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.

Focal polymicrogyria in children: Contribution of invasive explorations and epileptogenicity mapping in the surgical decision.

OBJECTIVE: Report of the contribution of invasive EEG (iEEG) and epileptogenicity mappings (EM) in a pediatric cohort of patients with epilepsy associated with focal polymicrogyria (PMG) and candidates for resective surgery. METHOD: Retrospective pediatric case series of patients presenting focal PMG-related refractory epilepsy undergoing an invasive exploration (iEEG) at Fondation Rothschild Hospital. We reviewed clinical data, structural MRI, and visual analysis of iEEG recordings. Moreover, time-frequency analysis of SEEG signals with a neuroimaging approach (epileptogenicity maps) was used to support visual analysis. RESULTS: Between 2012 and 2019, eight patients were selected. Five patients were explored with stereoelectroencephalography (SEEG) only, one patient with subdural exploration (SDE) only and two patients first underwent SEEG and then SDE. The mean age at seizure onset was 40.3 months (range 3-120), and the mean age for the iEEG 10.8 years (range 7-15). The epileptogenic zone (EZ) appeared concordant to the PMG lesion in only one case, was larger in three cases, smaller in two cases and different in one case. Four cases were selected for tailored resective surgery and one for total callosotomy. Two patients remained seizure-free at their last follow-up (mean 32.6 months, range 7-98). Epileptogenicity mapping (EM) refined the qualitative analysis, showing in four patients an EZ larger than visually defined. CONCLUSION: This study is the first pediatric study to analyze the value of iEEG and EM as well as operability in focal PMG-related refractory epilepsy. The results illustrate the complexity of this pathology with variable concordance between the EZ and the lesion and mixed response to surgery.

Epileptogenicity Mapping: A Quantitative Approach to Identify the Seizure Onset.

During the presurgical evaluation of patients with focal refractory epilepsies, the spatial mapping of the seizure onset zone (SOZ) and seizure propagation networks critically depends on the use of different features extracted from the intracranial electroencephalogram (IEEG). The identification of the SOZ is usually based on visual inspection by highly qualified neurophysiologists. However, quantitative IEEG analyses have recently been developed by exploiting signal and image characteristics in order to improve and expedite the SOZ detection. Here, the authors briefly review some of the latest methods proposed by different research groups and then present the recent implementation in Brainstorm software.

Intracranial stimulation for children with epilepsy.

OBJECTIVES: To evaluate the efficacy of intracranial stimulation to treat refractory epilepsy in children. METHODS: This is a retrospective analysis of a pilot study on all 8 children who had intracranial electrical stimulation for the investigation and treatment of refractory epilepsy at King's College Hospital between 2014 and 2015. Five children (one with temporal lobe epilepsy and four with frontal lobe epilepsy) had subacute cortical stimulation (SCS) for a period of 20-161 h during intracranial video-telemetry. Efficacy of stimulation was evaluated by counting interictal discharges and seizures. Two children had thalamic deep brain stimulation (DBS) of the centromedian nucleus (one with idiopathic generalized epilepsy, one with presumed symptomatic generalized epilepsy), and one child on the anterior nucleus (right fronto-temporal epilepsy). The incidence of interictal discharges was evaluated visually and quantified automatically. RESULTS: Among the three children with DBS, two had >60% improvement in seizure frequency and severity and one had no improvement. Among the five children with SCS, four showed improvement in seizure frequency (>50%) and one chid did not show improvement. Procedures were well tolerated by children. CONCLUSION: Cortical and thalamic stimulation appear to be effective and well tolerated in children with refractory epilepsy. SCS can be used to identify the focus and predict the effects of resective surgery or chronic cortical stimulation. Further larger studies are necessary.