Tissue Stimulation Systems

Abstract

To provide a system that allows for less restrictive stimulation patterns of biological tissue. The present invention relates to a system for magnetic stimulation of biological tissue, comprising at least two magnetic field generators (D1-D4) that generate time-varying magnetic fields, the at least two magnetic field generators (D1-D4) being positioned relative to the tissue such that the magnetic fields at least partially overlap within the tissue, and at least one control device (50) for controlling the at least two magnetic field generators (D1-D4). According to the present invention, the control device (50) is configured to control at least one device (D2, D4) of the two magnetic field generators (D1-D4) such that the time-varying magnetic field generated by at least one device (D2, D4) is phase-modulated.

Description

[Technical Field]

[0001] The invention relates to a system for stimulating biological tissue according to the preamble of claim 1 and to a computer program product according to claim 18. [Background technology]

[0002] Non-invasive brain stimulation (NIBS) devices are valuable tools that can be used to modulate neural activity, investigate the causal roles that different brain regions and oscillations play in behavior, and potentially treat various psychiatric disorders. The two most widely applied NIBS techniques are transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES). In TMS, an electromagnetic coil is attached to the scalp and driven by high-current pulses. These pulses induce a strong, time-varying magnetic field near the coil, which then induces an electric field in the brain region beneath the coil. Furthermore, a paper by M. Zaeimbashi et al., "Magnetic Temporal Interference for Noninvasive, High-resolution, and Localized Deep Brain Stimulation: Concept Validation" (bioRxiv doi: https: / / doi.org / 10.1101 / 2020 / 07.20.212845), describes the use of interfering radiofrequency magnetic fields of slightly different frequencies. The surrounding brain regions are affected by the high-frequency magnetic field, while the interference region creates a magnetic field with a low-frequency envelope that can stimulate the corresponding brain region. However, the shape of the envelope cannot be changed, limiting the stimulation patterns. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] bioRxiv doi:https: / / doi.org / 10.1101 / 2020 / 07.20.212845, “Magnetic Temporal Interference for Noninvasive, High-resolution, and Localized Deep Brain Stimulation: Concept Validation” Summary of the Invention [Problem to be solved by the invention]

[0004] It is an object of the present invention to provide a system that allows for less restrictive stimulation patterns. [Means for solving the problem]

[0005] According to the invention, there is provided a system for stimulating (in particular magnetically) biological tissue, comprising: - at least two magnetic field generating devices for generating a time-varying magnetic field, the two magnetic field generating devices being positioned relative to the tissue such that the time-varying magnetic fields and / or electric fields induced by the time-varying magnetic fields at least partially overlap in the tissue; at least one control device for controlling the two magnetic field generating devices, a control device configured to control at least one of the two magnetic field generating devices so as to modulate (time modulate, in particular phase modulate) the time-varying magnetic field generated by said at least one device; A system is provided that includes:

[0006] The time-varying magnetic field and / or the electric field induced in the tissue by the magnetic field generated by the magnetic field generator and emitted into biological tissue (e.g., neural tissue) will interfere with each other in the tissue region where the magnetic fields overlap. As a result, the magnetic field and / or the induced electric field in the overlapping region will be amplitude-modulated at a frequency equal to or at least dependent on the modulation frequency. In either case, the frequency of the amplitude modulation will be lower than the frequency of the time-varying magnetic field emitted into the tissue, so that the tissue (especially neural tissue) will not respond to the time-varying magnetic field and / or the induced electric field, but will only respond to the resulting amplitude-modulated field. Thus, the effect on the tissue may be limited to the overlap region of the time-varying magnetic field and / or the induced electric field. For example, the modulation frequency may be lower than one-third or one-fifth the frequency (i.e., carrier frequency) of the time-varying magnetic field. The carrier frequency of the time-varying magnetic field may be in the kHz range (e.g., at least 1 kHz), while the modulation frequency may be less than 500 Hz, less than 300 Hz, or less than 200 Hz. For example, the carrier frequency of at least one of the time-varying magnetic fields (e.g., phase-modulated) is at least 1 kHz. Furthermore, the carrier frequency of at least one of the time-varying magnetic fields (e.g., carrier frequency at least 1 kHz) may be less than 1 MHz, less than 900 kHz, less than 500 kHz, less than 200 kHz, less than 100 kHz, less than 50 kHz, or less than 10 kHz. Furthermore, the strength (magnetic flux density) of the time-varying magnetic field may be at least 0.1 T, at least 1 T, at least 2 T, at least 3 T, or at least 5 T; for example, the strength of the time-varying magnetic field is between 2 T and 3 T.

