Okay. Thank you very much for the invitation. We are going to review a little what I'm going to talk. I'm going to talk about patient selection, talk about the preoperative protocol that we are going to use for patient, to put the patient in the theater, some issue about bone flap and patient positioning, then talk a little about intraoperative surgical mapping strategy and to go deeply in the motor mapping and in the cognitive mapping. So how we select patients for this type of surgery, actually we talk along with the patient. We look at the social background, the education. We deeply analyze the symptoms, the duration of the history. We also go deeper in the seizure history to get information on the correlation between the anatomy and the function. Of course, we also look at the patient needs. Then we look at the tumor and location, tumor volume, tumor shape. We want to have an idea of the functional networks that are involved in these specific patients. So when this has been done, and we decide that the patient can go to surgery, we perform the preoperative protocol in which we want to understand, actually, how is the level of preoperative plasticity. This gives us an idea of the feasibility of the resection. Bone flap actually is done and should include not only the tumor itself, but particularly the critical vascular supply and the functional landmarks at the cortical level. And we have also to imagine which are the tracts that we are going to find. This is the usual position that we use for frontal tumor, even the insula, and this is the lateral position that we use for the temporal and the parietal tumor. Strategy. Strategy is quite quick cortical mapping that should define the point of entry. Most of the work in subcortical mapping in which we work at the periphery of the tumor to locate the functional boundary, so to have a functional tumor disconnection. This is quite quick because we are working with a Mediterranean population, so we have to be quite quick. And the wait time is quite short. Motor mapping. For the motor mapping, we start on the neurophysiological basis of the cortical spinal tract that we can summarize as follows. First of all, we know that the cortical spinal tract has multiple areas of origin, but the most important information are the following. It's composed of different types of axons. Most of these axons are very small and has low velocity contricity. And also the termination in the spinal cord, which is the last effector, is widespread. The technique has been already shown by Professor Sham. You have the low frequency, you have the pulse technique, the high frequency. I want to make the point that you are not to stay with the probe. The probe should be changed, so you have two different paradigms that you can play with according with the probe. The bipolar probe has the advantage to have a field of stimulation, which is quite discrete. The other one has a field of stimulation that is larger because it's going from the stimulation side to the reference electrode. We also use EMG because it gives us the opportunity to monitor different muscles at the same time in the ipsi and in the contralateral body. And a quite complex interoperative machine that includes the free-running EMG, and I'm going later in this importance, MEP, SACP, and ECG, EEG. So you have the two techniques. The point is we are adapting and making the choice of the technique according to the condition that we have. This is the low frequency when you apply hover the cortex, you have actually a progressive motor unit recruitment that depends on the intensity. This is the typical response. It's a qualitative response. You can say the type of muscles that has been involved. You cannot say anything else. Look, for example, at the latency from the starting of the stimulus and the starting of the response, 250 milliseconds. When you go into the tube, then the shape of the response change from the progressive motor unit recruitment to the tonic discharge, to the tonic motor unit recruitment. The other technique, Professor Sharma showed already, is the pulse technique. The standard is the 305, but you can play with the pulses. You have the MEP response, so you have a qualitative response, plus you have a quantitative one with the amplitude of the MEP, plus you can also have an idea of the latency, so you can understand which type of district you are going to stimulate on the cortex, and you can go deeply into the subcortical tract, so you can know how deep you are. You can do this also on repetitive issue. Which kind of paradigm should be used? You have low frequency, high frequency, probe, monopolar probe, and bipolar probe. The choice is that this is the clinical information. The clinical information, you have to estimate the distance between the site of the stimulation and the primary motor cortex. This is the reason why you have to use the motor threshold, which is the lowest response in EMG with the lowest current as possible. This is dependent on the corticospinal tract excitability that, on the other way, depends on patient characteristics and tumor characteristics. We match this in actually reviewing 600 cases in our experience, and we found that we can define low-risk motor tumor in which there is a short history of seizure and the corticospinal tract is mostly displaced. In this case, you can use either low frequency, high frequency, does not matter. It's working perfectly. On the other hand, if you want to go into tumor that are more complicated with the more in high level of involvement of the corticospinal tract or high rate of seizure in the preoperative period, taking a lot of drugs, what we call high-risk motor tumor, in this case, you have to choose according to the clinical context. Also, you can see that the parameters are changing. What we can say out of this experience that high frequency in most of the condition is more efficient in exciting N1 fibers. You can use high frequency as sort of rather to understand how deep and how far you are from the cortic form N1 fibers. There is a sort of relationship between 1 milliam and 1 millimeters, but this should not be taken so strict because it depends on the cortical excitability. You have some drawbacks, for example, in cases like this one when the N1 is highly pushed and you stimulate on the S1 and N1, you get the same type of the response. This is not a funny stuff because it's due to the fact that the motor cortex actually is divided between an old one and a new N1. The new N1 is close to S1. When you are pushing with the monopolar there, you are just exciting the new N1 that is rapidly firing. It's not a problem of paradigm, it's a problem of probe. In fact, you are just to shift to another type of probe, shifting to a bipolar probe and it works beautifully. Of course, you can use this type of paradigm at the cortical level to be really focal. What we are also doing is to combine mapping with the monitoring, MEP monitoring that is continuously. This is the typical advantage that we are feeling, the fact that you have some changes in MEP shape during vessel manipulation. Also, when you have a vessel in a mess like this that you don't know if it's important or not for the primary motor cortex, you