BODY-STATE-Dependent TRANCRANIAL STIMULATION WITH REAL-TIME COMMUNICATION BETWEEN AN ACTION MODULE AND AN EEG RECORDING MODULE

Description

[0001] The disclosure relates to a system for state-dependent stimulation with real-time communication between an action module and a detection module. This system stimulates biological tissue while simultaneously detecting signals of biological origin. The application of this method and arrangement primarily, but not exclusively, concerns all areas of medicine where biosignals are used for state-dependent stimulation. State of the art

[0002] A device for transcranial stimulation is known from Patel Yogi A. et al.: "Hard real-time closed-loop electrophysiology with the Real-Time experiment Interface (RTXI)", PLOS Computational Biology, Vol. 13, No. 5, January 2017. 1

[0003] There are medical treatment methods, as described in WO2017099603 (A1), that employ a focal neuromodulation technique. For this technique, the correct position on the cerebral cortex must be determined to better treat psychological or neurological problems. This treatment can be achieved using transcranial magnetic stimulation (TMS) while simultaneously measuring the heart rate. If a systematic change in the form of a reduction in heart rate (change in heart rate variability) is observed, the position is considered localized. The heart rate is displayed in direct response to repeated pulse sequences of repetitive TMS.

[0004] To verify this stimulus-response pattern, immediate measurement is necessary in order to correctly assign the response to the stimulation and thus also to be able to draw the correct conclusion about the medically suitable positions of the stimulation site.

[0005] However, the text does not reveal how the immediate reaction or rapid feedback can be technically implemented.

[0006] Typically, the modules for action (stimulation with TMS) and data acquisition (ECG measurement) are connected using a standard bus system. However, this does not guarantee immediate communication, let alone real-time communication.

[0007] Regardless, Ethernet transmitters exist, as described in the magazine "Elektronikpraxis" No. 8 of 16.04.2019 on p.19, which form a protective device, e.g. by means of galvanic isolation.

[0008] Starting from known systems for body-state-dependent stimulation, the invention aims to provide a system with which body-state-dependent stimulation can be carried out in a comparatively reliable and safe manner.

[0009] The invention solves this problem through a system according to claim 1. Preferred embodiments are explained in the dependent claims.

[0010] Biodata are data generated by measurements of biological parameters. Biological signals are also biodata, or more specifically, a data stream from various continuous or discrete-time measurements that provide information about the state of tissue or an organ. Such data or signals provide information about the function of organs within an organism (e.g., ECG, EEG, EMG, EOG, ERG, PPT, respiration, MKG, MEG, BP, SpO2), which can also be used to measure the effect of a previous (or quasi-simultaneous) stimulation on the body.A prerequisite for the quality of a (measurement-following) body-state-dependent stimulation is, in addition to adequate signal processing, feature extraction and targeted influencing of the human body, an artifact- and interference-free stimulation, which is guaranteed by the system according to the invention due to the real-time requirement (immediacy) for communication between the detection and action modules of the system.

[0011] Depending on a therapeutic guideline, biosignals are recorded from various parts of the body. This can be done, for example, at the head (EEG) or at other parts of the body (e.g., EMG, ECG, blood pressure, SpO2).

[0012] During a typical treatment, biosignals are continuously recorded before, during, and after a medical intervention by the same or different sensors. The time interval between recordings can range from instantaneous (within microseconds to milliseconds) to minutes or hours.

[0013] From signals that have been amplified and processed for digital signal processing, artifact-free signals and information relevant for therapeutic intervention can be obtained. These include, for example, changes in instantaneous band power, amplitude, frequency, and phase in the electroencephalogram (EEG), the individual alpha frequency in the EEG, the systolic interval of continuous blood pressure (BP or BP), the RMS value of the EMG, the pattern of the photoplethysmographic signal, blood oxygen saturation (SpO2), and other parameters or combinations thereof. Sensors for acquiring / measuring biodata, biosignals, or signals of biological origin are preferably located in the acquisition module, also called the acquisition unit. Such a module, also referred to here as a functional module, is equipped with an interface for connection to a real-time bus, in particular an EtherCAT bus.

[0014] The functional module includes an interface section that provides an interface to an externally connectable device, a device integrated into the functional module, or a downstream device. Furthermore, such a functional module contains a connection and control section. This connection and control section preferably includes a microcontroller as the control unit for the functional module and a contact section designed for connection to the device's real-time bus.

[0015] The signal processing or evaluation of the biodata or biosignals can either take place in the acquisition module, in the action module, or in a separate evaluation module, also called signal processing module or master module, which communicates with the action and acquisition module via the communication link.

[0016] The action module includes, for example, actuators that can act on tissue, organs, or the body in general. The action module can also simply provide the interface to such actuators, with the actual actuators then being connectable to the master module as external components.

[0017] In principle, biological organs or tissues can be influenced, for example, by means of electrical, magnetic, electromagnetic, mechanical, pneumatic, or hydraulic actuators. Electrical currents are applied to the body parts via electrodes, magnetic fields via coils, mechanical forces via actuators, and gases or liquids via hoses or cables.

[0018] For stimulation that depends on the body's condition, a feedback mechanism is needed that allows biodata or biosignals to influence how the actuators are controlled. A suitable control system or a (possibly closed) feedback loop is recommended here.

[0019] The following aspects can be taken into account: The actuators can preferably react quickly to information about the body's state (biodata or biosignals) for state-dependent stimulation; the actuators preferably only output the signals that are relevant or desired for influencing the human body / organs; the signal levels of the stimulation are preferably available as time- or value-discrete digital signals, which, after conversion and amplification (adaptation), are delivered to the actuator in the form of mechanical or electromagnetic energy; the signal levels for acquisition, after conversion, are available, for example, in the range of nanovolts to millivolts within a frequency band from zero to several kilohertz; in the frequency band used (e.g., the one used for feature extraction from the EEG), the stimulation and the environment cause, for example,strong interference signals are detected; these interference signals can be taken into account according to the invention and filtered out as needed; the signal sources to be investigated, e.g. of electrophysiological origin, are preferably high-impedance; the physical properties, e.g., of the stimulation and acquisition electrodes, change over time (e.g., due to changes in electrode junction impedances, electrode voltage, offset potentials, contact pressure, or motion artifacts).

[0020] Stimulation and signal acquisition systems are known that can partially overcome these problems, provided the recording method, amplifier, evaluation, and stimulation technology are carefully selected. However, high-quality commercial stimulation and polygraphy systems for state-dependent stimulation and simultaneous recording and evaluation of biosignals of various physiological origins are very expensive and usually intended only for stationary use.

[0021] The following is an example of body-state-dependent stimulation based on the detection of signals of biological origin, explaining the current procedure using actuators and sensors.

