JP2015521517A - Method and system for TMS dose evaluation and seizure detection - Google Patents

Abstract

A method and system for monitoring a patient's EEG (electroencephalogram) during TMS (transcranial magnetic stimulation) is disclosed. The system includes a TMS device that generates a plurality of magnetic pulses when in an active state, wherein the plurality of magnetic pulses is a burst comprising a plurality of pulses grouped together or individually according to a TMS treatment protocol. The pulse can be applied to the patient's head. An EEG system is provided that measures EEG data resulting from the TMS treatment protocol applied to the patient. The system further comprises control means in communication with the TDM device and the EEG system, the control means being configured to activate the EEG system during times when the TMS device is not generating pulses, thereby providing a therapeutic effect. The EEG data measurement is applied continuously or alternately with magnetic pulses being generated according to the TMS treatment protocol so that it can be monitored and potential seizures detected. [Selection] Figure 1

Description

  The present invention relates to methods and devices for TMS dose evaluation and seizure detection.

  Transcranial magnetic stimulation (TMS) is a technique for non-invasively stimulating the human brain. Specifically, TMS causes depolarization and hyperpolarization in brain neurons. TMS uses electromagnetic induction to induce a weak current using a rapidly changing magnetic field. This can cause activity in specific or large areas of the brain while minimizing discomfort, thereby allowing the brain to be investigated to function and interconnect. Thus, TMS uses the principle of inductance to obtain electrical energy across the scalp and skull without the pain of direct percutaneous electrical stimulation. TMS involves placing a wire coil on the scalp and passing a powerful, rapidly changing current in it. This causes a magnetic field that passes through the tissue of the head without being disturbed and relatively painful. This magnetic field also induces a much weaker current in the brain. In order to induce enough current to depolarize the neurons in the brain, the current flowing through the stimulation coil must start and stop within a few hundred microseconds or reverse its direction Must.

  TMS is currently used in several different forms. In a first form, called single pulse TMS, a single pulse of magnetic energy is delivered from the coil to the patient. In another form, repetitive TMS (rTMS), pulse trains are delivered over a specific time using different frequency patterns. The frequency series upregulates cortical excitability, and for some diseases (eg depression), the use of such a pattern may be advantageous. However, high frequency patterns are associated with high seizure risk. Safety limits on stimulus intensity and frequency are described in internationally agreed literature (Rossi et al., 2009, Wassermann et al., 1996).

  To monitor the safety and effectiveness of TMS application, one known method would be to visually monitor the patient's condition during and after TMS application. Thus, from a safety point of view, this subjective evaluation is available and is usually based on a questionnaire. However, there is a lack of online feedback to confirm the effectiveness of treatment, and this protocol cannot detect seizures in time for seizures.

  A further known method of monitoring the safety and effectiveness of TMS application is to monitor the patient's EEG before and after the TMS session.

  An electroencephalogram (EEG) is a record of a patient's specific electroencephalogram pattern. The EEG system makes it possible to record an electroencephalogram pattern. An EEG system typically includes a plurality of conductive electrodes placed on the patient's scalp. These electrodes are usually metal and are connected to a preamplifier, which processes the signal detected by the electrode and provides the amplified signal to the EEG device. The EEG device includes hardware and software that interprets the signal and provides a visual indication of the electroencephalographic activity detected by the electrodes. This electroencephalogram activity is usually displayed on a strip chart recorder or computer monitor.

  In practice, the use of EEG involves measuring the response induced before and after the TMS session and then measuring the spontaneous or non-magnetically induced EEG response after the treatment session. . However, applying EEG measurements after a TMS treatment session could significantly lengthen the entire treatment session.

  Yet another known method of monitoring the safety and effectiveness of TMS applications is to monitor the patient's EEG during a TMS session. However, the high energy dynamic magnetic field generated by the TMS device induces unwanted voltages in the EEG leads, so using conventional EEG hardware makes TMS treatment safe and effective. Monitoring a patient's EEG during a TMS pulse poses a technical problem because TMS-compliant EEG systems generally do not support TMS measurements because they are inappropriate to monitor. In particular, at least the preamplifiers used in current EEG systems are subject to saturation caused by the magnetic field generated by the TMS system. Since the electrodes used to monitor the EEG are usually in close proximity to the TMS coil, the magnetic pulse induces a signal on one or more of the EEG electrodes, which saturates the EEG preamplifier. To do. Conventional preamplifiers used in EEG systems require a relatively long time to recover after being saturated with TMS pulses.

