Systems and methods for modulating neurosynchronism

Abstract

Methods and systems for addressing issues related to synchronism of neural tissue signals. A spectrum of a neural signal of a patient may be measured when the patient is asymptomatic and compared to the signal during the onset of the symptom to determine whether the neural signal should be enhanced or interrupted. Depending on changes in the neural signal, enhanced or interrupted neural therapy is generated and confirmed or adjusted.

Description

Cross Reference to Related Applications

[0001] This application claims priority to U.S. Provisional Patent Application Serial No. 63 / 536,980, filed September 7, 2023, the disclosure of which is incorporated herein by reference. BACKGROUND

[0002] The primary disease states affecting the nervous system are characterized by abnormal or unusual neural synchrony. Abnormally high neural synchrony can be associated with chronic pain, Parkinson’s disease, epilepsy, and / or tremor. Abnormally low neural synchrony can be associated with Alzheimer’s disease, schizoid disorder, and / or bipolar disorder. Normalizing synchrony has been shown to have benefits such as symptom control for Parkinson’s disease, reduction of pathology for Alzheimer’s disease, and / or enhancement of cognition. Some research suggests that neural stimulation related to patient’s intrinsic neural oscillations can provide therapeutic benefits. New methods and alternatives are needed to configure and deliver neural therapy. SUMMARY

[0003] The present inventors have recognized, among other things, that a problem to be solved is the need for new and / or alternative systems and methods to modulate neural synchrony. Therapeutic benefits can be provided by reducing abnormally high neural synchrony for certain diseases and / or by enhancing abnormally low neural synchrony for other diseases.

[0004] A first illustrative and non-limiting example takes the form of a medical device system including an implantable pulse generator having pulse generator circuitry including each of communication circuitry for communicating with one or more external devices, output circuitry for generating output pulses, and sensing circuitry for sensing one or more signals; a lead having a plurality of electrodes thereon and adapted to position one or more electrodes within a patient and connectable to the implantable pulse generator; and an external device adapted to communicate with the implantable pulse generator, wherein the system is adapted for use with a patient having a neurological disease with symptom onset, characterized by: the implantable pulse generator configured to receive an indication of symptom onset; the implantable pulse generator configured to record symptomatic neural activity during symptom onset in response to the indication of symptom onset; the implantable pulse generator or the external device using data transmitted from the implantable pulse generator adapted to perform the following operations: identify a characteristic frequency of non-symptomatic neural activity and a characteristic frequency of symptomatic neural activity; and select the characteristic frequency that differentiates non-symptomatic neural activity from symptomatic neural activity; and the implantable pulse generator, in response to the identifying and selecting, emitting neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency.

[0005] Additionally or alternatively, the implantable pulse generator is configured to record non-symptomatic neural activity from the patient when the patient is not experiencing symptom onset.

[0006] Additionally or alternatively, the non-symptomatic neural activity is obtained from one of: a library of patients who have received an implanted lead; a patient with similar neurological disease, age, gender, and / or disease state; or an average of other patients.

[0007] Additionally or alternatively, the implanted pulse generator or external device identifies the characteristic frequency by performing a mathematical transform from time domain to frequency domain on data of the non-symptomatic neural activity and the symptomatic neural activity, and identifying peaks in the frequency domain of the non-symptomatic neural activity and the symptomatic neural activity.

[0008] Additionally or alternatively, the implanted pulse generator issuing the neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency is performed by the implanted pulse generator identifying a source of the symptomatic neural activity having the selected characteristic frequency.

[0009] Additionally or alternatively, the implanted pulse generator issuing the neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency is performed by the implanted pulse generator identifying a location of the symptomatic neural activity having the selected characteristic frequency, and issuing the neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency by selecting electrodes for delivering the neural stimulation to deliver an electric field to the location of the second neural activity.

[0010] Additionally or alternatively, the implanted pulse generator issuing the neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency is performed by the implanted pulse generator by: a) sensing the neural activity using each of a first subset of the plurality of electrodes and a second subset of the plurality of electrodes; b) determining which of the subsets of the plurality of electrodes used in a) acquires a stronger signal at the selected frequency; and c) using the subset of the plurality of electrodes identified in b) to issue the neural stimulation.

[0011] Additionally or alternatively, the implanted pulse generator issuing the neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency is performed by the implanted pulse generator by: sensing further neural activity; filtering the sensed further neural activity to obtain a signal at the selected characteristic frequency; determining a peak time at the characteristic frequency; and issuing the neural stimulation at the peak time to enhance neural activity at the selected characteristic frequency.

[0012] Additionally or alternatively, the implantable pulse generator emitting the neural stimulus to interrupt or enhance neural activity at a selected characteristic frequency is performed by the implantable pulse generator by: sensing further neural activity; filtering the sensed further neural activity to obtain a signal at the selected characteristic frequency; determining a peak time at the characteristic frequency; and emitting the neural stimulus with a delay relative to the peak time to interrupt neural activity at the selected characteristic frequency.

[0013] Additionally or alternatively, the implantable pulse generator emitting the neural stimulus to interrupt or enhance neural activity at a selected characteristic frequency is performed by the implantable pulse generator by: the implantable pulse generator emitting pulses at a frequency that is in a range of about 105% to 125% of a period of a period at the characteristic frequency to interrupt or enhance neural activity at the selected characteristic frequency.

[0014] Additionally or alternatively, the implantable pulse generator emitting the neural stimulus to interrupt or enhance neural activity at a selected characteristic frequency is performed by the implantable pulse generator by: the implantable pulse generator emitting pulses at the characteristic frequency to enhance neural activity at the selected frequency.

[0015] Additionally or alternatively, emitting the neural stimulus by the implantable pulse generator to interrupt or enhance neural activity at a selected characteristic frequency is performed in response to a trigger, wherein the trigger is one of: a patient indicating an occurrence of a symptom; detecting a characteristic frequency emerging in further sensed neural activity; or an indication that the patient is or is about to perform a cognitive or physical exercise.

[0016] Additionally or alternatively, the external device is a patient remote control or a clinician programmer. Additionally or alternatively, the lead has a proximal end for coupling to the pulse generator and a distal end carrying a plurality of electrodes, the distal end of the lead being configured to be positioned in a brain of the patient, and the pulse generator and the lead together form an implantable system for deep brain stimulation.

[0017] Another illustrative and non-limiting example takes the form of a method of treating a patient having a neurological disease with symptom onset, the method comprising: recording first neural activity while the patient is not experiencing a symptom onset; receiving an indication of a symptom onset; recording second neural activity during the symptom onset; identifying a characteristic frequency of the first neural activity and a characteristic frequency of the second neural activity; selecting a characteristic frequency that occurs only during the second neural activity; and emitting a neural stimulus to interrupt neural activity at the selected characteristic frequency.

[0018] Additionally or alternatively, the step of identifying the characteristic frequency comprises performing a mathematical transformation from time domain to frequency domain on data of the first neural activity and the second neural activity, and identifying a peak in the frequency domain of the first neural activity and the second neural activity.

[0019] Additionally or alternatively, the step of emitting the neural stimulus to interrupt neural activity at the selected characteristic frequency includes identifying a source of the second neural activity having the selected characteristic frequency.

[0020] Additionally or alternatively, the method further includes identifying a location of the second neural activity having the selected characteristic frequency; and emitting the neural stimulus to interrupt neural activity at the selected characteristic frequency by selecting an electrode for delivering the neural stimulus to deliver an electric field at the location of the second neural activity.

[0021] Additionally or alternatively, the step of emitting the neural stimulus is performed using an implantable neural stimulator having a lead with a plurality of electrodes, the neural stimulator configured to selectively use a subset of the plurality of electrodes to sense neural activity, and the method further includes: a) sensing neural activity using each of a first subset of the plurality of electrodes and a second subset of the plurality of electrodes; b) determining which of the subsets of the plurality of electrodes used in a) acquires a stronger signal at the selected characteristic frequency; and c) emitting the neural stimulus using the subset of the plurality of electrodes identified in b).

