WO2012017950A1 - Electroencephalographic electrode device for small laboratory animal and electroencephalographic method - Google Patents

Electroencephalographic electrode device for small laboratory animal and electroencephalographic method Download PDF

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WO2012017950A1
WO2012017950A1 PCT/JP2011/067469 JP2011067469W WO2012017950A1 WO 2012017950 A1 WO2012017950 A1 WO 2012017950A1 JP 2011067469 W JP2011067469 W JP 2011067469W WO 2012017950 A1 WO2012017950 A1 WO 2012017950A1
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electrode
electroencephalogram
electrode group
experimental
measuring
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PCT/JP2011/067469
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French (fr)
Japanese (ja)
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原田　秀樹
由貴 五反田
勝哉 津田
恭子 阿部
真由 佐保
一男 牛島
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学校法人 久留米大学
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Priority to JP2012527717A priority Critical patent/JP5924539B2/en
Publication of WO2012017950A1 publication Critical patent/WO2012017950A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]

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  • the present invention relates to an electroencephalogram measurement electrode device and an electroencephalogram measurement method for small experimental animals such as rodents. More specifically, an electroencephalogram measuring electrode device and an electroencephalogram that can be easily attached to a small experimental animal, the attached electrode is not detached or difficult to remove during the experiment, and furthermore, a weak electroencephalogram voltage can be measured with high sensitivity and stability. It relates to a measurement method.
  • the method for determining the depth of anesthesia is generally determined by the presence / absence of reflection to the stimulus, changes in respiratory rate and depth, changes in heart rate and blood pressure, responses to painful stimuli, and the like.
  • rodents such as mice and rats
  • the experiment is started assuming that the anesthesia depth is suitable for an experiment involving a surgical procedure.
  • the anesthesia depth is shallow and the experimental animal feels pain and pain and goes wild during the experiment, the data obtained in that experiment may contain errors, so that data will be removed from the series of experiments, The experiment itself can be wasted. As a result, an additional experimental animal is required, which is not preferable from the viewpoint of respecting the life of the experimental animal.
  • EEG is measured as an index of anesthesia depth (anesthesia state) for humans, and there is a BIS (Bispectral index) monitor device as such a measurement device (for example, Non-Patent Document 1).
  • BIS Breast index
  • the brain waves are amplified, filtered, and frequency analyzed, and quantitatively displayed on the display monitor as numerical values from 0 to 100 (dimensionless numerical values).
  • the measurement apparatus is used in many clinical cases because it has immediateness in measuring and analyzing the electroencephalogram.
  • the obtained EEG signal is analyzed. Since it takes time to analyze the electroencephalogram signal, the depth of anesthesia cannot be estimated from the electroencephalogram signal at the same time, but it was obtained when the electroencephalogram was measured with the BIS monitor device as described above. Since the electroencephalogram signals are simultaneously displayed on the display monitor, the apparatus is extremely suitable for observing the depth of anesthesia of animals that are difficult to express intentions.
  • JP 2006-14729 A (paragraph [0023] on page 5)
  • An object of the present invention It is an object of the present invention to easily attach an electroencephalogram measurement electrode to a small experimental animal, and the attached electrode does not or does not come off during the experiment, and furthermore, a weak electroencephalogram voltage can be stably measured with high sensitivity. There is in doing so. Another object of the present invention is to prevent the influence of noise from the heart or the like.
  • the present invention is an electrode device for measuring an electroencephalogram of a small experimental animal, and includes a first electrode group composed of a plurality of needle electrodes and a second electrode group composed of a plurality of needle electrodes.
  • the needle electrodes of the first electrode group and the second electrode group are fixed to a base, and the first electrode group and the second electrode group are located on both sides of the skull of the experimental small animal.
  • the needle electrode including the tip part which becomes the insertion part of each of the first electrode group and the second electrode group protrudes from the base so that the left and right temporal muscles are inserted and worn.
  • This is an electrode device for measuring an electroencephalogram of a small animal.
  • the base is made of a flat or U-shaped plate-like insulator material, and the tips of the needle electrodes of the first electrode group and the second electrode group fixed to the base It is preferable that the portion protrudes vertically or substantially vertically from each end of the base so as to be inserted into the left and right temporal muscles of the experimental small animal.
  • the distance between the distal end of the first electrode group fixed to the base and the distal end of the second electrode group is the maximum of the distance between the left and right temporal muscles of the target small experimental animal. It is preferable that the width is not less than the minimum width and not more than the maximum width.
  • the length of the distal end portion of each of the first electrode group and the second electrode group serving as the insertion portion into the temporal muscle is determined by the insertion direction of the temporal muscle into the experimental small animal. It is preferable that it is 1/5 or more and 1 or less of the length.
  • the interval between the plurality of needle electrodes constituting the first electrode group and the second electrode group is such that the interval between the adjacent electrodes is the length in the long axis direction of the cerebrum of the corresponding experimental small animal.
  • the length interval is preferably 1/5 to 1/25 of the length.
  • each of the first electrode group and the second electrode group is formed by arranging three or more needle electrodes, and one of the needle electrodes selected from other than both ends is used as the ground electrode.
  • the electroencephalogram is measured using two of each of the remaining electrodes.
  • the electroencephalogram measurement electrode device is preferably connected to the BIS monitor device and used as the electroencephalogram measurement electrode device in the BIS monitor device in order to measure the electroencephalogram of the experimental small animal using the BIS monitor device.
  • the electrode device for electroencephalogram measurement is an electrode device for electroencephalogram measurement of a BIS monitor device, and the first electrode group and the second electrode group are configured by arranging needle electrodes corresponding to the number of electrode terminals of the BIS monitor device, respectively.
  • one of the needle electrodes selected from other than both ends is the ground electrode, and the electroencephalogram is measured using two of the remaining electrodes.
  • the electroencephalogram measurement electrode device is configured by arranging four needle electrodes in each of the first electrode group and the second electrode group in the electroencephalogram measurement using the BIS monitor device having four electrode terminals. It is preferable to use the second electrode from the end of each electrode group as a ground electrode and measure the potential difference between the first and third electrodes from the end and the first and fourth electrodes from the end.
  • the experimental small animal is preferably a rodent such as a rat.
  • the scalp of an experimental small animal is incised to expose the temporal muscles located on both sides of the skull, and at least two needle electrodes are inserted into the temporal muscle as a ground electrode and a measurement electrode.
  • This is a method for measuring an electroencephalogram of an experimental small animal, which extracts an electroencephalogram signal and displays the extracted electroencephalogram signal in real time using a BIS monitor device.
  • the electroencephalogram measurement method preferably measures the electroencephalograms of the left hemisphere and right hemisphere of the brain of a small experimental animal at the same time or at least one of them.
  • the electroencephalogram measurement method uses two BIS monitor devices and an electrode device to connect the terminals of the first electrode group to the first BIS monitor device and connect the terminals of the second electrode group to the second BIS monitor device. It is preferable to connect and measure the brain waves of the left hemisphere and right hemisphere of the brain of a small experimental animal at the same time or at least one of them.
  • the interval between the plurality of needle electrodes constituting the first electrode group and the second electrode group positioned corresponding to the temporal muscles located on both sides of the skull of the small experimental animal to be inserted and mounted is 1 ⁇ 4 mm is preferred.
  • the first electrode group and the second electrode group are configured by arranging four needle electrodes, the second needle electrode from the end is the ground electrode, and two of the remaining electrodes are used. It is preferable to measure an electroencephalogram.
  • the electroencephalograms of the left hemisphere and the right hemisphere of the experimental small animal brain can be measured simultaneously or either.
  • the number of electrode terminals is limited as in the BIS monitor device, for example, a plurality of monitor devices, preferably two, are used, for example, the first electrode group is connected to one monitor device terminal.
  • the brain waves of the left and right hemispheres of the cerebrum can be measured efficiently without the need for simultaneous operation or removal of the electrode terminals. it can.
  • the first electrode group and the second electrode group as the electrode device according to the present invention are each composed of four electrodes (one of which is a ground electrode), two BISs are used.
  • the first electrode group is connected to one BIS monitor device, and the second electrode group is connected to the other BIS monitor device.
  • one BIS monitor device when measuring brain waves in the left and right hemispheres of the cerebrum, one BIS monitor device must disconnect one electrode group and connect the other electrode group. Such a complexity can be avoided by using a monitor device. However, in the present invention, in such a case, the use of two BIS monitor devices is not an essential requirement of the invention. Of course, when the electrode terminals of the BIS monitor device to be used have terminals that can connect all of the first electrode group and the second electrode group, even one BIS monitor device can efficiently perform the electroencephalogram. Can be measured.
  • the needle electrode used in the present invention a commercially available one can be used, and the structure thereof is not particularly limited as long as it can be inserted into the temporal muscle of a small experimental animal and the potential of the electroencephalogram can be derived. Since the needle electrode used in the present invention is inserted into the temporal muscle, the needle electrode does not come off or is difficult to come off even if the experimental small animal moves during the experiment or changes its position for the experiment. . In addition, since it can be inserted into the temporal muscles close to the brain, a weaker electroencephalogram voltage can be stably measured with high sensitivity compared to a normal planar electrode. By fixing and integrating the plurality of needle electrodes to the substrate, the apparatus can be handled easily.
  • the brain waves of small experimental animals are very small, and if the distance between the needle electrodes is too narrow, the difference in brain wave potential may not appear clearly. However, if the interval between each adjacent needle electrode is widened, a difference in electroencephalogram potential appears clearly. However, in that case, it may be affected by noise emitted from the heart or the like, making accurate electroencephalogram measurement difficult.
  • the interval differs depending on the size of the cerebrum of the experimental small animal, but it should be set to an interval of 1/5 or less and 1/25 or more of the length of the cerebrum in the long axis direction of the adjacent experimental small animal. preferable. Specifically, for example, in the case of a rat whose cerebral length in the long axis direction is about 25 mm, 4 mm or less and 1 mm or more are preferable. Moreover, it is more preferable if it is 3 mm or less.
  • the ground electrode is not located at the end of the arranged electrode group, and the needle electrode located inside is not placed. It is recommended in the present invention that the ground electrode be a measurement electrode even if it is a substantially narrow needle electrode interval.
  • each of the two BIS monitor devices having four electrode terminals includes a first electrode group and a second electrode group each including four needle electrodes fixed on a base.
  • the second needle electrode located inside is a ground electrode, the potential difference between the first needle electrode located at the end and the third needle electrode located inside and the first needle electrode
  • the distance between the needle electrodes for potential difference measurement is substantially 2 mm (measured with the first and third needle electrodes) even if the distance between adjacent needle electrodes is 1 mm. And 3 mm (measurement with the first and fourth needle electrodes), and the above-mentioned problem of antinomy can be solved.
  • the base material used in the present invention is not particularly limited, but an insulating material is recommended. Specifically, synthetic resins such as PET (polyethylene terephthalate) resin, polyethylene resin, polypropylene resin, acrylic resin, perfluoroethylene (trade name Teflon (registered trademark), etc.), and the like. Moreover, even if it is an electroconductive substance, if each electrode contacts each base
  • the shape and rigidity of the substrate are not particularly limited as long as they can be mounted on small experimental animals.
  • rodents such as rats and mice
  • the top of the head is relatively flat, the shape is flat and there is no problem.
  • the top of the head of the small animal for experiment has a curved surface, it can be formed according to the curved surface of the top.
  • a U-shaped configuration in which rising portions are provided at both end portions of a flat plate or a curved plate is also recommended for fixing the needle electrodes.
