So we'll speak about now neuroplasticity on the basis of what we have seen before. Everyone knows, of course, the history. Le Gall, we spoke about that yesterday. Brooker's, Wernicke's. But in fact, why I had this idea initially? Because I had the chance to meet many patients with this kind of tumor. Very voluminous tumor, but also located within so-called eloquent areas and without any problem. In fact, of course, once again, if you perform a neuropsychological examination, you can find some cognitive disorders in more than 80-90% cases. But finally, they compensated. And I tried to use this plasticity in order to be a little bit provocative, not only by performing one resection, but two resections, like in this patient, for instance, with two frontal lobectomies spaced by 10 years with no chemotherapy, and not only still alive, but working full-time, and with normal neuropsychological scores, a little bit maybe irritable, and that's it. So it means that you see that I don't know what means frontal syndrome if you use this slow-growing tumor potential in order to induce this reorganization without the regrowth of the tumor. I would like to speak about what we can learn and what we can hear very frequently from neurologists. They like, and we have seen some illustration yesterday in the talk by our colleague Nina Drunkard, to put everything within the same template and to do a segmentation, and all patients have the same pathology, like strokes, for instance, and have the same symptoms, like motor aphasia, for instance. And the conclusion most of the time is that the overlapping is the area explaining the deficit we have observed in all patients. In fact, we can have a different thinking also, which is in the first patient we have this symptom because this part of the network was damaged. In the second patient, this part of the network was damaged, and so on and so on. And according to this view, we can say also maybe the overlapping is not the area of speech in this example, but not really involved in speech. And it's exactly what happened with the history of the so-called Broca's area. And is it possible to demonstrate that? Of course, by removing the so-called Broca's area, but it's just an example, of course, against localizationism by telling, after that, the patient and five hours, five hours of cognitive examination in the Institute of Cognitive Neuroscience in Paris was considered as normal. So it means that this area does not exist, and then we have to evolve to a networking brain and dynamic brain. Once again, you have understood that we have some limitations, the pathways. If we cut the pathway, then we cannot have this kind of reorganization. So what are the mechanisms? I will not insist about that, but to show you some examples, and especially at the end of the talk, using the resting state now, because, of course, I love functional imaging. I am a PhD in functional imaging, so I can tell you the secret now. So, of course, I use it since 20 years. I was trained by Bernard Mazoyer, and I participate in the organization of the first human brain meeting in 1995 in Paris. But I know the limitations, so I will use it. In order to better understand brain processing, I will show you. But not in 2DR. So now, how to make the link with the functional oncology and, if possible, preventive functional oncology we spoke about this morning. So mapping, of course, at the individual level, but also knowing that within the same patient, you can have different maps over time. And it's very exciting to do, first of all, an fMRI before surgery, not to decide if the patient should be operated on or not, with in mind it's not the topic, but just to see the pattern of reorganization you can see in three patients with the same tumor, the same location, the same behavior of the tumor. And finally, you can have, unfortunately, sometimes in 10% may experience of a functional area still crucial within the tumor itself, in fact, because it's a diffuse disease, of course. And sometimes you can have a reorganization around the tumor, and sometimes you can have a reorganization before any treatment, thanks to the recruitment of the contralateral hemisphere. And, of course, the chance to perform a more effective resection is depending on the preoperative neuroplasticity pattern. And I'm very happy to listen to that guy find exactly the same thing also in 2D-ORG. You can have, sometimes, reorganization online just in 30 minutes. And, of course, it's related probably to the talk by Eddie Chang. Now to better understand what could happen online when we also perform surgery and probably by modifying the equilibrium within the network, because surgery is, of course, an aggression, a damage for the brain. What is very exciting, to my opinion, using fMRI is not to use it to make a decision, to operate or not, once again, but a longitudinal study before and after surgery. We had this discussion yesterday with Nina Drunkard, of course. Before stroke, you cannot predict that we will have stroke. But before surgery, we can predict that