 using cognitive neuroscience and the variety also different levels of precision of spatial precision and temporal precision that you can reach with these different methods. And also the importance in our studies to often combine different approaches because each of these approaches has a limitation. Okay, here you see in the y-axis you have the temporal resolution of these different techniques, right? So how precise you can be in targeting when a certain brain region is involved in the processing of information in the brain. And so you go from really millisecond range to, you know, hours, right? And so, and then, sorry, and I didn't say that what you have, we have in x-axis is the spatial resolution, all these different techniques have, okay? So, and you go from really from synapses, so from the level of the synapses that you and that you reach with microstimulation to the level of the cells that you reach with single cell recording and then you go from the different layers of the cortex and you cover the whole brain. So basically you have techniques, some techniques like those that have a very high temporal resolution and also high, pretty high spatial resolution are the techniques that involves animals, so that concerns animal studies, like the intracran recordings, even the optogenetics, right? So that's super precise in temporal and also in spatial resolution, although you have to bear in mind that if you look at cells, at single cells, you often lose the big picture, right? You lose the, you can focus in one, okay, maybe two, three brain regions maximum, but this is something very recent. So before, you know, the tophysiologists were looking just at a specific small portion of the brain, so they can really not look at the, for example, what happens simultaneously in different brain regions. Nowadays it's still possible, but it's still, it's a challenge for them. On the other hand, the techniques that you use with humans, they cannot reach that level of spatial precision. The techniques that somehow are approximate, so that try to approximate the tophysiologists, the ones that are closer to that is exactly the technique I'm talking today. So it's the transplant and magnetic stimulation and also the magnetic resonance techniques, especially at ultra-high fields, where basically you can have the precision of your investigation can reach, like, can go below a millimeter. So it can be at the level of, yeah, below millimeters, especially in structural MRI. Functional, you go below millimeter, but you have some costs to pay. But anyway, so normally neuroimaging techniques are good. TMS is pretty good, and we will see why today. Whereas, for example, other techniques like here, like EEG or MEG are very good in temporal resolution in the sense that you can target, so you can follow the information processing in a range of hundreds of milliseconds or few milliseconds even. But they're not very good in spatial resolution, because the spatial resolution of EEG and MEG, it basically depends on how many sensors, for example, in EEG you have or how many electrodes you have. And so normally you basically put caps on the head of the subject. So the density of this number of sensors or electrodes, it's limited, it's 128 channels, for example. So it's really the spatial resolution is the distance that you have between different sensors or different electrodes. So TMS is a technique you will see today that somehow has a good compromise of spatial and temporal resolution, and we will see how it comes. So TMS is a non-invasive technique, that's why you use it in humans that exploits the principle of electromagnetic induction, and you can basically allows you to have an indirect electrical stimulation of the brain. So basically, you induce a magnetic field, you induce an electric field underneath a coil that you use. This is a coil. So this is basically the old days when we start to use the TMS in the 80s, the early days, and this is how the machine looks like, basically. These are the generators, there are some generators of electrical currents. So, and then this is the coil, basically, that you apply on the subject's head, because of course, you stimulate from the outside of the brain. And basically, what happens is that the currents that hide amplitude, so flows into this coil, so there is this pulse, so this charge of current, very brief, that flows into the coil. So there is this rise in the amplitude of the current, then there is this magnetic field pulse, that the magnetic strength can be pretty high, so it can reach it according to the machine that you have available, it can be even the 3 Tesla. And then, of course, you have this very rapid rate of changes of the magnetic field that induces in the area underneath the coil an electric field. And of course, the intensity of this induced electric field basically varies, so decreases with distance from the coil. So you have a maximum induced electric field intensity at the coil, and then it decreases, this intensity decreases the deeper you go in the brain, because you have to imagine that you have the bones, you have your hair, you have the bones, you have the pia, and then you have the brain. So you have a few millimeters also to overcome. So this means that basically