Dysfunctional white‐matter networks in medicated and unmedicated benign epilepsy with centrotemporal spikes

Abstract

Benign epilepsy with centrotemporal spikes (BECT) is the most common childhood idiopathic focal epilepsy syndrome, which characterized with white‐matter abnormalities in the rolandic cortex. Although diffusion tensor imaging research could characterize white‐matter structural architecture, it cannot detect neural activity or white‐matter functions. Recent studies demonstrated the functional organization of white‐matter by using functional magnetic resonance imaging (fMRI), suggesting that it is feasible to investigate white‐matter dysfunctions in BECT. Resting‐state fMRI data were collected from 24 new‐onset drug‐naive (unmedicated [NMED]), 21 medicated (MED) BECT patients, and 27 healthy controls (HC). Several white‐matter functional networks were obtained using a clustering analysis on voxel‐by‐voxel correlation profiles. Subsequently, conventional functional connectivity (FC) was calculated in four frequency sub‐bands (Slow‐5:0.01–0.027, Slow‐4:0.027–0.073, Slow‐3:0.073–0.198, and Slow‐2:0.198–0.25 Hz). We also employed a functional covariance connectivity (FCC) to estimate the covariant relationship between two white‐matter networks based on their correlations with multiple gray‐matter regions. Compared with HC, the NMED showed increased FC and/or FCC in rolandic network (RN) and precentral/postcentral network, and decreased FC and/or FCC in dorsal frontal network, while these alterations were not observed in the MED group. Moreover, the changes exhibited frequency‐specific properties. Specifically, only two alterations were shared in at least two frequency bands. Most of these alterations were observed in the frequency bands of Slow‐3 and Slow‐4. This study provided further support on the existence of white‐matter functional networks which exhibited frequency‐specific properties, and extended abnormalities of rolandic area from the perspective of white‐matter dysfunction in BECT.

Exploring the functional connectome in white matter

“…Taken together, these findings suggest that there are no fundamental barriers or direct sources of evidence against the possibility of detecting neural activities of BOLD‐fMRI in WM (Gawryluk, Mazerolle, & D'Arcy, ). To date, many psychiatric and neurological disorders are characterized by WM functional abnormalities (Ji et al, ; Jiang et al, ; Jiang et al, ; Wang et al, ). It is therefore important to explore WM functional networks to allow for fMRI‐based investigations of WM brain disorders, such as multiple sclerosis (He et al, ), and WM dementia (Filley, ), which may allow further insight into our understanding of the pathological mechanisms of different neurological diseases.…”

“…More recently, Ji et al found that patients with Parkinson's disease showed increased small‐worldness in the WM functional network (Ji et al, ). Moreover, brain function profiles of WM function, including power spectra, coupling of WM and GM functional connectivity were found to be disrupted in various brain disorders, such as pontine stroke, Alzheimer's disease, and epilepsy (Jiang et al, ; Makedonov, Chen, Masellis, & MacIntosh, ; Wang et al, ). However, such previous studies focused on the extant functional modules and large‐scale networks in WM; used relatively small sample sizes; and failed to offer direct evidence for the different roles played by functional connectomes within WM and GM.…”

Functional engagement of white matter in resting-state brain networks

“…These and other relevant contributions were included in a recent Perspective by Grajauskas et al (2019) who argue strongly that WM activity should not be treated as a nuisance regressor but instead be recognized as important in analyses of brain function. Moreover, an increasing number of studies have reported that alterations of WM networks are associated with brain disorders including schizophrenia, Parkinson’s disease and epilepsy (; Ji et al, 2019 ; Jiang et al, 2019 , 2018 ). Taken together, these findings indicate that WM-GM and WM-WM correlations reveal an underlying organization and suggest further investigations are justified of the possible contributions of WM signals to the identification of well-established brain networks that by convention consist of GM alone.…”

The relationship between neuromagnetic activity and cognitive function in benign childhood epilepsy with centrotemporal spikes

“…In the 30-80 Hz band, the PCC region was inactivated, while in the 80-250 Hz band, the MFC region was inactivated. Some studies suggest that frequent interictal spike discharges, especially during sleep, may interfere with the development of white matter in children, thereby causing changes in the neuromagnetic field [13,39]. During the resting state, the brain is active in an organized way, and this active network is called the default mode network (DMN), which includes the PCC, the dorsal medial prefrontal cortex (middle frontal gyrus, superior frontal gyrus), dorsal anterior cingulate gyrus, and bilateral angular gyrus [40].…”