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Although executive function disorders are among the most prevalent cognitive impairments a consensus on diagnostic criteria has yet to be reached. With a view to harmonizing these criteria, the present position paper (i) focuses on the main dysexecutive disorders, (ii) examines recent approaches in both the behavioral and cognitive domains, (iii) defines diagnostic boundaries for frontal syndrome, (iv) reports on the frequency and profile of the executive function disorders observed in the main brain diseases, and (v) proposes an operationalization of diagnostic criteria. Future work must define the executive processes involved in human adaptive behavior, characterize their impairment in brain diseases, and improve the management of these conditions (including remediation strategies and rehabilitation).

International audience; Temporal lobe epilepsy (TLE) accounts for 70-80% of epilepsy in adults (1). The dysfunction (epileptic zone, EZ) is located in the temporal lobe and induces language and memory reorganization of cerebral networks and various degrees of cognitive efficiency. TLE patients should be explored according to a multimodal integrative perspective, based on multiple data on brain activation, cerebral structure and cognitive performance. We present two patients with left TLE compared to a control group (N=12). Data acquisition. Patients underwent neuropsychological, fMRI and MR-DTI. Control group underwent fMRI and MR-DTI. Neuropsychological scores for patients were compared to normative matched samples associated with each of the tests used. Functional MRI and MR-DTI experiments were performed in a whole-body 3T MR scanner (Philips Achieva). Parameters of diffusion tensor sequence for MR-DTI acquisition were: voxel size: 2 x 2 x 2 mm, 128 x 126 slices of 2 mm thickness and no gap, TE = 67.2 ms, TR = 14000ms, EPI factor = 63, field of view = 256 mm, b value = 1500sec / mm2. During fMRI we applied the NEREC protocol (2) to map lexical production. Parameters for manufacturer-provided gradient-echo/T2* weighted EPI used for fMRI were: voxel size 2.75 x 2.75 x 3.5 mm, field of view 220 x 220 x 131.75 acquired with a 88 x 85 pixels and a reconstruction matrix of 96 x 96; TR=2.5 sec, TE=30 msec and flip angle=77°. Data processing. DICOM raw data for MR-DTI was converted to NIFTI (dcm2niix toolbox) before concatenation and pre-processing with Diffusionist software (2,3) running on Linux and based on FSL (FMRIB Software Library v5.0, Oxford UK (4,5) and FMRIB Diffusion Toolbox (FDT). We measured Fractional Anisotropy (FA) to assess white matter (WM) modifications at (a) intra-hemispheric: inferior longitudinal (ILF), inferior fronto-occipital (IFOF), superior longitudinal SLF, arcuate (Arc), uncinate (Unc), cingulum (Cing), fornix (Fox), and (b) inter-hemispheric level in terms of sub-regions of the corpus callosum (CC): genu (GCC), body (BCC) and splenium (SCC). SPM (www.fil.ion.ucl.ac.uk/spm) implemented in MATLAB (Mathworks Inc., Natick, MA, USA) was used to analyse fMRI data. After pre-processing, statistical analyses were performed individually and then at a group level for controls (one-sample t-test; k > 5; p 5, frontal LI was -0.412, suggesting right hemisphere specialization of P1 compared to controls (left-hemisphere lateralized). Patient 2. P2 showed normal results for memory tests but was impaired for phonological (phonological fluency= -1,86 σ) and lexico-semantic (object naming= -1,65 σ) processes. Lower FA values (p ≤ .05) were obtained for left Unc (t'(12) = -1.671, p = .05) and right Arc (t'(12) = -3.431, p < .05). P2 also showed lower FA of BCC (t '(12) = -1.922, p 5, frontal IL was 0.165, suggesting bilateral representation of language. The integration of multimodal data is a current issue. While different information derived from MRI neuroimaging and cognitive scores is interrelated, it appears important to go beyond the descriptive approach and move towards a statistical integration of these different data. Indeed, the multimodal integration of anatomical, functional and cognitive data make possible to draw-up comprehensive neurocognitive patterns in patients with epilepsy. In this way, efficient versus less efficient reorganization profiles in this pathology will be identified. This will lead to fundamental and clinical advances such as the identification of functional areas, the prediction of post-surgical outcomes in case of curative neurosurgery, the anticipation/optimization of the rehabilitation if necessary and all this with a view to moving towards an individualized and customized medicine.