we will remove, for instance, the supplementary motor area in this case and then to induce supplementary motor areas and room transitory. So if you have a baseline, you can compare and to start to understand what happens when the patient recovers. In this case, for instance, you can see that it's really a network, bilateral network involving the recruitment of the contralateral SMA, premolar cortex, but also the involvement of the knob of the hand, but also the parietal control and so on and so on. You have the network in front of you. But what is very exciting is that when you cannot remove completely the tumor because functional boundaries and because patient told you, I want absolutely to continue to enjoy normal life, then you can follow the patient and to see a regrowth, unfortunately, of the tumor in all cases, not really a recurrence, but growth of the residue, and then to perform another MRI five years after. You have an error related to the methodology, but the error should be the same. And here you can see five years after the recruitment of the contralateral hemisphere and also a jump from the pre-central sulcus to the central sulcus by doing exactly the same task. Then we decided to reoperate the patient because, first of all, he was well. And the second time we removed a part of the pre-central gyrus. Here you have the central sulcus with a superior decision performed directly into the contact of this gyrus, this sulcus, with, of course, a compensation by the lateral and medial part of the cavity. And you can see the immediate post-operative MRI where we removed the knap of the hand. So it means that it's not a point-by-point somatotypical organization, as I said during the first talk yesterday. And it's very frequent in my experience to do that. I'm very happy to publish this paper with colleagues who came to Montpellier. And, in fact, why? Because this girl is now a guitarist, and she will give me the first album she published during the next consultation. So she's playing guitar without the knap of the hand. You can do that for the succul-vernicus area. The first time, this is the posterior part of the superior temporal gyrus. I was not able to remove it because the subcutaneous stimulation also told me, be careful. The second time, then, it was possible to remove it, of course, with normal neuropsychological scores. You can do that also for the left temporal lobe with very impressive reorganization because the first time you have seen, it was not only the cortical mapping. You can tell me, yes, it's because you don't use ECOG, then you have diffusion. No, because I have the pathway here. And then you have this coherency, once again, between the cortical and subcortical mapping. No, but the second time, it was possible to remove a complete left temporal lobectomy. Here, the resection of the succul-vernicus area behind the labia vein. You have the proof. Why? Because you should see, of course, the anterior part of the posterior portion of the inferior langitine fascicle, the inferior phantooccipital fascicle, and the arcuate fascicle. You have seen the previous two. Now, it's really its application into the UR. And then, what means the vernicus area? The bronchus area, once again, of course, I will not re-insist. We have seen exactly, more or less, the same case this morning. Once again, the ventral semantic pathway, the dorsal phonological pathway. Now, sometimes, the brain is not able to reshape. And in this case, it is a neuroradiologist who made the diagnosis by himself because he had some headaches after a marathon. So, incidental discovery. And I say, I would like to operate you. And unfortunately, I was not able to remove completely the tumor. Then, I came back three years after, and now I perform a complete resection, even supra-total resection, and everything is stable. And the patient is one, because we use this plastic potential. And never, he had a permanent deficit. I mean, he continued to run marathon and to be a neuroradiologist. You have seen this patient before, but now, to explain what happened. First of all, I perform the resection at the level of the left frontal lobe and so-called bronchus area. And I don't know why this tumor decided to run. I have no other image. I'm sorry about that. But only on the contralateral hemisphere through the corpus callosum. Not posteriorly. Otherwise, it would not have been possible to perform the second lobectomy in the right non-dominant hemisphere. What means? You can tell me, yes, you removed the pars opercularis because, in fact, plasticity occurred before surgery related to the tumor. No, because, as I told you, I hate to split the Silvian Fisher. I'm not so skilled, and I prefer to avoid any vascular problem. So, I prefer to go through the operculum, even if not invaded by the tumor. And what happened? Nothing. Of course, you should adapt sometimes so you can have some positive side. But not for speech, but for semantic processing, for instance. Then you will remove only the pars triangularis and not the pars opercularis. Once