Evoked responses to rhythmic visual stimulation vary across sources of intrinsic alpha activity in humans.

Rhythmic flickering visual stimulation produces steady-state visually evoked potentials (SSVEPs) in electroencephalogram (EEG) recordings. Based on electrode-level analyses, two dichotomous models of the underpinning mechanisms leading to SSVEP generation have been proposed: entrainment or superposition, i.e., phase-alignment or independence of endogenous brain oscillations from flicker-induced oscillations, respectively. Electrode-level analyses, however, represent an averaged view of underlying 'source-level' activity, at which variability in SSVEPs may lie, possibly suggesting the co-existence of multiple mechanisms. To probe this idea, we investigated the variability of SSVEPs derived from the sources underpinning scalp EEG responses during presentation of a flickering radial checkerboard. Flicker was presented between 6 and 12 Hz in 1 Hz steps, and at individual alpha frequency (IAF i.e., the dominant frequency of endogenous alpha oscillatory activity). We tested whether sources of endogenous alpha activity could be dissociated according to evoked responses to different flicker frequencies relative to IAF. Occipitoparietal sources were identified by temporal independent component analysis, maximal resting-state alpha power at IAF and source localisation. The pattern of SSVEPs to rhythmic flicker relative to IAF was estimated by correlation coefficients, describing the correlation between the peak-to-peak amplitude of the SSVEP and the absolute distance of the flicker frequency from IAF across flicker conditions. We observed extreme variability in correlation coefficients across sources, ranging from -0.84 to 0.93, with sources showing largely different coefficients co-existing within subjects. This result demonstrates variation in evoked responses to flicker across sources of endogenous alpha oscillatory activity. Data support the idea of multiple SSVEP mechanisms.

Dynamic regulation of interregional cortical communication by slow brain oscillations during working memory.

Transiently storing information and mentally manipulating it is known as working memory. These operations are implemented by a distributed, fronto-parietal cognitive control network in the brain. The neural mechanisms controlling interactions within this network are yet to be determined. Here, we show that during a working memory task the brain uses an oscillatory mechanism for regulating access to prefrontal cognitive resources, dynamically controlling interactions between prefrontal cortex and remote neocortical areas. Combining EEG with non-invasive brain stimulation we show that fast rhythmical brain activity at posterior sites are nested into prefrontal slow brain waves. Depending on cognitive demand this high frequency activity is nested into different phases of the slow wave enabling dynamic coupling or de-coupling of the fronto-parietal control network adjusted to cognitive effort. This mechanism constitutes a basic principle of coordinating higher cognitive functions in the human brain.

Altered modulation of intracortical excitability during movement preparation in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome is a neuropsychiatric disorder in which cortical disinhibition has been proposed as a pathophysiological mechanism involved in the generation of tics. Tics are typically reduced during task performance and concentration. How this task-dependent reduction of motor symptoms is represented in the brain is not yet understood. The aim of the current research was to study motorcortical excitability at rest and during the preparation of a simple motor task. Transcranial magnetic stimulation was used to examine corticospinal excitability, short-interval intracortical inhibition and intracortical facilitation in a group of 11 patients with Gilles de la Tourette syndrome and age-matched healthy controls. Parameters of cortical excitability were evaluated at rest and at six points in time during the preparation of a simple finger movement. Patients with Gilles de la Tourette syndrome displayed significantly reduced short-interval intracortical inhibition at rest, while no differences were apparent for unconditioned motor evoked potential or intracortical facilitation. During the premovement phase, significant differences between groups were seen for single pulse motor evoked potential amplitudes and short-interval intracortical inhibition. Short-interval intracortical inhibition was reduced in the early phase of movement preparation (similar to rest) followed by a transition towards more inhibition. Subsequently modulation of short-interval intracortical inhibition was comparable to controls, while corticospinal recruitment was reduced in later phases of movement preparation. The present data support the hypothesis of motorcortical disinhibition in Gilles de la Tourette syndrome at rest. During performance of a motor task, patients start from an abnormally disinhibited level of short-interval intracortical inhibition early during movement preparation with subsequent modulation of inhibitory activity similar to healthy controls. We hypothesize that while at rest, abnormal subcortical inputs from aberrant striato-thalamic afferents target the motor cortex, during motor performance, motor cortical excitability most likely underlies top-down control from higher motor areas and prefrontal cortex, which override these abnormal subcortical inputs to guarantee adequate behavioural performance.

Functional relevance of ipsilateral motor activation in congenital hemiparesis as tested by fMRI-navigated TMS.