[0022] Modern electrical stimulators for cranial electrotherapy are implemented as microcontroller-controlled constant current sources. This allows for electrical stimulation with any desired current waveform. To generate the analog current signal, the current waveforms are provided digitally by the microcontroller program. However, the necessary digital-to-analog conversion can lead to systematic errors in the analog stimulation current signal due to insufficient sampling and a limited dynamic range, resulting in undesired frequency lines in the EEG spectrum.

[0023] Measuring the EEG during electrical stimulation also places high demands on the EEG recording technology and the recording process itself. Requirements for EEG measurements include, for example: Avoidance of amplifier saturation through sufficient amplitude resolution; avoidance of mains interference through the use of battery-powered detection units; avoidance of the interfering capacitive influence of the outer skin layer on the signal through careful preparation of the skin.

[0024] In other applications, such as ECG measurements, the same requirements or some of these requirements may also apply.

[0025] Current arrangements generally have at least one of the following disadvantages: Slowness of processing, as there is no real-time system for body-state-dependent stimulation when artifact correction and feature extraction must be performed simultaneously; instability, if minor, especially non-constant, delays occur for a feedback-driven / control-coupled application; complexity, if significant testing or adjustments are required after changes to the setup or operating system.

[0026] In one embodiment, the invention provides a system for body-condition-dependent stimulation with two functional modules, for example an action module for stimulating tissue and a detection module for deriving or measuring biodata or biosignals, in which communication between the two modules takes place via a communication link that meets hard or at least fixed real-time requirements.

[0027] The action module and the acquisition module can, for example, include processing power for data processing, such as a central processing unit (CPU). They can also be equipped with electronic data storage devices, such as flash memory or a solid-state drive (SSD).

[0028] Both modules can be combined in a single housing and form components of a single device. However, it is also possible to design, for example, the action module and the detection module separately and / or as portable devices to facilitate application to a patient.

[0029] The biodata or biosignals acquired by the acquisition module can be analyzed in more detail using an evaluation system. This evaluation system can be located locally at the acquisition module, e.g., as a component in a device, or remotely, e.g., at a computer workstation. A communication link between the acquisition module and the evaluation system can be wired via fiber optic cable, copper cable, or directly via printed circuit boards in a suitable integrated device; however, it can also be wireless via, for example, one of the standards GPRS, 3G, 4G (LTE), 5G, or 6G, provided the necessary time requirements, especially real-time requirements, can be met.

[0030] The analysis and output of the data, for example on an integrated display device, may, particularly in a case where only a measurement and not a stimulation-dependent feedback modulation is necessary, have lower real-time accuracy than the communication between the master module and the functional modules, so that, for example, in one embodiment of the invention, non-real-time data transmission with latency times above 100ms is sufficient.

[0031] Suitable protocols for data transmission to external evaluation units include, for example, TCP / IP for internet use or Ethernet. When using the internet for data transmission, patient-related data is preferably transmitted using cryptographic encryption.

[0032] A remote evaluation setup, in the context of telemedicine applications, allows an expert to evaluate biodata or biosignals, for example, without needing to be physically present at the patient's location during data acquisition. Instead, they can remotely review real-time measurements, i.e., from a location separate from the patient. This makes the invention even more universally applicable.

[0033] The evaluation system can, for example, be set up as a server with a CPU and data storage. The analysis of the measurement data transmitted by the acquisition module can be performed by software. However, the evaluation system can also be offered as a purely software component in a cloud. A cloud is a computer network with numerous data processing and storage resources that can be centrally controlled and scaled, i.e., made available to an application as needed. This implementation has the advantage that many different datasets from different patients (possibly anonymized) can be combined and compared.

[0034] The evaluation system can incorporate machine learning software, such as neural networks and so-called "deep learning," to recognize patterns in the collected data of one or many patients (especially in a cloud solution). Such patterns can, for example, in the case of recording an electroencephalogram (EEG), i.e., electrical currents recorded from a patient's scalp using electrodes, relate to characteristic waveforms in the EEG resulting from stimulation by the action module.

[0035] In other words, the system according to the invention ensures that the real-time requirement (immediacy) for communication between the system modules is met. Stimulation of the human body can be intensified or more targeted due to the simultaneous acquisition of biodata and the body-state-dependent stimulations according to the invention. Furthermore, it is possible, for example by means of a control module, to trigger a pulse according to predetermined parameters.

[0036] The acquisition module must be able to quickly and in real time remove artifacts from the EEG signal during electrical stimulation. This requires not only technology for capturing signals with high dynamic ranges (1 µV to 250 mV) but also knowledge of the origin and interpretation of artifacts caused by electrical stimulation and how to avoid or eliminate them. Information about the behavior of the action module is also necessary, whether it behaves predictively or whether (indirect) communication occurs between the action module and the acquisition unit.Such an information flow between the modules would in turn take place via the real-time bus, so that information from the action module is uploaded into a data packet of the master module, which is then made available to the acquisition module for download from the next data packet in a subsequent packet, usually one millisecond later at the clocking of the integrated stimulation and measurement system (MIS) preferred according to the invention.

[0037] In particularly preferred embodiments of the invention, data processing, artifact removal, and similar operations are performed in the master module. The function modules are, for example, designed to acquire data and send it to the master module, to control actuators according to the commands of the master module, or to trigger signals for controlling external devices. In this way, for example, real-time execution of the master module's commands can be improved, since no complex calculations need to be performed by the function modules.

[0038] For the combined measurement of the EEG during stimulation (e.g., by tES), filter algorithms may be necessary or advantageous. These algorithms must be applied in real time, as provided by the system according to the invention, and tolerate minimal delay between the occurrence of the event and the extracted feature. They must meet the requirements in terms of both speed (goal: low delay) and noise suppression (goal: good signal reconstruction). Dynamic regression models are not suitable for this application because they require a template and can therefore be subject to a delay of several seconds. Such a template is a pattern that generally describes the artifacts and is generated from measurements. Since the biosignal can never be predicted, the influence of the artifact on the biosignal must be estimated.

[0039] The removal of artifacts from the measurement signals, particularly those caused by external environmental influences or the stimulation trigger(s), depends, among other things, on the neuromodulation modality, for example, whether TMS or tES is used. Depending on the application, this may involve recursive filtering methods, FIR filtering, and similar techniques if the measurement is to be performed during neuromodulation.

[0040] In a preferred embodiment of the system according to the invention, the acquisition module includes a filter device. The filter device is, for example, designed as a bandpass filter that filters out interference signals in the acquired biodata or biosignals. Interference signals have, for example, frequencies that lie outside a predefined frequency interval. A frequency interval has an upper and a lower threshold for the amplitude.

[0041] Furthermore, interference signals exhibit amplitudes that lie outside a predefined amplitude interval. An amplitude interval has an upper and a lower threshold for the amplitude.

[0042] The filtered-out interference signals are then disregarded for further analysis, which improves the quality of subsequent analyses.

