WO2023107024A1

WO2023107024A1 - Gamma frequency entrainment technique application device for the treatment of alzheimer's disease

Info

Publication number: WO2023107024A1
Application number: PCT/TR2021/051582
Authority: WO
Inventors: Bahar GÜNTEKİN; Mehmet Kemal Özdemi̇r; Furkan ERDAL; Zehra Betül KUZU; Mehmet Berke İŞLER
Original assignee: Istanbul Medipol Universitesi Teknoloji Transfer Ofisi Anonim Sirketi
Priority date: 2021-12-08
Filing date: 2021-12-29
Publication date: 2023-06-15

Abstract

A device enabling the Gamma frequency entrainment technique for the treatment of Alzheimer's disease to be used individually in scientific research and clinical applications, and to apply different frequencies at the same time, characterized in that; it comprises LED lights (1) placed in the eyewear apparatus (2) and/or monitor display (3) and partly connected to the first processor (9.1) and partly connected to the second processor (9.2) and providing light stimulation to the user, Buzzers (6) placed in the headphones (4) and/or speaker (5) and partly connected to the first processor (9.1) and partly connected to the second processor (9.2) and providing sound stimulus to the user, Electrodes (7), partly connected to the first processor (9.1) and partly connected to the second processor (9.2) and providing somatosensory stimulation to the user, A first processor (9.1) and a second processor (9.2) that enable the LED lights (1), buzzers (6) and electrodes (7) they are connected to give frequency and intensity stimuli of different sizes, Digital display (12) that enables the management of the frequency and intensity settings of the processes and stimuli, Buttons (13) for adjusting the frequency and intensity of the stimuli.

Description

GAMMA FREQUENCY ENTRAINMENT TECHNIQUE APPLICATION DEVICE FOR THE TREATMENT OF ALZHEIMER’S DISEASE

Technical Field of the Invention

The invention relates to a device that enables the use of the Gamma frequency entrainment technique for the treatment of Alzheimer’s disease in scientific research and clinical applications with personalized methods and allows applying different frequencies at the same time.

State of the Art of the Invention

Today, Alzheimer’s disease is a common disease that cannot be definitively cured and many people suffer from it. Many studies are conducted for the treatment of Alzheimer’s disease. One of these studies is Gamma 40 Hz Frequency entrainment application; with LED light application given in the gamma frequency band in studies conducted on Alzheimer model mice, showed an improvement at the molecular level in the diseases of Alzheimer model mice (laccarino et al., 2016). Similarly, this improvement at the molecular level was supported by signs of improvement in the behavior of mice (Martorell et al., 2019). Specifically, it was observed that the application at the gamma frequency of 40 Hz had a higher improvement compared to 60 and 80 Hz. In addition, it was observed that the sound stimulation at the same frequency increased the healing effect with the application of LED light, when they were applied together. It is thought that the application of 40 Hz LED light and sound may have a potential therapeutic effect for Alzheimer’s patients in light of these findings in animal models. Gamma Frequency Entrainment applications used in studies conducted with Alzheimer’ s patients so far are performed by giving 40 Hz gamma frequency with LED lights and sound by means of an eyewear apparatus. However, the gamma frequency band is not limited to 40 Hz, it is also possible to give stimuli in the gamma frequency band at different frequencies. It is not yet known at which frequency the effect of this application will be the highest. LED Light was applied 2 hours a day for 10 days, but the healing effect was not seen as in animals in a study conducted with Alzheimer’s patients (Ismail, et al., 2018). Accordingly, researchers have stated that longer periods of time should be applied in order to see the effect of LED light application on humans. The disadvantages of the current solutions are the application of light and sound for a very long time and the focus on 40 Hz frequency since it is not yet known at which frequency the highest effect will be seen in the 28-48 Hz band. It is possible to trigger two different frequencies in the brain at the same time by giving the stimuli to be given at the same frequency, not at a single frequency apart from that. For example, it is known that the increase in Theta (4-7 Hz) -Gamma (28-48 Hz) coupling in the signals released in the brain is related to cognitive functions. Cognitive functions can be increased by applying 4 Hz theta and 40 Hz gamma at the same time with the planned device. The device according to the invention can provide personalized signals at the natural frequencies of the brain, delta (0.5-3.5 Hz), theta (4-7 Hz), alpha (8-13 Hz), beta (15-28 Hz), gamma (28-48 Hz), and thus enable these frequencies to be revealed in the brain. The application of two different frequencies at the same time has the potential to strengthen the therapeutic effect. The device according to the invention can be stimulated in different frequency bands, not in a single gamma frequency band. It will also be possible to perform stimulation at two different frequencies at the same time as an innovative approach.

