SYSTEM FOR LOCAL ACTIVATION OF THE HUMAN EYE AND BRAIN FOR VISUAL PERFORMANCE TRAINING, IN PARTICULAR FOR ACTIVATION OF THE VISUAL CORTEX AND REORGANIZATION OF NEURAL NETWORKS IN THE HUMAN BRAIN TO STRENGTHEN RESIDUAL VISION

Description

[0001] The invention relates to a system for the local activation of the human eye and brain for visual performance training, in particular for the activation of nerve cells in the human eye and brain to strengthen residual vision in cases of existing visual field defects by means of non-invasive pulse treatment, in particular alternating current pulse treatment (tASC), comprising an applicator for directing a current flow to the eye and / or brain and for stimulating blood flow and activation of nerve cells of the visual system, in particular retinal ganglion cells, a pulse generator for generating electrical stimulation signals, and a data processing and control unit for providing patient-specific stimulation signal sequences, wherein the applicator has at least two electrodes which can be applied to the head of the subject, according to the preamble of claim 1.

[0002] Visual field defects have traditionally been considered irreversible, as nerve cells in the retina, optic nerve, and brain cannot regenerate. However, partial recovery from visual field defects has been shown to be possible because the brain, which processes and interprets retinal signals, can permanently amplify residual signals through certain mechanisms. Similarly, nerve cells in the retina reduce their function and become "silent" after a pathological event, as they can no longer transmit nerve signals, without, however, dying.

[0003] Since experience shows that almost all patients retain some residual vision, it has been suggested that reactivating these "silent" nerve cells and improving synaptic transmission can enhance this residual vision. Clinical studies demonstrate the success of treatment methods such as vision training or alternating current stimulation. In alternating current therapy, the entire retina and parts of the brain are activated and synchronized. The vast majority of patients respond well to the aforementioned therapies. Physiological investigations of the mechanisms of alternating current using EEG and fMRI indicate a significant local and global change in blood flow and the reorganization of neural networks in the brain. Local activation of nerve cells occurs in the eyes and the visual system of the brain via a global reorganization of neural networks.Since residual vision can be strengthened through the reactivation of nerve cells and modulation of neuroplasticity, not only the eyes but also the brain are of great importance for visual rehabilitation in ophthalmology.

[0004] For some time now, the brain's adaptability, also known as plasticity, has been used in ophthalmology. Through neuromodulation methods using weak alternating currents, partially impaired visual functions can be strengthened via the process of neuroplasticity.

[0005] More recently, methods for improving blood flow and resynchronizing brain network activity using alternating current pulses have been tested on partially blind patients. In these methods, alternating current is administered non-invasively over several days in defined sessions using special electrodes on the forehead. The alternating current flows from the electrodes to the eye, stimulating retinal ganglion cells to fire at predetermined frequencies, with the aim of resynchronizing brain networks. Damage to the optic nerve leads to a disorganization of functional networks in the brain, which manifests as neurophysiological desynchronization in the EEG. Treatments using alternating current can significantly improve this condition by enhancing blood flow and resynchronizing brain network activity.

[0006] However, the resynchronization of visual performance varies greatly from person to person and depends on a wide variety of factors.

[0007] In addition to optimizing the stimulation impulses, it is also crucial to keep the patient as stress-free as possible, at least during treatment. This requires the development of an optimized design for stimulation electrodes, including technical means for attaching these electrodes to the patient's head. Therefore, an applicator must be created that is both ergonomically optimal and particularly well-suited for treatment, meeting all requirements.

[0008] Furthermore, it is essential to optimize the stimulation in such a way that the treatment success is maintained beyond the stimulation period and for as long as possible.

[0009] Regarding the state of the art with respect to the aforementioned aspects, reference is made to EP 1 603 633 B1, which shows a special fastening part for a stimulation device at a desired position on the patient's head, wherein an adjustment structure is made of a deformable material which is able to adapt the device to the contours of the patient's head.

[0010] Fastening devices or arrangements for contacting stimulation electrodes are also disclosed in EP 1 708 787 and EP 1 734 877 B1.

[0011] With regard to the state of the art concerning brain stimulation with additional control of the blood flow behavior of adjacent vessels, attention should also be drawn to WO 2011 / 106660 A1 and WO 2016 / 115392 A1.

[0012] WO 2011 / 106660 A1 focuses on detecting the effect of stimulation and, in particular, on simultaneously stimulating and recording the effect of the stimulation in real time. For this purpose, functional near-infrared spectroscopy is used non-invasively during stimulation. Functional near-infrared spectroscopy is used to measure the oxygenation state of hemoglobin.

