JPH0347101B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a stimulation device for nerves or tissues to be stimulated.

[Prior Art] Most animals, including humans, survive by acting. For this reason, the behaviors necessary for survival have been learned and acquired through a long evolutionary process.
Nerves are located at the center of what controls this behavior.

The structure and function of the nervous system differs depending on the degree of evolution of the animal, and this is reflected in actual behavior. Animals with complex nervous systems also have complex behaviors. However, it is now well known from a physiological point of view that the mechanism of nerve excitation itself is basically the same. Regardless of the degree of evolution, the structural units of the nervous system are basically the same and consist of neuron cell bodies, axons, and dendrites. Because of these commonalities, it is basically accepted that the results obtained from research on neural excitation in lower animals are valid for more advanced animals and even humans.

Until now, conventional methods of directly stimulating the nervous system include electric current, electric fields, electromagnetic waves, radiation,
There was fever, drugs, contact, needles, etc.

[Problems to be solved by the invention] Electrical stimulation methods (current/electric field) require direct contact with the nervous system. If this was not possible, it was necessary to incise the tissue and bring it into contact, such as through surgery.

These methods involve considerable difficulty in attaching the electrodes to the biological system, setting the current, types of electrodes, moving the electrodes, detaching them, breaking them, etc., and require not only an extremely high degree of skill, but also dangerous also existed.

Stimulation by electromagnetic fields has the disadvantage that it is difficult to reach the target nervous system because it causes large attenuation in tissues. In addition, in order to ensure the arrival, an electromagnetic field of excessive energy density was required, which posed the risk of destroying tissue.
Not only that, but in this case, by stimulating the tissue over a wide range, it was impossible to stimulate the nerves only to the targeted local area.

Stimulation by a magnetic field is permeable, but local convergence is impossible due to the nature of the magnetic field.

In thermal stimulation, thermal energy diffuses only from the surface of the object, so it has been difficult to selectively stimulate the stimulation site.

Although stimulation with radiation, etc. is possible, there is a great risk of radiation damage to genes, etc.

Stimulation with drugs is generally carried out by ingestion, injection, etc., but there is a risk of adverse effects, habit-forming side effects, or inducing biological reactions in areas other than the target area of stimulation.

The deficiencies and insufficiencies of conventional methods of directly stimulating the nervous system have been described above.

With recent developments in medical technology, neuroscience, brain physiology, perceptual psychology, animal behavior science, and their interrelated application fields, new, safe and effective methods and devices for direct local pointing have been developed. Development was desperately needed.

Recognizing this importance, the present inventor conducted extensive research and discovered that safe and effective direct local stimulation using sound wave irradiation is possible from both physiological and physical viewpoints.

Note that there are various examples of adaptation of sound waves to living bodies. Usually, this type of sound wave is in the ultrasonic band because it requires energy density. It is well known that ultrasound irradiation is effective for mammary gland tumors and localized lesions in the brain. That is,
As reference examples, descriptions of breast tumor destruction surgery, left and right frontal lobe white matter destruction surgery, etc. can be found in the Ultrasonic Technology Handbook, edited by Nikkan Kogyo Shimbun, etc. These documents describe that the purpose of treatment is improved by literally destroying tissues in the living body, that is, by causing tissue spasmization and cell necrosis. According to these ultrasonic methods, focused ultrasonic waves are applied to in-vivo tissue so that destruction by ultrasonic waves progresses as desired. Especially when adapting to the head,
It was nearly impossible to transmit ultrasound through the skull. If you try to destroy the affected part of the brain tissue by irradiating it with ultrasonic waves, based on acoustic principles, the skull's ability to absorb sound waves is approximately 10% higher than that of the brain tissue. This is because they are so large that they can damage the skull due to heat, etc.

Therefore, it was necessary to make an incision in the head and administer the irradiation. However, even in this case, the brain dura mater did not need to be incised, so it had both a destructive therapeutic effect and a healing effect. Generally, in order to obtain the effects of such treatment, an energy density of several W/cm ² or more is required in the 1 MHz class.

