but what we learn from mapping and to try to constrain the model we have seen based on the structure, namely the better understanding of the anatomy and the function regarding the connectivity. Definitely we know that this model is not the right model, unfortunately, for us and for our patients. But what I would like now is to detail a little bit more what we learn from stimulation mapping in past decades, both regarding the new model, but also this kind of map, because here you have the first functional map of the subclinical connectivity in a MNI template. And I will show you in the next and last talk, I will give today, that it's absolutely crucial for neurosurgeons to know that in your mental imagery, because this is the limitation of brain plasticity. If you cut this map, then you will induce permanent deficit. Why? Because especially in gliomas, as you know, this tumor like to migrate along the Y-matter tract, and this is the reason why I was aware about the fact that this tumor knew the anatomy better than me. And then I said, finally, in order to try to better treat patients with glioma, I should absolutely better understand the functional connectivity. And thanks to correlation we did before any treatment in patients with this kind of tumor, and thanks to the preoperative neuropsychological scores, we demonstrated that there is a direct correlation between the deficit the patient can have before any treatment and the invasion not of one area of the brain, but of the pathways. For instance, if you have an invasion of the ventral semantic pathways underlain by the inferior frontal occipital fascicle, then you will have semantic disorders before any treatment related just to the fact that this pathway is involved by the tumor, which means is totally logical, finally. What I have learned 15 years ago approximately, when I saw a patient before any treatment with a deficit, it was not related to the location of the tumor. It was related to the fact that it was a modification of the whole equilibrium within both hemispheres, so modification of the functional and effective connectivity, inducing the deficit. Why it's important to know that? Because we will see in the next talk that you can use this knowledge in order to push plasticity and then by removing a part of the brain, lube, as we have seen during discussion of cases, then you can increase, strangely, the postoperative scores because you will induce a modification of this functional connectivity, a new equilibrium more efficient. To do that, of course, we should first of all burn the principle of localizationism. I mean, you have understood, I'm sure, during two days that there is no one area dedicated to one function, and it's what we have learned and what we continue to learn, unfortunately, in many universities in the world, definitely, we understood that it's a network. And as said by Dr. Chang, we have not to say we would like to find the site, the area of language, like speech, for instance. It means nothing. Of course, to do that, we awake the patient. I will not insist about that. And this is the reason why maybe you have a different view now of the same slide I showed this morning because now you see it's not just technology or technique into the oral. It's really the relationships between your knowledge of this functional anatomy and what you are doing online into the oral. So probably you better understand why also it's possible to do this kind of surgery based just on this knowledge. But be careful because sometimes you can have a negative mapping at the level of the cortex and to think that you can continue to remove until, for instance, the ventricle or the deep brain nuclei. And suddenly, in fact, you encountered another pathway not related to this area but connecting A to B, for instance, removed from the cavity. And suddenly, you will use a permanent deficit and you will say, I do not understand what happened because we should know the functional anatomy based on this structure. So what we learn about connectomics? First of all, definitely that we have networks and that there is no one area dedicated to speech. And if there was really an area dedicated to speech, it's not within the parsopercularis but within the ventral premotor cortex. We spoke about that many times during this meeting. I do not understand why neurosurgeons, neurologists were not so excited by white matter tract for one century. But we know that some guys like, of course, Klinger said, you should know better the anatomy. But finally, the sole interest I have seen really in tractography is that because we were able to give to neurosurgeons new tools with beautiful imaging, they said, oh, finally there is a connectivity and I should start to integrate it into my surgical planning. But I can tell you that, of course, the brain needs this connectivity far beyond. We've seen that on tractography. So the goal is to combine now, and not to speak about what kind of methodology, but to know the anatomy, to use tractography as a didactic tool and research tool and not at the individual level in 2D or, and of course, to use also electrophysiology, whatever the methodology you can use. And what we learned, first of all, of course, that if you cut the premotor pathways, you will induce permanent hemiplegia. Everyone knows that. Nonetheless, I can tell you that if you wake the patient during this kind of surgery and if you know your anatomy at the level of my nerve, then you will see that you will induce somatosensory deficit before to induce modification of the movement. Why? Because the thalamocortical pathways are more laterally located within the internal capsule. You should know that. And you cannot map that if the patient is under general anesthesia. Second, we have a motor control network, which is in front and posterior to the central area. And it's very crucial if you want to preserve bimanual coordination. For instance, this morning, I do not remember, but I have seen one guy wake in order to perform a fine task during, a great task during resection of supplementary motor area. It's true. We should do that, but bilaterally, because in fact, the SMA is controlling both movements. And now, we started to understand the connectivity underlying this kind of function is the fronto-striatal tract, very crucial in motor control. So it means that