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Introduction: Precise localization of the epileptogenic zone is critical for successful epilepsy surgery. However, imbalanced datasets in terms of epileptic vs. normal electrode contacts and a lack of standardized evaluation guidelines hinder the consistent evaluation of automatic machine learning localization models., Methods: This study addresses these challenges by analyzing class imbalance in clinical datasets and evaluating common assessment metrics. Data from 139 drug-resistant epilepsy patients across two Institutions were analyzed. Metric behaviors were examined using clinical and simulated data., Results: Complementary use of Area Under the Receiver Operating Characteristic (AUROC) and Area Under the Precision-Recall Curve (AUPRC) provides an optimal evaluation approach. This must be paired with an analysis of class imbalance and its impact due to significant variations found in clinical datasets., Conclusions: The proposed framework offers a comprehensive and reliable method for evaluating machine learning models in epileptogenic zone localization, improving their precision and clinical relevance., Significance: Adopting this framework will improve the comparability and multicenter testing of machine learning models in epileptogenic zone localization, enhancing their reliability and ultimately leading to better surgical outcomes for epilepsy patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Delirium, also known as acute confusional state, is an acute brain disorder characterized by cognitive disturbances, particularly attentional deficits, potential behavioral changes, and altered vigilance, with a sudden onset and fluctuating course. It is a common condition among hospitalized older patients and has serious consequences for the patient, their family, and the healthcare system. It is considered an "acute brain failure" that often occurs in the context of underlying cognitive and cerebral vulnerability, similar to how acute kidney injury complicates chronic kidney disease or how acute heart failure exacerbates chronic heart failure - usually in the presence of a precipitating medical factor, often infectious, metabolic, perioperative, or neurological. This narrative review aims to describe the symptoms that allow the diagnosis of delirium in older adults, the available diagnostic or screening tools, as well as the complex and bidirectional relationships between delirium and dementia. The management of delirium, including non-pharmacological measures, will be discussed, along with symptomatic pharmacological treatments, which should be reserved for severe cases despite their low level of evidence., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: [ 18 F]F13640 is a new PET radiopharmaceutical for brain molecular imaging of serotonin 5-HT 1A receptors. Since we intend to use this radiopharmaceutical in psychiatric studies, it is crucial to establish possible sensitivity modification of 5-HT 1A receptors availability during an acute stress exposure. In this study, we first assessed the cerebrometabolic effects of a new animal model of stress with [ 18 F]FDG and then proceeded to test for effects of this model on the cerebral binding of [ 18 F]F13640, a 5-HT 1A receptors PET radiopharmaceutical., Methods: Four groups of male Sprague-Dawley were used to identify the optimal model: "stressed group" (n = 10), "post-traumatic stress disorder (PTSD) group" (n = 9) and "restraint group" (n = 8), compared with a control group (n = 8). All rats performed neuroimaging [ 18 F]FDG μPET-CT to decipher which model was the most appropriate to test effects of stress on radiotracer binding. Subsequently, a group of rats (n = 10) underwent two PET imaging acquisitions (baseline and PTSD condition) using the PET radiopharmaceutical [ 18 F]F13640 to assess influence of stress on its binding. Voxel-based analysis was performed to assess [ 18 F]FDG or [ 18 F]F13640 changes., Results: In [ 18 F]FDG experiments, the PTSD group showed a pattern of cerebrometabolic activation in various brain regions previously implicated in stress (amygdala, perirhinal cortex, olfactory bulb and caudate). [ 18 F]F13640 PET scans showed increased radiotracer binding in the PTSD condition in caudate nucleus and brainstem., Conclusions: The present study demonstrated stress-induced cerebrometabolic activation or inhibition of various brain regions involved in stress model. Applying this model to our radiotracer, [ 18 F]F13640 showed few influence of stress on its binding. This will enable to rule out any confounding effect of stress during imaging studies., Competing Interests: Declaration of competing interest Nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses., Methods: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications., Results: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder., Conclusions: The proposed NDP constitutes a promising clinical tool for patient stratification in BD., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Hedonic perception deeply changes with aging, significantly impacting health and quality of life in elderly. In young adult mice, an odor hedonic signature is represented along the antero-posterior axis of olfactory bulb, and transferred to the olfactory tubercle and ventral tegmental area, promoting approach behavior. Here, we show that while the perception of unattractive odorants was unchanged in older mice (22 months), the appreciation of some but not all attractive odorants declined. Neural activity in the olfactory bulb and tubercle of older mice was consistently altered when attraction to pleasant odorants was impaired while maintained when the odorants kept their attractivity. Finally, in a self-stimulation paradigm, optogenetic stimulation of the olfactory bulb remained rewarding in older mice even without ventral tegmental area's response to the stimulation. Aging degrades behavioral and neural responses to some pleasant odorants but rewarding properties of olfactory bulb stimulation persisted, providing new insights into developing novel olfactory training strategies to elicit motivation even when the dopaminergic system is altered as observed in normal and/or neurodegenerative aging., Competing Interests: Declaration of Competing Interest The authors have no actual or potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Interictal biomarkers of the epileptogenic zone (EZ) and their use in machine learning models open promising avenues for improvement of epilepsy surgery evaluation. Currently, most studies restrict their analysis to short segments of intracranial EEG (iEEG)., Methods: We used 2381 hours of iEEG data from 25 patients to systematically select 5-minute segments across various interictal conditions. Then, we tested machine learning models for EZ localization using iEEG features calculated within these individual segments or across them and evaluated the performance by the area under the precision-recall curve (PRAUC)., Results: On average, models achieved a score of 0.421 (the result of the chance classifier was 0.062). However, the PRAUC varied significantly across the segments (0.323-0.493). Overall, NREM sleep achieved the highest scores, with the best results of 0.493 in N2. When using data from all segments, the model performed significantly better than single segments, except NREM sleep segments., Conclusions: The model based on a short segment of iEEG recording can achieve similar results as a model