Reevaluating the mechanisms of focal ictogenesis: The role of low-voltage fast activity.

The mechanisms that control the transition into a focal seizure are still uncertain. The introduction of presurgical intracranial recordings to localize the epileptogenic zone in patients with drug-resistant focal epilepsies opened a new window to the interpretation of seizure generation (ictogenesis). One of the most frequent focal patterns observed with intracranial electrodes at seizure onset is characterized by low-voltage fast activity in the beta-gamma range that may or may not be preceded by changes of ongoing interictal activities. In the present commentary, the mechanisms of generation of focal seizures are reconsidered, focusing on low-voltage fast activity patterns. Experimental findings on models of temporal lobe seizures support the view that the low-voltage fast activity observed at seizure onset is associated with reinforcement and synchronization of inhibitory networks. A minor role for the initiation of the ictal pattern is played by principal neurons that are progressively recruited with a delay, when inhibition declines and synchronous high-voltage discharges ensue. The transition from inhibition into excitatory recruitment is probably mediated by local increase in potassium concentration associated with synchronized interneuronal firing. These findings challenge the classical theory that proposes an increment of excitation and/or a reduction of inhibition as a cause for the transition to seizure in focal epilepsies. A new definition of ictogenesis mechanisms, as herewith hypothesized, might possibly help to develop new therapeutic strategies for focal epilepsies.

Brain electrical source differences between depressed subjects and healthy controls.

Many brain regions show metabolic and perfusion abnormalities in major depressive disorder (MDD), including anterior cingulate and prefrontal cortices. Some of these same areas also show abnormal function with low resolution electromagnetic tomography (LORETA). However, LORETA results are not always consistent across studies, nor with findings from other imaging modalities. These discrepancies may be due, among other factors, to the sensitivity of EEG source localization to different electrode montages. Thirty-six channel EEG was collected from healthy controls and age- and gender-matched unmedicated subjects with MDD (n = 74). EEGs were analyzed with LORETA to assess resting state current density at each of 2,394 cortical voxels. For comparison to previous studies, LORETA was performed using all electrodes or with specific prefrontal electrodes removed. Voxel-by-voxel differences between the depressed and healthy groups were calculated using non-parametric statistics. MDD subjects showed significantly elevated current density in delta, theta, alpha, beta1, and beta2 frequency bands relative to controls in anterior cingulate and prefrontal cortices. Removal of certain prefrontal electrodes from input to LORETA decreased or eliminated significant differences between groups. LORETA detects differences in brain activity between MDD subjects and healthy controls that are consistent with previous findings using other imaging modalities. Inconsistent findings among LORETA studies, and between LORETA studies and those using other functional imaging techniques, may result from differences in electrode montages.

Blinded, multi-center validation of EEG and rating scales in identifying ADHD within a clinical sample.

Previous validation studies of attention deficit/hyperactivity disorder (ADHD) assessment by rating scales or EEG have provided Class-IV evidence per standards of the American Academy of Neurology. To investigate clinical applications, we collected Class-I evidence, namely from a blinded, prospective, multi-center study of a representative clinical sample categorized with a clinical standard. Participating males (101) and females (58) aged 6 to 18 had presented to one of four psychiatric and pediatric clinics because of the suspected presence of attention and behavior problems. DSM-IV diagnosis was performed by clinicians assisted with a semi-structured clinical interview. EEG (theta/beta ratio) and ratings scales (Conners Rating Scales-Revised and ADHD Rating Scales-IV) were collected separately in a blinded protocol. ADHD prevalence in the clinical sample was 61%, whereas the remainder had other childhood/adolescent disorders or no diagnosis. Comorbidities were observed in 66% of ADHD patients and included mood, anxiety, disruptive, and learning disorders at rates similar to previous findings. EEG identified ADHD with 87% sensitivity and 94% specificity. Rating scales provided sensitivity of 38-79% and specificity of 13-61%. While parent or teacher identification of ADHD by rating scales was reduced in accuracy when applied to a diverse clinical sample, theta/beta ratio changes remained consistent with the clinician's ADHD diagnosis. Because theta/beta ratio changes do not identify comorbidities or alternative diagnoses, the results do not support the use of EEG as a stand-alone diagnostic and should be limited to the interpretation that EEG may complement a clinical evaluation for ADHD.

