In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human.

Brno Epilepsy Center Department of Neurology St Anne's University Hospital and Medical Faculty of Masaryk University Brno Czech Republic

Canton Sanjiu Brain Hospital Epilepsy Center Jinan University Guangzhou China

Centre Hospitalier Universitaire de Nancy Nancy France

Department of Basic and Clinical Neuroscience Institute of Psychiatry Psychology and Neuroscience London UK

Department of Functional Neurology and Epileptology Hospices Civils de Lyon and University of Lyon Lyon France

Department of Neuroscience Bambino Gesù Children's Hospital IRRCS Rome Italy

Department of Neurosurgery Sainte Anne Hospital Paris France

Department of Pediatric Neurosurgery Hôpital Necker Enfants Malades Université Paris 5 Descartes Sorbonne Paris Cité Paris France

Epilepsy Center Medical Center University of Freiburg Faculty of Medicine University of Freiburg Germany

Epilepsy Monitoring Unit Department of Neurology Hospital del Mar IMIM Barcelona Spain

Epilepsy Surgery Center Niguarda Hospital Milan Italy

Epilepsy Unit Department of Clinical Neurophysiology Lille University Medical Center Lille France

Epilepsy Unit Dept of Neurology Pitié Salpêtrière Hospital APHP Paris France

Epilepsy Unit Hospital for Children and Adolescents Helsinki Finland

Inserm U1216 Grenoble F 38000 France; Univ Grenoble Alpes Grenoble Institut des Neurosciences GIN Grenoble F 38000 France

Inserm U1216 Grenoble F 38000 France; Univ Grenoble Alpes Grenoble Institut des Neurosciences GIN Grenoble F 38000 France; CHU Grenoble Alpes Neurology Department Grenoble France

Montreal Neurological Institute and Hospital Montreal Canada

Multidisciplinary Epilepsy Unit Hospital Universitario y Politécnico La Fe Valencia Spain

Neurology Department CHU Rennes France

Neurology Department University Emergency Hospital Bucharest Romania

Neurophysiology and Epilepsy Unit Bicêtre Hospital France

Service de neurochirurgie pédiatrique Fondation Rothschild Paris France

Service de Neurophysiologie Clinique APHM Hôpitaux de la Timone Marseille France

University Hospital Department of Neurology Strasbourg France

University Hospital Department of Neurology Toulouse France

Yuquan Hospital Epilepsy Center Tsinghua University Beijing China

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Symmetry breaking organizes the brain's resting state manifold

A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials