Objective

Despite their possible importance in the design of novel neuromodulatory approaches and in understanding status epilepticus, the dynamics and mechanisms of seizure termination are not well studied. We examined intracranial recordings from patients with epilepsy to differentiate seizure termination patterns and investigated whether these patterns are indicative of different underlying mechanisms.

Methods

Seizures were classified into one of two termination patterns: (a) those that end simultaneously across the brain (synchronous), and (b) those whose termination is piecemeal across the cortex (asynchronous). Both types ended with either a burst suppression pattern, or continuous seizure activity. These patterns were quantified and compared using burst suppression ratio, absolute energy, and network connectivity.

Results

Seizures with electrographic generalization showed burst suppression patterns in 90% of cases, compared with only 60% of seizures which remained focal. Interestingly, we found similar absolute energy and burst suppression ratios in seizures with synchronous and asynchronous termination, while seizures with continuous seizure activity were found to be different from seizures with burst suppression, showing lower energy during seizure and lower burst suppression ratio at the start and end of seizure. Finally, network density was observed to increase with seizure progression, with significantly lower densities in seizures with continuous seizure activity compared to seizures with burst suppression.

Significance

Based on this spatiotemporal classification scheme, we suggest that there are a limited number of seizure termination patterns and dynamics. If this bears out, it would imply that the number of mechanisms underlying seizure termination is also constrained. Seizures with different termination patterns exhibit different dynamics even before their start. This may provide useful clues about how seizures may be managed, which in turn may lead to more targeted modes of therapy for seizure control.

There has been considerable speculation regarding the function of the dentate gyrus (DG) - a subregion of the mammalian hippocampus - in learning and memory. In this Perspective article, we compare leading theories of DG function. We note that these theories all critically rely on the generation of distinct patterns of activity in the region to signal differences between experiences and to reduce interference between memories. However, these theories are divided by the roles they attribute to the DG during learning and recall and by the contributions they ascribe to specific inputs or cell types within the DG. These differences influence the information that the DG is thought to impart to downstream structures. We work towards a holistic view of the role of DG in learning and memory by first developing three critical questions to foster a dialogue between the leading theories. We then evaluate the extent to which previous studies address our questions, highlight remaining areas of conflict, and suggest future experiments to bridge these theories.

Patients with Alzheimer's disease and other dementias often make poor financial decisions, but it remains unclear whether this reflects specific failures in decision-making or more general deficits in episodic and working memory. We investigated how patients with Alzheimer's disease, behavioral variant frontotemporal dementia (bvFTD), and semantic variant primary progressive aphasia (svPPA) apply information in an intertemporal choice task between smaller intermediate and larger delayed rewards, with minimal memory demands. Multilevel modeling estimated subject-level sensitivities to three attributes of choice (the relative difference in reward magnitude, delay length, and absolute reward magnitudes) as well as baseline impulsivity. While baseline impulsivity in patients with Alzheimer's disease did not differ from controls, patients with bvFTD and svPPA were more impulsive than controls overall. Patients with Alzheimer's disease or bvFTD were less sensitive than controls to all three choice attributes, whereas patients with svPPA were less sensitive than controls to two attributes. Attenuated sensitivity to information presented during the choice was associated across all subjects with dorsomedial prefrontal atrophy for all three choice attributes. Given the minimal memory demands of our task, these findings suggest specific mechanisms underlying decision-making failures beyond episodic and working memory deficits in dementia.