Increased Intrinsic Connectivity of the Default Mode Network in Temporal Lobe Epilepsy: Evidence from Resting-State MEG Recordings

<div><p>The electrophysiological signature of resting state oscillatory functional connectivity within the default mode network (DMN) during spike-free periods in temporal lobe epilepsy (TLE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in TLE, and we examined the effect of lateralized TLE on functional connectivity. Sixteen medically intractable TLE patients and 22 controls participated in this study. Whole-scalp 306-channel MEG epochs without interictal spikes generated from both MEG and EEG data were analyzed using a minimum norm estimate (MNE) and source-based imaginary coherence analysis. With this processing, we obtained the cortical activation and functional connectivity within the DMN. The functional connectivity was increased between DMN and the right medial temporal (MT) region at the delta band and between DMN and the bilateral anterior cingulate cortex (ACC) regions at the theta band. The functional change was associated with the lateralization of TLE. The right TLE showed enhanced DMN connectivity with the right MT while the left TLE demonstrated increased DMN connectivity with the bilateral MT. There was no lateralization effect of TLE upon the DMN connectivity with ACC. These findings suggest that the resting-state functional connectivity within the DMN is reinforced in temporal lobe epilepsy during spike-free periods. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction and prognosis in patients with TLE.</p></div

Difference of functional connectivity between control subjects and TLE patients.

<p>The p-value maps on the sagittal, coronal and axial MR images show the significant differences in mean functional connectivity within the DMN between control subjects and TLE patients in the delta, theta, alpha, beta and gamma bands. Cortical areas encircled by dashed circles indicate cortical areas with significant changes. The maps are color coded with significant values (p < 0.05) denoted in white. The number above the image indicates the slice number.</p

Clinical characteristic of TLE patients.

<p>R, right; L, left; T, temporal lobe; CPS, complex partial seizure</p><p>SPS, simple partial seizure; SGTCS, secondary generalized tonic-clonic seizure</p><p>MTS, mesial temporal sclerosis; VM, vascular malformation</p><p>Encephalom, encephalomalacia; F, frontal; AEDs, anti-epileptic drugs</p><p>Clinical characteristic of TLE patients.</p

Bar plots for the laterality effect on functional connectivity.

<p>(a) The difference in the delta functional connectivity in the left and right MT regions between controls, and left and right TLE patients is shown. (b) There were significant differences in the theta functional connectivity in the left and right ACC regions between controls, and left and right TLE patients. Each error bar represents the <i>standard error of the mean</i> (<i>SEM</i>). * p < 0.05; ** p < 0.01; *** p < 0.001.</p

Data analysis procedure.

<p>The procedure for resting-state MEG data analysis that was used in this study is shown.</p

Genetic and clinical features of the patients with PKD/IC harboring <i>PRRT2</i> mutations.

<p>Abbreviation: M  =  male; F  =  female; y  =  years; AS  =  apparently sporadic; SM  =  sudden movements; IM  =  intention to move; S  =  startle; s  =  stress; D  =  dystonia; C  =  choreoathetosis; CBZ  =  carbamazepine; m  =  month; w  =  week; PHT  =  phenytoin; OXC  =  oxcarbazepine; IC  =  infantile convulsions.</p>a<p>These patients have novel mutations.</p

Haplotype analyses of the patients carrying <i>PRRT2</i> p.R217Pfs*8 mutation.

<p>Five unrelated PKD/IC pedigrees carry the <i>PRRT2</i> p.R217Pfs*8. Patients 4 (A), 5 (B), 6 (C), 7 (D), and 8 (E) are indicated with arrows. Asterisks (*) depict the individuals who were haplotyped. The squares and circles denote males and females, and the close and open symbols represent affected and unaffected members, respectively. The grey symbols denote undetermined disease status. The <i>PRRT2</i> genotype is labeled below the symbols. The alleles with an unknown phase are labeled and separated with a slash. The haplotypes linked to the <i>PRRT2</i> p.R217Pfs*8 in the seven unrelated index patients are showed in (F). Five patients shared a common haplotype at loci rs9922666, rs7205278, rs4788186, rs7204252, and rs889695 linked to the <i>PRRT2</i> p.R217Pfs*8 (G-T-p.R217Pfs*8-A-T-T).</p

The <i>PRRT2</i> mutations identified in patients with paroxysmal kinesigenic dyskinesia with infantile convulsions in this study.

<p>The <i>PRRT2</i> heterozygous mutations, (A) c.272delC (p.P91Qfs*24), (B) c.595G>T (p.E199X), (C) c.604_607delTCAC (p.S202Hfs*16), (D) c.649_650insC (p.R217Pfs*8), (E) c.649del (p.R217Efs*12), (F) c.718C>T (p.R240X), and (G) c.922C>G (p.R308C) are shown by sequencing both the mutant and normal strands of the TA-subcloned PCR fragments.</p