CN113519411A - Experiment or training device for magnetic resonance imaging of primates - Google Patents
Experiment or training device for magnetic resonance imaging of primates Download PDFInfo
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- A—HUMAN NECESSITIES
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Abstract
The invention belongs to the field of neuroscience and brain function magnetic resonance imaging, and discloses an experiment or training device for magnetic resonance imaging of primates. The device comprises a non-invasive animal fixing system, a visual stimulation system, a behavior feedback system, a reward and punishment system and a central control system; preferably also a behaviour training box. The noninvasive animal fixing system adopts a helmet mode to fix the head, does not need to perform operations on animals, does not damage the animals, and simplifies experimental operation. The behavior feedback system allows the behavior output of two modes of eyes and arms, and the dimensionality of an experimental paradigm is expanded. The invention can be used for functional magnetic resonance imaging experiments of the conscious task state of primates and training of various cognitive behavior paradigms.
Description
Technical Field
The invention relates to the fields of neuroscience and brain function magnetic resonance imaging, in particular to an experiment or training device for magnetic resonance imaging of primates.
Background
Revealing the mystery of the brain is the biggest challenge facing humans in the new century, and brain science aiming at clarifying the working principle of the brain is one of the most important advanced fields of science today. The brain function magnetic resonance imaging is an important technology in the recent development history of brain science, realizes the non-invasive and rapid acquisition of the whole brain activity condition in the resting state and the task state, is widely applied to the brain science and brain disease research of human beings, and has obtained a great deal of research findings with significance. Non-human primates (macaques, etc.) have been widely used for brain science research since the mid-20 th century by virtue of their genetic, physiological, neuroanatomical, and behavioral similarities to humans. The conscious non-human primate brain functional magnetic resonance imaging provides a window for brain science research, has unique advantages in the aspects of brain science and brain disease research due to the technical characteristics of both functional magnetic resonance imaging and conscious non-human primate experiments, and is widely regarded in international brain science research in recent years. The data obtained by the technology can be directly compared with the research result of a human test, the defect that the cross-species research result is difficult to compare even can be overcome due to different experimental means in the past, and a foundation is provided for the final clinical transformation of the animal research result. Meanwhile, the technology can be combined with a classical mesoscopic and microscale experimental method, the development of cross-scale and multi-modal brain activity research is greatly promoted, the experimental flexibility and the data diversity are greatly increased, and the technology plays a significant promoting role in comprehensively and deeply performing mechanism research on brain functions and brain diseases. In addition, the technology can be used for monitoring the same individual for a long time, and provides possibility for long-term tracking of brain function and brain diseases.
However, due to the technical difficulties of realizing the fixation of the animal head, real-time task feedback and the like in a strong magnetic field environment, the realization of the magnetic resonance imaging of the brain function of the conscious non-human primate is a great technical challenge. Firstly, the most important point for developing the brain function magnetic resonance imaging is to limit the head from being fixed in the imaging process, but the experimental animal can not be realized in a waking state, and in order to ensure the realization of the necessary condition of head fixation, a firm head column needs to be installed on the skull of the animal before the existing waking non-human primate brain function magnetic resonance imaging experiment, so as to restrict the head movement of the animal. The method requires traumatic surgery on the animal, and a large amount of time is required for maintaining the wound after the surgery; secondly, as the animal is required to make a behavioral response according to the experimental task, the most common method at present is to feed back according to the eye jump of the animal, but the method needs to purchase expensive magnetic field compatible eye movement monitoring equipment, and a contradiction is generated when the animal is required to make a behavioral response and keep the fixation point of the eye unchanged. For the reasons described above, the number of institutional efforts to successfully and effectively use this technology for research is currently on a global scale.
Disclosure of Invention
The invention aims to provide an experimental or training device for magnetic resonance imaging of primates and application thereof.
In a first aspect of the invention, there is provided an experimental or training apparatus for magnetic resonance imaging of primates, comprising: the system comprises a non-invasive animal fixing system, a visual stimulation system, a behavior feedback system, a reward and punishment system and a central control system.
In a preferred embodiment, the non-invasive animal fixation system is used for restraining the body of a primate and fixing the head of the primate, and comprises: comprises an animal chair, a helmet and a dental bar; the dental bar is matched with the helmet to fix the head of the animal; preferably, the non-invasive animal fixing system is made of magnetic field compatible materials.
In another preferred example, the non-invasive animal fixing system further comprises: a converter.
In another preferred embodiment, the animal chair is a box structure comprising: the box body is internally used for accommodating body parts below the head and neck of the animal, and is provided with openings (head holes and arm holes) for the head and hands of the animal to extend out of the box body; preferably, the animal chair is a six-sided box-like structure; a door to allow entry and exit of the animal; the neck plate is used for fixing the neck of the animal and enabling the head of the animal to extend out of the box body; a lifting plate which can be lifted and lowered for coordinating with body position change and posture adjustment.
In another preferred embodiment, the neck plate is provided with a clamping groove which is matched with the animal neck ring.
In another preferred embodiment, the animal body positions include: the vertical position and the horizontal position.
In another preferred embodiment, the converter is fixed at one end to an animal chair (preferably a neck plate of the animal chair) and at the other end to a helmet and a dental bar.
In another preferred example, the helmet comprises an upper part and a lower part, a left part and a right part or a front part and a rear part; the two parts can be brought together to wrap around or restrict movement of the animal's head.