Next, the currently most commonly used technology for adapting ultrasound to living organisms is the ultrasound pulse diagnostic method. This diagnostic method is a branch of the conventional ultrasonic flaw detection method, and uses some method to emit directional ultrasonic waves to determine the sonic absorption level of in-vivo tissue,
It utilizes the fact that the attenuation rate differs depending on the type of tissue in the living body, and diagnoses the state of the distribution of living tissues by contrasting (imaging) the transmission or reflection of sound waves from tissues. It is something to do. However, this method does not aim at stimulating living tissue at all.

As mentioned above, conventional techniques for applying ultrasound to living organisms can be roughly divided into techniques for destroying abnormal tissues and diagnosing them. This is completely different in spirit from techniques related to stimulation methods or stimulation devices that provide desired nerve stimulation by irradiating the nerves into a state having a waveform with a shape and time constant.

Furthermore, the present invention utilizes the conventional wisdom that ultrasonic irradiation has no stimulation effect on nerves or stimulated tissues (for example, the Ultrasonic Technology Handbook, edited by Nikkan Kogyo Shimbun, etc.). 21.5.4), there is no prior art that corresponds to the present invention.

The purpose of the present invention is to safely promote or suppress the firing of nerves or stimulated tissues by applying sound waves to the nerves or stimulated tissues. Another object of the present invention is to provide a stimulator that effectively causes the conduction of excitation of nerves or stimulated tissues to afferent nerve units or efferent nerve units, and causes desired operating effects to be exerted on organs.

[Means for Solving the Problems] The present invention provides a sound wave oscillator that generates a sound wave that stimulates a living body from outside without directly contacting nerves or tissues to be stimulated, and a sound wave emitted from the sound wave oscillator. adjustment means for adjusting the intensity, irradiation time, or phase, amplitude, and frequency of the signal to specified values; and a detection means for detecting whether the nerve or tissue to be stimulated is promoting or suppressing firing by the sound waves. It is characterized by having the following.

[Function] In the present invention, the firing is stimulated or suppressed by sound waves from the outside to some or all of the nerves or tissues to be stimulated without direct contact with the living body. The drawbacks caused by contact are eliminated, local stimulation becomes easy, advanced skill is not required, and risks such as tissue destruction are avoided.

[Example] Hereinafter, specific experimental examples and examples related to the present invention will be described in detail.

The present invention was not made from the perspective of improving the prior art, but as a result of intensive research into the possibility and effectiveness of stimulating nerves or stimulated tissues by sound waves (ultrasound or sound waves in the audible range). This invention was made by creatively applying that knowledge.

That is, there has been no experimental evidence that ultrasonic energy or audible sound energy can reliably generate excitation in the nervous system or stimulated tissues. Furthermore, this can be understood from the fact that it has been stated that there are almost no positive facts that cause excitement in the nervous system among ultrasound users (for example, Ultrasound Technology Handbook, Nikkan Kogyo Shimbun) Sha, 21-5
-4 pages).

The present inventor investigated whether the firing of stimulated tissues in the nervous system is promoted or suppressed by sound waves of appropriate intensity or in the audible range,
We performed delicate experiments by combining single-cell intracellular potential measurement techniques, neurocytological knowledge, and advanced effects of ultrasound engineering. As a result, we have discovered through experiments that excitation occurs when ultrasonic energy or audible sound energy within an appropriate intensity range is applied to the nervous system or tissues to be stimulated. Since this fact is an important basis for disclosing the present invention, the details of this experiment will be explained below.

In general, with the exception of some lower animals (mainly coelenterates), the nervous system of normal animals consists of a central nervous system consisting of nerve cell bodies and some nerve fibers, and a central nervous system consisting of bundles of nerve fibers. It is made up of peripheral nerves that separate and reach various parts of the body.

As mentioned above, the structure and function of the nervous system varies depending on the degree of evolution of the animal.
It is physiologically recognized that the mode of nerve excitation itself is basically the same. Therefore, studies on the mode of neural excitation are being conducted in lower animals. In conducting experiments, the present inventor used Aplysia Kurodai (scientific name: Aplysia Kurodai, mollusk/gastropod).
The main reason for using this method is that individual neurons are about an order of magnitude larger than normal animals, making it easier to measure intracellular potentials with glass electrodes, etc. The nervous system (called firing) is basically the same as that of other animals.