  • the rigidity if there is too much flexibility, there is a case where the temporal muscle cannot be inserted by a single operation. Therefore, it is preferable that the rigidity is sufficient to allow the temporal muscle to be inserted by a single insertion operation. .
  • a commercially available BIS monitor apparatus has four electrode terminals, and in order to accurately measure the electroencephalogram of a small experimental animal, it is preferable to simultaneously measure the electroencephalogram of the right and left hemispheres of the brain. From this, when two BIS monitor devices are used simultaneously, the brain waves of the right hemisphere and the left hemisphere of the experimental small animal brain can be measured simultaneously.
  • the first electrode group and the second electrode group are fixed to the substrate and integrated.
  • the tip of the needle electrode of each electrode group fixed to the base is inserted into the left and right temporal muscles, so that it is stably attached and difficult to come off.
  • the needle electrode including the distal end portion constituting each electrode group and serving as the insertion portion protrudes vertically or substantially vertically from the base body, and the distal end portion is inserted into the temporal muscle.
  • the distance between the first electrode group and the second electrode group is the distance between the left and right temporal muscles of the target small experimental animal (there is a thickness). Therefore, it is recommended to use an intermediate thickness).
  • this interval it is possible to easily insert the electrodes into the left and right temporal muscles without requiring any special operation. For example, when a rat is used as an experimental small animal, the interval is about 12 to 18 mm.
  • the length of the tip portion (corresponding to the depth of insertion) of each needle electrode that is inserted into the temporal muscle is the length of the needle electrode in the insertion direction side. It is preferable that the length is 1/5 or more and 1 or less of the length of the head muscle. Even if the length is longer than this, it is possible to measure an electroencephalogram, but there is a risk that an experimental defect such as penetration of the tip of the needle electrode outside the body may occur. In addition, when the length is too short, it is difficult to stably insert and fix the needle electrode, and the needle electrode may be easily detached. Specifically, for example, about 3 mm to 10 mm is recommended for rats.
  • the base is U-shaped, the above-mentioned value is recommended as the length that can be inserted.
  • the lead wires connected to the needle electrode may be grouped near the base so that access to the target site is not disturbed during the experiment.
  • ⁇ EEG signals are extracted with the inserted needle electrode, and the extracted EEG signals are displayed in real time using a BIS monitor device.
  • BIS monitor device indicates that the depth of anesthesia for the experimental small animals has become shallow during the experiment, additional anesthesia may be performed so that the appropriate depth of anesthesia is obtained.
  • the first electrode group composed of a plurality of needle electrodes and the needle electrodes of the second electrode group are fixed to the base, and the first electrode group and the second electrode group are:
  • the tip of the needle electrode is in contact with the temporal muscle located on both sides of the skull and applied with pressure because it is located corresponding to the temporal muscle located on both sides of the skull of the small experimental animal to be inserted and worn.
  • the needle electrode can be inserted into the temporal muscle, and the electroencephalogram measurement electrode can be attached to the small experimental animal very easily.
  • the needle electrode is fixed by using the needle electrode as the electrode and inserting into the left and right temporal muscles, the animal does not move during the experiment, and the position of the electrode does not shift. Furthermore, even if the experimental small animal moves, the electrode does not come off from the fixed position or is difficult to come off unless a force is applied in the direction of pulling out the needle electrode.
  • the electroencephalogram signal of small experimental animals is very small compared to large animals such as humans, so it is necessary to collect the electroencephalogram signals by placing electrodes closer to the brain in order to obtain signals with high sensitivity. .
  • a needle electrode is used as an electrode, and an electroencephalogram signal can be collected by inserting into the temporal muscle adjacent to the right and left hemispheres of the brain, it is possible to acquire an electroencephalogram signal with high sensitivity. It becomes possible.
  • the present invention In order to accurately measure the blood flow in the brain of small experimental animals, it is necessary to simultaneously measure the brain waves in the right and left hemispheres of the brain. Since the present invention has two electrode groups, it becomes easy to simultaneously measure the brain waves in the right and left hemispheres of the brain.
  • the interval between the needle electrodes When the interval between the needle electrodes is wide, the difference in the observed electroencephalogram potential is large, but it is easily affected by noise caused by the heart or the like. On the other hand, if the distance between the needle electrodes is too narrow, the difference in electroencephalogram potential cannot be clearly seen. In the present invention, since the interval between the needle electrodes is set to 1 to 4 mm, the difference in electroencephalogram potential can be measured without being affected by noise caused by the heart or the like.
  • the electroencephalogram measurement electrode device 100 includes a plate-like substrate 1.
  • the substrate 1 is made of polyethylene terephthalate and is formed in a rectangular shape that is elongated in plan view.
  • the length in the width direction is set to 5 mm and the length in the longitudinal direction is set to 15 mm.
  • the length is not limited thereto.
  • the top of the head is relatively flat, so the shape of the substrate 1 is flat and has no problem.
  • the top of the head of the small animal for experiment has a curved surface, the small animal is formed according to the curved surface of the top.
  • substrate 1 it is set as the rigidity which can be pierced into the temporal muscle of the small animal for experiment by one insertion operation.
  • the base body 1 has rising portions 11 and 12 that reinforce the needle electrodes at both ends of the substrate 10.
  • the rising directions of the rising portions 11 and 12 are perpendicular or substantially perpendicular to the surface of the substrate 10.
  • the first electrode group 2 is disposed on one side along the rising portions 11 and 12, and the second electrode group 3 is disposed on the other side.
  • the first electrode group 2 is composed of four needle electrodes 21, 22, 23, and 24 that are arranged so as to protrude in a direction orthogonal to the surface of the substrate 10 of the base 1.
  • the second electrode group 3 is also composed of four needle electrodes 31, 32, 33, and 34 that are arranged so as to protrude in a direction perpendicular to the surface of the substrate 10 of the base 1.
  • the needle electrodes of the first electrode group 2 and the second electrode group 3 protrude in the temporal muscle insertion direction to facilitate attachment to small experimental animals.
  • the four needle electrodes are recommended to be straight or almost straight so that they can be easily inserted into the temporal muscles of the target small experimental animals.
  • the shape is particularly limited. However, any shape can be used as long as it can be inserted into the temporal muscle of the small experimental animal.
  • the length of the needle electrode is 5 mm in the present embodiment, but is not limited to this length. Basically, it is recommended to have a length that can be inserted into the temporal muscle stably and not easily removed. Specifically, it is about 1/5 to 1 of the length of the temporal muscle in the electrode insertion direction, and in the case of a rat, about 3 mm to 10 mm is recommended.
  • the distance between the first electrode group 2 and the second electrode group 3 is designed to correspond to the distance between the temporal muscles of the small experimental animals. For example, in the case of a rat, the distance is about 12 mm to 18 mm. .
  • the electroencephalogram of the experimental small animal has a very low potential, and in order to measure the brain potential difference as a significant value, the four electrode electrodes of each of the first electrode group 2 and the second electrode group 3 are measured.
  • the interval needs to maintain a certain distance or more.
  • the interval between the two needle electrodes for measuring the potential difference in the rat is at least 1 mm or more, preferably 2 mm or more. In the present embodiment, the interval between two adjacent needle electrodes is 1 mm.
  • the first electrode group 2 and the second electrode group 3 have the same structure, the first electrode group 2 is taken as an example to describe the electrodes used.
  • the second electrode 22 from the end is a ground electrode that is not used for the electroencephalogram measurement, and the potential difference is measured by the first needle electrode 21 and the third needle electrode 23 from the end, and the third from the end. Between the first needle electrode 23 and the fourth needle electrode 24, or between the first needle electrode 21 and the fourth needle electrode 24 from the end.
  • the distance between the four needle electrodes is 1 mm
  • the distance between the measurement electrodes is 2 mm when measuring with the first needle electrode 21 and the third needle electrode 23 from the end, and the needle electrodes 21, 24 at both ends. In the case of measurement between the intervals, it becomes 3 mm, and it becomes possible to significantly measure the electroencephalogram. Since the case of the second electrode group 3 is the same as that of the first electrode group 2, the description thereof is omitted.
  • the penetration depth of the needle electrode into the temporal muscle is basically determined by the standard of the temporal muscle of the experimental small animal, but it is sufficient if it can be inserted into the temporal muscle. It is possible to insert the needle electrode shallowly, but if the insertion is too shallow, the needle electrode may be easily detached. As a specific example, for example, in the case of a rat, it is inserted at a depth of 3 mm to 10 mm as described above.
  • Each needle electrode of the first electrode group 2 and the second electrode group 3 is connected to the distal end side of a lead wire (not shown in the figure, reference numerals), and the proximal end side of the lead wire is a BIS monitor device. 5 are electrically connected to electrode terminals (reference numeral omitted).
  • the eight lead wires are appropriately fixed to the base 1 by means, and are bundled by a bundling member 4 that is a contraction tube when it comes out of the base 1.
  • Electroencephalogram measurement method A method for measuring the electroencephalogram of a rat, which is a small experimental animal, using the apparatus according to the present invention will be described. First, anesthesia is applied to rat M while taking care not to exceed an appropriate depth of anesthesia. Whether the anesthesia is effective can be confirmed by clipping the tail and confirming that the anesthesia is effective if the tail does not move.
  • the scalp is incised to expose the temporal muscles M2 and M3 located on both sides of the skull, and then each of the four needles of the first electrode group 2 and the second electrode group 3 of the electroencephalogram measuring electrode device 100.
  • the electrodes are inserted into the left and right temporal muscles M2, M3 of the rat M, and the mounting of the electroencephalogram measuring electrode device 100 is completed.
  • the setting of the electroencephalogram measurement electrode device 100 is simple because the plurality of needle electrodes fixed to the substrate 1 are simply inserted into the left and right temporal muscles M2 and M3 of the rat M, The wearing time is short and the experimental efficiency can be improved.
  • the brain wave signal is extracted with the inserted needle electrode, and the extracted brain wave signal is displayed in real time using the BIS monitor device 5. Thereby, the anesthesia depth of a rat can be measured in real time.
  • each of the four needle electrodes of the first electrode group 2 and the second electrode group 3 is inserted into the left and right temporal muscles M2 and M3 of the rat, not only the electroencephalogram measurement in one hemisphere alone, It is possible to simultaneously measure the brain waves of the left and right hemispheres.
  • two BIS monitor devices are used, and each hemisphere electrode is connected to each BIS monitor device.
  • one BIS monitor device has two display functions and two processing functions, the same operation can be performed with one device.
  • the electroencephalogram measurement electrode device 100 is not detached from the temporal muscles M2 and M3 even if the rat M is moved during the experiment. Or difficult to remove.
  • the first electrode group composed of a plurality of needle electrodes and the needle electrodes of the second electrode group are fixed to the base, and the first electrode group and the second electrode group Since the group is located corresponding to the temporal muscles located on both sides of the skull of the small experimental animal to be inserted and worn, the tip of the needle electrode is in contact with the temporal muscles located on both sides of the skull and pressed.
  • the needle electrode may be inserted into the temporalis muscle by applying pressure, and the electroencephalogram measurement electrode can be attached to a small experimental animal very simply.
  • the needle electrode is fixed by using the needle electrode as the electrode and inserting into the left and right temporal muscles, the animal does not move during the experiment and the position of the electrode does not shift. Furthermore, even if the experimental small animal moves, the electrode does not come off from the fixed position or is difficult to come off unless a force is applied in the direction of pulling out the needle electrode.
