 I came to India way back in 87 when I started working with this in Delhi and that was the time when we look at the brain. Structure used to be very excited, oh well this is how you can see brain. You could see salsa, gaera is a grey matter and white matter. And I remember when I was in London in 92, 93 and that is the time that FMR I was getting generated and people are saying well I am not sure whether it is real data or the factitious data. And I worked with the great guy in one of the labs in Hammersmith and he will say well I am not sure what is the signal I am getting. And it was primarily because the you are expecting a change of about 1.5 percent those days field strength about 1.5 percent change and that you are looking into that particular thing and the noise level was about 2 percent. So, the functional number are initially the people who are not very you know inclined they say all I am not sure about this. But it has moved a long way and every specialty in neuroscience has accepted it as and more so with the neuro-cognition, sociology, psychiatry because they have nothing to look at that is the only way they can look at the brain actually. So, that is how it became very popular with them and with the clinician it is still remain a tool to look at the motor strip, the sensory strip and the language because a surgeon wants to know that how much far away it is from the tumor and how much you can exercise. And that is the magnet which we have and it is a special magnet is a very wide bore magnet 70 centimeter magnet and it has the themes and the light system you know which can vary according to the requirement of the patient. So, the mode elevation you know if somebody likes to see a dull light or some theme of something you know we have available there and that gives you at least special confidence with children small children that is why this lighting system was designed and this is the first time in the country we have this kind of lighting system in the machine which is not available anywhere in the country. Now, question is we are trying to measure the neural activity and the best way which we have been doing for ages to neural activity recording in the human brain is by electromagnetic techniques. Electroencephalography and MEG with the currently the MEG which is being used it has an excellent temporalization and it matches with the brain you know functional connectivity, but it lacks the resolution that is where people start looking at the other kind of methodology like hemodynamic techniques and pet was being used before the MRI came into picture for the functional MRI or the functional imaging. And the pet was based on the glucose utilization of cells and we will talk about that how the glucose is important and how the oxygen requirement is there and so on and so forth the brain, but the only problem the pet was pet had a poor temporal as well as a spatial resolution, but with the coming of the MRI the functional MRI system available the functional as it became available you could do it any number of times no need of any agent extraneous agent no radiation the resolution was good and that is why people thought that this is the way I think then everybody jumped on it from psychologist psychiatrist neuro cognitive scientist I mean all everybody in the world was looking at I think they use more scanner than we use scanner for this and so that is the truth. Now, why use the MRI the clinical use basically I have mentioned to be the pre-surgical planning for brain pathology the surgeon wants to know what exactly he should exercise and the basic research is being done by all over the disciplines for an animal as well as humans on the humans you know by all kind of specialist even I was surprised people in arts also they are interested in functional MRI that is the kind of interest it generated and the very fact there are more than 50,000, 60,000 papers actually currently on the and every every year every day you get addition of the papers on this it shows the interest is still there though it is more of getting I am getting bored of this reading this you know because the same kind of little bit of is there and same kind of things are there, but that you give the tool to a scientist to look at the brain the way he wants to look at the brain. So, why all excitement as I mentioned compared to pet in this spec which was the one which was being used before the MRI became available increase the temporal resolution increase the specialist no radiation no invasive same subject you can do number of times you can repeat paradigms in the morning in the evening in the night depending upon what is the paradigm you are looking at and on a modern scanner the currently available scanner the temporality is going pretty high the resolution has increased especially 1.5 to 3 tesla or 7 tesla field strength the resolution has tremendously gone up in terms of, but still we are not reached the level of neural to know what is neural activity you know. Now, the next issue what is the MRI it is a methodology by which we measure the indirect brain functions indirectly the brain function this is not a direct way of seeing the neural activity it is an indirect way as a lot of debate on this a lot of physiologists do not believe what we say actually to be very frank because there is a lot of contradiction between what we see on fMRI and what physiology shows you