient's brain to suppress bioelectrical brain signals in an area of the patient's brain. In some examples, the patient's bioelectrical brain signals may oscillate at a frequency that may be referred to as a pathological frequency of the patient because the frequency is associated with symptoms that do not occur during normal physiological frequencies. For example, when the patient's bio-brain signals oscillate at such a pathological frequency, a medical device may deliver electrical stimulation to an area of the patient's brain to disrupt or desynchronize the pathological frequency. The electrical stimulation may include a predetermined or dynamic sequence of pulse bursts. The medical device may deliver a sequence of pulse bursts to cause synaptic inhibition without entraining a larger network of bioelectrical brain signals. When the medical device causes synaptic inhibition, the medical device may suppress the pathological brain signals such that the pathological brain signals are attenuated or completely eliminated, which results in a reduction or elimination of symptoms associated with the pathological brain signals.

In some examples, a system includes processing circuitry configured to: receive information representing a bioelectrical brain signal recorded from a patient's brain; determine at least one pathological frequency of the bioelectrical brain signal based on the information; select a pulse burst sequence at a pulse burst frequency based on the at least one pathological frequency, the pulse burst sequence at least partially defining electrical stimulation deliverable to a region of the patient's brain, wherein adjacent pulse bursts within the sequence include different intra-burst pulse frequencies; and control a medical device to deliver the electrical stimulation including the pulse burst sequence to the region of the patient's brain.

In some examples, a method includes: receiving, by a processing circuit, information representing a bioelectrical brain signal recorded from a patient's brain; determining, by the processing circuit and based on the information, at least one pathological frequency of the bioelectrical brain signal; selecting, by the processing circuit and based on the at least one pathological frequency, a pulse burst sequence at a pulse burst frequency, the pulse burst sequence at least partially defining electrical stimulation deliverable to a region of the patient's brain, wherein adjacent pulse bursts within the sequence include different intra-burst pulse frequencies; and controlling, by the processing circuit, a medical device to deliver the electrical stimulation including the pulse burst sequence to the region of the patient's brain.

In some examples, a computer-readable medium includes instructions that, when executed by a processor, cause the processor to: receive information representing a bioelectrical brain signal recorded from a patient's brain; determine at least one pathological frequency of the bioelectrical brain signal based on the information; select a pulse burst sequence at a pulse burst frequency based on the at least one pathological frequency, the pulse burst sequence at least partially defining electrical stimulation deliverable to a region of the patient's brain, wherein adjacent pulse bursts within the sequence include different intra-burst pulse frequencies; and control a medical device to deliver the electrical stimulation including the pulse burst sequence to the region of the patient's brain.

This summary is intended to provide an overview of the subject matter described in this disclosure. This summary is not intended to provide an exclusive or exhaustive explanation of the systems, devices, and methods described in detail in the following figures and description. Further details of one or more examples of the present disclosure are set forth in the following figures and description. Other features, objectives, and advantages will be apparent from the description and drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

1 is a conceptual diagram illustrating an example system for delivering electrical stimulation to a patient, in accordance with one or more techniques of this disclosure.

2 is a functional block diagram illustrating components of the IMD of FIG. 1 , in accordance with one or more techniques of this disclosure.

3 is a conceptual block diagram of the programmer of FIG. 1 , in accordance with one or more techniques of this disclosure.

4 is a conceptual diagram illustrating an example first timing diagram of a first pulse burst sequence, in accordance with one or more techniques of this disclosure.

5 is a conceptual diagram illustrating a second timing diagram for a second pulse burst sequence in accordance with one or more techniques of this disclosure.

6 is a conceptual diagram illustrating a third timing diagram of a third pulse burst sequence in accordance with one or more techniques of this disclosure.

7 is a conceptual diagram illustrating a fourth timing diagram of a fourth pulse burst sequence in accordance with one or more techniques of this disclosure.

8 is a flow chart illustrating example operations for controlling an IMD to deliver stimulation having one or more patterns configured to suppress one or more pathological brain signals, in accordance with one or more techniques of this disclosure.

9 is a flow chart illustrating example operations for detecting one or more pathological brain signals and controlling an IMD to deliver stimulation having one or more patterns configured to suppress the one or more pathological brain signals, in accordance with one or more techniques of this disclosure.

Like reference characters represent like elements throughout the specification and drawings.

Detailed ways

The present disclosure describes examples of medical devices, systems, and techniques for delivering electrical stimulation to a patient's brain in order to suppress one or more bioelectrical brain signals of the patient. In some examples, the bioelectrical brain signals may correspond to frequency oscillations of pathological brain signals of the patient. Pathological brain signals may cause undesirable symptoms, such as rigidity, forgetfulness, bradykinesia, movement disorders, and/or resting tremors. Therefore, it may be beneficial to suppress these pathological brain signals without disrupting other normal or non-pathological brain functions of the patient. The medical device may detect pathological brain signals in an area of the patient's brain and deliver electrical stimulation to the area of the patient's brain. The medical device may deliver electrical stimulation to cause synaptic inhibition in an area of the patient's brain without entraining a larger network of bioelectrical brain signals. When the medical device causes synaptic inhibition, the medical device may suppress the pathological brain signals so that the effects of the pathological brain signals on the patient are attenuated or completely eliminated.

As will be further described below, in some examples, a medical device may deliver electrical stimulation to a patient's brain to manage or otherwise treat a patient's condition. In some examples, the oscillation of a bioelectrical computer signal at a specific frequency or frequency band or range may be associated with one or more symptoms of a patient's condition. These oscillations may be referred to as pathological signals or pathological frequencies. For example, a bioelectrical computer signal oscillating within a specific frequency range may be associated with one or more symptoms of a patient's condition, in the sense that such symptoms frequently occur or manifest when the bioelectrical computer signal oscillates at such a frequency range. The occurrence of such a situation may be the result of brain signal oscillations in one or more regions of the patient's brain interfering with the normal function of that region of the brain. As used herein, when a brain signal oscillates at a certain frequency or frequency range in such a manner as to be associated with one or more symptoms of a patient's condition, such a frequency or frequencies may be referred to as a pathological frequency or pathological frequency range. Similarly, a bioelectrical computer signal oscillating at one or more pathological frequencies may be referred to as a pathological brain signal.

As an example, in the case of Parkinson's disease, the frequency of beta oscillations in the subthalamic nucleus (STN), the internal globus pallidus (GPi), the external globus pallidus (GPe), and/or other areas of the basal ganglia (e.g., between about 12 Hz (Hz) and about 35 Hz) may be associated with one or more motor symptoms, including, for example, rigidity, forgetfulness, bradykinesia, dyskinesia, and/or resting tremor. These motor symptoms may be associated with bioelectrical computer signals oscillating in the beta frequency range, in the sense that such symptoms frequently occur when the bioelectrical computer signals oscillate in the beta frequency range. Continuous oscillations in the beta frequency range may result in oscillation "disturbance", which may limit the normal function of the above-mentioned areas of the brain. Oscillating neuronal networks can be synchronized by electrical and chemical signals that phase-lock the activity of the network and resonate at a certain frequency. In some examples, the symptoms of Parkinson's disease usually manifest themselves with the presence of beta frequency range (e.g., above a certain threshold activity level) oscillations. In some examples, the frequency of symptom manifestation may increase with the presence of beta frequency range oscillations.

In some examples, one or more symptoms of a patient's condition associated with oscillations of bioelectrical computer activity at a particular frequency or frequency band can be treated by reducing or substantially eliminating bioelectrical computer signals at such pathological frequencies when such activity occurs. For example, for a patient with Parkinson's disease, the manifestation of one or more symptoms associated with bioelectrical computer signals oscillating in the beta frequency range can be reduced or substantially eliminated by causing synaptic inhibition in an area of the patient's brain where bioelectrical computer signals in the beta frequency range are present. A medical device can cause synaptic inhibition by delivering a pulse burst sequence to an area of the patient's brain where bioelectrical computer signals in the beta frequency range are present, wherein the medical device delivers the pulse burst sequence at a pulse burst frequency that matches the frequency of the bioelectrical computer signals. In some examples, the medical device delivers a pulse burst in the pulse burst sequence that corresponds to a trough of the bioelectrical computer signal. By stimulating the trough of the bioelectrical computer signal, the medical device can suppress the bioelectrical computer signal in a localized area of the patient's brain without substantially affecting other areas of the brain.

A pulse burst sequence may include pulse bursts of varying frequencies. For example, each pulse burst in a pulse burst sequence may include a group of pulses having an intra-burst pulse frequency, wherein the intra-burst pulse frequency of one pulse burst may be different from the intra-burst pulse frequency of one or more other pulse bursts in the pulse burst sequence. It may be beneficial for the intra-burst pulse frequency of a pulse burst to be different from the intra-burst pulse frequency of an adjacent pulse burst in the pulse burst sequence. In addition, it may be beneficial for adjacent pulse bursts to be non-harmonic in frequency so as to prevent the pulse burst sequence from entraining bioelectrical computer signals. That is, a factor of the intra-burst pulse frequency of one pulse burst may be different from a factor of the intra-burst pulse frequency of an adjacent pulse burst in the pulse burst sequence. When a medical device delivers a pulse burst sequence in which adjacent pulse bursts have non-harmonic frequencies, the medical device may suppress bioelectrical computer signals oscillating at a frequency matching the pulse burst frequency of the pulse bursts delivered by the medical device. However, the medical device may avoid entraining bioelectrical computer signals by delivering pulse bursts at these non-harmonic frequencies, thereby affecting bioelectrical computer signals in the patient's brain.

The medical device may suppress the bioelectrical brain signal without entraining the bioelectrical brain signal, so that the electrical stimulation in one area of the brain does not affect brain activity in other areas of the brain, compared to the technique in which the medical device entrains the bioelectrical brain signal. The bioelectrical brain signal may be characterized as being entrained by the delivered electrical stimulation when the bioelectrical brain signal is pulled, attracted, or otherwise follows the frequency changes of the delivered electrical stimulation. Entrainment may be "following" the period and/or phase changes of the delivered electrical stimulation over a period of time, and may include situations where the changes in the bioelectrical brain signal are substantially the same as the changes in the delivered stimulation, and situations where the changes are substantially different but follow the changes in the electrical stimulation to some extent. When the bioelectrical brain signal follows the changes in the period and/or phase of the electrical stimulation in one area of the brain, the period and/or phase of the bioelectrical brain signal in other areas may also follow the changes. In some examples, the entrainment of the delivered electrical stimulation to the bioelectrical brain signal may be demonstrated by the oscillation frequency of the brain signal matching the frequency of the electrical stimulation and the constant phase relationship between the brain signal oscillation and the delivered electrical stimulation. In some cases, it may be beneficial to avoid entrainment of biological brain signals in order to deliver treatment without causing widespread changes in brain activity.