[0013] WO 2016 / 115392 A1 relates to devices and methods for determining neurovascular reactivity using stimulation of the neurovascular system and simultaneous recording of a neuronal hemodynamic response thereto.

[0014] With regard to the various possibilities for the design of stimulation electrodes and corresponding applicators, attention should be drawn to the state of the art briefly outlined below.

[0015] US Patent 5,522,864 A discloses a headband-like electrode holder. A first electrode is placed on the patient's closed eyelid. The second electrode is fixed in the headband. A third electrode is attached to the back of the neck. Such an electrode configuration, especially the placement of an electrode on a closed eyelid, is perceived as unpleasant by the patient and causes stress that negatively impacts the success of the treatment.

[0016] The patent family around EP 30 13 414 B1, which describes a stimulation device for transdermal electrical stimulation, also features multiple electrodes fixed at positions significantly separated from one another. A first electrode is attached to the patient's forehead. A second electrode is located on the patient's neck or shoulder. This electrode arrangement is difficult to customize and can only be optimally positioned by the patient with assistance, which represents a significant disadvantage for home therapy.

[0017] EP 33 49 844 A1 concerns treatment using microcurrents. This involves placing targeted stimulation electrodes above and below the eye in the eyelid area. Such positioning directly in the sensitive eye area is uncomfortable for many patients, particularly because the electrodes are relatively small and therefore do not deliver sufficient current intensity. Even very low currents are perceptible, but not therapeutically effective. The skin above and below the eye is particularly sensitive to irritation, which is why this type of electrode design has not become widely used.

[0018] EP 2 981 326 B1 shows a headset-like arrangement for electrical stimulation of the skin surface of the head.

[0019] German patent DE 10 2011 055 844 B4 discloses a spectacle-like support for stimulation electrodes, which also includes a nose bridge similar to typical eyeglasses. The electrodes are removable, i.e., replaceable. However, this arrangement uses hair electrodes that lie directly on the cornea of ​​the eyeball, which carries a risk of corneal damage.

[0020] EP 2 651 504 B1 features a headband as an electrode carrier for neurostimulation. The headband is placed on the patient's head, and corresponding electrodes are positioned symmetrically on the back of the patient's head. Electrical connections are also provided for connecting the electrodes to a separate pulse generator.

[0021] The device described in US patent 2006 / 129207 A for the electrical stimulation of ganglion cells again uses a spectacle-like structure with electrodes that are brought into contact with the subject's eyelid. A support is intended to minimize the otherwise uncomfortable pressure on the eyelids, but this results in the disadvantage of a contact resistance between the electrodes and the subject's skin that is not always clearly reproducible.

[0022] A device for stimulating the visual cortex in humans is known from CN 109045435 A. An electrode array is placed on both temples or in the area between the temple and cheek. The stimulation is intended to stimulate the nerves around the eye, relax the eye muscles, and improve blood circulation around the eyes. The primary focus of this invention is on the visual cortex's stimulation through visual stimulation, with electrical stimulation acting only as an adjunct, using current intensities between 0 and 10 mA. Using optics and eyecups on the stimulation device, the subject can perceive moving scenes on a display, thus receiving additional visual stimuli.

[0023] Stimulation electrodes with the disadvantages already described are known from WO 2013 / 037618 A1.

[0024] Another disadvantage is the arrangement of electrodes in the eyelid area, i.e. above and below the human eye, as shown in WO 2017 / 048731 A1.

[0025] Furthermore, optical stimulation is also known, as described in WO 2017 / 222997 A1.

[0026] In summary, the state of the art shows a variety of different applicators for electrical stimulation, also for the relevant case of local activation of the eyes and brain, whereby the majority of known applicators are not suitable for home therapy, i.e. in the sense of reproducible, simple, and risk-free application by the patient without medical or physician support.

[0027] For this reason—and ultimately also for cost reasons—large-area adhesive stimulation electrodes are currently the predominant method of application. These are applied to the respective test subject or patient based on the experience of medical personnel. The advantage of larger electrodes is that a sufficient current intensity can be administered, as the current flows over a larger area of ​​the skin, eyes, or skull. In this regard, a trial-and-error method is frequently used, resulting in very limited reproducibility. Home applications are virtually impossible, especially with adhesive electrodes, so outpatient preparation for the therapy is generally required.

