 Actually, in this one hour I will try to cover the vitamin B deficiency and the effect on the brain structure, microstructure and brain function. Now, what we find in this country as well as the rest of the world is that vitamin B 12 and B 1, they are very commonly deficient in individuals. And the belief for the B 12 deficiency, you see more in vegetarians, they know vegetarians, elderlies who do not take much meal, they do not have enough means to take those things. And that is why they are deficient and they develop dimensions, early dimensions or something to that extent even Alzheimer's disease, people say the B 12 is associated with the Alzheimer's. So, one of the things people try to do is to add B 12 to their treatment beside the standard treatment of Alzheimer's disease. Similarly, it has been shown in the neonates and children who are dependent on the milk from the breast, not taking the dairy rich B 12 milk. So, they were the one who also get deficiency in B 12, the mother is deficient, child gets deficient. And elderly age groups, the age group, the adult age group is the one which is not very much studied. Most of the work has been done on the developing brain as well as the extremes of age, but not in the one which are adult. And mostly these patients come to you with some neurological deficit, they come with sensory problems, weakness of the limbs and very, very, very known specific things, which if a good neurologist is there, he picks up the things and he asks for a B 12, he asks for imaging and imaging may not always be very productive in answering these questions. And that is the reason I thought this is one area which is easily correctable, have an impact on the cognition and no cognition has not been studied in the adult population with B 12. It has been studied in elderlies, there is a lot of studies from the west which have with their cohorts of elderly, they do all kind of things. And same with the B 1, the thymine deficiency is very common, even in the west. What effect it has, a lot of alcoholics have thymine deficiency, people who take alcohol, they have a liver disease, they have liver damage and they have thymine. And one link in the cephalopathy which you all know as a psychologist, one link is Corsicopsy syndrome and that is very commonly associated with all, Marchiforobiglamis disease where again there is a thymine is associated with that. So, I thought I will combine thymine, we have done some work with thymine, Dr. Dr. And we have worked and we quantified the blood thymine level, which is very difficult to quantify, no lab does that actually. So, we struggled, we had a grant from ICMR, we struggled a lot initially in how to quantify, we tried different methods, different means and we bought a column, we had to send it back, non-working problem in HPLC. And finally, we found a method which is more easily doable and we quantified and we published that work actually. So, with this I start with B 12 to begin with and then I move to the B 6 little bit and just to give you an idea, how those so innocuous vitamins can cause havoc to your you know systems and without realising that is the cause of the problem. So, we all know the vitamin B 12 necessary for normal red blood cell formation and its deficiency can lead to the macrositic enema. That is a classic thing which occurs is the size of the RBC increases, they call it a macrositic enema and one of the subcomponent of macrosities is a megalobelastic enema. It is also involved in the tissue repair and the DNA synthesis. It is a co-factor co-enzyme to many of the things you know as a chemical point of view. It is known to cause wide spread neurological symptoms and wide spread psychiatric manifestation usually attribute to the abnormal myelitis synthesis. So, it is the wires the connecting wires which get defective and this is one of the reason we try to study the wires in our study and to see that how the wires get affected even when only standard imaging these they look absolutely normal. Now, it is involved as you as you mentioned in the hematopoiesis that is the blood formation. Cellular growth and its deficiency can lead to serious neurological damage and because and can cause tingling and numbness on the hands and the limbs. That is the typical presentation people call it as a as a peripheral neuropathy or psychological problem, there is no problem, the imaging is normal you know. So, these are the one who get tossed around and they really have serious problems. There are very few reports which you mentioned the reversibility of leucosumelopathy on the brain. Only once in a while you find a report case note you will find there were changes in the brain which were like white blood changes and they reversed with B 12 injection. But everybody who gets those kind of changes is not a B 12 and everybody with B 12 hardly has a change in the brain. 