Double-target transcranial time interference electrical stimulation system and sleep regulation and control method

Abstract

The invention relates to the technical field of nerve regulation and control, discloses a double-target transcranial time interference electrical stimulation system and a sleep regulation and control method, and aims to solve the problems that target selection is fuzzy and a cooperative mechanism is missing in an existing method. Selecting a main target region and auxiliary target region combination corresponding to the current sleep stage from predefined sleep stage-target region combination mapping; based on a predefined stimulation parameter set, stimulation parameters are independently set for the main target area and the auxiliary target area, and the stimulation parameters comprise the polarization direction, the current intensity, the carrier frequency and the modulation frequency; and controlling the stimulation signal generation module and the multi-channel electrode array, and applying transcranial time interference electrical stimulation to the main target region and the auxiliary target region with independently set stimulation parameters. According to the method and the system, the accurate cooperative regulation and control of the whole sleep period and multiple target points are realized, and the accuracy and the efficiency of sleep regulation and control are improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of neuromodulation, in particular to a dual-target transcranial time-locked electrical stimulation system and a sleep regulation method. BACKGROUND

[0002] Sleep, as a core physiological process to maintain the homeostasis of the human body, its quality directly affects cognitive function, metabolic health and neural stability. The incidence of sleep disorders (such as chronic insomnia, sleep apnea syndrome, circadian rhythm disorders) is increasing year by year, and has become an important public health problem.

[0003] Sleep regulation is not a single brain region independent activity, but a complex network of cooperation composed of cortex and deep nuclei (such as thalamus, raphe nucleus, amygdala, etc.). From wakefulness to deep sleep, the whole link regulation of wakefulness inhibition, rhythm initiation and slow wave maintenance is involved, and the core neural mechanisms and key regulatory brain regions of different sleep stages (Wake period, N1 period, N2 period, N3 period, REM period) are significantly different.

[0004] Traditional transcranial electrical stimulation (TES) technology, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS) and transcranial pulsed electrical stimulation (tPES), has inherent limitations when applied to sleep regulation: First, in terms of targeting and penetration depth, traditional TES technology generally cannot effectively act on deep nuclei. The current of tDCS forms an attenuation barrier between the skull and the superficial layer of the cortex, and only activates the superficial layer of the cortex; tACS has a significant skin effect, and the current is mainly concentrated in the cortex; tRNS and tPES are also limited by penetration depth. This leads to low efficiency of regulation of thalamus, raphe nucleus and other core sleep nuclei.

[0005] Second, in terms of dynamic matching and parameter adjustment, traditional technology is not adaptive enough. tDCS has no frequency characteristics and cannot match sleep rhythms; tACS can set a fixed frequency, but switching frequencies need to interrupt stimulation, which can easily disrupt sleep continuity; tRNS signal lacks specificity; tPES frequency adjustment range is narrow. They are all difficult to achieve seamless and dynamic adaptation to changes in sleep stages.

[0006] Furthermore, in terms of multi-target area synergistic regulation, the traditional technology lacks the ability. The multi-channel tDCS can cause current field superposition ambiguity; tACS cannot allow multi-target area to use different frequencies independently; tRNS multi-target point signal cannot achieve precise regulation; and tPES multi-channel signal is easy to cross and superimpose. These technologies cannot achieve independent parameter stimulation of multi-target area with functional complementary type, and cannot construct a complete sleep regulation link.

[0007] The transcranial time interference electric stimulation (tTIS) technology generates low-frequency envelope modulation waves in deep brain areas through two high-frequency carriers, which improves the penetration depth to a certain extent. However, the existing tTIS technical solutions in the sleep field are still in the primary stage, and there are core problems such as ambiguous target area selection, lack of synergistic mechanism, rigid stage switching, and single regulation mode: first, the necessary core regulation brain area combination of each sleep stage is not clearly defined, especially the target pair is not constructed based on the neural logic of deep nuclei and cortical areas, resulting in lack of pertinence and physiological rationality of stimulation, and poor accuracy of sleep regulation. Second, there is a lack of effective multi-target area synergistic stimulation mechanism, which cannot achieve independent setting of parameters and complementary enhancement of functions of the main target area and the auxiliary target area, resulting in broken regulation link and insufficient synergistic effect. Third, when the sleep stage is switched, the stimulation parameters usually need to be completely reset, lacking a smooth transition mechanism, which is easy to cause regulation interruption and sleep rhythm disorder. Fourth, most of the solutions can only achieve one-way regulation of promoting sleep or depriving sleep, and the two-way switching of promoting sleep or depriving sleep needs to change the electrode position, which is complex and interferes with sleep. SUMMARY

[0008] The present application aims to solve the problems of ambiguous target area selection and lack of synergistic mechanism in existing sleep regulation schemes, and proposes a dual-target area transcranial time interference electric stimulation system and a sleep regulation method.

[0009] The technical solution adopted by the present application to solve the above technical problems is: In a first aspect, the present application provides a dual-target area transcranial time interference electric stimulation system for sleep regulation, comprising: a stimulation signal generation module for generating a transcranial time interference electric stimulation signal, the signal comprising a high-frequency carrier and a low-frequency modulation wave; a multi-channel electrode array configured to apply the transcranial time interference electric stimulation signal to at least two target areas of a user's head, the at least two target areas comprising a main target area and an auxiliary target area, wherein the main target area is a deep upstream center responsible for signal initiation or interference suppression, and the auxiliary target area is a subcortical downstream center responsible for function execution; an electroencephalogram signal acquisition module for real-time monitoring of the user's electroencephalogram signal to identify the sleep stage; a control module communicatively connected with the stimulation signal generation module, the multi-channel electrode array, and the electroencephalogram signal acquisition module; wherein the control module is configured to: select, from a predefined sleep stage-target region combination mapping, a primary target region and a secondary target region combination corresponding to a current sleep stage based on a real-time sleep stage monitored by the electroencephalogram signal acquisition module; independently set stimulation parameters for the primary target region and the secondary target region based on a predefined stimulation parameter set, the stimulation parameters including polarization direction, current intensity, carrier frequency, and modulation frequency; control the stimulation signal generation module and the multi-channel electrode array to apply transcranial temporal interference electric stimulation to the primary target region and the secondary target region with the independently set stimulation parameters.

[0010] Further, the predefined sleep stage-target region combination mapping includes: in the Wake stage, the primary target region is the thalamus, and the secondary target region is the dorsolateral prefrontal cortex; in the N1 stage, the primary target region is the nucleus raphe, and the secondary target region is the sensorimotor cortex; in the N2 stage, the primary target region is the reticular nucleus of the thalamus, and the secondary target region is the parietal central cortex; in the N3 stage, the primary target region is the insular lobe, and the secondary target region is the prefrontal cortex; in the REM stage, the primary target region is the amygdala, and the secondary target region is the temporal lobe.

[0011] Further, the control module is further configured to perform cross-stage target region parameter linkage, specifically including: when detecting that the sleep stage switches from a first sleep stage to a second sleep stage, at least one core stimulation parameter applied to the primary target region and the secondary target region of the first sleep stage is taken as an initial stimulation parameter applied to the primary target region and the secondary target region corresponding to the second sleep stage; wherein the core stimulation parameters include current intensity and modulation frequency, and for the modulation frequency, a gradient transition mode is adopted to adjust from the frequency of the first sleep stage to the target frequency of the second sleep stage.

[0012] Further, the completion time of the gradient transition is configured to match the neural rhythm cycle of the target sleep stage.

[0013] Further, the control module is configured to achieve bidirectional regulation of promoting sleep and depriving sleep by adjusting the polarization direction of the primary target region and the secondary target region, specifically including: in the sleep promotion mode, the primary target region and the secondary target region are both controlled to be depolarized; In the sleep-deprived mode, the main target region and the auxiliary target region are both controlled to be hyperpolarized.

[0014] Further, the electrodes in the multi-channel electrode array are configured to act as stimulation electrodes during a stimulation period and as acquisition electrodes of the brain electrical signal acquisition module during a non-stimulation period, realizing electrode multiplexing.

[0015] Further, the control module integrates a double oar rowing model, wherein: the sleep state is mapped to the heading of the boat; the main target region and the auxiliary target region are respectively mapped to the left oar controlling the heading and the right oar assisting the execution; the stimulation parameters are mapped to the direction and intensity of rowing; the control module dynamically adjusts the stimulation parameters based on the brain electrical signal and the double oar rowing model.

[0016] Further, the electrode placement positions of the multi-channel electrode array for each target region are determined based on simulation modeling, so that the target region current density is between 0.25 mA / cm² and 0.35 mA / cm², and the current density of the area 5 mm outside the target region is lower than 0.1 mA / cm².