[0043] Artifacts from the stimulation by the action module can also be detected as interference signals and filtered out. Since the temporal evolution of these artifacts is generally known due to the knowledge of the stimuli emitted by the action module, they can be filtered out in real time in a further development of the invention. For example, in transcranial stimulation with electromagnetic pulses, the applied pulse sequence could be filtered out or subtracted from the acquired biosignals or biodata. The influence of the transcranial stimulation on, for example, recording electrodes on a patient's head can occur, for instance, through direct induction if the action module and the acquisition module are positioned close together on the patient's head.

[0044] Other types of artifacts that can be detected and filtered out include, for example, disturbances caused by the electrical activity of the heart. If an electrocardiogram (ECG) is recorded simultaneously with the EEG, these artifacts can also be removed.

[0045] In advantageous embodiments of the invention, the real-time capability can be optimized, for example to a data packet rate of 1000 Hz, i.e., one data packet per millisecond, so that no prediction of the influence of measurements or stimulations is necessary, since the high temporal resolution and the precise timing of the measurement or stimulation can directly enable the consideration of artifacts.

[0046] Stimulation techniques include TMS (transcranial magnetic stimulation), a non-invasive neuromodulation technique that directly influences brain function. Short magnetic pulses are applied to the patient's head to induce electrical currents in the underlying neurons.

[0047] Other electrical stimulation techniques such as nTMS (navigated transcranial magnetic stimulation), tDCS (transcranial direct current stimulation), tACS (transcranial alternating current stimulation), tRNS (transcranial random noise stimulation), DBS (deep brain stimulation), FES (functional electrical stimulation), ultrasound, can also be used on the head as well as in the periphery (arm, leg, chest, neck), etc.

[0048] Examples of future applications for individualized, patient-specific adaptation of brain / neurostimulation using electrical currents (tES) to brain activity patterns (EEG) can be the preferred embodiments of the invention described below: In a preferred embodiment of the system according to the invention, the acquisition module is designed to record or measure an EEG. This is advantageous because brain activity can be determined using an EEG, and neuronal stimulation can then be performed based on this, for example. This is typically called neurofeedback.

[0049] EEG measurements can be performed using an electrode array to record brain waves. This array can comprise a plurality, preferably more than 10, of electrodes connected to an analog-to-digital converter. The electrodes can be mounted, for example, on a cap in such a way that various brain regions can be monitored for electrical activity. Each electrode can have an actuator for pressing it against the patient's head. The actuator can be electromechanically controlled. Preferably, each actuator is connected to a compressor via a fluid-tight hose. The compressor can generate overpressure in a fluid, e.g., a gas such as air, causing the actuator to expand and press the electrode against the patient's head. The actuator can consist of a pneumatic piston or an air-fillable plastic cushion.

[0050] The advantage of pneumatic pressure with compressed air is that a particularly uniform pressure is achieved on all electrodes of the hood.

[0051] The action module is designed for transcranial tissue stimulation. In this context, "transcranial" refers to stimulation through the skull. The tissue being stimulated is, for example, a patient's brain.

[0052] In a preferred further development of the aforementioned embodiment, the action module is configured to imprint a brain rhythm from the outside by means of transcranial alternating current stimulation (tACS).

[0053] In a further preferred embodiment of the aforementioned design, the action module is configured to trigger phase-related transcranial magnetic stimulation for targeted inhibition or excitation of corticospinal pathways.

[0054] In a further preferred embodiment of the system according to the invention, the acquisition module is configured to perform a measurement of the individual EEG alpha peak frequency (iAPF). The measured iAPF can, for example, be used to repeatedly control the action module for scientific studies regarding the treatment of people with depression. In this context, the action module can perform stimulation by means of transcranial magnetic stimulation.

[0055] Furthermore, other applications can be used: Acquisition of EEG and phase-related TMS for scientific studies regarding the treatment of people with depression; development, implementation, and evaluation of accurate and rapid techniques for the correction of artifacts (tES) in the recorded biosignal (EEG); development and realization of self-calibrating, low-noise, and real-time controllable current sources for tES; implementation and evaluation of techniques for phase-accurate detection of events in the EEG; development and realization of a generic platform for an integrated stimulation and measurement system (MIS) for combined EEG measurement and multichannel AC stimulation.

[0056] The central aspect of the invention relates to the communication between the sensing and action modules via a communication link (wired or wireless) that meets strict or at least fixed real-time requirements. Since biological processes also involve a temporal component, stimulation can only be meaningfully adaptive if the data underlying the adaptation are available in a timely manner (fixed real-time requirement). This requires, on the one hand, that the measurement be performed within certain time limits after stimulation, and on the other hand, that the measurement results be evaluated within another time limit and supplied to the action module for subsequent stimulation.

[0057] A hard real-time requirement is defined as follows: Exceeding the response time is considered a failure. After precisely timing the application to be deployed, calculations are necessary according to real-time system theory. Real-time systems always deliver the correct result within the specified time constraints. This characteristic can be relied upon when using a hard real-time system. A fixed real-time requirement, on the other hand, is defined as follows: With fixed real-time requirements, no immediate damage is likely. However, once the time constraints have expired, the result of the calculation is useless and can be discarded.

[0058] A fixed real-time requirement can be used for all measurements, whereby individual measurements that do not meet the hard real-time requirement are discarded or not considered for the analysis intended for output.

[0059] Discarding measurements is only relevant for data analysis. The samples themselves are retained, and the closed-loop process is not interrupted.

[0060] Real-time measurement should enable immediate evaluation and analysis of the signals. In one embodiment for measuring an EEG, the components are designed for frequencies up to 600 Hz. To detect such frequencies, the requirements for Shannon sampling must be met.

[0061] Especially in bus connections, i.e., with more than two participants, meeting strict real-time requirements for communication links can be challenging, for example, because collisions can occur when participants send data. Time-slicing methods or polling would traditionally be suitable for this.

[0062] A widespread, and therefore also tried and tested and inexpensive bus system is Ethernet, which, due to its CSMA / CD architecture, is prone to collisions and time delays and is not capable of real-time operation in itself.

[0063] There are extensions to the Ethernet standard, such as Time-Sensitive Networking (TSN) standards, that enable real-time capability. Widely available standard hardware can be used for this, as the TSN component operates at a higher layer of the protocol (ISO / OSI model).

[0064] Alternatively, there are specialized systems on the market that are optimized for high speeds and real-time, such as InfiniBand, which is used in supercomputers and enables very low latency, better than TSN.

[0065] According to the invention, the use of an EtherCAT bus system as a communication link for the detection and action modules is proposed.

[0066] The EtherCAT bus system, which is an international IEC standard, is considered the "Ethernet fieldbus" because it combines the advantages of Ethernet with the simplicity of classic fieldbus systems and avoids the complexity of IT technologies.

