Valproate treatment normalizes EEG functional connectivity in successfully treated idiopathic generalized epilepsy patients.

AIM: To investigate the effect of chronic VPA treatment of EEG functional connectivity in successfully treated idiopathic generalized epilepsy (IGE) patients. PATIENTS AND METHODS: 19-channel waking, resting-state EEG records of 26 IGE patients were analyzed before treatment (IGE) and after the 90th day of treatment (VPA), in seizure-free condition. Three minutes of artifact-free EEG background activity (without epileptiform potentials) was analyzed for each patient in both conditions. A group of 26 age-matched healthy normative control persons (NC) was analyzed in the same way. All the EEG samples were processed to LORETA (Low Resolution Electromagnetic Tomography) to localize multiple distributed sources of EEG activity. Current source density time series were generated for 33 regions of interest (ROI) in each hemisphere for four frequency bands. Pearson correlation coefficients (R) were computed between all ROIs in each hemisphere, for four bands across the investigated samples. R values corresponded to intrahemispheric, cortico-cortical functional EEG connectivity (EEGfC). Group and condition differences were analyzed by statistical parametric network method. MAIN RESULTS: p<0.05, corrected for multiple comparisons: (1) The untreated IGE group showed increased EEGfC in the delta and theta bands, and decreased EEGfC in the alpha band (as compared to the NC group); (2) VPA treatment normalized EEGfC in the delta, theta and alpha bands; and (3) degree of normalization depended on frequency band and cortical region. CONCLUSIONS: VPA treatment normalizes EEGfC in IGE patients.

Neurophysiology of juvenile myoclonic epilepsy: EEG-based network and graph analysis of the interictal and immediate preictal states.

INTRODUCTION: The neuronal mechanisms of enduring seizure propensity and seizure precipitation in juvenile myoclonic epilepsy (JME) are not known. We investigated these issues, within the framework of the "network concept" of epilepsy. METHODS: Design1: 19, unmedicated JME patients were compared with nineteen, age-, and sex-matched normal control persons (NC). A total of 120s, artifact-free, paroxysm-free, eyes-closed, resting state EEG background activity was analyzed for each person. Design2: interictal and immediate preictal periods of the JME patients were compared in order to explore interictal-preictal network differences. For both comparison designs, statistically significant differences of EEG functional connectivity (EEGfC), nodal and global graph parameters were evaluated. MAIN RESULTS: Design1: maximum abnormalities were: increased delta, theta, alpha1 EEGfC and decreased alpha2 and beta EEGfC in the JME group as compared to the NC group, mainly among cortical areas that are involved in sensory-motor integration. Nodal degree and efficiency of three, medial, basal frontal nodes were greater in JME than in NC, in the alpha1 band. Design2: preictal delta EEGfC showed further increase in the above-mentioned areas, as compared to the interictal state. DISCUSSION: Increased EEGfC indicates a hypercoupled state among the specified cortical areas. This interictal abnormality further increases in the preictal state. Nodal graph statistics indicates abnormal neuronal dynamics in the cortical area that is the ictal onset zone in JME. SIGNIFICANCE: Interictal and preictal neuronal dysfunction has been described in terms of network dynamics and topography in JME patients. Forthcoming investigations of seizure precipitation and therapeutic drug effects are encouraged on this basis.

Remission of benign epilepsy with rolandic spikes: an EEG-based connectivity study at the onset of the disease and at remission.

PURPOSE: The neuronal mechanisms of remission of epilepsy are not known. Based on the principles of the "network theory of epilepsy" we postulated the existence of abnormal cortico-cortical interactions at the onset of epilepsy (Hypothesis-1), and postulated that remission is associated with the decrease or disappearance of the abnormal quantitative EEG findings (Hypothesis-2). METHODS: Four children with benign epilepsy with rolandic sharp waves (BERS) were investigated. 21-channel EEG was recorded at the onset of the disease (Setting No. 1) and in remission (Setting No. 2). Local EEG synchronization was estimated by LORETA (low resolution electromagnetic tomography). Remote EEG synchronization (intra-hemispheric, cortico-cortical EEG functional connectivity, EEGfC) was computed by the LSC (LORETA Source Correlation) method, among 23 regions of interest (ROI) in both hemispheres. Both local and remote EEG synchronization were evaluated in very narrow frequency bands of 1Hz bandwidth (VNB), from 1 to 25Hz. RESULTS: Individual results were presented. Abnormal but topographically very dissimilar LORETA and LSC findings were found at the onset of the disease. The disappearance of the initial abnormalities was found in Setting No. 2. An unforeseen finding was the presence of abnormal EEGfC results in Setting No. 2. DISCUSSION: The authors confirmed both hypotheses. The dissimilarity of the initial abnormalities is in accord with the network concept of epilepsy and the etiology of BERS. The disappearance of the initial abnormalities reflects "normalization" of network dynamics while the emergence of new EEGfC abnormalities is interpreted as "compensation". CONCLUSION: EEG-based local and remote connectivity (EEGfC) are appropriate tools to describe network dynamics in the active state of BERS and in remission.