Figure 1 shows an overview of the anatomy of Aplysia, mainly showing the nervous system, used in this experiment. In this figure, 1 to 11 indicate the nervous system, 12 to 15 the sensory organs, 16 to 21 the digestive organs, and 22 the reproductive organs. Namely, 1 is the optic nerve, 2 is the olfactory angle nerve, 3 is the oral bulbar ganglion, 4 is the paraganglion, 5 is the ankle ganglion, 6 is the abdominal ganglion (right), 7 is the abdominal ganglion (left), 8 gill nerve, 9 ganglion, 10 genital ganglion, 11 purple gland nerve, 12 antennal, 13 olfactory horn, 14 oral bulb, 15 eye, 16 esophagus, 17
18 is a sandbag, 19 is a midgut gland, 20 is a stent, 21 is a rectum, and 22 is a sperm storage pouch.

The central part of the nervous system is the abdominal ganglion (right) 6, abdominal ganglion (left) 7,
These are the head ganglion group of the bulbar ganglion 3, the paraganglion 4, and the foot ganglion 5. The present inventors separated these four pairs of ganglia and the nerve fiber parts connecting these ganglia from the Aplysia body and subjected them to this experiment.

FIG. 2 is an enlarged view of the abdominal ganglia 6 and 7 of Aplysia in FIG. 1. Here, 3
1 is the para-ventral connective nerve (right), 32 is the para-abdominal connective nerve (left), 33 is the connective tissue membrane, 34 is the aqueduct nerve, 35 is the genital cardiac nerve, 36 is the gill nerve,
37 is a nerve cell.

Aplysia's nerve cells are relatively large, and their roles have been gradually discovered and differentiated in recent years.
The manner in which the neuron groups depicted in Figure 2 are excited can be broadly classified into non-discharge type R1, R1, and R1 as shown in this figure.
2, L1, regular discharge types R3 to R8, irregular discharge types R15, R16, L6 to L8, L11, and cluster discharge types L2 to L4, and their firing (that is, spike-like potential changes caused by some stimulus). They are distinguished by the form in which they occur.

In this experiment, ultrafine glass electrodes (500 Å to 1000 Å in diameter) are inserted into these cells while being monitored using a special microscope. When the electrode enters the cell, the potential is -60mV
At the same time, a spike is generated, which depends on the cell type, as described above. Conventionally, nerves have been excited by current stimulation in which a minute current is passed through this needle. The purpose of this experiment was to find out whether ultrasonic waves of appropriate intensity can be an effective stimulation method to induce excitement in the nervous system.

A conceptual diagram of this experimental apparatus is shown in Fig. 3. Here, 41 is a ganglion, 42 is seawater, 43 is a substrate, 44 is an ultrasonic oscillator, 45 is an ultrafine glass electrode, 46 is water, and 47 is an exciter. Ultrasonic waves are emitted by feeding a 3 MHz vibration current from an exciter 47 to an ultrasonic oscillator 44 . In order to easily focus the ultrasonic waves on a part of the ganglion 41, the oscillator 44 in this case was specially designed to have a shape in which a part of the spherical surface was cut into a circular shape.

It should be noted that the exciter 47 is preferably one that has a wide usable band ranging from an ultra-low frequency band to an ultra-high frequency sound wave, and its power can be made variable by a power adjuster. The oscillator 44 may be one using a piezoelectric, electrostrictive or magnetostrictive oscillator, an electrodynamic transducer, a capacitor transducer, an electromagnetic induction transducer, a discharge/impact oscillator, a siren oscillator,
The present invention includes a structure that generates oscillation by a Hartmann fume generator, a vortex generator, a nozzle jet generator, a cavitation generator, an oscillator photoacoustic mechanism using photoelasticity, a thermoacoustic mechanism, an elastic body vibration mechanism, etc. Applicable to In addition, the oscillator 44 has a sharp directivity so that it can project sound waves from the outside only to a target part of the nervous system or the entire nervous system without directly contacting the stimulated nervous system, etc. A material having an appropriate frequency band, appropriate dimensions, and a shape consisting of a part of a spherical surface or a part or all of a cylindrical surface as described above is used. In addition, the intensity of the sound wave emitted from this oscillator 44,
In order to control the irradiation time or adjust the phase, a sound wave focusing mechanism (not shown) provided at or around the sound wave oscillator 44 is also provided. This sound wave concentration/convergence mechanism is a geometric mechanism in which the oscillator 44 is arranged to coincide with an optical focal point, and the sound wave emitted from the oscillator 44 is reflected or transmitted to another focal point. Any material may be used as long as it has a curved surface.

