Familial clustering and DRD4 effects on electroencephalogram measures in multiplex families with attention deficit/hyperactivity disorder.

OBJECTIVE: The current study tests electroencephalogram (EEG) measures as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD) by examining sibling and parent-offspring similarity, familial clustering with the disorder, and association with the dopamine receptor D4 (DRD4) candidate gene. METHOD: The sample consists of 531 participants (191 parents and 340 children) from 132 multiplex families with ADHD who participated in a larger genetics study. All members of the families underwent extensive assessment including semi-structured diagnostic interviews and EEG recording. RESULTS: Strong sibling similarity and parent-offspring correlations in EEG power emerged, suggesting high trait heritability. Increased theta power was observed among children with ADHD when compared with unaffected children, and there were no differences according to ADHD subtype. Within the parent sample, ADHD diagnostic status and ADHD subtype group differences emerged in the theta, alpha, and beta frequency bands. DRD4 effects for both parents and children were apparent in the beta frequency band and for children only in the theta frequency band. CONCLUSIONS: This study suggests that EEG measures are a promising avenue of study in the search for putative endophenotypes for ADHD, and that variability at the DRD4 gene may contribute to this endophenotype.

Electroencephalogram theta/beta ratio and arousal in attention-deficit/hyperactivity disorder: evidence of independent processes.

BACKGROUND: For nearly 20 years, the theta/beta power ratio in the electroencephalogram (EEG) has been used within the attention-deficit/hyperactivity disorder (ADHD) literature as a marker of central nervous system (CNS) arousal, underpinning current models of the disorder. However, this usage has not been validated. We aimed to directly test the theta/beta ratio as a marker of arousal within this population. METHODS: Resting state EEG activity was investigated as a function of CNS arousal in two age-matched groups of boys (each n = 30), with and without ADHD. Arousal was defined in terms of skin conductance level (SCL), which has a long history as a measure of CNS arousal. RESULTS: Relative theta power and the theta/beta ratio were elevated, and SCL and relative alpha and beta power were reduced, in the ADHD group compared with control subjects. In both groups, mean alpha level correlated negatively with SCL. There was no significant correlation between the theta/beta ratio and SCL. CONCLUSIONS: These data contradict the supposed linkage between the theta/beta ratio and arousal in ADHD, confirming previous results from normal children. They suggest the need for reevaluation of current models of the disorder and reconceptualization of existing EEG data from both normal and atypical populations.

Prediction, sequences and the hippocampus.

Recordings of rat hippocampal place cells have provided information about how the hippocampus retrieves memory sequences. One line of evidence has to do with phase precession, a process organized by theta and gamma oscillations. This precession can be interpreted as the cued prediction of the sequence of upcoming positions. In support of this interpretation, experiments in two-dimensional environments and on a cue-rich linear track demonstrate that many cells represent a position ahead of the animal and that this position is the same irrespective of which direction the rat is coming from. Other lines of investigation have demonstrated that such predictive processes also occur in the non-spatial domain and that retrieval can be internally or externally cued. The mechanism of sequence retrieval and the usefulness of this retrieval to guide behaviour are discussed.

Event-related theta and alpha oscillations mediate empathy for pain.

Our recent event-related potential (ERP) studies showed that phase-locked electrophysiological activities mediate both early emotional sharing and late cognitive evaluation during empathy for pain. However, whether non-phase-locked neural oscillations are involved in empathic responses remains unknown. To investigate the functional role of non-phase-locked theta (3-8 Hz) and alpha (9-14 Hz) oscillations in empathy for pain, we recorded electroencephalogram (EEG) from healthy adults who performed pain judgment of pictures of hands in painful or neutral situations. Wavelet analysis was used to calculate EEG spectral power with high time-frequency (TF) resolution. We found that, relative to neutral stimuli, painful stimuli induced increased theta event-related synchronization (ERS) at 200-500 ms but decreased alpha event-related desynchronization (ERD) at 200-400 ms, providing evidence for the engagement of theta and alpha activity in empathy for pain. In addition, subjective ratings of perceived pain and self-unpleasantness positively correlated with theta band ERS but negatively correlated with alpha band ERD related to painful stimuli, suggesting that theta and alpha oscillations are respectively involved in emotional sharing and regulation during empathy for pain. Finally, the long-latency upper theta (6-8 Hz) and alpha band TF power significantly decreased by repeated exposure to painful stimuli, indicating short-term adaptive changes of empathy-related neural activity.

