Transcranial alternating current stimulation (TACS)

Abstract

A method of transcranial alternating current stimulation (tACS) is provided. The method involves generating an electric current and transmitting it to two electrodes in contact with the patient's scalp to deliver a therapeutic dose of tACS for a predetermined therapeutic time. The current has a constant average amplitude of 2.2 mA and has a bidirectional square waveform with a carrier wave at frequency 15 kHz, one modulated waveform at frequency 15 Hz, and another modulated waveform at frequency 500 Hz. The current includes subbursts within a burst duration, which includes a 50 ms burst-on duration containing the subbursts and a 16.7 ms burst-off duration without subsequent subbursts. The current switches polarity after each burst duration. Each subburst includes a pulse within a subburst duration, which includes a 1 ms subburst-on duration containing the pulse and a subsequent 1 ms subburst-off duration without pulses. Each pulse extends for approximately 33.33 ps, followed by a 33.33 ps pause.

Description

Background Art

[0001] Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent. In 2020, 48 million Americans were prescribed antidepressants and 49 million were prescribed anti-anxiety medications. Further, according to the Centers for Disease Control and Prevention, the rates of clinical depression and anxiety among U.S. adults have more than tripled since the start of the COVID-19 pandemic. Boston University has reported that one in three Americans may currently be suffering from one or both disorders. Additionally, approximately 60% of GAD patients also have MDD, and nearly half of MDD patients have GAD. This high level of comorbidity favors treatments that can address both conditions simultaneously. Of the two illnesses, MDD is considered more life-threatening due to the risk of suicide, high hospitalization rates, and other chronic health conditions and disorders such as substance use disorders associated with MDD.

[0002] For decades, limited access to psychiatrists has been recognized as a public health issue for large segments of the U.S. population. The majority of clinically depressed patients treated with antidepressants receive their prescriptions from primary care physicians rather than qualified psychiatrists. However, analysis of primary care practices has shown low use of depression treatment management processes, suggesting that primary care physicians may not be adequately prepared to effectively manage depression. Some researchers have argued that depression is "significantly undertreated," especially in the primary care setting. Other researchers have argued that antidepressants may be overprescribed to patients who are more suitable for low-risk psychotherapy. Additionally, the demand for psychotherapy far exceeds the number of therapists who can care for patients in a timely manner.

[0003] Common antidepressants and psychotherapies often take weeks to show results. The American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients with Major Depressive Disorder states that psychotherapeutic techniques should produce at least moderate improvement (e.g., more than 20% symptom relief) within 4-8 weeks of treatment, and recommends that physicians emphasize to patients that 2-4 weeks of medication are necessary before beneficial effects can be observed. However, this long period to achieve symptom improvement can be problematic. In particular, a slow response to treatment can lead to poor adherence, which affects treatment success, the risk of relapse, and the cost of the illness. For example, among individuals who show poor adherence to antidepressants early on, the first 6 weeks of treatment are recognized as a particularly critical period for promoting adherence, as the risk of dropping out, relapse, discontinuation, suicide, and financial burden increases. Fear and past experiences of side effects also contribute to patients not adhering to their medication. Controlled drugs that are not commonly prescribed, such as ketamine, and electroconvulsive therapy (ECT) are fast-acting but extremely expensive to administer and often cause serious side effects.

[0004] Therefore, there is a need for a fast-acting treatment for depression that poses a low risk to patients, promotes adherence, can be self-administered, is inexpensive, and can significantly reduce anxiety. [Overview of the project]

[0005] Transcranial alternating electrical stimulation (tACS) has been investigated as an alternative treatment for depression. tACS is a form of non-invasive neurostimulation that delivers low doses of alternating current to the brain to induce neuroplasticity. Therefore, tACS has been seen as promising for the treatment of depression, as well as anxiety disorders, insomnia, and other neuropsychiatric and cognitive disorders.

[0006] tACS devices can be self-administered by patients and can be safely used as a standalone therapy or in combination with medications. Although tACS devices are regulated as medical devices, they are not complex to manufacture and are inexpensive. Importantly, there is growing scientific evidence that tACS is safer than medication and, in certain forms, has a rapid effect.

[0007] The challenges facing tACS device development are finding ways to deliver current that is simultaneously therapeutic and comfortable for the patient, while successfully maintaining blinding in sham-controlled clinical trials. If patients perceive the stimulation as unpleasant, they may avoid using the device. If clinical trial participants can easily distinguish a real device from a sham device (which appears to function normally but produces no stimulation), the trial results are not easily defended.

[0008] Embodiments of this disclosure provide systems and methods for improving tACS suitable for the treatment of depression (e.g., major depressive disorder, MDD), as well as anxiety (e.g., generalized anxiety disorder, GAD), insomnia, and other neuropsychiatric disorders and cognitive impairments. A tACS device is provided that has been demonstrated to provide therapeutically effective treatment using a rapidly pulsed alternating current (AC) output in the form of a bipolar (bidirectional) square waveform modulated to two lower frequencies with a current amplitude of 2.2 mA (+ / - 5% manufacturing tolerance), using a high carrier frequency. By conducting a large-scale randomized controlled clinical trial, it was found that this combination of amplitude, pulse rate, waveform, and frequency delivered daily to the human brain through two electrodes placed at specific locations on both sides of the head for a predetermined treatment time (e.g., about 20 minutes) twice a day (immediately after the patient wakes up and again before going to sleep) provides effective treatment for depression and anxiety. The ability to provide effective treatment with lower current amplitudes reduces or substantially eliminates the discomfort experienced by the patient.

[0009] In one embodiment, a method of transcranial alternating current (tACS) stimulation is provided. The method includes a controller including a processor that generates and transmits a current for two electrodes in contact with opposing sides of the patient's scalp to receive, thereby delivering a therapeutic dose of tACS for a predetermined therapeutic time. The generated current has a bidirectional square waveform that utilizes a carrier waveform with a constant average amplitude of about 2.2 mA and a frequency of about 15 kHz, a first modulated waveform with a frequency of about 15 Hz, and a second modulated waveform with a frequency of about 500 Hz. The generated current includes multiple subbursts within a burst duration, which includes a burst-on duration of about 50 ms containing the multiple subbursts, followed by a burst-off duration of about 16.7 ms without the multiple subbursts. The current switches polarity after each burst duration. Each subburst contains multiple pulses within its subburst duration, which includes a 1 ms subburst-on duration containing multiple pulses, followed by a subburst-off duration of approximately 1 ms without multiple pulses. Each pulse in the multiple pulses is extended for approximately 33.33 μs, followed by a pause of approximately 33.33 μs.

[0010] In another embodiment, each of the two electrodes is positioned on the scaly temporal bone superior to the posterior surface of the zygomatic arch and is maintained in place during the delivery of a therapeutic dose of tACS for the treatment of major depressive disorder (MDD) or generalized anxiety disorder (GAD). Each electrode has a diameter of approximately 36 mm. The method further includes the processor retrieving a predetermined treatment time from memory communicating with the processor, the predetermined treatment time being approximately 20 minutes. The method also includes measuring the treatment time over which the therapeutic dose of tACS is delivered to the patient, comparing the treatment time to a predetermined treatment time, and ceasing the transmission of the generated current when the elapsed time is equal to the predetermined treatment time.