  One known method of monitoring EEG during TMS includes an amplifier in the EEG system that uses a sample and hold circuit to lock the amplifier to a constant level during the TMS pulse. The amplifier is said to recover within 100 milliseconds after the TMS pulse ends. Although this system appears to be able to monitor the EEG in a short time after the TMS pulse ends, additional gating and synchronization circuitry is required to control the operation of the EEG amplifier for the TMS system. Additional gating and sampling circuits are undesirable because they require additional circuitry and can be complex.

  A more complex situation that occurs when a patient's EEG is monitored during TMS arises from sensing the EEG signal using a metal electrode. Large eddy currents induced by one or more TMS pulses in the metal electrode can cause localized heating, which can result in burns on the patient's scalp. This raises a safety issue.

  U.S. Pat. No. 6,057,077 discloses yet another method for monitoring EEG during TMS. This prior art specification discloses a system and method for synchronizing the operation timing of the TMS system and the operation timing of the EEG system. Instead, the present disclosure provides a control arrangement that monitors signals provided by the EEG system during operation of the TMS system and stops operation of the TMS system if the EEG signal is in an undesirable state.

US Patent Application Publication No. 2002/007128

According to a first aspect of the present invention there is provided a system for monitoring a patient's EEG (electroencephalogram) during TMS (transcranial magnetic stimulation), the system comprising:
A TMS device that generates a plurality of magnetic pulses when in an active state, wherein the plurality of magnetic pulses is as a burst comprising a plurality of pulses grouped together or as individual pulses according to a TMS treatment protocol A TMS device that can be applied to the patient's head;
An EEG system for measuring EEG data resulting from a TMS treatment protocol applied to a patient;
Control means in communication with the TMS device and the EEG system, the control means being configured to activate the EEG system during times when the TMS device is not generating pulses, thereby monitoring the therapeutic effect; Control means in which EEG data measurements are applied continuously or alternately with magnetic pulses being generated according to the TMS treatment protocol so that potential seizures can be detected;
Is provided.

  In one embodiment, the TMS device is configured to generate a signal when not in the active state and send this signal to the control means, and accordingly the control means is when the TMS device is not in the active state. It is configured to trigger the operation of the EEG system.

  In one embodiment, the system comprises storage means for storing measured EEG data.

  In one embodiment, before the TMS device applies a plurality of pulses, the TMS device transmits a reserve signal to the EEG system, the reserve signal being a control means for triggering a recorder that records the EEG data in the storage means. Used by.

  In one embodiment, the system comprises a seizure monitoring module that detects or predicts patient seizures.

  In one embodiment, the seizure monitoring module results in measuring the spectral characteristics of spontaneous oscillatory brain activity when the TMS device is not generating a pulse so that a patient's seizure can be detected or predicted. Compare the measurement results to the expected or desired profile.

  In one embodiment, the seizure monitoring module communicates with the control means so that if a seizure is detected or predicted, the control means can stop the operation of the TMS device.

  In one embodiment, the seizure monitoring module is configured to be activated during times when TMS is not generating pulses, similar to an EEG system.

  In one embodiment, the system comprises a dose monitoring module that allows an operator to adjust the dose of pulses provided by the TMS device in a subsequent treatment protocol.

  In this embodiment, the TMS device is configured to apply multiple pulses during the waiting period, where the waiting period is defined as the time between bursts of pulses according to the treatment protocol.

  In one embodiment, the plurality of pulses are individual pulses generated at random intervals, and the control means stops the operation of the EEG system during transmission of these pulses, and then immediately activates the EEG system. And configured to monitor and measure patient response.

  In one embodiment, before applying a plurality of individual pulses during the waiting period, the TMS device sends a preliminary signal to the EEG system via the control means, allowing the EEG system to activate its protection circuit. .

