Hippocampal interictal spikes disrupt theta-band hippocampal-frontal eye field connectivity: fixation skewness as an indicator of transient network instability.

OBJECTIVE Hippocampal interictal epileptiform discharges (IEDs) could induce transient visual working memory (VWM) impairments, yet the effect of IEDs on VWM network remain unclear. Since VWM depends on dynamic coordination between memory representations in the hippocampus (HP) and visual exploration controlled by the frontal eye field (FEF), we tested whether hippocampal IEDs disrupt this circuit's functional connectivity and whether such disruption is reflected in altered viewing patterns, offering a behavioral readout of transient network dysfunction.

METHODS Seven epilepsy patients with hippocampal IEDs and fourteen healthy controls performed a VWM task with eye tracking. In patients, intracranial electroencephalogram (iEEG) was simultaneously recorded from the HP and FEF. We quantified IED-related changes in HP-FEF functional connectivity and examined fixation metrics across IED-related time windows, as well as their relationships with IED counts and task performance.

RESULTS Hippocampal IEDs were followed by a transient reduction in theta-band bidirectional connectivity between HP and FEF. Behaviorally, although average fixation durations increased during IED periods, the most robust change was a significant rightward skew in the fixation duration distribution. Critically, across patients, the skewness of fixation duration distribution showed strong positive correlations with FEF-to-HP theta-band connectivity and hippocampal IED counts.

CONCLUSIONS Hippocampal IEDs disrupt the functional coordination of the HP-FEF circuit, leading to transient processing interruptions manifested as skewed fixation distributions. This study provides a neurophysiological and behavioral basis for using eye-tracking as a non-invasive tool to monitor the transient cognitive impairments related to HP-FEF circuit disruptions in epilepsy patients, offering potential for clinical assessment in naturalistic settings.