Further, the stimulation by the sound waves emitted from the oscillator 44 includes continuous stimulation, intermittent stimulation, and single-shot stimulation. Additionally, these stimuli are modulated in amplitude, frequency, and phase. Furthermore, a device (not shown) such as an oscilloscope for determining whether or not nerves are excited is provided externally. This excitement is captured by minute electric potentials, minute sound waves, minute magnetic flux light, minute pressure, minute amounts of electricity, minute amounts of heat, minute displacements, neurotransmitters, secretions, and excretions. This capture includes visual, auditory, tactile, gustatory, olfactory, and other somatic senses.
This is also done by sensing changes in consciousness and behavior.

In the embodiment shown in Fig. 3, the ultrasonic waves are focused on the relevant part of the ganglion 41 with an accuracy of ±0.2 mm.The target nerve cell in this case is, for example, R3 (regular discharge type) shown in Fig. 2. Selected. The experimental results are shown in FIG.

As shown in FIG. 4, in Neuron A, such as R3, it was measured that the number of spikes increased for a certain period of time after applying sonic stimulation.
This phenomenon was repeated with good reproducibility, indicating that ultrasonic irradiation at an appropriate intensity clearly stimulates the nervous system and promotes firing for a certain period of time. It was also found that in another R5 neuron (neuron B), firing was suppressed for a certain period of time.

Next, when ultrasonic pulse stimulation was applied to the non-discharge type (in the case of no stimulation, the R2 cell body does not fire and is fixed at an intracellular potential of about -60 mV), the fifth
Single firings as shown in the figure were measured with good reproducibility. The ultrasonic pulse stimulus fires approximately 240 milliseconds after it is input to the nerve cell R2, which is called a silent cell.

Furthermore, various experiments similar to those described above were repeated for the group of nerve cells shown in FIG. Cluster discharge type L2 to L4, irregular discharge type R15, R16, L6
It was also found that ultrasonic stimulation or audible sound stimulation of appropriate intensity gave reproducible excitation to each nerve cell group L8 and L11 (not shown).

Next, the inventor conducted the following experiment in order to ensure the best performance of the present invention. The experiment concerned the use of an ultra-thin glass electrode 45, which is currently considered unavoidable as it is a reliable method of observing ignition. That is, this experiment was conducted in response to the question of whether ultrasonic irradiation acts on the ultra-fine glass electrode 45 for some reason, and as a result, excitement is excited within the cell.

Therefore, in order to obtain confirmation that neurons could be fired by ultrasonic stimulation alone, we conducted the experiment shown in FIG. 6. In other words, by irradiating only a part of the paraganglion with ultrasonic waves, the exciting potential propagates to the abdominal ganglion via the nerve fiber bundle at a position far away where the effect of the irradiation is ignored. In order to investigate this, an ultrafine glass electrode 45 was placed in the abdominal ganglion.

The results of this experiment are shown in Figure 7, where an increase in excitation spikes generated from a part of the paraganglion irradiated with ultrasound is transmitted via nerve fiber bundles to the abdominal ganglion at a distant location. The change in the excitatory potential was observed through the ultra-fine glass electrode 45 as shown in this figure. This clearly demonstrates that the nervous system can be excited only by appropriate ultrasonic stimulation.

