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Mapping the chimpanzee brain connectome and comparing it to that of humans is key to our understanding of similarities and differences in primate evolution that occurred after the split from their common ancestor around 6 million years ago. In contrast to studies on macaque species’ brains, fewer studies have specifically addressed the structural connectivity of the chimpanzee brain and its comparison with the human brain. Most comparative studies in the literature focus on the anatomy of the cortex and deep nuclei to evaluate how their morphology and asymmetry differ from that of the human brain, and some studies have emerged concerning the study of brain connectivity among humans, monkeys, and apes. In this work, we established a new white matter atlas of the deep and superficial white matter structural connectivity in chimpanzees. In vivo anatomical and diffusion-weighted magnetic resonance imaging (MRI) data were collected on a 3-Tesla MRI system from 39 chimpanzees. These datasets were subsequently processed using a novel fiber clustering pipeline adapted to the chimpanzee brain, enabling us to create two novel deep and superficial white matter connectivity atlases representative of the chimpanzee brain. These atlases provide the scientific community with an important and novel set of reference data for understanding the commonalities and differences in structural connectivity between the human and chimpanzee brains. We believe this study to be innovative both in its novel approach and in mapping the superficial white matter bundles in the chimpanzee brain, which will contribute to a better understanding of hominin brain evolution.

Sowing of wildflower strips has been integrated in agri-environment schemes of several European countries. Their beneficial effects on natural enemies of pest insects are well documented but (1) the desired spill-over into crop fields has not always been demonstrated, and (2) the need to adapt sown mixtures to regional climatic differences has been rarely addressed.We set up a multi-site experiment in different French climatic regions to compare effects of a wildflower strip with a grass mixture and spontaneous vegetation. The design included five regions, three to five fields per region and the three strip treatments being repeated in each field. We tested strip treatment effects on vegetation (plant species richness, plant and flower cover) and on natural enemies (hoverflies, ladybirds, aphid predation). In a subset, we further analysed the spill-over into winter wheat fields including natural enemies and pest insects (cereal aphids, leaf beetles).The wildflower strip mixture developed well in all regions and increased plant species richness and flower cover compared with grass strips and spontaneous vegetation. We found a corresponding higher hoverfly abundance and aphid predation in wildflower strips that were consistent in all regions, whereas ladybird abundance was not affected. A significantly higher hoverfly abundance, aphid predation and aphid parasitism in wheat fields close to wildflower strips indicated a spill-over. No corresponding margin treatment effects were observed for aphid and leaf beetle abundance in the field. A multivariate analysis comparing the influence of climate and vegetation parameters showed that floral cover better explained variation in natural enemy abundance and predation than climate. Our results demonstrated that similar mixtures of native plants can be used over large climatic gradients to improve biocontrol. Further research is needed to improve spill-over into crop fields and to obtain consistently strong effects in different climate zones.

Intracranial EEG (iEEG) performed during the pre-surgical evaluation of refractory epilepsy provides a great opportunity to investigate the neurophysiology of human cognitive functions with exceptional spatial and temporal precisions. A difficulty of the iEEG approach for cognitive neuroscience, however, is the potential variability across patients in the anatomical location of implantations and in the functional responses therein recorded. In this context, we designed, implemented, and tested a user-friendly and efficient open-source toolbox for Multi-Patient Intracranial data Analysis (MIA), which can be used as standalone program or as a Brainstorm plugin. MIA helps analyzing event related iEEG signals while following good scientific practice recommendations, such as building reproducible analysis pipelines and applying robust statistics. The signals can be analyzed in the temporal and time-frequency domains, and the similarity of time courses across patients or contacts can be assessed within anatomical regions. MIA allows visualizing all these results in a variety of formats at every step of the analysis. Here, we present the toolbox architecture and illustrate the different steps and features of the analysis pipeline using a group dataset collected during a language task.

Objectives: Our understanding of how societal conditions and educational policies influence cognitive development across the life course is improving. We tested the extent to which inequality of educational opportunity (IEO), the country- and cohort-specific correlation of parents' and their offspring's length of schooling, offers systematically different opportunities to contribute to cognitive development, which in turn influences cognitive abilities up to older ages. Methods: A total of 46,972 individuals of three cohorts born 1940–63 from 16 European countries and Israel provided up to six cognitive assessments and information on covariates in the SHARE survey 2004–2017. Individual-level data were linked to indicators of IEO at time of schooling, and economic, health, and human development, provided by World Bank, WHO, and the UN. Results: In multilevel (mixed-effects) models with random individual and country-cohort effects and adjusted for a large set of confounders, higher IEO was associated with lower levels of cognitive functioning in men and women. Interaction analyses suggested lower cognitive levels particularly of women who were schooled in higher IEO contexts and had lower educational attainment. Associations with rate of change in cognitive functioning were present only in women, however there was little clinically relevant cognitive decline across the window of observation. Result patterns were mostly consistent after including additional contextual indicators, and in a subsample with childhood information. Discussion: Findings suggest that IEO is able to substantially influence cognitive development with long-lasting impacts. Lower-educated women of the cohorts under investigation may have been particularly vulnerable to high-inequality educational contexts.

We describe a patient with unilateral periventricular nodular heterotopia (PNH) and drug-resistant epilepsy, whose SEEG revealed that seizures were arising from the PNH, with the almost simultaneous involvement of heterotopic neurons (“micronodules”) scattered within the white matter, and subsequently the overlying cortex. Laser ablation of heterotopic nodules and the adjacent white matter rendered the patient seizure free.This case elucidates that “micronodules” scattered in white matter between heterotopic nodules and overlying cortex might be another contributor in complex epileptogenicity of heterotopia. Detecting patient-specific targets in the epileptic network of heterotopia creates the possibility to disrupt the pathological circuit by minimally invasive procedures. Keywords: Periventricular nodular heterotopia, Stereo-EEG, Epileptogenicity

Neural oscillations in auditory cortex are argued to support parsing and representing speech constituents at their corresponding temporal scales. Yet, how incoming sensory information interacts with ongoing spontaneous brain activity, what features of the neuronal microcircuitry underlie spontaneous and stimulus-evoked spectral fingerprints, and what these fingerprints entail for stimulus encoding, remain largely open questions. We used a combination of human invasive electrophysiology, computational modeling and decoding techniques to assess the information encoding properties of brain activity and to relate them to a plausible underlying neuronal microarchitecture. We analyzed intracortical auditory EEG activity from 10 patients while they were listening to short sentences. Pre-stimulus neural activity in early auditory cortical regions often exhibited power spectra with a shoulder in the delta range and a small bump in the beta range. Speech decreased power in the beta range, and increased power in the delta-theta and gamma ranges. Using multivariate machine learning techniques, we assessed the spectral profile of information content for two aspects of speech processing: detection and discrimination. We obtained better phase than power information decoding, and a bimodal spectral profile of information content with better decoding at low (delta-theta) and high (gamma) frequencies than at intermediate (beta) frequencies. These experimental data were reproduced by a simple rate model made of two subnetworks with different timescales, each composed of coupled excitatory and inhibitory units, and connected via a negative feedback loop. Modeling and experimental results were similar in terms of pre-stimulus spectral profile (except for the iEEG beta bump), spectral modulations with speech, and spectral profile of information content. Altogether, we provide converging evidence from both univariate spectral analysis and decoding approaches for a dual timescale processing infrastructure in human auditory cortex, and show that it is consistent with the dynamics of a simple rate model.

