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

Abstract

The invention relates to a system for body-condition-dependent stimulation by means of function modules, e.g. an action module (2, D / A module) for stimulating tissue and a capture module (3, A / D module) for deriving / measuring bio data or bio signals, characterised in that the two modules communicate via a communication link (5) that meets hard or at least firm real-time requirements. The communication link (5) preferably comprises a real-time-capable bus to which the two modules are connected, above all an EtherCAT bus.

Description

[0001] Body state-dependent stimulation with real-time communication between an action module and a sensor module.

[0002] Description

[0003] The invention relates to a system for body-state-dependent stimulation with real-time communication between an action module and a detection module. Biological tissue is stimulated while signals of biological origin are simultaneously detected. The application of this method and arrangement applies primarily, but not exclusively, to all areas of medicine in which biosignals are used for body-state-dependent stimulation.

[0004] State of the art

[0005] There are medical treatment methods, as described in W02017099603 (Al), 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.

[0006] To verify this stimulus-response pattern, immediate measurement is necessary to correctly attribute the response to the stimulation and thus draw the correct conclusions about the medically appropriate positions for the stimulation site. However, the document does not disclose how this immediate response, or rapid feedback, can be technically implemented.

[0007] 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.

[0008] 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.

[0009] 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.

[0010] The invention solves this problem through a system according to claim 1. Preferred embodiments are explained in the dependent claims.

[0011] 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 body-condition-dependent stimulation (following the measurement) is, in addition to adequate signal processing, feature extraction and targeted influencing of the human body, an artifact- and interference-free stimulation, which is ensured 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.

[0012] Depending on therapeutic guidelines, 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).

[0013] 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.

[0014] 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.In advantageous embodiments of the invention, such a module, hereinafter also referred to as a function module, can be configured with an interface for connection to a real-time bus, in particular an EtherCAT bus. For this purpose, the function module has an interface section that provides access to an externally connectable device or a device integrated into the function module, or to a downstream device. Furthermore, such a function module includes a connection and control section. The connection and control section preferably comprises a microcontroller as a control unit for the function module and a contact section configured for connection to the real-time bus of the device.

[0015] The signal processing or evaluation of the biodata or biosignals can either take place already in the acquisition module or only 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 connection.

[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:

[0020] • The actuators can preferably respond quickly to information about the body's condition (the biodata or biosignals) for body-state-dependent stimulation;

[0021] • The actuators preferentially emit only the signals that are important or desired for influencing the human body / organs;

[0022] • The signal levels of the stimulation are preferably available as digital signals in a time- or value-discrete manner, which, after conversion and amplification (adaptation), are delivered to the actuator in the form of mechanical or electromagnetic energy;

[0023] • The signal levels for detection, after conversion, are e.g. in the range of nanovolts to millivolts within a frequency band from zero to several kilohertz;

[0024] • In the frequency band used (e.g., the one used for feature extraction from the EEG), strong interference signals occur due to stimulation and the environment; according to the invention, these interference signals can be taken into account and filtered out as needed;

[0025] • The signal sources to be investigated, e.g. of electrophysiological origin, are preferably high-impedance;

[0026] • The physical properties of, for example, the stimulation and recording electrodes change over time (e.g., due to changes in electrode junction impedances, electrode voltage, offset potentials, pressure conditions, or motion artifacts).

[0027] 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.

[0028] 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.

[0029] 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. 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 unwanted frequency lines in the EEG spectrum. 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:

[0030] • Avoidance of amplifier saturation through sufficient amplitude resolution;

[0031] • Avoidance of network interference through the use of battery-powered detection units;

[0032] • Avoidance of the disruptive capacitive influence of the outer skin layer on the signal by carefully preparing the skin.

[0033] In other applications, such as ECG measurements, the same requirements or some of these requirements may also apply.

[0034] Current arrangements generally have at least one of the following disadvantages:

[0035] • Slow processing due to the lack of a real-time system for state-dependent stimulation when artifact correction and feature extraction must be performed simultaneously;

[0036] • Instability occurs when smaller, especially non-constant, delays occur in a feedback-driven / control-coupled application;

[0037] • Complexity arises when significant testing or adjustments are required following changes to the architecture or operating system.

