CN113519411B - Experimental or training device for primate magnetic resonance imaging - Google Patents
Experimental or training device for primate magnetic resonance imaging Download PDFInfo
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Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K15/00—Devices for taming animals, e.g. nose-rings or hobbles; Devices for overturning animals in general; Training or exercising equipment; Covering boxes
- A01K15/02—Training or exercising equipment, e.g. mazes or labyrinths for animals ; Electric shock devices ; Toys specially adapted for animals
- A01K15/027—Exercising equipment, e.g. tread mills, carousels
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Animal Behavior & Ethology (AREA)
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- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
Abstract
The invention belongs to the fields of neuroscience and brain function magnetic resonance imaging, and discloses an experimental or training device for primate magnetic resonance imaging. The device comprises a noninvasive animal fixing system, a visual stimulation system, a behavior feedback system, a reward and punishment system and a central control system; preferably also comprising a behavioural training box. The noninvasive animal fixing system fixes the head in a helmet mode, does not need to operate on animals, has no damage to the animals, and simplifies experimental operation. The behavior feedback system allows the behavior output of two modes of eyes and arms, and expands the dimension of an experimental paradigm. The invention can be used for functional magnetic resonance imaging experiments of primate awake task states and training of various cognitive behavioral paradigms.
Description
Technical Field
The invention relates to the fields of neuroscience and brain function magnetic resonance imaging, in particular to an experimental or training device for primate magnetic resonance imaging.
Background
The mystery of revealing the brain is the biggest challenge facing new centuries of humans, and brain science aimed at elucidating the working principle of the brain is one of the most important scientific frontier fields today. The brain function magnetic resonance imaging is a technology which is extremely important in the development history of modern brain science, realizes non-invasive and rapid acquisition of the whole brain activity condition in a resting state and a task state, is widely applied to the research of brain science and brain diseases of human subjects, and has obtained a great deal of research findings with important significance. Non-human primates (macaque, etc.) have been widely used in brain research since the beginning of the mid 20 th century by virtue of their genetic, physiological, neuroanatomical and behavioral similarities to humans. The awake non-human primate brain function magnetic resonance imaging provides a window for brain science research, has unique advantages in brain science and brain disease research due to the technical characteristics of both the functional magnetic resonance imaging and the awake non-human primate experiments, and has been widely valued in international brain science research in recent years. The data obtained by the technology can be directly compared with the research results of human subjects, so that the defect that the cross-species research results are difficult or even impossible to compare due to different experimental means in the past is overcome, and a foundation is provided for finally transforming the animal research results into clinical transformation. Meanwhile, the technology can be combined with classical mesoscopic and microscopic experimental methods, so that the development of trans-scale and multi-mode brain activity research is greatly promoted, the flexibility of experiments and the diversity of data are greatly increased, and a great pushing effect is played on the mechanism research of brain functions and brain diseases comprehensively and deeply. In addition, the technology can monitor the same individual for a long time, and provides possibility for long-term tracking of brain functions and brain diseases.
However, due to the technical difficulties in various aspects such as fixing the head of an animal, feeding back a task in real time and the like in a strong magnetic field environment, achieving the brain function magnetic resonance imaging of a awake non-human primate is a great technical challenge. Firstly, the most important point of developing brain function magnetic resonance imaging is to limit the fixation of the head in the imaging process, but the experimental animal cannot be in a awake state, so that in order to ensure the realization of the necessary condition of head fixation, a firm head column is required to be installed on the skull of the animal before the existing awake non-human primate brain function magnetic resonance imaging experiment, thereby restricting the head movement of the animal. The method requires a traumatic operation on the animal, and a great deal of time is required to maintain the wound after the operation; secondly, as the animals are required to make behavioral responses according to the requirements of experimental tasks, the most common method at present is to feed back according to animal eye jumping, but the method needs to purchase expensive magnetic field compatible eye movement monitoring equipment, and contradiction is generated when the animals are required to make behavioral responses while keeping the eye gaze point unchanged. For the above reasons, organizations that can successfully and effectively use this technology for research are currently on a global scale.
Disclosure of Invention
The invention aims to provide an experimental or training device for primate magnetic resonance imaging and application thereof.
In a first aspect of the invention there is provided an experimental or training apparatus for primate magnetic resonance imaging comprising: 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 for restraining a primate body and securing an animal head, comprising: 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 fixation system is made of a magnetic field compatible material.
In another preferred embodiment, the non-invasive animal fixation 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 a body part below the head and neck of an animal, and is provided with an opening (a head hole and an arm hole) for the head and the hand of the animal to extend out of the box body; preferably, the animal chair is of a six-sided box type structure; a door allowing animals to enter and exit; the neck plate is used for fixing the neck of the animal so that the head of the animal extends out of the box body; and the lifting plate can be lifted and lowered and is used for matching with animal position transformation and posture adjustment.
