WO2021196652A1 - 用于对患者进行神经刺激的方法和装置 - Google Patents
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Definitions
- This application relates to a method and device for neurostimulation of a patient.
- Implantable medical devices are widely used in the diagnosis, monitoring and treatment of diseases, such as cardiac pacemakers, brain pacemakers, defibrillators, neurostimulators, and drug pumps.
- the electronic circuits and battery elements arranged in the enclosed casing are electrically connected to the sensors and electrodes outside the enclosed casing to monitor specific parts of the body or provide electrical/optical stimulation.
- the pulse generator set in the closed housing is connected to the electrode through an extended wire, so that the pulse generated by the pulse generator is transmitted to the electrode arranged in a specific position, so as to conduct electricity at that position. Stimulate.
- Deep brain stimulator is a nerve stimulator that electrically stimulates the patient's brain to treat diseases.
- deep brain stimulator products on the market that have entered clinical applications, such as the treatment of Parkinson's syndrome, drug addiction or other neurological diseases.
- the existing deep brain stimulators have a short service life, and some can only be used for six months to one year, or even shorter, which is difficult to meet the needs of long-term disease treatment.
- This application provides a method for neurostimulation of a patient, which can target the neurostimulation of the patient by detecting abnormal physiological activity signals of the patient.
- a method for neurostimulation of a patient comprising: detecting physiological activity signals of one or more brain regions of the patient through implantable electrodes; The physiological activity signal is compared with preset detection conditions to determine whether the detected physiological activity signal belongs to an abnormal physiological activity signal; Electrical stimulation is applied to the brain area.
- a device for neurostimulation of a patient comprising: a first implantable electrode for being set in a first brain region of the patient; and a second implantable electrode , Used to be set in the second brain area of the patient; the controller, used to obtain the detected physiological activity signals of the first brain area and the second brain area of the patient, and compare them with preset detection conditions To determine whether the detected physiological activity signal belongs to an abnormal physiological activity signal; and based on the comparison result, control whether the first implantable electrode or the second implantable electrode is used to perform Electrical stimulation is applied to at least one of a brain area and the second brain area.
- a device for neurostimulation of a patient wherein the device includes a non-transitory storage medium, and the non-transitory storage medium has instructions that can be executed by a processor , The instructions are executed to perform the following steps: detect physiological activity signals of one or more brain regions of the patient through implantable electrodes; compare the detected physiological activity signals with preset detection conditions to determine Whether the detected physiological activity signal belongs to an abnormal physiological activity signal; and based on the comparison result, controlling whether to apply electrical stimulation to the one or more brain regions through the implantable electrode.
- Fig. 1 shows a device for neurostimulating a patient according to an embodiment of the present application
- Figure 2 shows an implantable electrode according to an embodiment of the present application
- Fig. 3 shows a process of updating an abnormal state mode according to an embodiment of the present application
- FIG. 4 shows another process of updating the abnormal state mode according to an embodiment of the present application
- Figures 5 and 6 show two exemplary ways for applying electrical stimulation
- Fig. 7 shows a flow of electrical stimulation parameter adjustment according to an embodiment of the present application.
- the existing deep brain stimulators usually need to continuously apply electrical stimulation signals to the stimulated parts in the brain region, which is reasonable for persistent diseases such as Parkinson's syndrome.
- many other neurological diseases such as depression, obsessive-compulsive disorder, or drug addiction diseases (for example, prevention of relapse after withdrawal of heroin drugs), etc.
- the deep brain stimulator does not need to apply electrical stimulation signals to the stimulated part.
- electrical stimulation signals are continuously applied to the brain during this period, especially high-energy electrical stimulation signals applied to certain diseases, this will have a negative impact on the patient's daily mood.
- continuous application of electrical stimulation will cause excessive energy release, which will significantly shorten the service life of the brain depth stimulator.
- the inventor also found that for the aforementioned intermittent neurological diseases, during the onset of the disease, the EEG signal in certain areas of the brain will be abnormal, for example, the amplitude of the EEG signal will be more significant than that during the non-onset period. Increase, and this abnormal change or state of the brain electrical signal can be used as a condition to monitor whether the disease has occurred. Therefore, if it can detect this abnormal EEG signal and control the application of electrical stimulation signals to the brain area accordingly, then the deep brain neurostimulator does not need to continuously apply electrical stimulation to the stimulated part of the brain area. Signal.
- the inventor of the present application creatively integrated the device for monitoring the physiological activity of the patient’s brain area into the deep brain stimulator, and targeted the patient’s brain by monitoring the abnormal physiological activity of the patient’s brain Electrical stimulation, which greatly improves the efficiency of nerve stimulation and reduces the side effects of unnecessary electrical stimulation.
- the method and device of the present application can also generate personalized judgment conditions based on the historical data of the abnormal physiological activity signals of each patient, so that the application of electrical stimulation can more accurately adapt to the personal conditions of different patients. This further improves the treatment effect.
- Fig. 1 shows a device 100 for neurostimulating a patient according to an embodiment of the present application.
- doctors or other users can control the method of neurostimulation of the patient's brain area for the treatment of certain neurological diseases, such as drug addiction, obsessive-compulsive disorder, depression, epilepsy and other intermittent nerves.
- sexual diseases, or other neurological diseases, such as Parkinson’s syndrome It is understandable that the doctor can treat the patient according to the treatment needs of various diseases by using the device for neurostimulating the patient described in each embodiment of the present application, which is not limited in the present application.
- the method for neurostimulating a patient may be configured as an instruction that can be executed by a processor, and the instruction may be stored in a non-transitory storage medium and executed after being executed by the processor.
- the device 100 includes an implantable electrode device 102 and a controller 104.
- the implantable electrode device 102 can be surgically implanted in the patient's brain to detect physiological activity signals of one or more brain regions of the patient, and/or apply electrical stimulation signals to one or more brain regions of the patient .
- the implantable electrode device 102 may be configured as a probe or similar structure, and one or more electrode contacts may be exposed on the outer surface of the implantable electrode device 102 to respectively contact specific brain regions. These electrode contacts can be electrically coupled to the inside of the probe by conductive elements to be electrically connected to the controller 104.
- the implantable electrode device 102 may include an implantable electrode, on which one or more electrode contacts may be disposed.
- one or more electrode contacts can be used as both detection contacts and stimulation contacts.
- the detection and stimulation of an electrode contact can be performed in a time-sharing manner. The detection and stimulation are performed first, and then can be repeated. One or more times.
- some electrode contacts can be used as detection contacts to detect the physiological activity signals of the brain area they contact; while other electrode contacts can be used as stimulation contacts to Electrical stimulation signals are applied to the contacted brain area.
- the implantable electrode may include at least one detection contact for detection and at least one stimulation contact for stimulation; or, the implantable electrode may also include a plurality of detection contacts and a plurality of stimulation contacts.
- the detection contacts and the contact contacts may be arranged in pairs or groups.
- the number of detection contacts on the implanted electrode may be the same as the number of stimulation contacts, and the position of each detection contact substantially overlaps the position of the paired stimulation contact.
- the controller can apply electrical stimulation signals for therapeutic purposes to the brain area through the corresponding stimulation contact after the judgment.
- the implantable electrode may include a plurality of stimulation contacts, and each stimulation contact corresponds to at least one detection contact, so that each stimulation contact and its corresponding at least one detection contact form a detection-stimulation group And each detection-stimulation group can independently detect physiological activity signals and apply electrical stimulation signals.
- the time of performing electrophysiological signal detection and applying electrical stimulation signals in different detection-stimulation groups is not synchronized with at least another detection-stimulation group. In this way, the application of electrical stimulation signals can be adjusted according to the position of the electrode contacts on the implanted electrode in the brain area to meet different therapeutic purposes or requirements.
- the time for detecting physiological activity signals and applying electrical stimulation signals in different detection-stimulation groups are synchronized. The detection contacts and stimulation contacts in the same detection-stimulation group can be in the same brain area or in different brain areas.
- the implantable electrode device 102 may include multiple sets of implanted electrodes, where each set of implanted electrodes includes one or more implanted electrodes.
- at least one set of implantable electrodes may include both detection contacts and stimulation contacts; other implantable electrodes may only include stimulation contacts, or may only include detection contacts.
- the implantable electrode device 102 may include multiple sets of implantable electrodes, where some of the implanted electrodes may only include detection contacts, and another part of the implanted electrodes may only include stimulation contacts.
- the implantable electrode device 102 may include two implantable electrodes, wherein the first implantable electrode may be disposed in the first brain region of the patient, such as the deep region of the left brain, and the second implantable electrode The implantable electrode can be placed in a second brain region of the patient, such as the deep region of the right side of the brain.
- the two brain regions can be detected synchronously or asynchronously, or electrical stimulation can be applied to these two brain regions synchronously or asynchronously.
- each implantable electrode may be provided with a plurality of detection contacts and/or stimulation contacts, so as to further detect or apply electrical stimulation according to the local detection of the brain regions actually contacted by these electrode contacts.
- the implantable electrode device 102 may be implanted in at least one of the cerebral cortex area or the deep brain area.
- the detection contact and/or the stimulation contact of the implantable electrode may be placed in a deep brain region, such as at least one of the nucleus accumbens or the forelimb of the internal capsule.
- the stimulation contacts of the implantable electrode can be placed in other brain regions, such as the thalamus, hypothalamic nucleus, hippocampus, globus pallidus, and the like.
