A Generalized Framework for Quantifying the Dynamics of EEG Event-Related Desynchronization

Brains were built by evolution to react swiftly to environmental challenges. Thus, sensory stimuli must be processed ad hoc, i.e., independent—to a large extent—from the momentary brain state incidentally prevailing during stimulus occurrence. Accordingly, computational neuroscience strives to model the robust processing of stimuli in the presence of dynamical cortical states. A pivotal feature of ongoing brain activity is the regional predominance of EEG eigenrhythms, such as the occipital alpha or the pericentral mu rhythm, both peaking spectrally at 10 Hz. Here, we establish a novel generalized concept to measure event-related desynchronization (ERD), which allows one to model neural oscillatory dynamics also in the presence of dynamical cortical states. Specifically, we demonstrate that a somatosensory stimulus causes a stereotypic sequence of first an ERD and then an ensuing amplitude overshoot (event-related synchronization), which at a dynamical cortical state becomes evident only if the natural relaxation dynamics of unperturbed EEG rhythms is utilized as reference dynamics. Moreover, this computational approach also encompasses the more general notion of a “conditional ERD,” through which candidate explanatory variables can be scrutinized with regard to their possible impact on a particular oscillatory dynamics under study. Thus, the generalized ERD represents a powerful novel analysis tool for extending our understanding of inter-trial variability of evoked responses and therefore the robust processing of environmental stimuli

The Dynamics of Sensorimotor Cortical Oscillations during the Observation of Hand Movements: An EEG Study

Background The observation of action done by others determines a desynchronization of the rhythms recorded from cortical central regions. Here, we examined whether the observation of different types of hand movements (target directed, non-target directed, cyclic and non-cyclic) elicits different EEG cortical temporal patterns. Methodology Video-clips of four types of hand movements were shown to right-handed healthy participants. Two were target directed (grasping and pointing) motor acts; two were non-target directed (supinating and clenching) movements. Grasping and supinating were performed once, while pointing and clenching twice (cyclic movements). High-density EEG was recorded and analyzed by means of wavelet transform, subdividing the time course in time bins of 200 ms. The observation of all presented movements produced a desynchronization of alpha and beta rhythms in central and parietal regions. The rhythms desynchronized as soon as the hand movement started, the nadir being reached around 700 ms after movement onset. At the end of the movement, a large power rebound occurred for all bands. Target and non-target directed movements produced an alpha band desynchronization in the central electrodes at the same time, but with a stronger desynchronization and a prolonged rebound for target directed motor acts. Most interestingly, there was a clear correlation between the velocity profile of the observed movements and beta band modulation. Significance Our data show that the observation of motor acts determines a modulation of cortical rhythm analogous to that occurring during motor act execution. In particular, the cortical motor system closely follows the velocity of the observed movements. This finding provides strong evidence for the presence in humans of a mechanism (mirror mechanism) mapping action observation on action execution motor programs

Source analysis of beta-synchronisation and cortico-muscular coherence after movement termination based on high resolution electroencephalography

We hypothesized that post-movement beta synchronization (PMBS) and cortico-muscular coherence (CMC) during movement termination relate to each other and have similar role in sensorimotor integration. We calculated the parameters and estimated the sources of these phenomena.We measured 64-channel EEG simultaneously with surface EMG of the right first dorsal interosseus muscle in 11 healthy volunteers. In Task1, subjects kept a medium-strength contraction continuously; in Task2, superimposed on this movement, they performed repetitive self-paced short contractions. In Task3 short contractions were executed alone. Time-frequency analysis of the EEG and CMC was performed with respect to the offset of brisk movements and averaged in each subject. Sources of PMBS and CMC were also calculated.High beta power in Task1, PMBS in Task2-3, and CMC in Task1-2 could be observed in the same individual frequency bands. While beta synchronization in Task1 and PMBS in Task2-3 appeared bilateral with contralateral predominance, CMC in Task1-2 was strictly a unilateral phenomenon; their main sources did not differ contralateral to the movement in the primary sensorimotor cortex in 7 of 11 subjects in Task1, and in 6 of 9 subjects in Task2. In Task2, CMC and PMBS had the same latency but their amplitudes did not correlate with each other. In Task2, weaker PMBS source was found bilaterally within the secondary sensory cortex, while the second source of CMC was detected in the premotor cortex, contralateral to the movement. In Task3, weaker sources of PMBS could be estimated in bilateral supplementary motor cortex and in the thalamus. PMBS and CMC appear simultaneously at the end of a phasic movement possibly suggesting similar antikinetic effects, but they may be separate processes with different active functions. Whereas PMBS seems to reset the supraspinal sensorimotor network, cortico-muscular coherence may represent the recalibration of cortico-motoneuronal and spinal systems

Relationship between Activity in Human Primary Motor Cortex during Action Observation and the Mirror Neuron System