Many, but not all patients with congenital hemiparesis (i.e., hemiparesis due to a pre-, peri- or neonatally acquired brain lesion) control their paretic hands via ipsilateral cortico-spinal projections from the contra-lesional hemisphere (CON-H). Patients who still control their paretic hands via preserved crossed cortico-spinal projections from the damaged hemisphere nevertheless show increased fMRI activation during paretic hand movements in the CON-H. We used fMRI-navigated rTMS induced functional lesions over the primary motor cortex (M1) hand area, the dorsal premotor cortex (dPMC) and the superior parietal lobe (SPL) of the CON-H in four of these patients to investigate whether this increased ipsilateral activation during finger movements of the paretic hand contributes to movement performance. Functional lesions of the dPMC and M1 but not SPL of the CON-H induced decreased temporal preciseness of finger sequences. The present results argue for a possible role of dPMC and M1 of the CON-H on complex motor behavior even in those patients with congenital hemiparesis who control their paretic hands via crossed cortico-spinal projections from the damaged hemisphere.

Spontaneous locally restricted EEG alpha activity determines cortical excitability in the motor cortex.

There is growing interest in the functional meaning of rhythmical brain activity. For oscillatory brain activity around 10 Hz in the human electroencephalogram (EEG) it is discussed whether it is associated with the level of cortical excitation. However, it is not clear whether the relation between 10 Hz EEG oscillatory activity and cortical excitability is a global, locally very unspecific phenomenon or whether focal 10 Hz oscillations in the human brain are a highly specific correlate of the cortical excitation level. To determine this open question, multichannel EEG was combined with transcranial magnetic stimulation (TMS) applied to the primary motor cortex in this study. The present data showed that a motor evoked potential was elicited more easily when alpha power immediately preceding the magnetic pulse was low, and vice versa. Interestingly, this effect was only found for very local EEG alpha activity at sites overlying the cortical motor areas to which the TMS pulses were applied. This was verified using source localization in 3D space. These data provide evidence that the magnitude of motor cortical excitability is determined by the amount of topographically specific alpha oscillations in the sensorimotor cortex.

Frontal midline theta in the pre-shot phase of rifle shooting: differences between experts and novices.

In the present study the time course of frontal midline theta (Fmtheta) during the aiming period in rifle shooting was investigated. Experts (n=8) and novices (n=10) had to shoot repeatedly while EEG was recorded, and the time course of Fmtheta during the aiming period was significantly different between the two groups, showing a steady increase of power for the last 3s before the shot only for experts, but not for novices. Source analysis (LORETA) indicated a significantly stronger theta activity for experts strictly located at the anterior cingulate area and medial frontal cortex, locations well known for focused attention. The results suggest that experts and novices use different strategies during the aiming period. While novices keep a relatively constant amount of attention to the target, experts are able to increase attention exactly to the time point of the trigger pull.

Are event-related potential components generated by phase resetting of brain oscillations? A critical discussion.

The event-related potential (ERP) is one of the most popular measures in human cognitive neuroscience. During the last few years there has been a debate about the neural fundamentals of ERPs. Two models have been proposed: The evoked model states that additive evoked responses which are completely independent of ongoing background electroencephalogram generate the ERP. On the other hand the phase reset model suggests a resetting of ongoing brain oscillations to be the neural generator of ERPs. Here, evidence for either of the two models is presented and validated, and their possible impact on cognitive neuroscience is discussed. In addition, future prospects on this field of research are presented.

Dissociation of sustained attention from central executive functions: local activity and interregional connectivity in the theta range.

Human brain oscillatory activity was analysed in the electroencephalographic theta frequency range (4-7 Hz) while subjects executed complex sequential finger movements with varying task difficulty and memory load. Local frontal-midline theta activity was associated with the general level of cognitive demand, with the highest amplitudes in the most demanding condition. Using low-resolution electromagnetic tomography analysis (LORETA), this theta activity was localized in the anterior cingulate gyrus including the cingulate motor area. These results suggest that local theta activity in the anterior cingulate gyrus represents correlates of an attentional system that allocate cognitive resources. In addition, interregional connectivity in the theta frequency range was modulated by memory-related executive functions independently of task difficulty. Connectivity analyses revealed a more distributed long-range network including frontal and parietal cortices during execution of novel compared with well-trained finger movement sequences. Thus, these results are compatible with a model in which theta long-range coupling indicates integration of sensory information into executive control components of complex motor behaviour.

Relevance of EEG alpha and theta oscillations during task switching.

In a task switching design, we investigated the question whether long-range theta coupling primarily reflects top-down control processes. Switch and stay trials did not differ with respect to memory load or global working memory (WM) demands. The results revealed significantly stronger theta coupling (in a range of 4-7 Hz) between prefrontal and posterior regions during switch as compared to stay trials. Power differences, reflecting more local effects, were largest in the upper alpha band (10-13 Hz) and over posterior brain areas, possibly reflecting long-term memory activation. The conclusion of the present study is that long-range coherent oscillatory activity in the theta band reflects top-down activation rather than global WM functions.

Oscillatory EEG correlates of episodic trace decay.

