CN108096705A - Multichannel brain nerve impulse stimulating apparatus - Google Patents
Multichannel brain nerve impulse stimulating apparatus Download PDFInfo
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- CN108096705A CN108096705A CN201810041972.3A CN201810041972A CN108096705A CN 108096705 A CN108096705 A CN 108096705A CN 201810041972 A CN201810041972 A CN 201810041972A CN 108096705 A CN108096705 A CN 108096705A
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Abstract
A kind of multichannel brain nerve impulse stimulating apparatus, including host and multigroup output electrode, host includes pulses generation module and output module, host has further included output timing control circuit, for controlling the stimulation pulse signal of each output module output, make the boost pulse compared with reference electrode that each output electrode is exported that there is the front and rear sequential relationship being sequentially output.The present invention can be carried out at the same time the impulse stimulation with front and rear sequential relationship to the neuron of different nodes on a certain nerve pathway respectively by each group output electrode, nerve pathway is forced to generate the sustainable action potential granting with signal orientation transitive relation, so as to be applied to excite and recover some nervous activities with physiological function.
Description
The technical field present invention is the divisional application of the Chinese patent application of Application No. 2015101775882, is pair
Original bill application is improper to claims modification when examining to cause protection domain loss to remedy.Originally it is related to cranial nerve medical treatment neck
A kind of nerve stimulation device in domain.
Background technology carries out electric pulse stimulation by the neuron to brain, to influence the activity of neuron, so as to reach
It is the prior art in neuromedicine field to the purpose for treating some cerebral diseases.But it has been found that the prior art is mostly
Isolated stimulation is carried out to the neuron of some positions, influences the activity of these neurons, such as stimulating some nerve nucleus
Group makes its nervous function generate enhancing or the variation weakened or be transferred for intervening the signal of nerve nucleus, such as barrier pain
The transmission of pain signal achievees the purpose that electronics relieves pain.And to be used to start certain specific nervous activity, especially to generate
Or change the sustainable action potential granting that between nerve nucleus there is signal to orient transitive relation, due to brain centres nerve
Each neural link neuron between there is Nervons projection and signal transitive relation, so, existing isolated brain god
Through stimulating technology, just it is difficult to generate such technique effect, and it is found by the applicant that in some significant certain applications, it is past
It is past just to need that there is such technique effect.Moreover, the prior art is to the specific location of electro photoluminescence, applying mode and electric pulse
Details etc. without specific aim, the technology taken often with being used for peripheral nerve stimulation when be, but in fact, to maincenter god
Stimulation through member has its particularity, for example, being studied according to the electric discharge of brain some neural circuits, is applied to the electricity of neuron
When pulse, frequency and too low impulse amplitude can not the electric discharge of trigger action current potential, and then can be to god when frequency or excessively high impulse amplitude
It transfers to be formed through first signal and inhibits or even make its inactivation.
The content of the invention is suitable for logical to some nerves the present invention seeks to disclose a kind of nerve stimulation device of multichannel
The neuron of the different position on road is carried out at the same time impulse stimulation, and nerve pathway is promoted to generate with the dynamic of signal orientation transitive relation
Make Electric spike.
Invention additionally discloses being optimized to output signal, it can more effectively induce neuron and provide action potential
Technology.
The present invention nerve stimulation device, including host and connection host electrode, electrode include grounding electrode (or
Reference electrode) and output electrode, host include the pulses generation module for generating stimulation pulse signal, for arteries and veins will to be stimulated
Signal output is rushed to each output module of output electrode, it is characterised in that：The output electrode includes two groups or two groups
Above output electrode, (such as three groups of output electrodes)；Host has further included output timing control circuit, for controlling each output
The stimulation pulse signal of module output has the boost pulse compared with reference electrode that each group output electrode is exported front and rear
The sequential relationship being sequentially output.
Pulses generation module belongs to the prior art, generated pulse may be employed square wave, triangular wave, trapezoidal wave or
Imitate the waveform of neuron action potential pulse.Pulse width T0 is 0.5-10 milliseconds, is further suitable that 1-5 milliseconds, quite
In the pulse width of neuron action potential.The pulse signal of each output electrode output, compared with reference electrode (namely ground connection electricity
Pole) current potential, the crest voltage amplitude of pulse signal is adjusted between 20-1000 millivolts, according to electrode contact locations
And electrode enters the state of neuron and different.
The host of the present invention further includes pulse period adjusting circuit, for adjusting same group of output electrode (first, second He
3rd output electrode) the pulse period T of former and later two pulses that is exported.For different applications, pulse period T is different
, generally between 25 milliseconds to 1000 milliseconds, it is 1-40 hertz corresponding to frequency, sees below described in application obscure portions.
Host of the present invention further includes time delay adjusting circuit, front and rear for adjusting in same pulse exports the cycle
Time delay Ts between former and later two pulses of two electrode (such as the first output electrode and second output electrode) output.
Output timing control circuit is used to control the work of each output module so that the stimulation arteries and veins of each group output electrode output
The sequential relationship of punching is：In a pulse period T, after previous group output electrode exports a boost pulse, by setting
After time delay Ts, later group output electrode just exports a boost pulse.Specifically control method can be：Pulses generation mould
Block generates a pulse signal, then after a time delay Ts, then a pulse signal is generated, then using one
After time delay Ts, then a pulse signal being generated, the gating that sequential control circuit carries out three output modules successively exports,
These three pulse signals are exported successively from three output modules, so as to each output one successively in three groups of output electrodes
Pulse signal.(output pulse frequency for paying attention at this moment pulses generation module is 3 times of output electrode output pulse frequency), so
Control belong to common electronic technology, can be realized by simple MCU or digital circuit.