  • an electroencephalogram signal is collected by positioning an electrode closer to the brain.
  • an electroencephalogram signal can be collected by inserting into the temporal muscle adjacent to the right and left hemispheres of the brain, it is possible to acquire an electroencephalogram signal with high sensitivity. It becomes possible.
  • Electrode apparatus for electroencephalogram measurement 1 Base 2 First electrode group 21 Needle electrode, 22 Needle electrode, 23 Needle electrode, 24 Needle electrode 3 Second electrode group 31 Needle electrode, 32 Needle electrode, 33 Needle electrode, 34 Needle electrode 4 Bundling member 5 BIS monitoring device M Rat M1 temporal muscle, M2 temporal muscle

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Abstract

The present invention provides an electroencephalographic electrode device whereby electroencephalographic electrodes can be easily attached to a small laboratory animal with no or little drop-off during a test and a weak electroencephalographic voltage can be stably measured at a high sensitivity. The electroencephalographic electrode device comprises a first electrode group (2) consisting of a plurality of needle electrodes and a second electrode group (3) consisting of a plurality of needle electrodes, said needle electrodes of the first electrode group (2) and the second electrode group (3) being fixed to a base (1). The needle electrodes of the first electrode group and the second electrode group are positioned so as to correspond respectively to the positions of the temporal muscles that are located in both sides of the skull of a small laboratory animal into which the needle electrodes are pierced and attached.

Description

実験用小動物の脳波測定用電極装置及び脳波測定方法Electrode device for electroencephalogram measurement of small animal for experiment and electroencephalogram measurement method
　本発明は、齧歯類などの実験用小動物の脳波測定用電極装置及び脳波測定方法に関する。
　更に詳しくは、実験用小動物に簡便に装着でき、装着された電極が実験中に外れないか又は外れにくく、更には微弱な脳波電圧を高感度で安定的に測定できる脳波測定用電極装置及び脳波測定方法に関する。 The present invention relates to an electroencephalogram measurement electrode device and an electroencephalogram measurement method for small experimental animals such as rodents.
More specifically, an electroencephalogram measuring electrode device and an electroencephalogram that can be easily attached to a small experimental animal, the attached electrode is not detached or difficult to remove during the experiment, and furthermore, a weak electroencephalogram voltage can be measured with high sensitivity and stability. It relates to a measurement method.
　動物実験は、医学の発展のために必要なものとしてやむをえず実施されている。動物実験としては、薬理効果の安全性や薬物動態確認のための実験の他に、脳虚血障害の治療のための実験も行われている。
　当該実験は実験動物に外科的処置を施すことから、実験の適正な実施、実験動物の苦痛の軽減を図るため、実験動物に全身麻酔を施した後に実験を行っている。 Animal experiments are inevitable as necessary for medical development. As animal experiments, in addition to experiments for safety of pharmacological effects and confirmation of pharmacokinetics, experiments for treatment of cerebral ischemic injury have also been conducted.
Since the experiment involves surgical treatment of the experimental animal, the experimental animal is subjected to general anesthesia in order to properly perform the experiment and reduce the pain of the experimental animal.
　実験動物に全身麻酔を施す場合、実験動物が手術に適した麻酔深度（麻酔状態）であるかどうかを確認する必要がある。麻酔深度の判定方法としては、一般的には、刺激に対する反射の有無、呼吸数や深さの変化、心拍数や血圧の変化、痛み刺激に対する反応などによって判定される。マウス、ラット等の齧歯類の場合は、尾に刺激を与え、尾を動かさなくなれば、外科的処置を伴う実験に適した麻酔深度にあるものとして、実験が開始される。 When performing general anesthesia on experimental animals, it is necessary to confirm whether the experimental animals are at the depth of anesthesia (anesthetic state) suitable for surgery. The method for determining the depth of anesthesia is generally determined by the presence / absence of reflection to the stimulus, changes in respiratory rate and depth, changes in heart rate and blood pressure, responses to painful stimuli, and the like. In the case of rodents such as mice and rats, if the tail is stimulated and the tail is not moved, the experiment is started assuming that the anesthesia depth is suitable for an experiment involving a surgical procedure.
　麻酔深度が浅く実験用小動物が苦痛や疼痛を感じて実験中に暴れると、その実験で得られたデータが誤差を含む可能性があることから、一連の実験のシリーズから当該データが除かれ、実験そのものが無駄となる場合がある。その結果、追加の実験動物が必要となり、実験動物の生命尊重の観点からは好ましくない。 If the anesthesia depth is shallow and the experimental animal feels pain and pain and goes wild during the experiment, the data obtained in that experiment may contain errors, so that data will be removed from the series of experiments, The experiment itself can be wasted. As a result, an additional experimental animal is required, which is not preferable from the viewpoint of respecting the life of the experimental animal.
　実験中に麻酔深度が浅くなるのを防止するために、適正な麻酔深度を超えて麻酔を効かせる場合は、麻酔薬が実験動物の諸器官に作用し、得られた実験データの正確性が確保できない事態も懸念される。
　従って、実験動物が手術に適した麻酔深度（麻酔状態）にあるかどうかを確認する何らかの手段が要望されている。 In order to prevent the depth of anesthesia from becoming shallow during the experiment, when anesthesia is applied beyond the appropriate depth of anesthesia, the anesthetic acts on the organs of the experimental animal and the accuracy of the experimental data obtained is There is also concern about the situation that cannot be secured.
Therefore, there is a demand for some means for confirming whether or not a laboratory animal is in an anesthesia depth (anesthetic state) suitable for surgery.
　ヒトに対する麻酔深度（麻酔状態）の指標として脳波を測定することが行われており、そのような測定装置としてＢＩＳ（Bispectral index）モニター装置がある（例えば非特許文献１）。当該装置の測定アルゴリズムの詳細は公開されていないが、脳波を、増幅・フィルタリング・周波数解析し、表示モニターに０～１００までの数値（無次元数値）として定量表示する。前記測定装置は脳波の測定と解析に即時性を有するため多くの臨床例に使用されている。 EEG is measured as an index of anesthesia depth (anesthesia state) for humans, and there is a BIS (Bispectral index) monitor device as such a measurement device (for example, Non-Patent Document 1). Although the details of the measurement algorithm of the device are not disclosed, the brain waves are amplified, filtered, and frequency analyzed, and quantitatively displayed on the display monitor as numerical values from 0 to 100 (dimensionless numerical values). The measurement apparatus is used in many clinical cases because it has immediateness in measuring and analyzing the electroencephalogram.
　通常の脳波測定は、得られた脳波信号を解析する。脳波信号の解析には時間が費やされることから、同時的に脳波信号より、麻酔の深度を推測することはできないが、前記したようにＢＩＳモニター装置により脳波を測定した場合には、得られた脳波信号が、同時的に表示モニターに表示されることから、とりわけ、意思表示の難しい動物類の麻酔深度を観察するには極めて好適な装置である。 For normal EEG measurement, the obtained EEG signal is analyzed. Since it takes time to analyze the electroencephalogram signal, the depth of anesthesia cannot be estimated from the electroencephalogram signal at the same time, but it was obtained when the electroencephalogram was measured with the BIS monitor device as described above. Since the electroencephalogram signals are simultaneously displayed on the display monitor, the apparatus is extremely suitable for observing the depth of anesthesia of animals that are difficult to express intentions.
　ＢＩＳモニター装置を羊、馬、豚、猫、イルカ、犬のような大型の実験動物に使用した例は報告されているがマウスやラットのような小型の実験動物について使用した報告はない。これはＢＩＳモニター装置に使用する脳波測定用電極がヒト用に設計された平板型電極構造で、形状も大きく、ラットやマウス等の小型の実験動物には使用できないからと思われる。 例 There have been reports of using the BIS monitor device for large laboratory animals such as sheep, horses, pigs, cats, dolphins, and dogs, but there are no reports of using them for small laboratory animals such as mice and rats. This seems to be because the electroencephalogram measurement electrode used in the BIS monitor device is a flat electrode structure designed for humans and has a large shape and cannot be used for small laboratory animals such as rats and mice.
　実験用小動物としてのラットやマウスの齧歯類に脳波測定用の電極の取り付ける手法としては、ラットやマウスの頭皮を切開し、定位的頭蓋骨２カ所にドリルで穴をあけ、電極を埋め込んだ後に、歯科用セメントで固定するという手法が行われている（例えば特許文献１第５頁段落〔００２３〕参照。）。
　この手法を使えば、ＢＩＳモニター装置をラットやマウスなど齧歯類の動物実験に使用することは一応は可能であると推測される。 As a method of attaching electrodes for electroencephalogram measurement to rodents of rats and mice as experimental small animals, after incising the scalp of rats and mice, drilling holes in two stereotactic skulls, and embedding the electrodes A method of fixing with dental cement has been performed (see, for example, paragraph [0023] on page 5 of Patent Document 1).
If this method is used, it is presumed that it is possible to use the BIS monitor device for experiments on rodents such as rats and mice.
特開２００６－１４７２９号公報（第５頁段落〔００２３〕）JP 2006-14729 A (paragraph [0023] on page 5)
　しかし、頭蓋骨にドリルで穴を開ける外科的処置には、熟練した技術を必要とし、穴開けに失敗すると実験動物を無駄にしてしまうため慎重に行う必要があり、実験前の準備のために時間及び手間を必要とする課題がある。
　また、頭蓋骨にドリルで穴を開ける際に硬膜を露出させてしまう可能性があり、脳研究の結果に大きなバイアスを与える頭蓋内圧に影響を与える課題がある。 However, the surgical procedure for drilling holes in the skull requires skilled skills, and if the drilling fails, laboratory animals are wasted and must be done carefully. There is a problem that requires time and effort.
Moreover, there is a possibility that the dura mater may be exposed when a hole is drilled in the skull, and there is a problem that affects the intracranial pressure that exerts a great bias on the results of brain research.
（本発明の目的）
　本発明の目的は、実験用小動物に脳波測定用電極を簡便に装着でき、装着された電極が実験中に外れないか又は外れにくく、更には微弱な脳波電圧を高感度で安定的に測定できるようにすることにある。
　また、本発明の他の目的は、心臓等からもたらされるノイズの影響を防止することにある。 (Object of the present invention)
It is an object of the present invention to easily attach an electroencephalogram measurement electrode to a small experimental animal, and the attached electrode does not or does not come off during the experiment, and furthermore, a weak electroencephalogram voltage can be stably measured with high sensitivity. There is in doing so.
Another object of the present invention is to prevent the influence of noise from the heart or the like.
　前記課題を解決するために本発明が講じた手段は次のとおりである。
　本発明は、実験用小動物の脳波を測定するための電極装置であって、複数本の針電極で構成される第１の電極群と、複数本の針電極で構成される第２の電極群と、を備え、前記第１の電極群及び第２の電極群の針電極は基体に固定されており、前記第１の電極群と第２の電極群は、実験用小動物の頭蓋骨両側に位置する左右の側頭筋にそれぞれ刺入させ装着させるように、第１の電極群及び第２の電極群のそれぞれの刺入部分となる先端部を含む針電極が基体から突出している、実験用小動物の脳波測定用電極装置である。 Means taken by the present invention to solve the above-mentioned problems are as follows.
