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

Binding Mechanisms in Visual Perception and Their Link With Neural Oscillations: A Review of Evidence From tACS

Neurophysiological studies in humans employing magneto- (MEG) and electro- (EEG) encephalography increasingly suggest that oscillatory rhythmic activity of the brain may be a core mechanism for binding sensory information across space, time, and object features to generate a unified perceptual representation. To distinguish whether oscillatory activity is causally related to binding processes or whether, on the contrary, it is a mere epiphenomenon, one possibility is to employ neuromodulatory techniques such as transcranial alternating current stimulation (tACS). tACS has seen a rising interest due to its ability to modulate brain oscillations in a frequency-dependent manner. In the present review, we critically summarize current tACS evidence for a causal role of oscillatory activity in spatial, temporal, and feature binding in the context of visual perception. For temporal binding, the emerging picture supports a causal link with the power and the frequency of occipital alpha rhythms (8–12 Hz); however, there is no consistent evidence on the causal role of the phase of occipital tACS. For feature binding, the only study available showed a modulation by occipital alpha tACS. The majority of studies that successfully modulated oscillatory activity and behavioral performance in spatial binding targeted parietal areas, with the main rhythms causally linked being the theta (~7 Hz) and beta (~18 Hz) frequency bands. On the other hand, spatio-temporal binding has been directly modulated by parieto-occipital gamma (~40–60 Hz) and alpha (10 Hz) tACS, suggesting a potential role of cross-frequency coupling when binding across space and time. Nonetheless, negative or partial results have also been observed, suggesting methodological limitations that should be addressed in future research. Overall, the emerging picture seems to support a causal role of brain oscillations in binding processes and, consequently, a certain degree of plasticity for shaping binding mechanisms in visual perception, which, if proved to have long lasting effects, can find applications in different clinical populations

Alpha power increase after transcranial alternating current stimulation at alpha frequency (α-tacs) reflects plastic changes rather than entrainment

Background: Periodic stimulation of occipital areas using transcranial alternating current stimulation (tACS) at alpha (α) frequency (8–12 Hz) enhances electroencephalographic (EEG) α-oscillation long after tACS-offset. Two mechanisms have been suggested to underlie these changes in oscillatory EEG activity: tACS-induced entrainment of brain oscillations and/or tACS-induced changes in oscillatory circuits by spike-timing dependent plasticity.<p></p> Objective: We tested to what extent plasticity can account for tACS-aftereffects when controlling for entrainment “echoes.” To this end, we used a novel, intermittent tACS protocol and investigated the strength of the aftereffect as a function of phase continuity between successive tACS episodes, as well as the match between stimulation frequency and endogenous α-frequency.<p></p> Methods: 12 healthy participants were stimulated at around individual α-frequency for 15–20 min in four sessions using intermittent tACS or sham. Successive tACS events were either phase-continuous or phase-discontinuous, and either 3 or 8 s long. EEG α-phase and power changes were compared after and between episodes of α-tACS across conditions and against sham.<p></p> Results: α-aftereffects were successfully replicated after intermittent stimulation using 8-s but not 3-s trains. These aftereffects did not reveal any of the characteristics of entrainment echoes in that they were independent of tACS phase-continuity and showed neither prolonged phase alignment nor frequency synchronization to the exact stimulation frequency.<p></p> Conclusion: Our results indicate that plasticity mechanisms are sufficient to explain α-aftereffects in response to α-tACS, and inform models of tACS-induced plasticity in oscillatory circuits. Modifying brain oscillations with tACS holds promise for clinical applications in disorders involving abnormal neural synchrony

Lasting EEG/MEG aftereffects on human brain oscillations after rhythmic transcranial brain stimulation: Level of control over oscillatory network activity

A number of rhythmic protocols have emerged for non-invasive brain stimulation (NIBS) in humans, including transcranial alternating current stimulation (tACS), oscillatory transcranial direct current stimulation (otDCS) and repetitive (also called rhythmic) transcranial magnetic stimulation (rTMS). With these techniques, it is possible to match the frequency of the externally applied electromagnetic fields to the intrinsic frequency of oscillatory neural population activity ("frequency-tuning"). Mounting evidence suggests that by this means tACS, otDCS, and rTMS can entrain brain oscillations and promote associated functions in a frequency-specific manner, in particular during (i.e. online to) stimulation. Here, we focus instead on the changes in oscillatory brain activity that persist after the end of stimulation. Understanding such aftereffects in healthy participants is an important step for developing these techniques into potentially useful clinical tools for the treatment of specific patient groups. Reviewing the electrophysiological evidence in healthy participants, we find aftereffects on brain oscillations to be a common outcome following tACS/otDCS and rTMS. However, we did not find a consistent, predictable pattern of aftereffects across studies, which is in contrast to the relative homogeneity of reported online effects. This indicates that aftereffects are partially dissociated from online, frequency-specific (entrainment) effects during tACS/otDCS and rTMS. We outline possible accounts and future directions for a better understanding of the link between online entrainment and offline aftereffects, which will be key for developing more targeted interventions into oscillatory brain activity

Causal evidence that intrinsic beta frequency is relevant for enhanced signal propagation in the motor system as shown through rhythmic TMS

Correlative evidence provides support for the idea that brain oscillations underpin neural computations. Recent work using rhythmic stimulation techniques in humans provide causal evidence but the interactions of these external signals with intrinsic rhythmicity remain unclear. Here, we show that sensorimotor cortex precisely follows externally applied rhythmic TMS (rTMS) stimulation in the beta-band but that the elicited responses are strongest at the intrinsic individual beta-peak-frequency. While these entrainment effects are of short duration, even subthreshold rTMS pulses propagate through the network and elicit significant cortico-spinal coupling, particularly when stimulated at the individual beta-frequency. Our results show that externally enforced rhythmicity interacts with intrinsic brain rhythms such that the individual peak frequency determines the effect of rTMS. The observed downstream spinal effect at the resonance frequency provides evidence for the causal role of brain rhythms for signal propagation

After-effects of 10 Hz tACS over the prefrontal cortex on phonological word decisions

Introduction Previous work in the language domain has shown that 10 Hz rTMS of the left or right posterior inferior frontal gyrus (pIFG) in the prefrontal cortex impaired phonological decision-making, arguing for a causal contribution of the bilateral pIFG to phonological processing. However, the neurophysiological correlates of these effects are unclear. The present study addressed the question whether neural activity in the prefrontal cortex could be modulated by 10 Hz tACS and how this would affect phonological decisions. Methods In three sessions, 24 healthy participants received tACS at 10 Hz or 16.18 Hz (control frequency) or sham stimulation over the bilateral prefrontal cortex before task processing. Resting state EEG was recorded before and after tACS. We also recorded EEG during task processing. Results Relative to sham stimulation, 10 Hz tACS significantly facilitated phonological response speed. This effect was task-specific as tACS did not affect a simple control task. Moreover, 10 Hz tACS significantly increased theta power during phonological decisions. The individual increase in theta power was positively correlated with the behavioral facilitation after 10 Hz tACS. Conclusion Our results show a facilitation of phonological decisions after 10 Hz tACS over the bilateral prefrontal cortex. This might indicate that 10 Hz tACS increased task-related activity in the stimulated area to a level that was optimal for phonological performance. The significant correlation with the individual increase in theta power suggests that the behavioral facilitation might be related to increased theta power during language processing

Parietal tACS at beta frequency improves vision in a crowding regime

Abstract Visual crowding is the inability to discriminate objects when presented with nearby flankers and sets a fundamental limit for conscious perception. Beta oscillations in the parietal cortex were found to be associated to crowding, with higher beta amplitude related to better crowding resilience. An open question is whether beta activity directly and selectively modulates crowding. We employed transcranial alternating current stimulation (tACS) in the beta band (18-Hz), in the alpha band (10-Hz) or in a sham regime, asking whether 18-Hz tACS would selectively improve the perception of crowded stimuli by increasing parietal beta activity. Resting electroencephalography (EEG) was measured before and after stimulation to test the influence of tACS on endogenous oscillations. Consistently with our predictions, we found that 18-Hz tACS, as compared to 10-Hz tACS and sham stimulation, reduced crowding. This improvement was found specifically in the contralateral visual hemifield and was accompanied by an increased amplitude of EEG beta oscillations, confirming an effect on endogenous brain rhythms. These results support a causal relationship between parietal beta oscillations and visual crowding and provide new insights into the precise oscillatory mechanisms involved in human vision

Investigating the role of right parietal cortex in multistable perception using non-invasive brain stimulation

