The visual cortex produces gamma band echo in response to broadband visual flicker

The aim of this study is to uncover the network dynamics of the human visual cortex by driving it with a broadband random visual flicker. We here applied a broadband flicker (1–720 Hz) while measuring the MEG and then estimated the temporal response function (TRF) between the visual input and the MEG response. This TRF revealed an early response in the 40–60 Hz gamma range as well as in the 8–12 Hz alpha band. While the gamma band response is novel, the latter has been termed the alpha band perceptual echo. The gamma echo preceded the alpha perceptual echo. The dominant frequency of the gamma echo was subject-specific thereby reflecting the individual dynamical properties of the early visual cortex. To understand the neuronal mechanisms generating the gamma echo, we implemented a pyramidal-interneuron gamma (PING) model that produces gamma oscillations in the presence of constant input currents. Applying a broadband input current mimicking the visual stimulation allowed us to estimate TRF between the input current and the population response (akin to the local field potentials). The TRF revealed a gamma echo that was similar to the one we observed in the MEG data. Our results suggest that the visual gamma echo can be explained by the dynamics of the PING model even in the absence of sustained gamma oscillations.     

Functional dissociation of ongoing oscillatory brain states

The state of a neural assembly preceding an incoming stimulus is assumed to modulate the processing of subsequently presented stimuli. The nature of this state can differ with respect to the frequency of ongoing oscillatory activity. Oscillatory brain activity of specific frequency range such as alpha (8-12 Hz) and gamma (above 30 Hz) band oscillations are hypothesized to play a functional role in cognitive processing. Therefore, a selective modulation of this prestimulus activity could clarify the functional role of these prestimulus fluctuations. For this purpose, we adopted a novel non-invasive brain-computer-interface (BCI) strategy to selectively increase alpha or gamma band activity in the occipital cortex combined with an adaptive presentation of visual stimuli within specific brain states. During training, oscillatory brain activity was estimated online and fed back to the participants to enable a deliberate modulation of alpha or gamma band oscillations. Results revealed that volunteers selectively increased alpha and gamma frequency oscillations with a high level of specificity regarding frequency range and localization. At testing, alpha or gamma band activity was classified online and at defined levels of activity, visual objects embedded in noise were presented instantly and had to be detected by the volunteer. In experiment I, the effect of two levels of prestimulus gamma band activity on visual processing was examined. During phases of increased gamma band activity significantly more visual objects were detected. In experiment II, the effect was compared against increased levels of alpha band activity. An improvement of visual processing was only observed for enhanced gamma band activity. Both experiments demonstrate the specific functional role of prestimulus gamma band oscillations for perceptual processing. We propose that the BCI method permits the selective modulation of oscillatory activity and the direct assessment of behavioral consequences to test for functional dissociations of different oscillatory brain states.     

Noisy Galvanic Vestibular Stimulation Modulates the Amplitude of EEG Synchrony Patterns

Noisy galvanic vestibular stimulation has been associated with numerous cognitive and behavioural effects, such as enhancement of visual memory in healthy individuals, improvement of visual deficits in stroke patients, as well as possibly improvement of motor function in Parkinson’s disease; yet, the mechanism of action is unclear. Since Parkinson’s and other neuropsychiatric diseases are characterized by maladaptive dynamics of brain rhythms, we investigated whether noisy galvanic vestibular stimulation was associated with measurable changes in EEG oscillatory rhythms within theta (4–7.5 Hz), low alpha (8–10 Hz), high alpha (10.5–12 Hz), beta (13–30 Hz) and gamma (31–50 Hz) bands. We recorded the EEG while simultaneously delivering noisy bilateral, bipolar stimulation at varying intensities of imperceptible currents – at 10, 26, 42, 58, 74 and 90% of sensory threshold – to ten neurologically healthy subjects. Using standard spectral analysis, we investigated the transient aftereffects of noisy stimulation on rhythms. Subsequently, using robust artifact rejection techniques and the Least Absolute Shrinkage Selection Operator regression and cross-validation, we assessed the combinations of channels and power spectral features within each EEG frequency band that were linearly related with stimulus intensity. We show that noisy galvanic vestibular stimulation predominantly leads to a mild suppression of gamma power in lateral regions immediately after stimulation, followed by delayed increase in beta and gamma power in frontal regions approximately 20–25 s after stimulation ceased. Ongoing changes in the power of each oscillatory band throughout frontal, central/parietal, occipital and bilateral electrodes predicted the intensity of galvanic vestibular stimulation in a stimulus-dependent manner, demonstrating linear effects of stimulation on brain rhythms. We propose that modulation of neural oscillations is a potential mechanism for the previously-described cognitive and motor effects of vestibular stimulation, and noisy galvanic vestibular stimulation may provide an additional non-invasive means for neuromodulation of functional brain networks.     