International audience; – Increasing attention is being paid to the assessment of white matter properties and its structural connectivity, both in healthy subjects and patients with cerebral lesions. Within this framework, new neurocogni-tive models based on hodological properties have been developed under a connectomic perspective in order to explain substrates and cognitive mechanisms related to cerebral functions such as language and memory. With regards to focal and drug-resistant epilepsy conceived as a network disorder , new insights in terms of structural connectivity have led to significant advances in epilepsy research, concerning fundamental research (neu-rocognitive mechanisms of plasticity) and clinical application (optimization of decision making for curative surgery). We believe that such findings in the literature, focused on the role of white matter in cerebral functioning in relation to neurocognition, may be helpful for both researchers and clinicians working in the field of epilepsy. Structural connectivity and neurocognition: general information Structural connectivity refers to the study of the anatomical features of brain networks in terms of subcorti-cal white matter (WM) that underlies interconnections between different cortical regions. Within the current context of growing interest with a connectomic perspective, many MRI methods and parameters are now available to assess WM anatomical properties including architecture, spatial trajectory, density or integrity (Sporns, 2013). These structural properties, investigated in relation to cognitive functions and behavioral performance, allows the development of more

International audience; Drug-resistant temporal lobe epilepsy (TLE) is a severe neurological condition that causes brain injury due to the recurrence of epileptic seizures, with mostly language (L) and memory (M) impairments. Our research aims to: (i) specify the properties of functional modifications on a language and memory network (LMN), according to the hemispheric lateralization of the epileptogenic zone (LH/RH); (ii) evaluate the efficiency of the LMN reorganizations in terms of functional connectivity (FC). Using MRI (3T Philips) we performed resting state fMRI to assess FC. 17 TLE (n=8 Left TLE; n=9 Right TLE) and a group of 28 healthy subjects were included. Two types of FC analyzes have been carried out on the LMN: ROI-to-ROI (pairwise correlations) and graph theory (integration: Eglob, Enod; segregation: Eloc) with Conn toolbox (Whitfield-Gabrieli & Nieto-Castanon, 2012). Spearman correlations were then made between FC biomarkers and LM standardized performance (verbal comprehension index, auditory memory index, naming, verbal fluency). Our main results revealed that: (a) LMN FC is extensively modified in LTLE patients (temporo-frontal and bilateral), compared to RTLE (posterior-right) and healthy; (b) the type of FC modifications depend on the cognitive function (mainly segregation for language and integration for memory); (c) FC parameters correlate remarkably with cognitive scores; (d) hyperconnectivity (increased functional integration capacity) of certain brain regions is not necessarily efficient and can negatively correlate to LM performance (negative plasticity). Thus, we wish to extend the concept of connectome to “cognitome” that taking into account the behavioral consequences of the changes observed in term of connectivity.

International audience; : The exact role of the left ventral occipitotemporal cortex (VOTC) during the initial stages of reading acquisition is a hotly debated issue, especially regarding the comparative effect of learning on early stimulus-dependent vs. later task-dependent processes. We show that this controversy can be solved with high-temporal resolution intracerebral EEG recordings of the VOTC. We measured High-Frequency Activity (50-150Hz) as a proxy of population-level spiking activity while participants learned Japanese Katakana symbols, and found that learning primarily affects top-down/task-dependent neural processing, after a few minutes only. In contrast, adaptation of early bottom-up/stimulus-dependent processing takes several days to adapt and provides the basis for fluent reading. Such evidence that two consecutive stages of neural processing, stimulus- and task-dependent are differentially affected by learning, can reconcile seemingly opposite hypotheses on the role of the VOTC during reading acquisition.