KMS can be a very useful technique to stimulate cortical areas, but not so good if you want to go deep in the cortex and in the brain, and so it is impossible really to target directly subcortical brain regions. So, and this is, you know, and of course, as you can imagine, you are stimulating from the outside of the brain, right, so that there are levels of approximation here, but, and also the effects that you produce underneath the coil depends on the geometry on how is the orientation of the fibers that lies below the coil, okay, so underneath the coil. So you see that there needs to be a certain, so if the current flows parallel to the action membrane, you don't get any, you don't affect the cell, you don't induce any action potentials, okay, so that you need to have a certain orientation of the current that you induce with the orientation of the axons, okay, and you normally what you do, you create some action potentials in the most superficial layers of the cortex, okay, this is what you do, and what you create is just, you sort of introduce some noise in the system, because you create, you produce activations of neurons, you don't know what type of neurons you are affecting, right, it could be that there are, you don't know what type of synapses you are inducing, whether there are inhibitory or excitatory, what you know is just that you produce some random activity underneath the coil, and you can have, you can have the effects that you can produce are disruptive, so because if the subject is engaged, imagine that you have participants to perform a task, like to ask to discriminate the duration of two sounds, and if the area that you are stimulating with the coil, it's an area that is important to that specific function, it's important for the perception of the duration of the stimuli, if you introduce, so you are assuming that the first place that if the area is important, it is engaged, there should be some precise connectivity in the network, so any, that you can participate by introducing this noise, okay, so the effect is disrupting the sense that what you measure, of course, it's the behavior of your subject, so the subject get worse, and this worsening can be observed, can be measured in terms of accuracy of the performance or the speed at which the subject meets their response, but the effect can be also productive, in the sense that if the subject doesn't do anything, and for example, you stimulate your motor cortex, so the piece of the brain that is responsible for the movement of your hands, then you can, of your muscles, the muscles in the hands, then what happens, if you are on the good spot, because there is a problem of where to stimulate, so if the coil is placed in the appropriate place, you can evoke a muscle movement, okay, and you can, a muscle movement that you can measure, okay, because you can place electrodes on your, for example, on your thumb, and then you can record the muscle activity that is evoked with TMS, okay, with this stimulation, and you can measure even the amplitude of this evoked activity with TMS, so you, in this sense, this is a productive activity. Another type of productive activity is if I stimulate your primary visual cortex, so the piece of the cortex that receives information from that, you know, I even can induce some phosphins, phosphins are flashes of lights, you can exactly, you can induce this very, very weak percept, of course, you can imagine that TMS is not a technique that, so it induces noise, so you cannot create a very complex percept, okay, but you can create this very simple percept, has a flash of light, okay, or a muscle movement. Excuse me, yeah, in the previous slide, you showed us some samples, all of these are active neurons, or some of them are example of inactive neurons, and the problem is how the induction is occurring within these neurons. Well, we don't know what, so whether if they're active or not, right, what we know is that you want to change the potential of in the tissues, you want to, you basically change the balance between electric currents inside or outside the fibers, right, so you don't know whether this, if these neurons are active, you are inactive, which something, you know, neurons are never inactive, right, so anyway, yes, they are inactive in the sense that they don't discharge action potentials, but they might be influenced by some neighboring activities, right, so they might be postinaptic neurons that were basically the potential of the cell is not addressed, it's in between, it's not yet, it's not yet a threshold in order to get an action potential, so we really don't know what is really the target of these induced electric field, we know that by inducing this electric field, we perturbate the activity of the cells underneath, and so what we can cause is either, you know, we can just, some cells that are maybe closer to the threshold will become a threshold to have an action potential, for example, this can be possible, or a cell, if it depends on also the intensity of the stimulation, but we will see that there are some possibility of simulating in the brain the current that you induce. My question is this, in order to get a signal from some neurons, for example, when we move our hand, some special neurons