CN115153528A - System and method for noninvasive stimulation and detection of whole brain network connection - Google Patents
System and method for noninvasive stimulation and detection of whole brain network connection Download PDFInfo
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Abstract
The invention relates to a system and a method for noninvasive stimulation and detection of whole brain network connection, belonging to the technical field of biomedicine, wherein the system comprises a frame body, a control module, an illumination module, an image acquisition module, an ultrasonic stimulation module and an image processing module; the method comprises the following steps: fixing a mouse in a combined displacement platform of a frame body; the illumination module irradiates 470nm and 617nm to the brain of the mouse simultaneously; the image acquisition module acquires image information of a mouse brain; the ultrasonic stimulation module ultrasonically stimulates the whole brain of the mouse; the image processing module outputs image information into a calcium ion fluorescence signal, a deoxyhemoglobin metabolic signal and a brain function connecting signal, and the control module controls the ultrasonic stimulation module to perform regulation and control treatment on the brain of the mouse. The invention can automatically detect the relative change of the concentrations of the whole brain deoxyhemoglobin and the calcium ions, observe the influence of ultrasonic stimulation on nerve activity and blood oxygen metabolism activity, and realize the integration of detection and treatment.
Description
Technical Field
The invention relates to a system and a method for noninvasive stimulation and detection of whole brain network connection, belonging to the technical field of biomedicine.
Background
Measurement of neuronal activity and blood oxygenation signals across brain regions is important for understanding the neural relevance of cognitive and motor processes such as attention, decision making and action selection. However, high resolution devices tend to be expensive and require a great deal of expertise and have many limitations in their use. Multi-wavelength wide-area optical imaging is a high-throughput, cost-effective and flexible method for measuring the activity of specific cell populations with high temporal resolution and cortical-wide field of view.
Low-intensity Transcranial Ultrasonic Stimulation (TUS) has strong regulating effect on cerebral cortex nerve activity, cerebral hemodynamics and neurovascular coupling. TUS can induce action potentials (> 200 hz) in the rat cortex, with excitatory and inhibitory neurons producing action potentials that respond differently to the ultrasound pulse repetition frequency. Therefore, the ultrasonic stimulation has a significant modulating effect on nerve oscillations (frequency >4 hz), and the modulating effect is closely related to the ultrasonic parameters.
Brain functional connectivity is a correlation index for measuring spontaneous hemodynamic signals between brain regions, and is widely used for noninvasive brain network research. Typical multi-spectral imaging systems utilize cameras and illumination at several wavelengths, allowing for discrimination of deoxyhemoglobin concentrations. However, multispectral imaging systems multiplex the illumination wavelength slowly and have difficulty synchronizing high frame rates using a white light source and a mechanical filter wheel, and when driven by an external trigger, the camera is typically unable to acquire at the maximum frame rate; in addition, a filter wheel usually has 6 positions, and a filter needs to be configured for each position, unless the exact same filter is configured, the frame rate for acquiring one wavelength is limited to 1/6 of the frame rate of the camera, because each spectral image is captured at a different time point, which also affects the accuracy of the spectral analysis, and thus it is difficult to achieve high-resolution real-time monitoring of the whole brain deoxyhemoglobin concentration change and the calcium ion concentration change.
Disclosure of Invention
The invention aims to provide a system and a method for noninvasive stimulation and detection of whole brain network connection, which can accurately, continuously, real-timely measure the concentration change of whole brain deoxyhemoglobin and the concentration change of calcium ions at multiple points, and have low manufacturing cost.
In order to achieve the purpose, the invention adopts the technical scheme that:
a system for noninvasive stimulation and detection of whole brain network connection comprises a frame body, a control module, an illumination module, an image acquisition module, an ultrasonic stimulation module and an image processing module;
a combined displacement platform for fixing a mouse is arranged on the frame body;
the illumination module is used for illuminating the brain of the mouse;
the image acquisition module is used for acquiring image information of a mouse brain body;
the ultrasonic stimulation module is used for carrying out whole brain ultrasonic stimulation on the mouse;
the image processing module is electrically connected with the image acquisition module and is used for outputting a calcium ion fluorescence signal, a deoxyhemoglobin metabolic signal and a brain function connection signal according to image information;
the control module is used for controlling the image acquisition module, acquiring a shutter signal of the camera and carrying out external triggering on the ultrasonic stimulation module according to the acquired shutter signal of the camera to realize whole brain ultrasonic stimulation.
