Overactivated contextual visual perception and response to a single dose of methylphenidate in children with ADHD.

The pathogenesis of overactivated visual perception in attention-deficit hyperactivity disorder (ADHD) remains unclear, which is interpreted as a cognitive compensation. The existing studies have proposed that perceptual abnormalities in neurodevelopmental disorders are associated with dysfunction of the contextual knowledge system, which influences the development and formation of perception. We hypothesized that alterations in contextual states may also be responsible for inducing perceptual abnormalities in ADHD. Therefore, the present study evaluated the characteristics of pre-stimulus alpha and its response to a single dose of methylphenidate (MPH). A total of 135 Chinese children participated in the first study, including 70 children with ADHD (age = 10.61 ± 1.93 years, female = 17) and 65 age- and sex-matched control children (age = 10.73 ± 1.93 years, female = 20). The second clinical trial included 19 Chinese children with ADHD (age = 11.85 ± 1.72 years, female = 4), with an identical visual spatial search task. Pre-stimulus alpha oscillations and P1 activity were significantly greater in children with ADHD than in the controls. Overactivated pre-stimulus alpha positively predicted P1. Both pre-stimulus alpha and P1 overactivation have beneficial effects on cognitive performance in children with ADHD. No intervening effect of a single dose of MPH on the compensatory activation of pre-stimulus alpha and P1 were observed. Our findings extended the perceptual activation to the contextual knowledge system, suggesting that compensatory perception in children with ADHD is more likely to be a top-down regulated cognitive operational process.

Prestimulus amygdala spectral activity is associated with visual face awareness.

Alpha cortical oscillations have been proposed to suppress sensory processing in the visual, auditory, and tactile domains, influencing conscious stimulus perception. However, it is unknown whether oscillatory neural activity in the amygdala, a subcortical structure involved in salience detection, has a similar impact on stimulus awareness. Recording intracranial electroencephalography (EEG) from 9 human amygdalae during face detection in a continuous flash suppression task, we found increased spectral prestimulus power and phase coherence, with most consistent effects in the alpha band, when faces were undetected relative to detected, similarly as previously observed in cortex with this task using scalp-EEG. Moreover, selective decreases in the alpha and gamma bands preceded face detection, with individual prestimulus alpha power correlating negatively with detection rate in patients. These findings reveal for the first time that prestimulus subcortical oscillations localized in human amygdala may contribute to perceptual gating mechanisms governing subsequent face detection and offer promising insights on the role of this structure in visual awareness.

Dissociated amplitude and phase effects of alpha oscillation in a nested structure of rhythm- and sequence-based temporal expectation.

The human brain can utilize various information to form temporal expectations and optimize perceptual performance. Here we show dissociated amplitude and phase effects of prestimulus alpha oscillation in a nested structure of rhythm- and sequence-based expectation. A visual stream of rhythmic stimuli was presented in a fixed sequence such that their temporal positions could be predicted by either the low-frequency rhythm, the sequence, or the combination. The behavioral modeling indicated that rhythmic and sequence information additively led to increased accumulation speed of sensory evidence and alleviated threshold for the perceptual discrimination of the expected stimulus. The electroencephalographical results showed that the alpha amplitude was modulated mainly by rhythmic information, with the amplitude fluctuating with the phase of the low-frequency rhythm (i.e. phase-amplitude coupling). The alpha phase, however, was affected by both rhythmic and sequence information. Importantly, rhythm-based expectation improved the perceptual performance by decreasing the alpha amplitude, whereas sequence-based expectation did not further decrease the amplitude on top of rhythm-based expectation. Moreover, rhythm-based and sequence-based expectations collaboratively improved the perceptual performance by biasing the alpha oscillation toward the optimal phase. Our findings suggested flexible coordination of multiscale brain oscillations in dealing with a complex environment.

Pre-stimulus gamma power in human posteromedial cortex shows supra-modal mechanisms in predicting the amplitude and latency of task-induced suppression.