[0007] The modulation imposed on the time-varying magnetic field generated by at least one of the two magnetic field generating devices may be phase modulation or frequency modulation. When the time-varying magnetic field is phase (frequency) modulated, the phase (frequency) of the magnetic field varies over time (e.g., periodically). However, the present invention is not limited to a specific modulation method, for example, an amplitude modulation method may also be used. According to another embodiment of the present invention, the carrier frequencies of the time-varying magnetic fields generated by the magnetic field generating devices are the same. Note that the term "carrier frequency" refers to the frequency associated with the (unmodulated) time-varying magnetic field ("carrier magnetic field"). The carrier magnetic field may be continuous in time (e.g., non-pulsed), i.e., the time-varying magnetic field varies continuously (e.g., sinusoidally). The carrier magnetic field is modulated, for example, phase modulated or frequency modulated. Here, at least one of the time-varying magnetic fields is phase modulated. If the magnetic field and / or the induced electric field are not modulated (which may be the case for one of the magnetic fields), the carrier frequency is the (only) frequency of the time-varying magnetic field.

[0008] The control device may be configured to control the at least two magnetic field generating devices so that the time-varying magnetic field generated by one of the magnetic field generating devices is phase modulated and the time-varying magnetic field generated by the other magnetic field generating device is unmodulated.

[0009] Furthermore, the control device may be configured to adjust the ratio of the amplitudes of the time-varying magnetic fields generated by the two magnetic field generators. In particular, the degree of amplitude modulation depends on the vector sum of the two magnetic fields and / or induced electric fields at each location within the tissue. Modulation may be greatest when the magnitudes of the two magnetic fields are equal and least near each magnetic field generator, where one of the two fields may dominate over the other. By adjusting the relative amplitudes (i.e., amplitude ratio) of the generated time-varying magnetic fields, the location of maximum amplitude modulation, and therefore the location of maximum stimulation, may be controlled.

[0010] The modulation is generated, in particular, by applying a time-varying modulation function to the carrier magnetic field. The modulation function can, in principle, be chosen arbitrarily, resulting in an amplitude-modulated magnetic field whose envelope can be designed, for example, depending on the desired effect on the tissue. Thus, the present invention allows for high flexibility in generating stimulation waveforms. For example, the modulation (modulation function) can be simply sinusoidal. However, more time-complex fields can be created as a result, e.g., to emulate short stimulation "pulses." For this purpose, the modulation can be phase modulation, involving switching from a first state in which the time-varying magnetic fields have opposite phases to a second state in which the time-varying magnetic fields are in phase. At locations where the two magnetic and / or induced electric fields have equal magnitudes, the two fields normally cancel each other out and only transiently add when they are brought in phase, resulting in a stimulation pulse.

[0011] According to an embodiment of the present invention, at least one of the magnetic field generating devices consists of or includes at least one electromagnetic coil. However, the present invention is not limited to the specific embodiment of two magnetic field generating devices. For example, at least one of the magnetic field generating devices may consist of or include at least one rotatable permanent magnet for generating a time-varying magnetic field.

[0012] When the magnetic field generators are implemented as electromagnetic coils, each magnetic field generator may include at least one capacitor coupled to the coil to form a resonant circuit. The capacitance may be selected so that the resonant frequency of the resonant circuit matches the desired stimulus carrier frequency. The resulting circuit has very low impedance at the resonant frequency and can be easily driven by low-voltage electronics. In other embodiments, the capacitors may be eliminated and the coils may be driven directly using high-voltage electronics.

[0013] To overcome potential overheating issues, the coil may be actively cooled by a system that circulates water, oil, or a coolant around the coil. If necessary, stimulation can be performed intermittently, with the coil turned off when stimulation is not required and turned on only when a stimulation pulse is required. However, rapid on-off switching of the electric field is known to affect neural firing. To prevent this, the current may be slowly ramped up and down to its maximum value over short periods (tens to hundreds of milliseconds) during the on- and off-time of the stimulation pulse.

[0014] According to another embodiment of the invention, the two magnetic field generating devices belong to a first group, the system comprises a second group including at least two magnetic field generating devices for generating a time-varying magnetic field, and the control device is configured to control at least one of the two magnetic field generating devices of the second group so as to modulate the time-varying magnetic field generated by the device. Of course, more than two groups of at least two magnetic field generating devices may also be provided.