Background: Heterotopic neuroglial tissue is defined as a mass composed of mature brain tissue isolated from the cranial cavity or spinal canal. The nose and the naso-pharynx are the most common sites of location. Only 264 cases are reported in the world literature. In this study, we present cases of nasal glial heterotopia we treated in our department. The aim of this paper is to study clinicopathological aspects of these cases of nasal glial heterotopia. Methods: From 2013 to 2018, we included in our department all the babies who suffered from a neuroglial heterotopia in the head and neck region. Clinical and radiological findings of these cases were analyzed. Histopathological examination was the mainstay of diagnosis. Results: Four cases of glial heterotopia of the nasal cavity were included and presented in this study. Conclusions: Glial Heterotopias of head and neck are more common in the nasal cavity. Clinical and radiological findings as well as histopathology and immuno-histochemistry are essential to diagnose these lesions. Keywords: Nasal glial heterotopia, Nasal glioma

To develop and reproduce, animals need long-chain MUFAs and PUFAs. Although some unsaturated FAs (UFAs) can be synthesized by the organism, others must be provided by the diet. The gene, desat1, involved in Drosophila melanogaster UFA metabolism, is necessary for both larval development and for adult sex pheromone communication. We first characterized desat1 expression in larval tissues. Then, we found that larvae in which desat1 expression was knocked down throughout development died during the larval stages when raised on standard food. By contrast pure MUFAs or PUFAs, but not saturated FAs, added to the larval diet rescued animals to adulthood with the best effect being obtained with oleic acid (C18:1). Male and female mating behavior and fertility were affected very differently by preimaginal UFA-rich diet. Adult diet also strongly influenced several aspects of reproduction: flies raised on a C18:1-rich diet showed increased mating performance compared with flies raised on standard adult diet. Therefore, both larval and adult desat1 expression control sex-specific mating signals. A similar nutrigenetics approach may be useful in other metabolic mutants to uncover cryptic effects otherwise masked by severe developmental defects.

Background/purpose: Bisphosphonates (BPs) are synthetic drugs with antitumor and bone antiresorptive activities. The use of BPs is suspected to favor the emergence of osteonecrosis of the jaw (ONJ), a putative side effect whose pathogenesis remains unclear. Thus, we aimed to get insights about the impact of BPs on osteoblasts functions, using a three-dimensional (3D) culture model, which is suggested to be more similar to the in vivo tissues than monolayers. Materials and methods: Effects of low (0.1 μM) and high (10 μM) concentrations of zoledronic acid were investigated on osteoblasts (hFOB 1.19), cultured as multicellular spheroids (MCS). Proliferation, apoptosis, spheroid growth kinetics, and morphology were studied using the 3-(4,5-dimethyl-thiazoyl-2yl) 2,5-diphenyl-tetrazolium bromide (MTT) and acid phosphatase (APH) assays, caspase 3 Western-blotting, phase contrast imaging and scanning electron microscopy (SEM). Results: Proliferation, apoptosis, and spheroid morphology showed that 10 μM zoledronic acid (ZA) induced a significant reduction in the relative viable cell number, correlated with morphological alterations of spheroids, and induction of apoptosis. A lower ZA concentration (0.1 μM) promoted cell proliferation without affecting growth kinetics or spheroid morphology. Conclusion: ZA sensitivity of osteoblasts depends on concentration and experimental models. The dual dose-dependent effects of ZA on osteoblasts cultured as spheroids, thereby promoting or inhibiting cell proliferation, may provide opportunities in tissue engineering. At last, the hFOB spheroid culture system represents a valuable model for the exploration of the molecular basis of BPs action on osteoblasts and for the development and evaluation of implantable biomaterials in bone sites.

Cortical spreading depression (CSD) is the most likely cause of the migraine aura. Drugs with distinct pharmacological properties are effective in the preventive treatment of migraine. To test the hypothesis that their common denominator might be suppression of CSD we studied in rats the effect of three drugs used in migraine prevention: lamotrigine which is selectively effective on the aura but not on the headache, valproate and riboflavin which have a non-selective effect. Rats received for 4 weeks daily intraperitoneal injections of one of the three drugs. For valproate and riboflavin we used saline as control, for lamotrigine its vehicle dimethyl sulfoxide. After treatment, cortical spreading depressions were elicited for 2 h by occipital KCl application. We measured CSD frequency, its propagation between a posterior (parieto-occipital) and an anterior (frontal) electrode, and number of Fos-immunoreactive nuclei in frontal cortex. Lamotrigine suppressed CSDs by 37% and 60% at posterior and anterior electrodes. Valproate had no effect on posterior CSDs, but reduced anterior ones by 32% and slowed propagation velocity. Riboflavin had no significant effect at neither recording site. Frontal Fos expression was decreased after lamotrigine and valproate, but not after riboflavin. Serum levels of administered drugs were within the range of those usually effective in patients. Our study shows that preventive anti-migraine drugs have differential effects on CSD. Lamotrigine has a marked suppressive effect which correlates with its rather selective action on the migraine aura. Valproate and riboflavin have no effect on the triggering of CSD, although they are effective in migraine without aura. Taken together, these results are compatible with a causal role of CSD in migraine with aura, but not in migraine without aura.