Multifractal analysis as an aid in the diagnostics of mental disorders.

The digitalization of EEGs (electroencephalogram) has showed new possibilities for analyzing electrical activity of brain. This has offered new methods, e.g. multifractal analysis of 1/f(beta) EEG rhythms fluctuations. It is one of highly mathematical methods feasible in routine practice now that modern personal computers (PCs) have reached sufficient computing power. In this study, we applied the multifractal analysis of 1/f(beta) EEG rhythms fluctuations in 33 patients suffering from schizophrenia and schizophrenia-like syndromes, and we had 23 healthy controls. Our results indicated that the patients suffering from schizophrenia have statistically different values compared with the controls. This method is rather easy and quick to perform when using a standard PC. It may have the potential to become an important tool in the diagnostics and analysis of the patients with schizophrenia and schizophreniformic psychoses. It can help to understand the quasi-chaotic processes in neural processing and narrow the gap between the phenomenological psychiatry and bio-psychiatry.

ICTAL EEG fast activity in West syndrome: from onset to outcome.

PURPOSE: To characterize the fast EEG activities associated with infantile spasms in West syndrome, and their value in predicting the recurrence and localization of late seizures. METHODS: We selected 23 infants who were followed for at least 2 years. Selected EEG recordings underwent autospectra, coherence, and phase analyses in order to assess the changes during follow-up. RESULTS: Short discharges of fast-rhythms (331 +/- 190 ms) with a lateralized onset were detected in 18 of the 23 infants (78.3%). There were no significant differences in the parameters characterizing ICTAL beta-activity (frequency, duration, inter-hemispheric coherence, or transfer time) between the infants with or without seizure recurrence. However, beta-discharges with a consistent location formed part of the ICTAL EEG in all 10 infants with seizure recurrence, but only in eight (61.5%) of those who remained seizure-free (SF) (p < 0.05). In all but one of the infants experiencing seizure recurrence, the ICTAL discharges associated with the late seizures apparently originated from the same hemisphere as that involved at the beginning of the spasm-associated beta-activity, although the precise location varied. CONCLUSIONS: Spectral, coherence and phase analyses detected spasm-associated runs of lateralized beta-rhythms in many of our infants with West syndrome. This ICTAL pattern significantly correlated with seizure recurrence. The consistent lateralization of the ICTAL EEG events associated with both the early spasms and late seizures suggests that EEG beta-activities should be considered as indicating local cortical dysfunction in infants who fail to respond to early treatment and often progress toward severe epilepsy.

Coherence in children with Attention-Deficit/Hyperactivity Disorder and excess beta activity in their EEG.

OBJECTIVE: This study investigated differences in coherence measures between two groups of children with Attention-Deficit/Hyperactivity Disorder (ADHD) - with the typical EEG profile (increased theta and decreased beta activity), and with excess beta activity - and a normal control group. METHODS: Thirty-four children with ADHD were included in each of the typical and excess beta groups, and were age and sex matched with 34 control subjects. EEG was recorded from 21 sites during an eyes-closed resting condition. Wave-shape coherence was calculated for eight intrahemispheric and eight interhemispheric electrode pairs, for the delta, theta, alpha and beta bands. RESULTS: In comparison to the controls, the typical ADHD group primarily had increased intrahemispheric theta and beta coherence at short-medium inter-electrode distances, and increased interhemispheric coherence for theta in the frontal and central/parietal/occipital regions. Their laterality effect for interhemispheric short-medium inter-electrode distances was reduced in the theta band. Differences between the excess beta group and the control group were primarily found in laterality of the intrahemispheric theta coherence at short-medium electrode distances, and increased interhemispheric theta coherence in the frontal regions. Reduced delta coherence in the temporal regions was also found. CONCLUSIONS: These results suggest that ADHD children with excess beta power have an underlying brain dysfunction in the frontal lobes which is found in common with children with the typical EEG profile. However a number of qualitative differences exist which could be associated with other aspects of the ADHD diagnosis or another comorbid condition. SIGNIFICANCE: This is the first study to investigate EEG coherence in ADHD children who have increased beta power.