would be active, in order to get some signals, we have to change the manner that we induce the magnetic field through the apparatus, or we just, you know, sense it because we are moving our hand, you know, the neurons are changing the activity, or the apparatus is changing the way of induction. So are you asking whether? I mean, I mean, the apparatus is standard steel, and we're changing the manner, for example, changing the way that's grabbing something, or leaving something, or not, we are changing the way that the induction is occurring through the brain. We are changing the induction, if I understand, so we are changing somehow the, we are creating some activity that leads to this muscle movement, you can't induce an action, so you can, via TMS, you can't really make a subject to grasp something, okay? It's just a very subtle effect of what you use, okay? It's not a very, you know, in order to grasp an object, it requires a lot of coordination in the activity of the muscles, and so there is an engagement also of the neurons that are responsible for the movement of the muscles. It's much more complex task for the nervous system to reach, okay? So TMS can just slightly modify the balance of excitation in the tissues, okay? So it's just currents that you induce, and then this induced currents influence the electrical activity that is underneath, okay? But the intensity, so it's not so huge and also it's not well controlled, so it's really a slight change, so you can induce, you can place the electrode here, but this muscle that is the doctor of the Polychist Brevis, so these muscles that helps the thumb to just do this movement, if you see myself somewhere in your computer, and that's the only, it's a very simple movement, so you, because, and it's possible because you have neurons that directly from the cortex sends axons to the spinal cord, and from the spinal cord you reach the periphery, and you just, and you just cause the twitch of this muscle, but that's it, you cannot go beyond that level of complexity, okay? I have another question, in the picture that you compared the different methods, there were another axes like correlation, would you please describe these? Yeah, sorry. Yeah, I didn't do, so in the sense that this shows how the different techniques, so most of the, for example, in fMRI, as I said, all these new imaging techniques, and EG are more correlated compared to TMS, right? Are more correlated because they, what you measure, it's this, it's not, for example, what they, what you measure with it, it's not action potentials, you cannot reach that level, you measure post-synaptic activity, so you can measure the consequences of the action potentials, okay? So it's a sort of, you measure the environment that it's caused by an action potential, okay? So, and in this sense, ERP, MEG, EG, fMRI, they all, although via different means, they measure the same thing, okay? With TMS it's slightly different because here you are really, you can create action potentials, okay? Because of what I said, so you can change the balance of the charge, so the electrical charge is within and outside the cells, so in this sense it's different, and it's different also the approach of, because those are correlational techniques together with the single cell recordings, but compared to TMS, TMS is a causal technique, so because they, it allows you to make some claims about the importance of this region for a task, because if you stimulate that region and you find impairment, it means that that region, it's important for that task. It might not be the only regions, right? Because of course the brain is not made of isolated pool of neurons, there are a lot of connections between brain areas, but anyway it's part of a node that for sure is, might play a role in what you are measuring, okay? But the effects that you get, so the effects that you can induce with this technique are also depends on some, on the geometry and some, on the geometry of the brain, so how these actions, the fibers are oriented compared to the orientation of the coil that is outside, and that this geometry also interacts with, with parameters that you can manipulate with the technique itself. You can change the stimulus intensity of the, of the technique, and of course the greater the, the intensity of the stimulation, the stronger the induced electric field, right? You can also, you can, you can decide whether to have a single pulse or multiple pulses, so you can, in this way multiple pulses, so if you use just multiple pulses, your effects are stronger, the induced effects, you have summations of effects, but this means that because you, you elicit multiple electric fields in that regions, but this means that you lose the temporal precision, right, of the, of your investigation, because if I, if this induced electric fields summates over time and, and the frequency that you can use, I don't know, imagine that you are delivered, your train of, you deliver four pulses in half a second, but in half a second, 500 milliseconds, it's a long time for the brain, okay? So it's, it's, there are many things that happen in 500 milliseconds, so in this sense you cannot tell anything that, that covers a temporal scale that is below these 500 milliseconds, but