Decreased theta event-related synchronization during working memory activation is associated with progressive mild cognitive impairment.

BACKGROUND: Among the different quantitative electroencephalographic markers, theta activity is known to reflect neural resources involved in memory processes and directed attention. Previous studies suggested that synchronization likelihood analysis in theta-band frequency might be a sensitive method to identify early alterations of neuronal networks in mild cognitive impairment (MCI). METHODS: We report here a longitudinal study of 24 MCI patients with theta event-related synchronization (ERS) analysis during the n-back working memory task and neuropsychological follow-up after 1 year. Statistical analysis included analysis of variance and logistic regression to assess the relationship between cognitive decline and theta ERS. RESULTS: Upon follow-up, 13 MCI patients showed progressive MCI and 11 remained stable. In both groups, the phasic increase in theta amplitude after stimulus presentation did not depend on working memory load and electrode sites. Progressive MCI cases displayed significantly lower theta ERS power over all electrode sites compared to stable MCI cases. Theta ERS was significantly related to the cognitive outcome explaining 15.5% of its variability. In terms of MCI classification, the best combination of sensitivity and specificity was 0.87 and 0.60, respectively, with an area under the corresponding receiver operating characteristic curve reaching 76%. CONCLUSIONS: The present data indicate that a decrease in the early phasic theta ERS power during working memory activation may predict cognitive decline in MCI. This phenomenon is not related to working memory load but may reflect the presence of early deficits in directed attention-related neural circuits in MCI.

Nonpharmacological amelioration of age-related learning deficits: the impact of hippocampal theta-triggered training.

Age-related learning deficits are often attributed to deterioration of hippocampal function. Conversely, a well studied index of hippocampal activity, the rhythm, is known to enhance hippocampal plasticity and accelerate learning rate in young subjects, suggesting that manipulations of activity might be used as a means to counteract impairments related to the aging process. Here, young and older rabbits were given eyeblink conditioning trials either when exhibiting hippocampal (+) or regardless of hippocampal activity (yoked control). Although, as expected, older-yoked control animals showed a learning deficit, the older + group learned as fast as young controls, demonstrating that aging deficits, at least in eyeblink classical conditioning, can be overcome by giving trials during episodes of hippocampal activity. The use of several learning criteria showed that the benefits of hippocampal occur in multiple phases of learning that may depend on different cognitive or motor processes. Whereas there was a benefit of -triggered training in both age groups during the early phase of acquisition, the enhancement persisted in older animals, peaking during later performance. These findings have implications for theories of age-related memory deficits and may contribute to the development of beneficial treatments.

Effect of driving duration and partial sleep deprivation on subsequent alertness and performance of car drivers.

The effect of partial sleep deprivation and driving duration on subsequent alertness and performance in car drivers was investigated. Twenty healthy male subjects, between 25 and 55 years of age, free from any sleep disorder, took part in two simulated driving sessions carried out between 2 p.m. and 4 p.m. Before one session, subjects were sleep deprived as they were allowed to sleep only between 3 a.m. and 7 a.m. during the preceding night. Throughout the driving task, the subjects' driving performance, electroencephalogram and Karolinska Sleepiness Scale (KSS) score were recorded. The results revealed that sleep deprivation had an effect on KSS score but not on the (alpha+theta) spectral power, while driving duration had an effect on these two parameters. This effect was also influenced by sleep restriction. Time on driving task alone had a significant effect on driving performance; the sleep restriction having only an effect on one of the performances indices studied: the number of right edge-line crossings. These results are interpreted in terms of the relationship between level of alertness and performance impairment.

Event-induced theta responses as a window on the dynamics of memory.