you have not, once again, to decide for the patient. You are just to say to him or her, do you accept to have a fine movement deficit? If you are pianist, for instance, it's not acceptable. If you are not, then maybe we can remove it. So you see, just a tool also. In your mental imagery, in order to adapt to the patient and not to say, I will push or I prefer to preserve the quality of life. You are just to ask to the patient before surgery. And normally, you should know, thanks to the knowledge of the functional anatomy. For instance, I know that if you stimulate the fronto-striatal tract in the left dominant hemisphere, you can induce stuttering. And I know that at least in my career, in one patient, I have induced permanent stuttering. And the patient is still alive and continues to stutter 14 years after surgery. Maybe it's acceptable. But I was not able to propose that to the patient before surgery, simply because I did not know that 14 years ago. Recently, we published a paper with Guillaume Herbet, speaking about not only the frontal field, but also the oculomotor tract. Why it's important? Because probably Paolo Bartolomeu will say that we have relationships between this function and the attentional process. And if you are a manager, for instance, you need to have a high level of attention following surgery, especially in incidental low-grade glioma. Same thing when you are posterior. We had this discussion regarding one case. You should be careful about the somatosensory pathway. If you cut them, you will not have a complete recovery, especially if you cut the SAF2, and then you will induce a meneglect. Visual field, once again, you have just to adapt to each patient. But it's very easy to perform in a way procedure stimulation of the visual field and the optic trajection, and then to avoid, for instance, to induce amenopia. I will not insist about this paper, because Paolo will extensively describe the right non-dominant hemisphere and the spatial cognition, which is absolutely crucial, at least for some patients. I just explained to them before. But it's based on the fact that you should know that the second part of the superior longitudinal fascicle and so-called right non-dominant hemisphere is crucial for this function. Now, speaking about language, I will not insist, except the fact that we did this dissection, and we did also the DTI, and we did also the intraoperative mapping. And to make a long history short, as demonstrated by Marco Catani, but also now with the intraoperative physiology, we know that there is a lateral part, and this SAF3 is connecting the ventral premotor cortex, and not Broca's area, to supramarginal gyrus and T1. So this is typically the auditory motor loop described by Eddie Chang just before. And now you are into the aura, and when you stimulate this lateral part, you will induce speech apraxia. And I can tell you that if you cut this pathway, you will have a permanent anathema, because I have seen one of my colleagues cutting this pathway under a microscope at least one time in my life, and never the patient recovered. So I have the proof, unfortunately. And I can tell you also that you have, of course, a deep layer, which is the real arcuate fascicle connecting the so-called Broca's area, at least anatomically speaking, the parsopercularis and triangularis, to not Wernicke's area, but T2 and T3, according to the model of E. coli and purple. And when you stimulate, definitely you will induce phoneme proaphasia, and most of the time repetition disorders, too. But we have not understood everything. I know that a subpart of the SLF is also involved in syntactic processing. I know that another subpart is involved in language switching, not just speaking about the fact that we have different mosaic involved in different languages, but also the possibility to switch voluntarily or not. But I cannot tell you exactly how it's organized today. And it's crazy to me to go into the oral and to know that I don't know exactly what I will do, despite the fact that I have understood that the posterior dorsal phonological and articulatory pathways is involved in this kind of function. Now speaking about the ventral pathway, once again, this IFOF is running, of course, within the temporal stem. You saw that this morning during movies. But you have a superficial layer with some cortical termination, especially anteriorly, different from the deep layer. So it means that within this temporal stem, you have different layers with different subfunctions involved in semantic processing. The lateral part is much more involved in verbal processing. So you can use naming. You will have semantic proaphasia. But the deep layer is involved in nonverbal semantic processing. So it means that if you are doing just naming, you will cut this pathway by telling it's a false negative due to the stimulation. No, it's because you did not administrate the good task at the good moment, because we don't know the functional anatomy enough. But now we start, fortunately. And we think that it could be also involved in noetic consciousness. But I think that Yo-Mei will speak about that better than me. In the right non-dominant hemisphere, if you stimulate the pathway, you will have definitely some disorders regarding semantic processing at a higher level. So of course, if you don't administrate the good task, you will not find that. And then it means that you could induce modification of the behavior, for instance, in patients with extensive lobectomy in diffused legray glioma incidentally discovered. And then you will have some neurologist telling you, you see, you removed the tumor. But in fact, you induced disorders in this patient who is not able to continue to live normally. No, we should administrate the good task or not. But we should ask to the patient before, what do you want? For instance, if we cut the left incinae fascicle, I learned from Lorenzo that you will have some deficit regarding the lexical access of proper name. So it's not a problem for many people, but it could be for some people. If you are cutting the anterior part of the ILF, I can explain why on the paper by Wilson, we have seen that the yellow part at the level of the anterior temporal lobe by telling some naming disorders. In fact, it's a problem of lexical access when we cut the anterior part of the inferior