Illusions of inappropriate familiarity with the current experience or hallucinatory recall of memories are reported in temporal lobe seizures. Pathophysiological hypotheses have been proposed, involving temporal limbic regions (Hughlings-Jackson), temporal neocortex ("interpretive cortex", Penfield), or both (Bancaud). Recent data acquired from presurgical investigations using intracerebral electrode recordings, demonstrate a critical role for the sub- and para-hippocampal cortices. From this, a novel hypothesis of cortico-limbic networks emerged: déjà-vu results from an abnormal synchronization between rhinal cortices and hippocampus, and reminiscences ("dreamy state") from activation of the associational function of the hippocampus in re-assembling elements of the past experience networks. "Experiential" phenomena are better scrutinized during direct cortical stimulation than during spontaneous occurrence, because it allows precise spatiotemporal correlations to be made between the illusion/hallucination and the electrical discharge features and localization. Therefore, we present a summary of the stimulation data published since Penfield's seminal studies, review the anatomical and physiological correlations of stimulation findings, and question their functional significance. We reappraise the distinct and coactive roles of the various regions involved in perception-memory processes including the hippocampus, rhinal cortices, temporal neocortex and constituent elements of the ventral stream. Additionally, we draw insights from what is known about the perception-cognition continuum underlying the construction of episodic memories. Finally, we compare the results from cortical stimulation in the epileptogenic zone with the use of stimulation for memory enhancement and explore what this reveals about the mechanisms of stimulation., 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 International Federation of Clinical Neurophysiology. All rights reserved.)

Objective: Postencephalitic epilepsy is often resistant to antiseizure medications, leading to evaluation for epilepsy surgery. Characterizing its localization carries implications for optimal surgical approach. We aimed to determine whether a prior history of encephalitis is associated with specific epileptogenic networks among patients with drug resistant epilepsy undergoing stereotactic EEG (SEEG)., Methods: We conducted a retrospective cohort study of drug resistant epilepsy, with and without a prior history of encephalitis. We analyzed SEEG recordings to identify patterns of seizure onset and organization. Seventeen patients with a history of encephalitis (of infectious etiology in two subjects) were identified from a database of patients undergoing SEEG and were compared to seventeen drug-resistant epilepsy controls without a history of encephalitis matched for confounding variables including pre-implantation hypotheses, epilepsy duration, age, and sex., Results: Independent bilateral seizures were noted in 65% of the postencephalitic epilepsy cohort. We identified four SEEG-ictal patterns in patients with a prior history of encephalitis: (1) anteromesial temporal onset (24%), (2) anteromesial temporal onset with early spread to the perisylvian region (29%), (3) perisylvian (59%) and (4) synchronized anteromesial temporal and perisylvian (29%) onsets. Patterns 3 and 4, with perisylvian involvement at onset, were unique to the encephalitis group (p = 0.0003 and 0.04 respectively) and exhibited a "patchwork" organization. None of the encephalitis patients vs 5/7 matched controls had Engel I outcome (p = 0.0048)., Conclusions: Postencephalitic epilepsies involve anteromesial temporal and perisylvian networks, often in a bilateral independent manner. Unique ictal patterns involving the perisylvian regions was identified in the encephalitis group, but not in the matched control group., Significance: These findings may reflect a selective vulnerability of the perisylvian regions to epilepsy resulting from encephalitis, significantly mitigating the chances of success with SEEG-guided temporal resections., 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 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Identification and localization of the "epileptogenic process" in the brain of patients with drug-resistant epilepsy for surgical cure is the goal of presurgical investigations. Intracranial recordings are required when conflicting data between seizure clinical semiology and EEG prevent precise localization within one hemisphere or lateralization, when a visible lesion on MRI seems unrelated to the electroclinical data, or in MRI-negative cases. Two methods are currently used. The objective of the subdural grid electrocorticography with or without depth electrodes (SDG/DE) is the best possible identification of the area of onset of spontaneous seizures and localization of the eloquent cortex. The objective of stereoelectroencephalography (SEEG) is to define the epileptogenic zone (configured as a network) and its relation to an unmasked lesion. Two-dimensional (SDG) and three-dimensional (SEEG) brain sampling dictate different strategies for noninvasive presurgical phase I goals as well as for data analysis. SEEG must resolve several potential localization hypotheses in a manner that cannot be achieved with SDG. SDG operates through brain surface coverage, unlike SEEG, which samples networks. SDG estimates the extent of cortical resection through a lobar or sublobar localization of ictal onset and constraints from functional mapping. SEEG defines a tailored resection according to the results of anatomo-electro-clinical correlations in stereotaxic space that will guide the ablation of the epileptogenic zone. SEEG is currently expanding faster than SDG. The prerequisites (especially in the preimplantation hypothetical strategy) and technical tools (especially stimulation and functional mapping) in the two methods are very different. This chapter presents a comparative review of the rationale, indications, electrode implantation strategies, interpretation, and surgical decision making of these two approaches of presurgical evaluation for epilepsy surgery., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Picture naming is a standard task used to probe language processes in healthy and impaired speakers. It recruits a broad neural network of language related areas, among which the hippocampus is rarely included. However, the hippocampus could play a role during picture naming, subtending, for example, implicit learning of the links between pictured objects and their names. To test this hypothesis, we recorded hippocampal activity during plain picture naming, without memorization requirement; we further assessed whether this activity was modulated by contextual factors such as repetition priming and semantic interference. Local field potentials recorded from intracerebral electrodes implanted in the healthy hippocampi of epileptic patients revealed a specific and reliable pattern of activity, markedly modulated by repetition priming and semantic context. These results indicate that the hippocampus is recruited during picture naming, presumably in relation to implicit learning, with contextual factors promoting differential hippocampal processes, possibly subtended by different sub-circuitries., (Copyright © 2016. Published by Elsevier Inc.)

