• thalamus
• functional connectivity
• interictal activity
• surgical outcome
• focal epilepsy
• seeg

Purpose: Although the role of thalamus in epilepsy is now recognized and its stimulation is becoming more and more attractive in the treatment of drug-resistant epilepsies, only few data are yet available on thalamic interictal activity and functional connectivity in these patients. The present study aims to investigate the thalamic interictal epileptogenic biomarkers and functional connectivity and their association with clinical variables on a large cohort of patients explored by stereotactic-EEG (SEEG).
Method: We studied 121 patients (M/F=62/59; median age at SEEG=28, min-max=3-70) who underwent SEEG with thalamus implantation during pre-surgical evaluation for focal drug resistant epilepsy. For each patient, 10 minutes of rest and sleep SEEG records have been collected. First, we analyzed the thalamic interictal activities in SEEG records using Delphos, an automatic detector of Spikes and High Fast Oscillations (HFOs). Second, we studied the associations between interictal activities and clinical variables.
After that, we conduced a functional connectivity study, using a linear correlation method (R2), in order to define the interactions between the thalamus and the other brain regions during the interictal period. The functional connectivity analysis was conducted on a reduce montage, excluding all the white matter channels, because the signal’s origin in those areas is still unknown. Moreover, when constructing the connectivity matrix, we removed the values that referred to the connection of intrathalamic channels in order to highlight the connections between the thalamus and other cortical areas. So in each patient, for each thalamic bipolar channel we obtained an R2 value, representing the connection between that thalamic nucleus and all the other non-thalamic regions implanted for that patient. The analysis was realized on broadband signal, but also on raw signals filtered in classically defined EEG sub-bands: delta (0.5-3.4 Hz), theta (3.4-7.4 Hz), alpha (7.4-12.4 Hz), beta (12.4-24 Hz) and gamma (24-80 Hz).
Results: Spikes and HFOs, including fast ripples, were detected in the thalamus during rest-waking periods and sleep recordings. We found higher rate of Spikes (Wilcoxon test, p<0.01) and HFOs (Wilcoxon test, p<0.05) in the thalamus only during sleep in patients with a poorer surgical outcome, evaluated by the persistence of invalidating seizures (Engel 3 and 4 vs Engel 2 and 1). No significant differences in interictal activity were found with respect to type, lateralization, aetiology of epilepsy, epileptogenicity of the thalamus (assessed by the Epileptogenicity Index).
The R2 Mean values obtained for the thalamic and, when available, pulvinar channels were higher for patients with poorer prognosis. This type of results appeared in sleep records in the beta and gamma band. Also for these findings, an increasing trend of R2 Mean values, following the arise of the Engel class, occurred in the beta band.
Conclusion: Our work confirms the relevance of the study of the thalamus in the epileptogenic networks of focal epilepsies. Although not directly involved in the epileptogenic zone, the thalamus shows increased interictal activity (both Spikes and HFOs) and functional connectivity in sleep in patients with a poor outcome compared to patients with a good outcome after surgery and/or thermocoagulations. Further analysis may result important for the decision making when considering the possible treatments for drug-resistant epilepsy.