In some examples, the medical device can deliver a pulse burst sequence at a pulse burst frequency substantially the same as the frequency of the biological electrical computer signal oscillation. As described herein, the term "pulse burst frequency" refers to the frequency at which the medical device delivers a pulse burst sequence. For example, when the medical device delivers a pulse burst sequence at 20Hz, the medical device delivers the pulse burst sequence at a rate of 20 pulse bursts per second. In other examples, the pulse burst sequence can be delivered at a certain multiple (about 2 times, about 3 times and/or about 0.5 times) of the biological electrical computer signal oscillation. By delivering a pulse burst sequence at a frequency substantially the same as the brain signal oscillation frequency or at a frequency substantially the same as an integer multiple of the oscillation frequency (for example, about 2 times, about 3 times, etc.), each pulse burst in the pulse burst sequence may correspond to a corresponding event of the biological electrical computer signal. In some examples, each pulse burst in the pulse burst sequence corresponds to a corresponding peak of the biological electrical computer signal. In one example, the start of each pulse burst in the pulse burst sequence may appear at a corresponding peak of the biological electrical signal. In another example, the midpoint of each pulse burst in the pulse burst sequence may appear at a corresponding peak of the biological electrical signal. In some examples, each pulse burst in the pulse burst sequence corresponds to a corresponding valley of the biological electrical computer signal. In one example, the start of each pulse burst in the pulse burst sequence may occur at a corresponding valley of the bioelectric signal. In another example, the midpoint of each pulse burst in the pulse burst sequence may occur at a corresponding valley of the bioelectric signal. When each pulse burst in the pulse burst sequence corresponds to a corresponding valley of the bioelectric signal, the pulse burst sequence may suppress the bioelectric signal so that one or more symptoms caused by the bioelectric signal are attenuated or completely eliminated.

In other examples, the medical device may deliver a pulse burst sequence at a frequency that is a fraction (e.g., 1/2 or 1/4) of the brain signal oscillation frequency. In this case, each pulse burst in the pulse burst sequence may not match substantially all of the peaks or substantially all of the valleys of the bioelectrical brain signal at a given oscillation frequency. However, the pulse burst sequence may match a portion of the peaks of the brain signal or a portion of the valleys of the brain signal (e.g., approximately 50% for stimulation at a frequency of approximately half the oscillation frequency).

In some examples, such electrical stimulation therapy may be delivered to the patient's brain in response to detecting oscillations of bioelectrical brain signals at pathological frequencies and/or detecting the manifestation of one or more motor symptoms associated with the pathological frequencies. Additionally or alternatively, such electrical stimulation therapy may be delivered to the patient's brain periodically and not in response to detecting oscillations at pathological frequencies and/or detecting the manifestation of one or more motor symptoms associated with the pathological frequencies. In some examples, electrical stimulation therapy may be delivered in response to patient input. In some examples, electrical stimulation may be delivered to the patient continuously.

FIG. 1 is a conceptual diagram illustrating an exemplary system 10 for delivering electrical stimulation to a patient 12 in accordance with one or more techniques of the present disclosure. In FIG. 1 , system 10 may deliver electrical stimulation therapy to treat or otherwise manage a patient condition, such as a movement disorder of patient 12. An example of a movement disorder treated by delivering deep brain stimulation (DBS) via system 10 may include Parkinson's disease. Patient 12 will typically be a human patient. However, in some cases, system 10 may be applied to other mammals or non-mammalian, non-human patients.

For ease of illustration, examples of the present disclosure will be described primarily with respect to the treatment of movement disorders, particularly Parkinson's disease, such as by reducing or preventing the manifestation of symptoms exhibited by patients suffering from Parkinson's disease. As described above, such symptoms may include rigidity, forgetfulness, bradykinesia, dyskinesia, and/or resting tremor. However, it is contemplated that one or more patient conditions other than Parkinson's disease may be treated by employing the techniques described herein. For example, the described techniques may be used to manage or otherwise treat symptoms of other patient conditions, such as, but not limited to, psychological disorders, mood disorders, epilepsy, or other neurogenic disorders. In one example, such techniques may be employed to provide treatment to a patient to treat Alzheimer's disease.

System 10 includes programmer 14, implantable medical device (IMD) 16, lead extension 18, and one or more leads 20A and 20B (collectively referred to as "leads 20") having corresponding electrode groups 24, 26. Lead 20A may include electrode group 24, and lead 20B may include electrode group 26. IMD 16 includes a stimulation therapy module that includes a stimulation generator that generates electrical stimulation therapy via a subset of electrode groups 24, 26 of leads 20A and 20B, respectively, and delivers the electrical stimulation therapy to one or more regions of brain 28 of patient 12. In the example shown in FIG. 1, system 10 may be referred to as a DBS system because IMD 16 provides electrical stimulation therapy directly to tissue within brain 28 (e.g., tissue sites beneath the dura mater of brain 28). In other examples, leads 20 may be positioned to deliver therapy to the surface of brain 28 (e.g., the cortical surface of brain 28).

In some examples, delivering stimulation to one or more regions of brain 28, such as the anterior nucleus (AN), thalamus, or cortex of brain 28, provides effective therapy for managing the condition of patient 12. In some examples, IMD 16 may provide cortical stimulation therapy to patient 12, for example, by delivering electrical stimulation to one or more tissue sites in the cortex of brain 28. In the case where IMD 16 delivers electrical stimulation therapy to brain 28 to treat Parkinson's disease by modulating brain signals oscillating at pathological frequencies, the target stimulation sites may include one or more basal ganglia sites, including, for example, the subthalamic nucleus (STN), the internal globus pallidus (GPi), the external globus pallidus (GPe), the pedunculopontine nucleus (PPN), the thalamus, the substantia nigra reticulata (SNr), the internal capsule, and/or the motor cortex. Brain signals having oscillations in the beta frequency range may be considered pathological brain signals. As will be described below, IMD 16 may deliver electrical stimulation selected to entrain bioelectrical brain signals that oscillate within the beta frequency range, and adjust the frequency of the electrical stimulation to change the oscillation frequency to a higher or lower frequency, e.g., a frequency greater than about 40 Hz, such as, for example, between about 40 Hz and about 100 Hz or up to about 350 Hz. For situations in which IMD 16 senses bioelectrical brain signals at one or more sites of brain 28 to detect oscillations at pathological frequencies, the target stimulation site for the electrical stimulation delivered to brain 28 of patient 12 may be the same and/or different than the sensing site.

In the example shown in FIG. 1 , the IMD 16 may be implanted in a subcutaneous pocket above the clavicle of the patient 12. In other examples, the IMD 16 may be implanted in other areas of the patient 12, such as a subcutaneous pocket in the abdomen or buttocks of the patient 12 or near the skull of the patient 12. The lead extension 18 is coupled to the IMD 16 via a connector block 30 (also referred to as a header), which may include, for example, electrical contacts that are electrically coupled to corresponding electrical contacts on the lead extension 18. The electrical contacts electrically couple the electrode sets 24, 26 carried by the leads 20 to the IMD 16. The lead extension 18 traverses from the implantation site of the IMD 16 in the chest of the patient 12 along the neck of the patient 12 and through the skull of the patient 12 to enter the brain 28. Generally speaking, the IMD 16 is composed of a biocompatible material that resists corrosion and degradation by body fluids. The IMD 16 may include a housing 34 to substantially enclose components, such as a processor, a therapy module, and a memory. In some examples, housing 24 is sealed.

Leads 20A and 20B may be implanted in the right and left hemispheres of brain 28, respectively, to deliver electrical stimulation to one or more regions of brain 28, which may be selected based on a number of factors, such as the type of patient condition for which system 10 is implemented to manage. Other implantation sites for leads 20 and IMD 16 are contemplated. For example, IMD 16 may be implanted on or in skull 32, or leads 20 may be implanted in the same hemisphere, or IMD 16 may be coupled to a single lead implanted in one or both hemispheres of brain 28.

The lead 20 may be positioned to deliver electrical stimulation to one or more target tissue sites within the brain 28 to manage patient symptoms associated with a condition of the patient 12. The lead 20 may be implanted to position the electrode sets 24, 26 at desired locations within the brain 28 through corresponding holes in the skull 32. The lead 20 may be placed at any location within the brain 28 such that the electrode sets 24, 26 are able to provide electrical stimulation to target tissue sites within the brain 28 during treatment. For example, in the case of Parkinson's disease, for example, the lead 20 may be implanted to deliver electrical stimulation to one or more basal ganglia sites, including, for example, the subthalamic nucleus (STN), the globus pallidus internus (GPi), the globus pallidus externus (GPe), the pedunculopontine nucleus (PPN), the thalamus, the substantia nigra reticulata (SNr), the internal capsule, and/or the motor cortex.

Although leads 20 are shown in FIG1 as being coupled to lead extensions 18, in other examples, leads 20 may be coupled to IMD 16 via separate lead extensions, or directly coupled to IMD 16. Furthermore, although FIG1 shows system 10 as including two leads 20A and 20B coupled to IMD 16 via lead extensions 18, in some examples, system 10 may include one lead or more than two leads.

Lead 20 can deliver electrical stimulation to treat any number of neurological disorders or diseases other than movement disorders, such as epilepsy or psychiatric disorders. Examples of movement disorders include decreased muscle control, movement defects or other movement problems, such as rigidity, bradykinesia, rhythmic hyperkinesia, non-rhythmic hyperkinesia, dystonia, tremor and akinesia. Movement disorders may be associated with a patient's disease state, such as Parkinson's disease or Huntington's disease. Examples of psychiatric disorders include MDD, bipolar disorder, anxiety disorders, post-traumatic stress disorder, mood disorders and OCD. As described above, although the examples of the present disclosure are described primarily with respect to treating Parkinson's disease, it is contemplated to treat other patient conditions via delivery of therapy to the brain 28.

Lead 20 may be implanted in a desired location of brain 28 via any suitable technique, such as through a corresponding cranial burr hole in the skull of patient 12 or through a common cranial burr hole in skull 32. Lead 20 may be placed at any location within brain 28 so that electrode groups 24, 26 of lead 20 are able to provide electrical stimulation to target tissue during treatment. Electrical stimulation generated from a stimulation generator (not shown) within a treatment module of IMD 16 may help prevent the onset of an event associated with a patient's illness or alleviate the patient's symptoms. For example, electrical stimulation delivered to a target tissue site within brain 28 by IMD 16 may include a pulse burst sequence delivered at a pulse burst frequency, wherein the pulse burst frequency of the pulse burst sequence matches the pathological frequency of the detected bioelectrical circuit signal. Although IMD 16 delivers the pulse burst sequence at a consistent pulse burst frequency, IMD 16 may deliver the pulse burst itself at a variable frequency. When the pulse burst itself has a variable frequency, delivering a pulse burst sequence at a pulse burst frequency may suppress pathological brain signals without entraining pathological brain signals. Inhibiting pathological brain signals may reduce or completely eliminate symptoms associated with the pathological brain signals. In this manner, IMD 16 may deliver electrical stimulation to reduce or prevent the onset of an event associated with a patient's condition or to alleviate symptoms of the patient.