[0011] In a further embodiment, the method further comprises administering a therapeutic dose of tACS to the patient twice a day for a predetermined treatment period, one dose being administered within two hours after waking from sleep and the other dose being administered within two hours before going to sleep.

[0012] In one embodiment, a method for transcranial alternating current (tACS) stimulation is provided. The method comprises arranging two electrodes in contact with opposing outer surfaces of a patient's scalp. The method further comprises generating a current by a controller including a processor. The method further comprises transmitting the generated current to the electrodes to deliver a therapeutic dose of tACS for a predetermined treatment time (e.g., about 20 minutes). The generated current has an amplitude of about 2.2 mA. The generated current further comprises a waveform including a carrier waveform having a frequency of about 15 kHz, a first modulated waveform having a frequency of about 15 Hz, and a second modulated waveform having a frequency of about 500 Hz.

[0013] In another embodiment, each of the two electrodes is positioned on the scaly temporal bone above the posterior surface of the zygomatic arch and is maintained in place during stimulation.

[0014] In another embodiment, each of the two electrodes has a diameter of approximately 36 mm.

[0015] In another embodiment, a therapeutic dose of tACS is sufficient to treat at least one of major depressive disorder (MDD) or generalized anxiety disorder (GAD).

[0016] In another embodiment, the method further includes the processor retrieving a predetermined treatment time from memory communicating with the processor. The method also includes measuring the treatment time over which a therapeutic dose of tACS is delivered to the patient. The method further includes comparing the treatment time with a predetermined treatment time. The method also includes discontinuing the delivery of the therapeutic dose of tACS to the patient when the elapsed time is equal to or greater than the predetermined treatment time.

[0017] In another embodiment, the waveform is a pulsed alternating current in the form of a bidirectional square wave.

[0018] In another embodiment, the waveform includes a plurality of first square wave subbursts having a first polarity that repeat for the duration of the burst, followed by a plurality of second square wave subbursts having a second opposite polarity that repeat for the duration of the burst.

[0019] In another embodiment, the burst duration is approximately 66.7 ms and includes an on-duration and an off-duration, the on-duration being approximately 50 ms and extending from the start of the first sub-burst of the burst duration to the end of the last sub-burst of the burst duration, and the off-duration being approximately 16.7 seconds and extending from the end of the last sub-burst of the burst duration to the end of the burst duration.

[0020] In another embodiment, each of the multiple first and second subbursts has a subburst duration extension of approximately 2 ms, and the subburst duration includes a subburst-on duration of approximately 1 ms followed by a subburst-off duration of approximately 1 ms.

[0021] In another embodiment, each of the first and second plurality of square wave subbursts includes a plurality of pulses with a pulse duration of approximately 66.7 ms, the pulse duration including a pulse-on duration of approximately 33.3 ms followed by a pulse-off duration of approximately 33.3 ms.

[0022] In one embodiment, a transcranial alternating current stimulation (tACS) device is provided. The device includes a stimulator comprising a strap and two electrodes coupled to the strap. The strap is fixed to the human head and configured to position the two electrodes in contact with opposing sides of the patient's scalp. The method also includes a controller comprising a processor. The controller is configured to electrically communicate with a plurality of electrodes and perform various operations. The controller is configured to generate an electric current. The controller is further configured to transmit the electric current to the electrodes to deliver a therapeutic dose of tACS for a predetermined treatment time. The generated current has an amplitude of about 2.2 mA. The generated current has a waveform comprising a carrier waveform having a frequency of about 15 kHz, a first modulated waveform having a frequency of about 15 Hz, and a second modulated waveform having a frequency of about 500 Hz.

[0023] In one embodiment, the strap is configured to hold two electrodes on the scaly temporal bone above the posterior surface of the zygomatic arch.

[0024] In one embodiment, each of the two electrodes has a diameter of approximately 36 mm.

[0025] In one embodiment, the controller is further configured to retrieve a predetermined treatment time from a memory communicating with the processor, measure the treatment time during which the therapeutic dose of tACS is delivered to the patient, compare the treatment time with the predetermined treatment time, and if the elapsed time is equal to or greater than the predetermined treatment time, to stop the delivery of the therapeutic dose of tACS to the patient.

[0026] In one embodiment, the waveform is a pulsed alternating current in the form of a bidirectional square wave.

[0027] In one embodiment, the waveform includes a plurality of first square wave subbursts having a first polarity that repeat for the duration of the burst, and a plurality of second square wave subbursts having a second opposite polarity that repeat for the duration of the burst.

[0028] In one embodiment, the burst duration is about 66.7 ms and includes an on duration and an off duration. The on duration is about 50 ms and extends from the start of the first sub-burst of the burst duration to the end of the last sub-burst of the burst duration. The off duration is about 16.7 ms and extends from the end of the last sub-burst of the burst duration to the end of the burst duration.

[0029] In one embodiment, each of the plurality of first sub-bursts and second sub-bursts extends for a sub-burst duration of about 2 ms, and the sub-burst duration includes a sub-burst on duration of about 1 ms and a subsequent sub-burst off duration of about 1 ms.

[0030] In one embodiment, each of the plurality of first and second square wave sub-bursts includes a plurality of pulses that extend for a pulse duration of about 66.7 ms, and the pulse duration includes a pulse on duration of about 33.3 ms and a subsequent pulse off duration of about 33.3 ms.

[0031] These and other features and advantages will become more apparent from the following detailed description taken in conjunction with the accompanying drawings.

Brief Description of the Drawings

[0032] [Figure 1] FIG. 1 shows an exemplary embodiment of a treatment environment in which a transcranial alternating current stimulation (tACS) device including a controller and a stimulation device is used to deliver electrical stimulation to a patient's head. [Figure 2A] FIG. 2 is a rear perspective view of the stimulation device of FIG. 1. [Figure 2B] FIG. 3 is a top view of the stimulation device of FIG. 1. [Figure 3A] FIG. 4 is a schematic view of the exterior of the controller of FIG. 1. [Figure 3B] ` FIG. 5 is a block diagram showing the components of the controller of FIG. 1. [Figure 4A] FIG. 6 is a schematic view of a constant current waveform generated by the controller for tACS treatment. [Figure 4B] This is a schematic diagram of the constant current waveform generated by the controller for tACS treatment. [Figure 5] Figure 1 is a flowchart illustrating a treatment method using a tACS device. [Modes for carrying out the invention]

[0033] Please note that the drawings are not necessarily to scale. The drawings are intended to depict only typical aspects of the subject matter disclosed herein and should not be considered to limit the scope of this disclosure.

[0034] As used herein, “patient” means a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, mice, monkeys, humans, livestock, game animals, and pets.