The abstract of the application numbered 2013/06441 that emerged as a result of technical research is as follows: “The present invention relates to compositions and methods for the treatment of Alzheimer’s disease and related disorders. In particular, the invention relates to combined therapies that modulate cell stress responses for treating the disease in question.”

The invention relates to some therapeutic approaches, and it does not mention an embodiment that can provide a solution to the disadvantages mentioned above, as can be seen.

In conclusion, it was deemed necessary to make an improvement in the relevant technical field due to the disadvantages described above and the inadequacy of the existing solutions on the subject.

The Object of the Invention

The object of the invention is to provide a structure having different technical features that are novel in this field, different from the embodiments used in the known state of art. The invention is a modulation device that can be used in laboratories conducting research in the field of electrophysiology. It can be used in laboratories that conduct studies, especially for Alzheimer’s patients. It can also be used for therapeutic purposes in patients with Alzheimer’s disease with the guidance of a physician following that.

The primary object of the invention is to provide therapeutic effects in the use of the device with the guidance of a doctor, especially in Alzheimer’s disease, by frequency entrainment with visual, auditory and somatosensory stimuli in scientific research.

It is possible to apply the highest effective frequency since the frequency at which the light, sound, and somatosensory stimuli will be given will be determined by the researcher or the doctor in the device of the invention. Individual-specific research methods or treatment processes can be developed in this sense. In addition, some hardware added features allow different frequencies to be applied at the same time.

The frequency to be given is determined by the person who will use the device and the light, sound, and somatosensory stimuli at different frequencies can be produced at the same time with the invention. It is one of the advantages of providing individual-specific applications in use in scientific research and clinical use in this sense. The fact that different frequencies can be applied at the same time provides a great advantage in terms of investigating the relationship between these frequencies and the effects they create in the person.

The invention is a device enabling the Gamma frequency entrainment technique for the treatment of Alzheimer’s disease to be used individually in scientific research and clinical applications, and to apply different frequencies at the same time, in order to achieve the objects described above, characterized in that; it comprises the following:

• LED lights placed in the eyewear apparatus and/or monitor display and partly connected to the first processor and partly connected to the second processor and providing light stimulation to the user,

• Buzzers placed in the headphones and/or speaker, partly connected to the first processor and partly connected to the second processor and providing sound stimulus to the user,

• Electrodes, partly connected to the first processor and partly connected to the second processor and providing somatosensory stimulation to the user, • The first processor and the second processor that enables the LED lights, buzzers, and electrodes they are connected to give frequency and intensity stimuli of different sizes,

• Digital display that enables the management of the frequency and intensity settings of the processes and stimuli,

• Buttons for adjusting the frequency and intensity of the stimuli.

The structural and characteristic features and all the advantages of the invention will be understood more clearly by means of the figures and the detailed description with reference to these figures given below and therefore, the evaluation should be made by taking these figures and the detailed description into consideration.

Figures for Understanding of the Invention

Figure 1 is the illustration of the device together with the eyewear apparatus, the headphones, and the electrode.

Figure 2 shows the inner side of the eyewear apparatus.

Figure 3 shows the inner side of the headphones.

Figure 4 is the illustration of the monitor screen.

Figure 5 is the illustration of the speakers.

The drawings are not necessarily drawn to scale and details that are not necessary for the understanding of the present invention may be omitted. In addition, elements that are substantially identical or have substantially identical functions are denoted by the same reference signs.

Description of the Part References

1 LED light

1.1 LED light connected to the first processor

1.2 LED light connected to the second processor

2 Eyewear apparatus

2.1 Eyewear inner glass

3 Monitor Display

4 Headphones 5 Speaker

5.1 Left speaker

5.2 Right speaker

6 Buzzer

6.1 Buzzer connected to the first processor

6.2 Buzzer connected to the second processor

7 Electrode

7.1 Electrode connected to the first processor

7.2 Electrode connected to the second processor

8 Resistance

9.1 First processor

9.2 Second processor

10 Battery

11 Charging apparatus

12 Digital display

12.1 Protective container

13 Button

13.1 First processor frequency adjustment button

13.2 Second processor frequency adjustment button

13.3 Electrode intensity adjustment button

13.4 Sound adjustment button

13.5 Light adj ustment button

14 Cable

A. LED 1 - 12.5 ms - 40 Hz

B. LED 2 - 125 ms - 4 Hz

C. SOUND 1 - 12.5 ms - 40 Hz

D. SOUND 2 - 125 ms - 4 Hz

E. ELECTRODE 1 - 12.5 ms - 40 Hz

F. ELECTRODE 2 - 125 ms - 4 Hz

Detailed Description of the Invention The preferred embodiments of the invention are merely described for a better understanding of the subject matter and without any limiting effect in this detailed description.