[0015] The magnetic fields generated by the first group of devices may have the same carrier frequency, and the magnetic fields generated by the second group of magnetic field generating devices may have the same carrier frequency, but the carrier frequency of the first group may be different from that of the second group. Each group may operate at a different carrier frequency, for example, to ensure that low-frequency amplitude modulation occurs only where the fields from all magnetic field generating devices are essentially equal, i.e., to prevent "extraneous" low-frequency amplitude modulation spots caused by interference between fields generated by magnetic field generating devices from different (two or more) groups. The carrier frequencies are chosen, for example, so that the difference between any two of them is greater than a frequency to which neural tissue can respond (e.g., at least 0.2 kHz, at least 0.5 kHz, or at least 1 kHz). At the point where all fields are added equally, the combined field envelope consists of a low-frequency component at the modulation frequency and some high-frequency components resulting from beats between the different carrier frequencies. Neural tissue, for example, only responds to low frequencies, so it responds to the modulation frequency components and not to the higher-frequency components.

[0016] The control device of the system according to the present invention may include a programmable unit, e.g., a microcontroller. The programmable unit may generate at least one control signal (drive signal) for controlling the time-varying magnetic fields generated by the two magnetic field generating devices. For example, the control device may include an amplifier circuit configured to receive the control signal and provide an amplified control signal to the magnetic field generating devices. The control signal may determine both the time-varying magnetic field, i.e., the carrier magnetic signal, generated by the magnetic field generating devices and the modulation of the time-varying magnetic field. In particular, the control signal sets the waveform (including frequency, amplitude, and / or phase) of the modulated or unmodulated time-varying magnetic field. The corresponding control signal may also be generated by an analog circuit design instead of being provided by the programmable unit.

[0017] If the magnetic field generating devices each consist of an electromagnetic coil, the control signal generated by the programmable unit may determine the current supplied to the coil. In this embodiment, Hall-effect current sensors may be used to monitor the current in each coil (e.g., in real time). Other types of current sensors may also be utilized. The current may be read by a programmable unit (e.g., the microcontroller described above) that implements a controller (e.g., a PID controller) that sets the frequency, amplitude, and / or phase of the control signal for each coil to maintain the current's frequency, amplitude, and / or phase at desired values ​​and counteract changes due to temperature rise, phase modulation, and / or inductive coupling between the coils, etc. The controller may alternatively be implemented using analog electronics. The programmable unit may also monitor the coil temperature (e.g., in real time) using, for example, a temperature sensor located on the surface of each coil to ensure that the coil temperature remains within an acceptable range. Note that the control device of a system according to the present invention does not necessarily need to implement a feedback loop, i.e., it does not need to be configured as a controller (e.g., a PID controller described above), but simply to operate the magnetic field generating device to generate a time-varying magnetic field.

[0018] According to a further embodiment of the present invention, the system may be battery-powered, and a DC-DC converter (e.g., a step-down converter) may convert the battery voltage to a level suitable for powering components of the system, such as the magnetic field generator for generating the time-varying magnetic field and / or the programmable unit described above. Furthermore, communication with external devices (e.g., EEG amplifiers) may be supported via an optically isolated digital I / O interface and / or Bluetooth®. This allows the system to be completely isolated from the power grid and external devices, reducing noise and ensuring the subject's safety. Furthermore, an overcurrent protection fuse and / or an emergency stop button may be integrated to ensure safety in the event of any system failure.

[0019] The invention also relates to a computer program product having program code whose instructions, when executed by a programmable unit of a control device of a system according to any of the preceding claims, control the control device to cause each of two magnetic field generating devices of the system to generate a time-varying magnetic field, and wherein the time-varying magnetic field of at least one magnetic field generating device is modulated. [Brief explanation of the drawings]