- the deep brain regions include deep brain regions on the left and right sides.
- implantable electrodes can be implanted in the deep brain regions on the left and right sides at the same time, and electrical stimulation of these regions can be performed through the stimulation contacts on them. .
- the implantable electrode includes one or more detection contacts with a diameter of 0.1 to 3 mm, and each detection contact can detect a physiological activity signal of 5 uV to 12.5 mV, and the frequency of the physiological activity signal is 0.5 to 150Hz.
- the implantable electrode includes one or more detection contacts with a diameter of 0.1 to 0.5 mm, and each detection contact can detect a physiological activity signal of 5 uV to 10 mV, and the frequency of the physiological activity signal is 150 To 30000Hz.
- physiological activity signals roughly correspond to cortical EEG signals and local EEG signals in deep brain regions.
- the stimulation contact may have a size and configuration similar to the detection contact.
- Fig. 2 shows an implantable electrode according to an embodiment of the present application.
- the implantable electrode device 102 shown in FIG. 1 may include one or more implanted electrodes shown in FIG. 2.
- the implantable electrode can be configured as a probe structure with an elongated body, and the electrode contacts can be distributed longitudinally along the elongated body so as to contact different brain regions at predetermined intervals. .
- the implantable electrode shown in FIG. 2 includes 12 electrode contacts. In some other examples, the number of electrode contacts may be different.
- the electrode contacts shown in Figure 2 are shown as being arranged in series on the implanted electrode. In some other examples, the electrode contacts can also be arranged in a ring, alternately or in any other desired manner. The arrangement is set on the implanted electrode.
- the implantable electrode can also be configured in any other shape, such as a bent structure, a spiral shape, a ring shape, or other shapes.
- the physiological activity signals detected by multiple adjacent detection contacts can be collected in a differential manner.
- the physiological activity signal actually used for subsequent determination may be the signal difference of the physiological activity signal between a certain detection contact (as a sampling point) and other detection contacts (as a reference point).
- the differential signal acquisition method helps to reduce the interference of noise signals and extract useful signals.
- the number and positions of detection contacts as sampling points can be configured, and the number and positions of detection contacts as reference points can also be configured. In other words, any detection contact can be configured. It is selected as the sampling point or reference point. Still referring to FIG.
- adjacent detection contacts 4-6 can be used as a group of detection contacts, wherein detection contact 5 is used as a sampling point and detection contacts 4 and 6 are used as reference points.
- the three detection contacts can generate a physiological activity signal reflecting the physiological activity around the brain area where they are located.
- the physiological activity signal uses the detection contact 5 as the sampled signal input, and the detection contact 4 and 6 are short-circuited.
- the latter signal is used as the reference signal for sampling.
- the reference point can be one detection contact or multiple detection contacts; or, the reference point can be either the adjacent detection contacts around the sampling point or other detection contacts with a certain distance.
- the electrode contacts implanted in the brain usually need to be in contact with brain tissue or nerve tissue, and the electrical stimulation is released to the human tissue through the contact interface. Therefore, the material of the electrode contacts needs to be biocompatible, Conductive materials with good electrochemical corrosion resistance, such as platinum (Pt), platinum-iridium alloy (PtIr), etc.
- the shape of the electrode contact can be ring, dot, or sheet, and the specific shape needs to be determined according to the expected implantation position and use of the product.
- the size of the electrode contacts can be determined according to the number of nerve cells that need to be stimulated or detected, ranging from 0.01 to 6 mm.
- the size can be between 0.01 and 0.1mm; for hundreds to tens of thousands of neurons, the size can be between 0.1 and 0.5mm; and for functional nuclei Or larger size brain tissue applications, the size can be between 0.5 to 6mm.
- the device 100 for neurostimulating a patient further includes a controller 104, which is used to obtain the detected physiological activity signal of one or more brain regions where the implantable electrode device 100 of the patient is located, and It is compared with the preset detection conditions to determine whether the detected physiological activity signal is an abnormal physiological activity signal.
- the controller 104 further controls whether to apply electrical stimulation to one or more brain regions of the patient through the implantable electrode device 100 based on the comparison result.
- the controller 104 may include a physiological activity signal acquisition and processing unit 106 and an electrical stimulation signal generation unit 108.
- the physiological activity signal acquisition and processing unit 106 is coupled to the implantable electrode device 102 to receive the physiological activity signal collected by the implantable electrode device 102, and compares the physiological activity signal with preset detection conditions to determine whether it is an abnormal physiological activity signal.
- the brain electrical signal acquisition and processing unit 106 may further include a signal acquisition module and a signal processing module. Among them, the signal acquisition module is used to acquire physiological activity signals and convert the weak analog biological voltage and current signals embodied by them into analog or digital signals for subsequent processing, preferably digital signals.
- the signal acquisition module may include circuit elements such as signal isolation, signal amplification, signal filtering, sample/hold circuit, and signal analog-to-digital conversion circuit.
- the signal isolation circuit is used to isolate the physiological activity signal of the human body from the DC circuit of the acquisition circuit to prevent the physiological damage of the human body caused by the DC leakage current generated by the circuit.
- the signal amplification circuit has a variable amplification gain (for example, automatic gain adjustment or designated gain adjustment), which is used to adjust a small amplitude (for example, 10uV-100mV level) physiological activity signal to a voltage range that can be processed by the subsequent circuit.
- the filter circuit is used to filter out interference signals (such as power frequency interference, radiation noise, power supply noise, etc.), extract useful signals that are expected to be used, and improve the signal-to-noise ratio of the subsequent circuit when processing signals.
- the sample-and-hold circuit is used to ensure that the signal applied to the analog-to-digital conversion circuit remains unchanged during the time period when the analog-to-digital conversion circuit is completed, and to reduce the influence of signal fluctuations on the accuracy of the conversion result.
- the analog-to-digital conversion circuit is used to sample the amplified and filtered analog signal at high speed and convert it into a digital signal that can be stored and calculated by the program.
- the signal processing module is used to perform signal processing such as Fourier transform, filtering, and convolution operation on the converted digital signal to identify abnormal physiological activity signals when the disease occurs, and can generate corresponding instructions or marks. It can be understood that the foregoing description of the hardware circuit of the physiological activity signal acquisition and processing unit 106 is only illustrative, and those skilled in the art can perform various configurations, designs, and modifications according to actual application requirements.
- the preset detection conditions used may include, for example, a preset threshold or range of one or more parameters (such as voltage), if the voltage or other parameters of the physiological activity signal Exceeding the preset threshold or range indicates that it is a signal of abnormal physiological activity, and the patient is likely to be in a state of onset of disease at that time.
- the preset detection condition may include an abnormal state pattern, and the abnormal state pattern may include changes over time of one or more parameters of the physiological activity signal. In some examples, these parameters may be the strength and/or characteristic frequency of the physiological activity signal.
- the controller 104 can compare the known intensity variation curves according to the signal intensity changes collected by the implantable electrode device 102: if the similarity is higher than a judgment reference value (for example, 50%), it is considered that the collection
- a judgment reference value for example, 50%
- the physiological activity signal conforms to the abnormal state pattern, which is an abnormal physiological activity signal; on the contrary, if the similarity is lower than the judgment reference value, it is considered to be a normal physiological activity signal, that is, the disease did not occur at that time.
- the similarity comparison with the abnormal state mode can be performed based on a specific trigger condition, for example, the similarity comparison is started/triggered after the intensity of the physiological activity signal exceeds a predetermined threshold, which is beneficial to reduce the power consumption of unnecessary comparisons. .
- the physiological activity signal in a window period can be collected and the physiological activity signal included in the preset abnormal state mode is performed and related operations are performed: if the related operation result has a maximum value , It can be considered that the disease is onset and the stimulation is initiated; if the correlation calculation result does not show a maximum value, slide the window backward and collect another physiological activity signal for calculation, that is, perform the operation of cross-correlation calculation.
- the physiological activity signals collected during a period of time can be saved, and then the physiological activity signals collected afterwards can be operated on related calculations: similarly, if the calculation result shows a maximum value, the stimulation can be started; otherwise, the window will be turned to Then slide and continue to perform related operations, that is, perform auto-correlation operations.
- one or more parameters of the physiological activity signal included in the abnormal state pattern may be associated with a brain region; in other embodiments, one or more parameters of the physiological activity signal included in the abnormal state pattern are also It can be related to multiple brain regions, because multiple brain regions may be abnormal at the same time and may be abnormally related to each other at the onset of the disease. For example, there may be an abnormal intensity change first in the forelimb of the internal capsule, and then (e.g., after a few milliseconds or less) a similar abnormal intensity change in the nucleus accumbens.
- the controller 104 can acquire the parameter changes of the physiological activity signals of multiple brain regions at the same time, and determine whether the disease has occurred as a whole.
- the abnormal state pattern may be generated based on a preset abnormal state pattern, where the preset abnormal state pattern may be a statistical model generated in advance based on data collected when another patient has a disease onset.
- the abnormal state pattern may be generated using one or more historical abnormal physiological activity signals of a specific patient (for example, the patient in which the implantable electrode device is implanted).
- the abnormal state pattern can be updated in real time according to the historical abnormal physiological activity signal of the patient, and the update can be generated by training based on a machine learning algorithm.
- machine learning algorithms such as deep neural networks, can be used for the training of abnormal state patterns, and this application does not limit this.
