Elsevier

NeuroImage

Volume 59, Issue 1, 2 January 2012, Pages 616-624
NeuroImage

Visual awareness suppression by pre-stimulus brain stimulation; a neural effect

https://doi.org/10.1016/j.neuroimage.2011.07.090Get rights and content

Abstract

Transcranial magnetic stimulation (TMS) has established the functional relevance of early visual cortex (EVC) for visual awareness with great temporal specificity non-invasively in conscious human volunteers. Many studies have found a suppressive effect when TMS was applied over EVC 80–100 ms after the onset of the visual stimulus (post-stimulus TMS time window). Yet, few studies found task performance to also suffer when TMS was applied even before visual stimulus presentation (pre-stimulus TMS time window). This pre-stimulus TMS effect, however, remains controversially debated and its origin had mainly been ascribed to TMS-induced eye-blinking artifacts. Here, we applied chronometric TMS over EVC during the execution of a visual discrimination task, covering an exhaustive range of visual stimulus-locked TMS time windows ranging from − 80 pre-stimulus to 300 ms post-stimulus onset. Electrooculographical (EoG) recordings, sham TMS stimulation, and vertex TMS stimulation controlled for different types of non-neural TMS effects. Our findings clearly reveal TMS-induced masking effects for both pre- and post-stimulus time windows, and for both objective visual discrimination performance and subjective visibility. Importantly, all effects proved to be still present after post hoc removal of eye blink trials, suggesting a neural origin for the pre-stimulus TMS suppression effect on visual awareness. We speculate based on our data that TMS exerts its pre-stimulus effect via generation of a neural state which interacts with subsequent visual input.

Highlights

► Pre-stimulus TMS suppresses visual awareness during a visual discrimination task. ► The pre-stimulus TMS effect cannot be explained by TMS-induced eye blinking. ► TMS-induced masking affects subjective awareness and performance in a similar way. ► Alpha oscillations may be the neural mechanism causing the pre-stimulus TMS effect.

Introduction

The neural origin of consciousness is one of the most fundamental and controversially debated topics in cognitive neuroscience at present. Within the domain of vision, much research has centered on the relevance of early visual cortex (EVC), i.e. V1, V2 and V3, for visual awareness, which is still a matter of current debate (Tong, 2003). Several researchers believe EVC to be nothing more than a relay station, passing on the visual information to higher level brain areas (Crick and Koch, 1995, Zeki and Bartels, 1998), which they consider the actual loci of visual awareness. However, activity in EVC varies with the nature of the visual percept, as has been shown in fMRI studies on binocular rivalry (Haynes and Rees, 2005) and apparent motion (Muckli et al., 2005). From these findings, EVC indeed appears to be involved in the initiation of visual awareness. However, correlational measures of brain activity, like fMRI, can never lead to conclusive evidence on matters of functional relevance, as such techniques passively measure brain activity instead of actively manipulating it.

Transcranial magnetic stimulation (TMS) allows the transient disruption of regular neural processing with great temporal as well as spatial resolution. By inducing such a ‘virtual lesion’ in healthy humans and subsequently investigating behavioral performances, a causal relationship between the stimulated brain area and a cognitive or perceptual faculty can be established; an approach that already has been successfully employed in the study of visual awareness. In this way, an ample number of studies showed that a TMS pulse delivered to EVC roughly 80–100 ms post-stimulus onset can effectively impair performance on visual tasks (e.g. Amassian et al., 1989, Beckers and Homberg, 1991, Beckers and Zeki, 1995, Christensen et al., 2008, Corthout et al., 1999a, Corthout et al., 1999b, Sack et al., 2009), which is in accord with retinocortical transmission times. Thus, through TMS it was established that in normal vision EVC has a role to play in the generation of visual awareness, be it as the locus of visual awareness or by relaying the information to ascending ‘awareness’ regions. Moreover, TMS has established that EVC's role in visual awareness is restricted to a certain temporal window at which unperturbed neural activity within EVC is critical for visual awareness.

A remarkable finding was the discovery of an additional time window, when TMS applied prior to the onset of the visual stimulus caused a perceptual impairment (Beckers and Homberg, 1991, Corthout et al., 1999b, Corthout et al., 2000, Laycock et al., 2007, de Graaf et al., 2011). This pre-stimulus TMS effect caused debate in the literature, because it was not easily explainable based on the assumed mechanism by which TMS induces its suppressive effect in the brain. TMS presumably exerts its effect by suppressing the stimulus-related signal in EVC (Harris et al., 2008) or by adding random neural noise at the critical moment when a certain brain region attempts to process a given stimulus (Ruzzoli et al., 2010). But if visual information has not reached EVC yet, there is no neural signal for TMS to interfere with. Therefore, even those few studies that incorporated such pre-stimulus time windows in their experimental design doubt that the effect they find is actually neural in nature. In fact, our own group set aside as eye blink artifacts the pre-stimulus TMS effect found in a study of visual motion discrimination (Sack et al., 2006). Recently, however, the idea has been put forward that awareness depends on the neural state that the cortex is in when the visual signal arrives (Mathewson et al., 2009, Thut et al., 2006). The initiation of certain brain states is a conceivable mechanism of action of TMS. Generating a brain state that interacts with subsequent visual input might be a way in which TMS can influence awareness, even if the visual stimulus is not presented yet. These recent additions to the possible neural mechanisms of TMS led us to develop a renewed interest in this pre-stimulus TMS effect, and we wondered whether any empirical evidence exists that convincingly links it to eye blinks, as previously suggested, or to other non-neural effects TMS might have, such as multisensory integration of the visual stimulus with the clicking sound produced by TMS or an alteration in arousal or attention caused by the mildly aversive somatosensory sensations on the skull. It is reasonable to suggest that the auditory and somatosensory experiences that go along with TMS exert their effect in a time-dependent manner. They seem specifically relevant in the pre-stimulus period, because they herald the appearance of the visual stimulus.