based on prolonged recordings. The analyzed segment should, however, be carefully and systematically selected, preferably from NREM sleep., Significance: Random selection of short iEEG segments may give rise to inaccurate localization of the EZ., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Sudden and unexpected deaths in epilepsy (SUDEP) pathophysiology may involve an interaction between respiratory dysfunction and sleep/wake state regulation. We investigated whether patients with epilepsy exhibit impaired sleep apnea-related arousals., Methods: Patients with drug-resistant (N = 20) or drug-sensitive (N = 20) epilepsy and obstructive sleep apnea, as well as patients with sleep apnea but without epilepsy (controls, N = 20) were included. We explored (1) the respiratory arousal threshold based on nadir oxygen saturation, apnea-hypopnea index, and fraction of hypopnea among respiratory events; (2) the cardiac autonomic response to apnea/hypopnea quantified as percentages of changes from the baseline in RR intervals (RRI), high (HF) and low (LF) frequency powers, and LF/HF., Results: The respiratory arousal threshold did not differ between groups. At arousal onset, RRI decreased (-9.42%) and LF power (179%) and LF/HF ratio (190%) increased. This was followed by an increase in HF power (118%), p < 0.05. The RRI decrease was lower in drug-resistant (-7.40%) than in drug-sensitive patients (-9.94%) and controls (-10.91%), p < 0.05. LF and HF power increases were higher in drug-resistant (188%/126%) than in drug-sensitive patients (172%/126%) and controls (177%/115%), p < 0.05., Conclusions: Cardiac reactivity following sleep apnea is impaired in drug-resistant epilepsy., Significance: This autonomic dysfunction might contribute to SUDEP pathophysiology., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Bipolar disorders (BD) are characterized by cognitive impairment during the euthymic phase, to which treatments can contribute. The anticholinergic properties of medications, i.e., the ability of a treatment to inhibit cholinergic receptors, are associated with cognitive impairment in elderly patients and people with schizophrenia but this association has not been well characterized in individuals with remitted BD. Moreover, the validity of only one anticholinergic burden scale designed to assess the anticholinergic load of medications has been tested in BD. In a literature review, we identified 31 existing scales. We first measured the associations between 27 out of the 31 scales and objective cognitive impairment in bivariable regressions. We then adjusted the bivariable models with covariates: the scales significantly associated with cognitive impairment in bivariable and multiple logistic regressions were defined as having good concurrent validity to assess cognitive impairment. In a sample of 2,031 individuals with euthymic BD evaluated with a neuropsychological battery, two scales had good concurrent validity to assess cognitive impairment, whereas chlorpromazine equivalents, lorazepam equivalents, the number of antipsychotics, or the number of treatments had not. Finally, similar analyses with subjective anticholinergic side-effects as outcome variables reported 14 scales with good concurrent validity to assess self-reported peripheral anticholinergic side-effects and 13 to assess self-reported central anticholinergic side-effects. Thus, we identified valid scales to monitor the anticholinergic burden in BD, which may be useful in estimating iatrogenic cognitive impairment in studies investigating cognition in BD., Competing Interests: Conflicts of interest All authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. and ECNP. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mathematical expressions consist of recursive combinations of numbers, variables, and operators. According to theoretical linguists, the syntactic mechanisms of natural language also provide a basis for mathematics. To date, however, no theoretically rigorous investigation has been conducted to support such arguments. Therefore, this study uses a methodology based on theoretical linguistics to analyze the syntactic properties of mathematical expressions. Through a review of recent behavioral and neuroimaging studies on mathematical syntax, we report several inconsistencies with theoretical linguistics, such as the use of ternary structures. To address these, we propose that a syntactic category called Applicative plays a central role in analyzing mathematical expressions with seemingly ternary structures by combining binary structures. Besides basic arithmetic expressions, we also examine algebraic equations and complex expressions such as integral and differential calculi. This study is the first attempt at building a comprehensive framework for analyzing the syntactic structures of mathematical expressions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Amyloid-β (Aβ) plaques from Alzheimer's Disease (AD) can be visualized ex vivo in label-free brain samples using synchrotron X-ray phase-contrast tomography (XPCT). However, for XPCT to be useful as a screening method for amyloid pathology, it is essential to understand which factors drive the detection of Aβ plaques. The current study was designed to test the hypothesis that Aβ-related contrast in XPCT could be caused by Aβ fibrils and/or by metals trapped in the plaques. Fibrillar and elemental compositions of Aβ plaques were probed in brain samples from different types of AD patients and AD models to establish a relationship between XPCT contrast and Aβ plaque characteristics. XPCT, micro-Fourier-Transform Infrared spectroscopy and micro-X-Ray Fluorescence spectroscopy were conducted on human samples (one genetic and one sporadic case) and on four transgenic rodent strains (mouse: APPPS1, ArcAβ, J20; rat: TgF344). Aβ plaques from the genetic AD patient were visible using XPCT, and had higher β-sheet content and higher metal levels than those from the sporadic AD patient, which remained undetected by XPCT. Aβ plaques in J20 mice and TgF344 rats appeared hyperdense on XPCT images, while they were hypodense with a hyperdense core in the case of APPPS1 and ArcAβ mice. In all four transgenic strains, β-sheet content was similar, while metal levels were highly variable: J20 (zinc and iron) and TgF344 (copper) strains showed greater metal accumulation than APPPS1 and ArcAβ mice. Hence, a hyperdense contrast formation of Aβ plaques in XPCT images was associated with biometal entrapment within plaques. STATEMENT OF SIGNIFICANCE: The role of metals in Alzheimer's disease (AD) has been a subject of continuous interest. It was already known that amyloid-β plaques (Aβ), the earliest hallmark of AD, tend to trap endogenous biometals like zinc, iron and copper. Here we show that this metal accumulation is the main reason why Aβ plaques are detected with a new technique called X-ray phase contrast tomography (XPCT). XPCT enables to map the distribution of Aβ plaques in the whole excised brain without labeling. In this work we describe a unique collection of four transgenic models of AD, together with a human sporadic and a rare genetic case of AD, thus exploring the full spectrum of amyloid contrast in XPCT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: To identify initial features associated with significant recovery in patients with Graves' disease dysthyroid optic neuropathy (DON) treated according to EUGOGO guidelines by intravenous glucocorticoids (ivGC) and decompression