Tom A. de Graaf

Alpha-Band Rhythms in Visual Task Performance: Phase-Locking by Rhythmic Sensory Stimulation

Oscillations are an important aspect of neuronal activity. Interestingly, oscillatory patterns are also observed in behaviour, such as in visual performance measures after the presentation of a brief sensory event in the visual or another modality. These oscillations in visual performance cycle at the typical frequencies of brain rhythms, suggesting that perception may be closely linked to brain oscillations. We here investigated this link for a prominent rhythm of the visual system (the alpha-rhythm, 8–12 Hz) by applying rhythmic visual stimulation at alpha-frequency (10.6 Hz), known to lead to a resonance response in visual areas, and testing its effects on subsequent visual target discrimination. Our data show that rhythmic visual stimulation at 10.6 Hz: 1) has specific behavioral consequences, relative to stimulation at control frequencies (3.9 Hz, 7.1 Hz, 14.2 Hz), and 2) leads to alpha-band oscillations in visual performance measures, that 3) correlate in precise frequency across individuals with resting alpha-rhythms recorded over parieto-occipital areas. The most parsimonious explanation for these three findings is entrainment (phase-locking) of ongoing perceptually relevant alpha-band brain oscillations by rhythmic sensory events. These findings are in line with occipital alpha-oscillations underlying periodicity in visual performance, and suggest that rhythmic stimulation at frequencies of intrinsic brain-rhythms can be used to reveal influences of these rhythms on task performance to study their functional roles.

Brain network dynamics underlying visuospatial judgment: An fmri connectivity study

Previous functional imaging research has consistently indicated involvement of bilateral fronto-parietal networks during the execution of visuospatial tasks. Studies with TMS have suggested that the right hemispheric network, but not the left, is functionally relevant for visuospatial judgments. However, very little is still known about the interactions within these fronto-parietal networks underlying visuospatial processing. In the current study, we investigated task modulation of functional connectivity (instantaneous correlations of regional time courses), and task-specific effective connectivity (direction of influences), within the right fronto-parietal network activated during visuospatial judgments. Ten healthy volunteers performed a behaviorally controlled visuospatial judgment task (ANGLE) or a control task (COLOR) in an fMRI experiment. Visuospatial task-specific activations were found in posterior parietal cortex (PPC) and middle/inferior frontal gyrus (MFG). Functional connectivity within this network was task-modulated, with significantly higher connectivity between PPC and MFG during ANGLE than during COLOR. Effective connectivity analysis for directed influence revealed that visuospatial task-specific projections within this network were predominantly in a frontal-to-parietal direction. Moreover, ANGLE-specific influences from thalamic nuclei to PPC were identified. Exploratory effective connectivity analysis revealed that closely neighboring clusters, within visuospatial regions, were differentially involved in the network. These neighboring clusters had opposite effective connectivity patterns to other nodes of the fronto-parietal network. Our data thus reveal that visuospatial judgments are supported by massive fronto-parietal backprojections, thalamo-parietal influence, and multiple stages, or loops, of information flow within the visuospatial network. We speculate on possible functional contributions of the various network nodes and informational loops in a neurocognitive model.

TMS effects on subjective and objective measures of vision: stimulation intensity and pre- versus post-stimulus masking

Transcranial magnetic stimulation (TMS) can be used to mask visual stimuli, disrupting visual task performance or preventing visual awareness. While TMS masking studies generally fix stimulation intensity, we hypothesized that varying the intensity of TMS pulses in a masking paradigm might inform several ongoing debates concerning TMS disruption of vision as measured subjectively versus objectively, and pre-stimulus (forward) versus post-stimulus (backward) TMS masking. We here show that both pre-stimulus TMS pulses and post-stimulus TMS pulses could strongly mask visual stimuli. We found no dissociations between TMS effects on the subjective and objective measures of vision for any masking window or intensity, ruling out the option that TMS intensity levels determine whether dissociations between subjective and objective vision are obtained. For the post-stimulus time window particularly, we suggest that these data provide new constraints for (e.g. recurrent) models of vision and visual awareness. Finally, our data are in line with the idea that pre-stimulus masking operates differently from conventional post-stimulus masking.