In another preferred embodiment, the neck plate is provided with a clamping groove which is matched with the animal collar.
In another preferred embodiment, the animal position comprises: standing and lying.
In another preferred embodiment, the transducer is secured at one end to an animal chair (preferably the neck plate of the animal chair) and at the other end to a helmet and dental bar.
In another preferred embodiment, 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 portions can be folded to wrap the animal's head or to limit movement of the animal's head.
In another preferred embodiment, the helmet includes a window configured according to the eye and ear position of the animal.
In another preferred embodiment, the helmet includes a nose bridge clip groove for engaging the inside of the helmet to secure the animal's head.
In another preferred embodiment, the helmet further comprises side wings for securing the helmet to the transducer.
In another preferred embodiment, the helmet is made based on a 3D model of the animal's cranium, and the internal shape characteristics of the helmet conform to the characteristics of the animal's individual cranium.
In another preferred embodiment, one end of the dental bar is fixed on the converter, and the other end of the dental bar is used for being placed under the teeth of the animal after the head of the animal is fixed; preferably, the tooth bar is provided with a saw tooth shape at a portion contacting with the teeth.
In another preferred embodiment, the visual stimulus system is used to present visual stimuli required for an experimental or training animal; preferably, the visual stimulus system comprises a display connected to and controllable by the central control system; preferably, the visual stimulus system is made of a magnetic field compatible material.
In another preferred embodiment, the behavioral feedback system includes (but is not limited to): eye movement monitoring devices and/or rockers.
In another preferred embodiment, the eye movement monitoring device comprises a camera.
In another preferred embodiment, the eye movement monitoring device comprises a signal output end which is connected with the central control system and feeds back eye movement information of the animal to the central control system.
In another preferred embodiment, the body portion of the rocker is secured to an animal chair for manipulating the rocker by an animal to give a behavioral response to an experimental task.
In another preferred embodiment, 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.
In another preferred embodiment, the rocker is made of a magnetic field compatible material.
In another preferred embodiment, the punishment and punishment system comprises a component selected from the group consisting of a water supply section, a blowing section, a buzzer, a drive control circuit, the drive control circuit being connected to and controlled by the central control system.
In another preferred embodiment, the water supply portion comprises a mouthpiece, a conduit, a water bottle and a valve, the mouthpiece being located under the dental wand, the mouthpiece 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; more 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 drive control circuit and is controlled to be opened and closed by the drive control circuit to control water flow.
In another preferred embodiment, the blowing part 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; more preferably, the conduit C is connected with an air pump and a valve, the conduit D is connected with a valve and an air tap, the air tap is fixed on the animal chair, and the valve is connected with a drive control circuit and is controlled to be opened and closed by the drive control circuit to control air flow.
In another preferred embodiment, the buzzer is connected with the drive control circuit and is controlled to be opened and closed by the drive control circuit.
In another preferred embodiment, the central control system performs parameter setting and coordination control; preferably for controlling visual stimulus systems, reward and punishment systems, behavioral feedback systems (said control comprising receiving information and issuing instructions).
In another preferred embodiment, 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 also connected with the magnetic resonance system, receives a trigger signal from the magnetic resonance system, and the trigger signal is used for synchronizing brain signals acquired by magnetic resonance, visual stimulation output by the visual stimulation system, reward and punishment system instructions and animal behaviors recorded by the behavior feedback system; the lower computer is an NI data acquisition card, and outputs instructions from the upper computer to a drive control circuit in the reward and punishment system, and the eye movement or rocker signals recorded by the behavior feedback system are fed back to the upper computer.
In another preferred embodiment, the experimental or training apparatus for primate magnetic resonance imaging further comprises: the behavior training box is used for simulating the environment in the magnetic field and performing animal behavior training simulating the magnetic field.
In another preferred embodiment, the behavior training box comprises a box body, an exhaust system and a video monitoring system; preferably, the walls of the case are provided with a sound attenuating function; preferably, the exhaust system is used for keeping air circulation and air freshness in the box; preferably, the video monitoring system comprises an infrared camera, an infrared lamp and a display.
In a further aspect of the invention there is provided the use of an experimental or training apparatus for primate magnetic resonance imaging as described in any of the preceding claims for training a primate cognitive behavioural paradigm.
In a further aspect of the invention there is provided the use of an experimental or training apparatus for primate magnetic resonance imaging as described in any of the preceding claims for performing a primate magnetic resonance imaging experiment.
In a further aspect of the invention there is provided the use of an experimental or training apparatus for primate magnetic resonance imaging as described in any of the preceding claims for performing primate immobilization and monitoring.
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, gorilla, ape.
In another aspect of the invention, there is provided a method of performing primate magnetic resonance imaging or imaging experiments, the method comprising: (1) Providing an experimental or training apparatus for primate magnetic resonance imaging as described in any of the preceding claims; (2) Placing a primate in the non-invasive animal fixation system for fixation; (3) magnetic resonance imaging the animal.