As mentioned above, it is theoretically possible to irradiate stimulated tissue, especially the nervous system, with ultrasonic waves of appropriate intensity, which can be a superior stimulation method to the conventional current stimulation method using electrodes. Obtained experimental evidence. By the way, what I have been talking about so far as "appropriate intensity" refers to ultrasonic power that gradually increases from an extremely low level of ultrasonic power at which no ignition is detected, until it reaches an intensity that causes ignition, as used in the above example. This is because there is no need to limit the power intensity to a specific value if the intensity is adjusted to obtain the desired power intensity. Additionally, this ultrasonic intensity limit is generally set at the ultrasonic intensity (usually 20 W/cm ² or more) seen in conventional breast tumor destruction surgery, right and left frontal lobe white matter destruction surgery, stone destruction surgery, etc. The intensity is extremely small compared to the ultrasonic intensity (approximately 0.1 W/cm ² or less). The ability to reproducibly ignite using such extremely low intensities of ultrasound clearly sets the invention apart from the prior art.

By the way, it has already been mentioned that in the past, in order to investigate various neurological functions including brain function, it was necessary to infiltrate electrodes and the like in close proximity to in-vivo tissues. Furthermore, contact with such in-vivo tissues has been accompanied by minimal destruction of some tissue. For this reason, electrode insertion was limited only to people with special abilities and qualifications, and only to special parts.

However, according to the present invention, various neurological functions including higher brain functions can be investigated relatively easily without causing heat generation or tissue destruction. Therefore, according to the present invention, it is possible to provide a means for elucidating and treating mental and neurological diseases that are considered to be difficult even in current medicine. Furthermore, according to the present invention, it is possible to input non-invasive and effective stimulation to other stimulated tissues for the same reason as mentioned above, so diagnosis and treatment in various medical fields, which have been difficult in the past, are possible. It is possible to provide excellent means in such cases.

Next, some examples carried out by the present inventor will be described.

The inventor himself attempted to locally irradiate the primary visual cortex of the occipital lobe with ultrasonic waves using the method according to the present invention described above and an exciter as shown in FIG. 3 or 4. , I felt a bright light in the peripheral area of my visual field.

Next, regarding muscle tissue, which is a representative tissue to be stimulated, ultrasonic waves were irradiated to the biceps brachii muscle (biceps) using the same method and device as described above, and contraction of the muscle was observed.

Furthermore, to stimulate another sensory organ, which is a tissue to be stimulated, the Golgi organ, which is a sensory organ that senses tension in the patellar tendon, was irradiated with ultrasound using the same method and device as described above. The familiar patellar tendon reflex occurred.

[Effects of the Invention] As described above, according to the present invention, a part or all of a nerve or tissue to be stimulated can be stimulated by sound waves from the outside via a medium without direct contact with a living body. This eliminates the disadvantages of conventional direct contact, facilitates local stimulation, eliminates the need for advanced skill, and avoids risks such as heat generation and tissue destruction.
Further, although the implementation effects of the present invention were briefly described in the above-mentioned Examples section, it is believed that more specialized knowledge would enable more effective diagnosis and treatment.

Furthermore, in recent years, there has been a desire for advanced information processing technology that imitates the neural mechanisms of living organisms. To this end, it is essential to elucidate brain functions, but until now there have been no effective non-invasive local stimulation methods. In the present invention, as described above,
Since it is possible to provide a method and means for non-invasively and locally obtaining effective stimulation of stimulated tissues including the nervous system, the application of the present invention will dramatically advance the elucidation of brain functions, etc. As a result, remarkable effects can be obtained, such as making it possible to make a significant contribution to the realization of unprecedented advanced information processing technology, new functional bodies, and new energy technology.

Note that the present invention is not limited to ultrasonic waves, but covers the entire range of sound waves from an ultra-low frequency band to an ultra-high frequency.