[0038] In one embodiment, the invention provides a system for body-state-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.

[0039] 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).

[0040] 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 mobile units to facilitate application to a patient.

[0041] 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.

[0042] 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.

[0043] Suitable protocols for transmitting data 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.

[0044] A remote evaluation setup, in the context of a telemedicine application, allows, for example, an expert for the evaluation of biodata or biosignals not to be physically present at the patient's location during data collection, but rather remotely, i.e., geographically separated from the patient.

[0045] It can be used to review real-time measurements. This makes the invention even more universally applicable.

[0046] 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 many 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. The evaluation system can include machine learning software, i.e., for a neural network and so-called "deep learning," to recognize patterns in the acquired data of one or many patients (especially in a cloud solution).Such patterns can occur, for example, in the case of the detection of a

[0047] Electroencephalogram (EEG), i.e., from electrical currents recorded on the scalp of a patient using electrodes, to characteristic waveforms in the EEG as a result of stimulation by the action module.

[0048] 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 can be enabled, for example by means of a control module, to trigger an impulse according to predetermined parameters.

[0049] 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.

[0050] 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, control actuators according to the commands of the master module, or 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.

[0051] 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 with regard to both their 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.

[0052] 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.

[0053] 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.

[0054] Furthermore, interference signals exhibit amplitudes that lie outside a predefined amplitude interval. An amplitude interval¹¹ has an upper and a lower threshold for the amplitude.

[0055] The filtered-out interference signals are then disregarded for further analysis, which improves the quality of subsequent analyses.

[0056] 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.

[0057] 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.

[0058] 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.

[0059] 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. 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), and ultrasound, can also be used on the head and in the periphery (arm, leg, chest, neck), etc.

[0060] Examples of future applications of individualized, patient-specific adaptation of brain / neurostimulation using electrical currents (tES) to brain activity patterns (EEG) could be the preferred embodiments of the invention described below:

[0061] 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, for example, be based on this.

[0062] This is typically called neurofeedback.

[0063] 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 attached to it for pressing 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. Each actuator can have a compressed air cylinder or an air-fillable plastic cushion.

[0064] The advantage of pneumatic pressure with compressed air is that a particularly uniform pressure is achieved on all electrodes of the hood.

[0065] In a preferred embodiment of the system according to the invention, the action module is designed for transcranial tissue stimulation. In this context, the term transcranial refers to the action being applied through the skull. The tissue being stimulated is, for example, the brain of a patient.

[0066] 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).

[0067] 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.

[0068] 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 concerning the treatment of people with depression. In this context, the action module can perform stimulation by means of transcranial magnetic stimulation.

[0069] Furthermore, other applications can be used:

[0070] • Recording of EEG and phase-related TMS for scientific studies regarding the treatment of people with depression;

[0071] • Development, implementation and evaluation of accurate and / or rapid techniques for the correction of artifacts (tES) in the derived biosignal (EEG);

[0072] • Development and implementation of self-calibrating, low-noise and real-time controllable power sources for the tES;

[0073] • Implementation and evaluation of techniques for phase-accurate detection of events in the EEG;

[0074] • Development and implementation of a generic platform for an integrated stimulation and measurement system (MIS) for combined EEG measurement and multichannel AC stimulation.

[0075] 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 is 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 and supplied to the action module for subsequent stimulation within another time limit. A strict real-time requirement is defined as follows: Exceeding the response time is considered a failure.

[0076] After precisely recording the time required for the application to be deployed, calculations are necessary according to the theory of real-time systems. Real-time systems always deliver the correct result within the specified time constraints. This property 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.

[0077] 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.

[0078] Discarding measurements is only relevant for data analysis. The samples themselves are retained, and the closed-loop process is not interrupted.

[0079] 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.