The present invention nerve stimulation device have multigroup output electrode, each output electrode can the output phase for reference electrode
Stimulation pulse signal, and the stimulation pulse signal that is exported of each group output electrode has the front and rear sequential relationship being sequentially output.
Can tool be carried out at the same time to the neuron of different nodes on a certain nerve pathway by each group output electrode respectively using the present invention
There is the impulse stimulation of front and rear sequential relationship, nerve pathway is forced to generate the sustainable action electricity with signal orientation transitive relation
Position is provided, so as to be applied to excite and recover some nervous activities with physiological function.(see below the disclosed present invention's
Using).
As a kind of important optimization, the present invention is also accurately set the sequential relationship of this output pulse.Its
Two pulses of front and rear two groups of output electrodes (such as first and second output electrode, second with the 3rd output electrode) output are prolonged
Slow time Ts, with pulse period T, pulse width T0, three has following relation：0 ＜ Ts ＜ 1/2T-T0；It is expressed as：It is front and rear
The time delay of two groups of output electrode output pulses is more than 0, and less than " half of pulse period subtracts a pulse width "
Value.STDP synaptic plasticity principle of this set based on cranial nerve, (Spike Timing-Dependent Plasticity,
That is the synaptic plasticity of Temporal dependency), meaning is：To have the boost pulse of such sequential relationship, respectively to a certain nerve
The nerve nucleus of front and rear difference node carries out impulse stimulation on access, not only can force the god during boost pulse is provided
Orientation activation action is generated through access, so as to force to generate the nervous activity of signal transmission, moreover, this impulse stimulation has spy
Fixed sequential relationship can be transferred the cynapse between the front and rear two groups of neurons stimulated and generate enhancement effect, improve cynapse
Transfer efficiency.So such impulse stimulation, while having stimulates neuron and orientation to improve synaptic plasticity between neuron
Effect, be conducive to recover nerve pathway itself signal transfer efficiency, so as to recover its physiological function, it is possible to for one
The rehabilitation of the nerve pathway of a little operation irregularities.
In the present invention above-mentioned stimulating method and device, carrying out the output characteristics of the electric pulse string of neural stimulation is
Critically important.So applicant discloses three kinds to output electricity carefully according to the concrete operating principle of neuron snapping motion current potential
The scheme that the output signal of pole optimizes so that output pulse signal can more accurately induce neuron snapping motion electricity
Position, and this action potential can continue to provide, and be more advantageous to stimulated axoneuron and form sustainable letter
Number transfer.
The first output prioritization scheme of the present invention, including：The pulses generation module, with positive pulse output terminal and
Negative pulse output terminal, can respectively the output phase be for grounding electrode positive potential and negative potential two kinds of pulse output signals；(this
It can be generated by positive-negative power, be common electronic technology)；Two output terminals of positive pulse and negative pulse pass through switching switch
It switches over, the output of switching switch is re-used as the output terminal of pulses generation module, is connected to each output module.Switching switch
Can be mechanical switch or electronic switch.If it is by the way of cranium is opened, and using being exclusively used in brain when implementing brain stimulation
The patch-clamp or nerve microelectrode of nerve stimulation can will be then cut in the neuron membrane to be stimulated output electrode
Switching is changed to positive pulse output terminal, electrode output is made to be connected to positive pulse output terminal, at this moment output electrode is to export just
The pulse signal of current potential.This mode is the ways customary that current laboratory carries out neuronal activation, can reliably stimulate and lure
It goes crazy first snapping motion current potential, but microelectrode is accurately pierced into target nerve member film, it is obviously desirable to operation of opening cranium is carried out,
It is extremely troublesome.So if the switching switch of the present invention is switched on negative pulse output terminal, electrode output is made to be connected to negative arteries and veins
Output terminal is rushed, at this moment what output electrode exported is the pulse signal of negative potential, can be directly applied to outside the film of neuron, pass through drawing
Low film volta potential comes relative reduction film resting potential, and induced action potential.At this moment common electrode can be used, and in brainpan
On open aperture or aperture opened by nasal cavity or larynx deutomala, then output electrode is inserted under the cooperation auxiliary of neuroendoscopy
Enter required for being placed on the target location of stimulation, output electrode need to only contacted or outside the film of nerve cell, without
It is accurate to be pierced into neuron, so operation is more convenient.
Second of the present invention exports prioritization scheme, is used to connect the electrode output of each output electrode on host, with
Between the output terminal of each output module (including the first output module, the second output module and the 3rd output module), added with defeated
Go out control circuit, (a resistor R more suitably, can be also serially connected between the output terminal and output control circuit of output module,
For buffering and generating certain voltage difference)；Electrode output is also connected to the input terminal of a voltage detecting circuit, voltage detecting
The output terminal of circuit is connected to a voltage comparator circuit, compared with the output pulse signal from output module；Voltage ratio
Output terminal compared with circuit is connected to the control terminal of output control circuit, and pulse output signals are controlled by output control circuit
System.When between the voltage signal for the electrode output that voltage detecting circuit detects, and the voltage signal of output module output
When difference is more than setting numerical value, then output control circuit is closed, output module is closed to electricity in the pulse period remaining time
The output signal of pole output terminal, just reopens until next pulse period.Each output that each output module is connected to it
Electrode, control circuit are the same.
