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Nature Communications 13, 753 (2022). doi:10.1038/s41467-022-28331-7, Published by Nature Publishing Group UK, [London]

Introduction: Deep brain stimulation (DBS) is a well-established treatment for movement disorders. High magnetic fields could have an impact on distortion. We evaluated 1.5- and 3-T magnetic resonance imaging (MRI) sequences for accuracy, precision, and trueness of our MRI-guided direct targeting protocol. Methods: Effects of distortion on MR sequences (T1- and T2-weighted sequences) can be evaluated using a dedicated phantom (Elekta). Field strength capabilities were assessed on Siemens Avanto (1.5 T) and Skyra (3 T) scanners. We assessed the precision of our stereotactic MRI-guided procedure. Results: We focused on the risk of error due to a high field strength. Error values on the localizer box were between 0.4 and 0.7 mm at 1.5 T and between 0.6 and 2 mm at 3 T. The most accurate 1.5-T sequence is the 3D FLASH T1-weighted sequence, which had an accuracy value of 0.6 mm. At 3 T, the accuracy value of the isotropic 3D FLASH T1-weighted sequence was 1.6 mm. Conclusion: Given the millimetric size of stereotactic targets and electrodes, lead implantation for neuromodulation therapy needs to be accurate. We demonstrate that 3-T imaging could not be used for stereotaxy in our MRI-guided direct targeting protocol because of a risk of error induced by distortion.

International audience; Different lines of evidence have suggested an involvement of the insular cortex in pain processing. Direct electrical stimulation (ES) of the human insular cortex during surgical procedure sometimes induces painful sensations and painful stimuli induce activation of the insular cortex as shown by functional neuroimaging. Invasive evaluation of epileptic patients by deep brain stereotactically implanted electrodes provides an opportunity to analyze responses induced by ES of the insular cortex in awake and fully conscious patients. For this study, we included 25 patients suffering from drug refractory focal epilepsy with at least one electrode stereotactically implanted in the insular cortex using an oblique approach (transfrontal or transparietal). Out of the 83 responses induced by insular ES, eight (9.6%) were reported by five patients as painful sensations. Four were restricted to the cephalic region and four were felt on the ipsilateral or bilateral upper limbs, the shoulders and the trunk (pinprick sensations). The eight stimulation sites were anatomically localized via image fusion between pre-implantation 3D MRI and post-implantation 3D CT scans revealing the electrode contacts. All sites inducing painful sensations were restricted to the upper portion of the middle short gyrus of the insula. The findings of this study suggest that middle short gyrus is involved in the processing of pain-producing stimuli.

International audience; OBJECTIVE: Cerebral ventriculography (Vg) and magnetic resonance imaging (MRI) scanning are routine procedures to determine the implanted electrode placement into the subthalamic nucleus (STN) and are used in several centers that provide deep brain stimulation for Parkinson's disease patients. However, because of image distortion, MRI scan accuracy in determining electrode placement is still matter of debate. The objectives of this study were to verify the expected localization of the electrode contacts within the STN and to compare the stereotactic coordinates of these contacts determined intraoperatively by Vg with those calculated postoperatively by MRI scans. To our knowledge, this is the first study attempting to compare the "gold standard" of stereotactic accuracy (Vg) with the anatomic resolution provided by MRI scans. METHODS: Images from 18 patients with Parkinson's disease who underwent bilateral operation were used in this study. Among the 36 chronically stimulated contacts, 28 contacts (78%) were localized in the dorsolateral part of the STN. The remaining eight contacts (22%) were located more dorsally in the zona incerta, close to the upper border of the STN. RESULTS: Significant differences were found between Vg and MRI scans regarding the mediolateral x coordinate of the contacts for both left and right electrodes and regarding the right-sided anteroposterior y coordinate. No statistical difference was found for the left-sided y coordinate and the dorsoventral z coordinate for both sides. CONCLUSION: If we assume that Vg is an imaging gold standard, our results suggest that postoperative MRI scanning may induce a slight image translation compared with Vg. However, MRI scans allowed localization of most of the contacts within the STN.

International audience; Deep brain stimulation (DBS) is a widely accepted therapy for medically refractory Parkinson's disease (PD). Both globus pallidus internus (GPi) and subthalamic nucleus (STN) stimulation are safe and effective in improving the symptoms of PD and reducing dyskinesias. STN DBS is the most commonly performed surgery for PD as compared to GPi DBS. Ventral intermediate nucleus (Vim) DBS is infrequently used as an alternative for tremor predominant PD patients. Patient selection is critical in achieving good outcomes. Differential diagnosis should be emphasized as well as neurological and nonneurological comorbidities. Good response to a levodopa challenge is an important predictor of favorable long-term outcomes. The DBS surgery is typically performed in an awake patient and involves stereotactic frame application, CT/MRI imaging, anatomical targeting, physiological confirmation, and implantation of the DBS lead and pulse generator. Anatomical targeting consists of direct visualization of the target in MR images, formula-derived coordinates based on the anterior and posterior commissures, and reformatted anatomical stereotactic atlases. Physiological verification is achieved most commonly via microelectrode recording followed by implantation of the DBS lead and intraoperative test stimulation to assess benefits and side effects. The various aspects of DBS surgery will be presented.

