Resting-state functional connectivity alterations in periventricular nodular heterotopia related epilepsy

Wenyu Liu,Xinyu Hu,Qiyong Gong,Dong Zhou,Dongmei An

doi:10.1038/s41598-019-55002-3

Abstract

Periventricular nodular heterotopia (PNH) is a neural migration disorder which often presents clinically with seizures. However, the underlying functional neural basis of PNH is still unclear. We aimed to explore the underlying pathological mechanism of PNH by combining both whole brain functional connectivity (FC) and seed-based FC analyses. We utilized resting-state fMRI to measure functional connectivity strength (FCS) in 38 patients with PNH-related epilepsy and 38 control subjects. The regions with FCS alterations were selected as seeds in the following FC analyses. Pearson correlation analyses were performed to explore associations between these functional neural correlates and clinical features. In comparison with controls, PNH patients showed lower FCS in bilateral insula (P < 0.05, family wise error (FWE) correction), higher FC in the default mode network and lower FC in the fronto-limbic-cerebellar circuits (P < 0.05, FWE correction). Pearson correlation analyses revealed that FCS in bilateral insula was negatively correlated with the epilepsy duration (P < 0.05); medial prefronto-insular connectivity was negatively correlated with Hamilton Anxiety Scale (P < 0.05) and cerebellar-insular connectivity was also negatively correlated with Hamilton Depression Scale (P < 0.05). Using the resting-state FCS analytical approach, we identified significant insular hypoactivation in PNH patients, which suggests that the insula might represent the cortical hub of the whole-brain networks in this condition. Additionally, disruption of resting state FC in large-scale neural networks pointed to a connectivity-based neuropathological process in PNH.

Highlights

Periventricular nodular heterotopia (PNH) is a neural migration disorder which often presents clinically with seizures
All patients had been diagnosed with epilepsy with one patient naïve to any epileptic drugs before involved in this research
Of the remaining patients that had previously used treatment; all were diagnosed with epilepsy, 23 were treated on monotherapy, 14 on polytherapy, and all had a history of focal seizures. 18 of the patients reported having a history of only focal seizures

Summary

Introduction

Periventricular nodular heterotopia (PNH) is a neural migration disorder which often presents clinically with seizures. We utilized resting-state fMRI to measure functional connectivity strength (FCS) in 38 patients with PNH-related epilepsy and 38 control subjects. Previous rs-fMRI studies have demonstrated that, compared with normal controls, patients with PNH showed higher FC in the prefrontal cortices, supramarginal gyrus, dorsal cingulate gyrus, and lower FC in the parahippocampal gyrus and inferior temporal gyrus[7,11]. All of these resting-state fMRI literature adopted seed-based FC approach, which is the most commonly used method to identify the resting state networks. This approach is useful to discover regionally specific hypotheses of cerebral function but has limited ability to detect connectivity patterns not predicted a priori[13]

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Conclusion