- the preset abnormal state model can be updated according to the individual condition of the patient, so as to continuously improve the EEG signal model in the abnormal state model, that is, the process of self-learning and perfection is carried out.
- the controller stores the characteristic value of the disease or the doctor's experience value.
- the controller compares the collected physiological activity signal with the stored EEG signal model and determines that it is an onset
- the controller can store the physiological activity signal at the onset, and then compare the EEG signal model with the physiological activity signal at the onset Merge to obtain an optimized EEG signal model and update the previously stored EEG signal model.
- Figures 3 and 4 show two exemplary processes for updating the brain electrical signal model of the abnormal state pattern.
- step 302 the controller receives the physiological activity signal collected by the implantable electrode device.
- step 304 the controller determines whether the physiological activity signal exceeds a predetermined threshold, that is, whether to trigger an operation to compare with a preset abnormal state mode. If the judgment result is no, then go to step 322 and wait for signal collection during the next sampling period, after which the entire process of updating the status mode can be repeated. On the contrary, if the judgment result of step 304 is yes, then step 306 is triggered, that is, it is judged whether the parameter change of the collected physiological activity signal conforms to the preset abnormal state mode. If it does, then continue to step 308, and if it does not, then continue to step 310.
- Steps 308 and 310 are both used to determine whether the patient actually has the disease. If it is determined in step 308 that the patient is actually suffering from the disease, which means that the result of the previous abnormal state pattern determined in step 306 is accurate, then in step 312 the physiological activity signal received and being processed can be saved and combined with optimization and preset
- the default model for example, a mathematical model
- step 310 determines that the patient does not actually have the disease, it means that the result of the failure to conform to the preset abnormal state model determined in step 306 is accurate, then the preset model can be maintained unchanged in step 318; on the contrary, if Step 310 determines that the patient actually has the disease, which means that the result of the previous step 306 is inaccurate. Accordingly, the comparison threshold can be lowered in step 316, and/or the preset model can be combined and optimized. After that, for judging the actual disease, you can continue to step 320 to apply electrical stimulation to the patient through the implanted electrode device; on the contrary, for the judgment that the actual disease is not, you can continue to step 322 to perform the next sampling period. Signal Acquisition.
- the abnormal state mode can be updated according to the actual physical condition and disease state of each patient, so that the judgment of the abnormal state mode is more accurate, and misoperations and missed operations are reduced.
- the update method shown in Figure 3 is relatively complicated, and is particularly suitable for initializing the parameters of the physiological activity signal when the device is just implanted under hospital monitoring.
- Fig. 4 shows another process of updating the abnormal state mode according to an embodiment of the present application. Compared with the update process shown in FIG. 3, the process shown in FIG. 4 is relatively simple, and is more suitable for updating the abnormal state mode when the patient uses the device at home.
- step 402 the controller receives the physiological activity signal collected by the implantable electrode device.
- step 404 the controller determines whether the physiological activity signal exceeds a predetermined threshold, that is, whether to trigger an operation to compare with a preset abnormal state mode. If the judgment result is no, then go to step 416 and wait for signal collection during the next sampling period, after which the entire process of updating the state mode can be repeated. On the contrary, if the judgment result of step 404 is yes, then step 406 is triggered, that is, it is judged whether the parameter change of the collected physiological activity signal conforms to the preset abnormal state mode. If it does, continue to step 408, and if it does not, continue to step 416.
- Step 408 is used to determine whether the patient actually has the disease. If it is determined in step 408 that the patient is actually suffering from the disease, which means that the result of the previous abnormal state pattern determined in step 406 is accurate, then in step 410 the physiological activity signal received and being processed can be saved and combined with optimization and preset
- the default model (such as a mathematical model) associated with the abnormal state mode; on the contrary, if it is determined in step 408 that the patient does not actually have the disease, it means that the result of the previous step 406 is inaccurate, then continue to step 414 to maintain the default The model is unchanged, that is, the current physiological activity signal is not considered for updating. After step 414, step 416 can be continued.
- the controller can directly apply electrical stimulation or perform signal collection during the next sampling period according to the judgment result after judging whether it meets the preset abnormal state mode.
- the controller 104 also includes an electrical stimulation signal generating unit 108, which is coupled to the physiological activity signal acquisition and processing unit 106 and the implantable electrode device 102, and is used to receive whether the physiological activity signal generated by it belongs to abnormal physiological activity.
- the comparison result of the signals, and based on the comparison result, whether to apply electrical stimulation to one or more brain regions through the implantable electrode device 102 is controlled.
- the electrical stimulation signal generating unit 108 may generate an electrical stimulation signal with a therapeutic effect, usually an electrical stimulation pulse, according to the detection or processing result of the physiological activity signal collection and processing unit 106.
- the electrical stimulation signal generating unit 108 may be a current type stimulation source, a voltage type stimulation source or a charge transfer type stimulation source.
- One or more parameters of the electrical stimulation signal can be adjusted. These parameters include, for example, pulse frequency, pulse width, pulse amplitude, pulse shape (rising edge, falling edge, shape of pulse bottom), and duration.
- the implantable electrode device has multiple stimulation contacts, and the electrical stimulation pulses applied on each stimulation contact can be independent of each other or related to each other, for example, the same frequency, different phases, and the same frequency. Frequency is in phase, amplitude is increasing, etc. It can be understood that the doctor can adjust the parameters of the electrical stimulation pulse according to the actual conditions of different patients, or adjust the parameters of the electrical stimulation pulse according to the location of the brain region where the stimulation contact is located, or the relationship between them.
- each electrical stimulation can last from 1 s to 1 hour.
- at least one of the duration or amplitude of the electrical stimulation can be controlled or adjusted.
- the duration or amplitude of the electrical stimulation can be controlled according to the detected physiological activity signal.
- the duration and amplitude of the applied electrical stimulation can be positively correlated with the detected physiological activity signal, that is, the greater the intensity of the physiological activity signal, the longer the duration of the applied electrical stimulation, or the greater the amplitude .
- the electrical stimulation signal generating unit 108 may generate periodic electrical stimulation signals, so as to intermittently electrically stimulate the brain region through the implantable electrode device 102. Similarly, the amplitude, duration and frequency of the periodic electrical stimulation signal can be positively correlated with the detected physiological activity signal.
- the amplitude of the detected physiological activity signal is usually very small, which may be in the order of uV, while the amplitude of the electrical stimulation signal for treatment is usually much larger than the order of a few uV, which is, for example, between 100mV and 10V. , Preferably 0.5V to 10V. Therefore, if the physiological activity signal of the same brain area is detected immediately after stimulating a certain brain area, the sampling circuit will enter a saturated or supersaturated state due to the excessive electric charge introduced by electrical stimulation, thus failing to obtain an effective physiological activity signal .
- the next detection step may be executed after a predetermined time interval is completed for each stimulation step.
- the predetermined time interval may be 0.01 ms to 1 hour, for example.
- Figures 5 and 6 show two exemplary ways for applying electrical stimulation. Both of these methods can avoid the aforementioned problem of saturation of the sampling circuit.
- a period of time can be used for charge balancing, and the same brain region can be sampled after the charge is balanced. Since the charge balance interval effectively eliminates the excessive charge introduced by electrical stimulation, the physiological activity signal obtained by sampling can accurately reflect the physiological condition of the brain region.
- This stimulus-charge balance-sampling can be performed periodically, thereby enabling continuous detection and treatment of patients.
- the stimulation of the brain area can be performed in a time-sharing manner with the sampling, that is, after a period of stimulation, the charge balance can be waited for. Then, the brain area can be sampled for a period of time. After completing the sampling of the physiological activity signal, the brain area can be stimulated continuously.
- the duration of the stimulation operation can be adjusted according to actual needs, such as adjusting the number of stimulation pulses.
- the application methods of electrical stimulation shown in Figures 5 and 6 are performed after the abnormality has been determined and the electrical stimulation needs to be applied. of.
- the sampling operations shown in FIGS. 5 and 6 are used to determine whether the parameters of the electrical stimulation need to be adjusted, or whether the electrical stimulation needs to be stopped (for example, the patient is in a non-morbid state).
- the electrical stimulation signal generation unit can adjust the stimulation parameters according to the detection result of the physiological activity signal collection and processing unit to achieve a better therapeutic effect.
- the controller may store the stimulation parameters with better therapeutic effects as the stimulation parameters for the next onset.
- Fig. 7 shows a flow of electrical stimulation parameter adjustment according to an embodiment of the present application.
- the electrical stimulation parameters can be dynamically adjusted according to the patient's symptoms after the electrical stimulation is applied.
- the electrical stimulation signal generating unit receives the physiological activity signal collected by the physiological activity signal collection and processing unit.
- the electrical stimulation signal generating unit determines whether the abnormal physiological activity signal is received for the first time, that is, whether the patient has the first disease after the implantation. If it is the first onset, in step 708, the preset stimulation parameters are used, and the preset stimulation parameters are preset by the doctor according to the patient's condition, for example. If it is determined in step 706 that it is not the first onset, then in step 710, it is determined whether the current physiological activity signal (representing the symptoms of the current patient's onset) is improved compared to the patient's physiological activity signal after the previous stimulation.
- step 712 it is further judged whether this improvement is the first symptom improvement: if so, the current stimulation parameters are maintained for the next stimulation in step 714; on the contrary, if it is not the first symptom improvement, continue to step 716, The stimulus parameter is incremented, for example, the step is incremented by a preset value.