According to such output control program, during work, in each output pulse period of each output module, output
Control circuit is first switched on, and pulse output signals are applied to neuron, while voltage by electrode output and output electrode
Voltage signal on detection circuit detecting electrode output terminal (being equivalent to output electrode), and with the pulse output signals of output module
It is compared.When the pulse signal of output electrode reaches a certain level the stimulation of neuron, neuron snapping motion current potential produces
Raw ion overshot phenomenon, causes the current potential inside and outside film change dramatically occur, is transferred to electrode output by output electrode, causes
Larger fluctuation occurs in voltage on electrode output, and is significantly changed not with the pulse output signals of output module output
It is synchronous.This voltage fluctuation passes through voltage comparator circuit and is carried out with pulse output signals detected by voltage detecting circuit
To compare, be identified as neuron snapping motion current potential, the then output of voltage comparator circuit closes output control circuit,
The pulse period remaining time closes output module to the output of electrode output, is just beaten again until the next pulse cycle
It opens.Neuron can so be made to be no longer influenced by the stimulation of external pulse after the outburst of action potential each time, film can be recovered
Polarized state to prepare to carry out integration and again snapping motion current potential to stimulating next time, forms the action of sustainable progress
Electric spike.This technical solution more meets the working mechanism of axoneure, can either induce neuron snapping motion electricity
Position, but will not overstimulation neuron with cause neuron be suppressed inactivation or be damaged, can continue induction action electricity
Position, forms continuous pulse granting, and the ion motion of neuron and physiological function is made gradually to recover normal.
The third of the present invention exports prioritization scheme, is connected on host for connecting the electrode output of each output electrode
There is a voltage detecting circuit, (can be shared with the voltage detecting circuit of front other technologies), voltage detecting circuit is used to detect
The background voltage of electrode output, so alternatively referred to as background voltage detection circuit, the output of voltage detecting circuit are connected with one
Voltage hold circuit carries out holding memory to the background voltage value of voltage detecting circuit output, (voltage memory circuit is equivalent to,
If circuit is using analog circuit, capacitance cooperation operational amplifier circuit can be used to form, it, can if circuit is digital circuit
Directly remember its voltage value), the voltage value of voltage hold circuit output is connected to a voltage overlaying circuit, each output module
The pulse output signals of output, are overlapped in voltage overlaying circuit with background voltage, are connected to electrode output.Voltage
The work of holding circuit, voltage overlaying circuit and each output module is controlled be subject to a state switching circuit, (also can be by
The total control circuit of host is controlled), specific work process is：Carry out cranial nerve stimulation every time, by grounding electrode and defeated
Go out electrode be placed in behind target area or work in when readjusting the position of output electrode and grounding electrode, state switching circuit
Circuit work is switched in into " detection " state, the output of output module is closed, first by voltage detecting circuit detecting electrode output terminal
On voltage, (potential difference namely background voltage between this voltage namely current output electrode and grounding electrode, Ke Nengwei
Just may also be negative), output voltage values are kept (namely memory) by voltage hold circuit, and are sent to voltage overlaying circuit
On；Afterwards, circuit work is switched to " output " state by state switching circuit, closes the input terminal of voltage hold circuit, (make
The voltage value that inputs before of its output voltage holding), open the work of output module, the pulse signal of output module output,
It is overlapped in voltage overlaying circuit with background voltage, is connected to electrode output.In this way, the pulse that output electrode is exported
Signal just offsets the potential difference between two electrodes, can eliminate the shadow of background voltage pulse signals stimulating effect
It rings.
The nerve stimulation device of the present invention has multigroup output electrode, and each group output electrode the output phase is for reference electrode
Boost pulse, and the boost pulse that each group output electrode is exported has the front and rear sequential relationship being sequentially output.The present invention can be with
For being damaged to brain centres nerve and abnormal some Nervons projection accesses that work, such as the sense of hearing, the sensation input of tactile
Access or some motorial output channels, for the front and rear node to these nerve pathways different nerve nucleus simultaneously
The impulse stimulation with front and rear sequential relationship is carried out, nerve pathway is forced to generate the action potential with signal orientation transitive relation
It provides, and enhances its cynapse and transfer efficiency, so as to recover the signal transfer function of these injured nerve accesses.
Present invention may also apply to impaired perineural rehabilitation.Peripheral nerve includes somatic movement nerve and body sense
Feel nerve, when fractured, mechanical trauma, excessively compressing, pultrusion when, can be damaged and cause to lose sensibility or dyskinesia.Week
Perineural power of regeneration is stronger, even if without perform the operation mostly also can self-recovery, but generally require time several months could be by
Gradually recover.There is the device of two groups of output electrodes using the present invention, by two groups of output electrodes along the direction that nerve signal transfers
Across in the both sides of damaged peripheral nerves position, grounding electrode contact skin, before having to two sections before and after injured nerve
The impulse stimulation of sequential relationship afterwards, the transmission for being capable of analog neuron signal cross action, induce and accelerate its nerve regneration, greatly speed up
Rehabilitation speed, and the effect than being stimulated using Sing plus is more preferable.
The present invention more mainly can be in the stimulation and recovery of Central nervous.Including being used for being led due to brain is injured
The coma patient of cause, the brain stimulation of plant person stimulate and recover its cerebration so as to wake up the sense of independence of patient.Concrete application
Content refers to the original bill application of the present invention.