An important, but often ignored distinction in the analysis of EEG signals is that between evoked activity and induced activity. Whereas evoked activity reflects the summation of transient post-synaptic potentials triggered by an event, induced activity, which is mainly oscillatory in nature, is thought to reflect changes in parameters controlling dynamic interactions within and between brain structures. We hypothesize that induced activity may yield information about the dynamics of cell assembly formation, activation and subsequent uncoupling, which may play a prominent role in different types of memory operations. We then describe a number of analysis tools that can be used to study the reactivity of induced rhythmic activity, both in terms of amplitude changes and of phase variability. We briefly discuss how alpha, gamma and theta rhythms are thought to be generated, paying special attention to the hypothesis that the theta rhythm reflects dynamic interactions between the hippocampal system and the neocortex. This hypothesis would imply that studying the reactivity of scalp-recorded theta may provide a window on the contribution of the hippocampus to memory functions. We review studies investigating the reactivity of scalp-recorded theta in paradigms engaging episodic memory, spatial memory and working memory. In addition, we review studies that relate theta reactivity to processes at the interface of memory and language. Despite many unknowns, the experimental evidence largely supports the hypothesis that theta activity plays a functional role in cell assembly formation, a process which may constitute the neural basis of memory formation and retrieval. The available data provide only highly indirect support for the hypothesis that scalp-recorded theta yields information about hippocampal functioning. It is concluded that studying induced rhythmic activity holds promise as an additional important way to study brain function.

The role of theta-range oscillations in synchronising and integrating activity in distributed mnemonic networks.

It is well established that the occurrence of theta rhythm in the hippocampus is important in a variety of mnemonic tasks. However, in this review it will be argued that theta-rhythmic activity occurs across distributed networks within the diencephalon and neocortex as well as the hippocampus, and functions to temporally coordinate activity in distributed systems within these regions during mnemonic processes. Recent evidence strongly suggests that theta-range cellular activity occurs in the supramammillary nucleus (SuM) of the hypothalamus, and that this activity is independent of that occurring in the hippocampus. We have previously proposed in fact, that the frequency of theta activity in the hippocampus is determined in the SuM, rather than in the medial septum as previously assumed. The frequency-coded information from the SuM is then fed into at least two recurrent networks proposed by Aggleton and Brown (1999). Theta activity in these networks (the hippocampo-anterior thalamic system and the perirhinal-mediodorsal thalamic system) could potentially occur independently, but when simultaneously occurring in both may function to coordinate the integration of information in the two systems. Finally, we suggest that as the two systems include temporal and frontal neocortical areas that contribute to surface EEG, scalp recording of theta EEG activity from these regions may provide a "window" through which to assess the relative involvement of different cortico-limbic circuits in different mnemonic processes. The potential utility of this technique will be increased greatly by the use of high-density EEG and algorithms to more precisely map the topography of cortical sources of EEG activity.

Ecological validity of neurofeedback: modulation of slow wave EEG enhances musical performance.

Biofeedback-assisted modulation of electrocortical activity has been established to have intrinsic clinical benefits and has been shown to improve cognitive performance in healthy humans. In order to further investigate the pedagogic relevance of electroencephalograph (EEG) biofeedback (neurofeedback) for enhancing normal function, a series of investigations assessed the training's impact on an ecologically valid real-life behavioural performance measure: music performance under stressful conditions in conservatoire students. In a pilot study, single-blind expert ratings documented improvements in musical performance in a student group that received training on attention and relaxation related neurofeedback protocols, and improvements were highly correlated with learning to progressively raise theta (5-8 Hz) over alpha (8-11 Hz) band amplitudes. These findings were replicated in a second experiment where an alpha/theta training group displayed significant performance enhancement not found with other neurofeedback training protocols or in alternative interventions, including the widely applied Alexander technique.

Quantitative EEG analysis in obsessive compulsive disorder.

Quantitative analysis of the EEG (q-EEG) in patients with obsessive compulsive disorder (OCD) showed a decreased beta and an increased theta power at frontotemporal regions. The patients who had higher scores in doubting test (Maudsley Obsessive Compulsive Questionnaire) and more severely ill patients shared similar q-EEG features. The relative theta powers were significantly increased and alpha powers were significantly decreased in these patients, particularly in the frontotemporal region. It was suggested that the q-EEG may be useful in investigating the OCD patients with heterogeneous characteristics.

Disruption of early event-related theta synchronization of human EEG in alexithymics viewing affective pictures.

