 Another important which I am going to cover is the cerebral palsy, which is very common all over the world. The cause of the cerebral palsy could be early insult while the child is developing or the insult perinatal insult, when the child is coming out. An insult to the brain during delivery results in the damage to the brain and irreversible damage and both have different behaviors pattern different patterns and in India we get another condition where you get a cerebral palsy is the premature delivery. So, child is born a 6 month, child is born a 7 month and the children are being cared you know outside the mother's womb to 4, 2 or 3 months more become they become like a normal individuals but they also suffer a lot of damage to the brain because they are lot used to living in the environment you know so quickly so early and that is the reason they get a lot of suffering to the brain. And it is a pathetic situation actually to something which you can correct, something you can prevent especially the intrauterine while the child is very part of the child is being delivered, caught round the neck the child does not cry after birth immediately after birth you know it is relevant it is important actually the poor birth of delivery especially in this country even today and they are responsible for a large amount of cerebral palsy in this country. Now, what is cerebral palsy that is an expression which will be important for us to understand. Cerebral palsy is a term used to describe a variety of neurological syndromes with disorder of the moment or the posture it depends on which area of the brain is affected, if the cortex is affected then they develop seizures they have a mental decline, if the white motor traits are affected they are classically develop motor dysfunction people say they have a sensory followed by motor say motor followed by sensory we have shown I will show that how the sensory takes over the motor and finally the motor comes in. So, that is second thing the third thing which they develop is the moment disorders because of the involvement of the basal ganglia, what you call the corpus tritum or the basal ganglia that is the one which is responsible for the moment disorder of the child. And the fourth important thing is epilepsy So, it is a and they are not reversible whatever insult occurs in the beginning of the life it does not worsen, it does not improve that is how you define a cerebral palsy. In neurological condition there is a decline as a function of age as the pathology increases, but whatever insult here has occurred stays with you. Now, we have to find like that girl asked yesterday rehabilitation. So, this is where the rehabilitation is important to the children you know and this is a whole exercise, but people are trying to do the some of the very rich people have the children in the spastic. So, it is not disease of the poor of course, poor all involved the rich are as involved as a poor in this. So, it results from the damage to the brain and developing brain from causes such as hypoxia or infection, but in many cases no definite cause can be a certain, but mostly it is a infection intra uterine infection perinatal infection perinatal hypoxia. The injury to the white matter the perimetrical matter it is a major form of brain injury which you can see actually you number I and if at all or ultrasound in uterine or so on and so forth. And these injury result in the secondary affection of the tracts degeneration of the tracts what we call as valentine degeneration or degeneration of the tracts. And that is why we as a radiologist become interested in C p because you most of the time the imaging may not be abnormal. You find normal imaging 30 to 40 percent of patients, but they have a spastic C p. How do you understand? How do you define them? You know if you see an imaging abnormality yes the C p is there, if you do not see it is not C p, yes still C p. So, what are the methods by which we can define several powers beyond the conventional imaging and is there any way we can understand the neuro rehabilitation or what is called as the brain plosicity? How can we objectively assess the brain plosicity? So, there are two issues which we will I would like to address in this particular talk because when you give exercise therapy or constate therapy or vortex therapy combined with exercise the child improves, but is the improvement is child commensurates with the improvement of the brain function or the reorganization of the brain. What is called as brain plosicity? That is important. The proof of concepts come from objective assessment of the changes in the brain. We see this is the critical improvement of the patient that is what is important. Now, this is the classification which has been described depending upon the abnormality like spastic, C p hemiplegics depending upon which area of the brain is affected. Monoplegic all these things you know which I beside that I mentioned to you beside the motor function there is a cognition which goes of the epilepsy comes in the moment disorder comes. They all come into a part of the they are part of C p different kind of C p which are the various brain is affected in our cell that is what affects us you know. And this is about something which is reversible there is a reorganization and not reversibility there is a difference. So, people have designed different test to quantify the motor disfunction g m f m score is the one which is again we are ruled by the western world and that is how we follow them and you write these things no issue they will not question you. So, this is g f m score and g m f c score gross motor function classification system. So, these are the one which have been designed by the western world and this is what we follow all of us for the C p classification how much deficit is there. As I mentioned to you the cause of C p or intramendicular hemorrhage especially seen in the premature delivered baby. Conjuritl stroke means a child when he is born he had a stroke the artery is blocked maybe infection, maybe occlusion whatever the reason. And another one is perimental leukomolacea which is