Recent theory of physiology of language suggests a dual stream dorsal/ventral organization of speech perception. Using intra-cerebral Event-related potentials (ERPs) during pre-surgical assessment of twelve drug-resistant epileptic patients, we aimed to single out electrophysiological patterns during both lexical-semantic and phonological monitoring tasks involving ventral and dorsal regions respectively. Phonological information processing predominantly occurred in the left supra-marginal gyrus (dorsal stream) and lexico-semantic information occurred in anterior/middle temporal and fusiform gyri (ventral stream). Similar latencies were identified in response to phonological and lexico-semantic tasks, suggesting parallel processing. Typical ERP components were strongly left lateralized since no evoked responses were recorded in homologous right structures. Finally, ERP patterns suggested the inferior frontal gyrus as the likely final common pathway of both dorsal and ventral streams. These results brought out detailed evidence of the spatial-temporal information processing in the dual pathways involved in speech perception., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The phenomenon of 'déjà vu' is caused by acute disturbance of mnemonic systems of the medial temporal lobe (MTL). In epileptic patients investigated with intracerebral electrodes, déjà vu can be more readily induced by stimulation of the rhinal cortices (RCs) than the hippocampus (H). Whether déjà vu results from acute dysfunction of the familiarity system alone (sustained by RC) or from more extensive involvement of the MTL region (including H) is debatable., Methods: We analysed the synchronisation of intracerebral electroencephalography (EEG) signals recorded from RC, H and amygdala (A) in epileptic patients in whom déjà vu was induced by electrical stimulation. EEG signal correlations (between signals from RC, A and H) were evaluated using a nonlinear regression., Results: In comparison with RC stimulations that did not lead to déjà vu (DV-), stimulations triggering déjà vu (DV+) were associated with increased broadband EEG correlation (p=0.01). Changes in correlations were significantly different in the theta band for RC-A (p=0.007) and RC-H (p=0.01) and in the beta band for RC-H (p=0.001) interactions., Conclusion: Déjà vu is associated with increased EEG signal correlation between MTL structures., Significance: Results are in favour of a mechanism involving transient co-operation between various MTL structures, not limited to RC alone., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Regions involved in language processing have been observed in the inferior part of the left temporal lobe. Although collectively labelled 'the Basal Temporal Language Area' (BTLA), these territories are functionally heterogeneous and are involved in language perception (i.e. reading or semantic task) or language production (speech arrest after stimulation). The objective of this study was to clarify the role of BTLA in the language network in an epileptic patient who displayed jargonaphasia., Methods: Intracerebral evoked related potentials to verbal and non-verbal stimuli in auditory and visual modalities were recorded from BTLA. Time-frequency analysis was performed during ictal events., Results: Evoked potentials and induced gamma-band activity provided direct evidence that BTLA is sensitive to language stimuli in both modalities, 350 ms after stimulation. In addition, spontaneous gamma-band discharges were recorded from this region during which we observed phonological jargon., Conclusion: The findings emphasize the multimodal nature of this region in speech perception. In the context of transient dysfunction, the patient's lexical semantic processing network is disrupted, reducing spoken output to meaningless phoneme combinations., Significance: This rare opportunity to study the BTLA "in vivo" demonstrates its pivotal role in lexico-semantic processing for speech production and its multimodal nature in speech perception.

Objective: Our aim was to investigate relationships between heterotopic and remote cortical structures at seizure initiation, in a patient with bilateral periventricular nodular heterotopias (BPNH) explored by intracerebral electrodes., Methods: Stereoelectroencephalography (SEEG) was performed in a man with BPNH and refractory epilepsy to investigate the hypothesis of right temporal lobe epilepsy and the possible involvement of heterotopic structures during seizures. SEEG signals were analyzed with quantification of functional coupling between different brain structures during seizures, using nonlinear regression. We have used Z-score transformation of correlation values to reflect the change from the preictal period. Relationships between BPNH and cortical structures were investigated using analysis of stimulation-induced potentials., Results: Three spontaneous seizures were recorded and analyzed. Signal analysis of interdependencies in two seizures demonstrated a large initial network involving both heterotopia and cortical structures. Stimulations of heterotopia induced responses in remote cortical structures., Conclusions: Distinct epileptogenic networks were identified, in which leader structures were either the heterotopic or the mesial temporal structures, with functional connections between heterotopic and cortical areas., Significance: These results confirm that a vast epileptogenic network, including heterotopic and cortical neurons, may be responsible for seizure generation in BPNH. This may explain certain surgical failures in this group.

Objective: During focal epileptic seizures, patients may express intense agitation, screaming and facial expressions of rage, fear or anger. The precise anatomical origin of such intense ictal emotional behaviour is not fully understood and the mechanisms by which the epileptic discharges provoke these phenomena are unknown. In the present study, we analysed the neurophysiological mechanisms underlying ictal emotional behaviour in 3 patients with frontal lobe epilepsies undergoing intracerebral recordings for presurgical evaluation., Methods: We analyzed the interactions between regions forming 'emotional networks', before and during behavioural alterations. Intracerebral recordings (SEEG method) of seizures from 3 patients presenting with frontal lobe seizures were analyzed. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between brain structures., Results: We found that these intense emotional alterations were associated with a decrease of synchrony between signals recorded from the neural networks known to be involved in emotional processing, and in particular a loss of synchrony between the orbito-frontal cortex and the amygdala. This disruption of functional connections could then result in the disruption of emotional regulation leading to the release of altered behaviour, as observed in epileptic patients during seizures., Conclusions: We propose that the occurrence of intense ictal emotional behaviour disturbance in frontal lobe seizures is related to a disruption of the normal mechanisms of emotional regulation, Significance: These results provide some insight into our understanding of the pathophysiological processes involved in human partial epilepsies as well as in the interpretation of clinical semiology.

Objective: We present a novel quantitative method to statistically analyze the distribution of multichannel intracerebral interictal spikes (multi-IIS) in stereoelectroencephalographic (SEEG) recordings. The method automatically extracts groups of brain structures conjointly and frequently involved in the generation of interictal activity. These groups are referred to as 'subsets of co-activated structures' (SCAS). We applied the method to long duration interictal recordings in patients with mesial temporal lobe epilepsy (MTLE) and analyzed the reproducibility of subsets of structures involved in the generation of multi-IIS for each patient and among patients., Methods: Fifteen patients underwent long-term intracerebral EEG recording (SEEG technique) using depth electrodes. A 1 h period of continuous interictal EEG recording was selected for each patient with precautions regarding the time after anesthesia pre-SEEG, the temporal distance with respect to seizures, the vigilance state of the patient, and the anti-epileptic drug withdrawal. A research of SCAS was conducted on each recording using the developed method that includes 3 steps: (i) automatic detection of monochannel intracerebral interictal spikes (mono-IIS), (ii) formation of multi-IIS using a temporal sliding window, and (iii) extraction of SCAS. In the third step, statistical tests are used to evaluate the frequency of multi-IIS as well as their significance (with respect to the 'random distribution of mono-IIS' case)., Results: In each patient, several thousands of multi-IIS (mean+/-SD, 3322+/-2190) were formed and several SCAS (mean+/-SD, 3.80+/-1.47) were automatically extracted. Results show that reproducible subsets of brain structures are involved in the generation of interictal activity. Although SCAS were found to be variable from one patient to another, some invariant information was pointed up. In all patients, multi-IIS distribute over two distinct groups of structures: mesial structures (15/15) and lateral structures (7/15). Moreover, two particular structures, the internal temporal pole and the temporo-basal cortex, may be conjointly involved with either the first or the second group. Finally, some extracted SCAS seem to match well-defined anatomo-functional circuits of the temporal lobe., Conclusions and Significance: During interictal activity in MTLE, similar subsets of temporal lobe structures are involved in the generation of spikes. This paper brings statistical evidence for the existence of these subsets and presents a method to automatically extract them from SEEG recordings. Interictal activity is spatially organized in the temporal lobe and preferentially involves two functional systems of the temporal lobe (either mesial or lateral).

