Elsevier

Brain Research

Volume 1642, 1 July 2016, Pages 136-145
Brain Research

Research Report
Visual masking with frontally applied pre-stimulus TMS and its subject-specific neural correlates

https://doi.org/10.1016/j.brainres.2016.03.038Get rights and content

Highlights

  • Pre-stimulus masking occurs even if TMS is directed to the frontal cortex.

  • This effect is correlated with the timing of a late positive TMS-evoked potential.

  • At the critical SOA this late TEP overlaps with the visual N200 component.

Abstract

The visibility of a visual target stimulus depends on the local state of the early visual cortex shortly before the stimulus itself is presented. This view is supported by the observation that occipitally applied pre-stimulus TMS can disrupt subsequent information processing leading to visual masking effects. According to another line of accumulating evidence, however, global pre-stimulus connectivity patterns could be as crucial as local cortical states. In line with the latter view we show that pre-stimulus masking occurs even if TMS is directed to the frontal cortex. Importantly, the individual extent of this effect is strongly correlated with the subject-specific peak latency of a late positive TMS-evoked potential. Our results thus suggest a third type of masking occurring neither through direct interaction with visual areas nor by a modal visual masking input. Our results also shed light on the inter-individual differences in TMS research in general.

Introduction

The fact that a clear visual stimulus can be rendered invisible by transcranial magnetic stimulation (TMS) after the onset of the visual stimulus is well documented (reviews: Bachmann and Francis, 2014; de Graaf et al., 2014). However, a disruptive effect on conscious visual perception can also be achieved if the TMS pulse which is targeted to the early visual cortex (EVC) is given ca. 80–40 ms before the onset of a visual target stimulus (e.g. Corthout et al., 1999a, Corthout et al., 1999b; Jacobs et al., 2012). This phenomenon – called pre-stimulus masking with TMS – offers potentially valuable insight into the neural mechanisms underlying conscious visual perception. Unfortunately it is not yet clear why and how pre-stimulus TMS masking occurs (de Graaf et al., 2014, Tapia and Beck, 2014). After all, no visual stimulus has yet been presented and thus TMS cannot disrupt or modulate any ongoing stimulus related activity directly. The currently favored hypothesis to explain this phenomenon is that pre-stimulus TMS modulates EVC by creating a state that is not conductive enough for subsequent information processing (de Graaf et al., 2011a), possibly by modulating the processes marked by ongoing alpha activity (Jacobs et al., 2012). Some empirical observations suggest, however, that this hypothesis of local state changes may not be the whole story.

First of all, pre-stimulus masking in the time window between −80 to −40 ms is not retinotopically specific. Masking occurs even if the electric field is induced in the ipsilateral hemisphere with respect to the upcoming target stimulus (Jacobs et al., 2014). Furthermore, pre-stimulus TMS-masking does not seem to depend on the exact coil position at all. Stimulation of different occipital areas produces an equally strong disruption of perception (Corthout et al., 1999b). Thus, either the state-altering effect of TMS somehow evenly carries over to the whole EVC or perhaps the disruption of perception is caused by an event that is not located in the EVC at all. Indeed, a number of studies have indicated that more global connectivity patterns may be as crucial for subsequent perception as is local pre-stimulus activity in early sensory cortices (Weisz et al., 2014, Leonardelli et al., 2015, Sadaghiani et al., 2015, Godwin et al., 2015, Nierhaus et al., 2015). Consequently, activity in higher cortical areas or even areas that are not directly related to visual perception at all could have an impact on upcoming visual processes (e.g. Park et al., 2014). If this is true then it follows that pre-stimulus TMS-masking could be possible not only through stimulation of visual cortex but also by stimulating other, possibly non-visual, areas located far from the occiput. Despite this intriguing possibility pre-stimulus TMS masking through stimulation of areas outside the EVC has not yet been investigated. More generally, the research about the neural mechanisms associated with pre-stimulus TMS masking should be extended to include global network effects.