longitudinal fascicle. If you cut the posterior part of the longitudinal fascicle, you will induce Alexia. So it seems that here, just paper in human brain mapping in order to publish and to do science. No, it's exactly the answer to the patient we have seen previously with lexical disorders. Remember that I told you, in fact, that the tumor was located exactly at this level. And I spoke about the visual reform area and the posterior part of the ILF. So you can predict that just by looking at an MRI and by telling to the patient in consultation, can you accept to have disorders of reading or not? Now we start to understand that it's not one area compensating another area, but a subnetwork compensating another subnetwork. For instance, the anterior temporal lobe can be cut if you accept this increase of reaction time in order to have the lexical access. And it's exactly what was done for many decades at the level of epilepsy surgery. In fact, the inferior frontoccipital fascicle was preserved because running in the roof of the ventricle. It's crazy to me, but I go sometimes to the OR, and I don't know the function of some pathways, especially the middle longitudinal fascicle connecting the temporal pole to the ankular gyrus. And we know that we can cut a part, or at least the anterior part in the so-called left dominant hemisphere of this MDLF, but probably we will induce some degrees of semantic deficit. But I cannot tell you more about that today, but I hope I will in a couple of years. So I'm saying we have this vertical connectivity between the cortex and the head of the caudate and the striatum, and then we know that if you stimulate the left dominant head of the caudate, you will induce perseveration in 90 percent cases. You know, it's one symptom of the so-called frontal lobe. In fact, the frontal lobe is not related to the fact that you removed the frontal lobe because many of our patients have a lobectomy and have no frontal lobe. It's related to a disconnectionism syndrome if you push too much at the level of the frontal striatum tract. Same thing regarding the putamen. If you stimulate the lateral part of the lentiform nucleus, you will induce articulatory disorders. And I'm sure that it will be very exciting for Nina Drunkard to see that this is the quadrilateral of Pierre-Marie explaining perfectly that one century ago, Pierre-Marie said to Paul Broca, you're wrong. So now we start to understand this kind of new model based on the anatomy. Each arrow here, arrow here, correspond to one fibers we decided before, and we stimulate it into the oral. So it's not our imagination. And this is the minimal common brain we should have in our mental imagining in order to go to the oral and to say, I can use your navigation or not. And the next step, of course, we started and we spoke about that this morning, and you will have the explanation just after that, is to map also mentalizing, empathy, social cognition, emotional valence semantics in the ventral stream, because I know that I have induced permanent deficits regarding the behavior of some patients. For instance, they were depressed after surgery, and my master told me it's related to the fact that, of course, you perform surgery, they have a tumor, and you cannot cure them. They will have maybe chemotherapy and so on. No. It was related to the fact that I cut a part of the eye off, like in this girl I spoke about who is an actress and would like to continue to be empathic. And we can't avoid that today. And to make a long history short, in fact, we have different phasically involving in the emotional process with different level of empathy. The first one is just a perception of emotion of people in front of you, and underlying by the arcuate phasical, and the second level is the attribution of intention of people in front of you, and underlain by bilaterally, of course, the cingulate. And it's not enough, because there is an involvement of the eye. Now, in other words, we start also to have an access to consciousness, and to predict that before to go to the war. I will not insist about that, because I'm sure that Guillaume Herbet will do that better than me. Just to conclude, in fact, if we have this new view of how the topi, I mean, location topos and other pathways, so networking, in fact, then suddenly everything, or more or less, becomes possible into the brain, because you can deal with this model in order to induce neuroplasticity, as we will see in the next talk. Definitely, most important, if you had one slide to remember, is this slide. This is many, many stimulation we did at the level of the Y matter tract, and now it's not just DTI. It's not bio-metabolical model. This is the absolute truth we have observed since many years into the oral, in the MNI template. And if you cut definitely this pathway, you will induce permanent deficit. So it means that if you have in your mental imaging, this is the reason why you can predict by looking at a preoperative MRI without DTI, okay, I will remove approximately more than 10 cc or less than 10 cc, and then to do a neuroadjuvant protocol or not. And this is the reason why, also, I told you this morning, when I put my ACUSA or aspirator at this level, I should imagine the risk I will induce permanent deficit if I disconnect different sub-pathways and not just one, because I know that this pathway can be compensated or not at the individual level, speaking not about just language, movement, or movement control, somatosensory, visual, visuospatial cognition, but also emotional process and metacognition. So Guillaume Herbet will speak about that, the awareness about the fact that you know what you know, which is absolutely crucial for a human being. So my take-home message is, in fact, very easy. If you know the structural and functional connectivity, then you can do more or less what you want within the brain, and then to push more. If you think that it's better to induce an increase of the median survival, or to say in this patient, I will stop, and I will preserve the quality of life, and maybe I will have this chance to come back in a couple of years, and it will be in the next talk based on this connectivity view opening the door of neuroplasticity. Thanks a lot.

functional connectivity

anatomical connectivity

brain

neurosurgeons

language processing

motor control