classically this is the one which is one important this is seen in a peritone hypoxia this is typical to India also in India. The reason is mainly the reason the perimental leukomolacea is the peripartum insult to the child when the child is being delivered. There is a meconium aspiration there is a chord around the neck or the child did not cry whatever reason there is how they develop this hypoxia interpartum and peripartum you know. So, many time you must be hearing you know as a as a general population that the cesarean is required as a child is in distress. And this is the way they make money the gynecologist make money you know by saying that child is under stress and I want to take it out to prevent the any damage to the child. But, the fact remains we call it as a gynecology is distress rather than a child distress because she is in distress she does not want to come in the middle of the night delivered a child. She will have a dinner take out the baby go home and sleep that is where you really want to see that is really a child distress is there or you protect the child brain interest you know when you are doing this kind of exercise. Do you have irritation available to take care of the baby at that time as a child is coming out to a new world in your environment you know from the actual environment is living in for 9 months. It is different world world together for a child you know the temperature is different the oxygen is different the feed is different everything is different gynecology. So, that is what makes a difference you know for this they are typically they describe the call like trauma infection, toxic exposure like a lot of women who take alcohol and they are pregnant. So, they can damage the child brain also in India this may not be true, but western world yes it is a common practice and we can do that. So, that is how the perimental locomotion looks like on the cut brain surface the brain is damaged you can see it here, you can see it here, you can see it there this is how the brain looks like it is look a militia it means it is a soft brain with an area of glazes. And it may involve the cortex it may involve the cortex it may involve the brain ganglia it may involve thalamus any area depending upon what what the child result had at that time and depending upon the area the child develops a neurological deficit motor sensory brain ganglia involvement cortical involvement epilepsy it all depends on what where is lesion is in the p v l or this area and the p v l means the fibers are going there you know and the fibers get cut connection is lost and they become you know spastic. Now, this is interesting slide again from 1998 it is not a new thing which I am talking about most things are known we are only objectivizing it and it is not something we are inventing it first time in the world no there is something we all know about it you know when the child moves from 0 to 36 weeks age of 36 months and 48 months the c p children have a decline in IQ as compared to normal child they have a decline in IQ they have an improvement in IQ stabilization and here is the decline like it is about 1 year. And I call that if you take a child with an IQ of 80 or 90 with a c p then I am not worried about at least the gross IQ changes you know in the brain it is spastic. So, we did that exercise also you know to see that how the IQ affects this girl actually worked on the one you gave me she worked on that actually with us. Now, our purpose was that can we assess the white matter damage in the cerebral palsy using quantitative diffusion that is the one which you started way back in 2004 to 2005 when I think Richa Trivedi was a first student she started working on that with us the PhD on this. Conventional number I will miss a lot of c p's. So, we thought let us look at the tracks directly and see what is the damage to the tracks that is how we started in 2004 to 2005 getting the D T I images F A values and the color coded F A values look at the tracks post your name of the internal capsule the internal capsule the corpus callosum the white matter tracks very clearly defined and will put the region of interest actually in these areas that is how we started 2004 to 2005. And then we started realizing that this is not the whole truth we are only taking particular region and then trying to see rather look at the whole truth that is what the tetragraphy and the analysis started coming from them. So, these are the results on imaging in controls normal imaging and I am normal look at this is the paramedical accumulation can you see the white signal here this is classically described as a paramedical accumulation this is definitely c p I do not have to do anything just look at this you may say a cerebral palsy no question then why all this you are doing now this is the comparison with the normal imaging and I am normal imaging. So, red is the normal imaging and blue is the normal imaging c p and the controls is the green. So, what you find is there is a decline as you move from the green to red in the F A values irrespective of you know the location the medulla, the palms, the midbrain, postulum and the corona radiator and the m d values again showing increase. So, that is the first paper actually we published and saying that the involvement of the tract is there even when the imaging is normal that was the message when the imaging is normal I do not have to do this exercise, but if the imaging is normal then is worse why looking at this and seeing that is definitely c p. So, that was the first purpose we had these are the numbers just to show you that the numbers are abnormal and we concluded that the changes are widespread and the technograph is superior to conventional MRI because you can pick up the areas which are abnormal on D T I which are not seen on conventional MRI. So, then we move beyond that and say we will let us look at the tracts. So, that is when the technographic came into picture and we started looking at the tracts and the issue was is the sensory fibers involved first or the motor involved first because c p is the motor disease, but a fraction is mainly