99 percent of patients sufferers the B 12 deficiency hardly have changes which is visible on imaging on the brain. So, it means it is a disease difficult to and the only way to prove is by doing the level blood levels. So, this is how the pathology starts it begins with demyelination, axonal degeneration and irreversible damage. If the damage becomes too extensive the reversibility is not there, it may not reverse especially the spinal cord. The limb may not come back to normal they may still have some deficiency in that because once the neurodegeneration occurs after the axonal degeneration occurs then it becomes difficult to repair. Brain spinal cord is an optic nerve and the peripheral nerves can be affected. Convention MRI rarely shows the brain wide but I as I mentioned to you and the changes are mostly in the spinal cord if at all. So, that is why we thought let us look at the spectrography and look at the microstructural changes in the fiber bundles. How they behave and how they are different from the normal brain parenchyma in a B 12 deficiency even when they are absolutely looking normal on imaging. Now, this is a classic example of how do you look at the B 12 deficiency can you. So, this is what happens is that if you look at this look at this if you look at the posterior part of the cord if you can see here. This is definitely brighter than the anterior part of the cord and if you look at the axial you find the posterior columns the postulatal columns are normal and this is what if you know as a psychology this is called as a subicord commanding generation to God in the body. This is the classical picture of B 12 deficiency but this classical picture is seen in about 10 to 12 percent of patients with the clinical symptoms. Majority of the patients have a normal some have very extensive some have called atrophy but this picture is there definitely I can say as a radiologist this is a subicord commanding generation to God. But this picture is rarely you know visible in the B 12 deficiency. Now, this is what is the white matter changes I was talking about you get a gross white matter changes you can see this absolutely bright signal around and when you treat them they tend to regress. This is a classic picture of the B 12 and this is seen once in your lifetime. So, you do not see it every day you know and if I see that I cannot say this is better I cannot say this is better because this is so known specific of the white matter damage it can occur in anything and everything. So, I call it like a toxic demyelation I may call it as a metabolic demyelation I will not call it B 12 deficiency because this is not a typical feature of B 12 deficiency. Now, what we have done is we have done some of the standard the psychological test which are adult verified in the population and not some particularly in Lucknow population. But this is what we all get as a kids and this is what we done the digital symbol the number connection the picture completion block design picture arrangement object assembly figure connection and the figure connection were designed by us because the number connection the one which is used for people who are educated they know 1, 2, 3, 4. But the figure connection is the one which is used for uneducated who are illiterate. When I joined as H P G I there was a guy called Dr. Nayak who was interested in the particle supplementary and he converted the number connection into a figure connection test validated in large population in the healthy population as well as the population. And we now this is the standard term accepted worldwide in a people who are not educated who can read the things and that is where the test became available. Now, this is one example. Now, this is the method of technography which were designed by Dr. Galtore and it is a very objective method of segmenting the white matter tracks because if you draw with your hands there will be some kind of subjectivity and they will not be there. So, I was telling him all the time that I will not accept any test which has subjectivity. If I draw true fibers extra I will get the higher F A value if I get 2 fiber less I will get less F A value. So, there he came out with the automatic segmentation method by which you could segment the just click the area and the whole fibers comes out make 2 clicks the whole fibers connected. So, that is the contribution which he has made to the D T I he has published he is the first author of the technical paper here and we have published a lot as a clinical part of. So, this method gives you all the fibers you can see the single of S L F I L F I F O and the phonics. So, beautifully shown and this is what we are trying to show is in the patients who are B 12 deficiency and they are been treated and then they are see. So, this is a group of patients who was had a B 12 deficiency, proven B 12 deficiency on who was still was high the B 12 B 12 deficiency means the B 12 has to be low even if the M M A or B 12 if the M M A is low high and the B 12 is low we still normal it may not be there, but B 12 low is a different way to see the B 12 deficiency. So, what we did was just compare the data of the different fiber bandage available which we can we could which we could do by the Rattles method of a tectography and we could actually see look at the look at the motor fibers and look at this motor fibers and that is a sensory fibers very nicely you can see the different colors A T R P T R S T R and the different in the in the healthy and when I use the word healthy very interesting thing I will talk about here is see I always believe that people we all in the lab are healthy even me are healthy. So, I think just came to mind that some are vegetarian some are non vegetarian. So, why not you do the B 12 because we were in the