[0035] As used herein, “treating” or “treatment” of a condition, disease, or disorder, or symptoms associated with a condition, disease, or disorder, refers to a method for obtaining beneficial or desired outcomes, including clinical outcomes. Beneficial or desired clinical outcomes may include, but are not limited to, reduction or improvement of one or more symptoms or conditions, reduction of the severity of a condition, disorder, or disease, stabilization of the state of the disease, disorder, or disorder, prevention of progression of a condition, disorder, or disease, prevention of the spread of a condition, disorder, or disease, delay or slowing of the progression of a condition, disorder, or disease, delay or slowing of the onset of a condition, disorder, or disease, improvement or mitigation of the state of a condition, disorder, or disease, and remission, whether partial or complete. “Treating” may also mean inhibiting the progression of a condition, disorder, or disease, or temporarily slowing the progression of a condition, disorder, or disease. However, in some cases, treating involves permanently halting the progression of a condition, disorder, or disease.

[0036] Embodiments of systems and corresponding methods for transcranial alternating electrical stimulation (tACS) are described herein. These systems and methods can be used to treat depression (major depressive disorder), as well as anxiety and persistent sleep disorder (insomnia). However, it can be understood that embodiments of the disclosure can be used without limitation to treat other conditions.

[0037] Figure 1 shows the therapeutic environment in which a tACS device is used to treat a patient. As shown in the figure, the tACS device includes a controller that signals to the stimulator. As will be described in more detail below, the stimulator is configured to be coupled to the patient's head to deliver an electric current to the patient's brain. The controller is configured to allow the user (e.g., the patient) to control the tACS device and deliver an electric current to the electrodes with a predetermined waveform and controlled constant amplitude for a defined period (a predetermined treatment time).

[0038] Figures 2A and 2B show the stimulator in a rear view (Figure 2A) and a top view (Figure 2B). As shown, the stimulator includes a strap and a pair of electrodes mounted in electrode housings, each adjustablely fixed to the strap.

[0039] The strap may be a flexible band that forms a closed loop. In certain embodiments, the strap may be formed from an elastic material that can stretch to fit around the patient's head. In other embodiments, the strap may include an adjustment mechanism that adjusts the outer circumference of the closed loop to fit snugly to the patient's head. The adjustment mechanism may employ any form (e.g., strap adjuster, buckle, hook-and-loop fastener, strap, etc.) that allows the electrode to be securely positioned in contact with the patient at a selected location.

[0040] In one embodiment, each of a pair of electrodes may be removable from its housing. For example, the electrodes may be sponges. The sponges may have a selected diameter suitable for delivering a therapeutic dose of tACS. For example, the diameter of the electrodes may be about 36 mm (e.g., 36 mm ± 5%). When moistened with water, the sponge conducts electricity through the water. However, it can be understood that electrodes may employ other configurations that provide comparable clinical outcomes to the sponges described above without limitation. For example, the electrodes may be non-removable from the cavity and formed from a durable conductive material (e.g., a conductive polymer, a metal, etc.).

[0041] Each of the pair of electrode housings can be attached to the underside of the strap on the opposite side. As shown in the illustration, the electrode housing may include an opening that extends through it (for example, in the front-to-back direction). The opening may be sized to receive the strap through it.

[0042] In certain embodiments, the position of the receptacle relative to the strap can be adjusted. Such adjustments are beneficial in ensuring that the electrode is positioned correctly on the patient's head.

[0043] In one embodiment, this adjustment can be provided by a friction fit between the opening and the strap. For example, the thickness of the opening may be slightly less than the thickness of the strap to provide a friction fit. When sufficient sliding force is applied to overcome the friction between the electrode housing and the strap, the electrode housing can slide against the strap. When the application of sliding force is stopped, the electrode housing is held in place relative to the strap.

[0044] It can be understood that other mechanisms may be used without limitation to secure the electrode housing to the strap and to provide adjustment of the electrode housing to the strap. Examples may include, but are not limited to, reusable adhesives, hook-and-loop fasteners, snaps, etc.

[0045] Optionally, the stimulator may include a cushioning material secured to a strap at the front of the stimulator. When configured in this way, the cushioning material can come into contact with the patient's forehead when the stimulator is placed on the patient's head, improving the patient's comfort while using the stimulator.

[0046] Figures 3A and 3B show one embodiment of the controller. Figure 3A shows an external view of the controller housing, and Figure 3B is a schematic diagram of the controller's electronic circuit. As shown, the controller includes a power supply, a speaker, a constant current controller, a rotary switch, a light, a controller, and a voltage regulator. Each of these components is described in more detail below.

[0047] The power supply provides power to the entire tACS device. In one embodiment, the power supply may be one or more batteries. However, in an alternative embodiment, the controller may be configured to receive mains power after power adjustment.

[0048] The rotary switch is configured to act as a power on / off switch and to start / stop the delivery of current to electrodes for treatment. For example, by rotating it a certain amount from the off position to a first position, the tACS device is turned on and the device enters standby mode. Rotating it further to a second position delivers current to the electrodes. In one embodiment, the rotary switch may be a thumbwheel. However, other interface devices (not shown) may also be used without limitation. Examples may include, but are not limited to, buttons, sliders, and switches.

[0049] The controller may further include one or more lights (e.g., LEDs) to indicate the status of the tACS device (e.g., off, on, standby). For example, when the tACS device is on and in standby mode, one of the lights may be lit and green.

[0050] The tACS device is configured to output a constant current. This output is achieved by a constant current controller. According to Ohm's law, voltage and current are directly related to each other by the resistance of the load. In the context of the tACS device, the load is a human head. The constant current controller deals with the variation in the resistance of the human head. The constant current controller adjusts its own resistance so that the human head and the controller produce a fixed current as the output voltage. In this way, a constant current amplitude of 2.2 mA within the manufacturing tolerance (e.g., + / - 5%) can be output using a bidirectional square waveform.

[0051] A voltage regulator is an integrated circuit that provides a constant, fixed output voltage in response to a command from a controller, regardless of changes in the load or input voltage. This ensures that the power supply voltage remains within a range compatible with other electrical components of the tACS device.

[0052] The speaker is configured to provide an audio output to notify the patient / operator that a treatment session has been conducted or that there is a problem interrupting the power supply. In one embodiment, a buzzer can be used instead of the speaker.

[0053] The controller includes a processor and may include memory, or be able to electrically communicate with a memory device (not shown) and electrodes. The controller may power a light to provide visual confirmation that the tACS device is on. A voltage regulator takes power from the power supply and increases the voltage for the output circuit. The controller generates three frequencies, namely a carrier frequency and two modulation frequencies, and modulates the output using an analog switch. A constant current controller maintains the current through the output by using a resistive feedback circuit, which changes its own resistance so that a constant current output of 2.2 mA + / - 5% is maintained even when there is a difference in the output. The controller drives a speaker / buzzer to indicate the end of a treatment session.

[0054] Figures 4A and 4B are schematic diagrams of the constant current waveform generated by the controller for tACS treatment. As shown, the waveform is a pulsed alternating current in the form of a bidirectional square wave. The waveform parameters described below may vary from the stated values ​​within the manufacturing tolerance (e.g., + / - 5%).

[0055] As shown in Figure 4A, the waveform includes a plurality of first square wave subbursts with a first polarity that repeat during the burst duration, followed by a plurality of second square wave subbursts with a second opposite polarity that repeat during the burst duration.