sensory and the motor is secondary. This is the repeat was going on first paper came to an analogy just while we were working on this and they came with the first paper of three or four cases actually and we showed they showed the sensory involvement is earlier than the motor and we of course, did confirm that we as usual are delayed in writing as compared to the western world and this is just to show you that and the plasticity of the C S T has been shown by D T I in a blind subjects actually. So, earlier we used the ROI analysis I mentioned to you and then we decided to do a quantitative analysis to see the difference in this population. Now, this is a method we used for a sensory and motor I see we are not you still automated this is something which I have been telling him to automate this which we have not done it so far little challenge in doing this, but it can be done it is not something very big people have tried and done this in the western world and we should be able to do it and implement this is something which we are lacking. What we are doing is we just look at central circuits and T rate is central circuits in the motor cortex and that is how we identify central circuits put a region of interest on the by hand that is the that is the trick here. So, this is in a way subjective that is the only part we have subjected in our tracks look at all the C plane axial and coronal sagittal and then create the sensory and the motor track. So, central circuits on this side of central circuits is a sensory strip on the anterior part is a motor strip. So, that is how we generate the sensory and the motor give different colors to this motor pathway and the sensory pathway. There is something called supplementary motor area about talking about supplementary sensory area about talking about looking at the pre and the post central gyrus actually mainly this, but this area needs to be worked out by ourselves and the rest of the world. Now, these are results of the patients versus control with normal imaging with the normal imaging and look at the track difference sensory is more affected to the motor right away you can see that. This was actually shown by on imaging no trotography by the first people and they claim that actually that is the result is showing very clearly that how the quantitative analysis shows the sensory and the motor normality and we could actually classify the grade of the C p by the trotography. There are other people you published where you could classify the grade of the C p based on the tracks only along sensory and the motor. How much grade weakness like GFMS score and all which you talked about we could actually grade them. Now, this is important the treatment induced plasticity. So, when we started treating them with vortex and physiotherapy you know vortex is expensive chemical. So, everybody cannot afford in this country vortex and though they will sell their house to help the child to have a you know small improvement in this function, but it may not always possible. So, initially what we did we combined everything what we had we combined physiotherapy, vortex what we could what we could not give we did differentiate. We were looking for the point of view how much plasticity is the improvement is there in the brain. Improvement in the clinical function how does it affect the brain function, brain structurality in other words you know. So, this is what we tried and see what vortex does is vortex reduces the specificity for the muscle. So, when the muscle is specific it difficult to do exercise you know there is a cogwheel kind of rigidity you know you cannot move that well. When there is a flaccidity the muscles can be moved quick back and forth very more quickly you know. So, exercise effect is much better though the vortex effect lasts for couple of months it does not last for the whole life, but that is window gives you a window to improve the exercise. That was the whole purpose of doing the vortex effect. What it is it costs it costs a lot of money it may need one injection two injections you know so on and so forth. So, which is this kind of population which we have it may not be possible. So, initially we did R y and R c you can see we put the R y on the singular posterior with little capsicum, princestem, medulla and this is the story of this child children sensory specific quality parenthesis most of them are quadratic that is the grade of the score and that was the follow up score of this most children they showed improvement 4 to 3 for these children even a grade well improvement from 4 to 3 or 3 to 2 is important. If they cannot sit or they cannot stand if they start standing this is a big achievement for them and they are they can stand if they start walking a few steps this is big milestone for them. So, you can understand the how much child feels happy and how much the parent feel happy about that. So, this happened because of the plasticity changes the brain and the proof of concept came from the this is neuro rehabilitation which that girl was talking about and what we showed very clearly was that if you look at this single of now this is single of in the normal individual look at the single of fibers here and they showed improvement on the follow up and of course, you can show that by numbers that there is a definite improvement in the mid brain in the posterior with little capsicum in the coronary radiator and this gave you the relationship with the change in the functionality of the child. So, the child function was actually because of the changes of the brain not a local muscle power improved. So, I always believe that everything comes to the brain that is what that is the proof of the whole thing you know and similar thing we tried to show. So, this is what we said at the end of the story that this may act as a guide for the objective assessment of therapeutic response in the children. Most people say that the child improved it is subjective to objectivize the improvement you have to show the changes actual changes in the brain and that is what we showed for the first time that changes in the in the brain. Then the same question