Blind state maintaining system in nerve regulation random double-blind test

Abstract

The embodiment of the invention provides a blind state maintaining system in a nerve regulation random double-blind test, and relates to the field of intelligent medical treatment. The system comprises an information acquisition module used for acquiring grouping information of a plurality of detection objects including stimulation groups and pseudo stimulation groups; the execution receiving module is used for receiving an execution operation for the target detection object by using the experimental equipment; the first pre-stimulation module and the second pre-stimulation module are used for responding to the execution operation and controlling the execution mechanism to execute a first action and a second action on the target detection object based on the execution operation no matter whether the target detection object is the stimulation group or the pseudo-stimulation group; the test stimulation module is used for controlling an execution mechanism to execute an action for maintaining rated stimulation intensity on the target detection object based on execution operation when the target detection object is the stimulation group; and when the target detection object is the pseudo stimulation group, controlling the execution mechanism to execute an action with the stimulation intensity of 0 on the target detection object based on the execution operation.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of intelligent medical treatment, and more particularly, to a system for maintaining blind state in a neural modulation randomized double-blind test. BACKGROUND

[0002] A double-blind experiment refers to an experiment in which neither the tester nor the testee knows the group (experimental group or control group) to which the testee belongs, and the analyzer usually does not know which group the analyzed data belongs to. The double-blind experiment aims to eliminate subjective bias and personal preferences that may exist in the consciousness of the experimenter and the participants. In most cases, a double-blind experiment requires a very high degree of scientific rigor.

[0003] Although theoretically, a double-blind experiment can be achieved in clinical practice, the group information of the test drug may be inferred or known, for example, through differences in the operation modes of dispensing, administering, and sample collection corresponding to different groups of subjects, or according to the specificity of the group in the blood drug concentration, test results, or adverse drug reaction (ADR) types of a certain group of subjects, the subject's drug group information can be inferred. For example, in the treatment of refractory epilepsy, Parkinson's disease, and other neurological diseases, vagus nerve electrical stimulation (VNS) and deep brain electrical stimulation (DBS) are two different neural modulation techniques that have obvious therapeutic effects on diseases, but the double-blind test in the implementation process is relatively complex, and the risk of breaking the blind state is relatively high. SUMMARY

[0004] The present application aims to at least solve one of the technical problems existing in the prior art. To this end, the present application provides a system for maintaining blind state in a neural modulation randomized double-blind test; the method of the present application adds a pre-stimulation step before the actual test stimulation to avoid breaking the blind state during the implementation process.

[0005] The first aspect of the present application discloses a system for maintaining blind state in a neural modulation randomized double-blind test, the system comprising: an information acquisition module configured to acquire grouping information of a plurality of detection objects; the grouping information comprising a stimulation group and a pseudo-stimulation group; an execution receiving module configured to receive an execution operation for a target detection object using an experimental device, the target detection object being one of the plurality of detection objects, the execution operation being used to indicate an identifier of an execution parameter and a parameter value; a first pre-stimulation module configured to, in response to the execution operation, control an execution mechanism to perform a first action on the target detection object based on the execution operation, regardless of whether the target detection object belongs to the stimulation group or the pseudo-stimulation group; a second pre-stimulation module configured to control the execution mechanism to perform a second action on the target detection object based on the execution operation, regardless of whether the target detection object is the stimulation group or the pseudo-stimulation group; a test stimulation module configured to control the execution mechanism to perform an action of maintaining a rated stimulation intensity on the target detection object based on the execution operation when the target detection object is the stimulation group, and to perform an action of stimulating with an intensity of 0 on the target detection object based on the execution operation when the target detection object is the pseudo-stimulation group.

[0006] In some embodiments, the first action comprises: from an initial time point to a first time point, the stimulation intensity is raised from 0 to a first stimulation intensity, and the first stimulation intensity is maintained to a second time point; The second action comprises: from the second time point to a third time point, the stimulation intensity is raised from the first stimulation intensity to a second stimulation intensity as the rated stimulation intensity; Optionally, the second stimulation intensity is a pre-set maximum stimulation intensity; Optionally, between the second pre-stimulation module and the test stimulation module, the system further comprises: an adverse reaction judgment module configured to receive a reaction message of the target detection object, and to judge whether an adverse reaction occurs according to the reaction message, and if so, to perform the first action again in sequence for the target detection object with the adverse reaction; an adverse reaction judgment module configured to receive a reaction message of the target detection object, and to judge whether an adverse reaction occurs according to the reaction message, and if so, to perform the first action again in sequence for the target detection object with the adverse reaction;

[0007] In some embodiments, the time points are all calculated from an initial time point; Optionally, the first time point is 2-3 days; Optionally, the second time point is 4-5 days; Optionally, the third time point is 1-2 weeks.