The method that each output electrode is placed in each target location of brain described in present specification, may be employed existing
Electrical brain stimulation technology, such as：It opens cranium and electrode is directly punctured into target nerve member or in the pre-buried electrode in intracerebral target location,
More suitably scheme is that aperture is opened on brainpan or opens aperture by nasal cavity or larynx deutomala, then matching somebody with somebody in neuroendoscopy
It closes under auxiliary, output electrode insertion intracerebral is placed on target location.And used electrode, it may be employed and be currently used for brain
The electro photoluminescence of nerve and the electrode of electrical signal detection use the dedicated microelectrode of cranial nerve or patch-clamp, only when being pierced into neuron
Ordinary electrode is used when contacting outside neuron membrane.
Electrode described in present specification, including the first output electrode, the second output electrode, the 3rd output electrode etc., all
Can be an electrode or one group of (more) electrode, depending on need of work.Generally, for peripheral nerve, only
Single electrode need to be used, and for nervous centralis, it is further suitable that using more electrodes as same output electrode, while to same
Adjacent multiple neurons of one position carry out impulse stimulation, advantageously form signal integration, generate nervous activity.
Description of the drawings Fig. 1 is the structure diagram of the nerve stimulation device operation principle of the present invention.Fig. 2 is each output
The sequence diagram for the boost pulse that electrode is exported.Fig. 3 is a kind of operation principle more rationally controlled output pulse signal
Block diagram.Fig. 4 is another operation principle block diagram more rationally controlled output pulse signal.
It is the narration to the principle of the present invention and specific implementation below specific embodiment.
Fig. 1 is the structure diagram of the nerve stimulation device of the present invention.Electrode including host and connection host, electrode bag
Reference electrode (or grounding electrode) and output electrode are included, host includes the pulses generation for generating stimulation pulse signal
Module connects each output module for being used to stimulation pulse signal being output to output electrode of each output electrode, i.e., first is defeated
Go out module, the second output module, the 3rd output module, it is characterised in that：The output electrode include two groups or two groups with
On output electrode, first, second and the 3rd output electrodes of Fig. 1, totally three groups of output electrodes；When host has further included output
Sequence control circuit；Output timing control circuit is used to control the stimulation pulse signal of each output module output, makes each output electrode
The boost pulse compared with reference electrode exported has the front and rear sequential relationship being sequentially output.Such as Fig. 2.
Pulses generation module belongs to the prior art, generated pulse may be employed square wave, triangular wave, trapezoidal wave or
Imitate the waveform of neuron action potential pulse.Pulse width T0 is 0.5-10 milliseconds, is further suitable that 1-5 milliseconds, quite
In the pulse width of neuron action potential.Output module falls within the prior art, for receiving the pulse of pulses generation module
Signal, and output electrode is output to, effect is isolation buffer and the amplitude for adjusting output pulse.The arteries and veins of each output electrode output
Signal is rushed, compared with reference electrode (namely grounding electrode), crest voltage amplitude can be adjusted between 20-1000 millivolts
Section enters the state of neuron and different according to electrode contact locations and electrode.
The host of the present invention further includes pulse period adjusting circuit, for adjusting same group of output electrode (first, second He
3rd output electrode) the pulse period T of former and later two pulses that is exported.For different applications, pulse period T is different
, generally between 25 milliseconds to 1000 milliseconds, see below described in application obscure portions.
Host of the present invention further includes time delay adjusting circuit, for adjusting in same pulse exports the cycle, front and rear two
Time delay Ts between former and later two pulses of a electrode (such as the first output electrode and second output electrode) output.
Output timing control circuit is used to control the work of each output module so that the stimulation arteries and veins of each group output electrode output
The sequential relationship of punching is：In a pulse period T, after previous output electrode exports a boost pulse, by prolonging for setting
After slow time Ts, latter output electrode just exports a boost pulse.Such as：So there is three groups of output electrodes for Fig. 1
Device, in a pulse period, after the first output electrode exports a boost pulse, after a time delay Ts, the
Two output electrodes export a boost pulse again, then using a time delay Ts after, the 3rd output electrode exports one again
A boost pulse, and so on.Specifically control method can be：Pulses generation module generates a pulse signal, Ran Houjing
After crossing a time delay Ts, then generate a pulse signal, then using a time delay Ts after, then generate an arteries and veins
Rush signal, and the gating that output timing control circuit carries out three output modules successively exports, by these three pulse signals according to
It is secondary to be exported from three output modules, so as to respectively export a pulse signal successively in three groups of output electrodes.(pay attention at this moment
The output pulse frequency of pulses generation module is 3 times of output electrode output pulse frequency), such control belongs to common electricity
Sub- technology can be realized by simple MCU or digital circuit.
The present invention nerve stimulation device have multigroup output electrode, each output electrode can the output phase for reference electrode
Output pulse, and the stimulation pulse signal that is exported of each group output electrode has the front and rear sequential relationship being sequentially output.It uses
The present invention respectively can be carried out at the same time the neuron of different nodes on a certain nerve pathway by each group output electrode before having
The impulse stimulation of sequential relationship afterwards forces nerve pathway to generate the sustainable action potential hair with signal orientation transitive relation
It puts, so as to be applied to excite and recover some nervous activities with physiological function.(see below answering for the disclosed present invention
With).
