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Bugnon, T.

Publications and source records attributed to Bugnon, T..

2 recordsLinked to original sources

Sleep/wake changes in perturbational complexity in rats and mice

In humans, the level of consciousness can be assessed by quantifying the spatiotemporal complexity of cortical responses using the Perturbational Complexity Index (PCI) and related PCIst (st, state transitions). These measures are consistently high in wake and rapid eye movement (REM) sleep and low in dreamless non-REM (NREM) sleep, deep slow wave anesthesia, and coma. The neuronal mechanisms underlying the reduction of PCI/PCIst in unconscious states remain largely unexplored. The extent to which different cortical areas or layers contribute to these measures is also unknown. To address these questions, here we first validate the use of PCIst in freely moving rats (8 males) and mice (12, 4 females) by showing that its values are lower in NREM sleep and slow wave anesthesia than in wake or REM sleep, as in humans. We then show that low PCIst is associated with the occurrence of an OFF period of neuronal silence. Moreover, the stimulation of deep, but not superficial, cortical layers leads to reliable changes in PCIst across sleep/wake and anesthesia. Finally, consistent changes in PCIst can be measured independent of which single area is being stimulated or recorded, except for recordings in mouse prefrontal cortex. These experiments directly support the hypothesis that PCIst is low when an OFF period disrupts causal interactions in cortical networks. Moreover, they demonstrate that, as in humans, PCIst can be used for the reliable assessment of vigilance states in unresponsive animals, without the need to rely on behavioral outputs such as the righting reflex. Significance StatementThe level of consciousness can be assessed in humans by measuring the spatiotemporal complexity of cortical responses using the Perturbational Complexity Index (PCI) and related PCIst. These measures discriminate between conscious and unconscious conditions with high sensitivity and specificity and work in unresponsive patients. However, the neuronal mechanisms underlying PCI/ PCIst are largely unexplored. Moreover, since they reflect evoked responses from many cortical regions, it is unclear whether some areas or layers are more informative than others. Here we validate PCIst in rodents, provide direct evidence for the underlying neuronal mechanisms, and show that reliable changes in PCIst can almost always be obtained independent of which single area is stimulated or recorded, but only after stimulation of deep layers.

neuroscience↗

Distinct signatures of loss of consciousness during Focal Impaired Awareness (FIA) versus Focal to Bilateral Tonic-Clonic (FBTC) seizures

Loss of consciousness (LOC) is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany LOC during focal impaired awareness (FIA) seizures, the mechanisms of LOC during focal to bilateral tonic-clonic (FBTC) seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between FIA and FBTC seizures may also help to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of LOC and intracranial EEG (iEEG) activity during 129 FIA and 50 FBTC from 41 patients. We characterized iEEG changes both in the seizure onset zone (SOZ) and in areas remote from SOZ with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of iEEG sleep-like activities: slow-wave activity (SWA; 1-4 Hz) and beta/delta ratio (B/D; a validated marker of cortical activation) during FIA vs. FBTC. Second, we quantified differences between FBTC and FIA for a marker validated to detect ictal cross-frequency coupling: phase-locked high-gamma (PLHG; high gamma phased locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index (i.e. the number of channels crossing an energy ratio threshold for high vs. low frequency power). Third, we assessed changes in iEEG activity preceding and accompanying behavioral generalization onset and their correlation with electromyogram (EMG) channels. In addition, we analyzed human cortical multi-unit activity recorded with Utah arrays during three FBTC. Compared to FIA, FBTC seizures were characterized by deeper LOC and by stronger increases in SWA in parieto-occipital cortex. FBTC also displayed more widespread increases in cortical activation (B/D), ictal cross-frequency coupling (PLHG) and ictal recruitment (epileptogenicity index). Even before generalization, FBTC displayed deeper LOC; this early LOC was accompanied by a paradoxical increase in B/D in fronto-parietal cortex. Behavioral generalization coincided with complete loss of responsiveness and a subsequent increase in high-gamma in the whole brain, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of FBTC revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the SOZ. Unlike during FIA, LOC during FBTC is characterized by a paradoxical increase in cortical activation and neuronal firing. These findings suggest differences in the mechanisms of ictal LOC between FIA and FBTC and may account for the more negative prognostic consequences of FBTC.

neuroscience↗