Internodular functional connectivity in heterotopia‐related epilepsy

Abstract

Objective A vast network involving the nodules and overlying cortices is believed to be responsible for the epileptogenicity in gray matter heterotopia with multiple nodules, which often associated with difficult‐to‐treat epilepsy. We sought to determine if functional magnetic resonance imaging (fMRI) could detect internodular functional connectivity (FC), and if this connectivity reflects an actual synchronized neuronal activity and partakes in epileptogenicity. Methods We studied 16 epilepsy patients with multiple heterotopic nodules; eight underwent subsequent intracerebral EEG. We examined the internodular FC using fMRI and its correspondence with internodular synchrony of intracerebral interictal activity. We then compared the spreading speed of ictal activity between connected and unconnected nodules; and the FC among possible combinations of nodule pairs in terms of their involvement at seizure onset. Results Seventy nodules were studied: 83% have significant connection to at least one other nodule. Among the 49 pairs studied with intracerebral EEG, (1) synchronized interictal activity is more prevalent in fMRI‐connected pairs (P < 0.05), (2) ictal activity spreads faster between connected pairs (P < 0.0001), and (3) stronger FC was observed between pairs in which both nodules were involved at seizure onset (P < 0.01). Interpretation fMRI could reliably and noninvasively detect the FC between heterotopic nodules. These functional connections correspond to the synchrony of interictal epileptic activity between the nodules and to the ability of nodules to generate synchronous seizure onsets or rapid seizure spread. These findings may help in understanding the complexity of the epileptogenic network in multiple heterotopic nodules and better targeting the likely epileptogenic nodules.

"Epilepsy Associated with Periventricular Nodular Heterotopia: Case Report"

“…These connections would represent the ability of these nodules to initiate epileptic seizures or to spread rapidly through them [16,17]. The authors suggest that ictal activity spreads more quickly between connected nodes than between unconnected nodes [16]. Through these findings, the authors believe that internodular connections are responsible for providing a path that facilitates the propagation of ictal activity [16].…”

“…While electrophysiological studies demonstrate that they can be intrinsically epileptogenic, others indicate that a large epileptic network, instead of just a nodule, is responsible for epileptogenicity [16].…”

“…A study by Hui Ming Khoo et al evaluated the functional internodular connectivity in heterotopy-related epilepsy and suggested that the cortical heterotopic nodules are functionally connected through synapses, or that they connect to a third common area, without one node being directly connected to the other [16]. These connections would represent the ability of these nodules to initiate epileptic seizures or to spread rapidly through them [16,17]. The authors suggest that ictal activity spreads more quickly between connected nodes than between unconnected nodes [16].…”

fMRI functional connectivity as an indicator of interictal epileptic discharges

“…We used IED rates as measures of whether a region is in an epileptic network instead of the more commonly used correlation between channels showing epileptic discharges (Khoo et al., 2017; Khoo et al., 2019). A correlation measure or similar EEG functional connectivity metric might not account for interictal activity propagating with long latency.…”

“…fMRI images preprocessing for functional connectivity analysis was done following the pipeline of previous study (Khoo et al., 2019). Details are provided in supplementary information (Appendix S3).…”