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Physiological and behavioral effects induced through transcutaneous vagus nerve stimulation (tVNS) are under scrutiny in a growing number of studies, yet its mechanisms of action remain poorly understood. One candidate mechanism is a modulation of γ-aminobutyric acid (GABA) transmission through tVNS. Two recent behavioral studies suggest that such a GABAergic effect might occur in a lateralized fashion, i.e., the GABA modulation might be stronger in the left than in the right brain hemisphere after tVNS applied to the left ear. Using magnetoencephalography (MEG), we tested for GABA-associated modulations in resting and event-related brain oscillations and for a lateralization of those effects in a sample of 41 healthy young adults. Our data provide substantial evidence against all hypotheses, i.e., we neither find effects of tVNS on oscillatory power nor a lateralization of effects.

Ongoing oscillatory neural activity before stimulus onset influences subsequent visual perception. Specifically, both the power and the phase of oscillations in the alpha-frequency band (9-13 Hz) have been reported to predict the detection of visual stimuli. Up to now, the functional mechanisms underlying pre-stimulus power and phase effects on upcoming visual percepts are debated. Here, we used magnetoencephalography recordings together with a near-threshold visual detection task to investigate the neural generators of pre-stimulus power and phase and their impact on subsequent visual-evoked responses. Pre-stimulus alpha-band power and phase opposition effects were found consistent with previous reports. Source localization suggested clearly distinct neural generators for these pre-stimulus effects: Power effects were mainly found in occipital-temporal regions, whereas phase effects also involved prefrontal areas. In order to be functionally relevant, the pre-stimulus correlates should influence post-stimulus processing. Using a trial-sorting approach, we observed that only pre-stimulus power modulated the Hits versus Misses difference in the evoked response, a well-established post-stimulus neural correlate of near-threshold perception, such that trials with stronger pre-stimulus power effect showed greater post-stimulus difference. By contrast, no influence of pre-stimulus phase effects were found. In sum, our study shows distinct generators for two pre-stimulus neural patterns predicting visual perception, and that only alpha power impacts the post-stimulus correlate of conscious access. This underlines the functional relevance of prestimulus alpha power on perceptual awareness, while questioning the role of alpha phase.

It has been demonstrated that, while otherwise detrimental, noise can improve sensory perception under optimal conditions. The mechanism underlying this improvement is stochastic resonance. An inverted U-shaped relationship between noise level and task performance is considered as the signature of stochastic resonance. Previous studies have proposed the existence of stochastic resonance also in the human auditory system. However, the reported beneficial effects of noise are small, based on a small sample, and do not confirm the proposed inverted U-shaped function. Here, we investigated in two separate studies whether stochastic resonance may be present in the human auditory system by applying noise of different levels, either acoustically or electrically via transcranial random noise stimulation, while participants had to detect acoustic stimuli adjusted to their individual hearing threshold. We find no evidence for behaviorally relevant effects of stochastic resonance. Although detection rate for near-threshold acoustic stimuli appears to vary in an inverted U-shaped manner for some subjects, it varies in a U-shaped manner or in other manners for other subjects. Our results show that subjects do not benefit from noise, irrespective of its modality. In conclusion, our results question the existence of stochastic resonance in the human auditory system.

Imagine you are focusing on the traffic on a busy street to ride your bike safely when suddenly you hear the siren of an ambulance. This unexpected sound involuntarily captures your attention and interferes with ongoing performance. We tested whether this type of distraction involves a spatial shift of attention. We measured behavioral data and magnetoencephalographic alpha power during a crossmodal paradigm that combined an exogenous cueing task and a distraction task. In each trial, a task-irrelevant sound preceded a visual target (left or right). The sound was usually the same animal sound (i.e., standard sound). Rarely, it was replaced by an unexpected environmental sound (i.e., deviant sound). Fifty percent of the deviants occurred on the same side as the target, and 50% occurred on the opposite side. Participants responded to the location of the target. As expected, responses were slower to targets that followed a deviant compared to a standard. Crucially, this distraction effect was mitigated by the spatial relationship between the targets and the deviants: responses were faster when targets followed deviants on the same versus different side, indexing aspatialshift of attention. This was further corroborated by a posterior alpha power modulation that was higher in the hemisphere ipsilateral (vs. contralateral) to the location of the attention-capturing deviant. We suggest that this alpha power lateralization reflects a spatial attention bias. Overall, our data support the contention that spatial shifts of attention contribute to deviant distraction.

