Coupling of pupil- and neuronal population dynamics reveals diverse influences of arousal on cortical processing.

Fluctuations in arousal, controlled by subcortical neuromodulatory systems, continuously shape cortical state, with profound consequences for information processing. Yet, how arousal signals influence cortical population activity in detail has so far only been characterized for a few selected brain regions. Traditional accounts conceptualize arousal as a homogeneous modulator of neural population activity across the cerebral cortex. Recent insights, however, point to a higher specificity of arousal effects on different components of neural activity and across cortical regions. Here, we provide a comprehensive account of the relationships between fluctuations in arousal and neuronal population activity across the human brain. Exploiting the established link between pupil size and central arousal systems, we performed concurrent magnetoencephalographic (MEG) and pupillographic recordings in a large number of participants, pooled across three laboratories. We found a cascade of effects relative to the peak timing of spontaneous pupil dilations: Decreases in low-frequency (2-8 Hz) activity in temporal and lateral frontal cortex, followed by increased high-frequency (>64 Hz) activity in mid-frontal regions, followed by monotonic and inverted U relationships with intermediate frequency-range activity (8-32 Hz) in occipito-parietal regions. Pupil-linked arousal also coincided with widespread changes in the structure of the aperiodic component of cortical population activity, indicative of changes in the excitation-inhibition balance in underlying microcircuits. Our results provide a novel basis for studying the arousal modulation of cognitive computations in cortical circuits.

Rapid processing of neutral and angry expressions within ongoing facial stimulus streams: Is it all about isolated facial features?

Our visual system extracts the emotional meaning of human facial expressions rapidly and automatically. Novel paradigms using fast periodic stimulations have provided insights into the electrophysiological processes underlying emotional content extraction: the regular occurrence of specific identities and/or emotional expressions alone can drive diagnostic brain responses. Consistent with a processing advantage for social cues of threat, we expected angry facial expressions to drive larger responses than neutral expressions. In a series of four EEG experiments, we studied the potential boundary conditions of such an effect: (i) we piloted emotional cue extraction using 9 facial identities and a fast presentation rate of 15 Hz (N = 16); (ii) we reduced the facial identities from 9 to 2, to assess whether (low or high) variability across emotional expressions would modulate brain responses (N = 16); (iii) we slowed the presentation rate from 15 Hz to 6 Hz (N = 31), the optimal presentation rate for facial feature extraction; (iv) we tested whether passive viewing instead of a concurrent task at fixation would play a role (N = 30). We consistently observed neural responses reflecting the rate of regularly presented emotional expressions (5 Hz and 2 Hz at presentation rates of 15 Hz and 6 Hz, respectively). Intriguingly, neutral expressions consistently produced stronger responses than angry expressions, contrary to the predicted processing advantage for threat-related stimuli. Our findings highlight the influence of physical differences across facial identities and emotional expressions.

Spatial attention enhances cortical tracking of quasi-rhythmic visual stimuli.

Successfully interpreting and navigating our natural visual environment requires us to track its dynamics constantly. Additionally, we focus our attention on behaviorally relevant stimuli to enhance their neural processing. Little is known, however, about how sustained attention affects the ongoing tracking of stimuli with rich natural temporal dynamics. Here, we used MRI-informed source reconstructions of magnetoencephalography (MEG) data to map to what extent various cortical areas track concurrent continuous quasi-rhythmic visual stimulation. Further, we tested how top-down visuo-spatial attention influences this tracking process. Our bilaterally presented quasi-rhythmic stimuli covered a dynamic range of 4-20 â€‹Hz, subdivided into three distinct bands. As an experimental control, we also included strictly rhythmic stimulation (10 vs 12 â€‹Hz). Using a spectral measure of brain-stimulus coupling, we were able to track the neural processing of left vs. right stimuli independently, even while fluctuating within the same frequency range. The fidelity of neural tracking depended on the stimulation frequencies, decreasing for higher frequency bands. Both attended and non-attended stimuli were tracked beyond early visual cortices, in ventral and dorsal streams depending on the stimulus frequency. In general, tracking improved with the deployment of visuo-spatial attention to the stimulus location. Our results provide new insights into how human visual cortices process concurrent dynamic stimuli and provide a potential mechanism - namely increasing the temporal precision of tracking - for boosting the neural representation of attended input.