The attenuation of the beta cortical oscillations during action observation has been interpreted as evidence of a mirror neuron system (MNS) in humans. Here we investigated the modulation of beta cortical oscillations with the viewpoint of an observed action. We asked subjects to observe videos of an actor making a variety of arm movements. We show that when subjects were observing arm movements there was a significant modulation of beta oscillations overlying left and right sensorimotor cortices. This pattern of attenuation was driven by the side of the screen on which the observed movement occurred and not by the hand that was observed moving. These results are discussed in terms of the firing patterns of mirror neurons in F5 which have been reported to have similar properties

Long Lasting Modulation of Cortical Oscillations after Continuous Theta Burst Transcranial Magnetic Stimulation

Transcranial magnetic theta burst stimulation (TBS) differs from other high-frequency rTMS protocols because it induces plastic changes up to an hour despite lower stimulus intensity and shorter duration of stimulation. However, the effects of TBS on neuronal oscillations remain unclear. In this study, we used electroencephalography (EEG) to investigate changes of neuronal oscillations after continuous TBS (cTBS), the protocol that emulates long-term depression (LTD) form of synaptic plasticity. We randomly divided 26 healthy humans into two groups receiving either Active or Sham cTBS as control over the left primary motor cortex (M1). Post-cTBS aftereffects were assessed with behavioural measurements at rest using motor evoked potentials (MEPs) and at active state during the execution of a choice reaction time (RT) task in combination with continuous electrophysiological recordings. The cTBS-induced EEG oscillations were assessed using event-related power (ERPow), which reflected regional oscillatory activity of neural assemblies of θ (4–7.5 Hz), low α (8–9.5 Hz), µ (10–12.5 Hz), low β (13–19.5 Hz), and high β (20–30 Hz) brain rhythms. Results revealed 20-min suppression of MEPs and at least 30-min increase of ERPow modulation, suggesting that besides MEPs, EEG has the potential to provide an accurate cortical readout to assess cortical excitability and to investigate the interference of cortical oscillations in the human brain post-cTBS. We also observed a predominant modulation of β frequency band, supporting the hypothesis that cTBS acts more on cortical level. Theta oscillations were also modulated during rest implying the involvement of independent cortical theta generators over the motor network post cTBS. This work provided more insights into the underlying mechanisms of cTBS, providing a possible link between synchronised neural oscillations and LTD in humans

What Happens in Between? Human Oscillatory Brain Activity Related to Crossmodal Spatial Cueing

Previous studies investigated the effects of crossmodal spatial attention by comparing the responses to validly versus invalidly cued target stimuli. Dynamics of cortical rhythms in the time interval between cue and target might contribute to cue effects on performance. Here, we studied the influence of spatial attention on ongoing oscillatory brain activity in the interval between cue and target onset. In a first experiment, subjects underwent periods of tactile stimulation (cue) followed by visual stimulation (target) in a spatial cueing task as well as tactile stimulation as a control. In a second experiment, cue validity was modified to be 50%, 75%, or else 25%, to separate effects of exogenous shifts of attention caused by tactile stimuli from that of endogenous shifts. Tactile stimuli produced: 1) a stronger lateralization of the sensorimotor beta-rhythm rebound (15–22 Hz) after tactile stimuli serving as cues versus not serving as cues; 2) a suppression of the occipital alpha-rhythm (7–13 Hz) appearing only in the cueing task (this suppression was stronger contralateral to the endogenously attended side and was predictive of behavioral success); 3) an increase of prefrontal gamma-activity (25–35 Hz) specifically in the cueing task. We measured cue-related modulations of cortical rhythms which may accompany crossmodal spatial attention, expectation or decision, and therefore contribute to cue validity effects. The clearly lateralized alpha suppression after tactile cues in our data indicates its dependence on endogenous rather than exogenous shifts of visuo-spatial attention following a cue independent of its modality

Dissociable Influences of Auditory Object vs. Spatial Attention on Visual System Oscillatory Activity

Given that both auditory and visual systems have anatomically separate object identification (“what”) and spatial (“where”) pathways, it is of interest whether attention-driven cross-sensory modulations occur separately within these feature domains. Here, we investigated how auditory “what” vs. “where” attention tasks modulate activity in visual pathways using cortically constrained source estimates of magnetoencephalograpic (MEG) oscillatory activity. In the absence of visual stimuli or tasks, subjects were presented with a sequence of auditory-stimulus pairs and instructed to selectively attend to phonetic (“what”) vs. spatial (“where”) aspects of these sounds, or to listen passively. To investigate sustained modulatory effects, oscillatory power was estimated from time periods between sound-pair presentations. In comparison to attention to sound locations, phonetic auditory attention was associated with stronger alpha (7–13 Hz) power in several visual areas (primary visual cortex; lingual, fusiform, and inferior temporal gyri, lateral occipital cortex), as well as in higher-order visual/multisensory areas including lateral/medial parietal and retrosplenial cortices. Region-of-interest (ROI) analyses of dynamic changes, from which the sustained effects had been removed, suggested further power increases during Attend Phoneme vs. Location centered at the alpha range 400–600 ms after the onset of second sound of each stimulus pair. These results suggest distinct modulations of visual system oscillatory activity during auditory attention to sound object identity (“what”) vs. sound location (“where”). The alpha modulations could be interpreted to reflect enhanced crossmodal inhibition of feature-specific visual pathways and adjacent audiovisual association areas during “what” vs. “where” auditory attention

Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

BACKGROUND: Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. METHODOLOGY/PRINCIPAL FINDINGS: We characterized the genes generally involved in human advanced atherosclerotic (AHA type V-VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25). CONCLUSIONS: This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds

Two randomised and placebo-controlled studies of an oral prostacyclin analogue (Iloprost) in severe leg ischaemia [The Oral Iloprost in severe Leg Ischaemia Study Group]

Two separate studies are described using the same prostacyclin analogue in a similar group of patients. Objectives: to assess the tolerability and efficacy of two dose regimens of oral Iloprost compared with placebo in the treatment of patients with ischaemic ulcers, gangrene or rest pain due to severe arterial disease over a period of 4 weeks (Study A) and one year (Study B). Design: multicentre, placebo controlled, double-blind, randomized prospective studies. Subjects & Methods: 178 (study A) and 624 (study B) patients with trophic skin lesions (ulcers or gangrene) or ischaemic rest pain due to severe arterial disease. To confirm severe arterial disease patients were required to have a systolic ankle Doppler pressure of 70 mmHg or less or a toe systolic Doppler pressure of 50 mmHg or less in one leg.In both studies patients were randomly allocated to three treatment groups: placebo, low dose Iloprost (50\u2013100 g twice a day) or high dose (150\u2013200 g twice a day) In Study A the main outcome measures were tolerability of different doses of Iloprost and death, major amputation, healing of trophic lesions and relief of rest pain at the end of the follow up, which was 5 months after the end of the treatment. In Study B the primary end point was time to major amputation and stroke or death up to 12 months. Secondary pre-defined end points included the combined end point of patients alive without amputation, no trophic skin changes, no rest pain and not on regular analgesics. Results: the proportion of patients who completed the 4-week treatment period in Study A at the intended dose was 58%, 43%, 45% respectively in the placebo, low dose and high dose Iloprost groups. In an intention to treat analysis the proportion of patients who survived without major amputation, ulcers or gangrene and had no rest pain was 11% in the placebo group, 19% in the low dose iloprost group and 28% in the high dose Iloprost group. The pooled Iloprost groups showed a statistically significantly better result than the placebo group (p=0.04), as did the high dose Iloprost group compared to the placebo (p=0.014). In Study B there was no treatment benefit in terms of a primary end point of amputation and death. However the secondary combined end point of patients who survived without a major amputation, ulcers or gangrene and had no rest pain, nor a need for regular analgesia was favourable for Iloprost, with 18% of patients in the placebo group reaching this optimal secondary end point, compared to 23% in the low dose Iloprost group and 26% in the higher dose Iloprost group (p<0.05). Conclusions: oral Iloprost administered for a year showed no clear benefit in patients with advanced severe leg ischaemia (PAOD III and IV). The results obtained with 4 weeks\u2019 treatment in Study A and in previous trials of intravenous Iloprost could not be reproduce

Cortico-muscular synchronization during isometric muscle contraction in humans as revealed by magnetoencephalography

Magnetoencephalographic (MEG) and electromyographic (EMG) signals were recorded from six subjects during isometric contraction of four different muscles.Cortical sources were located from the MEG signal which was averaged timelocked to the onset of motor unit potentials. A spatial filtering algorithm was used to estimate the source activity. Sources were found in the primary motor cortex (M1) contralateral to the contracted muscle. Significant coherence between rectified EMG and M1 activity was seen in the 20 Hz frequency range in all subjects.Interactions between the motor cortex and spinal motoneuron pool were investigated by separately studying the non-stationary phase and amplitude dynamics of M1 and EMG signals.Delays between M1 and EMG signals, computed from their phase difference, were found to be in agreement with conduction times from the primary motor cortex to the respective muscle. The time-dependent cortico-muscular phase synchronization was found to be correlated with the time course of both M1 and EMG signals.The findings demonstrate that the coupling between the primary motor cortex and motoneuron pool is at least partly due to phase synchronization of 20 Hz oscillations which varies over time. Furthermore, the consistent phase lag between M1 and EMG signals, compatible with conduction time between M1 and the respective muscle with the M1 activity preceding EMG activity, supports the conjecture that the motor cortex drives the motoneuron pool