- step 718 is further performed to determine whether the current deterioration is the first symptom deterioration: if so, the previous symptom is used in step 720
- the stimulus parameter is used for the next stimulus; on the contrary, if the symptoms are not getting worse for the first time, continue to step 722, and the stimulus parameter is decreased, for example, the step is decreased by a preset value.
- the electrical stimulation signal generating unit generates electrical stimulation signals according to the determined stimulation parameters and applies electrical stimulation to the brain region of the patient through the implantable electrode device.
- the above process enables the controller to dynamically adjust the electrical stimulation parameters according to the improvement/deterioration effect of the patient's symptoms.
- the electrical stimulation signal can have multiple parameters that can be adjusted. Accordingly, one parameter, such as the stimulation voltage amplitude, can be adjusted first, and then one or more other parameters can be adjusted in turn after the adjustment is completed. Parameters such as the duration and frequency of the stimulation voltage.
- the controller 104 shown in FIG. 1 can be configured as a whole to be implanted in the patient's body, or can be constructed in two parts, one of which is implanted in the patient's body, and the other part is set outside the patient's body. , For example, set to a portable structure.
- the part of the controller 104 implanted in the body can be powered by an integrated battery, and the part outside the body can be powered by another battery, and the two parts can be coupled to each other through wireless communication.
- circuits or modules that require large data volume calculations can be installed outside the body and powered by a separate battery, which is beneficial to reduce the power consumption of the battery in the body, thereby prolonging the service life.
- the controller 104 may also be coupled to an external device, such as a server or a computer used by a doctor in a wireless communication manner, and may send detected physiological activity signals or stimulation history records to it, so that The doctor can monitor the patient's treatment status in real time.
- an external device such as a server or a computer used by a doctor in a wireless communication manner
- the device shown in Figure 1 can continuously monitor the physiological activity signals of the implanted electrodes and determine whether the signal level has reached the level of disease onset in real time. Once it reaches or exceeds the clinically confirmed disease onset pattern, it can be Apply a corresponding level of electrical stimulation to the brain area of this part (the energy level of electrical stimulation is determined by the doctor according to the patient's clinical efficacy). When it is detected that the physiological activity signal has not reached the level of disease onset, the stimulation can be stopped and the physiological activity signal detection state can be returned. This not only reduces the side effects of stimulating the patient in the non-seizure state, but also reduces the power consumption and prolongs the service life.
- modules or sub-modules of the device for neurostimulation of patients are mentioned in the above detailed description, this division is only exemplary and not mandatory.
- the features and functions of the two or more modules described above can be embodied in one module.
- the features and functions of a module described above can be further divided into multiple modules to be embodied.
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Abstract
一种用于对患者进行神经刺激的方法和装置(100)。用于对患者进行神经刺激的方法包括:通过植入式电极检测患者的一个或多个脑部区域的生理活动信号;将检测到的所述生理活动信号与预设检测条件进行比较以确定所检测的生理活动信号是否属于异常生理活动信号;以及基于所述比较结果,控制是否通过所述植入式电极对所述一个或多个脑部区域施加电刺激。
Description
本申请涉及一种用于对患者进行神经刺激的方法和装置。
植入式医疗设备被广泛用于疾病的诊断、监测和治疗,例如心脏起搏器、脑起搏器、除颤器、神经刺激器以及药物泵等等。在使用过程中,设置于封闭壳体内的电子电路和电池元件与封闭壳体外的传感器、电极之间电连接,以实现对身体具体部位的监测或提供电/光刺激等。以神经刺激器为例,设置于封闭壳体中的脉冲发生器通过延伸的导线与电极相连接,从而将脉冲发生器所产生的脉冲传输至布置于特定位置的电极,从而在该位置进行电刺激。
脑深部刺激器是一种通过电刺激患者脑部来进行疾病治疗的神经刺激器。目前在市场上已经有一些脑深部刺激器产品进入了临床应用,例如用于治疗帕金森综合征、药物成瘾或其他神经性疾病。然而,现有的脑深部刺激器的使用寿命较短,有一些仅能够使用半年到一年,甚至更短,难以满足长期疾病治疗的需要。