Frequency and power of human alpha oscillations drift systematically with time-on-task.

Oscillatory neural activity is a fundamental characteristic of the mammalian brain spanning multiple levels of spatial and temporal scale. Current theories of neural oscillations and analysis techniques employed to investigate their functional significance are based on an often implicit assumption: In the absence of experimental manipulation, the spectral content of any given EEG- or MEG-recorded neural oscillator remains approximately stationary over the course of a typical experimental session (∼1 h), spontaneously fluctuating only around its dominant frequency. Here, we examined this assumption for ongoing neural oscillations in the alpha-band (8-13 Hz). We found that alpha peak frequency systematically decreased over time, while alpha-power increased. Intriguingly, these systematic changes showed partial independence of each other: Statistical source separation (independent component analysis) revealed that while some alpha components displayed concomitant power increases and peak frequency decreases, other components showed either unique power increases or frequency decreases. Interestingly, we also found these components to differ in frequency. Components that showed mixed frequency/power changes oscillated primarily in the lower alpha-band (∼8-10 Hz), while components with unique changes oscillated primarily in the higher alpha-band (∼9-13 Hz). Our findings provide novel clues on the time-varying intrinsic properties of large-scale neural networks as measured by M/EEG, with implications for the analysis and interpretation of studies that aim at identifying functionally relevant oscillatory networks or at driving them through external stimulation.

Stimulus-Driven Brain Rhythms within the Alpha Band: The Attentional-Modulation Conundrum.

Two largely independent research lines use rhythmic sensory stimulation to study visual processing. Despite the use of strikingly similar experimental paradigms, they differ crucially in their notion of the stimulus-driven periodic brain responses: one regards them mostly as synchronized (entrained) intrinsic brain rhythms; the other assumes they are predominantly evoked responses [classically termed steady-state responses (SSRs)] that add to the ongoing brain activity. This conceptual difference can produce contradictory predictions about, and interpretations of, experimental outcomes. The effect of spatial attention on brain rhythms in the alpha band (8-13 Hz) is one such instance: alpha-range SSRs have typically been found to increase in power when participants focus their spatial attention on laterally presented stimuli, in line with a gain control of the visual evoked response. In nearly identical experiments, retinotopic decreases in entrained alpha-band power have been reported, in line with the inhibitory function of intrinsic alpha. Here we reconcile these contradictory findings by showing that they result from a small but far-reaching difference between two common approaches to EEG spectral decomposition. In a new analysis of previously published human EEG data, recorded during bilateral rhythmic visual stimulation, we find the typical SSR gain effect when emphasizing stimulus-locked neural activity and the typical retinotopic alpha suppression when focusing on ongoing rhythms. These opposite but parallel effects suggest that spatial attention may bias the neural processing of dynamic visual stimulation via two complementary neural mechanisms.SIGNIFICANCE STATEMENT Attending to a visual stimulus strengthens its representation in visual cortex and leads to a retinotopic suppression of spontaneous alpha rhythms. To further investigate this process, researchers often attempt to phase lock, or entrain, alpha through rhythmic visual stimulation under the assumption that this entrained alpha retains the characteristics of spontaneous alpha. Instead, we show that the part of the brain response that is phase locked to the visual stimulation increased with attention (as do steady-state evoked potentials), while the typical suppression was only present in non-stimulus-locked alpha activity. The opposite signs of these effects suggest that attentional modulation of dynamic visual stimulation relies on two parallel cortical mechanisms-retinotopic alpha suppression and increased temporal tracking.