In the example shown in FIG. 1 , the electrode groups 24, 26 of the lead 20 are shown as ring electrodes. Ring electrodes may be relatively easy to program and are generally capable of delivering an electric field to any tissue adjacent to the lead 20. In other examples, the electrode groups 24, 26 of the lead 20 may have different configurations. For example, the electrode groups 24, 26 of the lead 20 may have a complex electrode array geometry capable of generating a shaped electric field. The complex electrode array geometry may include multiple electrodes (e.g., partial rings or segmented electrodes) around the periphery of each lead of the lead 20, rather than ring electrodes. In this way, electrical stimulation can be directed from the lead 20 to a specific direction to enhance the efficacy of the treatment and reduce adverse side effects that may be caused by stimulating a large amount of tissue.

In some examples, housing 34 of IMD 16 may include one or more stimulation and/or sensing electrodes. For example, housing 34 may include a conductive material that is exposed to the tissue of patient 12 when IMD 16 is implanted in patient 12, or the electrodes may be attached to housing 34. In alternative examples, lead 20 may have a shape other than an elongated cylinder as shown in FIG. 1. For example, lead 20 may be a paddle lead, a ball lead, a bendable lead, or any other type of shape that is effective for treating patient 12.

IMD 16 may deliver electrical stimulation therapy to brain 28 of patient 12 according to one or more stimulation therapy programs. A therapy program may define one or more electrical stimulation parameter values for the therapy generated from IMD 16 and delivered to brain 28 of patient 12. In the case where IMD 16 delivers electrical stimulation in the form of electrical pulses, for example, the stimulation therapy may be characterized by selected pulse parameters such as pulse amplitude, pulse rate, and pulse width. In addition, if different electrodes can be used to deliver the stimulation, the therapy may also be characterized by different electrode combinations, which may include selected electrodes and their corresponding polarities. The exact therapy parameter values for the stimulation therapy that aids in managing or treating a patient's condition may be specific to the specific target stimulation site involved (e.g., brain region) as well as the specific patient and patient condition.

In addition to delivering therapy to manage the condition of patient 12, system 10 also monitors one or more bioelectrical electrical signals of patient 12. For example, IMD 16 may include a sensing module that senses bioelectrical electrical signals within one or more regions of brain 28. In the example shown in FIG1 , signals generated by electrode sets 24, 26 are conducted to the sensing module within IMD 16 via conductors within corresponding ones of leads 20. As described in further detail below, in some examples, a processor of IMD 16 may sense bioelectrical signals within brain 28 of patient 12 and control the delivery of electrical stimulation therapy to brain 28 via electrode sets 24, 26 when the bioelectrical signals oscillate at a pathological frequency.

In some examples, the sensing module of IMD 16 may receive bioelectric signals from electrode groups 24, 26 or other electrodes positioned to monitor brain signals of patient 12. Electrode groups 24, 26 may also be used to deliver electrical stimulation from the treatment module to a target site within brain 28, as well as to sense brain signals within brain 28. However, IMD 16 may also use separate sensing electrodes to sense bioelectric brain signals. In some examples, the sensing module of IMD 16 may sense bioelectric brain signals via one or more electrodes in electrode groups 24, 26, which are also used to deliver electrical stimulation to brain 28. In other examples, one or more electrodes in electrode groups 24, 26 may be used to sense bioelectric brain signals, while one or more different electrodes in electrode groups 24, 26 may be used to deliver electrical stimulation.

Depending on the specific stimulation electrodes and sensing electrodes used by IMD 16, IMD 16 may monitor brain signals and deliver electrical stimulation to the same area of brain 28 or to different areas of brain 28. In some examples, the electrodes used to sense bioelectrical brain signals may be located on the same lead used to deliver electrical stimulation, while in other examples, the electrodes used to sense bioelectrical brain signals may be located on a different lead than the electrodes used to deliver electrical stimulation. In some examples, brain signals of patient 12 may be monitored using external electrodes (e.g., scalp electrodes). In addition, in some examples, a sensing module that senses bioelectrical brain signals of brain 28 (e.g., a sensing module that generates electrical signals indicative of activity within brain 28) is in a housing that is physically separate from housing 34 of IMD 16. However, in the example shown in FIG. 1 and the examples primarily referenced herein for ease of description, the sensing module and treatment module of IMD 16 are enclosed within housing 34.

The bioelectrical brain signals monitored by IMD 16 may reflect changes in current resulting from the sum of potential differences across brain tissue. Examples of monitored bioelectrical brain signals include, but are not limited to, electroencephalogram (EEG) signals, evoked resonant neural activity (ERNA) signals, electrocorticogram (ECoG) signals, local field potentials (LFPs) sensed from one or more regions of the patient's brain, and/or action potentials of individual cells within the patient's brain.

Programmer 14 communicates wirelessly with IMD 16 as needed to provide or retrieve treatment information. Programmer 14 is an external computing device that a user (e.g., a clinician and/or patient 12) can use to communicate with IMD 16. For example, programmer 14 may be a clinician programmer that a clinician uses to communicate with IMD 16 and program one or more treatment programs for IMD 16. Alternatively, programmer 14 may be a patient programmer that allows patient 12 to select a program and/or view and modify treatment parameters. A clinician programmer may include more programming features than a patient programmer. In other words, only a clinician programmer may allow more complex or sensitive tasks to prevent untrained patients from making undesirable changes to IMD 16.

Programmer 14 may be a handheld computing device having a display visible to a user and an interface (i.e., a user input mechanism) for providing input to programmer 14. For example, programmer 14 may include a small display screen (e.g., a liquid crystal display (LCD) or a light emitting diode (LED) display) that presents information to the user. Additionally, programmer 14 may include a touch screen display, a keypad, buttons, a peripheral pointing device, or another input mechanism that allows a user to navigate the user interface of programmer 14 and provide input. If programmer 14 includes buttons and a keypad, the buttons may be dedicated to performing a certain function, i.e., a power button, or the buttons and keypad may be soft keys whose functions change depending on the portion of the user interface that the user is currently viewing.

In some examples, programmer 14 may be a separate application within a larger workstation or another multifunction device rather than a dedicated computing device. For example, the multifunction device may be a laptop, tablet computer, workstation, cellular phone, personal digital assistant, or another computing device that can run an application that enables the computing device to operate as a secure medical device programmer. A wireless adapter coupled to the computing device may enable secure communication between the computing device and IMD 16.

When programmer 14 is configured for use by a clinician, programmer 14 may be used to transmit initial programming information to IMD 16. This initial information may include hardware information, such as the type of lead 20, the arrangement of electrode sets 24, 26 on lead 20, the location of lead 20 within brain 28, an initial program defining therapy parameter values, and any other information that may be useful to program into IMD 16. Programmer 14 may also be able to perform functional testing (e.g., measuring the impedance of one or more electrodes in electrode sets 24, 26 of lead 20).

The clinician may also store therapy programs within IMD 16 with the aid of programmer 14. During a programming session, the clinician may determine one or more therapy programs that may provide effective therapy to patient 12 to address symptoms associated with epilepsy (or another patient condition). For example, the clinician may select one or more electrode combinations with which to deliver stimulation to brain 28. During a programming session, patient 12 may provide feedback to the clinician regarding the efficacy of a particular program being evaluated, or the clinician may evaluate efficacy based on one or more physiological parameters of the patient (e.g., heart rate, respiratory rate, or muscle activity). Programmer 14 may assist the clinician in creating/identifying therapy programs by providing an organized system for identifying potentially beneficial therapy parameter values.

Programmer 14 may also be configured for use by patient 12. When configured as a patient programmer, programmer 14 may have limited functionality (compared to a clinician programmer) to prevent patient 12 from altering critical functions of IMD 16 or applications that may be harmful to patient 12. In this manner, programmer 14 may only allow patient 12 to adjust values of certain therapy parameters or set an available range of values for a particular therapy parameter.

Programmer 14 may also provide indications to patient 12 when therapy is being delivered, when patient input has triggered a therapy change, or when a power source within programmer 14 or IMD 16 needs to be replaced or recharged. For example, programmer 14 may include an alert LED, may flash a message to patient 12 via a programmer display, generate an audible sound, or a physical sensory prompt to confirm receipt of patient input, e.g., to indicate a patient status or to manually modify a therapy parameter.

Regardless of whether programmer 14 is configured for use by a clinician or a patient, programmer 14 is configured to communicate with IMD 16 and optionally with another computing device via wireless communications. For example, programmer 14 may communicate with IMD 16 via wireless communications using radio frequency (RF) telemetry techniques known in the art. Programmer 14 may also communicate with another programmer or computing device via a wired or wireless connection using any of a variety of local wireless communication techniques, such as RF communications according to the 802.11 or Bluetooth specification sets, infrared (IR) communications according to the IRDA specification set, or other standard or proprietary telemetry protocols. Programmer 14 may also communicate with other programming or computing devices via the exchange of removable media, such as a magnetic or optical disk, a memory card, or a memory stick. In addition, programmer 14 may communicate with IMD 16 and another programmer via remote telemetry techniques known in the art, for example, via a local area network (LAN), a wide area network (WAN), a public switched telephone network (PSTN), or a cellular telephone network.

Therapeutic system 10 may be implemented to provide chronic stimulation therapy to patient 12 over the course of months or years. However, system 10 may also be used to evaluate therapy on a trial basis prior to full implantation. If implemented temporarily, some components of system 10 may not be implanted in patient 12. For example, patient 12 may be fitted with an external medical device, such as a trial stimulator, instead of IMD 16. The external medical device may be coupled to a percutaneous lead or implanted lead via a percutaneous extension. If the trial stimulator indicates that system 10 is providing effective therapy to patient 12, the clinician may implant a chronic stimulator in patient 12 for relatively long-term therapy.

FIG. 2 is a functional block diagram illustrating components of IMD 16 of FIG. 1 in accordance with one or more techniques of the present disclosure. As can be seen in FIG. 2 , IMD 16 includes processing circuitry 40, memory 42, stimulation generation circuitry 44, sensing circuitry 46, telemetry circuitry 50, and power supply 52. Processing circuitry 40 may include any one or more microprocessors, controllers, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or discrete logic circuits. The functionality described herein as being attributed to a processor (including processing circuitry 40) may be provided by hardware devices and embodied as software, firmware, hardware, or any combination thereof.