[0080] Especially with bus connections, i.e., with more than two participants, meeting strict real-time communication requirements can be challenging, for example, because collisions can occur when participants send data. Time-lapse methods or polling would traditionally be suitable for this.

[0081] 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.

[0082] There are extensions to the Ethernet standard, such as Time-Sensitive Networking (TSN) standards, that provide 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).

[0083] 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.

[0084] According to the invention, the use of an EtherCAT bus system as a communication link for the detection and action modules is proposed.

[0085] 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.

[0086] EtherCAT overcomes the disadvantages of Ethernet through its particularly high-performance 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 allows direct communication between the functional modules and the master, without port searches or other delays caused by communication protocols.

[0087] 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.

[0088] The master uses a standard Ethernet Medium Access Controller (MAC) without an additional

[0089] 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 performed entirely in hardware, making the network performance predictable and independent of the individual slave implementation.

[0090] 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.

[0091] This allows the created 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.

[0092] 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 the data of 1,000 distributed inputs / outputs is only 30 ps - including

[0093] Terminal throughput time;

[0094] • 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 ps;

[0095] • Performance 256 digital I / Os in 12 ps, 1,000 digital I / Os in 30 ps, ​​200 analog I / Os (16 bit) in 50 ps, ​​equivalent to 20 kHz sampling rate, 100 servo axes every 100 ps, ​​12,000 digital I / Os in 350 ps.

[0096] 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.

[0097] 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.

[0098] 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.

[0099] According to the invention, at least one functional module is equipped with an EtherCAT interface. This allows for improved real-time performance of the system, particularly the hard or fixed real-time requirements of 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, as slaves in a master-slave configuration.

[0100] 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 calculation 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.

[0101] Advantageous embodiments of the modules of the system according to the invention provide for

[0102] - 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

[0103] - 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

[0104] - that the control module for digital input / output control manages the signal flow of the digital control signals provided by the action module's D / A converter and the master module's digital control signals by means of signals generated by the master module and by the control module

[0105] Trigger signals are controlled.

[0106] Starting from known methods for body-condition-dependent stimulation, a further object of the invention can be seen as providing a method with which body-condition-dependent stimulation can be carried out in a comparatively reliable and safe manner.

[0107] The invention solves this problem by means of a method according to claim 11. Preferred embodiments are explained in the dependent claims. The same advantages result as those explained at the outset for the method and system according to the invention.

[0108] An advantageous method for body-condition-dependent stimulation based on the system according to one of the system claims provides for,

[0109] - that the modules communicate with each other in a closed-loop system and that the data from the action module affects the behavior / function of the acquisition module and vice versa,

[0110] - that the stimulation consists of neuromodulation excitation / inhibition,

[0111] - the action module controls magnetic, electromagnetic, mechanical, pneumatic and / or hydraulic actuators to directly influence biological tissue or organs,

[0112] - 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

[0113] - the acquisition module is designed to acquire EEG, ECG, EXG, EMG, EOG, ERG, PPT, respiratory, MKG, MEG, BD, SpO2 signals.

[0114] The invention 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 equipped with a real-time interface and is 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.

[0115] According to the invention, a system for body-state-dependent stimulation, which includes a feedback loop for the time-accurate stimulation of a biological tissue or for reading out biosignals or biodata in a feedback-modulated signal acquisition using the example of an EEG measurement, comprises at least the master module and associated with it an AD module and a DA module.

[0116] If only a trigger is to be activated at a predetermined time, without additional stimulation, then at least the master module and associated AD module (detection module) and DIO module (control module) would be necessary.

[0117] For more advanced applications, such as real-time measurement of biodata that triggers a stimulus, further modules can then be successively provided according to the invention.

[0118] 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.

[0119] Advantageous further developments and additional embodiments are described and explained in more detail below with reference to the attached figures.