[0067] EtherCAT overcomes the disadvantages of Ethernet through its particularly efficient operating principle: A single frame is generally sufficient to update the output information in all participants and to read the input information for the controller using the same frame. The telegram sent by the EtherCAT master passes through all participants. Each EtherCAT slave reads the output data addressed to it "on the fly" and places its input data in the forwarded frame. The telegram is only delayed by hardware transit times. The last participant in a segment (or branch) detects an open port and sends the telegram back to the master – thereby utilizing the full-duplex capability of Ethernet. Advantageously, all connected modules (slaves) are physically connected directly to the master via the real-time bus (MAC-to-MAC communication).This enables direct communication between the functional modules and the master, without port searches or other delays caused by communication protocols.

[0068] The maximum payload rate of a telegram is therefore over 90%, and the theoretical effective data rate, by utilizing the full-duplex capability, is even over 100 Mbit / s (> 90% of twice 100 Mbit / s). The EtherCAT master is the only participant in the segment that is allowed to actively send an EtherCAT frame; all other participants merely forward the frames. This avoids unpredictable delays and guarantees real-time capability. It is important to note that this does not mean "forwarding" in the conventional sense. According to the invention, the signal is not stopped in any of the functional modules. Rather, the circuit allows the data packets, as mentioned above, to simply pass through the individual modules, and the modules can download data from and upload data to the frame at that time.

[0069] The master uses a standard Ethernet Medium Access Controller (MAC) without an additional communication processor. This allows a master to be installed on any hardware platform that provides an Ethernet port. The real-time operating system or application software used is irrelevant. The EtherCAT slaves use an EtherCAT Slave Controller (ESC) for on-the-fly processing. This processing is therefore entirely hardware-based, making the network performance predictable and independent of the individual slave implementations.

[0070] The master creates the data packets according to the network architecture. Thus, according to at least one preferred embodiment of the invention, the configuration of the modules in the bus can be defined once and stored in the master. After this installation, the data packets can be created and processed according to the actual physical arrangement in the bus system. The modules can therefore download and process the commands specifically addressed to the respective module and upload data accordingly into the circulating data packets.

[0071] This allows the generated frame to reach all modules virtually simultaneously, limited only by the physical propagation time of the data packets through the lines. A frame, i.e., such a data packet, can reach all functional modules in the real-time bus within less than 100 ns, preferably less than 50 ns, and particularly less than 20 ns, for example, within 15 ns.

[0072] The EtherCAT bus system can therefore possess the necessary capabilities for the aforementioned applications and, in particular, for applications of the system according to the invention: The update time for data from 1,000 distributed inputs / outputs is only 30 µs – including terminal transit time; a single Ethernet frame can exchange up to 1,486 bytes of process data – equivalent to almost 12,000 digital inputs and outputs. Transmitting this amount of data requires only 300 µs; performance: 256 digital I / Os in 12 µs, 1,000 digital I / Os in 30 µs, 200 analog I / Os (16-bit) in 50 µs, corresponding to a 20 kHz sampling rate, 100 servo axes every 100 µs, 12,000 digital I / Os in 350 µs.

[0073] In a preferred embodiment of the system according to the invention, wired data communication via fiber optic cable or copper cable is used for the communication link between the action module and the detection module. This has the advantage that data transmission is comparatively reliable, secure, and fast.

[0074] In an advantageous embodiment of the system according to the invention, radio-based data communication according to the 5G or 6G standard is used for the communication link between the action module and the acquisition module or with the master module. This has the advantage that data transmission can take place in real time despite the use of a radio connection.

[0075] According to an advantageous embodiment of the invention, it is provided that, in addition to the action module for actuating actuators for tissue stimulation and the acquisition module for deriving / measuring biodata or biosignals, a control module for digital input / output control (DIO) of actuators of external devices, wherein the actuators are designed for tissue stimulation, and a master module for processing the module signals / data are connected to the real-time capable bus, in particular the EtherCAT bus, also referred to as ECAT.Furthermore, the modules are designed to exchange information with each other on the real-time bus in the same calculation step at a clock provided by the master module depending on its data processing, and that the data / signals measured by the acquisition module, preferably an A / D converter, are sent to the master module and processed by it, and the master module sends data / commands to the action module to activate tissue stimulation via the actuators.

[0076] Advantageously, at least one functional module is equipped with an EtherCAT interface. This allows for improved real-time compliance with the system's requirements, particularly the hard or fixed real-time demands placed on the device. Advantageously, a majority, and especially all, of the functional modules involved in stimulation, measurement, and / or evaluation have such a real-time capable EtherCAT interface. The functional modules are connected to the master bus, in this case the EtherCAT bus, in a master-slave configuration, acting as slaves.

[0077] This system enables the modules for signal measurement / acquisition, including the acquisition of biosignals such as EEG, ECG, EXG, etc., for digital input / output control of peripheral external devices, and for analog signal generation for the actuators controlled by the action module, to be designed within a while loop based on the EtherCAT bus in such a way that they simultaneously or in a single computation step provide each other with information on the bus. This typically occurs every 1 ms, determined by the bus clock and the data processing content of the master module.

[0078] Advantageous embodiments of the modules of the system according to the invention provide for that the acquisition module (3, module A / D) includes an A / D converter for converting analog biodata / biosignals acquired by this module into digital signals that are processed in the master module; and / or that the action module includes a D / A converter for converting digital control signals provided by the master module into analog signals that are supplied to the actuators for tissue stimulation; and / or that the control module for digital input / output control controls the signal flow of the digital control signals provided by the D / A converter of the action module and the digital control signals provided by the master module by means of trigger signals generated by the master module and by the control module.

[0079] Starting from known methods for body-state-dependent stimulation, a further object of the invention can be seen as providing a method with which body-state-dependent stimulation can be carried out in a comparatively reliable and safe manner.

[0080] An advantageous method for body-condition-dependent stimulation based on the system according to one of the system claims provides for, that the modules communicate with each other in a closed-loop system and that the data from the action module affect the behavior / function of the acquisition module and vice versa; that the stimulation consists of neuromodulation excitation / inhibition, to which the action module controls magnetic, electromagnetic, mechanical, pneumatic and / or hydraulic actuators for direct influence on biological tissue or organs; that the action module performs multi-channel stimulation of biological tissue based on features from the biodata acquisition of biosignals of different origins by the acquisition module in a frequency range from 0 to several kilohertz, in particular up to 100, 200 or 300 kHz; and that the acquisition module is designed to acquire EEG, ECG, EXG, EMG, EOG, ERG, PPT, respiratory, MKG, MEG, BD, and SpO2 signals.

[0081] The disclosure further relates to a device comprising a control module or master module, a real-time master bus, a plurality of module slots, preferably at least two, but at least one, and at least one function module, wherein at least one of the module slots is connected to the master module 4 via a real-time data connection, and the at least one function module is configured with a real-time interface and connected to the real-time master bus. The real-time capability can be provided such that hard or fixed real-time conditions are met. Furthermore, the at least one function module is configured by hardware or software to send the data to be processed to downstream internal and / or external components, for example, data acquisition devices, measuring units, output devices, etc., preferably also under the same real-time conditions.

