Aberrant fast spiking interneuronal activity precedes seizure transitions in humans.
medRxiv
; 2024 Jan 26.
Article
in En
| MEDLINE
| ID: mdl-38343792
ABSTRACT
There is active debate regarding how GABAergic function changes during seizure initiation and propagation, and whether interneuronal activity drives or impedes the pathophysiology. Here, we track cell-type specific firing during spontaneous human seizures to identify neocortical mechanisms of inhibitory failure. Fast-spiking interneuron activity was maximal over 1 second before equivalent excitatory increases, and showed transitions to out-of-phase firing prior to local tissue becoming incorporated into the seizure-driving territory. Using computational modeling, we linked this observation to transient saturation block as a precursor to seizure invasion, as supported by multiple lines of evidence in the patient data. We propose that transient blocking of inhibitory firing due to selective fast-spiking interneuron saturation-resulting from intense excitatory synaptic drive-is a novel mechanism that contributes to inhibitory failure, allowing seizure propagation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
MedRxiv
Year:
2024
Document type:
Article