Objective Transcutaneous vagus nerve stimulation (tVNS) has been hypothesized to modulate γ-aminobutyric (GABA) transmission in the human brain. GABA in the motor cortex is highly correlated to measures of automatic motor inhibition that can be obtained in simple response priming paradigms. To test the effects of tVNS on GABA transmission, we measured tVNS-induced alterations in behavioral and electrophysiology during automatic motor inhibition. Methods Participants were 16 young, healthy adults (8 female). We combined a subliminal response priming paradigm with tVNS and EEG measurement. In this paradigm, automatic motor inhibition leads to a reversal of the priming effect, a phenomenon referred to as the negative compatibility effect (NCE). We compute the NCE separated by response hands, hypothesizing a modulation of the left-hand NCE. Using EEG we measured readiness potentials, an established electrophysiological index of cortical motor preparation. Results As hypothesized, for the ipsilateral hand/contralateral hemisphere, compared to sham stimulation, tVNS increased the NCE and modulated the electrophysiological readiness potentials. Conclusion Our results indicate that tVNS is selectively affecting the GABAergic system in the motor system contralateral to the stimulated ear as reflected in a behavioral and electrophysiological modulation. Significance We provide first combined behavioral and electrophysiological evidence for direct GABAergic neuromodulation through tVNS.

Background One key mechanism thought to underlie speech processing is the alignment of cortical brain rhythms to the acoustic input, a mechanism termed entrainment. Recent work showed that transcranial electrical stimulation (tES) in speech relevant frequencies or adapted to the speech envelope can in fact enhance speech processing. However, it is unclear whether an oscillatory tES is necessary, or if transients in the stimulation (e.g., peaks in the tES signal) at relevant times are sufficient. Objective In this study we used a novel pulsed-tES-protocol and tested behaviorally if a transiently pulsed - instead of a persistently oscillating - tES signal, can improve speech processing. Methods While subjects listened to spoken sentences embedded in noise, brief electric direct current pulses aligned to speech transients (syllable onsets) were applied to auditory cortex regions to modulate comprehension. Additionally, we modulated the temporal delay between tES-pulses and speech transients to test for periodic modulations of behavior, indicative of entrainment by tES. Results Speech comprehension was improved when tES-pulses were applied with a delay of 100 ms in respect to the speech transients. Contradictory to previous reports we find no periodic modulation of behavior. However, we find indications that periodic modulations can be spurious results of sampling behavioral data too coarsely. Conclusions Subject’s speech comprehension benefits from pulsed-tES, yet behavior is not modulated periodically. Thus, pulsed-tES can aid cortical entrainment to speech input, which is especially relevant in a noisy environment. Yet, pulsed-tES does not seem to entrain brain oscillations by itself.

Unexpected novel sounds capture one's attention, even when irrelevant to the task pursued (e.g., playing video game). This often comes at a cost to the task (e.g., slower responding). The neural basis for this behavioral distraction effect is not well understood and is subject of this study. Our approach was motivated by findings from cuing paradigms suggesting a link between modulations in oscillatory activity and voluntary attention shifts. The current study tested whether oscillatory activity is also modulated by a task-irrelevant auditory distractor, reflecting a neural signature of an involuntary shift of attention and accounting for the impaired task performance. We reanalyzed magnetoencephalographic data collected via an auditory-visual distraction paradigm in which a task-relevant visual stimulus was preceded by a task-irrelevant sound on each trial. In 87.5% this was a regular sound (Standard); in 12.5% this was a novel sound (Distractor). We compared nonphase locked oscillatory activity in a time window prior to the visual target as a function of the experimental manipulation (Distractor, Standard). We found low power in the pretarget time window for Distractors compared to Standards in the alpha and beta frequency bands. Importantly, individual alpha power correlated with response speed on a trial-by-trial basis for the Distractor only. Sources were localized to the occipital cortex, and also to the parietal and supratemporal cortices. These findings support our hypothesis that the distractor-related alpha power modulation indexes an involuntary shift of attention which accounts for the impaired task performance.