Multistable perception describes the spontaneous fluctuation between two or more perceptual states when sensory input is ambiguous. An example hereof is bistability, which occurs when a stimulus has two competing interpretations that perceptually alternate over time. For instance, in structure- from-motion (SFM) bistable perception, the coherent movement of dots creates the illusion of a rotating sphere, where the direction of movement is uncertain. Another example is binocular rivalry (BR), which occurs when the two eyes are presented with dissimilar visual stimuli in the same retinal space, leading to an alternation of conscious awareness between the two stimuli. Multistable perception has been used to investigate the neural correlates of conscious experience, since an unchanging stimulus leads to a change in awareness, hence dissociating consciousness from sensory processing. Functional magnetic resonance imaging (fMRI) has consistently shown activity of the right intraparietal sulcus (IPS) and right superior parietal lobule (SPL) during perceptual transitions in multistable perception. Previously, transcranial magnetic stimulation (TMS) and in particular inhibitory theta burst stimulation (cTBS) has been used on the IPS to probe its causal role in multistable perception. That endeavour has produced inconsistent results on whether IPS inhibition shortens or lengthens multistable dominance durations. Problematically, the neural effects of cTBS over IPS during multistable perception are unknown, as is indeed the causal role of IPS in mediating perceptual reversals. Chapter 1 cTBS was applied over IPS or over vertex control site, between two sessions of fMRI, to illuminate the changes in neural activity accompanied by IPS cTBS. During the fMRI sessions, participants viewed alternating blocks of a bistable SFM stimulus or a replay condition using depth-cue disambiguated SFM. Behaviourally, it was found that IPS cTBS lengthened dominance durations when comparing pre vs post cTBS as well as when comparing IPS with vertex stimulation. Neurally, IPS cTBS led to a decrease in blood-oxygen-level dependent (BOLD) response in thalamus, foveal V1, right superior parietal lobule and middle frontal gyrus compared to vertex cTBS. Moreover, a decrease of functional connectivity between activity in IPS and ipsilateral hippocampus was observed. The present results suggest that the combined effects of a reduction of sensory processing as well as decoupling between IPS and the memory site hippocampus allows inhibitory TMS over parietal cortex to stabilise the current perceptual content. Together, these results provide a hitherto unreported insight into the brain networks that subserve the resolution of bistable perception and how IPS stimulation modulates them to bring about a behavioural effect. Chapter 2 Next to the IPS, also the more posterior SPL has been indicated as serving a causal role in multistable perception. TMS has been used to modulate bistable dominance durations for both sites, but in opposite directions. This led to the proposal that parietal cortex is fractionated, such that IPS and SPL serve opposing functions. However, neuroimaging evidence also suggests that higher cortical activity, including parietal cortex, is diminished when BR percept switches are either unreported or unreportable. This suggests that parietal regions have no causal role in multistable perception, but are active only as consequence thereof. To resolve this conflict, chapter 2 investigates whether cTBS to the IPS as well as the SPL affects the temporal dynamics of BR using regular button press rivalry as well as no-report and invisible rivalry paradigms. Specifically, it was hypothesised that cTBS would lead to a change in BR dominance when it was visible or unreported, but not when invisible. However, contrary to expectation, not only was it not possible to replicate the previously observed functional fractionation of parietal cortex, but also no difference was found between any cTBS condition. To verify if cTBS had its desired inhibitory effect, also motor-evoked potentials (MEP) were recording prior and following cTBS to primary motor cortex. It was found that cTBS to M1 decreases MEP amplitude. However, this effect did not correlate with the main findings over parietal cortex, leading to the conclusion that cTBS is not an apt neurostimulation technique to answer the present research question. Chapter 3 Relative intensities of steady-state responses (SSRs) over early visual cortex have been reported to correlate with conscious perception in paradigms like BR and have even be used to predict the content of consciousness. However, their causal role in perception remains uninvestigated despite their common use. Are modulations of SSRs mere epiphenomena of perception or do they aid in determining its content? To test this, it was enquired if interference with the SSR by means of transcranial alternating current stimulation (tACS) would affect conscious perception. Sham or real tACS across left and right parieto-occipital cortex was applied at either the same or a different frequency or in and out of phase with an SSR eliciting flicker stimulus, while participants viewed either BR or tried to detect stimuli masked by continuous flash suppression (CFS). It was found that tACS did not differentially affect conscious perception in the forms of BR predominance, CFS detection accuracy, reaction time, or metacognitive sensitivity. Importantly, the present null-findings are supported by Bayesian statistics. In conclusion, the application of tACS at frequencies and phases of stimulus-induced SSRs does not have perceptual effects. The relationship of tACS with SSRs and the possibility that SSRs are epiphenomenal to conscious perception is discussed. Chapter 4 One reason for the difference between findings of studies, which attempted to modulate multistable dominance durations thought cTBS to the IPS, may be that different stimuli were used, dissimilar properties of which modulated the TMS effect direction. To test this, cTBS was applied to the IPS between two sessions of SFM bistable perception (chapter 1), random dot motion BR (chapter 2), as well as checkerboard BR (chapter 3). It was foremost hypothesised that the findings of the first two chapters would be replicated, and moreover that the TMS effect would correlate between stimuli. Contrary to this hypothesis, cTBS neither consistently affected dominance durations in any of the stimuli, nor were effect sizes correlated across participants. This is supported by Bayesian statistics. Baseline dominance durations prior to TMS correlated across the three stimuli, suggesting a common mechanism to resolve multistability. However, the lack of correlation pertaining to the cTBS effect points towards the absence of any cTBS effect. Considering the present results, the small samples and effect sizes of previous studies, as well as recent literature of variable cTBS effects on motor cortex, this chapter concludes that there is good reason to cast general doubt over the ability of parietal cTBS to modulate dominance durations in multistable perception. Chapter 1 pointed towards the importance of multiple brain networks including the IPS in the resolution of multistability. Chapters 2 & 4 by contrast presented with null results that do not allow inference as to the causal role of IPS. Similarly, the use of tACS to modulate SSRs in chapter 3 was not able to demonstrate conclusively whether SSRs have a causal role in multistability. The search for the contribution of IPS by use of cTBS or tACS has been hindered by methodological concerns over whether these methods have an interpretable or even any effect on IPS activity. In summary, the causal role of IPS activity in multistable perception remains elusive