International audience; The generators and functional correlates of gamma oscillations within the sensorimotor cortex remain unclear. With the goal of locating the oscillations' sources precisely and then studying the relationship between oscillatory reactivity and ongoing movement, we recorded stereoelectroencephalograms with intracerebral electrodes in eight epileptic subjects awaiting surgical treatment. The sensorimotor cortex was free of lesions and was exhaustively explored with the electrodes. Subjects were asked to perform various self-paced movements contralateral to the exploration zone, brief and sustained, distal movements and a pointing movement. We used the event-related desynchronization method to quantify the reactivity of the 40-60-Hz band before, during and after the performance of movement. A very focused, event-related synchronization of gamma rhythms was found in all subjects. It was predominantly observed in the primary sensorimotor area and its distribution was consistent with the functional map established using electrical stimulations. Two different temporal patterns were observed, the event-related synchronization of gamma rhythms was related either to movement onset or to movement offset but was never recorded before movement. This observation suggests that gamma oscillations are more probably related to movement execution than to motor planning. The different patterns argue in favour of multiple functional roles; it has been shown that gamma oscillations may support the efferent drive to the muscles and here we show that they are also likely to be related to somatosensory integration. We therefore suggest that gamma oscillations in the 40-60-Hz band may support afferent sensory feedback to the sensorimotor cortex during the performance of movement.

α-Synuclein (α-syn) is a protein prevalent in neural tissue and known to undergo axonal transport. Intracellular α-syn aggregates are a hallmark of Parkinson’s disease (PD). Braak and collaborators have suggested that in people who are destined to eventually develop PD, α-syn aggregate pathology progresses following a stereotypic pattern, starting in the olfactory bulb (OB) and the gut. α-Synuclein aggregates are postulated to spread to interconnected brain regions over several years. Thus, propagation of the pathology via neural pathways can potentially explain how α-syn aggregates spread in PD. We have now studied if α-syn can transfer from the OB to other brain structures through neural connections, by injecting different molecular species of human α-syn (monomers, oligomers, fibrils) into the OB of wild-type mice. We found that non-fibrillar human α-syn is taken up very quickly by OB neurons. Within minutes to hours, it is also found in neurons in structures connected to the OB. Conversely, when we injected bovine serum albumin used as a control protein, we found that it does not diffuse beyond the OB, is rarely taken up by OB cells, and does not transfer to other structures. Taken together, our results show that OB cells readily take up α-syn, and that monomeric and oligomeric, but not fibrillar, forms of α-syn are rapidly transferred to interconnected structures within the timeframe we explored. Our results support the idea that α-syn can transfer along neural pathways and thereby contribute to the progression of the α-syn-related pathology. Electronic supplementary material The online version of this article (doi:10.1007/s00401-013-1160-3) contains supplementary material, which is available to authorized users.

International audience; Although there are numerous 3 T MRI research devices all over the world, only a few functional studies at 3 T have been done in anesthetized monkeys. In the past, anesthetized preparations were reported to be misleading when exploring cortical brain regions outside the primary sensory areas. Nonetheless, a great improvement has been achieved in the limited effect of anesthetic agents on the reactivity of the brain.Here, we re-address the feasibility and potential applications of the brain oxygen level dependent (BOLD) fMRI signal in Macaca mulatta monkeys that have been lightly anesthetized with sevoflurane and curarized. The monkeys were studied with commercially available coils and sequences using a 3 T clinical magnet. We obtained sagittal T1 scout images, gray matter double inversion recovery, standard gradient echo sequences and gradient echo functional imaging sequences. Given that fMRI signals are most readily identified in the cerebral cortices, we optimized Echo Planar Imaging sequences to reproduce significant changes in the BOLD signal subsequent to a visual stimulation paradigm.Our results provide a satisfactory signal to noise ratio with a limited standard deviation range, when compared with studies on alert macaques.We suggest that the 3 T magnet remains a valuable tool to analyze neural pathways in the macaque brain under light anesthesia and report the use of spatially resolved fMRI in higher visual areas of anesthetized monkeys. This methodology avoids the need for time-consuming training of awake monkeys, is stable over many hours, provides reproducible data and could be applied successfully to future functional studies.

International audience; Nicotine dependence is linked to single nucleotide polymorphisms in the CHRNB4-CHRNA3-CHRNA5 gene cluster encoding the a3b4a5 nicotinic acetyl-choline receptor (nAChR). Here we show that the b4 subunit is rate limiting for receptor activity, and that current increase by b4 is maximally competed by one of the most frequent variants associated with tobacco usage (D398N in a5). We identify a b4-specific residue (S435), mapping to the intracellular vestibule of the a3b4a5 receptor in close proximity to a5 D398N, that is essential for its ability to increase currents. Transgenic mice with targeted overexpres-sion of Chrnb4 to endogenous sites display a strong aversion to nicotine that can be reversed by viral-mediated expression of the a5 D398N variant in the medial habenula (MHb). Thus, this study both provides insights into a3b4a5 receptor-mediated mechanisms contributing to nicotine consumption, and identifies the MHb as a critical element in the circuitry controlling nicotine-dependent phenotypes.