International audience; Short-term changes of intrinsic properties of neural networks play a critical role in brain dynamics. In that context, epilepsy is a typical pathology where the fast transition between interictal and ictal states is probably associated to intrinsic modifications of underlying networks. In this study, we focused on the correlates of plastic neural mechanisms in the intracerebral electroencephalogram (iEEG). Data were obtained during 1 Hz electrical stimulation in twenty patients suffering from temporal lobe epilepsy and implanted with intracerebral electrodes for clinical evaluation before resective surgery. First, we developed a procedure of analysis for localisation of the seizure onset zone based on brain excitability and plasticity defined as the average, and as the first-order (linear) modulation respectively, of the standard deviation of iEEG responses over stimulations. Our results suggest that the candidate epileptic focus is particularly prone to exhibiting short-term plasticity. Second, we used Dynamic Causal Modelling (DCM) to model explicitly short-term plasticity as a fast modulation of synaptic efficacies in either intrinsic or extrinsic connections to the focus. We found the two types of modulation both likely. Third, we used DCM to study the fast modulation of synaptic connectivity of long-range connections in neuronal networks restricted to the temporal lobe. Using DCM, we were able to estimate which structures expressed a strong modulatory input to the epileptic focus. Such early changes in interregional connectivity might be important for the initiation of electrically-induced seizures. They may also reflect some aspects of the pathogenesis of epilepsy in those patients.

International audience; Synchrotron-generated X-ray (SRX) microbeams deposit high doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. This non-invasive method mimicks surgical multiple subpial transections and similarly prevents epileptic seizure propagation into non-resectable and/or eloquent brain regions. We made such image-guided microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high interlaced radiation doses (820Gy) in thin (200µm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arise, altered the horizontal propagation of abnormal neuronal activities for 9 weeks, as evidenced by a decrease of seizure power and the coherence between tissue slices in comparison to the contralateral cortex. The brain tissue sited between transections stayed functionally and histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre-clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery.

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

International audience

Emilie Cousin1, Monica Baciu1, Cédric Pichat1, Philippe Kahane2, Jean-François Le Bas31UMR CNRS/UPMF 5105, Laboratoire de Psychologie et Neurocognition; 2Laboratoire de Neurophysiopathologie de l’Epilepsie, CHU Grenoble; 3Unité IRM, CHU Grenoble, FranceAbstract: The present fMRI study explores the cerebral reorganisation of language in patients with temporal lobe epilepsy, according to the age of seizures onset (early or late) and the hippocampal sclerosis (associated or not). Seven right-handed control volunteers and seven preoperative adult epileptic patients performed a rhyme decision (language condition) and a visual detection (control condition) tasks in visually presented words and unreadable characters, respectively. All patients were left hemisphere dominant for language. Appropriate statistical analyses provided the following preliminary results: (1) patients compared with healthy subjects showed lower degree of hemispheric lateralization with supplementary involvement of the right hemisphere; (2) the degree of hemispheric specialization depends on the considered region; (3) patients with early seizures show signs of temporal and parietal reorganization more frequently than patients with late onset of seizures; (4) patients with early seizures show a tendency for intra-hemispheric frontal reorganisation; (5) associated hippocampal sclerosis facilitates the inter-hemispheric shift of temporal activation. Although our patients were left hemisphere predominant for language, the statistical analyses indicated that the degree of lateralization was significantly lower than in healthy subjects. This result has been considered as the indication of atypical lateralization of language.Keywords: language, fMRI, plasticity, temporal epilepsy, age, hippocampal sclerosis

International audience; In electroencephalographic (EEG) measurements performed during functional Magnetic Resonance Imaging (fMRI), imaging and cardiac artefacts strongly contaminate the EEG signal. Several algorithms have been proposed to suppress these artefacts and most of them have shown important improvements with respect to uncorrected signals. However, the relative performances of these algorithms have not been properly assessed. In particular, it is not known to what extent such algorithms deteriorate the EEG signal of interest. In this study, we propose to cross-validate different methods proposed for artefact correction, using a forward model to generate EEG and MR-related artefacts. The methods are assessed under various experimental conditions (described in terms of EEG sampling rate, artefacts amplitude, frequency band of interest, etc.). Using experimental data, we also tested the performance of the correction methods for alpha rhythm imaging and for epileptic spike reconstruction. Results show that most of the methods allow the observation of the modulation of alpha rhythms and the identification of spikes, despite subtle differences between algorithms. They also show that over-filtering the data may degrade the EEG. Our results indicate that the optimal artefact removal technique should be chosen according to whether one is interested in fast (>10 Hz) vs. slow (