[0082] By using feedback and evaluating specific features from biosignals, modulations can be modified depending on the signal or status. The specific parameters depend on the particular application. Examples include: analyzing the individual alpha frequency in an EEG and triggering a trigger signal for a TMS device at a 90° phase in the EEG; or analyzing a heartbeat in an ECG and triggering a current pulse during the systolic interval. In the EEG, for example, the amplitude, frequency, and phase can be analyzed. In the ECG, for example, the amplitude, the timing of the R-wave, and the time interval between R-waves can be analyzed. Advantageous further developments and additional embodiments are described and explained in more detail below with reference to the accompanying figures.

[0083] They show: Fig. 1an integrated stimulation and measurement system (MIS); Fig. 2 a first overview of various modules of the MIS; Fig. 3 a second module overview of various modules of the MIS; Fig. 4 an example of a closed-loop sequence for an embodiment of the integrated stimulation and measurement system; Fig. 5 a detection of an amplitude maximum of a synthetic sine signal; Fig. 6 a detection of the amplitude maximum of an EEG signal; and Fig. 7 An example of a device according to the invention with an integrated stimulation and measurement system.

[0084] Fig. 1 Figure 1 shows a schematic representation of an integrated stimulation and measurement system (MIS) 1 according to the invention. The MIS 1 can be designed as a device comprising a housing, in Fig. 1Indicated by the dashed surrounding border line, the MIS 1 features a signal processing module 4. This module comprises a real-time bus master and a processing unit. The processing unit can be a computer chip with an operating system installed on it. Advantageously, the signal processing module 4 features a Linux kernel with an embedded operating system (Embedded OS). The signal processing module 4, also referred to as the master module, can, for example, be an embedded board with a clock speed of 800 MHz to 1 GHz. It is understood that other clock speeds are also conceivable, provided they meet the strict real-time requirements applicable to the intended applications.

[0085] The real-time bus master, in Fig. 1Also referred to as the RT-BUS master (real-time bus master), it is connected via a real-time bus 5 to a plurality of module slots 9. Each module slot 9 is designed and intended to accommodate a function module 10. A function module 10 is defined as any module that is designed to enable the function of the MIS or to extend its functionality.

[0086] In Fig. 1Three module slots are shown as an example; however, more or fewer modules can also be provided in the MIS. For example, for a use of the MIS according to the invention, at least two functional modules 10 can be provided. The functional modules 10 are in turn connected to integrated or external components 14. These components 14 can be, for example, actuators, detection devices, display devices, electrodes, etc.For example, the components 14 can enable or implement the following functions: EEG measurements, setting trigger signals and / or reading trigger signals, power supply of the MIS and / or one or more of the components 14, data acquisition, data processing and / or data transfer, display of data, function menus or other information, maintenance and / or control functions for the MIS and / or one of the connected components 14 and / or operating functionalities, in particular touch-sensitive control of an integrated display device.

[0087] The in Fig. 1The double arrows with solid lines shown represent communication links that preferably meet real-time requirements. For example, the communication link between a module slot 9 and a function module 10 is necessarily bound to hard or fixed real-time requirements in order to enable the real-time operation of the MIS according to the invention. The Fig. 1 The double arrows with dashed lines shown represent additional data connection interfaces that typically do not meet real-time requirements; in this case, a USB interface and a LAN interface. Furthermore, in Fig. 1 A 12V power source is indicated.

[0088] As in the embodiment according to Fig. 1As shown, the integrated stimulation and measurement system (MIS) 1 is implemented in the form of functional modules 10, which can be expanded as desired on both the acquisition (acquisition module 3) and output sides (action module 2) without impairing the capacities for time-accurate and accurate data processing among themselves (cf. Fig. 2 and 3 The modules communicate via the common communication link 5, a real-time bus. The functional modules 10 can be used for current stimulation, control of electrical, mechanical, or pneumatic actuators, triggering of events, data acquisition, data output and display, and other functions. A functional module can also be configured, for example, for graphics processing, as a current source module, or as a 3D accelerator module.

[0089] Thus, the MIS 1 is a generic platform that can also enable investigations in other areas of medical technology by expanding the parameter range for biosignal acquisition and developing other forms of output. This can be achieved, for example, by integrating additional functional modules designed to acquire predefined parameters. Furthermore, it is conceivable that existing functional modules could be modified or expanded in their scope of operation by adapting their control mechanisms and / or programming.

[0090] In advantageous embodiments of the invention, the MIS 1 according to the invention can be configured for one or more of the following applications: Imprinting of the brain rhythm externally via transcranial alternating current stimulation (tACS) and triggering of phase-related TMS for targeted inhibition or excitation of corticospinal pathways in real time; measurement of the individual EEG alpha peak frequency (iAPF) and repetitive control of the TMS device with this frequency for scientific studies regarding the treatment of people with depression in real time; recording of the EEG and triggering of a phase-related event, e.g., TMS pulse, for scientific studies regarding the treatment of people with depression in real time; recording of the EEG and phase-related electrical peripheral stimulation (FES) for rehabilitation; recording of blood pressure (BP / BD) and phase-related electrical peripheral stimulation for pain management; recording of respiration or respiratory signals and corresponding stimulation of the diaphragm.

[0091] Based on the MIS, feedback-coupled modulation (stimulation) of brain function can be enabled based on the individual patient physiology, which is accessed in real time. Studies show that the proposed implementation not only allows for faster application, according to the invention in a closed-loop circuit (i.e., a closed control loop with rates of < 1 to 3 ms for EEG acquisition and processing and event triggering), but also enables higher temporal accuracy in acquisition and repeated stimulation without the need for future prediction, as is common in current systems.The phase deviation from the desired trigger times based on the acquired measurement data, which can be achieved with a MIS according to the invention, can be frequency-dependent. For example, in an EEG measurement, the deviation may be + / - 5° at a frequency of 4 Hz and + / - 12° at a frequency of 40 Hz. In ECG detection of the systolic interval, the deviation may be, for example, + / - 3 ms.

[0092] The following are some of the key advantages and beneficial developments of this arrangement, especially compared to conventional solutions: The complete signal processing chain (data acquisition - transmission - processing - transmission - action) is embedded in the real-time bus and can be synchronized by it; the four stages can be supplied with new data simultaneously in all modules via the real-time bus (only slowed down by the signal propagation time on the bus); the packet interval (bus clock) results in a maximum delay of one packet interval on the bus between data acquisition and action; the acquisition (with an acquisition module 3) can be adapted to all conceivable signals of biological origin, since the interface to the bus can be the same for all modules; the control of actuators for the stimulation of biological tissue (with an action module 2) requires no prediction, since these can also be coupled to the bus via an interface; modular design and any combination of acquisition module 3 and action module 2.Only the processing software needs to be adapted to the specific task; the data processing and the control of the real-time bus can be performed directly in the device using an embedded Linux OS (e.g., Toradex-SOM).

[0093] In the Figures 2 and 3 Examples of (functional) modules that can be connected to the real-time bus (RT-BUS) are shown.