hospital where the staff had a free access to the B 12 level without paying anything. So, all the staff members were coming to us for this test as a volunteer. So, we decided to do their B 12 and the homo system level and we were surprised a quite a good number of people had a B 12 deficiency. So, that made me realize that we should not take the individual healthy based on their healthy on the clinical examination. This should be because the cognition is not picked up the final cognition like the vice test which we do they are like fine testing they are not like the gross motor or gross you know this intelligence IQ or something you know which is grossly of lab and you can say by the say normal or the gross course which you do that minimental function test or something. So, they are not the one which are having they are fine changes that is what is important actually in terms of cognition in this individual. So, I decided to drop this those patients on the list I did not do further analysis of this patient I was considering on the patient and the control who are having a normal B 12 that became a definition for me to take the normal B 12. So, these controls are actually truly B 12 normal that is one I want to emphasize here and that may give me an idea that we discussed in the last few days with Dr. Brijbushan that something which is going on we do not know what is going on and once a guy is having a poor MMS MMSC or poor IQ. So, you do not have to do a rocket science to define them right only when there is a fine changes in the cognition is there like mathematical skills for example, just give an example. So, that is where the difference may come I do not know I mean you have to you guys have to do all these things to design those kind of methodologies to know how we can do that. Now, this is the callosum just click the thing everything comes out of this that is all beautifully you know Tepitum, Naminiskai, MCP and when we quantified what we found was you could see the significant changes you know in the different fibers I will say it is a pretty busy these slides and there are two measures we do in the DTI which is I think you should be interested not only in the FMRI, but, Tectrography as a psychologist because if you have a good light and there is a wall in between then you cannot see the light coming through right. So, I think the message has to be conveyed through the tracks whatever function you are trying to assess and I think that is where the role of if the hand is not moving what function you are going to assess right then people do passive movement this movement that is only equivalent to the motor movement. So, the bundles are defective right the conduction is not there. So, I think for a psychologist one request is that look at the tracks also do not think that FMRI is a net in the word and try to develop a connect on theory like connecting the function and the wires together because you can have a good power coming in, but, there is no wire is short the light is not going to go. So, I think wire is as important as the source of light. So, that is what I wanted to convey it is very important message and if you look at this what we are finding is that there are changes in all the tracks most of the tracks suggesting thereby B 12 is a disease or what you call is affecting the central arm system. The spinal cord may manifest first, but, changes are in all the white matters as you can see from these studies that M D and F A are which are the measure of those things and they are and look at the neuropsych test. These are the test which are abnormal in this individual system. This is surprising you know that you have changes which are obviously abnormal and these are the numbers which clearly show the significant difference you know if you look at the all the tracks are showing. So, disease is not confined to like the posterior column of the spinal cord it is because it should not be why should a particular segment be when there is a defect in myelination or it is affecting the myelination, it should affect the whole myelination of the all the brain in the system. So, that is what we are trying to prove this has not been done earlier that is why I am very excited about the study. We have taken adult population and we have taken the cognition adult population B 12 levels and not only see the spinal cord we have seen the brain which is normal looking on imaging. So, this is a very very significant study and what a whomever I have shown worldwide they are very excited you know I think we should put the best channel and something this is what I am working on actually through that. Now, this is another example of now look at the neuropsych you know PC, DS, BD all are showing gross changes you know this. Now, this is interesting thing from the point of view of the pre and post therapy. You find the changes are reversing you can see that this is pre and the post in the different fiber bundles changes are seen in the diffusion diffusivity and the neuropsychological changes are reversing. It means that these guys apparently are not normal they apparently they are really they are not normal in cognition and which can be reconformed by the microstructural change in the brain. That is what I am trying to say. So, we quantified the area which is usually affected by the BD1 and