actually on the brain. So, that is where the issue is I will talk about that MRI focuses on the anatomy of the brain it shows beautifully I mean there is no way to see brain better than MRI and fMRI focus on the brain activity what kind of activity it is pretty well known all over the world that the blood flow and the oxygenation are linked to the neural activity because any neural activity need the flow of the blood you need the oxygenation you need the glucose utilization and so on and so on this is not everybody. Ogawa was working on NIH at the time is a Japanese guy and there was another guy called Robert Knight who was working on the CAD model. So, these are two guys actually came simultaneously with both were in NIH I was there in at that time that is when people are saying that I mean I have seen actually the start of that those days you know and they talked about I think talked a lot to be discussed a lot about this and I said I still do not believe this you know what all this and so on and so forth. But, anyway this is how it started and that is when Ogawa came out with the idea that you can actually show the function of the brain and the assumption was that the brain requires oxygenation and we just carried by the vasculature any change in the functional requirement changes the blood flow and the blood flow causes the increase in the oxygenation in that area and that is what we are trying to make use of it all the time. Now, this is what is we know that hemoglobin is paramagnetic the deoxy hemoglobin is paramagnetic and oxy hemoglobin is diamagnetic. So, that is what we all playing in the FMRI you know basically trying to do the paradigm create the increase in blood flow the deoxy gets replaced by an oxy more oxygenation which is the requirement for the brain and the difference of the oxy and the deoxy we take it as a net function. So, basically it is a vascular change in the vascular oxygenation which we are trying to measure and presume that it is connected to the neurons in that area because the neurons are requiring the blood the neurons are requiring oxygen the neurons are requiring glucose. So, the FMRI the functional imaging was available for the FMRI we gave available on the pads and most validation initially was done on the pads scan. Whatever we are doing on the FMRI we will just cross check with the pads scan which was the one which was available you know and because it was dependent on the blood oxygen level and this signal was called by Oga and his group as the bold signal blood oxygen level dependent signal oxy hemoglobin deoxy hemoglobin diamagnetic versus paramagnetic and the interesting there is a terminology in M R I will talk about that is susceptibility more is the paramagnetic or a paramagnetic material is more is the susceptibility which you see in a magnetic field and this is what we call as a T 2 star effect the T 2 of any tissue is longer than the T 2 star and that is what we have used it in this methodology to quantify the changes in the blood flow. People keep asking why not to quantify the blood flow simply but this is a technique called ASL which is available today in the world or there is another method which I think Dr. Rathore and we have tried in other other models where we have used the FOS component diffuser bed imaging the FOS slope component any change in the functionality will affect the water molecule movement across cell membrane and that is what we have tried to quantify what is called as a FOS component and the Libhian is coming out as an idea why not to use that FOS component and see the function that is more close to neuron than the blood. We were actually we said see the change in the water molecule movement across cell membrane that is more close to the real reality than this reality actually this is what people keep talking about and there are number of where the papers are available where Libhian is shown the only problem right now is the FOS component signal change is still not good enough 1 to 3 Tesla. So, one has to move to higher field strength to see more and more of this kind of thing. Now, this is what I said what is the basis biological basis is the neural activity local consumption of an ATP local energy metabolism increase C M R glucose metabolic requirement of glucose oxidation requirement blood flow is the blood volume. So, what we are interested in the whole story is the CBF CBB is the C M R O 2 oxygen demand blood flow and the blood volume this is a whole story of the functional imaging I mean for me it is a very simple method it is the simplest methodology available for I to be used, but it gives you lot of fascination to my friends in psychology sociology and so on and so forth. But methodology is very simple for us it is no big deal doing this kind of technique. Now, this is what we call as a hemodynamic response means that hemodynamic response in response to the neural response. So, there is a whenever like even I am talking. So, there is a requirement for the neurons the blood flows and that is where the thing is the blood flow changes and the oxygen changes start coming that is what we are measuring is all about. Now, delay in activation peaking and then the base line coming to base line and the total signal change is about 0.2 to 3 percent I mean you can see what is the change we are looking at 1 is 3 tesla is 3 percent that is why you see, but the signal denies 1 is 7 