2, sensing circuit 46 senses bioelectrical electrical signals of patient 12 via a selected combination of electrodes in electrode sets 24, 26. Sensing circuit 46 may include circuitry to measure electrical activity of a particular region (e.g., the anterior nucleus, thalamus, or cortex of brain 28) via selected electrodes in electrode sets 24, 26. For the treatment of Parkinson's disease, sensing circuit 46 may be configured to measure electrical activity of the subthalamic nucleus (STN), globus pallidus internus (GPi), globus pallidus externus (GPe), and/or other regions of the basal ganglia.

The sensing circuit 46 may sample the bioelectrical computer signal substantially continuously or at regular intervals, such as, but not limited to, a frequency of about 1 Hz to about 1000 Hz, such as a frequency of about 250 Hz to about 1000 Hz or about 500 Hz to about 1000 Hz. The sensing circuit 46 includes circuitry for determining a voltage difference between two electrodes in the electrode sets 24, 26, which is generally indicative of electrical activity within a particular region of the brain 28. One of the electrodes in the electrode sets 24, 26 may be used as a reference electrode, and if the sensing circuit 46 is implanted in the patient 12, in examples where the sensing circuit 46 is separate from the IMD 16, the housing of the IMD 16 or sensing module may include one or more electrodes that may be used to sense the bioelectrical computer signal.

Processing circuit 40 may receive the output of sensing circuit 46. In some cases, processing circuit 40 may apply additional processing to the bioelectric signal, for example, converting the output to a digital value for processing and/or amplifying the bioelectric signal. Additionally, in some examples, sensing circuit 46 or processing circuit 40 may filter the signal from selected electrodes in electrode sets 24, 26 to remove undesirable artifacts from the signal, such as noise from cardiac signals generated within patient 12. Although sensing circuit 46 is incorporated into a common external housing with stimulation generation circuit 44 and processing circuit 40 in FIG. 2, in other examples, sensing circuit 46 is located in an external housing separate from the external housing of IMD 16 and may communicate with processing circuit 40 via wired or wireless communication techniques. In other examples, the bioelectric signal may be sensed via external electrodes (e.g., scalp electrodes).

In some examples, the sensing circuit 46 may include a circuit for tuning and extracting the power level of a specific frequency band of the sensed brain signal. Therefore, the power level of the specific frequency band of the sensed brain signal can be extracted before the processing circuit 40 digitizes the signal. By tuning and extracting the power level of the specific frequency band before the signal is digitized, the frequency domain analysis algorithm can be run at a relatively slow rate compared to a system that does not include extracting the power level of the specific frequency band of the sensed brain signal before the signal is digitized. In some examples, the sensing circuit 46 may include more than one channel to monitor simultaneous activity in different frequency bands, that is, to extract the power level of more than one frequency band of the sensed brain signal. These frequency bands may include an alpha band (e.g., 8 Hz to 12 Hz, a beta band (e.g., about 12 Hz to about 35 Hz), a gamma band (e.g., between about 35 Hz and about 200 Hz), or other frequency bands.

In some examples, sensing circuit 46 may include an architecture that merges chopper stabilization with heterodyne signal processing to support a low noise amplifier. In some examples, sensing circuit 46 may include a frequency selective signal monitor that includes a chopper stabilized superheterodyne instrumentation amplifier and a signal analysis unit.

The frequency selective signal monitor may utilize a heterodyne processing, chopper stabilized amplifier architecture to convert a selected frequency band of a physiological signal to baseband for analysis. The physiological signal may include a bioelectrical brain signal that may be analyzed in one or more selected frequency bands to detect a bioelectrical brain signal oscillating at a pathological frequency, and in response, deliver electrical stimulation to modulate the oscillation frequency of the bioelectrical brain signal according to some of the techniques described herein. The frequency selective signal monitor may provide a physiological signal monitoring device that includes: a physiological sensing element that receives a physiological signal; an instrument amplifier that includes a modulator that modulates the signal at a first frequency; an amplifier that amplifies the modulated signal; and a demodulator that demodulates the amplified signal at a second frequency different from the first frequency. The signal analysis unit may analyze characteristics of the signal in the selected frequency band. The second frequency may be selected so that the demodulator centers the selected frequency band of the signal substantially at baseband.

In some examples, sensing circuitry 46 may sense brain signals substantially simultaneously with IMD 16 delivering therapy to patient 12. In other examples, sensing circuitry 46 may sense brain signals and IMD 16 may deliver therapy at a different time.

In some examples, for example, in conjunction with the monitored bioelectrical brain signals of the patient, the sensing circuit 46 may monitor one or more physiological parameters of the patient in addition to the bioelectrical brain signals, which are indicative of the patient's condition. Suitable patient physiological parameters may include, but are not limited to, muscle tone (e.g., sensed by electromyography (EMG)), eye movement (e.g., sensed via electro-oculogram (EOG) or EEG), and body temperature. In some examples, the patient's movement may be monitored via an actigraph. In one example, the processing circuit 40 may monitor EMG signals reflecting the muscle tone of the patient 12 to identify the patient's body movement. Alternatively or additionally, the processing circuit 40 may monitor the patient's body movement via one or more motion sensors (such as, for example, one or more single-axis or multi-axis accelerometer devices).

In some examples, sensing circuit 46 may monitor one or more physiological parameters of the patient in addition to one or more physiological parameters of the bioelectrical brain signal, which are indicative of symptoms of Parkinson's disease. For example, sensing circuit 46 may monitor one or more parameters indicating muscle stiffness or movement (slowness of movement, tremor, and lack of movement), which may correspond to one or more symptoms of Parkinson's disease. Such parameters may be detected by EMG signals, actigraphy, accelerometer signals, and/or other suitable signals. In some examples, in response to detecting one or more symptoms of Parkinson's disease based on monitoring of such parameters, IMD 16 may deliver electrical stimulation selected to suppress brain signals oscillating at a frequency associated with the detected symptoms.

Memory 42 may include any volatile or non-volatile media, such as random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, etc. Memory 42 may store computer-readable instructions that, when executed by processing circuit 40, cause IMD 16 to perform various functions described herein. In some examples, memory 42 may be considered to be a non-transitory computer-readable storage medium including instructions that cause one or more processors (e.g., processing circuit 40) to implement one or more of the exemplary techniques described in the present disclosure. The term "non-transitory" may indicate that the storage medium is not embodied in a carrier or propagating signal. However, the term "non-transitory" should not be interpreted to mean that memory 42 is non-removable. As an example, memory 42 may be removed from IMD 16 and moved to another device. In some examples, a non-transitory storage medium may store data that may change over time (e.g., in RAM).

The stimulation generation circuit 44 may represent a single-channel or multi-channel stimulation generator. For example, the stimulation generation circuit 44 may be capable of delivering a single stimulation pulse, multiple stimulation pulses, or a continuous signal at a given time via a single electrode combination, or delivering multiple stimulation pulses at a given time via multiple electrode combinations. The stimulation generation circuit 44 may include independently controllable sources and sinks for each electrode. Switches or other circuits may be configured to connect and disconnect the sensing circuit 46 from the stimulation generation circuit as needed, for example to prevent the delivered stimulation from damaging the sensing circuit 46. However, in some examples, the stimulation generation circuit 44 may be configured to deliver multiple channels on a time-interleaved basis. For example, the processing circuit 40 time-divides the output of the stimulation generation circuit 44 across different electrode combinations at different times to deliver multiple programs or channels of stimulation energy to the patient 12.

According to one or more examples of the present disclosure, the processing circuit 40 and/or the processing circuit of another device (e.g., the processing circuit of the programmer 14) may control the stimulation generation circuit 44 to generate electrical stimulation and deliver the electrical stimulation to one or more areas of the brain 28 to adjust the oscillation frequency of the bioelectrical brain signal in the one or more areas of the brain 28. For example, when the bioelectrical brain signal oscillates at a pathological frequency in a certain area of the brain 28, the processing circuit 40 may control the stimulation generation circuit 44 to generate a pulse burst sequence at a pulse burst frequency and deliver the pulse burst sequence to the area of the brain 28. In some examples, the pulse burst frequency is similar to or equal to the pathological frequency of the pathological brain signal oscillation, but this is not required. In some examples, each pulse burst in the pulse burst sequence is associated with a corresponding intra-burst pulse frequency. Adjacent pulse burst pairs in the pulse burst sequence may have different intra-burst pulse frequencies. Adjacent pulse burst pairs in the pulse burst sequence may have intra-burst pulse frequencies that are not factors of each other.

Telemetry circuitry 50 may support wireless communication between IMD 16 and programmer 14 or another computing device under the control of processing circuitry 40. Processing circuitry 40 of IMD 16 may, for example, transmit bioelectrical computer signals, seizure probability metrics for specific sleep stages, seizure probability distributions for patient 12, etc. to a telemetry module within programmer 14 or another external device via telemetry circuitry 50. Telemetry circuitry 50 in IMD 16 and other devices and systems described herein, such as a telemetry module in programmer 14, may communicate via radio frequency (RF) communication techniques. In addition, telemetry circuitry 50 may communicate with programmer 14 via proximal sensing interactions of IMD 16 with programmer 14. Thus, telemetry circuitry 50 may send information to programmer 14 continuously, at periodic intervals, or upon request from IMD 16 or programmer 14.

Power source 52 delivers operating power to the various components of IMD 16. Power source 52 may include a small rechargeable or non-rechargeable battery and a power generation circuit for generating operating power. Recharging may be accomplished through proximal inductive interaction between an external charger and an inductive charging coil within IMD 16. In some examples, the power requirements may be small enough to allow IMD 16 to take advantage of patient motion and implement a kinetic energy scavenging device to trickle charge a rechargeable battery. In other examples, conventional batteries may be used for a limited time.

In some examples, the processing circuit 40 may determine that the bioelectrical brain signal is oscillating at a pathological frequency based on the bioelectrical brain signal sensed by the sensing circuit 46. When the oscillation of a brain signal at a certain frequency or frequency range is associated with one or more symptoms of a patient's illness, such a frequency or multiple frequencies may represent a pathological frequency or a pathological frequency range. For example, beta oscillations in the subthalamic nucleus, internal globus pallidus, external globus pallidus, and/or other areas of the basal ganglia may be associated with one or more motor symptoms, including, for example, rigidity, forgetfulness, bradykinesia, movement disorders, and/or resting tremor. Beta frequency oscillations may represent bioelectrical brain signals within a frequency band of 12 Hz to 35 Hz. Therefore, when the processing circuit 40 identifies a beta frequency oscillation above a threshold amplitude, the processing circuit 40 may determine that a pathological brain signal is present in an area of the brain 28 of the patient 12.