Upon repetitively performing the same well-practiced task on identical bottom-up stimuli, our performance still varies. Although it has been well documented that elevated pre-stimulus baseline activity in the human default-mode network impairs the subsequent task performance, it remains unknown (i) the fine-grained temporal dynamics and (ii) whether the underlying neural dynamics are supra-modal or modality-specific. We utilized intracranial recordings in the human posteromedial cortex (PMC) during a simple visual and an auditory detection task. Our findings suggested that the pre-stimulus gamma power in PMC predicted the subsequent task performance. Critically, the higher the pre-stimulus gamma power, the longer it took for it to be suppressed, and the less suppressed it was during the task performance, which eventually resulted in deleterious effects on task performance, i.e. longer reaction times. These fine-grained temporal dynamics were consistent between the visual and auditory simple detection task. In addition, a direct comparison between the visual and auditory modality showed that the between-modality difference emerged during the recovery period from the maximal gamma suppression back to the baseline. Taken together, the present results contribute novel spatio-temporal mechanisms in human PMC on how simple detection performance varies across multiple repetitions, irrespective of the sensory modality involved.

Pre-stimulus alpha activity modulates long-lasting unconscious feature integration.

Pre-stimulus alpha (α) activity can influence perception of shortly presented, low-contrast stimuli. The underlying mechanisms are often thought to affect perception exactly at the time of presentation. In addition, it is suggested that α cycles determine temporal windows of integration. However, in everyday situations, stimuli are usually presented for periods longer than ∼100 ms and perception is often an integration of information across space and time. Moving objects are just one example. Hence, the question is whether α activity plays a role also in temporal integration, especially when stimuli are integrated over several α cycles. Using electroencephalography (EEG), we investigated the relationship between pre-stimulus brain activity and long-lasting integration in the sequential metacontrast paradigm (SQM), where two opposite vernier offsets, embedded in a stream of lines, are unconsciously integrated into a single percept. We show that increases in α power, even 300 ms before the stimulus, affected the probability of reporting the first offset, shown at the very beginning of the SQM. This effect was mediated by the systematic slowing of the α rhythm that followed the peak in α power. No phase effects were found. Together, our results demonstrate a cascade of neural changes, following spontaneous bursts of α activity and extending beyond a single moment, which influences the sensory representation of visual features for hundreds of milliseconds. Crucially, as feature integration in the SQM occurs before a conscious percept is elicited, this also provides evidence that α activity is linked to mechanisms regulating unconscious processing.

Prestimulus alpha power signals attention to retrieval.

The human brain is in distinct processing modes at different times. Specifically, a distinction can be made between encoding and retrieval modes, which refer to the brain's state when it is storing new information or searching for old information, respectively. Recent research proposed the idea of a "ready-to-encode" mode, which describes a prestimulus effect in brain activity that signals (external) attention to encoding and predicts subsequent memory performance. Whether there is also a corresponding "ready-to-retrieve" mode in human brain activity is currently unclear. In this study, we examined whether prestimulus oscillations can be linked to (internal) attention to retrieval. We show that task cues to prepare for retrieval (or testing) in comparison with restudy of previously studied vocabulary word pairs led to a significant decrease of prestimulus alpha power just before the onset of word stimuli. Beamformer analysis localized this effect in the right secondary visual cortex (Brodmann area 18). Correlation analysis showed that the task cue-induced, prestimulus alpha power effect is positively related to stimulus-induced alpha/beta power, which in turn predicted participants' memory performance. The results are consistent with the idea that prestimulus alpha power signals internal attention to retrieval, which promotes the elaborative processing of episodic memories. Future research on brain-computer interfaces may find the findings interesting regarding the potential of using online measures of fluctuating alpha oscillations to trigger the presentation and sequencing of restudy and testing trials, ultimately enhancing instructional learning strategies.

Global, Low-Amplitude Cortical State Predicts Response Outcomes in a Selective Detection Task in Mice.

Spontaneous neuronal activity strongly impacts stimulus encoding and behavioral responses. We sought to determine the effects of neocortical prestimulus activity on stimulus detection. We trained mice in a selective whisker detection task, in which they learned to respond (lick) to target stimuli in one whisker field and ignore distractor stimuli in the contralateral whisker field. During expert task performance, we used widefield Ca2+ imaging to assess prestimulus and post-stimulus neuronal activity broadly across frontal and parietal cortices. We found that lower prestimulus activity correlated with enhanced stimulus detection: lower prestimulus activity predicted response versus no response outcomes and faster reaction times. The activity predictive of trial outcome was distributed through dorsal neocortex, rather than being restricted to whisker or licking regions. Using principal component analysis, we demonstrate that response trials are associated with a distinct and less variable prestimulus neuronal subspace. For single units, prestimulus choice probability was weak yet distributed broadly, with lower than chance choice probability correlating with stronger sensory and motor encoding. These findings support low amplitude and low variability as an optimal prestimulus cortical state for stimulus detection that presents globally and predicts response outcomes for both target and distractor stimuli.