Although paramount for a better and appropriate understanding and interpretation of TMS-induced masking effects, and the respective conclusions drawn for the neural mechanism underlying visual perception and awareness, only two studies have hitherto employed a measure of eye blink behavior during perceptual task execution. They demonstrated an early eye blink with an onset of approximately 10 ms post-TMS (Corthout et al., 2000) and a late eye blink delayed by around 35 ms (Beckers and Homberg, 1991, Corthout et al., 2000). Thus, a TMS pulse preceding the visual stimulus with roughly 10 ms or 35 ms can disturb perception by producing an eye blink at the moment of stimulus presentation. Unfortunately, the timing of the pre-stimulus masking effect is not consistent over studies, though in most cases it emerges in a rather narrow time window, particularly within single participants. This makes it hard to fit the eye blink data of Corthout et al. (2000) to the empirical results on perceptual tasks. Moreover, taking into account that an eye blink can take a full 200 ms (VanderWerf et al., 2003) from initiation to end, any pulse as early as 200 ms pre-stimulus could hinder normal visual processing. Still, as yet, no studies have implemented eye tracking to identify specific blinks on a trial-by-trial basis to evaluate the ‘clean’ trials in isolation, even though this would allow the disentanglement of the eye blinks from neural TMS consequences. If the trials, in which TMS did not elicit an eye blink, still show a relative decrease in visual performance, the effect can no longer be attributed to eye blinks as such.

Performance deterioration due to occipital TMS has been taken as a marker for the breakdown of visual awareness. However, behavior does not necessarily reflect subjective experience and measures of the two might show divergent results. Therefore, studies of visual awareness do not limit themselves any longer to the investigation of merely behavioral measures. Lately, ratings of subjective awareness have been included as dependent variable (Boyer et al., 2005, Christensen et al., 2008, Koivisto et al., 2010) leading to intriguing outcomes. Boyer et al. (2005) describe a dissociation between visual discrimination performance and awareness, which they named' TMS-induced blindsight’. It matches the symptoms of this neurological phenomenon in the sense that, even though people report to have no conscious percept, they are nevertheless able to identify the visual stimulus with accuracy levels surpassing chance. To the best of our knowledge, there have been no studies which explored such subjective awareness ratings with pre-stimulus TMS time windows. As mentioned before, a possible modus operandi of TMS might be the generation of particular cortical states. If the pre-stimulus TMS effect turns out to have a neural origin, it is conceivable that the induced state of the occipital cortex determines whether a stimulus reaches awareness or not. This process might be independent from the stimulus' behavioral consequences. Moreover, knowing that TMS can induce virtual blindsight, the effect TMS has on visual awareness might not show in the accuracy data. In this case, one needs a subjective measure of awareness to visualize the effect.

In the current study, we measured the effect of occipital TMS on a visual discrimination task over a wide range of time windows. We expected to find a breakdown in performance, if magnetic stimulation followed visual presentation with an approximate delay of 80–100 ms. Moreover, we tried to replicate the much less established pre-stimulus TMS effect in the same participant sample. We gathered electrophysiological data on participants' eye blinking behavior using electrooculographical recordings (EoG), to allow the post-hoc selection of trials without eye blinks. This way, we could systematically investigate whether TMS over EVC impairs visual performance both when applied at the critical time point after and before presentation of the visual stimulus, and whether these effects still hold after removal of eye blink trials. However, merely excluding eye blinks as causal to the pre-stimulus TMS effect is insufficient to ascribe it a neural nature. To be able to claim this, we included two control experiments. First, to control for the effects of auditory stimulation, we included a sham TMS session. Second, in a new group of subjects the full experiment was repeated, but this time, we stimulated a site irrelevant to the visual discrimination task, namely vertex. This second control experiment allowed us to rule out other non-neural side effects of TMS, like somatosensation. To allow the comparison of objective versus subjective measures of visual awareness, introspective visibility ratings were acquired in addition to the objective accuracy data in the experimental sessions, as well as in the sham control and vertex control experiments.

Section snippets

Participants

10 healthy participants (2 males, mean age 22.1 y, range 19–26) including one of the authors (CJ) with normal or corrected-to-normal vision participated in this study. All participants were screened by the medical supervisor prior to participation. They gave their written informed consent and were compensated financially. The study was approved by the Medical Ethics Committee of the University Medical Center, Maastricht, The Netherlands.

Two participants were excluded from further analysis, when

EoG

A time interval ranging from 200 ms prior until 100 post S1-onset was screened for eye blinks, as any blink within this interval might hinder visual perception of the target stimulus. In Experiment 1, participants blinked on 8% of the trials in this crucial 300 ms epoch on average, which might have prevented them from consciously perceiving the target stimulus. Across participants the frequency of eye blinks tended to vary considerably, ranging from 1.1 to 33.3% of the total number of trials. As

Discussion

The current study reliably reports a suppressive TMS effect in a visual discrimination task at the classical (i.e. 80–100 ms) time window post-stimulus onset as well as at the much less established pre-stimulus time window (− 60 ms). These results add evidence to the reality of such a pre-stimulus effect and validate the necessity of carefully looking into pre-stimulus time windows when investigating visual awareness with TMS. A very small number of studies so far have indeed looked into

Acknowledgments

The research leading to these results has received funding from the Netherlands Organization for Scientific Research (NWO; grant number 400-07-048), and the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) / ERC Grant agreement n° [263472]). We thank our medical supervisor Cees van Leeuwen, and our independent physician Martin van Boxtel. We also thank Annette Giani for her assistance with the psychophysical testing of the visual stimuli.

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