Anoxia-ischemia: a mechanism of seizure termination in ictal asystole.

Cerebral anoxia-ischemia (CAI) is a potent inhibitor of cerebral hyperactivity and a potential mechanism of seizure self-termination. Prolonged ictal asystole (IA) invariably leads to CAI and has been implicated as a potential cause of sudden unexplained death in epilepsy (SUDEP). IA was seen in eight consecutive patients (0.12% of all patients monitored). Ten of their seizures with IA had evidence of CAI on electroencephalography (EEG), manifested by bilateral hypersynchronous slowing (BHS), and were compared to 18 seizures without signs of CAI. The ictal EEG pattern resolved in all 10 CAI events with onset of the BHS. The period from IA onset to seizure end was reduced in events with BHS compared to events without BHS (10.5 s vs. 28.3 s, respectively; p = 0.005), and the total seizure duration tended to be shorter. Anoxia-ischemia as a result of IA may represent an effective endogenous mechanism for seizure termination and may explain why the hearts of patients with ictal asystole reported to date in the literature resumed beating spontaneously.

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.

Brains swinging in concert: cortical phase synchronization while playing guitar.

BACKGROUND: Brains interact with the world through actions that are implemented by sensory and motor processes. A substantial part of these interactions consists in synchronized goal-directed actions involving two or more individuals. Hyperscanning techniques for assessing fMRI simultaneously from two individuals have been developed. However, EEG recordings that permit the assessment of synchronized neuronal activities at much higher levels of temporal resolution have not yet been simultaneously assessed in multiple individuals and analyzed in the time-frequency domain. In this study, we simultaneously recorded EEG from the brains of each of eight pairs of guitarists playing a short melody together to explore the extent and the functional significance of synchronized cortical activity in the course of interpersonally coordinated actions. RESULTS: By applying synchronization algorithms to intra- and interbrain analyses, we found that phase synchronization both within and between brains increased significantly during the periods of (i) preparatory metronome tempo setting and (ii) coordinated play onset. Phase alignment extracted from within-brain dynamics was related to behavioral play onset asynchrony between guitarists. CONCLUSION: Our findings show that interpersonally coordinated actions are preceded and accompanied by between-brain oscillatory couplings. Presumably, these couplings reflect similarities in the temporal properties of the individuals' percepts and actions. Whether between-brain oscillatory couplings play a causal role in initiating and maintaining interpersonal action coordination needs to be clarified by further research.

Decomposing neural synchrony: toward an explanation for near-zero phase-lag in cortical oscillatory networks.

BACKGROUND: Synchronized oscillation in cortical networks has been suggested as a mechanism for diverse functions ranging from perceptual binding to memory formation to sensorimotor integration. Concomitant with synchronization is the occurrence of near-zero phase-lag often observed between network components. Recent theories have considered the importance of this phenomenon in establishing an effective communication framework among neuronal ensembles. METHODOLOGY/PRINCIPAL FINDINGS: Two factors, among possibly others, can be hypothesized to contribute to the near-zero phase-lag relationship: (1) positively correlated common input with no significant relative time delay and (2) bidirectional interaction. Thus far, no empirical test of these hypotheses has been possible for lack of means to tease apart the specific causes underlying the observed synchrony. In this work simulation examples were first used to illustrate the ideas. A quantitative method that decomposes the statistical interdependence between two cortical areas into a feed-forward, a feed-back and a common-input component was then introduced and applied to test the hypotheses on multichannel local field potential recordings from two behaving monkeys. CONCLUSION/SIGNIFICANCE: The near-zero phase-lag phenomenon is important in the study of large-scale oscillatory networks. A rigorous mathematical theorem is used for the first time to empirically examine the factors that contribute to this phenomenon. Given the critical role that oscillatory activity is likely to play in the regulation of biological processes at all levels, the significance of the proposed method may extend beyond systems neuroscience, the level at which the present analysis is conceived and performed.

Increased absolute magnitude of gamma synchrony in first-episode psychosis.