The present invention is an electrode device for measuring an electroencephalogram of a small experimental animal, and includes a first electrode group composed of a plurality of needle electrodes and a second electrode group composed of a plurality of needle electrodes. The needle electrodes of the first electrode group and the second electrode group are fixed to a base, and the first electrode group and the second electrode group are located on both sides of the skull of the experimental small animal. The needle electrode including the tip part which becomes the insertion part of each of the first electrode group and the second electrode group protrudes from the base so that the left and right temporal muscles are inserted and worn. This is an electrode device for measuring an electroencephalogram of a small animal.
　脳波測定用電極装置は、基体が、平板状もしくはコの字型の板状の絶縁体物質からなり、該基体に固定された第１の電極群と第２の電極群の各針電極の先端部が、前記基体のそれぞれの端から、実験用小動物の左右の側頭筋に刺入させるように垂直又は略垂直に突出しているのが好ましい。 In the electroencephalogram measurement electrode device, the base is made of a flat or U-shaped plate-like insulator material, and the tips of the needle electrodes of the first electrode group and the second electrode group fixed to the base It is preferable that the portion protrudes vertically or substantially vertically from each end of the base so as to be inserted into the left and right temporal muscles of the experimental small animal.
　脳波測定用電極装置は、基体に固定された第１の電極群の先端部と第２の電極群の先端部との間隔が、対象となる実験用小動物の左右の側頭筋の間隔の最小幅以上、最大幅以下であるのが好ましい。 In the electroencephalogram measurement electrode device, the distance between the distal end of the first electrode group fixed to the base and the distal end of the second electrode group is the maximum of the distance between the left and right temporal muscles of the target small experimental animal. It is preferable that the width is not less than the minimum width and not more than the maximum width.
　脳波測定用電極装置は、第１の電極群及び第２の電極群のそれぞれの側頭筋への刺入部となる先端部の長さが、実験用小動物への側頭筋の刺入方向長さの５分の１以上１以下となるのが好ましい。 In the electroencephalogram measurement electrode device, the length of the distal end portion of each of the first electrode group and the second electrode group serving as the insertion portion into the temporal muscle is determined by the insertion direction of the temporal muscle into the experimental small animal. It is preferable that it is 1/5 or more and 1 or less of the length.
　脳波測定用電極装置は、第１の電極群及び第２の電極群を構成する複数本の針電極の間隔は、その隣接する電極の間隔が、対応する実験小動物の大脳の長軸方向の長さの５分の１～２５分の１の長さ間隔となるのが好ましい。 In the electrode apparatus for electroencephalogram measurement, the interval between the plurality of needle electrodes constituting the first electrode group and the second electrode group is such that the interval between the adjacent electrodes is the length in the long axis direction of the cerebrum of the corresponding experimental small animal. The length interval is preferably 1/5 to 1/25 of the length.
　脳波測定用電極装置は、第１の電極群及び第２の電極群は、それぞれ３本以上の針電極を列設して構成され、両端以外から選択される針電極の１本をアース電極とし、残りの電極のうちのそれぞれ２本の電極を使用して脳波を測定するのが好ましい。 In the electroencephalogram measuring electrode device, each of the first electrode group and the second electrode group is formed by arranging three or more needle electrodes, and one of the needle electrodes selected from other than both ends is used as the ground electrode. Preferably, the electroencephalogram is measured using two of each of the remaining electrodes.
　脳波測定用電極装置は、ＢＩＳモニター装置を使用して実験用小動物の脳波を測定するために、ＢＩＳモニター装置に連結させ、ＢＩＳモニター装置における脳波測定用電極装置として用いるのが好ましい。 The electroencephalogram measurement electrode device is preferably connected to the BIS monitor device and used as the electroencephalogram measurement electrode device in the BIS monitor device in order to measure the electroencephalogram of the experimental small animal using the BIS monitor device.
　脳波測定用電極装置は、ＢＩＳモニター装置の脳波測定用電極装置であり、第１の電極群及び第２の電極群は、それぞれＢＩＳモニター装置の電極端子数の針電極を列設して構成され、両端以外から選択される針電極の１本をアース電極とし、残りの電極のうちのそれぞれ２本の電極を使用して脳波を測定するのが好ましい。 The electrode device for electroencephalogram measurement is an electrode device for electroencephalogram measurement of a BIS monitor device, and the first electrode group and the second electrode group are configured by arranging needle electrodes corresponding to the number of electrode terminals of the BIS monitor device, respectively. Preferably, one of the needle electrodes selected from other than both ends is the ground electrode, and the electroencephalogram is measured using two of the remaining electrodes.
　脳波測定用電極装置は、電極端子数が４であるＢＩＳモニター装置を用いた脳波の測定において、第１の電極群及び第２の電極群は、それぞれ４本の針電極を列設して構成され、それぞれの電極群の端から２番目の電極をアース電極とし、端から１番目と３番目及び端から１番目と４番目の電極間の電位差を測定するために使用するのが好ましい。 The electroencephalogram measurement electrode device is configured by arranging four needle electrodes in each of the first electrode group and the second electrode group in the electroencephalogram measurement using the BIS monitor device having four electrode terminals. It is preferable to use the second electrode from the end of each electrode group as a ground electrode and measure the potential difference between the first and third electrodes from the end and the first and fourth electrodes from the end.
　実験用小動物はラット等の齧歯類であるのが好ましい。 The experimental small animal is preferably a rodent such as a rat.
　本発明は、実験用小動物の頭皮を切開して頭蓋骨の両側に位置する側頭筋を露出し、当該側頭筋に、アース電極及び測定用電極として少なくとも二本の針電極を刺入して脳波信号を取り出し、取り出された脳波信号をＢＩＳモニター装置を使用してリアルタイムで表示する、実験用小動物の脳波測定方法である。 In the present invention, the scalp of an experimental small animal is incised to expose the temporal muscles located on both sides of the skull, and at least two needle electrodes are inserted into the temporal muscle as a ground electrode and a measurement electrode. This is a method for measuring an electroencephalogram of an experimental small animal, which extracts an electroencephalogram signal and displays the extracted electroencephalogram signal in real time using a BIS monitor device.
　脳波測定方法は、実験用小動物の脳の左半球と右半球の脳波を同時に又はいずれか一方を測定するのが好ましい。 The electroencephalogram measurement method preferably measures the electroencephalograms of the left hemisphere and right hemisphere of the brain of a small experimental animal at the same time or at least one of them.
　脳波測定方法は、ＢＩＳモニター装置２台及び電極装置を用いて、第１の電極群の端子を第１のＢＩＳモニター装置に接続し、第２の電極群の端子を第２のＢＩＳモニター装置に接続し、実験用小動物の脳の左半球と右半球の脳波を同時又はいずれか一方を測定するのが好ましい。 The electroencephalogram measurement method uses two BIS monitor devices and an electrode device to connect the terminals of the first electrode group to the first BIS monitor device and connect the terminals of the second electrode group to the second BIS monitor device. It is preferable to connect and measure the brain waves of the left hemisphere and right hemisphere of the brain of a small experimental animal at the same time or at least one of them.
　刺入して装着する実験用小動物の頭蓋骨両側に位置する側頭筋とそれぞれ対応して位置している第１の電極群及び第２の電極群を構成する複数本の針電極の間隔は１～４ｍｍが好ましい。
　第１の電極群及び第２の電極群は、四本の針電極を列設して構成され、端から２番目の針電極をアース電極とし、残りの電極のうちの二本を使用して脳波を測定するのが好ましい。 The interval between the plurality of needle electrodes constituting the first electrode group and the second electrode group positioned corresponding to the temporal muscles located on both sides of the skull of the small experimental animal to be inserted and mounted is 1 ˜4 mm is preferred.
The first electrode group and the second electrode group are configured by arranging four needle electrodes, the second needle electrode from the end is the ground electrode, and two of the remaining electrodes are used. It is preferable to measure an electroencephalogram.
　本発明に係る脳波測定用電極装置及び脳波測定方法を用いることで、実験用小動物の脳の左半球と右半球の脳波は、同時に又はいずれか一方を測定することができる。
　この際、ＢＩＳモニター装置のように、電極端子数が限られている場合には、例えば、モニター装置を複数台、好ましくは２台用いて、例えば、第１の電極群を一方のモニター装置端子に接続し、第２の電極群を他方のモニター装置端子に接続することで大脳の左右の半球の脳波をそれぞれ同時に又は電極端子の取り外し等の操作を必要とせず、効率的に測定することができる。 By using the electroencephalogram measurement electrode device and the electroencephalogram measurement method according to the present invention, the electroencephalograms of the left hemisphere and the right hemisphere of the experimental small animal brain can be measured simultaneously or either.
At this time, when the number of electrode terminals is limited as in the BIS monitor device, for example, a plurality of monitor devices, preferably two, are used, for example, the first electrode group is connected to one monitor device terminal. By connecting the second electrode group to the other monitor device terminal, the brain waves of the left and right hemispheres of the cerebrum can be measured efficiently without the need for simultaneous operation or removal of the electrode terminals. it can.
　例えば、通常市販のＢＩＳモニター装置においては、電極端子は４個所設けられている。その際に、本発明に係る電極装置として第１の電極群及び第２の電極群が、それぞれ４本の電極（そのうち１本はアース電極）で構成されている場合には、２台のＢＩＳモニター装置を用いて、第１の電極群を一方のＢＩＳモニター装置に接続し、他方のＢＩＳモニター装置に第２の電極群を接続する。このように接続することで、前記したように、同時に大脳の左右の半球の脳波を同時に測定することができる。 For example, in a commercially available BIS monitor device, four electrode terminals are provided. At that time, when the first electrode group and the second electrode group as the electrode device according to the present invention are each composed of four electrodes (one of which is a ground electrode), two BISs are used. Using the monitor device, the first electrode group is connected to one BIS monitor device, and the second electrode group is connected to the other BIS monitor device. By connecting in this way, as described above, the brain waves of the left and right hemispheres of the cerebrum can be simultaneously measured.
　また、大脳の左右の半球の脳波を測定しようとする場合、１台のＢＩＳモニター装置では、一方の電極群の接続をはずし、もう一方の電極群を接続しなければならないが、２台のＢＩＳモニター装置を用いればこのような煩雑さは回避される。
　しかしながら、本発明においてはこのような場合において、２台のＢＩＳモニター装置を用いることは発明の必須の要件ではない。
　無論、使用するＢＩＳモニター装置の電極端子が、第１の電極群と第２の電極群の総てを接続出来得る端子を有している場合には、ＢＩＳモニター装置１台でも効率的に脳波を測定することができる。 Also, when measuring brain waves in the left and right hemispheres of the cerebrum, one BIS monitor device must disconnect one electrode group and connect the other electrode group. Such a complexity can be avoided by using a monitor device.
However, in the present invention, in such a case, the use of two BIS monitor devices is not an essential requirement of the invention.
Of course, when the electrode terminals of the BIS monitor device to be used have terminals that can connect all of the first electrode group and the second electrode group, even one BIS monitor device can efficiently perform the electroencephalogram. Can be measured.
　本発明で使用される針電極は市販のものが使用でき、実験用小動物の側頭筋に刺入し脳波の電位を導出できればその構造などは特に限定されない。本発明に使用される針電極は、側頭筋に刺入されることから、実験中に実験用小動物が動いたり、実験のために体位を変えても、針電極は外れないか、外れにくい。また、脳に近接している側頭筋に刺入できるため、通常の平面電極に比較して、より微弱な脳波電圧を高感度で安定的に測定できる。
　複数の針電極を基体に固定して一体化することによって、装置の取扱いが簡便となる。 As the needle electrode used in the present invention, a commercially available one can be used, and the structure thereof is not particularly limited as long as it can be inserted into the temporal muscle of a small experimental animal and the potential of the electroencephalogram can be derived. Since the needle electrode used in the present invention is inserted into the temporal muscle, the needle electrode does not come off or is difficult to come off even if the experimental small animal moves during the experiment or changes its position for the experiment. . In addition, since it can be inserted into the temporal muscles close to the brain, a weaker electroencephalogram voltage can be stably measured with high sensitivity compared to a normal planar electrode.