[0008] In some embodiments, the grouping information is obtained by random grouping of the detection objects; Optionally, the information acquisition module further comprises a stimulation type of the plurality of detection objects, and the stimulation type comprises VNS and DBS.

[0009] In some embodiments, the system further comprises a blind state evaluation and correction module configured to evaluate the patient's blind state (including questions such as "What do you think the probability of receiving real treatment is?" and "Guessing basis") through a structured questionnaire, and if the correct rate of a certain group exceeds 60%, to start dynamic parameter adjustment (such as fine-tuning the current intensity difference between the treatment group and the control group).

[0010] In some embodiments, the system further comprises: a first pre-stimulation feedback module configured to receive feedback information sent by the execution mechanism as target feedback information when the first action is performed on the target detection object; a second pre-stimulation feedback module configured to receive feedback information sent by the execution mechanism as target feedback information when the second action is performed on the target detection object; a test stimulation feedback module configured to receive feedback information sent by the execution mechanism as target feedback information when the target detection object is the stimulation group or the pseudo-stimulation group.

[0011] The second aspect of the present application discloses an electronic device, which comprises a memory and a processor; the memory is configured to store a computer program; and the processor is configured to implement the following steps when executing the computer program: obtain grouping information of a plurality of detection objects; the grouping information comprises a stimulation group and a pseudo-stimulation group; receive an execution operation for a target detection object by using an experimental device; the target detection object is one of the plurality of detection objects; and the execution operation is configured to indicate an identifier of an execution parameter and a parameter value; in response to the execution operation, control an execution mechanism to perform a first action on the target detection object based on the execution operation, regardless of whether the target detection object is the stimulation group or the pseudo-stimulation group; in response to the execution operation, control the execution mechanism to perform a second action on the target detection object based on the execution operation, regardless of whether the target detection object is the stimulation group or the pseudo-stimulation group; when the target detection object is the stimulation group, control the execution mechanism to perform an action of maintaining a rated stimulation intensity on the target detection object based on the execution operation; and when the target detection object is the pseudo-stimulation group, control the execution mechanism to perform an action of having a stimulation intensity of 0 on the target detection object based on the execution operation.

[0012] The third aspect of the present application discloses a device for maintaining a blind state in a neural regulation randomized double-blind test, which comprises an experimental device, an execution mechanism, and the electronic device disclosed in the second aspect of the present application.

[0013] In some embodiments, the experimental device is a program-controlled device, and the execution mechanism is a stimulator arranged in the target detection object; or the experimental device is an electromagnetic wave control device, and the execution mechanism comprises an electromagnetic wave generating device and an electromagnetic wave detecting device.

[0014] In some embodiments, the experimental device is a drug delivery control device, and the execution mechanism comprises a mechanical hand and a sensor.

[0015] The present application has the following beneficial effects: This application innovatively discloses a system for maintaining blinding in randomized double-blind trials of neuromodulation. For example, in a vagus nerve stimulation (VNS) experiment, the maximum VNS stimulation intensity, such as 0.8 mA, is first set before the experiment. For all patients in the control and sham stimulation groups, the intensity is gradually adjusted to the maximum within 2-3 days, allowing all patients to experience the relevant adverse reactions. Most of these adverse reactions are transient and generally do not recur when the same intensity is reached again. Afterwards, the corresponding programming settings are performed according to the group, with the sham stimulation group set to 0. Since the diseases being treated are mostly chronic and require long-term stimulation, this short-term pre-stimulation before the experiment will not significantly affect the treatment results. Therefore, it can effectively avoid unblinding and ensure the authenticity of the experimental results. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 This is a schematic diagram of the system provided in the first aspect of the present invention; Figure 2 This is a schematic diagram of a computer device provided in an embodiment of the present invention; Figure 3 This is a schematic diagram of the architecture of an exemplary computing device provided in an embodiment of the present invention; Figure 4 This is a schematic diagram of the storage medium provided in an embodiment of the present invention; Figure 5 This is a comparison of the system process provided in this embodiment of the invention with previous methods. Detailed Implementation

[0018] To enable those skilled in the art to better understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0019] In some of the flowcharts described in the specification and claims of the present application and in the above-described figures, a plurality of operations are included that occur in a particular order, but it should be clearly understood that the operations can be performed in an order other than that in which they appear or in parallel, and the serial numbers of the operations, such as 101, 102, etc., are merely used to distinguish different operations, and the serial numbers themselves do not represent any execution order. In addition, the flowcharts can include more or fewer operations, and the operations can be performed in sequence or in parallel. It should be noted that the descriptions of "first", "second", etc. in this article are used to distinguish different messages, devices, modules, etc., and do not represent the order of precedence, nor do "first" and "second" represent different types.