Informative and uninformative prestimulus cues at encoding benefit familiarity and source memory.

Previous research has shown that neural activity elicited by informative prestimulus cues during encoding differ with respect to subsequent memory outcomes. These findings indicate prestimulus cues create a "brain state" associated with subsequent memory that, potentially, also has downstream effects benefitting processes associated with successful encoding and subsequent memory performance. However, previous studies have not included the conditions necessary to appropriately test this latter assumption. The present study examines how informative and uninformative prestimulus encoding cues affect memory accuracy for upcoming stimuli compared to a no cue condition. At encoding, participants made one of two semantic judgments on words preceded by an informative prestimulus cue that identified the upcoming semantic judgment, an uninformative prestimulus cue that signalled an upcoming trial but no information about the semantic judgment, or no cue. Dual process estimates of familiarity, but not recollection, demonstrated a graded pattern with the informativeness of the prestimulus cues (i.e., informative > uninformative > no cues). Moreover, both informative and uninformative prestimulus cues enhanced subsequent source memory accuracy for the encoding task compared to the no cue condition. These findings suggest that prestimulus cues can strengthen the processes that support successful memory encoding and benefit subsequent familiarity and source memory.

Cortical response variability is driven by local excitability changes with somatotopic organization.

Identical sensory stimuli can lead to different neural responses depending on the instantaneous brain state. Specifically, neural excitability in sensory areas may shape the brain´s response already from earliest cortical processing onwards. However, whether these dynamics affect a given sensory domain as a whole or occur on a spatially local level is largely unknown. We studied this in the somatosensory domain of 38 human participants with EEG, presenting stimuli to the median and tibial nerves alternatingly, and testing the co-variation of initial cortical responses in hand and foot areas, as well as their relation to pre-stimulus oscillatory states. We found that amplitude fluctuations of initial cortical responses to hand and foot stimulation - the N20 and P40 components of the somatosensory evoked potential (SEP), respectively - were not related, indicating local excitability changes in primary sensory regions. In addition, effects of pre-stimulus alpha (8-13 Hz) and beta (18-23 Hz) band amplitude on hand-related responses showed a robust somatotopic organization, thus further strengthening the notion of local excitability fluctuations. However, for foot-related responses, the spatial specificity of pre-stimulus effects was less consistent across frequency bands, with beta appearing to be more foot-specific than alpha. Connectivity analyses in source space suggested this to be due to a somatosensory alpha rhythm that is primarily driven by activity in hand regions while beta frequencies may operate in a more hand-region-independent manner. Altogether, our findings suggest spatially distinct excitability dynamics within the primary somatosensory cortex, yet with the caveat that frequency-specific processes in one sub-region may not readily generalize to other sub-regions.

Increased insula activity precedes the formation of subjective illusory Gestalt.

The constructive nature of human perception sometimes leads us to perceiving rather complex impressions from simple sensory input: for example, recognizing animal contours in cloud formations or seeing living creatures in shadows of objects. A special type of bistable stimuli gives us a rare opportunity to study the neural mechanisms behind this process. Such stimuli can be visually interpreted either as simple or as more complex illusory content on the basis of the same sensory input. Previous studies demonstrated increased activity in the superior parietal cortex during the perception of an illusory Gestalt impression compared to a simpler interpretation. Here, we examined the role of slow fluctuations of resting-state fMRI activity in shaping the subsequent illusory interpretation by investigating activity related to the illusory Gestalt not only during, but also prior to its perception. We presented 31 participants with a bistable motion stimulus, which can be perceived either as four moving dot pairs (local) or two moving illusory squares (global). fMRI was used to measure brain activity in a slow event-related design. We observed stronger IPS and putamen responses to the stimulus when participants perceived the global interpretation compared to the local, confirming the findings of previous studies. Most importantly, we also observed that the global stimulus interpretation was preceded by an increased activity of the bilateral dorsal insula, which is known to process saliency and gate information for conscious access. Our data suggest an important role of the dorsal insula in shaping complex illusory interpretations of the sensory input.