Transcranial alternating current stimulation (tACS) has been proposed as a tool to draw causal inferences on the role of oscillatory activity in cognitive functioning and has the potential to induce long-term changes in cerebral networks. However, the mechanisms of action of tACS are not yet clear, though previous modeling works have suggested that variability may be mediated by local and network-level brain states. We used magnetoencephalography (MEG) to record brain activity from 17 healthy participants as they kept their eyes open (EO) or closed (EC) while being stimulated either with sham, weak, or strong alpha-tACS using a montage commonly assumed to target occipital areas. We reconstructed the activity of sources in all stimulation conditions by means of beamforming. The analysis of resting-state data revealed an interaction of the external stimulation with the endogenous alpha power difference between EO and EC in the posterior cingulate. This region is remote from occipital cortex, which showed strongest EC vs. EO alpha modulation, thus suggesting state-dependency long-range effects of tACS. In a follow-up analysis of this online-tACS effect, we find evidence that this dependency effect could be mediated by functional network changes: connection strength from the precuneus, a region adjusting for a measure of network integration in the two states (EC vs. EO during no-tACS), was significantly correlated with the state-dependency effect in the posterior cingulate (during tACS). No analogous correlation could be found for alpha power modulations in occipital cortex. Altogether, this is the first strong evidence to illustrate how functional network architectures can shape tACS effects.

Scientific research from the last two decades has provided a vast amount of evidence that brain oscillations reflect physiological activity enabling diverse cognitive processes. The goal of this review is to give a broad empirical and conceptual overview of how ongoing oscillatory activity may support attention processes. Keeping in mind that definitions of cognitive constructs like attention are prone to being blurry and ambiguous, the present review focuses mainly on the neural correlates of ‘top-down’ attention deployment. In particular, we will discuss modulations of (ongoing) oscillatory activity during spatial, temporal, selective, and internal attention. Across these seemingly distinct attentional domains, we will summarize studies showing the involvement of two oscillatory processes observed during attention deployment: power modulations mainly in the alpha band, and phase modulations in lower frequency bands.This article is part of a Special Issue entitled SI: Prediction and Attention.

Brain oscillations are supposedly crucial for normal cognitive functioning and alterations are associated with cognitive dysfunctions. To demonstrate their causal role on behavior, entrainment approaches in particular aim at driving endogenous oscillations via rhythmic stimulation. Within this context, transcranial electrical stimulation, especially transcranial alternating current stimulation (tACS), has received renewed attention. This is likely due to the possibility of defining oscillatory stimulation properties precisely. Also, measurements comparing pre-tACS with post-tACS electroencephalography (EEG) have shown impressive modulations. However, the period during tACS has remained a blackbox until now, due to the enormous stimulation artifact. By means of application of beamforming to magnetoencephalography (MEG) data, we successfully recovered modulations of the amplitude of brain oscillations during weak and strong tACS. Additionally, we demonstrate that also evoked responses to visual and auditory stimuli can be recovered during tACS. The main contribution of the present study is to provide critical evidence that during ongoing tACS, subtle modulations of oscillatory brain activity can be reconstructed even at the stimulation frequency. Future tACS experiments will be able to deliver direct physiological insights in order to further the understanding of the contribution of brain oscillations to cognition and behavior.