In another preferred embodiment, the helmet includes a window that is positioned according to the eye and ear position of the animal.
In another preferred embodiment, the helmet comprises a nose bridge clamping groove for matching with the inner side part of the helmet and fixing the head of the animal.
In another preferred embodiment, the helmet further comprises a side fin for securing the helmet to the converter.
In another preferred example, the helmet is manufactured based on a skull 3D model of an animal, and the internal shape characteristics of the helmet are in accordance with the skull characteristics of the individual animal.
In another preferred example, one end of the dental rod is fixed on the converter, and the other end of the dental rod is used for being placed under the teeth of the animal after the head of the animal is fixed; preferably, the portion of the dental bar in contact with the teeth is provided in a zigzag shape.
In another preferred embodiment, the visual stimulus system is used for presenting a visual stimulus required for an experimental or training animal; preferably, the visual stimulation system comprises a display connected to and controllable by the central control system; preferably, the visual stimulation system is made of magnetic field compatible material.
In another preferred example, the behavior feedback system includes (but is not limited to): eye monitoring devices and/or joysticks.
In another preferred example, the eye movement monitoring device comprises a camera.
In another preferred embodiment, the eye monitoring device comprises a signal output end which is connected with the central control system and feeds back the eye movement information of the animal to the central control system.
In another preferred embodiment, the main body part of the rocker is fixed on the animal chair and used for the animal to operate the rocker to give behavior response to the experimental task.
In another preferred embodiment, the signal output end of the rocker is connected with a central control system, and the position information of the rocker is fed back to the central control system.
In another preferred embodiment, the rocker is made of a magnetic field compatible material.
In another preferred example, the reward and punishment system comprises components selected from a water supply part, a blowing part, a buzzer and a drive control circuit, and the drive control circuit is connected with and controlled by the central control system.
In another preferred example, the water supply part comprises a water nozzle, a conduit, a water bottle and a valve, the water nozzle is positioned below the dental bar, and the water nozzle can be set to prevent the animal from obtaining water by sucking; preferably, the conduit comprises a conduit A and a conduit B, and the valve is an electromagnetic valve; preferably, the conduit A is connected with the electromagnetic valve and the water nozzle, the conduit B is connected with the valve and the water bottle, and the valve is connected with the driving control circuit and is controlled to be opened and closed by the driving control circuit to control water flow.
In another preferred example, the air blowing part comprises an air pump, a conduit, a valve and an air nozzle; preferably, the conduit comprises a conduit C and a conduit D, and the valve is an electromagnetic valve; preferably, the conduit C is connected with an air pump and a valve, the conduit D is connected with the valve and an air nozzle, the air nozzle is fixed on the animal chair, and the valve is connected with a driving control circuit and is controlled to be opened and closed by the driving control circuit to control air flow.
In another preferred example, the buzzer is connected with the driving control circuit and is controlled to be opened and closed by the driving control circuit.
In another preferred example, the central control system performs parameter setting and coordination control; preferably for controlling the visual stimulus system, the reward and punishment system, the behavioral feedback system (the controlling including accepting information and issuing instructions).
In another preferred example, the central control system comprises an upper computer and a lower computer; the upper computer is a control program client, a user sets training parameters through a program interface, and the upper computer transmits the set parameters to the lower computer; preferably, the upper computer is further connected with the magnetic resonance system and receives a trigger signal from the magnetic resonance system, and the trigger signal is used for synchronizing brain signals acquired by magnetic resonance, visual stimuli output by the visual stimulus system, reward and punishment system instructions and animal behaviors recorded by the behavior feedback system; the lower computer is an NI data acquisition card, outputs an instruction from the upper computer to a drive control circuit in the reward and punishment system, and feeds back eye movement or rocker signals recorded by the behavior feedback system to the upper computer.
In another preferred example, the experimental or training device for magnetic resonance imaging of primates further comprises: and the behavior training box is used for simulating the environment in the magnetic field and carrying out animal behavior training of the simulated magnetic field.
In another preferred example, the behavior training box comprises a box body, an exhaust system and a video monitoring system; preferably, the wall of the box body is provided with a sound attenuation function; preferably, the air exhaust system is used for keeping the air circulation and air freshness in the box; preferably, the video monitoring system comprises an infrared camera, an infrared lamp and a display.
In another aspect of the invention there is provided the use of an experimental or training device for magnetic resonance imaging of primates as defined in any one of the preceding claims for training a cognitive behaviour paradigm of primates.
In another aspect of the invention there is provided the use of an experimental or training device for primate magnetic resonance imaging as described in any of the preceding claims for performing primate magnetic resonance imaging experiments.
In another aspect of the invention there is provided the use of any of the above described experimental or training devices for magnetic resonance imaging of primates for fixation and monitoring of primates.
In a preferred embodiment, the use is not for diagnostic or therapeutic purposes.
In another preferred embodiment, the primate is a non-human primate.
In another preferred embodiment, the non-human primate comprises: monkey, orangutan, ape.
In another aspect of the invention, there is provided a method of performing a primate magnetic resonance imaging or imaging experiment, the method comprising: (1) providing an experimental or training device for magnetic resonance imaging of primates as claimed in any one of the preceding claims; (2) placing the primate in the noninvasive animal fixing system for fixing; (3) the animal is subjected to magnetic resonance imaging.