[0020] The technical solutions in the embodiments of the present application will be described clearly and completely below in conjunction with the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0021] Figure 1 is a system schematic diagram for blind state maintenance in a neural regulation randomized double-blind test provided by an embodiment of the present application, specifically, the system includes the following steps: The information acquisition module 101 is configured to acquire grouping information of a plurality of detection objects; the grouping information includes a stimulation group and a pseudo-stimulation group. In some embodiments, the term "detection object" used in this article refers to any animal (for example, mammals), including but not limited to humans, non-human primates, rodents, etc., which will become the recipient of a specific treatment. Generally, the terms "subject" and "patient" are used interchangeably in this article when referring to human subjects. Preferably, the detection object is a human.

[0022] In some embodiments, the grouping information is obtained by random grouping for the detection objects.

[0023] In some embodiments, the information acquisition module further comprises a stimulation type acquisition module for acquiring a plurality of detection objects, the stimulation type comprising VNS, DBS. Among them, vagus nerve electrical stimulation (VNS) is an important way of neuromodulation, which can be used to treat a variety of diseases such as epilepsy, depression, cognitive impairment, post-stroke limb dysfunction, etc. by emitting electrical pulses to the vagus nerve, and achieving disease treatment. Deep brain electrical stimulation (DBS) is a neuromodulation technology that adjusts neural function by implanting electrodes in specific nuclei of the brain and applying controllable electrical pulses. It belongs to the category of "minimally invasive surgery" (without the need to remove brain tissue). Its core principle is similar to a "brain pacemaker", which intervenes in abnormal neural circuit activity through electrical signals, thereby improving disease symptoms caused by neural dysfunction. It has become an important treatment for a variety of refractory neurological diseases.

[0024] The execution receiving module 102 is configured to receive an execution operation for a target detection object by using an experimental device, the target detection object being one of the plurality of detection objects, and the execution operation being used to indicate an identifier of an execution parameter and a parameter value.

[0025] The first pre-stimulation module 103 is configured to, in response to the execution operation, control an execution mechanism to perform a first action on the target detection object based on the execution operation, regardless of whether the target detection object is a stimulation group or a pseudo-stimulation group. In some embodiments, the first action comprises: from an initial time point to a first time point, the stimulation intensity is increased from 0 to a first stimulation intensity, and the first stimulation intensity is maintained to a second time point. The second action comprises: from the second time point to a third time point, the stimulation intensity is increased from the first stimulation intensity to a second stimulation intensity as a rated stimulation intensity. In some embodiments, the second stimulation intensity is a pre-set maximum stimulation intensity.

[0026] The second pre-stimulation module 104 is configured to, in response to the execution operation, control an execution mechanism to perform a second action on the target detection object based on the execution operation, regardless of whether the target detection object is a stimulation group or a pseudo-stimulation group. In some embodiments, between the second pre-stimulation module and the test stimulation module, the system further comprises: An adverse reaction judgment module is configured to receive a reaction message of the target detection object, and determine whether an adverse reaction occurs according to the reaction message. If an adverse reaction occurs, the first action is performed again in sequence for the target detection object that has an adverse reaction. A tolerance judgment module is configured to receive a maintenance time of an adverse reaction of the target detection object after the first stimulation intensity, and determine whether the target detection object is tolerant according to the maintenance time. If not, the first stimulation intensity is maintained as the rated stimulation intensity. If yes, the second stimulation intensity is continued to be increased as the rated stimulation intensity.

[0027] In some embodiments, the time points are all calculated from an initial time point; the first time point is 2-3 days; the second time point is 4-5 days; and the third time point is 1-2 weeks.

[0028] The test stimulation module 105 is configured to control the execution mechanism to perform an action of maintaining a rated stimulation intensity on the target detection object based on the execution operation when the target detection object is the stimulation group, and to perform an action of stimulating the target detection object with a stimulation intensity of 0 based on the execution operation when the target detection object is the pseudo-stimulation group.

[0029] In some embodiments, the system further comprises a blind state evaluation and correction module configured to evaluate the patient's blind state (including questions such as "What do you think the probability of receiving real treatment is?" and "What is the basis for your guess?") through a structured questionnaire, and to start dynamic parameter adjustment (such as fine-tuning the difference in current intensity between the treatment group and the control group) if the correct rate of a certain group of guesses exceeds 60%. The related side effects or therapeutic effects of stimulation, high-frequency stimulation, and low-frequency stimulation have been listed above, and the patient can also search for them by himself / herself, and the patient can make an estimate based on these symptoms.