[0028] Current technology reports a wide variety of electrode sizes and positions, but their effects are highly variable and therefore not sufficiently reproducible. It is therefore desirable to enable a suitable electrode placement that can modulate the visual system even at lower currents and with less variability.

[0029] Based on the above, the object of the invention is to provide individual electrode customization based on the patient's specific physical characteristics. For this purpose, a novel system is to be created that, on the one hand, ensures an optimal arrangement of the stimulation electrodes and, on the other hand, guarantees a sustained effect after the stimulation treatment and not only during it.

[0030] The problem of the invention is solved by a system according to the combination of features according to claim 1, wherein the dependent claims include expedient embodiments and further developments.

[0031] A key aspect of the invention is to allow the intuitive use of the applicator, whereby an optimal stimulation sequence can be found via an arrangement for the non-invasive determination of the blood flow in the skin and brain of the subject and for determining the oxygen saturation, which leads to a maximum increase in blood flow and to the longest lasting after-effect, such that the increase in blood flow and neuronal activation lasts as long as possible even after the stimulation, which is a clear indicator of the desired treatment success.

[0032] The pulse generator for generating the stimulation signal sequences can be a single- or multi-channel stimulator that interacts with a data processing and control unit, so that patient-specific stimulation signal sequences are generated.

[0033] The temporal positioning allows both eyes to be stimulated simultaneously with only one channel, which reduces the cost of manufacturing the stimulation generator and improves effectiveness and reliability, i.e., less variability in success.

[0034] The optimal stimulation signal sequences can be determined during an initial treatment under medical supervision, then saved and given to the patient on a patient memory card for home use. Alternatively, data can be stored directly in a memory unit of the applicator.

[0035] The applicator is designed so that, after a brief explanation of its handling, it can be used intuitively, especially in the home environment.

[0036] The applicator includes an electrode holder that can be individually adjusted to the shape of the head. Furthermore, the electrodes are positioned at the temples for optimal stimulation. This offers the advantage that the current intensity of the pulse sequences can be reduced while still generating sufficient phosphenes. A NIR feedback system allows for maximizing the hemodynamic after-effect during non-invasive eye and brain stimulation.

[0037] Extensive investigations and studies, initiated by the applicant, have shown that the arrangement of the electrodes plays a crucial role in the success of stimulating the visual system.

[0038] In this regard, a so-called F7-F8 arrangement, according to the nomenclature of the EEG 10-20 system, is proposed in the temporal region of the patient. With this arrangement, phosphenes are recorded using extremely low current intensities, less than 2 mA, at an alternating current frequency of 8-25 Hz. When electrodes are positioned in the F7-F8 region, the patient can close their eyes or keep them open in a dark room. No unpleasant pressure occurs in the area of ​​the eyelid or above or below the eye from the electrodes being applied.

[0039] Furthermore, if wet electrodes are used and placed in the F7-F8 area, a very pleasant cooling effect occurs, which reduces stress, decreases skin resistance and also improves the treatment success.

[0040] With the foregoing, the invention relates to a system for the local activation of the human eyes and brain to reorganize neural networks for strengthening residual vision and improving blood flow in cases of existing visual field defects. In this regard, pulsed current therapy, in particular non-invasive alternating current pulse therapy, is used.

[0041] The system consists of an applicator to guide the flow of electricity to the eye and brain and to stimulate blood flow and activation of nerve cells, especially retinal ganglion cells.

[0042] The system also includes a pulse generator for generating electrical stimulation signals and a data processing and control unit for providing patient-specific stimulation signal sequences.

[0043] The applicator has at least two electrodes that can be attached to the subject's head in the manner described below.

[0044] The applicator has replaceable stimulation electrodes fixed in such a way that they lie on or against the right and left side of the eye in the area of ​​the temple of the patient's head, that is, in the so-called F7-F8 area.

[0045] Furthermore, according to the invention, the applicator has at least one arrangement for the non-invasive determination of blood flow in the skin and brain and for the determination of oxygen saturation, in particular on the basis of fNIR spectroscopy.

[0046] An NIR emitter and at least one associated NIR detector are positioned remotely from the stimulation electrodes on the patient's head and separately from the stimulation electrodes.

[0047] The NIR spectroscopy data, particularly during pauses or at the end of stimulation signal sequences, are recorded to determine the duration of sustained improved blood flow and / or oxygen saturation, so that the data processing and control unit can be updated accordingly via the system according to the invention.