The technical scheme of the invention is further improved as follows: the lighting module comprises a first LED component for emitting light waves with the wavelength of 470nm, a second LED component for emitting light waves with the wavelength of 617nm, a 30mm cage cube and a support; the input ends of the first LED assembly and the second LED assembly are connected with the driver and are powered by a power supply; the first LED assembly comprises a 470nm LED, an LED collimation adapter and an optical filter sleeve, wherein the emitting end of the 470nm LED is connected with the input end of the LED collimation adapter through threads, the output end of the LED collimation adapter is connected with the input end of the optical filter sleeve through threads, and the output end of the optical filter sleeve is connected with the input end I of the cage cube 2 through threads; the second LED component comprises an 617nm LED, an LED collimation adapter and an optical filter sleeve, wherein the emitting end of the 617nm LED is connected with the input end of the LED collimation adapter through a thread, the output end of the LED collimation adapter is connected with the input end of the optical filter sleeve through a thread, and the output end of the optical filter sleeve is connected with the input end II of the cage type cube through a thread; a dichroic mirror is arranged in the cage cube and used for reflecting light of 470nm and transmitting light of 617nm to the same position; the support is used for supporting the cage cube, and the support comprises optical extension rods and extension rod angle clamps, wherein the optical extension rods are connected through the extension rod angle clamps and are arranged on the cage cube.
The technical scheme of the invention is further improved as follows: the image acquisition module comprises a camera I, a camera II, a lens I, a lens II, a lens III, a light filter mounting rack I, a light filter mounting rack II and a 60mm cage cube, wherein the camera I and the camera II are respectively connected with the lens I and the lens II through adapter rings, and the lens I and the lens II are respectively connected with the light filter mounting rack I and the light filter mounting rack II through adapter rings; the optical filter mounting rack I and the optical filter mounting rack II are respectively provided with an optical filter, and the optical filter mounting rack I and the optical filter mounting rack II are connected with a 60mm cage cube through screws; the lens III is an inverted lens and is connected with the 60mm cage cube through the adapter ring; a dichroic mirror is installed inside the 60mm cage cube and used for transmitting fluorescence data and deoxyhemoglobin original data into different cameras; all the connecting positions are connected through adapter rings, and the optical connecting rods and the connecting rod adapter are arranged on the frame body.
The technical scheme of the invention is further improved as follows: the ultrasonic stimulation module comprises a function generator, a power amplifier, an ultrasonic transducer and a collimator, wherein the input end of the function generator is in communication connection with the output end of a control module acquisition card, the output end of the function generator is connected with the input end of the ultrasonic transducer through the power amplifier, the transmitting end of the ultrasonic transducer is connected with the collimator, and the collimator is used for collimating ultrasonic waves transmitted by the ultrasonic transducer.
The technical scheme of the invention is further improved as follows: the control module comprises a PC end and an acquisition card, and the PC end is connected with the camera through a USB; the acquisition card is connected to a PC end through a USB line; the acquisition card is connected to the camera signal output port through a data line; and the function generator is connected to the output port of the acquisition card through a signal line.
A non-invasive stimulation and detection method based on a system for non-invasive stimulation and detection of whole brain network connectivity, comprising the steps of:
s1, fixing a mouse in a combined displacement platform on a frame body 1;
s2, the illumination module simultaneously irradiates the brain of the mouse with wavelengths of 470nm and 617 nm;
s3, collecting image information of a mouse brain body by an image collecting module;
s4, performing ultrasonic stimulation on the whole brain of the mouse by an ultrasonic stimulation module;
and S5, the image processing module outputs the image information into a calcium ion fluorescence signal, a deoxyhemoglobin metabolic signal and a brain function connecting signal, and the control module controls the ultrasonic stimulation module to regulate and treat the brain of the mouse.
