CN101888875A

CN101888875A - Systems and methods for treatment of medical conditions related to the central nervous system and for enhancing cognitive functions

Info

Publication number: CN101888875A
Application number: CN2008801191526A
Authority: CN
Inventors: 乔纳森·本特威奇
Original assignee: Neuronix Ltd
Current assignee: Neuronix Ltd
Priority date: 2007-10-04
Filing date: 2008-10-03
Publication date: 2010-11-17
Also published as: JP2011517962A; IL204785A; WO2009044271A3; WO2009044271A2; IL204785A0; EP2207591A2

Abstract

Systems and methods for diagnosing and treating various brain-related conditions, and/or for modifying at least one of cognitive, behavioral, or affective functions or skills in individuals. The method of diagnosing and treating a brain-related condition includes the steps of: (i) identifying at least a brain region associated with the brain-related condition; (ii) stimulating the brain region by employing at least one electrical, magnetic, electromagnetic, and photoelectric stimulus; (iii) optionally, stimulating at least one cognitive feature associated with the brain region; and (iv) optionally, subjecting the brain region to a treatment including at least one of cell replacement therapy, cell regenerative therapy and cell growth.

Description

The system and method that is used for the treatment of the medical conditions relevant and is used to improve cognitive function with the central nervous system

The cross reference of related application

This application requires to submit on October 4th, 2007 be entitled as " Method and System forEnhancement of Cognitive Functions and Helmet for Treatment of CentralNervous System Medical Implications " the 60/960th, the excellent rights and interests of No. 574 U.S. Provisional Applications, the whole open of this application incorporated into by complete literary composition at this by reference.This application also is the 12/153rd of submission on May 13rd, 2008, the part continuity of No. 037 U. S. application, and the 12/153rd, No. 037 U. S. application is the 10/904th of submission on November 14th, 2004, the continuity of No. 505 U. S. applications, it requires the rights and interests of the 60/522nd, No. 286 U.S. Provisional Application of JIUYUE in 2004 submission on the 13rd conversely, and the whole open of this application also incorporated at this by reference in full.

This application relates to the application of the N2222.0008/P008 attorney docket of submitting on the same day that is entitled as " Systems and Methods for Assessing andTreating Medical Conditions Related to the Central Nervous System and forEnhancing Cognitive Functions ", and it is incorporated in full at this by reference, its non-provisional application requires to submit on October 4th, 2007 be entitled as " System and Method for Assessment and Treatment of CentralNervous System Medical Implications and Indications " the 60/960th, the rights and interests of No. 575 U.S. Provisional Applications, its whole disclosing is incorporated in full at this by reference.

Invention field

The present invention relates to be used to diagnose and medical conditions that treatment is associated with the central nervous system and the system and method that is used to improve s cognitive function.

Summary of the invention

The invention provides and be configured to discern and the method and system of the various medical conditions that treatment is associated with the central nervous system.The present invention also provides system and the equipment that is used to improve s cognitive function.

By the description of this invention with reference to the accompanying drawings, it is clear that other features and advantages of the present invention will become.

Description of drawings

Fig. 1 is the schematic block diagram of comprehensive neuro-cognitive system according to an illustrative embodiment of the invention;

Fig. 2 is the schematic block diagram of neural diagnostic module of the system of Fig. 1;

Fig. 3 is the schematic block diagram of region of interest computing module of the system of Fig. 1;

Fig. 4 is the schematic block diagram of brain feature calculation module of the system of Fig. 1;

Fig. 5 is the schematic block diagram of treatment module of the system of Fig. 1;

Fig. 6 is the schematic block diagram of stimulating module of the system of Fig. 1;

Fig. 7 is the schematic block diagram of brain stimulator of the stimulating module of Fig. 6;

Fig. 8 is another sketch map of brain stimulator of the stimulating module of Fig. 6;

Fig. 9 shows the system of embodiment A;

Figure 10 shows the system of embodiment B;

Figure 11 shows the system of embodiment C;

Figure 12 is the computer utility block diagram;

Figure 13 is end block figure;

Figure 14 is (ISAT) block diagram between the time dependent curee;

Figure 15 is normalized number (NDA) block diagram according to one's analysis;

Figure 16 is expert decision-making interactive system (EDMIS) block diagram;

Figure 17 is Alzheimer's disease diagnostic module (ADM) block diagram;

Figure 18 is cerebral lesion locating module (DBLM) block diagram;

Figure 19 shows the enhanced form of the stimulator of embodiment C; With

Figure 20 shows the gyrostabilized platform of comprehensive neuro-cognitive of the present invention system and the sketch map of feedback system.

The specific embodiment

The embodiment that provides below describes various embodiment of the present invention in detail.After having read detailed description provided herein, further feature of the present invention, embodiment and advantage discussing in describing in detail will become more obvious to this area person skilled.This area person skilled will be recognized, can much change the present invention under the situation that does not depart from scope of the present invention or spirit.

The invention provides the method and system that is configured to discern and treat the various medical conditions that are associated with the central nervous system.The present invention also provides the method and system that is used to improve s cognitive function.

The invention provides such system and device, it is configured to identification and treats various and brain diseases associated and/or assessment and adjusting (for example: improve) cognition, action or the emotive function of individuality or at least one in the technical ability.This system can comprise at least one stimulator.Suitable stimulator is including, but not limited to first stimulator and second stimulator, and first stimulator can comprise at least one in aggressive and the Non-Invasive brain stimulation equipment, and second stimulator is operably connected to first stimulator.First stimulator is configured to by utilizing at least one in stimulating of electricity irritation, magnetic stimulation, electromagnetic stimulation and photoelectricity to stimulate at least one brain area that is associated with brain diseases.Second stimulator is configured to regulate at least one cognitive function that is associated with the brain area of being discerned.First stimulator and second stimulator can form single integrated equipment, and perhaps selectively, first stimulator and second stimulator can form the individual components of this equipment.First stimulator and second stimulator are configured to operate simultaneously or operation sequentially.

The present invention also provides and has been used for diagnosing and treating various brain diseasess and/or regulates at least a cognition, behavior or the emotive function of individuality or the method for technical ability.Diagnosis and treatment can comprise the steps: that with the method for brain diseases associated or raising cognitive function (i) discerns the brain area that is associated with brain diseases associated or cognitive function at least; (ii) as stimulations such as electricity irritation, magnetic stimulation, electromagnetic stimulation and photoelectricity stimulations brain area is stimulated by using; (iii) selectively, stimulate at least one cognitive characteristics that is associated with the brain area of step (i) at least; (iv) selectively, the brain area of step (i) is received treatment, this treatment comprises at least a in cell replacement therapy, cell regeneration therapy and the cell growth; (v) selectively, make at least the brain area of step (i) accept Drug therapy.

The invention provides comprehensive neuro-cognitive system, this system is used for diagnosis and treats various and brain diseases associated, and/or be used for (according to the individuality comparison of structure or function or cognitive function and corresponding statistics health or brain diseases standard or with the individuality that is used for the cognitive statistical standard that improves function relatively) assessment and raising ordinary person's specific knowledge, behavior or the emotive function (or technical ability) of relevant cognitive function with brain.Comprehensive neuro-cognitive of the present invention system also provides nerve electric stimulation or electromagnetic stimulation subsequently, and to the fusion cognitive stimulation of the auxiliary raising cognitive function of the identification cerebral lesion zone of individuality or brain area.

The present invention also provides and has been used for nerve diagnosis computing system and the method that distinctiveness ground is diagnosed having the specific individuality with the brain diseases associated, and individual specific function, structure or cognitive unusual normalized illustration.Selectively, the invention provides the nerve diagnosis computing system and the method that are used to discern those specific knowledge functions, described specific knowledge function can be further improved in individuality with respect to the cognition raising standard of brain function.In addition, the present invention also provides and has been used to calculate accurately based on the brain stimulation of individuality and the apparatus and method of corresponding cognitive stimulation parameter, and it is required cognitive skill or function to stimulate the cerebral lesion site discerned or raising to be discerned.

Such apparatus and method have been the present invention further provides, the comparison of the neural diagnostic measures of preceding neural diagnostic measures of its stimulation and stimulation back according to relevant brain function, structure and corresponding cognitive function, stimulate relevant brain area and corresponding cognitive function, and constantly monitor and regulate simultaneously brain and the cognitive stimulation parameter that specified individual or disease or specific knowledge improve function.

The invention provides the method and system that is used for accurately locating the zone of relevant cerebral lesion with electricity irritation or electromagnetic stimulation, the stimulation in these zones can improve the cognitive function of ordinary person aspect certain skills.Electricity irritation or electromagnetic stimulation can with the fusion cognitive stimulation combination of identical brain area, and/or combine with the internal regeneration of neural plasticity method or neural the implantation, it has caused regeneration, replacement or growth by electricity, electromagnetism or the cognitive identical brain area that is stimulated, thereby maximize potential treatment or neural plasticity effect, perhaps electricity irritation or electromagnetic stimulation can combine with drug media or material, and it can promote the neural plasticity that is associated with the identical brain area that is just stimulated by electromagnetism or cognition etc. or the regeneration or the raising of cognitive function.

The present invention has also described the individuality that is used to distinguish the cognitive function with raising and ordinary person's computer statistics appraisal procedure and system.

Referring now to accompanying drawing, wherein similar assembly is to be referred to by similar reference number, Fig. 1 to Fig. 8 shows the various construction packages of system 200 of the present invention, the medical conditions that it is configured to diagnose and treatment is associated with the central nervous system and/or improve mammiferous cognitive function.

With reference to Fig. 1, it shows individual brain area 100, and they are individual pathology function or structure brain feature or cognitive function features, and it is and is associated with the brain diseases associated by the concrete of neural diagnostic module 101 (Fig. 1) identification.Neural diagnostic module 101 measurement function activity or structure charts, perhaps individual in particular task (a plurality of task) or in the corresponding cognitive performance of rest period.To region of interest computing module 102, set up health standards or those specific brain area of deviation occur with the corresponding statistical standard of cognition raising performance in the particular task in its identification individuality by structure, function or cognitive function and their corresponding statistics with this information transmission for neural diagnostic module 101.

The statistic bias of these identifications of region of interest computing module 102 output specified individual or the cognitive brain area that improves are to be used for the analysis in brain feature calculation module 103.Brain feature calculation module 103 judges whether these identifications any one in brain area meets specific and the known structure brain diseases associated, function or cognitive pathophysiology on statistics.Selectively, brain feature calculation module 103 judges that these identifications any one in brain area is in the standard of setting up that whether meets cognition raising or fabulous or behavioral performance (in particular task or technical ability time) on the statistics.Therefore, for example, under the situation of infantile autism obstacle (ASD), statistics is set up standard and has been indicated unusual shortage activity (and the size that reduces on the structure) in the language area of typical Bu Luoka that autism children or individuality show at left hemisphere (LH) and Wei Nike, the unusual over-activity of Bu Luoka and wernicke's area territory (or enlarging on the structure) of offside (RH) simultaneously.Therefore; under the situation of (having or do not exist the Bu Luoka of the offside RH that follows and the overacfivity in wernicke's area territory) is gone down in the abnormal movement of the language area of the Bu Luoka of this LH of region of interest computing module 102 identification and Wei Nike; region of interest computing module 102 exports these zones to brain feature calculation module 103 then, whether meets known structure, function or the cognitive pathophysiology of infantile autism obstacle (ASD) with in the brain area of judging these identifications any one on statistics.

Selectively, in Alzheimer's disease (or because the age, any other memory loss that dementia or mild cognitive impairment (MCI) cause) under the situation, it is minimizing 26S Proteasome Structure and Functions with Hippocampus and other inboard temporo structure that the standard that statistics is set up has been indicated this dysmnesia, and the connectedness that reduces between forehead and hindbrain zone and the facial recognition zone or the structure of cerebellum, function or cognitive disorder (being associated with coordination obstacle and semantic memory or linguistic competence's forfeiture) are associated, perhaps with emotion with carry out that functional area obstacle (for example: left side prefrontal area and cingule gyrus and frontal lobe) is associated.Therefore, under the situation of this unusual minimizing structure of these brain structures of region of interest computing module 102 identification or function value, these brain area are output to brain feature calculation module 103, whether meet Alzheimer's disease, MCI, dementia or the memory loss relevant with the age or known structure, function or the cognitive pathophysiology of other ageing disorders with in the brain area of judging these identifications any one on statistics.Meet brain diseases or meet under the situation of nervus centralis function, structure or cognitive level that auxiliary cognitive in particular task improve performance in the region-of-interest of identification or cognitive performance level, treatment module 104 is calculated needed accurate brain and the cognitive stimulation parameter based on individuality that stimulates the individual brain area of being discerned 100, and these parameters are essential for the performance of improving function, structure or cognitive illnesses index or improve in the particular task.

Region of interest computing module 102 is also exported the cognitive brain area that improves of identification of specified individual, being used for analysis, thereby judge that whether in the brain area of these identifications any one exist deviation with that improve or the fabulous cognition or the standard of setting up of behavioral performance (in particular task or technical ability) on statistics in brain feature calculation module 103.Therefore; for example; structure at normal individual; function or cognitive pattern are under the situation that is different from the raising linguistic competence standard of being indicated by extraordinary or outstanding cognitive linguistic competence on the statistics; the cognitive stimulation of the auxiliary raising brain area of these identifications or electromagnetic stimulation or electricity irritation or corresponding cognitive function will be performed so; extraordinary or outstanding cognitive linguistic competence including, but not limited to: the name; sound articulation; the oral memory of short-term; language intelligence tolerance; verbal association; vocabulary; grammer; practical language; semanteme etc., and these abilities also with improve the connective or effective brain activity pattern of functional activity or any other is associated to the tolerance that function or structure improve cognitive language function ability.The region-of-interest of identification or cognitive performance level be calculated as with particular task in auxiliary raising nerve centre function or the situation of structure or cognitive correlative coupling under, treatment module 104 will be calculated required accurately based on the brain and the cognitive stimulation parameter of individuality, so that improve function in the particular task, structure or cognitive at the raising performance.

Stimulating module 105 receives the input based on the brain and the cognitive stimulation of individuality about the comprehensive neuro-cognitive stimulus parameter that comprises them that comes from treatment module 104.In addition and/or selectively, body internal stimulus device 109 can combine with stimulating module 105.In exemplary embodiment, body internal stimulus device 109 can comprise in the body of the neurocyte of same individual brain area 100 or tissue or sustenticular cell transplanting or regeneration or stem cell and insert.