OBJECTIVES: Recent studies have explored a model of the disconnection hypothesis of schizophrenia through the demonstration of abnormal stimulus induced gamma phase synchrony (GPS). These studies have principally examined synchrony in the 40 Hz band elicited in post-stimulus time periods, relative to a pre-stimulus baseline. In this study we examined the absolute magnitude of GPS elicited by a selective attention task, in first-episode psychosis (FEP). We hypothesized that FEP would be associated with abnormalities in absolute GPS, particularly when required to selectively attend to task-relevant stimuli. METHODS: Fifty-five first-episode psychosis (FEP) subjects and one hundred and ten matched healthy control subjects underwent an auditory oddball selective attention task during EEG recording. The absolute magnitude of GPS was extracted for the range 35-45 Hz, and time-locked to stimulus onset. GPS averaged were computed for oddball 'target' (task-relevant) and 'non-target' (task-irrelevant) stimuli, for each subject. RESULTS: FEP subjects showed a significant elevation in absolute GPS relative to controls, apparent across the 35-45 Hz range. This elevation was most marked in the left centro-temporal region, across the 800 ms post-stimulus period. In FEP subjects, the elevation in GPS was also greater for target compared to non-target stimuli, while healthy controls did not show a stimulus effect. CONCLUSION: These findings complement previous evidence for reductions in peak gamma synchrony, calculated relative to a pre-stimulus baseline, in schizophrenia. The results an excess of absolute GPS in schizophrenia may contribute to an inability to effectively integrate task-relevant information, which underlie psychotic symptoms.

Synchronization clusters of interictal activity in the lateral temporal cortex of epileptic patients: intraoperative electrocorticographic analysis.

OBJECTIVE: Drug-resistant temporal lobe epilepsy (TLE) can be treated by tailored surgery guided by electrocorticography (ECoG). Although its value is still controversial, ECoG activity can provide continuous information on intracortical interactions that may be useful to understand the pathophysiology of TLE. The goal of this study is to characterize local interactions in multichannel ECoG recordings of the lateral cortex of TLE patients using three synchronization measures and to link this information with surgical outcome. METHODS: Intraoperative ECoG recordings from 29 TLE patients were obtained using grids of 20 electrodes (4 x 5) covering regions T1, T2, and T3 of the lateral temporal lobe. Linear correlation, mutual information, and phase synchronization were calculated to quantify lateral intracortical interactions. Surrogate data files were generated to test results statistically. RESULTS: By distributing locally the interactions between the electrodes, we characterized the spatial patterns of ECoG activity. We found clusters of synchronized activity at specific areas of the lateral temporal cortex in most patients. Methodologically, linear correlation and phase synchronization performed better than mutual information for cluster discrimination. ROC analysis suggested that surgical removal of sharply defined synchronization clusters correlated with seizure control. CONCLUSIONS: Our results show that synchronous intraoperative ECoG activity emerges from specific cortical areas that are highly differentiated from the rest of the temporal cortex. This suggests that synchronization analysis could be used to functionally map into the temporal cortex of TLE patients. Moreover, our results suggest that these sites might be involved in the circuits that participate in clinical seizures.

The impact of cerebral source area and synchrony on recording scalp electroencephalography ictal patterns.

PURPOSE: To determine the cerebral electroencephalography (EEG) substrates of scalp EEG seizure patterns, such as source area and synchrony, and in so doing assess the limitations of scalp seizure recording in the localization of seizure onset zones in patients with temporal lobe epilepsy. METHODS: We recorded simultaneously 26 channels of scalp EEG with subtemporal supplementary electrodes and 46-98 channels of intracranial EEG in presurgical candidates with temporal lobe epilepsy. We correlated intracranial EEG source area and synchrony at seizure onset with the corresponding scalp EEG. Eighty-six simultaneous intracranial- and scalp-recorded seizures from 23 patients were evaluated. RESULTS: Thirty-four intracranial ictal discharges (40%) from 9 patients (39%) had sufficient cortical source area (namely > 10 cm(2)) and synchrony at seizure onset to produce a simultaneous or nearly simultaneous focal scalp EEG ictal pattern. Forty-one intracranial ictal discharges (48%) from 10 patients (43%) gradually achieved the necessary source area and synchrony over several seconds to generate a scalp EEG ictal pattern. These scalp rhythms were lateralized, but not localizable as to seizure origin. Eleven intracranial ictal discharges (13%) from 4 patients (17%) recruited the necessary source area, but lacked sufficient synchrony to result in a clearly localized or lateralized scalp ictal pattern. CONCLUSIONS: Sufficient source area and synchrony are mandatory cerebral EEG requirements for generating scalp-recordable ictal EEG patterns. The dynamic interaction of cortical source area and synchrony at the onset and during a seizure is a primary reason for heterogeneous scalp ictal EEG patterns.