[0017] In a second aspect, the present application provides a sleep regulation method applied to the double-target transcranial time-encoded electrical stimulation system of the first aspect, the method comprising: monitoring the brain electrical signal of the user in real time through the brain electrical signal acquisition module; identifying the current sleep stage of the user based on the brain electrical signal; determining the main target region and the auxiliary target region corresponding to the current sleep stage according to the predefined sleep stage-target region combination mapping; independently generating stimulation parameters for the main target region and the auxiliary target region according to the predefined set of stimulation parameters; applying transcranial time-encoded electrical stimulation to the main target region and the auxiliary target region through the multi-channel electrode array with the independently generated stimulation parameters.

[0018] Further, when the sleep stage switches, cross-stage target region parameter linkage is performed, including taking at least one core stimulation parameter of the main target region and the auxiliary target region of the previous sleep stage as the initial stimulation parameter of the main target region and the auxiliary target region corresponding to the next sleep stage, and performing gradient transition adjustment on the modulation frequency.

[0019] The beneficial effects of the present application are: the dual-target transcranial time-interference electrical stimulation system and sleep regulation method provided by the present application, by constructing a closed-loop system integrating stimulation signal generation, multi-channel electrode array, EEG monitoring and processing control, and based on real-time identification of sleep stages, dynamically selecting a functionally complementary main target area (deep upstream central) and auxiliary target area (subcortical downstream central) combination, and setting independent stimulation parameters for them, realizing precise and coordinated regulation of the whole sleep cycle and multiple target points at the system level. The two core problems of existing technology, namely the ambiguity of target area selection and the lack of coordination mechanism, are fundamentally solved: through pre-defined, neural mechanism-based stage-target area mapping, the core brain area pairs that must be regulated in each sleep stage are determined, ensuring the targeting of the stimulation; by setting independent parameters for the main and auxiliary target areas that adapt to their functions, the synergy of upstream signal initiation and downstream function execution is achieved, and the regulation effect is optimized, thereby effectively covering the complete sleep regulation link from wakefulness suppression to deep sleep maintenance, significantly improving the accuracy and efficiency of sleep regulation. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 The structure schematic diagram of the dual-target transcranial time-interference electrical stimulation system provided for the embodiment is shown in the figure; Figure 2 The tTIS single-target and dual-target intracranial stimulation electric field intensity schematic diagram provided for the embodiment is shown in the figure; Figure 3 The flowchart of the sleep regulation method provided for the embodiment is shown in the figure; Figure 4 The dual-oar rowing model mapping schematic diagram provided for the embodiment is shown in the figure; Figure 5 The cortical current density topological map generated for the embodiment is shown in the figure; Figure 6 The deep nuclear group current density slice heat map generated for the embodiment is shown in the figure; Figure 7 The four-electrode placement position schematic diagram corresponding to the sensorimotor cortex target area in the embodiment is shown in the figure. DETAILED DESCRIPTION

[0021] Since the traditional and existing tTIS scheme does not clearly define the necessary target areas for each stage, the selection of core regulation brain areas in sleep stages is ambiguous, the adjustment lacks targeting, and the lack of multi-target coordination mechanism leads to insufficient coordination between nuclear groups, making it impossible to achieve precise, dynamic and coordinated regulation of the whole sleep cortex-deep nuclear group link. Therefore, there is an urgent need in the art for a tTIS system and method that can accurately select and dynamically switch functionally complementary target area pairs for each sleep stage and implement independent parameter setting, in order to meet the precise, full-stage and low-interference regulation needs of the sleep field.

[0022] Based on this, the technical solution of this invention is proposed. In this invention, the user's sleep stages are monitored and identified in real time by an EEG signal acquisition module. The control module dynamically selects a combination of functionally complementary primary and secondary target areas corresponding to the current stage based on a predefined sleep stage-target area mapping relationship. Then, stimulation parameters, including polarization direction, current intensity, and frequency, are independently generated for these two target areas based on a pre-stored parameter set. Finally, a multi-channel electrode array is controlled to apply two transcranial time-interference electrical stimulation signals, so that the high-frequency carrier penetrates the skull and forms effective low-frequency envelope modulation fields in the preset deep primary target area and cortical secondary target area, thereby achieving precise and coordinated regulation of key neural circuits in different sleep stages. The above solution clarifies the core brain regions that must be regulated in each sleep stage, ensuring the targeting of stimulation. By independently setting parameters adapted to the functions of the primary and secondary target areas, the synergistic effect of upstream signal initiation and downstream functional execution is achieved, optimizing the regulation effect and effectively covering the complete sleep regulation chain from arousal inhibition to deep sleep maintenance.

[0023] The technical solutions in this embodiment will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0024] Figure 1 A schematic diagram of a dual-target transcranial time-interferential electrical stimulation system for sleep regulation is shown. Please refer to [link / reference]. Figure 1 The system includes: A stimulation signal generation module is used to generate a transcranial time-interference electrical stimulation signal, the signal including a high-frequency carrier wave and a low-frequency modulation wave; A multi-channel electrode array is configured to apply the transcranial time-interference electrical stimulation signal to at least two target areas of the user's head, the at least two target areas including a primary target area and a secondary target area, wherein the primary target area is a deep upstream center responsible for signal initiation or interference suppression, and the secondary target area is a cortical downstream center responsible for functional execution. The EEG signal acquisition module is used to monitor the user's EEG signals in real time to identify sleep stages; The control module is communicatively connected to the stimulation signal generation module, the multi-channel electrode array, and the EEG signal acquisition module.

[0025] In practical applications, the stimulation signal generation module can utilize an existing tTIS stimulator to generate a 2.0-2.5kHz high-frequency carrier wave, superimposed with a 0.1-100Hz low-frequency modulation wave. The multi-channel electrode array can employ at least 8-channel electrode caps or adhesive electrodes, with electrode positions determined based on the simulation results described below. The EEG signal acquisition module can use medical-standard EEG acquisition equipment for all-night polysomnography (PSG) monitoring. The control module can be implemented using a computer system and control software, incorporating an automatic sleep staging algorithm, a target-parameter mapping database, a rowing model logic, parameter linkage algorithms, and real-time control commands.

[0026] In this embodiment, the electrodes in the multi-channel electrode array are configured to function as stimulating electrodes during the stimulation period and as acquisition electrodes of the EEG signal acquisition module during the non-stimulation period, thereby achieving flexible reuse of the electrodes.

[0027] This embodiment utilizes transcranial time-interfering electrical stimulation (tTIS) for sleep regulation. tTIS technology employs a high-frequency carrier and deep interference mechanism: a 2.0-2.5 kHz high-frequency carrier (far exceeding the excitation threshold of superficial sensory neurons <1 kHz, thus avoiding activation of superficial nerves) significantly enhances the skull penetration rate of the high-frequency current, effectively reaching deep brain regions 6-8 cm deep. Two high-frequency signals intersect in deep nuclei regions to form a low-frequency envelope wave, precisely targeting the membrane potential of deep neurons and triggering depolarization or hyperpolarization. Furthermore, tTIS, through its constant carrier + independent envelope modulation architecture, fundamentally avoids the problem of time-domain waveform breakage. Adjustable low-frequency modulation achieves dynamic rhythm matching; the low-frequency modulation frequency can be adjusted within the range of 0.1-100 Hz without interrupting stimulation. Combined with an EEG acquisition module to monitor sleep rhythms, the modulation frequency can be optimized. Furthermore, tTIS allows setting the carrier frequency and modulation parameters for the adaptation depth to the target area. After the high-frequency carrier penetrates deep layers, the signal is concentrated in the target area. The two frequencies form an interference effect in their respective target areas, eliminating crosstalk and superposition interference, and preventing coupling conflicts. Moreover, there are no current surges when switching parameters, resulting in an extremely low wake-up interruption rate. This achieves non-spreading current, non-coupling frequency, interference-free signal, and customizable parameters. Figure 2 A schematic diagram of intracranial electric field intensity under tTIS single-target and dual-target stimulation is provided. In the left schematic diagram, different shades of color represent the intracranial electric field intensity distribution under tTIS single-target stimulation mode, and in the right schematic diagram, different shades of color represent the intracranial electric field intensity distribution under tTIS dual-target stimulation mode. The legend numbers represent electric field intensity, and the unit is volts per meter (V / m).

[0028] Please see Figure 3 Based on the above system, the sleep regulation method provided in this embodiment includes the following steps: Step 1: Based on the real-time sleep stage monitored by the EEG signal acquisition module, select the main target area and auxiliary target area combination corresponding to the current sleep stage from the predefined sleep stage-target area combination mapping.

[0029] In this embodiment, the predefined sleep stage-target area combination mapping includes: During the Wake phase, the primary target area is the thalamus, and the secondary target area is the dorsolateral prefrontal cortex. In phase N1, the primary target area is the raphe nucleus, and the secondary target area is the sensorimotor cortex. In N2 phase, the primary target area is the thalamic reticular nucleus, and the secondary target area is the central cortex of the parietal lobe. In phase N3, the primary target area is the insula, and the secondary target area is the prefrontal cortex. During REM sleep, the primary target area is the amygdala, and the secondary target area is the temporal lobe.