Gamma Power Is Phase-Locked to Posterior Alpha Activity

Neuronal oscillations in various frequency bands have been reported in numerous studies in both humans and animals. While it is obvious that these oscillations play an important role in cognitive processing, it remains unclear how oscillations in various frequency bands interact. In this study we have investigated phase to power locking in MEG activity of healthy human subjects at rest with their eyes closed. To examine cross-frequency coupling, we have computed coherence between the time course of the power in a given frequency band and the signal itself within every channel. The time-course of the power was calculated using a sliding tapered time window followed by a Fourier transform. Our findings show that high-frequency gamma power (30–70 Hz) is phase-locked to alpha oscillations (8–13 Hz) in the ongoing MEG signals. The topography of the coupling was similar to the topography of the alpha power and was strongest over occipital areas. Interestingly, gamma activity per se was not evident in the power spectra and only became detectable when studied in relation to the alpha phase. Intracranial data from an epileptic subject confirmed these findings albeit there was slowing in both the alpha and gamma band. A tentative explanation for this phenomenon is that the visual system is inhibited during most of the alpha cycle whereas a burst of gamma activity at a specific alpha phase (e.g. at troughs) reflects a window of excitability.     

Simultaneous EEG-fMRI during a Working Memory Task: Modulations in Low and High Frequency Bands

Background

EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown.

Methodology

In 16 healthy adult subjects, we first investigated EEG-BOLD signal correlations for theta (5–7 Hz), alpha1 (8–10), alpha2 (10–12 Hz), beta1 (13–20), beta2 (20–30 Hz), and gamma (30–40 Hz) during the retention period of a WM task with set size 2 and 5. Secondly, we investigated whether load sensitive brain regions are characterised by effects that relate frequency bands to BOLD signals effects.

Principal Findings

We found negative theta-BOLD signal correlations in the MPFC, PPC, and cingulate cortex (ACC and PCC). For alpha1 positive correlations with the BOLD signal were found in ACC, MPFC, and PCC; negative correlations were observed in DLPFC, PPC, and inferior frontal gyrus (IFG). Negative alpha2-BOLD signal correlations were observed in parieto-occipital regions. Beta1-BOLD signal correlations were positive in ACC and negative in precentral and superior temporal gyrus. Beta2 and gamma showed only positive correlations with BOLD, e.g., in DLPFC, MPFC (gamma) and IFG (beta2/gamma). The load analysis revealed that theta and—with one exception—beta and gamma demonstrated exclusively positive load effects, while alpha1 showed only negative effects.

Conclusions

We conclude that the directions of EEG-BOLD signal correlations vary across brain regions and EEG frequency bands. In addition, some brain regions show both load sensitive BOLD and frequency band effects. Our data indicate that lower as well as higher frequency brain oscillations are linked to neurovascular processes during WM.     

To Perceive or Not Perceive: The Role of Gamma-band Activity in Signaling Object Percepts

The relation of gamma-band synchrony to holistic perception in which concerns the effects of sensory processing, high level perceptual gestalt formation, motor planning and response is still controversial. To provide a more direct link to emergent perceptual states we have used holistic EEG/ERP paradigms where the moment of perceptual “discovery” of a global pattern was variable. Using a rapid visual presentation of short-lived Mooney objects we found an increase of gamma-band activity locked to perceptual events. Additional experiments using dynamic Mooney stimuli showed that gamma activity increases well before the report of an emergent holistic percept. To confirm these findings in a data driven manner we have further used a support vector machine classification approach to distinguish between perceptual vs. non perceptual states, based on time-frequency features. Sensitivity, specificity and accuracy were all above 95%. Modulations in the 30–75 Hz range were larger for perception states. Interestingly, phase synchrony was larger for perception states for high frequency bands. By focusing on global gestalt mechanisms instead of local processing we conclude that gamma-band activity and synchrony provide a signature of holistic perceptual states of variable onset, which are separable from sensory and motor processing.     

Gamma Activity Coupled to Alpha Phase as a Mechanism for Top-Down Controlled Gating

Coupling between neural oscillations in different frequency bands has been proposed to coordinate neural processing. In particular, gamma power coupled to alpha phase is proposed to reflect gating of information in the visual system but the existence of such a mechanism remains untested. Here, we recorded ongoing brain activity using magnetoencephalography in subjects who performed a modified Sternberg working memory task in which distractors were presented in the retention interval. During the anticipatory pre-distractor period, we show that the phase of alpha oscillations was coupled with the power of high (80-120Hz) gamma band activity, i.e. gamma power consistently was lower at the trough than at the peak of the alpha cycle (9-12Hz). We further show that high alpha power was associated with weaker gamma power at the trough of the alpha cycle. This result is in line with alpha activity in sensory region implementing a mechanism of pulsed inhibition silencing neuronal firing every ~100 ms.     