[0048] In a further development of the invention, the applicator can be individually adapted to the patient's head shape. For this purpose, adjustment means known per se are provided for fixing the applicator to the forehead and back of the head.

[0049] In one embodiment of the invention, the applicator is designed as a ring- or crown-shaped structure that can be placed on the head, with a support for the bridge of the nose and / or an ear support and / or a support for the back of the head being provided.

[0050] Furthermore, a compartment for electronic components and weight compensation can be provided in the back of the head. The electronic components can include a battery or accumulator, allowing the applicator to be used without external power cables.

[0051] In one embodiment of the invention, the stimulation electrodes are designed as dry or wet cushion electrodes.

[0052] With a wet-pad electrode, an electrolyte solution can be used as a moistening agent to reduce the contact resistance between the conductive component in the electrode and the patient's skin surface. The lower the contact resistance, the lower the current can be for the pulse sequences, thus preventing the unpleasant tingling sensation associated with perceived electrical current flow. The applicator may be equipped with attachment points for attaching, particularly clipping, additional electrodes, enabling current application, especially alternating current, to the area below the patient's eyes if this is therapeutically advantageous.

[0053] The applicator has at least one interface for wired or wireless data transmission.

[0054] In this way, the applicator can exchange information with a higher-level system via a so-called air interface, register the course of the treatment duration and the treatment success, and make this data available to the treating physician for evaluation and further optimization of the treatment.

[0055] In one embodiment of the invention, sound-generating means, in particular designed as earphones or headphones, are provided on the applicator to guide the patient during treatment with information, in particular on the handling of the applicator, and / or to acoustically relax them.

[0056] For stand-alone operation, the applicator comprises both the pulse generator, in particular the AC pulse generator, and the data processing and control unit along with its power supply. The treatment sequence and / or the stimulation signal sequences are implemented by a computer program. Therefore, the applicator possesses all the necessary technical means for use and treatment. Consequently, it is no longer essential to provide a separate pulse generation unit that is either wired and positioned next to the patient or carried by the patient, as is the case with devices in the prior art that are attached to or carried in the patient's belt or pocket.

[0057] An electrolyte reservoir for electrode wetting can be provided on or in the applicator. This allows the patient to easily moisten the electrodes themselves if they begin to dry out. Alternatively, the supply of electrolyte via communicating tubes to the electrode holders can be automatically controlled by a suitable sensor.

[0058] In one embodiment of the invention, the applicator and / or electrode holders are made of a deformable plastic material. This makes it possible to individually adapt the applicator to specific head shapes, particularly in the forehead, nose, or neck area of ​​the patient, thus enabling actual individualization for the patient in question.

[0059] The holders and / or the stimulation electrodes can be made of a conductive plastic material, thus simplifying the design of the applicator and enabling the power supply or transmission of the stimulation pulse sequences via such a conductive material.

[0060] It is in line with the invention that the applicator has a pocket or similar receptacle for replacement electrodes. If a replaceable electrode is lost, treatment can continue, which is particularly advantageous if the patient is not near their usual medical practice.

[0061] Especially for stationary or clinical applications, the applicator can be designed to be combined with a known EEG electrode cap.

[0062] As already indicated, the applicator may have a unit for determining the contact resistance between the stimulation electrodes and the patient's skin surface in order to switch off the pulse generator or reduce the current flow in the event of abnormal, especially excessively high, contact resistances.

[0063] It has been shown that the system according to the invention for the local activation of the human eye and brain can also be used for improving visual performance, in particular for activating nerve cells in the human eye and brain for such persons or test subjects who have to perform sometimes complicated tasks under extreme gravitational and / or environmental conditions, as is the case, for example, with pilots, astronauts, but also deep sea divers.

[0064] Treating these individuals before, during and / or after their deployment under the extreme conditions described preserves their visual acuity and enables them to work in a more focused and safer manner.

[0065] In a further embodiment of the invention, it is possible to design or adapt the presented applicator so that it can be integrated into special equipment for the aforementioned persons. This particularly concerns the integration of the applicator into a pilot's, astronaut's, or deep-sea diver's helmet.

[0066] The invention will be explained in more detail below with reference to an exemplary embodiment and with the aid of figures.

[0067] This shows: Fig. 1 shows an exemplary applicator attached to the head of a subject in a front view; and Fig. 2 shows the applicator in a rear view, looking towards the back of the subject's head.

[0068] The applicator 1 according to the Figure 1 and 2 consists of a basic body 2 made of at least partially elastic material and is individually adaptable to the head shape of the indicated test subject 3.