Decreased Efficacy of GABAA-receptor modulation by midazolam in the kainate model of temporal lobe epilepsy.

PURPOSE: The objective of this investigation was to characterize quantitatively the time-dependent changes in midazolam (MDL) efficacy in the silent period after induction of status epilepticus (SE) in rats. The changes in MDL efficacy were correlated to changes in ex vivo GABA(A)-receptor expression. METHODS: MDL efficacy was quantified by pharmacokinetic-pharmacodynamic (PK-PD) modeling by using the beta-frequency of the EEG as PD end point. Two PK-PD experiments were performed in each animal: the first experiment before and the second experiment at either day 4 or day 14 after SE. SE was induced by repetitive intraperitoneal injections with kainate. GABA(A)-receptor expression was determined by ex vivo autoradiography with [(3)H]flumazenil. RESULTS: The concentration versus EEG effect relation of midazolam was successfully described by the sigmoidal E(max) model. The maximal effect on the beta-frequency of the EEG (E(max)) was reduced to 51.6 +/- 35.6% and 25.8 +/- 33.7% of the original value at 4 and 14 days after induction of SE. The ex vivo study with [(3)H]flumazenil showed that the observed reductions in E(max) were paralleled by a reduction in GABA(A)-receptor density. CONCLUSIONS: The efficacy of MDL is decreased in the silent period after SE, which can be partly accounted for by a reduction in GABA(A)-receptor density.

Characteristic distribution of interictal brain electrical activity in idiopathic generalized epilepsy.

PURPOSE: To demonstrate the anatomic localization of the cortical sources of the interictal EEG activity in human idiopathic generalized epilepsy (IGE). METHODS: Multiple cortical and hippocampal sources of the interictal spontaneous EEG activity were investigated by low-resolution electromagnetic tomography in 15 untreated IGE patients and in 15 healthy controls. EEG activity (current density) in four frequency bands (delta: 1.5-3.5 Hz, theta: 3.5-7.5 Hz, alpha: 7.5-12.5 Hz, beta: 12.5-25.0 Hz) was computed for 2,397 voxels. Voxel-by-voxel group comparison was done between the patient and the control group. Voxels with p < 0.01 differences (between the two groups) were correlated with cortical anatomy. RESULTS: Areas of significantly increased or decreased activity were characterized by their anatomical extension and the frequency bands involved. Five areas of bilaterally increased activity were found: rostral part of the prefrontal cortex (delta, theta); posterior part of the insula (delta); hippocampus and mediobasal temporal cortex (all frequency bands); medial parietooccipital cortex (theta, alpha, beta); dorsal and polar parts of the occipital cortex (alpha). Bilaterally decreased delta, theta, alpha activity was found in the majority of the frontal and anterior parietal cortex on the lateral surface, and in parts of the medial surface of the hemispheres. The area of decreased beta activity was less extensive. The right lateral and laterobasal temporal cortex showed decreased delta, theta, alpha, and beta activity, while its left counterpart only showed decreased delta and alpha activity in a limited part of this area. CONCLUSIONS: (1) Pathological interictal EEG activity is not evenly distributed across the cortex in IGE. The prefrontal area of increased activity corresponds to the area that is essential in the buildup of the ictal spike-wave paroxysms (absence seizures). The existence of the posterior "center of gravity" of increased EEG activity in IGE was confirmed. The frontal area of decreased activity might be related to the cognitive deficit described in IGE patients. (2) Increased activity in a lot of ontogenetically older areas (including the hippocampi) and decreased activity in the majority of the isocortex is a peculiar pattern that argues for a developmental hypothesis for IGE.

Beta activity in status epilepticus.

Focal beta activity on scalp EEG is a rare seizure pattern that has most extensively been studied in patients undergoing evaluation for epilepsy surgery. However, ictal beta activity is uncommon beyond this population and has not been reported in human status epilepticus. We observed ictal focal beta activity as the predominant seizure pattern in a patient with refractory status epilepticus. Continuous left temporal beta activity clinically correlated with complex partial semiology on video-EEG.

Alterations in human EEG activity caused by extremely low frequency electromagnetic fields.