tesla is about 5 percent because the T 2 star is linearly related to the field strength. As the field strength goes up that is why 7 tesla is going to be a future MRI on the humans in the next I think 3 to 4 years and we have kept our demand actually to all owners that we should have a 7 tesla in India you know and especially for brain and the musculoskeletal system we should have a 7 tesla because it gives you more power to look at the data more with a higher resolution. I would like to go to 30 microns 40 microns 50 microns on the brain rather than looking at the 1 millimeter data or a 0.5 millimeter or a 5 microns right. Now, this is the hardware I showed you the example of the magnet this is how the magnet hardware and the software are connected to the machine and that is what and the problem with MRI is that MRI is not something you can just walk in and walk out. It is a high field magnet you need to know what can go inside the machine even for the paradigm generation some of the things which you put inside the magnet have to be magnetic you know acceptable this should be anti magnetic this should be metallic which is attracting the magnet. So, that is the biggest challenge you know whenever you take anything lot of people are now working on different kind of things to get the anti magnetic designs or different things. The camera goes in now I think about 87 not allowed to take camera the shutter start moving you know now they are no shutter camera, but I am telling you those days the shutter will start flashing you know because the power is magnet so much. So, I think the things have to be designed I have to be very carefully looked into when you design your paradigms for functional MRI and this is the current technology allows you to 3 tesla machine which has the magnetic field strength is equal to 60,000 times as strong as the magnetic field look at the power of the magnet you cannot imagine the way it flies any iron flies but object flies it flies like a missile it we call the missile effect you know on the machine. So, you have to be very careful when you are going with this kind of things inside everything has to be removed has to be checked in properly the instrumentation which you want to look at has to be very carefully designed. So, that it is it allows acceptability by the machine itself now what is interesting in this whatever paradigms you want to play you need to have a camera inside you need to have the screen to project the camera and all the paradigms need to be looked in by the patient or a person or the individual lying inside the machine it has to be mirrored into the eyes. So, that all was developed right in front of us when we started looking at this and it is available actually in the new machine which we had bought I bought everything in that machine actually we had a complete set of FMRM machine actually has to be bought everything in that machine. So, this is what the design of the system is specially for like button response you want to push a response yes no whatever you want to do all things are designed into this. So, any paradigm which has to be decided by you it has to be acceptable the machine within the confine of the machine we have to design those parameters. Now, the other FMRI or MRI equipment whatever FMRI one I think you want to make it is a myth by people some lot of people say that FMRI and MRI are not the same they are the same they are done the same machine a lot of people say that the gradients and other thing they are the same you need a magnet high field you need a gradients you need the RF you need the same you need everything like you like same or the same calculator all this you need like any machine. So, if you I sometime we are some scientist saying you know all we have FMRI machine. So, any machine which is have a good field strength can do an FMRI provided you have the desired attached hardware you can use in you know extra to put in there. So, every machine is capable of doing RF coils are required the T 1 to relaxation times what is important is the T 2 which is the decay of the MR signal after the RF pulse is delivered and it measures as a T 2 relaxation or transfer less in time and the T 2 star which is gets quickly defaced because of the in how much it is the magnetic field and that is what we are using in the FMRI the T 2 star effect which we use every day on the clinical practice I use T 2 star effect every day you know in some form or the other. Now, what are the techniques which we are using the most we use initial technique before the API because the interesting thing which is about the functional MRI is before the EPI the eco-planet imaging became available people was using the flaw the fast low angle shot or a graded echo imaging to look at the function, but the graded echo imaging was very slow as compared to the EPI and EPI became available simultaneously in 93. So, the concept of EPI came I think even before the MRI was designed I think the the Peter Mansfield gave a gave a concept in 74 75 the theoretical concept of EPI you know for which he got normal rise actually and actually the implementation of the EPI was possible in 93 92 93. So, you can see that what how much difference in actually is is the believing and seeing it being done that is that is the kind of thing is there and once the EPI became available the EPI is even today all techniques were using in EPI best