1 This year, the Brain Conference was held in London on March 15.It was the first ever in-person Brain Conference and gave attendees the opportunity to attend high-quality talks, covering various aspects of neuroscience and neurology, with time for more informal discussions with leading scientists in their fields.The programme was designed to group talks by topic sessions (sleep, advanced therapies, neuroinflammation and stroke), and each session's Chair was involved in the selection of speakers.The organizers also reserved time for a 'Data Blitzes' session where authors of outstanding abstracts had the opportunity to present their work in 5 minutes.Moreover, each Data Blitzes speaker presented their work during the poster session.One of the Guarantors of Brain's missions is education and in line with this, Professor Colin Espie (University of Oxford) was invited to give a plenary lecture on sleep.Professor Espie addressed the main characteristics of the sleep-wake cycle, insisting on its highly dynamic nature and relevance for human
Dataset for the publication: 'Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity 'Rigoni et al. 2023, Neurobiology of Disease, doi: https://doi.org/10.1016/j.nbd.2023.106382 Dataset description Data\data2publish\sub- : 50 epochs of raw epicranial EEG data (31 x 8001 x 50, channels x time x n_epochs, Fs=4k Hz). The epochs are available for 29 mice, on different sessions (ses-d0, ses-d28, ses-d29) depending on the animal Data\data2publish\EA_info.xlsx: number of epileptiform activities automatically detected for each animal at d28 and d29 Data\data2publish\derivatives\eeg_preprocessing: results of the script A_EEG_preprocessing.m, for each animal and session Data\data2publish\derivatives\elec_layout: different layouts used to plot results. Mouse_layout_modif is the one used in Fig 4 Data\data2publish\derivatives\network_metrics_wpli: results of network analyses (script C_network_analyses.m) Data\data2publish\derivatives\wpli: connectivity matrices (30 x 30) obtained with the script B_connectivity_wpli.m for each animal, in each session, for each frequency band wit Code for analyses available here: https://github.com/IsottaR/ir_mice_project_Zenodo Abbreviations: EEG= electroencephalography
Background: Social cognition is widely studied in neurology. At present, such evaluations are designed for research or for specific diseases and simple general clinical tools are lacking. We propose a clinical evaluation tool for social cognition, the Geneva Social Cognition Scale (GeSoCS). Methods: The GeSoCS is a 100-point scale composed of 6 subtests (theory of mind stories, recognition of social emotions, false beliefs, inferences, absurdity judgement and planning abilities) chosen from different validated tests of social and cognitive evaluation. Eighty-four patients with neurological disorders and 52 controls participated in the study. Evaluation duration lasted 20-60 min. Results: Mean scores were 92.6 ± 4.5 for controls and 76.5 ± 15.3 for patients and differentiate patients and controls in all subtests. With a cut-off score of 84, the scale had a sensitivity of 62% and a specificity of 94%. In our stroke subgroup, right CVAs failed in cartoons, inferences, ‘mind in the eyes', and in the temporal rule task while left CVAs were impaired in verbal/discourse tasks (social cognition, inferences, absurd stories, and cartoons. Conclusions: The GeSoCS is a medium duration assessment tool that appears to detect and characterize significant social impairment in neurological patients.
Abstract Animal and human studies have shown that the seizure-generating region is vastly dependent on distant neuronal hubs that can decrease duration and propagation of ongoing seizures. However, we still lack a comprehensive understanding of the impact of distant brain areas on specific interictal or ictal epileptic activities (e.g., isolated spikes, spike trains, seizures). Such knowledge is critically needed since all kinds of epileptic activities are not equivalent in terms of clinical expression and impact on the progression of the disease. We used surface, high-density EEG and multisite intracortical recordings, combined with pharmacological silencing of specific brain regions in the well-known kainate mouse model of temporal lobe epilepsy. We tested the impact of selective regional silencing on the generation of epileptic activities within a continuum ranging from very transient to more sustained and long-lasting discharges reminiscent of seizures. Silencing the contralateral hippocampus completely suppresses sustained ictal activities in the focus, as efficiently as silencing the focus itself, but while focus silencing abolishes all focal activities, contralateral silencing fails to control transient spikes. In parallel, we observed that sustained epileptic discharges in the focus are preceded by contralateral firing and more strongly phase locked to bi-hippocampal delta/theta oscillations than transient spiking activities, reinforcing the presumed dominant role of the contralateral hippocampus in promoting long-lasting, but not transient, epileptic activities. Altogether, our work provides suggestive evidence that the contralateral hippocampus is necessary for the interictal-to ictal-state transition and proposes that cross-talk between contralateral neuronal activity and ipsilateral delta/theta oscillation could be a candidate mechanism underlying the progression from short to long-lasting epileptic activities. Key Points We study how regions remote from the focus influence epileptic activities in the kainate mouse model of temporal lobe epilepsy. The contralateral hippocampus plays a decisive role in the initiation of sustained epileptic activities Integration of contralateral activities and bi-hippocampal delta/theta oscillations precedes focal paroxysmal activities We propose that a large-scale epileptic network might be necessary for the transition from interictal to ictal states
Large-scale brain networks are increasingly recognized as important for the generation of seizures in epilepsy. However, how a network evolves from a healthy state through the process of epileptogenesis remains unclear. To address this question, here, we study longitudinal epicranial background EEG recordings (30 electrodes, EEG free from epileptiform activity) of a mouse model of mesial temporal lobe epilepsy. We analyze functional connectivity networks and observe that over the time course of epileptogenesis the networks become increasingly asymmetric. Furthermore, computational modelling reveals that a set of nodes, located outside of the region of initial insult, emerges as particularly important for the network dynamics. These findings are consistent with experimental observations, thus demonstrating that ictogenic mechanisms can be revealed on the EEG, that computational models can be used to monitor unfolding epileptogenesis and that both the primary focus and epileptic network play a role in epileptogenesis.