Analysis of initial slow waves (ISWs) at the seizure onset in patients with drug resistant temporal lobe epilepsy.

RATIONALE: The goal of this study is to analyze initial slow waves (ISWs) at seizure onset in patients with refractory temporal lobe epilepsy. ISWs are a specific type of ictal EEG pattern characterized by a slow wave at the seizure onset followed by low voltage fast activity. METHODS: Investigations were carried out on 14 patients from the UCLA hospital (USA) and 10 from the Ghent University Hospital (Belgium) implanted with depth and grid electrodes for localization of the epileptogenic zone. RESULTS: Sixty-one seizures in the UCLA group and 30 seizures in the Ghent group were analyzed. Fourteen UCLA and seven Ghent patients had ISWs at seizure onset. The duration of ISWs varied between 0.3 to 6.0 s and maximum amplitude varied from 0.2 to 1.4 mV. ISWs in three of 14 UCLA patients (30% of seizures) had a consistent positive polarity at the deepest contacts that were located in the amygdala, hippocampus, or entorhinal cortex and reversed polarity outside of these brain areas (ISWs1). ISWs in 11 of 14 UCLA patients (70% of seizures) had negative polarity at the deepest electrodes and their amplitude increased toward the recording contacts located in the white matter or neocortex (ISWs2). All ISWs from the seven Ghent patients were negative in the depth contacts (ISWs2) and positive on grid electrodes at the cortical surface. ISWs1 were associated with EEG spikes at the onset and on increase in amplitude of 10-20 Hz sinusoidal activity. In contrast, ISWs2 were associated with suppression of EEG amplitude, an increase in frequency in the range of 20-50 Hz, and did not have EEG spikes at the onset. Multiunit neuronal activity showed strong synchronization of neuronal discharges during interictal spikes, but multiunit synchronization was not obvious during ISWs2. CONCLUSION: The existence of EEG spikes and phase reversal with ISWs1 indicates this type of seizure may be triggered by hypersynchronous neuronal discharges; however, seizures with ISWs2 at the onset may be triggered by different mechanisms, perhaps nonneuronal.

Typical versus atypical absence seizures: network mechanisms of the spread of paroxysms.

PURPOSE: Typical absence seizures differ from atypical absence seizures in terms of semiology, EEG morphology, network circuitry, and cognitive outcome, yet have the same pharmacological profile. We have compared typical to atypical absence seizures, in terms of the recruitment of different brain areas. Our initial question was whether brain areas that do not display apparent paroxysmal discharges during typical absence seizures, are affected during the ictal event in terms of synchronized activity, by other, distant areas where seizure activity is evident. Because the spike-and-wave paroxysms in atypical absence seizures invade limbic areas, we then asked whether an alteration in inhibitory processes in hippocampi may be related to the spread seizure activity beyond thalamocortical networks, in atypical seizures. METHODS: We used two models of absence seizures in rats: one of typical and the other of atypical absence seizures. We estimated phase synchronization, and evaluated inhibitory transmission using a paired-pulse paradigm. RESULTS: In typical absence seizures, we observed an increase in synchronization between hippocampal recordings when spike-and-wave discharges occurred in the cortex and thalamus. This indicates that seizure activity in the thalamocortical circuitry enhances the propensity of limbic areas to synchronize, but is not sufficient to drive hippocampal circuitry into a full paroxysmal discharge. Lower paired-pulse depression was then found in hippocampus of rats that displayed atypical absence seizures. CONCLUSIONS: These observations suggest that circuitries in brain areas that do not display apparent seizure activity become synchronized as seizures occur within thalamocortical circuitry, and that a weakened hippocampal inhibition may predispose to develop synchronization into full paroxysms during atypical absence seizures.

Synch before you speak: auditory hallucinations in schizophrenia.