As a kind of important optimization, the present invention is also accurately set the sequential relationship of this output pulse.Its
Two pulses of front and rear two groups of output electrodes (such as first and second output electrode, second with the 3rd output electrode) output are prolonged
Slow time Ts, with pulse period T, pulse width T0, three has following relation：0 ＜ Ts ＜ 1/2T-T0；It is expressed as：It is front and rear
The time delay of two groups of output electrode output pulses is more than 0, and less than " half of pulse period subtracts a pulse width "
Value.This STDP synaptic plasticity principles accurately set based on neuron, (Spike Timing-Dependent
The synaptic plasticity of Plasticity, i.e. Temporal dependency), according to the STDP plasticity that cynapse is transferred, synaptic plasticity has tight
The time dependence of lattice, efficiency and the sequential of the pulse spike potential of presynaptic caudacoria are transferred in cynapse has substantial connection：If
The spike of presynaptic membrane then generates cynapse and transfers enhancing phenomenon, and the delay of spike earlier than the spike of postsynaptic membrane
It is bigger that enhancement effect is transferred in smaller then cynapse；If the spike of presynaptic membrane is slower than the spike of postsynaptic membrane, generate prominent
It touches and transfers suppression, and the smaller then cynapse transmission decrease effect of delay of spike is bigger.It is stimulated to make the present invention
Cynapse between the front and rear neuron of nerve pathway, which generates, transfers efficiency enhancing, then need to ensure the same pulse period (i.e.
Acted with pulsatile once stimulation) in, the time delay for the pulse that previous output electrode is exported with latter output electrode, after being more than
The time delay for the pulse that one output electrode is exported with previous output electrode.
With reference to the output pulse sequence figure of Fig. 2, calculate that process is as follows：In the case of there are two groups of output electrodes, then exist
In one pulse period T, comprising there are two pulse width T0 and two sections of time delays Ts1 and Ts2, in order to ensure the first output
Time delay Ts1 between first pulse of electrode output and first pulse of the second output electrode output, less than second
The time delay Ts2 of first pulse of output electrode output and second pulse of the first output electrode output, then need
2T0+2Ts1 ＜ T, according to this release have Ts1 ＜ 1/2T-2/2T0 namely require time delay Ts ＜ 1/2T-T0.For having
Three groups and the situation of more output electrodes, since each output electrode exports in order successively, as long as ensureing former and later two electricity
The output signal of pole meets situation analyzed above, so Ts ＜ 1/2T-T0 are equally needed, and because Ts needs
More than 0, so there is 0 ＜ Ts ＜ 1/2T-T0.For example, pulse period T is 50 milliseconds, pulse width T0 is 5 milliseconds, then when postponing
Between 0 20 milliseconds of ＜ Ts ＜, such as optional 10 milliseconds.
The meaning so set is：To have the boost pulse of such sequential relationship, go forward respectively to a certain nerve pathway
The nerve nucleus of different links carries out impulse stimulation afterwards, and the nerve pathway can singly not forced to produce during boost pulse is provided
Raw orientation activation action, so as to force to generate the nervous activity of signal transmission, moreover, this impulse stimulation has specific sequential
Relation can make the cynapse between the front and rear two groups of neurons stimulated generate STDP plasticity, especially LTP cynapses enhancing effect
Should, it improves cynapse and transfers efficiency.So such impulse stimulation, at the same have stimulate neuron and orientation improve neuron it
Between synaptic plasticity effect, be conducive to recover nerve pathway itself signal transfer efficiency, so as to recover its physiological function, institute
Can be used for the rehabilitation of the nerve pathway of a few thing exception.
In the nerve stimulation device of the present invention, the output characteristics of electric pulse string is also critically important.Be currently used for into
The technology of row brain stimulation, output signal often using with other human body electric pulse stimulations or treatment technology (such as it is various in
The electrotherapy technology of low-and high-frequency, acusector technology, Cardiac Pacing) equally, impulse waveform is setting output, that is, by pulse
Positive pulse or positive and negative alternating impulse that module adjusts certain frequency, waveform, duty cycle and voltage amplitude occurs, then directly acts on
In target stimulation sites.These existing electric pulse stimulation technologies if it is for stimulating myocyte or muscular nerve or cardiac muscle cell
On, if with enough pulse width and voltage amplitude, just can these cells of effective stimulus to generate reaction.But such as
Fruit will be used for the granting for stimulate and induce continuous action potential of the intrerneuron of Central nervous, that is with regard to different
, be at this moment just not only requirement neuron is carried out enough pulse widths and voltage amplitude stimulation can, it is inappropriate
Impulse stimulation not only has not been able to induce neuron granting action potential or even can also inhibit its physiological activity, obtains opposite knot
Fruit.
According to Neurobiology, due to the effect of ion motion, the electricity that can stablize in the inside and outside formation of the film of nerve cell
Potential difference namely resting potential, the resting potential of the intrerneuron of human brain is about in -70 to -90mV namely neuron membrane
Current potential is lower 70-90mV than film volta potential, forms film polarization.Make neuron snapping motion current potential, it is necessary to be its depolarising, drop
Potential difference inside and outside low film when depolarising meets or exceeds a certain threshold value, can open a large amount of valtage-gated type ions on film
Passage makes a large amount of interior streams of cation and forms positive feedback, so as to snapping motion current potential.The Time Of Release of action potential generally only has
Several milliseconds, afterwards, it is necessary to which having time is restored to original polarization for cation outflow after action potential granting completion
State, can when stimulating next time snapping motion current potential again.