even, and, but there is even another problem that if you use a train and you create a summation of effects, also what happens later, so these effects, they last in time, so that there are, okay, what we know about the physiological effects of KMS has been studied in, in, in animals as well, right, because there are people that use TMS in animals, and they, for example, simultaneously record activity from those brain regions, and what we know from studies in animals is that, of course, you have these summation effects and also you have this propagation in time of these effects, but if you use a single pulse, it's different because a single pulse lasts one millisecond, and the effects are supposed to last one millisecond, so, so you're, you're, you're, you're, you can say something more about what's going on at the temporal level, okay, then it's important also the color, the color orientation, the way you orient, the way, the way you, you change the orientation changes the way the current, because the current flows in this coil, right, so if you change the orientation of the coil, and you change also the orientation of the induced electric field underneath the coil, so this also can, can have an impact on the induced electric field, and also the coil shape and size can change the the physiological, the induced physiological effects, and all these, yeah, so I imagine that you can control for the intensity of the electric field, because I mentioned that in the coil, there's an electric current that's kind of, that's inducing a magnetic field, and that magnetic field is inducing an electric field in the brain, so I imagine that you can control for the intensity of the electric field and its frequency, could you kind of just kind of a bit elaborate qualitatively what are the influences of different, so I imagine different intensities of the electric field are directly proportional to the number of neurons that get, that get excited in the brain, but what's the, what's the effect of variating the frequency of the magnetic field, or that is of the induced electric field? Well, what we measure, okay, in the current research, unless you are really a methodologist or something that really wants to understand the physiological effects of TMS, you normally measure behavior, right, and so what we know that if you change the frequency of the stimulation, you get a stronger, so protocols that use repetitive, no, so effect induce a greatest effect, although it depends on the frequency, okay, so the, okay, the way you do it's, for example, apart from measuring behavior, you can measure the cortex excitability, okay, so and how do you measure the cortex excitability by looking at this evoked motor response, and you look at the amplitude of those, those evoked responses by changing the parameters of the stimulation, so you then change the intensity, you change the frequency, no, and you see how the amplitude of this evoked response changes the function of these parameters that you use, and for example, there are studies that show that a slow frequency, like one hertz stimulation induces, for example, an inhibition of the, of the, of the motor cortex excitability, so this amplitude of the, this evoked response becomes smaller, and these effects are long lasting, so for example, there are protocols where you stimulate for 10 minutes, it's a protocol that it's called one hertz TMS, and it's, you do offline, so you do for 10, for 10 minutes, you do, you stimulate at one hertz, so one pulse per second for 10 minutes, and if you do this, and then you measure the motor cortex excitability, you see that compared to before the stimulation, this amplitude is lower, decreases. Okay, so it's like the motor cortex has a resonant set, has an inhibitory resonant frequency of one hertz, right? Exactly. But can you do a map, can you do a map of different frequencies, frequencies across the brain? Oh, this, so, so let's say that you, if you want to measure how, by changing different frequencies of stimulation, what are the effects in the other areas? Yes, and if you can kind of, so if you can label, if you can attach the different brain areas, different inhibitory and or excitatory resonant frequencies, has that been done? Is that possible? No, and it's not possible, because how would you measure the activity? Well, you can do in animals, I guess, but you can't do in humans, no? Because the, for example, another possibility of measuring visual cortex excitability is the intensity that you need to elicit a phosphine in visual cortex. That's another way you do, because if you need more intensity, it needs that your, your, your, your inhibitory, so, so you, you basically, according to the intensity that you need to elicit, that percept, it's indicative, it tells you how much excitable is your cortex. But that's also, it's two areas. To do this in associative areas, in areas that have a much more complex behavior is difficult. So what is the output of that, of that region? What you can do though, and this is something that has been done only in recent years, is to do simultaneously, because you can do, you can stimulate the different cortical areas, and you can see what are the effects of the EEG level. So you measure the electrical activity from the