Dataset for the publication: 'Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity 'Rigoni et al. 2023, Neurobiology of Disease, doi: https://doi.org/10.1016/j.nbd.2023.106382 Dataset description Data\data2publish\sub- : 50 epochs of raw epicranial EEG data (31 x 8001 x 50, channels x time x n_epochs, Fs=4k Hz). The epochs are available for 29 mice, on different sessions (ses-d0, ses-d28, ses-d29) depending on the animal Data\data2publish\EA_info.xlsx: number of epileptiform activities automatically detected for each animal at d28 and d29 Data\data2publish\derivatives\eeg_preprocessing: results of the script A_EEG_preprocessing.m, for each animal and session Data\data2publish\derivatives\elec_layout: different layouts used to plot results. Mouse_layout_modif is the one used in Fig 4 Data\data2publish\derivatives\network_metrics_wpli: results of network analyses (script C_network_analyses.m) Data\data2publish\derivatives\wpli: connectivity matrices (30 x 30) obtained with the script B_connectivity_wpli.m for each animal, in each session, for each frequency band wit Code for analyses available here: https://github.com/IsottaR/ir_mice_project_Zenodo Abbreviations: EEG= electroencephalography
Most research on focal epilepsy focuses on mechanisms of seizure generation in the primary epileptic focus (EF). However, neurological deficits that are not directly linked to seizure activity and that may persist after focus removal are frequent. The recruitment of remote brain regions of an epileptic network (EN) is recognized as a possible cause, but a profound lack of experimental evidence exists concerning their recruitment and the type of pathological activities they exhibit. We studied the development of epileptic activities at the large-scale in male mice of the kainate model of unilateral temporal lobe epilepsy using high-density surface EEG and multiple-site intracortical recordings. We show that, along with focal spikes and fast ripples that remain localized to the injected hippocampus (i.e., the EF), a subpopulation of spikes that propagate across the brain progressively emerges even before the expression of seizures. The spatiotemporal propagation of these generalized spikes (GSs) is highly stable within and across animals, defining a large-scale EN comprising both hippocampal regions and frontal cortices. Interestingly, GSs are often concomitant with muscular twitches. In addition, while fast ripples are, as expected, highly frequent in the EF, they also emerge in remote cortical regions and in particular in frontal regions where GSs propagate. Finally, we demonstrate that these remote interictal activities are dependent on the focus in the early phase of the disease but continue to be expressed after focus silencing at later stages. Our results provide evidence that neuronal networks outside the initial focus are progressively altered during epileptogenesis. SIGNIFICANCE STATEMENT It has long been held that the epileptic focus is responsible for triggering seizures and driving interictal activities. However, focal epilepsies are associated with heterogeneous symptoms, calling into question the concept of a strictly focal disease. Using the mouse model of hippocampal sclerosis, this work demonstrates that focal epilepsy leads to the development of pathological activities specific to the epileptic condition, notably fast ripples, that appear outside of the primary epileptic focus. Whereas these activities are dependent on the focus early in the disease, focus silencing fails to control them in the chronic stage. Thus, dynamical changes specific to the epileptic condition are built up outside of the epileptic focus along with disease progression, which provides supporting evidence for network alterations in focal epilepsy.
Abstract Sleep can modulate epileptic activities, but our knowledge of sleep perturbation by epilepsy remains sparse. Interestingly, epilepsy and sleep both present with defining electrophysiological features in the form of specific graphoelements on EEG. This raises the possibility to identify, within ongoing EEG activity, how epilepsy impacts and disrupts sleep. Here, we asked whether the presence of a lateralized epileptic focus interferes with the expression of the dominant electrophysiological hallmarks of sleep: slow oscillations, slow waves and spindles. To this aim, we conducted a cross-sectional study and analysed sleep recordings with surface EEG from 69 patients with focal epilepsy (age range at EEG: 17–61 years, 29 females, 34 left focal epilepsy). Comparing patients with left and right focal epilepsy, we assessed inter-hemispheric asymmetry of sleep slow oscillations power (delta range, 0.5–4 Hz); sleep slow wave density; amplitude, duration and slope; and spindle density, amplitude, duration as well as locking to slow oscillations. We found significantly different asymmetries in slow oscillation power (P < 0.01); slow wave amplitude (P < 0.05) and slope (P < 0.01); and spindle density (P < 0.0001) and amplitude (P < 0.05). To confirm that these population-based differences reflect actual patient-by-patient differences, we then tested whether asymmetry of sleep features can classify laterality of the epileptic focus using a decision tree and a 5-fold cross-validation. We show that classification accuracy is above chance level (accuracy of 65%, standard deviation: 5%) and significantly outperforms a classification based on a randomization of epileptic lateralization (randomization data accuracy: 50%, standard deviation 7%, unpaired t-test, P < 0.0001). Importantly, we show that classification of epileptic lateralization by the canonical epileptic biomarker, i.e. interictal epileptiform discharges, improves slightly but significantly when combined with electrophysiological hallmarks of physiological sleep (from 75% to 77%, P < 0.0001, one-way ANOVA + Sidak’s multiple comparisons test). Together, we establish that epilepsy is associated with inter-hemispheric perturbation of sleep-related activities and provide an in-depth multi-dimensional profile of the main sleep electrophysiological signatures in a large cohort of patients with focal epilepsy. We provide converging evidence that the underlying epileptic process interacts with the expression of sleep markers, in addition to triggering well-known pathological activities, such as interictal epileptiform discharges.
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