Ongoing neural oscillations influence behavior and sensory representations by suppressing neuronal excitability.

The ability to process and respond to external input is critical for adaptive behavior. Why, then, do neural and behavioral responses vary across repeated presentations of the same sensory input? Ongoing fluctuations of neuronal excitability are currently hypothesized to underlie the trial-by-trial variability in sensory processing. To test this, we capitalized on intracranial electrophysiology in neurosurgical patients performing an auditory discrimination task with visual cues: specifically, we examined the interaction between prestimulus alpha oscillations, excitability, task performance, and decoded neural stimulus representations. We found that strong prestimulus oscillations in the alpha+ band (i.e., alpha and neighboring frequencies), rather than the aperiodic signal, correlated with a low excitability state, indexed by reduced broadband high-frequency activity. This state was related to slower reaction times and reduced neural stimulus encoding strength. We propose that the alpha+ rhythm modulates excitability, thereby resulting in variability in behavior and sensory representations despite identical input.

Effects of Age on Prestimulus Neural Activity Predictive of Successful Memory Encoding: An fMRI Study.

Prestimulus subsequent memory effects (SMEs)-differences in neural activity preceding the onset of study items that are predictive of later memory performance-have consistently been reported in young adults. The present functional magnetic resonance imaging experiment investigated potential age-related differences in prestimulus SMEs. During study, healthy young and older participants made one of two semantic judgments on images, with the judgment signaled by a preceding cue. In test phase, participants first made an item recognition judgment and, for each item judged old, a source memory judgment. Age-invariant prestimulus SMEs were observed in left dorsomedial prefrontal cortex, left hippocampus, and right subgenual cortex. In each case, the effects reflected lower blood oxygen level dependent signal for later recognized items, regardless of source accuracy, than for unrecognized items. A similar age-invariant pattern was observed in left orbitofrontal cortex, but this effect was specific to items attracting a correct source response compared to unrecognized items. In contrast, the left angular gyrus and fusiform cortex demonstrated negative prestimulus SMEs that were exclusive to young participants. The findings indicate that age differences in prestimulus SMEs are regionally specific and suggest that prestimulus SMEs reflect multiple cognitive processes, only some of which are vulnerable to advancing age.

Prestimulus feedback connectivity biases the content of visual experiences.

Ongoing fluctuations in neural excitability and in networkwide activity patterns before stimulus onset have been proposed to underlie variability in near-threshold stimulus detection paradigms-that is, whether or not an object is perceived. Here, we investigated the impact of prestimulus neural fluctuations on the content of perception-that is, whether one or another object is perceived. We recorded neural activity with magnetoencephalography (MEG) before and while participants briefly viewed an ambiguous image, the Rubin face/vase illusion, and required them to report their perceived interpretation in each trial. Using multivariate pattern analysis, we showed robust decoding of the perceptual report during the poststimulus period. Applying source localization to the classifier weights suggested early recruitment of primary visual cortex (V1) and ∼160-ms recruitment of the category-sensitive fusiform face area (FFA). These poststimulus effects were accompanied by stronger oscillatory power in the gamma frequency band for face vs. vase reports. In prestimulus intervals, we found no differences in oscillatory power between face vs. vase reports in V1 or in FFA, indicating similar levels of neural excitability. Despite this, we found stronger connectivity between V1 and FFA before face reports for low-frequency oscillations. Specifically, the strength of prestimulus feedback connectivity (i.e., Granger causality) from FFA to V1 predicted not only the category of the upcoming percept but also the strength of poststimulus neural activity associated with the percept. Our work shows that prestimulus network states can help shape future processing in category-sensitive brain regions and in this way bias the content of visual experiences.

From Shorter to Longer Timescales: Converging Integrated Information Theory (IIT) with the Temporo-Spatial Theory of Consciousness (TTC).

