OBJECTIVE: In @entity302 , interictal @entity302 spikes (IESs) and fast ripples (FRs) represent clinically relevant biomarkers @entity3290 . However, their specific significance and the pathophysiological changes leading to either FRs or IESs remain elusive. The objective of this study was to analyze the conditions in which hyperexcitable networks can generate either IESs or FRs and to reveal shared or distinct mechanisms that underlie both types of events. METHODS: This study is the first to comparatively analyze mechanisms that induce either IESs or FRs using an approach that combines computational modeling and experimental data (in vivo and in vitro). A detailed @entity1399 hippocampal network model is introduced. A parameter sensitivity analysis was conducted to determine which model parameters (cell related and network related) allow the most accurate simulation of FRs and IESs. RESULTS: Our model indicates that although FRs and IESs share certain common mechanisms (shifted @entity1246 [ @entity1246 ]A reversal potential, altered synaptic transmission), there are also critical differences in terms of number of @entity1358 involved (small vs large), spatial distribution of hyperexcitable @entity1358 (clustered vs uniform), and firing patterns (weakly vs highly synchronized). In vitro experiments verified that subtle changes in GABAergic and glutamatergic transmission favor either FRs or IESs, as predicted by the model. INTERPRETATION: This study provides insights into the interpretation of 2 interictal markers observed in intracerebral electroencephalographic data. Depending on the degree and spatiotemporal features of hyperexcitability, not only IESs or FRs are generated but also transitions between both types of events.

Distinct hyperexcitability mechanisms underlie fast ripples and XXXX spikes.

@entity1246 :: ('MESH:D005680', 'Chemical') :: ['gamma-aminobutyric acid', 'GABA'] @entity1399 :: ('759', 'Gene') :: ['CA1'] @entity1358 :: ('MESH:D002292', 'Disease') :: ['pyramidal cells'] @entity302 :: ('MESH:D004827', 'Disease') :: ['epileptic', 'partial epilepsies'] @entity3290 :: ('MESH:D062706', 'Disease') :: ['characteristic of epileptogenic networks']
@entity302 :: (MESH:D004827,Disease) :: ['epileptic']