No changes in parieto-occipital alpha during neural phase locking to visual quasi-periodic theta-, alpha-, and beta-band stimulation.

Recent studies have probed the role of the parieto-occipital alpha rhythm (8-12 Hz) in human visual perception through attempts to drive its neural generators. To that end, paradigms have used high-intensity strictly-periodic visual stimulation that created strong predictions about future stimulus occurrences and repeatedly demonstrated perceptual consequences in line with an entrainment of parieto-occipital alpha. Our study, in turn, examined the case of alpha entrainment by non-predictive low-intensity quasi-periodic visual stimulation within theta- (4-7 Hz), alpha- (8-13 Hz), and beta (14-20 Hz) frequency bands, i.e., a class of stimuli that resemble the temporal characteristics of naturally occurring visual input more closely. We have previously reported substantial neural phase-locking in EEG recording during all three stimulation conditions. Here, we studied to what extent this phase-locking reflected an entrainment of intrinsic alpha rhythms in the same dataset. Specifically, we tested whether quasi-periodic visual stimulation affected several properties of parieto-occipital alpha generators. Speaking against an entrainment of intrinsic alpha rhythms by non-predictive low-intensity quasi-periodic visual stimulation, we found none of these properties to show differences between stimulation frequency bands. In particular, alpha band generators did not show increased sensitivity to alpha band stimulation and Bayesian inference corroborated evidence against an influence of stimulation frequency. Our results set boundary conditions for when and how to expect effects of entrainment of alpha generators and suggest that the parieto-occipital alpha rhythm may be more inert to external influences than previously thought.

Trial-by-trial co-variation of pre-stimulus EEG alpha power and visuospatial bias reflects a mixture of stochastic and deterministic effects.

Human perception of perithreshold stimuli critically depends on oscillatory EEG activity prior to stimulus onset. However, it remains unclear exactly which aspects of perception are shaped by this pre-stimulus activity and what role stochastic (trial-by-trial) variability plays in driving these relationships. We employed a novel jackknife approach to link single-trial variability in oscillatory activity to psychometric measures from a task that requires judgement of the relative length of two line segments (the landmark task). The results provide evidence that pre-stimulus alpha fluctuations influence perceptual bias. Importantly, a mediation analysis showed that this relationship is partially driven by long-term (deterministic) alpha changes over time, highlighting the need to account for sources of trial-by-trial variability when interpreting EEG predictors of perception. These results provide fundamental insight into the nature of the effects of ongoing oscillatory activity on perception. The jackknife approach we implemented may serve to identify and investigate neural signatures of perceptual relevance in more detail.

Audio-visual synchrony and spatial attention enhance processing of dynamic visual stimulation independently and in parallel: A frequency-tagging study.

The neural processing of a visual stimulus can be facilitated by attending to its position or by a co-occurring auditory tone. Using frequency-tagging, we investigated whether facilitation by spatial attention and audio-visual synchrony rely on similar neural processes. Participants attended to one of two flickering Gabor patches (14.17 and 17 Hz) located in opposite lower visual fields. Gabor patches further "pulsed" (i.e. showed smooth spatial frequency variations) at distinct rates (3.14 and 3.63 Hz). Frequency-modulating an auditory stimulus at the pulse-rate of one of the visual stimuli established audio-visual synchrony. Flicker and pulsed stimulation elicited stimulus-locked rhythmic electrophysiological brain responses that allowed tracking the neural processing of simultaneously presented Gabor patches. These steady-state responses (SSRs) were quantified in the spectral domain to examine visual stimulus processing under conditions of synchronous vs. asynchronous tone presentation and when respective stimulus positions were attended vs. unattended. Strikingly, unique patterns of effects on pulse- and flicker driven SSRs indicated that spatial attention and audiovisual synchrony facilitated early visual processing in parallel and via different cortical processes. We found attention effects to resemble the classical top-down gain effect facilitating both, flicker and pulse-driven SSRs. Audio-visual synchrony, in turn, only amplified synchrony-producing stimulus aspects (i.e. pulse-driven SSRs) possibly highlighting the role of temporally co-occurring sights and sounds in bottom-up multisensory integration.