OBJECTIVE: Synchronization of neural activity preceding self-generated actions may reflect the operation of the forward model, which acts to dampen sensations resulting from those actions. If this is true, pre-action synchrony should be related to subsequent sensory suppression. Deficits in this mechanism may be characteristic of schizophrenia and related to positive symptoms, such as auditory hallucinations. If so, schizophrenia patients should have reduced neural synchrony preceding movements, especially patients with severe hallucinations. METHOD: In 24 patients with schizophrenia or schizoaffective disorder and 25 healthy comparison subjects, the authors related prespeech neural synchrony to subsequent auditory cortical responsiveness to the spoken sound, compared prespeech neural synchrony in schizophrenia patients and healthy comparison subjects, and related prespeech neural synchrony to auditory hallucination severity in patients. To assess neural synchrony, phase coherence of single-trial EEG preceding talking was calculated at a single site across repeated trials. To assess auditory cortical suppression, the N1 event-related brain potentials to speech sound onset during talking and listening were compared. RESULTS: In healthy comparison subjects, prespeech neural synchrony was related to subsequent suppression of responsiveness to the spoken sound, as reflected in reduction of N1 during talking relative to listening. There was greater prespeech synchrony in comparison subjects than in patients, especially those with severe auditory hallucinations. CONCLUSIONS: These data suggest that EEG synchrony preceding speech reflects the action of a forward model system, which dampens auditory responsiveness to self-generated speech and is deficient in patients who hallucinate.

Time-frequency microstructure and statistical significance of ERD and ERS.

ERD and ERS were introduced as the time courses of the average changes of energy in given frequency bands. These curves are naturally embedded in the time-frequency plane. Time-frequency density of signals energy can be estimated by means of a variety of transforms. In general, resolution of these methods depends on a priori choices of parameters regulating the tradeoff between the time and frequency resolutions. As an exception, adaptive time-frequency approximations adapt resolution to the local structures of the analyzed signal. Matching pursuit (MP) algorithm is a reliable implementation of this approach. Its application to the event-related EEG allows for a detailed presentation of the time-frequency microstructure of changes of the average energy density, as well as calculation of high-resolution maps of ERD/ERS in the time-frequency plane. However, even with such a detailed picture of the signal energy changes, their significance remains an open issue. Owing to a stochastic character of the EEG, a visible increase or decrease of energy can occur due to a pure chance or a phenomenon unrelated to the event. For a proper estimation of the statistical significance of ERD/ERS, that is, the average changes of signals energy density in relation to the reference period, we must take into account possibly non-normal distributions of energy, and, especially, the problem of multiple comparisons appearing in hypotheses related to different frequency bands and time epochs. This chapter presents and discusses a complete framework for high-resolution estimation of the ERD/ERS microstructure in the time-frequency regions, revealing statistically significant changes.

Upper alpha ERD and absolute power: their meaning for memory performance.

A variety of studies have shown that EEG alpha activity in the upper frequency range is associated with different types of cognitive processes, memory performance, perceptual performance and intelligence, but in strikingly different ways. For semantic memory performance we have found that resting or reference power is positively associated with performance, whereas during actual processing of the task, small power--reflected by a large extent of event-related desynchronization (ERD)--is related to good performance. We also have shown that the induction of large alpha reference power by neurofeedback training or repetitive transcranial magnetic stimulation (rTMS) at individual alpha frequency mimicked exactly the situation which is typical for good memory performance under normal situations: increased alpha reference power is associated with large ERD and good performance. Recent studies have demonstrated that this relationship holds true only for memory and not perceptual tasks that require the identification of simple visual stimuli under difficult conditions. In contrast to good memory performance, good perceptual performance is related to small pre-stimulus alpha power and a small ERD. We interpret this finding in terms of cortical inhibition vs. activation preceding task performance by assuming that large rhythmic alpha activity reflects inhibition. We assume that small reference alpha enhances perceptual performance because the cortex is activated and prepared to process the stimulus, whereas memory performance is enhanced if the cortex is deactivated before a task is performed because in typical memory tasks selective processing can start only after the to-be-remembered item or cue is presented. We also suggest that conflicting results about alpha ERD and the neural efficiency hypothesis (which assumes that highly intelligent exhibit a small ERD) can also be interpreted in terms of inhibition. Only if an intelligence test actually requires the activation of (semantic) memory, a large (because task specific) ERD can be observed. If other processing systems are required, the semantic memory system may even become suppressed, which is reflected by alpha event-related synchronization (ERS) or at least a largely decreased ERD.

Sensitivity of alpha band ERD to individual differences in cognition.