surgery in first and second-line, respectively., Patients and Methods: Consecutive patients referred to our expert multidisciplinary consultation over a 6-year period underwent systematic exploration: endocrine assessment, ophthalmic examination and radiological exploration. Visual recovery, based on best-corrected visual acuity (BCVA) and visual field (VF), were evaluated at baseline, 1week and 6months. Baseline parameters were then tested for prognostic value on univariate and multivariate analyses., Results: Thirty-eight patients (69 eyes) with DON were included. Significant recovery at 6months was found in 48/69 eyes (70%), partial recovery in 18/69 (26%), and no recovery in 3/69 (4%). Fifty-one eyes (28 patients) required surgical decompression after ivGC. These patients showed more severe presentation at diagnosis, had received significantly less GC for Graves' orbitopathy before onset of DON, and showed greater fat prolapse on CT scans compared to non-operated patients. On multivariate analysis, male gender (P=0.001), cumulative GC dose>1g before DON diagnosis (P=0.048) and initial BCVA≤0.3 (P=0.004) were significantly associated with better outcomes, whereas Clinical Activity Score>5 (P=0.013) was associated with a poorer outcome., Conclusion: This study confirms a generally favorable 6-month recovery rate in DON treated according to EUGOGO guidelines and provides new information on baseline predictors of poor evolution. These results may help the respective indications for medical and surgical treatment to be more effectively combined in the future., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Implanted devices destined for contact with sterile body tissues, vasculature or fluids should be free of any microbial contamination that could lead to disease transmission. The disinfection and sterilisation of implantable biofuel cells is a challenging and largely overlooked subject due to the incompatibility of fragile biocatalytic components with classical treatments. Here we report the development of a convenient "soft" chemical treatment based on immersion of enzymatic bioelectrodes and biofuel cells in dilute aqueous chlorhexidine digluconate (CHx). We show that immersion treatment in a 0.5 % solution of CHx for 5 min is sufficient to remove 10 -6 log colony forming units of Staphylococcus hominis after 26 h while shorter treatments are less effective. Treatments with 0.2 % CHx solutions were ineffective. Bioelectrocatalytic half-cell voltammetry revealed no loss in activity at the bioanode after the bactericidal treatment, while the cathode was less tolerant. A maximum power output loss of ca. 10 % for the glucose/O 2 biofuel cell was observed following the 5 min CHx treatment, while the dialysis bag had a significant negative impact on the power output. Finally, we report a proof-of-concept in vivo operation for 4 days of a CHx-treated biofuel cell with a 3D printed holder and additional porous surgical tissue interface. Further assessments are necessary to rigorously validate sterilisation, biocompatibility and tissue response performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Evidences suggest that inflammation is increased in a subgroup of patients with depression. Moreover, increased peripheral inflammatory markers (cells and proteins) are associated with some, but not all depressive symptoms. On the other hand, similar studies on bipolar disorders mainly focused on blood cytokines. Here, we analysed data from a large (N = 3440), well-characterized cohort of individuals with bipolar disorder using Kendall partial rank correlation, multivariate linear regression, and network analyses to determine whether peripheral blood cell counts are associated with depression severity, its symptoms, and dimensions. Based on the self-reported 16-Item Quick Inventory of Depressive Symptomatology questionnaire scores, we preselected symptom dimensions based on literature and data-driven principal component analysis. We found that the counts of all blood cell types were only marginally associated with depression severity. Conversely, white blood cell count was significantly associated with the sickness dimension and its four components (anhedonia, slowing down, fatigue, and appetite loss). Platelet count was associated with the insomnia/restlessness dimension and its components (initial, middle, late insomnia and restlessness). Principal component analyses corroborated these results. Platelet count was also associated with suicidal ideation. In analyses stratified by sex, the white blood cell count-sickness dimension association remained significant only in men, and the platelet count-insomnia/restlessness dimension association only in women. Without implying causation, these results suggest that peripheral blood cell counts might be associated with different depressive symptoms in individuals with bipolar disorder, and that white blood cells might be implicated in sickness symptoms and platelets in insomnia/agitation and suicidal ideation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Impaired emotion processing constitutes a key dimension of schizophrenia and a possible endophenotype of this illness. Empirical studies consistently report poorer emotion recognition performance in patients with schizophrenia as well as in individuals at enhanced risk of schizophrenia. Functional magnetic resonance imaging studies also report consistent patterns of abnormal brain activation in response to emotional stimuli in patients, in particular, decreased amygdala activation. In contrast, brain-level abnormalities in at-risk individuals are more elusive. We address this gap using an image-based meta-analysis of the functional magnetic resonance imaging literature., Methods: Functional magnetic resonance imaging studies investigating brain responses to negative emotional stimuli and reporting a comparison between at-risk individuals and healthy control subjects were identified. Frequentist and Bayesian voxelwise meta-analyses were performed separately, by implementing a random-effect model with unthresholded group-level T-maps from individual studies as input., Results: In total, 17 studies with a cumulative total of 677 at-risk individuals and 805 healthy control subjects were included. Frequentist analyses did not reveal significant differences between at-risk individuals and healthy control subjects. Similar results were observed with Bayesian analyses, which provided strong evidence for the absence of meaningful brain activation differences across the entire brain. Region of interest analyses specifically focusing on the amygdala confirmed the lack of group differences in this region., Conclusions: These results suggest that brain activation patterns in response to emotional stimuli are unlikely to constitute a reliable endophenotype of schizophrenia. We suggest that future studies instead focus on impaired functional connectivity as an alternative and promising endophenotype., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: The leading treatment for motor signs of Parkinson's disease is L-DOPA, but, upon extended use, it can lead to levodopa-induced dyskinesia (LID). Serotonergic neurons are involved in LID etiology and previous pre-clinical studies have shown that NLX-112, a 5-HT 1A biased agonist, has robust antidyskinetic effects. Here, we investigated its effects in hemiparkinsonian (HPK) rats with a unilateral nigrostriatal 6-OHDA lesion., Methods: We compared HPK rats with LID (i.e., sensitized