CN109924976A - The stimulation of mouse TCD,transcranial Doppler and brain electromyography signal synchronous - Google Patents
The stimulation of mouse TCD,transcranial Doppler and brain electromyography signal synchronous Download PDFInfo
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Abstract
The invention discloses the stimulation of mouse TCD,transcranial Doppler and brain electromyography signal synchronous, are related to TCD,transcranial Doppler stimulation study and signal synchronous collection field.The present invention includes TCD,transcranial Doppler stimulating module, pulse TCD,transcranial Doppler signal generating module, brain electromyographic signal collection processing module, power supply.Apparatus of the present invention have that signal acquisition is stable, extension storage ability is strong, the portable series of advantages such as small and exquisite, easy to operate, it can be effectively adapted in the TCD,transcranial Doppler stimulation test of multisample, the brain electromyography signal real-time synchronization acquisition that mouse regains consciousness and can move freely.And the problems such as extending memory module, avoiding the distortion with wirelessly transmitting data excessive using the amount of storage of data for a long time.Convenient for the processed offline of the subsequent brain electromyography signal to TCD,transcranial Doppler stimulation, technical support is provided for the Mechanism Study of the following TCD,transcranial Doppler stimulation and the clinical application as neuromodulation technology.
Description
Technical field
The present invention relates to TCD,transcranial Doppler stimulation study and signal synchronous collection field, apply in the stimulation of mouse TCD,transcranial Doppler
In brain myoelectricity synchronous acquisition, specially mouse TCD,transcranial Doppler stimulation and brain electromyography signal synchronous.
Background technique
Neuromodulation technology has all obtained extensive concern in terms of Neuroscience Research and neural engineer application in recent years.
Neuromodulation refers to using the mechanical-physicals such as light, electricity, magnetic, sound, temperature sexual stimulus and chemical irritation, acts on biological somatic nerves
System (organ, tissue, cell, body fluid etc.) and the process for causing reaction.Regulating effect according to nerve excitability enhancing or
The inhibition enhancing of nerve can be divided into two kinds.By neuromodulation, facilitate the constituent relation for studying nervous system and treatment mind
It through systemic disease, while being also research human brain nerve composition, corresponding actions, a kind of effective means of cognitive function.It is main at present
Neuromodulation means have: electrode deep brain stimulation (DBS), electrical transcranial stimulation (TDCS), transcranial magnetic stimulation (TMS) are super through cranium
Sound stimulat (TUS), light genetic technique (Optogenetics).
It is a kind of very promising neuromodulation technology that pulse TCD,transcranial Doppler, which stimulates (pTUS), is got in recent years
Carry out more extensive concern.Have many advantages, such as Noninvasive, high spatial resolution (< 2mm), high-penetration depth.Impulse ultrasound conduct
A kind of mechanical pressure ripple can be conducted by skull, and skull can also be focused ultrasound, promote or inhibit nerve living
It is dynamic.Nineteen twenty-nine is stimulated using muscle of the ultrasound to frog nerve and tortoise, and it is living to prove that ultrasound can adjust cell for the first time
It is dynamic.1958, research had shown that ultrasound can stimulate the lateral knee of cat to fill nerve nucleus.The group of Tyler W.J. and they in 2008
Team uses ultrasound stimulation hippocampal slices, it was demonstrated that ultrasound stimulation can directly act on neuron and cause action potential, and promote
Make calcium, the change of sodium-ion channel.Subsequent Tufail Y. et al. uses ultrasound stimulation on mouse, stimulates the movement skin of mouse
Layer, has observed apparent limbs and tail muscles activity.Since then, ultrasound stimulation causes extensively as a kind of neuromodulation means
General concern.
But the mechanism of action of ultrasound stimulation is still not clear.Other than being directed to the research of in vitro tissue slice and cell,
Research for living animal is also come into being.Ultrasound stimulation experiment for mouse is also had developed extensively.But at present
Ultrasound stimulation experiment for mouse all relies on ultrasound stimulation platform and realizes, entire platform is relatively cumbersome, at high cost, whole
A platform and mouse require to fix, and experiment requires adjustment again every time.And mouse needs to anaesthetize, and anesthesia can be to mouse
Electricity physiological signal generates interference.So design can apply to ultrasound stimulation device awake and that mouse can be allowed to move freely, together
When can synchronous acquisition mouse brain myoelectricity device, for ultrasound stimulation technology Neuscience research apply have huge promotion
Effect.