International audience; Changes in sensorimotor rhythms (mu, beta and gamma) and movement-related cortical potentials (MRCPs) are both generated principally by the contralateral sensorimotor areas during the execution of self-paced movement. They appear to reflect movement control mechanisms, which remain partially unclear. With the aim of better understanding their sources and significance, we recorded MRCPs and sensorimotor rhythms during and after self-paced movement using intracerebral electrodes in eight epileptic subjects investigated by stereoelectroencephalography. The results showed that: (i) there is a strong spatial relationship between the late components of movement--the so-called motor potential (MP) and post-movement complex (PMc)--and gamma event-related synchronization (ERS) within the 40-60 Hz band, as the MP/PMc always occurred in contacts displaying gamma ERS (the primary sensorimotor areas), whereas mu and beta reactivities were more diffuse; and (ii) MPs and PMc are both generated by the primary motor and somatosensory areas, but with distinct sources. Hence, this could mean that kinesthesic sensory afferences project to neurons other than those firing during the pyramidal tract volley. The PMc and low gamma ERS represent two electrophysiological facets of kinesthesic feedback from the joints and muscles involved in the movement to the sensorimotor cortex. It could be suggested that gamma oscillations within the 40-60 Hz band could serve to synchronize the activities of the various neuronal populations involved in control of the ongoing movement.

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

International audience; The premotor cortex is well known for its role in motor planning. In addition, recent studies have shown that it is also involved in nonmotor functions such as attention and memory, a notion derived from both animal neurophysiology and human functional imaging. The present study is an attempt to bridge the gap between these experimental techniques in the human brain, using a task initially designed to dissociate attention from intention in the monkey, and recently adapted for a functional magnetic resonance imaging (fMRI) study [Simon, S.R., Meunier, M., Piettre, L., Berardi, A.M., Segebarth, C.M., Boussaoud, D. (2002). Spatial attention and memory versus motor preparation: premotor cortex involvement as revealed by fMRI. J. Neurophysiol., 88, 2047-57]. Intracranial EEG was recorded from the cortical regions preferentially active in the spatial attention and/or working memory task and those involved in motor intention. The results show that, among the different intracranial EEG responses, only the high gamma frequency (60-200 Hz) oscillatory activity both dissociates attention/memory from motor intention and spatially colocalizes with the fMRI-identified premotor substrates of these two functions. This finding provides electrophysiological confirmation that the human premotor cortex is involved in spatial attention and/or working memory. Additionally, it provides timely support to the idea that high gamma frequency oscillations are involved in the cascade of neural processes underlying the hemodynamic responses measured with fMRI [Logothetis, N.K., Pauls, J., Augath, M., Trinath, T. and Oeltermann, A. (2001). Neurophysiological investigation of the basis of the fMRI signal. Nature, 412, 150-7], and suggests a functional selectivity of the gamma oscillations that could be critical for future EEG investigations, whether experimental or clinical.

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

International audience; This study assesses the interest of a simple fMRI rhyme detection paradigm to determine hemispheric predominance for language in epileptic patients. Nineteen patients were examined. The findings derived from the fMRI examinations were compared with those obtained on the same patients using the Wada test, stereotactic intracerebral EEG stimulations and recordings, and/or video-EEG recordings. For the seventeen patients for whom language dominance could be assessed by means of at least one of the latter procedures, the fMRI examination provided concordant results in sixteen. In two patients, the hemispheric predominance for language could only be determined by fMRI. Nine patients underwent surgery subsequent to the fMRI examination. None of them exhibited any aphasic problems following surgery. The rhyme detection task used in the fMRI examination generates robust responses in the language areas, permits easy monitoring of the patient's task performance and can be easily undertaken by the epileptic patients. Thus, this study demonstrates that the fMRI rhyme detection paradigm is particularly well-suited for determining hemispheric language predominance in epileptic candidates for surgery.