This study has investigated whether extremely low frequency (ELF) electromagnetic fields (EMFs) can alter human brain activity. Linearly polarised magnetic flux density of 20 muT (rms) was generated using a standard double Helmholtz coils and applied to the human head over a sequence of 1 minute stimulations followed by one minute without stimulation in the following order of frequencies 50, 16.66, 13, 10, 8.33 and 4 Hz. We collected recordings on 33 human volunteers under double-blind counter-balanced conditions. Each stimulation lasted for two minutes followed by one minute post-stimulation EEG recording. The same procedure was repeated for the EMF control sessions, where the order of control and exposure sessions was determined randomly according to the subject's ID number. The rest period between two conditions (exposure and control) was 30 minutes. The results indicate that there was a significant increase in Alpha1, Alpha2, and Beta1 at the frontal brain region, and a significant decrease in Alpha2 band in parietal and occipital region due to EMF exposure.

Frontal and central oscillatory changes related to different aspects of the motor process: a study in go/no-go paradigms.

We studied alpha and beta EEG oscillatory changes in healthy volunteers during two different auditory go/no-go paradigms, in order to investigate their relationship with different components of the motor process. In the first paradigm (S2-centered), the initial tone (S1) was constant (warning), and the second tone (S2) indicated the subject whether to move or not. In the second paradigm (S1-centered), S1 indicated whether to move or not, while S2 just indicated the timing of the movement. A medial frontal beta energy increase was found in all conditions after the stimulus that forces the subject to decide whether to move or not (S1 or S2 depending on the paradigm). In both go conditions, a central alpha and beta energy decrease began after the go decision, reaching minimum values during the movement; it was followed by a beta post-movement increase, limited to the central contralateral area. In the no-go conditions, a marked fronto-central beta synchronization appeared after the decision not to move. In conclusion, our study was able to dissociate the beta oscillatory changes related to movement preparation and execution (central decrease/increase) from those associated with decision-making (medial frontal increase) and motor inhibition (fronto-central increase).

Resting EEG in offspring of male alcoholics: beta frequencies.

This study examines the differences in beta (12-28 Hz) band power in offspring of male alcoholics from densely affected alcoholic families. We have attempted to investigate if the increase in beta power is a 'state' or 'trait' marker for alcoholism. This study also explores the gender differences in the expression of this potential risk marker. Absolute beta power in three bands-beta 1(12-16 Hz), beta 2 (16-20 Hz), and beta 3 (20-28 Hz)-in the eyes closed EEG of 171 high risk (HR) subjects who were offspring of male alcoholics and 204 low risk (LR) subjects with no family history of alcoholism, were compared for each gender separately using a repeated measures analysis of variance design. Alcoholic and non-alcoholic subjects within the high risk group were compared using a repeated measures design as a follow-up analysis. The present study demonstrated increased beta power in the resting EEG of offspring of male alcoholics. Male HR subjects had higher beta 1 (12-16 Hz) power and female HR subjects had increased power in beta 2 (16-20 Hz) and beta 3 (20-28 Hz) as compared with low risk participants. Female HR subjects also showed significantly increased beta 2 and beta 3 power if they had two or more alcoholic first-degree relatives when compared with HR females having only an affected father. Risk characteristics are expressed differentially in males and females and may be an index of differential vulnerability to alcoholism. The results indicate that increased EEG beta power can be considered as a likely marker of risk for developing alcoholism and may be used as a predictive endophenotype.

Quantitative electroencephalogram (qEEG) in combat veterans with post-traumatic stress disorder (PTSD).

Only a small number of studies have used quantitative electroencephalography (qEEG) in research of the post-traumatic stress disorder (PTSD). The results are not consistent. The aim of the present investigation was to compare qEEG in combat veterans with and without PTSD. The hypothesis is that differences among qEEG characteristics will be found regarding the presence/absence of PTSD. Seventy-nine combat veterans with PTSD comprised the experimental group and 37 veterans without PTSD were included as controls. After the informed consent, they were investigated by the resting EEG recordings. The results demonstrate that PTSD veterans had decreased alpha power and increased beta power. These results suggest an altered neurobiology in PTSD. Various explanations have been offered for alpha activity decrease observed in PTSD veterans. Increased beta rhythm may play a role as a potential marker in differentiating subtypes of PTSD.

