SUMMARYPurpose: In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction. Methods: We selected electroencephalography-functional magnetic resonance imaging (EEG-fMRI) resting state data without EEG spikes from 16 patients with right and 7 patients with left MTLE. EEG-fMRI resting state data of 23 healthy subjects matched for age, sex, and manual preference were selected as controls. Four volumes of interest in the left and right amygdalae and hippocampi (LA, RA, LH, and RH) were manually segmented in the anatomic MRI of each subject. The averaged BOLD time course within each volume of interest was used to detect brain regions with BOLD signal correlated with it. Group differences between patients and controls were estimated.Key Findings: In patients with right MTLE, group difference functional connectivity maps (RMTLE ) controls) showed for RA and RH decreased connectivity with the brain areas of the default mode network (DMN), the ventromesial limbic prefrontal regions, and contralateral mesial temporal structures; and for LA and LH, decreased connectivity with DMN and contralateral hippocampus. Additional decreased connectivity was found between LA and pons and between LH and ventromesial limbic prefrontal structures. In patients with left MTLE, functional connectivity maps (LMTLE ) controls) showed for LA and LH decreased connectivity with DMN, contralateral hippocampus, and bilateral ventromesial limbic prefrontal regions; no change in connectivity was detected for RA; and for RH, there was decreased connectivity with DMN, bilateral ventromesial limbic prefrontal regions, and contralateral amygdala and hippocampus. Significance: In unilateral MTLE, amygdala and hippocampus on the affected and to a lesser extent on the healthy side are less connected, and are also less connected with the dopaminergic mesolimbic and the DMNs. Changes in functional connectivity between mesial temporal lobe structures and these structures may explain cognitive and psychiatric impairments often found in patients with MTLE.

SUMMARYPurpose: To assess the extent of brain involvement during focal epileptic activity, we studied patterns of cortical and subcortical metabolic changes coinciding with interictal epileptic discharges (IEDs) using group analysis of simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) scans in patients with focal epilepsy. Methods: We selected patients with temporal lobe epilepsy (TLE, n = 32), frontal lobe epilepsy (FLE, n = 14), and posterior quadrant epilepsy (PQE, n = 20) from our 3 Tesla EEG-fMRI database. We applied group analysis upon the blood oxygen-level dependent (BOLD) response associated with focal IEDs. Key Findings: Patients with TLE and FLE showed activations and deactivations, whereas in PQE only deactivations occurred. In TLE and FLE, the largest activation was in the mid-cingulate gyri bilaterally. In FLE, activations were also found in the ipsilateral frontal operculum, thalamus, and internal capsule, and in the contralateral cerebellum, whereas in TLE, we found additional activations in the ipsilateral mesial and neocortical temporal regions, insula, and cerebellar cortex. All three groups showed deactivations in default mode network regions, the most widespread being in the TLE group, and less in PQE and FLE. Significance: These results indicate that different epileptic syndromes result in unique and widespread networks related to focal IEDs. Default mode regions are deactivated in response to focal discharges in all three groups with syndrome specific pattern. We conclude that focal IEDs are associated with specific networks of widespread metabolic changes that may cause more substantial disturbance to brain function than might be appreciated from the focal nature of the scalp EEG discharges.

Objectives:To evaluate the clinical relevance of EEG/fMRI in patients with focal epilepsy, by assessing the information it adds to the scalp EEG in the definition of the epileptic focus. Methods:Forty-three patients with focal epilepsy were studied with EEG/fMRI using a 3-T scanner. Blood oxygen levelϪdependent (BOLD) signal changes related to interictal epileptic discharges (IEDs) were classified as concordant or not concordant with the scalp EEG spike field and as contributory if the BOLD signal provided additional information to the scalp EEG about the epileptic focus or not contributory if it did not. We considered patients having intracerebral EEG or a focal lesion on MRI as having independent validation.Results: Thirty-three patients had at least 3 IEDs during the EEG/fMRI acquisition (active EEG), and all had a BOLD response. In 29 of 33 (88%) patients, the BOLD response was concordant, and in 21 of 33 (64%) patients, the BOLD response was contributory. Fourteen patients had an independent validation: in 12 of these 14, the BOLD responses were validated and in 2 they were invalidated. Conclusions:A BOLD response was present in all patients with active EEG, and more specific localization of the epileptic focus was gained from EEG/fMRI in half of the patients who were scanned, when compared with scalp EEG alone. This study demonstrates that EEG/fMRI, in the context of a clinical practice, may contribute to the localization of the interictal epileptic generator in patients with focal epilepsy. Neurology ® 2012;78:1479-1487 GLOSSARY BOLD ϭ blood oxygen levelϪdependent; EPI ϭ echoplanar imaging; FCD ϭ focal cortical dysplasia; IED ϭ interictal epileptic discharge; MTS ϭ mesial temporal lobe sclerosis; SEEG ϭ stereo-EEG; TE ϭ echo time; TR ϭ repetition time.Recording fMRI and EEG simultaneously is a noninvasive method detecting cerebral hemodynamic changes related to interictal epileptic discharges (IEDs) on scalp EEG. Several studies demonstrated the ability of EEG/fMRI to characterize various forms of focal and generalized epilepsy.1,2 In patients with focal epilepsy, especially those who are pharmacoresistant and surgical candidates, the significant clinical question is how the blood oxygenation levelϪde-pendent (BOLD) changes related to IEDs can contribute to localize the epileptic focus. The BOLD signal usually increases in regions generating focal IEDs, 3 but often in the context of more widespread, or even distant, responses.4 Simultaneous intracranial EEG/fMRI recordings 5 have shown IED-related BOLD changes in the immediate vicinity of the intracranial EEG focus, confirming spatial concordance between neuronal and BOLD changes. Distant BOLD changes related to specific IED patterns were also observed. EEG/fMRI may help in the evaluation of patients who are candidates for surgery 6 and, in patients with nonlesional frontal lobe epilepsy, EEG/fMRI contributed to localize foci subsequently confirmed by other imaging modalities or pathology.7 Finally, in a postsurgical population, it was shown that...