Objective: To study whether sensory afferents of the hand projected directly to the primary motor cortex (M1) as they have been well electrophysiologically described in monkeys but not in humans., Methods: We recorded intracerebrally in the central areas (pre- and/or postcentral gyrus) somatosensory evoked potentials (SEPs) to median nerve stimulation in 5 (4 women, 1 man; age 14-37 years) epileptic patients during presurgical evaluation., Results: The primary somatosensory cortex (S1) showed negative-positive components peaking at about 20 and 30 ms, respectively. By contrast, M1 disclosed SEPs of two types of waveforms depending on the portion of the precentral gyrus explored by the different contacts of the electrode. Here, we demonstrated, for the first time, in the medial portion of M1, shaped like an omega in the axial plane, corresponding to the motor hand area, the occurrence of a primary negative component as in S1, but of higher amplitude and peaking at about 4 ms later. In other respects, the lateral portion of M1 disclosed positive-negative components peaking at about 21 and 31 ms, respectively., Conclusions: These electrophysiological findings, based on accurate spatial and temporal resolution of intracerebral recordings, suggested that somatosensory inputs from the hand projected directly to M1 in its medial portion.

Context: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers. and specialists from French public universities,general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients., Objectives: To update clinical practice guidelines for the management of patients with salivary gland malignant tumors previously validated in 1997. These recommendations cover diagnosis, treatment and follow-up of patients with these tumors., Methods: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been defined, the document is submitted for review by independent reviewers., Results: This article presents the updated clinical practice guidelines concerning irradiation of patient with salivary gland tumors. The main recommendations are: 3 dimensional conformal radiotherapy (with or without intensity modulation) or 2D irradiation can be used; for surgical complete resected patients, postoperative photon radiotherapy should not be used in case of low grade stage I and 11 tumors(standard, level of evidence B2) but should be used for high grade stage II, II and IV tumors and for low grade stage III and IV tumors(standard, level of evidence B2). Neutron therapy should not be used in all of these cases (standard, level of evidence D); for patients presenting an incomplete macroscopic or microscopic surgical residual disease, postoperative irradiation must be delivered(standard). Neutron or photon therapy can be either delivered (options); for non operable patients neutron or photon therapy can be either delivered (options, level of evidence B2); for unresectable tumors or in case of recurrent neoplasms, exclusive neutron therapy or surgical tumor reduction combined with postoperative photon beam irradiation can be proposed (options, level of evidence C).

Context: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients., Objectives: To update clinical practice guidelines for the management of patients with salivary gland malignant tumors previously validated in 1997. These recommendations cover diagnosis, classification, treatment and follow-up of patients with these tumors., Methods: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPG s according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers., Results: This article is a summary version of the full document presenting the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concern the place of fine needle aspiration biopsy in preoperative diagnosis, the place of cervical lymph node area surgical treatment, the place of postoperative irradiation and neutron therapy in the treatment of unresectable tumors and also the place of medical imaging, especially RMI, for the diagnosis of these tumors., (Copyright John Libbey Eurotext 2003.)

Objective: Our main goal was to evaluate the accuracy of an original non-supervised spatio-temporal magnetoencephalography (MEG) localization method used to characterize interictal spikes generators., Methods: MEG and stereotactic intracerebral recordings (stereo-electro-encephalographic exploration, SEEG) data were analyzed independently in 4 patients. MEG localizations were performed with and without anatomical constraints., Results: We analyzed 1326 interictal spikes recorded using MEG. For each patient, 2-3 typical source patterns were described. These source configurations were compared with SEEG. SEEG findings and MEG spatio-temporal localization results were remarkably coherent in our 4 patients. Most of the MEG patterns were similar to interictal SEEG patterns from a spatio-temporal point of view., Conclusions: We were able to evaluate the usefulness of our non-invasive localization method. This approach described correctly the part of the epileptogenic network involved in the generation of interictal events. Our results demonstrate the potential of MEG in the non-invasive spatio-temporal characterization of generators of interictal spikes.

Objective: To compare the localizations of different neural sources (a) obtained from intracerebral evoked responses and (b) calculated from surface auditory evoked field responses recorded in the same subjects. Our aim was to evaluate the resolving power of a source localization method currently used in our laboratory, which is based on a recent spatio-temporal algorithm used in magneto-encephalography (MEG)., Methods: Auditory evoked responses were studied in 4 patients with medically intractable epilepsy. These responses were recorded from depth electrodes implanted in the auditory cortex for pre-surgical evaluation (stereo-electro-encephalography (SEEG)), as well as from surface captors (for MEG) placed on the scalp after removal of the depth electrodes. Auditory stimuli were clicks and short tone bursts with different frequencies., Results: All middle-latency components (from 13 to 70 ms post-stimulus onset) were recorded and localized (via SEEG) along Heschl's gyrus (HG). MEG reliably localized Pam and P1m in the same area of HG that intracerebral recordings localized them in. No significant delay between SEEG and MEG latencies was observed. Both methods suggest that N1 is generated from different sources in the intermediate and lateral parts of the HG and in the planum temporale (PT). The source of P2 (PT and/or Area 22) remains unclear and was in one case, localized in different regions according to the method used. This latter component may therefore also be generated by different sources., Conclusions: The results suggest that both techniques are useful and may be used together in a complementary fashion. Intracerebral recordings allow the researcher to validate and interpret surface recordings.

Objectives: In a previous study using the averaged coherence technique to study interactions between medial/limbic and lateral/neocortical regions, we observed that epileptogenic networks in temporal lobe epilepsy seizures (TLES) could be divided into 4 subtypes, i.e. medial (M), medial-lateral (ML), lateral-medial (LM), and lateral (L). In the ML and LM subtypes, medial structures and the anterior temporal neocortex are co-activated at the onset of seizures. However, using this approach, we were unable to determine the direction of coupling and may have overlooked non-linear variations in interdependency. The purpose of the present study using non-linear regression for analysis of stereoelectroencephalographic (SEEG) signal pairs was to measure the degree and direction of coupling between medial and neocortical areas during TLES in patients with the M, ML, and LM subtypes., Methods: Eighteen patients with drug-resistant TLEs who underwent SEEG recording were studied. We used a non-linear correlation method as a measure of the degree and the direction of coupling on SEEG signal pairs. Patients with pure lateral TLEs were not studied. We analyzed the functional coupling between 3 regions of the temporal lobe: the anterior temporal neocortex, the amygdala, and the anterior hippocampus. A physiological model of EEG generation was used to validate the non-linear quantification method and assess its applicability to real SEEG signals., Results: Results are first based on a physiological model of EEG data in which both degree and direction of coupling are explicitly represented, thus allowing construction of the neural systems inside which causality relationships are controlled and generation of multichannel EEG signals from these systems. These signals provide an objective way of studying the performance of non-linear regression analysis on real signals. In medial networks (10 patients), the ictal discharge is limited to the medial limbic structures and may propagate secondarily to the cortex. Quantified results demonstrated no significant coupling between medial and lateral structures at the beginning of the seizures. Conversely, almost constant unidirectional or bidirectional coupling was observed between hippocampus and amygdala. In medial-lateral (5 patients) and lateral-medial (3 patients) networks, the initial ictal discharge includes both limbic and neocortical regions. A rapid "tonic" discharge is observed over the temporal neocortex at the onset of seizure. Quantitative analysis showed an initial increase in the non-linear correlation coefficient between neocortex and medial structures. Quantification of the coupling direction demonstrated influence of medial over lateral structures (medial-lateral) or of the lateral neocortex over medial structures (lateral-medial)., Conclusions: These results confirm the existence of several generic and organized networks involving the medial structures during TLE seizures.

