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.

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 functional connectivity of the intrahemispheric cortico-cortical network of idiopathic generalized epilepsy.

AIMS: Intrahemispheric, cortico-cortical EEG functional connectivity (fC) was investigated in untreated patients with idiopathic generalized epilepsy (IGE) in this explorative study. PATIENTS AND METHODS: Group comparison was carried out between 19, drug-naive IGE patients and 19, matched healthy persons. 90×2s of 19 channels waking, interictal background EEG signal (without epileptiform potentials) were processed to the LORETA (low resolution electromagnetic tomography) software to compute current source density for 2394 voxels representing parcels of the cerebral cortex for 25 very narrow bands of 1Hz bandwidth (VNBs) from 1 to 25Hz. EEG fC was investigated among the already localized sources. Pearson correlation coefficients (R) were computed among the 33 regions of interest (ROI) within the left and within the right hemisphere, separately. Group differences were computed by means of t-statistics. Corrected p<0.05 differences were accepted as statistically significant. MAIN RESULTS: (1) The anatomical patterns of the fC differences showed great frequency-dependency. (2) Hemispheric asymmetry was prominent within most VNBs. (3) Decreased fC in the IGE group was found across all VNBs in the 1-6Hz frequency range as compared to mixed patterns comprising both increased and decreased fC at >6Hz frequencies. (4) In the 5-25Hz range, decreased fC dominated in the anterior, increased fC in the posterior parts of the cortex. (5) The results delineated an anterior and a posterior network. DISCUSSION: (1) Decreased fC in the 1-6Hz band might indicate some relationship to yet hidden structure network abnormalities. (2) The anatomical patterns of fC indicate frequency-dependent, pathological coupling and decoupling processes in the interictal state. (3) The two networks might help to understand seizure liability and seizure precipitation in IGE. SIGNIFICANCE: This is the first study to explore EEG fC in the interictal condition of IGE patients. The importance of EEG frequencies in evaluating fC in IGE was demonstrated and starting points for further research were given.

Theta EEG source localization using LORETA in partial epilepsy patients with and without medication.

OBJECTIVE: To investigate and localize the sources of spontaneous, scalp-recorded theta activity in patients with partial epilepsy (PE). METHODS: Nine patients with beginning, untreated PE (Group 1), 31 patients with already treated PE (Group 2), and 14 healthy persons were investigated by means of spectral analysis and LORETA, low resolution electromagnetic tomography (1 Hz very narrow band analysis, age-adjusted, Z-scored values). The frequency of main interest was 4-8 Hz. RESULTS: Group analysis: Group 1 displayed bilateral theta maxima in the temporal theta area (TTA), parietal theta area (PTA), and frontal theta area (FTA). In Group 2, theta activity increased all over the scalp as compared to the normative mean (Z=0) and also to Group 1. Maximum activity was found in the TTA, PTA, and FTA. However, in the PTA and FTA the centers of the abnormality shifted towards the medial cortex. Individual analysis: all the patients showed preferential activation (maximum Z-values) within one of the three theta areas. CONCLUSIONS: EEG activity in the theta band is increased in anatomically meaningful patterns in PE patients, which differs from the anatomical distribution of theta in healthy persons. SIGNIFICANCE: The findings contribute to our understanding of the sources of theta rhythms and the pathophysiology of PE.

Single-dose piracetam effects on global complexity measures of human spontaneous multichannel EEG.

Global complexity of 47-channel resting electroencephalogram (EEG) of healthy young volunteers was studied after intake of a single dose of a nootropic drug (piracetam, Nootropil UCB Pharma) in 12 healthy volunteers. Four treatment levels were used: 2.4, 4.8, 9.6 g piracetam and placebo. Brain electric activity was assessed through Global Dimensional Complexity and Global Omega-Complexity as quantitative measures of the complexity of the trajectory of multichannel EEG in state space. After oral ingestion (1-1.5 h), both measures showed significant decreases from placebo to 2.4 g piracetam. In addition, Global Dimensional Complexity showed a significant return to placebo values at 9.6 g piracetam. The results indicate that a single dose of piracetam dose-dependently affects the spontaneous EEG in normal volunteers, showing effects at the lowest treatment level. The decreased EEG complexity is interpreted as increased cooperativity of brain functional processes.

Smell and taste of chewing gum affect frequency domain EEG source localizations.