The 62-channel EEG was recorded while control non-alexithymic (n=21) and alexithymic (n=20) participants viewed sequentially presented neutral, pleasant and unpleasant pictures and subjectively rated them after each presentation. The event-related synchronization (ERS) to these stimuli was assessed in the theta-1 (4-6 Hz) and theta-2 (6-8 Hz) frequency bands. The obtained findings indicate that alexithymia influences perception of only emotional stimuli. Over anterior cortical regions alexithymia vs. control individuals in response to both pleasant and unpleasant stimuli manifested decreased left hemisphere ERS in the early test period of 0-200 ms along with enhanced ERS in response to negative vs. positive and neutral stimuli in the right hemisphere at 200-600 ms after stimulus onset. The findings provide the first EEG evidence that alexithymia construct, associated with a cognitive deficit in initial evaluation of emotion, is indexed by disrupted early frontal synchronization in the upper theta band that can be best interpreted to reflect disregulation during appraisal of emotional stimuli.

[Neural mechanism of hippocampal memory organized by theta rhythm].

The firing of hippocampal principal cells in freely running rats exhibits a progressive phase retardation as the animal passes through a cell's "place" field. It is called "phase precession" and is of interest as a possible neural mechanism of the hippocampus dependent memory. We analyze the complexity of phase-position distributions of spikes by estimating the probability density functions. Although these distributions vary among different cells and regions, this complexity is well described by a superposition of two normal distribution functions, suggesting that the firing behavior consists of two components. In one, the firing phase shifts over a range of about 180 degrees. The functional relevance is further elucidated by analyzing the experience-dependent change of spike distribution. These results suggest that the temporal relation among place cells endows the selective LTP for the memory of temporal sequence. It provides a fundamental neural mechanism of episodic memory.

Non-linear dynamic complexity of the human EEG during meditation.

We used non-linear analysis to investigate the dynamical properties underlying the EEG in the model of Sahaja Yoga meditation. Non-linear dimensional complexity (DCx) estimates, indicating complexity of neuronal computations, were analyzed in 20 experienced meditators during rest and meditation using 62-channel EEG. When compared to rest, the meditation was accompanied by a focused decrease of DCx estimates over midline frontal and central regions. By contrast, additionally computed linear measures exhibited the opposite direction of changes: power in the theta-1 (4-6 Hz), theta-2 (6-8 Hz) and alpha-1 (8-10 Hz) frequency bands was increased over these regions. The DCx estimates negatively correlated with theta-2 and alpha-1 and positively with beta-3 (22-30 Hz) band power. It is suggested that meditative experience, characterized by less complex dynamics of the EEG, involves 'switching off' irrelevant networks for the maintenance of focused internalized attention and inhibition of inappropriate information. Overall, the results point to the idea that dynamically changing inner experience during meditation is better indexed by a combination of non-linear and linear EEG variables.

Hippocampal theta oscillations and classical conditioning.

Studies are reviewed that support a hypothesized role for hippocampal theta oscillations in the neural plasticity underlying behavioral learning. Begun in Richard F. Thompson's laboratory in the 1970s, these experiments have documented a relationship between free-running 3- to 7-Hz hippocampal slow waves (theta) and rates of acquisition in rabbit classical nictitating membrane (NM) conditioning. Lesion and drug manipulations of septohippocampal projections have affected NM and jaw movement conditioning in ways consistent with a theta-related brain state being an important modulator of behavioral acquisition. These findings provide essential empirical support for the recently developed neurobiological and computational models that posit an important role for rhythmic oscillations (such as theta) in cellular plasticity and behavioral learning.

[Psychophysiological mechanisms of stress in subjects with different representation of activation]. / Psikhofiziologicheskie mekhanizmy stressa u lits s razlichnoi vyrazhennost'iu aktivatsii.