[0056] The burst duration is approximately 66.7 ms, including the on-duration and off-duration. The on-duration is approximately 50 ms, extending from the start of the first sub-burst of the burst duration to the end of the last sub-burst of the burst duration. The off-duration is approximately 16.7 seconds, extending from the end of the last sub-burst of the burst duration to the end of the burst duration.

[0057] Each of the multiple first and second subbursts extends the subburst duration by approximately 2 ms. The subburst duration includes a subburst-on duration of approximately 1 ms followed by a subburst-off duration of approximately 1 ms.

[0058] As further shown in Figure 4B, the first and second multiple square wave subbursts contain multiple pulses with extended pulse durations. The pulse duration is approximately 66.7 ms, including a pulse-on duration of approximately 33.3 ms followed by a pulse-off duration of approximately 33.3 ms.

[0059] In the above description, the constant current waveform is generated by the controller and transmitted to the electrodes. However, in alternative embodiments, one or more circuit components of the controller may be located within the electrode housing. In certain embodiments, all circuit components of the controller may be housed within the electrode housing. The controller's lights, speakers, and switches can also be replicated on the electrode housing. Thus, the tACS device may include a stimulator that combines the functions of the stimulator and controller shown in Figure 1.

[0060] With this configuration, the user can control the tACS device in various ways. In one embodiment, a user interface device (e.g., a switch, a button, etc.) can be provided on the electrodes to control the tACS device. In another embodiment, the tACS device can be configured to communicate wirelessly with a computing device (e.g., a smartphone, a tablet, a laptop computer, a desktop computer, etc.). The computing device may run one or more programs that virtually replicate the functions of the physical components of the controller (e.g., a light, a speaker, and / or a switch such as a rotary switch).

[0061] Figure 5 shows a treatment method 500 using the tACS device of Figure 1. As shown, an embodiment of method 500 includes operations 402-416. However, it can be understood that in alternative embodiments, the method may include more or fewer operations, and the order of one or more operations may be changed.

[0062] In operation 402, the stimulator is placed on the patient's head. To minimize the risk of dermatitis caused by the electrodes, the patient's scalp and hair must be clean. The sponge electrodes must be sufficiently moistened to moisten the scalp and hair on which the electrodes are placed in contact. This ensures proper electrical contact between the electrodes and the patient's head. The wires are electrically connected to the connector at the terminals and electrically connected to the sponge electrodes.

[0063] The headband is positioned over the patient's head so that the straps are positioned above the patient's eyebrows. The moistened electrodes are inserted into electrode housings to which the wires are attached. The electrodes are then firmly slid under the headband, directly above the temples, so that the bottom of the electrodes is lower than the top of the ear behind the electrodes, rather than directly below them. The physiological location of the electrode placement is the scaly temporal bone superior to the posterior surface of the zygomatic arch.

[0064] In operation 504, once the moist sponge electrode is in place, the tACS device is turned on (e.g., by rotating the rotary switch) to generate an electric current and transmit it to the patient through the electrode to deliver a therapeutic dose of tACS to the patient. Rotate the dial from the off position to the on position. The standby light should illuminate. Further rotation of the dial generates a fixed current which is delivered to the electrode. The waveform of the generated current has the predetermined waveform described above, including the carrier frequency and two modulation frequencies. The amplitude (of the generated current) is also fixed at 2.2 mA ± 5%.

[0065] In operation 506, the microprocessor measures the amount of time elapsed since the start of delivery of the generated current (tACS therapeutic dose) to the electrodes. For example, the processor starts a timer (e.g., a 20-minute timer) simultaneously with the delivery of the generated waveform to the electrodes.

[0066] In operation 510, the controller compares the amount of time elapsed since the timer started with a predetermined treatment time (e.g., 20 minutes). The predetermined treatment time can be retrieved from memory communicating with the microprocessor. In one embodiment, the predetermined treatment time may be 20 minutes; however, in an alternative embodiment, the predetermined treatment time may be a different value.

[0067] In operation 512, the controller determines whether the elapsed time is equal to a predetermined treatment time. If they are not equal, method 500 returns to operation 506. If they are equal, the controller stops outputting the waveform to the electrodes in operation 412 and discontinues the tACS treatment.

[0068] In a further embodiment, the tACS device may be configured to determine whether treatment is interrupted. If interrupted, the timer tracking the treatment is paused and can then be restarted when treatment resumes (unless the tACS device is turned off). Furthermore, when the tACS device is turned off, the timer can be reset to a predetermined treatment time (e.g., 20 minutes).

[0069] The method may further include administering a therapeutic dose of tACS to the patient multiple times a day (e.g., twice a day) for a predetermined treatment time (e.g., 20 minutes). For example, the first treatment of the day may be administered at a predetermined time at the beginning of the patient's day, such as within two hours of waking up from sleep. The second treatment of the day may be administered at a predetermined time at the end of the patient's day, such as within two hours before going to bed.

[0070] result Trial 1 - Treatment of Major Depressive Disorder (MDD) overview A triple-blind, randomized, sham-controlled clinical trial was conducted to demonstrate the efficacy of the tACS device embodied herein for the treatment of major depressive disorder (MDD) in adults. The patient population of this study consisted of subjects who met the criteria for moderate to severe major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-DSM-5), as diagnosed by the clinical staff of the trial, including certified psychiatrists and psychiatric mental health nurses. Patients' baseline Beck Depression Rating Scale (BDI-II) scores ranged from 20 to 63 (moderate to severe).

[0071] Participants self-administered the treatment at home for four weeks, twice daily, for 20-minute treatment sessions using either a real or sham tACS device: the first time after waking up on the day of treatment, and the second time before going to bed. The primary outcome was the change in BDI-II from baseline to week 2 in a comprehensive analysis, followed by analyses of patients pre-protocol ("treatment adherence" or "use-compliant"). Secondary analyses examined changes at weeks 1 and 4, responder rates, subgroup analyses, and safety.

[0072] 255 participants were randomized to receive either active treatment or placebo treatment. 185 female and 70 male participants aged 21–65 years residing in 47 US states were enrolled. In the general population, women are treated for MDD approximately twice as often as men. In a comprehensive analysis, significantly greater improvement occurred at week 1 and a higher response at week 4 using the tACS device. Importantly, protocol-fitted analyses concluded that active tACS treatment was significantly superior to placebo treatment at all time points. Improvement was significantly greater in female participants. Side effects were reported by a small number of participants and were mild and transient.

[0073] Studies have demonstrated that the tACS devices described herein result in rapid and significant improvement of depression in adults with MDD, particularly women. Compared to other treatments for depression, tACS devices offer advantages such as rapid and clinically significant therapeutic effects, patient self-administration, and a low and minimal frequency of adverse events.

[0074] Participants were randomly assigned to receive either the active drug or a placebo (approximately 1:1). Participants, evaluators, and sponsors were all blinded to the study conditions (triple-blinded). The James Blinding Index was used to assess the extent to which participants believed they were using the active or placebo device (participant blinded). The placebo device appeared to function like the active device but produced zero electrical output. This study was conducted in accordance with the standards for conducting clinical trials of pharmaceuticals (ISO 14155-2020).