EEG-LORETA endophenotypes of the common idiopathic generalized epilepsy syndromes.

OBJECTIVE: We tested the hypothesis that the cortical areas with abnormal local EEG synchronization are dissimilar in the three common idiopathic generalized epilepsy (IGE) phenotypes: IGE patients with absence seizures (ABS), juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures exclusively (EGTCS). PATIENTS AND METHODS: Groups of unmedicated ABS, JME and EGTCS patients were investigated. Waking EEG background activity (without any epileptiform potentials) was analyzed by a source localization method, LORETA (Low Resolution Electromagnetic Tomography). Each patient group was compared to a separate, age-matched group of healthy control persons. Voxel-based, normalized broad-band (delta, theta, alpha, and beta) and very narrow band (VNB, 1Hz bandwidth, from 1 to 25Hz) LORETA activity (=current source density, A/m(2)) were computed for each person. Group comparison included subtraction (average patient data minus average control data) and group statistics (multiple t-tests, where Bonferroni-corrected p<0.05 values were accepted as statistically significant). RESULTS: Statistically not significant main findings were: overall increased delta and theta broad band activity in the ABS and JME groups; decrease of alpha and beta activity in the EGTCS group. Statistically significant main findings were as follows. JME group: bilaterally increased theta activity in posterior (temporal, parietal, and occipital) cortical areas; bilaterally increased activity in the medial and basal prefrontal area in the 8Hz VNB; bilaterally decreased activity in the precuneus, posterior cingulate and superior parietal lobule in the 11Hz and 21-22Hz VNBs. ABS group: bilaterally increased theta activity emerged in the basal prefrontal and medial temporal limbic areas. Decreased activity was found at 19-21Hz in the right postcentral gyrus and parts of the right superior and medial temporal gyri. EGTCS group: decreased activity was found in the frontal cortex and the postcentral gyrus at 10-11Hz, increased activity in the right parahippocampal gyrus at 16-18Hz. DISCUSSION: Increased theta activity in the posterior parts of the cortex is the endophenotype for JME. Increased theta activity in the fronto-temporal limbic areas is the endophenotype for ABS. Statistically not significant findings might indicate diffuse biochemical abnormality of the cortex in JME and ABS. SIGNIFICANCE: EEG-LORETA endophenotypes may correspond to the selective propensity to generate absence and myoclonic seizures in the ABS and JME syndromes.

EEG background activity is abnormal in the temporal and inferior parietal cortex in benign rolandic epilepsy of childhood: a LORETA study.

INTRODUCTION: Benign rolandic epilepsy of childhood (BERS) is an epilepsy syndrome with presumably genetic-developmental etiology. The pathological basis of this syndrome is completely unknown. We postulated that a developmental abnormality presumably results in abnormal EEG background activity findings. PATIENTS AND METHODS: 20 children with typical BERS and an age- and sex-matched group of healthy control children underwent EEG recording and analysis. 60×2 s epochs of waking EEG background activity (without epileptiform potentials and artifacts) were analyzed in the 1-25 Hz frequency range, in very narrow bands (VNB, 1 Hz bandwidth). LORETA (Low Resolution Electromagnetic Tomography) localized multiple distributed sources of EEG background activity in the Talairach space. LORETA activity (current source density) was computed for 2394 voxels and 25 VNBs. Normalized LORETA data were processed to voxel-wise comparison between the BERS and control groups. Bonferroni-corrected p<0.05 Student's t-values were accepted as statistically significant. RESULTS: Increased LORETA activity was found in the BERS group (as compared to the controls) in the left and right temporal lobes (fusiform gyri, posterior parts of the superior, middle and inferior temporal gyri) and in the angular gyri in the parietal lobes, in the 4-6 Hz VNBs, mainly at 5 Hz. DISCUSSION: (1) Areas of abnormal LORETA activity exactly correspond to the temporal and parietal cortical areas that are major components of the Mirsky attention model and also the perisylvian speech network. Thus the LORETA findings may correspond to impaired attention and speech in BERS patients. (2) The LORETA findings may contribute to delineating the epileptic network in BERS. SIGNIFICANCE: The novel findings may contribute to investigating neuropsychological disturbances and organization of the epileptic network in BERS.