Temporal lobe epilepsy alters spatio-temporal dynamics of the hippocampal functional network

Mesial temporal lobe epilepsy (TLE) is characterized by transient abnormal electrical activity originating in the hippocampus. The objective of this study was to characterize dynamic spatio-temporal fluctuations in hippocampal network connectivity in mTLE using functional connectivity (FC) mapping in 41 unilateral mTLE patients (28 right, 13 left) and 56 healthy control participants using 3T MRI. Dynamic FC was computed across the scan using sliding 60-s windows. This was compared to static FC computed using the whole 10-min functional MRI scan, and to the variance in the hippocampal functional MRI signal. Four states of healthy hippocampal dynamic FC were identified and compared to TLE patients. TLE patients fluctuated between these four states, but the hippocampus ipsilateral to the seizure focus spent more time in a state distinguished by lower prefrontal and parietal FC than the dominant healthy state. Increased time spent in this state was associated with increased impairment in static FC and increased variance in the hippocampal functional MRI signal. Overall, this work provides evidence that increases in variance in signal fluctuations occurring at the seizure focus in the hippocampus in patients with mTLE may contribute to disruptions in healthy FC network dynamics within an fMRI scan that contribute to decreases in static hippocampal FC. These alterations result in decreased hippocampal connectivity to bilateral prefrontal and parietal regions in TLE which may be related to behavior and cognitive impairments in these patients. Therefore, characterization of an individual patient's hippocampal dynamics at different time scales may provide more specific spatio-temporal profiles of network impairment that may be related to hippocampal dysfunction in TLE.