[Brief explanation of drawings]

Figure 1 is a distribution map of Aplysia's nervous system, Figure 2 is a conceptual diagram of the abdominal ganglion of Aplysia, Figure 3 is a conceptual diagram of an experiment in which focused ultrasound stimulation is applied to the abdominal nerve center of Aplysia, and Figure 4 is a conceptual diagram of the abdominal ganglion of Aplysia. The figure shows the change in the firing state before and after applying ultrasound to the abdominal ganglion of Aplysia, Figure 5 shows the change in the firing state of silent cells due to ultrasound stimulation, and Figure 6 shows the change in the firing state of the Aplysia abdominal ganglion. Ultrasound is irradiated to a part of the paraganglion of the patient to cause excitation, and an action potential is generated at a glass electrode inserted into a cell in the abdominal nerve via nerve fibers. Fig. 7 is a conceptual diagram showing an experimental apparatus according to an embodiment of the present invention, which shows that excitation is propagated from the paraganglion of Aplysia to the nerve cells of the abdominal ganglion via nerve fibers. FIG. 3 is a diagram showing changes in the firing state before and after ultrasonic irradiation. 1... optic nerve, 2... olfactory angle nerve, 3... stomatal ganglion, 4... paraganglion, 5... foot ganglion, 6...
Abdominal ganglion (right), 7...Abdominal ganglion (left), 8...
...Gill nerve, 9...Gill ganglion, 10... Genital ganglion, 11... Violet gland nerve, 31... Para-ventral connecting nerve (right), 32... Para-ventral connecting nerve (left), 33...Connective tissue capsule, 34...Aqueduct nerve, 35...Genital cardiac nerve, 36...Gill nerve, 37...Nerve cell, 41...Ganglion, 42...
...Seawater, 43...Substrate, 44...Ultrasonic oscillator, 45...Extremely fine glass electrode, 46...
Water, 47...Exciter, R1, R2, L1...Non-discharge type, R3-R8...Regular discharge type, R15, R1
6,L6~L8,L11……Irregular discharge type, L
2 to L4... swarm discharge type.

Claims (1)

[Scope of Claims] 1. A sound wave oscillator that generates a sound wave that stimulates the living body from outside the living body through a medium without directly contacting nerves or tissues to be stimulated; and a sound wave emitted from the sound wave oscillator. adjustment means for adjusting the intensity, irradiation time, or phase, amplitude, and frequency of the sound wave to specified values; and a detection means for detecting whether the firing of the nerve or stimulated tissue is promoted or suppressed by the sound wave. 1. A stimulation device for nerves or tissues to be stimulated, characterized in that it comprises means. 2. In the device according to claim 1, the sound wave oscillator is a part of a spherical surface or a part of a cylindrical surface that sharpens the directivity of the sound wave and projects it only to the target area of the living body. or a stimulator for nerves or tissues to be stimulated, characterized in that the device has a shape consisting of the entire body. 3. The device according to claim 1, wherein the sound wave concentrator has a geometrically curved surface that allows the sound waves emitted from the sound wave oscillator placed at an optical focal point to be concentrated or converged at another focal point by reflection or transmission. 1. A stimulation device for nerves or stimulated tissues, characterized in that a means is provided around the sound wave oscillator. 4. In the device according to any one of claims 1 to 3, the sound wave oscillator is one using a piezoelectric, electrostrictive, or magnetostrictive vibrator, or an electrodynamic transducer,
Capacitor transformation converter, electromagnetic induction type converter, discharge shock type oscillator, siren type oscillator, Hartmann blow generator, vortex generation generator, nozzle injection generator, cavitation generator, oscillator photoacoustic mechanism using photoelasticity, thermoacoustics 1. A stimulation device for nerves or stimulated tissue, characterized in that it has a structure that oscillates sound waves using either a mechanism or an elastic body vibration mechanism. 5. In the device according to any one of claims 1 to 4, the detection means includes a minute electric potential, a minute sound wave, a minute magnetic flux, a minute light, a minute pressure, a minute amount of electricity, a minute amount of heat,
A stimulator for nerves or stimulated tissue, characterized in that it detects excitations captured by minute displacements, neurotransmitters, secretions, or excretions. 6. In the device according to any one of claims 1 to 4, the detection means detects the living body's sense of sight, hearing, touch,
A stimulating device for nerves or stimulated tissue, characterized in that the excitement is detected by sensing changes in taste, smell, other somatic sensations, consciousness, and behavior.