[0022] Additionally or alternatively, the step of emitting the neural stimulus includes: sensing neural activity; filtering the sensed neural activity to obtain a signal at the selected characteristic frequency; determining a peak time at the characteristic frequency; and emitting the neural stimulus with a delay relative to the peak time. Additionally or alternatively, the delay is selected to achieve a phase delay in the range of 120 to about 240 degrees.

[0023] Additionally or alternatively, the step of emitting the neural stimulus is performed at a frequency that is periodic in the range of about 105% to 125% of a period of the characteristic frequency.

[0024] Additionally or alternatively, the steps of recording the first neural activity and the second neural activity are performed with an implantable system.

[0025] Additionally or alternatively, the step of emitting the neural stimulus is performed in response to a trigger. Additionally or alternatively, the trigger is a patient input indicating an onset of a symptom. Additionally or alternatively, the trigger is a detection of a characteristic frequency that only occurs in the second neural activity.

[0026] Another illustrative and non-limiting example takes the form of a method of treating a patient having a neurological disease with symptom onset, the method including: obtaining a first neural activity representing a desired neural activity frequency spectrum data; receiving an indication of a symptom onset; recording a second neural activity during the symptom onset; identifying a characteristic frequency of the first neural activity and a characteristic frequency of the second neural activity; selecting the characteristic frequency that only occurs during the second neural activity; and emitting a neural stimulus to interrupt neural activity at the selected characteristic frequency.

[0027] Additionally or alternatively, the step of identifying characteristic frequencies includes performing a mathematical transformation from the time domain to the frequency domain on the data of the second neural activity and identifying the peak of the second neural activity in the frequency domain.

[0028] Additionally or alternatively, the step of emitting neural stimulation to interrupt a selected characteristic frequency includes identifying a source of second neural activity having the selected characteristic frequency.

[0029] Additionally or alternatively, the method further includes identifying the location of a second neural activity having a selected characteristic frequency; and emitting a neural stimulus to interrupt the neural activity at the selected characteristic frequency by selecting electrodes for delivering the neural stimulus to deliver an electric field at the location of the second neural activity.

[0030] Additionally or alternatively, the step of emitting neural stimulation is performed using an implantable neurostimulator with leads having multiple electrodes, the neurostimulator being configured to selectively use a subset of the multiple electrodes to sense neural activity, and the method further includes: a) using at least a first subset and a second subset of the multiple electrodes to sense neural activity; b) determining which of the subsets of the multiple electrodes used in a) acquires a stronger signal at a selected characteristic frequency; and c) using the subset of the multiple electrodes identified in b) to emit neural stimulation.

[0031] Additionally or alternatively, the step of emitting a neural stimulus includes: sensing neural activity; filtering the sensed neural activity to obtain a signal at a selected characteristic frequency; determining the peak time of the neural activity at the characteristic frequency; and emitting the neural stimulus at a delay relative to the peak time.

[0032] Alternatively or additionally, a delay is selected to achieve a phase delay in the range of 120 to approximately 240 degrees.

[0033] Additionally or alternatively, the steps of emitting neural stimulation are performed at a frequency that is approximately 105% to 125% of the period of the characteristic frequency.

[0034] Alternatively or additionally, the step of recording secondary neural activity is performed via an implanted system. Alternatively or additionally, the step of emitting neural stimulation is performed in response to a trigger. Alternatively or additionally, the trigger is a patient input indicating the occurrence of symptoms. Alternatively or additionally, the trigger is the detection of a characteristic frequency that occurs only in secondary neural activity.

[0035] Another illustrative and non-limiting example takes the form of a method for treating a patient with a neurological disorder experiencing symptom attacks, the method comprising: recording first neural activity when the patient is not experiencing a symptom attack; receiving instructions from the patient regarding a symptom attack; recording second neural activity during a symptom attack; identifying characteristic frequencies of the first neural activity and characteristic frequencies of the second neural activity; selecting characteristic frequencies that occur only during the first neural activity; and emitting neural stimulation to enhance neural activity at the selected characteristic frequencies.

[0036] Additionally or alternatively, the step of identifying characteristic frequencies includes performing a mathematical transformation from the time domain to the frequency domain on the data of the first and second neural activities, and identifying the peak values ​​of the first and second neural activities in the frequency domain.

[0037] Additionally or alternatively, the step of emitting neural stimulation to enhance selected characteristic frequencies includes identifying sources of neural activity having selected characteristic frequencies.

[0038] Additionally or alternatively, the method may include identifying the location of neural activity having a selected characteristic frequency; and emitting neural stimulation to enhance neural activity at the selected characteristic frequency by selecting electrodes for delivering neural stimulation to deliver an electric field at the identified location.

[0039] Additionally or alternatively, the step of emitting neural stimulation is performed using an implantable neurostimulator with leads having multiple electrodes, the neurostimulator being configured to selectively use a subset of the multiple electrodes to sense neural activity, and the method further includes: a) using at least a first subset and a second subset of the multiple electrodes to sense neural activity; b) determining which of the subsets of the multiple electrodes used in a) acquires a stronger signal at a selected characteristic frequency; and c) using the subset of the multiple electrodes identified in b) to emit neural stimulation.

[0040] Additionally or alternatively, the step of emitting a neural stimulus includes: sensing neural activity; filtering the sensed neural activity to obtain a signal at a selected characteristic frequency; determining the peak time of the neural activity at the characteristic frequency; and emitting a neural stimulus near the peak time.

[0041] Alternatively or additionally, the steps of emitting neural stimulation are performed at a characteristic frequency.

[0042] Alternatively or additionally, the step of emitting a neural stimulus is performed in response to a trigger. Alternatively or additionally, the trigger is a patient input indicating the occurrence of symptoms. Alternatively or additionally, the trigger is the absence of a characteristic frequency that occurs only in the first neural activity.

[0043] Another illustrative and non-limiting example takes the form of a method for treating a patient with a neurological disorder experiencing symptom episodes, the method comprising: obtaining a first neural activity representing spectral data of desired neural activity; receiving instructions from the patient regarding the symptom episode; recording a second neural activity during the symptom episode; identifying characteristic frequencies of the first neural activity and characteristic frequencies of the second neural activity; selecting characteristic frequencies that occur only in the first neural activity; and emitting neural stimulation to enhance neural activity at the selected characteristic frequencies.

[0044] Additionally or alternatively, the step of identifying characteristic frequencies includes performing a mathematical transformation of the data on the second neural activity from the time domain to the frequency domain, and identifying the peak value of the second neural activity in the frequency domain.

[0045] Additionally or alternatively, the step of emitting neural stimulation to enhance selected characteristic frequencies includes identifying sources of neural activity having selected characteristic frequencies.

[0046] Additionally or alternatively, the method further includes identifying the location of a second neural activity having a selected characteristic frequency; and emitting neural stimulation to enhance the neural activity at the selected characteristic frequency by selecting electrodes for delivering neural stimulation to deliver an electric field at the location of the second neural activity.

[0047] Additionally or alternatively, the step of emitting neural stimulation is performed using an implantable neurostimulator with leads having multiple electrodes, the neurostimulator being configured to selectively use a subset of the multiple electrodes to sense neural activity, and the method further includes: a) using at least a first subset and a second subset of the multiple electrodes to sense neural activity; b) determining which of the subsets of the multiple electrodes used in a) acquires a stronger signal at a selected characteristic frequency; and c) using the subset of the multiple electrodes identified in b) to emit neural stimulation.

[0048] Additionally or alternatively, the step of emitting a neural stimulus includes: sensing neural activity; filtering the sensed neural activity to obtain a signal at a selected characteristic frequency; determining the peak time of the neural activity at the characteristic frequency; and emitting a neural stimulus near the peak time.