the function which are connected to the wires those we have found out. So, this is the kind of correlation we have seen and some of the test you can see here show significant correlation you know with the our standard fibers showing the significant changes you know. I mean there are huge number of fibers and some of them are definitely showing the significant changes. Now, that is how a brain looks like on imaging. If you look at this brain is a perfect looking brain on T2 and if you look at the DTI maps as they do not show any gross changes unless you qualify. And if you qualify by putting the regions of interest in A, B or C and all these things it is very cumbersome and we do not know which all fibers are affected. So, I think that is where we use this methodology of quantify the bundles rather than quantifying the region of interest actually get the whole bundle out is the difference. And we hypothesize that we should have a defect in myelination affecting all the fibers not only 1 or 2 or 3 fibers. Now, this is the one which I wanted to share with you this data is based on about 55 patients where we have used technology, where we have used the FSL technique due to registration, MRI template whatever I talked to yesterday. This is absolutely done using VBM analysis everything has been done in this methodology as per the design of the west, but patient belongs to India design is west. And what is interesting you find is this is the TBSS tract based statistical analysis. The green are the green thing which you are seeing are the structure which are the fiber structure that is how they define the green area which you are seeing is the fiber defined structure. Now, the yellow areas of the one which are significantly different from the control. So, you can see how much white matter is different you know from the control look at the cerebellum look at the mid brain. So, wherever the white matter is there it is clearly showing abnormality this is important. Now, I think you can draw your own conclusion is it the cortex which is important for an intracognition or it is a white matter also is important. I am not sure you really guys bother about white matter anymore you only bother about the cortex. So, another message which I am trying to give. So, this methodology is that the white matter is as important as a cortex. And if you look at the cortex is the difference are very obvious and this is the highest significance. The yellow represents the maximum differences which are observed and red represents the lower part you know the significance goes down as a function of color. This look at the look at the similar fibers I mean this unbelievable which I which you mentioned in the technography the same fibers are actually seen even with technography still you will say well you collected your right or not what was wrong it did not do the right kind of technography. So, all criticism can be done, but even by an alternative method we are finding similar results what you are finding. So, that shows the power of the methodology being used by Rathore we say this standard method used worldwide and it confines to the hypothesis which we have. The violation de facto is there irrespective of the area of the brain and it has relationship with the functionality of the brain that is what you want to Now, this is another method we use and if you look at the changes in the F A which is a much sensitive measure of the fiber bundles then the M D mean diffusivity. And the mean diffusivity is not showing the similar changes in some of the area like this area is temporal area is confining to temporal area here. And look at the external capsule with external capsule here the occipital tracts occipital tracts here some occipital tracts here this is interesting. And what is interesting is the radial diffusivity see we did the radial and the axial diffusivity also there are number of parameters you can take to understand the microstructural changes in the brain. And the radial diffusivity was definitely showing much closer relationship in the F A if you look at this as compared to the mean diffusivity. So, you can just see that a normal looking brain on conventional MRI even on a conventional D T I can be unrewarding. And how this methodology they are independent methodology we are not doing anything I am not putting anything extra here and there it is an automatic approach 40 brain 50 this is 57 brains data and 47 controls is not a small number. So, how beautifully you can demonstrate the changes in different fiber bundles using different methodologies that is important. And if you just look at the neuropsych in the same group of patient like this is another one group this is another group actually. And we find the digit same number connection picture complies all are showing changes you can see that p values are different. The cortex is because this study can design the cortex as well as a white man it is the white part of bottom which is affected and we know from the basic science that how the B 2 1 affects the brain function. So, it is matching with what is means talked about 50 years back 100 years back it confirms to that what we are saying and it shows the commission deficit. So, that is pretty interesting now then we did the correlation studies. Now, this is one way of doing the correlation now