[0120] They show:

[0121] Fig. 1 an integrated stimulation and measurement system (MIS);

[0122] Fig. 2 shows a first overview of various modules of the MIS; Fig. 3 shows a second overview of various modules of the MIS;

[0123] Fig. 4 shows an example of a closed-loop sequence for an embodiment of the integrated stimulation and measurement system;

[0124] Fig. 5 shows a detection of an amplitude maximum of a synthetic sine signal;

[0125] Fig. 6 shows a detection of the amplitude maximum of an EEG signal; and

[0126] Fig. 7 shows an example of a device according to the invention with an integrated stimulation and measurement system. Fig. 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, indicated in Fig. 1 by the dashed circumferential frame line. The MIS 1 comprises a

[0127] Signal processing module 4. Signal processing module 4 has a real-time bus master and a processing unit.

[0128] 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

[0129] Module 4, also known as the master module, can, for example, feature an embedded board with a clock speed of 800 MHz to 1 GHz. It goes without saying that other clock speeds are also conceivable, provided they are hard or fixed.

[0130] Meet real-time requirements that apply to the correspondingly intended requirements.

[0131] The real-time bus master, also referred to as RT-BUS master (real-time bus master) in Fig. 1, is connected via a real-time bus.

[0132] 5 is connected to a plurality of module slots 9. Each module slot 9 is designed and intended to accommodate a functional module 10. A functional module 10 is understood to be any module that is designed to enable the function of the MIS or to extend its functionality.

[0133] Figure 1 shows three module slots by way of 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.

[0134] The double arrows with solid lines shown in Fig. 1 represent communication links that preferably meet real-time requirements. Thus, the

[0135] 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 double arrows with dashed lines shown in Fig. 1 represent further data connection interfaces that do not usually meet real-time requirements, here a USB interface and a LAN interface. In addition, a 12V power source is indicated in Fig. 1.

[0136] As shown in the embodiment according to Fig. 1, the integrated stimulation and measurement system (MIS) 1 is implemented in the form of functional modules 10, which can be expanded as needed on both the acquisition (acquisition module 3) and output sides (action module 2) without impairing the capacities for precise and accurate data processing between them (see Figs. 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, for example, also be configured for graphics processing, as a current source module, or as a 3D accelerator module.

[0137] 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.

[0138] In advantageous embodiments of the invention, the MIS 1 according to the invention can be configured for one or more of the following applications:

[0139] • Imprinting of the brain rhythm from the outside through transcranial alternating current stimulation (tACS) and triggering of phase-related TMS for targeted inhibition or excitation of corticospinal pathways in real time;

[0140] • 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;

[0141] • 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;

[0142] • Recording of the EEG and phase-related electrical peripheral stimulation (FES) for rehabilitation;

[0143] • Blood pressure (BP / BD) measurement and phase-related electrical peripheral stimulation for pain management;

[0144] • Detection of breathing or breathing signals and corresponding stimulation of the diaphragm.

[0145] Based on the MIS, feedback-coupled modulation (stimulation) of brain function can be achieved based on individual, real-time data.

[0146] Patient physiology is made possible. Studies show that the proposed implementation not only enables 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 allows for higher temporal accuracy in acquisition and repeated stimulation without the need for future prediction, as is common with 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, + / - 5° for an EEG measurement at a frequency of 4 Hz and + / - 12° at a frequency of 40 Hz.In ECG detection of the systolic interval, a deviation may be, for example, + / -3ms.

[0147] Key advantages and beneficial developments of this arrangement, especially compared to conventional solutions, can be the following: • The complete signal processing chain (data acquisition - forwarding - processing - forwarding - action) is embedded in the real-time bus and can be synchronized by it;

[0148] • 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);

[0149] • The packet interval (bus cycle) results in a maximum delay of one packet interval on the bus between data acquisition and action;

[0150] • 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;

[0151] • Controlling actuators for stimulating biological tissue (with an action module 2) does not require prediction, as these can also be coupled to the bus via an interface;

[0152] • Modular design and any combination of capture and action modules. Only the processing software needs to be adapted to the specific task;

[0153] • The processing of the data and the control of the real-time bus can be performed directly in the device using an embedded Linux OS (e.g., Toradex-SOM).