techniques. Now, we wanted to make it first much faster the EPI to be much faster and that is why a lot of ultra fast technique came like the half furrier sense smash kind of techniques where you could actually take the central case space which reduce the timing of the of the of the phase encoding steps and you could get much faster than what we are doing. So, today you can actually get typically a single scan about 100 milliseconds you know which is pretty fast actually is what it is. So, now the issue is why T to star I mean I told you why T to star because we are using the oxy the deoxy difference and T 1 does not show the difference it is basically the T to star that gives a difference that is why we have to use a T to star imaging for an EPI is not the best T to star imaging, but EPI is being used because that is the fastest it has a very high temporal resolution that is why we use it because moment there is a you think there is a change in the neural function that I cannot catch by the machine whatever best you can catch you should catch that that is why a lot of people say it is a stabilized function you are seeing not the actual function you are seeing in the brain I mean there is a lot of signatures there. So, this is what is the mixture of the bold effect we call it ultra neural activity changes the local hemodynamics in the f 1 this is what actually we are talking about the bold function and there is a conflict need of glucose need of oxygen combining both and what is causing the whole thing you know it is confusing, but for us for this talk for any of the talk in f m r i we know that indirectly we are measuring the neural signal that is all basically we are trying to see the hemodynamic response function basically the neural function there is no linearity between the response hemodynamic response and the neural function that we all know and that is what best we can do actually and this is correct because it is important because some of the f m r i and the neurophysiological experiments have yielded conflicting results you will surprise even the motor strip in the brain what you see when you go inside the machine and open the brain and stimulate the motor strip sometime it is not the same as what you see on the function m r i and to their extent. So, there is people have done the f m r i inside the machine inside the operation theater then they stimulate that area and again they look at the area there is a conflict in this. So, it is a gross make believe kind of thing in terms of functionality, but that is why I was saying that the blob comes in this way or that way most of the time these are the regions are involved and difficult to say what we are looking at. So, this is in order to the validity of the linear transfer model it is necessary to see how f m r i single correlates with measure of the neural activity, but doing this is not straight forward we all know that the relationship f m r i and the neural activity depends on the number of factors. So, one is that large region of the cortex over the long period of time that is what we are doing. Summertime the activity of the many neurons we are trying to catch up with this. So, that is what actually we are doing averaging firing rate of all the neural population and whether the activity is synaptic or dendritic we are not sure about what we are saying as I mentioned repeatedly. So, one of the guys who published in 2001 nature he said that it basically reflects the inter cortical processing of an area rather than a spiking of that area, but combining all the methods he concluded that bold f m r i is just an average function which we are trying to measure in that area rather. I want to make it very clear before we go into real thing and we believe that what we are saying is correct you know I am not sure about that even today. Now, what are the designs is used first of all whatever you are interested in you make a hypothesis create a paradigm the biggest challenge in f m r i is not the f m r i doing it or analyzing it is a generation of paradigms. What is your question and how you want to answer it how many subjects you want to take how you want to stimulate and what kind of design and paradigm you looking at is a block design even related to a mixture of all this and the parameters more or less fixed in m r i. I do not think we need to do great science to know the f m r i parameters for running a scanner what we need to know is the hypothesis how to generate the paradigms and how to get the answers you are interested in that is the most important part of this. So, this is a classic example of block design where you put on and off on and off then you can do space mixed trials or rapid mixed trials whatever you want to whichever one like you keep doing keep in a short interval or a long interval whichever way you want to design your methodology you can do that and everything has to come into the machine and pressure has to look at that and whatever method you want to design he has to practice his outside practice in a simulator before he has allowed to take inside. A lot of people say even to the extent that once you do this kind of practice the patient gets used to it habitual effect I mean we do not know there is so many things happening you know. So, a lot of people say habitual effect this effect that effect which comes on that trained you get trained you know you are training the