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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; 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.

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; 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.

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.

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; 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.