[0075] Adults who met the DSM-5 criteria for MDD, diagnosed by a study clinician, with moderate to severe severity on the Beck Depression Rating Scale (BDI-II), were eligible to participate. Eligibility was as follows: 21–65 years of age, US resident, literate in English, able to commit to a treatment protocol, no history of suicide attempts or active suicidal ideation with planned or intended in the past 30 days, no prior hospitalization for mental health disorder in the past year, no use of neuromodulators in the past year, no change in prescribed neurological medications in the past 30 days, no use of pleasure-seeking substances, hypnotics, steroids, and / or marijuana products in the past 30 days, no history of alcohol or drug abuse problems in the past 12 months, no history of mental health disorder other than MDD, no history of heart disease or trigeminal neuralgia, and no pacemaker or any form of medical electronic device. Sexually active women of potential pregnancy were required to commit to practicing at least one method of contraception during Study 1.

[0076] All data was entered into an electronic patient reporting results (ePRO) clinical trial software platform managed by the Clinical Research Organization (CRO), Climb Technologies. Potential participants completed an online pre-screening process. Eligible participants had a virtual meeting with the investigator, who discussed the trial's objectives, procedures, risks and benefits, compensation, and data confidentiality. Interested participants then electronically completed an informed consent form.

[0077] Participants began a 14-day induction period (without initiating treatment), after which they received self-report assessments and a computer-administered Mini International Neuropsychiatric Interview (MINI) again. The MINI is a primary assessment tool for mental disorders. In the study, the MINI was used in a participant self-administered format and confirmed during teletreatment visits with participants' clinicians to determine if any comorbid diagnoses might disqualify a participant from progressing to the treatment phase of the study.

[0078] To participate, participants were required to have a BDI-II score of 20–63 at both the initial pre-screening and baseline. The goal of this introductory approach was to exclude participants with transient depression, which could potentially bias the study results. Given the timing of these assessments, participants had to have experienced depression for at least one month prior to the initiation of treatment. During clinical interviews with clinicians, participants were assessed using the DSM-5 diagnostic criteria for MDD and other mental disorders, and their MINI responses were examined for final eligibility.

[0079] Eligible participants were randomized to either the active treatment group (active tACS device) or the control group (sham tACS device) by open-label study staff members who had no contact with participants and did not discuss group assignments with other members of the study team. Randomization assignments were performed sequentially. For the initial 250 randomizations required by the protocol, there were no restrictions or other inputs to determine the order of randomization. For excess randomizations beyond 250, a table was used in which the assignments between the active and sham groups were equal for every 10-person block.

[0080] The actual tACS device used by the test participants was the embodiment of the tACS device described above. The tACS device included an electrical pulse generator operated by a controller that included a processor that generated current and transmitted it to two electrodes (or sensor electrodes) in contact with the patient's scalp. The diameter of each electrode was approximately 36 mm. The actual tACS device generates a pulsed AC constant current. A third-party device test laboratory confirmed that the device generated current amplitudes between 2.1 mA and 2.2 mA, which were within ±5% of 2.2 mA. The device utilized a bidirectional square (also called rectangular) waveform with a carrier frequency of 15 kHz (+ / -5% manufacturing tolerance), a first modulation frequency of 15 Hz (+ / -5% manufacturing tolerance), and a second modulation frequency of 500 Hz (+ / -5% manufacturing tolerance). The current delivered in a series of bursts over a burst duration including an on-burst duration of 50 milliseconds and an off-burst duration of 16.7 milliseconds then switched polarity (direction). Each 50-millisecond burst contained a series of sub-bursts. Each sub-burst had a duration of 1 millisecond off-duration followed by a 1-millisecond on-duration. Each 1-millisecond sub-burst further contained multiple pulses. Each pulse had a duration of 33.33 μs (on-pulse duration) followed by a 33.33 μs pause (off-pulse duration). The actual tACS device delivered a predetermined 20-minute treatment duration, timed from memory communicating with the processor, and then automatically turned off, ending the treatment session.

[0081] Before participants began their first treatment session, research staff conducted usage training with each participant via video conference. During the training, patients assembled the device and practiced using it under the supervision of staff. Each of the two electrodes was moistened with tap water and placed on the scalp by positioning the electrodes under the headband included in the device kit. Each electrode was positioned on either side of the head, on the scaly temporal bone located posterior to the zygomatic arch. Participants were instructed to self-administer the treatment twice a day, the first time after waking up that day and the second time before going to bed, for 20 minutes each time.

[0082] Following the training session, participants were administered a standardized, validated questionnaire designed to detect the James Blinding Index, which is the success or failure of patient blinding (whether patients knew which study group they belonged to). The questionnaire asked participants what type of research device (real device or control) they thought they would receive and chose from five options to demonstrate the merits of this idea. Analysis of the James Blinding Index results determined that blinding was successful, confirming that participants could not distinguish between the real device and the fake device.

[0083] Daily after device training, participants reported whether they used the tACS device as instructed and any changes in their health status or medication. At 1, 2, and 4 weeks after treatment, participants completed measurements of clinical outcomes and reported any adverse events or changes in concomitant medications.

[0084] The Beck Depression Rating Scale, 2nd Edition (BDI-II) has been the primary tool used to assess the severity of depression. The BDI-II is a validated, widely used multiple-choice self-report scale for assessing the severity of depression. It consists of 21 items on a 4-point scale from 0 to 3, with a total score of 0 to 63. The BDI-II is commonly used in clinical research and mental health settings to assess mental disorders and is particularly useful for measuring the effectiveness of self-administered therapies.

[0085] statistical analysis The sample size for Trial 1 was based on the primary outcome metric: change in BDI-II. Sample size calculations were based on a planned sample size of 250 evaluable subjects in a 1:1 allocation. Trial 1 provided 80% power based on a two-sided, two-sample t-test with an alpha of 0.05, assuming a population mean difference of 3.2 between groups and a common standard deviation of 9. Previous data suggested a standard deviation of approximately 6.5 for improvement over two weeks, but a conservative estimate of 9 was used in these calculations.

[0086] All analyses were performed using SAS® version 9.4. The primary endpoint analysis was performed at a one-sided 0.025 alpha level, while all other analyses were based at a nominal two-sided 0.05 alpha level. Confidence intervals and p-values ​​for secondary endpoints and subgroup analyses were not adjusted for multiple comparisons. The primary analysis used an inclusive analysis (ITT) as a more conservative estimate of the treatment effect. Next, a selection analysis was performed of subjects who reported complete adherence to twice-daily treatment to determine whether the active treatment was significantly superior to the placebo treatment, assuming both participants in the active and placebo groups followed the instructions for use.

[0087] The primary efficacy endpoint was defined as the change in BDI-II score at week 2 compared to baseline in the active treatment group and the control group. Analysis was performed using a linear regression model for changes adjusted for each subject's baseline value. Missing data for the primary endpoint only were handled via multiple imputation based on fully conditional specifications using the following covariates: age, sex, baseline BDI-II, week 1 BDI-II, and available follow-up BDI. Imputation was performed separately for each treatment group. Several sensitivity analyses were performed. These were inherently supportive and used nominal confidence levels. The primary endpoint was repeated using both as-treated and per-protocol (per-use) populations. The same statistical methods used for the primary endpoint were employed. Secondary analyses were performed for PHQ-9 and QIDS-SR at week 1 and week 4, as well as at all time points, adjusted for baseline scores. Secondary analyses compared BDI-II response rates at weeks 1, 2, and 4, with response defined as a ≥50% improvement in score from baseline. Subgroup analyses of the primary endpoint were performed in the ITT analysis set by utilizing interactions between treatment groups and subgroups, defined by sex, race, and baseline BDI-II (moderate (20-28) vs. severe (29-63)). Interaction terms with p-values ​​< 0.15 were further investigated according to a pre-specified analysis plan. No adjustments were made for multiple comparisons. Exploratory analyses investigated whether concomitant use of antidepressants affected treatment outcomes.