scalp. This you can do. It's not because you have the, you have to get rid of the pulse artifact, but this is what it's what, what we do as well. And this is very important for us to understand the effect that you, that you do with this technique, because there is something that I haven't told you, and I think you might guess, that if I stimulate this visual cortex, the visual cortex is not isolated, you understand that easily, right? So it's also very likely that if I decide that piece of the brain, other pieces of the brain that are connected to this, to these brain regions might get active as well. And this has been shown and I will, I will show you in a second. Okay, this is for example, a simulation of the effects that you, an induced electric field is a simulation of the propagation of the induced electric field if you place the coil in the occipital pole, you see? So the exactly. So this is, and you can try to also, I will show you in an experiment, you can even correlate this simulation with the behavior that you see. So this is also a way of seeing whether the simulated induced electric field corresponds with the behavioral effect that you are expecting if the area is important to that task. Yes, okay. And so I've got then a question, could you, is there a way to estimate the area or the effective volume, let's say of this red region of the most activated regions with the TMS? Is there a way to estimate maybe the effective volume or the effective area that feels the effects of the TMS and thereby maybe calculate, well, in some way, the number of neurons that you're affecting, is it possible? Because I imagine you're talking about an astronomical number of neurons here, right? Exactly. So you are asking whether it is possible to identify, basically, the neurons. So to measure how many neurons are you affecting? Yes, yes, exactly. But this is very difficult, right? Because the resolution is very, because the electric field is inducing in the outside of the brain, right? And there are layers to go through. So it's very difficult to have this snapshot of the neurons. What you can do, you can record, you can see the effect in the neighboring regions. But again, in humans, this is what you can do. You can, the maximum you can do, you can just zap and observe in the centimeters around, let's say, in the electrodes around the area of stimulation, how you can change the electrical activity in these regions or even in far regions. But you cannot know, there is no way for the human brain to know how many neurons are you affecting. Okay, I understand. Thank you. Okay, so but I'm just to talk about this functional, so how precise you can be. So how, what is the spatial precision of TMS? One way is, for example, this is an old study that in the early days of TMS where basically we wanted to prove the, the spatial resolution, so how precise can be the, can be the effect that you induce by these electricals. Yes, magnetic stimulation. And here is an experiment where you basically look, okay, let's look at the bottom. This is an experiment where you induce phosphine. Okay, so these flashes. And so basically you, here you see a map which is drawn by the post-op processing. Okay, so you first induce the, you stimulate the occipital cortex, you induce those flashes, and you ask, of course, participants to report where was the flash and how big the flash was. Okay, and here it's just depiction of what you can see in the subjects. So you see that you have the possibility of, with these parameters, so single pulse, 70% of the maximum stimulator output, you can, you're able to induce phosphine with a precision of one or two degrees of visual angle, which is not too bad. At the top is, again, this is something that is measured in motor cortex, as I said before. So here you basically stimulate the motor cortex, and you basically record from different muscles of the hands of the hand. Okay, so this is the APB, the FCG, so the biceps, the deltoids. This is the adductor, Polygis brevis, the muscle I show you, this one. And then here is the area that you, so it's a depiction of the area of the brain that you have to stimulate in order to elicit those, the movement to evoke a response in those different muscles. So you see there is a lot of degree of overlap. But on the other hand, there is also some segregation. So you see that there is between, from the deltoids to the, to the, the, the, the, the abductor, Polygis brevis, there is quite a substantial difference. So you somehow can map functional, distant piece of the brain. But one thing that you have to bear in mind is the fact, what I said before, is the connectivity. The brain is not made of isolated units, but it's connected units. So for example, this is also has been done in the early days of TMS, when basically here you measure the, the, with the patch, with the positron emission to tomography, you measure, you measure the, you observe the activity. This is basically the piece of the cortex of your motor cortex that lights up when you induce a movement with TMS. Okay. And this is what you, you observed when you perform a voluntary movement. So this is evoked by TMS. This is performed by the subject. So you see, you have a greater engagement of circuit because you have