[0154] Figures 2 and 3 show examples of (functional) modules that can be connected to the real-time bus (RT-BUS).

[0155] Fig. 2 shows, as a first example of a functional module 10, a data acquisition module 3, here implemented as an EEG module for data acquisition (for example, ADS 1299) and connection to the bus. This data acquisition module 3, as well as the other functional modules 10, has an interface section or functional section with interfaces for external devices 14, as well as 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) (for example, Infineon XMC48xx).

[0156] 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.

[0157] 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.

[0158] 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 for data connection and

[0159] Data processing for real-time operation.

[0160] The other (functional) modules integrated into the MIS also have an analogous structure, i.e., functional section and connection and control section.

[0161] Figure 2 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.

[0162] A transistor-transistor logic (TTL) can preferably be 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 here and also in the other modules and galvanic isolations.

[0163] 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.

[0164] Figure 2 further shows an action module 2, 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 be controllable 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

[0165] The interface section is separate. Depending on the specific desired implementation for a predetermined application, a duration of more or less than 1ms can also be selected as the real-time interval.

[0166] Fig. 3 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 ADUMlxx series (Analog Devices). In the embodiment shown, the TFT module 11 has a control interface for a TFT screen via an FT813. The resolution of the display device is 800 x 400 pixels, and it features touch detection.

[0167] 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 integrated or provided 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, a

[0168] A majority of display devices should be provided.

[0169] Figure 3 further shows a functional module configured as a COM module (communication module) 15. The COM module 15 serves to connect other interfaces, including non-real-time interfaces, 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.

[0170] Another example of a module connectable to the MIS 1 is, as shown in Fig. 3, a LAN module (network module) 13. The LAN module 13 serves to connect 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 goes without saying that the interface can also be configured for other transmission rates.

[0171] 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 is designed as a data acquisition module with an interface to an accelerometer.

[0172] An accelerometer can, 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. Data processing in the MIS 1 is entirely digital. Simultaneous stimulation and acquisition of biosignals of different origins, dependent on the body's condition, is possible with various amplification factors and sampling rates. The modular design of the functional modules via the common digital interface over the real-time bus allows for arbitrary cascading.

[0173] 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.

[0174] 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.

[0175] 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.

[0176] 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.

[0177] 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).

[0178] Fig. 4 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.

[0179] In addition to the action module 2 of the real-time bus from Fig. 1 for actuating actuators for tissue stimulation, designated as module D / A in Fig. 4, and the acquisition module 3 of the real-time bus from Fig. 1, designated as module A / D in Fig. 4 for deriving / measuring biodata or biosignals, a control module 7, designated as module DIO in Fig. 4 for digital input / output control of actuators for tissue stimulation and external devices, and a master module 4, also designated as master in Fig. 4, for processing the module signals / data are connected to the EtherCAT bus ECAT.

[0180] 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.

[0181] 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.

[0182] 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).

[0183] 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.

[0184] 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).

[0185] The system shown in Fig. 4 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 calculation 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.

[0186] Figure 4 shows an exemplary data loop of the measuring device. The time course 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.

[0187] 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 occur simultaneously or at least approximately simultaneously.

[0188] 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.

[0189] 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.

[0190] In the closed-loop arrangement shown in Fig. 4, a data packet is generated by the master module and sent to the first functional module, here the acquisition module 3. The data packet can, for example, contain a command for acquisition module 3 to begin acquiring data. The acquisition module then begins acquiring data, in this case, biosignals from a patient.

[0191] The data frame then proceeds from the acquisition module 3 to a subsequent function module 10, in Fig. 4 the control module 7, also referred to as module DIO. The control module 7, for example, controls the digital input / output to actuators of the device. In doing so, the control module 7 generates a trigger, sends it to an external device, and / or reads a trigger, while the data packet has already proceeded to the downstream action module 2.

[0192] Action module 2 receives the data packet, recognizes the relevant digital control commands from master module 4 within the frame, converts these into an analog signal for actuators connected to action module 2, 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. As shown in Fig. 4, the data packet has already traveled back to master module 4 before the stimulation begins.