[0020] [Figure 1A] 1 shows the strength of two electric fields induced by two time-varying magnetic fields generated by a system according to the present invention, one of which is phase-modulated by a sinusoidal modulation function and has substantially the same amplitude as the unmodulated magnetic field. [Figure 1B] 1B shows the resultant electric field resulting from the interference of the electric fields shown in FIG. 1A. [Figure 2A] 1 shows the strength of two electric fields induced by two time-varying magnetic fields generated by a system according to the invention, one of which is phase modulated and has a smaller amplitude than the unmodulated field. [Figure 2B] 2B shows the resultant electric field resulting from the interference of the electric fields shown in FIG. 2A. [Figure 3A] 1 shows the strength of two electric fields induced by two time-varying magnetic fields generated by the system of the present invention, one of which is phase modulated by an arbitrary modulation function. [Figure 3B] The resultant electric field resulting from the interference of the electric fields depicted in Figure 3A is shown. [Figure 4A] 1 shows the strength of two electric fields induced by two time-varying magnetic fields generated by a system of the present invention, one of which is phase modulated by an on-off modulation function. [Figure 4B] The resultant electric field resulting from the interference of the electric fields depicted in Figure 4A is shown. [Figure 5A]1 shows measurements of the electric field induced by two time-varying magnetic fields generated by the system of the present invention. [Figure 5B] 1 shows measurements of the electric field induced by two time-varying magnetic fields generated by the system of the present invention. [Figure 5C] 1 shows measurements of the electric field induced by two time-varying magnetic fields generated by the system of the present invention. [Figure 6] 1 shows a block diagram of a system according to an embodiment of the present invention. [Figure 7] FIG. 1 is a perspective schematic diagram illustrating a system according to another embodiment of the present invention arranged to stimulate human brain tissue. DETAILED DESCRIPTION OF THE INVENTION

[0021] An embodiment of the present invention will now be described with reference to the accompanying drawings. Figure 1 shows a (simulated) course of the strengths of two electric fields E1 and E2, where the first electric field E1 is induced in human brain tissue by a first time-varying magnetic field generated by a first magnetic field generator of a system according to the present invention. The second electric field E2 is induced by a second time-varying magnetic field generated by a second magnetic field generator of the system according to the present invention. The magnetic and induced electric fields E1 and E2 are sinusoidal (having the same frequency), and the second magnetic and electric fields E2 are phase-modulated, while the first magnetic field is unmodulated. Each of the two magnetic field generators may include an electromagnetic coil supplied with a time-varying current that generates the waveform of the emitted magnetic field and, therefore, the induced electric field.

[0022] Two coils are placed on the scalp. Each coil may consist of multiple windings of copper wire with either an air core or a ferromagnetic core. The two coils may be manufactured to be as similar as possible. The coils may be made of Litz wire to minimize skin and proximity effects. Each coil is driven with a high-frequency (e.g., in the kHz range) sinusoidal current (e.g., several to tens of amperes). While the two coils are driven at the same frequency, the phase of the current in one coil, which induces the second electric field E2, is modulated at a low frequency (e.g., 100 Hz). When the two induced electric fields E1 and E2 combine in a region of the brain (the overlap region), the resulting electric field is amplitude-modulated at the phase modulation frequency. Figure 1A shows the electric field strength in the overlap region. The resulting electric field RE, resulting from the interference of the first and second electric fields E1 and E2, is shown in Figure 1A. The RE has the same carrier frequency as the first and second electric fields E1 and E2, and an envelope ENV with a phase modulation frequency. Of course, it is also possible to modulate the first magnetic field instead of the second magnetic field. Alternatively, both magnetic fields may be modulated.

[0023] The degree of amplitude modulation depends on the vector sum of the two electric fields E1 and E2 at each location in the brain. Modulation is greatest when the two fields are equal in magnitude and least near each coil, where one field dominates the other. As noted above, neural tissue responds to amplitude-modulated electric fields but not unmodulated radiofrequency electric fields, so neuromodulation is limited to regions where the combined electric field exhibits large amplitude modulation. The region of maximum amplitude modulation can be controlled by adjusting the relative magnitudes of the coil currents. Figures 1A and 1B illustrate the situation where the amplitudes of electric fields E1 and E2 in the overlap region are essentially the same, resulting in a maximum amplitude of the resulting electric field RE.

[0024] In contrast, Figures 2A and 2B relate to a situation in which the electric fields E1 and E2 have different amplitudes in the overlap region considered in Figures 1A and 1B. More specifically, the amplitude of the modulated second magnetic field, and thus the second induction electric field E2, is significantly smaller than the amplitude of the first magnetic field, and thus the first induction electric field E1. Therefore, the amplitude of the resulting electric field RE is small.

[0025] The phase modulation need not be sinusoidal. Rather, in principle, any modulation waveform can be imposed on the magnetic field. Figures 3A and 3B relate to an embodiment in which the second magnetic field, and thus the second electric field E2, is arbitrarily modulated so that the resultant magnetic field RE has an arbitrary envelope ENV, allowing for great flexibility in generating stimulation pulses.

[0026] Furthermore, by having two magnetic and electric fields that are normally out of phase and then briefly reversing the phase of one of the coils to temporarily bring the coils in phase, a short stimulation pulse can be emulated. This embodiment is illustrated in Figures 4A and 4B. At the point where the two fields overlap and have substantially equal magnitude, the two magnetic and electric fields will normally (during the anti-phase interval) cancel each other out. Temporarily (during the in-phase interval), they will add up to form a stimulation pulse (see the envelope ENV of the resulting electric field RE).