[0094] Fig. 2Figure 10 shows a first example of a function module 10, a data acquisition module 3, here implemented as an EEG module for data acquisition (e.g., ADS 1299) and connection to the bus. This data acquisition module 3, as well as the other function modules 10, has an interface section or function section with interfaces for external devices 14, and a connection and control section (RT-BUS interface) 12. In at least one preferred embodiment, the connection and control section 12 includes a microcontroller (µC) (e.g., Infineon XMC48xx).

[0095] In the illustrated embodiment, the interface section has four interfaces, each with 8 channels, thus enabling up to 32 channels, for example, for an EEG measurement. Each channel operates at 24-bit resolution. In alternative embodiments, the channels can also operate at other resolutions. The EEG module 3 is an analog-to-digital converter (ADC) and is also referred to as the A / D module in the following. The acquisition module 3 is designed for a sampling rate of 1000 samples / second, which allows a time of 1 ms per sample or data packet. The interface of the functional section to an external component can be wired, but advantageously, it can also be wireless, based on a sufficiently fast communication standard such as 5G or 6G, or even optical. This also applies analogously to the other functional modules.

[0096] The RT-BUS interface is designed and configured to be inserted into a module slot of the MIS. This establishes a connection to the MIS's real-time bus and integrates the function module into the MIS.

[0097] The RT-BUS interface 12 of the acquisition module 3 has a configuration specifically created for the acquisition module 3. The microcontroller serves to control the function module 10 and to provide data connection and data processing for real-time operation.

[0098] The other (functional) modules integrated into the MIS also have an analogous structure, i.e., functional section and connection and control section.

[0099] Fig. 2Figure 10 shows another example of a function module 10, a control module 7, also referred to as an I / O module or DIO module. The control module 7 serves to connect to the bus via a microcontroller (e.g., Infineon XMC48xx). The control module 7 shown here can be configured, in particular, to trigger or receive one or more trigger signals and / or to set a corresponding level for the trigger signal. In the embodiment shown, the control module 7 has four data inputs 7a and four data outputs 7b. A transistor-transistor logic (TTL) is preferably used. The inputs and outputs 7a and 7b are, in turn, galvanically isolated from the bus by means of a digital isolator (e.g., ISOW78xx Infineon). The galvanic isolation can, for example, correspond to a 6 kV barrier, both here and in the other modules and galvanic isolations.

[0100] The galvanic isolation advantageously provided here and in the functional modules makes it possible to electrically isolate a patient from the measuring device, or to isolate the individual components of the measuring device from each other. This can reduce interference signals and erroneous measurements.

[0101] Fig. 2Figure 2 further shows an action module, referred to here as the current module. The current module serves as an actuator for stimulation by outputting currents. The current module is shown here with two channels (Channel A and Channel B). In the proposed setup, current sources are used that are separate and therefore independent in their energy supply. This reduces interference between the current sources. The current sources can be self-calibrating, have lower noise, and can be controlled in real time, for example, within 1 ms with new parameters. Data buffering is therefore unnecessary. The RT-BUS interface is galvanically isolated from the interface section. Depending on the specific desired implementation for a predetermined application, the real-time interval can be set to a duration of more or less than 1 ms.

[0102] Fig. 3Figure 11 shows a functional module configured as a display device, specifically as a TFT module 11. The TFT module 11 serves to connect a display device to the bus. As previously described, the connection is made via a microcontroller (e.g., Infineon XMC48xx) with galvanic isolation of the display device via a digital isolator of the ADUM1xx series (Analog Devices). In the embodiment shown, the TFT module 11 features control of a TFT screen via an FT813. The resolution of the display device is 800 x 400 pixels, and it includes touch detection.

[0103] In at least one embodiment of the invention, the display device is permanently integrated into the MIS. It is understood that other display devices can also be integrated, either permanently or as external devices. These display devices can have various characteristics, for example, with or without touch detection, with different resolutions, monochromatic or color, etc. Furthermore, multiple display devices can also be provided.

[0104] Fig. 3The diagram further shows a functional module configured as a COM module (communication module) 15. The COM module 15 serves to connect other interfaces, including those not capable of real-time operation, such as one or more USB or RS232 interfaces. Other interfaces are also conceivable, for example, one or more CAN bus interfaces, and in particular, wireless interfaces for connecting to external devices.

[0105] Another example of a module that can be connected to MIS 1 is, as shown in Fig. 3 Shown is a LAN module (network module) 13. The LAN module 13 is used for connecting to a conventional local area network (Ethernet). For this purpose, the LAN module 13 has a corresponding LAN interface and a socket for a data cable. In this case, the interface is a 100 Mbit LAN interface. It is understood that the interface can also be configured for other transmission rates.

[0106] Another functional module 10 could, for example, be a power module for connecting the MIS to a power source. It is also conceivable that one of the modules could be configured as a detection module with an interface to an accelerometer. An accelerometer could, for example, be used to detect one or more frequencies of a tremor, such as those typically occurring in Parkinson's disease. Further interfaces and functional modules are also conceivable for integration into the real-time environment enabled by the invention.

[0107] Data processing in the MIS 1 is entirely digital. Simultaneous stimulation and acquisition of biosignals from different origins, dependent on the body's condition, is possible with varying amplification factors and sampling rates. The modular design of the functional modules, connected via a shared digital interface on the real-time bus, allows for flexible cascading.

[0108] Unlike conventional systems, the data is not acquired via time-division multiplexing, but due to the modular structure, it can be acquired simultaneously or sampled completely independently. According to the invention, this makes it possible to trigger a stimulation pulse within very low tolerance limits at a predetermined phase of a measurement signal while the signal is being acquired and, for example, a pain stimulus is being triggered in a patient.

[0109] To perform a measurement with tissue stimulation under real-time conditions, at least the master module 4 and two further functional modules 10 are necessary, in particular the acquisition module 3 for acquiring the measured values, and the action module 3 for stimulating a tissue.

[0110] To perform a measurement with a trigger signal under real-time conditions, at least the master module 4 and two further function modules 10 are necessary, in particular the acquisition module 3 for acquiring the measured values, and the control module 7 for triggering a trigger signal.

[0111] The digital interfaces between the functional modules enable highly efficient galvanic isolation of the measuring arrangement from the output and evaluation technology, thus eliminating the need for complex analog isolation amplifiers to ensure technical safety in medical applications, without compromising the safety of the person being measured (patient). Compliance with the EN 60601-1 standard concerning general requirements for safety, including essential performance characteristics, is therefore guaranteed.

[0112] Compared to conventional technology, the proposed solution is characterized by its small size and low energy consumption. This is due to the fact that only one central processing unit, namely the master module 4, is required, instead of several separate, interconnected computers. According to the invention, all modules necessary for measurements and stimulation can be combined in a single device within a housing (not shown here).