In another aspect of the invention, there is provided a method of training a primate, comprising: (1) providing an experimental or training device for magnetic resonance imaging of primates as described in any of the preceding paragraphs; (2) placing the primate in the noninvasive animal fixing system for fixing; (3) and the central control system outputs instructions, controls components in the visual stimulation system, the reward and punishment system and/or the behavior feedback system to stimulate the animal, and receives information fed back by the animal.
In a preferred embodiment, the method of magnetic resonance imaging or imaging experiments or the method of primate training is not for the direct purpose of diagnosis or therapy.
Other aspects of the invention will be apparent to those skilled in the art in view of the disclosure herein.
Drawings
FIG. 1 is a general schematic diagram of the system architecture of the present invention.
Figure 2 is a schematic diagram of the present invention entering a magnetic resonance scanner magnet bore portion.
FIG. 3 is a view showing the structure of an animal chair according to the present invention; wherein the left figure is a view of one side of the door of the animal chair structure, and the right figure is a view rotated by 180 degrees.
FIG. 4 is a view showing the structure of a helmet according to the present invention; wherein the left figure is a front view of the helmet structure and the right figure is a rear view of the helmet structure.
Fig. 5A illustrates a rocking-arm task performed by a macaque in the magnetic resonance imaging experimental apparatus according to the present invention.
Fig. 5B, head movement of the animal within 6 minutes; the upper diagram shows the horizontal movement in XYZ 3 directions, and the lower diagram shows the rotation angles in 3 axial directions.
Fig. 5C, 94 head motion profiles of 6 minute data.
Fig. 5D, brain region with rocker task activated.
The various reference numbers are described below:
100 a non-invasive animal fixation system;
200 a visual stimulation system;
300 a behavioral feedback system;
400 a reward and punishment system;
500 a central control system;
5001 an upper computer;
5002 lower computer;
5003 magnetic resonance imaging scanner;
600 task training box;
700 animals;
1, an animal chair;
2 a converter;
3, a helmet;
4, a tooth bar;
5, water nozzle;
6, a rocker;
7 a display;
8 eye movement monitoring means;
10, a guide rail;
11 a main body;
12 doors;
13 neck plate;
14 an intra-collar adjustment element;
15 external collar adjustment elements;
16 a lifter plate;
17 a bolt;
18 windows;
19 arm holes;
21 lower part;
22 nose bridge clamping grooves;
23 side wings;
24 an upper portion;
25 sides.
Detailed Description
Through intensive research, the inventor provides an experiment and training device for magnetic resonance imaging of primates, which comprises a non-invasive animal fixing system, a visual stimulation system, a behavior feedback system, a reward and punishment system and a central control system; preferably also a behaviour training box. The non-invasive animal fixing system limits the body of the primate and fixes the head of the primate; the visual stimulation system is used for presenting an experimental visual task; the behavior feedback system is used for tracking and recording the behavior response of the animal; the reward and punishment system is used for giving reward, punishment or sound feedback to the animals according to the instruction of the central control system; the central control system is used for parameter setting and coordination control. The behavior training box can simulate the environment in a magnetic field and is mainly used for daily animal behavior training outside the magnetic field.
As used herein, the "system" may also be referred to as a "device".
As used herein, the "primate" is preferably a non-human primate, including: monkey, orangutan, ape.
Animal fixation system
The inventor designs an animal fixing system which can effectively limit the body of the primate and fix the head of the primate and does not cause damage to animals aiming at the characteristics of the primate, and the animal fixing system is called as a non-invasive animal fixing system.
The non-invasive animal fixing system comprises an animal chair, a helmet and a dental bar. Wherein, the dental bar can be matched with a helmet to fix the head of an animal.
In a preferred mode of the present invention, the animal chair is a box-type structure of animal fixing device for effectively fixing an animal body, and comprises: the animal neck adjusting device comprises a box body used for accommodating a body part below the head and neck of an animal, a neck plate used for fixing the neck of the animal and enabling the head of the animal to extend out of the box body, and a lifting plate used for matching with the body position change or posture adjustment of the animal. The animal chair can enable the body of an animal to be in the box body, and the head of the animal to be placed outside the box body. The animal chair can be used for setting the body positions of animals, such as a standing position and a lying position, wherein the standing position is used for transporting the animals, and the lying position is used for behavior training or magnetic resonance imaging experiments.
In a preferred form of the invention, the various components of the animal chair are made of a magnetic field compatible material.
The helmet can be divided into an upper part and a lower part, a left part and a right part or a front part and a rear part, and the two parts can be folded to wrap the head of an animal or limit the movement of the head of the animal. In a preferred form of the invention, the helmet is divided into an upper part and a lower part, wherein the lower part covers the mandible, the cheekbones and the bridge of the nose of the animal and is responsible for the support of the whole head weight.
In a preferred form of the invention, the helmet includes a window arranged according to the position of the eyes and ears of the animal. Preferably, the helmet comprises a nose bridge clamping groove for matching with the inner side part of the helmet and fixing the head of the animal. Preferably, the helmet further comprises a side fin for securing the helmet to the converter. The periphery of the helmet is fixed with the animal chair through the converter, the upper part of the helmet covers the occiput and the frontal bone of the animal, the positions of eyes and ears of the animal are reserved, the sight of the animal is ensured not to be shielded, and the whole head can be completely wrapped after the two parts of the helmet are combined; one end of the converter is fixed on the animal chair neck plate, and the other end of the converter is used for fixing the helmet and the dental bar;
in a preferred form of the invention, the helmet is configured to have internal shape characteristics that conform to individual animal skull characteristics, preferably it is customizable based on a 3D model of the skull for each experimental animal. Preferably, the inner wall surface is adhered with a foam buffer layer, so that the whole animal head can be wrapped seamlessly, comfortably and completely, and the animal head cannot move in the helmet. Preferably, the external shape of the helmet is a regular geometric shape, which facilitates the placement of the magnetic resonance signal receiving coil.