Feedback also can combine with stimulating module 105, and its stimulating module 105 and then.Feedback is measured after can comprising the stimulation of being carried out by neural diagnostic module 101, neural then diagnostic module 101 carries out all order computation steps, and it comprises: region of interest computing module 102, brain feature calculation module 103, treatment module 104 and stimulating module 105.The purpose of all feedback calculation procedures is after management brain stimulation and corresponding cognitive stimulation, possible improvement according to function, structure or the corresponding cognitive stimulation of individuality, monitor constantly and regulate that (for example: the threshold values up to the Pathophysiology disease of determining is exceeded based on the brain of individuality and corresponding cognitive stimulation parameter, the clinical improvements that its indication is individual, perhaps selectively, improve threshold values up to the cognition of determining and be exceeded, the raising of the specific knowledge function that its indication is individual).

In the assembly of Fig. 1 (that is: neural diagnostic module 101, region of interest computing module 102, brain feature calculation module 103, treatment module 104 and stimulating module 105) each can be worked individually or independently, perhaps with any possible combination with one another work.

According to an embodiment of the invention, neural diagnostic module 101 is configured to function or structure neuroimaging data are converted to effective individual function activity pattern of statistics and the effective individual configurations figure of statistics.Neural diagnostic module 101 also can be configured to the health standards that individual cognition performance data and statistics are set up are compared.

Referring now to Fig. 2, it shows the simplified block diagram of neural diagnostic module 101 of the system 200 of Fig. 1.Neural diagnostic module 101 is configured to obtain functional neurosurgery iconography data 110, structure neuroimaging data 111 and cognitive data 112, and these data are fed in the statistical computation module 114 then.As shown in Figure 2, statistical computation module 114 is configured to calculate individual function activity data 116, individual configurations Figure 118 and individual cognition feature 120.

Functional neurosurgery iconography data 110 comprise the active various neuroimagings of the different brain area during concrete individual execution specific knowledge or behavior task and measure.Another possible measurement of functional neurosurgery iconography data 110 comprises that the neuroimaging when concrete individual rest measures.These data can obtain by using various technology, these technology especially comprise nuclear magnetic resonance (MRI), Functional MRI ((fMRI), positron emission computerized tomography (PET), single photon emission computed tomography (SPECT), electroencephalogram (EEG) and event related potential (ERP).

Structure neuroimaging data 110 comprise the various neuroimagings measurements of individual all brain structures.The unrestricted embodiment of structure chart is MRJ (although, as previously mentioned, also can the generating structure image as miscellaneous equipments such as PET and SPECT).

Cognitive data 112 are included in the interior measurement that the cognitive performance of individuality is carried out of broad range of possibility cognition or performance testing, except that other, can be including, but not limited to the measurement of response time, precision, attention, memory, study, execution function, language, intelligence, individual character tolerance, emotion and self-respect.Cognitive data can be passed through computer, paper and pencil, interview, operational testing or implement other form acquisition of cognition or performance testing.Cognitive data can be obtained via oral, written, vision that is transfused to computer in every way or tactile reaction.

As shown in Figure 2, functional neurosurgery iconography data 110, structure neuroimaging data 111 and cognitive data 112 are transfused to statistical computation module 114, statistical computation module 112 compares each standard set up with statistics in the data of these types, thereby determines individual function activity data 116, individual configurations Figure 118 and individual cognition feature 120.The various software for calculation that are used to carry out those calculating and analysis are obtainable, for example, except that other, ICA, SPM and AutoROI.

According to the analysis that 114 pairs of individual function patterns of statistical computation module are set up standard with respect to statistics, individual function activity data 116 provides unique brain activity pattern of the individual standard of setting up with respect to statistics during when carrying out concrete cognition or behavior task or in rest.

Similarly, according to the analysis that 114 pairs of individual configurations brain images of statistical computation module are set up standard with respect to statistics, individual configurations Figure 118 provides individual unique all brain structures.

According to the analysis that 114 pairs of individual cognition performances of statistical computation module settle the standard with respect to statistics, individual cognition feature 120 comprises individual unique cognitive competence, technical ability or function.

Neural diagnostic module 101 can be constituted together or independently constitute or be constituted with combination in any by functional neurosurgery iconography data 110, structure neuroimaging data 111 and cognitive data 112.Yet statistical computation module 114 is the parts with the neural diagnostic module 101 of combination in any formation.

The restriction that may make up that puts on these assemblies is: if functional neurosurgery iconography data 110 are present in the individuality in essence, individual function activity data 116 must exist so; Be present in essence in the individuality as fruit structure neuroimaging data 111, individual configurations Figure 118 must exist so; And if perception data 112 is present in the individuality individual cognition feature 120 necessary existence so in essence.

Referring now to Fig. 3, it is the reduced graph of region of interest computing module 102 of the system 200 of Fig. 1.Region of interest computing module 102 is configured to discern disease specific and concrete individual physiopathologic brain area.Selectively, region of interest computing module 102 is configured to discern specific function or structure brain site or corresponding cognitive characteristics, and they are different with the respective attributes of specifying ordinary person's statistical standard of fabulous or raising function in specific knowledge technical ability that is associated with specific brain area or function.

Coming from the input of individual function activity data 116, individual configurations Figure 118 and individual cognition feature 120 of Fig. 2 and function, structure, cognitive normal data 121 is departed from by the standard brain area and analyzes 122 and receive, it determines that departing from appears in which brain area and the health standards of setting up about the statistics of functional activity pattern, structure or corresponding cognitive function level, and is output as region of interest data 124.Selectively, the standard brain area depart from analyze 122 be configured to determine which brain area show with about functional activity pattern, all brain structures and specific fabulous or improve the standard that the cognitive characteristics statistics of cognition or behavioral performance sets up and occur departing from, it is output as region of interest data 124.

In three individual functional activity data 116, individual configurations Figure 118 and the individual cognition features 120 each can be worked individually or independently, perhaps with other two modules possible work in combination arbitrarily.Yet, in these three modules at least one must normal data 121 accompaniment functions, structure, cognitive and the standard brain area depart from and analyze 122, (it is specific function, structure or corresponding cognitive brain area to calculate and to export region of interest data 124, there is deviation value in these zones with respect to being distributed in of normal population on the statistics, perhaps, alternatively, there is deviation value in these zones with respect to being distributed in of raising cognitive function of function, structure or cognitive function level on the statistics).

According to an embodiment of the invention, the standard brain area departs from analysis 122 and depends on statistical computation, (it is when carrying out specific knowledge or behavior task or rest for the health standards that individual function activity pattern and statistics are set up in this statistical computation, can be depending on the active known standard of normal brain, perhaps it can be depending on one group of statistical of normally mating the functional activity pattern of large sample enough in the contrast individual and execution specific knowledge behavior task) compare.The health standards that individual function activity pattern, all brain structures or cognitive performance and statistics are set up relatively depend on individual cognition performance number (individual element, perhaps zone one by one, function and structure or specific brain area) with the normal healthy controls group of normal distribution or crowd's analog value between statistics contrast.

In this area as everyone knows, the purpose of any one in the various statistic processess is to determine that individual function, structure or cognitive value (being resolved by cell, zone, all brain structures, leaf or hemisphere level) belong to the probability of the normal distribution of corresponding function, structure or cognitive value in the normal control.The means of different confidence intervals, the threshold value of clinical meaning and minimizing error rate etc. can be used to determine those region of interest that are different from matched group in the individuality.

According to another implementation of the invention, the standard brain area departs from analysis 122 and can be depending on statistical computation, the standard that fabulous in individual function activity pattern and the super average individuality or the specific knowledge that improves or behavioral function statistics are set up in statistical computation compares, and perhaps is used for following raising corresponding to the brain stimulation in the zone of specific knowledge function or improve cognitive training to identical specific knowledge function or technical ability.The comparison that individual function activity pattern, all brain structures or cognitive performance and the statistics that shows function, structure or the cognitive performance of the individuality of fabulous cognitive performance in particular task or technical ability are set up standard, depend on individual individual element or one by one the statistics of zone, function and structure or cognitive performance number and normal distribution normal healthy controls group or crowd's analog value contrast.In this area as everyone knows, the purpose of any one in the various statistic processess is that to determine that individual function, structure or cognitive value (being resolved by cell, zone, all brain structures, leaf or hemisphere level) belong to individual normal control fabulous or improve the probability of (normal state) distribution of corresponding function, structure or the cognitive value of cognitive function in particular task or technical ability, cognition training to specific function perhaps as described below is perhaps by stimulating corresponding brain area to improve cognitive function.

The standard brain area departs from analyzes 122 output region of interest data 124, departs from the function of statistics foundation or ad hoc structure brain site, function brain area and the cognitive characteristics of structure brain standard that is:.Selectively, the standard brain area departs from analyzes 122 output region of interest data 124, its can comprise with for specific fabulous or improve the standard of cognitive performance and add up the function or different ad hoc structure brain site, function brain area and the cognitive characteristicss of structure brain standard of foundation.

Exist at individuality under the situation of risk of abnormal function, structure or corresponding cognitive performance abnormity that development (or having had) is associated with Alzheimer's disease, several examples of possible region of interest data 124 are as follows: unusual shortage activation left volume, left front volume, Bu Luoka, Wei Nike, Hippocampus and relevant area, anterior cingutate and motion, inboard temporal convolution, gyrus (anthreonal gyrus), cerebellum, and the function between some or all of these zones connects weakening of measure.Textural anomaly also can comprise the minimizing that these structural volume between these nervus centralis zones or optical fiber connect.Under the situation of infantile autism pedigree obstacle (ASD), textural anomaly is by the movable proof of reversing function, promptly, ASD child (and adult) substitutes left hemisphere LH language area activity pattern with respect to normal coupling contrast by right hemisphere RH, the overacfivity in the Broca's area territory of LH, wernicke's area territory for example, but non-ASD with respect to coupling to the overacfivity in these offside zones that impinge upon RH.For " theory of mind " ASD of social cognition shortcoming, the functional activity of tonsil, fusiform gyrus go down and cerebral hemisphere between connect the dysfunction of measuring and can take place.In addition, when rest or under the situation of language paradigm, the ASD individuality can take place with respect to the common RH dysfunction of the contrast that can be expressed as the common RH overacfivity in the theory of mind.

Referring now to Fig. 4, it has described the brain feature calculation module 103 of the system 200 of Fig. 1.Brain feature calculation module 103 is configured to judge whether the region of interest data of being discerned 124 represent the individual probability that tormented by concrete function, structure or the corresponding cognitive impairment relevant with concrete brain diseases.Selectively, the brain feature calculation module 103 of Fig. 1 is configured to judge whether the region of interest data of being discerned 124 represent the individual probability that always is lower than function raising or fabulous, structure or corresponding cognitive mission performance standard (for example, according to function, structure or cognitive value with respect to the analog value in the example of the individuality with fabulous function).

(it is that functional activity, structure or corresponding cognitive performance have been determined to be in statistics upward is different from matched group in individuality those brain area to region of interest data 124, perhaps selectively, improve the example of performance with respect to cognition) be transfused to brain feature threshold values and calculate 126.Brain feature threshold values calculates 126 and determines to have the functional activity that is different from disease specific statistics threshold values or those region of interest data 124 of architectural characteristic or corresponding perceptual performance value, because individuality has disease specific during in when test or expectedly at different time points, so these disease specifics statistics threshold values have high predictive value.Selectively, region of interest data 124 are output to brain feature threshold values calculating 126, it judges whether these region of interest data 124 have such functional activity or structured value, that is, function or structure threshold values that the statistics of itself and specific raising cognitive function is determined are identical or different.

Calculate 126 at brain feature threshold values and determine that region of interest (ROI) data 124 equal or exceed under the situation of the function of the specific region that is confirmed as describing specified disease or structure threshold values, it will export ROI threshold values data 128 and brain diseases data 129.For those features are the specific and function brain diseases associated, structure or the corresponding awareness energy threshold values that are lower than normal control crowd's statistical computation value, if individual region of interest data 124 are lower than above-mentioned disease specific threshold values, brain feature threshold values calculates 126 and will export ROI threshold values data 128 so, and it is made of brain diseases data 129 specified specific region of interest data 124 with the low valve valve district brain diseases associated all.Detect the important individual function of statistics in brain feature threshold values calculating 126, under those situations of structure or corresponding cognitive performance number, be that it exceeds the disease specific threshold values, perhaps selectively, in function, structure or corresponding cognitive function value have been determined to be in that it is lower than the disease specific threshold values under those situations that are lower than normal control on the statistics, brain feature threshold values calculates 126 also will export brain diseases data 129, and which type of these super threshold values specific and brain diseases associated and particular individual (or above-mentioned low valve valve) has been described, function, structure or corresponding cognitive performance number are related reliably on statistics.

Also do not exceed under the situation of disease specific threshold values (perhaps statistical value and the individual ROI threshold values data 128 that are lower than normal population at the disease specific threshold values are higher than under the situation of these disease specific threshold values) at function, structure or the corresponding cognitive performance number of individuality, brain feature threshold values calculates 126 will export no difference data 130 (for example: it is indicated in individuality and does not have the function different with ordinary person's statistical distribution, structure or cognitive pattern).In this case, no difference data 130 is initiated stopped treatments and the normal result 131 of report, and it stops diagnostic phases of the present invention by the mode of informing individuality or treatment doctor and should individuality can not suffer any and brain diseases associated and therefore need not to treat.

Calculate 126 at brain treatment threshold values and determine that region of interest data 124 equal or exceed under the situation of the threshold values that is determined to be in the function that shows the specific region of improving performance or function in specific knowledge task or the technical ability or structured value, it will export ROI threshold values data 128 and brain diseases data 129.For with the specific raising cognitive skill that shows as the statistical computation value that always is lower than the normal control crowd or those functions or structured value that function is associated, if individual region of interest data 124 are lower than above-mentioned cognition and carry super threshold values, brain feature threshold values calculates 126 and will export ROI threshold values data 128 so, and its all region of interest data 124 by the low valve valve zone constitute.Calculating 126 at brain feature threshold values detects under the situation of important individual function of such statistics or structured value, be that it exceeds cognition and carries super threshold values, perhaps selectively, when function or structured value have been determined to be in those that are lower than normal control on the statistics, it is lower than cognition and carries super threshold values, brain feature threshold values calculates 126 also will export brain diseases data 129, and it has illustrated which type of specific knowledge sharpens one's skills or function is related reliably on statistics with super threshold values (low valve valve as mentioned above), function, structure or the corresponding cognitive performance number of specified individual.