The technical scheme of the invention is further improved as follows: the relative change signal processing of the concentrations of the deoxyhemoglobin and the calcium ions of the S5 adopts head movement correction, and the head movement is carried out during data acquisition and comprises the states of translation in three directions and rotation in three directions; aligning the image to a first time point by using the rigid linear transformation of the parameters in the six directions, aligning the image to an average functional image, and performing band-pass filtering on each time process to remove slow drift and high-frequency noise, reduce noise influence such as breathing and heartbeat and obtain a digital signal after most interference is eliminated;
the relative change of deoxyhemoglobin and the relative change of calcium ion concentration of the whole brain are expressed by the following formula:
ΔF/F＝(F t -F baseline )/F baseline
wherein, F t Is the intensity of the deoxyhemoglobin or fluorescence signal, F, at different time points baseline Is the average of the data from two seconds prior to whole brain ultrasound stimulation.
Due to the adoption of the technical scheme, the invention has the following technical effects:
the invention adopts the LED for illumination, irradiates the whole brain of the mouse through the dichroic mirror, collects light by the series lens group and converges the light to the camera sensor, allows the camera to image at the maximum frame rate and is not influenced by external limitation. Most of interference signals in the original signals are removed through data processing links such as filtering, and finally, the whole brain network connection signals are output on the PC terminal.
The invention can automatically detect the relative change of the whole brain deoxyhemoglobin and the relative change of the calcium ion concentration, observe the influence of ultrasonic stimulation on nerve activity and blood oxygen metabolism activity, can acquire and detect the whole brain data and simultaneously give ultrasonic stimulation signals, and can carry out long-term stable imaging monitoring because the skull of a mouse does not need to be cleaned, thereby really realizing the integration of detection and treatment.
Drawings
FIG. 1 is a schematic diagram of the structure of the noninvasive stimulation and detection system for whole brain network connection of the present invention;
FIG. 2 is a flow chart of the non-invasive stimulation and detection method of the present invention for whole brain network connectivity;
FIG. 3 is a visual cortical calcium ion fluorescence signal and a deoxyhemoglobin signal collected by the present invention;
the device comprises a frame body 1, a cage type cube 2, a cage type cube 3, a first LED assembly 4, a second LED assembly 5, cameras I and 6, cameras II and 7, lenses I and 8, lenses II and 9, lenses III and 10, a function generator 11, a power amplifier 12, an ultrasonic transducer 13, a collimator 14, a PC terminal 15 and a collection card.
Detailed Description
The invention is described in further detail below with reference to the following figures and specific embodiments:
a system for noninvasive stimulation and detection of whole brain network connectivity, comprising: the frame body 1, control module, illumination module, image acquisition module, supersound stimulation module and image processing module.
A combined displacement platform for fixing a mouse is arranged on the frame body 1;
the illumination module is used for illuminating the brain of a mouse and comprises a first LED component 3 for emitting light waves with the wavelength of 470nm, a second LED component 4 for emitting light waves with the wavelength of 617nm, a 30mm cage cube 2 and a support; the input ends of the first LED assembly 3 and the second LED assembly 4 are connected with a driver and are powered by a power supply; the first LED assembly 3 comprises a 470nm LED, an LED collimation adapter and an optical filter sleeve, wherein the emitting end of the 470nm LED is in threaded connection with the input end of the LED collimation adapter, the output end of the LED collimation adapter is in threaded connection with the input end of the optical filter sleeve, and the output end of the optical filter sleeve is in threaded connection with the input end I of the cage cube 2. The second LED assembly 4 comprises an 617nm LED, an LED collimation adapter and an optical filter sleeve, wherein the transmitting end of the 617nm LED is in threaded connection with the input end of the LED collimation adapter, the output end of the LED collimation adapter is in threaded connection with the input end of the optical filter sleeve, and the output end of the optical filter sleeve is in threaded connection with the input end II of the cage cube 2. The cage cube 2 is internally provided with a dichroic mirror for reflecting light of 470nm and transmitting light of 617nm to the same position. The support is used for supporting and includes that optics connect the pole and connect pole angle anchor clamps, connect and set up on cage cube 2 by connecting pole angle anchor clamps between the optics connect the pole.