A kind of patent document " wear-type ultrasonic conducting device " of Publication No. CN107693962A, proposes animal nerve
Regulation device although there is structure to realize being reliably connected for ultrasonic transducer and skull, and may be implemented to moveing freely animal
Brain locus carry out ultrasound stimulation.But equipment is relatively large, structure is single, and does not have brain electromyography signal synchronous acquisition portion
The device divided, cannot achieve ultrasound stimulation simultaneously, obtains synchronous brain electromyography signal.
Summary of the invention
Present invention aims at above-mentioned the deficiencies in the prior art are made up, a kind of stimulation of mouse TCD,transcranial Doppler and brain flesh are provided
Electric signal synchronous pierce through cranium impulse ultrasound to mouse when mouse regains consciousness and in the case where moveing freely
Swash, and the brain electromyography signal of synchronous acquisition mouse.Different impulse ultrasound parameters is adjusted, repeats and ultrasound is carried out to mouse
Stimulation improves the utilization rate of mouse, and synchronous acquisition brain electricity, electromyography signal, is suitable for the synchronous coupling analysis of brain myoelectricity
Analysis method.
Technical solution provided by the invention are as follows: the stimulation of mouse TCD,transcranial Doppler and brain electromyography signal synchronous, it is special
Sign is: including TCD,transcranial Doppler stimulating module, pulse TCD,transcranial Doppler signal generating module, brain electromyographic signal collection processing module,
Electrode for encephalograms, electromyographic electrode and power supply；The brain electromyographic signal collection processing module is electric with electrode for encephalograms and electromyographic electrode respectively
Connection；The brain electromyographic signal collection processing module is electrically connected with pulse TCD,transcranial Doppler signal generating module, the TCD,transcranial Doppler
Stimulating module is electrically connected with pulse TCD,transcranial Doppler signal generating module；The brain electromyographic signal collection processing module passes through brain electricity electricity
Pole and electromyographic electrode collect EEG signals and electromyography signal, and are handled, and control TCD,transcranial Doppler stimulation according to processing result
Module issues TCD,transcranial Doppler stimulation；The power supply provides electric energy for whole system.
A further technical solution lies in the pulse TCD,transcranial Doppler signal generating module, power supply and brain electromyography signal are adopted
Collection processing module is placed in backpack package, and bandage is arranged in the package.
A further technical solution lies in the pulse TCD,transcranial Doppler signal generating module includes embedded main control module；
The embedded main control module obtains brain electromyographic signal collection processing module treated electric signal, is controlled according to electric signal through cranium
Ultrasound stimulation module issues TCD,transcranial Doppler stimulation.
A further technical solution lies in the pulse TCD,transcranial Doppler signal generating module further includes power amplifier, letter
Number modulation module, filtering processing circuit signal, modulation module and IF extension storage module；The embedded main control module and through cranium
Power amplifier, signal modulation module, filtering processing circuit, the filtering processing circuit are sequentially connected in series between ultrasound stimulation module
Output signal of the output signal through signal modulation module feedback regulation power amplifier；The IF extension storage module and insertion
The connection of formula main control module.
A further technical solution lies in, the brain electromyographic signal collection processing module include the synchronous input interface of signal,
High cmrr amplification module, Parameter adjustable section filter module and A/D conversion module；The synchronous input interface difference of the signal
It is connected with brain, electromyographic electrode, the synchronous input interface of the signal is connected with high cmrr amplification module, ginseng；It is described high total
Mould inhibition is connected with Parameter adjustable section filter module, A/D conversion module respectively than amplification module, the Parameter adjustable section filter
Wave module output end is connect with the input terminal of A/D conversion module.
A further technical solution lies in the high cmrr amplification module includes the sign-changing amplifier being sequentially connected in series
Difference amplifier, two-stage amplifier；The high cmrr amplification module converts follower by the impedance for offseting driving circuit
Common mode driving is carried out with sign-changing amplifier, realizes high cmrr characteristic.