Coherent activity between auditory and visual modalities during the induction of peacefulness

Multisensory integration involves combining information from different senses to create a perception. The diverse characteristics of different sensory systems make it interesting to determine how cooperation and competition contribute to emotional experiences. Therefore, the aim of this study were to estimate the bias from the match attributes of the auditory and visual modalities and to depict specific brain activity frequency (theta, alpha, beta, and gamma) patterns related to a peaceful mood by using magnetoencephalography. The present study provides evidence of auditory domination in perceptual bias during multimodality processing of peaceful consciousness. Coherence analysis suggested that the theta oscillations are a transmitter of emotion signals, with the left and right brains being active in peaceful and fearful moods, respectively. Notably, hemispheric lateralization was also apparent in the alpha and beta oscillations, which might govern simple or pure information (e.g. from single modality) in the right brain but complex or mixed information (e.g. from multiple modalities) in the left brain.     

Top-Down Control in Contour Grouping

Human observers tend to group oriented line segments into full contours if they follow the Gestalt rule of ''good continuation''. It is commonly assumed that contour grouping emerges automatically in early visual cortex. In contrast, recent work in animal models suggests that contour grouping requires learning and thus involves top-down control from higher brain structures. Here we explore mechanisms of top-down control in perceptual grouping by investigating synchronicity within EEG oscillations. Human participants saw two micro-Gabor arrays in a random order, with the task to indicate whether the first (S1) or the second stimulus (S2) contained a contour of collinearly aligned elements. Contour compared to non-contour S1 produced a larger posterior post-stimulus beta power (15–21 Hz). Contour S2 was associated with a pre-stimulus decrease in posterior alpha power (11–12 Hz) and in fronto-posterior theta (4–5 Hz) phase couplings, but not with a post-stimulus increase in beta power. The results indicate that subjects used prior knowledge from S1 processing for S2 contour grouping. Expanding previous work on theta oscillations, we propose that long-range theta synchrony shapes neural responses to perceptual groupings regulating lateral inhibition in early visual cortex.     

Driving oscillatory activity in the human cortex enhances motor performance

Voluntary movement is accompanied by changes in the degree to which neurons in the brain synchronize their activity within discrete frequency ranges. Two patterns of movement-related oscillatory activity stand out in human cortical motor areas. Activity in the beta frequency (15-30 Hz) band is prominent during tonic contractions but is attenuated prior to and during voluntary movement. Without such attenuation, movement may be slowed, leading to the suggestion that beta activity promotes postural and tonic contraction, possibly at a cost to the generation of new movements. In contrast, activity in the gamma (60-90 Hz) band increases during movement. The direction of change suggests that gamma activity might facilitate motor processing. In correspondence with this, increased frontal gamma activity is related with reduced reaction times. Yet the possibility remains that these functional correlations reflect an epiphenomenal rather than causal relationship. Here we provide strong evidence that oscillatory activities at the cortical level are mechanistically involved in determining motor behavior and can even improve performance. By driving cortical oscillations using noninvasive electrical stimulation, we show opposing effects at beta and gamma frequencies and interactions with motor task that reveal the potential quantitative importance of oscillations in motor behavior.     

Enhanced Stimulus-Induced Gamma Activity in Humans during Propofol-Induced Sedation

Stimulus-induced gamma oscillations in the 30–80 Hz range have been implicated in a wide number of functions including visual processing, memory and attention. While occipital gamma-band oscillations can be pharmacologically modified in animal preparations, pharmacological modulation of stimulus-induced visual gamma oscillations has yet to be demonstrated in non-invasive human recordings. Here, in fifteen healthy humans volunteers, we probed the effects of the GABA_A agonist and sedative propofol on stimulus-related gamma activity recorded with magnetoencephalography, using a simple visual grating stimulus designed to elicit gamma oscillations in the primary visual cortex. During propofol sedation as compared to the normal awake state, a significant 60% increase in stimulus-induced gamma amplitude was seen together with a 94% enhancement of stimulus-induced alpha suppression and a simultaneous reduction in the amplitude of the pattern-onset evoked response. These data demonstrate, that propofol-induced sedation is accompanied by increased stimulus-induced gamma activity providing a potential window into mechanisms of gamma-oscillation generation in humans.     