The image acquisition module is used for acquiring image information of a mouse brain body and comprises a camera I5, a camera II 6, a lens I7, a lens II 8, a lens III 9, a light filter mounting rack I, a light filter mounting rack II and a 60mm cage cube 2, wherein the camera I5 and the camera II 6 are respectively connected with the lens I7 and the lens II 8 through adapter rings, and the lens I7 and the lens II 8 are respectively connected with the light filter mounting rack I and the light filter mounting rack II through adapter rings; the filter mounting frame I and the filter mounting frame II are respectively provided with an optical filter, and the filter mounting frame I and the filter mounting frame II are connected with the 60mm cage type cube 2 through screws. The lens III 9 is an inverted lens and is connected with the 60mm cage cube 2 through the adapter ring. A dichroic mirror is arranged inside the 60mm cage cube 2 and used for transmitting fluorescence data and deoxyhemoglobin original data into different cameras. All the connecting positions are connected through adapter rings, and the optical connecting rods and the connecting rod adapter are arranged on the frame body 1.
The ultrasonic stimulation module is used for performing whole brain ultrasonic stimulation on a mouse and comprises a function generator 10, a power amplifier 11, an ultrasonic transducer 12 and a collimator 13, wherein the input end of the function generator 10 is in communication connection with the output end of a control module acquisition card 15, the output end of the function generator 10 is connected with the input end of the ultrasonic transducer 12 through the power amplifier 11, the transmitting end of the ultrasonic transducer 12 is connected with the collimator 13, and the collimator 13 is used for collimating ultrasonic waves transmitted by the ultrasonic transducer 12.
The control module is used for controlling the operation of the camera, collecting shutter signals of the camera and externally triggering the function generator 10 according to the collected camera signals to realize whole brain ultrasonic stimulation. The control module comprises a PC end 14 and an acquisition card 15, wherein the PC end 14 is connected with the camera through a USB; the acquisition card 15 is connected to the PC end 14 through a USB line; the acquisition card 15 is connected to a camera signal output port through a data line; the function generator 10 is connected to the output port of the acquisition card 15 via a signal line.
The image processing module is electrically connected with the image acquisition module and is used for outputting calcium ion fluorescence signals, deoxyhemoglobin metabolic signals and brain function connecting signals according to image information.
A method for noninvasive stimulation and detection of whole brain network connectivity, as shown in fig. 2, comprising the steps of:
s1, fixing a mouse in a combined displacement platform on a frame body 1;
s2, the illumination module simultaneously irradiates the brain of the mouse with radiation with the wavelength of 470nm and the wavelength of 617nm
Two LEDs were operated to emit light waves with wavelengths of 470nm, 617nm, respectively, which illuminated the whole mouse brain via filters, dichroic mirrors.
S3, the image acquisition module acquires image information of mouse brain
And adjusting the lighting module to a proper position, controlling the two cameras to operate simultaneously by the control module when a clear image is obtained, acquiring the whole brain image of the mouse in real time, and counting by the acquisition card 15 during acquisition. As shown in fig. 1, the image acquisition module selects two fixed-focus lenses to be connected in series in an anisotropic manner to obtain a proper magnification, and can be freely switched as required, so that the image acquisition module has good flexibility.
S4, performing ultrasonic stimulation on the whole brain of the mouse by the ultrasonic stimulation module
The acquisition card 15 outputs a digital signal to perform external triggering on the function generator 10 according to the frame frequency of the camera until the set time is calculated, the signal output by the function generator 10 is stimulated to the brain of the mouse after passing through the power amplifier 11, the ultrasonic transducer 12 and the collimator 13, and the whole brain of the mouse is subjected to ultrasonic stimulation.