The tooth bar is used for preventing the head of an animal from twisting (left and right and up and down twisting), one end of the tooth bar is fixed on the converter for fixing the helmet, and the other end of the tooth bar is arranged below the incisors of the animal after the head of the animal is fixed. In a preferred form of the invention, the portion of the dental bar that is fixed under the teeth is of a serrated design to prevent falling off due to head twisting.
In a preferred form of the invention, the various components of the helmet are made of a magnetic field compatible material.
Visual stimulation system
The visual stimulation system is used for presenting visual stimulation required by an experimental or training animal and is connected with the central control system. Preferably, the visual stimuli are generated by a central control system according to user program settings.
The visual stimulus system comprises a device capable of administering a visual stimulus to an animal; preferably the device is at least one display, more preferably the display is a magnetic resonance compatible liquid crystal display. Other devices capable of imparting a visual stimulus to an animal may also be included in the present invention, such as some that are capable of relative movement to attract the animal's vision.
In a preferred form of the invention, the various components of the visual stimulation system are made of magnetic field compatible materials.
Behavior feedback system
The behavior feedback system is used for receiving the behavior response of the animal and transmitting the behavior response to the central control system.
The behavioral feedback systems include (but are not limited to): eye monitoring devices and/or joysticks. In addition, other devices that can be used to study or monitor animal responses or behaviors can be included in the present invention.
As a preferred mode of the present invention, the eye movement monitoring device (e.g., an eye tracker) includes a camera. The camera may be placed near the display in the visual stimulation system, and other suitable locations are possible as long as the eyes of the animal are monitored and eye changes are captured. Preferably, the eye movement monitoring device can adopt a commercial magnetic resonance compatible eye movement instrument for monitoring the eye movement of the animal in the experimental process in real time. Preferably, the eye tracker camera part can be arranged below a display in the visual stimulation system, and the signal output end is connected with the central control system to feed back the eye movement information to the central control system.
As a preferred mode of the invention, the rocker is formed by modifying a magnetic field compatible material instead of a metal part in a commercial rocker, the main body part of the rocker is fixed on an animal chair and used for controlling the rocker by an animal to give a behavior response to an experimental task, and the signal output end is connected with the central control system and feeds back the position information of the rocker to the central control system.
In a preferred form of the invention, the individual components of the behavioral feedback system are made of magnetic field compatible materials.
Reward punishment system
The reward and punishment system is used for giving reward, punishment or sound feedback to the animals according to the instruction of the central control system.
As a preferred aspect of the present invention, the reward and punishment system includes: a water supply part. The water supply part comprises a water nozzle, a guide pipe, a water bottle and a valve. Preferably, the water nozzle is located below the dental wand and may be arranged such that the animal cannot obtain water by sucking. Preferably, the conduit comprises a conduit A and a conduit B, and the valve is a solenoid valve. Preferably, the conduit A is connected with the electromagnetic valve and the water nozzle, the conduit B is connected with the valve and the water bottle, and the valve is connected with the driving control circuit and is controlled to be opened and closed by the driving control circuit to control water flow. Preferably, the water nozzle is arranged in a structure that three copper pipes are horizontally arranged side by side, the water outlet end is flush, the length of the middle copper pipe is longer, the middle copper pipe is connected with the conduit A, and the structure prevents an animal from sucking water in the water pipe; the water nozzle fixing element enables the water nozzle to be positioned right in front of the animal mouth.
As a preferred aspect of the present invention, the reward and punishment system includes: and the air blowing part comprises an air pump, a conduit, a valve and an air nozzle. Preferably, the air pump is an oxygen pump. Preferably, the conduit comprises a conduit C and a conduit D, and the valve is an electromagnetic valve; preferably, the conduit C is connected with an oxygen pump and a valve, the conduit D is connected with the valve and an air faucet, the air faucet is fixed on the animal chair, and the valve is connected with the driving control circuit and is controlled to be opened and closed by the driving control circuit to control air flow.
As a preferred aspect of the present invention, the reward and punishment system includes: and the buzzer is directly connected with the drive control circuit.
Each component in the reward punishment system comprises a water supply part, a blowing part, a buzzer and the like, and is connected with and controlled by a drive control circuit. The driving control circuit is connected with and controlled by the central control system.
In a preferred form of the invention, the individual components of the reward and punishment system are made of a magnetic field compatible material.
Central control system
The central control system can be directly or indirectly connected with the noninvasive animal fixing system, the visual stimulation system, the behavior feedback system, the reward and punishment system visual stimulation system, the behavior feedback system and/or the reward and punishment system, the operation of the noninvasive animal fixing system, the visual stimulation system, the behavior feedback system and/or the reward and punishment system is controlled, and feedback information is obtained.
As a preferred mode of the invention, an upper computer in a central control system is a control program client, a user sets training parameters through a program interface, and the upper computer transmits the set parameters to a lower computer; the upper computer is also connected with the magnetic resonance imaging scanner and receives a trigger signal from the magnetic resonance imaging scanner, and the trigger signal is used for acquiring brain signals of the time synchronous magnetic resonance imaging scanner, outputting visual stimulation by the visual stimulation system, giving and punishing system instructions and recording animal behaviors by the behavior feedback system.