[0030] This embodiment redesigns the target area combinations for each sleep stage based on the neuromodulation logic that signal initiation / interference suppression is dominated by deep upstream centers, while functional execution is completed by downstream cortical centers. The primary target areas are all deep nuclei (responsible for upstream functions such as rhythm initiation and interference suppression), while the secondary target areas are all cortical regions (responsible for downstream functions such as slow-wave amplification and signal integration). This ensures a complete closed loop in the regulatory chain from deep initiation to cortical execution, addressing the problem of insufficient cortical primary target area initiation capacity in traditional combinations. It ensures that the multi-target area combination can accurately match the needs of each stage and achieve a synergistic effect greater than the sum of its parts. This embodiment uses the following target area combinations according to the sleep cycle (Wake stage → REM stage): (1) Wake phase: primary target area: thalamus, secondary target area: dorsolateral prefrontal cortex (DLPFC) The core challenge of the wake phase is the difficulty in transitioning from wakefulness to sleep. Its neural mechanisms involve two key aspects: first, overactivation of wakefulness-related neural activities (such as norepinephrine secretion from the locus coeruleus), requiring inhibition through prefrontal cortex regulation; and second, slow initiation of thalamic rhythms, necessitating accelerated switching and regulation for relief. Based on this, the target area combination design logic is as follows: The thalamus is the upstream pacemaker of the sleep rhythm. The core of the transition from wakefulness to sleep is the thalamus switching from the wakefulness rhythm (alpha waves) to the sleep rhythm (theta waves). The thalamus initiates the initial signals of the sleep rhythm by regulating the firing frequency of the thalamus-cortex circuit. If the thalamic rhythm switching is slow, even if the cortex inhibits arousal, the sleep latency will still be prolonged. By selecting the thalamus as the primary target area, depolarization can accelerate the alpha-to-theta wave switching, providing a rhythmic basis for sleep onset.

[0031] The DLPFC is the downstream executive center for arousal inhibition. After the thalamus initiates the sleep rhythm, the DLPFC needs to inhibit the excitability of arousal nuclei such as the locus coeruleus, blocking the interference of arousal signals on the thalamic rhythm. If only the thalamus initiates the rhythm, and the DLPFC does not perform arousal inhibition, arousal neurotransmitters will still interfere with theta wave synchronization, leading to awakening upon falling asleep. Choosing the DLPFC as a secondary target area, in conjunction with upstream thalamic initiation, forms a complete link between rhythm initiation and arousal inhibition, avoiding the unprotected problem of initiation of a single target area (thalamus only).

[0032] (2) N1 phase: the raphe nucleus in the main target area and the sensorimotor cortex in the secondary target area (M1). Stage N1 is a transitional phase of light sleep. The core challenge is its susceptibility to external stimuli, leading to a rebound awakening. The neural mechanism involves somatosensory input (such as sound and touch) easily activating the sensorimotor cortex, disrupting the initial synchronization of theta waves (4-7Hz), resulting in a prolonged N1 stage or a direct return to the wake stage. The target area combination design logic is as follows: The raphe nucleus (MRN) is an upstream center for the inhibition of interoceptive interference during N1 stage sleep. N1 stage light sleep is easily disturbed by interoceptive signals (such as breathing, heartbeat, and mild pain). The raphe nucleus inhibits the transmission of interoceptive signals to the cortex by secreting serotonin, providing an interference-free environment for theta wave stability. If raphe nucleus inhibition is insufficient, even if the cortex blocks somatosensory input, interoceptive signals will still lead to theta wave fragmentation. Choosing the raphe nucleus as the primary target area and depolarizing it can enhance serotonin secretion, reducing interference at its source.

[0033] M1 is the downstream executive center for somatosensory input blocking in stage N1. After the raphe nucleus inhibits interoceptive interference, M1 needs to block the transmission of peripheral somatosensory signals to the cortex to prevent the superposition of somatosensory signals with interoceptive signals, which would exacerbate theta wave interference. If only the raphe nucleus inhibits interoceptives without blocking somatosensory input from M1, mild external stimuli can still trigger arousal. Choosing M1 as a secondary target area, in conjunction with upstream interference inhibition of the raphe nucleus, forms a dual protection of interoceptive inhibition and somatosensory blocking, avoiding the problem of incomplete interference inhibition in a single target area (raphe nucleus only).

[0034] (3) N2 phase: primary target area: thalamic reticular nucleus (TRN); secondary target area: parietal central cortex (PC). Stage N2 is a crucial stage for transitioning to deep sleep. The core challenge lies in the fragmentation of spindle waves (12-14Hz) and the insufficient number of K-complex waves (0.5-2Hz). The neural mechanism involves the synergistic regulation of spindle waves and K-complex waves by the TRN and other thalamic nuclei, both of which jointly determine the efficiency of the N2→N3 transition. The target area combination design logic is as follows: The TRN is the upstream initiation center for spindle waves in phase N2. Spindle wave generation originates from the synchronized firing of the TRN and other thalamic nuclei, with the TRN responsible for initiating the high-frequency rhythm (12-14 Hz) of the spindle waves. If the TRN initiation is insufficient, even if the thalamus (PC) has amplification capabilities, there will be no initial spindle wave signal to amplify, resulting in insufficient spindle wave density. Selecting the TRN as the primary target area and depolarizing it can enhance the 12-14 Hz rhythmic firing, providing the PC with the initial spindle wave signal.

[0035] The pyramidal nucleus (PC) is the downstream amplification center for the N2 phase spindle wave. After the TRN initiates the spindle wave, the PC pyramidal cell network needs to fire synchronously, and its excitability directly determines the density and duration of the spindle wave. If only the TRN is initiated without PC amplification, the spindle wave amplitude will be less than 50 μV, which cannot effectively suppress the arousal signal, and the N2→N3 transition efficiency will still be reduced. Choosing the PC as a secondary target area, in conjunction with the upstream initiation of the TRN, forms a complete link for spindle wave initiation and amplification, avoiding the problem of no amplification when initiating a single target area (only the thalamic reticular nucleus).

[0036] (4) N3 phase: main target area insula, secondary target area prefrontal cortex (PFC) Stage N3 is the deep sleep stage, and the core challenge is insufficient delta wave (0.5-4Hz) power and short deep sleep duration. The neural mechanism involves delta waves relying on the coordinated firing of the prefrontal cortex and insula. The insula, as a subcortical homeostatic regulatory center, can prevent metabolic signals from interfering with deep sleep. The target area combination design logic is as follows: The insula is the upstream center for maintaining N3 sleep homeostasis. The core of deep sleep is the continuous synchronization of delta waves without interference from metabolic signals. The insula integrates metabolic signals (such as blood glucose and blood oxygen) and inhibits the transmission of abnormal metabolic signals to the cortex, preventing delta waves from being interrupted due to metabolic fluctuations (such as hunger or mild hypoxia). Choosing the insula as the main target area, depolarization can enhance the filtering capacity of metabolic signals and provide a stable environment for delta waves. The percutaneous cochlea (PFC) is the downstream executive center for delta wave amplification in stage N3. After the insula maintains homeostasis, the PFC is needed to enhance delta wave synchronicity in the thalamic-cortical circuit and increase delta wave power density. If only the insula maintains homeostasis and the PFC does not amplify, the delta wave power will be less than 50 μV² / Hz, and the quality of deep sleep will still be low. Choosing the PFC as a secondary target area, in conjunction with the upstream homeostasis of the insula, forms a complete link of homeostasis maintenance and slow wave amplification, avoiding the problem of no homeostasis enhancement in a single target area (only the insula).

[0037] (5) REM phase: primary target area: amygdala (deep upstream), secondary target area: temporal lobe (downstream cortex) REM sleep is the rapid eye movement sleep stage. The core challenge is the disruption of memory-related activities and the overactivation of emotions leading to nightmare awakenings. The neural mechanisms show that memory consolidation during REM sleep depends on the temporal lobe (especially the hippocampus), while emotional stability depends on the amygdala. Abnormal activity in either leads to REM sleep disturbances. The target area combination design logic is as follows: The amygdala is an upstream center for emotional stability during REM sleep; nightmares and emotional arousal during REM sleep originate from amygdala overactivation. The amygdala regulates the emotional responses of the limbic system, suppressing excessive fear and anxiety signals, thus providing an emotionally stable environment for REM dreams. By selecting the amygdala as the primary target area, depolarization can inhibit excessive amygdala firing, reducing emotional arousal at its source. The temporal lobe is the downstream executive center for REM memory maintenance. After the amygdala stabilizes emotions, the temporal lobe (including the hippocampus) is needed to maintain the normal consolidation of dream memories. If only the amygdala stabilizes emotions and the temporal lobe does not perform memory maintenance, the efficiency of REM memory consolidation will decrease, and dreams will be more easily fragmented. Choosing the temporal lobe as a secondary target area, in conjunction with the upstream emotional stabilization of the amygdala, forms a complete link between emotional stability and memory maintenance, avoiding the problem of stabilization without memory in a single target area (only the amygdala).