In some examples, IMD 16 may treat one or more symptoms of a patient condition associated with pathological brain signals by reducing or substantially eliminating bioelectrical brain signals at such pathological frequencies when such activity occurs. For example, when processing circuitry 40 detects a pathological brain signal in a region of brain 28, processing circuitry 40 may control stimulation generation circuitry 44 to deliver electrical stimulation to the region of brain 28 of patient 12. In some examples, delivery of electrical stimulation to the region of brain 28 of patient 12 causes synaptic inhibition so as to inhibit the pathological brain signal detected in the region of brain 28. When IMD 16 causes synaptic inhibition in the region of the brain 28 where the pathological brain signal oscillates, manifestation of one or more symptoms associated with the patient's condition (e.g., Parkinson's disease) may be reduced or substantially eliminated.

IMD 16 can cause synaptic inhibition by delivering electrical stimulation including a pulse burst sequence to an area of the patient's brain where pathological brain signals are present. In some examples, IMD 16 can deliver the pulse burst sequence at a pulse burst frequency that matches the frequency of one or more detected pathological brain signals. Additionally, each pulse burst in the pulse burst sequence may include a corresponding intra-burst pulse frequency. Therefore, the "pulse burst frequency" represents the rate at which the IMD 16 delivers the pulse bursts in the pulse burst sequence, and the "intra-burst pulse frequency" corresponding to each pulse burst in the pulse burst sequence represents the rate at which the IMD 16 delivers the pulses of each corresponding pulse burst. In some examples, IMD 16 can deliver the pulse burst sequence so that the pulse burst frequency matches the frequency of one or more detected pathological brain signals, or matches a factor of the frequency of one or more detected pathological brain signals.

When the IMD 16 delivers a pulse burst sequence such that the pulse burst frequency matches the frequency of the detected pathological brain signal, each pulse burst in the pulse burst sequence delivered by the IMD 16 may correspond to a corresponding cycle of the pathological brain signal, and the IMD 16 may deliver a pulse burst in each cycle of the pathological brain signal. For example, when the medical device delivers a pulse burst sequence at 20 Hz, the medical device delivers the pulse burst sequence at a rate of 20 pulse bursts per second. In some examples, the IMD 16 may align the pulse bursts so that the IMD 16 delivers the pulse bursts substantially at the valley of the pathological brain signal. In some examples, the IMD 16 may align the pulse bursts with the valley of the pathological brain signal so that the first pulse of each pulse burst appears at the corresponding valley of the pathological brain signal. In some examples, the IMD 16 may align the pulse bursts with the valley of the pathological brain signal so that the midpoint of each pulse burst appears at the corresponding valley of the pathological brain signal. In some examples, the IMD 16 may align the pulse bursts so that the IMD 16 delivers the pulse bursts substantially at the peak of the pathological brain signal. In some examples, IMD 16 may align the pulse bursts with the valleys of the pathological brain signal such that the first pulse of each pulse burst occurs at a corresponding peak of the pathological brain signal. In some examples, IMD 16 may align the pulse bursts with the valleys of the pathological brain signal such that the midpoint of each pulse burst occurs at a corresponding peak of the pathological brain signal.

When the processing circuit 40 controls the stimulation generation circuit 44 to align the pulse burst with the valley of the pathological brain signal, the processing circuit 40 can cause synaptic inhibition and inhibit the pathological brain signal. By controlling the stimulation generation circuit 44 to align the pulse burst with the valley of the pathological signal, the processing circuit 40 can attenuate the amplitude of the pathological brain signal, thereby reducing or completely eliminating the symptoms associated with the pathological brain signal, or the processing circuit 40 can completely eliminate the pathological brain signal, thereby completely eliminating the symptoms associated with the pathological brain signal.

In some examples, processing circuitry 40 may control stimulation generation circuitry 44 to deliver a pulse burst sequence at a certain multiple (approximately 2 times, approximately 3 times, and/or approximately 0.5 times) of the frequency of the detected pathological brain signal. By delivering a pulse burst sequence at a frequency that is an integer multiple (e.g., approximately 2 times, approximately 3 times, etc.) of the frequency of the pathological brain signal, each pulse burst in the pulse burst sequence may correspond to a corresponding event of the pathological brain signal, and more than one pulse burst may correspond to a single cycle of the pathological brain signal. When IMD 16 delivers a pulse burst sequence at a certain frequency that is a fraction (e.g., 1/2 or 1/4) of the frequency of the detected pathological brain signal, then not every cycle of the pathological brain signal may correspond to a pulse burst in the pulse burst sequence.

The processing circuit 40 may control the stimulation generation circuit 44 to deliver a pulse burst sequence including pulse bursts of varying frequencies. That is, the processing circuit 40 may control the stimulation generation circuit 44 to deliver a pulse burst sequence at a pulse burst frequency, wherein each pulse burst in the pulse burst sequence is delivered at a burst-internal pulse frequency that is not necessarily the same as the pulse frequency within the burst of one or more other pulse bursts. For example, a first pulse burst may include a first burst-internal pulse frequency, and a second pulse burst may include a second burst-internal pulse frequency that is different from the first burst-internal pulse frequency. In some examples, it may be beneficial for the pulse frequency within the burst of a pulse burst to be different from the pulse frequency within the burst of adjacent pulse bursts in the pulse burst sequence. That is, when the pulse burst sequence includes a first pulse burst at a first burst-internal pulse frequency, a second pulse burst at a second burst-internal pulse frequency after the first pulse burst, and a third pulse burst at a third burst-internal pulse frequency after the second pulse burst, it may be beneficial for the processing circuit 40 to control the stimulation generation circuit 44 to deliver the pulse burst sequence so that the first frequency is different from the second frequency and the third frequency is different from the second frequency. Changing the pulse frequency within the burst of pulse bursts within the pulse burst sequence can prevent the pulse burst sequence from entraining pathological brain signals while still suppressing pathological brain signals.

In addition, it may be beneficial for the processing circuit 40 to control the stimulation generation circuit 44 to deliver a pulse burst sequence such that adjacent pulse bursts are non-harmonic in frequency so as to prevent the pulse burst sequence from entraining bioelectrical brain signals. That is, a factor of the intra-burst pulse frequency of one pulse burst may be different from a factor of the intra-burst pulse frequency of an adjacent pulse burst in the pulse burst sequence. For example, when the pulse burst sequence includes a first pulse burst at a first intra-burst pulse frequency, a second pulse burst at a second intra-burst pulse frequency after the first pulse burst, and a third pulse burst at a third intra-burst pulse frequency after the second pulse burst, it may be beneficial for the processing circuit 40 to control the stimulation generation circuit 44 to deliver a pulse burst sequence such that the factor of the first frequency is different from the factor of the second frequency and the factor of the third frequency is different from the factor of the second frequency. When the IMD 16 delivers a pulse burst sequence in which adjacent pulse bursts have non-harmonic frequencies, the IMD 16 may suppress pathological brain signals. However, the IMD 16 may avoid entraining pathological brain signals and thus avoid affecting bioelectrical brain signals across the brain 28.

IMD 16 can suppress pathological brain signals without entraining pathological brain signals, so that electrical stimulation in one area of the brain does not affect brain activity in other areas of the brain, compared to the technology of medical device entraining bioelectrical brain signals. When entraining bioelectrical brain signals, the electrical stimulation delivered by IMD 16 can "pull" or "attract" the bioelectrical brain signals to match the frequency of the electrical stimulation. When the frequency of the electrical stimulation changes, the frequency of the entrained bioelectrical brain signals can also change to match the frequency of the electrical stimulation. Therefore, the entrained brain signals can "follow" the period, frequency and/or phase of the delivered electrical stimulation within a certain period of time. When the bioelectrical brain signals follow the changes in the period, frequency and/or phase of the electrical stimulation in one area of the brain 28, the period, frequency and/or phase of the bioelectrical brain signals in other areas of the brain 28 can also follow the changes. Therefore, in some examples, it may be beneficial for IMD 16 to suppress some brain bioelectrical signals without entraining these signals, so that IMD 16 can suppress pathological signals in local areas of the brain without affecting brain bioelectrical signals in other areas of the brain by entrainment.

In some examples, IMD 16 may deliver electrical stimulation therapy to brain 28 of patient 12 upon detection of bioelectrical brain signal oscillations at pathological frequencies and/or detection of the manifestation of one or more symptoms associated with pathological brain signals. Additionally or alternatively, IMD 16 may deliver electrical stimulation therapy to brain 28 periodically and not in response to detection of pathological brain signals and/or detection of the manifestation of one or more symptoms associated with pathological brain signals. In some examples, IMD 16 may deliver electrical stimulation therapy based on patient input. In some examples, IMD 16 may deliver electrical stimulation to brain 28 of patient 12 continuously.

FIG. 3 is a conceptual block diagram of the programmer 14 of FIG. 1 according to one or more techniques of the present disclosure. As can be seen in FIG. 3, the programmer 14 includes a processing circuit 60, a memory 62, a telemetry circuit 64, a user interface 66, and a power supply 68. The processing circuit 60 controls the user interface 66 and the telemetry circuit 64, and stores information and instructions to the memory 62 and retrieves the information and instructions from the memory. The programmer 14 can be configured to be used as a clinician programmer or a patient programmer. The processing circuit 60 may include any combination of one or more processors, including one or more microprocessors, DSPs, ASICs, FPGAs, or other equivalent integrated or discrete logic circuits. Therefore, the processing circuit 60 may include any suitable structure, whether hardware, software, firmware, or any combination thereof, to perform the functions attributed to the processing circuit 60 herein.

A user, such as a clinician or patient 12, may interact with programmer 14 through user interface 66. User interface 66 includes a display (not shown), such as an LCD or LED display or other type of screen, to present information related to the treatment of epilepsy in patient 12. User interface 66 may also include an input mechanism to receive input from the user. The input mechanism may include, for example, buttons, a keypad (e.g., an alphanumeric keypad), a peripheral pointing device, or another input mechanism that allows a user to navigate a user interface presented by processing circuitry 60 of programmer 14 and provide input.

Memory 62 may include instructions for operating user interface 66 and telemetry circuit 64 and for managing power supply 68. Memory 62 may also store any therapy data retrieved from IMD 16 during therapy and sensed bioelectrical electrical signals. A clinician may use the therapy data to determine the progression of a patient's condition in order to plan future therapy. Memory 62 may include any volatile or nonvolatile memory, such as RAM, ROM, EEPROM, or flash memory. Memory 62 may also include a removable memory portion that may be used to provide memory updates or increases in memory capacity. Removable memory may also allow sensitive patient data to be removed before programmer 14 is used with a different patient.

In some examples, memory 62 may be considered a non-transitory computer-readable storage medium including instructions that cause one or more processors (e.g., processing circuit 60) to implement one or more of the exemplary techniques described in this disclosure. The term "non-transitory" may indicate that the storage medium is not embodied in a carrier wave or propagating signal. However, the term "non-transitory" should not be interpreted to mean that memory 62 is non-removable. As an example, memory 62 may be removed from programmer 14 and moved to another device. In some examples, non-transitory storage media may store data that may change over time (e.g., in RAM).

