Carrier-frequency specific omission-related neural activity in ordered sound sequences is independent of omission-predictability.

Regularities in our surroundings lead to predictions about upcoming events. Previous research has shown that omitted sounds during otherwise regular tone sequences elicit frequency-specific neural activity related to the upcoming but omitted tone. We tested whether this neural response is depending on the unpredictability of the omission. Therefore, we recorded magnetencephalography (MEG) data while participants listened to ordered or random tone sequences with omissions occurring either ordered or randomly. Using multivariate pattern analysis shows that the frequency-specific neural pattern during omission within ordered tone sequences occurs independent of the regularity of the omissions. These results suggest that the auditory predictions based on sensory experiences are not immediately updated by violations of those expectations.

Decoding across sensory modalities reveals common supramodal signatures of conscious perception.

An increasing number of studies highlight common brain regions and processes in mediating conscious sensory experience. While most studies have been performed in the visual modality, it is implicitly assumed that similar processes are involved in other sensory modalities. However, the existence of supramodal neural processes related to conscious perception has not been convincingly shown so far. Here, we aim to directly address this issue by investigating whether neural correlates of conscious perception in one modality can predict conscious perception in a different modality. In two separate experiments, we presented participants with successive blocks of near-threshold tasks involving subjective reports of tactile, visual, or auditory stimuli during the same magnetoencephalography (MEG) acquisition. Using decoding analysis in the poststimulus period between sensory modalities, our first experiment uncovered supramodal spatiotemporal neural activity patterns predicting conscious perception of the feeble stimulation. Strikingly, these supramodal patterns included activity in primary sensory regions not directly relevant to the task (e.g., neural activity in visual cortex predicting conscious perception of auditory near-threshold stimulation). We carefully replicate our results in a control experiment that furthermore show that the relevant patterns are independent of the type of report (i.e., whether conscious perception was reported by pressing or withholding a button press). Using standard paradigms for probing neural correlates of conscious perception, our findings reveal a common signature of conscious access across sensory modalities and illustrate the temporally late and widespread broadcasting of neural representations, even into task-unrelated primary sensory processing regions.

Cochlear activity in silent cue-target intervals shows a theta-rhythmic pattern and is correlated to attentional alpha and theta modulations.

BACKGROUND: A long-standing debate concerns where in the processing hierarchy of the central nervous system (CNS) selective attention takes effect. In the auditory system, cochlear processes can be influenced via direct and mediated (by the inferior colliculus) projections from the auditory cortex to the superior olivary complex (SOC). Studies illustrating attentional modulations of cochlear responses have so far been limited to sound-evoked responses. The aim of the present study is to investigate intermodal (audiovisual) selective attention in humans simultaneously at the cortical and cochlear level during a stimulus-free cue-target interval. RESULTS: We found that cochlear activity in the silent cue-target intervals was modulated by a theta-rhythmic pattern (~ 6 Hz). While this pattern was present independently of attentional focus, cochlear theta activity was clearly enhanced when attending to the upcoming auditory input. On a cortical level, classical posterior alpha and beta power enhancements were found during auditory selective attention. Interestingly, participants with a stronger release of inhibition in auditory brain regions show a stronger attentional modulation of cochlear theta activity. CONCLUSIONS: These results hint at a putative theta-rhythmic sampling of auditory input at the cochlear level. Furthermore, our results point to an interindividual variable engagement of efferent pathways in an attentional context that are linked to processes within and beyond processes in auditory cortical regions.

A backward encoding approach to recover subcortical auditory activity.

Several subcortical nuclei along the auditory pathway are involved in the processing of sounds. One of the most commonly used methods of measuring the activity of these nuclei is the auditory brainstem response (ABR). Due to its low signal-to-noise ratio, ABR's have to be derived by averaging over activity generated by thousands of artificial sounds such as clicks or tone bursts. This approach cannot be easily applied to natural listening situations (e.g. speech, music), which limits auditory cognitive neuroscientific studies to investigate mostly cortical processes. We propose that by individually training backward encoding models to reconstruct evoked ABRs from high-density electrophysiological data, spatial filters can be tuned to auditory brainstem activity. Since these individualized filters can be applied (i.e. generalized) to any other data set using the same spatial coverage, this could allow for the estimation of auditory brainstem activity from any continuous sensor level data. In this study, we established a proof-of-concept by using backward encoding models generated using a click stimulation rate of 30 â€‹Hz to predict ABR activity recorded using EEG from an independent measurement using a stimulation rate of 9 â€‹Hz. We show that individually predicted and measured ABR's are highly correlated (r â€‹~ â€‹0.7). Importantly these predictions are stable even when applying the trained backward encoding model to a low number of trials, mimicking a situation with an unfavorable signal-to-noise ratio. Overall, this work lays the necessary foundation to use this approach in more interesting listening situations.

