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Salami, P.

Publications and source records attributed to Salami, P..

3 recordsLinked to original sources

Sleep spindles stabilize human thalamocortical networks, inhibiting pathological disruptions

The thalamus coordinates sleep-dependent brain function including memory consolidation, sensory gating, and network stability through spindle oscillations. Thalamocortical circuits are also affected in many neurological and neuropsychiatric disorders. Yet how human thalamocortical circuits respond to pathological disruptions remain poorly understood. Here, we leveraged interictal epileptiform discharges (IEDs) as spontaneous perturbations to probe spindle-generating circuits and thalamocortical dynamics in vivo. Using multi-night intracranial recordings spanning multiple thalamic nuclei and cortical regions in 55 individuals with epilepsy, we investigated interactions between sleep spindles and epileptic activity across timescales from milliseconds to days. Sleep spindles were associated with IED suppression, whereas IEDs increased subsequent spindle probability, revealing bidirectional interactions between physiological and pathological activity. Nights with lower IEDs corresponded to increased spindle occurrence, longer duration, and faster frequency, reflecting a more stable thalamocortical state. These findings propose sleep spindles as potential regulators of thalamocortical networks that actively respond to and regulate pathological activity.

neuroscience↗

The Impact of subicular VIP-expressing interneurons on seizure dynamics in temporal lobe epilepsy: Insights from preclinical models

The subiculum, a key output region of the hippocampus, is increasingly recognized as playing a crucial role in seizure initiation and spread. The subiculum consists of glutamatergic pyramidal cells, which show alterations in intrinsic excitability in the course of epilepsy, and multiple types of GABAergic interneurons, which exhibit varying characteristics in epilepsy. In this study, we aimed to assess the role of the vasoactive intestinal peptide interneurons (VIP-INs) of the ventral subiculum in the pathophysiology of temporal lobe epilepsy. We observed that an anatomically restricted inhibition of VIP-INs of the ventral subiculum was sufficient to reduce seizures in the intrahippocampal kainic acid model of epilepsy, changing the circadian rhythm of seizures, emphasizing the critical role of this small cell population in modulating TLE. As we expected, permanent unilateral or bilateral silencing of VIP-INs of the ventral subiculum in non-epileptic animals did not induce seizures or epileptiform activity. Interestingly, transient activation of VIP-INs of the ventral subiculum was enough to increase the frequency of seizures in the acute seizure model. Our results offer new perspectives on the crucial involvement of VIP-INs of the ventral subiculum in the pathophysiology of TLE. Given the observed predominant disinhibitory role of the VIP-INs input in subicular microcircuits, modifications of this input could be considered in the development of therapeutic strategies to improve seizure control.

neuroscience↗

Seizure onset location shapes dynamics of initiation

ObjectiveIctal electrographic patterns are widely thought to reflect underlying neural mechanisms of seizures. Here we studied the degree to which seizure patterns are consistent in a given patient, relate to particular brain regions and if two candidate biomarkers (high-frequency oscillations, HFOs; infraslow activity, ISA) and network activity, as assessed with cross-frequency interactions, can discriminate between seizure types. MethodsWe analyzed temporal changes in low and high frequency oscillations recorded during seizures, as well as phase-amplitude coupling (PAC) to monitor the interactions between delta/theta and ripple/fast ripple frequency bands at seizure onset. ResultsSeizures of multiple pattern types were observed in a given patient and brain region. While there was an increase in HFO rate across different electrographic patterns, there are specific relationships between types of HFO activity and onset region. Similarly, changes in PAC dynamics were more closely related to seizure onset region than they were to electrographic patterns while ISA was a poor indicator for seizure onset. ConclusionsOur findings suggest that the onset region sculpts neurodynamics at seizure initiation and that unique features of the cytoarchitecture and/or connectivity of that region play a significant role in determining seizure mechanism. SignificanceClinicians should consider more than just overt electrographic patterns when considering seizure mechanisms and regions of onset. Examination of onset pattern in conjunction with the interactions between different oscillatory frequencies in the context of different brain regions might be more informative and lead to more reliable clinical inference as well as novel therapeutic approaches.

neuroscience↗