neuron before that actually. So, is it not a habituation effect but may compromise signal strands the problem if you do a short thing short kind of a paradigm then SNR becomes very poor signal is very poor that is why people do it for 30 seconds do it repeatedly that particular paradigm. So, that you get a good signal noise otherwise the short spiked paradigm is not going to give you a good signal and so many times you put your statistical analysis you may actually become a noise rather than a signal. So, that is the case phase I think you have not known more about the case phase anybody else to transform the case phase into image on MRI and that is the software which is available currently is being used. The Unix based software are available FLE SPM which is the available Welcome Department of Imaging Neuroscience FSL is again a very technique which I have used a little bit not enough more in other other methods I will talk about that tomorrow morning and there are vendor based techniques like GE has a brain wave that is available at HPGI Philips has a Braille Voyager which is bought by the Philips actually I view we have I view but Braille Voyager again bought of Philips and advanced neurosemals has that kind of system. So, everybody has own system which is available and you can use any system you like which you feel comfortable with the most commonly used techniques are the FSL free downloaded from the net SPM and FLE. FLE so NIS is free you know it is anything which is the government of US does it is free to everybody. So, these are the software which are Unix based but they are freely available on the net SPM also has a known Unix like even in the windows you can run the windows but FSL definitely is Unix. Now, analysis is special processing estimating parameter of statistical model and making inference about those parameter estimating with appropriate statistics. So, basically how you play with your statistics data and how you lot of analysis has to be done this is how the analysis is done realigning if you are doing a group analysis you have to realign register the data together smoothing kernel is being used normalization template and lot of people using the there is something called as MNI template you call it. So, the MNI logic is to develop a template which everybody wants to put their everybody's brain into the template and try to register the template actually. But you can make a role template create your own data set and create a role template and you can use that also. But the most commonly designed template is MNI template everybody is using that and we all use that may not be MNI is not only in FMR it can be used in any way any type of brain function you are understanding not only in FMR and then statistical analysis you do and how much it should be your cutoff is 0.01 0.001. So, you can decide and you can actually check whether the function is actually coming from that by the functional paradigm which is attached to that. So, this is the various removal realignment co-registration normalization smoothies I talked about improves SNR and this is the different method models used for statistical model analysis and this is what actually typically comes as an observed function as you do the functional analysis. You find that the on and off can be picked up by the computer and when that point is picking up you can put your cursor and see whether the function was there you can put the area which is there estimated look at this and see whether the function was there or not. So, many times a lot of artifact has become in there and that becomes a function. So, a lot of rigorous analysis because now it is now more than 20 years old technology. So, people have done a lot of rigorous analysis and removed lot of things which were there earlier and lot of people reported artifact as a function in earlier days you know that is why in the first five years everybody used to call it as fictitious image not a function actually. So, that is the combination I just talked about both we have. So, that is the regression two sample T peer test whatever you want to use for activation maps and what we use is use a standard T 1 maps high resolution imaging of the brain and overlay the functional maps on top of this. Otherwise the maps that you get on a on a E P I images are pretty bad. So, you just collect your function and overlay on top of the standard high resolution imaging. So, you can define the not be 2 D and 3 D whatever you want to do the reconstruction of the brain and do that. Now, positive is a negative of more I know that is very important for us to know what are positive potential high temporal and special resolution. Lacks of radioactivity can be repeatedly number of times performed increasingly common state of the art MRI machines. You do not have to that is why you do not have to design a special machine to do FMI. It is a same machine you can use for patient use for you you can use for social sciences you can use for anything you want you know. And it has definitely much better temporal resolution than the pet even today with the time of flight and what about the pet is available today even that is people are using pet at all today in FMI. 20 years back yes not today negatives are extremely sensitive to head motion awkward environment for emotional paradigms inside the machine to create an emotional environment paradigm is very