According to the Burst mechanism of action potential, if will be by external electric pulse come Induced by Stimulation neuron snapping motion electricity
Position, can there is two kinds of modes：1st, it is that electrode is pierced into the cell membrane of neuron (and cannot be with being connected outside cell membrane), in film
The interior electro photoluminescence for applying positive potential when the rising value for the film inner potential that this stimulation generates is more than activation threshold value, just can make
Membrane depolarization and snapping motion current potential.2nd, it is that electrode is placed in outside neuron membrane, but needs to apply outside film the electricity thorn of negative potential
Swashing, the electro photoluminescence of this negative potential has dragged down the current potential outside film, so as to relatively also drag down the potential difference in film outside counter film,
When the changing value of this potential difference is more than threshold value, it can equally make membrane depolarization and snapping motion current potential.So prior art
Electrode is usually placed in a certain brain position, then applies strong positive pulse or positive and negative alternating impulse, caused knot to electrode
Fruit actually not induces neuron and generates normal orderly action potential granting, but since strong potential fluctuation stimulates
Neuron generates sporadic action potential, but often inhibits the ion proper motion of neuron afterwards, makes it that can not generate
Lasting action potential granting can not more make it recover spontaneous normal nervous activity.Typically, it is before real in brain stimulation
It is frequently not algesiogenic sensation when the neuron to epithalamic pain transmission path applies electric pulse stimulation in testing,
But pain is inhibited, this is also often used as brain stimulation analgesic (SPA), although being not aware that its specific analgesic machine
System.
So applicant is carefully according to the concrete operating principle of neuron snapping motion current potential, the output to output electrode
Signal optimizes, enabling more accurately induces neuron snapping motion current potential, and this action potential is can to hold
What supervention was put, it is more advantageous to stimulated axoneuron and forms sustainable signal transmission.
The first output pulse signal prioritization scheme of the present invention, including：The pulses generation module, with positive pulse
Output terminal and negative pulse output terminal the output phase can be believed for two kinds of pulses that grounding electrode is positive potential and negative potential respectively
Number；(this can be generated by positive-negative power, be common electronic technology)；Two output terminals of positive pulse and negative pulse are by cutting
It changes switch to switch over, the output of switching switch is re-used as the output terminal of pulses generation module, is connected to each output module.It cuts
It can be mechanical switch or electronic switch to change switch.If it is by the way of cranium is opened, and using special when implementing brain stimulation
The patch-clamp or nerve microelectrode stimulated for cranial nerve, (this microelectrode is usually used in neuroanatomical laboratory, is used for
The electric signal of neuron is detected, is made of wire or micro- glass tube, tip only has 1 micron or smaller, and only electrode tip
Can be conductive at end, can directly be pierced into the cell space of neuron or the film of aixs cylinder), output electrode can be stimulated
In neuron membrane, then switching switch can be switched to positive pulse output terminal, electrode output is made to be connected to positive pulse output terminal, this
When output electrode be export positive potential pulse signal.This mode is the usual side that current laboratory carries out neuronal activation
Formula, can reliably Induced by Stimulation neuron snapping motion current potential, but microelectrode is accurately pierced into target nerve member film, show
It so needs to carry out operation of opening cranium, it is extremely troublesome.So if the switching switch of the present invention is switched on negative pulse output terminal, make
Electrode output is connected to negative pulse output terminal, and at this moment what output electrode exported is the pulse signal of negative potential, can directly be applied
In outside the film of neuron, by dragging down film volta potential, come relative reduction film resting potential, and induced action potential.At this moment can adopt
It with common electrode, and opens aperture on brainpan or aperture is opened by nasal cavity or larynx deutomala, then matching somebody with somebody in neuroendoscopy
It closes on the target location stimulated required for output electrode insertion is placed under auxiliary, output electrode need to only contacted or close to god
Outside film through cell, without being accurately pierced into neuron, so operation is more convenient, wound is also smaller.
In addition, if the electric pulse stimulation being applied on neuron is excessively strong, particularly when neuron has been induced
After action potential, strong electro photoluminescence is nevertheless suffered from, then can seriously affect the normal ion motion inside and outside neuron membrane, make nerve
It can not recover normal film polarization after first snapping motion current potential, so also can not just carry out the triggering of action potential next time.Institute
The activity of neuron can be inhibited in turn instead with such electric pulse stimulation or even make its inactivation, can not be carried out lasting
It integrates and activates.(strong electric pulse stimulation usually is applied to the brain area domain of pain transmission path before, it is real for being relieved pain
It is this reason on border, it, can not because at this moment the neuron of its pain transmission path inhibits even to be damaged by strong stimulation
Transfer the sensation of pain).So the signal of existing electric pulse stimulation technology export, available for brain stimulation, but often god
Simple unordered electric discharge is generated due to being subject to strong impulse through member, and sustainable multiple regular event current potential can not be generated
It provides, even plays inhibitory action, available for the disease for relieving pain or treating various neuron paradoxical discharges, such as epilepsy, but will
Wish that inducing neuron continues the multiple application scenario for providing action potential for this, then it is and improper, it to adjust in other words
It obtains suitably stimulating width and amplitude, is relatively difficult.
Applicant is improved this, of the invention second output signal prioritization scheme, such as Fig. 3, is used to connect on host
The electrode output of each output electrode (including first, second, and third output electrode) is connect, (electrode output that is to say host
The leading-out terminal for being used to connect each output electrode outside host of upper setting, generally using electric connector), with each output mould
Between the output terminal of block (including first, second, and third output module), added with an output control circuit, (electronic cutting is equivalent to
Powered-down road, more suitable scheme are also serially connected with a resistor R between the output terminal and output control circuit of output module,
For buffering and generating certain voltage difference)；Electrode output is also connected to the input terminal of a voltage detecting circuit, voltage detecting
The output terminal of circuit is connected to a voltage comparator circuit, compared with the output pulse signal from output module；Voltage ratio
Output terminal compared with circuit is connected to the control terminal of output control circuit, and pulse output signals are controlled by output control circuit
System.When between the voltage signal for the electrode output that voltage detecting circuit detects, and the voltage signal of output module output
When difference is more than setting numerical value, then output control circuit is closed, output module is closed to electricity in the pulse period remaining time
The output signal of pole output terminal, just reopens until next pulse period.Due to the first output module to the first output electrode,
Second output module to the second output electrode, the control circuit of the 3rd output module to the 3rd output electrode is the same, so
Fig. 3 is only drawn all the way.