again, variability from one patient to another one. This is the same pattern principle if you want to remove, of course, the pre- and retrocentral GRI. It's not really a scoop because you know that you have a compensation by the contralateral side. But be careful about this corona radiata. Normally, you should imagine here the negative motor network, the perimodal pathways, the somatosensory pathways, and so on and so on. And the SLF, too, we spoke about also. Now, you should see that now. You don't need postoperative DTI. But, of course, we will do that in order to better understand, but just for research purpose. Be careful about this SLF3. If you cut it, I can tell you that you will induce a permanent anarthria. So, it's not the same thing. We had very frequently this discussion with Mitch regarding the primary motor cortex in the left hemisphere. So, really, Brodman area 4, and the ventral premotor cortex more laterally located, Brodman area 6. And the function is not the same, but the connectivity is not the same because the primary motor cortex will have perimodal pathways, of course, running to the corona radiata, while the ventral premotor cortex will be, once again, connected to the supramotor general drivers and T1, posterior T1, through the SLF3. So, we know that it's not the same cortex because the connectivity is not the same. You can remove the parietal lobe, even in the left dominant hemisphere. You can, of course, perform this very impressive research. And I can tell you, of course, that the patient was not epileptic. He had 10 seizures a day before surgery, despite three antiepileptic drugs, and no seizures anymore following surgery. So, the quality of life was improved. Nonetheless, I can tell you that this patient had modification of the behavior. And I did not understand that because it was more than 10 years ago that I cut the inferior frontal occipital fascicle in the right non-dominant hemisphere. Now, I know. So, once again, we had the discussion during the rest, the break. Should we left more tumor, leave more tumor? You have not to decide. Please say that to the patient. But now, yes, I can say I will avoid depression if you don't want to have modification of the behavior. You can cut the corpus callosum. At the discussion yesterday, also, you see that sometimes you can remove the splenium. Be careful about that. The last slide of Paolo Bertolomeo's talk was, be careful, avoid to cut the splenium. Otherwise, you have a risk to not see recovery. But if you cut the intra-hemispheric connectivity. In this case, I love music, so it was very exciting for me to be careful because I operate this patient with a musician and was able to play piano Rachmaninoff three months after surgery. And the impresario told me, I remember that very well, she's playing better now. And I understood a posteriori that, in fact, I have also induced modification of the behavior, but positively for this girl. But I did a mistake, in fact. Now, I can avoid to reproduce. So, finally, the results about the first 600 diffused Legray-Gleymer operated on, you know, in the so-called eloquent areas, the brachiospermic central insula corpus callosum, and so on. The rate, first of all, of patients not selected for surgery, in my experience, is around 10%, as I told you. And in these cases, I do just biopsy with preoperative neurodegenerative chemotherapy. So, the mortality is zero. And, as I said this morning, 0.5% of severe permanent deficit. I don't speak about the deficit. If you perform three hours of neuropsychological examination, because you have deficit more or less in 100% cases. Because they have already deficit before surgery. Even in incidental discovery, we published that recently. Why two deficit? Because the anterior perforating substance. Because I did not understand 15 years ago that the right inferior frontal occipital fascicle run into the temporal stem, and then I cut it, and I was into the contact of the perforating arteries. Now, I use this functional information, even in the so-called right non-dominant hemisphere, in order to be protected from the perforating arteries. So, functional information, in fact, will give you anatomical information. And the rate of stroke I had since more than 10 years is now zero. But we understand why. Encephalial dissection, of course. What is very exciting, because it's a talk about neuroplasticity, 30% of improvement when you compare three months to one year after surgery, thanks to post-operative specific rehabilitation, of course adapted to the immediate post-operative neuropsychological examination, in comparison with the pre-operative status, plus 80% of positive impact of epilepsy, but independent factors. The impact on the survival, and now the perspective to better guide this plasticity at the individual level. And then, first of all, if you have, once again, something for young people to remember this talk, is the minimal common brain. I mean, here, it's not DTI. It looks like. But, in fact, it's only the residue I have left in my career during the first 10 