  In one embodiment, the control means is configured to automatically adjust the profile of the pulses generated by the TMS device and recommend an adjusted profile of the pulses that will be generated by the TMS device in subsequent treatment sessions. The

  In one embodiment, the TMS device comprises a capacitor that generates a current and thereby induces a magnetic field to provide a magnetic pulse, a coil or probe that delivers the magnetic pulse, and a high voltage charging circuit that charges the capacitor.

  In one embodiment, the TMS device is configured to generate a signal indicating when the TMS device is not active during the time when the TMS device is not charging the capacitor and send the signal to the control means.

  In one embodiment, the system comprises a navigation system that assists in positioning the TMS device.

  In one embodiment, the system is a patient-response device that induces visual, sensory, auditory or other types of stimuli for subsequent measurements when the TMS device is not generating pulses. Typically embedded in an EEG system).

  In one embodiment, the EEG system comprises an amplifier and a protection circuit designed to accommodate the high voltages and currents associated with the TMS device, and the control means is capable of activating the protection circuit before the TMS magnetic pulse. And configured to transmit a reserve signal to the EEG system.

According to a second aspect of the invention, there is provided a method of monitoring a patient's EEG (electroencephalogram) during TMS (transcranial magnetic stimulation), the method comprising:
Generating a plurality of magnetic pulses, wherein the plurality of magnetic pulses are applied to the patient's head as a burst comprising a plurality of pulses grouped together or as individual pulses according to a TMS treatment protocol. That can be applied,
Measuring EEG data resulting from a TMS treatment protocol applied to a patient, wherein the EEG data is measured during times when no magnetic pulses are being generated, and the step of measuring EEG data monitors the therapeutic effect. Applied sequentially or alternately with magnetic pulses generated according to the TMS treatment protocol so that potential seizures can be detected;
including.

  In one embodiment, the method includes generating a signal when a magnetic pulse is not generated, which further triggers measurement of EEG data.

  In one embodiment, the method includes storing measured EEG data.

  In one embodiment, prior to generating a magnetic pulse, the method includes generating a preliminary signal that further triggers storage of EEG data.

In one embodiment, the method comprises:
Measuring the spectral characteristics of spontaneous oscillatory brain activity when no magnetic pulse is generated;
Comparing the resulting measurement to an expected or desired profile so that a patient's seizure can be detected or predicted;
including.

  In one embodiment, the method includes stopping the generation of a magnetic pulse if a seizure is detected or predicted.

In one embodiment, the method comprises:
Applying a plurality of individual pulses at random intervals during times when magnetic pulses are not being generated according to the treatment protocol;
Measuring the resulting EEG data so that the operator can adjust the dose of the TMS pulse in subsequent treatment protocols;
including.

In this embodiment, the method is:
Stopping the measurement of EEG data while applying a plurality of individual pulses at random intervals;
Measuring EEG data immediately thereafter to monitor and measure patient response;
including.

  In this embodiment, the method includes automatically adjusting the profile of the pulse and / or recommending an adjusted profile of the pulse that will be generated in a subsequent treatment session.

  In one embodiment, the method includes inducing a visual type, sensory type, auditory type or other type of stimulus for subsequent EEG data measurements when a magnetic pulse is not generated according to the treatment protocol. Including.

  The present invention is described by way of example only with reference to the accompanying drawings.

1 is a high-level schematic diagram of a system for monitoring a patient's EEG (electroencephalogram) during TMS (transcranial magnetic stimulation), according to one embodiment of the present invention. FIG. FIG. 4 is a schematic diagram of a time frame of a TMS protocol and an adjacent EEG protocol for detecting a patient's seizure according to one aspect of the present invention. FIG. 4 is a schematic diagram of a time frame of a TMS protocol and an adjacent EEG protocol for dose monitoring according to a further aspect of the invention. FIG. 6 is a time frame schematic of the TMS protocol and adjacent EEG protocol for dose monitoring using intermediate random TMS pulses according to yet another aspect of the present invention. 6 is a high-level flow chart representing a method for monitoring a patient's EEG (electroencephalogram) during TMS (transcranial magnetic stimulation) according to yet another aspect of the present invention.