Visual cortex responses reflect temporal structure of continuous quasi-rhythmic sensory stimulation.

Neural processing of dynamic continuous visual input, and cognitive influences thereon, are frequently studied in paradigms employing strictly rhythmic stimulation. However, the temporal structure of natural stimuli is hardly ever fully rhythmic but possesses certain spectral bandwidths (e.g. lip movements in speech, gestures). Examining periodic brain responses elicited by strictly rhythmic stimulation might thus represent ideal, yet isolated cases. Here, we tested how the visual system reflects quasi-rhythmic stimulation with frequencies continuously varying within ranges of classical theta (4-7Hz), alpha (8-13Hz) and beta bands (14-20Hz) using EEG. Our findings substantiate a systematic and sustained neural phase-locking to stimulation in all three frequency ranges. Further, we found that allocation of spatial attention enhances EEG-stimulus locking to theta- and alpha-band stimulation. Our results bridge recent findings regarding phase locking ("entrainment") to quasi-rhythmic visual input and "frequency-tagging" experiments employing strictly rhythmic stimulation. We propose that sustained EEG-stimulus locking can be considered as a continuous neural signature of processing dynamic sensory input in early visual cortices. Accordingly, EEG-stimulus locking serves to trace the temporal evolution of rhythmic as well as quasi-rhythmic visual input and is subject to attentional bias.

Flicker-Driven Responses in Visual Cortex Change during Matched-Frequency Transcranial Alternating Current Stimulation.

We tested a novel combination of two neuro-stimulation techniques, transcranial alternating current stimulation (tACS) and frequency tagging, that promises powerful paradigms to study the causal role of rhythmic brain activity in perception and cognition. Participants viewed a stimulus flickering at 7 or 11 Hz that elicited periodic brain activity, termed steady-state responses (SSRs), at the same temporal frequency and its higher order harmonics. Further, they received simultaneous tACS at 7 or 11 Hz that either matched or differed from the flicker frequency. Sham tACS served as a control condition. Recent advances in reconstructing cortical sources of oscillatory activity allowed us to measure SSRs during concurrent tACS, which is known to impose strong artifacts in magnetoencephalographic (MEG) recordings. For the first time, we were thus able to demonstrate immediate effects of tACS on SSR-indexed early visual processing. Our data suggest that tACS effects are largely frequency-specific and reveal a characteristic pattern of differential influences on the harmonic constituents of SSRs.

Sustained Splits of Attention within versus across Visual Hemifields Produce Distinct Spatial Gain Profiles.

Visual attention can be focused concurrently on two stimuli at noncontiguous locations while intermediate stimuli remain ignored. Nevertheless, behavioral performance in multifocal attention tasks falters when attended stimuli fall within one visual hemifield as opposed to when they are distributed across left and right hemifields. This "different-hemifield advantage" has been ascribed to largely independent processing capacities of each cerebral hemisphere in early visual cortices. Here, we investigated how this advantage influences the sustained division of spatial attention. We presented six isoeccentric light-emitting diodes (LEDs) in the lower visual field, each flickering at a different frequency. Participants attended to two LEDs that were spatially separated by an intermediate LED and responded to synchronous events at to-be-attended LEDs. Task-relevant pairs of LEDs were either located in the same hemifield ("within-hemifield" conditions) or separated by the vertical meridian ("across-hemifield" conditions). Flicker-driven brain oscillations, steady-state visual evoked potentials (SSVEPs), indexed the allocation of attention to individual LEDs. Both behavioral performance and SSVEPs indicated enhanced processing of attended LED pairs during "across-hemifield" relative to "within-hemifield" conditions. Moreover, SSVEPs demonstrated effective filtering of intermediate stimuli in "across-hemifield" condition only. Thus, despite identical physical distances between LEDs of attended pairs, the spatial profiles of gain effects differed profoundly between "across-hemifield" and "within-hemifield" conditions. These findings corroborate that early cortical visual processing stages rely on hemisphere-specific processing capacities and highlight their limiting role in the concurrent allocation of visual attention to multiple locations.