to the dyskinetic effects of chronic L-DOPA) and without LID (HPK-non-LID), using [ 18 F]FDG PET imaging and fMRI functional connectivity following systemic treatment with saline, L-DOPA, NLX-112 or L-DOPA + NLX-112., Results: In HPK-non-LID rats, [ 18 F]FDG PET experiments showed that L-DOPA led to hypermetabolism in motor areas (cerebellum, brainstem, and mesencephalic locomotor region) and to hypometabolism in cortical regions. L-DOPA effects were also observed in HPK-LID rats, with the additional emergence of hypermetabolism in raphe nuclei and hypometabolism in hippocampus and striatum. NLX-112 attenuated L-DOPA-induced raphe hypermetabolism and cingulate cortex hypometabolism in HPK-LID rats. Moreover, in fMRI experiments NLX-112 partially corrected the altered neural circuit connectivity profile in HPK-LID rats, through activity in regions rich in 5-HT 1A receptors., Conclusion: This neuroimaging study sheds light for the first time on the brain activation patterns of HPK-LID rats. The 5-HT 1A receptor agonist, NLX-112, prevents occurrence of LID, likely by activating pre-synaptic autoreceptors in the raphe nuclei, resulting in a partial restoration of brain metabolic and connectivity profiles. In addition, NLX-112 also rescues L-DOPA-induced deficits in cortical activation, suggesting potential benefit against non-motor symptoms of Parkinson's disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pain is a private experience, whose assessment relies on subjective self-reporting. Inaccurate communication renders pain evaluation unreliable in individuals with alteration of consciousness, lack of verbal interaction, cognitive dysfunction or simple malingering, hence the importance of developing reliable objective assessment tools., Objectives: Since pain is associated with autonomic arousal, here we used readouts of autonomic activity to assess objectively the arousing effect of somatic stimuli in a human model of hyperalgesia., Methods: We used topical capsaicin to induce cutaneous hypersensitivity in the right arm of 20 healthy volunteers, and recorded sympathetic skin responses (SSR) and numerical perceptive ratings (NRS) to stimulation of the sensitized region and its homologous contralateral site, using brush (Aβ), pinprick (Aδ) and laser (C-Warmth) stimuli., Results: Both subjective ratings and SSRs were significantly enhanced to stimulation of the sensitized region, and their respective ratios of maximal enhancement were positively correlated. At individual level, a significant association was observed between SSR and NRS behavior (χ2(1)= 11.03; p < 0.001), with a positive predictive value of 87% (CI95 [77-97%]) for SSR increase predicting enhancement of subjective reports. A "lie experiment" asking subjects to simulate elevated NRS failed to enhance SSRs. Significant habituation of SSRs appeared when stimuli were repeated at ∼15s intervals, hence decreasing their negative predictive value when several consecutive stimuli were averaged (NPV=46%; CI95 [30-62%])., Conclusion: The SSR may represent a rapid and reliable procedure to assess cutaneous hypersensitivity, simple to use in clinical practice and resistant to simulation. Rapid habituation is a drawback that can be countered by using few repetitions and low stimulus rates., Competing Interests: Conflict of interest The authors declare that there are no financial or other relationships that might lead to a conflict of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

We report the case of a 19-year-old patient with an acute-onset non-traumatic coma. Brain MRI scan was normal, CSF showed mild pleocytosis and moderately elevated protein, and continuous EEG-monitoring was compatible with spindle-coma. Cortical somatosensory evoked potentials (SSEPs) and middle-latency auditory evoked potentials (MLAEPs) were bilaterally absent, and brainstem auditory evoked potentials suggested a brainstem dysfunction. Serum anti-GQ1b and anti-GT1a IgG antibodies positivity suggested Bickerstaff's brainstem encephalitis (BBE). The clinical and functional outcomes were favorable and normal cortical SSEPs/MLAEPs reappeared in a few weeks. Based on this report, in cases of unexplained MRI-negative coma with neurophysiological evidence of brainstem dysfunction, BBE should be eliminated before considering withdrawal of life-sustaining therapy (WLST)., Competing Interests: Declaration of Competing Interests None., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The auditory mismatch negativity (MMN) is a well characterized event-related potential component which has gained recent attention in theoretical models describing the impact of various styles of mindfulness meditation on attentional processes and perceptual inference. Previous findings highlighted a distinct modulation of the MMN amplitude by different meditation practices and degrees of expertise. In the present study, we attempted to replicate results from the recent literature with a data sample that allowed for increased statistical power compared to previous experiments. Relying on traditional frequentist analysis, we found no effect of focused attention and open monitoring meditation on the auditory MMN amplitude compared to a control condition (silent movie) in expert or novice practitioners (all p > 0.17), providing a non-replication of our previous work (Fucci et al. 2018). Using a Bayesian approach, we found strong evidence against an interaction effect on the MMN amplitude between expertise groups and meditation practices (BF 01  = 11.0), strong evidence against effects of either meditation practices compared to the control condition (BF 01 between 11.9 and 16.1) and moderate evidence against an effect of expertise during meditation (BF 01 between 5.3 and 7.9). On the other hand, we replicated previous evidence of increased alpha oscillatory power during meditation practices compared to a control state (p < 0.001). We discuss our null findings in relation to factors that could undermine the replicability of previous research on this subject, namely low statistical power, use of flexible analysis methods and a possible publication bias leading to a misrepresentation of the available evidence., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Normal brain aging is associated with deficits in cognitive and sensory processes, due to subtle impairment of synaptic contacts and plasticity. Impairment may be discrete in basal conditions but is revealed when cerebral plasticity is involved, such as in learning contexts. We used olfactory perceptual learning, a non-associative form of learning in which discrimination between perceptually similar odorants is improved following exposure to these odorants, to better understand the cellular bases of olfactory aging in mice. We first evaluated learning ability and memory retention in 2-, 6-, 12-, and 18-month-old mice, and identified 12 months as a pivotal age when memory retention subtly declines before learning becomes totally impaired at later ages. We then showed that learning-induced structural plasticity of adult-born granule cells is specific to cells responding to the learned odorants in the olfactory bulb of young adult mice and loses its specificity in 12-month-old mice, in parallel to memory impairment. Taken together, our data refine our understanding of aging-related impairment of plasticity mechanisms in the olfactory bulb and consequent induction of olfactory learning and memory deficits., (Copyright © 2022. Published by Elsevier Inc.)