A further technical solution lies in described can include the filtering processing being sequentially connected in series to Parameter adjustable section filter module
Circuit, filtering performance determination module, RC parameter regulation circuit, secondary filtering processing circuit.
The present invention compared with prior art the advantages of:
1. ultrasound stimulation module is minimized, the signal acquisition in a variety of situations, signal stabilization, wearing side can satisfy
Just, small in size, it is light-weight.
2. using the wearable adjustable parameter TCD,transcranial Doppler stimulation of mouse and brain electromyography signal synchronous.It is clear in mouse
It wakes up and the stimulation of pulse TCD,transcranial Doppler is carried out to mouse in the case where can moveing freely, avoid anesthesia and non-movable to ultrasound stimulation
When, the interference of collected brain electromyography signal.And ultrasound stimulation parameter can be adjusted.
3., by pretreatment, storage to TF stores mould by the post-stimulatory brain electromyography signal of collected pulse TCD,transcranial Doppler
On block expansion card, not only can to avoid data it is excessive can not full storage the problem of, wireless transmission can also be avoided passing through and caused
Data transmit lose the problems such as, save the integrality of data, be conducive to subsequent Off-line data analysis.The electricity of adjustable filtering
The RC of road part realizes the adjusting to filter effect.
4. the brain electricity and electromyography signal of mouse can be acquired simultaneously, facilitate single brain when the subsequent stimulation to pulse TCD,transcranial Doppler
Electricity, single myoelectricity, the analysis such as brain myoelectricity coupling.Subsequent usable animal disease model carries out stimulating synchronous brain flesh through cranium impulse ultrasound
Electricity acquisition provides front-end collection and sets for the mechanism of research TCD,transcranial Doppler stimulation, and application of the ultrasound regulation on neurological disease
Standby and technical support.
Detailed description of the invention
Fig. 1 is the TCD,transcranial Doppler stimulation of present system and the signal of brain myoelectricity synchronous connection mouse head
Figure.
Fig. 2 is the TCD,transcranial Doppler stimulating module of present system.
Fig. 3 is the front end acquisition module of present system, the acquisition of brain myoelectricity and processing module and pulse TCD,transcranial Doppler signal
Module flow diagram occurs.
Drawing reference numeral: 1, TCD,transcranial Doppler stimulating module；2, pulse TCD,transcranial Doppler signal generating module；3, brain electromyography signal is adopted
Collect processing module；4, power supply；5, electrode for encephalograms；6, electromyographic electrode；7 myoelectricity reference electrodes；8, spiral shell button is adjusted；9, brain electricity is with reference to electricity
Pole；10, adjusting screw structure；11, ultrasonic transducer；12, collimator.
Specific embodiment
The purpose of the present invention, technical solution, structure are constituted, and advantage etc. is illustrated in conjunction with attached drawing and exemplary application.
The present invention will be further described with reference to the accompanying drawing:
Disclosure sets forth the stimulation of mouse TCD,transcranial Doppler and brain electromyography signal synchronous comprising TCD,transcranial Doppler thorn
Swash module 1, pulse TCD,transcranial Doppler signal generating module 2, brain electromyographic signal collection processing module 3, electrode for encephalograms 5, electromyographic electrode 6
With power supply 4；The brain electromyographic signal collection processing module 3 is electrically connected with electrode for encephalograms 5 and electromyographic electrode 6 respectively；The brain flesh
Electrical signal collection processing module 3 is electrically connected with pulse TCD,transcranial Doppler signal generating module 2, the TCD,transcranial Doppler stimulating module 1 with
Pulse TCD,transcranial Doppler signal generating module 2 is electrically connected；The brain electromyographic signal collection processing module 3 passes through electrode for encephalograms 5 and flesh
Electrode 6 collects EEG signals and electromyography signal, and is handled, and controls TCD,transcranial Doppler stimulating module 1 according to processing result
Issue TCD,transcranial Doppler stimulation；The power supply 4 provides electric energy for whole system.
In the preferred embodiment of the present invention, the pulse TCD,transcranial Doppler signal generating module 2, power supply 4 and brain electromyography signal are adopted
Collection processing module 3 is placed in backpack package, and bandage is arranged in the package.