[0193] 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.

[0194] The data collected by the acquisition module 3 can be appended to a data packet 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.

[0195] 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.

[0196] The data processing by Master Module 4 can include the calculation of an instantaneous phase, an amplitude, a trigger point, or a digital / analog data set. Thus, Master Module 4 can define, modify, or adjust trigger points 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.

[0197] 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.

[0198] Figures 5 and 6 show measurements of a synthetic signal (Figure 5) and an EEG signal (Figure 6) during the detection of the maximum amplitude of the sine wave (phase: 90°):

[0199] Figure 5 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 setup. This signal 20 has a maximum 21 at a phase of 90°. For analysis and triggering, 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 into the filtered signal 22 in the measuring device.

[0200] 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 frequency shown 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 5100 mV in the figure shown. 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 curve 24 shown in Fig. 5 represents the phase of the signal.

[0201] Figure 6 shows the detection of an amplitude maximum 33 of an actual EEG signal 30, labeled "online-re-referenced Pz" in the figure caption, with a sufficient signal-to-noise ratio. The 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, for example, based on a Görtzel algorithm. The phase signal 34, also referred to in the caption as "online-Görtzel phase," always progresses linearly from phase 0° to 360°. From this progression, the 90° phase can be determined and the trigger pulse is triggered at this time 37, as can be seen from the trigger signal 36 in Figure 6. According to the invention, the triggering of the event can occur 1 to 3 ms after reaching the actual maximum of the measurement signal 30.

[0202] Due to its application in a real-time environment, the measurement result is quickly obtained and evaluated, eliminating the need for future predictions by the algorithm for stimulation. Using a simple Görtzel algorithm, the spectral component, e.g., in the a-EEG band (8 to 12 Hz), can be decomposed, the phase calculated within just two cycles, and the event (here:

[0203] Maximum amplitude, phase 90°) can be detected.

[0204] 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.

[0205] 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.

[0206] Fig. 7 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 a plurality of 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). A display device 18 is provided on one front side 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 above.

[0207] 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.

[0208] Further aspects of the invention are listed below:

[0209] Aspect 1: Method for body-state-dependent stimulation with an action module 2 for stimulating tissue and a detection module 3 for deriving (measuring) biodata or biosignals and a signal processing module 4 which connects the action module 2 and the detection module 3, characterized in that the modules communicate by means of a protocol which meets hard or at least fixed real-time requirements.

[0210] Aspect 2: Method for body state-dependent stimulation according to Aspect 1, characterized in that the protocol is encapsulated within Ethernet frames.

[0211] Aspect 3: Method for body-state-dependent stimulation according to aspect 2, characterized in that at least one of the modules 2, 3 evaluates or processes data from a received Ethernet frame even when the Ethernet frame has not yet been completely received by the module.

[0212] Aspect 4: A method for body-state-dependent stimulation according to Aspect 3, characterized in that the module begins to send response data based on the evaluated or processed data even before the Ethernet frame has been fully received by the module. Aspect 5: A method for body-state-dependent stimulation according to one of the previous aspects, characterized in that the modules communicate with each other in a closed-loop system and the data from the action module affect the behavior / function of the acquisition module, and vice versa.

[0213] Aspect 6: Method for state-dependent stimulation according to one of the preceding aspects, characterized in that the stimulation consists of neuromodulation excitation or inhibition.

[0214] Aspect 7: System 1 for body-state-dependent stimulation with an action module 2 for stimulating tissue and a detection module 3 for deriving (measuring) biodata or biosignals, characterized in that the communication between the two modules takes place via a communication link 5 that meets hard or at least fixed real-time requirements.

[0215] Aspect 8: System 1 for body state-dependent stimulation according to aspect 7, characterized in that the processing of at least one part of a protocol stack of the communication link 5 is implemented in hardware, e.g. by means of AS IC or FPGA.

[0216] Aspect 9: System 1 for body state-dependent stimulation according to one of aspects 7 and 8, characterized in that a bus protocol, protocol stack or hardware from the EtherCAT bus system is used.