Wireless telemetry in programmer 14 may be implemented through RF communication or proximal inductive interaction of programmer 14 with IMD 16. Such wireless communication may be performed using telemetry circuit 64. Thus, telemetry circuit 64 may be similar to a telemetry module included within IMD 16. In other examples, programmer 14 may be capable of infrared communication or direct communication via a wired connection. In this way, other external devices may be able to communicate with programmer 14 without establishing a secure wireless connection.

Power supply 68 may deliver operating power to the components of programmer 14. Power supply 68 may include a battery and a power generation circuit for generating operating power. In some examples, the battery may be rechargeable to allow long-term operation.

FIG4 is a conceptual diagram illustrating a first timing diagram 70 of a first pulse burst sequence 72 according to one or more techniques of the present disclosure. As can be seen in FIG4, the first pulse burst sequence 72 includes a set of pulse bursts 74A-74D (collectively referred to as "pulse bursts 74"). Each pulse burst in the set of pulse bursts 74 may start at the beginning of a corresponding pulse burst interval in pulse burst intervals 76A-76D. Pulse burst 74A starts at the beginning of pulse burst interval 76A, pulse burst 74B starts at the beginning of pulse burst interval 76B, pulse burst 74C starts at the beginning of pulse burst interval 76C, and pulse burst 74D starts at the beginning of pulse burst interval 76D.

The processing circuit 40 may control the stimulus generation circuit 44 to deliver the first pulse burst sequence 72 such that each pulse burst interval in the pulse burst interval 76 is extended by the same amount of time. That is, the pulse burst interval 76A, the pulse burst interval 76B, the pulse burst interval 76C, and the pulse burst interval 76D may all be extended by an equal amount of time. The pulse burst frequency of the first pulse burst sequence 72 may represent the inverse of the amount of time of each pulse burst interval in the pulse burst interval 76. For example, when each pulse burst interval in the pulse burst interval 76 is extended by 50 milliseconds (ms), then the pulse burst frequency is 20 Hz because the processing circuit 40 controls the stimulus generation circuit 44 to deliver the first pulse burst sequence 72 at a rate of 20 pulse bursts per second.

As can be seen in FIG. 4 , each pulse burst in the set of pulse bursts 74 may correspond to a respective intra-burst pulse frequency. Pulse burst 74A may correspond to a first intra-burst pulse frequency, pulse burst 74B may correspond to a second intra-burst pulse frequency, pulse burst 74C may correspond to a third intra-burst pulse frequency, and pulse burst 74D may correspond to a fourth intra-burst pulse frequency. In one example, the first intra-burst pulse frequency corresponding to pulse burst 74A is 250 Hz, the second intra-burst pulse frequency corresponding to pulse burst 74B is 70 Hz, the third intra-burst pulse frequency corresponding to pulse burst 74C is 500 Hz, and the fourth intra-burst pulse frequency corresponding to pulse burst 74D is 140 Hz. Thus, in the example of FIG. 4 , each pulse burst in the set of pulse bursts 74 corresponds to a respective intra-burst pulse frequency that is different from and non-harmonic to the intra-burst pulse frequency of an adjacent pulse burst. For example, the second intra-burst pulse frequency of 70 Hz corresponding to pulse burst 74B is different from the first intra-burst pulse frequency of 250 Hz corresponding to pulse burst 74A, and is different from the third intra-burst pulse frequency of 500 Hz corresponding to pulse burst 74C. Additionally, the second intra-burst pulse frequency of 70 Hz corresponding to pulse burst 74B is non-harmonic with the first intra-burst pulse frequency of 250 Hz corresponding to pulse burst 74A because 70 Hz is not a factor of 250 Hz, and the second intra-burst pulse frequency of 70 Hz corresponding to pulse burst 74B is non-harmonic with the intra-burst pulse frequency of 500 Hz corresponding to pulse burst 74C because 70 Hz is not a factor of 500 Hz.

It may be beneficial for adjacent pulse bursts in the set of pulse bursts 74 to have different and non-harmonic intra-burst pulse frequencies so that the first pulse burst sequence 72 can suppress one or more pathological brain signals without entraining one or more pathological brain signals. By delivering the first pulse burst sequence 72 at the pulse burst frequency, the IMD 16 can suppress one or more detected pathological brain signals. Delivering the first pulse burst sequence 72 to include the set of pulse bursts 74 (including the varying intra-burst pulse frequency) can prevent the first pulse burst sequence 72 from entraining pathological brain signals. Using a varying and non-harmonic intra-burst pulse frequency prevents the first pulse burst sequence 72 from entraining pathological brain signals because pathological brain signals are less likely to follow the pulse burst frequency when the pulse bursts include pulse bursts of varying and non-harmonic frequencies.

As can be seen in FIG. 4 , pulse burst 74A extends from time T1 to time T1′, pulse burst 74B extends from time T2 to time T2′, pulse burst 74C extends from time T3 to time T3′, and pulse burst 74D extends from time T4 to time T4′. Additionally, interval 76A extends from time T1 to time T2, interval 76B extends from time T2 to time T3, interval 76C extends from time T3 to time T4, and interval 76D extends from time T4 to time T5. Since the set of pulse bursts 74 has varying intra-burst pulse frequencies, the pulse bursts 74 extend by varying amounts of time. For example, the difference between T1 and T1′ is less than the difference between T2 and T2′ because the intra-burst pulse frequency of pulse burst 74A is greater than the intra-burst pulse frequency of pulse burst 74B. Since interval 76A extends by the same amount of time as interval 76B, the percentage of interval 76A covered by pulse burst 74A is less than the percentage of interval 76B covered by pulse burst 74B. Although each pulse burst in the set of pulse bursts 74 is shown as including three pulses, this is not required. In one or more examples not shown in FIG. 4 , a pulse burst may include more than three pulses or less than three pulses. Additionally, each pulse burst in a pulse burst sequence does not necessarily have the same number of pulses. In some examples, a pulse burst in a pulse burst sequence may have a different number of pulses than one or more other pulse bursts in the pulse burst sequence.

In some examples, processing circuit 40 may control stimulation generation circuit 44 to deliver another pulse burst sequence that is substantially identical to first pulse burst sequence 72 that begins at T5. In some examples, processing circuit 40 may control stimulation generation circuit 44 to repeat first pulse burst sequence 72 for a period of time until IMD 16 detects that pathological brain signals are suppressed. In response to detecting that pathological brain signals are suppressed, processing circuit 40 may stop delivering first pulse burst sequence 72, or if additional therapy is being delivered to the brain, stop delivering all electrical stimulation altogether. In some examples, processing circuit 40 may control stimulation generation circuit 44 to repeat first pulse burst sequence 72, but with time gaps between delivering pulse burst sequences. In some examples, IMD 16 may deliver multiple pulse burst sequences, each of which is different from the other pulse burst sequences.

FIG5 is a conceptual diagram of a second timing diagram 80 illustrating a second pulse burst sequence 82 according to one or more techniques of the present disclosure. As can be seen in FIG5, the second pulse burst sequence 82 includes a set of pulse bursts 84A-84F (collectively referred to as "pulse bursts 84"). Each pulse burst in the set of pulse bursts 84 may start at the beginning of a corresponding pulse burst interval in pulse burst intervals 86A-86F. Pulse burst 84A starts at the beginning of pulse burst interval 86A, pulse burst 84B starts at the beginning of pulse burst interval 86B, pulse burst 84C starts at the beginning of pulse burst interval 86C, pulse burst 84D starts at the beginning of pulse burst interval 86D, pulse burst 84E starts at the beginning of pulse burst interval 86E, and pulse burst 84F starts at the beginning of pulse burst interval 86F.

The second pulse burst sequence 82 is similar to the first pulse burst sequence 72 of FIG. 4 , except that the second pulse burst sequence 82 includes six pulse bursts, while the first pulse burst sequence 72 includes four pulse bursts. The IMD 16 may deliver the second pulse burst sequence 82 according to any of the techniques described in FIGS. 1 to 4 . As can be seen in FIG. 5 , each pulse burst in the set of pulse bursts 84 may correspond to a corresponding intra-burst pulse frequency. Pulse burst 84A may correspond to a first intra-burst pulse frequency, pulse burst 84B may correspond to a second intra-burst pulse frequency, pulse burst 84C may correspond to a third intra-burst pulse frequency, pulse burst 84D may correspond to a fourth intra-burst pulse frequency, pulse burst 84E may correspond to a fifth intra-burst pulse frequency, and pulse burst 84F may correspond to a sixth intra-burst pulse frequency. In one example, the first intra-burst pulse frequency corresponding to pulse burst 84A is 250 Hz, the second intra-burst pulse frequency corresponding to pulse burst 84B is 70 Hz, the third intra-burst pulse frequency corresponding to pulse burst 84C is 200 Hz, the fourth intra-burst pulse frequency corresponding to pulse burst 84D is 500 Hz, the fifth intra-burst pulse frequency corresponding to pulse burst 84E is 140 Hz, and the sixth intra-burst pulse frequency corresponding to pulse burst 84F is 250 Hz. Thus, in the example of FIG5 , each pulse burst in the set of pulse bursts 84 corresponds to a respective intra-burst pulse frequency that is different from and non-harmonic to the intra-burst pulse frequency of an adjacent pulse burst.

FIG6 is a conceptual diagram illustrating a third timing diagram 90 of a third pulse burst sequence 92 in accordance with one or more techniques of the present disclosure. As can be seen in FIG5, the third pulse burst sequence 92 includes a set of pulse bursts 94A-94F (collectively referred to as "pulse bursts 94"). Each pulse burst in the set of pulse bursts 94 may start at the beginning of a corresponding pulse burst interval in pulse burst intervals 96A-96F. Pulse burst 94A starts at the beginning of pulse burst interval 96A, pulse burst 94B starts at the beginning of pulse burst interval 96B, pulse burst 94C starts at the beginning of pulse burst interval 96C, pulse burst 94D starts at the beginning of pulse burst interval 96D, pulse burst 94E starts at the beginning of pulse burst interval 96D, and pulse burst 94F starts at the beginning of pulse burst interval 96F.

