Dynamic evolution of frontal-temporal network connectivity in temporal lobe epilepsy: A magnetoencephalography study

Temporal lobe epilepsy (TLE) frequently involves an intricate, extensive epileptic frontal-temporal network. This study aimed to investigate the interactions between temporal and frontal regions and the dynamic patterns of the frontal-temporal network in TLE patients with different disease durations. The magnetoencephalography data of 36 postoperative seizure-free patients with long-term follow-up of at least 1 year, and 21 age- and sex-matched healthy subjects were included in this study. Patients were initially divided into LONG-TERM (n = 18, DURATION >10 years) and SHORT-TERM (n = 18, DURATION ≤10 years) groups based on 10-year disease duration. For reliability, supplementary analyses were conducted with alternative cutoffs, creating three groups: 0 < DURATION ≤7 years (n = 11), 7 < DURATION ≤14 years (n = 11), and DURATION >14 years (n = 14). This study examined the intraregional phase-amplitude coupling (PAC) between theta phase and alpha amplitude across the whole brain. The interregional directed phase transfer entropy (dPTE) between frontal and temporal regions in the alpha and theta bands, and the interregional cross-frequency directionality (CFD) between temporal and frontal regions from the theta phase to the alpha amplitude were further computed and compared among groups. Partial correlation analysis was conducted to investigate correlations between intraregional PAC, interregional dPTE connectivity, interregional CFD, and disease duration. Whole-brain intraregional PAC analyses revealed enhanced theta phase-alpha amplitude coupling within the ipsilateral temporal and frontal regions in TLE patients, and the ipsilateral temporal PAC was positively correlated with disease duration (r = 0.38, p <.05). Interregional dPTE analyses demonstrated a gradual increase in frontal-to-temporal connectivity within the alpha band, while the direction of theta-band connectivity reversed from frontal-to-temporal to temporal-to-frontal as the disease duration increased. Interregional CFD analyses revealed that the inhibitory effect of frontal regions on temporal regions gradually increased with prolonged disease duration (r = -0.36, p <.05). This study clarified the intrinsic reciprocal connectivity between temporal and frontal regions with TLE duration. We propose a dynamically reorganized triple-stage network that transitions from balanced networks to constrained networks and further develops into imbalanced networks as the disease duration increases.