Objective: To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD). Data Sources and Study Selection: An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion. Data Extraction and Synthesis: A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members. Conclusions: (1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients. Arch Neurol. 2011; 68(2):165-171. Published online October 11, 2010. doi:10.1001/archneurol.2010.260

International audience; PURPOSE: Different lines of evidence suggest that the insular cortex has many important functional roles. Direct electrical stimulation (ES) of the human insular cortex during surgical procedures for epilepsy, functional imaging techniques, and lesion studies also occasionally induces clinical responses. METHODS: In this study, we evaluated 25 patients with drug-refractory focal epilepsy by stereotactically implanting at least one electrode into the insular cortex using an oblique approach (transfrontal or transparietal). One hundred twenty-eight insular sites (each situated between two contiguous contacts within the same electrode) were examined within the gyral substructures. We located each stimulation site by fusing preimplantation three-dimensional (3D) magnetic resonance imaging (MRI) images with the postimplantation 3D computed tomography (CT) scans that revealed the electrode contacts. RESULTS: Sixty-seven stimulations induced at least one clinical response. Stimulation from within the insular cortex evoked 83 responses, without evidence of afterdischarge in the insular or extrainsular regions. We classified the principal responses as sensory (paresthesias and localized warm sensations), motor, pain, auditory, oropharyngeal, speech disturbances (including speech arrest and reduced voice intensity) and neurovegetative phenomena, such as facial reddening, generalized sensations of warmth or cold, hypogastric sensations, anxiety attacks, respiratory accelerations, sensations of rotation, and nausea. CONCLUSIONS: These findings may indicate a functional specificity for the insular gyri and show the need for exploring this structure during invasive presurgical evaluation of epileptic patients according to seizure manifestations.

International audience; PURPOSE: The determination of epileptogenic structures in partial epilepsy is crucial in the context of epilepsy surgery. In this study we have quantified the "epileptogenicity" of mesial temporal lobe structures (M), lateral neocortical regions (L), and extratemporal perisylvian structures (ET) in patients with temporal lobe epilepsy (TLE), in order to classify the brain networks involved in seizure generation. METHODS: Thirty-four patients having TLE investigated by intracerebral recordings using stereotactic electroencephalography (EEG) (SEEG) were selected. Epileptogenicity of M, L, and ET structures was quantified according to the "epileptogenicity index" (EI), a new way to quantify rapid discharges at seizure onset, ranging from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). RESULTS: Automatic clustering using EI values from M, L, and ET separated patients into four classes: mesial group (max EI in M), lateral group (max EI in L), mesiolateral group (high EI in both M and L) and temporoperisylvian group (TPS) (high values in ET). The median number of highly epileptogenic structures (defined by EI >0.3) was four, a result confirming that most TLE is organized as "epileptogenic networks." We found that the duration of epilepsy was correlated with the number of epileptogenic structures and that surgical prognosis was also related to the extent of the epileptogenicity in the brain. CONCLUSIONS: Several distinct epileptogenic networks are involved in seizure generation in TLE. Findings advocate for a progressive recruitment of epileptogenic structures in human brain with time.

International audience; Radiation therapy is commonly used in the treatment of cancer. The normal tissue tolerance can be a limit to deliver enough dose to the tumor to be curative. The synchrotron beam presents some interesting physical properties, which could decrease this limitation. Synchrotron beam is a medium energy X-ray nearly parallel beam with high intensity. Three methods are under preclinical investigations: the microbeam, the minibeam and the stereotactic radiotherapy. The first two use a geometric irradiation effect called spatial fractioning. The last one use highly conformational irradiation geometry combined with a dose enhancement due to the presence of high-Z element in the target. Synchrotron radiotherapy preclinical experiments have shown some curative effect on rodent glioma models. Following these encouraging results a phase I/II clinical trial of iodinated enhanced stereotactic synchrotron radiotherapy is currently being prepared at the European Synchrotron Radiation Facility.

Summary Purpose: Different lines of evidence have suggested an involvement of the insular cortex in speech production. These have included results from lesion studies, functional imaging techniques, and electrical stimulation of the human insular cortex during invasive evaluation of epileptic patients. Methods: We evaluated 25 patients who had drug refractory focal epilepsy with at least one electrode stereotactically implanted in the insular cortex. Results: Eight responses to insular cortex electrical stimulation were reported by five patients as speech arrest (five responses) and a lowering of voice intensity (three responses). Conclusions: Data from this study implicate the middle short gyrus of the insula in the production of speech and show the importance of intrainsular electrode implantation during invasive pre-resection evaluation by stereo-electroencephalography (SEEG) when speech arrest occurs early in seizure semiology.

OBJECT: Given that improvement is variable from one patient to another, the authors analyzed the impact of globus pallidus internus (GPi) volume on the result of deep brain stimulation (DBS) by comparing highly and less improved patients with primary dystonodyskinetic syndromes. METHODS: A stereotactic model was developed to visualize and quantify the relationship between the isofield lines generated by the DBS lead and GPi target. The model was used in 30 right-handed selected patients with primary dystonodyskinetic syndromes who had been treated using bilateral stimulation of the sensorimotor GPi. Ten healthy control individuals were also included in the study. First, the authors compared the GPi volumes between patients and healthy controls. Second, the stimulated GPi volumes, that is, the intersection between the volume of each isofield value and the GPi volumes, were compared between less improved and highly improved patients. RESULTS: Improvement in the Burke-Fahn-Marsden Dystonia Rating Scale's motor score was rated > 90% in 20 patients (97 +/- 4.6%) and < 60% in 10 patients (56.9 +/- 6%). The mean volume of the right (461.8 +/- 81.8 mm(3)) and left (406.6 +/- 113.2 mm(3)) GPi in patients showing less response to DBS was significantly smaller than the GPi volume of patients who responded well (right 539.9 +/- 86.6 mm(3), left 510.6 +/- 88.7 mm(3)) and healthy controls (right 557.8 +/- 109.1 mm(3), left 525.1 +/- 40.8 mm(3)). CONCLUSIONS: On the left side, the mean stimulated volumes (isofield line range 0.2-1 V/mm) were significantly larger in highly improved than in less improved patients. In this model, the threshold for functional effect was calculated at 0.2 V/mm.