[0038] Step 2: Based on a predefined set of stimulation parameters, independently set stimulation parameters for the main target region and the secondary target region. The stimulation parameters include polarization direction, current intensity, carrier frequency, and modulation frequency.

[0039] In this embodiment, the primary target area of ​​the thalamus is subjected to a 1.5mA current and a 0.5Hz modulation frequency (to match the theta wave initiation requirements), while the secondary target area of ​​the DLPFC is subjected to a 1.2mA current and a 0.6Hz modulation frequency, slightly higher than that of the thalamus, to enhance the execution of arousal inhibition, and both target areas are simultaneously depolarized. If sleep deprivation during wake phase is required, the primary target area of ​​the thalamus is hyperpolarized with a 1.6mA current and a 10Hz modulation frequency to inhibit rhythm initiation, while the secondary target area of ​​the DLPFC is hyperpolarized with a 1.4mA current and an 8Hz modulation frequency to block slow wave execution, and both target areas are simultaneously hyperpolarized.

[0040] The main target region of the raphe nucleus uses a current of 1.3mA and a modulation frequency of 3.5Hz (to match the θ wave stabilization requirements), while the secondary target region of M1 uses a current of 0.8mA and a modulation frequency of 4.0Hz, which is slightly higher than that of the raphe nucleus, to enhance the somatosensory blocking execution and achieve synchronous depolarization of the two target regions.

[0041] The TRN main target region uses a 1.4mA current and a 13Hz modulation frequency (to match the spindle wave start-up requirements), while the PC auxiliary target region uses a 1.5mA current and a 12Hz modulation frequency, slightly lower than the main target region, to enhance amplification and execution, and the dual target regions are depolarized synchronously.

[0042] The main target region of the island blade uses a current of 1.8mA and a modulation frequency of 0.5Hz (to match the steady-state requirements of delta waves), while the auxiliary target region of the PFC uses a current of 2.0mA and a modulation frequency of 0.8Hz, which is slightly higher than that of the main target region, to enhance amplification and execution, and the dual target regions are depolarized synchronously.

[0043] The amygdala primary target area uses a 0.7mA current and a 4.5Hz modulation frequency (matching the emotional stability requirements of REM sleep), while the temporal lobe secondary target area uses a 0.8mA current and a 5.0Hz modulation frequency, slightly higher than the primary target area, to enhance memory execution and achieve simultaneous depolarization of both target areas.

[0044] This embodiment is based on the complementary logic of the main target area initiation signal and the auxiliary target area execution amplification, constructing a precise combination logic of the deep main target area and the cortical auxiliary target area. Coordination parameters (frequency, current, polarization direction) are designed for each combination to form a positive feedback loop of forward support and backward reinforcement, ensuring coverage of the entire regulatory pathway. Combining the core neural mechanisms of each stage from the Wake to the REM phase, the functional division of the target areas is dynamically adapted to the stage characteristics, and target area combinations and stimulation schemes are designed in stages. Please refer to Table 1 for specific combination mapping relationships and mechanisms.

[0045] Table 1. Mapping Relationship between Sleep Stage and Target Area In this embodiment, the method also includes performing cross-stage target region parameter linkage, specifically including: When a sleep stage transitions from a first sleep stage to a second sleep stage is detected, at least one core stimulation parameter applied to the primary and secondary target areas of the first sleep stage is used as the initial stimulation parameter applied to the primary and secondary target areas corresponding to the second sleep stage. The core stimulation parameter includes current intensity and modulation frequency. For the modulation frequency, a gradient transition method is used to adjust the frequency from the first sleep stage to the target frequency of the second sleep stage. The completion time of the gradient transition is configured to match the neural rhythm cycle of the target sleep stage.

[0046] Specifically, this embodiment designs a cross-stage target area parameter linkage mechanism. The core logic is: based on the neural rhythm correlation of the sleep stages, the core parameters (current intensity, frequency, polarization direction) of the primary and secondary target areas of the previous stage are transferred to the corresponding primary and secondary target areas of the next stage in a way of "partial inheritance and gradient transition". This avoids rhythm interruption caused by sudden parameter changes, and at the same time shortens the rhythm initiation time of the new stage, so as to achieve seamless connection of the entire process from Wake stage → N1 stage → N2 stage → N3 stage → REM stage.

[0047] An example of a cross-stage target region parameter linkage mechanism is as follows: (1) Switching from Wake phase to N1 phase (from "awakening inhibition" to "theta wave stabilization") Parameters for the previous stage (Wake phase): Main target area (thalamus): depolarization, 2.3kHz carrier wave, 0.5Hz modulation frequency, 1.1mA current; Secondary target region (DLPFC): depolarization, 2.0kHz carrier, 0.6Hz modulation frequency, 0.9mA current; Parameter inheritance logic: Functional correlation parameters (current intensity): Wake phase main target area (thalamus) 1.1mA → N1 phase main target area (raphe nucleus) 1.0mA (91% retention, as both main target areas are "deep upstream centers" with similar current sensitivity); Wake phase secondary target area (DLPFC) 0.9mA → N1 phase secondary target area (M1) 0.8mA (89% retention, both are "downstream cortical executive areas" with matched current carrying capacity). Functionally unrelated parameters (frequency): 0.5Hz in the main target area during the Wake phase → 3.5Hz in the main target area during the N1 phase (the basic frequency of theta waves), using a gradient transition of "0.5Hz → 1Hz → 2Hz → 3Hz → 3.5Hz" (completed in 0.8 seconds, matching the theta wave period of 0.28 seconds, to avoid neuronal overexcitation caused by sudden frequency changes). Polarization direction: Completely inherits "depolarization" (both promote sleep, with the same functional direction).

[0048] (2) N1 phase → N2 phase switching (from "theta wave stability" to "spindle wave enhancement") Parameters for the previous stage (N1): Main target region (mid-raphe nucleus): depolarization, 2.3kHz carrier, 3.5Hz modulation frequency, 1.3mA current; Secondary target region (M1): depolarization, 2.0kHz carrier, 4.0Hz modulation frequency, 0.8mA current; Parameter inheritance logic: Functional correlation parameters (current intensity): N1 main target area 1.3mA → N2 main target area (thalamic reticular nucleus) 1.4mA (an increase of 7.7%, because the thalamic reticular nucleus is the "spindle wave initiation center", requiring slightly higher current to enhance the generation of high-frequency rhythms); N1 auxiliary target area 0.8mA → N2 auxiliary target area (PC) 1.5mA (an increase of 87.5%, because the PC requires higher current to amplify spindle waves. Although the increase is large here, it is based on the preset "upper limit of current in the cortical executive area" to avoid overload). Functional non-correlated parameters (frequency): 3.5Hz in the main target area of ​​N1 phase → 13Hz in the main target area of ​​N2 phase (spindle wave frequency), using a gradient transition of "3.5Hz → 5Hz → 8Hz → 11Hz → 13Hz" (completed in 1.2 seconds, matching the spindle wave period of 0.077 seconds to ensure smooth generation of high-frequency rhythms); Polarization direction: Fully inherits "depolarization".

[0049] (3) Switching from N2 to N3 Parameters for the previous stage (N2): Main target area (thalamic reticular nucleus): depolarization, 2.3kHz carrier wave, 13Hz modulation frequency, 1.4mA current; Secondary target region (PC): depolarization, 2.0kHz carrier, 12Hz modulation frequency, 1.5mA current; Parameter inheritance logic: Functional correlation parameters (current intensity): N2 phase main target area 1.4mA → N3 phase main target area (island) 1.8mA (28.6% increase, because the insula is the center of metabolic homeostasis in deep sleep, requiring higher current to filter metabolic interference); N2 phase auxiliary target area 1.5mA → N3 phase auxiliary target area (PFC) 2.0mA (33.3% increase, because PFC requires stronger current to amplify delta waves, based on the current upper limit preset in the cortical execution area to avoid overload); Functional non-correlated parameters (frequency): N2 phase main target area 13Hz (spindle wave) → N3 phase main target area 0.5Hz (δ wave), using a gradient transition of "13Hz→10Hz→5Hz→1Hz→0.5Hz" (completed in 1.5 seconds, matching the δ wave 2-second cycle to ensure a smooth transition from high-frequency rhythm to low-frequency slow wave); Polarization direction: Fully inherits "depolarization".