FMRI effective connectivity and TMS chronometry: complementary accounts of causality in the visuospatial judgment network

Background While traditionally quite distinct, functional neuroimaging (e.g. functional magnetic resonance imaging: fMRI) and functional interference techniques (e.g. transcranial magnetic stimulation: TMS) increasingly address similar questions of functional brain organization, including connectivity, interactions, and causality in the brain. Time-resolved TMS over multiple brain network nodes can elucidate the relative timings of functional relevance for behavior (“TMS chronometry”), while fMRI functional or effective connectivity (fMRI EC) can map task-specific interactions between brain regions based on the interrelation of measured signals. The current study empirically assessed the relation between these different methods. Methodology/Principal Findings One group of 15 participants took part in two experiments: one fMRI EC study, and one TMS chronometry study, both of which used an established cognitive paradigm involving one visuospatial judgment task and one color judgment control task. Granger causality mapping (GCM), a data-driven variant of fMRI EC analysis, revealed a frontal-to-parietal flow of information, from inferior/middle frontal gyrus (MFG) to posterior parietal cortex (PPC). FMRI EC-guided Neuronavigated TMS had behavioral effects when applied to both PPC and to MFG, but the temporal pattern of these effects was similar for both stimulation sites. At first glance, this would seem in contradiction to the fMRI EC results. However, we discuss how TMS chronometry and fMRI EC are conceptually different and show how they can be complementary and mutually constraining, rather than contradictory, on the basis of our data. Conclusions/Significance The findings that fMRI EC could successfully localize functionally relevant TMS target regions on the single subject level, and conversely, that TMS confirmed an fMRI EC identified functional network to be behaviorally relevant, have important methodological and theoretical implications. Our results, in combination with data from earlier studies by our group (Sack et al., 2007, Cerebral Cortex), lead to informed speculations on complex brain mechanisms, and TMS disruption thereof, underlying visuospatial judgment. This first in-depth empirical and conceptual comparison of fMRI EC and TMS chronometry thereby shows the complementary insights offered by the two methods.

Time- and task-dependent non-neural effects of real and sham TMS.

Transcranial magnetic stimulation (TMS) is widely used in experimental brain research to manipulate brain activity in humans. Next to the intended neural effects, every TMS pulse produces a distinct clicking sound and sensation on the head which can also influence task performance. This necessitates careful consideration of control conditions in order to ensure that behavioral effects of interest can be attributed to the neural consequences of TMS and not to non-neural effects of a TMS pulse. Surprisingly, even though these non-neural effects of TMS are largely unknown, they are often assumed to be unspecific, i.e. not dependent on TMS parameters. This assumption is inherent to many control strategies in TMS research but has recently been challenged on empirical grounds. Here, we further develop the empirical basis of control strategies in TMS research. We investigated the time-dependence and task-dependence of the non-neural effects of TMS and compared real and sham TMS over vertex. Critically, we show that non-neural TMS effects depend on a complex interplay of these factors. Although TMS had no direct neural effects, both pre- and post-stimulus TMS time windows modulated task performance on both a sensory detection task and a cognitive angle judgment task. For the most part, these effects were quantitatively similar across tasks but effect sizes were clearly different. Moreover, the effects of real and sham TMS were almost identical with interesting exceptions that shed light on the relative contribution of auditory and somato-sensory aspects of a TMS pulse. Knowledge of such effects is of critical importance for the interpretation of TMS experiments and helps deciding what constitutes an appropriate control condition. Our results broaden the empirical basis of control strategies in TMS research and point at potential pitfalls that should be avoided.

Using brain stimulation to disentangle neural correlates of conscious vision

Research into the neural correlates of consciousness (NCCs) has blossomed, due to the advent of new and increasingly sophisticated brain research tools. Neuroimaging has uncovered a variety of brain processes that relate to conscious perception, obtained in a range of experimental paradigms. But methods such as functional magnetic resonance imaging or electroencephalography do not always afford inference on the functional role these brain processes play in conscious vision. Such empirical NCCs could reflect neural prerequisites, neural consequences, or neural substrates of a conscious experience. Here, we take a closer look at the use of non-invasive brain stimulation (NIBS) techniques in this context. We discuss and review how NIBS methodology can enlighten our understanding of brain mechanisms underlying conscious vision by disentangling the empirical NCCs.

The temporal dynamics of early visual cortex involvement in behavioral priming.