Purpose: Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors., Patients and Methods: From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21-day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (750 mg/m2/day at 1st course; 430 mg/m2/day at 2nd and 3rd courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy., Results: Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 2 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall survival were the Karnofsky index (71% survival at 3 years for patients with a Karnofsky index of 90-100% versus 30% for patients with a Karnofsky index of 80% versus 0% for patients with a Karnofsky index of 60-70%, p = 0.0001) and tumor location (55% at 3 years for oropharynx versus 37% for panpharynx versus 28% for hypopharynx, p = 0.009)., Conclusion: These results confirm the efficacy of concomitant bid radiotherapy and chemotherapy in advanced unresectable tumor of the pharynx. The improvement in results will essentially depend on our capacity to restore in a good nutritional status the patients before beginning this heavy treatment.

This paper presents a neurophysiologically relevant model in which vectorial epileptiform electroencephalographic (EEG) signals are produced from multiple coupled neural populations. This model is used to evaluate the performances of non-linear regression analysis as a method to characterize couplings between neural populations from EEG signals they produce. Two quantities, estimated on generated signals, namely the non-linear correlation coefficient and the direction index, are related to the degree and direction of coupling parameters of the model. Their statistical behavior is first studied on a set of signals simulated for relevant configurations of the model. They are then measured on real stereoelectroencephalographic (SEEG) signals. Results obtained in three patients suffering from temporal lobe epilepsy (TLE) show that abnormal functional couplings between cerebral structures, that establish during seizures, can be interpreted in terms of causality. Perspectives are oriented to the identification of epileptogenic networks in TLE.

This work is focused on the study of the organization of the epileptogenic zone (E.Z.) in humans based on the analysis of stereo-electroencephalographic (SEEG) signals with signal processing methods, and more especially those dedicated to the estimation of signal interdependencies. In order to evaluate quantities provided by these methods and in order to relate them to the notion of functional coupling between cerebral structures, we developed a neurophysiologically relevant model able to generate EEG signals from organized networks of neural populations. We showed that the model can produce realistic multichannel epileptiform signals (when compared to real SEEG signals) under certain conditions (excitation/inhibition ratio within populations, uni/bi-directional coupling between populations). In this paper, the model framework is used to evaluate the performances of nonlinear regression analysis as a method to characterize couplings between cerebral structures from the SEEG signals they produce. Two quantities, a nonlinear correlation coefficient and a direction index, respectively related to coupling parameters in the model (degree/direction) are presented. These two quantities are measured on real SEEG signals recorded in patients suffering from temporal lobe epilepsy and candidate to surgical treatment. Results show that the characterization of functional couplings leads to the identification of networks referred to as 'epileptogenic networks', which might be responsible for the triggering of seizures. These results also corroborate our previous results on the classification of temporal lobe epilepsies, showing that there exist recurrent seizure patterns that can be classified on the basis of interactions between medial and lateral neocortical structures.

We explored the degree to which the duration of acoustic cues contributes to the respective involvement of the two hemispheres in the perception of speech. To this end, we recorded the reaction time needed to identify monaurally presented natural French plosives with varying VOT values. The results show that a right-ear advantage is significant only when the phonetic boundary is close to the release burst, i.e., when the identification of the two successive acoustical events (the onset of voicing and the release from closure) needed to perceive a phoneme as voiced or voiceless requires rapid information processing. These results are consistent with the recent hypothesis that the left hemisphere is superior in the processing of rapidly changing acoustical information., (Copyright 2000 Academic Press.)

If low LET radiation therapy (photons, electrons), following radical microscopically and complete surgery can improve results in term of local control from 34 to 74% for salivary gland tumors, local control is more difficult to achieve in advanced tumors and only palliative treatment is usually attempted. In this survey, all the patient series treated worldwide were reviewed. They show an overall control rate of 31% with photon vs 64% with neutron therapy. A prospective randomised trial sponsored by the RTOG and the MRC published in 1988 and reviewed in 1993 showed an overall locoregional complete tumor clearance of 67% for neutrons and 17% for photons (P < 0.005), with 68% and 25% survival at two years for neutrons and photons respectively. This study was closed for ethical reasons. In Orleans, since 1987, 59 patients have been treated. At five years the persistent local control probability was 69.5%, the five-year crude survival probability 66% and the five-year tumor free survival probability was 64.5%. This review provides evidence that surgical treatment for salivary gland tumors should be limited to patients presenting a high likelihood of negative surgical margin and a small risk of facial nerve damage. Others patients should receive neutron radiation therapy alone as definitive treatment.