difficult. Contraindications are they are extremely claustrophobic interval magnitude while loud sounds from the magnet cannot perform receptor ligand study like pet inspect. And there is a time lag of 3 to 6 seconds between the brain region and activated in the blood flow increases. So, there is always a lag. So, you are not actually measuring the neural activity you are measuring the flow changes and you can use simply a dynamic contrast whatever you can use any flow method and you can quantify that why only FMI. You know these are the question people keep asking you know. Now, this is typically I use a lot motor function assessment of the motor task and this is probably I do almost once a day one patient a day I get on a brain tumor and the surgeon wants to know where is the motor speed. And it can be designed in different way you can do a tongue movement as you can do the passive movement of the limb you can do the hand movement finger spreading finger tapping finger tapping whatever you use basically it has to be motor activity. And you can combine all also to see the whole of the motor state and on and off like 10 second 10 seconds of 30 seconds on and off you can do you know for 6 minutes 6 times. And then you take an average of the on and off to get something whatever they are getting this. So, this is a classic example of the motor function which we have and this is what we do in the brain tumors. Now, this is example if you look at the motor strip here for example you know and the motor strip there. So, the mass is pushing the motor strip anteriorly the function is anterior. The surgeon left about 1.5 nanometer he did not go beyond the tumor. So, this we do along with the technography day in and day out that is our routine clinical stuff which we use every day you know in the clinical practice. This is how it is and this is how the function is coming you know like a curve you can see the curve and the peak is the function and then down and you can just take any of the brightest object put your ROI and you will get the function is right or not. So, pretty automatic I mean that respect nothing no great deal at all you know as far as doing FMRI is a simple thing to do FMRI. The paradigm and the processing these are the one which are important which you have either to do. Now, I just took some of the examples from the literature that pain understanding pain that is another interesting area where you need to know about the pain and once you prick a pin in the hand. So, I always believe that whatever I do here whatever I do the guy on top controls it. The brain is the fastest of everybody here. People will say there is a spinal reflex nothing even spinal reflex has to go through the brain and look at the speed with which it functions you know. If you see a loin you did not even wait for a second to look at the loin and say immediately back. So, look at the functional connectivity is so fast and people say you should call it earlier in the spinal reflex no the reflex is coming through the top. So, that is what the pin prick or whatever type of you know stimulus you give to the it goes through the brain and brain takes a call or has to be done over this. So, I have realized over 20 years in neuroscience that brain is a master whatever you do you know it controls everything and anything you know not in the spine. So, pain is not mechanical is that mechanical or that emotional or it is something to do with the sensory effect on the body why some people take much more pain than the others. Is there an emotional component in pain these guys have tried to do this number of papers have come on that. So, this is how people have designed the paradigm you can see a lot of expectation is there and where they have tried to painful heat and try to look at the function. And another interesting which I liked about number of people have come in that you put a pressure in the in the rectum the visceral pain. Visceral pain is much more different than the somatic pain it is more discomforting than the somatic pain. So, this later designed the methodology for the visceral pain and published number of papers in that putting something inside the rectum balloon it put a pressure in the rectum get a feeling of discomfort and see what is happening in the brain. This is related to the autonomic system you know which is getting involved in this. So, look at the stimulus look at the heat temperature 40 degree and beyond 40 degree noxious heat versus the normal heat I mean 40 degrees still not that bad. And stimulation prefrontal I mean this I see everywhere prefrontal insulin anterior singulate prefrontal cortex and the other one which are thalamus the other one which are actively get involved in this. The thalamus of course, controls this and that is what they shown is the main effect of laser induced pain on the brain regions and this is the intensity. If it is unpleasant or pleasant the intensity can be correlated with the type of pain you are giving you know it means the emotion comes into picture when the unpleasantness is there that is what they have tried to differentiate emotion from the pain. Some people even smallest pain they are more emotional and the pain get exaggerated some people they have no emotion. So, that is another issue you know that if you have the random population when you have the guys who is from the village and I remember when I was a student of