The eyewear apparatus (2), in which strip LED lights (1) are positioned, is used in the system subject to the invention. The eyewear apparatus (2) is designed to be comfortable and as light as possible so that the people who will use the device can wear it for a long time. Alternatively, to the eyewear apparatus (2), a monitor display (3) on which the LED lights (1) are positioned can also be used.

Two processors (9.1, 9.2) are used in the system subject to the invention. Said processors (9.1, 9.2) allow the frequency and intensity settings to be made. Arduino Nano is preferably used as the processor. However, microprocessor, fpga and other processor platforms can also be used.

The LED lights (1), which are positioned in the eyewear apparatus (2) or the monitor display (3), are used to create visual stimulation in the user. It is ensured that light stimuli are given at certain frequencies by flashing with the circuit to be installed with the processors (9.1, 9.2) at a certain interval. The strip LED lights (1) are placed inside of the eyewear apparatus (2) and covered with a transparent protective cover. The connection with the circuit is provided with the help of a protected cable (14) that will come out of the eyewear. Two different strips LED lights (1) are individually connected to the first processor (9.1) and the second processor (9.2).

The headphones (4) in the system of the invention are used to create a sound stimulation to the user’s ear. 4 buzzers (6) are preferably positioned in the headphones (4). It will be ensured that the circuit to be installed with the processors (9.1, 9.2) gives the sound at a certain interval and ends it. The first processor (9.1) controls the buzzer (6.1) connected to the first processor, and the second processor (9.2) controls the buzzer (6.2) connected to the second processor. Headphones (4) are preferred as the kind of over-ear headphones that people can easily wear. Speakers (5) are also used as an alternative to headphones (4). The first processor (9.1) and the second processor (9.2) are connected to both the left speaker (5.1) and the right speaker (5.2). It is ensured that the processors (9.1, 9.2) give sound at two different frequencies from the buzzers (6) in the two speakers (5.1, 5.2).

Said buzzers (6) and LED lights (1) are connected to the same processors (9.1, 9.2). LED lights (1) and buzzers (6) are turned on and off at the same time in this way. Thus, their frequencies are the same. The connection of the buzzers (6) and the LED lights (1) with the processors (9.1, 9.2) is provided by the cables (14) in the cover protected box on which the digital display (12) is located.

Preferably four large head electrodes (7) with fixing apparatus are used to create a somatosensory stimulus in the user in the system of the invention. Two of these electrodes (7) are electrodes (7.1) connected to a first processor, while the other two are electrodes (7.2) connected to a second processor. It is ensured that stimuli are produced at two different frequencies from two processors (9.1, 9.2) at the same time in this way. One electrode (7) is the electrode to which the stimulus is transmitted, while the other electrode (7) is the reference electrode in each of the pairs of electrodes. The current to be generated by the processors (9.1, 9.2) is transferred between the stimulating electrode (7) and the reference electrode (7) and the somatosensory stimulus is created.

Resistances (8) are used in the installation of the circuits of the processors (9.1, 9.2). The resistances (8) are located in the cover protected structure. There is a rechargeable battery (10) to power the circuits of the processors (9.1, 9.2). The battery (10) is charged by the charging apparatus (11).

The management of the frequency and intensity settings of the processes and stimuli is provided through the digital display (12). The digital display (12) is connected to the circuit to be used to control the processors (9.1, 9.2) that are encoded in such a way that the frequency can be adjusted. The digital display (12) is disposed on the cover protected box so that the connection places remain in the inner part.

The buttons (13) on which the intensity of the light, sound, and somatosensory stimuli can be adjusted are placed on the cover protected box and connected to the processor (9.1, 9.2) circuits. The first processor frequency adjustment button (13.1) and second processor frequency adjustment button (13.2) enable frequency adjustment. The electrode intensity adjustment button (13.3) allows you to adjust the intensity of the somatosensory stimuli, the sound adjustment button (13.4) adjusts the sound intensity, and the light adjustment button (13.5) adjusts the intensity of the LED lights (1).

The device according to the invention operates as a closed system by supplying current to the circuits through the battery (10). The visible light, the audible sound, and the sensed somatosensory stimulus can be changed by means of the adjustment buttons (13.3, 13.4, 13.5). In addition, it is numerically written at what frequencies the light is given from two different strip LED lights (1) on the digital display (12) on the cover protected box. The frequencies applied by the buttons (13.1, 13.2) can be changed. After the people install the eyewear apparatus (2) and the headphones (4), they start the application by operating the circuit.