  Referring initially to FIGS. 1-4, a system 10 for monitoring a patient's EEG (electroencephalogram) during TMS (transcranial magnetic stimulation) is shown. The system 10 includes a TMS device 12 that generates a plurality of magnetic pulses when in an active state. Those pulses are in accordance with the TMS treatment protocol as a burst comprising a plurality of pulses grouped together, as indicated by arrows 14 in FIGS. 2-4, or as indicated by arrows 16 in FIG. Can be applied to the patient's head 18 as individual pulses.

  Based on established safety guidelines, TMS treatment protocols are often active stimuli (corresponding to arrow 14 in FIGS. 2-4) and in FIGS. 2-4 (as indicated by arrow 20). ) In combination with a long break in between. The duration of these interruptions is often longer than the duration of active stimulation, as will be demonstrated. The waiting time defined by the interruption will be used to measure diagnostic data that can be interpreted in real time and used to guide the TMS treatment protocol, as will be described in more detail later. . The usual treatment protocol used for the treatment of depression using rTMS is a 40 pulse burst delivered at 10 Hz (arrow 14 in FIGS. 2-4) followed by a 26 second waiting time (FIG. 2). To 20) in FIG. 4 and repeat until 3000 pulses are delivered.

  The system 10 further comprises an EEG system 22 that measures spontaneous EEG data associated with the TMS treatment protocol being applied to the patient. The purpose of the EEG system 22 is to monitor the patient's brain activity to extract diagnostic information during the treatment protocol, as will be described in more detail later.

  The system 10 further comprises control means 24 in communication with the TMS device 12 and the EEG system 22. The control means 24 comprises a controller 26 that activates the EEG system 22 during times when the TMS device 12 is not generating pulses, as indicated by block 28 in FIGS. In this way, EEG data measurements are applied continuously or alternated with TMS treatment so that treatment effects can be monitored and potential seizures can be detected.

  In one embodiment, the TMS device 12 generates a signal when not in an active state (ie, corresponding to an “unstimulated” event in the treatment protocol, ie, arrow 20 in FIGS. 24 to be transmitted. The control means 24 is accordingly configured to trigger the operation of the EEG system 22 when the TMS device 12 is not active.

  The system 10 can comprise storage means 30 for storing measured EEG data. In one embodiment, before the TMS device 12 applies a plurality of pulses, the TMS device 12 sends a reserve signal to the EEG system 22, which records the EEG data in the storage means 30. Used by the control means 24 to trigger

  In one embodiment, the system 10 includes a seizure monitoring module 34 (which may be embodied within the EEG system 22) that detects or predicts patient seizures. The seizure monitoring module 34 measures spectral characteristics including frequency, burst suppression and phase-locked oscillations of spontaneous oscillatory brain activity when the TMS device 12 is not generating pulses, and the resulting measurement results are Compare with expected or desired profile. In other words, module 34 matches the measured spectral characteristics with individual EEG characteristics (ie, the patient's normal pre-seizure activity) so that the effects of operation of TMS device 12 on the patient can be determined.

  The seizure monitoring module 34 communicates with the control means 24 so that if a seizure is detected or predicted, the control means 24 can stop the operation of the TMS device 12. In this application, the spectral characteristics of the measured EEG signal are quantified and recorded in the storage means 30, after which this quantified data is compared with the benchmark EEG. Typically, if pre-seizure activity is detected, the operator is notified to determine if treatment should be stopped. If seizure activity is detected, the operator is notified to stop treatment.

  In one embodiment, seizure monitoring module 34 is configured to be activated during times when TMS device 12 is not generating pulses, corresponding to block 20 of FIGS. 2-4, similar to EEG system 22. The

  In a further application, the EEG system 10 includes an amplifier 36 that amplifies the biopotential associated with brain neural activity and high voltages and currents associated with the TMS device to enable monopolar and bipolar EEG measurements. It comprises a protection circuit 38 designed to accommodate and a control unit 40 for connecting and controlling the components of the EEG system 22. The control means 24 can be configured to send a preliminary signal to the EEG system 22 before the TMS magnetic pulse is generated so that the protection circuit 38 can be activated, thereby preventing amplifier saturation.