[0088] Patient characteristics Table 1 summarizes the baseline demographic and clinical characteristics. [Table 1]

[0089] Based on baseline BDI-II scores, 32.6% and 67.5% of the sample reported moderate and severe depressive symptoms, respectively, as shown in Table 2. [Table 2]

[0090] The James blinding index (0.718, 95% CI [0.668~0.768]) indicated a lower confidence boundary above 0.5, which is considered a success in blinding. Overall, 56% and 45% in the active treatment group and the control group, respectively, did not believe they knew which treatment they were assigned. Self-reported adherence was high, with 85.1% of participants reporting two doses per day throughout the first 14 days. Broken down by group, 86.5% of subjects in the active treatment group and 83.7% in the sham group were involved in complete use throughout the 14 days. Results judgment method

[0091] Tables 3, 4, and 5 present the results for the primary and secondary effect assessment items regarding the change in BDI-II scores in protocol compliance (full device use). [Table 3] [Table 4] [Table 5]

[0092] Analysis of participants who fully adhered to the use of the device during the first 14 days showed a significantly higher BDI-II improvement with active treatment compared to controls at week 2 (difference: 3.72, p=0.005, CI[1.103~6.340]), whereas the difference between groups in the comprehensive analysis population fell just short of statistical significance by 6 / 1000 points (0.006) (difference of 2.04, one-sided p=0.056, 95% CI[-0.476~4.549]). The ITT population showed a significant effect at the secondary week 1 time point, and the effect in the protocol-adhering population was significant at all time points. These results validate that the tACS device is rapid, effective, and safe.

[0093] Finally, in the responder analysis up to week 4, the active drug treatment group showed a significantly higher responder rate than the control group not only in the protocol-compliant group but also in the ITT group, as shown in Table 6 (65.08% vs. 52.71%, p=0.045). [Table 6]

[0094] Concomitant use of antidepressants was fairly common, with 43.7% of the active treatment group and 36.4% of the placebo group reporting their use (Table 2). Within the active treatment group, there was no difference in week 2 outcomes between patients taking antidepressants and those not taking them (p=0.543).

[0095] Safety performance The number of adverse events was low. 19 subjects (15.1%) in the active treatment group reported 34 events, while 10 subjects (7.8%) in the control group reported 13 events. No serious adverse events were reported. There was only one case of AE (skin discomfort) that led to device discontinuation.

[0096] In conclusion, this study validated the use of a real tACS device as a rapid, effective, and safe treatment for major depressive disorder. Further research is needed to establish results in male patients to the same extent as this study established results in female patients.

[0097] Study 2-Anxiety Treatment The second trial was conducted to demonstrate the efficacy of the tACS device for the treatment of generalized anxiety disorder in the responders of the first trial. The tACS device used in this trial was from the same manufacturing batch as the device used in the previously summarized MDD trial. The device specifications and usage were identical. As in the MDD trial, subjects in the GAD trial were instructed to self-administer the tACS twice daily for 20 minutes, once at the beginning and once at the end of each day.

[0098] This study was a randomized, queue-controlled clinical trial. Upon eligibility, participants were randomly assigned to either the “immediate” or “delayed” group. Both groups received the actual device and identical treatment instructions. The immediate group began treatment immediately after enrollment. The queue-list (delayed) group received treatment after a programmed delay of 10 days in the shipping logistics process and up to 4 days in transit (the target was a 14-day delay). 220 participants were enrolled. A Beck Anxiety Rating Scale (BAI) score ≥ 7 was included as a patient eligibility criterion. Scores and participation were monitored in near real-time (via the CRO, Climb Technologies) and reassessed weekly. The primary endpoint was the change in BAI score from baseline to week 2, comparing the immediate and delayed treatment groups.

[0099] Study patient eligibility criteria 1) Read and write English. 2) Used by the tissue of the first reactant. 3) I have not used a "brain stimulation device" in the past year. 4) Commit to two 20-minute sessions per day for a maximum of 8 weeks, one in the morning and one in the evening. 5) Willing to wear a ReadBand actigraph and share research and data. 6) You do not have a pacemaker or electronic stent, or any other electronic implants that you do not use or regularly use for health purposes. 7) You have not started or plan to start any new medical treatment or any health program (including any new weight loss or fitness program) over the next eight weeks. 8) I have not considered suicide in the past year. 9) I have never been institutionalized due to mental health problems. 10) Not under medical supervision due to a serious medical condition (sleep apnea, restless legs syndrome, mental health problems, and / or heart disease). 11) I am not currently taking any medications that affect the nervous system (e.g., psychotropic drugs). 12) I am not allergic to nickel. 13) You are not currently participating in, or will not be participating in, any other research (including the NIJ Fatigue Study) related to insomnia, anxiety, or other mental health issues over the next 8 weeks. 14) I am not pregnant, or I do not intend to become pregnant within the next 10 weeks. 15) Baseline Beck Anxiety Rating Scale score is >7.

[0100] Participants were randomized to either an immediate treatment group, which received active medication, or a delayed treatment group, which initially waited two weeks before initiating active medication. The Beck Anxiety Rating Scale was administered to participants at enrollment, week 2, and week 4. Participants who agreed to extend treatment were observed up to week 8.

[0101] Table 7 below details the treatment status of the subjects in Study 2. [Table 7]

[0102] A total of 358 subjects were screened for the trial, of which 220 met the eligibility criteria. Eligible subjects were randomly assigned equally to two groups (110 in each). In the immediate group, 105 subjects (95.5%) received treatment, and in the delayed group, 95 subjects (86.4%) received treatment. At week 4, 28 subjects (26.7%) in the immediate group and 25 subjects (26.3%) in the delayed group lost track of time. Six subjects (5.7%) in the immediate group and seven subjects (7.4%) in the delayed group voluntarily dropped out. Two subjects (1.9%) dropped out of the immediate group due to side effects, and one subject (1.1%) dropped out of the delayed group for the same reason. Of the treated subjects, 50 (47.6%) in the immediate treatment group indicated their intention to continue beyond week 4, and 51 (53.7%) in the delayed treatment group indicated their intention to continue further.