[0217] Aspect 10: System 1 for body condition-dependent stimulation according to one of aspects 7 to 9, characterized in that a galvanic isolation 6 is provided between at least one module and the communication connection 5.

[0218] Aspect 11: System 1 for body-state-dependent stimulation according to one of aspects 7 to 10, characterized in that the biodata or biosignals are sent to the action module 2 and the action module 2, taking into account the biodata, controls electrical, magnetic, electromagnetic, mechanical, pneumatic and / or hydraulic actuators to directly influence the biological tissue or organs.

[0219] Aspect 12: System 1 for body-state-dependent stimulation according to one of aspects 7 to 11, characterized in that the action module 2 performs multi-channel stimulation of biological tissue, based on features from the biodata acquisition of biosignals of different origins by the acquisition module 3 in a frequency range from 0 to several kilohertz, in particular 100, 200 or 300 kHz.

[0220] Aspect 13: System 1 for body-condition-dependent stimulation according to one of aspects 7 to 12, characterized in that the action module 2 comprises a current pulse converter, the detection module 3 has an EEG or ECG measuring unit and both modules are connected to a bus.

[0221] Aspect 14: System 1 for body-condition-dependent stimulation according to one of aspects 7 to 13, characterized in that, in addition to the action module 2 and the sensing module 3, a signal processing module 4 is present, wherein a common bus enables the communication links 5 between all modules, wherein the data measured by the sensing module 3 are sent to the signal processing module 4 and are processed, prepared and further processed by it, and the signal processing module 4 sends data or commands to the action module 2 to activate stimulation.

[0222] Aspect 15: System 1 for body-state-dependent stimulation according to one of aspects 6 to 14, characterized in that a processor-controlled module is part of the bus which monitors the system 1 and a

[0223] It has a communication interface to other computers connected via the Internet.

[0224] Aspect 16: System 1 according to one of Aspect 14 or 15, characterized in that the signal processing module 3 is integrated into the action module 2 or detection module 3.

[0225] Abbreviations

[0226] ECG - Electrocardiogram

[0227] EEG - Electroencephalogram

[0228] EMG - Electromyogram

[0229] EOG - Electrooculogram

[0230] ERG - Electroretinogram

[0231] PPT - Photoplethysmography

[0232] MKG - Magnetocardiogram

[0233] MEG - Magnetoencephalogram

[0234] BP / BP - blood pressure / blood pressure

[0235] SpO2 - Oxygen saturation

[0236] RT-BUS - Real-Time Bus

[0237] USB - Universal Series Bus

[0238] LAN - Local Area Network

[0239] FES - Functional Electrical Stimulation

[0240] OS - Operating System

[0241] MIS - Integrated Stimulation and Measurement System

[0242] TMS - Transcranial magnetic stimulation tES - Transcranial electrical stimulation nTMS - Navigated transcranial magnetic stimulation tDCS - Transcranial direct current stimulation

[0243] Direct current stimulation tACS - transcranial alternating current stimulation tRNS - transcranial random noise stimulation -

[0244] Noise stimulation DBS deep brain stimulation iAPF EEG alpha peak frequency