In another aspect of the invention, there is provided a method of performing primate training, comprising: (1) Providing an experimental or training apparatus for primate magnetic resonance imaging as described in any of the preceding claims; (2) Placing a primate in the non-invasive animal fixation system for fixation; (3) And the central control system outputs instructions to control components in the visual stimulation system, the reward and punishment system and/or the behavior feedback system to stimulate animals and receive information fed back by the animals.
In a preferred embodiment, the method of magnetic resonance imaging or imaging experiments or primate training is not diagnostic or therapeutic for immediate purposes.
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 schematic diagram of a system architecture according to the present invention.
Figure 2, a schematic view of a portion of the invention entering a magnet bore of a magnetic resonance scanner.
FIG. 3 is a diagram of the animal chair of the present invention; wherein the left view is a view of the side of the animal chair structure which is the door, and the right view is a view of the right view rotated 180 degrees.
FIG. 4 is a diagram of the helmet construction of the present invention; wherein the left view is a front view of the helmet structure and the right view is a rear view of the helmet structure.
Fig. 5A, macaque, shake rocker task performed in the magnetic resonance imaging experimental apparatus of the present invention.
Figure 5B, animal head movements within 6 minutes; the upper graph shows the horizontal movement in XYZ 3 directions, and the lower graph shows the rotation angle in 3 axial directions.
Fig. 5C, head movement distribution of 94 6 minute data.
Fig. 5D, brain area activated by rocking rocker task.
The respective reference numerals are explained as follows:
100. a non-invasive animal fixation system;
200. a visual stimulus system;
300. a behavioral feedback system;
400. a reward and punishment system;
500. a central control system;
5001. an upper computer;
5002. a lower computer;
5003. a magnetic resonance imaging scanner;
600. a task training box;
700. an animal;
1. an animal chair;
2. a converter;
3. a helmet;
4. a dental bar;
5. a water tap;
6. a rocker;
7. a display;
8. an eye movement monitoring device;
10. a guide rail;
11. a main body;
12. a door;
13. a neck plate;
14. an intra-collar adjustment element;
15. a collar external adjustment element;
16. a lifting plate;
17. a door bolt;
18. a window;
19. an arm hole;
21. a lower portion;
22. a nose bridge clamping groove;
23. side fins;
24. An upper portion;
25. a side edge.
Detailed Description
Through intensive researches, the inventor provides an experimental and training device for primate magnetic resonance imaging, which comprises a noninvasive animal fixing system, a visual stimulation system, a behavior feedback system, a punishment and punishment system and a central control system; preferably also comprising a behavioural training box. The non-invasive animal fixation system limits the body of the primate and fixes the animal's head; the visual stimulus system is used for presenting experimental visual tasks; the behavior feedback system is used for tracking and recording the behavior response of the animal; the reward and punishment system is used for rewarding animals, punishment or sound feedback according to instructions 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 animal behavior training outside the magnetic field on a daily basis.
As used herein, the "system" may also be referred to as a "device".
As used herein, the "primate" is preferably a non-human primate comprising: monkey, gorilla, ape.
Animal fixation system
The present inventors devised an animal fixing system, which is called a noninvasive animal fixing system, for effectively restricting the body of a primate and fixing the head of the animal, without causing damage to the animal, aiming at the characteristics of the primate.
The non-invasive animal fixation system includes an animal chair, a helmet, and a dental wand. Wherein, the dental bar can be matched with the helmet to fix the head of the animal.
In a preferred mode of the present invention, the animal chair is an animal fixing device of a box-type structure, which can effectively fix animal bodies, comprising: the box body is used for accommodating the body parts below the head and neck of the animal, is used for fixing the neck of the animal, extends the head of the animal out of the neck plate of the box body and is used for being matched with the lifting plate for animal body position transformation or posture adjustment. The animal chair can enable animal bodies to be in the box body, and the heads are arranged outside the box body. The animal chair may set the animal's body position, for example, a stand position for transporting the animal and a recumbent position for behavioral training or magnetic resonance imaging experiments.
In a preferred form of the invention, the individual 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 animal head or limit the movement of the animal head. In a preferred form of the invention, the helmet is divided into an upper and a lower part, wherein the lower part covers the animal mandible, cheekbones and bridge of the nose, responsible for the support of the entire head weight.
In a preferred form of the invention, the helmet includes a window that is positioned in accordance with the eye and ear positions of the animal. Preferably, the helmet comprises a nose bridge clamping groove which is used for being matched with the inner side part of the helmet to fix the head of the animal. Preferably, the helmet further comprises side wings for securing the helmet to the transducer. The periphery of the helmet is fixed with the animal chair through the converter, the upper part covers the occipital bone and the frontal bone of the animal, the positions of eyes and ears of the animal are reserved, the vision of the animal is not blocked, 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 neck plate of the animal chair, and the other end is used for fixing the helmet and the dental bar;
in a preferred form of the invention, the helmet is configured such that the internal shape characteristics conform to the individual animal's cranium characteristics, preferably it is customizable based on a cranium 3D model of each experimental animal. Preferably, the foam buffer layer is adhered to the inner wall surface of the helmet, so that the whole animal head can be seamlessly, comfortably and completely wrapped, and the animal head cannot move in the helmet. Preferably, the outer shape of the helmet is a regular geometric shape, so that the magnetic resonance signal receiving coil is conveniently placed.