International audience; Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is an established surgical technique for the treatment of movement disorders. The objective of this study was to propose a computational stereotactic model of the electrical distribution around the electrode within the targeted GPi in order to optimize parameter adjustment in clinical practice. The outline of the GPi can be defined precisely by using stereotactic magnetic resonance imaging (MRI) and from this it is possible to model its three-dimensional structure. The electrode and the distribution of the patient-specific parameters can then be co-registered with the GPi volume. By using this methodology, it is possible to visualize and measure the relationship between the electrical distribution of patient-specific parameters and the morphology of the GPi. The model could be applied in clinical practice to help determine the threshold for achieving a therapeutic effect and consequently may aid in optimizing parameter settings for individual patients.

International audience; In animals, the pedunculopontine (PPN) and the sub-cuneiform (SCU) nuclei located in the upper brainstem are involved during the processing of gait. Similar functional nuclei are suspected in humans but their role in gait is unclear. Here we show that, using extra-cellular recordings of the PPN/SCU region obtained in two parkinsonian patients, the SCU neurons increased their firing rate without modifying their firing pattern during mimicked steps. We conclude that SCU neurons are activated during gait processes.

Objective: This study aimed to create a stereotactic two-dimensional description of the human insula based on accurate radiological morphometric studies. Methods: Seventy-five normal cerebral MRIs were selected and drawings of the insula then obtained from serial sagittal slices. These drawings were digitalized before superimposing the anterior (AC) and posterior (PC) commissures as references. This allowed us to quantify interindividual anatomical variations in a large cohort of subjects. Results: The morphometric analysis of the insula revealed a more complex shape than previously described. This structure is delimited by four peri-insular sulci (anterior, superior, posterior and inferior) instead of the three sulci classically mentioned. Males have a statistically larger surface area than females, according to a correlated index. Precise measurements of the different insular components allowed us to quantify their potential interindividual anatomical variations and to define their average shapes and stereotactic locations. Conclusion: These data create a two-dimensional template of the human insula, with regard to the classical AC-PC stereotactic reference system. They furthermore allow us to quantify the probability that a given element of this structure is located at a predefined position. This should be useful in functional neuroimaging studies and in insular surgery for diagnostic and therapeutic goals.

International audience; BACKGROUND: The misplacement of electrodes is a possible explanation for suboptimal response to bilateral subthalamic nucleus (STN) stimulation in patients with Parkinson disease. OBJECTIVE: To evaluate whether reimplantation of electrodes in the STN can produce improvement in patients with poor results from surgery and with suspected electrode misplacement based on imaging findings. DESIGN: Prospective follow-up study. SETTING: Academic research. PATIENTS: A 1-year postoperative study was undertaken in 7 consecutive patients with Parkinson disease who, despite bilateral STN stimulation, experienced persistent motor disability and who were operated on for reimplantation a median of 16.9 months later. MAIN OUTCOME MEASURES: The primary outcome was measured as the change in the Unified Parkinson Disease Rating Scale (UPDRS) motor score 1 year after reimplantation. The secondary outcome was measured as the extent of pharmacologic and electrical treatments required and the threshold at which the first stimulation-induced adverse effect appeared. The distances between the electrode contacts used for chronic stimulation and the STN theoretical effective target, defined as the mean position of the clinically efficient contact from 193 previously implanted electrodes, were compared. RESULTS: Except for a single patient, all patients displayed improvement following reimplantation. Under off-medication (ie, the patient is taking no medication) condition, STN stimulation improved the basal state UPDRS motor score by 26.7% before reimplantation and by 59.4% at 1 year after reimplantation. The median off-medication Schwab and England score improved from 51% to 76%. The median levodopa equivalent daily dose was reduced from 1202 mg to 534 mg. The stimulation varibles changed from a mean of 2.6 V/73.0 micros/163.0 Hz to 2.8 V/60. 0 micros/ 140.0 Hz. The mean threshold of the first stimulation-induced adverse effect increased from 2.6 to 4.4 V. The mean distance between the contacts used for chronic stimulation and the theoretical effective target decreased from 5.4 to 2.0 mm. This distance correlated inversely with the percentage improvement in theUPDRS motor score. CONCLUSION: Patients demonstrating poor response to STN stimulation as a result of electrode misplacement can benefit from reimplantation in the STN closer to the theoretical target.

International audience; OBJECTIVE: This study investigates the feasibility, safety, and usefulness of depth electrodes stereotactically implanted within the insular cortex. METHODS: Thirty patients with suspected insular involvement during epileptic seizure underwent presurgical stereotactic electroencephalographic recordings using 10 to 16 depth electrodes per patient. Among these, one or two electrodes were implanted via an oblique approach to widely sample the insular cortex. RESULTS: Thirty-five insular electrodes were implanted in the 30 patients without morbidity. A total of 226 recording contacts (mean, 7.5 contacts/patient) explored the insular cortex. Stereotactic electroencephalographic recordings of seizures allowed the differentiation into groups: Group 1, 10 patients with no insular involvement; Group 2, 15 patients with secondary insular involvement; and Group 3, five patients with an initial insular involvement. In temporal epilepsy (n = 17), the insula was never involved at the seizure onset but was frequently involved during the seizures (11 out of 17). In frontotemporal or frontal epilepsy, the insula was involved at the onset of seizure in five out of 13 patients. All patients in Groups 1 and 2 underwent surgery, with a seizure-free outcome in 76.2% of patients. In Group 3, only two of the five patients underwent surgery, with a poor outcome. In temporal lobe epilepsy, surgical outcome tended to be better in Group 1 compared with Group 2 in this small series: results were good in 83.3% (Engel I) versus 72.7%. CONCLUSION: Insula can be safely explored with oblique electrodes. In temporal lobe epilepsy, insular involvement does not significantly modify the short-term postoperative outcome. Future larger studies are necessary to clarify the long-term prognostic value of insular spread.