Objectives: Two subtypes of temporal lobe epilepsy (TLE) according to the structures initially involved during seizures are currently recognized: medial TLE (MTLE) and lateral (or neocortical) TLE (LTLE). A few reports have suggested that the classification of TLE subtypes might be larger according to variations in the interactions between medial structures and the neocortex. In this study, we analyzed these interactions using coherence analysis of stereo-encephalographic (SEEG) signals during spontaneous seizures., Methods: Twenty-seven patients with drug-resistant TLE, diagnosed from ictal SEEG recordings obtained during pre-surgical evaluation, were studied. Orthogonally implanted depth electrodes with multiple leads according to Talairach's method were used to sample medial and neocortical structures. Coherence analysis of ictal discharges was performed between two SEEG bipolar signals from adjacent leads located either in medial structures (amygdala and hippocampus) or in neocortical regions of the temporal lobe. A new algorithm, which was designed to reduce the bias inherent in coherence estimation, was used to compute the coherence., Results: We were able to classify TLE seizures (TLES) into 4 distinct categories: (1) 'medial' TLES, characterized by medial onset with later involvement of the neocortex in the form of a 'phasic' discharge. High ictal coherence values were observed between medial structures; (2) 'medial-lateral' TLES which started in medial structures with a fast low-voltage discharge (FLVD) which rapidly affects the neocortex (< or = 3 s). High coherence values were observed between medial and lateral structures; (3) 'lateral-medial' TLES, which are different from medial-lateral TLES in that the FLVD starts in the lateral neocortex and involves the amygdala and/or hippocampus almost immediately after; (4) 'lateral' TLES: characterized by a neocortical onset, a delayed involvement of medial structures (when present), and high coherence values between neocortical structures., Conclusions: These results demonstrate the existence of numerous interactions between medial limbic structures and the neocortex during TLE seizures. Such findings could have implications for surgical strategies and the prognosis of epilepsy surgery, particularly when limited resection is indicated.

Objectives: This study investigated the relative participation of each cerebral hemisphere during a lateralized task that can be performed by a single hemisphere. This first of two articles focuses on recordings from visual and motor cortices., Methods: Intracranial event-related potentials (ERPs) were recorded from occipital and/or peri-Rolandic sites in 8 patients with intractable epilepsy while they performed a lateralized visual oddball task., Results: As expected, lateralized visual (N150, P200, N250) and motor (N/P400, N/P550) ERP effects were found for occipital and peri-Rolandic recordings, respectively. These reflect an advantage for direct over indirect sensory/motor pathways. More surprisingly, some occipital recordings were paradoxically larger in amplitude for indirect than for direct visual stimulus lateralization, and other occipital sites were sensitive to motor response factors. Likewise, one peri-Rolandic site exhibited a slow wave component that was sensitive to visual sensory factors. There was also pervasive bilaterally-symmetric ERP activity as reflected by P3-like and slow wave-like components., Conclusions: These findings argue against a hemispheric independence model of information processing. With the exception of initial stimulus input and final response output pathway effects, the processing in this simple task engages both hemispheres in a roughly symmetrical fashion, even though a single hemisphere may be adequate for task performance.

Objective: We investigated the relative participation of each cerebral hemisphere during a lateralized task that can be performed by a single hemisphere. While our companion article ( Clarke et al. 1999) focused on visual and motor event-related potentials (ERPs) recorded from occipital and peri-Rolandic sites, the present article is concerned with ERP correlates of intermediate stages of information processing from remaining cerebral regions., Methods: Intracranial ERPs were recorded from temporal, parietal and frontal lobe sites in 13 patients with intractable epilepsy while they performed a lateralized visual oddball task., Results: Visually-responsive N2 and/or P3 effects were recorded from medial temporal and supramarginal sites that appear to reflect activity along ventral and dorsal visual streams, respectively. Likewise, certain prefrontal sites, that are probably involved in working memory, were also visually-responsive. The majority of sites exhibiting N2, P3 and/or slow wave components, however, were unaffected by lateralized visual field or response hand effects. Target-evoked P3-like components were most frequently recorded from medial temporal and prefrontal sites. Post-response slow wave components were pervasive, and polarity reversals were present in the insula/operculum region, apparently reflecting somatosensory activity from SII., Conclusions: The general absence of lateralized ERP effects despite lateralized stimulus input and response output suggests the importance of interhemispheric integration over hemispheric independence in the processing of this type of task.

Recordings directly within the brain can establish local evoked potential generation without the ambiguities always associated with extracranial electromagnetic measures. Depth recordings have found that sensory stimuli activate primary cortex and then material-specific encoders. Sensory-specific areas remain active for long periods, but by about 200 ms are joined by activation in widespread brain systems. One system is related to the orientation of attention. It is centered in paralimbic and attentional frontoparietocingular cortex, and associated with the P3a. A second system associated with P3b envelopes cognitive contextual integration. It engages the ventral temporofrontal event-encoding cortices (inferotemporal, perirhinal, and ventrolateral prefrontal), association cortices (superior temporal sulcal and posterior parietal), and the hippocampus. Thus, even in simple tasks, activation is widespread but concentrated in particular multilobar systems. With this information, the late cognitive potentials can be used to monitor the probable location, timing and intensity of brain activation during cognitive tasks.

In the field of epilepsy, the analysis of stereoelectroencephalographic (SEEG) signals recorded with depth electrodes provides major information on interactions between brain structures during seizures. A methodology of comparing SEEG seizure recordings is applied in 4 patients suffering from temporal lobe epilepsy. It proceeds in 3 steps: (i) segmentation of SEEG signals, (ii) characterization and labeling of segments and (iii) comparison of observations coded as sequences of symbol vectors. The third step is based on a vectorial extension of Wagner and Fischer's algorithm to first, quantify similarities between observations and second, extract invariant information, referred to as spatio-temporal signatures. These are automatically extracted by the algorithm without the need to make a priori assumptions on the 'patterns' to be searched for. Theoretical results show that two observations of non-equal duration can be matched by deforming the first one (using insertion/deletion operations on vectors) to optimally fit the second, under a minimal cost constraint. Clinical results show that the study brings objective results on reproducible mechanisms occurring during seizures: for a given patient, quantified descriptions of seizure periods are compared and similar ictal patterns, or signatures, are extracted from SEEG signals. Some of these signatures (particularly those containing spikes, spike-and-waves, slow waves and rapid discharges) are relevant: they seem to reflect reproducible propagation schemes whose analysis may help in the understanding of epileptogenic networks.

Neutron capture irradiation aims to selectively destroy tumor cells using 10B(n,alpha)7Li nuclear reactions produced within themselves. Following the capture reaction, an alpha particle and a, 7Li ion are emitted. Carrying an energy of 2.79 MeV, they destroy all molecular structures along their path close to 10 microns. These captures, used exclusively with a 'slow' neutron irradiation, provide a neutron capture therapy (BNCT). If they are used in addition to a fast neutron beam irradiation, they provide a neutron capture potentiation (NCP). The Centre Antoine-Lacassagne in Nice is actively involved in the European Demonstration Project for BNCT of grade IV glioblastomas (GBM) after surgical excision and BSH administration. Taking into account the preliminary results obtained in Japan, work on an 'epithermal' neutron target compatible with various cyclotron beams is in progress to facilitate further developments of this technique. For NCP, thermalized neutron yield has been measured in phantoms irradiated in the fast neutron beam of the biomedical cyclotron in Nice. A thermal peak appears after 5 cm depth in the tissues, delayed after the fast neutron peak at 1.8 cm depth. Thus, a physical overdosage of 10% may be obtained if 100 ppm of 10B are assumed in the tissues. Our results using CAL 58 GBM cell line demonstrate a dose modification factor (DMF) of 1.19 when 100 ppm of boric acid are added to the growth medium. Thus for the particles, issued from neutron capture, a biological efficiency at least twice that of fast neutrons can be derived. These results, compared with historical data on fast neutron irradiation of glioblastoma, suggest that a therapeutic window may be obtained for GBM.

