Abnormal Brain Areas Common to the Focal Epilepsies: Multivariate Pattern Analysis of fMRI

Abstract

Individuals with focal epilepsy have heterogeneous sites of seizure origin. However, there may be brain regions that are common to most cases of intractable focal epilepsy. In this study, we aim to identify these using multivariate analysis of task-free functional MRI. Fourteen subjects with extratemporal focal epilepsy and 14 healthy controls were included in the study. Task-free functional MRI data were used to calculate voxel-wise regional connectivity with regional homogeneity (ReHo) and weighted degree centrality (DCw), in addition to regional activity using fraction of amplitude of low-frequency fluctuations (fALFF). Multivariate pattern analysis was applied to each of these metrics to discriminate brain areas that differed between focal epilepsy subjects and healthy controls. ReHo and DCw classified focal epilepsy subjects from healthy controls with high accuracy (89.3% and 75%, respectively). However, fALFF did not significantly classify patients from controls. Increased regional network activity in epilepsy subjects was seen in the ipsilateral piriform cortex, insula, and thalamus, in addition to the dorsal anterior cingulate cortex and lateral frontal cortices. Decreased regional connectivity was observed in the ventromedial prefrontal cortex, as well as lateral temporal cortices. Patients with extratemporal focal epilepsy have common areas of abnormality (ReHo and DCw measures), including the ipsilateral piriform cortex, temporal neocortex, and ventromedial prefrontal cortex. ReHo shows additional increase in the "salience network" that includes anterior insula and anterior cingulate cortex. DCw showed additional effects in the ipsilateral thalamus and striatum. These brain areas may represent key regional network properties underlying focal epilepsy.

The dynamics of functional connectivity in neocortical focal epilepsy

“…1C). These are commensurate with our previous findings of static fMRI connectivity abnormalities in focal epilepsy using an unrelated machine learning approach (Pedersen et al, 2016), and also simultaneous EEG-fMRI correlates of inter-ictal epileptiform discharges in frontal lobe and temporal lobe epilepsy (Fahoum et al, 2012). Contrary to previous reports, we observed no between-group differences in either the ipsilateral piriform cortex or the precuneus.…”

“…No statistical difference of age and gender was seen between the groups. We have previously published data from 15 of these patients in unrelated analyses of fMRI graph theory (Pedersen et al, 2015b) and multivariate pattern analysis (Pedersen et al, 2016). Here, an additional six patients with focal epilepsy were included.…”

“…The DRePS time series at a typical voxel represents time-varying phase coherence relationships between a central voxel and its immediate 26 neighbouring voxels over the course of the scan. We developed this measure as a dynamic extension of Regional Homogeneity (Zang et al, 2004), which has previously been used for static connectivity analysis of epilepsies (Pedersen et al, 2015a, Pedersen et al, 2016, Weaver et al, 2013, Zeng et al, 2013, Zhong et al, 2011). Amplitude of DRePS ranges between 0 and 1 covering low to high dynamic local connectivity.…”

“…This was first demonstrated by Laufs et al (2011) who used simultaneous electroencephalogram and fMRI (EEG-fMRI) to demonstrate that across temporal and non-temporal focal epilepsy patients with variable foci, ipsilateral piriform cortex was activated during inter-ictal epileptiform discharges (see also Fahoum et al, 2012, Flanagan et al, 2014, Pedersen et al, 2016). Another simultaneous EEG-fMRI study demonstrated that several other brain regions are also commonly activated or deactivated during heterogeneous inter-ictal epileptiform discharges in frontal lobe epilepsy (Fahoum et al, 2012), namely the ipsilateral fronto-insular cortex, mid-cingulate cortex, precuneus, and cerebellum.…”

Multimodal MRI profiling of focal cortical dysplasia type II

“…Increased ReHo in type IIA may reflect enhanced synchronization of local epileptogenic circuits. 30 Such anomalies, reported in other focal syndromes 31,32 and generalized epilepsies, 33 suggest enhanced local connectivity as a common marker of chronic seizure activity. Conversely, decreased ReHo in type IIB may be specific to balloon cells, not necessarily a marker of epileptogenicity.…”