Selective Modulation of Interhemispheric Functional Connectivity by HD-tACS Shapes Perception

Oscillatory neuronal synchronization between cortical areas has been suggested to constitute a flexible mechanism to coordinate information flow in the human cerebral cortex. However, it remains unclear whether synchronized neuronal activity merely represents an epiphenomenon or whether it is causally involved in the selective gating of information. Here, we combined bilateral high-density transcranial alternating current stimulation (HD-tACS) at 40 Hz with simultaneous electroencephalographic (EEG) recordings to study immediate electrophysiological effects during the selective entrainment of oscillatory gamma-band signatures. We found that interhemispheric functional connectivity was modulated in a predictable, phase-specific way: In-phase stimulation enhanced synchronization, anti-phase stimulation impaired functional coupling. Perceptual correlates of these connectivity changes were found in an ambiguous motion task, which strongly support the functional relevance of long-range neuronal coupling. Additionally, our results revealed a decrease in oscillatory alpha power in response to the entrainment of gamma band signatures. This finding provides causal evidence for the antagonistic role of alpha and gamma oscillations in the parieto-occipital cortex and confirms that the observed gamma band modulations were physiological in nature. Our results demonstrate that synchronized cortical network activity across several spatiotemporal scales is essential for conscious perception and cognition.     

Different origins of gamma rhythm and high-gamma activity in macaque visual cortex

During cognitive tasks electrical activity in the brain shows changes in power in specific frequency ranges, such as the alpha (8-12 Hz) or gamma (30-80 Hz) bands, as well as in a broad range above ～80 Hz, called the high-gamma band. The role or significance of this broadband high-gamma activity is unclear. One hypothesis states that high-gamma oscillations serve just like gamma oscillations, operating at a higher frequency and consequently at a faster timescale. Another hypothesis states that high-gamma power is related to spiking activity. Because gamma power and spiking activity tend to co-vary during most stimulus manipulations (such as contrast modulations) or cognitive tasks (such as attentional modulation), it is difficult to dissociate these two hypotheses. We studied the relationship between high-gamma power, gamma rhythm, and spiking activity in the primary visual cortex (V1) of awake monkeys while varying the stimulus size, which increased the gamma power but decreased the firing rate, permitting a dissociation. We found that gamma power became anti-correlated with the high-gamma power, suggesting that the two phenomena are distinct and have different origins. On the other hand, high-gamma power remained tightly correlated with spiking activity under a wide range of stimulus manipulations. We studied this relationship using a signal processing technique called Matching Pursuit and found that action potentials are associated with sharp transients in the LFP with broadband power, which is visible at frequencies as low as ～50 Hz. These results distinguish broadband high-gamma activity from gamma rhythms as an easily obtained and reliable electrophysiological index of neuronal firing near the microelectrode. Further, they highlight the importance of making a careful dissociation between gamma rhythms and spike-related transients that could be incorrectly decomposed as rhythms using traditional signal processing methods.     

High Gamma Oscillations in Medial Temporal Lobe during Overt Production of Speech and Gestures

The study of the production of co-speech gestures (CSGs), i.e., meaningful hand movements that often accompany speech during everyday discourse, provides an important opportunity to investigate the integration of language, action, and memory because of the semantic overlap between gesture movements and speech content. Behavioral studies of CSGs and speech suggest that they have a common base in memory and predict that overt production of both speech and CSGs would be preceded by neural activity related to memory processes. However, to date the neural correlates and timing of CSG production are still largely unknown. In the current study, we addressed these questions with magnetoencephalography and a semantic association paradigm in which participants overtly produced speech or gesture responses that were either meaningfully related to a stimulus or not. Using spectral and beamforming analyses to investigate the neural activity preceding the responses, we found a desynchronization in the beta band (15–25 Hz), which originated 900 ms prior to the onset of speech and was localized to motor and somatosensory regions in the cortex and cerebellum, as well as right inferior frontal gyrus. Beta desynchronization is often seen as an indicator of motor processing and thus reflects motor activity related to the hand movements that gestures add to speech. Furthermore, our results show oscillations in the high gamma band (50–90 Hz), which originated 400 ms prior to speech onset and were localized to the left medial temporal lobe. High gamma oscillations have previously been found to be involved in memory processes and we thus interpret them to be related to contextual association of semantic information in memory. The results of our study show that high gamma oscillations in medial temporal cortex play an important role in the binding of information in human memory during speech and CSG production.     