was that there are two questions which we raised from this study there is improvement in plasticity is the vortex required can we do without vortex can we do with physiotherapy alone or we combine physiotherapy with vortex because there is a large chunk of population which actually is deficient in money. So, they cannot afford a vortex they will keep the child they leave the child you know dump the child there sometimes they get tired of this the mother and the father gets more tired of a child the child himself you could have carried to the hospital do exercise the child does not show much improvement according to them. A child is sitting on the floor cannot start running at the most he will get up he will work a few steps with a with a caliper or with you know those kind of things and for some parents not enough this is it is it is tiring for them in whole life. So, we decided to look at this this we got a dvd grad dst grad where we try to look at this effective physiotherapy with or without vortex and using technography not the R y analysis. So, this same thing which we did earlier this is now published and the interesting thing were the if you look at the two groups one group is with physiotherapy and one is physiotherapy with the vortex both are showing improvement only with exercise and vortex exercise both are showing improvement. So, as far as the improvement is concerned both are showing improvement then what is the benefit of b over a that is the next thing we had I think we had discussed we talked about a our statistician how to show the difference if it is there or not then it is listed the what is called as the relative index of improvement change delta change or something divided by delta or relative along the same. So, that was suggested to me by a couple of people u s actually that one do not take this as a direct measures and create a kind of a delta difference between the two and that is what we did actually in this paper and that took couple of years to publish it actually after the work was done primary because we were not sure methodology what to do use in this you know a number of queries on this. Now, this is the comparison of the mean F a values in the motor and then sensory fiber, but the baseline and follow up. So, what we showed on the score GFS score improvement the same thing is shown on the motor and sensory both are showing improvement. So, the plasticity changes are seen not only in the sensory, but in both and the same was true with the vortex through that also, but still does not answer the question should we use vortex or should we not use vortex. Now, that is where it all when we compared the vortex directly the two groups you know because they were everything identical except the vortex no vortex we took the subjects over in the same grade same psychology, same cognitive decline everything same and same IQ everything we did change no epilepsy. So, it is a very selected group patient we took just to ensure that we do not kind of a confound results based on that and if you look at this there is no difference in the F a value the baseline F a value of the follow up and then we did the delta the difference and there were no difference in delta and relative delta when we can get the load difference. So, just there were that the vortex may not be of much value except that temporarily it will cause a flux in detail you can start exercising, but the end result is 6 month the same for both of these. So, you can say money for this now that this is the GFM score baseline and follow up follow up this improvement group 1 to 2 not significant, but still there, but you look this is critical score as well as the imaging score did show much difference you know look at this. Now, this is the sensory and motor bundle PSN correlation with the scores that they show relatively correlation with the F a values of sensory and motor with the GFM score actually. So, what we concluded by the study was that children with identical kind of disease may not need a vortex which is a big relief to the patients. So, physiotherapy done well is as good as using the vortex if it is a bit together. So, that was the question DSD wanted me to ask answer and we have answered his question. The next this is just an example the same in the graphics which we are trying to show same thing in graphics which we are trying to show again this GFM score whatever I have talked about the table the same thing showing that. Now, this I added on in the slide this is a guy who is considered world authority in CP and he is worked he does the similar work which I do actually on DTI also. And we have a lot of data from this group also on the FC testing data format also which you will not be at later in published there is a next in combining I mean you need some staff to do all kind of things you know data is there with us. And you are welcome if you want data from us I will give it to you no problem somebody has to write this you know. Now, this is an example of the functional MRI in two weeks treadmill training this guy especially works on the treadmill with the children. He has specially designed that he has a lot of funding in the vast you know and he does all kind of things he is a neurologist he does kind of this kind of thing. And he has shown there is improvement in the functionality here in the this children we cannot do active exercise. See do we do a passive exercise any short changes in the brain function by f m r i you know. So, what we showed on the DTI is again shown by the functional MRI the placid changes are there in the brain following therapy and it is important. He is a believer of vortex because he is funded by the company you know for his projects. But for me I am funded by the government of India and I do not believe this because I basically want to support the patient not support the company in this you know. Now, this is the last story I want to this is another story which means we decided we had another very sophisticated technique which we talked about yesterday also is ASL artisanal laboring. See you are actually quantifying the flow blood in f m r i right bold celibate