Patients with a Klinefelter syndrome (KS), defined by a 47 XXY karyotype, were long considered infertile. Testicular sperm extraction (TESE) now allows them to access fatherhood. We will present the data of studies since first experiment of TESE. Several factors influencing TESE outcome were proposed in these different studies. Among them, clinical and hormonal parameters have reported by few studies, age has been one of the most discussed prognostic factor of positive sperm retrieval rate. Data seems to show that TESE carried out before an age greater than 30 has a poorer prognosis for positive sperm retrieval. In few studies performed in younger patient, before 20 years, SRR was closed to result for 20 to 30 year old patients. Offering a TESE before 16 years old does not improve positive sperm extraction rate. In fact, the few studies carried out before the age of 16 were of poorer prognosis, most often linked to insufficient maturation of the residual gametes. In addition, androgen therapy, frequently prescribed in case of Klinefelter syndrome, did not seem to show any effect on sperm retrieval but only few studies were interested in the possible impact of this treatment. In conclusion, further studies are necessary to determine the interest of new markers to predict the chance of sperm retrieval, taking into account age, hormonal therapy., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Listening to task-irrelevant speech while performing a cognitive task can involuntarily deviate our attention and lead to decreases in performance. One explanation for the impairing effect of irrelevant speech is that semantic processing can consume attentional resources. In the present study, we tested this assumption by measuring performance in a non-linguistic attentional task while participants were exposed to meaningful (native) and non-meaningful (foreign) speech. Moreover, based on the tight relation between pupillometry and attentional processes, we also registered changes in pupil diameter size to quantify the effect of meaningfulness upon attentional allocation. To these aims, we recruited 41 native German speakers who had neither received formal instruction in French nor had extensive informal contact with this language. The focal task consisted of an auditory oddball task. Participants performed a duration discrimination task containing frequently repeated standard sounds and rarely presented deviant sounds while a story was read in German or (non-meaningful) French in the background. Our results revealed that, whereas effects of language meaningfulness on attention were not detectable at the behavioural level, participants' pupil dilated more in response to the sounds of the auditory task when background speech was played in non-meaningful French compared to German, independent of sound type. In line with the initial hypothesis, this suggested that semantic processing of the native language required attentional resources, which lead to fewer resources devoted to the processing of the sounds of the focal task. Our results highlight the potential of the pupil dilation response for the investigation of subtle cognitive processes that might not surface when only behaviour is measured., (Copyright © 2022 Elsevier B.V. All rights reserved.)

TCF4 gene (18q21.1) encodes for a transcription factor with multiple isoforms playing a critical role during neurodevelopment. Molecular alterations of this gene are associated with Pitt-Hopkins syndrome, a severe condition characterized by intellectual disability, specific facial features and autonomic nervous system dysfunction. We report here three patients presenting with structural variations of the proximal part of TCF4 associated with a mild phenotype. The first patient is a six-years-old girl carrier of a pericentric inversion of chromosome 18, 46,XX,inv(18)(p11.2q21.1). Whole genome sequencing (WGS) characterized the breakpoint at the base-pair level at chr18:1262334&#95;1262336 and chr18:53254747&#95;53254751 (hg19). This latter breakpoint disrupted the proximal promotor region of TCF4 in the first intron of the gene. The second and third patients are a son and his mother, carrier of a 46 kb deletion characterized by high-resolution chromosomal micro-array and WGS (chr:18:53243454&#95;53287927, hg19) encompassing the first three exon of TCF4 gene and including the proximal promotor region. Expression studies on blood lymphocytes in these patients showed a marked decrease of mRNA level for long isoforms of TCF4 and an increased level for shorter isoforms. The patients described here, together with previously reported patients with proximal structural alterations of TCF4, help to delineate a phenotype of mild ID with non-specific facial dysmorphism without characteristic features of PTHS. It also suggests a gradient of phenotypic severity inversely correlated with the number of intact TCF4 promotor regions, with expression of short isoforms compensating in part the loss of longer isoforms., (Copyright © 2022. Published by Elsevier Masson SAS.)

Objective: We hypothesized that spatio-temporal dynamics of interictal spikes reflect the extent and stability of epileptic sources and determine surgical outcome., Methods: We studied 30 consecutive patients (14 good outcome). Spikes were detected in prolonged stereo-electroencephalography recordings. We quantified the spatio-temporal dynamics of spikes using the variance of the spike rate, line length and skewness of the spike distribution, and related these features to outcome. We built a logistic regression model, and compared its performance to traditional markers., Results: Good outcome patients had more dominant and stable sources than poor outcome patients as expressed by a higher variance of spike rates, a lower variance of line length, and a lower variance of positive skewness (ps < 0.05). The outcome was correctly predicted in 80% of patients. This was better or non-inferior to predictions based on a focal lesion (p = 0.016), focal seizure-onset zone, or complete resection (ps > 0.05). In the five patients where traditional markers failed, spike distribution predicted the outcome correctly. The best results were achieved by 18-h periods or longer., Conclusions: Analysis of spike dynamics shows that surgery outcome depends on strong, single and stable sources., Significance: Our quantitative method has the potential to be a reliable predictor of surgical outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. All rights reserved.)