Transcranial magnetic stimulation (TMS) allows for non-invasive interference with ongoing neural processing. Applied in a chronometric design over early visual cortex (EVC), TMS has proved valuable in indicating at which particular time point EVC must remain unperturbed for (conscious) vision to be established. In the current study, we set out to examine the effect of EVC TMS across a broad range of time points, both before (pre-stimulus) and after (post-stimulus) the onset of symbolic visual stimuli. Behavioral priming studies have shown that the behavioral impact of a visual stimulus can be independent from its conscious perception, suggesting two independent neural signatures. To assess whether TMS-induced suppression of visual awareness can be dissociated from behavioral priming in the temporal domain, we thus implemented three different measures of visual processing, namely performance on a standard visual discrimination task, a subjective rating of stimulus visibility, and a visual priming task. To control for non-neural TMS effects, we performed electrooculographical recordings, placebo TMS (sham), and control site TMS (vertex). Our results suggest that, when considering the appropriate control data, the temporal pattern of EVC TMS disruption on visual discrimination, subjective awareness and behavioral priming are not dissociable. Instead, TMS to EVC disrupts visual perception holistically, both when applied before and after the onset of a visual stimulus. The current findings are discussed in light of their implications on models of visual awareness and (subliminal) priming.

On the feasibility of concurrent human TMS-EEG-fMRI measurements.

Simultaneously combining the complementary assets of EEG, functional MRI (fMRI), and transcranial magnetic stimulation (TMS) within one experimental session provides synergetic results, offering insights into brain function that go beyond the scope of each method when used in isolation. The steady increase of concurrent EEG-fMRI, TMS-EEG, and TMS-fMRI studies further underlines the added value of such multimodal imaging approaches. Whereas concurrent EEG-fMRI enables monitoring of brain-wide network dynamics with high temporal and spatial resolution, the combination with TMS provides insights in causal interactions within these networks. Thus the simultaneous use of all three methods would allow studying fast, spatially accurate, and distributed causal interactions in the perturbed system and its functional relevance for intact behavior. Concurrent EEG-fMRI, TMS-EEG, and TMS-fMRI experiments are already technically challenging, and the three-way combination of TMS-EEG-fMRI might yield additional difficulties in terms of hardware strain or signal quality. The present study explored the feasibility of concurrent TMS-EEG-fMRI studies by performing safety and quality assurance tests based on phantom and human data combining existing commercially available hardware. Results revealed that combined TMS-EEG-fMRI measurements were technically feasible, safe in terms of induced temperature changes, allowed functional MRI acquisition with comparable image quality as during concurrent EEG-fMRI or TMS-fMRI, and provided artifact-free EEG before and from 300 ms after TMS pulse application. Based on these empirical findings, we discuss the conceptual benefits of this novel complementary approach to investigate the working human brain and list a number of precautions and caveats to be heeded when setting up such multimodal imaging facilities with current hardware.

A causal role for inferior parietal lobule in emotion body perception

Recent investigations of emotion body perception have established that perceiving fearful body expressions critically triggers activity in dorsal stream structures related to action preparation. However, the causal contributions of these areas remain unclear. In the current experiment, we addressed this issue using online transcranial magnetic stimulation (TMS) of the inferior parietal lobule (IPL) in the dorsal stream and visual areas (extrastriate body area - EBA in the ventral stream and early visual cortex - EVC). Participants performed a delayed-match-to-sample task requiring detection of a change in posture of body expressions that were either neutral or fearful. Results revealed a significant interaction between the stimulation site and the emotional valence of stimuli, indicating that processing of emotional versus neutral bodies is affected differentially by stimulation of different central areas in body processing. IPL stimulation specifically enhanced fearful body processing. These findings relate emotion processing to separate processing streams, and moreover provide the first evidence that IPL plays a causal role in processing of fearful bodies.

Thinking caps for everyone? The role of neuro-enhancement by non-invasive brain stimulation in neuroscience and beyond

Neuro-enhancement by non-invasive brain stimulation (NIBS) has recently made considerable progress, triggering discussions regarding future applications to enhance human performance. We show that neuroscientific research does not aim at improving brain functions per se. Instead, neuro-enhancement is a research tool that has great potential to reveal the neural mechanisms underlying perception, cognition, and behavior. We provide instructive examples that showcase the relevance of neuro-enhancement by NIBS in neuroscience. Importantly, we argue that the scientific value of neuro-enhancement critically depends on our understanding of why enhancing effects occur. This is in contrast to applications of neuro-enhancement in other domains, where such knowledge may not be required. We conclude that neuro-enhancement as a therapeutic tool or in healthy people outside of neuroscience should be kept conceptually distinct, as these are separate domains with entirely different motives for enhancing human performance. Consequently, the underlying principles that justify the application of NIBS will be different in each domain and arguments for or against neuro-enhancement in one domain do not necessarily generalize to other domains.