By fixing and integrating the plurality of needle electrodes to the substrate, the apparatus can be handled easily.
　実験用小動物の脳波は微少電位であり、針電極の間隔が余りに狭いと、脳波電位の差が明瞭にあらわれない場合も生じる。しかしながら、それぞれの隣接した針電極間の間隔を広くすると脳波電位の差が明瞭にあらわれるが、そうすると心臓等から発せられるノイズの影響を受ける場合もあり、正確な脳波測定が困難となる。 The brain waves of small experimental animals are very small, and if the distance between the needle electrodes is too narrow, the difference in brain wave potential may not appear clearly. However, if the interval between each adjacent needle electrode is widened, a difference in electroencephalogram potential appears clearly. However, in that case, it may be affected by noise emitted from the heart or the like, making accurate electroencephalogram measurement difficult.
　この二律背反を克服するためには、針電極の間隔を調節する必要がある。その間隔は実験用小動物の大脳の大きさによりそれぞれ異なるが、隣接する対象となる実験用小動物の大脳の長軸方向長さの５分の１以下、２５分の１以上の間隔とすることが好ましい。具体的には例えば、大脳の長軸方向の長さが、約２５ｍｍであるラットの場合には４ｍｍ以下、１ｍｍ以上が好ましい。また、３ｍｍ以下であればさらに好ましい。 To overcome this trade-off, it is necessary to adjust the distance between the needle electrodes. The interval differs depending on the size of the cerebrum of the experimental small animal, but it should be set to an interval of 1/5 or less and 1/25 or more of the length of the cerebrum in the long axis direction of the adjacent experimental small animal. preferable. Specifically, for example, in the case of a rat whose cerebral length in the long axis direction is about 25 mm, 4 mm or less and 1 mm or more are preferable. Moreover, it is more preferable if it is 3 mm or less.
　ラットの場合、隣接する針電極の間隔を例えば１ｍｍとし、隣接する針電極間の電位差を測定した場合には、電位差が小さく、有意な脳波測定が出来ない場合が生じる恐れがある。こういった場合、できるだけ隣接する針電極の間隔を狭くし、かつ、有効に電位差を測定するために、アース電極を配置された電極群の末端に位置させずに、内部に位置する針電極をアース電極とすることが、実質的に狭い針電極間隔であっても、測定電極を広くすることができ、本発明においては推奨される。 In the case of rats, when the distance between adjacent needle electrodes is set to 1 mm, for example, and the potential difference between adjacent needle electrodes is measured, the potential difference is small, and there is a possibility that significant electroencephalogram measurement cannot be performed. In such a case, in order to reduce the interval between the adjacent needle electrodes as much as possible and to effectively measure the potential difference, the ground electrode is not located at the end of the arranged electrode group, and the needle electrode located inside is not placed. It is recommended in the present invention that the ground electrode be a measurement electrode even if it is a substantially narrow needle electrode interval.
　例えば、電極端子が４端子である２台のＢＩＳモニター装置にそれぞれ、基体上に固定された４本の針電極から構成される第１の電極群と第２の電極群からなる、本発明の電極装置において、内部に位置する２番目の針電極をアース電極とし、末端に位置する第１番目の針電極と内部に位置する第３番目の針電極との間の電位差及び第１番目の針電極と他の末端に位置する第４番目の針電極との電位差を測定することで、有効な電位差が得られ、脳波測定が精度良く達成される。 For example, each of the two BIS monitor devices having four electrode terminals includes a first electrode group and a second electrode group each including four needle electrodes fixed on a base. In the electrode device, the second needle electrode located inside is a ground electrode, the potential difference between the first needle electrode located at the end and the third needle electrode located inside and the first needle electrode By measuring the potential difference between the electrode and the fourth needle electrode located at the other end, an effective potential difference can be obtained, and electroencephalogram measurement can be achieved with high accuracy.
　このような場合、電位差測定の針電極との間隔は、隣接する針電極との間隔がそれぞれ１ｍｍであっても、実質的には２ｍｍ（第１番目と第３番目の針電極での測定）及び３ｍｍ（第１番目と第４番目の針電極での測定）となり、上記した二律背反の問題を解消することができる。 In such a case, the distance between the needle electrodes for potential difference measurement is substantially 2 mm (measured with the first and third needle electrodes) even if the distance between adjacent needle electrodes is 1 mm. And 3 mm (measurement with the first and fourth needle electrodes), and the above-mentioned problem of antinomy can be solved.
　本発明で使用される基体の素材には、特に限定はされないが、絶縁体物質であることが推奨される。具体的には、ＰＥＴ（ポリエチレンテレフタレート）樹脂、ポリエチレン樹脂、ポリプロピレン樹脂、アクリル樹脂、パーフルオロエチレン（商品名テフロン（登録商標）等）等の合成樹脂等である。また、導電物質であっても、各電極をそれぞれ、基体と接触する部分を絶縁物質によりシールしておけば、金属或いはこれらの樹脂と金属等の複合物等が使用できる。無論、針電極とＢＩＳモニター装置等の脳波測定器とを接続するリード線は、合成樹脂等の絶縁物により被覆されている。 The base material used in the present invention is not particularly limited, but an insulating material is recommended. Specifically, synthetic resins such as PET (polyethylene terephthalate) resin, polyethylene resin, polypropylene resin, acrylic resin, perfluoroethylene (trade name Teflon (registered trademark), etc.), and the like. Moreover, even if it is an electroconductive substance, if each electrode contacts each base | substrate with the insulating substance, a metal or these composites, such as resin and metal, etc. can be used. Of course, the lead wire connecting the needle electrode and an electroencephalograph such as a BIS monitor device is covered with an insulator such as a synthetic resin.
　また、基板の形状や剛性は実験用小動物に装着できれば特に限定されるものではない。ラットやマウスのような齧歯類の場合は、頭部頂部は比較的平坦であるから、形状は平板状で支障はない。実験用小動物の頭部頂部が曲面を有する場合は、頂部曲面に合わせて形成できる。また、平板や湾曲した板の両末端部分に立ち上がり部を設けてコの字型となった形態も、針電極をそれぞれ固定するためには推奨される。 Also, the shape and rigidity of the substrate are not particularly limited as long as they can be mounted on small experimental animals. In the case of rodents such as rats and mice, since the top of the head is relatively flat, the shape is flat and there is no problem. When the top of the head of the small animal for experiment has a curved surface, it can be formed according to the curved surface of the top. In addition, a U-shaped configuration in which rising portions are provided at both end portions of a flat plate or a curved plate is also recommended for fixing the needle electrodes.
　剛性については、あまり柔軟性を有すると、一回の操作で側頭筋に刺入できない場合が生じるので、一回の刺入操作で側頭筋に刺入できる程度に剛性を有することが好ましい。 As for the rigidity, if there is too much flexibility, there is a case where the temporal muscle cannot be inserted by a single operation. Therefore, it is preferable that the rigidity is sufficient to allow the temporal muscle to be inserted by a single insertion operation. .
　一般的に市販されているＢＩＳモニター装置は電極端子が四箇所であり、実験用小動物の脳波を正確に測定するためは、脳の右半球と左半球の脳波測定を同時に行うのが好ましい。
　このことから、ＢＩＳモニター装置を２台同時に使用すると、実験用小動物の脳の右半球および左半球の脳波を同時に測定することができる。 In general, a commercially available BIS monitor apparatus has four electrode terminals, and in order to accurately measure the electroencephalogram of a small experimental animal, it is preferable to simultaneously measure the electroencephalogram of the right and left hemispheres of the brain.
From this, when two BIS monitor devices are used simultaneously, the brain waves of the right hemisphere and the left hemisphere of the experimental small animal brain can be measured simultaneously.
　本発明に係る電極装置は前記したように、第１の電極群と第２の電極群を基体に固定し一体化している。基体に固定されているそれぞれの電極群の針電極の先端が左右の側頭筋に刺入されることにより、安定に装着され且つ外れにくくなる。 As described above, in the electrode device according to the present invention, the first electrode group and the second electrode group are fixed to the substrate and integrated. The tip of the needle electrode of each electrode group fixed to the base is inserted into the left and right temporal muscles, so that it is stably attached and difficult to come off.
　本発明に係る電極装置においては、それぞれの電極群を構成し刺入部分となる先端部を含む針電極が基体から垂直またはほぼ垂直に突出しており、この先端部が側頭筋に刺入される。
　この時、第１の電極群と第２の電極群との間隔（ほぼ、基体の両端間の間隔となる）は、対象となる実験用小動物の左右の側頭筋との間隔（厚みがあるので、厚みの中間間隔）とすることが推奨される。この間隔とすることで、特段の操作も必要としなくて簡便に電極を左右の側頭筋に刺入することが可能となる。例えば、実験用小動物としてラットを用いた場合、前記の間隔は１２～１８ｍｍ程度となる。 In the electrode device according to the present invention, the needle electrode including the distal end portion constituting each electrode group and serving as the insertion portion protrudes vertically or substantially vertically from the base body, and the distal end portion is inserted into the temporal muscle. The
At this time, the distance between the first electrode group and the second electrode group (approximately the distance between both ends of the base) is the distance between the left and right temporal muscles of the target small experimental animal (there is a thickness). Therefore, it is recommended to use an intermediate thickness). By setting this interval, it is possible to easily insert the electrodes into the left and right temporal muscles without requiring any special operation. For example, when a rat is used as an experimental small animal, the interval is about 12 to 18 mm.
　また、本発明に係る電極装置において、各針電極の側頭筋への刺入部分となる先端部の長さ（刺入深さに対応）は、針電極の長さを刺入方向の側頭筋の長さの５分の１以上１以下とすることが好ましい。
　これ以上の長さであっても、脳波を測定することは可能であるが、体外へ針電極先端が貫通する等の実験上の不備が生じる恐れがある。また、余りに、短い場合には安定的に刺入し、針電極を固定することが難しくなり、また、針電極が外れやすくなる恐れがあるためである。
　具体的には、たとえば、ラットでは３ｍｍ～１０ｍｍ程度が推奨される。無論、基体がコの字型のものであっても、刺入可能な長さとして、前記の値が推奨される。
　なお、針電極と接続されているリード線が実験中に対象部位へのアクセスを邪魔しないように、基体近傍でまとめるとよい。 In the electrode device according to the present invention, the length of the tip portion (corresponding to the depth of insertion) of each needle electrode that is inserted into the temporal muscle is the length of the needle electrode in the insertion direction side. It is preferable that the length is 1/5 or more and 1 or less of the length of the head muscle.
Even if the length is longer than this, it is possible to measure an electroencephalogram, but there is a risk that an experimental defect such as penetration of the tip of the needle electrode outside the body may occur. In addition, when the length is too short, it is difficult to stably insert and fix the needle electrode, and the needle electrode may be easily detached.
Specifically, for example, about 3 mm to 10 mm is recommended for rats. Of course, even if the base is U-shaped, the above-mentioned value is recommended as the length that can be inserted.
It should be noted that the lead wires connected to the needle electrode may be grouped near the base so that access to the target site is not disturbed during the experiment.