[0049] Alternatively or additionally, the steps of emitting neural stimulation are performed at a characteristic frequency.

[0050] Alternatively or additionally, the step of emitting a neural stimulus is performed in response to a trigger. Alternatively or additionally, the trigger is a patient input indicating the occurrence of symptoms. Alternatively or additionally, the trigger is the absence of a characteristic frequency that occurs only in the first neural activity.

[0051] The aforementioned method examples can also be performed by systems used to treat neurological disorders, such as deep brain stimulation (DBS) systems that include an implantable pulse generator, associated leads, and one or more external devices.

[0052] This invention is intended to provide an overview of the subject matter of this patent application. It is not intended to provide an exclusive or exhaustive interpretation. A detailed description is included to provide further information regarding this patent application. Attached Figure Description

[0053] In accompanying drawings that are not necessarily drawn to scale, the same numbers may describe similar parts in different views. Similar numbers with different letter suffixes may represent different instances of similar parts. The accompanying drawings are illustrated in general terms by way of example and not limitation, of the various embodiments discussed in this document.

[0054] Figure 1 An example of an implanted deep brain stimulation (DBS) system is shown;

[0055] Figure 2 Detailed information about the directional DBS conductor is shown;

[0056] Figures 3A to 3C The illustrative method is shown in boxes;

[0057] Figure 4 Frequency domain comparison is shown; and

[0058] Figures 5 to 6 An illustrative user interface is shown. Detailed Implementation

[0059] Figure 1 An illustrative deep brain stimulation (DBS) system implanted in a patient is shown. The system includes a pulse generator 10, implanted as shown in the pectoral region of patient 20. The pulse generator 10 is coupled to a lead 12, which extends subcutaneously to the head of patient 20 through a drilled hole formed in the patient's skull and then into the patient's brain. In the example shown, the lead 12 includes multiple electrodes positioned near the distal end 14 of the lead, such as... Figure 2 As shown. The lead 12 can be placed in any suitable location in the brain to identify the therapeutic target. For example, the lead 12 can be positioned such that the distal end 14 is close to the midbrain and / or in various structures known in the art for providing stimulation to treat various diseases. Electrodes on the lead 12 can be used to generate stimulation pulses / signals and / or to sense signals in the brain.

[0060] DBS can target neural tissues such as, but not limited to, the thalamus, globus pallidus, subthalamic nucleus, pontine peduncle nucleus, substantia nigra reticularis, cerebral cortex, lateral globus pallidus, medial anterior tract, periaqueductal gray matter, periventricular gray matter, habenular nucleus, subgenual cingulate gyrus, ventral intermediate nucleus, anterior nucleus, other thalamic nuclei, zona valgum, ventral internal capsule, ventral striatum, nucleus accumbens, and / or white matter tracts connecting these and other structures. Data related to DBS may include the identification of neural tissue regions, determined through analysis, that are associated with side effects or benefits observed in practice. As used in this art, “target” can refer to brain structures associated with therapeutic benefits, while “avoided” or “forbidden” areas can refer to brain structures associated with side effects.

[0061] The diseases treated may include dementia, Alzheimer's disease, Parkinson's disease, various tremors, depression, anxiety or other mood disorders, sleep-related disorders, etc. Treatment benefits may include, for example, but not limited to, improved cognition, alertness, and / or memory; enhanced mood or sleep; avoidance of pain or tremors; reduction of motor injury; and / or protection of existing functions and / or cellular structures, such as preventing tissue loss and / or cell death. Treatment benefits can be monitored using, for example, patient surveys, performance tests, and / or physical monitoring (such as monitoring gait, tremors, etc.). Side effects may include a range of problems, such as, for example, but not limited to, decreased cognition, alertness, and / or memory; decreased sleep quality; depression; anxiety; unexplained weight gain / loss; tinnitus; pain; tremors, etc. These are merely examples, and the discussion of ailments, benefits, and side effects is illustrative and not exhaustive.

[0062] The illustrative system of claim 1 includes various external devices. The clinician programmer (CP) 30 can be used to determine / select treatment procedures, including direction (explained further below) and stimulation parameters. Stimulation parameters may include the amplitude of the stimulation pulses, the frequency or repetition rate of the stimulation pulses, the pulse width of the stimulation pulses, and more complex parameters known in the art, such as pulse train definitions. Biphasic square waves are typically used, but nothing in this invention is limited to biphasic square waves; ramp, triangle, sine, monophasic, and other stimulation types may be used as needed. The CP 30 may be, for example, a laptop or tablet computer, and can be used by a physician, or under the physician's guidance, to acquire data from and provide instructions to the pulse generator 10 via a suitable communication protocol (such as Bluetooth or MedRadio or other wireless communication protocols) and / or via other means (such as inductive telemetry).

[0063] The patient can use the patient remote control (RC) 40 to perform various actions related to the pulse generator 10. These can be physician-defined options and may include, for example, turning treatment on and / or off, entering requested information (such as answering questions about the activity, treatment benefits, and side effects), and making (limited) adjustments to the treatment, such as selecting and adjusting amplitude settings from available treatment programs. The RC 40 can communicate via telemetry technology similar to the CP 30 to control the pulse generator 10 and / or acquire data from it. The patient RC 40 can also be self-programmed or can communicate with or link to the CP 30.

[0064] If the pulse generator 10 is rechargeable, a charger 50 can be provided to the patient to allow the patient to recharge the pulse generator 10. Some pulse generators 10 are not rechargeable, and therefore the charger 50 can be omitted. The charger 50 can operate, for example, by using known methods to generate a changing magnetic field to activate an inductor associated with the pulse generator 10, thereby providing power to recharge the pulse generator.

[0065] Some systems may include an external test stimulator (ETS) 60. After the lead 12 has been positioned within the patient, the ETS 60 can be used during surgery to test treatment procedures to determine if or how effective the treatment is for the patient 20. For example, initial implantation of the lead 12 can be performed using, for instance, a stereotactic guidance system, where the pulse generator 10 is temporarily placed externally. The proximal end of the lead 12 can be connected to an intermediate connector (sometimes referred to as an operating room cable) coupled to the ETS 60. After the lead 12 has been implanted and coupled to the ETS 60, the ETS can be programmed using a CP 30 with various treatment procedures and stimulation parameters that are tested to determine therapeutic efficacy. During this process, the lead position can be adjusted as needed. Once the suitability for treatment for the patient has been determined, a permanent pulse generator 10 is implanted and the lead 12 is connected to it, and the ETS is then deactivated.

[0066] The pulse generator 10 may include operating circuitry for generating output stimulation programs and / or pulses according to stored instructions, and for sensing signals, including electrical signals emanating from various tissues. Examples of prior versions of such circuitry, as well as planned future examples, can be found in U.S. Patent 10,716,932, the disclosure of which is incorporated herein by reference. The pulse generator circuitry may include circuitry from various commercially known implantable pulse generators for spinal cord stimulation, vagus nerve stimulation, and deep brain stimulation, which are also well known. Additional examples of the pulse generator 10, CP 30, RC 40, charger 50, and ETS 60 can be found, for example, but not limited to, U.S. Patent Nos. 6,895,280, 6,181,969, 6,516,227, 6,609,029, 6,609,032, 6,741,892, 7,949,395, 7,244,150, 7,672,734, 7,761,165, 7,974,706, 8,175,710, 8,224,450, and 8,364,278, the entire disclosure of which is incorporated herein by reference.