Time is a key element of consciousness as it includes multiple timescales from shorter to longer ones. This is reflected in our experience of various short-term phenomenal contents at discrete points in time as part of an ongoing, more continuous, and long-term 'stream of consciousness'. Can Integrated Information Theory (IIT) account for this multitude of timescales of consciousness? According to the theory, the relevant spatiotemporal scale for consciousness is the one in which the system reaches the maximum cause-effect power; IIT currently predicts that experience occurs on the order of short timescales, namely, between 100 and 300 ms (theta and alpha frequency range). This can well account for the integration of single inputs into a particular phenomenal content. However, such short timescales leave open the temporal relation of specific phenomenal contents to others during the course of the ongoing time, that is, the stream of consciousness. For that purpose, we converge the IIT with the Temporo-spatial Theory of Consciousness (TTC), which, assuming a multitude of different timescales, can take into view the temporal integration of specific phenomenal contents with other phenomenal contents over time. On the neuronal side, this is detailed by considering those neuronal mechanisms driving the non-additive interaction of pre-stimulus activity with the input resulting in stimulus-related activity. Due to their non-additive interaction, the single input is not only integrated with others in the short-term timescales of 100-300 ms (alpha and theta frequencies) (as predicted by IIT) but, at the same time, also virtually expanded in its temporal (and spatial) features; this is related to the longer timescales (delta and slower frequencies) that are carried over from pre-stimulus to stimulus-related activity. Such a non-additive pre-stimulus-input interaction amounts to temporo-spatial expansion as a key mechanism of TTC for the constitution of phenomenal contents including their embedding or nesting within the ongoing temporal dynamic, i.e., the stream of consciousness. In conclusion, we propose converging the short-term integration of inputs postulated in IIT (100-300 ms as in the alpha and theta frequency range) with the longer timescales (in delta and slower frequencies) of temporo-spatial expansion in TTC.

Prestimulus dynamics blend with the stimulus in neural variability quenching.

Neural responses to the same stimulus show significant variability over trials, with this variability typically reduced (quenched) after a stimulus is presented. This trial-to-trial variability (TTV) has been much studied, however how this neural variability quenching is influenced by the ongoing dynamics of the prestimulus period is unknown. Utilizing a human intracranial stereo-electroencephalography (sEEG) data set, we investigate how prestimulus dynamics, as operationalized by standard deviation (SD), shapes poststimulus activity through trial-to-trial variability (TTV). We first observed greater poststimulus variability quenching in those real trials exhibiting high prestimulus variability as observed in all frequency bands. Next, we found that the relative effect of the stimulus was higher in the later (300-600ms) than the earlier (0-300ms) poststimulus period. Lastly, we replicate our findings in a separate EEG dataset and extend them by finding that trials with high prestimulus variability in the theta and alpha bands had faster reaction times. Together, our results demonstrate that stimulus-related activity, including its variability, is a blend of two factors: 1) the effects of the external stimulus itself, and 2) the effects of the ongoing dynamics spilling over from the prestimulus period - the state at stimulus onset - with the second dwarfing the influence of the first.

Subliminal perception is continuous with conscious vision and can be predicted from prestimulus electroencephalographic activity.

Individuals are able to discriminate visual stimuli they report not consciously seeing. This phenomenon is known as "subliminal perception." Such capacity is often assumed to be relatively automatic in nature and rely on stimulus-driven activity in low-level cortical areas. Instead, here we asked to what extent neural activity before stimulus presentation influences subliminal perception. We asked participants to discriminate the location of a briefly presented low-contrast visual stimulus and then rate how well they saw the stimulus. Consistent with previous studies, participants correctly discriminated with slightly above chance-level accuracy the location of a stimulus they reported not seeing. Signal detection analyses indicated that while subjects categorized their percepts as "unconscious," their capacity to discriminate these stimuli lay on the same continuum as conscious vision. We show that the accuracy of discriminating the location of a subliminal stimulus could be predicted with relatively high accuracy (AUC = 0.70) based on lateralized electroencephalographic (EEG) activity before the stimulus, the hemifield where the stimulus was presented, and the accuracy of previous trial's discrimination response. Altogether, our results suggest that rather than being a separate unconscious capacity, subliminal perception is based on similar processes as conscious vision.

Prestimulus Activity in the Cingulo-Opercular Network Predicts Memory for Naturalistic Episodic Experience.