（作　用）
　本発明の作用を説明する。
　実験用小動物の脳波を測定する場合は、まず、実験用小動物の頭皮を切開して頭蓋骨の両側に位置する側頭筋を露出させる。次いで電極装置の第１の電極群と第２の電極群の針電極の先端を頭蓋骨の両側に位置する側頭筋に当接し、押圧力をかけて針電極を側頭筋に刺入する。針電極の刺入作業は、基本的には一回で済むために、実験用小動物への電極の取付作業が簡便に、且つ短時間で行うことができる。 (Work)
The operation of the present invention will be described.
When measuring the electroencephalogram of a small experimental animal, first, the scalp of the small experimental animal is incised to expose the temporal muscles located on both sides of the skull. Next, the tips of the needle electrodes of the first electrode group and the second electrode group of the electrode device are brought into contact with the temporal muscle located on both sides of the skull, and the needle electrode is inserted into the temporal muscle by applying a pressing force. Since the needle electrode insertion operation is basically performed only once, the electrode attachment operation to the experimental small animal can be performed easily and in a short time.
　刺入した針電極で脳波信号を取り出し、取り出された脳波信号をＢＩＳモニター装置を使用してリアルタイムで表示する。これにより、実験用小動物の麻酔深度がリアルタイムに測定できるため、麻酔深度の深浅による前記課題が解決できる。 脳 EEG signals are extracted with the inserted needle electrode, and the extracted EEG signals are displayed in real time using a BIS monitor device. Thereby, since the depth of anesthesia of the experimental small animal can be measured in real time, the above-described problem due to the depth of the anesthetic depth can be solved.
　実験中に実験用小動物の麻酔深度が浅くなったことがＢＩＳモニター装置で表示された場合は、適正な麻酔深度になるように追加麻酔を施せばよい。 If the BIS monitor device indicates that the depth of anesthesia for the experimental small animals has become shallow during the experiment, additional anesthesia may be performed so that the appropriate depth of anesthesia is obtained.
　本発明によれば、複数本の針電極で構成される第１の電極群及び第２の電極群の針電極は基体に固定されており、第１の電極群と第２の電極群は、刺入して装着する実験用小動物の頭蓋骨両側に位置する側頭筋と対応して位置しているので、針電極の先端を頭蓋骨の両側に位置する側頭筋に当接し、押圧力をかけて針電極を側頭筋に刺入すれば良く、実験用小動物への脳波測定用電極の装着が極めて簡便に行える。 According to the present invention, the first electrode group composed of a plurality of needle electrodes and the needle electrodes of the second electrode group are fixed to the base, and the first electrode group and the second electrode group are: The tip of the needle electrode is in contact with the temporal muscle located on both sides of the skull and applied with pressure because it is located corresponding to the temporal muscle located on both sides of the skull of the small experimental animal to be inserted and worn. The needle electrode can be inserted into the temporal muscle, and the electroencephalogram measurement electrode can be attached to the small experimental animal very easily.
　また、電極に針電極を使用し、左右の側頭筋に刺入することによって針電極が固定されるため、実験中に動物が動いて針も電極の位置がずれたりしない。更には、実験用小動物が動いても針電極を引き抜く方向に力を加えない限り電極が固定箇所から外れないか、外れにくい。 Also, since the needle electrode is fixed by using the needle electrode as the electrode and inserting into the left and right temporal muscles, the animal does not move during the experiment, and the position of the electrode does not shift. Furthermore, even if the experimental small animal moves, the electrode does not come off from the fixed position or is difficult to come off unless a force is applied in the direction of pulling out the needle electrode.
　実験用小動物の脳波信号は、ヒト等の大きな動物に比較して非常に小さいことから、信号を感度良く取得するには、より脳の近傍に電極を位置させて脳波信号を採取する必要がある。本発明では、電極に針電極を使用し、脳の右半球と左半球に近接する側頭筋に刺入して脳波信号を採取することができるため、高感度で脳波信号を取得することが可能となる。 The electroencephalogram signal of small experimental animals is very small compared to large animals such as humans, so it is necessary to collect the electroencephalogram signals by placing electrodes closer to the brain in order to obtain signals with high sensitivity. . In the present invention, since a needle electrode is used as an electrode, and an electroencephalogram signal can be collected by inserting into the temporal muscle adjacent to the right and left hemispheres of the brain, it is possible to acquire an electroencephalogram signal with high sensitivity. It becomes possible.
　実験用小動物の脳内血流量を精度良く測定するには脳の右半球と左半球の脳波を同時に測定する必要がある。本発明では二つの電極群を有するので、脳の右半球と左半球の脳波を同時に測定することが容易となる。 In order to accurately measure the blood flow in the brain of small experimental animals, it is necessary to simultaneously measure the brain waves in the right and left hemispheres of the brain. Since the present invention has two electrode groups, it becomes easy to simultaneously measure the brain waves in the right and left hemispheres of the brain.
　針電極間の間隔が広い場合は観察される脳波電位の差は大きくなるが、心臓等からもたらされるノイズの影響を受けやすくなる。逆に、針電極間の間隔が狭過ぎると脳波電位の差が明瞭にあらわれない。
　本発明では、針電極間の間隔を１～４ｍｍとしたので、心臓等からもたらされるノイズの影響を受けずに脳波電位の差を測定することができる。 When the interval between the needle electrodes is wide, the difference in the observed electroencephalogram potential is large, but it is easily affected by noise caused by the heart or the like. On the other hand, if the distance between the needle electrodes is too narrow, the difference in electroencephalogram potential cannot be clearly seen.
In the present invention, since the interval between the needle electrodes is set to 1 to 4 mm, the difference in electroencephalogram potential can be measured without being affected by noise caused by the heart or the like.
実験用小動物の脳波測定用電極装置の要部を示す模式図である。It is a schematic diagram which shows the principal part of the electrode apparatus for electroencephalogram measurement of the small animal for experiment. 実験用小動物の脳波測定用電極装置を使用してマウスの脳波を測定している状態を示す説明図である。It is explanatory drawing which shows the state which is measuring the electroencephalogram of a mouse | mouth using the electrode apparatus for electroencephalogram measurement of a small animal for experiment.
　本発明を図に示した実施の形態に基づき詳細に説明する。
　図１を参照する。 脳波測定用電極装置１００は、板状の基体１を備えている。基体１は、ポリエチレンテレフタレート（Polyethylene Terephthalate）で作られており、平面視細長の長方形に形成されている。本実施例の場合は、幅方向の長さは５ｍｍ、長手方向の長さは１５ｍｍに設定しているが、これらの長さに限定されない。 The present invention will be described in detail based on the embodiments shown in the drawings.
Please refer to FIG. The electroencephalogram measurement electrode device 100 includes a plate-like substrate 1. The substrate 1 is made of polyethylene terephthalate and is formed in a rectangular shape that is elongated in plan view. In this embodiment, the length in the width direction is set to 5 mm and the length in the longitudinal direction is set to 15 mm. However, the length is not limited thereto.
　実験用小動物、特にラットやマウスのような齧歯類の場合は、頭部頂部は比較的平坦であるから、基体１の形状は平板状で支障はない。実験用小動物の頭部頂部が曲面を有する場合は、頂部曲面に合わせて形成する。
　基体１の剛性については、一回の刺入操作で実験用小動物の側頭筋に刺入できる剛性としている。 In the case of small experimental animals, particularly rodents such as rats and mice, the top of the head is relatively flat, so the shape of the substrate 1 is flat and has no problem. When the top of the head of the small animal for experiment has a curved surface, the small animal is formed according to the curved surface of the top.
About the rigidity of the base | substrate 1, it is set as the rigidity which can be pierced into the temporal muscle of the small animal for experiment by one insertion operation.
　基体１は、基板１０の両側端に針電極を補強する立ち上がり部１１，１２を有する。立ち上がり部１１，１２の立ち上がり方向は、基板１０の表面に対して垂直又は略垂直である。これらの立ち上がり部１１，１２に沿って一方側に第１の電極群２が、他方側に第２の電極群３が配置される。
　第１の電極群２は、基体１の基板１０表面に対して直交する方向に突出して列設されている４本の針電極２１，２２，２３，２４から構成されている。
　第２の電極群３も、基体１の基板１０表面に対して直交する方向に突出して列設されている４本の針電極３１，３２，３３，３４から構成されている。 The base body 1 has rising portions 11 and 12 that reinforce the needle electrodes at both ends of the substrate 10. The rising directions of the rising portions 11 and 12 are perpendicular or substantially perpendicular to the surface of the substrate 10. The first electrode group 2 is disposed on one side along the rising portions 11 and 12, and the second electrode group 3 is disposed on the other side.
The first electrode group 2 is composed of four needle electrodes 21, 22, 23, and 24 that are arranged so as to protrude in a direction orthogonal to the surface of the substrate 10 of the base 1.
The second electrode group 3 is also composed of four needle electrodes 31, 32, 33, and 34 that are arranged so as to protrude in a direction perpendicular to the surface of the substrate 10 of the base 1.
　第１の電極群２と第２の電極群３の針電極は、それぞれ側頭筋刺入方向に突出して実験用小動物への装着を容易にしている。本実施例では、前記４本の針電極は、対象となる実験用小動物の側頭筋に刺入し易いように、真っ直ぐもしくはほぼ真っ直ぐな形状が推奨されるが、特にその形状は限定されることはなく、対象となる実験用小動物の側頭筋に刺入出来る形状であればいずれの形状であっても差し支えない。 The needle electrodes of the first electrode group 2 and the second electrode group 3 protrude in the temporal muscle insertion direction to facilitate attachment to small experimental animals. In the present embodiment, the four needle electrodes are recommended to be straight or almost straight so that they can be easily inserted into the temporal muscles of the target small experimental animals. However, the shape is particularly limited. However, any shape can be used as long as it can be inserted into the temporal muscle of the small experimental animal.
　針電極の長さは、本実施例の場合は５ｍｍとしているが、この長さに限定されるものではない。基本的には側頭筋に安定的に且つ、容易に外れない程度に刺入することが可能である長さが推奨される。具体的には側頭筋の電極刺入方向の長さの５分の１から１程度であり、ラットの場合では３ｍｍ～１０ｍｍ程度が推奨される。
　第１の電極群２及び第２の電極群３間の間隔は、実験用小動物の側頭筋肉の間隔に対応して設計されるが、例えばラットであれば、１２ｍｍ～１８ｍｍ程度の間隔となる。 The length of the needle electrode is 5 mm in the present embodiment, but is not limited to this length. Basically, it is recommended to have a length that can be inserted into the temporal muscle stably and not easily removed. Specifically, it is about 1/5 to 1 of the length of the temporal muscle in the electrode insertion direction, and in the case of a rat, about 3 mm to 10 mm is recommended.
The distance between the first electrode group 2 and the second electrode group 3 is designed to correspond to the distance between the temporal muscles of the small experimental animals. For example, in the case of a rat, the distance is about 12 mm to 18 mm. .
　既に説明したように、実験用小動物の脳波は微少電位であり、脳の電位差を有意ある値として測定するには第１の電極群２及び第２の電極群３の各４本の針電極の間隔は、一定以上の距離を保持する必要がある。具体的には、ラットにおける電位差を測定する２本の針電極の間隔は、少なくとも１ｍｍ以上、好ましくは２ｍｍ以上である。本実施例の場合は隣り合う２本の針電極の間隔は、１ｍｍである。 As already explained, the electroencephalogram of the experimental small animal has a very low potential, and in order to measure the brain potential difference as a significant value, the four electrode electrodes of each of the first electrode group 2 and the second electrode group 3 are measured. The interval needs to maintain a certain distance or more. Specifically, the interval between the two needle electrodes for measuring the potential difference in the rat is at least 1 mm or more, preferably 2 mm or more. In the present embodiment, the interval between two adjacent needle electrodes is 1 mm.