The dental bar is used for preventing the head of the animal from twisting (twisting left and right and up and down), one end of the dental bar is fixed on the converter for fixing the helmet, and the other end of the dental 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 secured under the teeth is of a saw tooth design to prevent removal due to twisting of the head.
In a preferred form of the invention, the various components of the helmet are made of magnetic field compatible materials.
Visual stimulation system
The visual stimulus system is used for presenting visual stimulus required by an experiment or training animal, and is connected with a central control system. Preferably, the visual stimulus is generated by a central control system according to user program settings.
The visual stimulus system includes a device capable of imparting 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 means for imparting visual stimuli to the animal may also be included in the present invention, such as means for imparting relative movement to attract the animal's line of sight.
In a preferred form of the invention, the components of the visual stimulus system are made of a magnetic field compatible material.
Behavior feedback system
The behavioral feedback system is configured to receive the behavioral response of the animal and transmit it to the central control system.
The behavioral feedback system includes (but is not limited to): eye movement monitoring devices and/or rockers. In addition, other devices useful for studying or monitoring animal response or behavior may also be included in the present invention.
As a preferred mode of the present invention, the eye movement monitoring device (e.g., an eye movement monitor) includes a camera. The camera may be positioned near a display in the visual stimulus system, as well as other suitable locations, provided that the eyes of the animal can be monitored, and eye changes captured. Preferably, the eye movement monitoring device can adopt a commercial magnetic resonance compatible eye movement instrument for monitoring the eye movement of animals in the experimental process in real time. Preferably, the camera part of the eye movement instrument 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 eye movement information to the central control system.
As a preferable mode of the invention, the rocking bar is formed by reforming a magnetic field compatible material instead of a metal part in a commercial rocking bar, and the main body part of the rocking bar is fixed on an animal chair and is used for responding to the behavior of an experimental task by operating the rocking bar by an animal, and the signal output end is connected with a central control system and feeds back the position information of the rocking bar to the central control system.
In a preferred form of the invention, the components of the behavioral feedback system are fabricated from magnetic field compatible materials.
Prize and punishment system
The reward and punishment system is used for giving rewards, punishments or sound feedback to animals according to the instructions of the central control system.
As a preferred mode of the present invention, the reward and punishment system includes: and a water supply part. The water supply part comprises a water nozzle, a conduit, a water bottle and a valve. Preferably, the mouthpiece is located below the dental wand and the mouthpiece may be arranged so that the animal is unable to obtain water by sucking. Preferably, the conduit comprises a conduit A and a conduit B, and the valve is an electromagnetic valve. More 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 drive control circuit and is controlled to be opened and closed by the drive control circuit to control water flow. Preferably, the water nozzle is in a structure that three copper pipes are arranged side by side and horizontally, the water outlet end is flush, the copper pipe in the middle is longer in length, and the water nozzle is connected with the guide pipe A, so that animals cannot suck water in the water suction pipe; the water nozzle fixing element enables the water nozzle to be positioned right in front of the animal nozzle.
As a preferred mode of the present invention, the reward and punishment system includes: and the blowing part comprises an air pump, a conduit, a valve and an air tap. 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; more preferably, the conduit C is connected with an oxygen pump and a valve, the conduit D is connected with a valve and an air tap, the air tap is fixed on the animal chair, and the valve is connected with a drive control circuit and is controlled to be opened and closed by the drive control circuit to control air flow.
As a preferred mode of the present invention, the reward and punishment system includes: and the buzzer is directly connected with the driving control circuit.
Each component in the reward and punishment system comprises a water supply part, a blowing part, a buzzer and the like, and is connected with a drive control circuit and controlled by the drive control circuit. The driving control circuit is connected with the central control system and is controlled by the central control system.
In a preferred form of the invention, the components of the reward and punishment system are made of magnetic field compatible materials.
Central control system
The central control system can be directly or indirectly connected with the non-invasive animal fixing system, the visual stimulation system, the behavior feedback system, the reward and punishment system, the visual stimulation system, the behavior feedback system and/or the reward and punishment system, and is used for controlling the operation of the non-invasive animal fixing system, the visual stimulation system, the behavior feedback system, the reward and punishment system and/or the reward and punishment system and obtaining feedback information.
As a preferable mode of the invention, an upper computer in the 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, wherein the trigger signal is used for synchronizing the magnetic resonance imaging scanner to acquire brain signals in time, the visual stimulation system outputs visual stimulation, the reward and punishment system instruction and the behavior feedback system records animal behaviors.
