Pathological uncoupling between amplitude and connectivity of brain fluctuations in epilepsy

Amplitude and functional connectivity are two fundamental parameters for describing the spontaneous brain fluctuations. These two parameters present close coupling in physiological state, and present different alteration patterns in epilepsy revealed by functional MRI (fMRI). We hypothesized that the alteration of coupling between these two imaging parameters may be underpinned by specific pathological factors of epilepsy, and can be employed to improve the capability for epileptic focus detection. Forty-seven patients (26 left- and 21 right-sided) with mesial temporal lobe epilepsy (mTLE) and 32 healthy controls underwent resting-state fMRI scans. All patients were detected to have interictal epileptic discharges on simultaneous electroencephalograph (EEG) recordings. Amplitude-connectivity coupling was calculated by correlating amplitude and functional connectivity density of low-frequency brain fluctuations. We observed reduced amplitude-connectivity coupling associated with epileptic discharges in the mesial temporal regions in both groups of patients, and increased coupling associated with epilepsy durations in the posterior regions of the default-mode network in the right-sided patients. Moreover, we proposed a new index of amplitude subtracting connectivity, which elevated imaging contrast for differentiating the patients from the controls. The findings indicated that epileptic discharges and chronic damaging effect of epilepsy might both contribute to alterations of amplitude-connectivity coupling in different pivotal regions in mTLE. Investigation on imaging coupling provides synergistic approach for describing brain functional changing features in epilepsy.