As a preferred mode of the present invention, the lower computer in the central control system is an NI data acquisition card, outputs an instruction from the upper computer to the drive control circuit in the reward and punishment system, and simultaneously feeds back an eye movement or rocker signal recorded by the behavior feedback system to the upper computer.
Behavior training box
In an alternative embodiment, the apparatus of the present invention further comprises a behavior training box. When the device of the invention is used for carrying out a magnetic resonance imaging experiment, the behavior training box can not be used; when the device of the invention is used for animal training in order to cooperate with a magnetic resonance imaging experiment, the behavior training box can be used for simulating the environment in the magnetic field and carrying out animal behavior training simulating the magnetic field (outside the magnetic field).
In a preferred embodiment of the present invention, the behavior training box includes a box body, an exhaust system, and a video monitoring system. The box body is of a cuboid structure, preferably has six faces, preferably each face of the box body comprises a three-layer sandwich structure, the middle of the box body is provided with a foam layer, and the two sides of the box body are provided with organic glass plates, so that the training box has a sound attenuation function; the exhaust system consists of an exhaust pipe and an exhaust fan, the exhaust pipe is connected with the box body and the exhaust fan, and the exhaust fan exhausts air in the box to the outside of the training room to keep the air in the box to circulate and the indoor air to be fresh; the video monitoring system comprises an infrared camera, an infrared lamp and a display, and has the function of monitoring the behavior state of animals.
The device can be used for functional magnetic resonance imaging experiments of the conscious task state of primates and training of various cognitive behavioral paradigms.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers.
The invention can be better understood after reading the detailed description of embodiments of the disclosure in conjunction with the following drawings. In the drawings, components are not necessarily drawn to scale, and components having similar relative characteristics or features may have the same or similar reference numerals.
Example 1 Experimental facility for magnetic resonance imaging
As shown in fig. 1, the experimental apparatus for magnetic resonance imaging of the present invention includes a non-invasive animal fixing system 100, a visual stimulation system 200, a behavior feedback system 300, a reward and punishment system 400, and a central control system 500. The figure shows a relative positional relationship of the parts in space. The dashed box portion of the figure would enter the scanner magnet bore during imaging experiments. The arrow line in the figure shows the information transfer direction between the central control system 500 and the visual stimulation system 200, the behavior feedback system 300 and the reward and punishment system 400. The central control system transmits visual stimulation information to the visual stimulation system 200 through the upper computer 5001, transmits reward and punishment information to the reward and punishment system 400 through the lower computer 5002, and transmits behavior feedback of animals to the central control system 500 through the lower computer 5002. The host computer 5001 receives a synchronized trigger signal from the magnetic resonance imaging scanner 5003.
Fig. 2 shows the part of the invention that enters the magnetic body cavity of a magnetic resonance scanner, which comprises an animal chair 1, a converter 2, a helmet 3, a dental bar 4, a water nozzle 5, a rocker 6, a display 7 and an eye movement monitoring device 8. The animal chair 1, the converter 2, the helmet 3 and the dental bar 4 form a non-invasive animal fixing system. The positions of the elements are shown in the figure, the animal chair 1 is connected with the helmet 3 through the converter 2, and the dental bar 4 is fixed on the converter 2. The water nozzle 5 is arranged below the tooth bar 4. The position of the tooth bar 4 and the water nozzle 5 on the converter 2 can be adjusted so as to facilitate the tooth bar 4 and the water nozzle 5 to be placed in the mouths of animals with different body types. The rocker 6 is directly fixed on the animal chair 1. The display 7 is placed 57 cm in front of the animal's eye. The camera of the eye tracker 8 is arranged below the display to monitor the eye movement of the animal.
Fig. 3 shows the structure of the animal chair of the present invention, which comprises a main body 11, a door 12, a neck plate 13, an in-collar adjusting member 14, an out-collar adjusting member 15, and a lifting plate 16. The door is secured by 4 bolts 17. The animal chair has two posture positions: the vertical position is used for animal transfer, and the horizontal position is used for training or imaging experiments. When the door is in the standing position, the two door bolts 17 at the same side are pulled out, and the door can be opened. One face of the animal chair comprises an external collar adjusting element 15, the collar of an animal can be clamped into the clamping groove of the neck plate, and the animal can be fixed by inserting the external collar adjusting element 15. Two windows 18 with doors are opened on both sides of the animal chair for the trainee to grasp the arms and legs of the animal. The right arm of the animal can extend from the arm hole 19 to operate the rocker. Guide rails 10 are arranged on two sides of the animal chair, and the width of the guide rails is matched with that of the guide rails of the magnetic resonance imaging scanner bed.
Fig. 4 shows the structure of the helmet of the present invention, which comprises an upper part and a lower part. The lower part 21 covers the lower jaw and the cheekbones of the animal and is responsible for supporting the weight of the whole head, and the nose bridge clamping groove 22 is used for fixing the bridge of the nose of the animal and forms a three-point fixing surface with the left and right cheekbones fixing points to limit the left and right swinging and pitching of the head. The lower part 21 is secured to the transducer shown in figure 2 by means of side fins 23. The upper part 24 covers the occiput and frontal bone of the animal, is responsible for limiting the up-and-down movement and rotation of the head, and reserves the windows of eyes and ears for the animal according to the anatomical structure characteristics of the animal, so as to facilitate the implementation of visual stimulation and auditory stimulation. The upper part and the lower part of the helmet can completely wrap the head of the whole animal after being closed by the bolts through the side edges 25, and the head movement is limited in all directions.