[0050] (3) N3 phase → REM phase transition (from “delta wave enhancement” to “emotional stability + memory maintenance”) Parameters for the previous stage (N3): Main target region (island): depolarization, 2.3kHz carrier, 0.5Hz modulation frequency, 1.8mA current; Secondary target area (PFC): depolarization, 2.0kHz carrier, 0.8Hz modulation frequency, 2.0mA current; Parameter inheritance logic: Functional correlation parameters (current intensity): N3 phase main target area 1.8mA → REM phase main target area (amygdala) 0.7mA (38.9% retention, because the amygdala is the "emotion center" and is more sensitive to current, so the intensity needs to be reduced to avoid excessive inhibition); N3 phase secondary target area 2.0mA → REM phase secondary target area (temporal lobe) 0.8mA (40% retention, because the temporal lobe memory function requires gentle stimulation to avoid high intensity interference with memory integration); Functional non-correlated parameters (frequency): N3 phase main target area 0.5Hz → REM phase main target area 4.5Hz (REM phase β wave low frequency band), using a gradient transition of "0.5Hz → 1Hz → 2Hz → 3.5Hz → 4.5Hz" (completed in 1.5 seconds, matching the REM phase rhythm cycle of 0.22 seconds, avoiding awakening caused by the sudden disappearance of the delta wave); Polarization direction: Fully inherits "depolarization".

[0051] Step 3: Control the stimulation signal generation module and the multi-channel electrode array to apply transcranial time-interference electrical stimulation to the main target area and the auxiliary target area with the independently set stimulation parameters.

[0052] In this embodiment, the control module integrates a double-oar rowing boat model, wherein: Sleep state is mapped to the ship's course; The main target area and the auxiliary target area are respectively mapped to the left propeller for controlling the heading and the right propeller for assisting execution; The stimulation parameters are mapped to the direction and force of paddling; The control module dynamically adjusts the stimulation parameters based on the EEG signals and the double-oar rowing model.

[0053] Specifically, to clearly illustrate the synergistic logic of multi-target tTIS stimulation, this embodiment proposes a double-oar rowing model. Please refer to [link / reference needed]. Figure 4 The model uses the analogy of sleep state to "ship's course," multi-target areas to "two oars," tTIS stimulation parameters to "rowing direction and force," individual basal sleep differences to "water resistance," potential sleep-affecting factors to "river rocks," and external disturbances to "environmental disturbances during navigation." The model uses "course control" to intuitively explain the synergistic mechanism of "promoting / depriving sleep": "Both oars rowing forward simultaneously propels the ship forward, resulting in deeper sleep and fewer awakenings," and "Both oars rowing backward simultaneously causes the ship to move backward, temporarily preventing the body from entering deep sleep, which can be used for treatment / research." A precise mapping between the two-oar rowing model and its technical elements is established to ensure the mechanism is understandable and practical. The mapping relationship of the two-oar rowing model is shown in Table 2.

[0054] Table 2 Mapping Relationships for the Twin-Oar Rowing Model The mapping relationships described above are explained one by one below: (1) Mapping between “left paddle” and “deep main target area” (main navigation direction) In the double-oar rowing model, the "left oar" corresponds to the deep main target area in the combination (such as the thalamus in the Wake phase and the raphe nucleus in the N1 phase), which is the core that determines the course of the boat (sleep state).

[0055] The "rowing direction" of the left oar corresponds to the polarization type of the main target area: rowing forward (depolarization) means that the main target area initiates positive upstream signals (such as sleep rhythm, interference suppression), propelling the boat towards deeper water (promoting sleep); rowing backward (hyperpolarization) means that the main target area suppresses upstream signals (such as blocking rhythm initiation, enhancing wakefulness interference), pulling the boat towards shallower water (depriving sleep). The "stretching force" of the left paddle corresponds to the tTIS stimulation parameters of the main target area (such as current magnitude and modulation frequency matching degree): the greater the force, the deeper the paddle enters the water, which means that the upstream signal of the main target area is stronger and more matched with the stage requirements (such as 1.8mA and 0.5Hz for the island lobe in the N3 stage, which is significantly greater than 0.7mA and 4.5Hz for the amygdala in the REM stage). The "length" of the left propeller corresponds to the depth characteristics of the main target area: the left propeller is longer, simulating a deep nucleus, and can go deep underwater. This corresponds to the tTIS high-frequency carrier penetrating deep layers, ensuring that upstream signals can be effectively transmitted to the bottom of the ship (the core link of sleep regulation). This is a depth advantage that the right propeller (cortical auxiliary target area) cannot replace.

[0056] (2) Mapping between “right paddle” and “cortical secondary target area” (assisted execution) In the double-spinner rowing model, the "right paddle" corresponds to the cortical auxiliary target area (such as DLPFC in the Wake phase and M1 in the N1 phase) in the combination, which is the key to assisting the left paddle in executing the course and improving the driving efficiency.

[0057] The right propeller moves in the same direction as the left propeller, forward / backward, and its downstream function in the secondary target area coordinates with the upstream signal in the primary target area. When the left propeller moves forward, the right propeller moves forward synchronously (primary target area depolarization → secondary target area depolarization, executing upstream signal); when the left propeller moves backward, the right propeller moves backward synchronously (primary target area hyperpolarization → secondary target area hyperpolarization, strengthening upstream suppression). The "strike force" of the right paddle should be slightly lower than that of the left paddle to avoid excessive interference from the upstream signal by the downstream execution. For example, during the Wake phase, the main target area of ​​the thalamus is 1.5mA (left paddle force level 5), and the secondary target area of ​​the DLPFC is 1.2mA (right paddle force level 4). The "propeller length" of the right propeller corresponds to the depth characteristics of the auxiliary target area: the right propeller is shorter, simulating the cortical region, and only acts on the shallow water surface. This corresponds to the focusing of the tTIS high-frequency carrier in the cortex, focusing on transmitting and executing the deep signal of the left propeller, and avoiding signal interference with the left propeller due to excessive propeller length (going deep into the water).

[0058] (3) The mapping between “ship” and “sleep state” (course and efficiency) In the double-oar rowing model, the "boat" corresponds to the actual sleep state. Its course is determined by the left oar (deep main target area), and its driving efficiency is improved by the right oar (cortical secondary target area).

[0059] Sailing towards deep water, i.e. promoting sleep: the left propeller moves forward (the main target area depolarization initiates the upstream signal), and the right propeller moves forward simultaneously (the auxiliary target area depolarization executes the downstream function), and the ship sails smoothly and efficiently towards deep water (deep sleep / stable REM period). Navigating to shallow waters, i.e. sleep deprivation: the left oar is rowed backward (hyperpolarization of the main target area suppresses upstream signals), and the right oar is rowed backward in sync (hyperpolarization of the secondary target area blocks downstream functions), allowing the ship to sail smoothly and efficiently to shallow waters (extending the wake period / shortening deep sleep). If the "rowing directions" of the left and right oars are inconsistent, the left oar stimulates the deep primary target area, while the right oar stimulates the shallow secondary target area. The overall course of the boat is still determined by the left oar, and the reaction force of the right oar will cause the boat to turn in circles. The boat will not effectively enter the next sleep stage and will maintain the current sleep state.

[0060] (4) Analogy between “left-handed single-oar rowing” and “single-target stimulation” (left-handed oar movement only) The boat's "stability" corresponds to sleep homeostasis: when both oars are used in coordination, the boat is balanced by forces on both sides (signals from the deep layer and the cortex match), and there is no turbulence (no frequent awakenings); when a single oar is used, the boat is prone to tilting (signal imbalance), and the journey is bumpy (sleep fragmentation).

[0061] If a single target area only stimulates the deep primary target area, this can be likened to "a left-handed person rowing a boat with the left oar alone." Although a left-handed person can navigate using the left oar, the lack of assistance from the right oar will lead to the following results.

[0062] Risk of heading deviation: When the left propeller moves forward alone, the thrust of the left propeller will also propel the boat forward when the main target area is depolarized. However, because the boat has no power support on the right side, the thrust is asymmetrical, and the boat will continue to turn to the left while moving forward. If only the thalamus is depolarized during the wake phase, although the rhythm is initiated, the DLPFC does not perform arousal inhibition. Although the boat deviates towards the sleep area, the sleep latency is still very long. Low propulsion efficiency: The left propeller requires greater force and higher current to propel the boat forward, which not only increases the propeller load and the risk of overstimulation of the main target area, but also results in slow speed. For example, in the N3 phase, if only the island blades are depolarized, the current needs to be increased from 1.8mA to 2.5mA to maintain delta wave stability; Weak anti-interference ability: When encountering navigational environmental interference (such as external stimuli and metabolic fluctuations), the left propeller alone cannot quickly adjust the balance. For example, in the N1 phase, only the mid-slit nucleus is depolarized. When encountering external sound stimulation, the boat is easily pushed back to the shallow water area by the water flow, and the number of awakenings increases. However, the two propellers working together can make fine adjustments to the force of the right propeller. For example, in the M1 phase, the somatosensory blocking is enhanced, which can quickly resist interference.

[0063] (5) The mapping of individual differences and external interference In the rowing model, "water resistance" corresponds to "individual differences in sleep baseline." A gentle current indicates a good sleep baseline (e.g., occasional insomnia, minimal circadian rhythm fluctuations), while a turbulent current indicates severe sleep disorders (e.g., chronic insomnia, deep nucleus dysfunction). The rowing force needs to be adjusted according to the water flow: in turbulent water (e.g., for patients with insufficient deep sleep), the forward force of the oars needs to be increased, such as raising the N3 phase PFC current to 2.2 mA and the island current to 1.8 mA, to propel the boat into deeper water. In gentle water, if healthy individuals require a slight boost to sleep, the force should be reduced to avoid overstimulation.