[0027] Figures 5A-5C show different configurations of two magnetic field generators D1 and D2 in a system according to the present invention. According to Figure 5A, the magnetic field generators D1 and D2 are positioned close to each other to target cortical regions at the midline of the frontal plane. The devices D1 and D2 may be electromagnetic coils with equal coil currents in both coils. Figure 5A shows measurements of this configuration of the devices D1 and D2, showing the profile of the electric field induced by the magnetic field emitted by the devices D1 and D2 in the approximation of the spherical conductor 10 of the human brain. The induced electric field was probed at different positions in a two-dimensional plane in the frontal plane by measuring the induced voltage in a triangular loop of copper wire. The gray scale indicates the degree of amplitude modulation of the normalized electric field. Because the currents supplied to the coils of the magnetic field generators D1 and D2, and thus the magnetic and induced electric fields, are substantially equal, the primary stimulation location S appears at the midline.

[0028] According to Figure 5B, the positions of the magnetic field generators D1 and D2 remain unchanged. However, the current in the coil of the first magnetic field generator D1 is reduced relative to the second magnetic field generator D2. Correspondingly, the stimulation position S moves towards the first (left) generator D1.

[0029] To target deeper brain regions, the magnetic field generators D1 and D2 can be positioned at a greater distance from the midline (Figure 5C). In this configuration, the point of maximum stimulation S is located deep within the brain, e.g., at a depth of approximately 45 mm.

[0030] FIG. 6 is a block diagram of a system 100 according to the present invention. The system 100 comprises first and second magnetic field generators D1 and D2, each having at least one electromagnetic coil 11 and 12. Each coil 11 and 12 is combined with a capacitor (e.g., a film capacitor) 111 and 121 to form a resonant circuit RC1 and RC2 (series LC tank). The capacitances of the capacitors 111 and 121 are selected so that the resonant frequency of the LC tanks RC1 and RC2 matches the desired stimulus carrier frequency of the magnetic field they generate. As a result, the circuits RC1 and RC2 have very low impedance at the resonant frequency and can be easily driven by low-voltage electronics. It is also possible to omit the capacitors 111 and 121 and drive the coils 11 and 12 directly with high voltage.

[0031] In the embodiment shown in FIG. 6, a class D amplifier circuit 13 is utilized to drive each LC tank RC1, RC2 with a sinusoidal voltage at the stimulus carrier frequency. The sinusoidal signal is generated using a digital-to-analog converter driven by a programmable unit in the form of a microcontroller 14. Alternatively, the LC tanks RC1, RC2 can be driven using an H-bridge circuit that generates a square wave voltage at the stimulus carrier frequency with the appropriate phase. Furthermore, multiple amplifier circuits 13 may be provided, with each coil 11, 12 operated by its own amplifier circuit. The amplitude of the square wave may be controlled by a DC-DC buck step-down converter. The resonant characteristics of the LC tank filter the square wave voltage into a sinusoidal current at the fundamental frequency. Both implementations are highly efficient in terms of energy consumption, using highly efficient switching electronics, although other implementations using analog electronics (e.g., class AB amplifiers) are also possible. The amplifier circuit 13 and microcontroller 14 form part of the control unit 50 of the system 100 for controlling the magnetic field generators D1, D2 (particularly the coils 11, 12). Using the control device 50, the current supplied to the first and / or second coils 11, 12 can be modulated, for example phase modulated. In particular, a control signal CS generated by the microcontroller 14 manipulates the coil current, resulting in a modulation of the current in one of the coils which generates a modulated magnetic field.

[0032] The coils 11, 12 can be actively cooled by a system that circulates water or oil around them. If desired, stimulation can be performed in an intermittent manner, with the coils turned on only around the time a stimulation pulse is required and turned off when stimulation is not required. For example, as previously mentioned, the current supplied to the coils can be slowly ramped up to and down from a maximum value over a short period of time (e.g., tens to hundreds of milliseconds) at the onset and offset of the stimulation pulse.

[0033] Additionally, current sensors 15 (e.g., Hall effect sensors) are used to monitor in real time the current flowing through each of the coils 11, 12. The measured current values ​​are sent to the microcontroller 14. The microcontroller 14 implements a PID controller that sets the amplitude and phase of the control signals sent from the microcontroller 14 to the amplifier circuit 13 for each of the coils 11, 12 in order to maintain the amplitude and phase of the current supplied to the coils 11, 12 at the desired values ​​and to counteract changes due to temperature rise, phase modulation (other than the desired phase modulation), and / or inductive coupling between the coils 11, 12.