[0103] Table 8 shows descriptive statistics of subject characteristics in the two groups. [Table 8]

[0104] The mean age of subjects in the immediate group was 42.39 years (SD: 9.49 years), and the mean age of subjects in the delayed group was 43.52 years (SD: 9.85 years). The mean difference was not statistically significant (p=0.388). Regarding gender, 66.4% of the immediate group were male compared to 49.1% in the delayed group, and the proportion of females was lower in the immediate group (33.6%) compared to the delayed group (50.9%). The gender distribution differed significantly between the two groups, as indicated by a p-value of 0.009. The overall mean height of subjects in the immediate group was 69.45 inches (SD: 4.14 inches), and the overall mean height of subjects in the delayed group was 68.07 inches (SD: 4.15 inches). The mean difference was statistically significant with a p-value of 0.015. The mean weight of subjects in the immediate group was 197.90 pounds (SD: 48.67 pounds), while in the delayed group it was 187.48 pounds (SD: 44.05 pounds). The difference in mean weight was not statistically significant (p=0.097).

[0105] Table 9 shows descriptive statistics of Beck Anxiety Rating Scale (BAI) scores in two groups at different time points. [Table 9]

[0106] At baseline, the parameters violated the normality assumption by the Shapiro-Wilk test, so nonparametric assessments were performed to compare scores between the two groups. At baseline, the mean BAI score in the immediate group was 20.14 (SD: 10.45) with a median of 19, and the mean BAI score in the delayed group was 19.80 (SD: 9.40) with a median of 18. The difference in median scores was not statistically significant (p=0.905). At week 2, the mean BAI in the immediate group was 12.79 (SD: 7.86) with a median of 11, and in the delayed group, the mean was 19.24 (SD: 9.29) with a median of 18. The difference in median BAI scores between the two groups at week 2 was statistically significant (p<0.001). Furthermore, in week 4, the mean for the immediate group was 10.64 (SD: 6.93) and the median was 10, while the mean for the delayed group was 13.08 (SD: 7.10) and the median was 11. The difference in medians was statistically significant, with a p-value of 0.024.

[0107] Table 10 provides descriptive statistics on the change in BAI scores from baseline to week 2. [Table 10]

[0108] Comparing the changes in scores, it was found that in week 2, the mean change in score in the immediate group was 6.33 (SD: 7.83) and the median was 5, while in the delayed group, the mean change in score was 0.38 (SD: 7.67) and the median was 0. The difference in median scores between the groups was statistically significant, with p<0.001.

[0109] Table 11 is a cross-tabulation showing the frequency of subjects in each BAI category at baseline and at week 2 for the immediate response group. [Table 11]

[0110] At baseline, 54 participants (66.7%) were in the low category, of which 53 remained in the low category at week 2, while one moved to the moderate category. At baseline, 20 participants (24.7%) were in the moderate category, of which 13 moved to the low category and 7 remained in the moderate category. Furthermore, of the 7 participants (8.6%) in the severe category at baseline, 4 moved to the low category, 2 moved to the moderate category, and 1 remained in the severe category. At week 2, 70 participants (86.4%) were in the low category, 10 (12.3%) were in the moderate category, and 1 (1.2%) was in the severe category.

[0111] The marginal distribution changed significantly from baseline to week 2, with a significantly higher proportion of subjects in the lower category at week 2 compared to baseline, as indicated by p<0.001.

[0112] Table 12 is a cross-tabulation showing the frequency of subjects in each BAI category at baseline and at week 2 for the postponement group. [Table 12]

[0113] At baseline, 53 participants (60.9%) were in the low category, of which 46 remained in the low category in week 2, 6 moved to the moderate category, and 1 moved to the severe category. At baseline, 28 participants (32.2%) were in the moderate category, of which 7 moved to the low category, 18 remained in the moderate category, and 3 moved to the severe category. Furthermore, of the 6 participants (6.9%) in the severe category at baseline, 2 moved to the low category, 3 moved to the moderate category, and 1 remained in the severe category. At week 2, 55 participants (63.2%) were in the low category, 27 (31.0%) were in the moderate category, and 5 (5.7%) were in the severe category. The marginal distribution did not change significantly from baseline to week 2 in the postponement group (p=0.590).

[0114] An intention to continue beyond four weeks was indicated by 53 subjects from the immediate group and 50 subjects from the delayed group. Therefore, a subset analysis was performed on these subjects, and parameters were compared between the two groups at week 8, as shown in Table 13. [Table 13]

[0115] Table 13 reveals that the BAI score demonstrated a median / mean difference between the two groups at week 8 (p>0.05). The BAI score at week 8 in the immediate group was significantly lower than that of the delayed group (p=0.010).

[0116] Therefore, this study aims to achieve its primary endpoint and validate the tACS device as a rapid and effective treatment for generalized anxiety disorder (GAD).

[0117] Comparative study - Deeming 1 mA of tACS unsuitable as a therapeutic dose. In 2015, the MDD study conducted at Harvard Medical School concluded that administering patients only 1 mA once daily, five days a week, using an earlier version of a tACS device that generated an average amplitude of 1 mA (half the amplitude of tACS as embodied herein), was ineffective. The following is a summary of the study.

[0118] We investigated the efficacy and safety of a single, specific cranial electrical stimulation (CES) device in a fixed setting in patients with treatment-resistant major depressive disorder (MDD). Thirty subjects (57% female, mean age 48.1 ± 12.3 years) with MDD and inadequate response to standard antidepressants were randomized to a 3-week treatment with either CES (15 / 500 / 15,000 Hz, 1–4 mAmp, 40 V symmetrical rectangular bipolar current) or sham CES (device off) for 20 minutes, 5 days a week. The primary outcome measure was improvement on the 17-item Hamilton Depression Rating Scale (HAM-D-17). Adverse events (AEs) were assessed using the Patient-Related Adverse Event Assessment (PRISE). Completion rates were 88% with CES and 100% with sham. Both treatment groups showed an improvement of approximately 3–5 points on the HAM-D-17 score. The effects were demonstrated (p<0.05 in both groups), and no significant difference was observed between the groups. The remission rate was 12% in the CES group and 15% in the sham group, with no significant difference. CES was considered safe and well-tolerated. Decreased concentration and fatigue were the only distressing AEs that differed significantly between CES and sham (p=0.019 and p=0.043, respectively). Limitations include the small sample size and the lack of actual comparator drug therapy. Although both treatment groups showed significant improvement, this CES in the selected setting did not isolate it from the sham in this sample. Therefore, it cannot be ruled out that the benefit of this setting used with this particular form of CES was due to the placebo effect. Since this form of CES has other settings, future studies should test these settings and compare them with other CES devices. In conclusion, this comparative study deems 1 mA tACS administered twice daily, five days a week, unsuitable for the treatment of MDD. The MDD and GAD studies summarized above validated the use of embodiments of the tACS device embodied herein, using a target mean amplitude of 2.2 mA (+ / - 5% manufacturing tolerance) and treatment twice daily, seven days a week.

[0119] To provide an overall understanding of the structural, functional, manufacturing, and specification principles of the systems, devices, and methods disclosed herein, certain exemplary embodiments have been described. One or more examples of these embodiments are shown in the accompanying drawings. Those skilled in the art will understand that the systems, devices, and methods specifically described herein and shown in the accompanying drawings are non-limiting exemplary embodiments, and that the scope of the invention is defined solely by the claims. Features illustrated or described in relation to one exemplary embodiment may be combined with features of other embodiments. Such modifications and variations are intended to fall within the scope of the invention. Furthermore, in this disclosure, components with similar names in embodiments generally have similar features, and therefore, each feature of each component with a similar name within a particular embodiment is not necessarily fully detailed.

