Epileptic networks are strongly connected with and without the effects of interictal discharges.

OBJECTIVE: Epilepsy is increasingly considered as the dysfunction of a pathologic neuronal network (epileptic network) rather than a single focal source. We aimed to assess the interactions between the regions that comprise the epileptic network and to investigate their dependence on the occurrence of interictal epileptiform discharges (IEDs). METHODS: We analyzed resting state simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) recordings in 10 patients with drug-resistant focal epilepsy with multifocal IED-related blood oxygen level-dependent (BOLD) responses and a maximum t-value in the IED field. We computed functional connectivity (FC) maps of the epileptic network using two types of seed: (1) a 10-mm diameter sphere centered in the global maximum of IED-related BOLD map, and (2) the independent component with highest correlation to the IED-related BOLD map, named epileptic component. For both approaches, we compared FC maps before and after regressing out the effect of IEDs in terms of maximum and mean t-values and percentage of map overlap. RESULTS: Maximum and mean FC maps t-values were significantly lower after regressing out IEDs at the group level (p < 0.01). Overlap extent was 85% ± 12% and 87% ± 12% when the seed was the 10-mm diameter sphere and the epileptic component, respectively. SIGNIFICANCE: Regions involved in a specific epileptic network show coherent BOLD fluctuations independent of scalp EEG IEDs. FC topography and strength is largely preserved by removing the IED effect. This could represent a signature of a sustained pathologic network with contribution from epileptic activity invisible to the scalp EEG.

Altered directed functional connectivity in temporal lobe epilepsy in the absence of interictal spikes: A high density EEG study.

OBJECTIVE: In patients with epilepsy, seizure relapse and behavioral impairments can be observed despite the absence of interictal epileptiform discharges (IEDs). Therefore, the characterization of pathologic networks when IEDs are not present could have an important clinical value. Using Granger-causal modeling, we investigated whether directed functional connectivity was altered in electroencephalography (EEG) epochs free of IED in left and right temporal lobe epilepsy (LTLE and RTLE) compared to healthy controls. METHODS: Twenty LTLE, 20 RTLE, and 20 healthy controls underwent a resting-state high-density EEG recording. Source activity was obtained for 82 regions of interest (ROIs) using an individual head model and a distributed linear inverse solution. Granger-causal modeling was applied to the source signals of all ROIs. The directed functional connectivity results were compared between groups and correlated with clinical parameters (duration of the disease, age of onset, age, and learning and mood impairments). RESULTS: We found that: (1) patients had significantly reduced connectivity from regions concordant with the default-mode network; (2) there was a different network pattern in patients versus controls: the strongest connections arose from the ipsilateral hippocampus in patients and from the posterior cingulate cortex in controls; (3) longer disease duration was associated with lower driving from contralateral and ipsilateral mediolimbic regions in RTLE; (4) aging was associated with a lower driving from regions in or close to the piriform cortex only in patients; and (5) outflow from the anterior cingulate cortex was lower in patients with learning deficits or depression compared to patients without impairments and to controls. SIGNIFICANCE: Resting-state network reorganization in the absence of IEDs strengthens the view of chronic and progressive network changes in TLE. These resting-state connectivity alterations could constitute an important biomarker of TLE, and hold promise for using EEG recordings without IEDs for diagnosis or prognosis of this disorder.

All-in-one interictal presurgical imaging in patients with epilepsy: single-session EEG/PET/(f)MRI.

PURPOSE: In patients with pharmacoresistant focal epilepsy, resection of the epileptic focus can lead to freedom from seizures or significant improvement in well-selected candidates. Localization of the epileptic focus with multimodal concordance is crucial for a good postoperative outcome. Beyond the detection of epileptogenic lesions on structural MRI and focal hypometabolism on FDG PET, EEG-based Electric Source Imaging (ESI) and simultaneous EEG and functional MRI (EEG-fMRI) are increasingly applied for mapping epileptic activity. We here report presurgical multimodal interictal imaging using a hybrid PET/MR scanner for single-session FDG PET, MRI, EEG-fMRI and ESI. METHODS: This quadrimodal imaging procedure was performed in a single session in 12 patients using a high-density (256 electrodes) MR-compatible EEG system and a hybrid PET/MR scanner. EEG was used to exclude subclinical seizures during uptake of the PET tracer, to compute ESI on interictal epileptiform discharges and to guide fMRI analysis for mapping haemodynamic changes correlated with interictal epileptiform activity. RESULTS: The whole multimodal recording was performed in less than 2 hours with good patient comfort and data quality. Clinically contributory examinations with at least two modalities were obtained in nine patients and with all modalities in five patients. CONCLUSION: This single-session quadrimodal imaging procedure provided reliable and contributory interictal clinical data. This procedure avoids multiple scanning sessions and is associated with less radiation exposure than PET-CT. Moreover, it guarantees the same medication level and medical condition for all modalities. The procedure improves workflow and could reduce the duration and cost of presurgical epilepsy evaluations.