2. Visual stimulation system
The visual stimulation system comprises a liquid crystal display 7 which is connected with and can be controlled by the central control system.
3. Behavior feedback system
The behavior feedback system 300 includes: eye movement monitoring device 8 and rocker lever 6. The eye movement monitoring device 8 comprises an eye movement camera. The rocker includes a handle adapted for grasping and manipulation by an animal.
4. Reward punishment system
The reward and punishment system includes: the water supply part, the air blowing part, the buzzer and the drive control circuit are connected with and controlled by the central control system.
The water supply part comprises a water nozzle 5, a conduit, a water bottle and a valve. The water nozzle 5 is positioned below the dental bar 4. The conduit comprises a conduit A and a conduit B, and the valve is an electromagnetic valve. The conduit A is connected with the electromagnetic valve and the water nozzle 5, the conduit B is connected with the valve and the water bottle, and the valve is connected with the driving control circuit and is controlled to be opened and closed by the driving control circuit to control water flow. The water nozzle 5 is a structure in which three copper pipes are horizontally arranged side by side, the middle copper pipe is longer in length and is connected with the conduit A, and the structure prevents an animal from sucking water in the water pipe; the water nozzle 5 is positioned right in front of the animal mouth by a fixed element of the water nozzle.
The air blowing part comprises an oxygen pump, a conduit, a valve and an air nozzle; the conduit comprises a conduit C and a conduit D, and the valve is an electromagnetic valve; the conduit C is connected with the oxygen pump and the valve, the conduit D is connected with the valve and the air faucet, the air faucet is fixed on the animal chair, and the valve is connected with the driving control circuit and is controlled to be opened and closed by the driving control circuit to control air flow.
The buzzer is directly connected with the drive control circuit.
5. Central control system
The central control system 500 includes an upper computer 5001 and a lower computer 5002. The upper computer 5001 is a control program client, a user sets training parameters through a program interface, and the upper computer 5001 transmits the set parameters to the lower computer 5002; the upper computer 5001 is also connected to the magnetic resonance system and receives a trigger signal from the magnetic resonance imaging scanner.
The lower computer 5002 in the central control system is an NI data acquisition card, and the lower computer 5002 outputs an instruction from the upper computer 5001 to a drive control circuit in the reward and punishment system, and simultaneously feeds back an eye movement or rocker signal recorded by the behavior feedback system to the upper computer 5001.
The magnetic resonance imaging training device comprises the magnetic resonance imaging experimental device and a behavior training box, wherein the magnetic resonance imaging experimental device is described in embodiment 1.
The part outlined by the dotted line in fig. 1 enters the magnetic body cavity of the magnetic resonance imaging scanner during the imaging experiment and is placed in the behavior training box during the behavior training.
EXAMPLE 3 use of the training apparatus for magnetic resonance imaging
In this example, the training apparatus for magnetic resonance imaging described in example 2 was used to train an animal.
During training, the primate 700 is placed in the non-invasive animal fixation system and fixed. The method comprises the following steps: and opening the door 12 of the animal chair, after the door is opened, extracting the external adjusting element 15 of the collar, clamping the collar of the animal into the clamping groove of the neck plate, enabling the body of the animal to enter the main body 11, and inserting the external adjusting element 15 of the collar to fix the animal. The height of the lift plate 16 is adjusted so that the animal can just sit on the lift plate. The door 12 is closed and the animal chair is lowered so that the door 12 is at the bottom surface on which the animal squats. Two windows 18 with doors are opened on both sides of the animal chair for the trainee to grasp the arms and legs of the animal. The right arm of the animal can extend from the arm hole 19 to operate the rocker.
And a loudspeaker is placed in the behavior training box to play the sound generated by the magnetic resonance imaging scanner during the magnetic resonance imaging experiment. The volume of the speaker is adjusted to achieve about 70 decibels of sound in the training box. The behavior training box can attenuate the sound by 30-40 decibels, so that the sound in the training box is about 30-40 decibels when being transmitted to the outside of the training box, which is equivalent to the sound of light voice of a person and can not cause noise interference to an experimenter. Meanwhile, the conversation of the experimenter does not influence the animals in the training box. And opening an exhaust system to ensure that the air in the training box is fresh and the temperature in the training box is kept at 21-25 ℃.
The central control system runs a user-defined program, and can automatically control the components in the visual stimulation system 200, the reward and punishment system 400 and the behavior feedback system 300 to train the animal behaviors. In this example, the program is written via the public MonkeyLogic toolkit.
Compared with the traditional way of fixing the head post, the training device for magnetic resonance imaging provided by the invention does not need to perform operation on animals to install the head post, so that the operation and postoperative recovery time are saved, and about 2 weeks are saved. Regular nursing of the wound by mounting the head post is omitted, and time and labor cost are greatly saved. The inventor trains the awake macaques for a plurality of batches for one year, and proves that the device is simple and easy to use, the animal coordination degree is high, and the animals are never injured. The device is well applicable to the cognitive behavior training of the tested monkey.