[0064] In the rowing boat model, the "rocks in the river" correspond to "potential underlying causes affecting sleep in individuals." These causes do not directly determine the boat's course, but they can create sudden obstacles during the journey. These rocks include metabolic insomnia caused by thyroid dysfunction, latent anxiety in the limbic system, and sleep apnea, with the density of the rocks corresponding to the severity of the underlying cause.

[0065] In the rowing boat model, "environmental disturbances during navigation" corresponds to "external disturbances." Sudden winds, waves, and passing ships during navigation are temporary external disturbances to the boat (in a sleeping state), just like external noise or light stimuli that affect sleep.

[0066] In the rowing model, the "rower" corresponds to the "EEG closed-loop feedback module," which is the core of the dynamic course adjustment. The rower adjusts the direction and force of the oars in real time by "observing the water flow and boat position" (corresponding to EEG monitoring of sleep rhythms and phase characteristics, such as delta wave proportion and eye movement signals). If the boat deviates from the deep water area, such as insufficient delta wave amplitude in phase N3, the forward force of the oars is increased to enhance PFC and island depolarization intensity. If the boat is found to be too close to the deep water area, such as slow wave intrusion during REM sleep, the rearward force of the right oar is finely adjusted to enhance amygdala hyperpolarization. If a "reef" is detected, such as epileptiform discharges in the EEG, rowing is immediately stopped, stimulation is paused, and navigation and stimulation use are ensured to be safe. This embodiment uses a double-oar rowing model to transform the abstract multi-target electrophysiological synergy mechanism into an intuitive logic of "rowing direction and force," reducing the threshold for technical understanding and clinical application, and improving operational convenience and treatment compliance.

[0067] In this embodiment, the control module is configured to achieve bidirectional regulation of promoting sleep and depriving sleep by adjusting the polarization directions of the primary target area and the secondary target area, specifically including: In the sleep-promoting mode, both the primary target area and the secondary target area are depolarized. In sleep deprivation mode, both the primary target area and the secondary target area are controlled to be hyperpolarized.

[0068] Specifically, this embodiment combines multiple target areas for each sleep stage. The double-oar rowing model can intuitively explain the synergistic mechanism of promoting / depriving sleep, clarifying how the two target areas achieve a 1+1>2 effect through rowing in the same direction: (1) Sleep-promoting scenario: Paddle forward with both oars in the same direction and push the boat into deep water. The core of promoting sleep is the depolarization of the primary target area (left paddle forward) and the depolarization of the secondary target area (right paddle forward). Both paddles exert force in the same direction, propelling the boat towards the deep water area (deep sleep / stable REM period). The specific logic of each stage is as follows.

[0069] Transition from Wake to N1: The left paddle (main target area of ​​the thalamus, 1.5mA, 0.5Hz) moves forward, initiating the alpha-theta wave switching; the right paddle (secondary target area of ​​the DLPFC, 1.2mA, 0.6Hz) moves forward synchronously, executing arousal inhibition. The boat remains balanced, without deviation, and smoothly enters the inner shallow water area (N1 stage), reducing the sleep latency. Transition from N2 to N3: The left oar (main target area of ​​the thalamic reticular formation, 1.4mA, 13Hz) moves forward, initiating a high-frequency spindle wave rhythm; the right oar (secondary target area of ​​the PC, 1.5mA, 12Hz) moves forward synchronously, amplifying the spindle wave amplitude. The hull stabilizes, and the ship rapidly enters the deep-water entrance (N3), where the spindle wave density increases. N3 phase maintenance: The right propeller (island blade primary target area, 1.8mA, 0.5Hz) moves forward to maintain metabolic homeostasis; the right propeller (PFC secondary target area, 2.0mA, 0.8Hz) moves forward synchronously to amplify delta wave power. With continuous propulsion from both propellers, the boat travels stably in the center of the deep water zone (N3 phase), the proportion of N3 phase increases, the number of deep sleep interruptions decreases, and there are no awakenings triggered by metabolic signals.

[0070] REM phase stability: The left paddle (primary target area of ​​the amygdala, 0.7mA, 4.5Hz) moves forward to stabilize emotions; the right paddle (secondary target area of ​​the temporal lobe, 0.8mA, 5.0Hz) moves forward simultaneously to maintain memory. With the paddles working steadily, the boat travels smoothly at the edge of the deep water zone (REM phase), the proportion of REM phase is stable, and the number of awakenings is reduced.

[0071] (2) Sleep deprivation scenario: Both oars paddle backward in the same direction and work together to pull the boat back to shallow water. The core of sleep deprivation is hyperpolarization of the primary target area (left paddle backward) and hyperpolarization of the secondary target area (right paddle backward). The two paddles exert force in opposite directions to pull the boat from deep water back to shallow water (prolonging the wake period / shortening deep sleep). The specific logic of each stage is as follows.

[0072] Wake deprivation (maintaining wakefulness): The left paddle (thalamus, primary target area) moves backward synchronously (hyperpolarization, 1.6mA, 10Hz) to inhibit sleep rhythm pacing and avoid theta wave synchronization. The right paddle (DLPFC, secondary target area) moves backward (hyperpolarization, 1.4mA, 8Hz) to block the slow wave generation pathway and inhibit sleep initiation; with the combined force of the two paddles, the boat is firmly fixed at the edge of the shallow water area (wake period), sleep efficiency is reduced, the proportion of N3 stage is reduced, and the requirements of sleep deprivation experiments are met.

[0073] REM deprivation (shortening REM): The left paddle (amygdala, primary target area) moves backward (hyperpolarization, 1.3mA, 9Hz), inhibiting emotional memory activity and interrupting the REM dream cycle; the right paddle (temporal lobe, secondary target area) moves backward simultaneously (hyperpolarization, 1.2mA, 10Hz), blocking the maintenance of the REM rhythm and promoting the transition from REM to N1. Under the combined force of the two paddles, the boat is pulled from the edge of the deep water zone (REM) back to the inner side of the shallow water zone (N1), the proportion of REM decreases, there is no complete dream cycle, and it shifts towards the dream disorder zone.

[0074] Specifically, based on the core characteristics of the deep primary target area and the cortical secondary target area in this embodiment—functional complementarity and reversible polarization direction—the system achieves bidirectional switching of the control target by precisely controlling the polarization state of the two target areas (depolarization activates positive regulation to promote sleep, while hyperpolarization inhibits core signals to deprive sleep). Furthermore, a flexible reuse mechanism for the system's EEG acquisition and stimulation electrodes is designed. During non-stimulation periods, all electrodes continuously acquire EEG signals (real-time monitoring of sleep stages and rhythm states to provide a basis for parameter adjustment). When stimulation of a specific target area is required, the system automatically switches the corresponding electrode to stimulation mode and outputs a preset current. Through the synergistic design of polarization direction adjustment and flexible electrode reuse, flexible switching between promoting sleep and depriving sleep can be achieved without replacing electrode hardware, simplifying the operation process and avoiding interference with sleep rhythms during electrode replacement. For the specific switching logic, please refer to Table 3.

[0075] Table 3 Polarization Direction Switching Logic Table In this embodiment, the electrode placement positions of the multi-channel electrode array for each target region are determined based on simulation modeling, so that the target region current density is between 0.25mA / cm² and 0.35mA / cm², and the current density in the 5mm area outside the target region is less than 0.1mA / cm².

[0076] In practical applications, the electrode placement positions in each target area are determined through processes such as simulation modeling, current distribution analysis, and thermal map generation to ensure that the target area current density meets the standard. The specific steps are as follows: Step A: Establish a three-dimensional anatomical model of the head.

[0077] The ICBM152 standard brain template (including anatomical structures of the scalp, skull, cerebrospinal fluid, gray matter, white matter, and deep nuclei) was used with a resolution of 1mm×1mm×1mm to ensure an error of less than 5% compared to the actual human head structure. Based on literature parameters, the conductivity of the simulated current was set for different tissues: scalp 0.43 S / m, skull 0.01 S / m, cerebrospinal fluid 1.65 S / m, gray matter 0.465 S / m, white matter 0.126 S / m, thalamus 0.45 S / m, and amygdala 0.44 S / m. Key structures relevant to the target area (e.g., DLPFC corresponding to prefrontal gray matter and thalamus corresponding to deep nuclei) were retained, while irrelevant small structures were removed to balance simulation accuracy and computational efficiency. Step B: Import electrode placement parameters and tTIS stimulation model.

[0078] The coordinates (converted to three-dimensional coordinates based on the 10-20 system), dimensions (diameter 12mm), and impedance (5kΩ) of the four electrodes for each target region were imported into SimNiBS simulation software. The tTIS stimulation model was set to a 2.0-2.5kHz sinusoidal carrier wave, superimposed with a 0.1-5Hz low-frequency modulation wave. The current intensity was set to 0.5-2.2mA according to the requirements of each target region. The reference electrode was grounded to simulate the current return path of the mastoid process behind the ear. Step C: Current distribution simulation and brain topography heatmap generation.