International audience; In the stereo-electro-encephalography (SEEG) methodology developed by Talairach and Bancaud in Sainte-Anne Hospital in Paris, France, the objective of placing depth electrode recordings in presurgical evaluation is to study the spatial and temporal organization of a seizure. This defines for each patient the cortical onset zone, the propagation pattern of the seizure, and the possible involvement of eloquent areas of the cortex. This methodology requires a meticulous stereotactic surgical technique. We report here the SEEG methodology, surgical technique, and morbidity.

International audience; BACKGROUND: In our stereotactic procedure, intraoperative radiological documentation of electrode localization is performed using the Stereoplan. The aim of the study was to evaluate its accuracy. PATIENTS AND METHODS: Data of 20 consecutive patients, treated for Parkinson's disease by implantation of deep brain stimulators into the subthalamic nucleus, were collected prospectively. During surgery, Stereoplan coordinates of the tip of the central macroelectrodes were compared with intended coordinates along the central trajectory at 4 levels: (1) 10 mm above the anatomical target, (2) in the target, (3) in the substantia nigra pars reticulata, and (4) at the depth of contact 1. Before the frame's removal, Stereoplan coordinates of the contacts of the definitive electrode were compared with postoperative MRI coordinates. The mean of the differences was calculated in the x-, y-, and z-axis. Clinical results at 6 months were recorded. RESULTS: The mean of the differences between Stereoplan coordinates and intended coordinates for the macroelectrodes was lower than 1 mm. A submillimeter difference was also found for the definitive contacts. At 6 months, the Unified Parkinson's Disease Rating Scale III score improved by 70.6% compared with the baseline score. Dyskinesia and motor fluctuations decreased by 85.7 and 87%, respectively (p < 0.0001). CONCLUSION: Stereoplan could be considered an accurate intraoperative radiological system which assures the correct position of the electrode in the anatomical target.

International audience; This work addresses the spatial correlation between the anatomical and functional human subthalamic nucleus (STN). The anatomical STN (A-STN), derived from the Schaltenbrand-Wahren brain atlas, is histology based. The functional STN (F-STN) is probabilistic, constructed from neuroelectrophysiological and neuroimaging data of 184 Parkinson's disease patients. The A-STN and F-STN are placed in the same space and compared in terms of mutual relative overlapping of anatomy with function. The F-STN and A-STN correlate well for medium and high probabilities of the F-STN. For probability p >or= 0.3, >95% of F-STN is inside the A-STN, and for p >or= 0.5, the complete F-STN is inside the A-STN for each left and right STN. Therefore, the F-STN for p = 0.5 can potentially be used for identification of the STN in neuroimages.

International audience; The definition of the epileptogenic zone, as proposed by Talairach and Bancaud, is an ictal electro-clinical definition based on the results of stereotactic intracerebral EEG (SEEG) recordings. It takes into account not only the anatomical location of the "site of the beginning and of the primary organization" of the epileptic discharge, but also how this discharge gives rise to the accompanying clinical symptoms. This definition is different from the North American view since, for the French authors, the epileptogenic zone is not synonymous with what can be called the "what-to-remove area". In fact, it is above all a conceptual definition which emphazises the importance of studying the spatio-temporal dynamics of seizure discharges, and not only their starting point.

Purpose: Heavy-atom-enhanced synchrotron stereotactic radiotherapy (SSR) is a treatment that involves selective accumulation of high-Z elements in tumors followed by stereotactic irradiation with X-rays from a synchrotron source. The purpose of this study was to determine whether the efficacy of iodine-enhanced SSR could be further improved in the F98 rodent glioma model, by using a concomitant injection of an iodinated contrast agent and a transient blood–brain barrier opener (mannitol) during irradiation. Methods and Materials: Fourteen days after intracerebral inoculations of F98 cells, the rats were irradiated with 50-keV X-rays while receiving an infusion of hyperosmotic mannitol with iodine, either intravenously or via the carotid (9 to 15 rats per group, 117 rats total). Results: For doses ≤15 Gy, the intracarotid infusion of mannitol and iodine improved the rats’ survival compared with intravenous injection or irradiation alone. The percentage-increased life spans (ILS) were 91%, 116%, and 169% without iodine, after infusion of iodine and mannitol intravenously, and intracarotid, respectively (15 Gy). At 25 Gy, the rats irradiated without iodine had the longest survival (ILS = 607%), but no additional benefit was obtained with iodine and mannitol. Conclusions: Iodine-enhanced SSR is significantly improved with concomitant intracarotid infusion of iodine and mannitol for radiation doses ≤15 Gy.