Modulating Brain Oscillations to Drive Brain Function

Do neuronal oscillations play a causal role in brain function? In a study in this issue of PLOS Biology, Helfrich and colleagues address this long-standing question by attempting to drive brain oscillations using transcranial electrical current stimulation. Remarkably, they were able to manipulate visual perception by forcing brain oscillations of the left and right visual hemispheres into synchrony using oscillatory currents over both hemispheres. Under this condition, human observers more often perceived an inherently ambiguous visual stimulus in one of its perceptual instantiations. These findings shed light on the mechanisms underlying neuronal computation. They show that it is the neuronal oscillations that drive the visual experience, not the experience driving the oscillations. And they indicate that synchronized oscillatory activity groups brain areas into functional networks. This points to new ways for controlled experimental and possibly also clinical interventions for the study and modulation of brain oscillations and associated functions.How does the brain work? How does it code, transfer, and store information? How are conscious experiences generated? These, among others, are long-standing questions neuroscientists try to answer. One way to approach this is to study how the brain orchestrates behaviour, for instance, by measuring brain activity and relating it to behaviour. Yet, studying the brain–behaviour relationship raises another series of questions: What type of brain activity should one look at? Do we need to record directly from single neurons? Or can we make inferences also by recording from larger pools of neurons? And importantly, do these measures of brain activity provide mechanistic accounts of how the brain implements function, or are they just inevitable side-products, with limited explanatory power for the neural mechanisms underlying our experiences, thoughts, or actions?Certainly, one would have a good argument for brain activity causally underlying brain function if (i) this brain activity not only relates to sensory experiences or behavioural performance measures (revealing a correlative brain-behaviour relationship), but (ii) interventions into this brain activity would also modulate our experiences or performance (revealing a causal link). Recent developments allow addressing these central points for oscillatory brain activity, which is what Helfrich et al. [1] did in their study published in this issue of PLOS Biology.At the basis of Helfrich et al.''s study are two lines of research, one of which is concerned with the interpretation of a special type of brain activity, namely, brain oscillations. This type of brain activity represents voltage fluctuations of neuronal elements and was initially observed from one scalp electrode by Hans Berger [2]. Today, brain oscillations are typically recorded from multiple sensors distributed over the scalp or brain, for instance using electro- or magneto-encephalography (EEG/MEG), in order to make inferences about the orchestration of brain activity across distinct neuronal elements [3]. A prominent view is that these oscillations represent essential network activity. They become visible when neuronal elements of a network start to synchronize their oscillatory activity, i.e., temporarily couple together [4]. Notably, brain oscillations vary in frequencies depending on the task that is being executed and the region of the brain they are recorded from [3] (see Box 1 for example frequencies relevant for Helfrich et al.''s study). It is understood that this may reflect nested networks that oscillate at different frequencies and spatial scales [4] and that define functional architecture not only by synchronizing at the same frequency but also through complex cross-frequency interactions; this to allow for integration of processes at different temporal and spatial scales [5]–[7]. With respect to the above questions on how the brain operates, the most exciting aspect of oscillatory brain activity is probably that it offers mechanistic accounts. One example is the communication-through-coherence theory [8], which states that the relative timing of oscillatory activity of two neuronal elements enables the control of information transfer, with communication being maximal when phases of high excitability of these elements cycle in synchrony, and minimal when they cycle out of synchrony (see Fig. 1B Model).Open in a separate windowFigure 1Schematic representation of design, objectives, and insights from the study by Helfrich et al. A. Design and questions: Participants viewed an apparent motion stimulus, which elicits a bistable percept consisting of either horizontal (percept 1) or vertical motion (percept 2). A bi-hemispheric network of two posterior areas (blue and red squares) was interrogated as to the functionality of inter-area synchrony (see “?”) in generating these percepts, by recording of brain oscillations through electro-encephalography (EEG), and interventions into these oscillations through transcranial alternating current stimulation (tACS). B. Results and conclusion: EEG revealed that the horizontal motion percept was associated with enhanced synchrony (coherence) between oscillatory brain activity of the two posterior areas (as compared to vertical motion percept), in line with coupling of the two areas to a functional network by synchronization of their respective phases of high excitability (see Model). This provides information on a correlative relationship between network activation and function but cannot disentangle whether it is the percept that drives the network, or the network that drives the percept. Intervention with tACS supports the latter. Applying tACS in synchrony over the two areas enhances inter-area coherence of oscillatory activity as well as the horizontal motion percept (as opposed to applying tACS out of synchrony). Hence, synchrony of oscillatory brain activity underlies the formation of functional networks and mediates its associated functions.