  In one embodiment, the TMS device 12 generates a current, thereby inducing a magnetic field to provide a magnetic pulse, a coil or probe 44 that delivers the magnetic pulse, and a high voltage charge that charges the capacitor 42. A circuit 46 and a control unit 48 are provided. Capacitor 42 is charged for a few seconds and the stored energy is then released into coil 44 as a single pulse or multiple pulses.

  In one embodiment, the TMS device 12 is configured to generate and send a signal to the control means 24 that indicates when the TMS device 12 is not active during the time that the capacitor 42 is not charging. This allows the EEG system 22 to operate in an environment that is not subject to commonly known artifacts.

  Thus, in use, in one embodiment, as shown in FIGS. 2-4, the system 10 uses a treatment sequence, eg, a 10 Hz / 4 second continuous stimulus and a 26 second interval between bursts. Start. During stimulation, the EEG system 22 is switched off so that amplifier saturation can be prevented, as indicated above. After stimulation, EEG monitoring is activated in response to TMS device 12 sending a “non-stimulation” signal to EEG system 22 corresponding to the start of a waiting period. If the TMS capacitor 42 needs to be charged, the TMS device 12 sends a preliminary signal to the EEG system 22 to prevent recording during the charging procedure.

  In a further application, with specific reference to FIGS. 1, 2 and 4, the system 10 is typically embodied within the EEG system 22 and allows the operator to use pulses of TMS system 12 in subsequent treatment protocols. A dose monitoring module 50 is provided that allows the dose to be adjusted. This dose monitoring capability can be done in one of two ways, referenced in FIGS. 3 and 4 respectively.

  Referring initially to FIG. 3, applying the TMS treatment sequence as usual, ie, as described above, with a continuous stimulation of 10 Hz / 4 seconds and an interval of 26 seconds between bursts defining a waiting period. Normal treatment includes 75 such sequences. In this application, the dose monitoring module 50 of the EEG system 22 facilitates the collection of averaged EEG epochs with a reasonable signal-to-noise ratio and provides quantitative monitoring (eg, spectrum, coherence and connectivity). Configured to run.

  Referring now to FIG. 4, the TMS treatment sequence described above can be applied, i.e., a 10 Hz / 4 second continuous stimulus and a 26 second interval between bursts. Furthermore, in this application, the TMS device 12 is configured to apply a plurality of, eg 3-7, individual pulses 16 at random intervals during the waiting period 20. As described above, the waiting period 20 is defined as the time between bursts 14 of pulses from the perspective of the treatment protocol.

  The control means 24 stops the operation of the EEG system 22 during the transmission of these pulses, as indicated by the rectangular block 52 of FIGS. 2-4, and then immediately thereafter, as indicated by the block 28. 22 is configured to monitor and measure patient response.

  As described above, before applying a plurality of individual pulses 16 during the waiting period 20, the TMS device 12 sends a preliminary signal to the EEG system 22 via the control means 24, and the EEG system 22 has its protection circuit. 38 can be activated.

  In use, to extract measures of local excitability (eg, amplitude, latency, surface characteristics, etc.) and global connectivity (eg, interhemispheric conduction time, amplitude ratio, etc.) after each treatment sequence The characteristics of the induced response are quantified. At the end of the treatment session, the resulting data is stored in the storage means 30 for comparison or trend confirmation. Based on the information recorded during the treatment session, the operator can adjust the dose as needed.

  In one embodiment, the control means 24 automatically adjusts the profile of the pulses generated by the TMS device 12 and / or the adjusted profile of the pulses that will be generated by the TMS device 12 in a subsequent treatment protocol. Configured to recommend.

  In one embodiment, the system 10 includes a navigation system that assists in accurate positioning of the TMS device (ie, positioning of the coil or probe 44).