medicine. So, a person will come village will come you put a stitch on his finger he said do it do it is required. On the other hand from the city is very sensitive not let you touch inlet let you clean this. So, that is the I mean I mean solve the brain what kind of development you have. Even in that you have to your selection of patient the selection of your subject has to be very very you know same kind of I mean difficult design to make. So, it looks nice in a picture what to design that kind of thing it is not easy and you get some blob somewhere I can tell you that is what I have. So, this is the difference between the visceral pain and the somatic pain the different area for the different pain and the lower GI versus the stretching in the and the somatic in the tonic in the phasic kind of pain which you can see the difference. So, it is nice to see that you can see different areas, but where does it lead us to I mean we do not still know we know something, but you do not know anything I am not sure about that. Pain clearly activates a large amount of neural tissue consistent with the original broad hypothesis that the pain is coming from the brain, but how to interpret in terms of you know real life situation you know if the guy is having a pain had a trauma this that how to relate in terms of functionality improving the functionality improving the pain of that individual that is another issue you know the chronic pain is all the more problematic. It helps you to understand pain to some extent, but where do you stand after at the end of the day that is another question. So, the very good question which you can understand, but what it leads to further we do not know there are issues which are still you know being talked about. So, this is a review a line from the review which says how neuroimaging studies have challenged us to rethink about the chronic pain in disease. Imaging study has shown that chronic pain is associated functional structure and chemical change in the brain that is putting into the range of disease state. So, chronic pain is like a functional is not doing thing properly that is why we are doing it. So, something has happened it makes you understand something is going wrong somewhere what does it mean we do not know. So, that is another thing which I have talked about very good tool to understand, but this is another example of block design which they have done actual stimuli no stimuli of the pain and seeing the difference you know and the rating they did the reticule pain the physical reticule pain of the physically induced pain, but versus the one which where you are told we are giving you pain, but not actually doing the pain and there was difference in the if you just tell the guy you know I as a doctor can tell you that when you go and inject something to the patient even while you are not even touching the patient patients are crying. This is called as hypnotically induced pain or perceived pain when you actually put in love for the pain comes in there and so many times the patient feels pain even after you take out everything and he said no I am still having problem and some guy said no I have no problem. So, these are the interesting issues which you know which I mean I like this some things I thought they should talk about those things. So, that is what he says the actual pain and hallucinated pain it means there is some activity in the brain even when he is perceiving pain without giving you pain, but it gets intensified the more you are getting activated look at the fall it is the way the fall it is becoming. So, they become all the more activated you know that is what he is trying to say pain versus emotion you know how much is emotional component how much is the pain component and I am not sure how to how to separate that I mean they have tried to do that I do not know if you paradise. So, when you give I remember when I was started doing psychology work with MRI I basically started with hepatic encephalopathy that is the one which actually made me think that psychology or a neuro commission as important for MRI you know and I was doing one paradigms you know neuropsychological paradigms and my timing was much worse than the normal individuals. So, then I asked them that is it I have a hepatic encephalopathy or my brain is not functioning properly or is it the way I am I am designed to work like this you know. So, some people are very slow learn they take more time to learn, but once they learn they do well some people learn very quickly, but they forget very quickly you know I mean everybody is like memory comes into play the short term memory the long term memory is all coming into play. So, I think this is another issue which is interesting important and I say that emotion versus the known emotion the difference in the couple of things I will just talk about now is which I thought very current you know magnitude and the chordal activation on imaging. So, when you tell something something you are pleasant some things are unpleasant how the pleasantness affect the functionality and the unpleasantness affect the functionality it is very interesting in 2012 at K. So, what they are trying to show is that the unpleasantness gives you more stimulus to the brain and the different areas are activated as compared to the one which are you know pleasant things you know and by subtracting they can tell that this is unpleasant