Calculate at brain feature threshold values under the situation of 126 output ROI threshold values data 128 and brain diseases data 129, ROI threshold values data 128 comprise the identification to all such pixels or cell or zone or hemisphere brain area, promptly, their functions in individuality, structure or corresponding cognitive performance level are calculated as and exceed individual disease specific threshold values or be lower than disease specific threshold values (as implied above), and ROI threshold values data 128 also comprise in these pixels or cell or zone or the hemisphere site each precise function or structure or cognitive value with respect to the indication of their corresponding disease specific threshold values.Calculate at brain feature threshold values under those situations of 126 output ROI threshold values data 128 and brain diseases data 129, and wherein ROI threshold values data 128 comprise individual function, structure or corresponding cognitive performance level have been calculated all pixels of the raising cognitive function level that is lower than specific knowledge task or function (perhaps being lower than the cognitive threshold values of above-mentioned specific raising) or the identification of cell or zone or hemisphere brain area, and ROI threshold values data 128 are also pointed out the pixel discerned, the precise function at each place in cell or zone or the hemisphere site, structure or cognitive value and their corresponding statistical computation threshold values.

Also do not exceed under the situation of disease specific threshold values (perhaps statistical value and the individual ROI threshold values data 128 that are lower than normal population at the disease specific threshold values are higher than under the situation of those disease specific threshold values) at function, structure or the corresponding cognitive performance number of individuality, brain feature threshold values calculates the no difference data 130 of 126 outputs (for example: it is indicated in individuality and does not have the function different with ordinary person's statistical distribution, structure or cognitive pattern).In this case, no difference data 130 is initiated stopped treatments and the normal result 131 of report, and it stops diagnostic phases of the present invention by the mode of informing individuality or treatment doctor and should individuality can not suffer any and brain diseases associated and therefore need not to treat.

Also do not exceed under the situation of the cognitive threshold values that improves (perhaps improving threshold values in cognition is lower than the statistical value of normal population and individual ROI threshold values data 128 and is higher than under the situation that these specific knowledge improve threshold values) at the function of individuality or structured value, brain feature threshold values calculates the no difference data 130 of 126 outputs (for example, not existing in the indication individuality and cognitive different function, structure or the cognitive patterns of statistical distribution that improves function or architectural feature).In this case, no difference data 130 is initiated stopped treatments and the normal result 131 of report, and it is by informing that individuality or treatment doctor should individuality can not benefit from any cognitive mode that improves treatment and stop diagnostic phases of the present invention.

Calculate the statistical that 126 calculating of carrying out are based on the statistical distribution of function corresponding, structure or cognitive performance in individual function activity, all brain structures or cognitive performance and specific and the brain diseases associated by brain treatment threshold values.Selectively, calculating 126 calculating of carrying out by brain feature threshold values can be based on the statistical of the statistical distribution of corresponding function, structure or the cognitive performance of individual function activity, all brain structures or cognitive performance and specific raising cognitive skill or function.These statistical are that perhaps selectively, the individual element of its corresponding statistical standard of specific raising cognitive function, cell, zone or hemisphere relatively constitute by the region of interest data 124 of individuality and disease specific.These statistical standard of normal function, structure or corresponding cognitive performance can obtain by integration analysis (or other statistic processes), this analysis is used for scientifically the data of announcing is averaged, thereby to different pixels, cell, zone or hemisphere level place and run through disease specific and function, structure or corresponding cognitive performance level that the specific auxiliary phenotype of this disease specific or the different images in stage are learned normal form are carried out quantitatively.

Selectively, these statistical computation standards of normal brain function, structure and corresponding cognitive performance can obtain with the abundant sample of the patient's who suffers from disease specific comparison by ordinary person, ensuing statistical method is used to that normal control is distributed and patient's relatively standardization, and this will cause the calculating to the concrete statistics threshold values of each pixel, cell, zone or hemisphere--in individuality, be higher or lower than auxiliary phenotype or stage that this value may be represented disease specific, specified disease.Selectively, these statistical computation standards of normal brain function, structure and corresponding cognitive performance can relatively obtain with individuality at the raising cognitive skill function of concrete technical ability by abundant ordinary person, ensuing statistical method is used to make the normal control and the distribution of the individuality that improves cognitive performance to standardize, and this will cause the calculating to the concrete statistics threshold values of each pixel, cell, zone or hemisphere--and in individuality, be higher or lower than this value and may represent specifically to improve cognitive performance or technical ability.In addition, to the change of significant levels, confidence interval, power of test, sphere of action or other statistical measurement can allow people obtain to be used to distinguish with brain diseases associated and normal control value between different statistics (prediction) threshold values, described statistical measurement is used for according to specific ill crowd and normal control crowd are sampled so that the difference between them is carried out quantitatively.

Brain feature threshold values calculates 126 pairs of such statistics threshold values and determines to depend on to the analysis normal and comparison that disease sample distributes, function wherein, structure or corresponding cognitive performance level are higher or lower than this statistics threshold values may represent specific brain diseases, auxiliary phenotype or disease stage are (promptly, shown for specific pixel at statistical analysis, cell, zone or hemisphere, normal sample has produced under the situation than higher function of disease sample statistical reliability or structured value, and brain feature threshold values calculates 126 these specific pixel that will determine to be lower than in the individuality calculating threshold values of normal population, cell, the value of zone hemisphere etc. will be marked the disease zone with specified disease).Therefore, for example, statistical analysis has shown that normal sample has produced than autism sample higher function or structured value of reliability on statistics at Bu Luoka and the wernicke's area of LH.Therefore, brain feature threshold values calculates 126 individualities that will determine to show functional activity, structural volume or the cognitive value of those specific brain area of the calculating threshold values that is lower than corresponding normal population and will be noted as autistic disease zone in this particular individual.Similarly, statistical analysis has shown that for connection or facial recognition or cerebellum or cingulum value between Hippocampus, temporo structure, forehead and the back volume normal sample has produced than Alzheimer's disease or the moonstruck or aging sample of the MCI functional activity that reliability is higher on statistics, structural volume or cognitive value.Therefore, brain feature threshold values calculates the 126 disease zones that will determine will be noted as at the individuality that specific brain area shows function, structure or the cognitive value of the calculating threshold values that is lower than corresponding normal population value Alzheimer's disease or MCI or ageing disorders.

On the contrary, shown for the normal sample of specific pixel, cell, zone or hemisphere at those statistical analysiss to have produced under the situation of function lower or structured value that brain feature threshold values calculates 126 and will determine will be marked the disease zone with specified disease for the value that is higher than the calculating threshold values of normal population value in the individualities such as this specific pixel, cell, regional hemisphere than disease sample statistical reliability.Therefore, for example, statistical analysis has shown that normal sample has produced than autistic children belong lower function or structured value of reliability on statistics at offside Bu Luoka or the wernicke's area of RH.Therefore, brain feature threshold values calculates the disease zone that 126 values that will determine to be higher than in the individuality offside Bu Luoka of RH of corresponding calculating threshold values of normal population or wernicke's area will be marked infantile autism pedigree obstacle.

Similarly, calculate the individual threshold values that improves function, structure or the analog value of cognitive performance when the particular task of indication in order to make brain feature threshold values calculate 126, normal sample or crowd and raising sample or crowd's statistical will and be performed at individual element, cell, zone or hemisphere function, structure or corresponding cognitive measurement.Shown for specific pixel, cell, zone or hemisphere at those statistical analysiss, improve sample and produced under the situation than higher function of normal sample or crowd's statistical reliability or structured value, brain feature threshold values calculates 126 and will determine will be confirmed as auxiliary raising function, structure or the corresponding cognitive performance level of indicating these cells, zone or hemispherical area to represent this particular individual for these values that specific pixel, cell, zone or hemisphere etc. in the individuality are lower than the calculating threshold values of raising crowd or sample.Therefore, the excitement of the auxiliary raising brain area of these identifications in the individuality is stimulated to improve their corresponding cognitive performances.

On the contrary, shown for specific pixel, cell, zone or hemisphere at those statistical analysiss, improve sample and produced than normal sample or crowd under the situation of lower function of statistical reliability or structured value, brain feature threshold values calculates 126 will determine to be higher than in the individuality of auxiliary raising function, structure or the corresponding cognitive level to(for) the individuality of specific knowledge feature, performance or technical ability of indicating that improves sample or crowd's threshold values.Therefore, the inhibition of the auxiliary raising brain area of these identifications in the individuality is stimulated to improve their corresponding cognitive performances.

Brain feature threshold values calculating 126 judges that it is " identical " or " different " that individual function, structure or the corresponding cognitive performance level of specified individual are added up with respect to the analog value of normal population.In case calculating 126, brain feature threshold values determined that specific region of interest data 124 exceed disease specific statistics threshold values really, perhaps selectively, be lower than specific raising function threshold values, its exports brain characteristic 127 so, these data are indicated which brain area function, textural anomaly, perhaps related according to the cognitive performance of specific weakening, perhaps selectively, thereby which brain area is these data indicate to be improved specific knowledge function or technical ability by nerve stimulation or cognitive stimulation.

Brain feature threshold values calculates 126 and also exports brain threshold values data 128, it comprises individual element, cell, brain area or hemisphere value and awareness energy threshold values, this awareness can threshold values be the awareness energy threshold values of normal brain function, perhaps selectively, this awareness energy threshold values is for raising and as significant levels, the brain function that those calculating threshold values such as confidence interval are associated and the awareness energy threshold values of various statistical indicators, perhaps this awareness can threshold values be to improve region of interest data 124 functions, structure or cognitive value and the normal statistics of brain function are set up the awareness energy threshold values of any other statistical measurement that the statistics difference between the threshold values assesses.On the other hand, if calculating, brain feature threshold values determines that all region of interest data 124 do not exceed disease specific statistics threshold values, perhaps, selectively, be not lower than specific raising awareness energy threshold values, brain feature threshold values calculates the no difference data 129 of 126 outputs so, it enters stopped treatment and the normal result 130 of report (it stops the operation of Medical Equipment and informs the patient or doctor's individuality is to suffer from significantly normally and not and the brain diseases associated then, perhaps selectively, carry out the specific knowledge task admirably, and therefore can not benefit from brain and the cognitive stimulation that is used to improve specific knowledge technical ability).

Referring now to Fig. 5, it shows the treatment module 104 of the system 200 of Fig. 1.Treatment module 104 is configured to determine to have specifically and accurate brain stimulation, cognitive stimulation and the neuro-cognitive stimulus parameter of the individuality of brain diseases associated.Selectively, treatment module 104 can be determined accurate brain stimulation, cognitive stimulation and the neuro-cognitive stimulus parameter of normal individual, to improve the specific knowledge function.

Treatment module 104 comprises ROI threshold values data 128 and the brain diseases data 129 of Fig. 4, they are transfused to feature threshold values recuspine and swash calculating 132, it comprises that brain stimulation analyser 133, cognitive stimulation analyser 134 and neuro-cognitive stimulate analyser 136, and they produce corresponding brain stimulation data 138, cognitive stimulation data 140 and neuro-cognitive stimulus data 140 successively.

Feature threshold values recuspine swash to calculate 132 and is configured to compare being higher or lower than the disease specific threshold values or being higher or lower than function, structure or the cognitive performance level and the brain diseases data 129 that improve the ROI threshold values data 128 that cognitive function level and their function corresponding, structure or corresponding awareness can threshold values in the individuality, with definite best brain, cognition or neuro-cognitive stimulus parameter.

The key that instructs feature threshold values recuspine to swash the function of calculating 132 is calculated principle, suffer function, structure or corresponding cognitive performance level specific and the individuality brain diseases associated in order to improve, perhaps selectively, for function, structure or the corresponding cognitive performance level that improves normal individual, must be according to respect to the contrary excited of the super threshold values of specified individual or low valve valve threshold level or suppress direction of stimulation, ROI threshold values data 128 zones of specific identification are stimulated.In this way, be lower than in individual function, structure or corresponding cognitive performance level under those situations of threshold values of corresponding normal function, structure or cognitive performance, feature threshold values recuspine swashs and calculates 132 and will calculate the brain or the cognitive stimulation of common excitement.For example, shown as in those individual function, structure or corresponding cognitive performance level under the situation of hypopraxia (or unusual little structural volume) of the infantile autism pedigree obstacle of the Bu Luoka of the LH that belongs to the threshold values that is lower than corresponding normal function, structure or cognitive performance and Wei Nike language area or tonsil or fusiform gyrus, feature threshold values recuspine swashs and calculates 132 cognitive stimulations that will calculate common excited brain or these brain area.Similarly, shown as under the situation that belongs to Alzheimer's disease, aging, dementia or MCI in those individual function, structure or corresponding cognitive performance level, these diseases are that the infringement that connects between the hypopraxia (perhaps unusual little structural volume) by Hippocampus, inboard temporo structure, forehead and the back volume or facial recognition district or cerebellum or cingulum function or structure are detected, and feature threshold values recuspine swashs and calculates 132 cognitive stimulations that will calculate common excited brain or these brain area.

On the contrary, be higher than under the situation of corresponding normal function, structure or corresponding cognitive performance level in individual function, structure or corresponding cognitive performance level, feature threshold values recuspine swashs calculating 132 will calculate common inhibition brain or cognitive stimulation.For example, shown as in individual function, structure or corresponding cognitive performance level under the situation of infantile autism pedigree obstacle of the hypopraxia (or unusual little structural volume) that belongs to the offside Bu Luoka that is characterized as RH and wernicke's area territory, feature threshold values recuspine swashs and calculates 132 cognitive stimulations that will calculate common excited brain or these brain area.

Identical feature threshold values recuspine swashs principle and also is applied to the sharp calculating 132 of feature threshold values recuspine to be used for cognitive the raising.Particularly, be lower than under the situation that the awareness of raising can threshold values in those individual function, structure or corresponding cognitive performance level, feature threshold values recuspine swashs and calculates 132 and will calculate common stimulation brain or cognitive stimulation.On the contrary, be higher than in individual function, structure or corresponding cognitive performance level under the situation of cognitive raising threshold values, feature threshold values recuspine swashs calculating 132 will calculate common inhibition brain or cognitive stimulation.

The function, structure or the cognitive performance that are higher than corresponding raising in those individual function, structure or corresponding cognitive performance level are (promptly, for example opposite with taking in sail of the specific brain area that has the individuality that improves cognitive performance in certain skills or function aspects, under the situation of the threshold values overacfivity of certain brain area that is associated with normal cognitive performance), feature threshold values recuspine swashs calculating 132 will calculate common inhibition brain or cognitive stimulation.Therefore, feature threshold values recuspine swashs principle and also is applied to the sharp calculating 132 of feature threshold values recuspine, to be used for cognitive the raising, that is to say: be lower than under the situation that the awareness of raising can threshold values in individual function, structure or corresponding cognitive performance level, feature threshold values recuspine swashs and calculates 132 and will calculate common excited brain or cognitive stimulation.On the contrary, be higher than in individual function, structure or corresponding cognitive performance level under the situation of cognitive raising threshold values, feature threshold values recuspine swashs calculating 132 will calculate common inhibition brain or cognitive stimulation.