In fast neutron therapy, the relative biological effectiveness (RBE) of a given beam varies to a large extent with the neutron energy spectrum. This spectrum depends primarily on the energy of the incident particles and on the nuclear reaction used for neutron production. However, it also depends on other factors which are specific to the local facility, eg, target, collimation system, etc. Therefore direct radiobiological intercomparisons are justified. The present paper reports the results of an intercomparison performed at seven neutrontherapy centres: Orléans, France (p(34)+Be), Riyadh, Saudi Arabia (p(26)+Be), Ghent, Belgium (d(14.5)+Be), Faure, South Africa (p(66)+Be), Detroit, USA (d(48)+Be), Nice, France (p(65)+Be) and Louvain-la-Neuve, Belgium (p(65)+Be). The selected radiobiological system was intestinal crypt regeneration in mice after single fraction irradiation. The observed RBE values (ref cobalt-60 gamma-rays) were 1.79 +/- 0.10, 1.84 +/- 0.07, 2.24 +/- 0.11, 1.55 +/- 0.04, 1.51 +/- 0.03, 1.50 +/- 0.04 and 1.52 +/- 0.04, respectively. When machine availability permitted, additional factors were studied: two vs one fraction (Ghent, Louvain-la-Neuve), dose rate (Detroit), influence of depth in phantom (Faure, Detroit, Nice, Louvain-la-Neuve). In addition, at Orléans and Ghent, RBEs were also determined for LD50 at 6 days after selective abdominal irradiation and were found to be equal to the RBEs for crypt regeneration. The radiobiological intercomparisons were always combined with direct dosimetric intercomparisons and, when possible in some centres, with microdosimetric investigations.

Neutron dosimetry intercomparison studies have been undertaken at the Nice neutrontherapy facility with the staff at Louvain-la-Neuve which has had wide experience in both dosimetric and radiobiological intercomparisons. Tissue equivalent (TE) ionization chambers were first calibrated in 60Co beams and then exposed in the neutron beam at different depths in a water phantom; the largest difference observed in neutron beam measurements with all the chambers tested was 0.89%, and most of them agreed to within less than 0.5%. The gamma component at four depths was derived from measurements with Geiger-Müller counters; the results obtained with the two counters (Nice and Louvain-la-Neuve), expressed as a percentage of the total dose (neutron + gamma), agreed to within less than 0.03% and the value increased from 1.4 to 4.2% between 2 and 20 cm in depth.

V79 cells were exposed to fast neutrons generated by 60 MeV p-->Be produced by the cyclotron Medicyc at four different depths: 1.3, 25.8, 72.2 and 116.8 mm. Survival was assessed by the in vitro colony method. Mean inactivation doses (MID) were significantly different among the four points. The ratio of MID was used to determine the relative efficiency of the neutron beam at these points. Compared to 25.8 mm depth, a 40% increase in biological effect was observed at the superficial point versus a 14 to 16% decrease in effect for the deeper points. This is ascribed to absorption of low energy neutrons near the surface and to beam hardening with depth. Taking in consideration the relative physical dose delivered, these findings suggest that skin-sparing may be markedly reduced and that the lower effectiveness with depth should be kept in mind when dealing with deep tumours.

The proton therapy facility of the Centre Antoine-Lacassagne in Nice began treatment of ocular tumors in June 1991. Up to October 1995, a total number of 600 patients were treated. An overview of the cases treated during the first 4 years of activity is given and the main problems encountered in the field, possibly interacting with the accuracy and reliability of the dose distribution, are listed.

Event-related potentials were recorded from 537 sites in the superior temporal plane and parietal lobe of 41 patients. Depth electrodes were implanted to localize seizure origin prior to surgical treatment. Subjects received an auditory discrimination task with target and non-target rare stimuli ("standard oddball paradigm"). In some cases, the target, distracting and frequent tones were completely balanced across blocks for pitch and volume. Variants included an analogous visual discrimination task, or auditory tasks where the rare target event was the omission of a tone, or the repetition of a tone within a series of alternating tones. In some subjects, the same auditory stimuli were delivered but the patient ignored them while reading. Three general response patterns could be distinguished on the basis of their wave forms, latencies and task correlates. First, potentials apparently related to rarity per se, as opposed to differences in sensory characteristics, or in habituation, were observed in the posterior superior temporal plane, beginning with a large positivity superimposed on early components. This positivity peaked at 150 msec after stimulus onset and inverted in sites superior to the Sylvian fissure. Subsequent components could be large, focal and/or inverting in polarity, and usually included a positivity at 230 msec and a negativity at 330 msec. All components in this area were specific to the auditory modality. Second, in the posterior cingulate and supramarginal gyri, a sharp triphasic negative-positive-negative wave form with peaks at about 210-300-400 msec was observed. This wave form was of relatively small amplitude and diffuse, and seldom inverted in polarity. It was multimodal but most prominent to auditory stimuli, appeared to remain when the stimuli were ignored, and was not apparent to repeated words and faces. Third, a broad, often monophasic, wave form peaking at about 380 msec was observed in the superior parietal lobe, similar to that which has been recorded in the hippocampus. This wave form could be of large amplitude, often highly focal, and could invert over short distances. It was equal to visual and auditory stimuli and was also evoked by repeating words and faces. The early endogenous activity in auditory cortex may embody activity that is antecedent to the other patterns in multimodal association cortex. The "triphasic" pattern may embody a diffuse non-specific orienting response that is also reflected in the scalp P3a. The later broad pattern may embody the cognitive closure that is also reflected in the scalp P3b or late positive component.

The authors present the summary of a workshop of a group of radiation oncologists and radiation physicists on three dimensional treatment planning and conformal radiation therapy with multileaf collimator. It appears that this technic must be considered as experimental and that it cannot be promoted in all radiotherapy departments without scientific and clinical evaluation.

The success of proton therapy depends on its cost. Hospital based equipment in fabrication for the Massachusetts General Hospital in Boston costs in the excess of 17 millions dollars, the accelerator being only a fraction of the cost. We think that price can be significantly decreased. We review the different new ways of accelerating protons currently under study in France in order to build a smaller, less expensive but reliable treatment device.