[0030] In some embodiments, the system further comprises: The first pre-stimulation feedback module is configured to receive feedback information sent by the execution structure as target feedback information when the first action is performed on the target detection object. The second pre-stimulation feedback module is configured to receive feedback information sent by the execution structure as target feedback information when the second action is performed on the target detection object. The test stimulation feedback module is configured to receive feedback information sent by the execution structure as target feedback information when the target detection object is the stimulation group or the pseudo-stimulation group.

[0031] The second aspect of the present application discloses an electronic device, which comprises a memory and a processor; the memory is configured to store a computer program; and the processor is configured to implement the following steps when executing the computer program: Obtain grouping information of a plurality of detection objects; the grouping information comprises a stimulation group and a pseudo-stimulation group; Receive an execution operation for a target detection object using an experimental device; the target detection object is one of the plurality of detection objects; and the execution operation is used to indicate an identifier and a parameter value of an execution parameter. In response to the execution operation, control the execution mechanism to perform a first action on the target detection object based on the execution operation regardless of whether the target detection object is the stimulation group or the pseudo-stimulation group. In response to the execution operation, control the execution mechanism to perform a second action on the target detection object based on the execution operation regardless of whether the target detection object is the stimulation group or the pseudo-stimulation group. When the target detection object is the stimulation group, the control execution mechanism performs an action of maintaining the rated stimulation intensity on the target detection object based on the execution operation; and when the target detection object is the pseudo-stimulation group, the control execution mechanism performs an action of 0 stimulation intensity on the target detection object based on the execution operation.

[0032] The third aspect of the present application discloses a device for maintaining blindness in a neuroregulation randomized double-blind test, characterized in that the device comprises an experimental equipment, an execution mechanism and the electronic equipment disclosed in the second aspect of the present application.

[0033] In some embodiments, the experimental equipment is a program-controlled equipment, and the execution mechanism is a stimulator arranged in the target detection object; or the experimental equipment is an electromagnetic wave control equipment, and the execution mechanism comprises an electromagnetic wave generating device and an electromagnetic wave detecting device.

[0034] In some embodiments, the experimental equipment is a drug delivery control equipment, and the execution mechanism comprises a mechanical hand and a sensor.

[0035] Figure 2 is a schematic diagram of a computer device provided by an embodiment of the present application, as shown in Figure 2 The device 2000 can include one or more processors 2010 and one or more memories 2020. The memory stores computer readable code which, when executed by the one or more processors, can perform the method described above.

[0036] The processor in the embodiment can be an integrated circuit chip with a signal processing capability. The processor can be a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components. The methods, operations and logical block diagrams disclosed in the embodiments of the present disclosure can be implemented or executed by the processor. The general purpose processor can be a microprocessor or the processor can also be any conventional processor, etc., which can be of X86 architecture or ARM architecture.

[0037] In general, various example embodiments of the present disclosure can be implemented in hardware or special-purpose circuitry, software, firmware, logic, or any combination thereof. Certain aspects can be implemented in hardware, while other aspects can be implemented in firmware or software which can be executed by a controller, microprocessor or other computing device. While aspects of the present disclosure have been described and illustrated with a block diagram and flowchart, it is understood that the blocks, devices, systems, techniques or methods described herein can be implemented in hardware, software, firmware, special-purpose circuitry or logic, general-purpose hardware or controller or other computing device, or some combination thereof, as non-limiting examples.

[0038] For example, the method or the apparatus according to the embodiments of the present disclosure can also be implemented by means of Figure 3 The architecture of the computing device 3000 shown is merely an example, and when implementing different devices, one or more components shown in the computing device can be omitted Figure 3 As shown, the computing device 3000 can include a bus 3010, one or more CPUs 3020, a read-only memory (ROM) 3030, a random access memory (RAM) 3040, a communication port connected to a network 3050, an input / output component 3060, a hard disk 3070, etc. The storage device in the computing device 3000, such as the ROM 3030 or the hard disk 3070, can store various data or files used in processing and / or communication of the method provided by the present disclosure and program instructions executed by the CPU. The computing device 3000 can also include a user interface 3080. Of course, Figure 3 The architecture shown is merely an example, and when implementing different devices, one or more components shown in the computing device can be omitted Figure 3 One or more components shown in the computing device.