S5, the image processing module outputs the image information into a calcium ion fluorescence signal, a deoxyhemoglobin metabolic signal and a brain function connecting signal
The acquired irradiated brain image information is transmitted to an image processing module, as shown in fig. 3, the acquired image is read by matlab, and the corresponding algorithm formula is used for outputting the calcium ion fluorescence signal and the deoxygenated hemoglobin metabolic signal of the whole brain, the calcium ion concentration is increased due to ultrasonic stimulation, the deoxygenated hemoglobin concentration is decreased, the reaction of the calcium ion concentration reaches the peak value more quickly and recovers the baseline level, and the deoxygenated hemoglobin reaction speed is relatively slow and lasts for a relatively long time.
The relative change signal processing of the concentrations of the deoxyhemoglobin and the calcium ions of the whole brain adopts head movement correction, and the head movement is difficult to avoid during data acquisition, including the translation in three directions and the rotation in three directions. The images are aligned to a first time point by using the rigid linear transformation of the parameters in the six directions, and then are aligned to an average functional image, so that the influence of head movement during data acquisition is reduced as much as possible. Each time process is firstly subjected to band-pass filtering (0.1-2 Hz, second-order Butterworth) to remove slow drift and high-frequency noise, reduce noise influence such as breathing heartbeat and the like, and obtain a digital signal after most interference is eliminated.
The relative change of the deoxyhemoglobin and the relative change of the calcium ion concentration of the whole brain are shown as the following formula:
ΔF/F＝(F t -F baseline )/F baseline
wherein, F t Is the intensity of the deoxyhemoglobin or fluorescence signal, F, at different time points baseline Is the average of the data from two seconds prior to whole brain ultrasound stimulation.
Selecting a region in the brain as a seed point, calculating the time sequence of the average deoxyhemoglobin and the calcium ion signal of the region, and calculating the correlation between the time sequence of the average deoxyhemoglobin and the calcium ion signal between other regions and the region to obtain the functional connection information of the seed point. The correlations between calcium oscillations and HBO, HBr and HBT were analyzed using pearson correlation coefficient (PPC) in the time domain. For column X in matrix X a And column Y in matrix Y b ，
The pearson correlation coefficient is defined as:
where n denotes the length of each column, the PPC values range from-1 to 1, the values of-1 and +1 denote a complete negative and positive correlation, respectively, and 0 denotes that the two time series are independent of each other. Therefore, a positive correlation between deoxyhemoglobin and calcium ion concentration signals in two brain regions indicates a functional synergy, while a negative correlation indicates antagonism between the two brain regions.
Because the selection of the seed points needs certain basic knowledge and possibly omits some important information, the analysis method is improved by dividing the whole brain into a plurality of brain areas, then extracting the time sequence of the average data of each brain area, then calculating the Pearson correlation coefficient between the time sequences of any two brain areas, further obtaining the functional connection between any two brain areas, and finally obtaining the whole brain function connection network.
Changes in neural-to-vascular coupling are calculated within the respective brain regions.
The time-frequency analysis of calcium oscillations and the wavelet transform of the deoxyhemoglobin signal x (T) with respect to the wavelet Ψ are a series of convolutions: w is a group of x (t,f)＝∫Ψ(t-u)x(u)du＝Ψ*x(t)
The signal is time-frequency analyzed using a complex Morlet wavelet. Complex Morlet wavelets are used in which a real-valued gaussian is tapered to a complex-valued sine wave. The complex Morlet wavelet is then convolved with the time series signal. For a time series, the complex Morlet wavelet Ψ can be defined as the product of a complex sine wave and a gaussian window:
where i is the imaginary operator (i = √ (-1)), and f is the frequency in hertz. Further, t is time in seconds. To avoid introducing a phase shift, t should be centered at t = 0.σ is the width of the gaussian distribution, which is defined as σ = n/2 π f. The parameter n defines a trade-off between time-frequency accuracy. Discretizing the time series can be converted into:
wherein f is b As a bandwidth parameter, f c Is the wavelet center frequency. Because the frequency of data analyzed in this study was low, we set FB and Fc to 3 and 0.3 hz, respectively. Then, the norm | W | of the small spectrum is calculated. The time-frequency analysis of the signal has better resolution effect, and can identify the time-frequency change information expressed in the signal. The method of calculating the small spectrum is as follows.