　第１の電極群２と第２の電極群３とは同じ構造であるから、第１の電極群２を例に取り、使用電極の説明をする。
　４本の針電極のうち、端から２番目の電極２２を脳波測定に使用されないアース電極とし、電位差の測定は、端から１番目の針電極２１と３番目の針電極２３、端から３番目の針電極２３と４番目の針電極２４、又は端から１番目の針電極２１と４番目の針電極２４の間で行う。 Since the first electrode group 2 and the second electrode group 3 have the same structure, the first electrode group 2 is taken as an example to describe the electrodes used.
Of the four needle electrodes, the second electrode 22 from the end is a ground electrode that is not used for the electroencephalogram measurement, and the potential difference is measured by the first needle electrode 21 and the third needle electrode 23 from the end, and the third from the end. Between the first needle electrode 23 and the fourth needle electrode 24, or between the first needle electrode 21 and the fourth needle electrode 24 from the end.
　４本の針電極間の間隔は１ｍｍであるから、測定電極の間隔は、端から１番目の針電極２１と３番目の針電極２３で測定する場合は２ｍｍとなり、両端の針電極２１，２４間での測定の場合には３ｍｍとなり、有意的に脳波測定を行うことが可能となる。
　第２の電極群３の場合も第１の電極群２の場合と同様であるので、説明を省略する。 Since the distance between the four needle electrodes is 1 mm, the distance between the measurement electrodes is 2 mm when measuring with the first needle electrode 21 and the third needle electrode 23 from the end, and the needle electrodes 21, 24 at both ends. In the case of measurement between the intervals, it becomes 3 mm, and it becomes possible to significantly measure the electroencephalogram.
Since the case of the second electrode group 3 is the same as that of the first electrode group 2, the description thereof is omitted.
　側頭筋への針電極の刺入深さは、基本的には実験用小動物の側頭筋肉の規格によって決定されるが、側頭筋内に刺入できれば良い。浅く刺入することも可能であるが、余りに浅い刺入の場合は、針電極が外れやすい恐れがある。具体的な例として、たとえばラットの場合であれば、前記したように３ｍｍ～１０ｍｍの深さに挿入する。 The penetration depth of the needle electrode into the temporal muscle is basically determined by the standard of the temporal muscle of the experimental small animal, but it is sufficient if it can be inserted into the temporal muscle. It is possible to insert the needle electrode shallowly, but if the insertion is too shallow, the needle electrode may be easily detached. As a specific example, for example, in the case of a rat, it is inserted at a depth of 3 mm to 10 mm as described above.
　第１の電極群２及び第２の電極群３の各針電極には、リード線（図示、符号共省略する。）の先端側が接続されており、リード線の基端側は、ＢＩＳモニター装置５の電極端子（符号省略）に電気的に接続される。８本のリード線は、基体１に適宜手段で固定しており、基体１から出たところで収縮チューブである結束部材４で束ねられている。 Each needle electrode of the first electrode group 2 and the second electrode group 3 is connected to the distal end side of a lead wire (not shown in the figure, reference numerals), and the proximal end side of the lead wire is a BIS monitor device. 5 are electrically connected to electrode terminals (reference numeral omitted). The eight lead wires are appropriately fixed to the base 1 by means, and are bundled by a bundling member 4 that is a contraction tube when it comes out of the base 1.
　（脳波の測定方法）
　本発明に係る装置を使用して実験用小動物であるラットの脳波を測定する方法を説明する。
　まず、ラットＭに適正な麻酔深度を超えないように注意をしながら麻酔を効かせる。麻酔が効いたかどうかは、尾をクリップし、尾が動かないようであれば麻酔が効いていることが確認できる。 (Electroencephalogram measurement method)
A method for measuring the electroencephalogram of a rat, which is a small experimental animal, using the apparatus according to the present invention will be described.
First, anesthesia is applied to rat M while taking care not to exceed an appropriate depth of anesthesia. Whether the anesthesia is effective can be confirmed by clipping the tail and confirming that the anesthesia is effective if the tail does not move.
　その後、頭皮を切開し頭蓋骨の両側に位置する側頭筋Ｍ２，Ｍ３を露出させた後、脳波測定用電極装置１００の第１の電極群２及び第２の電極群３の各４本の針電極をラットＭの左右の側頭筋Ｍ２，Ｍ３に刺入し、脳波測定用電極装置１００の装着は終わる。
　このように脳波測定用電極装置１００の設定は、基板１に固定されている複数の針電極をラットＭの左右の側頭筋Ｍ２，Ｍ３に刺入するだけであるから装着が簡便であり、装着時間も短時間ですみ、実験効率の向上を図ることができる。 Thereafter, the scalp is incised to expose the temporal muscles M2 and M3 located on both sides of the skull, and then each of the four needles of the first electrode group 2 and the second electrode group 3 of the electroencephalogram measuring electrode device 100. The electrodes are inserted into the left and right temporal muscles M2, M3 of the rat M, and the mounting of the electroencephalogram measuring electrode device 100 is completed.
As described above, the setting of the electroencephalogram measurement electrode device 100 is simple because the plurality of needle electrodes fixed to the substrate 1 are simply inserted into the left and right temporal muscles M2 and M3 of the rat M, The wearing time is short and the experimental efficiency can be improved.
　刺入した針電極で脳波信号を取り出し、取り出された脳波信号をＢＩＳモニター装置５を使用してリアルタイムで表示する。これにより、ラットの麻酔深度がリアルタイムに測定できる。 The brain wave signal is extracted with the inserted needle electrode, and the extracted brain wave signal is displayed in real time using the BIS monitor device 5. Thereby, the anesthesia depth of a rat can be measured in real time.
　 第１の電極群２及び第２の電極群３の各４本の針電極はラットの左右の側頭筋Ｍ２，Ｍ３に刺入しているので、片側半球単独での脳波測定のみならず、左右両脳半球の脳波を同時測定することが可能である。
　左右両脳半球の脳波を同時測定する場合は、ＢＩＳモニター装置を２台使用し、各半球用電極を、それぞれのＢＩＳモニター装置に接続する。１台のＢＩＳモニター装置で、表示機能と処理機能を二つずつ有している場合は１台の装置でも同じ作業が行える。 Since each of the four needle electrodes of the first electrode group 2 and the second electrode group 3 is inserted into the left and right temporal muscles M2 and M3 of the rat, not only the electroencephalogram measurement in one hemisphere alone, It is possible to simultaneously measure the brain waves of the left and right hemispheres.
When simultaneously measuring the electroencephalograms of the left and right hemispheres, two BIS monitor devices are used, and each hemisphere electrode is connected to each BIS monitor device. When one BIS monitor device has two display functions and two processing functions, the same operation can be performed with one device.
　このように両半球の脳波を同時測定することで、より正確な脳波測定および同調性の測定、更には、より正確な脳内血流量の測定が可能となる。
　また、針電極はラットＭの左右の側頭筋Ｍ２，Ｍ３に刺入しているので、実験中にラットＭを動かしても脳波測定用電極装置１００は側頭筋Ｍ２，Ｍ３から取り外れないか、取り外れにくい。 By simultaneously measuring the electroencephalograms of both hemispheres in this manner, more accurate electroencephalogram and synchrony measurements, and more accurate intracerebral blood flow can be measured.
Further, since the needle electrode is inserted into the left and right temporal muscles M2 and M3 of the rat M, the electroencephalogram measurement electrode device 100 is not detached from the temporal muscles M2 and M3 even if the rat M is moved during the experiment. Or difficult to remove.
　なお、本明細書で使用している用語と表現は、あくまでも説明上のものであって、なんら限定的なものではなく、本明細書に記述された特徴およびその一部と等価の用語や表現を除外する意図はない。また、本発明の技術思想の範囲内で、種々の変形態様が可能であるということは言うまでもない。 Note that the terms and expressions used in this specification are merely explanatory and are not limiting at all, and terms and expressions equivalent to the features described in this specification and parts thereof. There is no intention to exclude. It goes without saying that various modifications are possible within the scope of the technical idea of the present invention.
　（１）本発明によれば、複数本の針電極で構成される第１の電極群及び第２の電極群の針電極は基体に固定されており、第１の電極群と第２の電極群は、刺入して装着する実験用小動物の頭蓋骨両側に位置する側頭筋と対応して位置しているので、針電極の先端を頭蓋骨の両側に位置する側頭筋に当接し、押圧力をかけて針電極を側頭筋に刺入すれば良く、実験用小動物への脳波測定用電極の装着が極めて簡便に行える。 (1) According to the present invention, the first electrode group composed of a plurality of needle electrodes and the needle electrodes of the second electrode group are fixed to the base, and the first electrode group and the second electrode group Since the group is located corresponding to the temporal muscles located on both sides of the skull of the small experimental animal to be inserted and worn, the tip of the needle electrode is in contact with the temporal muscles located on both sides of the skull and pressed. The needle electrode may be inserted into the temporalis muscle by applying pressure, and the electroencephalogram measurement electrode can be attached to a small experimental animal very simply.
　（２）また、電極に針電極を使用し、左右の側頭筋に刺入することによって針電極が固定されるため、実験中に動物が動いて針も電極の位置がずれたりしない。更には、実験用小動物が動いても針電極を引き抜く方向に力を加えない限り電極が固定箇所から外れないか、外れにくい。 (2) Also, since the needle electrode is fixed by using the needle electrode as the electrode and inserting into the left and right temporal muscles, the animal does not move during the experiment and the position of the electrode does not shift. Furthermore, even if the experimental small animal moves, the electrode does not come off from the fixed position or is difficult to come off unless a force is applied in the direction of pulling out the needle electrode.
　（３）実験用小動物の脳波信号は、ヒト等の大きな動物に比較して非常に小さいことから、信号を感度良く取得するには、より脳の近傍に電極を位置させて脳波信号を採取する必要がある。本発明では、電極に針電極を使用し、脳の右半球と左半球に近接する側頭筋に刺入して脳波信号を採取することができるため、高感度で脳波信号を取得することが可能となる。 (3) Since the electroencephalogram signal of a small experimental animal is much smaller than that of a large animal such as a human, in order to acquire the signal with high sensitivity, an electroencephalogram signal is collected by positioning an electrode closer to the brain. There is a need. In the present invention, since a needle electrode is used as an electrode, and an electroencephalogram signal can be collected by inserting into the temporal muscle adjacent to the right and left hemispheres of the brain, it is possible to acquire an electroencephalogram signal with high sensitivity. It becomes possible.
　（４）実験用小動物の脳内血流量を精度良く測定するには脳の右半球と左半球の脳波を同時に測定する必要がある。本発明では二つの電極群を有するので、脳の右半球と左半球の脳波を同時に測定することが容易となる。 (4) To accurately measure the blood flow in the brain of small experimental animals, it is necessary to simultaneously measure the brain waves in the right and left hemispheres of the brain. Since the present invention has two electrode groups, it becomes easy to simultaneously measure the brain waves in the right and left hemispheres of the brain.