Different types of white matter hyperintensities (WMH) can be observed through MRI in the brain and spinal cord, especially Multiple Sclerosis (MS) lesions for patients suffering from MS and age-related WMH for subjects with cognitive disorders and/or elderly people. To better diagnose and monitor the disease progression, the quantitative evaluation of WMH load has proven to be useful for clinical routine and trials. Since manual delineation for WMH segmentation is highly time-consuming and suffers from intra and inter observer variability, several methods have been proposed to automatically segment either MS lesions or age-related WMH, but none is validated on both WMH types. Here, we aim at proposing the White matter Hyperintensities Automatic Segmentation Algorithm adapted to 3D T2-FLAIR datasets (WHASA-3D), a fast and robust automatic segmentation tool designed to be implemented in clinical practice for the detection of both MS lesions and age-related WMH in the brain, using both 3D T1-weighted and T2-FLAIR images. In order to increase its robustness for MS lesions, WHASA-3D expands the original WHASA method, which relies on the coupling of non-linear diffusion framework and watershed parcellation, where regions considered as WMH are selected based on intensity and location characteristics, and finally refined with geodesic dilation. The previous validation was performed on 2D T2-FLAIR and subjects with cognitive disorders and elderly subjects. 60 subjects from a heterogeneous database of dementia patients, multiple sclerosis patients and elderly subjects with multiple MRI scanners and a wide range of lesion loads were used to evaluate WHASA and WHASA-3D through volume and spatial agreement in comparison with consensus reference segmentations. In addition, a direct comparison on the MS database with six available supervised and unsupervised state-of-the-art WMH segmentation methods (LST-LGA and LPA, Lesion-TOADS, lesionBrain, BIANCA and nicMSlesions) with default and optimised settings (when feasible) was conducted. WHASA-3D confirmed an improved performance with respect to WHASA, achieving a better spatial overlap (Dice) (0.67 vs 0.63), a reduced absolute volume error (AVE) (3.11 vs 6.2 mL) and an increased volume agreement (intraclass correlation coefficient, ICC) (0.96 vs 0.78). Compared to available state-of-the-art algorithms on the MS database, WHASA-3D outperformed both unsupervised and supervised methods when used with their default settings, showing the highest volume agreement (ICC = 0.95) as well as the highest average Dice (0.58). Optimising and/or retraining LST-LGA, BIANCA and nicMSlesions, using a subset of the MS database as training set, resulted in improved performances on the remaining testing set (average Dice: LST-LGA default/optimized = 0.41/0.51, BIANCA default/optimized = 0.22/0.39, nicMSlesions default/optimized = 0.17/0.63, WHASA-3D = 0.58). Evaluation and comparison results suggest that WHASA-3D is a reliable and easy-to-use method for the automated segmentation of white matter hyperintensities, for both MS lesions and age-related WMH. Further validation on larger datasets would be useful to confirm these first findings., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: High-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce neuropathic pain, but intermittent "theta-burst" stimulation (iTBS) could be a better alternative because of shorter duration and greater ability to induce cortical plasticity. Here we compared head-to-head the pain-relieving efficacy of the two modalities when applied daily for 5 days to patients with neuropathic pain., Methods: Forty-six patients received 20 Hz-rTMS and/or iTBS protocols and 39 of them underwent the full two procedures in a random cross-over design. They rated pain intensity, sleep quality, fatigue and general health status daily during 5 consecutive weeks., Results: Pain relief during the month following stimulation was superior after 20 Hz-rTMS relative to iTBS (F(1,38) = 4.645; p = 0.037). Correlation between respective levels of maximal relief showed a significant deviation toward the 20 Hz-rTMS effect. A greater proportion of individuals responded to 20 Hz-rTMS (52% vs 32%, 95 %CI[0.095-3.27]; p = 0.06), and reports of fatigue significantly improved after 20 Hz-rTMS relative to iTBS (p = 0.01). General health and sleep quality scores did not differentiate both techniques., Conclusions: High-frequency rTMS appeared superior to iTBS for neuropathic pain relief., Significance: Adequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Developmental dyslexia is a reading disorder that features difficulties in perceiving and tracking rhythmic regularities in auditory streams, such as speech and music. Studies on typical healthy participants have shown that power fluctuations of neural oscillations in beta band (15-25 Hz) reflect an essential mechanism for tracking rhythm or entrainment and relate to predictive timing and attentional processes. Here we investigated whether adults with dyslexia have atypical beta power fluctuation., Methods: The electroencephalographic activities of individuals with dyslexia (n = 13) and typical control participants (n = 13) were measured while they passively listened to an isochronous tone sequence (2 Hz presentation rate). The time-frequency neural activities generated from auditory cortices were analyzed., Results: The phase of beta power fluctuation at the 2 Hz stimulus presentation rate differed and appeared opposite between individuals with dyslexia and controls., Conclusions: Atypical beta power fluctuation might reflect deficits in perceiving and tracking auditory rhythm in dyslexia., Significance: These findings extend our understanding of atypical neural activities for tracking rhythm in dyslexia and could inspire novel methods to objectively measure the benefits of training, and predict potential benefit of auditory rhythmic rehabilitation programs on an individual basis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The new paradigm of precision medicine in oncology questions today the respective place of evidence-based medicine and doctor-patient relationship. Based on the results of a randomized study comparing the efficacy of a homeopathic molecule in the prevention of nausea and vomiting induced by chemotherapy in non-metastatic breast cancer, this article extends and develops the discussion of maintaining an unresolved tension between medical art and medical science, between care and cure. This tension sets a base for the authors of the therapeutic alliance in medicine, defined as a dialectic constantly adjourned between the alliance of the doctor with the patient and his therapy, and the therapeutic effect of this alliance. Because if a policy or a public opinion were to promote an exclusively rational medicine deprived of the field of relation to care, or on the contrary a medicine based only on clinical sense and intuition, then respectively the ethics of care and the progress of therapy would be threatened. It is advisable to be aware of erring from the truth, amplified today by social networks, as much due to a tide of scientific positivism, as an excess of the "good caring soul". Taking into account the therapeutic alliance makes it possible to no longer oppose scientific medicine and care relationship., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Young children are not only prepared to learn from teaching, but they also start to spontaneously teach others, indicating that