Wherein the image imag (W) and the real number real (W) represent the imaginary part and the real part of W, respectively.
For the small spectrum | W |, the ridge of the small spectrum is calculated on the time and frequency scales. To assess the temporal changes in neuronal calcium oscillations and BOM at different frequencies, we calculated the temporal changes in the main features of the small spectrum with frequency as time scale wavelet ridges (TWR). Wherein t is ∈ [0,8]. And calculating the relative time change of the neuron calcium oscillation wavelet ridges of different frequency bands after TUS relative to the deoxyhemoglobin signal.
Wherein TWR BOM Is the time scale wavelet ridge, TWR, of deoxyhemoglobin Ca Is the time scale wavelet ridge of calcium oscillations. To assess neuronal calcium oscillations and BOM changes at different times, we calculated the increase in the dominant characteristic frequency of the small spectrum over time as the wavelet ridge on the frequency scale.
R t ＝max(|W(t,f)|)
Wherein f is equal to [0,2], and the relative frequency change of the neuron calcium oscillation wavelet ridge relative to the deoxyhemoglobin signal in different time periods before and after TUS is calculated.
ΔFWR/FWR＝(FWR After_TUS -TWR Before_TUS )/TWR Before_TUs
Wherein TWR Before_TUS And FWR After_TUS Representing the frequency scale wavelet ridges of calcium oscillations and deoxyhemoglobin before and after TUS, respectively.
Finally, the PPC values obtained from different brain areas are compared with the set threshold value, and the ultrasonic transducer 12 can be controlled to work to regulate and treat the brain.
Claims (7)
1. A system for noninvasive stimulation and detection of whole brain network connectivity, characterized by: comprises a frame body (1), a control module, a lighting module, an image acquisition module, an ultrasonic stimulation module and an image processing module;
a combined displacement platform for fixing a mouse is arranged on the frame body (1);
the illumination module is used for illuminating the brain of the mouse;
the image acquisition module is used for acquiring image information of a mouse brain body;
the ultrasonic stimulation module is used for performing whole brain ultrasonic stimulation on the mouse;
the image processing module is electrically connected with the image acquisition module and is used for outputting a calcium ion fluorescence signal, a deoxyhemoglobin metabolic signal and a brain function connection signal according to image information;
the control module is used for controlling the image acquisition module, acquiring a shutter signal of the camera and carrying out external triggering on the ultrasonic stimulation module according to the acquired shutter signal of the camera to realize whole brain ultrasonic stimulation.
2. A system for noninvasive stimulation and detection of whole brain network connectivity of claim 1, characterized in that: the lighting module comprises a first LED component (3) for emitting light waves with the wavelength of 470nm, a second LED component (4) for emitting light waves with the wavelength of 617nm, a 30mm cage cube (2) and a bracket; the input ends of the first LED assembly (3) and the second LED assembly (4) are connected with a driver and are powered by a power supply; the first LED assembly (3) comprises a 470nm LED, an LED collimation adapter and an optical filter sleeve, wherein the emitting end of the 470nm LED is connected with the input end of the LED collimation adapter through a thread, the output end of the LED collimation adapter is connected with the input end of the optical filter sleeve through a thread, and the output end of the optical filter sleeve is connected with the input end I of the cage type cube 2 through a thread; the second LED assembly (4) comprises a 617nm LED, an LED collimation adapter and an optical filter sleeve, wherein the emission end of the 617nm LED is connected with the input end of the LED collimation adapter through threads, the output end of the LED collimation adapter is connected with the input end of the optical filter sleeve through threads, and the output end of the optical filter sleeve is connected with the input end II of the cage cube (2) through threads; a dichroic mirror is arranged in the cage type cube (2) and used for reflecting 470nm light and transmitting 617nm light to the same position; the support is used for supporting the cage cube (2), and comprises optical connecting rods and connecting rod angle clamps, wherein the optical connecting rods are connected through the connecting rod angle clamps and are arranged on the cage cube (2).