Particularly, brain stimulation analyser 133 compares being higher or lower than the disease specific threshold values in the specified individual or being higher or lower than ROI threshold values data 128 functional levels and their the function corresponding threshold values that specific knowledge improves threshold values, and consider that simultaneously specific the and brain diseases associated of brain diseases data 129 or specific knowledge improve purpose, to determine the best brain stimulation parameter of specified individual.For example, be lower than under the situation of normal threshold values in some ROI threshold values data 128 zone in individual function or structure movement parameter, brain stimulation analyser 133 will be exported excited brain stimulation parameter.On the contrary, be higher than under the situation of normal threshold values in some ROI threshold values data 128 zone in individual function or structure movement parameter, brain stimulation analyser 133 will be exported and suppress brain stimulation data 138 parameters.

Similarly, cognitive stimulation analyser 134 compares being higher or lower than the disease specific threshold values in the specified individual or being higher or lower than ROI threshold values data 128 levels and their the corresponding cognitive threshold values that specific knowledge improves threshold values, and consider that simultaneously specific the and brain diseases associated of brain diseases data 129 or specific knowledge improve purpose, to determine the best cognitive stimulation parameter of specified individual.For example, the individual cognition performance level is lower than under the situation of normal threshold values in particular task or function, and brain stimulation analyser 133 will be exported excited cognitive stimulation parameter.On the contrary; individual cognition performance level in the specific knowledge function is higher than under the situation of normal threshold values; brain stimulation analyser 133 will be exported and suppress cognitive stimulation data 142 parameters (that is: attempt directly or by training or stimulate it opposite or express or mode of other cognitive function suppresses unusually the cognitive stimulation normal form or the training method of (or auxiliary raising) cognitive function, it suppresses effectively or weakens specific exceptions or assist the raising cognitive function).

Similarly, neuro-cognitive stimulates analyser 136 to compare being higher or lower than the disease specific threshold values in the specified individual or being higher or lower than ROI threshold values data 128 functions, structure or corresponding cognitive performance level and their the function corresponding threshold values that specific knowledge improves threshold values, consider that simultaneously specific and the brain diseases data 129 brain diseases associated or specific knowledge improve purpose, to determine the best brain stimulation parameter of specified individual.Yet, stimulate at neuro-cognitive under the situation of analyser 136, calculating is (for example to be used to discern best neuro-cognitive stimulus parameter, according to stimulate concrete brain area (or a plurality of zone) in mode excitement or that suppress and in mode excitement or that suppress to the concordance between the corresponding cognitive stimulation in identical brain area (or a plurality of zone), interim overlapping between neural brain stimulation between the identical or different brain area and the cognitive stimulation or separate, etc.).Therefore, be higher or lower than the indication of disease specific or the cognitive specific brain area (or a plurality of zone) that improves threshold values and to the indication of brain diseases data 129 diseases under those super threshold values or the low valve valve individual level, neuro-cognitive stimulates analyser 136 to calculate above-mentioned best neuro-cognitive stimulus parameter according to 128 pairs of ROI threshold values data.

Concrete intensity, persistent period, site, interval and other parameter of the brain stimulation of calculating by brain stimulation analyser 133 be based on that the input that comes from brain diseases data 129 and above-mentioned feature threshold values recuspine swash that principle is determined (that is: under individual ROI threshold values data 128 functions or structure level and brain diseases data 129 disease threshold values or cognition raising threshold values differ bigger situation, inhibition or excited stimulus parameter will have more high strength, persistent period, a plurality of brains site etc., and vice versa).

In order to improve various cognitive functions or technical ability, corresponding brain area should excitedly be stimulated, that is, be used to remember or learn Hippocampus or the temporal lobe or the cingule gyrus of raising, be used to carry out function, be absorbed in, the frontal cortex or the prefrontal lobe cortex of study and intelligence, the motor cortex or the cerebellum that are used for motor function and coordination, be used to improve the visual cortex of visual performance, has or do not have the inhibition tonsil that reduces fear and worry under the excited situation about stimulating of left frontal lobe or left front frontal lobe, improve sense of personal worth or mood or happiness--left front frontal lobe or left frontal lobe are carried out the excitement stimulation or right front frontal lobe gyrus is suppressed stimulation.In all these examples, corresponding cognitive stimulation can be employed, for example, and its improvement or improved ill brain or cognitive function or improved the cognitive function of expectation.

Illustrative embodiments of the present invention comprises the specific and experimental ROI threshold values data 128 brain diseases associated for the treatment of module 104, for example brain diseases data 129 of Alzheimer's disease and ASD etc.Particularly, under the situation of Alzheimer's disease, ROI threshold values data 128 are hoped to comprise any one or their combination in any in these zones, wherein: the unusual shortage activity of left frontal lobe, left front frontal lobe, cloth network card, Wei Nike, Hippocampus and relevant range, anterior cingutate and motion, inboard temporal convolution, gyrus, cerebellum etc., and these zones partly or entirely between function connect to measure and descend.Because reducing of these structural volume between these neurological region or connection fiber, textural anomaly also can exist.

Under the situation of infantile autism pedigree obstacle (ASD), ROI threshold values data 128 are hoped to comprise any one or their combination in any in these zones, wherein: ASD child (and adult) with respect to normal coupling contrast by right hemisphere RH substitute left hemisphere LH language area activity pattern the reverse function activity (for example: the Broca's area territory of LH, the overacfivity in wernicke's area territory, but non-ASD with respect to coupling to the hypopraxia in these offside zones that impinge upon RH).For " theory of mind " ASD of social cognition shortcoming, connecting the dysfunction of measuring between the function overacfivity of tonsil, fusiform gyrus and the cerebral hemisphere can take place.In addition, when rest or under the situation of language paradigm, the ASD individuality can take place with respect to the common RH dysfunction of the contrast that can be expressed as the common RH overacfivity in the theory of mind.

Therefore, exemplary and the only illustrative embodiment of system of the present invention comprises brain stimulation data 138 or cognitive stimulation data 142 or neuro-cognitive stimulus data 140, it is that the excitement of left frontal lobe or left front frontal lobe or cloth network card or Wei Nike or Hippocampus and relevant range or anterior cingutate or motion or inboard temporal convolution or gyrus or cerebellum etc. is stimulated, perhaps these zones partly or entirely between function connect or these zones in the stimulation of combination in any--under the situation of Alzheimer's disease.Similarly, the mild cognitive functional lesion can carry out similar stimulation to some or all in these brain area than mild case (or the hypomnesis or the dementia relevant with the age of other form) arbitrarily.Under the situation of ASD, the illustrative embodiments of system of the present invention can comprise brain stimulation data 138 or cognitive stimulation data 140 or neuro-cognitive stimulus data 140, it stimulates for the excitement that the combination of any one or they in the following zone is carried out, that is: Broca's area or wernicke's area or tonsil or fusiformis are returned or striden hemisphere and connect.In addition, ASD can need brain stimulation data 138 or cognitive stimulation data 140 or neuro-cognitive stimulus data 140, and it is that the inhibition in the RH zone of offside Bu Luoka or Wei Nike stimulates or the common inhibition of RH is stimulated.

In order to improve various cognitive functions or technical ability, corresponding brain area should excitedly be stimulated, that is, be used to remember or learn Hippocampus or the temporal lobe or the cingule gyrus of raising, be used to carry out function, be absorbed in, the frontal cortex or the prefrontal lobe cortex of study and intelligence, the motor cortex or the cerebellum that are used for motor function and coordination, be used to improve the visual cortex of visual performance, has or do not have the inhibition tonsil that reduces fear and worry under the excited situation about stimulating of left frontal lobe or left front frontal lobe, improve sense of personal worth or mood or happiness--left front frontal lobe or left frontal lobe are carried out the excitement stimulation or right front frontal lobe gyrus is suppressed stimulation.Under all these situations, corresponding cognitive stimulation can be employed (the stimulation that for example, has improved or improved ill brain or cognitive function or improved the cognitive function of expectation.)

The importance of feature threshold stimulus calculating 132 is disease specific or the cognitive principle that improves the calculating of specificity neural plasticity, and it is the basis that is stimulated the calculating of analyser 136 execution by neuro-cognitive.This principle has embodied the adaptability that various neuro-cognitive stimulus parameters and concrete brain diseases or specific knowledge improve agreement based on the concrete neural plasticity Feature Recognition to being associated with these specific brain diseasess and cognitive raising agreement.Therefore, neuro-cognitive stimulates analyser 136 to consider the brain diseases or the cognitive purpose that improves of the particular individual of concrete brain diseases data 129, and based on combining of this information and the known neural plasticity information that relates to ROI threshold values data 128 and brain diseases data 129, ROI threshold values data 128 are determined best neuro-cognitive stimulus datas 140.

For example, except that other, the neural plasticity stimulus parameter can comprise following following: the intensity of brain and corresponding cognitive stimulation, they persistent period, zero-time and termination time, temporarily overlap or separates, the order and the combination of possible brain stimulation site and corresponding cognitive stimulation thereof.These parameters all can be based on stimulating neural diagnostic module 100 in back and region of interest computing module 102 and brain feature calculation module 103 and treatment module 105 to be dynamically altered or regulating.

It is the loss of memory or other MCI that are used for the treatment of Alzheimer's disease that this neuro-cognitive stimulates an example of analyser 136, dull-witted, the calculating that the best neural plasticity of memory loss disease or hypermnesia disease stimulates, it can comprise: the 10-20Hz TMS to the excitement of Hippocampus or other volume temporal lobe zone or frontal lobe zone or prefrontal lobe zone or cingule gyrus stimulates with possible arbitrarily combination, it will with memory raising or coding or recovery or memory or cognition or memory or consciousness or audition or semantic memory improves cognitive training or stimulating method is synchronous, (for example: based on to best neural plasticity CALCULATION OF PARAMETERS, it allows the great majority relevant with these specific ROI threshold values data 128 and brain diseases data 129 to learn to obtain improving the relevant potential change of best neural plasticity with memory, coded memory recovers or forms).

The definite of best neural plasticity parameter who stimulates analyser 136 pairs of specific ROI threshold values data 128 and brain diseases data 129 to make by neuro-cognitive can find obtain according to prior art, and these prior aries find to relate to the random specific combination of ROI threshold values data 128 and brain diseases data 129.Selectively, it can be calculated according to dynamical feedback loop, stimulation of the present invention back, and this dynamical feedback loop, stimulation back has neural diagnostic module 100 above-mentioned, region of interest computing module 102, brain feature calculation module 103, treatment module 105 and stimulating module 105.The feedback circuit of back calculates and can allow or by dynamic monitoring or adjusting to specified individual, perhaps by statistics meta-analysis or other statistical analysis, calculating to the neuro-cognitive stimulus data 140 of the most effective learning curve or specific ROI threshold values data 128 and 129 combinations of brain diseases data, other statistical analysis is the statistical analysis of effectiveness that is used to analyze the various neuro-cognitive stimulus parameters of specific ROI threshold values data 128 between a plurality of individualities and brain diseases data 129, and described individuality has identical ROI threshold values data 128 and 129 combinations of brain diseases data.By this mode, neuro-cognitive stimulates analyser 136 (after being embedded into and being integrated in above-mentioned stimulation in the feedback circuit time) to provide the neuro-cognitive stimulus parameter that is used for any specific ROI threshold values data 128 and 129 combinations of brain diseases data to carry out optimized automatic study potential.

Importance of the present invention is the ability that brain feature calculation module 103 provides the Differential Diagnosis statistical tool, this Differential Diagnosis statistical tool be used for examination, assessment and diagnosis individuality when test specific with the existence brain diseases associated, the reliable deviation of the importance perhaps of the present invention statistics that to be brain feature calculation module 103 distribute based on corresponding function, structure or the cognitive function of region of interest 124 and normal population or sample provides the ability of reliable prediction diagnostic tool.By this mode, brain feature calculation module 103 can be considered to independently Differential Diagnosis instrument, it is used for being subjected to the specific probability that torments with the brain diseases associated in that when test or assessment expectedly are individual always, this instrument has the predictive ability (for example: combine with neural diagnostic module 101 of the present invention, region of interest computing module 102, perhaps form fully independently Differential Diagnosis neurobehavioral instrument) of definite probability.

More particularly, because region of interest computing module 102 can comprise with arbitrarily possible combination or any one in three individual functional activity data 116, individual configurations Figure 118 and the individual cognition features and the cognitive normal data 121 of functional structure independently, therefore standard brain area variance analysis 122 can be exported region of interest data 124, its function as individuality, structure or the important deviation feature of cognitive statistics.Therefore, brain feature threshold values calculates 126 and can differentiate that the ground diagnosis is individual based on the region of interest data 124 of function, structure or cognitive deviation (independently or with possible combining arbitrarily) and be subjected to the specific probability that torments with the brain diseases related always.

Therefore, brain feature calculation module 103 can also provide the Differential Diagnosis instrument, it is used for based on independently individual function activity data 116, individual configurations Figure 118 or individual cognition feature 120 or their combination in any, in when test or expectedly at one section setting-up time in the cycle, assessment is individual to be subjected to the specific probability that torments with the brain diseases associated always.Therefore, brain feature calculation module 103 also can be used as independently or dependent neurobehavioral Differential Diagnosis instrument, they can be based on (obtaining from various cognitions or performance testing) simple cognitive data 112 or based on functional neurosurgery image 108 and structure neuroimaging data 111 widely, that examination has any existence or expection with the extensive crowd of brain diseases associated (perhaps selectively this instrument can examination has the individuality that improves the cognitive function ability), simple cognitive data 112 be analyze by statistical computation module 114 and to cause individual cognition feature 120, functional neurosurgery image 108 and structure neuroimaging data 111 also be that analyze and cause individual function activity data 116 and individual configurations Figure 118 and above-mentioned cognitive data 112 (with possible combination arbitrarily) by statistical computation module 114.

In fact, consider only obtained cognitive data 112 (yet, it can calculate by statistical computation module 114 and standard brain area variance analysis 122, thereby produce statistics important Differential Diagnosis or predictive diagnosis ability) the low cost of main examination test, this cognition or performance testing can be used as initial extensive crowd's screening instruments, and it is used to assess the existence or the probability of the development of various brain diseasess.Low-cost common examination the general population who is used for specific brain diseases is tested (it has the Differential Diagnosis or the future anticipation diagnosis capability of fair to good) afterwards, people can utilize the second level, more complicated, the expense costliness, complete neural diagnostic module 101, it has utilized individual function activity data 116, individual configurations Figure 118 and individual cognition feature 120 (perhaps arbitrarily possible combination), with the Differential Diagnosis of the specific brain diseases that obtains more accurate (having lower false positive rate).