Box 1. Glossary

Brain oscillations in the gamma frequency band (gamma-oscillations): This is a class of brain oscillations cycling at rapid frequencies (35–100 Hz). Gamma-oscillations are prominent in visual cortex (among other areas) and become evident also in scalp recordings when participants view specific types of visual stimuli. Alpha-band brain oscillations cycle at 8–12 Hz. Alpha-oscillations can co-occur with gamma-oscillations in visual areas, where these two classes of oscillations show an inverse relationship in terms of amplitude. Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) use electrical currents applied through two or more scalp electrodes for transient, non-invasive brain stimulation, whereas transcranial magnetic stimulation (TMS) uses the principle of electromagnetic induction. In tACS, the currents are modulated in an oscillatory (sinusoidal) pattern, and can therefore be frequency-tuned to underlying brain oscillations. Likewise, TMS in its rhythmic form (rhythmic TMS) allows for periodic brain stimulation at frequencies of brain oscillations.The other line of research that is at the heart of Helfrich et al.''s study is concerned with interventions into brain activity by non-invasive brain stimulation techniques; this to probe the brain–behaviour relationship along a more causal dimension [9]. Such techniques are widely used in cognitive and clinical neuroscience, and employ either magnetic or electric fields to stimulate neurons directly (i.e., transcranially) to then test the behavioural consequences. Currently available techniques use transcranial magnetic stimulation (TMS), or a variety of electrical currents such as with transcranial direct current stimulation (tDCS) or transcranial alternating current stimulation (tACS) (see Box 1) [10]. While these techniques have been successfully employed in numerous studies, a recurrent question is how to improve specificity of effects in terms of enhancing focality [11] or targeting specific subpopulations within the stimulated neuronal pool [12]. In addition, simultaneous neuroimaging studies have revealed that the effect of the magnetic or electric field on the stimulated area (under the TMS coil or the stimulation electrode) is spreading to other areas, in many instances along anatomical connections [13],[14]. Hence, any behavioural outcome needs to be interpreted in the context of network effects. Intriguingly, and relevant for interactions with oscillatory brain activity, recent findings indicate that the specificity of these interventions into functionally relevant brain activity may be improved by taking into account not only the spatial dimension (i.e., what anatomical network to stimulate) but also the temporal dimension (what frequency to apply). This is suggested by recent studies using periodic transcranial stimulation protocols (such as tACS or rhythmic TMS) allowing a frequency tuning of stimulation (see Box 1). These studies demonstrate an immediate behavioural effect at specific stimulation frequencies, namely those that match the frequencies of intrinsic brain oscillations[15]–[21]; which may be caused by the periodic stimulation promoting the intrinsic oscillations [22]–[24].Capitalizing on the above, Helfrich et al. convincingly address in healthy human volunteers the long-standing issue of whether oscillatory brain activity indeed coordinates functional brain architecture, as opposed to representing a mere by-product, and thereby bridge a gap between recordings and interventional studies into brain oscillations (see Fig. 1 for a schematic representation of design, objectives, and insights of the study). They do so by examining the link between visual network activity and specific sensory experiences. To manipulate sensory experience (without changing sensory input), Helfrich et al. employed a visual motion paradigm (see Fig. 1A), in which pairs of diagonally opposed dots are presented on a screen in two alternating configurations (upper left/lower right dots followed by lower left/upper right dots, etc.). This leads to a bistable percept, consisting of time periods during which the two dots are perceived as moving horizontally (see Fig. 1A, apparent motion percept 1), alternating with time periods during which the same dots are perceived as moving vertically (Fig. 1A, apparent motion percept 2). Interestingly, recordings of brain oscillations from left and right occipito-parietal EEG sensors, i.e., from areas processing the right- versus left-sided dots respectively, revealed a temporally stable pattern of relative timing between these oscillations, depending on the percept (replicating [25]): during horizontal motion percepts when the demands for interhemispheric communication can be assumed to be high (as opposed to vertical percepts where motion integration can be resolved within each hemisphere) [26], these left and right oscillations show high coherence in the gamma frequency band (at approximately 35–100 Hz) (Fig. 1B EEG). In other words, oscillations in the left and right occipito-parietal areas are synchronized. This is suggestive of these areas forming a temporally stable network during horizontal as opposed to vertical motion integration, in line with models of network coordination by synchronization of brain oscillations (Fig. 1B Model) [8],[27]. Importantly, applying rhythmic brain stimulation in synchrony over the left and right occipito-parietal cortex using tACS at gamma frequency enhances both the gamma-band EEG coherence between the two hemispheres (without affecting gamma-power) and its associated percept (i.e., horizontal motion), as opposed to applying gamma-tACS out of synchrony (Fig. 1B tACS). See also Polania et al. [19] for a conceptually similar tACS result, without the direct evidence for concurrently enhanced EEG synchrony. This shows that in-synchrony tACS versus out-of-synchrony tACS over two elements of an oscillatory visual network can be used to stabilize/destabilize this network, and with meaningful perceptual consequences. This is in accord with brain oscillations not only indexing network coordination and associated functions, but causing them.The findings of Helfrich et al. make an important contribution. They more firmly link the dynamics of oscillatory brain activity to the formation of functional networks, as well as the orchestration of brain function (here phenomenological experience) and this along a causal dimension. This corroborates and extends a growing number of studies showing that brain oscillations can serve as targets for controlled interventions into brain activity and function, by non-invasive brain stimulation in periodic patterns [22]–[24]. The principle idea is to promote brain oscillations that have been associated with specific functions (as inferred from correlative brain-behavioural links) to cause performance changes, provided a causal relationship underlies the correlative data. For instance, it has been shown that promoting oscillations of the parietal cortex known to be related to attentional selection using frequency-tuned rhythmic TMS [22] biases perception towards the expected stimulus dimension [17],[20]. Likewise, tACS (or oscillatory tDCS) tuned to fronto-temporal oscillations, which have been associated with memory consolidation during slow-wave sleep or dream patterns during REM-sleep (e.g., lucid dreaming), have been shown to enhance memory or lucid dream content, respectively [15],[21]. And equivalent effects have been found for oscillatory motor system activity [16],[18]. This opens powerful opportunities for neuroscience and clinical interventions, not only allowing to test models of how brain activity implements function but also how it relates to dysfunction, to inform controlled intervention into the brain–behaviour relationship.These findings are exciting and indicate that it is promising to study brain oscillations, even at a macroscopic scale (such as measured with EEG/MEG), to answer some of the long-standing questions of how the brain works. They also take the emerging new approach of using periodic transcranial stimulation to interact with brain oscillations and function beyond the proof-of-principle stage. However, the usefulness of this approach will depend on the extent to which its specificity can be improved (e.g., up- versus down-regulating oscillations, tailoring to individual differences) and its mechanisms of actions understood. One unresolved point is the spatial extent of stimulation. With tACS, the conventional stimulation electrodes are large (several cm²) and require a “return” electrode which excites widespread areas. To render stimulation more focal, special electrode montages have been proposed [11], as also used by Helfrich et al., and which may explain some of the differences to a previous study of the same group using a less focal electrode montage [28]. Other developments are underway to funnel stimulation to specific target areas by the use of multichannel electrode configurations and computational (forward) models of electrical field distributions [29]. In this context, it will be of interest to compare the efficiency of frequency-tuned tACS with frequency-tuned rhythmic TMS, the latter thought to be more focal, but also more superficial. In addition, it is still largely unknown how these forms of rhythmic stimulation interact with intrinsic brain oscillations. There is growing evidence that the periodic electric or magnetic force may entrain the underlying oscillations during stimulation [22],[23], and that long-lasting effects may arise from this entrainment, possibly by inducing plasticity effects via spike-timing dependent plasticity in the circuits generating these oscillations [30]. It is the former, short-term effects that are of interest for experimental interventions in cognitive neuroscience for testing theory (because of their limited duration), but the latter, longer-lasting effects that are of relevance for clinical interventions. Finally, while Helfrich et al. report cross-frequency effects of gamma-tACS, in particular in the alpha frequency band (8–12 Hz), it remains to be studied in detail how the induced oscillations resonate in other, nested oscillatory networks. These and other points will need to be resolved in future work to be able to fully assess the extent of the impact of this emerging approach.     