[0034] As already mentioned above, the PID controller can alternatively be implemented using analog electronics, and the microcontroller 14 monitors the coil temperature in real time using temperature sensors 16 located on the surface of each coil 11, 12 to ensure that the coil temperature remains within an acceptable range.

[0035] The system 100 is battery-powered by at least one battery 2, and the battery voltage is converted by a step-down converter 3 to an appropriate level for powering the microcontroller 14. Additionally, the system 100 includes an opto-isolator digital I / O and Bluetooth interfaces 4, 5 to enable communication with external devices (e.g., EEG amplifiers). This allows the system to be isolated from the power grid and external devices to reduce noise and ensure the subject's safety. Additionally, an overcurrent protection fuse 6 and an emergency disconnect button 7 may be provided to respond to device failure.

[0036] To increase stimulation intensity and spatial resolution, a system 100 according to the present invention may include more than two coils (or other types of magnetic field generators), as shown in FIG. 7. In this multi-coil embodiment, four magnetic field generators D1-D4 are provided, each consisting of coils 11, 12, 21, and 22. The magnetic field generators D1-D4, and thus the coils 11, 12, 21, and 22, are assigned to two groups: the generators D1 and D2 (coils 11 and 12) belong to the first group 10, and the generators D3 and D4 (coils 21 and 22) belong to the second group 20. The coils in each group 10, 20 are operated, inter alia, using a control device 50, as described above, for example, in connection with FIG. 6. This allows the magnetic field generated by at least one of the magnetic field generators D1-D4 to be modulated, e.g., the generators D2 (coil 12) and D4 (coil 22) generate modulated signals. A common amplifier circuit 13 can be used to operate the coils in each group 10, 20. However, it is also possible that at least one amplifier circuit is assigned to each of the groups 10, 20.

