Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings.

'Claudio Munari' Centre for Epilepsy Surgery; Neuroscience Department GOM Niguarda Milano Italy

Aix Marseille Université Inserm INS Institut de Neurosciences des Systèmes Marseille France

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 Lyon's Neurosciences Research Center INSERM U1028 CNRS UMR5292 Lyon 1 University Lyon France

Department of Neurology Epilepsy Unit AP HP Hôpital de la Pitié Salpêtrière F 75013 Paris France

Department of Neurophysiological Explorations CerCo CNRS UMR5549 Centre Hospitalier Universitaire de Toulouse and University of Toulouse Toulouse France

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

Department of Radiology Lausanne University Hospital Lausanne Switzerland

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 Unit Department of Clinical Neurophysiology Lille University Medical Center Lille France

Epilepsy Unit Hospital for Children and Adolescents Helsinki Finland

Montreal Neurological Institute and Hospital Montreal Canada

Multidisciplinary Epilepsy Unit Hospital Universitario y Politécnico La Fe Valencia Spain

Neurology Department CHU Grenoble Alpes Grenoble France

Neurology Department CIC 1414 Rennes University Hospital; LTSI INSERM U 1099 F 35000 Rennes France

Neurology Department University Emergency Hospital Bucharest Romania

Neurophysiology and Epilepsy Unit Bicêtre Hospital France

Neuroscience Department Children's Hospital Meyer University of Florence Florence Italy

Service de Neurochirurgie Pédiatrique Fondation Rothschild Paris France

Service de Neurophysiologie Clinique APHM Hôpitaux de la Timone Marseille France

Sorbonne Université Institut du Cerveau Paris Brain Institute ICM Inserm CNRS Centre MEG EEG and Experimental Neurosurgery Team F 75013 Paris France

Université Grenoble Alpes Inserm U1216 Grenoble Institut Neurosciences 38000 Grenoble France

University Hospital Department of Neurology Strasbourg France

Yuquan Hospital Epilepsy Center Tsinghua University Beijing China

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