According to the neural efficiency hypothesis, brighter individuals might be characterized by lower and topographically more differentiated brain activation than less intelligent individuals, presumably reflecting a more specialized recruitment of task-related areas. The findings of several studies analyzing the event-related desynchronization (ERD) in the (upper) alpha frequency band have corroborated and elaborated the original neural efficiency hypothesis. In this chapter, we review classical and recent findings and argue in favor of a more differentiated picture of this phenomenon, emphasizing the role of participants' sex, task complexity, and material specificity, as well as the importance to select an adequate external criterion (intelligence measure). Also, recent ERD findings related to emotional intelligence and creativity as well as recent studies focusing on practice, learning ability, and expertise are presented, which point to the need of a broader neurophysiological ability concept. The reviewed findings point at the high suitability of the ERD method to uncover consistent and stable individual differences in people's brain activation patterns when engaged in performing cognitively demanding tasks.

Psychophysiological evidence of altered neural synchronization in cannabis use: relationship to schizotypy.

OBJECTIVE: Cannabis use may produce neurophysiological disturbances similar to those observed in schizophrenia, particularly in relation to altered neural synchronization. Therefore, the current experiment examined the effect of cannabis use on EEG neural synchronization using the auditory steady-state evoked potential. METHOD: Auditory steady-state evoked potentials were assessed using varying rates of stimulation (auditory click-trains of 20, 30, 40 Hz) in current cannabis users (N=17) and drug-naive comparison subjects (N=16). EEG spectral power and signal-to-noise ratio at each stimulation frequency were compared between groups. RESULTS: Cannabis users showed decreased EEG power and signal-to-noise ratio at the stimulation frequency of 20 Hz. In addition, current cannabis users demonstrated increased schizotypal personality characteristics as assessed with the Schizotypal Personality Questionnaire, which positively correlated with total years of cannabis use. Finally, within the cannabis group, 20-Hz power values were negatively correlated with Schizotypal Personality Questionnaire scores. CONCLUSIONS: These data provide evidence for neural synchronization and early-stage sensory processing deficits in cannabis use. This finding, along with the observed increased rates of schizotypy in cannabis users, adds support for a cannabinoid link to schizophrenia spectrum disorders.

Frequency flows and the time-frequency dynamics of multivariate phase synchronization in brain signals.

The quantification of phase synchrony between brain signals is of crucial importance for the study of large-scale interactions in the brain. Current methods are based on the estimation of the stability of the phase difference between pairs of signals over a time window, within successive frequency bands. This paper introduces a new approach to study the dynamics of brain synchronies, Frequency Flows Analysis (FFA). It allows direct tracking and characterization of the nonstationary time-frequency dynamics of phase synchrony among groups of signals. It is based on the use of the one-to-one relationship between frequency locking and phase synchrony, which applies when the concept of phase synchrony is not taken in an extended 'statistical' sense of a bias in the distribution of phase differences, but in the sense of a continuous phase difference conservation during a short period of time. In such a case, phase synchrony implies identical instantaneous frequencies among synchronized signals, with possible time varying frequencies of synchronization. In this framework, synchronous groups of signals or neural assemblies can be identified as belonging to common frequency flows, and the problem of studying synchronization becomes the problem of tracking frequency flows. We use the ridges of the analytic wavelet transforms of the signals of interest in order to estimate maps of instantaneous frequencies and reveal sustained periods of common instantaneous frequency among groups of signal. FFA is shown to track complex dynamics of synchrony in coupled oscillator models, reveal the time-frequency and spatial dynamics of synchrony convergence and divergence in epileptic seizures, and in MEG data the large-scale ongoing dynamics of synchrony correlated with conscious perception during binocular rivalry.

Decreased coherence in higher frequency ranges (beta and gamma) between central and frontal EEG in patients with schizophrenia: A preliminary report.