[0079] The simulation calculation uses the finite element method to solve the current conduction equation and calculates the current density and electric field intensity distribution of each voxel (1 mm³) in the head model. The simulation time step is 0.1 ms and the total duration is set to cover one low-frequency modulation cycle of 1 s.

[0080] Please see Figure 5 The current density data of the cortical surface (gray matter-cerebrospinal fluid interface) were extracted, and a cortical topology map was generated by dividing the color gradient into 0-0.4 mA / cm² (based on 10-20 system coordinates). Figure 5 In the diagram, different colors represent current density. Blue areas (current density < 0.1 mA / cm²) indicate weak or ineffective stimulation in non-target areas. Green areas (current density between 0.1-0.2 mA / cm²) represent transitional areas with moderate stimulation intensity. Red areas (current density > 0.3 mA / cm²) represent core target areas where effective stimulation intensity has been achieved. Verify current focusing in cortical target areas (e.g., DLPFC) (red areas should cover more than 90% of the target area). Extract current density data from the central layer of deep nuclei (e.g., 4.5 cm depth in the thalamus, 5.5 cm depth in the raphe nucleus) to generate deep nucleus slice heatmaps. Please refer to [link to relevant documentation]. Figure 6 Ensure that the current density in the deep nucleus region is >0.28 mA / cm². Figure 6(Red area), surrounding unrelated areas <0.1 mA / cm² ( Figure 6 (Blue area) Verify the attenuation rate of the tTIS high-frequency carrier to ensure the target area current meets the standard. Finally, determine the placement positions of the four electrodes corresponding to the target area. For example, for the placement positions of the sensorimotor cortex electrodes, please refer to [reference needed]. Figure 7 The red area in the middle.

[0081] Step D: Simulation result verification and electrode position optimization.

[0082] Standards for meeting the requirements: Target current density: 0.25-0.35 mA / cm² in the cortical target area, and 0.28-0.32 mA / cm² in the deep nucleus. Signal diffusion range: Current density < 0.1 mA / cm² in the 5 mm region outside the target area; heat Figure 1 Consistency: The overlap rate of heatmaps from multiple simulations (n=5) is >90%, ensuring stability; Optimization strategy: If the target current is insufficient: adjust the spacing between the excitation electrodes (reduce to 1-1.5 cm) or increase the carrier frequency; If the signal spreads too much: increase the number of reference electrodes (e.g., add one distal reference electrode) or adjust the current direction (perpendicular to the unrelated brain region).

[0083] Please refer to Table 4 for the electrode placement positions of each target area determined by the above process in this embodiment.

[0084] Table 4 Electrode Placement for Each Target Area In summary, the dual-target transcranial time-interference electrical stimulation (tTIS) system and sleep regulation method provided in this embodiment overcome the limitations of cortical targets. Utilizing tTIS technology, it achieves multi-target synergistic stimulation of the cortex and deep nuclei, clearly defining the core regulatory brain regions for each sleep stage and resolving the issue of ambiguous target selection. Targeting the neural mechanisms of each stage from Wake to REM sleep, it designs a phased, functionally complementary multi-target combination, addressing the insufficient activation capacity of the main cortical target region in traditional stimulation, and achieving precise synergistic regulation at each stage. Based on the multi-channel independent parameter design of tTIS technology, it independently regulates depolarization / hyperpolarization, allowing for flexible reuse of EEG acquisition and stimulation electrodes, achieving bidirectional flexible adjustment of sleep promotion and sleep deprivation, and reducing the adverse reaction rate. The proposed "double-oar rowing model" transforms the abstract multi-target electrophysiological synergistic mechanism into an intuitive logic of "rowing direction and force," lowering the technical understanding and clinical application threshold, and improving operational convenience and treatment compliance. The design incorporates a "cross-stage parameter linkage logic" that allows core parameters (such as current intensity and frequency offset) of the primary and secondary target areas in the previous stage to be "partially inherited" to the next stage, ensuring seamless control.

[0085] The following human experiments illustrate the specific implementation process of the system and method described in this invention in terms of promoting sleep and depriving sleep.

[0086] 1. Experimental System Composition The experiment used the dual-target transcranial time-interference electrical stimulation system described in this invention, which integrates the following modules: Stimulation signal generation module: outputs a high-frequency carrier wave with a frequency of 2.0-2.5kHz and superimposed a low-frequency modulation wave of 0.1-100Hz to the tTIS stimulator.

[0087] Multi-channel electrode array: adopts Ag / AgCl electrodes conforming to the 10-20 system, with an electrode diameter of 12mm, and fixed by electrode caps.

[0088] EEG signal acquisition module: Employs polysomnography (PSG) equipment to continuously acquire EEG, EOG, and EMG signals.

[0089] Control module: The computer system running the customized software, possessing the following core functions: Real-time sleep staging algorithm (based on AASM standard).

[0090] It contains a pre-stored database of "primary target area - secondary target area" combinations and basic stimulation parameters corresponding to each sleep stage.

[0091] A closed-loop control algorithm is developed to achieve cross-stage parameter linkage and the logic of the double-oar rowing model.

[0092] It displays EEG signals, sleep stages, and stimulation parameters in real time and records all data.

[0093] 2. Experimental Preparation 2.1 Subject selection and grouping The sleep promotion group recruited 30 patients with chronic insomnia who met the ICSD-3 diagnostic criteria (15 males and 15 females, aged 25-65 years). Exclusion criteria included: history of epilepsy, severe organic brain disease, pregnancy, lactation, long-term use of sedative-hypnotic drugs, and implanted metal or electronic medical devices. Patients were further subdivided according to their primary symptoms into: difficulty falling asleep (10 cases), insufficient deep sleep (10 cases), and REM sleep disturbance (10 cases).

[0094] Sleep deprivation group: 10 healthy volunteers (5 males and 5 females, aged 20-30 years) were recruited. They had no history of sleep disorders and had no history of irregular staying up late, shift work, excessive drinking, or caffeine intake in the past month.

[0095] 2.2 Baseline Data Acquisition All participants underwent polysomnography (PSG) for three consecutive nights prior to the experiment, conducted in a standard soundproof sleep laboratory. The following baseline data were collected: Objective PSG indicators: sleep latency, percentage of each sleep stage (Wake, N1, N2, N3, REM), power density of delta waves (0.5-4Hz) in N3 stage, density of spindle waves (12-14Hz) in N2 stage, and number of awakenings.

[0096] Subjective scale rating: All participants completed the Pittsburgh Sleep Quality Index (PSQI).

[0097] The sleep promotion group also completed the Insomnia Severity Index (ISI).

[0098] The sleep-deprived group also completed the Epworth Sleepiness Scale (ESS).

[0099] 2.3 Equipment Commissioning and Ethical Preparation Before the experiment, the subject's scalp was cleaned with 75% alcohol at the electrode attachment site, and the skin was lightly exfoliated to ensure that the electrode impedance was below 5kΩ.

[0100] All participants fully understood the experimental procedures, potential risks and benefits, and signed written informed consent forms.

[0101] 3. Experiment Execution 3.1 Experimental Procedure for the Sleep-Promoting Group Sleep preparation: Subjects enter the laboratory, and the experimenter assists in attaching the tTIS stimulation electrodes and PSG acquisition electrodes according to their grouping and target area mapping. After connecting all equipment, the closed-loop intervention monitoring system is activated.

[0102] Wake-time intervention: The system was initially set to wake-time sleep-inducing parameters: primary target area - thalamus (2.3kHz, 0.5Hz, 1.5mA, depolarization), secondary target area - DLPFC (2.00kHz, 0.6Hz, 1.2mA, depolarization). After the lights were turned off, the system monitored EEG in real time.

[0103] Stage switching and parameter linkage: When the system detects that the alpha wave power ratio is <30% and the theta wave power ratio is >40%, it automatically determines that it has entered stage N1. It then initiates cross-stage parameter linkage, smoothly switching to stage N1 parameters: primary target area - raphe nucleus (2.03kHz, 3.5Hz, 1.3mA, depolarization), secondary target area - M1 (2.00kHz, 4.0Hz, 0.8mA, depolarization). If sleep is not achieved within 30 minutes (alpha wave >50%), the system alarms and the experimenter manually fine-tunes the thalamic current to 1.3mA to enhance the "left paddle" force.

[0104] N1 phase: Monitor the stability of the theta wave. If its proportion is <60%, the system automatically increases the M1 current to 1.0mA (enhancing the "right propeller" force). When the first spindle wave is detected, switch to N2 phase parameters (TRN and PC).

[0105] N2 phase: If the spindle wave density is less than 15 waves / minute, automatically increase the thalamic reticular nucleus (TRN) current to 1.6 mA. When the delta wave proportion is >20%, switch to N3 phase parameters (insula and PFC).