[0120] The subject matter described herein can be implemented in analog electronic circuits, digital electronic circuits, and / or computer software, firmware, or hardware, or in combination thereof, including the structural means disclosed herein and their structural equivalents. The subject matter described herein can be implemented as one or more computer program products, e.g., one or more computer programs embodied in tangible form on an information carrier (e.g., a machine-readable memory device) or embodied in propagating signals, for execution by or control of a data processing device (e.g., a programmable processor, computer, or multiple computers). A computer program (also known as a program, module, engine, software, software application, or code) can be written in any form of programming language, including compiled or interpreted languages, and a computer program can be deployed in any form, including as a standalone program or as modules, components, subroutines, or other units suitable for use in a computing environment. A computer program does not necessarily correspond to a file. A program can be stored in part of a file that holds other programs or data, in a single file dedicated to the program itself, or in multiple collaborative files (for example, a file containing one or more modules, subprograms, or sections of code). A computer program can be deployed to run on a single computer, or on multiple computers located in one location or distributed across multiple locations and interconnected by a communication network.

[0121] The processes and logic flows described herein, including the method steps of the subject matter described herein, can be executed by one or more programmable processors that execute one or more computer programs to perform the functions of the subject matter described herein by acting on input data and producing outputs. The processors and logic flows can also be executed by dedicated logic circuits, such as FPGAs (Field-Programmable Gate Arrays) or ASICs (Application-Specific Integrated Circuits), and the devices of the subject matter described herein can be implemented as such dedicated logic circuits.

[0122] Processors suitable for executing computer programs may include, for example, both general-purpose microprocessors and special-purpose microprocessors, as well as any one or more processors of any type of digital computer. Generally, processors receive instructions and data from read-only memory (ROM) or random-access memory (RAM), or both. Essential elements of a computer are a processor for executing instructions and one or more memory devices for storing instructions and data. Generally, a computer includes, for example, one or more mass storage devices for storing data, such as magnetic disks, magneto-optical disks, or optical disks, or is operablely coupled for receiving data from or transmitting data to mass storage devices, or both. Suitable information carriers for embodying computer program instructions and data include all forms of non-volatile memory, including, for example, semiconductor memory devices (e.g., EPROM, EEPROM, and flash memory devices), magnetic disks (e.g., internal hard disks or removable disks), magneto-optical disks, and optical disks (e.g., CDs and DVDs). Processors and memory may be supplemented by or incorporated into dedicated logic circuits.

[0123] To provide user interaction, the subject matter described herein can be implemented on a computer having a display device for displaying information to the user, such as a CRT (cathode ray tube) or LCD (liquid crystal display) monitor, as well as a keyboard and pointing device (e.g., mouse or trackball) through which the user can provide computer input. Other types of devices can also be used to provide user interaction. For example, the feedback provided to the user may be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback), and user input may be received in any form, including acoustic, verbal, or tactile input.

[0124] The technologies described herein can be implemented using one or more modules. As used herein, the term “module” refers to computing software, firmware, hardware, and / or various combinations thereof. However, at the very least, a module should not be interpreted as software that is not implemented in hardware or firmware, or recorded on a non-temporary processor-readable recordable storage medium (i.e., a module is not software in itself). In practice, a “module” should always be interpreted as including at least some physical, non-temporary hardware, such as a processor or part of a computer. Two different modules can share the same physical hardware (for example, two different modules can use the same processor and network interface). The modules described herein can be combined, integrated, separated, and / or duplicated to support various applications. Furthermore, functions described herein as being performed in a particular module can be performed in place of, or in addition to, functions performed in a particular module by one or more other modules and / or one or more other devices. In addition, modules can be implemented across multiple devices and / or other components, local or remote to each other. Furthermore, modules can be moved from one device to another, added to another device, and / or included in both devices.

[0125] As used herein and throughout the claims, approximate terms can be applied to modify any quantitative expression that may vary within an acceptable range without altering the fundamental function to which it relates. Thus, values ​​modified with one or more terms such as “about,” “approximately,” and “substantially” should not be limited to the exact value specified. In at least some examples, approximate terms may correspond to the precision of an instrument used to measure a value or manufacturing tolerance. For example, a specified value may vary by ±10%, ±9%, ±8%, ±7%, ±6%, ±5%, ±4%, ±3%, ±2%, ±1%, 0.9%, ±0.8%, ±0.7%, ±0.6%, ±0.5%, ±0.4%, ±0.3%, ±0.2%, ±0.1%. For example, a manufacturing tolerance may be ±5%. Herein, and throughout this specification and the claims, any limitations on scope may be combined and / or interchangeable, such scopes being specified and including all partial scopes contained therein unless otherwise indicated by the context or word.

[0126] Those skilled in the art will understand further features and advantages of the present invention based on the embodiments described above. Therefore, this application should not be limited by what is specifically shown and described, except as indicated by the appended claims. All publications and references cited herein are expressly incorporated by their entirety.

Claims

1. A method of transcranial alternating current (tACS) stimulation, A controller including a processor generates and transmits an electric current to be received by two electrodes in contact with opposing sides of the patient's scalp, thereby delivering a therapeutic dose of tACS for a predetermined treatment time. Includes, The generated current has a constant average amplitude of approximately 2.2 mA and has a bidirectional square waveform utilizing a carrier waveform with a frequency of approximately 15 kHz, a first modulated waveform with a frequency of approximately 15 Hz, and a second modulated waveform with a frequency of approximately 500 Hz. The generated current includes a plurality of sub-bursts within the burst duration, the burst duration including a burst-on duration of approximately 50 ms including the plurality of sub-bursts, and a subsequent burst-off duration of approximately 16.7 ms without the plurality of sub-bursts. The current switches polarity after each burst duration. Each subburst includes multiple pulses within its subburst duration, the subburst duration including a 1 ms subburst-on duration containing the multiple pulses, and a subsequent subburst-off duration of approximately 1 ms without the multiple pulses. Each of the aforementioned multiple pulses extends for approximately 33.33 μs, followed by a pause of approximately 33.33 μs. The aforementioned method.

2. Each of the two electrodes is positioned on the scaly temporal bone superior to the posterior surface of the zygomatic arch and is maintained in place during the delivery of the therapeutic dose of tACS for the treatment of major depressive disorder (MDD) or generalized anxiety disorder (GAD). Each of the electrodes has a diameter of approximately 36 mm. The process involves the processor retrieving the predetermined treatment time from the memory communicating with the processor, wherein the predetermined treatment time is approximately 20 minutes, and the retrieval process is as follows: The treatment time at which the aforementioned therapeutic dose of tACS is delivered to the patient is measured, Comparing the aforementioned treatment time with the aforementioned predetermined treatment time, When the elapsed time is equal to the predetermined treatment time, the transmission of the generated current is stopped. The method according to claim 1, further comprising:

3. The method according to claim 2, further comprising administering the therapeutic dose of tACS to the patient twice a day during the predetermined treatment time, wherein one administration is performed within two hours after waking from sleep and the other administration is performed within two hours before going to sleep.

Images