Another importance of the present invention is the ability of brain feature calculation module 103, it provides such prediction statistical tool, promptly this instrument is used for the probability that examination, assessment and diagnosis individuality have certain skills, perhaps selectively, this instrument is used to diagnose or assesses the probability that improves individual specific knowledge function, and it is calculated that it is based on the statistical of corresponding function structure in region of interest 124 and normal population or the sample or cognitive performance profile.Brain feature calculation module 103 can be considered to so independent Differential Diagnosis instrument, promptly, it is used for when test or the individual probability that tormented by specific brain diseases of assessment expectedly, this instrument has the predictive ability of a certain probability, promptly, combine with neural diagnostic module 101 of the present invention, region of interest computing module 102, perhaps form fully independently Differential Diagnosis neurobehavioral instrument.

More particularly, consider region of interest computing module 102 be with may make up arbitrarily or independently any one in three individual functional activity data 116, individual configurations Figure 118 and the individual cognition features and the above-mentioned probability of the cognitive normal data 121 of functional structure, standard brain area variance analysis 122 can be exported region of interest data 124, and it is individual and cognitive function or structure or the important deviation feature of cognitive statistics that improves between the statistical standard.Therefore, brain feature threshold values calculates 126 and can differentiate that the ground diagnosis is individual based on the region of interest data 124 of function, structure or cognitive deviation (independently or with possible combining arbitrarily) and have a probability that improves cognitive function or selectively have auxiliary cognitive performance in certain skills.Therefore, brain feature calculation module 103 can also provide such Differential Diagnosis instrument, that is, it is based on independently or the individual function activity data 116 of combination in any, individual configurations Figure 118 or the individual probability that has auxiliary (or raising) cognitive function in certain skills of individual cognition feature 120 assessments.Therefore, brain feature calculation module 103 also can be used as independent or neurobehavioral forecast assessment statistical tool independently, they can be based on (obtaining by various cognitions or performance testing) simple cognitive data 112 or based on functional neurosurgery image 108 and structure neuroimaging data 110 are judged the individual cognitive performance capability of raising that whether has widely, simple cognitive data 112 be analyze by statistical computation module 114 and cause individual cognition feature 120, and functional neurosurgery image 108 and structure neuroimaging data 110 also are that analyze and cause individual function activity data 116 and individual configurations Figure 118 and above-mentioned cognitive data 112 (with possible combination arbitrarily) by statistical computation module 114.

In fact, consider the potential low cost of the main examination test that only obtains cognitive data 112, yet it can calculate by statistical computation module 114 and standard brain area variance analysis 122, thereby produce the important discriminating forecast assessment ability of statistics, this cognition or performance testing can be used as initial extensive crowd's screening instruments, and it is used for assessing the raising or the auxiliary cognitive function that improves of any specific technical ability.It can be such situation, promptly, in the low-cost common examination test (it has the Differential Diagnosis or the future anticipation diagnosis capability of fair to good) that is used for the general population that specific knowledge sharpens one's skills afterwards, people can utilize the second level, more complicated, the expense costliness, complete neural diagnostic module 101, it has utilized individual function activity data 116, individual configurations Figure 118 and individual cognition feature 120 (perhaps possible combination arbitrarily), to obtain Differential Diagnosis more accurate and that have the specific cognition raising feature relevant with brain of lower false positive rate.

Referring now to Fig. 6, it has at length provided the stimulating module 105 of the system 200 of Fig. 1.Stimulating module 105 is configured to stimulate the specific brain area or the corresponding cognitive stimulation of particular individual.Stimulating module 105 comprises brain stimulation data 138, cognitive stimulation data 140 and the neuro-cognitive stimulus data 140 of Fig. 5, and they are input to neuro-cognitive stimulator 144.Sequentially, neuro-cognitive stimulator 144 comprises brain stimulator 146 and cognitive stimulation device 148.Particularly, brain stimulation data 138 and neuro-cognitive stimulus data 140 are transfused to brain stimulator 146, and neuro-cognitive stimulus data 140 and cognitive stimulation data 142 are transfused to cognitive stimulation device 148.Based on brain stimulation data 138, cognitive stimulation data 140 and neuro-cognitive stimulus data 140, brain stimulator 146 and cognitive stimulation device 148 are determined individual brain area 100, it is the actual stimulation of the brain area discerned, and it comprises according to swashed inhibition or excited brain and the cognitive stimulation that calculates the 132 particular stimulation parameters of determining by feature threshold values recuspine.

The illustrative embodiments of neuro-cognitive stimulator 144 comprises integrated brain stimulator 146 and cognitive stimulation device 148, it can possible arbitrarily order, side by side or according to the interval between the corresponding cognitive stimulation in brain site and these brain sites, stimulate individuals with same brain area 100.Therefore, neuro-cognitive stimulator 144 stimulates single or multiple individual brain area 100 according to excited or inhibition brain stimulation parameter, these parameters comprise each the intensity, persistent period or at interval independently or one change that stimulates in the brain site, and each cognition " excitement " or " inhibition " that changes independently or together in these brain sites (for example stimulates, cognitive stimulation or training are provided in the brain area that is stimulated each, it is corresponding to the excited of the brain stimulation of specific site or suppress feature).For example, the stimulation 10-20Hz TMS that is intended to improve or improve the left front volume cortex of individual emotion or happiness can be coupled with expression calculating, audition or vision based on the change of " the positive thinking " of Bake or self-construction cognitive stimulation or training pattern, and the separation of any temporo is put together and had to the order that they can be possible arbitrarily also between their time started, termination time and stimulation lengths.

Similarly, the 10-20Hz of the excitement of cingule gyrus stimulates can be by with order and the length or the intensity of any temporo of the cognitive stimulation of excitement or training and put coupling, cognitive stimulation that this is excited or training can be distributed to take exercise and form by cognitive exercise of impermanent memory power or attention, the 10-20Hz of the excitement of cingule gyrus stimulate be used to improve attention or concentration degree or with combining that the 10-20Hz TMS of excitement temporo or Hippocampus stimulates, to improve or to improve the memory that lacks, to carry out function or attention or make it and strengthen.Selectively, to suffer from the schizoid right hemisphere temporo that is associated with " vision " or " audition " illusion or parietal bone suppress 1Hz TMS and stimulate and can be coupled with random order and temporo length or intensity with cognitive stimulation or training, with the probability that reduces to take place hallucination gradually (for example, by the perceptual training that improves, as the consciousness that improves in consciousness illusion pattern or other perceptual pattern hints, perhaps selectively, by improve accurate perceptual training or by consciousness stimulate or training to improve attention or attention distribution capability or to increase psychological judgement).

Selectively, shown have autistic function, structure or cognitive unusual individuality can be stimulated in this manner, promptly, Bu Luoka by 144 couples of LH of neuro-cognitive stimulator and wernicke's area territory are carried out that excited 10-20Hz TMS stimulates and Bu Luoka and the Wei Nike language area of the offside RH of unusual overacfivity (perhaps structure is amplified) are suppressed the combination that 1Hz TMS stimulates, they and cognition or behavior stimulate coupling, especially to improve language development, sound articulation, name, indication or common attention technical ability.

In another illustrative embodiments, neuro-cognitive stimulator 144 also can promote neural plasticity to change, to improve function, structure or the corresponding cognitive performance capability that joins with specific brain disease association, perhaps selectively, with by single or multiple individual brain area 100 brain sites being carried out excited brain stimulation or suppress brain stimulation and improve the specific knowledge function, described stimulation suppresses with " rightabout " or excited cognitive stimulation combines.In another embodiment, neuro-cognitive stimulator 144 can be by carrying out excited brain stimulation or suppress brain stimulation and improve the specific knowledge function to single or multiple individual brain area 100 brain sites, described stimulation is with obviously the inhibition or the excited cognitive stimulation of " rightabout " combine.

The brain stimulation of this " rightabout " and the example of cognitive stimulation can be the 1Hz TMS brain stimulation (overacfivity of ASD individuality during when it has been shown in facial recognition and social cognition's task or in non-social communication pattern or rest) of the inhibition of when rest or when carrying out the cognitive task of asocial tonsil or fusiformis being returned, and described stimulation can stimulate with the social cognition that pays close attention to tempers combine (before or after the inhibition TMS during resting state or the non-social communication task stimulates).Selectively, neuro-cognitive stimulator 144 can be when identical or different time points or interval, in identical or different brain site, respectively or by relative excitement and the contrast that suppresses stimulus parameter, activate brain stimulator 146 or cognitive stimulation device 148.

The intensity or the interval of the brain or the cognitive stimulation in single or multiple individual brain area 100 brain sites also dynamically regulated or changed to neuro-cognitive stimulator 144, perhaps swash to calculate 132 may change and the arranged side by side and corresponding cognitive stimulation of the temporo in single or multiple brain stimulation site is regulated or changed according to feature threshold values recuspine, described feature threshold values recuspine swashs and calculates 132 and measure and region of interest computing module 102 as feedback after the stimulation of neural diagnostic module 101, brain feature calculation module 103 produces with the ensuing result calculated for the treatment of module 105.

In another embodiment, neuro-cognitive stimulator 144, brain stimulator 146 and cognitive stimulation device 144 have formed single integrated medical equipment, it can make the cognitive stimulation in the brain stimulation in single or multiple individual brain area 100 brain sites and identical brain site synchronous, and this can swash by feature threshold values recuspine, and to calculate 132 output brain stimulation data 138, cognitive stimulation data 140 and neuro-cognitive stimulus data 140 controlled.Selectively, neuro-cognitive stimulator 144 can comprise at least two independently armarium: brain stimulator 146 and cognitive stimulation device 148, they are controlled by the sharp calculating 132 output brain stimulation data 138 of identical feature threshold values recuspine, cognitive stimulation data 140 and neuro-cognitive stimulus data 140.

Cognitive stimulation device 148 can have the single or multiple demonstrations as various sensing morphogenetic stimuluses such as vision, audition and senses of touch, for example, the various response forms of always being used with any possible combination, its including, but not limited to key response, have or (for example do not have the responsive feedback element, it provides about in the degree of accuracy of different time point main body response or the feedback of performance, and perhaps it provides the feedback about each stage of task on the horizon) pronunciation, written, sense of touch or vision guide response.

Brain stimulator 146 can comprise such armarium, it can be to the brain pixel of single or multiple individual brain area 100, the zone, tissue, functional neurosurgery unit or hemisphere carry out electromagnetic stimulation, electricity irritation, magnetic stimulates and/or photoelectricity stimulates and suppress to stimulate or excitement stimulates, by brain feature threshold values calculating 126 and based on the control of brain stimulation analyser 133 and the direct input of brain stimulation data 138, the brain pixel of described single or multiple individual brain area 100, the zone, tissue, functional neurosurgery unit or hemisphere are considered in function, be ill in structure or the cognition.Selectively, brain stimulator 146 can be such armarium, it can be to the brain pixel of single or multiple individual brain area 100, the zone, tissue, functional neurosurgery unit or hemisphere carry out electromagnetic stimulation, electricity irritation, magnetic stimulates, or photoelectricity stimulates, by brain feature threshold values calculating 126 and based on the control of brain stimulation analyser 133 and the direct input of brain stimulation data 138, the brain pixel of described single or multiple individual brain area 100, the zone, tissue, functional neurosurgery unit or hemisphere are being associated with specific auxiliary raising cognitive function on the function or on the structure.

In another embodiment, brain stimulator 146 can comprise such armarium, its can by with the set of at least two electricity, magnetic, electromagnetic or photoelectric source or the stimulation that may make up arbitrarily to single or multiple brain pixels, zone, tissue, functional neurosurgery unit or hemisphere carry out electromagnetic stimulation, electricity irritation, magnetic stimulates and/or photoelectricity stimulates and suppress to stimulate or excited the stimulation.These single or multiple power supplys, magnetic source, electromagnet source or photoelectric source can be placed on the top of skull, the place, arbitrfary point of scalp surface, face or cervical region, it is any opening that invasion that define widely or non-ground is arranged in head, for example: ear, nose, nasal sinuses, oral cavity, throat and eyes.In addition, each in power supply, magnetic source, electromagnet source or the photoelectric source these stimulations or that receive is controlled individually or together by neuro-cognitive stimulator 144, and more particularly, controlled by the dynamic input that comes from brain stimulation data 138.

Stimulate after 150 at the ROI neuro-cognitive, the feedback measurement is to be carried out by neural diagnostic module 101, region of interest computing module 102, brain feature calculation module 103, treatment module 104 and stimulating module 105 that Fig. 1 describes, as preceding detailed description.The inclusion of this " feedback circuit " (that is: from stimulating module 105 to neural diagnostic module 101) allows constantly to monitor after stimulation and regulate based on the stimulus parameter that improves individual disease or cognitive.It also allows to occur in the dynamic auto study at quality module 104 places, promptly, based on stimulating comparisons preceding and stimulation back ROI threshold values 128 and the ill data 129 of brain, swashing the optimization of calculating 132 pairs of specified diseases or individuality according to feature threshold values recuspine (that is to say, statistics meta-analysis or any other statistic processes, these statistic processess can be to according to the disease of concrete brain diseases data 129 or specific knowledge improves agreement and specific ROI threshold values 128 changes by brain stimulation analyser 133, ROI threshold values 128 and the relation between the brain diseases data 129 that cognitive stimulation analyser 134 or neuro-cognitive stimulate the preceding parameter of the stimulation of analyser 136 outputs and stimulate the back to measure add up assessment, with the most effective definite brain stimulation, cognitive stimulation and corresponding neuro-cognitive stimulus parameter).

Referring now to Fig. 7, it describes the brain stimulator 146 of Fig. 6 in detail.Brain stimulator 146 is configured to according to the input that comes from brain stimulation data 138 and neuro-cognitive stimulus data 140 specific single or multiple brains site be stimulated, it exports the information relevant with direction with location, site, the stimulation axle of electrode stimulating device 108 to electrode activation module 107, is used to stimulate single or multiple brains site.Conversely, the monitoring that electrode activation module 107 receives current location, axle, direction of stimulation and brain area, it is output to electrode stimulating device 108.Positioning of electrode module 106 is auxiliary electrode activation module 107 constantly, and (or other electrical stimulation apparatus or electromagnetic stimulation equipment) arbitrarily is positioned at position and axle place that the individual brain area 100 of determined single or multiple brain area are stimulated or the accurate location that is positioned at stimulation so that electrode.In case electrode stimulating device 108 is positioned in this single or multiple brains position, electrode stimulating device 108 will stimulate the individual brain area 100 of expectation, described position allows the single or multiple individual brain area 100 of expectation is stimulated, as determined by the continuous phase mutual effect between electrode activation module 107 and the positioning of electrode module 106.