In the preferred embodiment of the present invention, the pulse TCD,transcranial Doppler signal generating module 2 includes embedded main control module；Institute
It states embedded main control module and obtains brain electromyographic signal collection processing module 2 treated electric signal, controlled according to electric signal through cranium
Ultrasound stimulation module 1 issues TCD,transcranial Doppler stimulation.
In the preferred embodiment of the present invention, the pulse TCD,transcranial Doppler signal generating module 2 further includes power amplifier, signal
Modulation module, filtering processing circuit signal, modulation module and IF extension storage module；The embedded main control module and super through cranium
Power amplifier, signal modulation module, filtering processing circuit, the filtering processing circuit are sequentially connected in series between Sound stimulat module 1
Output signal of the output signal through signal modulation module feedback regulation power amplifier；The IF extension storage module and insertion
The connection of formula main control module.
In the preferred embodiment of the present invention, the brain electromyographic signal collection processing module 3 includes signal synchronous input interface, height
Common-mode rejection ratio amplification module, Parameter adjustable section filter module and A/D conversion module；The synchronous input interface of the signal respectively with
Brain, electromyographic electrode are connected, and the synchronous input interface of the signal is connected with high cmrr amplification module, ginseng；The high common mode
Inhibition is connected with Parameter adjustable section filter module, A/D conversion module respectively than amplification module, the Parameter adjustable section filtering
Module output end is connect with the input terminal of A/D conversion module.
In the preferred embodiment of the present invention, the high cmrr amplification module includes that the sign-changing amplifier that is sequentially connected in series is poor
Divide amplifier, two-stage amplifier；The high cmrr amplification module by offset driving circuit impedance convert follower and
Sign-changing amplifier carries out common mode driving, realizes high cmrr characteristic.
In the preferred embodiment of the present invention, described can include the filtering processing electricity being sequentially connected in series to Parameter adjustable section filter module
Road, filtering performance determination module, RC parameter regulation circuit, secondary filtering processing circuit.
As shown in Figure 1, the wearable adjustable parameter TCD,transcranial Doppler of mouse of the present invention stimulates and brain electromyography signal is synchronous
Acquisition system includes TCD,transcranial Doppler stimulating module 1, pulse TCD,transcranial Doppler signal generating module 2, brain electromyographic signal collection processing mould
Block 3, power supply 4, electrode for encephalograms 5, electromyographic electrode 6, myoelectricity reference electrode 7.Whole system is divided into three parts: the warp of head part
Cranium ultrasound stimulation module 1, electrode for encephalograms 5, brain electricity reference electrode 9；Pulse TCD,transcranial Doppler signal generating module 2 in the knapsack of back,
Brain electromyographic signal collection processing module 3, power supply 4；And electromyographic electrode 6, the myoelectricity reference electrode 7 of tail portion and thigh.
As shown in Fig. 2, being TCD,transcranial Doppler stimulating module 1 of the invention, one end is curved, is added by mouse sphenotresia
Medical glue or dental cement are fixed, and do not damage the brain tissue of mouse, and fixing-stable is bonded, and includes an electrode for encephalograms,
Motor 9 is referred to as brain electricity, using collected EEG signals as reference signal.Top is the connection of adjusting screw structure 10
Axis can finely tune the position of ultrasonic transducer 11 by movable axis, and ultrasonic transducer 11 is fixed on the groove of 3D printing
In, whole upper end has spiral link structure (adjusting spiral shell button 8), can finely tune the position of ultrasonic transducer 11, ultrasonic transducer 11
There is a dismountable ultrasonic collimator 12 in lower end, ultrasonic coupling agent can be filled in collimator 12, and in collimator and mouse head
Couplant adhesion is used between skin.
Electrode for encephalograms 5 is connected to by collimator 12, electrode for encephalograms 5 is fixed on the collimator.It is fixed by brain map solid
Position method, the ultrasound stimulation target area of surgical exposure mouse: S1 motor cortex position.One is opened at the skull of surface with dental drill
Electrode for encephalograms is inserted by the small window of a 0.5mm*0.5mm, and in fixed collimator.As brain wave acquisition part.