As a preferable mode of the invention, the lower computer in the central control system is an NI data acquisition card, and the lower computer outputs instructions from the upper computer to the driving control circuit in the punishment and punishment system and simultaneously feeds back eye movement or rocker signals 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 behavioral training box. When the device is used for performing the magnetic resonance imaging experiment, the behavior training box can be omitted; when the device is used for animal training for matching with a magnetic resonance imaging experiment, the behavior training box can be used for simulating the environment in a magnetic field and performing animal behavior training simulating the magnetic field (outside the magnetic field).
As a preferable mode of the invention, the behavior training box comprises a box body, an exhaust system and a video monitoring system. The box body is of a cuboid structure, preferably six sides, preferably each side of the box body comprises a three-layer sandwich structure, the middle of the box body is a foam layer, and the two sides of the box body are 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 is used for exhausting the air in the box to the outside of the training room so as to keep the air in the box circulating and the indoor air fresh; the video monitoring system comprises an infrared camera, an infrared lamp and a display, and is used for monitoring the behavior state of animals.
The device provided by the invention can be used for functional magnetic resonance imaging experiments of the awake task state of the primate and training of various cognitive behavioral paradigms.
The invention will be further illustrated with reference to specific examples. It is to be understood that these examples are illustrative of the present invention and are not intended to limit the scope of the present invention. The experimental methods, in which specific conditions are not noted in the following examples, are generally conducted under conventional conditions or under conditions recommended by the manufacturer.
The invention may be better understood upon reading the detailed description of the embodiments of the present disclosure in conjunction with the following drawings. In the drawings, the components are not necessarily to scale and components having similar related features or characteristics may have the same or similar reference numerals.
Example 1 Experimental apparatus for magnetic resonance imaging
As shown in fig. 1, the magnetic resonance imaging experimental apparatus of the present invention includes a non-invasive animal fixation system 100, a visual stimulation system 200, a behavior feedback system 300, a punishment system 400, and a central control system 500. The figure shows a relative positional relationship of the parts in space. The figure is outlined by the dashed line and enters the scanner magnet bore during imaging experiments. The arrow lines in the figure show the direction of information transfer between the central control system 500 and the visual stimulus system 200, the behavioural feedback system 300, the reward and punishment system 400. The central control system transmits visual stimulus information to the visual stimulus system 200 through the upper computer 5001, the central control system transmits punishment information to the punishment system 400 through the lower computer 5002, and animal behavior feedback is transmitted to the central control system 500 through the lower computer 5002. The host computer 5001 receives a synchronization trigger signal from the magnetic resonance imaging scanner 5003.
Figure 2 shows the part of the invention that enters the magnetic cavity of a magnetic resonance scanner comprising an animal chair 1, a transducer 2, a helmet 3, a dental wand 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 noninvasive animal fixing system. The position of the elements is shown, the animal chair 1 is connected with the helmet 3 through the transducer 2, and the dental bar 4 is fixed on the transducer 2. The water tap 5 is arranged below the dental bar 4. The position of the dental wand 4 and the mouthpiece 5 on the transducer 2 can be adjusted to facilitate placement of the dental wand 4 and the mouthpiece 5 in animal mouths of different sizes. The rocking bar 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 movement instrument 8 is arranged below the display to monitor the movement of the eyes of the animals.
Fig. 3 shows the structure of the animal chair of the invention, which comprises a main body 11, a door 12, a neck plate 13, an intra-collar adjustment element 14, an extra-collar adjustment element 15 and a lifting plate 16. The door is secured by 4 door bolts 17. The animal chair has two posture positions: a standing position for animal transfer and a lying position for training or imaging experiments. When standing, the two door bolts 17 on the same side are pulled out, and the door can be opened. The animal chair comprises a necklace outer modulation element 15 on one surface, the necklace of the animal can be clamped into the clamping groove of the neck plate, and the animal can be fixed by inserting the necklace outer modulation element 15. Two windows 18 with doors are provided on both sides of the animal chair for a trainer to grasp the arms and legs of the animal. The right arm of the animal can extend from the arm aperture 19 to operate the rocker. Two sides of the animal chair are provided with guide rails 10, the width of which is matched with the guide rail of the magnetic resonance imaging scanner bed.
Fig. 4 shows the structure of the helmet of the present invention, comprising an upper and a lower part. The lower part 21 covers the mandible 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 nose bridge of the animal, and forms a three-point fixing surface with the fixing points of the left and right cheekbones and is used for limiting the left and right swing and the head tilting of the head. The lower part 21 is fixed to the converter shown in fig. 2 by means of side fins 23. The upper portion 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 windows of eyes and ears for the animal according to anatomical features of the animal, facilitating the implementation of visual and auditory stimuli. The upper and lower parts of the helmet can completely wrap the whole animal head after being closed by the side 25 through bolts, and can limit the head movement in all directions.