The operation principle of the device subject to the invention is as follows;

First, an electrical circuit is established with the cables (14), two processors (9.1, 9.2) (preferably Arduino Nano), the resistances 8, and the rechargeable battery (10). The two processors (9.1, 9.2) in this circuit are first connected to the digital display (12) through the cables (14). Afterward, the processors (9.1, 9.2) are encoded on the computer to keep the circuit open for a certain millisecond and closed for a certain millisecond. After this stage, the information that the two different processors (9.1, 9.2) will keep the circuit open and closed for which milliseconds are set to appear on the digital display (12) in both milliseconds and frequency response. In other words, this information is reflected on the digital display (12), with which millisecond the processor (9.1, 9.2) is encoded. The user can see at which frequency the stimulation will be given through this digital display (12). An interface program that can be reflected on the digital display (12) is encoded for the two processors (9.1, 9.2) in the next uses of the device so that this frequency can be adjusted directly through the digital display (12). The user can see and change how many milliseconds the two different processors (9.1, 9.2) keep the circuit open and closed for how many milliseconds through this program. Further, it can also be seen which frequency these milliseconds correspond to at the same time. After this stage, the buzzers (6) to be used to provide auditory stimulation, the LED lights (1) to be used to provide visual stimulation and the large head electrodes (7) to be used to provide somatosensory stimulation are connected to the two different processors (9.1, 9.2) through the cables (14). When the circuit is powered by this connection, the buzzers (6) make a sound and stop at the frequency shown on the digital display (12), the LED lights (1) flash at the frequency shown on the digital display (12), and the large head electrodes (7) give an electrical stimulation at the frequency shown on the digital display (12) and turn it off. Afterward, the buzzers (6) are connected to the headphones (4) and the sound is prevented from being released to the outside environment. Two of the buzzers (6), which will be 4 in total, are connected to the first processor (9.1) and are placed on the right and left side of the headphone, while the remaining two are placed on the right and left side of the headphones in connection with the second processor (9.2). There are two buzzers (6) in each of the right and left ears that are connected to the two processors (9.1, 9.2) in this way. However, both speakers (5) are set to be connected to the buzzers (6) and can be used as an alternative to the headphones (4) when necessary.

The LED lights (1), which provide visual stimulation, are also divided into two parts as in the auditory stimulus. Half of the LED lights are connected to the first processor (9.1) and the other half are connected to the second processor (9.2). The LED lights (1) are then placed in the eyewear apparatus (2) in such a way that they are in the eyes of the person who will attach the eyewear apparatus (2). However, half of the LED lights (1) connected to the first processor (9.1) are in the right eye and the other half are in the left eye. The same is true for the LED light (1) connected to the second processor (9.2). In other words, there are LED lights (1) in the right eye and in the left eye of the eyewear apparatus (2), which provide visual stimulation from both processors (9.1, 9.2). Thus, both eyes are exposed to visual stimuli at two different stimulation frequencies at the same time. A monitor display (3) is also prepared by using LED lights (1) within the framework of the same logic. Half of the LED lights (1) are connected to the first processor (9.1) and the other two are connected to the processor (9.2). The LED lights (1) connected to these two different circuits are placed in the grid model on the monitor display (3). In other words, a LED light (1) connected to the first processor (9.1), then a LED light (1) connected to the second processor (9.2), and then again a LED light (1) connected to the first processor (9.1) are placed on the monitor display (3). Two of the large-headed electrodes (7) that provide somatosensory stimulation are connected to the first processor (9.1) and the other two are connected to the second processor (9.2). The electrodes (7) can be placed on the skin surface of the person to be used and are exposed to two different excitation frequencies at the same time thanks to the fixing apparatus. The buttons (13) on which the intensities of the light, sound, and somatosensory stimuli can be adjusted are made by connecting an element for increasing and decreasing the resistance to the cable (14) on which the power output of the circuit is provided. The user can reduce and increase the power to the circuit through these buttons (13). Therefore, more or less power goes into the circuit, changing the intensity of visual, auditory, and somatosensory stimuli. The stimuli can be reduced to a certain intensity and increased with these buttons (13), which will be a gradual resistance. Finally, transparent plastic protection is placed on the LED lights (1) placed in the eyewear apparatus (2) and the monitor display (3).