  In one embodiment, the system 10 typically includes a patient-response device 54 that is implanted within the EEG system 22 to induce visual, sensory, auditory or other types of stimuli. This stimulus is applied when TMS 12 is not generating a pulse for subsequent measurements. Again, the result of the patient's response to the induced stimulus is usually stored in the storage means 30.

  Finally, referring to FIG. 5, a method 80 for monitoring a patient's EEG during TMS will now be described. The method includes generating a plurality of magnetic pulses, as indicated by block 82, wherein the magnetic pulses are as a burst comprising a plurality of pulses grouped together or as individual pulses. It can be applied to the part. This can be done according to the TMS treatment protocol.

  The method 80 further includes measuring EEG data resulting from the TMS treatment protocol being applied to the patient, as indicated by block 84. EEG data is measured during times when no magnetic pulses are being generated, and the step of measuring EEG data is applied continuously or TMS can be monitored so that therapeutic effects can be monitored and potential seizures detected. Alternately, magnetic pulses are generated according to the treatment protocol.

  In this way, the present disclosure provides a configuration that allows spontaneous EEG and evoked responses to be measured without subjecting artifacts during a TMS treatment protocol configured by a stimulation pattern. Incorporating EEG measurements during TMS treatment or alternating with TMS treatment allows the treatment sequence to be personalized and optimized.

  The disclosed embodiments of the invention are not limited to the specific structures, process steps, or materials disclosed herein, but are extended to their equivalents as will be appreciated by those skilled in the art. I want you to understand. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

  Reference to “one embodiment” or “one embodiment” throughout this specification includes that particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment of the invention. Means that Thus, the appearances of the phrases “in one embodiment” or “in one embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment.

  As used herein, multiple articles, structural elements, compositional elements and / or materials may be presented in a common list for convenience. However, these lists should be interpreted as if each component of the list was individually identified as a separate and unique component. Thus, individual components of such lists, unless indicated to the contrary, are effectively equivalent to any other component of the same list based solely on being presented in a common group. Should not be interpreted. Moreover, various embodiments and examples of the invention may be referred to herein with alternatives to their various components. It is to be understood that such embodiments, examples, and alternatives should not be construed as substantially equivalent to each other, but should be considered separate and independent representations of the invention.

  Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are given, such as examples of lengths, widths, shapes, etc., in order to provide a thorough understanding of embodiments of the present invention. However, one skilled in the art will recognize that the invention may be practiced without using one or more of these specific details, or with other methods, components, materials, and the like. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring aspects of the invention.

  The above examples illustrate the principles of the present invention in one or more specific applications, but without the training of inventive capabilities and without departing from the principles and concepts of the present invention, It will be apparent to those skilled in the art that many changes can be made in terms of usage and details. Accordingly, the invention is not intended to be limited except as by the claims set forth below.

Claims (24)