Schizophrenia is associated with a dysfunction of cognitive integration that may be due to abnormalities in inhibitory neural circuitry. A previous study found a failure of gamma band (25-45 Hz) synchronization in patients with schizophrenia compared to controls. Another recent study also stressed the importance of investigating high frequencies in the scalp-recorded sleep electroencephalogram (EEG). In this study, we compared coherence between first episode drug-naïve patients with schizophrenia (n=8) and age- and sex-matched normal controls (n=8) using two 32-s epochs of C4 and F4 EEG. The coherence was obtained using 4096 data points (128 Hz signal) using cross-spectral analysis with Blackman-Tukey window in beta (15.25-24.75 Hz) and gamma (25-44.75 Hz) frequency bands. We used wake, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep periods for the analyses. Our results show a significant decrease in coherence in both beta and gamma frequency bands in patients. Post-hoc 't' tests revealed a significantly lower coherence only during the wake stage in patients with schizophrenia in beta as well as gamma frequency bands. These results further support the importance of the analyses of high-frequency bands in the EEG and support previous findings of abnormal neural synchrony in patients with schizophrenia. These results have been discussed further in relation to wake and sleep stages.

Do false predictions of seizures depend on the state of vigilance? A report from two seizure-prediction methods and proposed remedies.

PURPOSE: Available seizure-prediction algorithms are accompanied by high numbers of false predictions to achieve high sensitivity. Little is known about the extent to which changes in EEG dynamics contribute to false predictions. This study addresses potential causes and the circadian distribution of false predictions as well as their relation to the sleep-wake cycle. METHODS: In 21 patients, each with 24 h of interictal invasive EEG recordings, two methods, the dynamic similarity index and the mean phase coherence, were assessed with respect to time points of false predictions. Visual inspection of the invasive EEG data and additional scalp electroencephalogram data was performed at times of false predictions to identify possible correlates of changes in the EEG dynamics. RESULTS: A dependency of false predictions on the time of day is shown. Renormalized to the duration of the period patients are asleep and awake, 86% of all false predictions occurred during sleep for the dynamic similarity index and 68% for the mean phase coherence, respectively. Combining two reference intervals, one during sleep and one in an awake state, the dynamic similarity index increases its performance by reducing the number of false predictions by almost 50% without major changes in sensitivity. No obvious dependence of false predictions was noted on visible epileptic activity, such as spikes, sharp waves, or subclinical ictal patterns. CONCLUSIONS: Changes in the EEG dynamics related to the sleep-wake cycle contribute to limits of specificity of both seizure-prediction methods investigated. This may provide a clue for improving prediction methods in general. The combination of reference states yields promising results and may offer opportunities to increase further the performance of prediction methods.

The influence of methylphenidate on the power spectrum of ADHD children - an MEG study.

BACKGROUND: The present study was dedicated to investigate the influence of Methylphenidate (MPH) on cortical processing of children who were diagnosed with different subtypes of Attention Deficit Hyperactivity Disorder (ADHD). As all of the previous studies investigating power differences in different frequency bands have been using EEG, mostly with a relatively small number of electrodes our aim was to obtain new aspects using high density magnetoencephalography (MEG). METHODS: 35 children (6 female, 29 male) participated in this study. Mean age was 11.7 years (+/- 1.92 years). 17 children were diagnosed of having an Attention-Deficit/Hyperactivity Disorder of the combined type (ADHDcom, DSM IV code 314.01); the other 18 were diagnosed for ADHD of the predominantly inattentive type (ADHDin, DSM IV code 314.0). We measured the MEG during a 5 minute resting period with a 148-channel magnetometer system (MAGNES 2500 WH, 4D Neuroimaging, San Diego, USA). Power values were averaged for 5 bands: Delta (D, 1.5-3.5 Hz), Theta (T, 3.5-7.5 Hz), Alpha (A, 7.5-12.5 Hz), Beta (B, 12.5-25 Hz) and Global (GL, 1.5-25 Hz).). Additionally, attention was measured behaviourally using the D2 test of attention with and without medication. RESULTS: The global power of the frequency band from 1.5 to 25 Hz increased with MPH. Relative Theta was found to be higher in the left hemisphere after administration of MPH than before. A positive correlation was found between D2 test improvement and MPH-induced power changes in the Theta band over the left frontal region. A linear regression was computed and confirmed that the larger the improvement in D2 test performance, the larger the increase in Theta after MPH application. CONCLUSION: Main effects induced by medication were found in frontal regions. Theta band activity increased over the left hemisphere after MPH application. This finding contradicts EEG results of several groups who found lower levels of Theta power after MPH application. As relative Theta correlates with D2 test improvement we conclude that MEG provide complementary and therefore important new insights to ADHD.