[0039] The embodiments of the present disclosure also provide a computer-readable storage medium, such as Figure 4 As shown, the architecture of the computing device 3000 is merely an example, and when implementing different devices, one or more components shown in the computing device can be omitted

[0040] The embodiment of the present disclosure further provides a computer program product or system, comprising a computer program which, when executed by a processor, implements the following method steps: Obtain grouping information of a plurality of detection objects; the grouping information comprises a stimulation group and a pseudo-stimulation group; Receive an execution operation for a target detection object using an experimental device, the target detection object being one of the plurality of detection objects, the execution operation being used to indicate an identification of an execution parameter and a parameter value; In response to the execution operation, whether the target detection object is the stimulation group or the pseudo-stimulation group, control an execution mechanism to perform a first action on the target detection object based on the execution operation; In response to the execution operation, whether the target detection object is the stimulation group or the pseudo-stimulation group, control an execution mechanism to perform a second action on the target detection object based on the execution operation; When the target detection object is the stimulation group, control the execution mechanism to perform an action of maintaining a rated stimulation intensity on the target detection object based on the execution operation; when the target detection object is the pseudo-stimulation group, control the execution mechanism to perform an action of a stimulation intensity of 0 on the target detection object based on the execution operation.

[0041] In a specific application, the process is as follows: I. Programmed scheme of vagus nerve electrical stimulation randomized double-blind controlled trial (on vs off): Vagus nerve electrical stimulation (VNS) is an important way of neural regulation. By emitting electrical pulses to the vagus nerve, it can achieve disease treatment and can be used to treat various diseases such as epilepsy, depression, cognitive impairment, post-stroke limb dysfunction, etc. However, its clinical research is greatly limited. Different patients have a huge difference in response to VNS stimulation. Many patients can experience related adverse reactions such as hoarseness, water choking cough, etc. at the first programmed stimulation with smaller stimulation parameters. Patients will feel this adverse reaction, which will cause unblinding, leading to the failure of clinical trials.

[0042] To avoid this phenomenon, we first set the maximum VNS stimulation intensity of this project, such as 0.8 mA, before the experiment. For the control group and the pseudo-stimulation group, all patients are adjusted to the maximum stimulation intensity within 2-3 days, gradually and gradually adjusted, so that all patients experience related adverse reactions. Most of these adverse reactions are transient, and they will not appear again when the same intensity is reached again. Then, according to the group they belong to, the corresponding programmed setting is made, and the pseudo-stimulation group is set to 0 mA.

[0043] Steps: 1. Group all patients according to random numbers into a stimulation group and a pseudo-stimulation group; 2. All patients (stimulation group and sham stimulation group) will be increased to a certain stimulation intensity (called low intensity stimulation, such as 0.5 mA) within 2-3 days from 0 mA (set pulse width and frequency according to experimental design), and patients may have hoarseness, difficulty swallowing. In most cases, it will be alleviated within a certain period of time (about 4-5 days); 3. Gradually adjust the intensity to the rated stimulation intensity (such as 0.8 mA 1.0 mA) within a certain period of time (such as 1-2 weeks), and repeat the process of 2 if adverse reactions occur again (such as hoarseness, difficulty swallowing, etc.), and increase the stimulation intensity after waiting for relief. (If the adverse reactions do not subside after a week or so, the stimulation intensity will be increased to the rated intensity if it can be tolerated, and if it cannot be tolerated, the stimulation intensity will be maintained (whether it is the stimulation group or the sham stimulation group; the stimulation group will use this stimulation intensity as the long-term stimulation parameter, and the sham stimulation group will temporarily maintain this stimulation intensity until it is reduced to 0 mA later) 4. After reaching the rated stimulation intensity, the true stimulation group will be maintained, and the sham stimulation group will adjust the stimulation intensity to 0 mA; Note: In most cases, VNS uses constant current stimulation (i.e. using rated current, the unit is usually mA), and in a few cases, constant voltage stimulation can also be used (i.e. using rated voltage, the unit is usually v) II. Brain deep electrical stimulation randomized double-blind controlled trial program (on vs off): Brain deep electrical stimulation (DBS) is also a kind of neural regulation therapy. Brain deep electrical stimulation (DBS) is a kind of neural regulation technology that adjusts neural function by implanting electrodes in specific nuclei of the brain and applying controllable electrical pulses, which belongs to the category of "minimally invasive surgery" (without the need to remove brain tissue). Its core principle is similar to "brain pacemaker", which intervenes abnormal neural circuit activity through electrical signals, thereby improving the symptoms of diseases caused by neural dysfunction. It has become an important treatment for many refractory diseases in neurology.

[0044] Face similar present situation with VNS. Also will produce certain adverse reactions, such as abnormal limb sensation, abnormal vision, etc. Similar methods can be used.