因此,有必要提供一种改进的神经刺激装置。
发明内容
本申请提供了一种用于对患者进行神经刺激的方法,能够通过检测患者的异常生理活动信号来针对性地对患者进行神经刺激。
在本申请的一个方面,提供了一种用于对患者进行神经刺激的方法,所述方法包括:通过植入式电极检测患者的一个或多个脑部区域的生理活动信号;将检测到的所述生理活动信号与预设检测条件进行比较以确定所检测的生理活动信号是否属于异常生理活动信号;以及基于所述比较结果,控制是否通过所述植入式电极对所述一个或多个脑部区域施加电刺激。
在本申请的另一个方面,提供了一种用于对患者进行神经刺激的装置,包括:第一植入式电极,用于被设置在患者的第一脑部区域;第二植入式电极,用于被设置在患者的第二脑部区域;控制器,用于获取患者所述第一脑部区域和第二脑部区域的检测到的生理活动信号,并且与预设检测条件进行比较以确定所检测的生理活动信号是否属于异常生理活动信号;以及基于所述比较结果,控制是否通过所述第一植入式电极或所述第二植入式电极中的至少一个对所述第一脑部区域和所述第二脑部区域中的至少一个施加电刺激。
在本申请的又一方面,还提供了一种用于对患者进行神经刺激的装置,其中,所述装置包括非暂时性存储介质,所述非暂时性存储介质具有可被处理器运行的指令,所述指令被运行以执行下述步骤:通过植入式电极检测患者的一个或多个脑部区域的生理活动信号;将检测到的所述生理活动信号与预设检测条件进行比较以确定所检测的生理活动信号是否属于异常生理活动信号;以及基于所述比较结果,控制是否通过所述植入式电极对所述一个或多个脑部区域施加电刺激。
以上为本申请的概述,可能有简化、概括和省略细节的情况,因此本领域的技术人员应该认识到,该部分仅是示例说明性的,而不旨在以任何方式限定本申请范围。本概述部分既非旨在确定所要求保护主题的关键特征或必要特征,也非旨在用作为确定所要求保护主题的范围的辅助手段。
通过下面说明书和所附的权利要求书并与附图结合,将会更加充分地清楚理解本申请内容的上述和其他特征。可以理解,这些附图仅描绘了本申请内容的若干实施方式,因此不应认为是对本申请内容范围的限定。通过采用附图,本申请内容将会得到更加明确和详细地说明。
图1示出了根据本申请一个实施例的用于对患者进行神经刺激的装置;
图2示出了根据本申请一个实施例的植入式电极;
图3示出了根据本申请一个实施例的更新异常状态模式的流程;
图4示出了根据本申请一个实施例的另一种更新异常状态模式的流程;
图5和图6示出了两种示例性的用于施加电刺激的方式;
图7示出了根据本申请一个实施例的电刺激参数调整的流程。
在下面的详细描述中,参考了构成其一部分的附图。在附图中,类似的符号通常表示类似的组成部分,除非上下文另有说明。详细描述、附图和权利要求书中描述的说明性实施方式并非旨在限定。在不偏离本申请的主题的精神或范围的情况下,可以采用其他实施方式,并且可以做出其他变化。可以理解,可以对本申请中一般性描述的、在附图中图解说明的本申请内容的各个方面进行多种不同构成的配置、替换、组合,设计,而所有这些都明确地构成本申请内容的一部分。
本申请的发明人发现,现有的脑深部刺激器通常需要持续性地向脑部区域中的被刺激部位施加电刺激信号,这对于帕金森综合征这一类持续发作的疾病是合理的。然而,例如抑郁症、强迫症或者药物成瘾疾病(例如海洛因药物戒断后的防止复吸)等很多其他的神经性疾病,其通常并不是持续发作,而是不定期地间歇发作。在疾病的非发作期间,脑深部刺激器并不需要向被刺激部位施加电刺激信号。相反,如果在此期间仍然持续地向脑部施加电刺激信号,特别针对某些疾病所施加的高能量水平的电刺激信号,这会对患者的日常情绪产生负面影响。此外,持续性地施加电刺激会导致过多的能量释放,这会显著缩短脑深度刺激器的使用寿命。
此外,发明人还发现,对于前述的间歇性发作的神经性疾病,在疾病发作期间,脑部某些区域的脑电信号会出现异常,例如脑电信号的幅度相比于未发作期间会显著增大,而脑电信号的这种异常变化或状态可以作为监控疾病是否发作的条件。因此,如果能够检测这种异常的脑电信号,并且相应地来控制向脑部区域施加电刺激信号,那么脑深部神经刺激器就不需要持续地向脑部区域中的被刺激部位施加电刺激信号。
基于上述发现,本申请的发明人创造性地将监测患者脑部区域的生理活动的装置集成到脑深部刺激器中,并且通过监测患者脑部的异常生理活动来有针对性地向患者脑部施加电刺激,这大大提高了神经刺激的效率,并且减少了不必要电刺激产生的副作用。此外在一些例子中,本申请的方法和装置还能够根据每位患者的异常生理活动信号的历史数据生成个人化的判断条件,从而使得电刺激的施加能够更准确地适应不同患者的个人情况,这进一步改善了治疗效果。
以下将结合具体的实施例对本申请的方法和装置进行说明。
图1示出了根据本申请一个实施例的用于对患者进行神经刺激的装置100。通过该装置100,医生或其他用户能够控制对患者的脑部区域进行神经刺激的方法,以用于治疗某些神经性疾病,例如药物成瘾、强迫症、抑郁症、癫痫等间歇发作的神经性疾病,或者其他神经性疾病,例如帕金森综合征等。可以理解,医生可以根据各种疾病的治疗需要采用结合本申请各个实施例所描述的用于对患者进行神经刺激的装置来对患者进行治疗,本申请并不对此进行限制。在一些实施例中,用于对患者进行神经刺激的方法可以被设置为可被处理器运行的指令,该指令可以被存储在非暂时性存储介质中,并且在被处理器运行后执行。
如图1所示,该装置100包括植入式电极装置102和控制器104。植入式电极装置102可以通过手术被植入于患者的脑部,用于检测患者一个或多个脑部区域的生理活动信号,和/或对患者一个或多个脑部区域施加电刺激信号。在一些实施例中,植入式电极装置102的可以被构造为探针或类似结构,其外侧表面上可以露出一个或多个电极触点以分别与特定的脑部区域接触。这些电极触点可以被导电元件电耦接至探针内部,以与控制器104电连接。
在一些实施例中,植入式电极装置102可以包括一个植入式电极,其上可以设置有一个或多个电极触点。在一些例子中,一个或多个电极触点可以既作为检测触点又作为刺激触点,例如,一个电极触点的检测和刺激可以分时进行,先进行检测并随后进行刺激,之后可以重复一次或多次。在另一些例子中,一些电极触点可以作为检测触点,以用于检测其所接触的脑部区域的生理活动信号;而另一些电极触点可以作为刺激触点,以用于对其所接触的脑部区域施加电刺激信号。例如,植入式电极可以包括至少一个用于检测的检测触点和至少一个用于刺激的刺激触点;或者,植入式电极也可以包括多个检测触点和多个刺激触点。优选地,检测触点和接触触点可以成对地或成组地设置。例如,植入式电极上的检测触点的数量可以刺激触点的数量相同,并且每个检测触点的位置与配对的刺激触点的位置大体重叠。这样,在某个检测触点检测到其所在的脑部区域存在异常生理活动信号后,控制器可以在判断后通过对应的刺激触点来向该脑部区域施加用于治疗目的的电刺激信号。可选地,植入式电极可以包括多个刺激触点,而每个刺激触点均对应于至少一个检测触点,从而每个刺激触点与其对应的至少一个检测触点形成检测-刺激组,并且每个检测-刺激组可以独立地检测 生理活动信号和施加电刺激信号。在一些例子中,不同检测-刺激组进行电生理信号检测和施加电刺激信号的时间与至少另一个检测-刺激组不同步。这样,可以根据植入式电极上电极触点在脑部区域的位置来调整电刺激信号的施加,以满足不同治疗目的或要求。在另一些例子中,不同检测-刺激组进行生理活动信号的检测和施加电刺激信号的时间均同步。同一检测-刺激组中的检测触点与刺激触点可以在相同的脑部区域或者在不同的脑部区域。
在一些实施例中,植入式电极装置102可以包括多组植入式电极,其中每组植入式电极都包括一个或多个植入式电极。可选地,至少一组植入式电极可以既包括检测触点又包括刺激触点;另一些植入式电极可以仅包括刺激触点,或者可以仅包括检测触点。在另一些实施例中,植入式电极装置102可以包括多组植入式电极,其中部分植入式电极可以仅包括检测触点,而另一部分植入式电极可以仅包括刺激触点。
可以理解,植入式电极装置102包括的植入式电极的数量,以及每个植入式电极上包括的电极触点的数量与类型可以根据实际应用需要灵活地设置。在一些实施例中,植入式电极装置102可以包括两个植入式电极,其中第一植入式电极可以被设置在患者的第一脑部区域,例如左侧脑深部区域,而第二植入式电极可以被设置在患者的第二脑部区域,例如右侧脑深部区域。通过这两个植入式电极,可以同步或不同步地检测这两个脑部区域,或者同步或不同步地对这两个脑部区域施加电刺激。进一步地,每个植入式电极上都可以设置有多个检测触点和/或刺激触点,从而进一步地根据这些电极触点实际接触的脑部区域的局部检测或施加电刺激。
根据实际应用的不同,植入式电极装置102可以被植入于脑皮层区域或脑深部区域中的至少一个区域。在一些实施例中,植入式电极的检测触点和/或刺激触点可以被置于脑深部区域,例如伏隔核或内囊前肢中的至少一个。发明人发现对这两个脑深部区域施加电刺激信号可以有效抑制某些神经性疾病,例如药物成瘾。在另一些实施例中,植入式电极的刺激触点可以被置于其他脑部区域,例如丘脑、丘脑下神经核、海马体、苍白球等。在一些实施例中,脑深部区域包括左右两侧脑深部区域,优选地,可以同时在左右两侧脑深部区域植入植入式电极并对通过其上的刺激触点对这些区域进行电刺激。
在一些实施例中,植入式电极包括直径为0.1至3mm的一个或多个检测触点,每个检测触点可以检测5uV至12.5mV的生理活动信号,该生理活动信号的频率为 0.5至150Hz。在另一些实施例中,植入式电极包括直径为0.1至0.5mm的一个或多个检测触点,每个检测触点可以检测5uV至10mV的生理活动信号,该生理活动信号的频率为150至30000Hz。这些生理活动信号大体对应于皮层脑电信号与脑深部区域的局部脑电信号。在一些实施例中,刺激触点可以具有类似于检测触点的尺寸和构造。