OBJECTIVE: The optimal imaging modality for preoperative targeting of the subthalamic nucleus (STN) for high-frequency stimulation is controversially discussed. Commonly used methods were stereotactic magnetic resonance imaging (MRI), stereotactic ventriculography, and fusion between MRI and stereotactic computer tomography. All of these techniques not only have their own advantages but also specific limitations and drawbacks. The purpose of this study was to evaluate the accuracy of the preoperative MRI targeting as compared with ventriculography in terms of both the STN target as well as the internal landmarks. METHODS: Thirty patients with Parkinson's disease who underwent bilateral surgery for STN-high-frequency stimulation received both stereotactic ventriculography and stereotactic MRI. The theoretical target was determined by each of these two imaging modalities. The final electrode placement was performed after extensive electrophysiological evaluation using microrecording and microstimulation. The real target was assumed to be given by the electrode contact with the best clinical result assessed by the United Parkinson's Disease Rating Scale in the postoperative follow-up. In addition, the coordinates of the two landmarks, anterior commissure and posterior commissure, were determined using both imaging methods. RESULTS: The mean targeting error was 4.1 ± 1.7 mm (mean ± standard deviation) for MRI and 2.4 ± 1.1 mm for ventriculography (P < 0.0001). The mean target mismatch between the two imaging methods was 2.9 ± 1.2 mm. The length of the anterior commissure-posterior commissure distance differed significantly (P < 0.0001) between MRI (27.6 ± 1.6 mm) and ventriculography (25.0 ± 1.3 mm). The mismatch was mainly induced by an anterior diplacement of the anterior commissure by 1.9 ± 2.2 mm (P < 0.0001) in MRI determination, as compared with ventriculography. CONCLUSION: Our findings show that the indirect targeting of the STN using coordinates based on radiological landmarks is more accurate than the direct targeting using anatomic visualization of the target structure. Regardless of the imaging procedure, electrophysiological mapping is required for optimal electrode placement, although in 20% of cases, the target determined by MRI falls out of the radius explored by electrophysiology.

International audience; OBJECTIVE: To report on indications, surgical technique, results, and morbidity of stereoelectroencephalography (SEEG) in the presurgical evaluation of patients with drug-resistant focal epilepsy. METHODS: Two-hundred fifteen stereotactic implantations of multilead intracerebral electrodes were performed in 211 patients (4 patients were explored twice), who showed variable patterns of localizing incoherence among electrical (interictal/ictal scalp electroencephalography), clinical (ictal semeiology), and anatomic (magnetic resonance imaging [MRI]) investigations. MRI scanning showed a lesion in 134 patients (63%; associated with mesial temporal sclerosis in 7) and no lesion in 77 patients (37%; with mesial temporal sclerosis in 14 patients). A total of 2666 electrodes (mean, 12.4 per patient) were implanted (unilaterally in 175 procedures and bilaterally in 40). For electrode targeting, stereotactic stereoscopic cerebral angiograms were used in all patients, coupled with a coregistered three-dimensional MRI scan in 108 patients. RESULTS: One hundred eighty-three patients (87%) were scheduled for resective surgery after SEEG recording, and 174 have undergone surgery thus far. Resections sites were temporal in 47 patients (27%), frontal in 55 patients (31.6%), parietal in 14 patients (8%), occipital in one patient (0.6%), rolandic in one patient (0.6%), and multilobar in 56 patients (32.2%). Outcome on seizures (Engel's classification) in 165 patients with a follow-up period of more than 12 months was: Class I, 56.4%; Class II, 15.1%; Class III, 10.9%; and Class IV, 17.6%. Outcome was significantly associated with the results of MRI scanning (P = 0.0001) and with completeness of lesion removal (P = 0.038). Morbidity related to electrode implantation occurred in 12 procedures (5.6%), with severe permanent deficits from intracerebral hemorrhage in 2 (1%) patients. CONCLUSION: SEEG is a useful and relatively safe tool in the evaluation of surgical candidates when noninvasive investigations fail to localize the epileptogenic zone. SEEG-based resective surgery may provide excellent results in particularly complex drug-resistant epilepsies.

OBJECTIVE: Statistical analysis of patients previously operated on may improve our methods of performing subsequent surgical procedures. In this article, we introduce a method for studying the functional properties of cerebral structures from electrophysiological and neuroimaging data by using the probabilistic functional atlas (PFA). The PFA provides a spatial distribution of the clinically most effective contacts normalized to a common space. This distribution is converted into a probability function for a given point in space to be inside an effective contact. The PFA was used to analyze spatial properties of the functional subthalamic nucleus (STN), defined as the spatial volume corresponding to the distribution of effective contacts. These results may potentially be useful in planning subthalamic implantation of electrodes. METHODS: In all, 168 bilateral subthalamic stimulations were examined. An algorithm was developed for converting these data into the PFA. The PFA for the STN (here called “atlas”) was calculated with 0.25-mm3 resolution, and several features characterizing the left and right STN were studied. The analysis was performed with and without lateral compensation against the width of the third ventricle. The key feature introduced here used for analysis of the functional STN is a (probabilistic) functional volume of structure (defined for a given probability as the volume of a region whose every point has a probability equal to or greater than this given probability). RESULTS: The analysis has been performed for two situations: with and without lateral compensation against the width of the third ventricle. Without lateral compensation, the differences between the mean values and standard deviations of their barycenter coordinates for the left and right functional STNs are 0.31 and 0.18 mm, respectively. The left STN and right STN exhibit differences in functional volume size and probability distribution. The entire functional volume is 240 mm3 for the left and 229 mm3 for the right STN. A more prominent difference exists in the region of high probabilities (0.7 or higher), called “hot STN.” The volume of the left hot STN is 5.52 mm3, whereas that of the right is 3.92 mm3. The left hot STN is 1.41 times bigger and 20% more dense than the right hot STN. For a given probability, the corresponding functional volume for the left hot STN is up to 43 times larger than that for the right STN. Practically speaking, lateral compensation does not change these results qualitatively. Quantitatively, differentiation between the left and right STNs is lower. For instance, for a given probability, the corresponding functional volume for the left hot STN is only up to 11 times larger than that for the right one. In either situation (i.e., with and without lateral compensation), the size of the hot STN in relation to the whole STN remains very small (1–2%). In addition, statistical analysis shows that in either situation, the means of the left and right functional STNs are significantly different. CONCLUSION: PFA-based planning may be superior to the current practice of using anatomic atlases that provide delineation of the target structure only, because it is more precise and provides a unique target point in the stereotactic space. This best stereotactic target is the point in the individualized atlas with the highest probability, meaning the highest probability of having the best target on the basis of the patients previously operated on. This best target is located in the hot STN, the size of which determines the precision of targeting. Because the size of the hot STN in comparison to the whole STN remains very small (1–2%) independent of whether or not lateral compensation is applied, target planning and execution have to be performed with high precision. The methodology presented, based on the PFA and on the functional volume, is general and can be applied to other structures and data sets. As numerous centers keep gathering large amounts of electrophysiological human and animal data, this work may facilitate opening new avenues in exploiting these data.