3. A system for noninvasive stimulation and detection of whole brain network connectivity according to claim 1, characterized by: the image acquisition module comprises a camera I (5), a camera II (6), a lens I (7), a lens II (8), a lens III (9), a light filter mounting rack I, a light filter mounting rack II and a 60mm cage cube (2), wherein the camera I (5) and the camera II (6) are respectively connected with the lens I (7) and the lens II (8) through adapter rings, and the lens I (7) and the lens II (8) are respectively connected with the light filter mounting rack I and the light filter mounting rack II through adapter rings; the optical filter mounting rack I and the optical filter mounting rack II are respectively provided with an optical filter, and the optical filter mounting rack I and the optical filter mounting rack II are connected with the 60mm cage cube (2) through screws; the lens III (9) is an inverted lens and is connected with the 60mm cage type cube (2) through a transfer ring; a dichroic mirror is arranged in the 60mm cage cube (2) and is used for transmitting fluorescence data and deoxyhemoglobin original data into different cameras; all the connecting positions are connected through adapter rings, and the optical connecting rods and the connecting rod adapter are arranged on the frame body (1).
4. A system for noninvasive stimulation and detection of whole brain network connectivity according to claim 1, characterized by: the ultrasonic stimulation module comprises a function generator (10), a power amplifier (11), an ultrasonic transducer (12) and a collimator (13), wherein the input end of the function generator (10) is in communication connection with the output end of a control module acquisition card (15), the output end of the function generator (10) is connected with the input end of the ultrasonic transducer (12) through the power amplifier (11), the transmitting end of the ultrasonic transducer (12) is connected with the collimator (13), and the collimator (13) is used for collimating ultrasonic waves transmitted by the ultrasonic transducer (12).
5. A system for noninvasive stimulation and detection of whole brain network connectivity according to claim 1, characterized by: the control module comprises a PC (personal computer) end (14) and an acquisition card (15), wherein the PC end (14) is connected with the camera through a USB (universal serial bus); the acquisition card (15) is connected to the PC end (14) through a USB wire; the acquisition card (15) is connected to a camera signal output port through a data line; the function generator (10) is connected to the output port of the acquisition card (15) through a signal line.
6. A method for non-invasive stimulation and detection based on the system for non-invasive stimulation and detection of global brain network connectivity of any one of claims 1 to 5, characterized in that: the method comprises the following steps:
s1, fixing a mouse in a combined displacement platform on a frame body 1;
s2, the illumination module simultaneously irradiates the brain of the mouse with the wavelengths of 470nm and 617 nm;
s3, collecting image information of the mouse brain body by an image collecting module;
s4, performing ultrasonic stimulation on the whole brain of the mouse by an ultrasonic stimulation module;
and S5, the image processing module outputs the image information into a calcium ion fluorescence signal, a deoxyhemoglobin metabolic signal and a brain function connecting signal, and the control module controls the ultrasonic stimulation module to regulate and treat the brain of the mouse.
7. A method for noninvasive stimulation and detection of whole brain network connectivity according to claim 6, characterized by: the relative change signal processing of the concentrations of the deoxyhemoglobin and the calcium ions of the S5 adopts head movement correction, and the head movement is carried out during data acquisition and comprises the states of translation in three directions and rotation in three directions; aligning the image to a first time point by using the rigid linear transformation of the parameters in the six directions, aligning the image to an average functional image, and performing band-pass filtering on each time process to remove slow drift and high-frequency noise, reduce noise influence such as breathing and heartbeat and obtain a digital signal after most interference is eliminated;
the relative change of the deoxyhemoglobin and the relative change of the calcium ion concentration of the whole brain are shown as the following formula:
ΔF/F＝(F t -F baseline )/F baseline
wherein, F t Is the intensity of the deoxyhemoglobin or fluorescence signal, F, at different time points baseline Is the average of the data from two seconds prior to whole brain ultrasound stimulation.
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