The physical operations of electrode stimulating device 108 or structure can be so that it need or do not need the physically activated of electrode activation module 107 hardly, and on the contrary, it is based on, and brain stimulation data 138 are activated.The example of this embodiment comprises electrode stimulating device 108, a large amount of electromagnetism, magnetic, electricity and/or photoelectricity stimulator that it comprises a plurality of positions that are placed on the scalp top or is placed on the One's name is legion in mouth, nose, eye, the ear hole, and each is controlled by Computer signal, and described Computer signal allows their electromagnetism direction or electric direction or stimulates axle or by the rotation in the zone of each stimulation in them.In addition, electrode stimulating device 108 can be constructed to so that it sends or receive the signal of telecommunication, electromagnetic signal, magnetic signal and/or photosignal (or their combination in any) between electrode.Electrode stimulating device 108 also can comprise magnetic, electricity, electromagnetism and/or the photoelectricity stimulator that is placed on any one place in the above-mentioned position, and described stimulator is controlled by interactive computer, so it allows any single or multiple points, site and the zone of brain are converged stimulation, emission stimulation or received stimulation.

Individual brain area 100 ongoing continued stimuluses according to 146 pairs of expectations of brain stimulator, the function of brain stimulator 146 can constantly be regulated, according to depicted in figure 1 and foregoing invention identical or different individual brain area 100 are stimulated.Therefore, brain stimulator 146 can be used as such device, it is used for the treatment of the various and brain diseases associated such as Alzheimer's disease, depression, infantile autism or other disease above-mentioned etc., and perhaps brain stimulator 146 can be used as and is used to improve ordinary person's the specific knowledge function or the device of technical ability.

Referring now to Fig. 8, it has described another sketch map of the brain stimulator 146 of Fig. 6 in detail.The form of brain stimulator 146 is that the helmet or like device 300 (are schematically shown as Fig. 8, it has covered at least a portion of individual's head 301), it comprises single or multiple electrode stimulating devices 108, and they are the electricity irritation medium or the electromagnetic stimulation media that can stimulate single or multiple brain area, point, cell, leaf or hemisphere.Electrode stimulating device 108 is being controlled jointly by brain stimulation data 138 and neuro-cognitive stimulus data 142 of Fig. 7.In the single or multiple electrode stimulating devices 108 each also can be by positioning of electrode module 106 assessments adjacent or that be associated, positioning of electrode module 106 can be determined each position and their respective regions with respect to people's individual all brain structures in these electrode stimulating devices 108, and it can be by electrode stimulating device 108 in this position or stimulate the axle place to stimulate.Then, the individual brain particular location of each electrode stimulating device 108 is utilized with the concrete input of the stimulant that comes from brain stimulation data 138, and neuro-cognitive stimulus data 142 is output to positioning of electrode module 106, regulates any requirement of location, stimulation axle, direction requirement or zone, cell, leaf, hemisphere or single or multiple brain point or position to pass through electrode activation module 107.Conversely, electrode activation module 107 is sent to positioning of electrode module 106 with feedback, thereby the pinpoint continuous adjusting and the optimization of each in the permission counter electrode stimulator 108 are so that single or multiple individual brain area 100 that it can stimulate all to determine.In case each in these electrode stimulating devices 108 is determined by the positioning of electrode module 106 that it is followed, so single or multiple electrode stimulating devices 108 will begin to stimulate determined individual brain area 100 with the cognitive stimulation device 148 of Fig. 6, and described positioning of electrode module 106 will be positioned in suitable position based on corresponding brain stimulation data 138 and based on the input that comes from neuro-cognitive stimulus data 142 corresponding single or multiple individual brain area 100 are stimulated.

As shown in Figure 8, the electrode stimulating device 108 of equipment 300 can be placed on scalp, head, face or the cervical region or can be placed in eyes, ear, mouth or severe rhinorrhea or the hole/gap, and they can be rotated or move, and perhaps otherwise different single or multiple brains positions, zone or the direction of stimulation put are changed.The permission of converging, transmit and receive of different such electrode stimulating devices 108 stimulates any three-dimensional point, cell, tissue, zone, leaf or hemisphere in the individual brain, and each in these electrode stimulating devices 108 can independently be controlled based on the input that comes from brain stimulation data 138 and in conjunction with neuro-cognitive stimulus data 142, thereby treats any cognitive function any and brain diseases associated or raising individuality.

The illustrative embodiments of brain stimulator 146 comprises a plurality of electrode stimulating devices 108, they are placed on people's the tooth by this way independently, or be placed on the oral cavity, throat, ear, interior and the scalp of nose and eyes, facial, Anywhere lip-deep with cervical region, promptly, this mode allows electrode activation module 107 to change, change or control each electricity irritation in these concrete electrode stimulating devices 108, the direction of the combination in any of electromagnetic stimulation or this stimulation of two types, this mode allows each electrode stimulating device 108 to send by any single or multiple brain points or zone, transmit or receive this stimulation, and wherein, owing to come from the converging or, can make the free-throw line of stimulation of stimulation of a plurality of electrode stimulating devices 108 by the electricity of single or multiple kind electrode stimulators 108 or transmitting and receiving of electromagnetic stimulation, section, the precision in direction or zone is accurate more or accurate.Therefore, emission by single or multiple kind electrode stimulators 108 or reception or by converging, whole brain has become the place of a large amount of points, line, ball, zone, organ, leaf, cell or hemisphere of the One's name is legion of potential stimulation, and they are by the input that comes from brain stimulation data 138 and controlled based on foregoing invention.

Now, present invention is described with reference to Fig. 9 to Figure 20, embodiment A-C and variant thereof and enhanced form.

Embodiment A

The system of embodiment A comprises the element of describing below with reference to Fig. 9 to Figure 13.Embodiment A can provide comprehensive TMS magnetic to stimulate and the cognitive training stimulation to the patient by the position of health doctor identification or by the Alzheimer brain region of algorithm identified.This system can comprise: computer, TMS stimulator (905,907), be suitable for patient's the shielding cell with TMS coil (904).

Computer can comprise two screens (901,908) and keyboard (902,908), and a screen (908) allows and operator (909) reciprocal action, and another screen (901) provides cognitive stimulation and carried out control module (ECM) domination.Patient (910) can provide feedback for computer (905) by using keyboard (902).In addition, after using the TMS stimulation, computer (905) is by using output pulse in order TMS unit (907) in the preset time cycle that is connected between two unit (911).

Patient (910) is sitting on the comfortable chair (912).Chair allows to take one's seat with the axial mode or the mode of swaying.Patient's head can be limited to move by using limiter (903), and shielding cell (904) can be fixed in the patient by using suitable tightening technology.

By using shielding cell, the stimulation of TMS magnetic is applied to patient (910) via TMS coil (904), and the TMS coil is a Controllable Temperature.TMS magnetic stimulating unit will be discussed below in more detail.

The computer utility (906,1400) that is used for the system of illustrative embodiments A of the present invention can provide following function, and the details of preferred assembly module will be described respectively hereinafter.Carrying out control module is in charge of the course of treatment (1408) and stimulates sequencing and the state of using.ISAT (1505) assembly of END (1404,1505) uses the MRI image sequence, As time goes on to discern the change of brain quality or structure.The ISAT (1505) of END (1404,1505) also can utilize other END of combination in any to select in (NDA or ADM) any one.EDMIS module (1405) is used the recognition tests result, is come from the output of END (1404) and come from the caretaker or not staff's on the scene input, to determine optimal stimulus position and training regime based on stored script information (1413).Cognitive training module CSM (1412) is applied to patient (910) based on the script (1413) of dynamically changeable with stimulation.Cerebral lesion locating module (DBLM) (1406) obtains the position by EDMIS (1405) identification, and the position of being discerned is associated with concrete patient's analysis, and based on the correct stimulation sites in brain figure (1407) location.Brain registration assembly (907,1409) is determined the accurate coordinates of patient's the position that will be stimulated, and the registration between the stimulation sites of indication and control TMS coil position (904), the magnetic field impulse of using and patient's expectation.

According to another exemplary embodiment of the present invention, the selection of embodiment A is customizable to be at the cognitive function that improves ordinary person, for example, substitute EDMIS fully by utilizing equivalent modules, this equivalence module is known as and improves cognitive function decision system (ECFDM).This module can be discerned the concrete brain area that be stimulated similarly, so that the input based on END and recognition tests module improves specific knowledge function or technical ability, and be connected to the execution control module like this module class, then, carry out control module and adjust (and synchronously) between the transmission to the electromagnetic stimulation in brain area that ECFDM discerned or site and cognitive stimulation, described brain area or site need to be stimulated the specific knowledge function with raising ordinary person.

During the stimulation that use comes from the system of embodiment A is treated or after any single or multiple courses of treatment, EDMIS (1405)--based on response (902) of patient or based on the change of constantly or off and on measuring patient's all brain structures, function, neural plasticity or neuro physiology etc. by END-ISAT (1505), NDA (1507) or ADM (1506)--makes such decision based on this response, that is: change operator (909) or adjusting script (1413) as required, so that the cognitive training optimization.

In this embodiment, before the single or multiple courses of treatment of electromagnetic stimulation and/or cognitive stimulation and after the single or multiple courses of treatment, feedback circuit measurement patient's function, structure, neural plasticity or neuro physiology state are (for example, according to degenerating or stimulating back regeneration/neural plasticity along with the change of time, ISAT; Or with respect to normal age, education or other parameter matching crowd, NDA; Or with respect to the patient of Alzheimer's disease or with respect to the crowd of any other brain diseases).Therefore this feedback circuit utilizes END (ISAT, NDA or ADM) repeated measure, and EDMIS regulates the parameter of brain stimulation site, intensity, persistent period, frequency etc., and the also corresponding cognitive stimulation of these electromagnetic stimulation brain area of scalable.

Embodiment B

The system of embodiment B has improved the function of the system of embodiment A, and the function below it has added: the complete function of END module, it preferred embodiment will be described in detail below.One or more below the utilization of END module in the algorithm determine stimulation sites:

(ISAT) (END-ISAT) (1505,1600) between the time dependent curee.

Normalized number is (END-NDA) (1507,1800) according to one's analysis.

The diagnostic module of Alzheimer's disease (END-ADM) (1506,2000).

The system of embodiment B can further add the computer control that magnetic stimulates (1010).This feature can realize in closed-loop process by the function of utilizing the brain registration.

Embodiment C

The system of embodiment C has improved the function of the system of embodiment B, and assembly and function below it has added comprise stimulator shown in Figure 19.The stimulator of Figure 19 provides the raising to brain area to stimulate by utilizing electricity irritation, electromagnetic stimulation and magnetic stimulation or any or all of combination in these.This stimulation can comprise the nerve electrode of a plurality of coils, surface electrode and implantation or any or all of combination in these, they be placed on around patient's the head and implanted property ground or non-implantation be placed in the hole of patient's head (2501) so that at the intensity optimization of specific brain area (2505).

The stimulator of Figure 19 comprises the helmet and/or framework (2506), it has the position feedback utilized and such as the coil position of rotary position pick off and gyrostabilized platform system speed feedback mechanisms such as (2501) control and stable, with accurately and control automatically stimulate and make its optimum.Gyro black assembly constantly sensing, adjusting, move and the magnet of the control helmet or framework (2506) or each position and the vector in the electrode.

By feedback being provided for boost controller (2503), the stimulator of Figure 19 provides the magnetic field of using to control with respect to the vector magnitude and the direction of patient's head or brain area, and it can comprise cooling management and heat management (1105).In addition, the stimulator of Figure 19 comprises the adjusting of stimulation sites and intensity being carried out according to standard or other indication of feedback.

The stimulator of Figure 19 can manually be controlled or computer control stimulating coil and electrode (2502,1104), positional actuator and pick off.Under computer control (1106), system provides the real-time feedback to stimulation sites and intensity, and correction is provided on demand.

The computer utility of the system of embodiment C has improved following feature:

A. magnetic field control module, it is used for controlling applied magnetic field vector by the stimulator that uses Figure 19.

B. electric stimulation pulse module, it is used to the property implanted ground and non-implantation ground is controlled and electrical stimulation.

C. turn round control module, the rotary stability of the stimulator of the feedback of its monitoring inertial sensor and control Figure 19.

D. the progress of the cognition during course of treatment monitoring, the recognition tests result is followed the tracks of in its computer utility by embodiment C during the course of treatment, allows by the feedback of using the EDMIS module cognitive function to be carried out real-time assessment during the course of treatment.

E. the data base of the data of session collection stores and fetches, and it comprises patient's stimulation sites precision, patient's irritation level and cognitive training result.

According to an illustrative embodiment of the invention, the system of above-mentioned embodiment C comprises all subsystems of describing in the following embodiment.

The sub-component of system

Carry out control module (ECM):

ECM (1408) can be the computer utility assembly, the excited application that stimulates (1411) and cognitive stimulation (1410) of its control.ECM can: (1) manages the gathering stimulation sites input data that come from DBLM (1406); (2) by DBLM (1406) appointed positions place the TMS application of stimulus and the cognitive stimulation that are applied to the patient are being arranged in order; And/or (3) monitor the output of EDMIS (1405) and DBLM (1406), so that the modification to the treatment profile of being determined by EDMIS and DBLM to be provided.

ECM (1408) can: (4) after excitement stimulates (1411) with regularly about 50 to 500 milliseconds of cognitive stimulations (1410); (5) provide for the TMS unit and trigger output with the application of order to applied TMS pulse (1410); (6) utilize of ideal position and control and the location TMS stimulation (1410) of brain registration (1409) module with identification coil (904,1004 and 1104).

In addition, ECM (1408) can indicate the errors present of coil, and the control location (1010) that perhaps uses a computer is to proofread and correct stimulation sites and to communicate to adjust and to control the cognitive stimulation to the patient with CSM (1412).

END module (1500):

END module (1500) comprises one group of algorithm that is used for determining Alzheimer's disease (AD) existence.These algorithms can be the part of bigger application, perhaps can be with EDMIS (1405) to combine to be used in early days or the independent diagnostic application of the medical diagnosis on disease in late period.The END module receives the input of MRI (1503), FMRI (1502) data, expert diagnosis (1501) or recognition tests result (1504) form, and the diagnosis of output AD Differential Diagnosis (1511,1607,1807 and 2008) output.The END module is used one or more following algorithms, is used for determining stimulation sites:

(END-ISAT) (1505,1600) between the time dependent curee:

ISAT can be implemented as the computerized algorithm in the application (1400), and required a plurality of MRI images (1601) in cycle service time, and it is acquired in interval to be used for determining the brain tissue's quality or the structural change of indication Alzheimer's disease.ISAT module (1505,1600) is obtained MRI and is carried out rotation and convergent-divergent, to realize the best correlation between the image.ISAT module (1505,1600) is also differentiated these images, and the image of image after the discriminating high-pass filtering and edge raising, changes with the structural change and the quality of searching in the brain.ISAT module (1505,1600) allows user's input, check and input or adjustment of treatment position to the position that the user indicates suspicious region of variation.The ISAT module reads the MRI data that come from industrywide standard MRI equipment (1503).