Electrical stimulation of the temporal cortex in patients with epilepsy sometimes elicits experiential phenomena such as recollection of vivid memories. The neurophysiological substrate of such phenomena is poorly understood. Furthermore, the relation between the site of stimulation and the type of memory elicited has only recently started to be investigated. We investigated these issues in patient FGA who had intracerebral electrodes stereotaxically implanted in the right temporal lobe for investigation of drug-resistant epilepsy. We report the results of electrical stimulations of the perirhinal region. Two stimulations elicited experiential phenomena consisting of visual memories that belonged to FGA's past, but which were not related to any particular episode. These visual memories consisted of objects or of details of objects. These two stimulations were contrasted with other stimulations in the same subhippocampal region. Cross-correlation analysis of the depth-EEG signals filtered in frequency sub-bands revealed that experiential phenomena occurred only when the various brain structures involved in the after-discharge were synchronized in the theta range. These structures included the perirhinal region, the hippocampus, other limbic structures as well as a primary visual area. Our results suggest that recollection of vivid memory after electric stimulation of the cortex may rely on wide networks of brain areas that transiently synchronize. These results also highlight the role of the perirhinal region in human memory. Experiential phenomena are rarely obtained after brain stimulation. Replication of these results is thus required due to the small number of observations reported.

We have previously introduced a concept of a probabilistic functional atlas (PFA) to overcome limitations of the current electronic stereotactic brain atlases: anatomical nature, spatial sparseness, inconsistency and lack of population information. The PFA for the STN has already been developed. This work addresses construction of the PFA for the ventrointermediate nucleus (PFA-VIM). The PFA-VIM is constructed from pre-, intra- and postoperative electrophysiological and neuroimaging data acquired during the surgical treatment of Parkinson’s disease patients. The data contain the positions of the chronically implanted electrodes and their best contacts. For each patient, the intercommissural distance, height of the thalamus and width of the third ventricle were measured. An algorithm was developed to convert these data into the PFA-VIM, and to present them on axial, coronal and sagittal planes and in 3-D. The PFA-VIM gives a spatial distribution of the best contacts, and its probability is proportional to best contact concentration in a given location. The region with the highest probability corresponds to the best target. The PFA-VIM is calculated with 0.25-mm3 resolution from 107 best contacts in two situations: with and without lateral compensation against the width of the third ventricle. For the PFA-VIM compensated laterally, the anterior, lateral and dorsal coordinates of the mean value are (in mm) 6.24, 13.83, 1.68 for the left VIM and 6.54, –13.84, 2.10 for the right VIM. The coordinates of the mean value of the highest probability region along with the highest number of the best contacts (P) are: 6.25, 14.25, 1.75, P = 16, for the left VIM, and 6.0, –14.0, 1.00, P = 18, for the right VIM. The coordinate system origin is at the posterior commissure. For the PFA-VIM not compensated laterally, the coordinates of the mean value are 6.24, 13.99, 1.68 for the left VIM and 6.53, –14.13, 2.10 for the right VIM. The coordinates of the mean value of the highest probability region along with the highest number of the best contacts are 5.58, 13.67, 1.33, P = 14, for the left VIM, and 6.36, –14.03, 1.11, P = 17, for the right VIM. The PFA-VIM atlas overcomes several limitations of the current anatomical atlases and can improve targeting of thalamotomies and thalamic stimulations. It is dynamic and can easily be extended with new cases.

Objective : To record somatosensory evoked potentials (SEPs) to median nerve stimulation by chronically implanted electrodes in the parieto-rolandic opercular area of 9 epileptic patients, in order to evaluate whether somatosensory evoked responses could be generated in the second somatosensory area (SII) earlier than 40 ms after stimulus. Methods : Nine patients (4 males, 5 females) with drug-resistant partial epileptic seizures were investigated using stereotactically implanted electrodes in the parietal cortex, posterior to vertical anterior commissure plane and in the frontal opercular region rostral to vertical anterior commissure (VAC). Results : The main finding of this study is the recording of an early somatosensory evoked potential, (N30op), by chronically implanted electrodes in the SII area of 8 epileptic patients. In 3 patients where SEPs were performed after ipsilateral median nerve (MN) stimulation, a N30op was recorded 5.8±2 ms later than contralateral one. Conclusions : This is the first report of early SEPs recorded by electrodes implanted in SII area. The N30op potential, even if less consistent than later potentials, confirmed the important role of the SII area in the early processing of somatosensory inputs.