As shown in figure 3, pulse TCD,transcranial Doppler signal generating module schematic diagram.It receives and is exported from embedded main control module
Ultrasound stimulation occur signal, by stimulus signal pass through D/A power amplifier module, digital signal is become into analog signal and is put
Greatly, pulse electrical signal is modulated signals into further according to signal modulation module, is filtered to modulated.
If you need to the pulse signal in pulse nesting, stimulation occurs that signal is filtered to be also again introduced into signal modulation mould
Block enters circulation by power amplifier module, so that it may realize that the pulse signal in single pulse is nested, then by as above step
Suddenly.Signal feeding TCD,transcranial Doppler stimulating module finally is occurred into for target pulse TCD,transcranial Doppler and becomes TCD,transcranial Doppler stimulation.
According to external button, key can be carried out to pre-set ultrasound parameter and transferred the files, realize the ultrasound thorn of different parameters
Sharp exchange.
As shown in figure 3, brain electromyographic signal collection processing module schematic diagram.Brain is collected by electrode for encephalograms and electromyographic electrode
Electromyography signal is inputted as synchronization signal.Follower is converted by impedance, using inverting amplifier, is joined according to brain electricity, myoelectricity
The signal of electrode is examined as reference, carries out the main enhanced processing of difference.The algorithm integrated using embedded main control module is to filtering
The judgement of performance, then according to judgement as a result, the size of the capacitor of filter circuit, resistance can be adaptively adjusted in system.It adjusts
Brain electromyography signal is re-entered into transformed RC circuit again afterwards, carries out secondary filtering.Global voltage is finally lifted to A/D
The middle line of conversion module range is horizontal, and analog signal is converted to digital signal using A/D conversion module, then passes through I/O
Digital signal is passed through the further step processing of embedded main control module by mouth.Finally will be according to set program, it will treated signal
Partition packetization, the storage card in TF expansion module carry out data storage.
The extension storage card that insertion different capabilities may be selected in TF expansion module, according to must identify to different expansion cards and
The reading of residual capacity can enter the storage protection program write in embedded main control module, then exceed before memory capacity, meeting
Suspend the work of whole system, and starts buzzer and alarm, the new expansion card of prompting changing.It is stored using TF expansion card,
Although being unable to the acquisition of real-time implementation data, it is that of avoiding the wireless networking challenge of multisample, and does not have to pass in real time
Transmission of data protect collected brain electromyography signal true and accurate, avoid because of dropout in wireless transmission and logical
Letter interference, and the power supply pressure of whole system is reduced, improve the wearable TCD,transcranial Doppler stimulation of entire mouse and brain myoelectricity letter
The cruise-ability of number synchronous can support that the data of longer time acquire or the experiment meter of environmental condition rather harsh
It draws.
Power supply module adds corresponding Voltage stabilizing module, ensure that the stability that the electricity of whole system uses, while also having
The electricity warning function of buzzer rings, prompting changing power supply module avoid system because powerup issue generates hardware damage.
Pulse TCD,transcranial Doppler signal generating module is according to the signal generator of embedded middle control module control, according to write-in
Program, I/O mouthfuls of outputs modulate by signal modulation module, finally export stimulus signal, ultrasonic transducer is allowed to generate different ginsengs
Several impulse ultrasound stimulations.According to external control button, exchanged according to the ultrasound parameter for the different parameters having been written into,
By modulation module, new pulse TCD,transcranial Doppler stimulus signal is generated.
The eeg signal acquisition part of brain electromyographic signal collection processing module is by electrode for encephalograms, preamplifying circuit, second order
Active filter circuit, rear class amplifying circuit and match circuit composition.Electromyographic signal collection is by electromyographic electrode, the main amplification electricity of difference
Road, second-order active power filter circuit and match circuit composition.It is by faint mouse EEG signals, by preceding in brain wave acquisition
Grade amplifying circuit and second-order active power filter circuit, carry out differential amplification, and high cmrr can inhibit the common mode in small-signal
The signal of amplification, can be smoothed by interference by low-pass filter.High frequency filter can filter out high-frequency noise interference,
So that signal-to-noise ratio is improved.Rear class amplifying circuit amplifies EEG signals again, it is suppressed that the null offset of signal.Flesh
Electrical signal collection part is acquired by myoelectricity acquisition electrode, by the main amplification of difference and second-order active power filter circuit, passes through resistance
It is filtered with capacitor.Brain electromyography signal is matched to the intermediate water of the A/D range of embedded system by voltage matches circuit
It is flat, convenient for the post transition of embedded system, also avoid signal more than range and caused by dropout.