also activity in the, in the promoter cortex here, not just primary motor cortex. Okay. So this is a comparison. And this is something very useful. Again, it's the combination of the techniques. This is TMS together with Pat or MRI, like this is a cerebral blood flow measuring measure. And here you see that here what you stimulating is you stimulating the, the, the PCO, the posterior cortex, this posterior part of the, this is somewhere in between the parietal and occipital cortex in PO means that, and this is basically the piece of the brain that you're sort of stimulating from the outset. So from with TMS. And this is basically the response that you observed with the, so you see observed a change in the cerebral blood flow in this area, which is called frontal eye fields. And we know from physiology that these areas are interconnected. So you have a very distal effects of TMS in an area that is functionally interconnected. Same thing here, right. So here what you stimulate is motor cortex. So this is, this is the site of stimulation. And what you see, it's activation. This is fMRI TMS. You have to understand that combining this technique is something challenging. It's not something that you do like this. So there are some technical challenges that you have to face in order to do that. Anyway, so this is the, so you have stimulation here. You have activity or in areas like in the premotor cortex, in areas that are functionally connected, like the contralateral motor cortex. You have activity in the cerebellum even, and then you have activity in the auditory cortex. This is here, this is what you, this is where my mouse is, is because when you, when you deliver a pulse, you have this click. You have also a sound. You produce a sound. Okay. But now let's go back to the, to what we want to investigate, which is time perception. Okay. So, and what you, what you want to do, it's a TMS experiment I want to share again with you. This is what I want to share. So, and then you can use, no, you can use this technique to show that a certain brain region is important for temporal computations. Okay. So, you want to see which brain areas is necessary to estimate the duration of a visual image in this case. And what is important as well, this is something I didn't mention. You don't, so you have to choose, there is a big problem for TMS, which is basically where to place the coil, right? And where to place the coil can be, can have a certain level of precision. If you have an MRI, if you have also a picture of the morphology of the structure of the brain of your participants. So, if you have this T1 weighted image, you can use a tool that enables you to register the, the basically the, some external landmarks on the subject's head. So, like, so you have external landmarks like the two ears, the tip, the tip of the bridge of your nose, this, the bone that is called the enion that gets the back of the brain. You can register this external landmark in the subject head with the brain, with the inside of your subject. Okay. And this techniques enables you then to travel. So, from the outside you have a pointer and you travel in the brain of the subject. And so, to have, in order to have a sort of match from the, to match the outside of the brain with the inside of the brain. Okay. And basically be able to try to, to aim to target that piece of the cortex. Okay. So, this is also to reduce the degrees of freedom that this type of investigation might have from the spatial point of view. And so, here the target regions of this experiment that aim at finding out the role of visual regions in visual time discrimination were basically was placed in, in an area, in a visual area that is important for the discrimination of speed. So, this is an area that lights up when you see something moving, when see something moving in a certain direction. Here there are cells that are active when you see something moving. Some cells prefer lower speed, higher speed. There are cells that are selective to motion directions as well. So, and we decided to stimulate this area. And also an area that it's, so this is clearly a visual region. So, whereas this is an area that integrates visual information with other with information that comes from distance and from, from different sensory modalities like from auditory cortex, for example, is an associative area that is important to coordinates to integrates the information that comes from the visual regions from the visual regions of other sensory cortexes like auditory regions and creates some sort of some plan for, for future actions. Okay, so it's an area that mediates something that comes from sensory regions and gets ready to implement a motor plan, which is a job that frontal areas and promoter and primary motor areas do. Okay, so it's a high level, we call it region. And what we do is simply like that. So, we have a task. So, we have a duration T and I think I will try to go to the point. So, we have a duration, first duration, then we have a a standard that is 600 milliseconds. And then we have a comparison duration that could be either shorter or longer than the standard. So, nothing new. We, we, we, we, we, we talk about this earlier, right? And then the subject has to decide by pressing response