2. Visual stimulation system
The visual stimulus system comprises a liquid crystal display 7 which is connected to and controllable by a central control system.
3. Behavior feedback system
The behavioral feedback system 300 includes: eye movement monitoring means 8 and rocker 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. Prize and punishment system
The reward and punishment system comprises: the device comprises a water supply part, a blowing part, a buzzer and a driving control circuit, wherein the driving control circuit is connected with and controlled by a central control system.
The water supply part comprises a water nozzle 5, a conduit, a water bottle and a valve. The water tap 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 drive control circuit and is controlled to be opened and closed by the drive control circuit to control water flow. The water nozzle 5 is of a structure that three copper pipes are arranged side by side and horizontally, the copper pipe in the middle is longer in length and is connected with the guide pipe A, and the structure enables animals to be incapable of sucking water in the water suction pipe; the water nozzle 5 is fixed by a fixing element so that the water nozzle is positioned right in front of the animal mouth.
The blowing part comprises an oxygen pump, a conduit, a valve and an air tap; the conduit comprises a conduit C and a conduit D, and the valve is an electromagnetic valve; the conduit C is connected with an oxygen pump and a valve, the conduit D is connected with a valve and an air tap, the air tap is fixed on the animal chair, and the valve is connected with a drive control circuit and is controlled to be opened and closed by the drive control circuit to control air flow.
The buzzer is directly connected with the driving 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 host computer 5001 is also coupled to the magnetic resonance system for receiving trigger signals from the magnetic resonance imaging scanner.
The lower computer 5002 in the central control system is an NI data acquisition card, the lower computer 5002 outputs an instruction from the upper computer 5001 to a driving control circuit in the punishment and punishment system, and simultaneously feeds back an eye movement or rocker signal recorded by the behavior feedback system to the upper computer 5001.
Example 2 training apparatus for magnetic resonance imaging
The training device for magnetic resonance imaging comprises the experimental device for magnetic resonance imaging described in the embodiment 1 and a behavior training box.
The part outlined by the dotted line in fig. 1 enters the magnetic cavity of the magnetic resonance imaging scanner during imaging experiments and is placed in a behavior training box during behavior training.
Example 3 use of a training apparatus for magnetic resonance imaging
In this example, the training apparatus for magnetic resonance imaging described in example 2 was used to train animals.
During training, primate 700 is placed in the non-invasive animal fixation system for fixation. Comprising the following steps: opening the door 12 of the animal chair, after opening the door, extracting the external necklace modulating component 15, clamping the necklace of the animal into the neck plate clamping groove, enabling the animal body to enter the main body 11, and inserting the external necklace modulating component 15 to fix the animal. The height of the lift plate 16 is adjusted so that the animal can sit just on the lift plate. The door 12 is closed and the animal chair is laid down so that the door 12 is on the floor and the animal squats on the floor. Two windows 18 with doors are provided on both sides of the animal chair for a trainer to grasp the arms and legs of the animal. The right arm of the animal can extend from the arm aperture 19 to operate the rocker.
And a loudspeaker is arranged in the behavior training box, and sound generated by the magnetic resonance imaging scanner during the magnetic resonance imaging experiment is played. The speaker volume was adjusted to bring the sound in the training box to about 70 db. The behavior training box can attenuate the sound by 30-40 db, so the sound in the training box is transmitted to the outside of the training box by about 30-40 db, which is equivalent to the sound of light voice of a person, and the noise interference to an experimenter can not be caused. Meanwhile, the conversation of the experimenter can not affect the animals in the training box. And (3) opening an exhaust system to ensure that the air in the training box is fresh, and simultaneously ensuring that the temperature in the training box is kept at 21-25 ℃.
The central control system runs a user-defined program, and the central control system automatically controls the components in the visual stimulus system 200, the reward and punishment system 400 and the behavior feedback system 300 to train animal behaviors. In this example, the program is written by the published MonkeyLogic toolkit.
Compared with the traditional head column fixing mode, the magnetic resonance imaging training device does not need to perform an operation on animals to install the head column, saves operation and postoperative recovery time, and is about 2 weeks. The regular nursing of the wound in a head column mounting mode is omitted, and time and labor cost are greatly saved. The inventor performs a plurality of batches of training on the macaque in a waking state for up to one year, and proves that the device is simple and easy to use, has high animal matching degree and never causes animal injury. It is shown that the device is well suitable for the cognitive training of tested monkeys.
Example 4 effects of magnetic resonance imaging experiment apparatus
In this example, an animal functional magnetic resonance imaging experiment was performed using the magnetic resonance imaging experimental apparatus described in example 1, and the effect of the apparatus was evaluated: including the animal's head movements and brain regions involved in specific cognitive tasks.