Hearing through your eyes: neural basis of audiovisual cross-activation, revealed by transcranial alternating current stimulation

Some people experience auditory sensations when seeing visual flashes or movements. This prevalent synaesthesia-like ‘visual-evoked auditory response’ (vEAR) could result either from over-exuberant cross-activation between brain areas, and/or reduced inhibition of normally-occurring cross-activation. We have used transcranial alternating current stimulation (tACS) to test these theories. We applied tACS at 10Hz (alpha-band frequency) or 40Hz (gamma-band), bilaterally either to temporal or occipital sites, while measuring same/different discrimination of paired auditory (A) versus visual (V) 'Morse code' sequences. At debriefing, participants were classified as vEAR or non-vEAR depending on whether they reported 'hearing' the silent flashes. In non-vEAR participants, temporal 10Hz tACS caused impairment of A performance, which correlated with improved V; conversely under occipital tACS, poorer V performance correlated with improved A. This reciprocal pattern suggests that sensory cortices are normally mutually inhibitory, and that alpha-frequency tACS may bias the balance of competition between them. vEAR participants showed no tACS effects, consistent with reduced inhibition, or enhanced cooperation between modalities. In addition, temporal 40Hz tACS impaired V performance, specifically in individuals who showed a performance advantage for V (relative to A). Gamma-frequency tACS may therefore modulate the ability of these individuals to benefit from recoding flashes into the auditory modality, possibly by disrupting cross-activation of auditory areas by visual stimulation. Our results support both theories, suggesting that vEAR may depend on disinhibition of normally-occurring sensory cross-activation, which may be expressed more strongly in some individuals. Furthermore, endogenous alpha and gamma-frequency oscillations may function respectively to inhibit or promote this cross-activation

A cross-modal investigation into the relationships between bistable perception and a global temporal mechanism

When the two eyes are presented with sufficiently different images, Binocular Rivalry (BR) occurs. BR is a form of bistable perception involving stochastic alternations in awareness between distinct images shown to each eye. It has been suggested that the dynamics of BR are due to the activity of a central temporal process and are linked to involuntary mechanisms of selective attention (aka exogenous attention). To test these ideas, stimuli designed to evoke exogenous attention and central temporal processes were employed during BR observation. These stimuli included auditory and visual looming motion and streams of transient events of varied temporal rate and pattern. Although these stimuli exerted a strong impact over some aspects of BR, they were unable to override its characteristic stochastic pattern of alternations completely. It is concluded that BR is subject to distributed influences, but ultimately, is achieved in neural processing areas specific to the binocular conflict