today with the F S L methods you can actually put your correlation test and define the area vis-a-vis where the correlation correlation is coming. And look at the F A and the D S digit symbol that showed correlation is in number of areas in the brain. Can you see that brain stem temporal lobes, cerebellum, singulum the frontal white matter, external capsule, occipital area. So, that is the kind of relationship that it symbol had with this. So, you can define the your areas you know on the brain directly through this methodology. So, you do not have to guess from which areas connectivity is coming for that particular test. So, there is something I liked about this and this is very powerful become very powerful in terms of understanding the psychology vis-a-vis. Now, when we looked at the correlation with the F A with the N C T these are two tests which are showing correlation we did we tried 3 or 4 we did not try all of this we takes a lot of time it takes about 2 to 3 days to do each analysis high computation method is required. And you could see this is the area the singulum area showing you the negative correlation with F A the number connection test the rest was not showing that this is combining the control and the patient together. Now, this is looking at the correlation between the at the N P T and the R D the negative correlation of radial diffusivity with the D S and you can see similar area what I showed you earlier like less exactly similar to what we are saying in the changes in the R D values compared to the F A values similar correlations seen in the similar areas. So, look at the look at the reproduction the correlation and look the reproduction of the whole thing which we are saying here in this. Now, positive correlation with R D and the N C T these are the two areas singulum which you can see and part of this occipital zone or the auditory area which is showing you some changes and these are the green color shows the tracks. Now, then with what we do it for we try to get those numbers out from the regions and try to look for the correlation with the digit symbol and with the radial diffusivity exactly same thing what you say and there is actually which you can see the numbers are also coming out correctly what you are saying except in this particular thing the triangle is patient in this thing I was finding that the control is also in the relationship, but patient situation relationship the triangle. So, what I am trying to say is that you go back and forth you do R Y analysis of same again you find changes. So, you just take the global picture put the R Y individual patient from the same region and again you find changes are there. So, you can always confirm by any methodology it is there it is not a false it is not something which is coming from somewhere it is not just a matter of chance you got this it is actually there that is what is important. So, that is why it took us 3 to 4 months to do a rigorous analysis no because when we had somebody coming from US he said why not to check the R Y as well and see whether they are correct or not it will be doubly sure what is there everybody wants to have doubt and he wants to be sure what is what we are talking about and it turned out to be right it is a very extensive kind of exercise, but it is what is doing it because it gives you answers. So, this is a part of the story I wanted to cover with you with respect to B 12 I think this is something which should be the futuristic way to understand how the B 12 that the technology may not be available to you at this point in time in the field, but the proof of the technologies the proof of the concept is there in terms of technology Neurosyke versus a microstructure change of the brain that is what is significant and B 12 is something which is not uncommon to have a reduction. I think about 30 to 40 percent of population they say what you see not even the tip of the iceberg. So, you see a huge population which may be neglected and the calcium and vitamin D same way is the B 12 is the one which is responsible. So, moving quickly to another area which interest also is the time which is again as common as that if you look at literature time is as common as B 12 may be more common than B 12, but when you only know in from the history the Walik psychosis, Corsico psychosis and you know the Marchi Parvig Nami syndrome they are two thing you know which are seen only once in a lifetime. Now, we all knew the time in the efficiency you see why became interested in time in efficiency there is a reason for that. When we were working on time in efficiency not working time in efficiency I happened to spend some time at UCLA and my student who was also a student doctor Rajesh and he showed me the data of the obstructive sleep apnea. He wanted to look at the data from the radiologist point of view do you have any changes in the brain in this before the write a paper actually. So, they want the validation of the normality of the brain typically done by all basic scientist. So, I will look at the data I said well I do not find happy with the memory body they do not look size they are sub normal in size and I just pointed out number of time we are asking the sub normal that is not normal look the size. So, he told supervisor who was a very well known neuroscientist yesterday Dr. Gupta