Concrete brain area and ISAT output (1606) that ISAT output (1606) indication will be stimulated comprise each regional control aiming dot, allow to determine fast to degenerate or improve.

Normalized number is (END-NDA) (1800) according to one's analysis:

NDA (1805) is implemented as computerized algorithm, and utilizes MRI (1802) and FMRI (1803) data or recognition tests result (1801).NDA (1805) compares the indication of following disease with standardized value (1804), this standardized value (1804) is that the analysis of the criterion of generally acknowledging according to industry or the standard that proposed by the applicant obtains.NDA standardized data (1804) is mated with patient's age.NDA (1805) carries out convergent-divergent, rotation and standardization to data, to represent that with the normal agent structure of same age and the internal sorting of quality (1806) compare.

NDA (1804) uses such algorithm, it comprises the data differences between convergent-divergent, rotation and the strength criterion image and the reference picture of application, differential data and reservation threshold are compared, and this threshold values is to be determined by standardized standard patient data and the comparison that comes from the patient data of cerebral lesion tissue.

The NDA disease determines that threshold values is the space threshold values in the 3 degree spaces, and it comprises 4 dimension values.Maybe with the level of the disease process that is determined, NDA comprises a plurality of threshold values based on the type of disease.These NDA utilize a plurality of threshold values to calculate the labelling in disease process gradient, the output, the quantity and the direction of disease process, and it has indicated index of being calculated and the brain area of being discerned for EDMIS algorithm (1808).The NDA dateout can be used separately, is used for the disease process of diagnostic purpose with identification and tracking.The NDA module selectively receives the awareness energy measurement of input form.

The diagnostic module of Alzheimer's disease (END-APM) (2000):

ADM (2005) can be implemented as computerized algorithm.The existence of the disease that ADM (2005) indication is very early stage, ideally, outbreak precontract 4 to 10 years.The output of ADM is the cerebral lesion zone (2006) that will be stimulated.ADM utilizes MRI (2003), FMRI (2004) and accumulative recognition tests result data (2002) during FMRI (2004) imaging.By the analysis that the feature that is associated with Alzheimer's disease or MCI patient (2001) is carried out, ADM (2005) determines the zone of cerebral lesion.ADM (2005) carries out convergent-divergent rotation and standardization to data, to represent that with the ill agent structure and the internal sorting of quality (2008) compare.

ADM (2005) uses such algorithm, it comprises the data differences between convergent-divergent, rotation and the strength criterion image and the reference picture of application, thereby differential data and reservation threshold are compared, and this threshold values is determined by the comparison with standardized patient data.

The ADM disease determines that threshold values is the space threshold values in the 3 degree spaces, and it comprises 4 dimension values.Maybe with the level of the disease process that is determined, ADM (2005) comprises a plurality of threshold values based on the type of disease.These ADM (2005) utilize a plurality of threshold values to calculate the labelling in disease process gradient, the output, the quantity and the direction of disease process, and it has indicated index of being calculated and the brain area of being discerned for EDMIS algorithm (2007).ADM (2005) dateout can be used separately, is used for the disease process (2008) of diagnostic purpose with identification and tracking.ADM standard threshold values calculates according to ADNI data base, external data base or other AD designation data (2001).

The output of ADM (2005) is cerebral lesion zone (2006), and it can be used for diagnosing clinical symptoms precontract 4 to about 10 years disease, perhaps is used for stimulating in treatment these cerebral lesion zones.

Cerebral lesion locating module (DBLM) (2100):

DBLM (2100) can be implemented as software module or computer utility.DBLM (2100) is based on brain figure (2102) and patient's the ill brain position of MRI (2106) identification.By allowing the user to click computer " mouse " on the image of representing brain or patient's reconstruct MRI image, DBLM (2100) allows the user to indicate the position (2104) of the brain that will be stimulated.DBLM (2100) receives the input that comes from EDMIS (2105), to set up concrete patient's treatment position.DBLM (2100) connects the TMS stimulator, and boost pulse is placed in place.

DBLM uses location algorithm (2103) by utilizing MRI data (2106) best fit to be carried out in the output of brain figure (2101) and patient's exact position.DBLM location algorithm (2103) carries out convergent-divergent rotation and standardization to image, so that this image and brain figure internal image (2102) are compared.DBLM (2100) carries out being correlated with between the expression, the deviation index that is used being orientated as the brain figure image of storage and the dependent deviation between patient's image.Deviation, convergent-divergent and rotation value will be used to the stimulation point in the position patient data (2104).

DBLM (2100) determines 3 degree space coordinates positions of stimulation point, and exports those positions to be used to stimulate ECM (1408).DBLM (2100) is connected with ECM, sorts by one group of desired stimulation application site with permission.

Brain figure (1407):

Preferably, brain figure (1407) is that DBLM uses the assembly of (1406,2100).Brain figure (1407) comprises the data base of known structure brain area.Brain figure (1407) comprises a plurality of expressions of brain, and it is by the value index that depends on input patient data, age and size etc.Brain figure (1407) is by DBLM (1406,2100) reference, set up ideal stimulation sites for one group of particular result by EDMIS (1405).

Expert decision-making interactive system (EDMIS) (1900):

EDMIS (1900) is such process, it comprise software module or computer utility and with internal database, personnel not on the scene and/or strange land data base's interface.EDMIS (1900) utilizes output, recognition tests result (1903) and the user's of END (1902) input (1901), to determine the optimal stimulus position.EDMIS (1900) output is used for the information (1912) of diagnostic purpose.By input and/or recognition tests result (1903) and the start-up (1901) who utilizes END (1902), EDMIS system (1900) is based on treatment doctor's (1909) expert diagnosis and/or the definite zone and the treatment characteristics that will be stimulated of expert decision system (1906).

EDMIS (1900) is during the course of treatment or afterwards, utilization comes from patient's feedback (1908) of CSM (1412), and stimulation characteristic is reevaluated and CSM is indicated to regulate its operation by data are analyzed during the course of treatment again.The input that EDMIS (1900) allows during treatment (1901), treats the back and come from the result (1909) of the early stage output of system, so that the patient is reevaluated, based on the analysis again of END or to the reexamining of cognitive performance (1905), the treatment profile is carried out suitable change.EDMIS computer utility or module comprise user interface (1904).EDMIS (1900) determines the type and the feature (1905,1907) of the stimulation that will carry out the patient.EDMIS (1900) determines during treating the type (1907) of the cognitive stimulation that will be used.EDMIS (1900) is connected with DMLB (1911), positions with the accurate stimulation sites to concrete patient (1906), determines as MRI image (2106).

Brain registration (1409):

Brain registration (1409) can be implemented as software module or computer utility.This system can utilize ready-made brain registration assembly, and it carries out one or more following function.The definite brain area that will be stimulated or that in coil alignment or stimulating course, always stimulate of brain registration (1409) by TMS coil (1411).Brain registration (1409) is the registration between evaluate application magnetic field and stimulation sites and/or the intensity in real time.Brain registration (1409) allows manually or mechanically to make stimulation sites with respect to identification object region optimization in advance.Brain registration (1409) is informed the brain position that the user is stimulated always by the 3-D image that uses brain.Brain registration (1409) is informed the relative length of stimulation by using color coding.

Cognitive stimulation module (CSM) (1412):

CSM (1412) is the assembly of embodiment A to C, and can comprise the assembly of computer utility or Another application, and can be by being operated by the script (1413) of ECM (1408) control.CSM script (1413) can be indicated the time delay between the cognitive stimulation (1410) that will be employed, applied magnetic stimulation or electricity irritation and the applied cognitive stimulation (1410).Script (1413) can comprise the scoring response to patient feedback, and it allows to determine patient's process, and response is labeled mark, is used for definite by the CSM of patient's process.After ECM (1408) and TMS (1411) application of stimulus pulse, CSM (1412) can be applied to patient monitor with the script stimulation in suitable interval.CSM (1412) can receive the patient's feedback to the answer of cognitive stimulation or response forms, the path of decision treatment in real time.

Magnetic stimulates embodiment A and B

Preferably, be suitable for the exemplary TMS (transcranial magnetic stimulation device) (907) that in embodiment A and B, uses FDA 510K, and can be used to clinical trial and the scheduling of treatment clinic for approval.TMS stimulator (907) can provide the stimulation to selected brain area, and allows manually to be placed on the patient's who is always treated the head (904).Suitable adapter sleeve for fixing to patient's head is provided.

Position at treatment interim TMC stimulator should be consistent, and is connected to ECM (905) and reaches+/-5 milliseconds precision with the timing of the magnetic field impulse that allows to use.The stimulus frequency that was fit in about 1 to 5 second period can be about 1 to 20Hz, and for each cortex zone that is stimulated always, pulse envelope continues 20 minutes.The coil of TMS stimulator (907) should not make the patient be subjected to being higher than 40 ℃ temperature at any point of application place.

The magnetic of embodiment C stimulates

Also the exemplary magnetic stimulator (2503) of the embodiment C that can use by embodiment A and B be a plurality of magnetic stimulating coils adjustable around the position of patient's head (2501) (for example: 12 coils).Integrated system is in conjunction with a plurality of magnetic ejectors and/or electric emitter and/or electronic chip and/or the revolution that is associated, and described revolution can detect the exact position and the vector of the electromagnetic stimulation of each electromagnetism/electrostimulator.In addition, each electromagnetism/electrostimulator has sensor associated, it can detect intensity and the vector and the electromagnetic stimulation of other electromagnetism/electrostimulator of each electromagnetism/electrostimulator, so that integrated rotary sensor system can discern or the accurate three-dimensional of triangulation, single or multiple cortex or branch cortex point in real time.

Extra pick off can be placed on other position on the scalp or in the skull hole.In addition, cortex or branch cortex brain navigation system allow when the electromagnetism vector is applied to specific cortex or divide the cortex zone cortex that is stimulated or the deduction/calculating that divides the cortex zone always.And, based on integrated revolution-pick off-cortex-minute cortex navigation system, to the cortex that stimulated always or divide the Real time identification of cortex zone and stimulus intensity to be provided.These features allow that each the stimulus parameter in electromagnetism/electrostimulator is carried out real-time continuous ground and regulate and monitoring, up to obtaining target (single or multiple) cortex or dividing the optimization of the stimulation in cortex zone.

System's perception constantly of revolution combination that is associated with magnetic stimulator and pick off, regulate, start and control each position and the vector in magnet or the electrode.In addition, measure the exact position that magnetic stimulator can be provided by use revolution-sensor interaction triangle of vectors, and the energy centralization position in the specific brain area can be identified.The intensity of each coil of corresponding magnetic stimulator can be controlled by computer (1107).Magnetic stimulator (2503) can comprise the coil that can insert in the nose, can insert the coil in the ear and be used for the oral cavity and the suitable coil of eyes (2501).As mentioned above, perhaps under the guidance of commercially available brain registration or like device, the electric current in magnetic stimulator (2503) regulating winding (2501) is so that control the exact position and the intensity in applied magnetic field in the manner described above.Big stimulator coil (2501) can produce about 2 to 3 teslas in coil, and the about 5cm depths in scalp produces about 0.5 to 0.75 tesla.Little magnetic coil can produce about 1.5 to 2 teslas in coil, and about 3 to the 4cm depths in scalp produce about 0.1 to 0.5 tesla.

The applied revolution rate of magnetic stimulator control system (2503) controlling magnetic field of embodiment C, and the magnetic field rise time that produces about 50 to 2000 microseconds.Under the guidance of computer (2501), nose and oral cavity coil can guide and optimize the brain area of magnetic field gradient (intensity) to the depths, as Hippocampus.Stimulator coil (2501) can be installed in the helmet or place analog structure or framework on patient's head (2502).

The magnetic field vector that the stimulator of embodiment C (2501) allows to use by control stimulates with the brain area to single or multiple cortexes or branch cortex.Carry out to the control of magnetic field gradient with to the coil in the helmet or the framework by computer that machinery moves or inertia moves, the magnetic stimulation sites can be controlled.The ancillary coil in the hole of the magnetic stimulator of embodiment C (2503) by being arranged in head (2504,2501) provides magnetic field to optimize, and allows the field to reach darker and more accurate position.Under the suitable situation, coil can be Controllable Temperature.

Stimulator as embodiment A and B, the magnetic stimulator of embodiment C (2503) can have the interface with ECM (1408), to allow applied magnetic field impulse regularly to+/-5 milliseconds precision, and allow to can be about 1 to 20Hz, and continue 30 minutes for each cortex that is stimulated zone pulse envelope always about 1 to 5 second period internal stimulus frequency.

The electricity irritation of embodiment C

By using suitable locating surface, implant electrode (2501), electric coil, solenoid, conductor electrical stimulation, the electrostimulator of embodiment C (2503) provides brain stimulation.By the brain figure that obtains according to the MRI (1403) at the patient, electrostimulator (2503) provides accurate electrode implantation position details.Electrostimulator (2503) can provide the interface with ECM, to allow to combine or individually pulse-triggered is applied to applied TMS pulse patient's brain.The electrode that electrostimulator can allow to use surface electrode or subintegumental electrode or internally or neurally place or be located at patient's brain.

Electrostimulator (2503) can use a plurality of electrodes (for example: about 20 electrodes), by ECM (1408) control, provide 10 to 100 microamperes of boost pulses.Pulse can have about frequency of 1 to 20Hz, and pulse width is about 0.5 millisecond to about 10 milliseconds, and the envelope persistent period is between 10 to 200 milliseconds.Electrostimulator (2503) should be controlled the electric current that is applied to stimulating electrode, so that the current gradient maximum is positioned at the stimulation sites place of expectation.

Figure 20 schematically shows the gyrostabilized platform of integrated neuro-cognitive of the present invention system and the illustrative embodiments of feedback system (2700).System (2700) comprises gyrostat (2701), motor (2702), rotary sensor and feedback controller (2703).System (2700) also comprises at least one magnetic stimulating coil (2704) and installing rack (2705).

Although in conjunction with preferred embodiment being described, a lot of modifications and variant will be tangible for this area related personnel in the present invention.Though preferred implementation of the present invention is described and illustrates, should recognize that they are examples of the present invention and are not considered to limit by any way in the above.Therefore, do not mean that the embodiment shown in limiting the invention to, and it only is to be limited by claims.