EXAMPLE 4 Effect of magnetic resonance imaging experiment apparatus
In this example, the experimental apparatus for magnetic resonance imaging described in example 1 was used to perform a functional magnetic resonance imaging experiment on an animal, and the effect of the apparatus was evaluated: including the animal's head movement and the brain regions involved in specific cognitive tasks.
The inventor utilizes the magnetic resonance imaging experimental device to acquire the head image of a macaque when the macaque shakes a rocker task, evaluates the head movement index and finds out the brain region activated by the task. Theoretically, the primary motor cortex M1 and the auxiliary motor cortex SMA of the brain responsible for hand motion would be activated.
Briefly describing the rocker-rocker task as follows (fig. 5A): the animal operates the rocker with the right hand, the animal needs to place the white dot (similar to a mouse) operated by the rocker on the red dot in the center of the screen so as to start the test, after 0.2 second, the visual stimulation system randomly presents a colored square block (the square block appears at 180 degrees in the example of fig. 5A) in 4 directions of 0 degrees, 90 degrees, 180 degrees and 270 degrees of the display, the animal needs to shake the rocker within 2 seconds, the white dot is operated and placed on the square block, and the reward (water) given by the reward system can be obtained after success, so that the animal finishes shaking the rocker once. After one rocker shake, the animal is allowed to rest for 27 seconds and then the next rocker shake task is performed. The animals had to complete a total of 12 trials, i.e. 12 shakes of the rocker, for a total time of 6 minutes.
Fig. 5B shows the head movement of the animal within 6 minutes, including X, Y, Z3 translations in 3 dimensions (up in fig. 5B) and 3 rotations (down in fig. 5B), both translations less than 0.5mm and rotations less than 0.5 °.
In another cognitive task (not the rocker rocking task described above), the inventors collected 94 times 6 minutes of data. The present inventors calculated the arithmetic sum of absolute values of 6 parameters of head movement (in the calculation, the rotation angle is converted into a distance in accordance with the maximum diameter of the brain of 80 mm), and evaluated the head movement with one numerical value. The header motion distribution of the 94 data is shown in fig. 5C. The average head movement is 0.46mm, the maximum head movement is not more than 0.7mm, and most head movements are 0.4-0.5 mm, so that the requirements of magnetic resonance imaging are completely met. It is particularly emphasized that the algorithm yields results that are larger than the true head movement, so the true head movement should be smaller than the head movement calculated by the inventors.
Fig. 5D shows the brain region where the rocker task is activated. Left and right lateral primary motor cortex M1, and the auxiliary motor cortex SMA activate, and the left primary motor cortex activates more strongly, consistent with right hand motion (left brain innervates right hand). The activation results of the cerebral cortex are consistent with the theoretical results.
The brain areas of the animals with the activated head movements and tasks show that the device can well fix the heads of the conscious animals, the head movements completely meet the requirements of the conscious primate magnetic resonance imaging experiments, and reliable brain function results can be obtained.
It will be appreciated that various alterations and modifications of the invention will occur to those skilled in the art upon reading the above teachings, and that such equivalents are intended to fall within the scope of the invention as defined by the appended claims.
Claims (23)
1. An experimental or training device for magnetic resonance imaging of primates, comprising: the system comprises a non-invasive animal fixing system, a visual stimulation system, a behavior feedback system, a reward and punishment system and a central control system.
2. The experimental or training device for magnetic resonance imaging of primates according to claim 1, wherein the non-invasive animal fixation system for restraining the primate body and fixing the animal head comprises: comprises an animal chair, a helmet and a dental bar; the dental bar is matched with the helmet to fix the head of the animal; preferably, the non-invasive animal fixing system is made of magnetic field compatible materials.
3. An experimental or training device for primate magnetic resonance imaging as in claim 2, wherein the non-invasive animal fixation system further comprises: a converter.
4. An experimental or training device for primate magnetic resonance imaging as claimed in claim 2, wherein the animal chair is a box like structure comprising:
the box body is internally used for accommodating body parts below the head and neck of the animal, and is provided with openings for the head and hands of the animal to extend out of the box body; preferably, the animal chair is a six-sided box-like structure;
a door to allow entry and exit of the animal;
the neck plate is used for fixing the neck of the animal and enabling the head of the animal to extend out of the box body;
a lifting plate which can be lifted and lowered for coordinating with body position change and posture adjustment.
5. The experimental or training device for primate magnetic resonance imaging as claimed in claim 3 or 4,
the neck plate is provided with a clamping groove which is matched with the animal neck ring;
the animal body positions comprise: a standing position and a lying position;
one end of the converter is fixed on the animal chair, and the other end of the converter is fixed on the helmet and the dental bar.
6. The experimental or training apparatus for primate magnetic resonance imaging as in claim 2, wherein the helmet comprises two upper and lower sections, a left and right section or a front and back section; the two parts can be folded to wrap the head of the animal or limit the movement of the head of the animal;
preferably, the helmet comprises a window arranged according to the position of the eyes and ears of the animal;
preferably, the helmet comprises a nose bridge clamping groove for matching with the inner side part of the helmet and fixing the head of an animal;
preferably, the helmet further comprises a side fin for securing the helmet to the converter;
preferably, the helmet is manufactured based on a 3D model of the skull of the animal, and the internal shape characteristics of the helmet are in accordance with the skull characteristics of the individual animal.
7. An experimental or training device for magnetic resonance imaging of primates as claimed in claim 3 wherein the dental bar is fixed at one end to the transducer and at the other end for placement under the animal's teeth after the animal's head has been fixed; preferably, the portion of the dental bar in contact with the teeth is provided in a zigzag shape.