Early Visual Cortex Dynamics during Top-Down Modulated Shifts of Feature-Selective Attention.

Shifting attention from one color to another color or from color to another feature dimension such as shape or orientation is imperative when searching for a certain object in a cluttered scene. Most attention models that emphasize feature-based selection implicitly assume that all shifts in feature-selective attention underlie identical temporal dynamics. Here, we recorded time courses of behavioral data and steady-state visual evoked potentials (SSVEPs), an objective electrophysiological measure of neural dynamics in early visual cortex to investigate temporal dynamics when participants shifted attention from color or orientation toward color or orientation, respectively. SSVEPs were elicited by four random dot kinematograms that flickered at different frequencies. Each random dot kinematogram was composed of dashes that uniquely combined two features from the dimensions color (red or blue) and orientation (slash or backslash). Participants were cued to attend to one feature (such as color or orientation) and respond to coherent motion targets of the to-be-attended feature. We found that shifts toward color occurred earlier after the shifting cue compared with shifts toward orientation, regardless of the original feature (i.e., color or orientation). This was paralleled in SSVEP amplitude modulations as well as in the time course of behavioral data. Overall, our results suggest different neural dynamics during shifts of attention from color and orientation and the respective shifting destinations, namely, either toward color or toward orientation.

Audio-visual synchrony and feature-selective attention co-amplify early visual processing.

Our brain relies on neural mechanisms of selective attention and converging sensory processing to efficiently cope with rich and unceasing multisensory inputs. One prominent assumption holds that audio-visual synchrony can act as a strong attractor for spatial attention. Here, we tested for a similar effect of audio-visual synchrony on feature-selective attention. We presented two superimposed Gabor patches that differed in colour and orientation. On each trial, participants were cued to selectively attend to one of the two patches. Over time, spatial frequencies of both patches varied sinusoidally at distinct rates (3.14 and 3.63 Hz), giving rise to pulse-like percepts. A simultaneously presented pure tone carried a frequency modulation at the pulse rate of one of the two visual stimuli to introduce audio-visual synchrony. Pulsed stimulation elicited distinct time-locked oscillatory electrophysiological brain responses. These steady-state responses were quantified in the spectral domain to examine individual stimulus processing under conditions of synchronous versus asynchronous tone presentation and when respective stimuli were attended versus unattended. We found that both, attending to the colour of a stimulus and its synchrony with the tone, enhanced its processing. Moreover, both gain effects combined linearly for attended in-sync stimuli. Our results suggest that audio-visual synchrony can attract attention to specific stimulus features when stimuli overlap in space.

Visual, auditory and tactile stimuli compete for early sensory processing capacities within but not between senses.

We investigated whether unattended visual, auditory and tactile stimuli compete for capacity-limited early sensory processing across senses. In three experiments, we probed competitive audio-visual, visuo-tactile and audio-tactile stimulus interactions. To this end, continuous visual, auditory and tactile stimulus streams ('reference' stimuli) were frequency-tagged to elicit steady-state responses (SSRs). These electrophysiological oscillatory brain responses indexed ongoing stimulus processing in corresponding senses. To induce competition, we introduced transient frequency-tagged stimuli in same and/or different senses ('competitors') during reference presentation. Participants performed a separate visual discrimination task at central fixation to control for attentional biases of sensory processing. A comparison of reference-driven SSR amplitudes between competitor-present and competitor-absent periods revealed reduced amplitudes when a competitor was presented in the same sensory modality as the reference. Reduced amplitudes indicated the competitor's suppressive influence on reference stimulus processing. Crucially, no such suppression was found when a competitor was presented in a different than the reference modality. These results strongly suggest that early sensory competition is exclusively modality-specific and does not extend across senses. We discuss consequences of these findings for modeling the neural mechanisms underlying intermodal attention.