The EEG spectral power was calculated in 102 students aged 18-25 years in three experimental conditions (during the common educational process, immediately before and after an examination). Before the examination (stress situation), predominant activation of the right anterior cortical quadrant (the area related with negative emotions, according to R. Davidson, 1993) was revealed by the asymmetry coefficient of the beta rhythm. Subjects with low amplitude of the alpha rhythm (more activated) manifested not only emotional but also autonomic disturbances, while only emotional signs were pronounced in students with high alpha (less activated). Increase in the theta rhythm spectral power during stress and its decrease in the poststress period were observed in the less activated persons, which is considered to be a normal reaction to emotionally negative stimuli. On the contrary, in students with low alpha the theta rhythm power in the stress situation was decreased pointing to their emotional instability. In this group, as distinct from the first one, the beta 2 rhythm recorded in the right anterior cortical quadrant did not decrease in the poststress situation. Together with the observed theta rhythm, decrease in the left-hemisphere and bilateral prefrontal areas in the stress situation, this deviation testifies to a predisposition to the reactive depression of these subjects.

Theta band power changes in normal and dyslexic children.

OBJECTIVE: Tonic and phasic (event-related) theta band power changes were analyzed in a sample of 8 dyslexic and 8 control children. Previous research with healthy subjects suggests that electroencephalograph (EEG) theta activity reflects the encoding of new information into working memory. The aim of the present study was to investigate whether the processing deficits of dyslexics are related to a reduced phasic theta response during reading. METHOD: The EEG was recorded while subjects were reading numbers, words and pseudowords and analyzed in a lower and upper theta band (4--8 Hz). A phasic response is measured in terms of an increase in event related band power during reading with respect to a reference interval. Tonic power is measured in terms of (log) band power during a reference interval. RESULTS: Large group differences in tonic and phasic lower theta were found for occipital sites where dyslexics show a complete lack of pseudoword processing. For words, only controls show a highly selective left hemispheric processing advantage. CONCLUSIONS: Dyslexics have a lack to encode pseudowords in visual working memory with a concomitant lack of frontal processing selectivity. The upper theta band shows a different pattern of results which can be best interpreted to reflect the effort during the encoding process.

Episodic retrieval is reflected by a process specific increase in human electroencephalographic theta activity.

Is an increase in theta during retrieval due (primarily) to the access of a stored code or to more general processes? The electroencephalogram was recorded while subjects performed a recognition task with pictures. According to the event-related desynchronization/synchronization method, the percentage of band power changes was calculated during encoding and retrieval for a theta and three alpha bands. Significant results were obtained (with minor exceptions) only in the theta band. The increase in theta was significantly larger during retrieval than during encoding but did not differ significantly between new and successfully retrieved old pictures. Because a memory trace is lacking for new pictures, the increase in theta during retrieval reflects primarily general processing demands of a complex episodic memory system.

Binaural-beat induced theta EEG activity and hypnotic susceptibility.

Six participants varying in degree of hypnotizability (2 lows, 2 mediums, and 2 highs) were exposed to 3 20-minute sessions of a binaural-beat sound stimulation protocol designed to enhance theta brainwave activity. The Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) was used for pre- and post-stimulus measures of hypnotic susceptibility. A time-series analysis was utilized to evaluate anterior theta activity in response to binaural-beat sound stimulation over baseline and stimulus sessions. The protocol designed to increase anterior theta activity resulted in a significant increase in percent theta for 5 of 6 participants. Hypnotic susceptibility levels remained stable in the high-susceptible group and increased significantly in the low and medium-susceptible groups.

Brain dynamics in theta and alpha frequency bands and working memory performance in humans.

In this study non-linear and linear global electroencephalogram (EEG) changes during a visual working memory task were studied using a separate analysis of theta, lower alpha and upper alpha band filtered data. EEGs were recorded in 21 healthy subjects (62.5 year; SD 2.1; 12 females, nine males) during an eyes-closed no-task condition and a working memory condition. Coarse-grained dimension was estimated for both conditions from spatially embedded EEG data filtered in the theta band and both alpha bands. Linear measures of coupling and mean amplitude were also computed. During the working memory condition lower alpha band dimension increased. Linear analysis showed alpha1 band desynchronization. Female subjects had a higher dimension in the theta band as well as more desynchronization in the theta and alpha1 band. Working memory capacity correlated with a lower theta band dimension during the no-task condition in female subjects. The increase in alpha1 band complexity can be interpreted as increased desynchronization corresponding with attentional processes. Higher complexity/desynchronization in females seems to be a more structural phenomenon and may be more intimately related to task performance.