said let us verify that and he decided to develop a software methodology and quantify the volume of the memory body objectively Rajesh objectively and once he found there was significant difference in the volume of the versus the control he got very excited and we had a paper in I think the Neural Report or I think we had a paper Neural Report on this I do not remember exactly I was in one of the co-authors he put me as a co-authors because I picked up the findings actually. So, he had no reason to not to keep keep me in that paper and he put that. So, then I realized why not to look at our patients of the apatica and sublamity who are known alcoholic cirrhosis alcoholic we all know you know they will have time in. So, you give time in no issue with that and that was the genesis of this whole work see I started from somewhere else and I how I went to look to look at Simon and ours people are the first people in the world actually of this by the way I should tell you that. Now, we know the most common co-authors have deficiency is a poor intake in the food reduced absorption small bowel including alcohol abuse, crash dieting and needle dialysis these are the standard methods available for time in deficiency patient of kidney failure and dialysis who do a crash course in dieting because they have their own method of you know it is a major factor in the metabolism of glucose known that ingestion of simple carbohydrate processed in the body mainly to glucose automatically increase the need for a dietary time in deficiency of time in the results in axonal loss, one is disease peripheral neuropathy, alternation of memory and the seribility generation. This we know from our one is encephalopathy or one is corkscrew syndrome you know which is astrology can prove when everybody has shown astrology you know the guys who described their names have this they showed it on astrology. In fact, I had a big debate with one of the groups actually I was in Spain giving a talk on this. So, they were pretty excited very critical as you know imaging findings are known if you see them they are there you can say that yes they are there there is no problem with that, alternation in the signal intensity in the memory body, the middle thalamine, periaqueductal area and selective involvement of the carotidinol of cerebellum, red nuclei, dented nuclei, pharynx, spalanium, cerebral cortex in the basal ganglia and they characterize the nolial colic that is what they say nolial colic onyx encephalopathy I had a patient actually who came from Gorapur she was a medical she was a gynecologist she had I think something like for one week she continuously doing deliveries you know she had so many deliveries in nursing home she did not take her meal properly and she came in coma to King George medical college with an MRI and then they brought the MRI to me I said looks like a one nix encephalopathy and then I did repeat MRI at my place and I say well looks like one it does not look like J E J E is very common in that area and J E does not affect the memory body I said this is definitely looks like one nix encephalopathy she was given by what I mean B 1 and next day third day I saw the same boy and I called her with a girl I said how is your wife yes she is there so that is so that is the kind of response you know if you are aware of the methodology you are aware of the conditions and you can pick up a disease that is the difference she the woman who was in coma she was standing next to him and I asked how is your wife he said she is fine we gave her time and she got up so that is the kind of response you get so what I am trying to say it is an important efficiency it can call havoc to your life and it can be devastating so I think it is important for us to ambient the following volumes are reduced in conditions such as obstructive sleep apnea which because this is the paper from Kumar and metabolic this is a paper from us Mandel metabolic brain disease and sleep apnea and Alzheimer's this is what they have shown Alzheimer's has been everything has been integrated in them because we do not know what is Alzheimer's so we say everything is Alzheimer's right B 12 B 1 B 6 calcium and everything is whatever in D everything is in this M B D C is the fibers of the hippocampus where the phonics send effort into anterior dorsal thalapine and essential to root the signal between the brain area and integrate the memory function so I think this is what the this is from the brain behavioral sciences the importance of these apparatus hippocampal apparatus that is very important for memory and you know cognition we all know that right and time in effect that MRI if you have one of the several of the yes it is a good tool it can tell you but every patient does not have one of the several of the however it is not abnormal in all subjects with one of the several of the simultaneously you know if you see it is fine we do not see it is not fine that is not the problem you know the measurements of ambulatory body with MRI provides a means of identifying the cases of warning during the life it means it is not easy to define warning and several of the in the absence of quantifying the volume of the memory body or a single change in the memory body this has been commented by these guys from radiology. Now, this is the method I was