Faith and oscillations recovered: On analyzing EEG/MEG signals during tACS.

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.

Prestimulus oscillatory power and connectivity patterns predispose conscious somatosensory perception.

Which aspects of our sensory environment enter conscious awareness does not only depend on physical features of the stimulus, but also critically on the so-called current brain state. Results from magnetoencephalography/EEG studies using near-threshold stimuli have consistently pointed to reduced levels of α- (8-12 Hz) power in relevant sensory areas to predict whether a stimulus will be consciously perceived or not. These findings have been mainly interpreted in strictly "local" terms of enhanced excitability of neuronal ensembles in respective cortical regions. The present study aims to introduce a framework that complements this rather local perspective, by stating that the functional connectivity architecture before stimulation will predetermine information flow. Thus, information computed at a local level will be distributed throughout a network, thereby becoming consciously accessible. Data from a previously published experiment on conscious somatosensory near-threshold perception was reanalyzed focusing on the prestimulus period. Analysis of spectral power showed reduced α-power mainly in the contralateral S2 and middle frontal gyrus to precede hits, thus overall supporting the current literature. Furthermore, differences between hits and misses were obtained on global network (graph theoretical) features in the same interval. Most importantly, in accordance with our framework, we could show that the somatosensory cortex is "more efficiently" integrated into a distributed network in the prestimulus period. This finding means that when a relevant sensory stimulus impinges upon the system, it will encounter preestablished pathways for information flow. In this sense, prestimulus functional connectivity patterns form "windows" to conscious perception.

Neural correlates of finger gnosis.

Neuropsychological studies have described patients with a selective impairment of finger identification in association with posterior parietal lesions. However, evidence of the role of these areas in finger gnosis from studies of the healthy human brain is still scarce. Here we used functional magnetic resonance imaging to identify the brain network engaged in a novel finger gnosis task, the intermanual in-between task (IIBT), in healthy participants. Several brain regions exhibited a stronger blood oxygenation level-dependent (BOLD) response in IIBT than in a control task that did not explicitly rely on finger gnosis but used identical stimuli and motor responses as the IIBT. The IIBT involved stronger signal in the left inferior parietal lobule (IPL), bilateral precuneus (PCN), bilateral premotor cortex, and left inferior frontal gyrus. In all regions, stimulation of nonhomologous fingers of the two hands elicited higher BOLD signal than stimulation of homologous fingers. Only in the left anteromedial IPL (a-mIPL) and left PCN did signal strength decrease parametrically from nonhomology, through partial homology, to total homology with stimulation delivered synchronously to the two hands. With asynchronous stimulation, the signal was stronger in the left a-mIPL than in any other region, possibly indicating retention of task-relevant information. We suggest that the left PCN may contribute a supporting visuospatial representation via its functional connection to the right PCN. The a-mIPL may instead provide the core substrate of an explicit bilateral body structure representation for the fingers that when disrupted can produce the typical symptoms of finger agnosia.

Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation.

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.

Eavesdropping on Tinnitus Using MEG: Lessons Learned and Future Perspectives.

Tinnitus has been widely investigated in order to draw conclusions about the underlying causes and altered neural activity in various brain regions. Existing studies have based their work on different tinnitus frameworks, ranging from a more local perspective on the auditory cortex to the inclusion of broader networks and various approaches towards tinnitus perception and distress. Magnetoencephalography (MEG) provides a powerful tool for efficiently investigating tinnitus and aberrant neural activity both spatially and temporally. However, results are inconclusive, and studies are rarely mapped to theoretical frameworks. The purpose of this review was to firstly introduce MEG to interested researchers and secondly provide a synopsis of the current state. We divided recent tinnitus research in MEG into study designs using resting state measurements and studies implementing tone stimulation paradigms. The studies were categorized based on their theoretical foundation, and we outlined shortcomings as well as inconsistencies within the different approaches. Finally, we provided future perspectives on how to benefit more efficiently from the enormous potential of MEG. We suggested novel approaches from a theoretical, conceptual, and methodological point of view to allow future research to obtain a more comprehensive understanding of tinnitus and its underlying processes.