[0045] Steps: 1. According to the random number, all patients are divided into stimulation group and sham stimulation group 2. All patients (stimulation group and sham stimulation group) will be increased to a certain stimulation intensity (called low intensity stimulation, such as 1.0v) within 2-3 days from 0v (set pulse width and frequency according to experimental design), and patients may have abnormal vision, abnormal limb sensation, autonomic nervous dysfunction (such as sweating, flushing, etc.) etc. In most cases, it will be alleviated within a certain period of time (about 4-5 days).

[0046] 3. In a certain period of time (such as 1-2 weeks), gradually adjust the intensity to the rated stimulation intensity (such as 2.0 3.0v), if the adverse reactions (such as visual abnormalities, limb paresthesia, autonomic nervous dysfunction, etc.) occur again, repeat the process of 2, and increase the stimulation intensity after waiting for relief. (If the adverse reactions do not subside after a week or so, if it can be tolerated, continue to increase to the rated intensity, if it cannot be tolerated, maintain this stimulation intensity (whether it is a stimulation group or a false stimulation group; the stimulation group will use this stimulation intensity as the long-term stimulation parameter, and the false stimulation group will temporarily maintain this stimulation intensity until it is reduced to 0v later) ) ; 4. After reaching the rated stimulation intensity, the true stimulation group remains unchanged, and the false stimulation group adjusts the stimulation intensity to 0mA; Note: In most cases, DBS uses constant voltage stimulation (i.e. uses rated voltage, the unit is usually v), and in a few cases, constant current stimulation can also be used (i.e. uses rated current, the unit is usually mA).

[0047] Three, brain deep electrical stimulation randomized double-blind controlled trial program (different frequencies are compared with each other, such as low frequency (<100hz) vs high frequency stimulation (>100hz)); The frequency of deep brain electrical stimulation (DBS) is different, and its mechanism of action and clinical effect also differ. It can be generally divided into high frequency stimulation and low frequency stimulation. The following is a specific introduction: Take STN-DBS (subthalamic nucleus deep brain stimulation, which belongs to target-specific deep brain stimulation technology) as an example. This technology implants electrodes in the deep brain subthalamic nucleus (STN) area to emit high-frequency weak electrical pulses to stimulate the target nucleus in the brain for a long time to regulate abnormal neural activity. As an example, other targets also have different frequency mechanisms and differences in efficacy as follows: High frequency stimulation: Frequency range: usually higher than 100Hz, commonly used frequency between 130-185Hz.

[0048] Mechanism of action: High frequency DBS targeting the subthalamic nucleus (STN) can significantly inhibit the synchronicity of neural network electrical activity. Studies have found that high-frequency electrical stimulation (such as 130Hz) can induce strong desynchronization of neurotransmitter gamma-aminobutyric acid (GABA) release, desynchronize STN neuronal electrical activity, and thus relieve motor dysfunction in a mouse model of Parkinson's disease.

[0049] Clinical application: High frequency DBS is an effective means of treating advanced Parkinson's disease, which can long-term improve the main symptoms of Parkinson's disease, such as bradykinesia, tremor, and muscle rigidity, etc. In addition, globus pallidus high-frequency electrical stimulation can also have a significant improvement effect on diseases such as essential tremor and dystonia.

[0050] Low frequency stimulation: Frequency range: generally 60-80 Hz.

[0051] Mechanism of action: low-frequency stimulation (e.g., 20 Hz) induces weak GABA desynchronization release, which has little effect on STN neuronal activity. However, specific knockdown of the calcium sensor protein Synaptotagmin-1 in PV neurons in GPe through RNA interference technology can enhance the intensity of low-frequency stimulation-induced desynchronization release, allowing low-frequency DBS to also improve motor function.

[0052] Clinical application: High-frequency stimulation, commonly used in DBS, has poor efficacy for midline symptoms (e.g., balance function, gait disturbance, language impairment, and swallowing dysfunction). Low-frequency stimulation has some effect on midline symptoms such as freezing gait in Parkinson's disease patients, but it is only effective for a small number of patients, has a short duration of effect, and may exacerbate symptoms such as bradykinesia, tremor, and rigidity.

[0053] Therefore, it is crucial to study the differences in disease efficacy of different frequencies. However, different frequencies of DBS may lead to different adverse reactions and clinical efficacy, High-frequency stimulation (>100 Hz): may induce gait freezing and speech impairment, such as 130 Hz stimulation, which can cause dysarthria in 23% of patients. In addition, high-frequency stimulation is also significantly associated with depression (18% incidence) and cognitive decline, and may also decrease step velocity.