According to such output control program, during work, each output module each output pulse period (i.e. singly
The cycle of a pulse output), output control circuit is first switched on, and output pulse signal passes through electrode output and output electrode
It is applied to neuron, while the voltage signal on voltage detecting circuit detecting electrode output terminal (being equivalent to output electrode), and with
The output pulse signal of output module is compared, (the two is allowed to have certain difference).When the pulse signal of output electrode
The stimulation of neuron is reached a certain level, neuron depolarizes, and opens the ion channel on film, is flowed simultaneously in a large amount of ions
Positive feedback is formed, makes neuron snapping motion current potential.At this moment due to a large amount of ions, drastically interior stream, formation overshot phenomenon make nerve
First film inner potential becomes positive potential by negative potential, and film is outer to become negative potential by positive potential, this potential change drastically can pass through
Output electrode is transferred to electrode output, and the voltage on electrode output is caused larger fluctuation occur, and is and output module
The pulse output signals of output significantly change asynchronous.This voltage fluctuation passes through detected by voltage detecting circuit
Voltage comparator circuit, when the difference of the two is more than setting value (such as 10%), can recognize that compared with pulse output signals
For neuron snapping motion current potential, then, the output of voltage comparator circuit closes output control circuit, in pulse week
The phase remaining time closes output module to the output signal of electrode output, is just reopened until the next pulse cycle.
Neuron can so be made to be no longer influenced by the stimulation of external electric pulse after the outburst of action potential each time, made normal inside and outside its film
Ion motion is unaffected, can recover film polarized state, to stimulating next time integrate and the electricity of snapping motion again
Position forms sustainable multiple action potential granting.This technical solution more meets the working mechanism of axoneure,
Can either induce neuron snapping motion current potential, but will not overstimulation neuron with cause neuron be suppressed inactivation or by
To damage, for stimulating the neuron at the positions such as thalamus, net structure, hypothalamus, induced action potential can be continued, the company of being formed
Continuous pulse granting, and the ion motion of neuron and physiological function is made gradually to recover normal, finally there is spontaneous synchronous arteries and veins
Punching is provided.
In addition, as previously described, it is different with other pulse electrotherapy technologies, electro photoluminescence is carried out in Central nervous to induce
During the sustainable granting of action potential, the stimulation amplitude to electric impulse signal is than more sensitive, should be enough to make its depolarising,
But it is not so large that and inhibits its physiological activity.Applicant have also noticed that it there is also an issue here：When electricity will be exported
When pole and grounding electrode are placed in different brain positions, due to the liquid around cerebral neuron, there are heterogeneity and various concentrations
Negative ions, when not working just there are certain potential difference between output electrode and grounding electrode, (can be described as background voltage),
And this potential difference, with the difference of the different and residing brain position of the relative position of two electrodes, potential difference is also different.
When providing electric impulse signal between output electrode and grounding electrode, if exported with a kind of impulse amplitude of setting,
Then this just existing potential difference originally, will the amplitudes of pulse signals form overlaying influence, disturb pulse signal stimulation
The accuracy of intensity.
So the third prioritization scheme of the present invention to output pulse signal, such as Fig. 4.Its electrode output is connected with one
Voltage detecting circuit, (can be shared with the voltage detecting circuit of front other technologies), voltage detecting circuit are used for detecting electrode
The background voltage of output terminal, so alternatively referred to as background voltage detection circuit, the output of voltage detecting circuit is connected with a voltage
Holding circuit carries out holding memory to the background voltage value of voltage detecting circuit output, (voltage memory circuit is equivalent to, if
Circuit is using analog circuit, then capacitance cooperation operational amplifier circuit can be used to form, can be direct if circuit is digital circuit
Remember its voltage value), the voltage value of voltage hold circuit output is connected to a voltage overlaying circuit, the output of pulses generation module
Pulse output signals, be overlapped in voltage overlaying circuit with background voltage, (if circuit use analog circuit, can adopt
With operational amplifier circuit or using technology virtually, the two is overlapped, if using digital circuit, then by the two number
Value carries out plus and minus calculation), it is connected to electrode output.Voltage hold circuit, voltage overlaying circuit and pulse output module (bag
Include the first output module and the second output module) work, controlled be subject to a state switching circuit, (also can be total by host
Control circuit controlled), specific work process is：Carry out cranial nerve stimulation every time, by grounding electrode and output electrode
Be placed in behind target area or work in when readjusting the position of output electrode and grounding electrode, state switching circuit is by circuit
Work switches in " detection " state, the output of output module is closed, first by the electricity on voltage detecting circuit detecting electrode output terminal
Pressure, (potential difference namely background voltage between this voltage namely current output electrode and grounding electrode may be just
May be negative), output voltage values are kept (namely memory) by voltage hold circuit, and are sent on voltage overlaying circuit；
Afterwards, circuit work is switched to " output " state by state switching circuit, closes the input terminal of voltage hold circuit, (make it
The voltage value that inputs before of output voltage holding), open the work of output module, the pulse signal of output module output, in electricity
It is overlapped in pressure supercircuit with background voltage, is connected to electrode output.In this way, the pulse letter that output electrode is exported
Number, just the potential difference between two electrodes is offseted, the influence of background voltage pulse signals stimulating effect can be eliminated.