[0106] N3 phase: If the delta wave power density is below 50 μV² / Hz, automatically increase the PFC current to 2.2 mA. If a delta wave interruption lasts for more than 30 seconds, temporarily increase the island blade current to 2.0 mA.

[0107] REM phase: When rapid eye movements (>60 times / minute) are detected and the theta wave percentage is >70%, switch to REM phase parameters (amygdala and temporal lobe). If slow wave intrusion (δ wave >5%) occurs, increase the amygdala current to 0.9mA.

[0108] Experiment End: The following morning, after the subject woke up, the system stimulation was stopped. The experimenter removed the electrodes and recorded any adverse reactions that occurred overnight (such as scalp itching or headache). The subject completed the ISI and PSQI scales again.

[0109] 3.2 Experimental Procedure for Sleep Deprivation Group Sleep preparation: Same as the sleep promotion group, attach electrodes and connect the device.

[0110] Wake phase deprivation intervention: System settings for wake phase deprivation parameters: primary target area - thalamus (2.3kHz, 10Hz, 1.6mA, hyperpolarization), secondary target area - DLPFC (2.00kHz, 8Hz, 1.4mA, hyperpolarization). This is the "dual-paddle backward stroke" mode.

[0111] Maintaining wakefulness: Real-time monitoring of EEG. If the theta wave power percentage is >20% (indicating drowsiness), the system automatically increases the thalamic current to 1.8mA and the DLPFC current to 1.6mA. If alpha wave weakening occurs (power <40%), the stimulation frequency is temporarily increased to 12Hz (thalamus) and 10Hz (DLPFC) respectively to enhance wakefulness maintenance.

[0112] End of Experiment and Recovery: After the pre-set deprivation time (e.g., 8 hours), stimulation was stopped. Electrodes were removed, and adverse reactions were recorded. Participants were then given a 2-hour recovery sleep period, and their sleep rebound was monitored. Participants completed the ESS scale.

[0113] 4. Data Processing and Effect Evaluation Data processing: Data segments with poor PSG signal quality (impedance > 10kΩ) and those with a wake-up time of more than 30 minutes were removed.

[0114] Statistical methods: MATLAB and SPSS software were used for statistical analysis. Paired t-tests were used to compare baseline data before and after intervention in the facilitation group; objective drowsiness indicators (such as the proportion of alpha waves) and subjective ESS scores were compared before and after deprivation in the deprivation group.

[0115] Criteria for judging effectiveness: The sleep-promoting group is considered "effective" if it meets all three of the following criteria: Sleep latency shortened by ≥30%; The proportion of N3 stage sleep increased by ≥5 percentage points; The ISI score decreased by ≥8 points.

[0116] The sleep deprivation group was considered "effective" if it met all three of the following criteria: Overall sleep efficiency <45% within 8 hours; N3 stage sleep accounts for less than 5%; At the end of the experiment, the ESS somnolence score was <8.

[0117] 5. Key technology support Stimulation safety: Strictly adhere to safety parameter ranges throughout the process: single electrode current intensity ≤2.2mA (current density ≤0.35mA / cm²), carrier frequency strictly limited to 2.0-2.5kHz.

[0118] Closed-loop reliability: The system ensures the accuracy and dynamic adaptation of stimuli through real-time EEG monitoring and a "rowing boat model" logic. The experimenter observes in real time from the monitoring room and can immediately interrupt the stimulation if the subject experiences discomfort.

[0119] Ethical compliance: The entire process adheres to ethical standards to ensure the rights and safety of participants.

[0120] This embodiment, through the above-described systematic experimental design and practice, fully demonstrates the implementation process of the technical solution of the present invention, and sets clear quantitative standards to verify its dual efficacy and safety in improving sleep and depriving sleep, providing a reliable example for the clinical application and scientific research of this technology.

Claims

1. A dual-target transcranial time-interference electrical stimulation system for sleep regulation, characterized in that, include: A stimulation signal generation module is used to generate a transcranial time-interference electrical stimulation signal, the signal including a high-frequency carrier wave and a low-frequency modulation wave; A multi-channel electrode array is configured to apply the transcranial time-interference electrical stimulation signal to at least two target areas of the user's head, the at least two target areas including a primary target area and a secondary target area, wherein the primary target area is a deep upstream center responsible for signal initiation or interference suppression, and the secondary target area is a cortical downstream center responsible for functional execution. The EEG signal acquisition module is used to monitor the user's EEG signals in real time to identify sleep stages; A control module, which is communicatively connected to the stimulation signal generation module, the multi-channel electrode array, and the electroencephalogram signal acquisition module; The control module is configured as follows: Based on the real-time sleep stages monitored by the EEG signal acquisition module, the main target area and auxiliary target area combination corresponding to the current sleep stage are selected from the predefined sleep stage-target area combination mapping. Based on a predefined set of stimulation parameters, stimulation parameters are independently set for the main target region and the secondary target region. The stimulation parameters include polarization direction, current intensity, carrier frequency and modulation frequency. The stimulation signal generation module and the multi-channel electrode array are controlled to apply transcranial time-interference electrical stimulation to the main target area and the auxiliary target area with the independently set stimulation parameters.

2. The dual-target transcranial time-interference electrical stimulation system according to claim 1, characterized in that, The predefined sleep stage-target area combination mapping includes: During the Wake phase, the primary target area is the thalamus, and the secondary target area is the dorsolateral prefrontal cortex. In phase N1, the primary target area is the raphe nucleus, and the secondary target area is the sensorimotor cortex. In N2 phase, the primary target area is the thalamic reticular nucleus, and the secondary target area is the central cortex of the parietal lobe. In phase N3, the primary target area is the insula, and the secondary target area is the prefrontal cortex. During REM sleep, the primary target area is the amygdala, and the secondary target area is the temporal lobe.

3. The dual-target transcranial time-interference electrical stimulation system according to claim 1 or 2, characterized in that, The control module is further configured to perform cross-stage target region parameter linkage, specifically including: When a sleep stage is detected to switch from the first sleep stage to the second sleep stage, at least one core stimulation parameter applied to the primary and secondary target areas of the first sleep stage is used as the initial stimulation parameter applied to the primary and secondary target areas of the corresponding second sleep stage. The core stimulation parameters include current intensity and modulation frequency. For the modulation frequency, a gradient transition method is used to adjust the frequency from the first sleep stage to the target frequency of the second sleep stage.

4. The dual-target transcranial time-interference electrical stimulation system according to claim 3, characterized in that, The completion time of the gradient transition is configured to match the neural rhythm cycle of the target sleep stage.

5. The dual-target transcranial time-interference electrical stimulation system according to claim 1, characterized in that, The control module is configured to achieve bidirectional regulation of promoting sleep and depriving sleep by adjusting the polarization directions of the primary target area and the secondary target area, specifically including: In the sleep-promoting mode, both the primary target area and the secondary target area are depolarized. In sleep deprivation mode, both the primary target area and the secondary target area are controlled to be hyperpolarized.

6. The dual-target transcranial time-interference electrical stimulation system according to claim 1, characterized in that, The electrodes in the multi-channel electrode array are configured to function as stimulating electrodes during stimulation periods and as acquisition electrodes of the EEG signal acquisition module during non-stimulation periods, thereby achieving electrode reuse.

7. The dual-target transcranial time-interference electrical stimulation system according to claim 1, characterized in that, The control module integrates a twin-oar rowing boat model, wherein: Sleep state is mapped to the ship's course; The main target area and the auxiliary target area are respectively mapped to the left propeller for controlling the heading and the right propeller for assisting execution; The stimulation parameters are mapped to the direction and force of paddling; The control module dynamically adjusts the stimulation parameters based on the EEG signals and the double-oar rowing model.

8. The system according to claim 1, characterized in that, The multi-channel electrode array determines the electrode placement for each target region based on simulation modeling, so that the target region current density is between 0.25mA / cm² and 0.35mA / cm², and the current density in the 5mm area outside the target region is less than 0.1mA / cm².

9. A method for regulating sleep, characterized in that, The method, applied to the dual-target transcranial time-interference electrical stimulation system as described in any one of claims 1-8, comprises: The EEG signal acquisition module monitors the user's EEG signals in real time. Based on the electroencephalogram (EEG) signals, the user's current sleep stage is identified; Based on the predefined sleep stage-target area combination mapping, determine the primary target area and secondary target area corresponding to the current sleep stage; Stimulation parameters are generated independently for the primary target region and the secondary target region based on a predefined set of stimulation parameters. Transcranial time-interference electrical stimulation is applied to the primary and secondary target areas using a multi-channel electrode array with independently generated stimulation parameters.

10. The method according to claim 9, characterized in that, When a sleep stage changes, cross-stage target area parameter linkage is performed, including using at least one core stimulation parameter of the primary and secondary target areas of the previous sleep stage as the initial stimulation parameters of the primary and secondary target areas of the next sleep stage, and performing gradient transition adjustment on the modulation frequency.

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