[0037] As already mentioned above, to ensure that low-frequency amplitude modulation occurs only where the fields from all coils 11, 12, 21, 22 are equal and to prevent unwanted low-frequency amplitude modulation regions between the coils of different groups 10, 20, the coils 11, 12, 21, 22 of each group 10, 20 operate at different carrier frequencies. That is, the coils 11, 12 of the first group operate at a first carrier frequency, and the coils 21, 22 of the second group 20 operate at a second carrier frequency different from the first carrier frequency. The overlap region is therefore the region of maximum stimulation S. The carrier frequencies of the groups 10, 20 are selected so that the difference between them is much greater than the frequency to which the neural tissue can respond (e.g., greater than 1 kHz). Thus, where the fields generated and / or induced by coils 11, 12, 21, 22 interfere, the resulting field envelope will have a low frequency component at the modulation frequency and some high frequency components due to the different carrier frequencies of the two groups 10, 20. Of course, more than two groups may be used, and at least one of the groups may comprise more than two coils. The present invention includes the following embodiments. [Aspect 1] 1. A system for stimulating tissue of a living body, comprising: at least two magnetic field generators (D1, D2, D3, D4) for generating a time-varying magnetic field, the magnetic field generators (D1, D2, D3, D4) being positioned with respect to the tissue such that their time-varying magnetic fields at least partially overlap within the tissue; at least one control device (50) for controlling the at least two magnetic field generating devices (D1, D2, D3, D4); 1. A system for stimulating tissue of a living body, comprising: the control device (50) is configured to control at least one magnetic field generating device (D2, D4) of the at least two magnetic field generating devices (D1, D2, D3, D4) so ​​that the phase of the time-varying magnetic field generated by at least one magnetic field generating device (D2, D4) is modulated. A system for stimulating living tissue. [Aspect 2] In the system described in aspect 1, the control device (50) is configured to control the at least one magnetic field generating device (D2, D4) so ​​that the frequency of the time-varying magnetic field generated by the at least one magnetic field generating device (D2, D4) is modulated. Aspect 3 In the system described in aspect 1 or 2, the control device (50) is configured to control the at least two magnetic field generating devices (D1, D2, D3, D4) so ​​that the carrier frequencies of at least two of the time-varying magnetic fields generated by the at least two magnetic field generating devices (D1, D2, D3, D4) are the same. Aspect 4 In a system described in any one of aspects 1 to 3, the control device (50) is configured to adjust the ratio of the amplitudes of the time-varying magnetic fields generated by the at least two magnetic field generating devices (D1, D2, D3, D4). Aspect 5 5. The system of any one of aspects 1 to 4, wherein the modulation is at least partially sinusoidal. Aspect 6 6. The system of any one of aspects 1 to 5, wherein the frequency of the modulation is less than one-third or one-fifth of the frequency of the time-varying magnetic field. Aspect 7 In a system described in any one of aspects 1 to 6, the modulation is phase modulation including switching from a first state in which the time-varying magnetic field is in opposite phase to a second state in which the time-varying magnetic field is in the same phase. Aspect 8 A system according to any one of aspects 1 to 7, wherein at least one of the magnetic field generating devices consists of or includes at least one electromagnetic coil (11, 12, 21, 22). Aspect 9 A system according to any one of aspects 1 to 8, wherein at least one of the magnetic field generating devices (D1, D2, D3, D4) consists of or includes at least one rotatable permanent magnet. Aspect 10 In the system according to any one of aspects 1 to 9, the at least two magnetic field generating devices (D1, D2) belong to a first group (10) of devices, the system (100) comprises a second group (20) of devices including at least two magnetic field generating devices (D3, D4) for generating a time-varying magnetic field; The control device (50) is configured to control at least one magnetic field generating device (D4) of the two magnetic field generating devices (D3, D4) of the second group (20) so that the time-varying magnetic field generated by the at least one magnetic field generating device (D4) is modulated. Aspect 11 In the system described in aspect 10, the magnetic fields generated by the magnetic field generating devices (D1, D2) of the first group (10) have the same carrier frequency, and the magnetic fields generated by the magnetic field generating devices (D3, D4) of the second group (20) have the same carrier frequency, and the carrier frequency of the first group (10) is a different carrier frequency from the carrier frequency of the second group (20). Aspect 12 In the system described in aspect 11, the difference in carrier frequency between the first group and the second group (10, 20) is at least 0.2 kHz, at least 0.5 kHz, or at least 1 kHz. Aspect 13 13. The system of any one of the preceding aspects, wherein the control device (50) comprises a programmable unit (14). Aspect 14 In the system described in aspect 13, the programmable unit (14) generates at least one control signal (CS) for controlling the time-varying magnetic field generated by the at least two magnetic field generating devices (D1, D2, D3, D4). Aspect 15 15. The system of any one of aspects 1 to 14, wherein the carrier frequency of at least one of the time-varying magnetic fields is at least 1 kHz. Aspect 16 16. The system of any one of aspects 1 to 15, wherein the carrier frequency of at least one of the time-varying magnetic fields is less than 1 MHz, less than 900 kHz, less than 500 kHz, less than 200 kHz, less than 100 kHz, less than 50 kHz, or less than 10 kHz. Aspect 17 In a system described in any one of aspects 1 to 16, the control device (50) is configured to control the at least two magnetic field generating devices (D1, D2, D3, D4) so ​​that the time-varying magnetic field generated by one of the magnetic field generating devices (D2, D4) is phase-modulated and the time-varying magnetic field generated by the other of the magnetic field generating devices (D2, D4) is unmodulated. Aspect 18 18. A computer program product having program code, which, when executed by a programmable unit (14) of the control device (50) of the system (100) of any one of aspects 1 to 17, causes the control device (50) to control the at least two magnetic field generating devices (D1, D2, D3, D4) of the system (100) such that each of the at least two magnetic field generating devices (50) generates a time-varying magnetic field, wherein the time-varying magnetic field of at least one (D2, D4) of the magnetic field generating devices (D1, D2, D3, D4) is phase-modulated.

Claims

1. 1. A system for stimulating tissue of a living body, comprising: at least two magnetic field generators (D1, D2, D3, D4) for generating magnetic fields having time-varying magnitude and / or direction, the magnetic field generators (D1, D2, D3, D4) being positioned with respect to the tissue such that their time-varying magnetic fields at least partially overlap within the tissue in an overlap region; at least one control device (50) for controlling said at least two magnetic field generating devices (D1, D2, D3, D4); 1. A system for stimulating tissue of a living body, comprising: the control device (50) is configured to control at least one magnetic field generating device (D2, D4) of the at least two magnetic field generating devices (D1, D2, D3, D4) such that a phase of the time-varying magnetic field generated by at least one magnetic field generating device (D2, D4) is modulated at a modulation frequency by a modulation function; The control device (50) is configured to control the at least one magnetic field generating device (D2, D4) of the at least two magnetic field generating devices (D1, D2, D3, D4) so ​​that a magnetic field and / or an induced electric field generated by interference of the time-varying magnetic fields in the overlap region is amplitude-modulated at a frequency that depends on the modulation frequency. A system for stimulating living tissue.