The third pulse burst sequence 92 is similar to the second pulse burst sequence 82 of FIG. 5 , except that the intra-burst pulse frequency of at least some of the pulse bursts in the pulse bursts 94 may be different from the corresponding pulse bursts of the pulse bursts 84 of FIG. 5 . IMD 16 may deliver the third pulse burst sequence 92 according to any of the techniques described in FIG. 1 to FIG. 5 . As can be seen in FIG. 5 , each pulse burst in the set of pulse bursts 94 may correspond to a corresponding intra-burst pulse frequency. Pulse burst 94A may correspond to a first intra-burst pulse frequency, pulse burst 94B may correspond to a second intra-burst pulse frequency, pulse burst 94C may correspond to a third intra-burst pulse frequency, pulse burst 94D may correspond to a fourth intra-burst pulse frequency, pulse burst 94E may correspond to a fifth intra-burst pulse frequency, and pulse burst 94F may correspond to a sixth intra-burst pulse frequency. In one example, the first intra-burst pulse frequency corresponding to pulse burst 94A is 250 Hz, the second intra-burst pulse frequency corresponding to pulse burst 94B is 70 Hz, the third intra-burst pulse frequency corresponding to pulse burst 94C is 100 Hz, the fourth intra-burst pulse frequency corresponding to pulse burst 94D is 500 Hz, the fifth intra-burst pulse frequency corresponding to pulse burst 94E is 140 Hz, and the sixth intra-burst pulse frequency corresponding to pulse burst 94F is 50 Hz. Thus, in the example of FIG5 , each pulse burst in the set of pulse bursts 94 corresponds to a respective intra-burst pulse frequency that is different from and non-harmonic to the intra-burst pulse frequency of an adjacent pulse burst.

FIG7 is a conceptual diagram of a fourth timing diagram 100 illustrating a fourth pulse burst sequence 102 in accordance with one or more techniques of the present disclosure. As can be seen in FIG7, the fourth pulse burst sequence 102 includes a set of pulse bursts 104A-104F (collectively, "pulse bursts 104"). Each pulse burst in the set of pulse bursts 104 may start at the beginning of a corresponding pulse burst interval in the pulse burst intervals 106A-106F. Pulse burst 104A starts at the beginning of pulse burst interval 106A, pulse burst 104B starts at the beginning of pulse burst interval 106B, pulse burst 104C starts at the beginning of pulse burst interval 106C, pulse burst 104D starts at the beginning of pulse burst interval 106D, pulse burst 104E starts at the beginning of pulse burst interval 106E, and pulse burst 104F starts at the beginning of pulse burst interval 106F.

The first pulse burst sequence 72 of FIG. 4 , the second pulse burst sequence 82 of FIG. 5 , and the third pulse burst sequence 92 of FIG. 6 are examples of pulse burst sequences that the IMD 16 may deliver to the brain 28 of the patient 12 , but the techniques described herein are not limited to these examples. The IMD 16 may deliver a fourth pulse burst sequence 102 according to any of the techniques described in FIGS. 1 to 5 . Additionally or alternatively, the IMD 16 may deliver other pulse burst sequences. For example, the fourth pulse burst sequence 102 includes the group of pulse bursts 104.

Although FIG. 7 shows the group of pulse bursts 104 as including five pulse bursts, the group of pulse bursts 104 may include more than five pulse bursts or less than five pulse bursts. Each pulse burst in the group of pulse bursts 104 may include two or more pulses. For example, the pulse burst 104A may include a first pulse delivered at time T1 and a second pulse delivered at time T1'. In some examples, the pulse burst 104A may include one or more intervening pulses between the first pulse and the second pulse delivered between time T1 and time T1'. The IMD 16 may deliver the pulse burst 104A at a first pulse burst frequency. The amount of time between T1 and T1' may vary depending on the number of pulses in the pulse burst 104A and the pulse frequency within the first burst of the pulse burst 104A. The pulse burst 104B may include a first pulse delivered at time T2 and a second pulse delivered at time T2'. In some examples, the pulse burst 104B may include one or more intervening pulses delivered between time T2 and time T2'. The IMD 16 may deliver the pulse burst 104B at a second pulse burst frequency. The amount of time between T2 and T2' may vary depending on the number of pulses in the pulse burst 104A and the first intra-burst pulse frequency of the pulse burst 104A. The pulse burst 104C, the pulse burst 104D, and the pulse burst 104X may each be associated with a corresponding intra-burst pulse frequency and a corresponding number of two or more pulses. Thus, the pulse burst 104 may represent many different exemplary pulse bursts. In some examples, each pulse burst in the set of pulse bursts 104 has a uniform pulse frequency (e.g., the spacing between each pair of consecutive pulses in the pulse burst is equal to the spacing between each other pair of consecutive pulses in the pulse burst).

In some examples, adjacent pulse bursts in the group of pulse bursts 104 have different and non-harmonic intra-burst pulse frequencies, so that the fourth pulse burst sequence 102 can suppress one or more pathological brain signals without entraining one or more pathological brain signals. It may be beneficial. By delivering the fourth pulse burst sequence 102 at the pulse burst frequency, the IMD 16 can suppress one or more detected pathological brain signals. Delivering the fourth pulse burst sequence 102 to include the group of pulse bursts 104 (including the varying intra-burst pulse frequency) can prevent the fourth pulse burst sequence 102 from entraining pathological brain signals. Using a varying and non-harmonic intra-burst pulse frequency prevents the fourth sequence of pulse bursts 102 from entraining pathological brain signals because when the pulse bursts include pulse bursts of varying and non-harmonic frequencies, pathological brain signals are less likely to follow the pulse burst frequency. In some examples, the IMD 16 can deliver more than one pulse burst sequence continuously. In some examples, the IMD 16 can cycle between delivering one or more pulse burst sequences and pausing stimulation delivery.

FIG8 is a flow chart illustrating exemplary operations for controlling IMD 16 to deliver stimulation having one or more patterns configured to suppress one or more pathological brain signals, in accordance with one or more techniques of the present disclosure. FIG8 is described with respect to programmer 14 and IMD 16 of FIGS. 1-3. However, the techniques of FIG8 may be performed by different components of programmer 14 and IMD 16, or by additional or alternative medical devices.

The processing circuit 40 of the IMD 16 may control the stimulation generation circuit 44 of the IMD 16 to deliver one or more pulse burst sequences to a region of the brain 28 of the patient 12 in order to suppress one or more pathological brain signals (802). In some examples, the processing circuit 40 may detect one or more pathological brain signals or detect one or more symptoms associated with one or more pathological brain signals, so that the processing circuit 40 determines the pulse burst frequency and/or the pulse frequency within the burst for each burst based on one or more detected pathological frequencies of the patient. However, not all examples require this sensing feature. In some examples, the processing circuit 40 may control the stimulation generation circuit 44 to deliver a pulse burst sequence, wherein the frequency of each pulse burst in the pulse burst sequence is different from the frequency of an adjacent pulse burst in the pulse burst sequence. By delivering a pulse burst sequence with pulse bursts having varying frequencies, the IMD 16 can suppress one or more pathological signals without entraining one or more pathological brain signals. Additionally or alternatively, the processing circuit 40 may control the stimulation generation circuit 44 to deliver a pulse burst sequence such that the frequency of each pulse burst in the pulse burst sequence is non-harmonic with the frequency of each adjacent pulse burst in the pulse burst sequence. By delivering adjacent pulse bursts that are non-harmonic in frequency, IMD 16 may also prevent the pulse burst sequence from entraining pathological brain signals while suppressing the pathological brain signals.

Processing circuitry 40 may control stimulation generation circuitry 44 to stop delivering one or more pulse burst sequences (808). In some examples, processing circuitry 40 may control stimulation generation circuitry 44 to stop delivering one or more pulse burst sequences based on determining that one or more pathological brain signals are suppressed, but this is not required. IMD 16 may stop delivering one or more pulse burst sequences when a predetermined amount of time has passed, or in response to a user input to programmer 14 to stop delivering electrical stimulation. IMD 16 may restart stimulation at a later scheduled time according to one or more pulse burst sequences or in response to detecting a pathological brain signal.

FIG9 is a flow chart illustrating exemplary operations for detecting one or more pathological brain signals and controlling IMD 16 to deliver stimulation having one or more patterns configured to suppress the one or more pathological brain signals, in accordance with one or more techniques of the present disclosure. FIG9 is described with respect to programmer 14 and IMD 16 of FIGS. 1-3. However, the techniques of FIG9 may be performed by different components of programmer 14 and IMD 16, or by additional or alternative medical devices.

Sensing circuit 46 of IMD 16 is configured to sense bioelectrical brain signals in a region of brain 28 of patient 12. (902) Processing circuit 40 may receive the sensed bioelectrical brain signals from sensing circuit 46. Processing circuit 40 may determine whether the bioelectrical brain signals represent pathological brain signals (904). In some examples, processing circuit 40 may analyze any one or a combination of the frequency of the bioelectrical brain signals, the amplitude of the bioelectrical brain signals, and the phase of the bioelectrical brain signals to determine whether the bioelectrical brain signals represent pathological brain signals. For example, bioelectrical brain signals oscillating in the beta frequency range (e.g., 12 Hz to 35 Hz) in the subthalamic nucleus, internal globus pallidus, external globus pallidus, and/or other regions of the basal ganglia may be associated with one or more motor symptoms, including, for example, rigidity, amnesia, bradykinesia, dyskinesia, and/or resting tremor. Therefore, processing circuit 40 may determine that these bioelectrical brain signals oscillating in the beta frequency range represent pathological brain signals.

Based on determining that the sensed bioelectrical brain signal does not represent a pathological brain signal (the "No" branch of box 904), the processing circuit 40 may control the sensing circuit 46 to continue sensing the bioelectrical brain signal. Based on determining that the sensed bioelectrical brain signal represents a pathological brain signal (the "Yes" branch of box 904), the processing circuit 40 may control the stimulation generation circuit 44 to deliver one or more pulse burst sequences to the area in the brain 28 of the patient 12 where the sensing circuit 46 senses the pathological brain signal (906). In some examples, the processing circuit 40 may control the stimulation generation circuit 44 to deliver a pulse burst sequence, wherein the frequency of each pulse burst in the pulse burst sequence is different from the frequency of an adjacent pulse burst in the pulse burst sequence. By delivering a pulse burst sequence with pulse bursts having varying frequencies, the IMD 16 can suppress one or more pathological signals without entraining one or more pathological brain signals. Additionally or alternatively, the processing circuit 40 may control the stimulation generation circuit 44 to deliver a pulse burst sequence such that the frequency of each pulse burst in the pulse burst sequence is non-harmonic with the frequency of each adjacent pulse burst in the pulse burst sequence. By delivering adjacent pulse bursts that are non-harmonic in frequency, IMD 16 may also prevent the pulse burst sequence from entraining pathological brain signals while suppressing the pathological brain signals.

Processing circuit 40 may determine whether the sensed pathological brain signal is suppressed (908). In some examples, to determine whether the sensed pathological brain signal is suppressed, processing circuit 40 may compare the current amplitude of the pathological brain signal with the amplitude of the pathological brain signal before delivering one or more pulse burst sequences. When the current amplitude is less than the amplitude before delivering electrical stimulation by more than a threshold difference, processing circuit 40 may determine that the sensed pathological brain signal is suppressed. In some examples, processing circuit 40 may determine that the sensed pathological brain signal is suppressed when IMD 16 can no longer detect the pathological brain signal.

