A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials
Authors: Lemaréchal Jean-Didier , Jedynak Maciej , Trebaul Lena , Boyer Anthony , Tadel François , Bhattacharjee Manik , Deman Pierre , Tuyisenge Viateur , Ayoubian Leila , Hugues Etienne , Chanteloup-Forêt Blandine , Saubat Carole , Zouglech Raouf , Reyes Mejia Gina Catalina , Tourbier Sébastien , Hagmann Patric , Adam Claude , Barba Carmen , Bartolomei Fabrice , Blauwblomme Thomas , Curot Jonathan , Dubeau François , Francione Stefano , Garcés Mercedes , Hirsch Edouard , Landré Elizabeth , Liu Sinclair , Maillard Louis , Metsähonkala Eeva-Liisa , Mindruta Ioana , Nica Anca , Pail Martin , Petrescu Ana Maria , Rheims Sylvain , Rocamora Rodrigo , Schulze-Bonhage Andreas , Szurhaj William , Taussig Delphine , Valentin Antonio , Wang Haixiang , Kahane Philippe , George Nathalie , David Olivier ,   F-TRACT consortium, Adam Claude , Navarro Vincent , Biraben Arnaud , Nica Anca , Menard Dominique , Brazdil Milan , Kuba Robert , Kočvarová Jitka , Pail Martin , Doležalová Irena , Dubeau François , Gotman Jean , Ryvlin Philippe , Isnard Jean , Catenoix Hélène , Montavont Alexandra , Rheims Sylvain , Bartolomei Fabrice , Trébuchon Agnès , McGonigal Aileen , Zhou Wenjing , Wang Haixiang , Liu Sinclair , Wei Zhang , Dan Zhu , Qiang Guo , Xiangshu Hu , Hua Li , Gang Hua , Wensheng Wang , Xi Mei , Yigang Feng , Nabbout Rima , Bourgeois Marie , Kaminska Anna , Blauwblomme Thomas , Garcés Mercedes , Valentin Antonio , Singh Rinki , Metsähonkala Liisa , Gaily Eija , Lauronen Leena , Peltola Maria , Chassoux Francine , Landré Elizabeth , Derambure Philippe , Szurhaj William , Chochois Maxime , Hirsch Edouard , Paola Valenti Maria , Scholly Julia , Valton Luc , Denuelle Marie , Curot Jonathan , Rocamora Rodrigo , Principe Alessandro , Ley Miguel , Mindruta Ioana , Barborica Andrei , Francione Stefano , Mai Roberto , Nobili Lino , Sartori Ivana , Tassi Laura , Maillard Louis , Vignal Jean-Pierre , Jonas Jacques , Tyvaert Louise , Chipaux Mathilde , Taussig Delphine , Kahane Philippe , Minotti Lorella , Job Anne-Sophie , Michel Véronique , de Montaudoin Marie , Aupy Jérôme , Bouilleret Viviane , Maria Petrescu Ana , Masnou Pascal , Dussaule Claire , Quirins Marion , Taussig Delphine , Barba Carmen , Guerrini Renzo , Lenge Matteo , Nacci Elisa 
Published: October 2021

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 (&gt;15 years) and younger patients (&lt;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.