2. 2. The system of claim 1, wherein the control device (50) is configured to control the at least one magnetic field generating device (D2, D4) such that the frequency of the time-varying magnetic field generated by the at least one magnetic field generating device (D2, D4) is modulated.

3. 3. The system according to claim 1 or 2, wherein the control device (50) is configured to control the at least two magnetic field generating devices (D1, D2, D3, D4) so ​​that the carrier frequencies of at least two of the time-varying magnetic fields generated by the at least two magnetic field generating devices (D1, D2, D3, D4) are the same.

4. 4. The system according to claim 1, wherein the control device (50) is configured to adjust the ratio of the amplitudes of the time-varying magnetic fields generated by the at least two magnetic field generating devices (D1, D2, D3, D4).

5. 5. A system according to any one of claims 1 to 4, wherein the modulation function is at least partially sinusoidal.

6. 6. A system according to any one of claims 1 to 5, wherein the frequency of the modulation function is less than one third or one fifth of the frequency of the time-varying magnetic field.

7. 7. The system of claim 1, wherein the modulation by the modulation function is a phase modulation that includes switching from a first state in which the two time-varying magnetic fields are in antiphase with each other to a second state in which the two time-varying magnetic fields are in phase with each other.

8. 8. A system according to any one of the preceding claims, wherein at least one of the magnetic field generating devices consists of or comprises at least one electromagnetic coil (11, 12, 21, 22).

9. 9. A system according to any one of the preceding claims, wherein at least one of the magnetic field generating devices (D1, D2, D3, D4) consists of or comprises at least one rotatable permanent magnet.

10. 10. The system according to claim 1, the at least two magnetic field generating devices (D1, D2) belong to a first group (10) of devices, The system (100) comprises a second group (20) of devices comprising at least two magnetic field generating devices (D3, D4) for generating a time-varying magnetic field, The control device (50) is configured to control at least one magnetic field generating device (D4) of the two magnetic field generating devices (D3, D4) of the second group (20) so that a time-varying magnetic field generated by at least one magnetic field generating device (D4) of the two magnetic field generating devices (D3, D4) of the second group (20) is modulated.

11. 11. The system of claim 10, wherein the magnetic fields generated by the magnetic field generating devices (D1, D2) of the first group (10) have the same carrier frequency, and the magnetic fields generated by the magnetic field generating devices (D3, D4) of the second group (20) have the same carrier frequency, and the carrier frequency of the first group (10) is a different carrier frequency from the carrier frequency of the second group (20).

12. 12. The system of claim 11, wherein the difference in carrier frequency between the first group and the second group (10, 20) is at least 0.2 kHz, at least 0.5 kHz, or at least 1 kHz.

13. The system according to any one of the preceding claims, wherein the control device (50) comprises a programmable unit (14).

14. 14. The system according to claim 13, wherein the programmable unit (14) generates at least one control signal (CS) for controlling the time-varying magnetic fields generated by the at least two magnetic field generating devices (D1, D2, D3, D4).

15. 15. A system according to any one of the preceding claims, wherein the carrier frequency of at least one of the time-varying magnetic fields is at least 1 kHz.

16. 16. The system of any one of claims 1 to 15, wherein the carrier frequency of at least one of the time-varying magnetic fields is less than 1 MHz, less than 900 kHz, less than 500 kHz, less than 200 kHz, less than 100 kHz, less than 50 kHz or less than 10 kHz.

17. 17. A system according to any one of claims 1 to 16, wherein the control device (50) is configured to control the at least two magnetic field generating devices (D1, D2, D3, D4) so ​​that the time-varying magnetic field generated by one of the magnetic field generating devices (D2, D4) is phase-modulated and the time-varying magnetic field generated by the other of the magnetic field generating devices (D2, D4) is unmodulated.

18. 18. A computer program product having a program code, which, when executed by a programmable unit (14) of the control device (50) of the system (100) according to any one of claims 1 to 17, causes the control device (50) to control the at least two magnetic field generating devices (D1, D2, D3, D4) of the system (100) such that each of the at least two magnetic field generating devices (50) generates a magnetic field whose magnitude and / or direction varies over time, wherein the time-varying magnetic field of at least one of the magnetic field generating devices (D2, D4) is phase-modulated by a modulation function at a modulation frequency, and wherein a magnetic field and / or an induced electric field resulting from interference of the time-varying magnetic fields in an overlap region is amplitude-modulated at a frequency that depends on the modulation frequency.

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