can do a test clamp. These are very quite rapid take-home messages that we are using for N1 cortex and originating fibers. We are choosing high frequency, low frequency according to the clinical context. We always prefer the motor threshold at cortical, subcortical level. These are the subcortical threshold that we are using according to the clinical context. Of course, we can go deeper and higher using another feature of the cortical spinal tract during the evolution, which is the fact that in humans, in primates and particularly in humans, the most important control is the direct control from the primary motor cortex to the last effector, which is the spinal cord. And so we can do that by changing the number of pulses going to two or one pulses from five pulses. And what you get actually is a faster response and a high focal response. And you can do that even also at subcortical level, going deeper, you look at the change between the current intensity and to be more focal when you are with a bipolar probe. We investigated the feasibility of this technique in a group of N1 tumor in the last years, and we applied to different type of tumors is a consecutive series. This type of technique, Marco Rossi reviewed these results and showed that the feasibility of the technique is around 38%. If you compare with the standard technique, what you get when for N1 tumor is an increase in extent of resection and a decrease in the post-operative deficit. This is for N1 primary motor cortex. The point is that the movement, the grasping, the most important movement depends not only on the last effector, but depends on the interaction between areas. So we should know about the mapping of the no primary motor areas. Again, we can use low frequency. Low frequency, for example, in the ventral premotor in the resting condition is not really working, but is working when the patient is performing a task. So you should know that you should use the low frequency when the patient is performing a task. On the other way, high frequency is working in the resting condition, in the primary motor cortex, in the ventral premotor. There is no motor output out of Broca area, and it is also working when the patient is performing a task. So you can use both and decide according to your needs. Another advantage of the high frequency in no primary motor area is that you can calculate and you can detect very, very precisely the type of motor neurons and the function of the motor neurons in N1 and in the no primary motor cortices. You can apply this to the clinical condition like this one to have, for example, a somatotopy of the Treno1 in a tumor that is lying between the primary motor cortex and the ventral premotor. And this is just to make the story easy to understand that this is the activity of the NUED1. This is the activity of the ventral premotor, and this is the point of entrance. The other advantage of the high frequency in this setting is the fact that you can play with the latency. So not only you have the information of the type of motor neurons and how the motor neurons are firing, but also on the latency. And when you play with latency and with the number of pulses, you can dissect at a cortical level, for example, fibers from the primary motor cortex of the face and fibers of the ventral premotor. This is introducing the concept of motor cognition, which is highly important for keeping the normal quality of life of patients. And particularly the sensory motor integration is the key point. In this sense, we are not only using and judging behavioral changes during a task, grasping, reaching, precision grasping, but we are also using free-running EMG. By this, you can detect, if you look at the patients, actually the behavioral change is more or less the same, but you can detect the level of interference in the muscle activation coming from S1 and S1 originating fibers from the supramarginal gyrus and from the ventral premotor area that are quite different. And so you can dissect that clearly. To test the motor cognition is important. Mark Rossi again checked this in a number of patients and showed that when we started to use this, we decreased the number of permanent deficits, particularly the postoperative apraxia, long-term one, and there was no need of rehabilitation. This is just to tell you that I totally agree with you that for a test condition, the patient should be awake. And we are performing a sleep case only when the primary motor cortex is really involved. In this case, to have the patient asleep is the best way because you do not have the changes in the cortex excitability due to the fact that the patient is awake. This is introducing the cognitive mapping in which, again, the standard is low-frequency technique. This is optional. You can use. You cannot use. I agree with you that the number of seizures is very low if you are using the working current that is established on the ventral premotor. If you are using this and the working current is the lowest current that is inducing an artery, as you can see here, it's due to the fact that the model of language is that the ventral premotor is the last factor involved in speech production. So you can use this current at any level, epsicortical level, and you can see there is not much difference according to the different lobe because what we want to look is actually at the circuits. I agree that if you are doing this, you have a postoperative deficit that are mostly recovering. Now the percentage of postoperative deficits in our series is between 0.5 and 1% and are due actually to vascular problem, particularly in the high-grade glioma group. Open point, particularly in the patients with long history in which we are performing supratotal resection, which is the point, is to maintain executive function and memory. We follow that, and since three years ago, we introduced some short memory tasks. More recently, some decision-making and mentalization tasks. I cannot say anything about that, just that it's highly feasible. Just a few words. The standard is low frequency, but for cognitive mapping, you can also use high frequency, particularly in the group of patients that have a long history of seizure. In this case, what you have to do is to use the TREN05 with a standard method just to change the repetition rate from one hertz to three hertz, and you can see that you can have interferences from the ventral premotor and you have a motor output. Of course, it's a motor output, but you can have semantic paraphagia and also phonemic paraphagia without any MEP response, just to tell you that it's working. So just to tell you that you have basic standard, advanced standard. When you have advanced standard, the limitation is the cost of the equipment, the personnel. You should have a neurophysiologist that is working with you, and you have to be aware of the electricity, but it's very nice to play with electricity inside the OR. This is our group. I have to say not only thanks to the people of the neurosurgical unit, but particularly the people of the lab, of the neurophysiology lab, which helps us, and this is our university. Thank you.

patient selection

surgery

preoperative protocol

bone flap

surgical mapping strategy