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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; 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.