Altered temporal dynamics of brain activity in patients with generalized tonic-clonic seizures

Generalized seizures engage bilateral networks from their onset at a low temporal scale. Previous studies findings have demonstrated focal/local brain activity abnormalities in the patients with generalized tonic-clonic seizures (GTCS). Resting state functional magnetic resonance imaging (fMRI) allows the detection of aberrant spontaneous brain activity in GTCS. Little is known, however, about alterations of dynamics (temporal variability) of spontaneous brain activity. It also remains unclear whether temporal variability of spontaneous brain activity is associated with disease severity. To address these questions, the current study assessed patients with GTCS (n = 35), and age- and sex-matched healthy controls (HCs, n = 33) who underwent resting state fMRI. We first assessed the dynamics of spontaneous brain activity using dynamic amplitude of low-frequency fluctuation (dALFF). Furthermore, the temporal variability of brain activity was quantified as the variance of dALFF across sliding window. Compared to HCs, patients with GTCS showed hyper-temporal variability of dALFF in parts of the default mode network, whereas they showed hypo-temporal variability in the somatomotor cortex. Furthermore, dynamic ALFF in the subgenual anterior cingulate cortex was positively correlated with duration of disease, indicating that disease severity is associated with excessive variability. These results suggest both an excessive variability and excessive stability in patients with GTCS. Overall, the current findings from brain activity dynamics contribute to our understanding of the pathophysiological mechanisms of generalized seizure.