All these parts provide visual, auditory, and somatosensory stimuli at certain frequencies. Electrical power goes from the rechargeable battery (10) to the processors (9.1, 9.2) when the device is started. The processors (9.1, 9.2) start to work with this power and it is ensured that the circuit remains open for milliseconds in the amount determined by the coding on the computer and displayed on the digital display (12) and remains closed for the same milliseconds. The circuit starts to open and close at a certain frequency in this way. LED lights (1), buzzers (6), and large-head electrodes (7) connected to the processors (9.1, 9.2) at the same time start to work. The LED lights (1) in the eyewear apparatus (2) or the monitor display (3) of the device remain on for the milliseconds in which the processors (9.1, 9.2) are encoded and remain closed for the same milliseconds. Visual stimulus is obtained at a certain frequency in this way. The buzzers (6) in the headphones (4) or speaker (5) apparatus of the device are also open for the milliseconds in which the processors (9.1, 9.2) are encoded and remain closed for the same milliseconds. Auditory stimulus is obtained at a certain frequency in this way. The large-head electrodes (7) of the device with the fixing apparatus remain on for the milliseconds in which the processors (9.1, 9.2) are encoded and remain closed for the same milliseconds. Somatosensory stimulus is obtained at a certain frequency in this way. The intensity of the visual, auditory and somatosensory stimuli obtained can be changed with buttons (13) where the light, sound and electrical intensity can be adjusted. The user can provide visual, auditory and somatosensory stimulation at different frequencies by changing how many milliseconds processors (9.1, 9.2) keep the circuit open and closed for how many milliseconds through the digital display (12) in the next uses of the device. In addition, it is ensured that two stimuli at different frequencies are given at the same time since there are two different processors (9.1, 9.2).

Claims

1. A device enabling the Gamma frequency entrainment technique for the treatment of Alzheimer’s disease to be used individually in scientific research and clinical applications, and to apply different frequencies at the same time, characterized in that; it comprises the following:

• LED lights (1) placed in the eyewear apparatus (2) and/or monitor display (3) and partly connected to the first processor (9.1) and partly connected to the second processor (9.2) and providing light stimulation to the user,

• Buzzers (6) placed in the headphones (4) and/or speaker (5) and partly connected to the first processor (9.1) and partly connected to the second processor (9.2) and providing sound stimulus to the user,

• Electrodes (7), partly connected to the first processor (9.1) and partly connected to the second processor (9.2) and providing somatosensory stimulation to the user,

• The first processor (9.1) and the second processor (9.2) that enable the LED lights (1), buzzers (6), and electrodes (7) they are connected to give frequency and intensity stimuli of different sizes,

• Digital display (12) that enables the management of the frequency and intensity settings of the processes and stimuli,

• Buttons (13) for adjusting the frequency and intensity of the stimuli.

2. A device according to claim 1, characterized in that; it comprises resistances (8) that enable the processors (9.1, 9.2) to the circuit to the LED lights (1), buzzers (6), and electrodes (7).

3. A device according to claim 1, characterized in that; it comprises cables (14) that provide the connection of the processors (9.1, 9.2) with the LED lights (1), the buzzers (6), and the electrodes (7).

4. An apparatus according to claim 1, characterized in that; it comprises LED light (1.1) connected to a plurality of first processors and LED light (1.2) connected to the second processor placed sequentially and evenly in the interior of the eyewear apparatus (2) and/or the monitor display (3).

5. A device according to claim 1, characterized in that; it comprises two buzzers (6.1) connected to the first processor and two buzzers (6.2) connected to the second processor placed in the headphones (4) and/or speaker (5).

6. A device according to claim 1, characterized in that; it comprises two electrodes (7.1) connected to the first processor and two electrodes (7.2) connected to the second processor.

7. A device according to claim 1, characterized in that; it comprises a first processor frequency adjustment button (13.1) and a second processor frequency adjustment button (13.2) that enable frequency adjustment through the processors (9.1, 9.2).

8. A device according to claim 1, characterized in that; it comprises an electrode intensity adjustment button (13.3) that allows the intensity of the somatosensory stimuli given from the electrodes (7) to be adjusted.

9. A device according to claim 1, characterized in that; it comprises a sound adjustment button (13.4) that allows the sound emitted from the buzzers (6) to be adjusted.

10. A device according to claim 1, characterized in that; it comprises a light adjustment button (13.5) that allows the intensity of the LED lights (1) to be adjusted.

11. A device according to claim 1, characterized in that; it comprises a battery (10) that supplies energy to the LED lights (1), the buzzers (6), the electrodes (7), and the processors (9.1, 9.2).

12. A device according to claim 1 or 11, characterized in that; it comprises a charging apparatus (11) that allows the battery (10) to be charged.