Objectives : To investigate the possible contribution of the second somatosensory (SII) area in the generation of the N60 somatosensory evoked potential (SEP). Methods : In 7 epileptic patients and in 6 healthy subjects scalp SEPs were recorded by 19 electrodes placed according to the 10–20 system. All epileptic patients but one were also investigated using depth electrodes chronically implanted in the parieto-rolandic opercular cortex. Scalp SEPs underwent brain electrical source analysis. Results : In both epileptic patients and healthy subjects, scalp recordings showed two middle-latency components clearly distinguishable on the basis of latency and scalp distribution: a fronto-central N60 potential contralateral to stimulation and a later bilateral temporal N70 response. SEP dipolar source modelling showed that a contralateral perisylvian dipole was activated in the scalp N70 latency range whereas separate perirolandic and frontal sources were activated at the scalp N60 latency. Depth electrodes recorded a biphasic N60/P90 response in the parieto-rolandic opercular regions contra- and ipsilateral to stimulation. Conclusions : Two different middle-latency SEP components N60 and N70 can be distinguished by topographic analysis and source modelling of scalp recordings , the sources of which are located in the fronto-central cortex contralateral to stimulation and in the supra-sylvian cortex on both sides, respectively. The source location of the scalp N70 in the SII area is strongly supported by its spatio-temporal similarities with SEPs directly recorded in the supra-sylvian opercular cortex.

International audience; Median nerve somatosensory-evoked potentials (SEPs) have been recorded using intracortical electrodes stereotactically implanted in the frontal lobe of eight epileptic patients in order to assess the waveforms, latencies and surface-to-depth distributions of somatosensory responses generated in the anterior subdivision of supplementary motor areas (SMAs), the so-called pre-SMA. Intracortical responses were analysed in two latency ranges: 0--50 ms and 50--150 ms after stimulus. In all patients, we recorded in the first 50 ms after stimulus two positive P14 and P20 potentials followed by a N30 negativity. In the hemisphere contralateral to stimulation, the P20--N30 potentials showed a clear amplitude decrease from the outer to the inner aspect of the frontal lobe with minimal amplitudes in the pre-SMA. In the hemisphere ipsilateral to stimulus, P20 and N30 amplitudes were decreasing from mesial to lateral frontal cortex. In the 50--150 ms latency range, contacts implanted in the pre-SMA recorded a negative potential in the 60--70 ms latency range which, in five patients, was followed by a positive response peaking 80--110 ms after stimulus. These potentials were not picked up by more superficial contacts. We conclude that no early SEP is generated in pre-SMA in the first 50 ms after stimulation, while some potentials peaking in the 60--100 ms after stimulus are likely to originate from this cortical area. The latency of the pre-SMA responses recorded in our patients supports the hypothesis that the pre-SMA does not receive short-latency somatosensory inputs via direct thalamocortical projections. More probably the pre-SMA receives somatosensory inputs mediated by a polysynaptic transcortical transmission through functionally secondary motor and somatosensory areas.

International audience; Together with the frontal and parietal eye fields, the supplementary eye field (SEF) is involved in the performance and control of voluntary and reflexive saccades and of ocular pursuit. This region was first described in non-human primates and is rather well localized on the dorsal surface of the medial frontal cortex. In humans the site of the SEF is still ill-defined. Functional imaging techniques have allowed investigation of the location and function of the SEF. However, there is great variability with regard to the published standardized coordinates of this area. We used here the spatial precision of functional magnetic resonance imaging (fMRI) in order to better localize the SEF in individuals. We identified as the SEF a region on the medial wall that was significantly activated when subjects executed self-paced horizontal saccades in darkness as compared to rest. This region appeared to be predominantly activated in the left hemisphere. We found that, despite a discrepancy of >2 cm found in the standardized Talairach coordinates, the location of this SEF-region could be precisely and reliably described by referring to a sulcal landmark found in each individual: the upper part of the paracentral sulcus.

International audience; 3D imaging systems and algorithms give virtual representations of the real world. New emergent hardware systems can combine virtual information and the real world. Virtual and real information must be also visually confronted in order to facilitate our comprehension of the data. We propose a solution which entails the superimposition of a real image of the anatomical areas visualised in a surgical operation with 3D digital data sets. Unlike other solutions which display virtual images in the real world, our method involves ray traced texture mapping which displays real images in a computed world.

Object. The goal of this study was to investigate the anatomical localization and functional role of human frontal eye fields (FEFs) by comparing findings from two independently conducted studies. Methods. In the first study, 3-tesla functional magnetic resonance (fMR) imaging was performed in 14 healthy volunteers divided into two groups: the first group executed self-paced voluntary saccades in complete darkness and the second group repeated newly learned or familiar sequences of saccades. In the second study, intracerebral electrical stimulation (IES) was performed in 38 patients with epilepsy prior to surgery, and frontal regions where stimulation induced versive eye movements were identified. These studies showed that two distinct oculomotor areas (OMAs) could be individualized in the region classically corresponding to the FEFs. One OMA was consistently located at the intersection of the superior frontal sulcus with the fundus of the superior portion of the precentral sulcus, and was the OMA in which saccadic eye movements could be the most easily elicited by electrical stimulation. The second OMA was located more laterally, close to the surface of the precentral gyrus. The fMR imaging study and the IES study demonstrated anatomical and stereotactic agreement in the identification of these cortical areas. Conclusions. These findings indicate that infracentimetric localization of cortical areas can be achieved by measuring the vascular signal with the aid of 3-tesla fMR imaging and that neuroimaging and electrophysiological recording can be used together to obtain a better understanding of the human cortical functional anatomy.