8. An experimental or training device for magnetic resonance imaging of primates according to claim 1 wherein the visual stimulus system is for presenting a visual stimulus required to experiment or train the animal; preferably, the visual stimulation system comprises a display connected to and controllable by the central control system; preferably, the visual stimulation system is made of magnetic field compatible material.
9. An experimental or training device for primate magnetic resonance imaging as claimed in claim 1, wherein the behavioral feedback system comprises: eye monitoring devices and/or joysticks.
10. The experimental or training device for primate magnetic resonance imaging as in claim 9, wherein the eye movement monitoring device comprises a camera; or
The eye movement monitoring device comprises a signal output end which is connected with the central control system and feeds back the eye movement information of the animal to the central control system.
11. An experimental or training device for magnetic resonance imaging of primates as claimed in claim 9 wherein the main body portion of the rocker is secured to an animal chair for manipulation of the rocker by the animal to give a behavioral response to the experimental task; or
The signal output end of the rocker is connected with the central control system, and the position information of the rocker is fed back to the central control system; or
The rocker is made of magnetic field compatible materials.
12. An experimental or training device for primate magnetic resonance imaging as claimed in claim 1, wherein the reward and punishment system comprises components selected from a water supply part, an air blowing part, a buzzer, and a drive control circuit, the drive control circuit being connected to and controlled by a central control system.
13. An experimental or training apparatus for magnetic resonance imaging of primates as claimed in claim 12 wherein said water supply portion comprises a water nozzle, a conduit, a water bottle and a valve, said water nozzle being located under the dental bar, the water nozzle being arranged such that the animal cannot obtain water by sucking; preferably, the conduit comprises a conduit A and a conduit B, and the valve is an electromagnetic valve; preferably, the conduit A is connected with the electromagnetic valve and the water nozzle, the conduit B is connected with the valve and the water bottle, and the valve is connected with the driving control circuit and is controlled to be opened and closed by the driving control circuit to control water flow.
14. The experimental or training set for magnetic resonance imaging of primates according to claim 12 wherein said insufflation portion comprises an air pump, a conduit, a valve and an air tap; preferably, the conduit comprises a conduit C and a conduit D, and the valve is an electromagnetic valve; preferably, the conduit C is connected with an air pump and a valve, the conduit D is connected with the valve and an air nozzle, the air nozzle is fixed on the animal chair, and the valve is connected with a driving control circuit and is controlled to be opened and closed by the driving control circuit to control air flow.
15. The experimental or training device for magnetic resonance imaging of primates according to claim 12 wherein said buzzer is connected to and opened and closed by a drive control circuit.
16. An experimental or training device for primate magnetic resonance imaging as claimed in claim 1 wherein the central control system performs parameter setting and coordination control; preferably for controlling the visual stimulus system, the reward and punishment system, the behavior feedback system.
17. An experimental or training device for primate magnetic resonance imaging as in claim 16 wherein the central control system comprises an upper computer and a lower computer;
the upper computer is a control program client, a user sets training parameters through a program interface, and the upper computer transmits the set parameters to the lower computer; preferably, the upper computer is further connected with the magnetic resonance system and receives a trigger signal from the magnetic resonance system, and the trigger signal is used for synchronizing brain signals acquired by magnetic resonance, visual stimuli output by the visual stimulus system, reward and punishment system instructions and animal behaviors recorded by the behavior feedback system;
the lower computer is an NI data acquisition card, outputs an instruction from the upper computer to a drive control circuit in the reward and punishment system, and feeds back eye movement or rocker signals recorded by the behavior feedback system to the upper computer.
18. An experimental or training device for primate magnetic resonance imaging as claimed in claim 1, the device further comprising: and the behavior training box is used for simulating the environment in the magnetic field and carrying out animal behavior training of the simulated magnetic field.
19. An experimental or training device for magnetic resonance imaging of primates according to claim 18 wherein said behavioural training box comprises a box, an air exhaust system, a video monitoring system; preferably, the wall of the box body is provided with a sound attenuation function; preferably, the air exhaust system is used for keeping the air circulation and air freshness in the box; preferably, the video monitoring system comprises an infrared camera, an infrared lamp and a display.
20. Use of an experimental or training device for magnetic resonance imaging of primates according to any one of claims 1 to 19 for:
training a cognitive behavioral paradigm of the primate;
performing a primate magnetic resonance imaging experiment;
the primates were fixed and monitored.
21. The use of claim 20, wherein the primate is a non-human primate.
22. A method of performing a primate magnetic resonance imaging or imaging experiment, the method comprising:
(1) providing an experimental or training device for magnetic resonance imaging of primates according to any one of claims 1 to 19;
(2) placing the primate in the noninvasive animal fixing system for fixing;
(3) the animal is subjected to magnetic resonance imaging.
23. A method of training a primate, the method comprising:
(1) providing an experimental or training device for magnetic resonance imaging of primates according to any one of claims 1 to 19;
(2) placing the primate in the noninvasive animal fixing system for fixing;
(3) and the central control system outputs instructions, controls components in the visual stimulation system, the reward and punishment system and/or the behavior feedback system to stimulate the animal, and receives information fed back by the animal.
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| CN114128671A (en) * | 2021-11-26 | 2022-03-04 | 广州鼎飞航空科技有限公司 | Animal training method and control device |
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