Traveling waves in the prefrontal cortex during working memory

Neural oscillations are evident across cortex but their spatial structure is not well- explored. Are oscillations stationary or do they form “traveling waves”, i.e., spatially organized patterns whose peaks and troughs move sequentially across cortex? Here, we show that oscillations in the prefrontal cortex (PFC) organized as traveling waves in the theta (4-8Hz), alpha (8-12Hz) and beta (12-30Hz) bands. Some traveling waves were planar but most rotated. The waves were modulated during performance of a working memory task. During baseline conditions, waves flowed bidirectionally along a specific axis of orientation. Waves in different frequency bands could travel in different directions. During task performance, there was an increase in waves in one direction over the other, especially in the beta band.     

Functional Roles of 10 Hz Alpha-Band Power Modulating Engagement and Disengagement of Cortical Networks in a Complex Visual Motion Task

Alpha band power, particularly at the 10 Hz frequency, is significantly involved in sensory inhibition, attention modulation, and working memory. However, the interactions between cortical areas and their relationship to the different functional roles of the alpha band oscillations are still poorly understood. Here we examined alpha band power and the cortico-cortical interregional phase synchrony in a psychophysical task involving the detection of an object moving in depth by an observer in forward self-motion. Wavelet filtering at the 10 Hz frequency revealed differences in the profile of cortical activation in the visual processing regions (occipital and parietal lobes) and in the frontoparietal regions. The alpha rhythm driving the visual processing areas was found to be asynchronous with the frontoparietal regions. These findings suggest a decoupling of the 10 Hz frequency into separate functional roles: sensory inhibition in the visual processing regions and spatial attention in the frontoparietal regions.     