Concurrent visual and tactile steady-state evoked potentials index allocation of inter-modal attention: a frequency-tagging study.

We investigated effects of inter-modal attention on concurrent visual and tactile stimulus processing by means of stimulus-driven oscillatory brain responses, so-called steady-state evoked potentials (SSEPs). To this end, we frequency-tagged a visual (7.5Hz) and a tactile stimulus (20Hz) and participants were cued, on a trial-by-trial basis, to attend to either vision or touch to perform a detection task in the cued modality. SSEPs driven by the stimulation comprised stimulus frequency-following (i.e. fundamental frequency) as well as frequency-doubling (i.e. second harmonic) responses. We observed that inter-modal attention to vision increased amplitude and phase synchrony of the fundamental frequency component of the visual SSEP while the second harmonic component showed an increase in phase synchrony, only. In contrast, inter-modal attention to touch increased SSEP amplitude of the second harmonic but not of the fundamental frequency, while leaving phase synchrony unaffected in both responses. Our results show that inter-modal attention generally influences concurrent stimulus processing in vision and touch, thus, extending earlier audio-visual findings to a visuo-tactile stimulus situation. The pattern of results, however, suggests differences in the neural implementation of inter-modal attentional influences on visual vs. tactile stimulus processing.

Early visual and auditory processing rely on modality-specific attentional resources.

Many everyday situations require focusing on visual or auditory information while ignoring the other modality. Previous findings suggest an attentional mechanism that operates between sensory modalities and governs such states. To date, evidence is equivocal as to whether this 'intermodal' attention relies on a distribution of resources either common or specific to sensory modalities. We provide new insights by investigating consequences of a shift from simultaneous ('bimodal') attention to vision and audition to unimodal selective attention. Concurrently presented visual and auditory stimulus streams were frequency-tagged to elicit steady-state responses (SSRs) recorded simultaneously in electro- and magnetoencephalograms (EEG/MEG). After the shift, decreased amplitudes of the SSR corresponding to the unattended sensory stream indicated reduced processing. We did not observe an amplitude increase of the SSR corresponding to the attended sensory stream. These findings are incompatible with a common-resources account. A redistribution of attentional resources between vision and audition would result in simultaneous processing gain in the attended sensory modality and reduction in the unattended sensory modality. Our results favor a modality-specific-resources account, which allows for independent modulation of early cortical processing in each sensory modality.

Independent effects of attentional gain control and competitive interactions on visual stimulus processing.

Attention filters behaviorally relevant stimuli from the constant stream of sensory information comprising our environment. Research into underlying neural mechanisms in humans suggests that visual attention biases mutual suppression between stimuli resulting from competition for limited processing resources. As a consequence, processing of an attended stimulus is facilitated. This account makes 2 assumptions: 1) An attended stimulus is released from mutual suppression with competing stimuli and 2) an attended stimulus experiences greater gain in the presence of competing stimuli than when it is presented alone. Here, we tested these assumptions by recording frequency-tagged potentials elicited in early visual cortex that index stimulus-specific processing. We contrasted the processing of a given stimulus when its location was attended or unattended and in the presence or the absence of a nearby competing stimulus. At variance with previous findings, competition similarly suppressed processing of attended and unattended stimuli. Moreover, the magnitude of attentional gain was comparable in the presence or the absence of competing stimuli. We conclude that visuospatial selective attention does not directly modulate mutual suppression between stimuli but instead acts as a signal gain, which biases processing toward attended stimuli independent of competition.