blood flow in the volume and this method is being now tried more and more in the f m r i. So, we decided to look at how the celibate blood flow changes this was somebody publication actually now. In this children we did everything on the c p whatever you could do you know with our methodology. We even tried f m r i it did not work very well actually on this what he showing. So, we are getting lot of artifacts in the data I do not know why you are getting data artifacts on this. So, the basis why did we start doing the c b is the blood flow blood flow quantization. I was personally interested to see my initial thinking was that blood flow should decrease if the area is damaged and this was decreased or the normal c b f has been reported in patient with c p gives a 0 and 133 yesterday. In fact, this was the question which was very critical a lot of people when we presented the data and not only me other people also seeing the same thing which I am saying. Initially people thought that I have not done the right things in the right way I told them I am saying the right what is should be done right in the word when couple of more people said start seeing the same thing. Then only I was right, but initially I had faced lot of criticism when I presented this first time in the paper I s m r m and lot of criticism came to me people are after my life this is how do you explain this how do you explain this. I do not know this observation right now and alteration a s l is possible because it is a simple technique low radiation no non-inducative technique available and the c b f wide metal university correlates the structure and function connective to the brain. This has been shown in 2011 that is the only thing I told them look this is universal relationship between the connection and the function c b f. Now, this is how the a s l image looks like you have seen the d t i t 2 and the flare, but this is how the a s l looks like the wide metal has low flow and the grain metal has more flow that is what you expect right that is what is beautifully shown on this. So, my issue was what we did was we co-registered the data of the d t i which is the job Dr. Rathore bring all registration this whatever we want us to do and then the issue was that whatever r y we are taking is it a r y we have to do or we should do a global analysis. So, I waited for practically 2 years before actually I wrote the paper actually we have the data available with us then we do it what is called a v b m analysis in this whole group you know and this is the result of the v b m analysis. Now, significant increase in c b f this is the color you can color scale you can see this is 0.001 highly significant you know difference is seen increase significant in c b f the grain metal has been shown not only the wide metal grain look at the grain metal showing the changes in the different engines of the brain. So, c b f was increased even by the automatic analysis what we initially said was a r y analysis which I discarded because they were very critical of whatever I was doing and these were the wide metal changes as you can see that lot number of areas showing a variety of the wide metal. Now, then what we did was this is a comparison of the fallout was the fallout of the same children there was definitely a decrease in some of the areas you know they were the further increase in this area you know in the in the grain metal areas you can see there is increase in the grain metal areas some of the regions in the grain metal which were abnormal initially and what is interesting was there was a decrease in the wide metal area flow. It means the grain metal damage needed more flow in the one exercising how about the wide metal flow decreases in the some of the regions which we have seen that automatic analysis this is 6 months following therapy you know and these are some of the numbers which we got from those coordinates that there is increase and you can see the c b f is definitely very high as compared to controls a d c is high and the f a low low f a and the high a d c very consistent what is happening. So, this is a fallout comparison of the grain wide metal number what I showed you on the images increase and decrease and what is interesting was it was some of the area where the c b f was increasing the f a and m d was also going to changes. So, we concluded from this paper probably the c b f is better measure of damage than the the technology because some of the regions we went back with abnormal c b f to quantify the values of wide metal f a values they were not really abnormal maybe it is a more sensitive indicator of the damage than this that is what we tried to conclude this paper actually. Now, this is a loss with this girl actually she is the first lead author in this she was very keen to as a person in cognition she said I want to write a paper in cognition not the not what we are doing therapy and all this is interesting you know and she did all the exercise of doing the ROI analysis this paper has come already in psychology she had I think 4 or 5 papers with us in short time. Now, this I showed example how it looks normal and abnormal grain on c p and this is the test which I think you have a copy and we gave you the same thing which we used in this children from 3 to 4 years to 10 years we had children and most of the range was between 4 and 7 years I think that we excluded very different ranges of children in this group and you can see a significant difference in the little side and these are the changes of course you see in the f a values and these are the correlations memory exclusion closure they all showed some relationship some areas of the brain function for this. Now, this was the question which was very interesting which was asked that there are some of the children which had a low IQ as compared to the normal verbal IQ and the low IQ and he said maybe it is affecting the re-recycle you know with the f a values and what you found there was significant areas in the brain like the temporal white matter and the occipital white matter which showed a significant difference in the f a versus with the 2 groups