Network topology in brain tumor patients with and without structural epilepsy: a prospective MEG study.

Background: It was proposed that network topology is altered in brain tumor patients. However, there is no consensus on the pattern of these changes and evidence on potential drivers is lacking. Objectives: We aimed to characterize neurooncological patients' network topology by analyzing glial brain tumors (GBTs) and brain metastases (BMs) with respect to the presence of structural epilepsy. Methods: Network topology derived from resting state magnetoencephalography was compared between (1) patients and controls, (2) GBTs and BMs, and (3) patients with (PSEs) and without structural epilepsy (PNSEs). Eligible patients were investigated from February 2019 to March 2021. We calculated whole brain (WB) connectivity in six frequency bands, network topological parameters (node degree, average shortest path length, local clustering coefficient) and performed a stratification, where differences in power were identified. For data analysis, we used Fieldtrip, Brain Connectivity MATLAB toolboxes, and in-house built scripts. Results: We included 41 patients (21 men), with a mean age of 60.1 years (range 23-82), of those were: GBTs (n = 23), BMs (n = 14), and other histologies (n = 4). Statistical analysis revealed a significantly decreased WB node degree in patients versus controls in every frequency range at the corrected level (p1-30Hz = 0.002, pγ = 0.002, pß = 0.002, pα = 0.002, pθ = 0.024, and pδ = 0.002). At the descriptive level, we found a significant augmentation for WB local clustering coefficient (p1-30Hz = 0.031, pδ = 0.013) in patients compared to controls, which did not persist the false discovery rate correction. No differences regarding networks of GBTs compared to BMs were identified. However, we found a significant increase in WB local clustering coefficient (pθ = 0.048) and decrease in WB node degree (pα = 0.039) in PSEs versus PNSEs at the uncorrected level. Conclusion: Our data suggest that network topology is altered in brain tumor patients. Histology per se might not, however, tumor-related epilepsy seems to influence the brain's functional network. Longitudinal studies and analysis of possible confounders are required to substantiate these findings.

The contribution of primary and secondary somatosensory cortices to the representation of body parts and body sides: an fMRI adaptation study.

Although the somatosensory homunculus is a classically used description of the way somatosensory inputs are processed in the brain, the actual contributions of primary (SI) and secondary (SII) somatosensory cortices to the spatial coding of touch remain poorly understood. We studied adaptation of the fMRI BOLD response in the somatosensory cortex by delivering pairs of vibrotactile stimuli to the finger tips of the index and middle fingers. The first stimulus (adaptor) was delivered either to the index or to the middle finger of the right or left hand, and the second stimulus (test) was always administered to the left index finger. The overall BOLD response evoked by the stimulation was primarily contralateral in SI and was more bilateral in SII. However, our fMRI adaptation approach also revealed that both somatosensory cortices were sensitive to ipsilateral as well as to contralateral inputs. SI and SII adapted more after subsequent stimulation of homologous as compared with nonhomologous fingers, showing a distinction between different fingers. Most importantly, for both somatosensory cortices, this finger-specific adaptation occurred irrespective of whether the tactile stimulus was delivered to the same or to different hands. This result implies integration of contralateral and ipsilateral somatosensory inputs in SI as well as in SII. Our findings suggest that SI is more than a simple relay for sensory information and that both SI and SII contribute to the spatial coding of touch by discriminating between body parts (fingers) and by integrating the somatosensory input from the two sides of the body (hands).

Mislocalization of near-threshold tactile stimuli in humans: a central or peripheral phenomenon?