[0067] The pulse generator may include, for example, but not limited to, one or more battery-type power sources, which, as described above, may be rechargeable or primary (non-rechargeable). The pulse generator circuitry may include a current or voltage generation architecture with multiple channels / outputs of current and / or voltage. For example, a set of current mirrors may serve as the output architecture of a current control system, each current mirror providing discrete current outputs (as a source or sink), which can be summed via a low-impedance switching network. The pulse generator circuitry may include an input signal selector (such as a multiplexer or switch array) that allows one or more selected electrodes to be used as anodes / cathodes of a sensing electrode pair to obtain a desired signal, such as a signal emanating from a part of the brain. The received signal may be filtered in the analog domain to remove non-physiological signals (e.g., DC, line noise, and / or high frequencies), amplified, and digitized for analysis by a microcontroller also present in the pulse generator circuitry. Digital filtering may also be performed as needed. The received signal may be stored for later communication with external devices using wireless technology, as described above.

[0068] Figure 2Detailed information about the directional DBS lead is shown. The distal end 14 is shown, as are multiple electrodes. Two ring electrodes 16a and 16b (collectively referred to as ring electrodes 16) are provided, and multiple segmented electrodes (collectively referred to as segmented electrodes 18) are shown at 18a, 18b, 18c, 18d, 18e, and 18f. Each electrode 16, 18 is individually addressable within the system, such as by using a pulse generator with multiple independent current controls (MICCs) or multiple voltage sources. A MICC is a stimulation control system that provides multiple independently generated output currents, each of which can have an independent current magnitude. The use of MICCs allows for the generation of spatially selective fields during therapeutic output. The term "fractionalization" can refer to how the total current emitted by the pulse generator via the electrodes is distributed among the electrodes 16, 18 on the lead.

[0069] It should be noted that the pulse generator canister can be used as a neutral electrode or a return electrode for therapeutic output; if desired, one of the electrodes (such as the ring electrode 16 or one or more segmented electrodes 18) can be used alternatively as a return electrode. Thus, for example, during one phase of stimulation pulse delivery, the electrode on the lead wire can be used as a cathode, while the pulse generator canister serves as an anode. In another example, during one phase of stimulation pulse delivery, some lead wire electrodes 16, 18 serve as cathodes, while other lead wire electrodes serve as anodes. Any suitable combination and number of anodes and cathodes can be used for therapeutic purposes, and any lead wire electrode and / or canister electrode can be used in any of these roles as needed.

[0070] Examples of electrical conductors having segmented or oriented conductor structures include, but are not limited to, those disclosed in U.S. Patent Publications 20100268298, 20110005069, 20110078900, 20110130803, 20110130816, 20110130817, 20110130818, 20110238129, 20110313500, 20120016378, 20120046710, 20120071949, 20120165911, and 2012019. 7375, 20120203316, 20120203320, 20120203321, 20130197602, 20130261684, 20130325091, 20130317587, 20140039587, 20140353001, 20140358207, 20140358 / 209, 20140358210, 20150018915, 20150021817, 20150045864, 2015002181 The disclosures shown in 7,20150066120, 20130197424, and 20150151113, and in U.S. Patent Nos. 8,483,237 and 8,321,025, are incorporated herein by reference.

[0071] MICCs used in conjunction with directional leads can facilitate precise therapeutic targeting. For example, as... Figure 2 The directional wires shown can be used to generate, for example... Figure 2 The stimulation field is shown at point 80. For illustrative purposes, the outer boundary of field 80 can be understood as representing an isoelectric or isofield boundary within which the electric field is above the activation threshold, and outside of which the electric field is below that threshold. The activation threshold can represent or approximate the voltage / field threshold at which a nerve cell will activate or “fire.” The activation threshold can be determined based on a population, such as by relating it to a voltage / field at which 50% of the cell population has a 50% probability of activation, but other boundaries / thresholds can also be used. The shape of the field can be adjusted by modifying the current distribution of the current emitted via the electrodes using the MICC, as described in the reference cited above. For example, by using electrode 18c as the cathode and surrounding electrodes 18a, 18e, and 18d as the anode, an output that generates the activation field boundary, as shown at point 80, can be generated (roughly). The actual characteristics of the current distribution may be more complex than this simple example.

[0072] Figure 2The boundary shown at point 80 can be used to illustrate the stimulus field effect and can be generated using stimulus field modeling (SFM) for display purposes. In SFM, for example, a finite element model is used to model the tissue, where the conductor body is treated as an insulator, surrounded by a thin encapsulation sheath, and then by neural tissue. The neural tissue can be modeled as isotropic and homogeneous, but more complex modeling can be used if desired. A set of model voxels is defined around the conductor, decomposing the volume into smaller segments, each of which can be analyzed within the model. As mentioned above, the outer boundary of the SFM can be determined using a population-based activation threshold. The result can be that, given a current distribution and total stimulus current, the SFM can be generated as a three-dimensional surface surrounding a portion of the conductor and containing a certain volume of neural tissue. For example, field 80 can be understood as a two-dimensional representation of a slice of SFM. As mentioned above, SFM can be used as a visual tool to explain to patients or physicians which tissues are stimulated or not stimulated with a given current distribution and total current.

[0073] Because electrodes 16 and 18 can be addressed individually, each electrode 16 and 18 can also be used as a separate sensing node. The operating circuitry of the implantable system may include, for example, but not limited to, analog and digital filtering circuitry, and amplifiers, allowing the operating circuitry to selectively sense one or more signals within the patient's body. For example, switching circuitry may be provided to allow sensing to be performed using the desired pair of electrodes 16 and 18 or other combinations (and, if necessary, electrodes from the implantable pulse generator housing). Multiple sensing channels are available if desired. The input signal may be DC filtered and subjected to any other desired analog filtering before entering the amplifier, which amplifies the received signal (sometimes using variable gain) to an amplitude that can be converted into a digital data stream.

[0074] Frequency-selective digital filters can be used, for example, to remove residual non-physiological signals (such as filters with 50Hz or 60Hz to remove line noise from the environment), and to obtain specific frequency bands of interest. For example, digital filtering can help identify certain signals present in the brain, such as: Delta waves are found in the range of approximately 0.5 to 3.5 Hz. Excessive delta frequencies may be associated with sleep disorders, anxiety, and poor concentration. Theta waves are found in the range of approximately 3.5 to 7 Hz. They are sometimes associated with movement and / or waking from sleep; however, they have been studied less in humans. Alpha waves are found in the range of approximately 8 to 13 Hz. Increased alpha waves have been hypothesized to enhance cognition and / or reduce anxiety or depression. Beta waves are found in the range of approximately 18 to 25 Hz. Increased beta may be associated with attention span and other cognitive skills. Gamma waves are found in the range of approximately 30 to 60 Hz. A decrease in gamma waves may have a negative impact on mood and memory; while an increase in gamma waves may have the opposite effect.

[0075] In some examples, filtering can be performed to obtain signals of approximately 60 Hz or lower, or 50 Hz or lower (depending on the location and whether a line frequency of 50 Hz or 60 Hz is used), and the obtained signals can be recorded as needed for later processing. For example, in some of the examples below, triggering can prompt the pulse generator to record specific signals during symptom episodes of what is considered abnormal neural activity. The signal spectrum in the range of approximately 0.5 to approximately 60 Hz may be of interest and can therefore be recorded in the pulse generator at sampling frequencies, for example, in the range exceeding 200 Hz, including, for example, 256 Hz, 512 Hz, and / or 1 kHz or higher. Such signal data can be recorded in the pulse generator memory (or ETS memory) and transmitted to external devices, such as the patient RC 40 and / or CP 30 (now referred to as...). Figure 1 ( ) for further processing.

[0076] In implementations, the processing power of the CP 30 (which may be a tablet, laptop, etc.) or even the RC 40 (e.g., a smartphone) should be sufficient to perform spectrum analysis, which may include Fourier transform. Other data processing for identifying frequency components of interest may include, for example, but not limited to, principal component analysis, wavelet decomposition, and / or any orthogonal or non-orthogonal basis function decomposition. Such processing may strain the resources of the current generation pulse generator 10 or ETS 60, requiring excessive battery / power consumption, or taking a relatively long time, although future iterations of these technologies may be better suited for these activities. In some other examples, spectrum data may be transmitted from the CP 30 and / or RC 40 to a central server. Some examples may use bedside monitors, if bedside or other home monitoring systems are provided ( Figure 1 (Not shown in the image, but known in the art), the monitor can also obtain periodic data from a pulse generator, such as through daily or weekly downloads.