　（５）針電極間の間隔が広い場合は観察される脳波電位の差は大きくなるが、心臓等からもたらされるノイズの影響を受けやすくなる。逆に、針電極間の間隔が狭過ぎると脳波電位の差が明瞭にあらわれない。本発明では、針電極間の間隔を１～４ｍｍとしたので、心臓等からもたらされるノイズの影響を受けずに脳波電位の差を測定することができる。 (5) When the interval between the needle electrodes is wide, the difference in the observed electroencephalogram potential is large, but it is easily affected by noise caused by the heart or the like. On the other hand, if the distance between the needle electrodes is too narrow, the difference in electroencephalogram potential cannot be clearly seen. In the present invention, since the interval between the needle electrodes is set to 1 to 4 mm, the difference in electroencephalogram potential can be measured without being affected by noise caused by the heart or the like.
１００　脳波測定用電極装置
１　基体
２　第１の電極群
２１　針電極，２２　針電極，２３　針電極，２４　針電極
３　第２の電極群
３１　針電極，３２　針電極，３３　針電極，３４　針電極
４　　　結束部材
５　　　ＢＩＳモニター装置
Ｍ　　　ラット
Ｍ１　側頭筋，Ｍ２　側頭筋 100 Electrode apparatus for electroencephalogram measurement 1 Base 2 First electrode group 21 Needle electrode, 22 Needle electrode, 23 Needle electrode, 24 Needle electrode 3 Second electrode group 31 Needle electrode, 32 Needle electrode, 33 Needle electrode, 34 Needle electrode 4 Bundling member 5 BIS monitoring device M Rat M1 temporal muscle, M2 temporal muscle

Claims (14)

  1. 　実験用小動物の脳波を測定するための電極装置であって、
    　複数本の針電極で構成される第１の電極群と、複数本の針電極で構成される第２の電極群と、を備え、前記第１の電極群及び第２の電極群の針電極は基体に固定されており、
    　前記第１の電極群と第２の電極群は、実験用小動物の頭蓋骨両側に位置する左右の側頭筋にそれぞれ刺入させ装着させるように、第１の電極群及び第２の電極群のそれぞれの刺入部分となる先端部を含む針電極が基体から突出している、
    　実験用小動物の脳波測定用電極装置。     An electrode device for measuring an electroencephalogram of a small experimental animal,
    A first electrode group composed of a plurality of needle electrodes; and a second electrode group composed of a plurality of needle electrodes, the needle electrodes of the first electrode group and the second electrode group Is fixed to the base,
    The first electrode group and the second electrode group are formed by inserting the first electrode group and the second electrode group into left and right temporal muscles located on both sides of the skull of the experimental small animal. The needle electrode including the tip part which becomes each insertion part protrudes from the base,
    Electrode device for measuring EEG of small experimental animals.
  2. 　基体が、平板状若しくはコの字型の板状の絶縁体物質からなり、該基体に固定された第１の電極群と第２の電極群の各針電極の先端部が、前記基体のそれぞれの端から、実験用小動物の左右の側頭筋に刺入させるように垂直又は略垂直に突出している、
    　請求項１記載の実験用小動物の脳波測定用電極装置。     The base is made of a plate-like or U-shaped plate-like insulator material, and tip portions of the needle electrodes of the first electrode group and the second electrode group fixed to the base are respectively provided on the bases. Projecting vertically or substantially vertically from the end of the limb so as to be inserted into the left and right temporal muscles of the experimental small animal,
    The electrode device for measuring an electroencephalogram of an experimental small animal according to claim 1.
  3. 　基体に固定された第１の電極群の先端部と第２の電極群の先端部との間隔が、対象となる実験用小動物の左右の側頭筋の間隔の最小幅以上、最大幅以下である、
    　請求項１又は２記載の実験用小動物の脳波測定用電極装置。     The distance between the distal end portion of the first electrode group and the distal end portion of the second electrode group fixed to the base is not less than the minimum width and not more than the maximum width of the left and right temporal muscles of the subject small experimental animal. is there,
    The electrode device for measuring an electroencephalogram of an experimental small animal according to claim 1 or 2.
  4. 　第１の電極群及び第２の電極群のそれぞれの側頭筋への刺入部となる先端部の長さが、実験用小動物への側頭筋の刺入方向長さの５分の１以上１以下となる、
    　請求項１乃至３のいずれか１項に記載の実験用小動物の脳波測定用電極装置。     The length of the tip part which becomes the insertion part to each temporal muscle of each of the first electrode group and the second electrode group is 1/5 of the insertion direction length of the temporal muscle to the experimental small animal. 1 or less,
    The electrode device for measuring an electroencephalogram of an experimental small animal according to any one of claims 1 to 3.
  5. 　第１の電極群及び第２の電極群を構成する複数本の針電極の間隔は、その隣接する電極の間隔が、対応する実験小動物の大脳の長軸方向の長さの５分の１～２５分の１の長さ間隔となる、
    　請求項１乃至４のいずれか１項に記載の実験用小動物の脳波測定用電極装置。     The interval between the plurality of needle electrodes constituting the first electrode group and the second electrode group is such that the interval between the adjacent electrodes is 1/5 to the length in the long axis direction of the cerebrum of the corresponding experimental small animal. With a length interval of 1/25.
    The electrode device for measuring an electroencephalogram of an experimental small animal according to any one of claims 1 to 4.
  6. 　第１の電極群及び第２の電極群は、それぞれ３本以上の針電極を列設して構成され、両端以外から選択される針電極の１本をアース電極とし、残りの電極のうちのそれぞれ２本の電極を使用して脳波を測定する、
    　請求項１乃至５のいずれか１項に記載の実験用小動物の脳波測定用電極装置。     Each of the first electrode group and the second electrode group is configured by arranging three or more needle electrodes, and one of the needle electrodes selected from other than both ends serves as a ground electrode, EEG is measured using two electrodes each.
    The electrode device for measuring an electroencephalogram of an experimental small animal according to any one of claims 1 to 5.
  7. 　ＢＩＳモニター装置を使用して実験用小動物の脳波を測定するために、ＢＩＳモニター装置に連結させ、ＢＩＳモニター装置における脳波測定用電極装置として用いる、
    　請求項１乃至６のいずれか１項に記載の実験用小動物の脳波測定用電極装置。     In order to measure the electroencephalogram of a small experimental animal using the BIS monitor device, it is connected to the BIS monitor device and used as an electroencephalogram measuring electrode device in the BIS monitor device.
    The electrode device for measuring an electroencephalogram of a small experimental animal according to any one of claims 1 to 6.
  8. 　ＢＩＳモニター装置の脳波測定用電極装置であり、第１の電極群及び第２の電極群は、それぞれＢＩＳモニター装置の電極端子数の針電極を列設して構成され、両端以外から選択される針電極の１本をアース電極とし、残りの電極のうちのそれぞれ２本の電極を使用して脳波を測定する、
    　請求項７記載の実験用小動物の脳波測定用電極装置。     This is an electroencephalogram measurement electrode device of a BIS monitor device, and the first electrode group and the second electrode group are configured by arranging needle electrodes corresponding to the number of electrode terminals of the BIS monitor device, and are selected from other than both ends. One of the needle electrodes is used as the ground electrode, and the electroencephalogram is measured using two of each of the remaining electrodes.
    The electrode device for measuring an electroencephalogram of an experimental small animal according to claim 7.
  9. 　電極端子数が４であるＢＩＳモニター装置を用いた脳波の測定において、第１の電極群及び第２の電極群は、それぞれ４本の針電極を列設して構成され、それぞれの電極群の端から２番目の電極をアース電極とし、端から１番目と３番目及び端から１番目と４番目の電極間の電位差を測定するために使用する、
    　請求項８記載の実験用小動物の脳波測定用電極。     In the electroencephalogram measurement using the BIS monitor apparatus having four electrode terminals, each of the first electrode group and the second electrode group is configured by arranging four needle electrodes, Use the second electrode from the end as the ground electrode, and measure the potential difference between the first and third electrodes from the end and the first and fourth electrodes from the end.
    The electrode for measuring an electroencephalogram of an experimental small animal according to claim 8.
  10. 　実験用小動物がラット等の齧歯類である、
    　請求項１乃至９のいずれか１項に記載の実験用小動物の脳波測定用電極装置。     The experimental small animal is a rodent such as a rat,
    The electrode device for measuring an electroencephalogram of a small experimental animal according to any one of claims 1 to 9.
  11. 　実験用小動物の頭皮を切開して頭蓋骨の両側に位置する側頭筋を露出し、
    　当該側頭筋に、アース電極及び測定用電極として少なくとも二本の針電極を刺入して脳波信号を取り出し、
    　取り出された脳波信号をＢＩＳモニター装置を使用してリアルタイムで表示する、
    　実験用小動物の脳波測定方法。     Cut the scalp of a small experimental animal to expose the temporal muscles located on both sides of the skull,
    In the temporal muscle, at least two needle electrodes are inserted as an earth electrode and a measurement electrode, and an electroencephalogram signal is taken out,
    The extracted electroencephalogram signal is displayed in real time using the BIS monitor device.
    A method for measuring the electroencephalogram of small experimental animals.
  12. 　実験用小動物の脳の左半球と右半球の脳波を同時に又はいずれか一方を測定する、
    　請求項１１記載の実験用小動物の脳波測定方法。     Measure the brain waves of the left and right hemispheres of the small animal brain at the same time or either,
    The method for measuring an electroencephalogram of an experimental small animal according to claim 11.
  13. 　請求項８又は９記載のＢＩＳモニター装置２台及び電極装置を用いて、第１の電極群の端子を第１のＢＩＳモニター装置に接続し、第２の電極群の端子を第２のＢＩＳモニター装置に接続し、実験用小動物の脳の左半球と右半球の脳波を同時又はいずれか一方を測定する、
    　請求項１１又は１２記載の実験用小動物の脳波の測定方法。     A terminal of the first electrode group is connected to the first BIS monitor device using two BIS monitor devices and an electrode device according to claim 8 or 9, and a terminal of the second electrode group is connected to the second BIS monitor. Connect to the device and measure the brain waves of the left hemisphere and right hemisphere of the small animal brain at the same time or either,
    The method for measuring an electroencephalogram of a small experimental animal according to claim 11 or 12.
  14. 　実験用小動物がラット等の齧歯類である、
    　請求項１１乃至１３のいずれか１項に記載の脳波の測定方法。     The experimental small animal is a rodent such as a rat,
    The method for measuring an electroencephalogram according to any one of claims 11 to 13.
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Cited By (6)

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CN105011943A (en) * 2015-07-14 2015-11-04 山东师范大学 Rat behavior infrared identification system, using method and application thereof
US11617540B2 (en) 2016-11-10 2023-04-04 Kurume University Sensor connector apparatus for use in electroencephalographic spectrum analyzer, provided with conductive connection electrodes connected to sensor electrodes
US11944456B2 (en) 2018-01-31 2024-04-02 Kyocera Corporation Ceramic guide, ceramic guide device, and cermic guide module
WO2021230377A1 (en) 2020-05-15 2021-11-18 京セラ株式会社 Biomedical tube and biometric device
RU216028U1 (en) * 2022-04-18 2023-01-13 Федеральное государственное бюджетное образовательное учреждение высшего образования "Московская государственная академия ветеринарной медицины и биотехнологии - МВА имени К.И. Скрябина" (ФГБОУ ВО МГАВМиБ - МВА имени К.И. Скрябина) ERGONOMICLY ADAPTABLE ELECTRODE PAD FOR ANIMAL ELECTROENCEPHALOGRAPHY
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