part this is unpleasant part and so on and so forth they have designed paradigms for that. So, the magnitude of intensity what the guy what they have done is interesting paradigm they keep the guy hungry then they do the imaging and functional imaging and then as they are at rest and then they give a taste of sucrose which is a pleasant thing you know like sugar. So, if they give some bitter it is unpleasant thing. So, that is how they are trying to file out that how the functional activity changes in the fasting in the fasting stomach because the fasting you are actually hungry it comes from the brain the satiety center gets you get stimulated it comes from the brain. So, I mean it is all kind of things people have tried I mean if you look at the this literature it is full of everything you know. Now, this is another example of grammatical categories of objective noun event noun verb in order to say cortical user activation. So, noun and verb how they affect the you know brain activity you know. So, this is an example of the noun words pseudo words and true words and there is a difference in the activity of the brain. Now, this is by masking the pseudo and then you see the true activity coming in from there you know. Now, this is other interesting that probably like it the difficult question versus the simple question in mathematics you know and they found somebody who knows the problem how the brain function differs in the guy who is find get stuck to the problem you know they get a very new article actually. So, this is like they give you some kind of a paradigm you know like 2 and 4 and 3 is equal to 9. So, they create some 4 dollar 3 they want to push a button and then they change the paradigm and that is the that is how they want to look at this paradigm. And what they find is the different areas talk about the difficulty in mathematics versus the you know like metacognitive, anti-cognitive, mixed in the cognition you know and its relationship to the to the brain. There is another example is the holding disorders there is another called as like the guy who hold you know and OCD is again a kind of composite disorder. Now, how to differentiate a holding disorder from OCD. So, they have designed a very interesting paradigm you are saying if the guy has something which is of his own then what is given to him. So, what they found is if the guy who is has his own thing and you give him back he like to hold it you know keep it and the person who whom you give things which does not belong to him he is not very you know interested in that as opposed to the OCD. And this is a paradigm which is very interesting paradigm they design and they have shown that they can create difference in activity of the holders versus the OCD versus controls. So, there is all the different activation maps they are showing and another interesting thing which they are talking about is the hearing criticism like some people react differently to criticism from their own parents you know as compared to the others you know. So, the different design this again 2012 plus 1 it published and how the depression and what are the relation depression and the different activity you know. Criticism and rest then different like the hippocampal, the single arm, the frontal cortex how they are affecting the criticism versus the reaction of criticism to the praise how they are perceived by the individuals. And this is an example of criticism versus and the diagnosis of criticism versus the non-criticism. The lastly I will talk about MCI and how the functional neural correlates over tension deficits affect the MCI you know which is the one which we talk about in Alzheimer's early Alzheimer's disease which you as psychologists you are more interested in this. That is a paradigm they have designed and what they have shown is the difference between the MCI with the controls which are the areas which are affected with this paradigms in MCI aspect to healthy controls alerting an orientation effect. And the same way they talk about the different maps this is actually it is a smoothing nothing is an MCI versus the RC is more than MCI. This what you are seeing in the brain shape is very simple to make. If you go to the FLE or you go to this FSL these are the standard software methodology available on this. So, nothing great about looking at these images in terms of that. So, I think with this I just give you the brief idea of that what all the potential it has what all likelihood it has what all it can do and how far we can understand this I am not still sure we can understand everything about the brain function. But certainly it is a direction in which you go and little more positivity is there more objectivity is there then what a psychologist will tell you otherwise well you have some paradigm which are affected that is why you are and it may depend on your mood if I give you another example if a mood is not good I may not do any paradigm correct and that may gives an impression that I am having some psychological decline or a concrete decline. But if you have some objectivity then it makes it more meaningful in terms of understanding the you know your domains whatever you are doing. So, I think it is a simple technique it can be done very easily on any instrumentation. But you have to have the right kind of design of the paradigms to assess your question this is most important part of this.