[0245] FES phase-related electrical peripheral stimulation reference symbol

[0246] 1 System for body condition-dependent stimulation

[0247] 2 Action Module / Current Module

[0248] 3 Data acquisition module / EEG module

[0249] 4 Signal processing module / master module

[0250] 5 Communication link

[0251] 6. Galvanic isolation

[0252] 7 Control module

[0253] 7a Data input

[0254] 7b Data output

[0255] 9 module slots

[0256] 10 Functional module

[0257] 11 Display module, TFT module

[0258] 12 Control section, RT-BUS interface

[0259] 13 Network module, LAN module

[0260] 14 components, external devices

[0261] 15 communication module, COM module

[0262] 16 connections

[0263] 17 cases

[0264] 18 ads

[0265] 20 Measurement signal

[0266] 21 Maximum of the measurement signal

[0267] 22 filtered signal

[0268] 23 Maximum of the filtered signal

[0269] 24-phase signal

[0270] 26 Trigger signal

[0271] 27 Trigger point

[0272] 30 Measurement signal

[0273] 31 Maximum of the measurement signal

[0274] 32 filtered signal

[0275] 33 Maximum of the filtered signal

[0276] 34 Phase signal

[0277] 36 Trigger signal

[0278] 37 Trigger time

Claims

Patent claims 1. System for body state-dependent stimulation comprising a master module (4, Master) for processing module signals / data, and at least two functional modules, in particular an action module (2, Module D / A) for stimulating tissue and a detection module (3, Module A / D) for deriving / measuring biodata or biosignals, characterized in that the communication between the modules takes place via a communication link (5) which meets hard or at least fixed real-time requirements.

2. System for body-state-dependent stimulation according to claim 1, characterized in that the Communication link (5) comprises a real-time capable bus (ECAT) to which at least two function modules are connected.

3. System for body-condition-dependent stimulation according to claim 2, characterized in that an action module (2, module D / A) for actuating actuators for tissue stimulation, a detection module (3, module A / D) for deriving / measuring biodata or biosignals and a control module (7, module DIO) for digital input / output control of actuators for tissue stimulation of external devices are connected to the real-time capable bus (ECAT).

4. System for body-state-dependent stimulation according to claim 2 or 3, characterized in that the modules (2, 3, 4, 7) are designed to transmit information on the real-time bus (ECAT) in the same computation step in one from the master module (4, Master) exchange information with each other depending on the clock signal provided for data processing by its master module.

5. System for body-condition-dependent stimulation according to one of claims 1 to 4, characterized in that the sensing module (3, module A / D) is configured to send the measured data / signals via the communication link (5) to the master module (4, master), the master module (4, master) is configured to process the received data, and the master module (4, master) is further configured to send data / commands to the action module (2, module D / A) to activate tissue stimulation via the actuators.

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

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

8. System for body-condition-dependent stimulation according to one of claims 1 to 7, characterized in that the 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 digital control signals provided by the master module (4, master) by means of trigger signals (26, 36) generated by the master module (4, master) and by the control module (DIO module).

9. System for body state-dependent stimulation according to one of claims 2 to 8, characterized in that a galvanic isolation (6) is provided between at least one module (4, 7) and the real-time capable bus (ECAT).

10. System for body state-dependent stimulation according to one of claims 2 to 9 characterized in that the real-time capable bus (ECAT) is an EtherCAT bus.

11. Method for body-state-dependent stimulation based on the system according to one of claims 1 to 10, wherein the modules communicate with each other in a closed-loop system and the data of a functional module, in particular an action module (2, module D / A), have an effect on the behavior or function of another functional module, in particular a sensing module (3, module A / D) and vice versa, wherein the master module (4, master) creates a data packet, in particular one data packet per millisecond, at a predetermined rate, which is continuously sent to the functional modules via the communication link (5) and returns to the master module.

12. Methods for body-condition-dependent stimulation according to Claim 11, wherein an action module (2, module D / A) is provided which receives and triggers a control command for stimulation in the form of neuromodulation excitation / inhibition.

13. Method for body-condition-dependent stimulation according to claim 11 or 12, wherein the action module (2, module D / A) controls magnetic, electromagnetic, mechanical, pneumatic and / or hydraulic actuators for direct influencing of biological tissue or organs.

14. Method for body state-dependent stimulation according to claim 11, 12 or 13, wherein the action module (2, module D / A) performs multi-channel stimulation of biological tissue based on features from the biodata acquisition of biosignals of different origins by a detection module (3, module A / D) in a frequency range from 0 to several kilohertz, in particular up to 100, 200 or 300 kHz.

15. Method for body state-dependent stimulation according to one of claims 11 to 14, with a detection module (3, module A / D) configured to detect EEG, ECG, EXG, EMG, EOG, ERG, PPT, respiratory, MKG, MEG, BD, SpO2 signals.