Neural oscillations in the gamma range are the dominant rhythmic activation pattern in the human auditory cortex. These gamma oscillations are functionally relevant for the processing of rapidly changing acoustic information in both speech and non-speech sounds. Accordingly, there is a tight link between the temporal resolution ability of the auditory system and inherent neural gamma oscillations. Transcranial random noise stimulation (tRNS) has been demonstrated to specifically increase gamma oscillation in the human auditory cortex. However, neither the physiological mechanisms of tRNS nor the behavioral consequences of this intervention are completely understood. In the present study we stimulated the human auditory cortex bilaterally with tRNS while EEG was continuously measured. Modulations in the participants’ temporal and spectral resolution ability were investigated by means of a gap detection task and a pitch discrimination task. Compared to sham, auditory tRNS increased the detection rate for near-threshold stimuli in the temporal domain only, while no such effect was present for the discrimination of spectral features. Behavioral findings were paralleled by reduced peak latencies of the P50 and N1 component of the auditory event-related potentials (ERP) indicating an impact on early sensory processing. The facilitating effect of tRNS was limited to the processing of near-threshold stimuli while stimuli clearly below and above the individual perception threshold were not affected by tRNS. This non-linear relationship between the signal-to-noise level of the presented stimuli and the effect of stimulation further qualifies stochastic resonance (SR) as the underlying mechanism of tRNS on auditory processing. Our results demonstrate a tRNS related improvement in acoustic perception of time critical auditory information and, thus, provide further indices that auditory tRNS can amplify the resonance frequency of the auditory system.

Multiple theories of conscious phenomenology have been postulated within neuroscience; here we put evidence towards the "windowsto consciousness" (Win2Con) framework. This framework predicts that high connectivity states between the modular sensory hubs, and the frontalparietal network, before stimulus onset is a crucial factor in guiding the contents of consciousness. We tested this prediction by using the Rubin9s vase illusion - an image that evokes a bistable perception that alters between a pair of faces or a vase - while measuring magnetroencephalographic (MEG) response in 18 human subjects. Behavioural results indicated a stochastic trial-by-trial report of the vase or faces, subjects fluctuate between reporting a vase or faces. Sensor analysis revealed pristimulus differences in 12-17Hz low-frequency power, subsequent source projection suggested part of the power effect was present in the right lateral occipital area (LO) an area functionally relevant in object perception. Evoked effects were present in the sensor analysis, with a difference during the 350 - 375 msec time window. Source projection revealed that part of this difference resided in the right face-sensitive occipital face area (OFA). Using these two sources (i.e. LO and OFA) as seeds, we conducted a source space connectivity analysis, revealing variant connectivity to right inferior frontal gyrus (IFG): for the LO seed there was greater connectivity for vase vs. faces reports, conversely, for the OFA seed there was greater connectivity for face vs. vase reports. Our results support the framework of the Win2Con, as well as showing frontal and OFA connectivity effects face perception.

Despite recent success in analyzing brain oscillations recorded during transcranial alternating current stimulation (tACS), the field still requires further research to establish standards in artifact removal methods. This includes taking a step back from the removal of the tACS artifact and thoroughly characterizing the to-be-removed artifact. A recent study by Noury et al. (2016) contributed importantly to this endeavour by showing the existence of nonlinear artefacts in the tACS signal as seen by MEG and EEG. Unfortunately however this paper conveys the message that current artifact removal attempts have failed altogether and that—based on these available tools—brain oscillations recorded during tACS cannot be analyzed using MEG and EEG. Here we want to balance this overly pessimistic conclusion: In-depth reanalyses of our own data and phantom-head measurements indicate that nonlinearities can occur, but only when technical limits of the stimulator are reached. As such they are part of the “real” stimulation and not a specific MEG analysis problem. Future tACS studies should consider these technical limits to avoid any nonlinear modulations of the tACS artifact. We conclude that even with current approaches, brain oscillations recorded during tACS can be meaningfully studied in many practical cases.