A functional gamma-band defined by stimulus-dependent synchronization in area 18 of awake behaving cats.

During the past decade, numerous studies have demonstrated stimulus-specific synchronization of neuronal activity in the gamma-frequency range. However, it appears that the different analyses are based on widely different assumptions about which frequency range to investigate. Therefore, the term "gamma-synchronization" refers to an inhomogeneous spectrum of definitions and corresponding frequency bands. Moreover, most studies have been performed in anesthetized animals or in awake animals by use of fixation paradigms. Thus, it is difficult to relate these results to alert animals behaving under natural conditions. Here, we investigate stimulus specific synchronization in primary visual cortex of awake cats in a tracking paradigm. We record local field potentials and multiunit activity simultaneously from multiple electrodes. (1) We demonstrate that visual stimulation induces neuronal synchronization in a broad frequency range reaching well above 100 Hz. (2) We derive a functional gamma-band based on an objective criterion: We show that synchronization of neuronal activity is optimally orientation-tuned when a broad frequency band is considered. This band starts above 40 Hz, a frequency that is typically related to the term gamma-synchronization, and extends to very high frequencies. Interestingly, the frequency of maximum synchronization is different from the frequency at which synchronization is most stimulus specific. (3) We demonstrate synchronization of neuronal activity in a distinct low-frequency band with different properties suggesting separate functional roles of low- and high-frequency synchronization.

Topographic quantitative EEG response to acute caffeine withdrawal: a comprehensive analysis of multiple quantitative variables.

Most previous studies of the neurophysiological effects of caffeine have focused on the effects of caffeine ingestion, and few studies have examined the effects of caffeine withdrawal. This open study evaluated the quantitative EEG (QEEG) changes occurring during a 4-day period of abstinence in subjects who habitually consume 300 mg or more of caffeine daily. Thirteen subjects underwent QEEG studies during their usual caffeine consumption (baseline) and on days 1, 2, and 4 of a 4-day period of caffeine abstinence. Ten of the subjects underwent a second QEEG on day 4 that consisted of a period of recording after reinstitution of caffeine. A comprehensive analysis of multiple quantitative variables was performed for each study during the abstinence period and compared to the variables obtained at baseline for each subject. Changes occurring during caffeine abstinence included: 1) increases in theta absolute power over all cortical areas, 2) increases in delta absolute power over the frontal cortex, 3) decreases in the mean frequency of both the alpha and beta rhythm, 4) increase in theta relative power and decrease in beta relative power, and 5) significant changes in interhemispheric coherence. Most of these changes tended to return to pre-abstinence baseline levels rapidly after resumption of caffeine consumption. The caffeine withdrawal state affects a number of neurophysiological variables. Further investigation of the neurophysiological aspects of caffeine withdrawal using placebo controlled double blind assessment methods is warranted.

The relationship between rhythmic activities during a mental task and sleep spindles: a correlative analysis.

In a previous study, we suggested that the characteristics of theta, alpha, and beta rhythms during a mental task were similar to those during sleep. Building upon the previous data, correlations between rhythmic activities during a mental task and during sleep were investigated in the present study. Patterns of correlation and no correlation between rhythmic activities during the mental task were similar to those during sleep for subjects with and without frontal midline theta (Fmtheta) activity. In the Fmtheta group, there were no correlations between rhythmic activities in the two situations, while in the non-Fmtheta subjects, theta and alpha rhythms showed a positive correlation with one another, and theta and beta rhythms correlated negatively during sleep. In both groups, there were many correlations between rhythmic activities during the mental task and those in Sleep Stage 2, while there were few correlations between rhythmic activities during the mental task and those in other sleep stages. These results suggest that the mechanism generating rhythmic activities during the appearance of rhythmic activities induced by a mental task may be closely related to those of rhythmic activities during sleep, and that the membrane potentials in reticular thalamic (RE) neurons during the appearance of rhythmic activities induced by a mental task may be nearly equivalent to that in Sleep Stage 2, and that the correlation pattern between the rhythmic activities in each group may be well explained by the appearance pattern of each rhythm in the previous report.