key whether the second stimulus was longer or shorter than the first one. Okay, so, and then we, we basically apply TMS while the subject was seeing the second stimulus. Okay, and the stimuli that we use were in the first place moving dots. And what we saw, so here you see plotted is the Weber ratio, which is basically, it's basically the difference between the two stimuli, this one and this one, that, that basically enables the subject to reach 75% accuracy performance. Okay, so higher Weber fractions means worse performance, so bigger difference between the two stimuli. And so you see that basically the areas that were mostly that lead, lead to a, a worsening of performance where both the, the, the V five, this area and T and the, the right posterior parietal cortex, not the left, we use also those two areas, the left parietal cortex. So we simulate left and right. So two hemispheres. And the vertex is basically the stimulation on the top of the head. We use, so this is a control side because the stimulation should go into this inter hemispheric sulcus. So should spread and not reach any area in particularly of the brain. So we see nice this effect. So it means that these areas are important for time, but there is a problem in this experiment. And the problem is the moving, the motion of the stimuli, right? So stimuli were moving. And what you were stimulating with TMS was an area that was sensitive to motion. So it might be possible that the effect that you see after stimulation of V five were due to the fact that V five doesn't switch off, right? It's as nearly as sensitive to motion, even if the task was not a task, a motion task, we didn't ask subject to judge motion. But nevertheless, we might affect motion perception. So we run then a second experiment that basically the, when we use static stimuli, so stimuli were not moving. And again, so in order to control for this confound and again, we did see this effect for parietal and area V five and T. But then there is another confound here. And it's the fact that we are stimulating a visual region and we are using visual tasks. So someone might argue, okay, you are stimulating a visual region. So who doesn't tell you that you are affecting the perception of low level visual feature in the stimuli that you are using? Okay, maybe the subject doesn't see well the stimuli. And that's why you get an effect of V five. And for this to control for that, you just devise another task where again, you use exactly the same task structure, you use the same stimuli, but rather than asking participants to judge the duration, you ask to focus on some visual feature in the stimuli. In this case, we made the dots to basically the dots from time to time they were creating these lines. And we asked participants to identify this visual shape and to decide whether this visual shape were present in the first or in the second stimulus. And basically you measure again behavior. And if you don't see any difference, so you don't see any effect, because you see that is the performance accuracy is similar across different stimulation conditions, you might basically, you might exclude, you rule out the possibility that your effect were due to low level visual processing. And as the last thing, in order to know how specific was the stimulation in terms of sensory modality, you use an auditory task. So you want to know whether this visual area was important for visual time, but not for auditory time. And this is what you do, you just use the term of the auditory discrimination task where the task is the same subject out to decide which of the two sounds were longer. And you stimulate again the parietal cortex and the visual area. And here what you see is an effect only for parietal cortex, which is indeed is an area that integrates from that receives information for visual, but also for auditory areas, but you don't see an effect of visual regions. And I stop. But I wanted really to show also the flow of reasoning that is behind all these experiments. Okay, so that you don't do just random things, you just try to control for many different possible compounds in your research. Thank you. Thank you. Tomorrow, we will talk about a different model. Are there questions? Yes, I have a question. Yeah. The clinician, you usually use the the brain, the deep and they use the brain deep simulation to cure the Parkinson. We can't hear you. No, we can't hear you anymore. Yeah, I will say there is problem with the old audio. The clinician usually mess method. Can you hear me? No, not really. Can you write in the chat? Yeah, maybe if you write in the chat, yeah. They use the brain stimulation, but this is often in basal ganglia. So they target very deep structure. And with TMS, if the question is whether you can do the same with TMS, you count because the basal ganglia, the areas that you normally target are very deep in the brain. And you cannot reach them with TMS. There are now the technology provides us with coils. There is a cone coil that allows you to go deeper, but not as much as in deep structure like the basal ganglia. Okay, I don't see a question in the chat, so I think we can stop here. So thank you very much again, Domenica. And thanks, guys. See you tomorrow. See you tomorrow. Grazie.