We investigated brain electric field signatures of subjective feelings after chewing regular gum or gum base without flavor. 19-channel eyes-closed EEG from 20 healthy males before and after 5 minutes of chewing the two gum types in random sequence was source modeled in the frequency domain using the FFT-Dipole-Approximation. 3-dimensional brain locations and strengths (Global Field Power, GFP) of the equivalent sources of five frequency bands were computed as changes from pre-chewing baseline. Gum types differed (ANOVA) in pre-post changes of source locations for the alpha-2 band (to anterior and right after regular gum, opposite after gum base) and beta-2 band (to anterior and inferior after regular gum, opposite after gum base), and of GFP for delta-theta, alpha-2 and beta-1 (regular gum: increase. gum base: decrease). Subjective feeling changed to more positive values after regular gum than gum base (ANOVA).--Thus, chewing gum with and without taste-smell activates different brain neuronal populations.

Global dimensional complexity of multichannel EEG in mild Alzheimer's disease and age-matched cohorts.

Multichannel EEG as sequence of momentary brain field maps constitutes a trajectory through K-dimensional state space (K = number of channels); the complexity of this trajectory is assessed by the nonlinear measure of global correlation dimension (Global Dimensional Complexity, GDC) with the number of electrodes as embedding dimension. We analyzed eyes-closed EEG of three age-matched subject groups: mild Alzheimer's disease (AD; n = 21), mild cognitive impairment (29) and subjective memory complaint (29). Kruskal-Wallis statistics showed an overall effect between groups. AD patients differed significantly (GDC = 4.56) from mild cognitive impairments (GDC = 4.98) and from subjective memory complaints (GDC = 4.93). GDC also had significant positive correlations with mental condition and performance (MMSE and WAIS-R scores). Thus, the dynamics of brain state development over time in mild AD differs from that in mild cognitive impairment and in subjective memory complaint cases.

Multichannel EEG fields during and without visual input: frequency domain model source locations and dimensional complexities.

27-Channel EEG potential map series were recorded from 12 normals with closed and open eyes. Intracerebral dipole model source locations in the frequency domain were computed. Eye opening (visual input) caused centralization (convergence and elevation) of the source locations of the seven frequency bands, indicative of generalized activity; especially, there was clear anteriorization of alpha-2 (10.5-12 Hz) and beta-2 (18.5-21 Hz) sources (alpha-2 also to the left). Complexity of the map series' trajectories in state space (assessed by Global Dimensional Complexity and Global OMEGA Complexity) increased significantly with eye opening, indicative of more independent, parallel, active processes. Contrary to PET and fMRI, these results suggest that brain activity is more distributed and independent during visual input than after eye closing (when it is more localized and more posterior).

Prestimulus EEG microstates influence visual event-related potential microstates in field maps with 47 channels.

The influence of the immediate prestimulus EEG microstate (sub-second epoch of stable topography/map landscape) on the map landscape of visually evoked 47-channel event-related potential (ERP) microstates was examined using the frequent, non-target stimuli of a cognitive paradigm (12 volunteers). For the two frequent prestimulus microstate classes (oriented left anterior-right posterior and right anterior-left posterior), ERP map series were selectively averaged. The post-stimulus ERP grand average map series was segmented into microstates; 10 were found. The centroid locations of positive and negative map areas extracted as landscape descriptors. Significant differences (MANOVAs and t-tests) between the two prestimulus classes were found in four of the ten ERP microstates. The relative orientation of the two ERP microstate classes was the same as prestimulus in some ERP microstates, but reversed in others. Thus, brain electric microstates at stimulus arrival influence the landscapes of the post-stimulus ERP maps and therefore, information processing; prestimulus microstate effects differed for different post-stimulus ERP microstates.

Chewing-gum flavor affects measures of global complexity of multichannel EEG.

Global complexity of spontaneous brain electric activity was studied before and after chewing gum without flavor and with 2 different flavors. One-minute, 19-channel, eyes-closed electroencephalograms (EEG) were recorded from 20 healthy males before and after using 3 types of chewing gum: regular gum containing sugar and aromatic additives, gum containing 200 mg theanine (a constituent of Japanese green tea), and gum base (no sugar, no aromatic additives); each was chewed for 5 min in randomized sequence. Brain electric activity was assessed through Global Omega (Omega)-Complexity and Global Dimensional Complexity (GDC), quantitative measures of complexity of the trajectory of EEG map series in state space; their differences from pre-chewing data were compared across gum-chewing conditions. Friedman Anova (p < 0.043) showed that effects on Omega-Complexity differed significantly between conditions and differences were maximal between gum base and theanine gum. No differences were found using GDC. Global Omega-Complexity appears to be a sensitive measure for subtle, central effects of chewing gum with and without flavor.

Event-related potential map differences depend on the prestimulus microstates.