teaching is a natural instinct of the humankind. During childhood, teaching seems to precede the emergence of several cognitive abilities, so the question arises: how does teaching affect the development of later emerging cognitive skills? Since teaching requires explicit, accessible representations of the knowledge of the teacher, we hypothesized that the motivation to teach might impact the way children encode novel information, by biasing them towards a model-based encoding, which can help them to structure the incoming information in a more abstract and explicitly accessible way. In our study, 7-10-year-old children were presented with a well-established probabilistic sequence learning task on two consecutive days, after receiving an instruction that on the second day, they would have to teach a peer about the task. During the task, we could simultaneously measure two different types of learning: model-free learning of local (lower-level) statistical correlations and model-based learning of the global (higher-level) statistical structures of the sequences. We predicted that in case the motivation to teach facilitates model-based encoding, children who received the instruction to teach would perform better in learning the higher-level statistical structures than children in the control group, who did not receive an instruction to teach. Furthermore, since previous studies showed competition between the two types of encoding processes during development, we also predicted that facilitating children's model-based learning will impair their model-free learning of the lower-level statistical correlations. Our results confirmed both predictions, showing an improved model-based higher-level structure learning and an impaired model-free lower-level statistical correlation learning in the Teaching Group, compared to the controls. Thus, prompting teaching affects children's encoding of the novel information, by biasing them to learn in a model-based way, which can help to build more abstract and explicitly accessible representations that could be shared with others., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

It is unclear how implicit prior knowledge is involved and remains persistent in the extraction of the statistical structure underlying sensory input. Therefore, this study investigated whether the implicit knowledge of second-order transitional probabilities characterizing a stream of visual stimuli impacts the processing of unpredictable transitional probabilities embedded in a similar input stream. Young adults (N = 50) performed a four-choice reaction time (RT) task that consisted of structured and unstructured blocks. In the structured blocks, more probable and less probable short-range nonadjacent transitional probabilities were present. In the unstructured blocks, the unique combinations of the short-range transitional probabilities occurred with equal probability; therefore, they were unpredictable. All task blocks were visually identical at the surface level. While one-half of the participants completed the structured blocks first followed by the unstructured blocks, this was reversed in the other half of them. The change in the structure was not explicitly denoted, and no feedback was provided on the correctness of each response. Participants completing the structured blocks first showed faster RTs to more probable than to less probable short-range transitional probabilities in both the structured and unstructured blocks, indicating the persistent effect of prior knowledge. However, after extended exposure to the unstructured blocks, they updated this prior knowledge. Participants completing the unstructured blocks first showed the RT difference only in the structured blocks, which was not constrained by the preceding exposure to unpredictable stimuli. The results altogether suggest that implicitly acquired prior knowledge of predictable stimuli influences the processing of subsequent unpredictable stimuli. Updating this prior knowledge seems to require a longer stretch of time than its initial acquisition., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In schizophrenia, abnormal synaptic pruning during adolescence may be due to altered expression of the Complement component 4 (C4). Overexpression of C4 genes has been identified in the total cerebral cortex and in 6 different brain regions of schizophrenic patients compared to controls. These alterations should be replicated and extended to other brain regions relevant to schizophrenia. Moreover, it remains unknown whether cerebral and peripheral C4 expression levels are related., Methods: We explored C4 genes expression both at the cerebral and peripheral levels. Using shinyGEO application we analyzed C4 expression from eight Gene Expression Omnibus datasets obtained from 196 schizophrenic patients and 182 control subjects. First, we compared C4 expression between schizophrenic patients and controls in postmortem cerebral samples from 7 different brain regions. Then, we compared C4 expression between schizophrenic patients and controls in 4 peripheral tissues., Results: At the cerebral level, we provide further evidence of C4 overexpression in schizophrenic patients. Consistently with a previous report, we found C4 overexpression in the dorsolateral prefrontal cortex and in the parietal cortex of schizophrenic patients. The observation of C4 overexpression was further extended to the superior temporal cortex and the associative striatum of schizophrenic patients. Conversely, no significant alteration of C4 expression was observed in peripheral tissues., Conclusions: Our results support the hypothesis of an excessive Complement activity in various brain regions of schizophrenic patients which may disrupt the synaptic pruning process occurring during adolescence. C4 overexpression may be specific to the cerebral tissue while other alterations of the Complement system may be detected at the systemic level., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Lockdown measures can differentially affect mental wellbeing in populations depending on individual determinants. We aim to investigate the sociodemographic and environmental determinants of wellbeing on the French population during lockdown due to the SARS-CoV-2 pandemic with an online survey. Among 11,391 participants who completed the questionnaire, various factors negatively impacted wellbeing: being a female, a student, disabled, having no access to outdoor spaces, or living in a small home. Conversely, being employed and having more social contacts had a positive impact. During lockdowns, authorities should consider the vulnerability of specific populations, especially when they live in constrained housing conditions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Most reasoning tasks used in behavioral and neuroimaging studies are abstract, triggering slow, effortful processes. By contrast, most of everyday life reasoning is fast and effortless, as when we exchange arguments in conversation. Recent behavioral studies have shown that reasoning tasks with the same underlying logic can be solved much more easily if they are embedded in an argumentative context. In the present article, we study the neural bases of this type of everyday, argumentative reasoning. Such reasoning is both a social and a metarepresentational process, suggesting it should share some mechanisms, and thus some neural bases, with other social, metarepresentational process such as pragmatics, metacognition, or