A method of monitoring a subject's electroencephalogram (EEG) during a transcranial magnetic stimulation (TMS) session comprising:
Sending an unstimulated signal to the EEG device after a stimulation pulse from the TMS coil;
Activating the EEG device based on a no stimulus signal;
Measuring a spontaneous EEG signal from the subject;
Comparing the spontaneous EEG signal to a predetermined EEG template;
Detecting pre-seizure activity and / or seizure activity in the comparison;
A method of monitoring an electroencephalogram of a subject during a transcranial magnetic stimulation session. Measuring a spontaneous EEG signal from the subject prior to any stimulation pulse from the TMS coil;
Generating a predetermined EEG template for the subject based on an EEG signal measured prior to the stimulation;
Further including
The method of claim 1, wherein the generated predetermined EEG template is used in comparison with an EEG signal measured after a stimulation pulse.   3. The method of claim 1 or 2, wherein the predetermined EEG template includes known pre-seizure activity. Sending a stimulation signal to the EEG device before activating the TMS coil;
Stopping the operation of the EEG device based on the stimulus signal;
The method according to any one of claims 1 to 3, further comprising: Transmitting the no stimulation signal after a capacitor or capacitor bank of a TMS device connected to the TMS coil has finished charging after a stimulation pulse;
The method according to any one of claims 1 to 4, further comprising: After sending a no-stimulus signal to the EEG device, the EEG device has one or more capacitors of the TMS device connected to the TMS coil being charged after a stimulation pulse or having finished charging. Transmitting an additional signal indicating;
Activating the EEG device based on at least the no-stimulus signal and the additional signal;
The method according to any one of claims 1 to 4, further comprising: Notifying the user of the TMS coil of the presence and / or absence of detected pre-seizure activity;
The method according to any one of claims 1 to 6, further comprising: If pre-seizure activity and / or seizure activity is identified, sending a stop signal to the TMS coil device connected to the TMS coil;
Preventing TMS stimulation from the TMS coil based on the stop signal;
The method according to any one of claims 1 to 7, further comprising: Transmitting a stimulation signal to the EEG device prior to the TMS stimulation pulse;
Activating a compensation mechanism in the EEG device, preventing EEG saturation;
The method according to claim 1, further comprising:   The method of claim 9, wherein the compensation mechanism is gating. A method of monitoring transcranial magnetic stimulation (TMS) dose accumulation in a subject comprising:
Transmitting a preliminary signal to the EEG device during a waiting period after a predetermined sequence of TMS stimulation pulses;
Starting recording and averaging of the subject's evoked EEG response based on the preliminary signal;
Sending a stop signal to the EEG device prior to a subsequent predetermined sequence of TMS stimulation pulses;
Ending recording and averaging of the subject's evoked EEG response based on the stop signal; and
Determining local excitability and / or global connectivity based on the recorded and averaged evoked EEG responses during the waiting period;
Storing the determined local excitability and / or global connectivity for the waiting period;
The stored determined local excitability and / or global connectivity for the waiting period is compared to the local excitability and / or global connectivity determined for a previous waiting period. Steps,
Making adjustments to the predetermined sequence of TMS stimuli for subsequent sequences of TMS stimuli if it is determined that adjustments should be made based on the comparison;
A method of monitoring transcranial magnetic stimulation dose accumulation in a subject, comprising:   12. The method of claim 11, wherein based on the preliminary signal, the EEG initiates a compensation mechanism that prevents EEG saturation.   The method of claim 12, wherein the compensation mechanism is gating.   14. A method according to any one of claims 11 to 13, wherein the determined local excitability comprises local amplitude (s), latency, surface characteristics or a combination thereof.   15. The method according to any one of claims 11 to 14, wherein the determined global connectivity includes global conduction time, amplitude comparison between electrodes, latency or a combination thereof. Determining a local excitability and / or global connectivity extraction measure after a plurality of waiting periods;
Making adjustments to a predetermined sequence of TMS stimuli for a subsequent sequence or set of sequences of TMS stimuli based on the determined extracted measurements of local excitability and / or global connectivity When,
16. The method according to any one of claims 11 to 15, further comprising:   The method of claim 16, wherein the determined extracted measurement of the local excitability includes amplitude, latency, signal power, area under a curve characteristic, or a combination thereof.   18. A method according to claim 16 or 17, wherein the determined global connectivity includes interhemispheric conduction time and / or amplitude ratio.   19. The adjustment according to any one of claims 11 to 18, wherein the adjustments made to subsequent sequences of TMS stimulation comprise adjusting the intensity, duration, frequency and / or number of stimulation pulses, or a combination thereof. The method described.   20. The method of any one of claims 11-19, further comprising stimulating the subject at least once via a TMS coil during each waiting period.   21. The method of claim 20, further comprising stimulating the subject less than 20, preferably less than 10, more preferably 3 to 7 times during each waiting period.   A temporary or non-transitory computer readable medium storing a set of computer readable instructions for performing the method of any one of claims 1-21. A transcranial magnetic stimulation (TMS) coil device;
An electroencephalogram (EEG) device having at least one compensation mechanism to prevent EEG saturation during stimulation from the TMS coil device;
A TMS device having a processor in electronic communication with a non-transitory computer readable medium and a capacitor, the TMS device being connected to the TMS coil and communicating with the EEG device;
A system comprising:   24. The system of claim 23, wherein the non-transitory computer readable medium stores a set of computer readable instructions for performing the method of any one of claims 1-21.

Images