Based on determining that the sensed pathological brain signal is not suppressed (the "No" branch of block 908), processing circuitry 40 may control stimulation generation circuitry 44 to continue delivering one or more pulse burst sequences. Based on determining that the sensed pathological brain signal is suppressed (the "Yes" branch of block 908), processing circuitry 40 may control stimulation generation circuitry 44 to stop delivering one or more pulse burst sequences to the region of brain 28 of patient 12 (910).

The following examples are exemplary of the systems, devices, and methods described herein.

Embodiment 1: A system comprising: a processing circuit configured to: receive information representing a bioelectrical brain signal recorded from a patient's brain; determine at least one pathological frequency of the bioelectrical brain signal based on the information; select a pulse burst sequence at a pulse burst frequency based on the at least one pathological frequency, the pulse burst sequence at least partially defining electrical stimulation capable of being delivered to a region of the patient's brain, wherein adjacent pulse bursts within the sequence include different intra-burst pulse frequencies; and control a medical device to deliver the electrical stimulation including the pulse burst sequence to the region of the patient's brain.

Embodiment 2: The system of embodiment 1, wherein by delivering the electrical stimulation to the brain of the patient, the processing circuit causes synaptic inhibition so as to suppress the bioelectrical computer signal in the region of the brain of the patient.

Embodiment 3: The system according to any one of embodiments 1 to 2, wherein the intra-burst pulse frequency of each pulse burst in the pulse burst sequence is non-harmonic with the intra-burst pulse frequency of each adjacent pulse burst in the pulse burst sequence.

Embodiment 4: A system according to any one of embodiments 1 to 3, wherein the pulse burst frequency matches at least one pathological frequency of the bioelectrical computer signal.

Embodiment 5: A system according to Embodiment 4, wherein in order to select the pulse burst frequency based on the bioelectrical computer signal, the processing circuit is configured to select the pulse burst frequency so that each pulse burst in the pulse burst sequence is aligned with a characteristic of a corresponding cycle of the bioelectrical computer signal.

Embodiment 6: A system according to embodiment 5, wherein each pulse burst in the pulse burst sequence is aligned with a valley of the bioelectrical computer signal.

Embodiment 7: The system according to any one of embodiments 1 to 6, wherein the intra-burst pulse frequency of each pulse burst in the pulse burst sequence is in the range of 70 Hertz (Hz) to 500 Hz.

Embodiment 8: A system according to any one of Embodiments 1 to 7, wherein the pulse burst sequence comprises a first pulse burst having a first intra-burst pulse frequency of 250 Hz, a second pulse burst having a second intra-burst pulse frequency of 70 Hz, a third pulse burst having a third intra-burst pulse frequency of 500 Hz, and a fourth pulse burst having a fourth intra-burst pulse frequency of 70 Hz.

Embodiment 9: The system of Embodiment 8, wherein the range of pathological frequencies comprises a beta band extending within the range of 12 Hz to 35 Hz.

Embodiment 10: A system according to any one of Embodiments 1 to 9, wherein the processing circuit is further configured to: determine that the pathological brain signal is suppressed based on the information representing the bioelectrical brain signal received after the delivery of the electrical stimulation; and control the medical device to stop delivering the electrical stimulation to the area of the patient's brain based on the determination that the pathological brain signal is suppressed.

Embodiment 11: A system according to any one of embodiments 1 to 10, wherein the medical device comprises an implantable medical device.

Embodiment 12: A method, the method comprising: receiving, by a processing circuit, information representing a bioelectrical computer signal recorded from a patient's brain; determining, by the processing circuit and based on the information, at least one pathological frequency of the bioelectrical computer signal; selecting, by the processing circuit and based on the at least one pathological frequency, a pulse burst sequence at a pulse burst frequency, the pulse burst sequence at least partially defining electrical stimulation capable of being delivered to a region of the patient's brain, wherein adjacent pulse bursts within the sequence include different intra-burst pulse frequencies; and controlling, by the processing circuit, a medical device to deliver the electrical stimulation including the pulse burst sequence to the region of the patient's brain.

Example 13: The method according to Example 12, wherein delivering the electrical stimulation to the brain of the patient causes synaptic inhibition so as to inhibit the bioelectrical computer signal in the area of the brain of the patient.

Embodiment 14: The method according to any one of Embodiments 12 to 13, wherein the intra-burst pulse frequency of each pulse burst in the pulse burst sequence is non-harmonic with the intra-burst pulse frequency of each adjacent pulse burst in the pulse burst sequence.

Embodiment 15: A method according to any one of embodiments 12 to 14, wherein the pulse burst frequency matches at least one pathological frequency of the bioelectrical computer signal.

Embodiment 16: A method according to Embodiment 15, wherein selecting the pulse burst frequency based on the bioelectrical computer signal includes selecting the pulse burst frequency so that each pulse burst in the pulse burst sequence is aligned with a feature of a corresponding cycle of the bioelectrical computer signal.

Embodiment 17: The method according to Embodiment 16, wherein each pulse burst in the pulse burst sequence is aligned with a valley of the bioelectrical computer signal.

Embodiment 18: The method according to any one of Embodiments 12 to 17, wherein the intra-burst pulse frequency of each pulse burst in the pulse burst sequence is in the range of 70 Hertz (Hz) to 500 Hz.

Example 19: According to the method described in any one of Examples 12 to 18, the method further includes: determining that the pathological brain signal is suppressed based on the information representing the bioelectrical brain signal received after delivering the electrical stimulation; and based on determining that the pathological brain signal is suppressed, controlling the medical device to stop delivering the electrical stimulation to the area of the patient's brain.

Embodiment 20: A computer-readable medium comprising instructions which, when executed by a processor, causes the processor to: receive information representing a bioelectrical brain signal recorded from a patient's brain; determine at least one pathological frequency of the bioelectrical brain signal based on the information; select a pulse burst sequence at a pulse burst frequency based on the at least one pathological frequency, the pulse burst sequence at least partially defining electrical stimulation capable of being delivered to a region of the patient's brain, wherein adjacent pulse bursts within the sequence include different intra-burst pulse frequencies; and control a medical device to deliver the electrical stimulation comprising the pulse burst sequence to the region of the patient's brain.

For various aspects implemented in software, at least some of the functionality attributed to the systems and devices described in this disclosure may be embodied as instructions on a computer-readable storage medium, such as RAM, DRAM, SRAM, FRAM, magnetic disk, optical disk, flash memory, or various forms of EPROM or EEPROM. The instructions may be executed to support one or more aspects of the functionality described in this disclosure.

In addition, in some aspects, the functions described herein can be arranged in dedicated hardware and/or software modules. Describing different features as modules or units is intended to highlight different functional aspects, and does not necessarily imply that such modules or units must be implemented by separate hardware or software components. On the contrary, the functions associated with one or more modules or units can be performed by separate hardware or software components, or integrated in common or separate hardware or software components. In addition, these techniques can be fully implemented in one or more circuits or logic elements. The technology disclosed herein can be implemented in various devices or equipment, including an IMD, an external programmer, a combination of an IMD and an external programmer, an integrated circuit (IC) or a group of ICs and/or discrete circuits residing in an IMD and/or an external programmer.

Claims (15)

1. A system, the system comprising:

Processing circuitry configured to:

Receiving information representative of a biometric computer signal recorded from a brain of a patient;

Determining at least one pathological frequency of the bio-computer signal based on the information;

selecting a pulse burst sequence at a pulse burst frequency based on the at least one pathological frequency, the pulse burst sequence at least partially defining electrical stimulation capable of being delivered to a region of a brain of a patient, wherein adjacent pulse bursts within the sequence comprise different intra-burst pulse frequencies; and

Controlling a medical device to deliver the electrical stimulation comprising the pulse burst sequence to the region of the brain of the patient.

2. The system of claim 1, wherein the processing circuit causes synaptic inhibition by delivering the electrical stimulus to the brain of the patient so as to inhibit the bio-computer signal in the region of the brain of the patient.

3. The system of claim 1, wherein an intra-burst pulse frequency of each pulse burst in the pulse burst sequence is non-harmonic to an intra-burst pulse frequency of each adjacent pulse burst in the pulse burst sequence.

4. The system of claim 1, wherein the pulse burst frequency matches at least one pathological frequency of the bio-computer signal.

5. The system of claim 4, wherein to select the pulse burst frequency based on the bio-computer signal, the processing circuit is configured to select the pulse burst frequency such that each pulse burst in the pulse burst sequence is aligned with a feature of a respective cycle of the bio-computer signal.

6. The system of claim 5, wherein each pulse burst in the sequence of pulse bursts is aligned with a valley of the bio-computer signal.

7. The system of claim 1, wherein an intra-burst pulse frequency of each pulse burst in the sequence of pulse bursts is in a range of 70 hertz (Hz) to 500 Hz.

8. The system of claim 1, wherein the pulse burst sequence includes a first pulse burst having a first intra-burst pulse frequency of 250Hz, a second pulse burst having a second intra-burst pulse frequency of 70Hz, a third pulse burst having a third intra-burst pulse frequency of 500Hz, and a fourth pulse burst having a fourth intra-burst pulse frequency of 70 Hz.

9. The system of claim 8, wherein the range of the pathological frequencies includes a beta band extending in a range of 12Hz to 35 Hz.

10. The system of claim 1, wherein the processing circuit is further configured to:

determining that the pathological brain signal is inhibited based on receiving the information representative of the biological computer signal after delivering the electrical stimulus; and

Based on determining that the pathological brain signal is inhibited, the medical device is controlled to cease delivering the electrical stimulus to the region of the brain of the patient.

11. The system of claim 1, wherein the medical device comprises an implantable medical device.

12. A method, the method comprising:

receiving, by the processing circuit, information representative of a biometric computer signal recorded from the brain of the patient;

determining, by the processing circuit and based on the information, at least one pathological frequency of the bio-computer signal;

Selecting, by the processing circuit and based on the at least one pathological frequency, a pulse burst sequence at a pulse burst frequency, the pulse burst sequence at least partially defining electrical stimulation that can be delivered to a region of a brain of a patient, wherein adjacent pulse bursts within the sequence include different intra-burst pulse frequencies; and

Controlling, by the processing circuit, a medical device to deliver the electrical stimulation comprising the pulse burst sequence to the region of the brain of the patient.

13. The method of claim 12, wherein an intra-burst pulse frequency of each pulse burst in the pulse burst sequence is non-harmonic to an intra-burst pulse frequency of each adjacent pulse burst in the pulse burst sequence.

14. The method of claim 12, wherein the pulse burst frequency matches at least one pathological frequency of the bio-computer signal.

15. The method of claim 15, wherein selecting the pulse burst frequency based on the bio-computer signal comprises selecting the pulse burst frequency such that each pulse burst in the pulse burst sequence is aligned with a feature of a respective cycle of the bio-computer signal.