The inventor uses the magnetic resonance imaging experimental device to collect head images when the macaque shakes the rocker task, evaluates the head movement index and finds the brain area activated by the task. In theory, the primary motor cortex M1 and the auxiliary motor cortex SMA of the brain responsible for hand exercises are activated.
Briefly describing this rocking rocker task is as follows (fig. 5A): the right hand of the animal operates the rocker, the animal needs to place a white dot (similar to a mouse) operated by the rocker on a red dot in the center of the screen so as to start the test, after 0.2 seconds, the visual stimulus system randomly presents a square with color in the directions of 0 DEG, 90 DEG, 180 DEG and 270 DEG of the display (the square appears at 180 DEG in the example of fig. 5A), the animal needs to shake the rocker within 2 seconds, the white dot is operated, the white dot is placed on the square, and rewards (water) given by the rewarding system are obtained after success, so that the animal completes one shake of the rocker. After one rocking motion, the animal is at rest for 27s, and then the next rocking motion task is performed. The animals were subjected to a total of 12 trials, i.e. 12 rockers, for a total of 6 minutes.
Figure 5B shows the animal's head movements in 6 minutes, including X, Y, Z3 dimensional translations (up in figure 5B) and 3 rotational movements (down in figure 5B), where both translations are less than 0.5mm and both rotations are less than 0.5 °.
In another cognitive task (not the rocker shake task described above), the inventors collected 94 times 6 minutes of data. The inventors calculated the sum of absolute values of 6 head movements parameters (the rotation angle was converted into a distance according to 80mm of the maximum diameter of the brain at the time of calculation), and evaluated head movements with one value. The 94 data head movement distribution 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, thereby completely meeting the requirements of magnetic resonance imaging. It is particularly emphasized that the algorithm yields results that are greater than the actual head movements, so the actual head movements should be smaller than the head movements calculated by the inventors.
Fig. 5D illustrates a brain region activated by a rocking rocker task. Left and right primary motor cortex M1, and auxiliary motor cortex SMA are activated, and left primary motor cortex activation is stronger, consistent with right hand movement (left brain dominates right hand). The activation of the cortex is consistent with theoretical results.
The brain area activated by the head movements and tasks of the animals shows that the device disclosed by the invention can well fix the head of the awake animal, the head movements completely meet the requirements of the magnetic resonance imaging experiment of the awake primate, and reliable brain function results can be obtained.
It will be appreciated that various changes and modifications may be made by those skilled in the art after reading the above teachings, and such equivalents are intended to fall within the scope of the application as defined in the appended claims.
Claims (28)
1. A method of performing magnetic resonance imaging of a awake primate, the primate being a non-human primate, the method comprising:
(1) An experimental or training apparatus for primate magnetic resonance imaging is provided, comprising: a non-invasive animal fixing system, a visual stimulation system, a behavior feedback system, a reward and punishment system and a central control system; the noninvasive animal fixing system is used for limiting primate bodies and fixing animal heads and comprises an animal chair, a helmet, a dental bar and a converter; one end of the converter is fixed on the animal chair, and the other end of the converter is fixed with the helmet and the dental bar; the tooth bar is arranged in a zigzag shape at the contact part with teeth;
the dental bar is matched with the helmet to fix the head of the animal; one end of the dental bar is fixed on the converter, and the other end of the dental bar is used for being placed under the teeth of the animal after the head of the animal is fixed; the helmet comprises side wings for fixing the helmet to the transducer position; the helmet comprises a nose bridge clamping groove which is used for being matched with the inner side part of the helmet to fix the head of an animal;
The reward and punishment system comprises a water supply part, a water bottle and a valve, wherein 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 is arranged so that the animal cannot suck water;
the animal chair is a box-type structure comprising: the box body is internally used for accommodating body parts below the head and neck of the animal, and is provided with an opening for the head and the hand of the animal to extend out of the box body; a door allowing animals to enter and exit; the neck plate is used for fixing the neck of the animal so that the head of the animal extends out of the box body; lifting plate, it can rise and descend for cooperation animal body position transform and posture adjustment, noninvasive animal fixing system is magnetic field compatible material preparation, visual stimulation system is magnetic field compatible material preparation, behavioral feedback system includes: the eye movement monitoring device and/or the rocker, the main part of rocker is fixed on animal chair for by animal manipulation rocker give the action response to experimental task, the rocker is the preparation of magnetic field compatible material, and the device still includes: the behavior training box is used for simulating the environment in the magnetic field and performing animal behavior training of the simulated magnetic field;
(2) Placing a primate in the non-invasive animal fixation system for fixation;
(3) Performing magnetic resonance imaging on the animal; the non-human primate is selected from the group consisting of: monkey, gorilla, ape.
2. The method of claim 1, wherein the neck plate is provided with a slot that mates with an animal collar.
3. The method of performing awake state primate magnetic resonance imaging of claim 1, wherein the helmet comprises an upper and lower portion, a left and right portion, or a front and rear portion; the two portions can be folded to wrap the animal's head or to limit movement of the animal's head.