The frequency range of brain wave acquisition is 0.1-100Hz, and electromyographic signal collection frequency is 1 to 200Hz.
Claims (7)
1. the stimulation of mouse TCD,transcranial Doppler and brain electromyography signal synchronous, which is characterized in that stimulate mould including TCD,transcranial Doppler
Block, pulse TCD,transcranial Doppler signal generating module, brain electromyographic signal collection processing module, electrode for encephalograms, electromyographic electrode and power supply；Institute
Brain electromyographic signal collection processing module is stated to be electrically connected with electrode for encephalograms and electromyographic electrode respectively；The brain electromyographic signal collection processing
Module is electrically connected with pulse TCD,transcranial Doppler signal generating module, and the TCD,transcranial Doppler stimulating module and pulse TCD,transcranial Doppler signal are sent out
Raw module electrical connection；The brain electromyographic signal collection processing module by electrode for encephalograms and electromyographic electrode collect EEG signals and
Electromyography signal, and handled, TCD,transcranial Doppler stimulating module is controlled according to processing result and issues TCD,transcranial Doppler stimulation；The power supply
Electric energy is provided for whole system.
2. mouse TCD,transcranial Doppler stimulation according to claim 1 and brain electromyography signal synchronous, which is characterized in that
The pulse TCD,transcranial Doppler signal generating module, power supply and brain electromyographic signal collection processing module are placed in backpack package, institute
State package setting bandage.
3. mouse TCD,transcranial Doppler stimulation according to claim 1 and brain electromyography signal synchronous, which is characterized in that
The pulse TCD,transcranial Doppler signal generating module includes embedded main control module；The embedded main control module obtains brain myoelectricity letter
Number acquisition processing module treated electric signal, controls TCD,transcranial Doppler stimulating module according to electric signal and issues TCD,transcranial Doppler stimulation.
4. mouse TCD,transcranial Doppler stimulation according to claim 3 and brain electromyography signal synchronous, which is characterized in that
The pulse TCD,transcranial Doppler signal generating module further includes power amplifier, signal modulation module, filtering processing circuit signal, adjusts
Molding block and IF extension storage module；Power is sequentially connected in series between the embedded main control module and TCD,transcranial Doppler stimulating module to put
Big device, signal modulation module, filtering processing circuit, the output signal of the filtering processing circuit is fed back through signal modulation module to be adjusted
Save the output signal of power amplifier；The IF extension storage module is connect with embedded main control module.
5. mouse TCD,transcranial Doppler stimulation according to claim 1 and brain electromyography signal synchronous, which is characterized in that
The brain electromyographic signal collection processing module includes signal synchronous input interface, high cmrr amplification module, Parameter adjustable
Save filter module and A/D conversion module；The synchronous input interface of the signal is connected with brain, electromyographic electrode respectively, and the signal is same
Step input interface is connected with high cmrr amplification module, ginseng；The high cmrr amplification module respectively can with parameter
Adjust filter module, A/D conversion module is connected, the Parameter adjustable section filter module output end and A/D conversion module
Input terminal connection.
6. mouse TCD,transcranial Doppler stimulation according to claim 5 and brain electromyography signal synchronous, which is characterized in that
The high cmrr amplification module includes sign-changing amplifier difference amplifier, the two-stage amplifier being sequentially connected in series；The height
Common-mode rejection ratio amplification module converts follower by the impedance for offseting driving circuit and sign-changing amplifier carries out common mode driving, realizes
High cmrr characteristic.
7. mouse TCD,transcranial Doppler stimulation according to claim 5 and brain electromyography signal synchronous, which is characterized in that
Described can include the filtering processing circuit, filtering performance determination module, RC parameter being sequentially connected in series to Parameter adjustable section filter module
Adjust circuit, secondary filtering processing circuit.
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