图2示出了根据本申请一个实施例的植入式电极。在一些例子中,图1所示的植入式电极装置102可以包括一个或多个图2所示的植入式电极。
如图2所示,植入式电极可以被构造为具有伸长主体的探针结构,电极触点可以沿该伸长主体纵向地分布,从而按照预设的间隔与不同位置的脑部区域接触。图2所示的植入式电极包括12个电极触点,在一些其他的例子中,电极触点的数量可以不同。此外,图2所示的电极触点被表示为直列排布于植入式电极上,在一些其他的例子中,电极触点也可以环状排布、交替排布或以任何其他所需的排布方式设置在植入式电极上。此外,植入式电极也可以被构造为任何其他的形状,例如弯折结构、螺旋形状、环状或其他形状。
在一个植入式电极上设置多个电极触点是有利的。例如,当这些电极触点中的一部分作为检测触点时,多个相邻的检测触点检测到的生理活动信号可以被采用差分方式采集。换言之,实际用于后续判断的生理活动信号可以是某个检测触点(作为采样点)与其他检测触点(作为参考点)之间的生理活动信号的信号差异。这样差分信号采集方式有助于减少噪声信号的干扰,提取有用信号。此外,在一些实施例中,作为采样点的检测触点的数量和位置可以被配置,而作为参考点的检测触点的数量和位置也同样可以被配置,换言之,任意一个检测触点均可以被选择作为采样点或参考点。仍参考图2所示,例如,相邻的检测触点4-6可以作为一组检测触点,其中检测触点5作为采样点而检测触点4和6作为参考点。这样,这3个检测触点可以生成反映其所在的脑部区域周围生理活动的一个生理活动信号,该生理活动信号以检测触点5作为采样的信号输入,而以检测触点4和6短路后的信号作为采样的参考信号。类似地,参考点可以是一个检测触点,也可以是多个检测触点;或者,参考点既可以是采样点周围的临近检测触点,也可以是有一定距离的其他检测触点。
一般来说,被植入脑部的电极触点通常需要与脑组织或神经组织相接触,通过接触界面将电刺激释放至人体组织,因此,电极触点的材料需要为生物相容性好、电化 学耐腐蚀性好的导体材料,例如铂(Pt)、铂铱合金(PtIr)等。电极触点的形状可以是环状、点状、片状,具体形状需要根据产品预期植入的位置和用途确定。此外,电极触点的尺寸可以根据需要刺激或检测的神经细胞数量确定,从0.01至6mm不等。例如,针对单个或数个神经元的触点,尺寸可在0.01至0.1mm之间;针对数百至数万神经元的触点,尺寸可在0.1至0.5mm之间;而针对功能核团或更大尺寸脑组织的应用,尺寸可在0.5至6mm之间。
回到图1,用于对患者进行神经刺激的装置100还包括控制器104,其用于获取患者植入式电极装置100所在的一个或多个脑部区域的检测到的生理活动信号,并且与预设检测条件进行比较以确定所检测的生理活动信号是否属于异常生理活动信号。控制器104进一步地基于比较结果控制是否通过植入式电极装置100对患者的一个或多个脑部区域施加电刺激。
在一些实施例中,例如如图1所示的实施例中,控制器104可以包括生理活动信号采集处理单元106和电刺激信号产生单元108。其中,生理活动信号采集处理单元106耦接到植入式电极装置102以接收其采集的生理活动信号,并且将该生理活动信号与预设检测条件进行比较,以判断是否为异常生理活动信号。在一些实施例中,脑电信号采集处理单元106可以进一步包括信号采集模块和信号处理模块。其中,信号采集模块用于采集生理活动信号,并将其所体现的微弱的模拟生物电压、电流信号转换为可供后续处理模拟或数字信号,优选为数字信号。在一个例子中,信号采集模块可以包括信号隔离、信号放大、信号滤波、采样/保持电路、信号模数转换电路等电路元件。具体地,信号隔离电路用于将人体的生理活动信号与采集电路的直流电路进行隔离,防止由于电路产生的直流漏电流造成的人体生理损伤。信号放大电路具备可改变的放大增益(例如,自动增益调节或指定增益调节),用于将小幅值(例如10uV~100mV级别)的生理活动信号,调节至可供后续电路处理的电压范围。滤波电路用于滤除干扰信号(例如工频干扰、辐射噪声、电源噪声等),将预期需要使用的有用信号提取出来,提高后级电路处理信号时的信噪比。采样保持电路,用于确保模数转换电路在一次转换完成的时间段内,施加在模数转换电路上的信号保持不变,减小信号波动对转换结果准确性的影响。模数转换电路用于将经过放大、滤波之后的模拟信号经过高速采样,转换为可供程序进行存储、运算的数字信号。信号处理模块用于将转换的数字信号进行傅里叶变换、滤波、卷积运算等信号处理,以识别出疾病发 作时的异常生理活动信号,并且可以生成对应的指示或标识。可以理解,上述关于生理活动信号采集处理单元106的硬件电路的描述仅仅是示意性的,本领域技术人员可以根据实际应用的需要进行各种配置、设计和修改。
控制器104,或者具体地生理活动信号采集处理单元106,所采用的预设检测条件可以包括例如一个或多个参数(例如电压)的预设阈值或范围,如果生理活动信号的电压或其他参数超出了预设阈值或范围,则说明其为异常生理活动信号,患者当时很可能出于疾病发作状态。在一些实施例中,预设检测条件可以包括异常状态模式,该异常状态模式可以包括生理活动信号的一个或多个参数随时间的变化。在一些例子,这些参数可以是生理活动信号的强度和/或特征频率。例如,当疾病未发作时,脑部区域的生理活动信号的幅值或强度可能相对较低,其周期也是随机无序的;然而当疾病发作时,生理活动活动信号的强度可能相对较高,并且可能以某种变化曲线周期性地变化。相应地,控制器104可以根据植入式电极装置102采集的信号强度变化来对已知的强度变化曲线进行相似度比较:如果相似度高于一判断参考值(例如50%),则认为采集的生理活动信号符合异常状态模式,其为异常生理活动信号;相反如果相似度低于判断参考值,则认为其是正常的生理活动信号,也即疾病当时并未发作。优选地,与异常状态模式的相似度比较可以是基于特定触发条件进行的,例如生理活动信号的强度超出预定阈值后才启动/触发相似度比较,这有利于降低不必要比较所占用的功耗。
在一些实施例中,进行相似度比较时,可以采集一段窗口时期内的生理活动信号与预设的异常状态模式包括的生理活动信号进行并相关运算的操作:如果相关运算结果出现一个极大值,则可认为疾病发作,启动刺激;如果相关运算结果没有出现极大值,则将窗口向后滑动,采集另一段生理活动信号进行运算,也即进行互相关运算的操作。在一个例子中,可以保存一段时间内采集的生理活动信号,与之后采集的生理活动信号进行相关运算的操作:同样的,如果运算结果出现一个极大值,则可启动刺激;否则将窗口向后滑动并继续进行相关操作,也即进行自相关运算的操作。
在一些实施例中,异常状态模式包括的生理活动信号的一个或多个参数可以关联于一个脑部区域;在另一些实施例中,异常状态模式包括的生理活动信号的一个或多个参数也可以关联于多个脑部区域,这是因为在疾病发作时多个脑部区域可能同时出现异常并且有可能异常相互关联。例如,可能出现首先在内囊前肢出现异常的强度变 化,并且随后(例如几个毫秒或更短的时间后)在伏隔核出现类似的异常强度变化。相应地,控制器104可以同时获取多个脑部区域的生理活动信号的参数变化,并且整体地判断疾病是否发作。
在一些实施例中,异常状态模式可以是基于预设异常状态模式生成的,其中该预设异常状态模式可以是基于其他患者疾病发作时采集的数据事前生成的统计模型。在另一些实施例中,异常状态模式可以是利用特定患者(例如植入式电极装置所植入的患者)的一个或多个历史异常生理活动信号生成的。优选地,可以根据患者历史异常生理活动信号对异常状态模式进行即时更新,该更新可以通过基于机器学习算法训练生成。各种机器学习算法,例如深度神经网络,都可以用于异常状态模式的训练,本申请对此不作限制。
特别地,由于患者个体的差异,在判断生理活动信号水平是否达到疾病发作的程度时,如果采用统一的标准可能会不够准确。因此,优选地,可以根据患者个体情况来对预设异常状态模式进行更新,以不断改进异常状态模式中的脑电信号模型,也即进行自我学习完善的过程。具体地,在脑深部刺激器初始植入患者脑部时,控制器中存储可以是该疾病的特征值或者是医生的经验值。当控制器将采集的生理活动信号与所存储的脑电信号模型进行比较并判断为发病时,控制器可以存储发病时的生理活动信号,进而将脑电信号模型与发病时的生理活动信号进行合并,得到优化的脑电信号模型并更新之前存储的脑电信号模型。
图3和图4示出了更新异常状态模式的脑电信号模型的两种示例性流程。
如图3所示,该流程始于步骤302,控制器接收植入式电极装置采集的生理活动信号。接着,在步骤304,控制器判断该生理活动信号是否超出预定阈值,也即是否触发与预设异常状态模式比较的操作。如果判断结果为否,则进入步骤322,等待进行下一采样期间的信号采集,之后可以重复整个更新状态模式的流程。相反,如果步骤304的判断结果为是,则触发进行步骤306,也即判断采集的生理活动信号的参数变化是否符合预设异常状态模式。如果符合则继续步骤308,而如果不符合则继续步骤310。步骤308和310均用于判断患者是否实际发病。如果在步骤308判断患者实际发病,这说明之前步骤306判断的符合预设异常状态模式的结果是准确的,那么在步骤312可以将该接收并正在处理的生理活动信号保存并合并优化与预设异常状态模式相关联的预设模型(例如一数学模型);相反,如果在步骤308判断患者实际并未 发病,这说明之前步骤306判断的结果是不准确的,相应地,可以在步骤314提高比较阈值。类似地,如果在步骤310判断患者实际并未发病,这说明之前步骤306判断的不符合预设异常状态模式的结果是准确的,那么在步骤318可以维持预设模型不变;相反,如果在步骤310判断患者实际发病,这说明之前步骤306判断的结果是不准确的,相应地,可以在步骤316降低比较阈值,和/或合并优化预设模型。在此之后,对于判断实际发病的情况,可以继续步骤320,通过植入式电极装置向患者施加电刺激;相反,对于判断实际并未发病的情况,可以继续步骤322,进行下一采样期间的信号采集。