[0069] The basic body 2 is realized as a ring- or crown-shaped structure that can be placed on the head of the subject 3, and includes a nasal bridge support 4 which provides an adjustment option to adapt to anatomical conditions.

[0070] Furthermore, the basic body 2 is connected to ear supports 5 for the left and right ear 6 of the subject 3.

[0071] The base body 2 is equipped with a receptacle for electronic components in the rear head area.

[0072] This can be, firstly, a storage unit 7, which contains stimulation programs. Furthermore, a pulse generator for generating electrical stimulation signals, along with a control unit for providing patient-specific stimulation signal sequences, can preferably be housed or attached in this area of ​​the back of the head.

[0073] Data transmission can take place via an interface 8, for example implemented as a USB port, but also charging of secondary cells 9 for the purpose of supplying power to the necessary electrical or electronic components.

[0074] Such a secondary cell 9 can, for example, be a replaceable lithium battery housed in a corresponding recess in the base body 2.

[0075] Stimulation electrodes 10 are interchangeably attached to the base body 2 and are arranged so that they lie on or against the right and left of the eye in the area of ​​the temple of the indicated patient's head.

[0076] In the front area of ​​the base body 2 there is an adjustment device 12 which can be provided with a labeling field 11 to create space for a company logo, handling instructions or for attaching a user name or user identification.

[0077] Sensors 13 can be attached to or embedded in the base body 2 to perform non-invasive measurements of blood flow in the skin and brain and to determine oxygen saturation. These sensors are located remotely from the stimulation electrodes 10.

Claims

1. System for local activation of the human eye and brain for visual performance training, in particular for activating nerve cells in the human eye and brain to strengthen residual vision in existing visual field defects by means of non-invasive alternating current pulse treatment (tACS), consisting of an applicator (1) for conducting a current flow to the eye and brain and for stimulating blood circulation and activating nerve cells, in particular retinal ganglion cells, a pulse generator for generating electrical stimulation signals, and a data processing and control unit for providing patient-specific stimulation signal sequences, wherein the applicator has at least two stimulation electrodes (10) that can be applied to the head of the test subject (3), wherein the stimulation electrodes are fixed to the applicator in such a way that they rest on or are applied to the right and left sides of the eye in the temple area of the patient's head, characterized in that the applicator has at least one arrangement for non-invasive determination the blood flow in the skin and brain and for determining the oxygen saturation based on fNIR spectroscopy, wherein the NIR emitter and the at least one associated NIR detector are positioned at a distance from the stimulation electrodes on the patient's head and separately from the stimulation electrodes, and the NIR spectroscopy data is recorded during pauses or at the end of stimulation signal sequences in order to determine the duration of sustained, improved blood flow and / or oxygen saturation, so that thereafter, updated operation of the data processing and control unit is realized with an optimal stimulation sequence that leads to a maximum increase in blood flow and the longest lasting aftereffect, such that after stimulation, the increase in blood flow and neuronal activation lasts as long as possible.

2. System according to claim 1, characterized in that the applicator is designed as a ring- or crown-shaped structure that can be placed on the head, with a bridge support and / or an ear support and / or a back-of-the-head support and a receptacle for electronic components and for weight balancing provided in the back-of-the-head area.

3. System according to claim 1 or 2, characterized in that the stimulation electrodes are designed as dry or wet pad electrodes.

4. System according to one of the preceding claims, characterized in that fixing points are provided on the applicator for attaching, in particular clipping on, further electrodes, which enable alternating current to be applied also in the area below the patient's eyes.

5. System according to one of the preceding claims, characterized in that an interface for wired or wireless data transmission is formed on or in the applicator.

6. System according to one of the preceding claims, characterized in that a moisture reservoir for electrode wetting is provided on or in the applicator.

7. System according to one of the preceding claims, characterized in that the applicator and / or holders for receiving electrodes are made of a deformable plastic material.

8. System according to claim 10, characterized in that the holders and / or the stimulation electrodes are made of a conductive plastic material.

9. System according to one of the preceding claims, characterized in that a pocket for holding replacement electrodes is provided on the applicator.

10. System according to one of the preceding claims, characterized in that a unit for determining the contact resistance between the stimulation electrodes and the patient's skin surface is designed to switch off the pulse generator in the event of abnormal, in particular excessively high, resistance.

11. System according to one of the preceding claims, characterized in that the position of the stimulation electrodes corresponds to an F7-F8 arrangement according to the nomenclature of the EEG 10-20 system.