[0077] Other processes, such as digitally filtering a signal to a narrow passband with a high quality factor, can be more easily performed in a pulse generator. That is, for example, but not limited to, in some of the following examples, a pulse generator can be tasked with determining the signal strength at a specific frequency or narrow frequency band. This can be done relatively easily because filtering can be performed in the digital domain by supplying carefully designed filter coefficients to a digital filter (or even, if necessary, to a dedicated digital signal processing chip).

[0078] Figure 3AAn illustrative method is shown. First neural activity (NA) is obtained or recorded at 100. For example, data from other patients can be used to obtain the first NA. For example, in some examples, the approach could be to obtain data from patients who are not currently experiencing abnormal neural activity. Some patients may have chronic symptoms, making it impossible to record first neural activity when the patient is symptom-free. For such patients, canonical data for "healthy" patients can be used alternatively. For example, neural activity data during symptom-free periods can be recorded from another person with similar characteristics (such as comparable age, neurological condition, sex, brain anatomy, and / or other characteristics) and used as the first neural activity. Similarly, the average of data from similar patients can be obtained. In another example, neural activity can be obtained from a patient cohort, and characteristic frequencies of asymptomatic states can be obtained from the patient cohort data. In yet another example, data can be obtained from other patients with similar or related neurological disorders or symptom episodes. Data can be obtained from these "similar" patients who do indeed have periods of asymptomatic states, and whose lead positions are also similar to those of the treated patients, as lead positions can influence the obtained set of characteristic frequencies. For example, data can be obtained from different patients who have been successfully treated using a DBS system. Therefore, at box 100, a set of feature frequencies from the normative data can be obtained, rather than a patient-specific comparison.

[0079] Recording the first neural network (NA) at box 100 can, for example, involve recording several seconds of received neural activity data using one or more channels. For example, multiple channel-specific recordings can be performed. See again briefly. Figure 2 A selected subset of available sensing combinations can be chosen to record "normal" NA, and each sensing electrode combination defines a "sensing vector" between them. In one example, multiple and spatially diverse sensing vectors can be obtained for a single wire, such as by selecting a relatively closer electrode (one of ring 16a or segmented electrodes 18a, 18b) with a more distant neutral electrode (such as a pulse generator canister) as one sensing vector, selecting a more distant electrode (one of ring 16b or segmented electrodes 18e, 18f) with the neutral electrode as a second sensing vector, and using the two wire electrodes as opposite poles for a third sensing vector. The idea is to obtain spatially diverse sensing data. This is just one example. In other examples, a single sensing vector can be defined.

[0080] If more than one lead is implanted in the patient, a sensing vector can be defined using a sensing electrode on the first lead and a second electrode on the second lead; again, multiple vectors can be configured. It may be necessary to record two or more sensing vectors simultaneously to allow for concurrent monitoring. In some examples, two or more sensing vectors may be recorded at non-overlapping times. If needed, data from box 100 can be recorded periodically, such as daily or weekly as required.

[0081] The trigger is then received at 102. The trigger can be an input to an implantable pulse generator (or ETS, if needed) indicating that the patient is experiencing symptoms of a neurological disorder. For example, the implantable system may include an accelerometer configured to determine that the patient is experiencing gait instability or tremor, and when this occurs, this can indicate that a symptom episode is occurring and can be identified as a trigger in box 102. In another example, the patient may use a patient RC to indicate that symptoms are occurring, which can also serve as a trigger for a symptom episode. For example, the patient may indicate the occurrence of a seizure, manic episode, depressive episode, or hallucination.

[0082] In response to trigger 102, the system records a second NA at 104. If desired, and in some examples, the data recorded at 104 may be the same as that recorded at 100, although differences may exist between boxes 100 and 104. Characteristic frequencies are then identified at 106. Box 106 may include, for example, but not limited to, an implantable device or an external device (RC, CP, bedside monitor, or computer coupled to a remote database server) analyzing the data collected at 100 and 104 to identify peak frequency data. For example, a Fast Fourier Transform (FFT) may be performed to convert the time-domain sensed data to the frequency domain. Peak frequency data can be identified as characteristic frequencies, such as those related to… Figure 4 The explanation given.

[0083] refer to Figure 4 The figures illustrate a comparison of hypothetical frequency bands of the sensed data. As indicated, the upper figure shows the first NA, and the lower figure shows the second NA. As mentioned above, the second NA may correspond to a patient experiencing the neurological phenomenon of symptom onset. For example, these figures may show an FFT performed on a block of sensed data spanning a frequency range from approximately 0.5 Hz to approximately 60 Hz. While FFT as Figure 4 As shown, however, any mathematical transformation that allows the sensed time-domain data to be transformed for frequency analysis can be used. The FFT is one such analysis. Others can include principal component analysis, wavelet decomposition, or any other orthogonal or non-orthogonal basis function decomposition, each of which can be understood as transforming the time-domain data into the frequency domain, since the frequency can be analyzed after the transformation or decomposition.

[0084] As can be seen, there are several frequency peaks in the illustrated frequency band, including F1, F2, F3, and F4. Characteristic frequencies may include such peaks; determining which peaks are identified as characteristic peaks can be performed in any suitable manner. In some examples, peaks at least twice the transformed average amplitude, or peaks exceeding twice the root mean square (RMS) amplitude of the signal, may be considered. In other examples, statistical analysis may be used to identify peaks exceeding two, three, or more standard deviations or variances of the average signal.

[0085] Comparing the first and second NAs, F1 and F4 remain largely consistent; however, as symptom episodes persist, frequency F2 shows a significant decrease at 190°, and frequency F3 shows a significant increase at 192°. Any suitable measure of “difference” can be used; in one example, overall spectral intensity is observed, and any change exceeding 25% or some other proportion at a given frequency or band can be identified as a change or difference from the first NA to the second NA. The number (1, 2, or more) and type (increase, decrease, etc.) of the change may vary from patient to patient and symptom to illustrative example, and this example is not intended to precisely simulate an actual signal. For some patients, a single change may be observed; Figure 4 The examples provided illustrate the increase at characteristic frequency F3 and the decrease at characteristic frequency F4. The phrase "at a certain frequency" should be understood as having a meaning within a narrow frequency band, such as near the center frequency. or or center frequency However, it does not intend to impose specific restrictions on this concept.

[0086] Back Figure 3A Box 106 indicates that the characteristic frequency has been identified. Of particular interest is any frequency varying from the first NA recorded at 100 to the second NA recorded at 104. If the characteristic frequency does not change, the method can terminate as shown at 108. If one or more new peaks appear in the spectral analysis, the method terminates... Figure 3B Continue at this point. If one or more peaks are lost or no longer appear, the method will continue. Figure 3C Continue.

[0087] In another example, boxes 100 and 104 could reflect a sequence of events within a clinic or hospital. If within a clinic or hospital, the data collected at each step could be from an electroencephalogram (EEG) machine, in which case electrodes would be placed on the patient's skull, or inserted / implanted as needed. Frequency identification at 106 could then be performed by an EEG machine or a computer coupled to or receiving data from an EEG machine. Allowing the implantable system to also record data can still be useful, at least to allow for the configuration of the implantable system's sensing circuitry to ensure, for example, that an optimal sensing vector can be used to identify the signal / frequency of interest.

[0088] Go to Figure 3B With the appearance of an additional characteristic frequency ("CF" in the figure), as shown at 120, the next step of the method is to interrupt the signal, as shown at 122. Several interruption methods 122 can be used individually or in combination.