Principles of brain function can be disclosed by studying their limits during performance. Tactile stimuli with near-threshold intensities have been used to assess features of somatosensory processing. When stimulating fingers of one hand using near-threshold intensities, localization errors are observed that deviate significantly from responses obtained by guessing - incorrectly located stimuli are attributed more often to fingers neighbouring the stimulated one than to more distant fingers. Two hypotheses to explain the findings are proposed. The 'central hypothesis' posits that the degree of overlap of cortical tactile representations depends on stimulus intensity, with representations less separated for near-threshold stimuli than for suprathreshold stimuli. The 'peripheral hypothesis' assumes that systematic mislocalizations are due to activation of different sets of skin receptors with specific thresholds. The present experiments were designed to decide between the two hypotheses. Taking advantage of the frequency tuning of somatosensory receptors, their contribution to systematic misclocalizations was studied. In the first experiment, mislocalization profiles were investigated using vibratory stimuli with frequencies of 10, 20 and 100 Hz. Unambiguous mislocalization effects were only obtained for the 10-Hz stimulation, precluding the involvement of Pacinian corpuscles in systematic mislocalization. In the second experiment, Pacinian corpuscles were functionally eliminated by applying a constant 100-Hz vibratory masking stimulus together with near-threshold pulses. Despite masking, systematic mislocation patterns were observed rendering the involvement of Pacinian corpuscles unlikely. The results of both experiments are in favor of the 'central hypothesis' assuming that the extent of overlap in somatosensory representations is modulated by stimulus intensity.

Auditory cortical alpha/beta desynchronization prioritizes the representation of memory items during a retention period.

To-be-memorized information in working-memory could be protected against distracting influences by processes of functional inhibition or prioritization. Modulations of oscillations in the alpha to beta range in task-relevant sensory regions have been suggested to play an important role for both mechanisms. We adapted a Sternberg task variant to the auditory modality, with a strong or a weak distracting sound presented at a predictable time during the retention period. Using a time-generalized decoding approach, relatively decreased strength of memorized information was found prior to strong distractors, paralleled by decreased pre-distractor alpha/beta power in the left superior temporal gyrus (lSTG). Over the entire group, reduced beta power in lSTG was associated with relatively increased strength of memorized information. The extent of alpha power modulations within participants was negatively correlated with strength of memorized information. Overall, our results are compatible with a prioritization account, but point to nuanced differences between alpha and beta oscillations.

Head magnetomyography (hMMG): A novel approach to monitor face and whole head muscular activity.

Muscular activity recording is of high basic science and clinical relevance and is typically achieved using electromyography (EMG). While providing detailed information about the state of a specific muscle, this technique has limitations such as the need for a priori assumptions about electrode placement and difficulty with recording muscular activity patterns from extended body areas at once. For head and face muscle activity, the present work aimed to overcome these restrictions by exploiting magnetoencephalography (MEG) as a whole head myographic recorder (head magnetomyography, hMMG). This is in contrast to common MEG studies, which treat muscular activity as artifact in electromagnetic brain activity. In a first proof-of-concept step, participants imitated emotional facial expressions performed by a model. Exploiting source projection algorithms, we were able to reconstruct muscular activity, showing spatial activation patterns in accord with the hypothesized muscular contractions. Going one step further, participants passively observed affective pictures with negative, neutral, or positive valence. Applying multivariate pattern analysis to the reconstructed hMMG signal, we were able to decode above chance the valence category of the presented pictures. Underlining the potential of hMMG, a searchlight analysis revealed that generally neglected neck muscles exhibit information on stimulus valence. Results confirm the utility of hMMG as a whole head electromyographic recorder to quantify muscular activation patterns including muscular regions that are typically not recorded with EMG. This key advantage beyond conventional EMG has substantial scientific and clinical potential.

Automatic and feature-specific prediction-related neural activity in the human auditory system.

Prior experience enables the formation of expectations of upcoming sensory events. However, in the auditory modality, it is not known whether prediction-related neural signals carry feature-specific information. Here, using magnetoencephalography (MEG), we examined whether predictions of future auditory stimuli carry tonotopic specific information. Participants passively listened to sound sequences of four carrier frequencies (tones) with a fixed presentation rate, ensuring strong temporal expectations of when the next stimulus would occur. Expectation of which frequency would occur was parametrically modulated across the sequences, and sounds were occasionally omitted. We show that increasing the regularity of the sequence boosts carrier-frequency-specific neural activity patterns during both the anticipatory and omission periods, indicating that prediction-related neural activity is indeed feature-specific. Our results illustrate that even without bottom-up input, auditory predictions can activate tonotopically specific templates.

Detecting Pre-Stimulus Source-Level Effects on Object Perception with Magnetoencephalography.

