Brain networks involved in Generalized Periodic Discharges (GPD) in post-anoxic-ischemic encephalopathy

Abstract Aim Generalized periodic discharge (GPD) is an EEG pattern of poor neurological outcome, frequently observed in comatose patients after cardiac arrest. The aim of our study was to identify the neuronal network generating ≤2.5 Hz GPD using EEG source localization and connectivity analysis. Methods We analyzed 40 comatose adult patients with anoxic-ischemic encephalopathy, who had 19 channel-EEG recording. We computed electric source analysis based on distributed inverse solution (LAURA) and we estimated cortical activity in 82 atlas-based cortical brain regions. We applied directed connectivity analysis (Partial Directed Coherence) on these sources to estimate the main drivers. Results Source analysis suggested that the GPD are generated in the cortex of limbic system in the majority of patients (87.5%). Connectivity analysis revealed main drivers located in thalamus and hippocampus for the large majority (80%) of patients, together with important activation also in amygdala (70%). Conclusions We hypothesize that the anoxic-ischemic dysfunction, leading to hyperactivity of the thalamo-cortical (limbic presumably) circuit, can result in an oscillatory thalamic activity capable of inducing periodic cortical (limbic, mostly medial-temporal and orbitofrontal) discharges, similarly to the case of generalized rhythmic spike-wave discharge in convulsive or non-convulsive status epilepticus.