Contrasting behavior of beta event-related synchronization and somatosensory evoked potential after median nerve stimulation during finger manipulation in man.

Electrical median nerve stimulation during rest results in two cortical responses: the somatosensory evoked potential (SEP); and the induced beta oscillations (beta event-related synchronization (ERS)). Both types of responses were recorded with electroencephalography and studied during rest and motor behavior in eight normal subjects. During manipulation of a cube with the fingers of the right hand, the beta ERS around 20 Hz, induced by right hand median nerve stimulation, is significantly suppressed, whereas the long-latency SEP components are significantly enhanced. The results suggest that both phenomena can be interpreted as responses of different neuronal structures in sensorimotor areas.

Abnormal pattern of cortical activation associated with voluntary movement in obsessive-compulsive disorder: an EEG study.

OBJECTIVE: Converging evidence in patients with obsessive-compulsive disorder (OCD) shows abnormalities of prefrontal areas and basal ganglia, which are also involved in motor control. Event-related desynchronization of mu and beta EEG rhythms is considered a correlate of motor activation during motor preparation and execution, followed by cortical idling or inhibition indicated by event-related synchronization. The authors investigated the circuits involved in motor behavior in OCD by using event-related desynchronization/synchronization. METHOD: Data on alpha and beta event-related desynchronization/synchronization with self-paced movement of the right thumb were obtained by using 29-channel EEG in 10 untreated OCD patients and 10 normal subjects. RESULTS: OCD patients showed delayed onset of mu event-related desynchronization with movement preparation and less postmovement beta synchronization, compared to normal subjects. CONCLUSIONS: Delayed event-related desynchronization in OCD is consistent with involvement of structures related to motor programming, such as basal ganglia. Lower levels of postmovement beta synchronization suggest impairment of the inhibitory system in OCD.

Quantitative electroencephalogram of posterior cortical areas of fluent and stuttering participants during reading with normal and altered auditory feedback.

In the left and right hemisphere, posterior quantitative electroencephalogram Beta band activity (13.5-25.5 Hz) of seven adult participants who stutter and seven age-matched normal controls was obtained while subjects read text under three experimental conditions of normal auditory feedback, delayed auditory feedback, and frequency-altered feedback. Data were obtained from surface electrodes affixed to the scalp using a commercial electrode cap. Electroencephalogram activity was amplified, band-pass analog-filtered, and then digitized. During nonaltered auditory feedback, stuttering participants displayed Beta band hyperreactivity, with the right temporal-parietal lobe region showing the greatest activity. Under conditions of delayed auditory feedback and frequency-altered auditory feedback, the stuttering participants displayed a decrease in stuttering behavior accompanied by a strong reduction in Beta activity for the posterior-temporal-parietal electrode sites, and the left hemisphere posterior sites evidenced a larger area of reactivity. Such findings suggest than an alteration in the electrical fields of the cortex occurred in the stuttering participants under both conditions, possibly reflecting changes in neurogenerator status or current dipole activity. Further, one could propose that stuttering reflects an anomaly of the sensory-linguistic motor integration wherein each hemisphere generates competing linguistic messages at hyperreactive amplitudes.

Masking effect of motivation on ultradian rhythm.

To test the masking effect of motivation on ultradian fluctuations in arousal, we examined the self-rating scores for sleepiness, fatigue, and motivation and the electroencephalographic data for 5 male university students (age range, 18 to 20 years). They watched either an animated video series (Animation condition) intended to enhance motivation or interest or a landscape video series (Landscape condition) intended to induce lack of interest due to boredom. Each subject watched the two series for more than one week in a 3.1 x 3.1 m isolation unit. Each series was presented for 12 min. every 20 min. from 0900 to 1800. Subjective sleepiness and fatigue increased, and motivation was decreased for Landscape condition, suggesting the validity of the experimental manipulation. Closed-eye Oz-EEG alpha and beta activities fluctuated in an ultradian manner for both conditions, although slower cycles were observed at an interval of the Animation condition. The coefficients of variation of time series data were also lower for the Animation condition. These data suggest that either high motivation or absence of sleepiness or fatigue mask ultradian arousal cycles by producing fewer or slower fluctuations.