Brain activation and connection across resting and motor-task states in patients with generalized tonic-clonic seizures

Abstract

Aims: Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism.

Methods: Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups.

Results: All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients.

Conclusion: Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.

Keywords: activation; fMRI; generalized tonic–clonic seizures; motor‐task state; network connectivity; resting state; white matter.

FIGURE 1

Comparisons of motor task activation and its spatial correlation with functional gradients. (A–C) Group comparisons between patients with GTCS and healthy controls, and between subgroups of patients. (D, E) Functional gradient maps from our previously published work. (F, G) Spatial correlation in HC and GTCS. (H, I). Spatial correlation in HC, AEDs_GTCS, and ND_GTCS. The read star (*) indicates p < 0.05.

FIGURE 2

Twelve white‐matter networks clustered using resting and motor‐task state fMRI together. ACRN, anterior corona radiate network; CWN, cerebellar white‐matter network; DWN, deep white‐matter network; FTWN, frontotemporal white‐matter network; GCCN, genu of corpus callosum network; OFWN, orbitofrontal white‐matter network; OWN, occipital white‐matter network; PCCN, posterior corpus callosum network; PCWN, precentral/postcentral white‐matter network; PTRN, posterior thalamic radiation network; SCRN, superior corona radiate network; STWN, Superior temporal white‐matter network.

FIGURE 3

Connections with interaction effects of group and state. The yellow star represents the comparison between the resting and motor‐task states in the HC, the blue star represents the comparison between the resting and motor‐task states in the GTCS, and the black star represents the comparison between GTCS and HC in the motor‐task state. In subgroup analysis, both the ND_GTCS and AEDs_GTCS showed significant alterations in network connectivity between states with the same trend, including five increased connections and three decreased connections.

FIGURE 4

The similarity between white‐matter networks clustered resting and motor‐task states. (A) The spatial similarity between resting and motor‐task states. (B) The dice coefficient between white‐matter networks varies across states. (C) In all subjects, HFC between mFTN and mSTN, and HFC between rACRN1 and rACRN2 were compared between resting and motor‐task states. (D) FC comparisons between patients and controls between states. (E) HFC comparisons between subgroups of patients and controls between states. The stars (*) represent significant between‐group differences.

FIGURE 5

Across‐state connectivity in patients relative to the HC (p < 0.001). (A) Comparisons of AS‐FC between GTCS and HC. (B) Comparisons of AS‐FC between ND_GTCS, AEDs_GTCS, and HC. (C) Comparisons of AS‐HFC between GTCS and HC. (D) Comparisons of AS‐HFC between ND_GTCS, AEDs_GTCS, and HC.