Time and Frequency-Dependent Modulation of Local Field Potential Synchronization by Deep Brain Stimulation

High-frequency electrical stimulation of specific brain structures, known as deep brain stimulation (DBS), is an effective treatment for movement disorders, but mechanisms of action remain unclear. We examined the time-dependent effects of DBS applied to the entopeduncular nucleus (EP), the rat homolog of the internal globus pallidus, a target used for treatment of both dystonia and Parkinson’s disease (PD). We performed simultaneous multi-site local field potential (LFP) recordings in urethane-anesthetized rats to assess the effects of high-frequency (HF, 130 Hz; clinically effective), low-frequency (LF, 15 Hz; ineffective) and sham DBS delivered to EP. LFP activity was recorded from dorsal striatum (STR), ventroanterior thalamus (VA), primary motor cortex (M1), and the stimulation site in EP. Spontaneous and acute stimulation-induced LFP oscillation power and functional connectivity were assessed at baseline, and after 30, 60, and 90 minutes of stimulation. HF EP DBS produced widespread alterations in spontaneous and stimulus-induced LFP oscillations, with some effects similar across regions and others occurring in a region- and frequency band-specific manner. Many of these changes evolved over time. HF EP DBS produced an initial transient reduction in power in the low beta band in M1 and STR; however, phase synchronization between these regions in the low beta band was markedly suppressed at all time points. DBS also enhanced low gamma synchronization throughout the circuit. With sustained stimulation, there were significant reductions in low beta synchronization between M1-VA and STR-VA, and increases in power within regions in the faster frequency bands. HF DBS also suppressed the ability of acute EP stimulation to induce beta oscillations in all regions along the circuit. This dynamic pattern of synchronizing and desynchronizing effects of EP DBS suggests a complex modulation of activity along cortico-BG-thalamic circuits underlying the therapeutic effects of GPi DBS for conditions such as PD and dystonia.     

Neural mechanisms of human perceptual learning: electrophysiological evidence for a two-stage process

Background

Humans and other animals change the way they perceive the world due to experience. This process has been labeled as perceptual learning, and implies that adult nervous systems can adaptively modify the way in which they process sensory stimulation. However, the mechanisms by which the brain modifies this capacity have not been sufficiently analyzed.

Methodology/Principal Findings

We studied the neural mechanisms of human perceptual learning by combining electroencephalographic (EEG) recordings of brain activity and the assessment of psychophysical performance during training in a visual search task. All participants improved their perceptual performance as reflected by an increase in sensitivity (d'') and a decrease in reaction time. The EEG signal was acquired throughout the entire experiment revealing amplitude increments, specific and unspecific to the trained stimulus, in event-related potential (ERP) components N2pc and P3 respectively. P3 unspecific modification can be related to context or task-based learning, while N2pc may be reflecting a more specific attentional-related boosting of target detection. Moreover, bell and U-shaped profiles of oscillatory brain activity in gamma (30–60 Hz) and alpha (8–14 Hz) frequency bands may suggest the existence of two phases for learning acquisition, which can be understood as distinctive optimization mechanisms in stimulus processing.

Conclusions/Significance

We conclude that there are reorganizations in several neural processes that contribute differently to perceptual learning in a visual search task. We propose an integrative model of neural activity reorganization, whereby perceptual learning takes place as a two-stage phenomenon including perceptual, attentional and contextual processes.     

Learning-induced modulation of oscillatory activities in the mammalian olfactory system: The role of the centrifugal fibres

In the mammalian olfactory system, oscillations related to odour representation have been described in field potential activities. Previous results showed that in olfactory bulb (OB) of awake rats engaged in an olfactory learning, odour presentation produced a decrease of oscillations in gamma frequency range (60-90 Hz) associated with a power increase in beta frequency range (15-40 Hz). This response pattern was strongly amplified in trained animals. The aim of this work was twofold: whether learning also induces similar changes in OB target structures and whether such OB response depends on its centrifugal inputs. Local field potentials (LFPs) were recorded through chronically implanted electrodes in the OB, piriform and enthorhinal cortices of freely moving rats performing an olfactory discrimination. Oscillatory activities characteristics (amplitude, frequency and time-course) were extracted in beta and gamma range by a wavelet analysis. First, we found that odour induced beta oscillatory activity was present not only in the OB, but also in the other olfactory structures. In each recording site, characteristics of the beta oscillatory responses were dependent of odour, structure and learning level. Unilateral section of the olfactory peduncle was made before training, and LFPs were symmetrically recorded in the two bulbs all along the acquisition of the learning task. Data showed that deprivation of centrifugal feedback led to an increase of spontaneous gamma activity. Moreover, under this condition olfactory learning was no longer associated with the typical large beta band. As a whole, learning modulation of the beta oscillatory response in olfactory structures may reflect activity of a distributed functional network involved in odour representation.