Perhaps the main reason why pre-stimulus TMS masking remains so poorly understood concerns the fact that this effect is highly variable over subjects. The optimal stimulus onset asynchrony (SOA) between the pre-stimulus TMS and the visual stimulus can range over several tens of milliseconds between individuals and consequently the extent of masking at a fixed SOA also varies considerably over subjects (Corthout et al., 1999a, Jacobs et al., 2012). In general, there has been a lot of concern recently with the variability in brain stimulation studies and the resulting small effect sizes (e.g. Wiethoff et al., 2014; Horvath et al., 2015). Thus, it is possible that TMS as a technique is simply not reliable enough to produce robust pre-stimulus masking effects across subjects. On the other hand, pre-stimulus TMS masking has been paralleled with paracontrast masking which also shows considerable inter-individual variability (e.g. Tapia and Beck, 2014) similarly to metacontrast masking showing common genetic variability related individual effects (Maksimov et al., 2015). A quite likely reason for the varying pre-stimulus TMS masking results may therefore be that the critical neural events underlying this phenomenon are naturally variable across subjects. For example, the critical TMS-evoked and/or visually evoked processes may have varying latencies and they might not overlap optimally within each subject if TMS is given at a fixed SOA. Evidence along these lines is already available for interactions between TMS-evoked and visually evoked EEG markers (Thut et al., 2003, Reichenbach et al., 2011). Investigating the electrophysiological correlates of pre-stimulus TMS masking could therefore not only explain why and how pre-stimulus masking occurs, but also why it is so variable from one subject to another.

Taken together, the present study was designed to answer the following two questions. First, taking into account that global network dynamics prior to stimulus presentation may be more important than the local state of EVC, is it possible to produce pre-stimulus masking with TMS by stimulating a cortical area located far from visual cortices, e.g., the frontal cortex? Second, anticipating large inter-individual variability in the extent of pre-stimulus TMS masking, does the individual latency of TMS/visual stimulus related EEG components offer any explanatory power for the varying extent of behavioral effects?

Subjects performed a simple discrimination task while TMS or SHAM stimulation was targeted to right frontal cortex (electrode F2) and the pulse was given either −140/−60 or +20 ms relative to visual stimulus onset (Fig. 1a). Based on previous findings with EVC stimulation (e.g. Jacobs et al., 2012) we hypothesized that frontal TMS will mask visual stimuli specifically at −60 ms SOA, but the size of this effect will vary considerably between individual subjects. We concurrently recorded EEG activity from posterior scalp sites and analyzed subject-specific peak latencies of TMS as well as visual task related ERP components. We expected that the latency of one or several of these components will be associated with behavioral outcomes of spatially remote TMS-masking.

Section snippets

Behavioral results

In each trial, a light gray square Landolt target stimulus was briefly presented in the middle of the screen. TMS or SHAM stimulation was delivered to the right frontal cortex (electrode F2; assumingly corresponding to Brodmann area 8 or 9, depending on the subject; see S1). On each trial a single pulse was given −140 ms,−60 ms or +20 ms with respect to the appearance of the target stimulus. First, subjects had to indicate on which side the gap of the square Landolt was located (objective

Discussion

The main goal of the present study was to test whether it is possible to produce pre-stimulus TMS masking by stimulating a far locus from visual cortex, e.g., the frontal cortex. Our goal was also to investigate the neural mechanisms associated with pre-stimulus TMS masking and whether they can explain the varying extent of behavioral effects. TMS or SHAM stimulation was targeted to the right frontal cortex while subjects performed a simple discrimination task. In the critical −60 ms SOA

Subjects

17 subjects participated in the EEG experiment. All subjects were healthy and had normal or corrected-to-normal vision. The subjects (9 male) were 20–48 years old (mean=26.9, median=26, SD=6.7). Two subjects were left-handed. All subjects gave written informed consent prior to participation. The study was approved by the ethics committee of University of Tartu and the experiment was undertaken in compliance with national legislation and the Declaration of Helsinki.

Stimuli

The experiment was programmed

Acknowledgments

Research reported in this paper is supported by the Estonian Research Agency (IUT20-40; within-university specification TSHPH14140I/TSVPH14140I).

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