可以理解,通过上述方式,可以针对每个患者的实际身体状况和发病状态更新异常状态模式,从而使得异常状态模式的判断更准确,减少误操作和漏操作。图3所示的更新方式相对复杂,特别适合在医院监护下刚植入设备时对生理活动信号的参数进行初始化。
图4示出了根据本申请一个实施例的另一种更新异常状态模式的流程。相比于图3所示的更新流程,图4所示的流程相对简单,比较适合患者在家自行使用装置时更新异常状态模式。
如图4所示,该流程始于步骤402,控制器接收植入式电极装置采集的生理活动信号。接着,在步骤404,控制器判断该生理活动信号是否超出预定阈值,也即是否触发与预设异常状态模式比较的操作。如果判断结果为否,则进入步骤416,等待进行下一采样期间的信号采集,之后可以重复整个更新状态模式的流程。相反,如果步骤404的判断结果为是,则触发进行步骤406,也即判断采集的生理活动信号的参数变化是否符合预设异常状态模式。如果符合则继续步骤408,而如果不符合则继续步骤416。步骤408用于判断患者是否实际发病。如果在步骤408判断患者实际发病,这说明之前步骤406判断的符合预设异常状态模式的结果是准确的,那么在步骤410可以将该接收并正在处理的生理活动信号保存并合并优化与预设异常状态模式相关联的预设模型(例如一数学模型);相反,如果在步骤408判断患者实际并未发病,这说明之前步骤406判断的结果是不准确的,则继续步骤414,维持预设模型不变,也即不考虑当前生理活动信号用于更新。在步骤414之后,可以继续步骤416。
可以理解,在不需要对异常状态模式的脑电信号模型进行更新时,控制器在判断是否符合预设异常状态模式后,可根据判断结果直接进行施加电刺激或者进行下一采 样期间的信号采集。
回到图1,控制器104还包括电刺激信号产生单元108,其耦接到生理活动信号采集处理单元106与植入式电极装置102,用于接收其生成的生理活动信号是否属于异常生理活动信号的比较结果,并且基于该比较结果控制是否通过植入式电极装置102向一个或多个脑部区域施加电刺激。
在一些实施例中,电刺激信号产生单元108可以根据生理活动信号采集处理单元106的检测或处理结果,生成具有治疗效果的电刺激信号,通常是电刺激脉冲。电刺激信号产生单元108可以是电流型刺激源,也可是电压型刺激源或电荷转移型刺激源。电刺激信号的一个或多个参数可以调整,这些参数例如包括脉冲频率、脉冲宽度、脉冲幅度、脉冲形状(上升沿、下降沿、脉冲底部的形状)以及持续时长等。
在一些实施例中,植入式电极装置具有多个刺激触点,而每个刺激触点上施加的电刺激脉冲可以是相互独立的,也可以是相互关联的,例如同频不同相、同频同相、幅值递增等。可以理解,医生可以根据不同患者的实际病况来调整电刺激脉冲的参数,或者根据刺激触点所在的脑部区域的位置来调整电刺激脉冲的参数,或者其相互之间的关系。
在一些实施例中,每次电刺激可以持续1s至1小时。在一些实施例中,电刺激的持续时间长度或幅度中的至少一个可以被控制或调整。优选地,可以根据检测到的生理活动信号来控制电刺激的持续时间长度或幅度。例如,所施加的电刺激持续的时间长度和幅度可以与检测到的生理活动信号正相关,也即生理活动信号的强度越大,则施加的电刺激的持续时间长度越长,或者幅度越大。
在一些优选的实施例中,电刺激信号产生单元108可以生成周期性电刺激信号,从而通过植入式电极装置102间歇性地对脑部区域进行电刺激。同样地,周期性电刺激信号的幅度、持续时间长度和频率可以与检测到的生理活动信号正相关。
一般来说,检测到的生理活动信号的幅值通常很小,可能在uV的量级,而治疗用电刺激信号的幅值通常远大于几uV的量级,其例如为100mV至10V之间,优选为0.5V至10V。因此,如果在刺激某一脑部区域后紧接着就检测同一脑部区域的生理活动信号,采样电路会因为电刺激引入的过量电荷而进入饱和或过饱和状态,从而无法获得有效的生理活动信号。为了避免这一问题,在一些实施例中,可以在每个刺 激步骤结束预定时间间隔之后,执行下一次检测步骤。预定时间间隔例如可以是0.01ms至1小时。
图5和图6示出了两种示例性的用于施加电刺激的方式。这两种方式均可以避免前述采样电路饱和的问题。
如图5所示,在对脑部区域进行刺激(例如采用脉冲信号进行电刺激)一段时间之后,可以间隔一段时间用于电荷平衡,并且在电荷平衡之后再对同一脑部区域进行采样。由于电荷平衡区间有效消除了电刺激引入的过量电荷,因此采样得到的生理活动信号能够准确地反映脑部区域的生理状况。这种刺激-电荷平衡-采样可以周期性地进行,从而使得能够持续检测并治疗患者。
如图6所示,对脑部区域进行刺激可以与采样分时进行,也即可以刺激一段时间之后,等待电荷平衡。接着,可以再对脑部区域进行一段时间的采样。在完成生理活动信号的采样之后,可以继续对脑部区域进行刺激。刺激操作的持续时间可以根据实际需要进行调节,例如调节刺激脉冲的数量。
可以理解,正如前述,由于电刺激的触发或启动是基于异常生理活动信号的出现,因而图5和图6所示的电刺激的施加方式均是在已确定存在异常并需要施加电刺激所进行的。在一些实施例中,图5和图6所示的采样操作是用于确定是否需要调整电刺激的参数,或者是否需要停止电刺激(例如患者处于非发病状态)。
在刺激的过程中,电刺激信号产生单元可以根据生理活动信号采集处理单元的检测结果来调整刺激的参数,以达到较好的治疗效果。在一些实施例中,控制器可以将较好治疗效果的刺激参数存储下来,作为下次发病时的刺激参数。
图7示出了根据本申请一个实施例的电刺激参数调整的流程。在该流程中,电刺激参数可以被根据患者被施加电刺激后的症状变化动态地调整。
如图7所示,在步骤702,电刺激信号产生单元接收生理活动信号采集处理单元采集的生理活动信号。在步骤706,电刺激信号产生单元确定是否首次接收到异常生理活动信号,也即患者是否植入后首次发病。如果是首次发病,则在步骤708,采用预设刺激参数,该预设刺激参数例如是医生根据患者病情预先设置的。如果在步骤706判断不是首次发病,则在步骤710,判断当前的生理活动信号(代表了当前患者发病症状)相比于前次刺激后的患者生理活动信号是否改善。如果相比而言有所改善,则 说明当前的刺激参数效果较好。相应地,在步骤712,进一步判断本次的改善是否是首次症状变好:如果是则在步骤714维持本次刺激参数用于下一次刺激;相反如果不是首次症状变好,则继续步骤716,刺激参数递增,例如步进增加一预设值。如果在步骤710判断相比前次刺激症状并未改善(也即变差),则进一步进行步骤718,判断本次的变差是否是首次症状变差:如果是则在步骤720中采用前次刺激参数用于下一次刺激;相反如果不是首次症状变差,则继续步骤722,刺激参数递减,例如步进减少一预设值。在步骤708、714、716、720和722确定刺激参数后,在步骤724,电刺激信号产生单元根据确定的刺激参数产生电刺激信号并通过植入式电极装置向患者脑部区域施加电刺激。
可以看出,上述流程使得控制器能够根据患者症状的改善/变差效果动态地调整电刺激参数。可以理解,在于一些实施例中,电刺激信号可以有多个参数能够被调节,相应地,可以先调整一个参数,例如刺激电压幅值,并且在调整结束后再依次调整其他的一个或多个参数,例如刺激电压的持续时间长度和频率。
需要说明的是,图1所示的控制器104可以被整体构造为适于植入患者体内,也可以被构造为两部分,其中一部分被植入患者体内,而另一部分则被设置于患者体外,例如设置为便携式结构。其中,控制器104被植入体内的部分可以由集成在一起的电池供电,而设置体外的部分则可以由另一电池供电,并且这两部分可以通过无线通信方式相互耦接。优选地,可以将例如需要进行大数据量计算的电路或模块设置于体外,由单独的电池供电,这有利于减少体内电池的功耗,从而延长使用寿命。在一些实施例中,控制器104还可以耦接至外部设备,例如以无线通信方式耦接至例如医生使用的服务器或计算机,并且可以向其发送检测的生理活动信号或刺激历史记录,从而使得医生能够实时监控患者的治疗状况。
可以看出,图1所示的装置能够持续监测植入式电极所在部位的生理活动信号,并实时判断信号水平是否达到疾病发作的程度,一旦达到或超过临床上确认的疾病发作模式,即可以向该部位脑部区域施加相应水平的电刺激(电刺激的能量水平由医生根据患者的临床疗效确定)。当检测到生理活动信号未达到疾病发作的程度,则可以停止刺激,返回生理活动信号检测状态。这既减少了非发作状态下对患者刺激所带来的副作用,也减少了功耗,延长了使用寿命。
应当注意,尽管在上文详细描述中提及了用于对患者进行神经刺激的设备的若干 模块或子模块,但是这种划分仅仅是示例性的而非强制性的。实际上,根据本申请的实施例,上文描述的两个或更多模块的特征和功能可以在一个模块中具体化。反之,上文描述的一个模块的特征和功能可以进一步划分为由多个模块来具体化。
那些本技术领域的一般技术人员可以通过研究说明书、公开的内容及附图和所附的权利要求书,理解和实施对披露的实施方式的其他改变。在权利要求中,措词“包括”不排除其他的元素和步骤,并且措辞“一”、“一个”不排除复数。在本申请的实际应用中,一个零件可能执行权利要求中所引用的多个技术特征的功能。权利要求中的任何附图标记不应理解为对范围的限制。
Claims (64)
- 一种用于对患者进行神经刺激的方法,其特征在于,所述方法包括:通过植入式电极装置检测患者的一个或多个脑部区域的生理活动信号;将检测到的所述生理活动信号与预设检测条件进行比较以确定所检测的生理活动信号是否属于异常生理活动信号;以及基于所述比较结果,控制是否通过所述植入式电极装置对所述一个或多个脑部区域施加电刺激。
- 根据权利要求1所述的方法,其特征在于,所述预设检测条件包括异常状态模式,所述异常状态模式包括生理活动信号的一个或多个参数随时间的变化。
- 根据权利要求2所述的方法,其特征在于,所述一个或多个参数包括生理活动信号的强度和/或特征频率。
- 根据权利要求2所述的方法,其特征在于,所述一个或多个参数关联于所述一个或多个脑部区域。