The ability to represent the emerging regularity of sensory information from the external environment has been thought to allow one to probabilistically infer future sensory occurrences and thus optimize behavior. However, the underlying neural implementation of this process is still not comprehensively understood. Through a convergence of behavioral and neurophysiological evidence, we establish that the probabilistic inference of future events is critically linked to people's ability to maintain the recent past in working memory. Magnetoencephalography recordings demonstrated that when visual stimuli occurring over an extended time series had a greater statistical regularity, individuals with higher working-memory capacity (WMC) displayed enhanced slow-wave neural oscillations in the θ frequency band (4-8 Hz.) prior to, but not during stimulus appearance. This prestimulus neural activity was specifically linked to contexts where information could be anticipated and influenced the preferential sensory processing for this visual information after its appearance. A separate behavioral study demonstrated that this process intrinsically emerges during continuous perception and underpins a realistic advantage for efficient behavioral responses. In this way, WMC optimizes the anticipation of higher level semantic concepts expected to occur in the near future.

Unexpected novel sounds capture one's attention, even when irrelevant to the task pursued (e.g., playing video game). This often comes at a cost to the task (e.g., slower responding). The neural basis for this behavioral distraction effect is not well understood and is subject of this study. Our approach was motivated by findings from cuing paradigms suggesting a link between modulations in oscillatory activity and voluntary attention shifts. The current study tested whether oscillatory activity is also modulated by a task-irrelevant auditory distractor, reflecting a neural signature of an involuntary shift of attention and accounting for the impaired task performance. We reanalyzed magnetoencephalographic data collected via an auditory-visual distraction paradigm in which a task-relevant visual stimulus was preceded by a task-irrelevant sound on each trial. In 87.5% this was a regular sound (Standard); in 12.5% this was a novel sound (Distractor). We compared nonphase locked oscillatory activity in a time window prior to the visual target as a function of the experimental manipulation (Distractor, Standard). We found low power in the pretarget time window for Distractors compared to Standards in the alpha and beta frequency bands. Importantly, individual alpha power correlated with response speed on a trial-by-trial basis for the Distractor only. Sources were localized to the occipital cortex, and also to the parietal and supratemporal cortices. These findings support our hypothesis that the distractor-related alpha power modulation indexes an involuntary shift of attention which accounts for the impaired task performance.

An ever-increasing number of studies are pointing to the importance of network properties of the brain for understanding behavior such as conscious perception. However, with regards to the influence of prestimulus brain states on perception, this network perspective has rarely been taken. Our recent framework predicts that brain regions crucial for a conscious percept are coupled prior to stimulus arrival, forming pre-established pathways of information flow and influencing perceptual awareness. Using magnetoencephalography (MEG) and graph theoretical measures, we investigated auditory conscious perception in a near-threshold (NT) task and found strong support for this framework. Relevant auditory regions showed an increased prestimulus interhemispheric connectivity. The left auditory cortex was characterized by a hub-like behavior and an enhanced integration into the brain functional network prior to perceptual awareness. Right auditory regions were decoupled from non-auditory regions, presumably forming an integrated information processing unit with the left auditory cortex. In addition, we show for the first time for the auditory modality that local excitability, measured by decreased alpha power in the auditory cortex, increases prior to conscious percepts. Importantly, we were able to show that connectivity states seem to be largely independent from local excitability states in the context of a NT paradigm. published

Introduction Transcranial alternating current stimulation (tACS) is used to modulate brain oscillations to measure changes in cognitive function. It is only since recently that brain activity in human subjects during tACS can be investigated. Objectives In the current study we examine entrainment effects caused by tACS at the individual alpha frequency (IAF) in humans. Material & methods We analyze magnetoencephalographic (MEG) data transformed to source space following a method we recently showed to diminish the tACS artifact, which makes analysis of brain activity during tACS possible. Using source level data from our previous study here we investigate the phase relationship (coherence) between the external tACS and the neural signal in two resting state condition. Results We find proof of entrainment in visual cortex areas. Interestingly, this entrainment is only significant when subjects had their eyes open; visual areas were not significantly entrained to tACS when subjects closed their eyes. Furthermore, we find considerable variation across subjects in the delay between tACS and the entrained brain activity. Conclusion In conclusion, tACS at individual alpha frequency entrains brain activity in visual cortices, however, in a state dependent manner as this effect can only clearly be observed with eyes open.