[0054] Low-frequency stimulation (≤100 Hz): 60 Hz stimulation can reduce the incidence of dysphagia, but low-frequency stimulation for midline symptoms such as freezing gait in Parkinson's disease patients is only effective for a small number of patients, has a short duration of effect, and may exacerbate symptoms such as bradykinesia, tremor, and rigidity. Studies have shown that 50 Hz stimulation can cause fatigue, and 80 Hz may cause abnormal eye movements.

[0055] Therefore, in a randomized controlled trial (RCT) study, if we want to study the differences in the effects of different frequencies on a certain symptom, it may cause the patient to know, which may cause potential blinding.

[0056] The cross method of high and low frequencies is commonly used in clinical trials, and single cross is more practical in clinical practice. If multiple crosses are used, it will take a longer time. We designed the following steps for the clinical trial process, assuming it is divided into high-frequency and low-frequency groups: 1. All patients are randomly divided into high-frequency and low-frequency groups according to the randomization requirements; 2. High frequency group patients: first low frequency stimulation, if there is an adverse reaction, then observe for a period of time (usually one week), most of the adverse reactions will disappear during the observation period, if it continues to appear, then reduce the stimulation intensity (i.e. voltage), most of them can disappear. After 2 weeks (or adjust the time according to the experimental requirements), gradually adjust the stimulation frequency to the rated frequency (i.e. change low frequency stimulation to high frequency stimulation), pay attention to the change as a gradual process, such as increasing 10hz per day. Low frequency group: first high frequency stimulation, then gradually adjust to low frequency, the method is the same as the high frequency group patients.

[0057] 3. The final stimulation frequency of the high frequency group patients is set to high frequency, and the final stimulation frequency of the low frequency group is set to low frequency. The stimulation voltage and pulse width are set according to the experimental requirements.

[0058] In this material, by comparing the system process with the previous method, it is found that the results of the system are better, as shown in Figure 5 In clinical practice, the blind state maintenance system of the present application is compared with the previous method, and it is found that when the previous method is used for research, as high as 79% (accurately 78.95%) of the patients can accurately perceive the group they belong to, while in the present application, only 55% of the patients can accurately perceive (i.e. their perception is consistent with the true group they belong to), and the accurate perception rate is greatly reduced, which means that the double-blind test of the present application has very good effect. In addition, the value of 55% is close to the correct perception rate of random perception (50%). This shows that the present application can greatly reduce the possibility of unblinding, reduce the psychogenic effect, and improve the accuracy of the randomized double-blind experiment.

[0059] It should be noted that the flowcharts and block diagrams in the drawings illustrate the possible architectural, functional, and operational architectures of systems, methods, and computer program products according to various embodiments of the present disclosure. In this regard, each block in the flowcharts or block diagrams can represent a module, a program segment, or a part of code that contains one or more executable instructions for implementing the specified logical functions. It should also be noted that in some alternative implementations, the functions indicated in the blocks can occur in different order than that indicated in the drawings. For example, two blocks indicated in succession can actually be executed substantially in parallel, and sometimes they can be executed in reverse order, depending on the functions involved. It should also be noted that each block in the block diagram and / or flowchart, and the combination of blocks in the block diagram and / or flowchart, can be implemented by a dedicated hardware-based system that performs the specified functions or operations, or can be implemented by a combination of dedicated hardware and computer instructions.

[0060] Those skilled in the art can clearly understand that, for the convenience and brevity of description, the specific working processes of the above-described system, device and unit can refer to the corresponding processes in the foregoing method embodiments, and will not be described here again.

[0061] The example embodiments of the present disclosure described in detail above are merely illustrative, rather than limiting. Those skilled in the art should understand that various modifications and combinations of these embodiments or features thereof can be made without departing from the principles and spirits of the present disclosure, and such modifications shall fall within the scope of the present disclosure.

Claims

1. A system for blind maintenance in a neuroregulatory randomized double-blind trial, characterized by, The system comprises: an information acquisition module configured to acquire grouping information of a plurality of detection objects, the grouping information comprising a stimulation group and a pseudo-stimulation group; an execution receiving module configured to receive, by using an experimental device, an execution operation for a target detection object, the target detection object being one of the plurality of detection objects, the execution operation being used to indicate an identification of an execution parameter and a parameter value; a first pre-stimulation module configured to, in response to the execution operation, control an execution mechanism to perform a first action on the target detection object based on the execution operation, regardless of whether the target detection object is the stimulation group or the pseudo-stimulation group; a second pre-stimulation module configured to, in response to the execution operation, control the execution mechanism to perform a second action on the target detection object based on the execution operation, regardless of whether the target detection object is the stimulation group or the pseudo-stimulation group; a test stimulation module configured to, when the target detection object is the stimulation group, control the execution mechanism to perform an action on the target detection object based on the execution operation, the action maintaining a rated stimulation intensity; and when the target detection object is the pseudo-stimulation group, control the execution mechanism to perform an action on the target detection object based on the execution operation, the action having a stimulation intensity of 0.