The dependency of the landscapes of visually evoked, 47-channel, event-related potential (ERPs) on the functional microstates (momentary map landscape) just before stimulus arrival was investigated, in 12 volunteers. The prestimulus microstates were determined using the map at the last peak of Global Field Power before the stimulus. The landscapes of these maps were described by the electrode locations of the positive and negative extreme potentials, and assigned to basic classes. The two most frequently occurring map-classes were used (left anterior-right posterior, and right anterior-left posterior). ERP map series were averaged for each subject and each prestimulus microstate class. The Randomization-Monte Carlo MANOVA test was used to test the significance of the difference between the ERP map landscapes at each sample point (n = 128, 500 ms) associated with the two prestimulus microstates. At 16 samples the difference was significant at p < 0.05. The longest uninterrupted sequence (n = 9) of significant differences occurred between 164 and 195 ms, i.e. during the conventional component P200. The results demonstrate that the brain electric microstate at stimulus arrival crucially influences the active neuronal populations that contribute to the ERP. This suggests that the processing of information will differ as a function of the momentary brain microstate at information arrival.

Cellular activity of intracerebrally transplanted fetal hippocampus during behavior.

Hippocampal tissue derived from 12-, 20-, 25- and 34-mm rat fetuses was placed in a cavity formed by unilateral aspiration of the fimbria-fornix and the overlying neocortical tissue in adult rats. From 4 to 6 months after transplantation the rats were equipped with chronic recording and stimulating electrodes. Single cell activity of the transplant was monitored during running in a wheel, drinking, and sleeping. Both complex-spike cells (n = 151) and single-spike cells (n = 80) were recorded from the graft. A portion of the neurons changed their firing rates and discharge patterns as a function of ongoing behavior. About half of the single-spike cells increased their firing frequency during running. Fifteen per cent of the single-spike cells fired rhythmically at about 8 Hz during running, and the paradoxical phase of sleep and the discharge pattern correlated with rhythmic slow activity (theta) recorded concurrently from the contralateral (intact) hippocampus. These patterns were most frequently obtained from grafts of 20- and 25-mm (16 to 18 embryonic days) fetuses. Graft neurons could be activated by stimulating the ipsilateral hippocampus or the ipsilateral perforant path, with latencies of 8-30 ms. The most common electrical pattern in grafts of all groups was the synchronous bursts of several neighboring cells and concurrent electroencephalogram sharp-waves. Sharp-waves occurred during all behaviors. Large amplitude, high-frequency electroencephalogram spindles (14-18 Hz and 30-50 Hz) and associated neuronal bursts were recorded in grafts of 12-, 20-, and 25-mm fetuses. Based on these findings we suggest that both subcortical afferents and host hippocampal afferents send axons to hippocampal grafts and form viable synaptic connections with a portion of the neurons in the graft. The frequently encountered population bursts are explained by assuming that excitatory collaterals in the graft are more potent in the graft than in the normal hippocampus, and/or GABAergic inhibition is less efficient in the graft.

Laminar distribution of hippocampal rhythmic slow activity (RSA) in the behaving rat: current-source density analysis, effects of urethane and atropine.

This study investigated the laminar distribution of rhythmic slow wave activity (RSA) in the dorsal hippocampus of the rat during running. Depth analyses of field EEG were performed by stepping the recording electrode in 82.5 micron increments and sampling RSA at each depth. One-dimensional current-source density (CSD) was calculated from the RSA profiles to enhance spatial resolution of current sources and sinks. Laminar analysis of power, coherence, and phase of RSA with respect to a stationary electrode in the stratum oriens of CA1 was performed with spectral methods. RSA waves in the CA1-dentate axis had power maxima at about the hippocampal fissures, hilus, outer molecular layer of the endal leaf of dentate gyrus and stratum oriens of CA1, in that order. A gradual shift of phase occurred in stratum radiatum of CA1. Large phase-shifts were found in both the endal and ectal leaves of the fascia dentata. A null zone and associated sudden phase-reversal of RSA were observed in stratum lucidum of CA3. Multiunit activity showed phase-locked modulation with RSA in the granule cell layer of the dentate gyrus and pyramidal cell layer of CA1, CA3, and subiculum. CSD analysis in the CA1-dentate axis revealed multiple source-sink pairs. The sinks and sources showed cyclic changes with RSA, and were attributed to the rhythmic, but time-shifted, activity of hippocampal afferents from the septum and entorhinal cortex. The gradual phase-shift in CA1, and the configurational changes of RSA waves with depth, are explained by the summation of extracellular currents produced by time-delayed sink-source pairs (RSA dipoles). When the cholinergic septohippocampal path was blocked by atropine a null zone in the middle of stratum radiatum of CA1 occurred and the phase-shift of RSA became steeper. Under urethane anesthesia a null zone was present in the inner stratum radiatum associated with a sudden phase-reversal of RSA. Urethane reduced the power of RSA in the hilus and decreased the firing rate of the granule cells. It is suggested that field RSA is produced by several rhythmical dipoles along the somadendritic surface of pyramidal cells and granule cells and the spatiotemporal relations of the individual dipoles determine the actually observed extracellular RSA.