years. And I decided to put everything within the same template in order to see if there was a so important variability or not, because you know that I stop only according to functional boundaries. And you can see you have not the Brocaux's error. You have the ventral premotor cortex, a little bit the primary motor cortex, but most of all, the connectivity. If you cut the connectivity, you will induce a permanent deficit. It's so clear. So now, we started to use this theory of graph in order to compare normal people with pre- and post-operative, in this case, a rejection of supplementary motor area. And you can see not modification of activation, as shown before, but a modification of the connectivity between the right and left hemisphere. And, of course, you can put this on the anatomy, but also to try to better understand what happens when the patient has a transient supplementary motor area syndrome, because you cannot ask him to do fMRI and to perform, for instance, a movement. So we will publish this paper very soon by demonstrating that you have a modification, a transient decrease of the connectivity, not only within the hemisphere you operate, but between both hemispheres. And then three months after, you will have a reconnection, not speaking about the structure, of course, because we should avoid to cut it, but speaking about the effective connectivity, explaining why the patient has a very impressive post-operative deficit and then recovered. And more or less, we started to do that also using resting state in patients for language. Here, you can see a modification of the balance between the right and left hemisphere. What was very exciting, that patient was not perfect before surgery. And, in fact, he used more his right hemisphere, but also left, so balance. And then I removed the so-called Broca's area, and you can see that it changed his connectivity, and the left hemisphere started again to be dominant, if I can say. And the patient improved. So it means that it's strange, yes, but my message is that you can remove a major part of the frontal lobe, for instance, and to improve the patient who was considered to enjoy normal life before. But it's not the truth if you perform extensive neuropsychological examination. And we use also the functional connectivity using resting state in order now to map before and after surgery what happened at the level of the cerebellum and the thalamus, because, of course, I'm not able to do that using trial-operative mapping. It's not good. And, in fact, I will not insist about that, but we have seen also modification before, just after surgery, and three months after. So it means that we start to understand the whole network, not speaking about one hemisphere, both hemispheres, but also the corticothalamo-cerebellum pathways. Once again, now you start probably to understand why I insist on this slide, because if you know this connectivity, you will not get lost anymore within the brain. The last slide, in order to also give an opportunity to my colleague, neuropsychologist Dr. Herbet, to speak a little bit more about emotional process, is to say that we published recently a paper in Brain, which is the first and the sole atlas in the literature in the MNI template, giving you for each voxel an estimation of the plasticity index. So it means that you know if a patient will recover or not, and it's not just in order to calculate before surgery the extent of reservation a priori, but it's also to see if a patient will recover after surgery, or after stroke, or after what you want. I mean brain damage. So we start now to predict the recovery of a patient by better understanding the reorganization within the networks. So we are so far from the localizationism. Just to dream the last slide, I think that we have a chance not only to apply this concept, of course, to brain surgery, in oncology, low-grade, high-grade, metastasis, cavernoma, epilepsy. We listened to that today. But also using new methodology of brain-computer interface, because, of course, if you put just an electrode and you give to the scientist in front of you in January one output and they have to solve the inverse problem, they will fail. But if you start to put different electrodes at different places within the network of this patient at this moment because the cortex is not damaged, but the disconnection syndrome, we can start to dream by telling probably we have a chance just to resynchronize the process in order to allow co-activation within the network because we start to understand the hubs at the individual level. So the last message will be, if you know this reorganization potential at the individual level before, during, and after surgery, then you can deal with the natural story of the disease and to apply to epilepsy, high-grade, low-grade. And you understand probably now a little bit more why. Sorry about that, but my protocol is that I have no protocol. Thank you very much.

neuroplasticity

brain tumor surgery

cognitive disorders

plasticity

functional imaging

surgical interventions