telling you was a lot to develop segmenting automatically the fibers and this is how typically you see the warnings you know the cortical involvement of memory body involvement the thalamine the middle thalamine involvement very classic of the pontiff busy politics involvement very classic of onyx. Now, this is what we did we took the patient of acute liver failure very interesting acute liver failure acute and chronic liver failure and controls and this is the control and very interesting ACLF ALF and as you go down this is the one which showing the maximum reduction size of the memory body and the chronic liver failure. So, we had a control chronic liver failure acute liver failure and acute and chronic liver failure. So, acute liver failure is the one which causes cell reduction the size of the memory body not the chronic in a patient who is not alcoholic cirrhosis this is all nonalcoholic and what we did was we actually did the tetrography look at the phoenix in control ACLF and ALF that the phoenix and we quantified the thalamine levels in the controls ACLF and ALF ALF showed the ALF is the one you know what is ALF is acute liver failure. The person develops a certain loss of the liver volume because of acute infection the liver like a like hepatitis hepatitis A hepatitis A is the one which is commonly caused liver shrinkage, but sometimes B also can cause a certain shrinkage of the liver C does not cause that much and which is very common as the rain starts coming can put you know as the worst area for liver disease liver failure because of water contamination and look at the thymine concentration in the memory body volume relationship the phoenix volume and the thymine relationship more beautifully in the ALF than the AC look at the ALF and the ACLF both are there, but you can see the difference you know and this is the interesting story about children we had children who actually come for a acute liver failure they had no question of alcohol they are like 10 years, 8 years, 9 years you know and this is the profile at the diagnosis time and the follow up and the second follow up we followed this patient till 6 months and if you look at the liver enzyme they are absolutely normal they become more or less you know perfect, but they still suffer from abnormalities continue suffer the form abnormalities. Now, this was the clinical profile this is what all we did in this patients is always published actually and we quantify the IL-6 the immune cytokines chemokines IL-6 TNF alpha and the thymine levels in all this controls and you find as they recover the thymine level improves. Now, liver is very interesting, but why liver shrinkage should cause thymine deficiency the patient comes to you in coma the liver shrinks very quickly we do we are not supplementing thymine when the the guy is not eating anything it is sufficient in the food if you take your food sufficiently and you do not supplement thymine while the patient is in coma. So, the liver stores quickly declines and that is why this decline in the thymine is there as the liver begins to come back the moral story is you must inject thymine over here even the liver is going down the thymine level should be there to maybe that is the reason that to improve the functionality of the children at later date. Now, this is the main diffusivity values in all the regions this is C S values and this is neuropsychological test look at the neuropsychic test first time you could not do because patient was in coma as they recovered six weeks there is a six weeks and there is a six months look at the recovery even though it has not reached the normalcy in terms of you know, but child has recovered and you can see the relationship of this this is published already this is what. So, what I am telling you in other words is how important this small small you know things are like thymine and B 12 calcium which people do not care and for a normal visual in the medical terminology I call it is a person can walk you can eat you can talk is normal, but that is not true there is much more to normal than what we see and this is what all we see. So, I think this is what we should the moral story is that this is not something uncommon this is seen wherever we are and I think if you can help this guy by getting the B complex or thymine or calcium you know, newtage supplements. So, that is where it is going to make a better quality of cognition and better quality of life to the individuals I think this is all I want to say about the vitamin deficiency and the cognition and it is important. So, I have a general experience when the staff was called and we found that in many of the so apparent normal population there was deficiency of these vitamins. So, is it possible that in across the entire population some of us might be deficient in at least some aspect of nutrition some some nutrition. So, why not I mean we have a general profiling of all the individuals and then see the impact of. See I give you an interesting story if you go to the US you find that they find every material food ingredient supplementary you know with iron with B 12 with B 1 all the kind of things supplementation is there. In this country the supplementation is only there for the iodine this is by law because a lot of human cry was made by already issued medical conducted a huge