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

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.

A semiological marker of emotional insulo-cingulate network activation in epileptic human brain.

There are limited reports on the "chapeau de gendarme" (CDG) sign, which is considered reliable evidence for the verification of frontal epilepsy. However, several recent reports of scattered cases of extra-frontal epilepsy suggest the complexity of the cortical networks underlying CDG generation. The present study aimed to investigate the anatomo-electro-clinical correlations and explore the cortical mechanisms of the generation of CDG via video-stereoelectroencephalography (SEEG). Patients with focal epilepsy who underwent SEEG and epilepsy surgery in our center from March 2017 to December 2019 were retrospectively reviewed. Ten patients with epilepsy with habitual seizures presenting with CDG were included. Most CDG signs were discerned visually into two chronological components referred to as the "prodromal component" and the "major component." The CDG signs occurred at 2.4-26.1 s after electrical onset and lasted for 2.2-16.6 s. The two sequential components were visually discerned in 64 included seizures of the six patients. The epileptogenic zones were diverse in distribution. Cluster analysis was performed based on the neurophysiological features of distinct cortical areas, and the agranulo-dysgranular insular and cingulate cortices were emphasized. Pearson correlation and linear regression showed a linear relationship between the latencies of CDG onset and the latencies of co-activation of agranulo-dysgranular cingulate and insular cortex in gamma bands. Our results suggest that (1) the CDG sign should be interpreted as a type of facial behavior with social-emotional features and considered a semiological marker of emotional insulo-cingulate cortex involvement in focal epilepsy, and (2) epileptic discharges arising directly from or propagating indirectly into this anterior limbic network have a high likelihood of evoking the CDG sign.

The chapeau de gendarme sign can be evoked by lateral prefrontal epileptic seizures.

PURPOSE: The 'chapeau de gendarme' (CDG) sign, characterised by a symmetric down-turned mouth, has been considered as a semiological hallmark of focal epileptic seizures with cingulate or insular involvement. We report three cases in which the CDG sign featured in habitual seizures. METHODS: The epileptogenic zones of these three patients were localized in the lateral prefrontal cortex by video-stereoelectroencephalography monitoring. A sulcal resection has led to a seizure-free outcome in each patient. RESULTS: Ictal stereoelectroencephalography demonstrated that ictal discharges arising from the lateral prefrontal cortices were immediately followed by low-voltage fast activity, concomitantly involving the anterior insulo-cingulate cortices, and preceding the onset of the CDG signs. Limited sulcal resection and seizure freedom after surgery confirmed the restricted distributions of the epileptogenic zones in the lateral prefrontal cortex. CONCLUSION: Our observations led us to speculate that the epileptic discharges could enter the emotional insulo-cingulate cortical system through the prefrontal-cingulate inhibitory projections (feedforward pattern) -arising from the supragranular layers of the lateral prefrontal cortex-and proceed to the deeper layers of the anterior-middle cingulate cortex, trigger the co-occurrence of gamma bands, and evoke a set of exaggerated behaviours, which is often accompanied by the unique facial sign.

Probabilistic functional tractography of the human cortex revisited.

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.