Regional Connectivity Changes According to Seizure Outcome of Temporal Epilepsy Surgery: A Magnetoencephalography Study

For patients with medically intractable temporal lobe epilepsy (TLE), anterior temporal resection has been mostly frequent treatment. However, there is a substantial variability in success rate of the surgery. Studies examining 1-year outcomes of TLE showed seizure free rate is largely 60 – 80% [1,2]. Prediction of success after TLE surgery for each patient is often of a great issue and several studies addressed it. Clinical and neuroimaging factors predicting favorable outcome are focal findings of mesial temporal sclerosis seen either neuroimaging and pathologic finding, unilateral and less extensive hypometabolism on positron emission tomography (PET), neuropsychological findings suggestive of unilateral dysfunction ipsilateral to probable epileptogenic side, shorter duration, and absence of generalized tonic-clonic seizure history [3,4]. Unlike functional magnetic resonance imaging, electrophysiologic studies such as electroencephalography (EEG) and magnetoenecephalography(MEG)[1,4] techniques directly measure local field potential of electric brain activity [5].

signal distortion by skull and scalp [6]. On the other hand, MEG has a few advantages over EEG in mapping epileptogenic focus owing to higher spatial resolution and sensitivity to tangential dipole. Therefore, theoretically, epilepsy surgery based on MEG and has substantial benefits compared to EEG. Recent reports support this concept that regional spikes and their clusters evaluated by dipole localization based on MEG data is found to be highly accurate in localizing epileptic source and prediction of outcome [7,8]. Another method, phase synchronization which can be calculated by resting state dynamics based on correlation of pairs of brain signal of each area in whole brain is used to elucidate abnormal synchrony of epileptic brain [9]. Abnormal hypersynchrony of seizure generating areas and adjacent brain regions was found in intracranial EEG, and moreover, surgical removal of synchronized clusters was correlated with good seizure outcome [10].
Also, MEG recordings with TLE patients revealed altered functional network [11,12] and a few studies showed its feasibility for prediction of postsurgical outcome [13,14]. But to date, there has been few studies which demonstrates usefulness of longitudinal analysis of both pre-and post-operative MEG recording for predicting seizure outcome [13]. Our main aim was to find neurophysiologic biomarkers that can help predict seizure outcome after temporal lobectomy using data acquired in two phases. In this study we used a 152 channel MEG to investigate local dynamics, especially spectral power and synchronization characteristics using both pre-and immediate post-surgical MEG data.  (Table 1). We investigated duration of illness, total number of seizures, presence of GTCS, the state of antiepileptic drugs treatment until the surgery. The seizure outcome of those who were followed up for 2 years or more was assessed with presence of any seizures over 1 year at their last visit (Engel I and the others) Lachaux et al. [15]. According to the calculation method of PLV introduced in the above paper, this PLV has a value within the range of 0 to 1. This value indicated that the size of the connectivity between the 2 ROIs (Region of interest) is the closer to 1, means the higher the connectivity and a PLV close to 0 is the opposite.

Subjects
PLV map of each condition was thresholded by a value of 0.6. All of analyses described above were performed in brainstorm software.

Spectral Power Analysis
Although it did not reach statistical significance, a tendency (p = 0.056) for increase of delta frequency power after the surgery in ROI 6 of patients with persistent seizures compared to seizure-free patients was noted. Normalized spectral powers for delta frequency band on each ROIs of pre-and post-op conditions were demonstrated in (Figure 1). There was no significant difference in change of spectral powers in other frequency bands between the two groups.

Patient 2.
specific surgical pathology is not related with worse surgical outcome even though diffuse or no obvious abnormality is a risk factor for a seizure recurrence [18]. No focal pathologic diagnosis was made in one patient in each group, respectively. Considering that generally poorer prognosis is reported in patients with no histologic diagnosis or pathology other than classical hippocampal sclerosis, a careful caution is needed when interpreting our result on data with heterogenous pathology findings.
Although we did not observe difference of spectral power between the two groups that reach statistical significance, a tendency for decrease of delta power in areas (ROI 6) in seizurefree patients compared to ones with persistent seizures. A previous study on EEG free from visual abnormality showed difference of spectrum-based metrics between TLE and healthy subjects [19]. Because interictal lesional slowing is related with epileptic network in TLE patients [20], our data suggest that still remaining abnormal network is related with recurrence of seizures. A recently published paper presented comparable finding to ours, in which increase of MEG delta activity was noted in patients with unsuccessful epilepsy surgery [14]. Synaptic reorganization of both glutamatergic and GABAergic networks in epileptic brain region even following temporal lobe surgery might explain increase of connectivity in patients with seizure recurrence. The higher interregional correlation might reflect localized physiologic dysfunction even in the absence of spikes [1,21]. These findings are also shown in other neuroimaging studies [22,23].
Our study has few limitations. First, despite of heterogeneity in surgical pathology, clinical and demographic variables, we analyzed very limited number of subjects. Therefore, a lack of statistical power due to small number of patients is of a main issue. Second, it should be noted that cognitive function of the subjects was not included in our current study. Considering that the functional connectivity changes of epilepsy surgery are known to be related with functional reorganization of cognitive network, further studies including pre-and post-surgical cognitive function will be needed.
Third, we could not observe changes in very long term (up to 10 years) follow-up of temporal lobectomy, because seizure prognosis after temporal lobectomy is often variable [24]( Table 2).