Pulse artifact detection in simultaneous EEG-fMRI recording based on EEG map topography.

One of the major artifact corrupting electroencephalogram (EEG) acquired during functional magnetic resonance imaging (fMRI) is the pulse artifact (PA). It is mainly due to the motion of the head and attached electrodes and wires in the magnetic field occurring after each heartbeat. In this study we propose a novel method to improve PA detection by considering the strong gradient and inversed polarity between left and right EEG electrodes. We acquired high-density EEG-fMRI (256 electrodes) with simultaneous electrocardiogram (ECG) at 3 T. PA was estimated as the voltage difference between right and left signals from the electrodes showing the strongest artifact (facial and temporal). Peaks were detected on this estimated signal and compared to the peaks in the ECG recording. We analyzed data from eleven healthy subjects, two epileptic patients and four healthy subjects with an insulating layer between electrodes and scalp. The accuracy of the two methods was assessed with three criteria: (i) standard deviation, (ii) kurtosis and (iii) confinement into the physiological range of the inter-peak intervals. We also checked whether the new method has an influence on the identification of epileptic spikes. Results show that estimated PA improved artifact detection in 15/17 cases, when compared to the ECG method. Moreover, epileptic spike identification was not altered by the correction. The proposed method improves the detection of pulse-related artifacts, particularly crucial when the ECG is of poor quality or cannot be recorded. It will contribute to enhance the quality of the EEG increasing the reliability of EEG-informed fMRI analysis.

Specificity of Quantitative Functional Brain Mapping with Arterial Spin-Labeling for Preoperative Assessment.

BACKGROUND AND PURPOSE: Arterial spin-labeling is a noninvasive MR imaging technique allowing direct and quantitative measurement of brain perfusion. Arterial spin-labeling is well-established in clinics for investigating the overall cerebral perfusion, but it is still occasionally employed during tasks. The typical contrast for functional MR imaging is blood oxygen level-dependent (BOLD) imaging, whose specificity could be biased in neurologic patients due to altered neurovascular coupling. This work aimed to validate the use of functional ASL as a noninvasive tool for presurgical functional brain mapping. This is achieved by comparing the spatial accuracy of functional ASL with transcranial magnetic stimulation as the criterion standard. MATERIALS AND METHODS: Twenty-eight healthy participants executed a motor task and received a somatosensory stimulation, while BOLD imaging and arterial spin-labeling were acquired simultaneously. Transcranial magnetic stimulation was subsequently used to define hand somatotopy. RESULTS: Functional ASL was found more adjacent to transcranial magnetic stimulation than BOLD imaging, with a significant shift along the inferior-to-superior direction. With respect to BOLD imaging, functional ASL was localized significantly more laterally, anteriorly, and inferiorly during motor tasks and pneumatic stimulation. CONCLUSIONS: Our results confirm the specificity of functional ASL in targeting the regional neuronal excitability. Functional ASL could be considered as a valid supplementary technique to BOLD imaging for presurgical mapping when spatial accuracy is crucial for delineating eloquent cortex.

MP2RAGE and Susceptibility-Weighted Imaging in Lesional Epilepsy at 7T.

BACKGROUND AND PURPOSE: Surgery is the first choice therapeutic approach in case of drug-resistant epilepsy. Unfortunately, up to 43% of patients referred for presurgical assessment do not have a lesion detectable by routine 3T magnetic resonance imaging (MRI) (MRI-negative), although most of them likely have an underlying epileptogenic lesion. Thus, new MRI modalities with increased sensibility for epileptogenic lesions are required. This paper describes the magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE) and susceptibility-weighted imaging (SWI) findings at 7T in a series of patients with drug-resistant epilepsy of different etiologies. METHODS: Prospective pilot study of 7 patients with drug-resistant lesional epilepsy and absence of contraindications for MRI underwent a research 7T head-only scanner. Qualitative analysis of the high-resolution MP2RAGE and SWI sequences is given for each case. This study was approved by the local ethics committee. Written informed consent was obtained from each participant. RESULTS: This study shows that such sequences at ultra-high field are new and valuable approaches to unravel and characterize epileptogenic lesions. Particularly, MP2RAGE shows a better delineation of lesions due to high gray-white matter contrast and structural resolution, and SWI reveals new imaging signs related to improved magnitude and phase contrast imaging. CONCLUSION: MRI at ultra-high field is very promising for the detection of inconspicuous epileptogenic lesions and may facilitate epilepsy surgery of a great number of to-date MRI-negative patients.