[0113] Fig. 4 Figure 1 shows an example of a closed-loop sequence for an embodiment of the integrated stimulation and measurement system, which includes a real-time bus. The real-time bus is preferably an EtherCAT bus, also referred to as ECAT in the figure.

[0114] In addition to action module 2 of the real-time bus, the following are connected to the EtherCAT bus ECAT: Fig. 1 for actuating actuators to stimulate tissue, in Fig. 4designated as module D / A, and the acquisition module 3 of the real-time bus of Fig. 1 , in Fig. 4 designated as module A / D for deriving / measuring biodata or biosignals, a control module 7, in Fig. 4 designated as module DIO for digital input / output control of actuators, for tissue stimulation, external devices, and a master module 4, in Fig. 4 also referred to as master, connected for processing the module signals / data.

[0115] The modules of the EthernetCAT bus ECAT are designed to exchange information with each other on the real-time capable bus (ECAT) in the same calculation step at a clock frequency provided by the master module 4 (master), depending on its data processing.

[0116] The data / signals measured by the acquisition module 3 (module A / D) are sent to the master module 4 (master) and processed by it, and the master module 4 sends data / commands to the action module 2 (module D / A) to activate tissue stimulation via the associated actuators.

[0117] The acquisition module 3 (module A / D) includes an A / D converter for converting analog biodata / biosignals acquired in this module 3 into digital signals, which are processed in the master module 4 (master).

[0118] The action module modul D / A includes a D / A converter for converting digital control signals provided by the master module master into analog signals that are supplied to the actuators for tissue stimulation.

[0119] The control module 7 (module DIO) performs digital input / output control of the signal flow of the digital control signals provided by the D / A converter of the action module 2 (module D / A) and the master module 4 (master) by means of trigger signals generated by the master module 4 (master) and by the control module 7 (module DIO).

[0120] With the in Fig. 4The system shown achieves this by enabling the modules for signal measurement / acquisition, including the acquisition of biosignals such as EEG, ECG, EXG, etc., for digital input / output control of peripheral external devices, and for analog signal generation for the actuators controlled by the action module, to be configured within a while loop based on the EtherCAT bus. This allows them to simultaneously, or in a single computation step, provide information to each other on the bus. This typically occurs every 1 ms, determined by the bus clock and the data processing content of the master module.

[0121] Fig. 4 This shows an example of a data loop from the measuring device. The time progression is shown vertically from top to bottom. The time shown here for such a data loop is 1 ms, which corresponds to a frequency of 1000 Hz.

[0122] Other frequencies are of course conceivable in other embodiments of the invention without deviating from the inventive concept of maintaining real-time conditions. Events arranged horizontally at the same height in Fig. 4 These events occur simultaneously or at least almost simultaneously.

[0123] As previously described, the master module 4 generates a data packet that is sent via the real-time bus, specifically the EtherCAT bus, to the function modules 10, namely the acquisition module 3, the control module 7, and the action module 2. The real-time bus is designed such that the data packets, figuratively speaking, pass through the function modules. During this passage, data is read from and written to the data packet by the function modules. The data packets are therefore not temporarily stored by the function modules before being forwarded. This enables quasi-simultaneous reception of the data packets by all function modules.

[0124] Each module is designed to exchange information with each other on the real-time bus (ECAT) in the same calculation step, using a real-time communication link 5, within a clock cycle provided by the master module 4, depending on its data processing capabilities. In this arrangement, the master module 4 is the only module capable of generating a frame, i.e., a data packet, while the function modules 10 downstream of the master module 4 can only read this frame and supplement it with their own data.

[0125] Thus, in the Fig. 4 In the closed-loop configuration shown, a data packet is generated by the master module and sent to the first functional module, here the acquisition module 3. This data packet can, for example, contain a command for acquisition module 3 to begin data acquisition. The acquisition module then begins data acquisition, in this case, of biosignals from a patient.

[0126] The data frame then passes from the acquisition module 3 to a subsequent function module 10, in Fig. 4 The control module 7, also known as module DIO, controls, for example, the digital input / output to the actuators of the device. In doing so, control module 7 generates a trigger, sends it to an external device, and / or reads a trigger, while the data packet has already passed on to the downstream action module 2.

[0127] Action module 2 receives the data packet, recognizes the relevant digital control commands from master module 4 within the frame, and converts these into an analog signal for actuators connected to action module 2. It then generates a signal and begins stimulating a patient, or sends a data set containing stimulation data to an external device that may be connected to a patient for stimulation purposes. Even before the stimulation begins, as shown in the diagram, Fig. 4 It is evident that the data packet has returned to master module 4.

[0128] The master module 4 sends the frames or data packets at a predetermined rate, for example one packet per ms, which are continuously sent through the closed-loop in real time.

[0129] The data collected by the acquisition module 3 can be appended to a data package and forwarded to the master module for processing, so that the master module can issue new control commands for the control module and the action module in one of the following frames, if necessary.

[0130] In the version shown, the acquisition module 3 has an A / D converter to convert the analogously acquired data, in this case the biosignals of a patient, into a digital signal for further processing.

[0131] The data processing by Master Module 4 can include the calculation of an instantaneous phase, an amplitude, a trigger time, or a digital / analog data set. Thus, Master Module 4 can define, modify, or adjust trigger times based on the received data. It is also conceivable that, for example, trigger cascades adapted to the biodata could be created in this way. Furthermore, the real-time system or device according to the invention allows combinations of trigger signals, acquisition data, and stimulation data to be combined on previously unattainable timescales. This can enable improved analysis of biological, biophysical, and / or biochemical phenomena.

[0132] The master module 4 can be connected to an operator and receive control commands from them. The operator can be, for example, a person performing the measurement or a control device, such as a digital one. This allows for the advantageous performance of semi- or fully automated measurements. Based on the data processing, the master module 4 outputs a system response to the operator.

[0133] In the illustrations of Figures 5 and 6 are measurements of a synthetic signal ( Figure 5 ) and an EEG signal ( Figure 6 ) shown during the detection of the maximum amplitude of the sine wave (phase: 90°): Figure 5Figure 1 shows the detection of the amplitude maximum 21 of a synthetic sine signal 20 and the triggering of an event trigger 26. The x-axis represents time in ms and the y-axis represents the signal amplitude in mV. The sine signal 20 is a signal measured by the device. This signal 20 has a maximum 21 at a phase of 90°. To analyze and trigger the event, the sine signal 20 is first converted into a filtered signal 22. The filtered signal 22 lags the original signal 20 by 1-2 ms, which is due to the processing time and conversion of the original signal 20 to the filtered signal 22 in the measuring device.

[0134] The filtered signal 22 accordingly exhibits a maximum 23, which occurs with a delay of 1-2 ms relative to the actual maximum 21 of the measurement signal 20. At the shown frequency of approximately 10 Hz, this time delay corresponds to a phase of approximately 5°. Upon reaching the maximum 23 thus determined, a trigger signal 26 is triggered at time 27. This trigger signal 26 is shown to be Figure 5 100 mV. It is understood that in actual tissue measurements, the voltage values ​​can be adjusted accordingly and can, for example, be used for measuring or stimulating tissue. The in Fig. 5 Curve 24 shown represents the phase of the signal.