also. It means the white matter damage is more in children with the poor performance you can see like for 0.4 and 0.4 0.6 0.27 as compared to the and it means these are involved the IQ the temporal and occipital leaders are involved in the IQ as well this was pointed out by the review also we had to realize the data and he said why did you look this and have a look and see what it is and we found it out. So, I think with this I conclude that there is a defected condition as you can see they have a relationship with the white matter relationship with the grey matter changes in blood flow are there which are being affected by the C P and the changes of plasticity are seen on the therapy. So, it is the area which involves in neurologist and orthopedic surgeon psychologist psychiatrist and radiologist. So, this is a very wide area which involves everybody for the point of view of the neuroscience all spectrum neuroscience are involved in this kind of disease process and which can be very you know gratifying if you can help these children with little bit in anyway may be in the cognitive improvement may be in motor improvement may be in psychological improvement whatever. So, these children really deserve it and lot their fault when they are born and we can definitely make some difference little bit in by whatever way it is to and there are number of societies spare societies are aware of the country they do hardly anything except making money that is the most discomforting part of the whole story you know. I have tried to contact number of these agencies because I want these children C P and that is how I was contacted them and they will say you know we want this and we want that and so you know kind of thing as well I can do a number I free I cannot do more than that. So, these are the commercial organization not really the philanthropic organization and they are the one which are harming the kids rather helping them you know they give you some wheelchair this and that you know to make them comfortable, but what is goes behind that nobody knows in that. So, I it if a person in a computing science is interested in this area especially if you can help them by improving their you know IQ improving their by what is called as psychotherapy. So, this is where we have a chair you can help actually with this children with this thing I conclude I think my presentation on this. I did understand probably it is related to one of the first slides that we showed you said that C P something which does not person and it does not increase once the injury is caused. Then why is it that between 1 to 4 years of age there was actually the difference IQ difference was increasing of changing between normal and C P. See normally what about damage it occurred at the early stages. So, the IQ in the first three months is not no way to quantify IQ actually whatever the Billy score is there whatever you do you know you calculate that and once you start to calculate the IQ it is at the bottom wherever it is. So, what I am saying is that though the child is the normal child IQ is going up here the IQ is not bottom from practically the time you start quantifying the IQ that is what I mean this is from the published literature I am saying that is what is important that is how they show that and C P is once the injury is occurred to the brain. The only way you can improve function is by improving the plasticity by physiotherapy or whatever psychotherapy or they call it as a different kind of therapies people are now giving to see their condition improvement see their motor improvement this is just a way to improve their plasticity and brain has a lot of reserve. The beauty of brain is that whatever is damaged is not that is all is available in the brain you have to get the area out which is can become more functional and become more active in this. That is by definition C P is it does not it does not worsen you will never find a child of grade 4 grade 2 become grade 3 no he will remain grade 2. He can become grade 1 improve if you help them with you know all kind of things, but certainly he will not go to grade 3. What another idea disease you see like for example, tumor for example, some of the metabolic disorders you know like A D H this is non-liquidistrophy or something this is a constant decline as a function of age it is a progressive disease, but this is a progressive disease whatever had to happen has happened you cannot go beyond what you are you can go only improve you cannot go down. That is why in fact people were saying initially now people are diagnosed C P as early as 1 month and 2 months and so on and so forth, but if you look at the literature about 10 years back the definition of C P a child has to be at 2 years no progression at 2 years we call it as C P. Now this definition is changing because of new technologies available new methods are available to say C P to show it is hypoxia. We have done a study where we did show the child see the child is birth showing hypoxia classic hypoxia we followed them as a function of age that some of you could publish actually it was a work which was done by one of the students actually and we just could publish that study where we showed repeated studies that how the tissue is changing with age in that area most of the time area does not change very much yesterday is there actually. So, you can call C P as early as 1 month or as early as 1 day rather than calling it 2 years that is how the definition is evolving, but not like 5 years we need a textbook they say 2 years you can find definition, but that definition not accepted in the academic community it is still accepted as textbook level, but not at the recent level not accepted any more. It leads to the DTI correlates of combination what were your measures of combination where you measuring the process where it was going on or was it a test like an IQ test. It was like the kids which are available for testing the different like I gave the names of the kids which we used and those kids were done at the baseline and after 6 months of therapy. No, you will like test tissue, better test tissue performed.