Recent studies suggest that human theta oscillations appear to be functionally associated with memory processes. It is less clear, however, to what type of memory sub-processes theta is related. Using a continuous word recognition task with different repetition lags, we investigate whether theta reflects the strength of an episodic memory trace or general processing demands, such as task difficulty. The results favor the episodic trace decay hypothesis and show that during the access of an episodic trace in a time window of approximately 200-400 ms, theta power decreases with increasing lag (between the first and second presentation of an item). LORETA source localization of this early theta lag effect indicates that parietal regions are involved in episodic trace processing, whereas right frontal regions may guide the process of retrieval. We conclude that episodic encoding can be characterized by two different stages: traces are first processed at parietal sites at approximately 300 ms, then further processing takes place in regions of the medial temporal lobe at approximately 500 ms. Only the first stage is related to theta, whereas the second is reflected by a slow wave with a frequency of approximately 2.5 Hz.

A shift of visual spatial attention is selectively associated with human EEG alpha activity.

Event-related potentials and ongoing oscillatory electroencephalogram (EEG) activity were measured while subjects performed a cued visual spatial attention task. They were instructed to shift their attention to either the left or right visual hemifield according to a cue, which could be valid or invalid. Thereafter, a peripheral target had to be evaluated. At posterior parietal brain areas early components of the event-related potential (P1 and N1) were higher when the cue had been valid compared with invalid. An anticipatory attention effect was found in EEG alpha magnitude at parieto-occipital electrode sites. Starting 200 ms before target onset alpha amplitudes were significantly stronger suppressed at sites contralateral to the attended visual hemifield than ipsilateral to it. In addition, phase coupling between prefrontal and posterior parietal electrode sites was calculated. It was found that prefrontal cortex shows stronger phase coupling with posterior sites that are contralateral to the attended hemifield than ipsilateral sites. The results suggest that a shift of attention selectively modulates excitability of the contralateral posterior parietal cortex and that this posterior modulation of alpha activity is controlled by prefrontal regions.

Intelligence related upper alpha desynchronization in a semantic memory task.

Recent evidence shows that event-related (upper) alpha desynchronization (ERD) is related to cognitive performance. Several studies observed a positive, some a negative relationship. The latter finding, interpreted in terms of the neural efficiency hypothesis, suggests that good performance is associated with a more 'efficient', smaller extent of cortical activation. Other studies found that ERD increases with semantic processing demands and that this increase is larger for good performers. Studies supporting the neural efficiency hypothesis used tasks that do not specifically require semantic processing. Thus, we assume that the lack of semantic processing demands may at least in part be responsible for the reduced ERD. In the present study we measured ERD during a difficult verbal-semantic task. The findings demonstrate that during semantic processing, more intelligent (as compared to less intelligent) subjects exhibited a significantly larger upper alpha ERD over the left hemisphere. We conclude that more intelligent subjects exhibit a more extensive activation in a semantic processing system and suggest that divergent findings regarding the neural efficiency hypotheses are due to task specific differences in semantic processing demands.

Phase synchronization between theta and upper alpha oscillations in a working memory task.

Motivated by findings that theta and upper alpha oscillations respond selectively to different types of memory demands, we investigated the role of phase synchronization in a memory scanning task. During retention, we found a load dependent increase in upper alpha power at O2 and P4 and a significant upper alpha:theta phase synchronization between right posterior, central and left anterior sites. During retrieval, a load dependent increase in upper alpha phase locking was observed at O2 and an increase in upper alpha:theta phase synchronization between right posterior and left anterior sites. We suggest that theta reflects central executive functions whereas upper alpha may be important for the reactivation of long-term memory codes in short-term memory. The interplay between theta and upper alpha may be reflected by phase synchronization between these frequencies.

Intelligence related differences in EEG-bandpower.

Several studies on the relationship between event-related desynchronization/synchronization (ERD/ERS) and cognitive performance revealed contradictory results particularly for the alpha band. Studies from our laboratory have shown that good performers show a larger upper alpha ERD (interpreted in terms of larger cortical activation) than bad performers. In contrast, other researchers found evidence for the neural efficiency hypothesis, which states that more intelligent subjects exhibit a smaller extent of cortical activation, which is assumed to be reflected by a smaller upper alpha ERD. Here we address the question whether these divergent results may be due to differences in general task difficulty. Using a modified version of the RAVEN, individually divided into easy and difficult tasks, a group of average and a group of highly intelligent subjects (IQ- and IQ+) have been investigated. While in the theta frequency IQ+ subjects generally exhibited a significantly stronger activation, we found a significant interaction of task difficulty and IQ group in the upper alpha band, indicating both, a weaker activation for the high IQ group during the easy tasks, and a significant increase from easy to difficult tasks for IQ+ only.

The interplay between theta and alpha oscillations in the human electroencephalogram reflects the transfer of information between memory systems.

The exchange of information between the working and long-term memory system (WMS and LTMS) was investigated. We analyzed evoked theta and upper alpha desynchronization in a special memory task, designed to study the transfer of information between both memory systems. The results show that during attempts to retrieve information from the LTMS, evoked theta oscillations spread from anterior to posterior recording sites. When information actually is retrieved, the direction reverses and theta spreads to frontal sites. This time point--when direction reverses--varies between subjects to a large extent but is significantly correlated with memory performance and the onset of upper alpha desynchronization. We conclude that this phenomenon reflects the transfer of information between the WMS and LTMS

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.