[0089] The locations where signals are generated at 124 points can be identified, and treatments targeting the signal sources can be generated. For example, multiple sensing vectors can be available in the system. The location of the signal source can be estimated by monitoring specific frequencies of additional characteristic frequency signals and comparing the relative intensities between the multiple sensing vectors. For example, monitoring specific frequencies can be performed using bandpass filtering or by using the mathematical transformations described earlier.

[0090] Then, for example, using Figure 2 The directional leads in the system can manipulate the system's output current or voltage to send a modulated signal to the source. The modulated signal can be delivered within system constraints at any frequency, bandwidth, and amplitude (and waveform shape) suitable for the system. In another example, the location of the signal source can be identified using an imaging and / or measurement system of an external application (such as EEG, functional MRI, etc.). Similarly, treatment can be targeted at this location. While much of the present invention focuses on the use of electroneurometric modulation, other therapeutic methods such as photobiological modulation can be used if desired, or alternative methods such as ablation can be used to target location 124 as needed.

[0091] Signal sources can be identified, as shown at position 126, and modulation can be directed to a specific source. For example, a database of patients with similar disease states, symptoms, and particularly similar frequency bands or at least similar additional frequencies can be used to identify sources by referencing patient data in the database. This step can be somewhat similar to the use at position 124; however, source targeting can include frequency selection or the use of other factors, such as identifying neural structures that may influence the source within the therapeutic range. For example, if nerve fibers can be targeted for stimulation / modulation, where the nerve fibers are connected to neural structures that can be identified as sources of characteristic frequencies (again, possibly by means of an external imaging or measurement system), the fibers may be affected by the stimulation / modulation signal in an attempt to limit the influence of the new characteristic frequency source. Once the frequency and signal source of interest have been identified through analysis, other types of treatment, such as ablation, or alternatives, can also be used.

[0092] Maximum amplitude 128 is another variation of the use of position 124. Here, the system can first employ an analytical approach for sensing. That is, neural activity (during symptom onset) can be monitored using at least the first and second sensing electrode pairs or other subsets of the multiple electrodes available in the system (or combinations of three or more electrodes if desired, although this may be less location-sensitive in some examples). Using frequency filtering, amplitudes within a narrow frequency band near the additional characteristic frequency can be monitored to determine which sensing electrode combination receives a stronger or maximum signal at the additional characteristic frequency. Subsequently, a neural stimulation signal can be delivered using the same electrodes as the output electrodes, placing the treatment at the spatial location with the highest signal amplitude.

[0093] Other methods can utilize an understanding of the characteristics of the interfering wave / frequency. For example, the output therapeutic pulses can be delivered at frequencies that the system recognizes as additional characteristic frequencies; however, these pulses can be delivered with an offset relative to the signal peak (i.e., a non-peak 130°). This can cause destructive interference to the signal. For example, the therapeutic delivery is out of phase, i.e., the non-peak is out of phase with the intrinsic signal by at least 90°, and more preferably in the range of about 120° to about 240°, or about 135° to about 225°, or about 150° to about 210°, or 170° to 190°, or 180°. Even if the output signal is a square wave and the intrinsic signal is not, the output out-of-phase has an interfering effect, thereby reducing signal propagation. In another alternative, a sinusoidal or other shaped signal can be used to deliver a signal that is more accurately characterized as out of phase than the non-peak 130. In some examples, filtering can be used to limit the signal frequency observed when attempting to identify the peak. Filtering itself causes a phase shift in the analyzed signal; when emitting a non-peak signal (such as... Figure 3B (as shown in Figure 130) and / or the signal at the peak ( Figure 3CAs shown in Figure 160, the phase shift caused by filtering can be addressed by adjusting the timing of the treatment output to account for the filtering-induced phase shift. That is, the treatment can be output at a time point adjusted relative to the peak observed in the filtered signal to account for the phase shift. Such an output can be generated by first assuming the periodic nature of the sensed signal, thereby identifying the peak in the sensed signal, and then adding or subtracting the phase change caused by filtering using a time delay determined as a fraction of the signal period (1% to 150%) after peak identification. In other examples, the output signal can be generated at a rate selected to match the characteristic frequency to be enhanced or interfered with, and the timing of the output signal can be repeatedly adjusted until the desired effect (interruption or enhancement) is achieved.

[0094] In another example, a random method can be used to introduce signal noise within a range of additional characteristic frequencies, as shown at 132. For example, the output can be generated at frequencies above and below the characteristic frequency. This can be done using a square wave with a varying inter-pulse period that varies above and below the period of the additional characteristic frequency. If a sine wave or an approximation thereof is available, the frequency can vary above and below the center point of the additional characteristic frequency. For example, random noise 132 can be selected for use in response to specific patient symptoms, rather than in response to a specific signal frequency, such as by emitting a random signal directed to a location associated with a seizure.

[0095] In another example, a treatment can be generated using frequencies close to but deviating from the additional characteristic frequency, as shown at 134. For example, the overdrive frequency would be higher than the characteristic frequency, such as in the range of about 105% to about 150% of the characteristic frequency, or in the range of about 105% to about 125% of the additional characteristic frequency. Lower frequencies can be used, such as in the range of about 75% to about 99% of the additional characteristic frequency. These different methods 124, 126, 128, 130, 132, and 134 can be combined as needed.

[0096] The interrupt signal generated at point 122 can be emitted, and the patient's response can be monitored. Treatment can be initially confirmed by monitoring changes in the additional characteristic frequency signal, as shown at point 136. Whether changes in the additional characteristic frequency signal translate into an effect on the patient's symptoms can also be determined, for example, using monitoring of any signals initially relied upon for symptom identification, as discussed above. Figure 3A As taught in box 102. If the characteristic frequency and / or symptoms are not affected, further adjustments can be made, as shown at 138. Adjustment 138 may include, for example, switching from one interruption strategy to another, or combining two such strategies, or changing parameters of the strategy being used, such as increasing or decreasing one or more of amplitude, frequency, etc.

[0097] In some examples, the result can be viewed as an interrupt procedure that can be stored in the device for later execution. That is, if a change is observed and the additional frequency appears to be interrupted, the treatment procedure can be stored in memory and subsequently invoked in response to a trigger. For this purpose, the method may include box 140, which will trigger the use of the interrupt signal by inputting the method at box 122, as shown. The trigger at box 140 (prompting the use of the stored interrupt signal) can be related to... Figure 3A The trigger at box 102 is the same. In another example, the trigger at 140 may rely on sensing additional characteristic frequencies; if additional characteristic frequencies are observed, they can be considered as indicators of the occurrence, likelihood, or possible future onset of symptoms and can be used to trigger treatment interruption. Box 140 may also include storing one or more sensed signals prior to the start of treatment—for example, if the sensed data is stored in a circular register (such as a first-in-first-out memory), signals associated with or prior to the trigger may be stored for later review by the physician (if needed). Furthermore, boxes 122 and / or 136 may also include recording one or more neural signals to observe, for example, what occurs when treatment is interrupted at 122, or to observe neural activity after treatment delivery.

[0098] Back Figure 3A If the frequency peak is lost at box 106, the method can continue to... Figure 3C Here, as shown at 150, the characteristic frequency is missing. The next step is to deliver a therapeutic output that enhances neural activity at the missing frequency, as shown at 152. This can be achieved in several ways.

[0099] At position 154, the location of the missing signal generation can be identified, and a treatment targeting the signal source can be generated. For example, multiple sensing vectors can be available in the system. By analyzing the previously recorded first NA, monitoring specific frequencies of additional characteristic frequency signals, and comparing the relative intensities between multiple sensing vectors, the location of the signal source can be estimated. Then, for example, using... Figure 2 The directional leads in the system can manipulate the system's output current or voltage to deliver modulated or stimulating signals to the source. Within the system's limitations, the modulated or stimulating signals can be delivered at any frequency, bandwidth, and amplitude (and waveform shape) suitable for the system. In another example, the signal source location 154 can be identified using an external imaging and / or measurement system, such as EEG, functional MRI, etc. Treatment can then be targeted at this location.