- 根据权利要求2所述的方法,其特征在于,所述异常状态模式是基于预设异常状态模式生成的。
- 根据权利要求5所述的方法,其特征在于,所述异常状态模式是利用所述患者的一个或多个历史异常生理活动信号对所述预设异常状态模式进行更新得到的。
- 根据权利要求6所述的方法,其特征在于,所述异常状态模式是基于机器学习算法训练生成的。
- 根据权利要求2所述的方法,其特征在于,所述检测步骤包括:将所检测的生理活动信号的一个或多个参数随时间的变化与所述异常状态模式包 括的生理活动信号的一个或多个参数随时间的变化进行相似度比较。
- 根据权利要求8所述的方法,其特征在于,所述相似度比较采用自相关算法或互相关算法。
- 根据权利要求1所述的方法,其特征在于,所述方法还包括:周期性地重复所述检测步骤和所述刺激步骤中的至少一个。
- 根据权利要求10所述的方法,其特征在于,在每个刺激步骤结束预定时间间隔之后,执行所述检测步骤。
- 根据权利要求11所述的方法,其特征在于,所述预定时间间隔是0.01毫秒至1小时。
- 根据权利要求1所述的方法,其特征在于,所述植入式电极装置对所述一个或多个脑部区域施加的电刺激持续1秒至1小时。
- 根据权利要求1所述的方法,其特征在于,基于所述比较结果,控制所述植入式电极装置对所述一个或多个脑部区域施加电刺激持续的时间长度和/或电刺激的幅度。
- 根据权利要求14所述的方法,其特征在于,所施加的电刺激持续的时间长度和幅度与所检测到的生理活动信号正相关。
- 根据权利要求1所述的方法,其特征在于,所述刺激步骤包括:通过所述植入式电极装置间歇性地对所述一个或多个脑部区域施加电刺激。
- 根据权利要求16所述的方法,其特征在于,所述间歇的电刺激时间长度、幅度和频率与所检测到的生理活动信号正相关。
- 根据权利要求1所述的方法,其特征在于,所述电刺激的幅度为0.5V至10V。
- 根据权利要求1所述的方法,其特征在于,所述植入式电极装置包括至少一个用于检测的检测触点,以及至少一个用于刺激的刺激触点。
- 根据权利要求19所述的方法,其特征在于,所述植入式电极装置包括多个所述检测触点,以及多个所述刺激触点。
- 根据权利要求20所述的方法,其特征在于,所述检测触点的个数与所述刺激触点的个数相同,并且所述检测触点的位置与所述刺激触点的位置大体重叠。
- 根据权利要求21所述的方法,其特征在于,所述植入式电极装置被植入于脑皮层区域或脑深部区域中的至少一个区域。
- 根据权利要求22所述的方法,其特征在于,所述植入式电极装置的检测触点被置于脑皮层区域或脑深部区域中的至少一个区域。
- 根据权利要求22所述的方法,其特征在于,所述植入式电极装置的刺激触点被置于脑深部区域。
- 根据权利要求22所述的方法,其特征在于,所述脑深部区域包括伏隔核或内囊前肢中的至少一个。
- 根据权利要求25所述的方法,其特征在于,所述脑深部区域包括左右两侧脑深部区域。
- 根据权利要求1所述的方法,其特征在于,所述植入式电极装置包括多组植入式电极,其中至少一组植入式电极既包括检测触点又包括刺激触点。
- 根据权利要求1所述的方法,其特征在于,所述植入式电极装置包括直径为0.1至3mm的一个或多个检测触点,每个检测触点所获取的生理活动信号的幅值为5uV至12.5mV,所述生理活动信号的频率为0.5至150Hz。
- 根据权利要求1所述的方法,其特征在于,所述植入式电极装置包括直径为0.1至0.5mm的一个或多个检测触点,每个检测触点所获取的生理活动信号的幅值为5uV至10mV,所述生理活动信号的频率为150至30000Hz。
- 根据权利要求1所述的方法,其特征在于,所述患者患有药物成瘾、强迫症或抑郁症。
- 根据权利要求30所述的方法,其特征在于,所述患者患有药物成瘾,所述电刺激抑制所述患者的药物瘾性。
- 根据权利要求1所述的方法,其特征在于,所述植入式电极装置包括多个用于刺激的刺激触点,并且每个刺激触点施加的电刺激信号是相同的。
- 根据权利要求1所述的方法,其特征在于,所述植入式电极装置包括多个用于刺激的刺激触点,并且每个刺激触点施加的电刺激信号是不同的。
- 根据权利要求1所述的方法,其特征在于,所述植入式电极装置包括多个用于刺激的刺激触点,并且每个刺激触点施加的电刺激信号的至少一个参数是相互关联的。
- 根据权利要求1所述的方法,其特征在于,所述植入式电极装置包括多个用于刺激的刺激触点,并且每个刺激触点均对应于至少一个检测触点,每个刺激触点和其所对应的至少一个检测触点形成检测-刺激组,每个检测-刺激组独立地检测生理活动信号和施加电刺激信号。
- 根据权利要求35所述的方法,其特征在于,不同检测-刺激组进行生理活动信号 检测和施加电刺激信号的时间与至少另一个检测-刺激组不同步。
- 根据权利要求35所述的方法,其特征在于,不同检测-刺激组进行生理活动信号检测和施加电刺激信号的时间均同步。
- 一种用于对患者进行神经刺激的装置,其特征在于,包括:第一植入式电极,用于被设置在患者的第一脑部区域;第二植入式电极,用于被设置在患者的第二脑部区域;控制器,用于获取患者所述第一脑部区域和第二脑部区域的检测到的生理活动信号,并且与预设检测条件进行比较以确定所检测的生理活动信号是否属于异常生理活动信号;以及基于所述比较结果,控制是否通过所述第一植入式电极或所述第二植入式电极中的至少一个对所述第一脑部区域和所述第二脑部区域中的至少一个施加电刺激。
- 根据权利要求38所述的装置,其特征在于,所述控制器还被用于同步或异步地向所述第一脑部区域和所述第二脑部区域施加电刺激。
- 根据权利要求39所述的装置,其特征在于,施加到所述第一脑部区域和施加到所述第二脑部区域的电刺激的时间长度、幅度、频率和脉宽中的至少一个参数不同。
- 根据权利要求38所述的装置,其特征在于,所述第一植入式电极还被用于检测所述第一脑部区域的生理活动信号;所述第二植入式电极还被用于检测所述第二脑部区域的生理活动信号。
- 根据权利要求41所述的装置,其特征在于,所述预设检测条件包括异常状态模式,所述异常状态模式包括生理活动信号的一个或多个参数随时间的变化。
- 根据权利要求41所述的装置,其特征在于,所述一个或多个参数包括生理活动信号的强度和/或特征频率。
- 根据权利要求31所述的装置,其特征在于,所述异常状态模式是基于预设异常状态模式生成的。
- 根据权利要求44所述的装置,其特征在于,所述异常状态模式是利用所述患者的一个或多个历史异常生理活动信号对所述预设异常状态模式进行更新得到的。
- 根据权利要求45所述的装置,其特征在于,所述异常状态模式是基于机器学习算法训练生成的。
- 根据权利要求41所述的装置,其特征在于,所述控制器还被用于:将所检测的生理活动信号的一个或多个参数随时间的变化与所述异常状态模式包括的生理活动信号的一个或多个参数随时间的变化进行相似度比较。
- 根据权利要求47所述的装置,其特征在于,所述相似度比较采用自相关算法或互相关算法。
- 一种用于对患者进行神经刺激的装置,其中,所述装置包括非暂时性存储介质,所述非暂时性存储介质具有可被处理器运行的指令,所述指令被运行以执行下述步骤:通过植入式电极装置检测患者的一个或多个脑部区域的生理活动信号;将检测到的所述生理活动信号与预设检测条件进行比较以确定所检测的生理活动信号是否属于异常生理活动信号;以及基于所述比较结果,控制是否通过所述植入式电极装置对所述一个或多个脑部区域施加电刺激。
- 根据权利要求49所述的装置,其特征在于,所述预设检测条件包括异常状态模式,所述异常状态模式包括生理活动信号的一个或多个参数随时间的变化。
- 根据权利要求50所述的装置,其特征在于,所述一个或多个参数包括生理活动信号的强度和/或特征频率。
- 根据权利要求50所述的装置,其特征在于,所述异常状态模式是基于预设异常状态模式生成的。
- 根据权利要求52所述的装置,其特征在于,所述异常状态模式是利用所述患者的一个或多个历史异常生理活动信号对所述预设异常状态模式进行更新得到的。
- 根据权利要求50所述的装置,其特征在于,所述检测步骤包括:将所检测的生理活动信号的一个或多个参数随时间的变化与所述异常状态模式包括的生理活动信号的一个或多个参数随时间的变化进行相似度比较。
- 根据权利要求49所述的装置,其特征在于,所述装置还包括:周期性地重复所述检测步骤和所述刺激步骤中的至少一个。
- 根据权利要求49所述的装置,其特征在于,基于所述比较结果,控制所述植入式电极装置对所述一个或多个脑部区域施加电刺激持续的时间长度和/或电刺激的幅度。
- 根据权利要求49所述的装置,其特征在于,所述刺激步骤包括:通过所述植入式电极装置间歇性地对所述一个或多个脑部区域施加电刺激。
- 根据权利要求49所述的装置,其特征在于,所述植入式电极装置包括多个用于检测的检测触点,以及多个用于刺激的刺激触点。
- 根据权利要求58所述的装置,其特征在于,所述检测触点的个数与所述刺激触点的个数相同,并且所述检测触点的位置与所述刺激触点的位置大体重叠。
- 根据权利要求59所述的装置,其特征在于,所述植入式电极装置被植入于脑皮层区域或脑深部区域中的至少一个区域。
- 根据权利要求60所述的装置,其特征在于,所述脑深部区域包括伏隔核或内囊前肢中的至少一个。
- 根据权利要求61所述的装置,其特征在于,所述脑深部区域包括左右两侧脑深部区域。
- 根据权利要求49所述的装置,其特征在于,所述植入式电极装置包括多个用于刺激的刺激触点,并且每个刺激触点施加的电刺激信号的至少一个参数是相互关联的。
- 根据权利要求49所述的装置,其特征在于,所述植入式电极装置包括多个用于刺激的刺激触点,并且每个刺激触点均对应于至少一个检测触点,每个刺激触点和其所对应的至少一个检测触点形成检测-刺激组,每个检测-刺激组独立地检测生理活动信号和施加电刺激信号。
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