Human memory is strongly influenced by brain states occurring before an event, yet we know little about the underlying mechanisms. We found that activity in the cingulo-opercular network (including bilateral anterior insula [aI] and anterior prefrontal cortex [aPFC]) seconds before an event begins can predict whether this event will subsequently be remembered. We then tested how activity in the cingulo-opercular network shapes memory performance. Our findings indicate that prestimulus cingulo-opercular activity affects memory performance by opposingly modulating subsequent activity in two sets of regions previously linked to encoding and retrieval of episodic information. Specifically, higher prestimulus cingulo-opercular activity was associated with a subsequent increase in activity in temporal regions previously linked to encoding and with a subsequent reduction in activity within a set of regions thought to play a role in retrieval and self-referential processing. Together, these findings suggest that prestimulus attentional states modulate memory for real-life events by enhancing encoding and possibly by dampening interference from competing memory substrates.

Dissociable neural correlates of stimulation intensity and detection in somatosensation.

Somatosensory stimulation intensity and behavioral detection are positively related, and both correlate with neural responses. However, it is still controversial as to what extent stimulus intensity and early somatosensory evoked potentials (SEP) predict detection and how these parameters interact with pre-stimulus brain oscillatory states, which also influence sensory processing. Here we investigated how early SEP components encode stimulation intensity, how pre-stimulus alpha- and beta-band amplitudes interact with SEPs, and which neural markers predict stimulus detection. To this end, we randomly presented electrical finger nerve stimulation with various intensities distributed along the individual psychometric response function (including catch trials) while recording the EEG. Participants reported stimulus presence on a trial-by-trial basis (one-alternative-forced-choice). For the lowest (imperceptible) intensities, participants showed zero (behavioral) sensitivity despite measurable early cortical processing reflected by the P50 component. The P50 amplitude scaled with increasing stimulation intensities but was not predictive of stimulus detection. Instead, detection was associated with the later negative N150 component, as well as with pre-stimulus lowered somatosensory alpha- and increased frontal beta-band amplitudes. Our results give evidence for a serial representation of stimulus intensity and detection, as reflected by the P50 and N150 amplitude, respectively. Furthermore, stimulus detection seems to depend on the current brain state, rendering upcoming stimulation being reportable or not.

Direct Evidence for Prediction Signals in Frontal Cortex Independent of Prediction Error.

Predictive coding (PC) has been suggested as one of the main mechanisms used by brains to interact with complex environments. PC theories posit top-down prediction signals, which are compared with actual outcomes, yielding in turn prediction error (PE) signals, which are used, bottom-up, to modify the ensuing predictions. However, disentangling prediction from PE signals has been challenging. Critically, while many studies found indirect evidence for PC in the form of PE signals, direct evidence for the prediction signal is mostly lacking. Here, we provide clear evidence, obtained from intracranial cortical recordings in human surgical patients, that the human lateral prefrontal cortex evinces prediction signals while anticipating an event. Patients listened to task-irrelevant sequences of repetitive tones including infrequent predictable or unpredictable pitch deviants. The broadband high-frequency amplitude (HFA) was decreased prior to the onset of expected relative to unexpected deviants in the frontal cortex only, and its amplitude was sensitive to the increasing likelihood of deviants following longer trains of standards in the unpredictable condition. Single-trial HFA predicted deviations and correlated with poststimulus response to deviations. These results provide direct evidence for frontal cortex prediction signals independent of PE signals.

Consistent pre-stimulus influences on auditory perception across the lifespan.

As we get older, perception in cluttered environments becomes increasingly difficult as a result of changes in peripheral and central neural processes. Given the aging society, it is important to understand the neural mechanisms constraining perception in the elderly. In young participants, the state of rhythmic brain activity prior to a stimulus has been shown to modulate the neural encoding and perceptual impact of this stimulus - yet it remains unclear whether, and if so, how, the perceptual relevance of pre-stimulus activity changes with age. Using the auditory system as a model, we recorded EEG activity during a frequency discrimination task from younger and older human listeners. By combining single-trial EEG decoding with linear modelling we demonstrate consistent statistical relations between pre-stimulus power and the encoding of sensory evidence in short-latency EEG components, and more variable relations between pre-stimulus phase and subjects' decisions in longer-latency components. At the same time, we observed a significant slowing of auditory evoked responses and a flattening of the overall EEG frequency spectrum in the older listeners. Our results point to mechanistically consistent relations between rhythmic brain activity and sensory encoding that emerge despite changes in neural response latencies and the relative amplitude of rhythmic brain activity with age.