[0135] Figure 6Figure 33 shows the detection of an amplitude maximum 33 of an actual EEG signal 30, labeled "online-re-referenced Pz" in the figure legend, with a sufficient signal-to-noise ratio. Curve 32 represents a sine wave signal calculated based on offline signal filtering—which may not meet real-time requirements. To meet real-time requirements, a phase signal 34 is generated by online processing of the measurement signal 30, based on a Görtzel algorithm. The phase signal 34, also referred to as the "online-Görtzel phase" in the legend, always progresses linearly from phase 0° to 360°. From this progression, phase 90° can be determined, and the trigger pulse is triggered at this time 37, as indicated by the trigger signal 36. Figure 6 According to the invention, the event trigger can be activated 1 to 3 ms after reaching the actual maximum of the measurement signal 30.

[0136] Due to its application in a real-time environment, the measurement result is quickly acquired and evaluated, eliminating the need for future predictions by the algorithm for stimulation. A simple Görtzel algorithm decomposes the spectral component in the a-EEG band (8 to 12 Hz), calculates the phase within just two cycles, and detects the event (here: maximum amplitude, phase 90°).

[0137] Due to the very low jitter of the packet intervals, it is possible to include filter throughput times in the calculation and thus generate even smaller constant deviations.

[0138] The curves shown here as examples were generated without resorting to conventional methods for predicting the signal waveform. Signal prediction is a previously common method for triggering impulses at the correct phases. The real-time method according to the invention allows for greater accuracy than prediction. However, it is conceivable that prediction could also be performed in the methods enabled by the invention.

[0139] Fig. 7Figure 1 shows an example of a device with an integrated stimulation and measurement system. The device comprises a housing 17 containing a master module 4 and several function modules 10, including a detection module 3, a control module 7, an action module 2, and a display module 10, for example, a TFT module. The function modules are connected via a bus structure (not shown here). A display device 18 is mounted on the front of the housing 17. The display device 18 is connected to the display module 11. The display device 18 can have various functionalities, as described previously.

[0140] Furthermore, in the illustrated embodiment, a number of connections 16 are provided on the front. Some of the connections are data inputs 7a and / or data outputs 7b of the control module 7. Other connections 16 are connections for other functional modules used or for other functions in the device. Abbreviations

[0141] ECG - Electrocardiogram EEG - Electroencephalogram EMG - Electromyogram EOG - Electrooculogram ERG - Electroretinogram PPT - Photoplethysmography MKG - Magnetocardiogram MEG - Magnetoencephalogram BD / BP - Blood pressure SpO2 - Oxygen saturation RT-BUS - Real-Time Bus USB - Universal Series Bus LAN - Local Area Network FES - Functional Electrical Stimulation OS - Operating System MIS - Integrated Stimulation and Measurement System TMS - Transcranial Magnetic Stimulation tES - Transcranial Electrical Stimulation nTMS - Navigated Transcranial Magnetic Stimulation tDCS - Transcranial Direct Current Stimulation tACS - Transcranial Alternating Current Stimulation tRNS - Transcranial Random Noise Stimulation DBS - Deep Brain Stimulation iAPF - EEG Alpha Peak Frequency FES -phase-related electrical peripheral stimulation Reference sign

[0142] 1 System for body-condition-dependent stimulation 2 Action module / Current module 3 Acquisition module / EEG module 4 Signal processing module / Master module 5 Communication link 6 Galvanic isolation 7 Control module 7a Data input 7b Data output 9 Module slot 10 Function module 11 Display module, TFT module 12 Control section, RT-BUS interface 13 Network module, LAN module 14 Components, external devices 15 Communication module, COM module 16 Connections 17 Housing 18 Display 20 Measurement signal 21 Maximum of measurement signal 22 Filtered signal 23 Maximum of filtered signal 24 Phase signal 26 Trigger signal 27 Trigger time 30 Measurement signal 31 Maximum of measurement signal 32 Filtered signal 33 Maximum of filtered signal 34 Phase signal 36 Trigger signal 37Trigger time

Claims

1. System for body-state-dependent stimulation, comprising a master module (4, Master) for processing module signals / data, and functional modules, wherein the functional modules include an action module (2) for stimulating tissue and a detection module (3) for deriving / measuring biodata or biosignals and a control module for triggering a trigger pulse for controlling the action module, wherein the system is designed such that communication between the functional modules takes place via a communication link (5) which meets hard or at least firm real-time requirements, wherein the detection module is designed for deriving or measuring an EEG and the action module is designed for transcranial tissue stimulation, wherein the communication link (5) comprises a real-time-capable bus to which the functional modules are connected, characterized in that the system is designed to trigger the trigger pulse at a point in time during a predetermined phase of the EEG, wherein a Goertzel algorithm is used to break down the EEG into a band of 8 to 12 Hz and, within two cycles of the EEG, to determine the predetermined phase of the EEG.

2. System for body-state-dependent stimulation according to claim 1, characterized in that the control module (7) for digital input / output control of actuators of external devices, which actuators are intended for tissue stimulation, is connected to the real-time-capable bus.

3. System for body-state-dependent stimulation according to claim 1 or claim 2, characterized in that the functional modules (2, 3, 4, 7) are designed to exchange information with one another on the real-time-capable bus (ECAT) in the same calculation step in a clock cycle provided by the master module (4) depending on the data processing thereof.

4. System for body-state-dependent stimulation according to any of claims 1 to 3, characterized in that the detection module (3) is designed to send measured data / signals via the communication link (5) to the master module (4), the master module (4) is designed to process the received data, and the master module (4) is further designed to send data / commands to the action module (2) to activate tissue stimulation by means of actuators.

5. System for body-state-dependent stimulation according to any of claims 1 to 4, characterized in that the detection module (3) comprises an A / D converter for converting analog biodata / biosignals detected by this module into digital signals which can be processed in the master module (4).

6. System for body-state-dependent stimulation according to any of claims 1 to 5, characterized in that the action module (2) comprises a D / A converter for converting digital control signals provided by the master module (4) into analog signals which are supplied to actuators for tissue stimulation.

7. System for body-state-dependent stimulation according to any of claims 1 to 6, characterized in that the control module (7) is designed to carry out, by means of trigger signals (26, 36) generated by the master module (4) and by the control module, digital input / output control of the signal flow of the digital control signals provided by a D / A converter of the action module (2) and by the master module (4).

8. System for body-state-dependent stimulation according to any of claims 1 to 7, characterized in that galvanic isolation (6) is provided between at least one module (4,7) and the real-time-capable bus.

9. System for body-state-dependent stimulation according to any of claims 1 to 8, characterized in that the real-time-capable bus is an EtherCAT bus.