2. The system for blind state maintenance in a neuromodulation randomized double blind trial of claim 1, wherein, The first action comprises: from an initial time point to a first time point, the stimulation intensity is raised from 0 to a first stimulation intensity, and the first stimulation intensity is maintained to a second time point; The second action comprises: from the second time point to a third time point, the stimulation intensity is raised from the first stimulation intensity to a second stimulation intensity as a rated stimulation intensity; Optionally, the second stimulation intensity is a pre-set maximum stimulation intensity; Optionally, between the second pre-stimulation module and the test stimulation module, the system further comprises: an adverse reaction judging module configured to receive a reaction message of the target detection object, and determine whether an adverse reaction occurs according to the reaction message, and if so, sequentially perform the first action again on the target detection object for which the adverse reaction occurs; an adverse reaction judging module configured to receive a reaction message of the target detection object, and determine whether an adverse reaction occurs according to the reaction message, and if so, sequentially perform the first action again on the target detection object for which the adverse reaction occurs; 3. The system for blind maintenance in a neuroregulatory randomized double-blind trial according to claim 1, characterized in that, The time points are all calculated from the initial time point; Optionally, the first time point is 2-3 days; Optionally, the second time point is 4-5 days; Optionally, the third time point is 1-2 weeks.

4. The system for blind maintenance in a neuromodulation randomized double-blinded trial of claim 1, wherein, The grouping information is obtained by randomly grouping the detection objects; Optionally, the information acquisition module further comprises a stimulation type of the plurality of detection objects, the stimulation type comprising VNS and DBS.

5. The system for blind maintenance in a neuromodulation randomized double-blinded trial of claim 1, wherein, The system further comprises a blind state evaluation and correction module configured to evaluate a patient's blind state through a structured questionnaire, and if a certain group has a correct guessing rate of more than 60%, dynamic parameter adjustment is started.

6. The system for blind maintenance in a neuromodulation randomized double-blinded trial of claim 1, wherein, The system further comprises: a first pre-stimulation feedback module configured to, when the first action is performed on the target detection object, receive feedback information sent by the execution mechanism as target feedback information; a second pre-stimulation feedback module configured to, when the second action is performed on the target detection object, receive feedback information sent by the execution mechanism as target feedback information; The test stimulus feedback module is configured to receive feedback information sent by the execution mechanism as target feedback information when the target detection object is a stimulus group or a pseudo-stimulus group.

7. An electronic device, comprising: The device comprises a memory and a processor; the memory is configured to store a computer program; the processor is configured to execute the computer program to implement the following steps: Obtain grouping information of a plurality of detection objects; the grouping information comprises a stimulus group and a pseudo-stimulus group; Use the experimental equipment to receive an execution operation for a target detection object, the target detection object being one of the plurality of detection objects, the execution operation being used to indicate an identifier of an execution parameter and a parameter value; In response to the execution operation, control the execution mechanism to perform a first action on the target detection object based on the execution operation, regardless of whether the target detection object is a stimulus group or a pseudo-stimulus group; In response to the execution operation, control the execution mechanism to perform a second action on the target detection object based on the execution operation, regardless of whether the target detection object is a stimulus group or a pseudo-stimulus group; When the target detection object is a stimulus group, control the execution mechanism to perform an action on the target detection object based on the execution operation to maintain the rated stimulus intensity; when the target detection object is a pseudo-stimulus group, control the execution mechanism to perform an action on the target detection object based on the execution operation to have a stimulus intensity of 0.

8. An apparatus for blind maintenance in a neuroregulatory randomized double-blind trial, characterized by The device comprises an experimental equipment, an execution mechanism and the electronic device of claim 7.

9. The device for blind state retention in a neuroregulatory randomized double-blind trial according to claim 8, characterized in that, The experimental equipment is a program-controlled device, and the execution mechanism is a stimulator arranged in the target detection object; Alternatively, the experimental equipment is an electromagnetic wave control device, and the execution mechanism comprises an electromagnetic wave generating device and an electromagnetic wave detecting device.

10. The device for blind state retention in a neuroregulatory randomized double-blind trial according to claim 8, characterized in that, The experimental equipment is a drug delivery control device, and the execution mechanism comprises a mechanical hand and a sensor.

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