number of studies and he showed that iodine is important like mental radiation iodine you know must be going on Gorapur area was the one which was very famous belt for iodide deficiency and coitre. And it became a law and it became like everybody time you get a iodide salt you know you here in this paper and the TV also. But, some of these areas have not been taken seriously neither by the nutritionist nor by psychologist and we do not come into picture I am by mistake I am doing this because that is not possible. So, I am nobody in the picture my interest was in nutrition from the point of view it is I come from a country which is deficit in nutrition you can see a lot of Kaposi whatever they call it Hindi you know malnutrition is there in this country. This is a part of malnutrition what we had like. So, the quality of human beings are dependent on the quality of food they take it will not be in terms of like a burger or something it may be standard roti and the all and chawal well it should be have good supplementation they should have proper food that is what is required to make them good human beings good means good in inflect good in functions see we want population we should be good in inflect in function. I am not sure what the criminals come from which may go on and what they have or something that is another story you can you can think about why certain people have you know different front and low than the other guys is the nutritionist something we do not know about this nobody has done this nobody thought about this it seems. But, this is one area I think I thought it will be good point to excite the psychologist to get into this area and to understand why it is happening rather than going into typical ADHD this which is a standard care practice care you know in neuropsychology and that is that does not give you anything what gives you importance is if you can define this problems in a population and resolve this problems and may be create in the next 5 years a legislation the supplementation of vitamin B12 thymine this is what is required in this country I am the odd man to talk about you have a radiologist I am not a clinician not a nutrition I am not a psychologist I cannot talk about this I can only give you what I can I can do the proof of concept the rest you guys have to take forward and do this. I have a data actually on this study also on a connectivity which I have not analyzed Fc the functional identity. So, I want to write a grant actually of a connect home and the B12 that is what I am trying to propose that if you can do a connect home and B12 and that is the way to go actually and get to understand how this whole thing you know and I will be happy if you could be a part of us and you could involve you where the part of a study of course there you could also be part of a study where you could at least ask you to provide us the right kind of test which we should perform in this way patient you want to design certain tests for us and that is where it is important to and I will certainly put you as one of the co investigator in the study which you are trying to get from in the US forum and it is important that this is done in this country. No one talks about this everyone talks about standard who care about schedule or OCD these are standard things which you have been doing for ages you know talk something different you know which you which you and me have not heard of and I am sure most psychologists do not think about B12 or a B1. Different thing by extension I mean the one thing that we are focusing is one why not it also be then that living in a polluted city for a longer period I mean even that maybe can have an impact on your cognitive functions. See when you see the polluted city no I understand I also want to say you know arsenic is one which is known to affect the brain function that is the one affect the brain function but if you look at the blood levels of arsenic they are not high in like for example in Kanpur they are not high in Lucknow they are small area in Lucknow where they we had some arsenic problem issues you know where the fluorine is high this is arsenic also has some areas you know in now but that is all but B12 is something which is like you know pollution in general in the air pollution if you think it is water pollution air pollution all these are important and how the air pollution is affecting the brain I cannot say anything about this at this point but this something I will label like I can I can I can show that it affect the respiratory function people talk about the air pollution but certainly not talked about the brain function. But this has a proven track record of the myelin synthesis myelin requirement carbohydrate metabolism brain function these are certain things you know which we are talking about which we know from our hundred years story of astrology, brain atopsies, brain functions you know we are no no but this is no way this is a way to prove that there has to be a way to prove that something we are not we are reinventing it we are not saying that we have we have invented it we are revisiting the area which was told by our forefathers you know how it happens I am not doing something different only thing I am rediscovering the same story in a in a different fashion that is all I am talking about and make sense.