The original bill application of the present invention, is accompanied with the largely research data on brain working mechanism in specification, contributes to
In the application scenario for understanding original bill application, coma patient and Patients with Brain Death are stimulated and are waken up the working machine of sense of independence
Reason.In view of this divisional application is not related to these applications, thus delete to reduce length by the research data, it is necessary to when can refer to
Original bill application.
Claims (3)
1. a kind of multichannel brain nerve impulse stimulating apparatus, the electrode including host and connection host, electrode include ground connection electricity
Pole or reference electrode and output electrode, host include the pulses generation module for generating stimulation pulse signal, for inciting somebody to action
Stimulation pulse signal is output to each output module of output electrode, it is characterised in that：The output electrode includes three groups
Above output electrode；Host has further included output timing control circuit, for controlling the boost pulse of each output module output
Signal makes the boost pulse compared with reference electrode that each group output electrode is exported that there is the front and rear sequential being sequentially output to close
System；
The sequential relationship of the boost pulse of each group output electrode output is：Previous group output electrode exports a boost pulse
Afterwards, after the time delay of setting, later group output electrode just exports a boost pulse；
The time delay Ts of two pulses of its front and rear two groups of output electrodes output, with pulse period T, pulse width T0, three
With following relation：0 ＜ Ts ＜ 1/2T-T0；Character express is：The time delay of front and rear two groups of output electrodes output pulse is big
In 0, and less than the value of " half of pulse period subtracts a pulse width ".
2. a kind of multichannel brain nerve stimulation device according to claim 1, it is characterised in that：The pulses generation mould
Block can the output phase be respectively positive potential and negative potential for grounding electrode with positive pulse output terminal and negative pulse output terminal
Two kinds of pulse output signals；Two output terminals of positive pulse and negative pulse are switched over by switching switch, switching switch it is defeated
Go out and be connected to each output module.
3. a kind of multichannel brain nerve stimulation device according to claim 1, it is characterised in that：Host further includes pulse week
Phase adjusts circuit, for adjusting the pulse period for former and later two output pulses that same group of output electrode is exported；Host also wraps
Time delay adjusting circuit is included, for adjusting the time delay between former and later two pulses of former and later two electrodes output.
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| CN201810153676.2A Active CN108175939B (en) | 2014-12-21 | 2015-04-15 | Brain activation device for pulse stimulation of the brain |
| CN201810080558.3A Active CN108126274B (en) | 2014-12-21 | 2015-04-15 | Multichannel nerve stimulation device for pulse stimulation of deep coma brain |
| CN201810139079.4A Active CN108379736B (en) | 2014-12-21 | 2015-04-15 | Cranial nerve stimulation device capable of eliminating background voltage influence |
| CN201810060813.8A Active CN108079435B (en) | 2014-12-21 | 2015-04-15 | Multi-channel nerve stimulation device capable of avoiding over-stimulation of neurons |
| CN201810041972.3A Active CN108096705B (en) | 2014-12-21 | 2015-04-15 | Multi-channel brain nerve pulse stimulation device |
| CN201810075091.3A Active CN108042916B (en) | 2014-12-21 | 2015-04-15 | Multi-channel nerve stimulation device capable of eliminating background voltage influence |
| CN201810091788.XA Active CN108126275B (en) | 2014-12-21 | 2015-04-15 | Multi-channel nerve stimulation device for pulse stimulation of brain |
| CN201510177588.2A Active CN104888347B (en) | 2014-12-21 | 2015-04-15 | Multi-channel nerve stimulating apparatus and its application |
| CN201810134243.2A Active CN108273191B (en) | 2014-12-21 | 2015-04-15 | Cranial nerve stimulation device capable of avoiding over-stimulation of neurons |
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| CN201810153676.2A Active CN108175939B (en) | 2014-12-21 | 2015-04-15 | Brain activation device for pulse stimulation of the brain |
| CN201810080558.3A Active CN108126274B (en) | 2014-12-21 | 2015-04-15 | Multichannel nerve stimulation device for pulse stimulation of deep coma brain |
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| CN108096705B (en) | 2021-09-17 |
| CN108126275A (en) | 2018-06-08 |
| CN104888349B (en) | 2021-08-20 |
| CN104888347B (en) | 2018-04-10 |
| CN104888346A (en) | 2015-09-09 |
| CN108079435B (en) | 2021-09-17 |
| CN108273191B (en) | 2021-11-19 |
| CN108187228A (en) | 2018-06-22 |
| CN108042916A (en) | 2018-05-18 |
| CN108379736B (en) | 2021-11-19 |
| CN108175939B (en) | 2021-06-04 |
| CN108126274A (en) | 2018-06-08 |
| CN104888347A (en) | 2015-09-09 |
| CN108379736A (en) | 2018-08-10 |
| CN108187228B (en) | 2022-04-05 |
| CN108126274B (en) | 2022-04-08 |
| CN108079435A (en) | 2018-05-29 |
| CN108273191A (en) | 2018-07-13 |
| CN108042916B (en) | 2021-09-17 |
| CN108126275B (en) | 2021-11-26 |
| CN104888346B (en) | 2020-10-13 |
| CN104888349A (en) | 2015-09-09 |
| CN108175939A (en) | 2018-06-19 |
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