[0100] Similarly, using a pre-recorded first NA, the source of the signal can be identified, as shown at position 156, and modulation can be targeted at a specific source. For example, using a database of patients with similar disease states, symptoms, and particularly those whose frequencies of “normal” neural activity disappear or decay during symptom attacks, the source can be identified by referring to patient data in the database. This step can be somewhat similar to the use at position 154; however, source targeting can include frequency selection or the use of other factors, such as identifying neural structures that may influence the source within the therapeutic range. For example, if a nerve fiber can be targeted for stimulation / modulation, where the nerve fiber is connected to a neural structure that can be identified as a source of characteristic frequency (again, possibly with the aid of an external imaging or measurement system), the fiber may be affected by the stimulation / modulation signal in an attempt to stimulate the neural structure to regenerate the characteristic frequency that was lost or decayed during symptom attacks.

[0101] Maximum amplitude 158 is another variation of the use of position 124. Here, the system can first employ an analytical approach for sensing. That is, neural activity (during symptom-free periods) can be monitored using at least first and second sensing electrode pairs or other subsets of multiple electrodes available in the system (or combinations of three or more electrodes if desired, although this may be less position-sensitive in some examples). Using frequency filtering, amplitudes within a narrow frequency band near the missing characteristic frequency can be monitored to determine which sensing electrode combination receives a stronger or maximum signal at the missing characteristic frequency. Subsequently, a neural stimulation signal can be delivered using the same electrodes as the output electrodes, placing the treatment at the spatial location with the highest signal amplitude.

[0102] In some examples, it can be done first. Figure 3A After observation, boxes 154, 156, and 158 are executed, and then the symptoms are allowed to stop before additional sensing is performed to identify any of location 154, source 156, or maximum sensing location 158. Then, when the symptoms reappear, a routine may be performed at box 152 to deliver treatment to enhance the missing characteristic signal, as well as confirmation 164 and adjustment 166, which are explained further below.

[0103] In some examples, the missing characteristic frequency may still exist, but has simply decayed to the point where it is no longer dominant. If so, another approach is to pulse at or near the signal peak, as shown at 160. For example, if the decaying characteristic frequency can be sensed using, for instance, a narrow-bandpass filter, then the output pulse can be synchronized with the signal by detecting the peak or the slope that causes the peak and emitting a therapeutic pulse in a closed-loop manner.

[0104] Another approach is to determine the frequency of the missing characteristic frequency and simply deliver an output whose frequency matches the missing or attenuated characteristic frequency, as shown at 162. A square wave can be emitted, or more complex waves can be generated, such as actual sine waves or simulated sine waves, such as digital approximations of sine waves.

[0105] The enhanced signal generated at point 152 can be emitted, and the patient's response can be monitored. As shown at point 164, treatment can be initially confirmed by monitoring changes in the missing or attenuated characteristic frequency signal. Whether changes in the missing or attenuated characteristic frequency signal translate into an effect on the patient's symptoms can also be determined, for example, using monitoring of any signals initially used to identify symptoms, as described above. Figure 3A As taught in box 102. If the missing or attenuated characteristic frequencies and / or symptoms are not affected, further adjustments can be made, as shown at 166. Adjustment 166 may include, for example, switching from one enhancement strategy to another, or combining two such strategies, or changing parameters of the strategy in use, such as increasing or decreasing one or more of amplitude, frequency, etc.

[0106] In some examples, the results can be viewed as enhancement procedures that can be stored in the device for later execution. That is, if a change is observed in 164 / 166, and the frequency of missing or decaying signals appears to be enhanced, the treatment procedure can be stored in memory and then invoked again in response to a trigger. For this purpose, the method may include box 170, which will trigger the use of the enhancement signal by entering the method at box 152, as shown.

[0107] The trigger at box 170 (prompting the use of the stored enhanced signal) can be used with... Figure 3A The trigger at box 102 is the same. The trigger may also include determining that a previously identified missing characteristic frequency is no longer present in the sensed neural signal. This can be seen as indicating the probability, likelihood, or future occurrence of symptom onset, and can be used as a trigger for treatment at box 170 if needed. Box 170 may also include storing one or more sensed signals before treatment begins—for example, if the sensed data is stored in a circular register (such as a first-in-first-out memory), signals associated with or prior to the trigger may be stored for later review by the physician (if needed). Furthermore, boxes 152 and / or 164 may also include recording one or more neural signals to observe, for example, what occurs during the delivery of enhanced treatment at 152, or to observe neural activity after treatment delivery.

[0108] Briefly back Figure 3A If there are multiple variations in the frequency peak at box 106, the output response can be as described above. Figure 3B and 3CEach of the above. For example, as needed, interruptive and enhancing outputs can be generated within the same treatment procedure or as two separate treatment procedures running simultaneously and / or in alternating or sequential modes. If multiple additional frequency peaks have occurred, or if multiple frequency peaks are missing, two separate treatment procedures can be generated, one procedure for each additional or missing frequency peak. Alternatively, a single treatment procedure can be generated that attempts to address two additional or missing frequencies in one procedure through interruption or enhancement. Various combinations can be used as needed.

[0109] As described above Figure 4 And therefore turned to Figure 5 Here, a simplified representation of a graphical user interface, such as that that may appear in a clinician programmer (CP), is shown. At point 200, several available procedures for issuing enhancements or interruptions to treatment are available. These procedures can be issued as part of the schedule shown at point 202.

[0110] If needed, triggers can be identified, as shown at 204. Triggers may include previous information regarding... Figures 3A to 3C The triggers described. In some examples, treatment may be triggered by the time of day or by patient activity that may be about to occur. For example, if the patient is waking up or falling asleep, and was previously undergoing treatment... Figures 3A to 3C When a type of approach is used to detect symptoms that interfere with a patient's activity, an amplifying or disruptive signal may be generated as a preventative step, even in the absence of current symptoms. Triggers may include tasks, such as memory games or other patient activities that may cause changes in characteristic frequencies. In some examples, cognitive tasks are expected to amplify the zeta and / or gamma bands, and stimulation may increase these same frequencies, thereby improving performance. For example, therapeutic output may be prompted by the patient interacting with the RC to indicate a desired cognitive task or exercise to be performed; in response, stimulus outputs in gamma frequencies or other precognitive bands may be generated. Physical tasks or exercises may be triggers; for example, if a patient is prone to falls, instability, or physical impairments (e.g., tremors), the implanted device may determine that the patient has changed posture, such as from sitting or lying down to standing, and this may be a trigger for treatment to prevent tremors caused by anticipated physical exercise (including movements such as walking). Therefore, a treatment procedure can be configured to begin in response to predetermined triggering conditions.

[0111] At 210, it can be seen that the nature of the responsive treatment can be determined based on the frequency. The slider at 212 can be used to select a frequency that is conventionally known for interruption or enhancement. In other examples, the inherent signal 214 can be used as a trigger, or at the signal to be enhanced or interrupted.

[0112] Figure 6 Another illustrative graphical user interface is shown. At 250, another set of programs and schedulers is shown, similar to... Figure 5 At 260, a manual control block for configuring the nature of the output signal to be used is shown. Here, the synchronization index can be set using slider 262, indicating how much additional synchronization a particular patient requires. The phase shift for the output therapeutic pulse can be set using slider 264. At 270, a toggle bar allows the user to determine whether the goal is to create additional synchronicity or desynchronize neural activity. Here, for block 270, options such as... Figures 3A to 3C The automated method is shown. Alternatively, for block 270, a simplified form of the method could be repeated testing and sensing, such as by monitoring changes in responsiveness to the administered treatment, as... Figure 3B As described in boxes 122, 136 and 138 (for interrupting synchronization), or Figure 3C As described in boxes 152, 164 and 166 (for enhancing synchronization).