In cognitive neuroscience, prerequisites of consciousness are of high interest. Within recent years it has become more commonly understood that ongoing brain activity, mainly measured with electrophysiology, can predict whether an upcoming stimulus is consciously perceived. One approach to investigate the relationship between ongoing brain activity and conscious perception is to conduct near-threshold (NT) experiments and focus on the pre-stimulus period. The current review will, in the first part, summarize main findings of pre-stimulus research from NT experiments, mainly focusing on the alpha band (8-14 Hz). It is probable that the most prominent finding is that local (mostly sensory) areas show enhanced excitatory states prior to detection of upcoming NT stimuli, as putatively reflected by decreased alpha band power. However, the view of a solely local excitability change seems to be too narrow. In a recent paper, using a somatosensory NT task, Weisz et al. (2014) replicated the common alpha finding and, furthermore, conceptually embedded this finding into a more global framework called ‘Windows to Consciousness’ (Win2Con). In this review, we want to further elaborate on the crucial assumption of ‘open windows’ to conscious perception, determined by pre-established pathways connecting sensory and higher order areas. Methodologically, connectivity and graph theoretical analyses are applied to source-imaging magnetoencephalographic data to uncover brain regions with strong network integration as well as their connection patterns. Sensory regions with stronger network integration will more likely distribute information when confronted with weak NT stimuli, favoring its subsequent conscious perception. First experimental evidence confirms our aforementioned ‘open window’ hypothesis. We therefore emphasize that future research on prerequisites of consciousness needs to move on from investigating solely local excitability to a more global view of network connectivity.

Prestimulus oscillatory neural activity in the visual cortex has large consequences for perception and can be influenced by top-down control from higher-order brain regions. Making a causal claim about the mechanistic role of oscillatory activity requires that oscillations be directly manipulated independently of cognitive instructions. There are indications that a direct manipulation, or entrainment, of visual alpha activity is possible through visual stimulation. However, three important questions remain: (1) Can the entrained alpha activity be endogenously maintained in the absence of continuous stimulation?; (2) Does entrainment of alpha activity reflect a global or a local process?; and (3) Does the entrained alpha activity influence perception? To address these questions, we presented human subjects with rhythmic stimuli in one visual hemifield, and arhythmic stimuli in the other. After rhythmic entrainment, we found a periodic pattern in detection performance of near-threshold targets specific to the entrained hemifield. Using magnetoencephalograhy to measure ongoing brain activity, we observed strong alpha activity contralateral to the rhythmic stimulation outlasting the stimulation by several cycles. This entrained alpha activity was produced locally in early visual cortex, as revealed by source analysis. Importantly, stronger alpha entrainment predicted a stronger phasic modulation of detection performance in the entrained hemifield. These findings argue for a cortically focal entrainment of ongoing alpha oscillations by visual stimulation, with concomitant consequences for perception. Our results support the notion that oscillatory brain activity in the alpha band provides a causal mechanism for the temporal organization of visual perception.

When a perceiver performs a task, rarely occurring sounds often have a distracting effect on task performance. The neural mismatch responses in event-related potentials to such distracting stimuli depend on age. Adults commonly show a negative response, whereas in children a positive as well as a negative mismatch response has been reported. Using electro- and magnetoencephalography (EEG/MEG), here we investigated the developmental changes of distraction processing in school-aged children (9-10 years) and adults. Participants took part in an auditory-visual distraction paradigm comprising a visuo-spatial primary task and task-irrelevant environmental sounds distracting from this task. Behaviorally, distractors delayed reaction times (RTs) in the primary task in both age groups, and this delay was of similar magnitude in both groups. The neurophysiological data revealed an early as well as a late mismatch response elicited by distracting stimuli in both age groups. Together with previous research, this indicates that deviance detection is accomplished in a hierarchical manner in the auditory system. Both mismatch responses were localized to auditory cortex areas. All mismatch responses were generally delayed in children, suggesting that not all neurophysiological aspects of deviance processing are mature in school-aged children. Furthermore, the P3a, reflecting involuntary attention capture, was present in both age groups in the EEG with comparable amplitudes and at similar latencies, but with a different topographical distribution. This suggests that involuntary attention shifts toward complex distractors operate comparably in school-aged children and adults, yet undergoing generator maturation.