Claims

1. neuromedicine equipment comprises:

Analyzer system, this analytical system comprises at least one in brain analyser and the cognitive analysis instrument, described analyzer system is operating as the characteristic of at least one characteristic to obtain to measure of measuring individual disease, measured characteristic relates at least one at least one brain area and at least one cognitive characteristics, wherein said analyzer system is also according to described at least one brain area or described at least one cognitive characteristics basis of calculation value of healthy individual group or diseased individuals group, described analyzer system compares measured characteristic and described standard value, and consequent value is provided; With

The stimulator system, this stimulator system is connected with described analyzer system, described stimulator system comprises at least one in brain stimulator module and brain stimulator and the cognitive stimulation device, wherein said brain stimulator comprises at least one non-implantation brain stimulator, this non-implantation brain stimulator is operating as by discharging stimulation energy excited or that suppress selectively stimulates single or multiple brains site at least one brain area, described stimulator module is operating as and described stimulator is set so that stimulation energy is directed to the described single or multiple brains site at least one brain area place, wherein according to described consequent value, described brain area is positioned at territory, left front frontal region, frontal lobe, cingule gyrus, hemisphere, temporal lobe, frontal lobe, top, occipital lobe, the tonsil zone, cerebellum, Hippocampus, anthreonal, corpus callosum, plaques, tangle, brain stem, bone marrow, organ colla, the cortex lower area, cortex, gyrus, in white matter and the grey matter and

The cognitive stimulation device, this cognitive stimulation device is configured to provide at least one cognitive stimulation, to regulate at least one cognitive characteristics that is associated with described brain area according to described consequent value.

2. neural armarium comprises:

Analyzer system, this analyzer system comprises at least one in brain analyser and the cognitive analysis instrument, described analyzer system be operating as provide with at least one brain area and at least one cognitive characteristics in the characteristic of at least one relevant measurement, described analyzer system is according to described at least one brain area or described at least one cognitive characteristics basis of calculation value of healthy individual group or diseased individuals group, and described analyzer system provides consequent fiducial value; With

The stimulator system, this stimulator system is connected with described analyzer system, and described stimulator system is operating as by discharging stimulation energy excited or that suppress, selectively non-at least implantation ground stimulates single or multiple brains site and at least one brain area place, described stimulator system comprises a plurality of independent non-stimulator for implantation discharging stimulation energy, and described stimulator system is orientable according to described consequent value stimulation energy is directed at territory, left front frontal region, frontal lobe, cingule gyrus, hemisphere, temporal lobe, frontal lobe, top, occipital lobe, the tonsil zone, cerebellum, Hippocampus, anthreonal, corpus callosum, plaques, tangle, brain stem, bone marrow, organ colla, the cortex lower area, cortex, gyrus, single or multiple brain site in white matter and the grey matter at least one.

3. armarium according to claim 1, wherein said brain stimulator and described cognitive stimulation device have formed single integrated equipment.

4. armarium according to claim 3, wherein said single integrated equipment comprise with individual ear, nose, scalp and mouth at least one at least one electrode that communicates.

5. armarium according to claim 1, wherein said brain stimulator comprises at least one stimulator for implantation, this stimulator for implantation is operating as provides single or multiple positions to stimulate selectively for described at least one brain area or different brain area.

6. armarium according to claim 1, wherein said brain stimulator are configured to provide at least one in electricity irritation, magnetic stimulation, electromagnetic stimulation and the photoelectricity stimulation.

7. armarium according to claim 1, wherein said brain stimulator comprise at least one electromagnetic stimulation device and another nerve stimulation source.

8. armarium according to claim 1 further comprises the controller that is connected with described stimulator system with described analyzer system, to operate at least one in described brain stimulator and the described cognitive stimulation device.

9. armarium according to claim 1 further comprises:

Treatment module, this treatment module operation be for being connected to described analyzer system, and described treatment block configuration is for arriving described stimulator system in response to described consequent value dateout; With

Body internal stimulus device, this body internal stimulus device is configured to make described brain area to receive treatment, and described treatment comprises at least one in cell replacement therapy, cell regeneration therapy and the cell growth.

10. armarium according to claim 1; wherein said stimulator is orientable, with the single or multiple brains site in stimulation energy guiding and the brain area that the following is associated: Alzheimer's disease; senile dementia; infantile autism pedigree obstacle; the mild cognitive functional lesion; the loss of memory; aging; ADHD; Parkinson's disease; depressed; take drugs; drug dependence; schizophrenia; bipolar affective disorder; memory improves; intelligence improves; attention improves; happiness or emotion improve; self-confidence improves; the linguistic competence; linguistic skill; vocabulary technical ability; pronunciation technical ability; vigilance; focus on; loosen; perception; thinking; analysis ability; carry out function; sleep improves; motor skill; coordination skills; motor skill; musical technique; interpersonal skills; interpersonal skill and emotion skill.

11. armarium according to claim 10, wherein said stimulator is orientable, with the single or multiple brains site in stimulation energy guiding and the brain area that Alzheimer's disease is associated.

12. one kind is used for the treatment of with the brain diseases associated or is used to improve the armarium of s cognitive function, comprising:

The stimulator system, this stimulator system comprises:

At least one brain stimulator, this at least one brain stimulator is configured at least selectively

Stimulate localized brain area with non-implantation ground, wherein localized brain area be with described and

Brain diseases associated or be associated with described cognitive function; With

At least one cognitive stimulation device, this at least one cognitive stimulation device is configured to selectively stimulate

With at least one cognitive characteristics of being associated of localized brain area; With

Body internal stimulus device, this body internal stimulus device is configured to make localized brain area to receive treatment, and described treatment comprises at least one in cell replacement therapy, cell regeneration therapy and the cell growth.

13. armarium according to claim 12 further comprises:

Analyzer system, this analyzer system comprises at least one in brain analyser and the cognitive analysis instrument, described analyzer system is operating as measures the characteristic of at least one characteristic to obtain to measure described and the brain diseases associated, measured characteristic is to be associated with at least one brain area and at least one cognitive characteristics at least one, wherein said analyzer system is also according at least one brain area or at least one cognitive characteristics basis of calculation value of healthy individual group or diseased individuals group, described analyzer system compares measured characteristic and described standard value, and consequent value is provided for described stimulator system; With

Controller, this controller is connected with described stimulating system to operate at least one in described brain stimulator and the described cognitive stimulation device with described analyzer system.

14. armarium according to claim 12, wherein said brain stimulator system is the helmet.

15. an armarium comprises:

Analyzer system, this analyzer system comprises at least one in brain analyser and the cognitive analysis instrument, described analyzer system is operating as the characteristic of at least one characteristic to obtain to measure of measuring individual disease, measured characteristic relates at least one at least one brain area and at least one cognitive characteristics, wherein said analyzer system also comes basis of calculation value according to described at least one brain area or described at least one cognitive characteristics of healthy individual group or diseased individuals group, described analyzer system compares measured characteristic and described standard value, and consequent value is provided;

The treatment module is connected in described analyzer system this treatment module operation, and described treatment block configuration is in response to described consequent value dateout;

First stimulator, this first stimulator are operating as and discharge the excitement stimulation or suppress stimulation, and are configured to discharge stimulator reception data from described treatment module and position energy, to stimulate described at least one brain area; With

Second stimulator, this second stimulator is associated with described first stimulator, and described second stimulator is configured to activate described at least one cognitive characteristics of described individuality.

16. armarium according to claim 15, wherein said first stimulator comprises at least one non-implantation brain stimulator and at least one implantation brain stimulator, and wherein said at least one non-implantation brain stimulator and described at least one implantation brain stimulator are configured to selectively stimulate described at least one brain area.

17. armarium according to claim 15, wherein said non-implantation brain stimulator comprises at least one in electrode, carbon electrode, electromagnetic electrode and the photovoltaic electrodes.

18. armarium according to claim 15, wherein said first stimulator comprise at least one implantation brain stimulator, this implantation brain stimulator is configured to selectively stimulate described at least one brain area.

19. armarium according to claim 15, wherein said second stimulator is configured to provide at least one cognitive stimulation that is associated with described cognitive characteristics.

20. armarium according to claim 15, wherein said first stimulator provides non-implantable stimulation energy.

21. armarium according to claim 15, further comprise assessment apparatus, described assessment apparatus is configured to according to the response to the stimulation that comes from described first stimulator and described second stimulator, feedback is provided in described first stimulator and described second stimulator at least one.

22. armarium according to claim 15 further comprises controller, this controller is configured to operate described first stimulator and described second stimulator in response to described consequent value.

23. a method for the treatment of cognitive impairment comprises the steps:

The brain area that identification is associated with cognitive impairment;

Make described brain area accept at least one in stimulating of electricity irritation, magnetic stimulation, electromagnetic stimulation and photoelectricity; With

Simultaneously, regulate the cognitive function that is associated with described brain area.

24. method according to claim 23 further comprises the steps:

Described brain area is received treatment, and described treatment comprises at least one in cell replacement therapy, cell regeneration therapy and the cell growth; With

Selectively, make described brain area accept pharmacological treatment.

25. a method that is used for the treatment of impaired cognitive function, described method comprises the steps:

Under the situation that need not the adjacent brain area of physical stimulation, first stimulation to the predetermined brain area of individuality is provided, described predetermined brain area is associated with impaired cognitive function on function; With

Provide at least one cognitive stimulation to the patient, to cause the response that relates to described impaired cognitive function.

26. method according to claim 25 further comprises the steps:

At least one local brain function of measuring described predetermined brain area is to obtain local measurement;

Described local measurement and standard value are compared to obtain evaluating data; With

Adjusting in response to described evaluating data provides first to stimulate and at least one step in the step of at least one cognitive stimulation is provided.

27. method according to claim 25 further comprises:

Measurement is to the response of described first stimulation and described cognitive stimulation, to obtain cognitive data; With

Based on described cognitive data, adjust at least one step in the step that first stimulation is provided and at least one cognitive stimulation is provided.

28. a brain Therapeutic Method comprises:

Analyzer system is provided, and described analyzer system comprises at least one in brain analyser and the cognitive analysis instrument;

Described analyzer system is measured at least one characteristic in the individual disease, with obtain with at least one brain area and at least one cognitive characteristics in the characteristic of at least one relevant measurement;

Described analyzer system comes basis of calculation value according at least one brain area or at least one cognitive characteristics of healthy individual group or diseased individuals group; With

Described analyzer system compares measured characteristic and described standard value, so that consequent value to be provided.

29. a Therapeutic Method comprises:

Measure the local brain function of at least one brain area, to produce local measurement with respect to the normal value of individuality;

Estimate described local measurement with respect to the standard value of one group of individuality, to produce evaluating data;

Regulate at least one in one or more non-stimulator for implantation and the one or more cognitive stimulation device in response to described evaluating data; With

According at least one or a plurality of non-stimulator for implantation and described at least one or a plurality of cognitive stimulation device, stimulation is provided for described at least one brain area.

30. method according to claim 29 further comprises:

Measurement is to the response of described stimulation, to produce cognitive the measurement; With

Regulate at least one in described non-stimulator for implantation and the cognitive stimulation device in response to described cognitive the measurement.

31. method according to claim 29 wherein provides the step of non-implantable stimulation to comprise: provide the nerve stimulation of electromagnetic stimulation and another kind of form, selectively to stimulate described at least one brain area.

32. the Therapeutic Method of the cognitive symptom of a disease comprises:

Adjacent domain is carried out under the situation of physical stimulation need not, selectively stimulate and at least one related functionally brain area of cognitive symptom; With

Provide selecteed at least one cognitive stimulation, to draw the response that comprises described cognitive symptom.

33. method according to claim 32 further comprises:

Measure local brain function at described at least one brain area place, to produce local measurement;

Estimate described local measurement with respect to standard value, to produce evaluating data; With

Regulate at least one in brain area stimulation and described at least one cognitive stimulation in response to described evaluating data.

34. method according to claim 32 further comprises:

Regulate at least one in selected stimulation and described at least one cognitive stimulation in response to described cognitive the measurement.

35. method according to claim 32, wherein said at least one brain area is the brain defect area.

36. method according to claim 32, wherein said at least one brain area joins with the memory function disease association.

37. method according to claim 32, wherein said at least one brain area is associated with Alzheimer's disease.

38. the method for a Neurotherapeutic comprises:

Analyzer system is provided, and this analyzer system comprises at least one in brain analyser and the cognitive analysis instrument;

Described analyser is measured at least one characteristic of individual disease, and measured characteristic is to be associated with at least one brain area and at least one cognitive characteristics at least one;

Described analyser comes basis of calculation value according at least one brain area or at least one cognitive characteristics of healthy individual group or diseased individuals group;

Described analyser compares measured characteristic and described standard value, and consequent value is provided;

The stimulator system is provided, comprises:

One or more non-stimulator for implantation are provided, provide single or multiple positions to stimulate with at least one brain area of selectively being associated for described characteristic;

One or more cognitive stimulation devices are provided, provide cognitive stimulation selectively to give at least one cognitive function relevant with described at least one characteristic; With

Controller is provided and described controller and described analyzer system are connected at least one of the described one or more non-implantation brain stimulator of described controller function and one or more cognitive stimulation devices with described stimulator system.

39. a Neurotherapeutic method comprises:

Provide and have the module that a plurality of discrete energy are launched stimulator;

Described module is placed on the patient;

Described discrete stimulator is positioned, with the single or multiple brains site in stimulation energy guiding and the brain area that the following is associated: Alzheimer's disease, senile dementia, infantile autism pedigree obstacle, the mild cognitive functional lesion, the loss of memory, aging, ADHD, Parkinson's disease, depressed, take drugs, drug dependence, schizophrenia, bipolar affective disorder, memory improves, intelligence improves, attention improves, happiness or emotion improve, self-confidence improves, the linguistic competence, linguistic skill, vocabulary technical ability, articulatory skill, vigilance, focus on, loosen, perception, thinking, analysis ability, carry out function, sleep improves, motor skill, coordination skills, motor skill, musical technique, interpersonal skills, interpersonal skill and emotion skill; With

Stimulate the described single or multiple brains site that is associated.

40. a system that is used for neural assessment and treatment comprises:

Computer and optional control module;

User's energy stimulating module, this user's energy stimulating module selectively comprises the TMS stimulator;

The cognitive stimulation module;

The cerebral lesion locating module; With

Optional recognition tests module.

41., further comprise the cognitive process monitoring module according to the described system of claim 40.

42., comprise that further the correlation ratio that is connected with described computer is than the normal data library module according to the described system of claim 40.

43. a medical therapy equipment comprises:

Computer system with user's visit;

Be used to apply the synchronous magnetic stimulator system and the cognitive training stimulator system of stimulation;

Carry out control module, be used to manage the order of the course of treatment and applying of state and stimulation;

Based on the decision system of patient's response, this decision system is made decision according to this response, changes the operator or regulates script so that the cognitive training optimization; With

The END module is used for determining the existence of Alzheimer's disease.