[0113] Each of these unrestricted examples can exist independently or can be combined with one or more other examples in various permutations or combinations.

[0114] The above detailed description includes references to the accompanying drawings, which form part of the detailed description. The drawings illustrate specific embodiments by way of illustration. These embodiments are also referred to herein as "examples." These examples can also include elements other than those shown or described. However, the inventors also contemplate examples that provide only those elements shown or described. Furthermore, the inventors contemplate examples using any combination or arrangement of those elements (or one or more aspects thereof) shown or described, whether concerning a particular example (or one or more aspects thereof) or other examples (or one or more aspects thereof) shown or described herein.

[0115] In the event of any inconsistency between the usage in this document and any other document incorporated by reference, the usage in this document shall prevail.

[0116] In this document, the terms “a” or “an” are common in patent documents and include one or more, regardless of any other instances or uses of “at least one” or “one or more.” Furthermore, in the claims, the terms “first,” “second,” and “third,” etc., are used merely as labels and are not intended to impose numerical requirements on their objects.

[0117] The methods described herein can be implemented, at least in part, by a machine or computer. Some examples can include computer-readable or machine-readable media encoded with instructions operable to configure an electronic device to perform the methods described in the examples above. Implementations of such methods can include code, such as microcode, assembly language code, high-level language code, etc. Such code can include computer-readable instructions for performing various methods. The code can form part of a computer program product. Furthermore, in one example, the code can be tangibly stored on one or more volatile, non-transient, or non-volatile tangible computer-readable media, such as during execution or at other times. Examples of such tangible computer-readable media can include, but are not limited to, hard disks, removable disks or optical discs, magnetic tape cassettes, memory cards or memory sticks, random access memory (RAM), read-only memory (ROM), and similar devices.

[0118] The above description is intended to be illustrative and not restrictive. For example, the above examples (or one or more aspects thereof) can be used in combination with each other. Other embodiments can be used, such as those used by those skilled in the art after reviewing the above description.

[0119] An abstract is provided to comply with 37 CFR § 1.72(b) so that the reader can quickly determine the nature of the technical disclosure. When submitting this abstract, it should be understood that it will not be used to interpret or limit the scope or meaning of the claims.

[0120] Furthermore, in the above detailed description, various features may be grouped together to simplify this disclosure. This should not be construed as meaning that disclosed features not protected by any claim are essential to any claim. Rather, the subject matter of the invention may be contained in fewer than all features of a particular disclosed embodiment. Therefore, the following claims are incorporated herein by way of example or embodiment, wherein each claim exists independently as a separate embodiment, and these embodiments are contemplated to be able to be combined with each other in various combinations or arrangements. The scope of protection should be determined with reference to the appended claims and the full scope of their equivalents.

Claims

1. A medical device system, the system comprising: An implantable pulse generator having a pulse generator circuit, the pulse generator circuit including each of a communication circuit for communicating with one or more external devices, an output circuit for generating output pulses, and a sensing circuit for sensing one or more signals. A lead having multiple electrodes and adapted to position one or more electrodes in a patient's body and connectable to the implantable pulse generator; and External devices, adapted to communicate with the implanted pulse generator, The system is suitable for use by patients with neurological disorders experiencing symptom onset, characterized in that: The implantable pulse generator is configured to receive indications of symptom onset; The implantable pulse generator is configured to record symptom neural activity during a symptom attack in response to an indication of the symptom attack. The implanted pulse generator or the external device, using data transmitted from the implanted pulse generator, is adapted to perform the following operations: Identify the characteristic frequencies of non-symptom neural activity and the characteristic frequencies of symptom neural activity; and Select characteristic frequencies that distinguish the non-symptom neural activity from the symptom neural activity; and The implantable pulse generator, in response to the identification and selection, emits neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency.

2. The medical device system according to claim 1, wherein, The implantable pulse generator is configured to record non-symptom neural activity from the patient when the patient is not experiencing a symptom onset.

3. The medical device system according to claim 1, wherein, The non-symptom neural activity is obtained from one of the following: A database of patients with implanted leads; Patients with similar neurological disorders, age, sex, and / or disease states; or The average value of other patients.

4. The medical device system according to any of the preceding claims, wherein, The implanted pulse generator or the external device identifies characteristic frequencies by performing a mathematical transformation from the time domain to the frequency domain on the data used for the non-symptom neural activity and the symptom neural activity, and identifying the peak values ​​of the non-symptom neural activity and the symptom neural activity in the frequency domain.

5. The medical device system according to any one of the preceding claims, wherein, The implantable pulse generator delivers neural stimulation to interrupt or enhance neural activity at a selected characteristic frequency by identifying the source of symptom neural activity with the selected characteristic frequency.

6. The medical device system according to any one of claims 1 to 4, wherein, The implantable pulse generator delivers nerve stimulation to interrupt or enhance neural activity at a selected characteristic frequency by identifying the location of symptom neural activity with the selected characteristic frequency and delivering the nerve stimulation to the location of the second neural activity by selecting electrodes for delivering the nerve stimulation to deliver an electric field to the location of the second neural activity, thereby interrupting or enhancing the neural activity at the selected characteristic frequency.

7. The medical device system according to any one of claims 1 to 4, wherein, The implantable pulse generator delivers neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency, which is performed by the implantable pulse generator in the following manner: a) Sensing neural activity using a first subset of the plurality of electrodes and each of a second subset of the plurality of electrodes; b) Determine which of the subsets of electrodes used in a) acquires the stronger signal at the selected characteristic frequency; as well as c) Use a subset of the plurality of electrodes identified in b) to deliver the neural stimulation.

8. The medical device system according to any one of claims 1 to 4, wherein, The implantable pulse generator delivers neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency, which is performed by the implantable pulse generator in the following manner: Sensing further neural activity; The sensed neural activity is then filtered to obtain a signal at the selected characteristic frequency. Determine the peak time at the characteristic frequency; as well as The neural stimulus is delivered at the peak time to enhance neural activity at the selected characteristic frequency.

9. The medical device system according to any one of claims 1 to 4, wherein, The implantable pulse generator delivers neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency, which is performed by the implantable pulse generator in the following manner: Sensing further neural activity; The sensed neural activity is then filtered to obtain a signal at the selected characteristic frequency. Determine the peak time at the characteristic frequency; and The neural stimulus is delivered with a delay relative to the peak time to interrupt neural activity at the selected characteristic frequency.

10. The medical device system according to any one of claims 1 to 4, wherein, The implantable pulse generator delivers neural stimulation to interrupt or enhance neural activity at a selected characteristic frequency by delivering pulses at a frequency that is approximately 105% to 125% of the period of the characteristic frequency to interrupt neural activity at the selected frequency.

11. The medical device system according to any one of claims 1 to 4, wherein, The implantable pulse generator delivers neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency by delivering pulses at the characteristic frequency to enhance neural activity at the selected frequency.

12. The medical device system according to any one of the preceding claims, wherein, The implanted pulse generator delivers neural stimulation to interrupt or enhance neural activity at the selected characteristic frequency, which is executed in response to a trigger, wherein the trigger is one of the following: The appearance of patient-indicating symptoms; Detection of characteristic frequencies appearing in further sensed neural activity; or Instructions for patients to engage in cognitive or physical exercise, whether they are currently doing so or about to do so.

13. The medical device system according to any one of the preceding claims, wherein, The external device is a patient remote control.

14. The medical device system according to any one of the preceding claims, wherein, The external device is a programmer for clinicians.

15. The medical device system according to any one of the preceding claims, wherein, The lead has a proximal end for coupling to the pulse generator and a distal end carrying the plurality of electrodes, the distal end of the lead being configured to be positioned in the patient's brain, and the pulse generator and the lead together form an implantable system for deep brain stimulation.

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