4. The method of performing awake state primate magnetic resonance imaging of claim 1, wherein the helmet comprises a window configured according to the eye and ear position of the animal.
5. The method of performing awake state primate magnetic resonance imaging of claim 1, wherein the helmet is based on animal's skull 3D model, and the helmet internal shape characteristics conform to the animal's individual skull characteristics.
6. A method of performing magnetic resonance imaging of an awake state primate as claimed in claim 1 wherein the visual stimulus system is used to present visual stimuli required for experimental or training animals.
7. The method of performing magnetic resonance imaging of an awake state primate of claim 6, wherein the visual stimulus system comprises a display coupled to and controllable by a central control system.
8. A method of performing awake state primate magnetic resonance imaging as set forth in claim 1 wherein the eye movement monitoring device comprises a camera.
9. A method of performing magnetic resonance imaging of an awake state primate as in claim 1 wherein the eye movement monitoring device comprises a signal output connected to the central control system for feeding back eye movement information of the animal to the central control system.
10. A method of performing awake state primate magnetic resonance imaging as claimed in claim 1 wherein the body portion of the rocker is fixed to an animal chair for manipulating the rocker by an animal to give a behavioral response to an experimental task.
11. The method for performing awake state primate magnetic resonance imaging of claim 1, wherein the signal output of the rocker is connected to a central control system, and the position information of the rocker is fed back to the central control system.
12. A method of performing awake state primate magnetic resonance imaging as in claim 1 wherein the reward and punishment system comprises a component selected from the group consisting of a watering section, a blowing section, a buzzer, and a drive control circuit connected to and controlled by a central control system.
13. The method of performing awake state primate magnetic resonance imaging of claim 12, wherein the catheter comprises a catheter a and a catheter B, and the valve is an electromagnetic valve.
14. The method of performing magnetic resonance imaging of an awake state primate as set forth in claim 12 wherein the circuit is controlled by a drive control circuit to open and close and control the flow of water.
15. The method of performing magnetic resonance imaging of an awake state primate of claim 12, wherein the air blowing section comprises an air pump, a conduit, a valve, and an air tap.
16. The method of performing awake state primate magnetic resonance imaging of claim 15, wherein the catheter comprises catheter C and catheter D, and the valve is an electromagnetic valve.
17. The method of claim 16, wherein conduit C connects to an air pump and a valve, conduit D connects to a valve and an air tap, the air tap is secured to an animal chair, and the valve is connected to a drive control circuit and is controlled to open and close by the drive control circuit to control air flow.
18. The method of performing awake state primate magnetic resonance imaging of claim 12, wherein the buzzer is connected to and controlled by a drive control circuit.
19. The method of performing awake state primate magnetic resonance imaging of claim 1, wherein the central control system performs parameter setting and coordinated control.
20. The method of performing awake state primate magnetic resonance imaging of claim 19, wherein the central control system is used to control a visual stimulation system, a reward and punishment system, a behavioral feedback system.
21. The method of performing awake state primate magnetic resonance imaging of claim 19, wherein the central control system comprises a host computer and a slave 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;
the lower computer is an NI data acquisition card, and outputs instructions from the upper computer to a drive control circuit in the reward and punishment system, and the eye movement or rocker signals recorded by the behavior feedback system are fed back to the upper computer.
22. The method of claim 21, wherein the host computer is further coupled to a magnetic resonance system and receives a trigger signal from the magnetic resonance system for synchronizing the brain signals acquired by the magnetic resonance, visual stimuli output by the visual stimulus system, reward and punishment system instructions, and animal behavior recorded by the behavior feedback system.
23. The method of performing awake state primate magnetic resonance imaging of claim 1, wherein the behavioral training box comprises a box, an exhaust system, a video monitoring system.
24. A method of performing awake state primate magnetic resonance imaging as set forth in claim 23 wherein the wall of the enclosure is configured to have a sound attenuation function.
25. The method of performing awake state primate magnetic resonance imaging of claim 23, wherein the exhaust system is used to keep the air in the tank circulating and fresh.
26. The method of performing awake state primate magnetic resonance imaging of claim 23, wherein the video monitoring system comprises an infrared camera, an infrared light and a display.
27. Use of the method of performing awake state primate magnetic resonance imaging of any of claims 1-26 for:
training a primate cognitive behavioral paradigm; and
primate magnetic resonance imaging experiments were performed.
28. A method of performing awake state primate training, the primate being a non-human primate, the method comprising:
(1) Providing an experimental or training apparatus for performing magnetic resonance imaging of a awake state primate of any of claims 1-26;
(2) Placing a primate in the non-invasive animal fixation system for fixation;
(3) And the central control system outputs instructions to control components in the visual stimulation system, the reward and punishment system and/or the behavior feedback system to stimulate animals and receive information fed back by the animals.
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