When a sound occurs at a predictable time, it gets processed more efficiently. Predictability of the temporal structure of acoustic inflow has been found to influence the P3b of event-related potentials in young adults, such that highly predictable compared to less predictable input leads to earlier P3b peak latencies. In our study, we wanted to investigate the influence of predictability on target processing indexed by the P3b in children (10-12 years old) and young adults. To do that, we used an oddball paradigm with two conditions of predictability (high and low). In the High-predictability condition, a high-pitched target tone occurred most of the time in the fifth position of a five-tone pattern (after four low-pitched non-target sounds), whereas in the Low-predictability condition, no such rule was implemented. The target tone occurred randomly following 2, 3, 4, 5, or 6 non-target tones. In both age groups, reaction time to predictable targets was faster than to non-predictable targets. Remarkably, this effect was largest in children. Consistent with the behavioral responses, the onset latency of the P3b response elicited by targets in both groups was earlier in the predictable than the unpredictable conditions. However, only the children had significantly earlier peak latency responses for predictable targets. Our results demonstrate that target stimulus predictability increases processing speed in children and adults even when predictability was only implicitly derived by the stimulus statistics. Children did have larger effects of predictability, seeming to benefit more from predictability for target detection.

Objective When investigating auditory perceptual regularity processing, mismatch negativity (MMN) is commonly used. MMN is computed as a difference signal between the event-related potentials (ERPs) elicited by repeated standard tones and rarely occurring deviant tones. This procedure leads to an underestimation of the N1 component elicited by standards compared to the N1 to deviants which might affect the MMN. Consequently, a random control design was previously introduced. This design, however, overestimates the N1 to the deviant. Here, we developed a new paradigm that avoids previous drawbacks. Methods We designed a regular cascadic sequence as a control to the deviant. ERPs were measured while presenting conventional oddball blocks (standards, deviants), random control blocks and a cascadic control block. Results MMN was observed in each difference signal. Regarding the N1, standards elicited smallest amplitudes. The N1 for the deviant and the cascadic control was comparable. The largest N1 was elicited by the random control. Conclusion Standards underestimate N1 refractoriness effects in the responses to deviants, while random control tones overestimate. Cascadic control tones, however, provide a reasonable estimation for the N1. Significance The new cascadic control design is suitable to investigate auditory perceptual regularity processes while controlling for N1 refractoriness effects.

Neural auditory responses are known to change from childhood to adulthood. The most prominent components of the event-related potentials (ERPs) found in children are the P1 and N2, while the P1 and N1 are strongest in adults. Previous dipole localizations showed regions of the auditory cortex (AC) underlying these responses. An N1 in children, however, has only been observed in older age or under certain experimental conditions different than commonly applied in adults. The current study aimed to further elucidate on auditory processing and related components in school-aged children. To do this, MEG and EEG was recorded in adults and 9 to 10 year old children, while presenting pure tones either repetitively or randomly among tones of different pitch. Furthermore, the current paradigm was explicitly designed to not only investigate the P1 and N2 in children, but moreover to examine N1 modulations based on different refractory states caused by the two conditions. Our results are clear cut. In adults, P1(m) and N1(m) components were localized in AC regions, with the N1(m) largely attenuated for repetitive tones. The P1(m) and N2(m) components observed in children were also localized in AC regions. Most importantly, ERP modulations in the N1 time window (i.e., larger responses for random than repetitive tones) were remarkably similar for adults and children, both in amplitude and latency. This effect indicates that the N1 sub-component reflecting frequency-specific refractoriness is fully developed in 9 to 10 year old children. Thus, previous interpretations on the function and maturation of the N1 need reconsideration.