Pre-stimulus oscillatory brain activity influences upcoming perception. The characteristics of this pre-stimulus activity can predict whether a near-threshold stimulus will be perceived or not perceived, but can they also predict which one of two competing stimuli with different perceptual contents is perceived? Ambiguous visual stimuli, which can be seen in one of two possible ways at a time, are ideally suited to investigate this question. Magnetoencephalography (MEG) is a neurophysiological measurement technique that records magnetic signals emitted as a result of brain activity. The millisecond temporal resolution of MEG allows for a characterization of oscillatory brain states from as little as 1 second of recorded data. Presenting an empty screen around 1 second prior to the ambiguous stimulus onset therefore provides a time window in which one can investigate whether pre-stimulus oscillatory activity biases the content of upcoming perception, as indicated by participants' reports. The spatial resolution of MEG is not excellent, but sufficient to localise sources of brain activity at the centimetre scale. Source reconstruction of MEG activity then allows for testing hypotheses about the oscillatory activity of specific regions of interest, as well as the time- and frequency-resolved connectivity between regions of interest. The described protocol enables a better understanding of the influence of spontaneous, ongoing brain activity on visual perception.

tACS-mediated modulation of the auditory steady-state response as seen with MEG.

BACKGROUND: Previous studies have shown that transcranial electrical stimulation can be successfully applied during simultaneous MEG measurements. In particular, using beamforming they have established that changes of stimulus induced as well as evoked activity can be inspected during transcranial alternating current stimulation (tACS). OBJECTIVE/HYPOTHESIS: We studied tACS-mediated changes of the auditory steady-state response (ASSR), hypothesizing that-due to the putatively inhibitory role of alpha oscillations-these evoked responses would be diminished. METHODS: We compared ASSRs in conditions with and without 12-Hz and 6.5-Hz sinusoidal 1.5 mA tACS, applied bilaterally over temporal areas. Source-level activity was estimated using a linearly constrained minimum variance beamformer and compared across tACS conditions using paired t-tests following a condition-internal normalization procedure. CONCLUSIONS: By separating the electrical and auditory stimulation to non-overlapping parts of the frequency spectrum, we were able to compare auditory-evoked steady-state activity across tACS conditions. We observed a significant decrease in normalized ASSR power in the 12-Hz tACS condition, illustrating that tACS could induce immediate changes in auditory evoked activity. This study sets a methodology to further interrogate the causal roles of oscillatory dynamics in auditory cortices, as well as suggests perspectives for employing tACS in clinical contexts.

Eyes wide shut: Transcranial alternating current stimulation drives alpha rhythm in a state dependent manner.

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. The present study aims to investigate the phase relationship between the external tACS signal and concurrent brain activity. Subjects were stimulated with tACS at individual alpha frequency during eyes open and eyes closed resting states. Electrodes were placed at Cz and Oz, which should affect parieto-occipital areas most strongly. Source space magnetoencephalography (MEG) data were used to estimate phase coherence between tACS and brain activity. Phase coherence was significantly increased in areas in the occipital pole in eyes open resting state only. The lag between tACS and brain responses showed considerable inter-individual variability. In conclusion, tACS at individual alpha frequency entrains brain activity in visual cortices. Interestingly, this effect is state dependent and is clearly observed with eyes open but only to a lesser extent with eyes closed.

Waves of regret: a meg study of emotion and decision-making.

Recent fMRI studies have investigated brain activity involved in the feeling of regret and disappointment by manipulating the feedback participants saw after making a decision to play certain gambles: full-feedback (regret: participant sees the outcomes from both the chosen and unchosen gamble) vs. partial-feedback (disappointment: participant only sees the outcome from chosen gamble). However, regret and disappointment are also characterized by differential agency attribution: personal agency for regret, external agency for disappointment. In this study, we investigate the neural correlates of these two characterizations of regret and disappointment using magnetoencephalography (MEG). To do this, we experimentally induced each emotion by manipulating feedback (chosen gamble vs. unchosen gamble), agency (human vs. computer choice) and outcomes (win vs. loss) in a fully randomized design. At the behavioral level the emotional experience of regret and disappointment were indeed affected by both feedback and agency manipulations. These emotions also differentially affect subsequent choices, with regret leading to riskier behavior. At the neural level both feedback and agency affected the brain responses associated with regret and disappointment, demonstrating differential localization in the brain for each. Notably, feedback regret showed greater brain activity in the right anterior and posterior regions, with agency regret producing greater activity in the left anterior region. These findings extend the evidence for neural activity in processing both regret and disappointment by highlighting for the first time the respective importance of feedback and agency, as well as outlining the temporal dynamics of these emotions.