Functional network dynamics between the anterior thalamus and the cortex in deep brain stimulation for epilepsy

Due to its unique connectivity profile with cortical brain regions, and its suggested role in the subcortical propagation of seizures, the Anterior Nucleus of the Thalamus (ANT) has been proposed as a key Deep Brain Stimulation (DBS) target in drug-resistant epilepsy (DRE). However, the spatio-temporal interaction dynamics of this brain structure, and the functional mechanisms underlying ANT DBS in epilepsy, remain unknown. Here, we study how the ANT interacts with the neocortex in vivo in humans and provide a detailed neurofunctional characterization of mechanisms underlying the effectiveness of ANT DBS, aiming at defining intraoperative neural biomarkers of responsiveness to therapy, assessed at 6 months post-implantation as the reduction in seizure frequency. A cohort of 15 DRE (N = 6 males, age = ) patients underwent bilateral ANT DBS implantation. Using intraoperative cortical and ANT simultaneous electrophysiological recordings, we found that the ANT is characterized by high amplitude (4-8 Hz) oscillations, mostly in its superior part. The strongest functional connectivity between the ANT and the scalp EEG was also found in the band in ipsilateral centro-frontal regions. Upon intraoperative stimulation in the ANT, we found a decrease in higher EEG frequencies (20-70 Hz) and a generalized increase in scalp-to-scalp connectivity. Crucially, we observed that responders to ANT DBS treatment were characterized by higher EEG oscillations, higher power in the ANT, and stronger ANT-to-scalp θ connectivity, highlighting the crucial role of oscillations in the dynamical network characterization of these structures. Our study provides a comprehensive characterization of the interaction dynamic between the ANT and the cortex, delivering crucial information to optimize and predict clinical DBS response in patients with DRE