Background We investigated the processing of task-irrelevant and unexpected novel sounds and its modulation by working-memory load in children aged 9-10 and in adults. Environmental sounds (novels) were embedded amongst frequently presented standard sounds in an auditory-visual distraction paradigm. Each sound was followed by a visual target. In two conditions, participants evaluated the position of a visual stimulus (0-back, low load) or compared the position of the current stimulus with the one two trials before (2-back, high load). Processing of novel sounds were measured with reaction times, hit rates and the auditory event-related brain potentials (ERPs) Mismatch Negativity (MMN), P3a, Reorienting Negativity (RON) and visual P3b. Results In both memory load conditions novels impaired task performance in adults whereas they improved performance in children. Auditory ERPs reflect age-related differences in the time-window of the MMN as children showed a positive ERP deflection to novels whereas adults lack an MMN. The attention switch towards the task irrelevant novel (reflected by P3a) was comparable between the age groups. Adults showed more efficient reallocation of attention (reflected by RON) under load condition than children. Finally, the P3b elicited by the visual target stimuli was reduced in both age groups when the preceding sound was a novel. Conclusion Our results give new insights in the development of novelty processing as they (1) reveal that task-irrelevant novel sounds can result in contrary effects on the performance in a visual primary task in children and adults, (2) show a positive ERP deflection to novels rather than an MMN in children, and (3) reveal effects of auditory novels on visual target processing.

s / Brain Stimulation 8 (2015) 378e394 386 of this variability, but they are not taken into account in the treatment procedure. Objective: This study proposes to specifically study the links between anatomical characteristics underlying the temporal cortex target and the efficacy of the rTMS treatment used to alleviate AVH in patients with schizophrenia. Methods: In each of the fifteen recruited schizophrenic patients (DSM IV), we measured scalp to cortex distances (SCDs), gray matter densities (GMDs) in two regions of interest: the motor cortex where the resting motor threshold (rMT) was measured and the superior temporal sulcus where the treatment was delivered. We studied the correlations between these measures and the clinical efficacy assessed with the Auditory Hallucinations Rating Scale (AHRS) before and after rTMS. Results: We found correlations between the clinical efficacy of the treatment and on one hand the temporal target SCD (p 1⁄4 0.0396) and on the other hand the GMD (p 1⁄4 0.0331). No correlations between rMT and GMD or SCD in the motor cortex region were observed. Conclusion: These results support the idea that the treatment efficacy could be related to the depth of the temporal target. The closer the temporal target to scalp was, the greater efficacy of the treatment was. Furthermore, rMT may not be a so relevant tool to assay a temporal rTMS treatment.

Visual rhythmic stimulation evokes a robust power increase exactly at the stimulation frequency, the so-called steady-state response (SSR). Localization of visual SSRs normally shows a very focal modulation of power in visual cortex and led to the treatment and interpretation of SSRs as a local phenomenon. Given the brain network dynamics, we hypothesized that SSRs have additional large-scale effects on the brain functional network that can be revealed by means of graph theory. We used rhythmic visual stimulation at a range of frequencies (4–30 Hz), recorded MEG and investigated source level connectivity across the whole brain. Using graph theoretical measures we observed a frequency-unspecific reduction of global density in the alpha band “disconnecting” visual cortex from the rest of the network. Also, a frequency-specific increase of connectivity between occipital cortex and precuneus was found at the stimulation frequency that exhibited the highest resonance (30 Hz). In conclusion, we showed that SSRs dynamically re-organized the brain functional network. These large-scale effects should be taken into account not only when attempting to explain the nature of SSRs, but also when used in various experimental designs., Highlights • Visual entrainment is considered mostly to modulate cortical power locally. • Instead, we hypothesized large-scale effects in the brain functional network. • Graph theoretical analysis combined with MEG source localization. • Visual entrainment indeed yielded network-level effects.