theory of mind. To isolate the neural bases of argumentative reasoning, we measured fMRI activity of participants who read the same statement presented either as the conclusion of an argument, or as an assertion. We found that conclusions of arguments, compared to assertions, were associated with greater activity in a region of the medial prefrontal cortex that was identified in quantitative meta-analyses of studies on theory of mind. This study shows that it is possible to use more ecologically valid tasks to study the neural bases of reasoning, and that using such tasks might point to different neural bases than those observed with the more abstract and artificial tasks typically used in the neuroscience of reasoning. Specifically, we speculate that reasoning in an argumentative context might rely on mechanisms supporting metarepresentational processes in the medial prefrontal cortex., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To evaluate alterations of top-down and/or bottom-up attention in migraine and their cortical underpinnings., Methods: 19 migraineurs between attacks and 19 matched control participants performed a task evaluating jointly top-down and bottom-up attention, using visually-cued target sounds and unexpected task-irrelevant distracting sounds. Behavioral responses and magneto- and electro-encephalography signals were recorded. Event-related potentials and fields were processed and source reconstruction was applied to event-related fields., Results: At the behavioral level, neither top-down nor bottom-up attentional processes appeared to be altered in migraine. However, migraineurs presented heightened evoked responses following distracting sounds (orienting component of the N1 and Re-Orienting Negativity, RON) and following target sounds (orienting component of the N1), concomitant to an increased recruitment of the right temporo-parietal junction. They also displayed an increased effect of the cue informational value on target processing resulting in the elicitation of a negative difference (Nd)., Conclusions: Migraineurs appear to display increased bottom-up orienting response to all incoming sounds, and an enhanced recruitment of top-down attention., Significance: The interictal state in migraine is characterized by an exacerbation of the orienting response to attended and unattended sounds. These attentional alterations might participate to the peculiar vulnerability of the migraine brain to all incoming stimuli., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

When individuals are exposed to a constant change of the interplay with their environment, they are able to develop compensatory alterations of visuo-motor coordination in order to counteract the perturbation. Prism adaptation (PA) is a very simple tool that has been used for several decades to investigate adaptive processes. However, the specific terminology used in PA literature has continuously evolved and is still subjected to broad inconsistency. Growing confusion about the choice of terms used to describe specific processes and methods has yielded the critical need for clarifying the adaptation vocabulary. The aim of this terminology review is to consider and to describe the most common terms used in PA literature in order to ensure more consistent communication in future research. On the basis of a descriptive examination of previous studies on PA, we provide specification for each term, indicating whether it refers to a classical term in PA literature, and whether it is recommended or should be used with particular attention. This glossary represents a useful instrument to both new readers and experts in the field of PA in order to facilitate unambiguous communication and consensual comparisons between individual investigations. Recommendations for the use of consistent paradigms and reliable vocabulary are provided for future investigations, in both basic and clinical research., (Copyright © 2019 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Stereoelectroencephalography-guided radiofrequency-thermocoagulation (SEEG-guided RF-TC) consists of coupling SEEG investigation with RF-TC stereotactic lesioning directly through the recording electrodes. In this systematic review the surgical technique, indications, and outcomes are described. Maximum accuracy is reached when a frame-based procedure with a robotic assistance and a per-operative vascular X-ray imaging are performed. Monitoring of the lesioning procedure based on the impedance, a sharp modification of which indicates that the thermocoagulation has reached its maximum volume, allows the optimization of the lesion size. The first indication concerns patients in whom a SEEG is required to determine whether surgery is feasible and in whom resection is indeed possible. Even if surgery is performed owing to insufficient efficacy of SEEG-guided RF-TC, the procedure remains interesting owing to its high positive predictive value for good outcome after surgery. The second indication concerns patients in whom phase I non-invasive investigations have concluded to surgical contraindication and who may still undergo SEEG in a purely therapeutic perspective (small deep zones inaccessible to surgery and network nodes of large epileptic networks). Lastly, SEEG-guided RF-TC can be considered as a first-line treatment for periventricular nodular heterotopia (PNH). Independently of indication, the overall seizure-free rate is 23% and the responder rate is 58%. The best results are obtained for PNH (38% seizure-free and 81% responders), while the worst results have been reported for temporal lobe-epilepsy in a dedicated study. The overall complication rate is 2.5%. More evidence is needed to help determine the exact place of SEEG-guided RF-TC in the surgical management algorithm., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to perform in-vitro and in-vivo radiopharmacological characterizations of [ 18 F]2FNQ1P, a new PET radiotracer of 5-HT 6 receptors, in rat, pig, non-human primate and human tissues. The 5-HT 6 receptor is one of the more recently identified serotonin receptors in central nervous system and, because of its role in memory and cognitive processes, is considered as a promising therapeutic target., Methods: In-vitro autoradiography and saturation binding assays were performed in postmortem brain tissues from rat, pig, non-human primate and human caudate nucleus, completed by serum stability assessment in all species and cerebral radiometabolite and biodistribution studies in rat., Results: In all species, autoradiography data revealed high binding levels of [ 18 F]2FNQ1P in cerebral regions with high 5-HT 6 receptor density. Binding was blocked by addition of SB258585 as a specific antagonist. Binding assays provided K D and B max values of respectively 1.34 nM and 0.03 pmol·mg - 1 in rat, 0.60 nM and 0.04 pmol·mg - 1 in pig, 1.38 nM and 0.07 pmol·mg - 1 in non-human primate, and 1.39 nM and 0.15 pmol·mg - 1 in human caudate nucleus. In rat brain, the proportion of unmetabolized [ 18 F]2FNQ1P was >99% 5 min after iv injection and 89% at 40 min. The biodistribution studies found maximal radioactivity in lungs and kidneys (3.5 ± 1.2% ID/g and 2.0 ± 0.7% ID/g, respectively, 15 min post-injection)., Conclusion: These radiopharmacological data confirm that [ 18 F]2FNQ1P is a specific radiotracer for molecular imaging of 5-HT 6 receptors and suggest that it could be used as a radiopharmaceutical in humans., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)