Elements of exogenous attentional cueing preserved during optokinetic motion of the visual scene.

Navigating through our environment raises challenges for perception by generating salient background visual motion and eliciting prominent eye movements to stabilise the retinal image. It remains unclear if exogenous spatial attentional orienting is possible during background motion and the eye movements it causes and whether this compromises the underlying neural processing. To test this, we combined exogenous orienting, visual scene motion, and electroencephalography (EEG). A total of 26 participants viewed a background of moving black and grey bars (optokinetic stimulation). We tested for effects of non-spatially predictive peripheral cueing on visual motion discrimination of a target dot, presented either at the same (valid) or opposite (invalid) location as the preceding cue. Valid cueing decreased reaction times not only when participants kept their gaze fixed on a central point (fixation blocks) but also even when there was no fixation point, so that participants performed intensive, repetitive tracking eye movements (eye movement blocks). Overall, manual response reaction times were slower during eye movements. Cueing also produced reliable effects on neural activity on either block, including within the first 120 ms of neural processing of the target. The key pattern with larger event-related potential (ERP) amplitudes on invalid versus valid trials showed that the neural substrate of exogenous cueing was highly similar during eye movements or fixation. Exogenous peripheral cueing and its neural correlates are robust against distraction from the moving visual scene, important for perceptual cognition during navigation.

Right frontal eye field has perceptual and oculomotor functions during optokinetic stimulation and nystagmus.

The right frontal eye field (rFEF) is associated with visual perception and eye movements. rFEF is activated during optokinetic nystagmus (OKN), a reflex that moves the eye in response to visual motion (optokinetic stimulation, OKS). It remains unclear whether rFEF plays causal perceptual and/or oculomotor roles during OKS and OKN. To test this, participants viewed a leftward-moving visual scene of vertical bars and judged whether a flashed dot was moving. Single pulses of transcranial magnetic stimulation (TMS) were applied to rFEF on half of trials. In half of blocks, to explore oculomotor control, participants performed an OKN in response to the OKS. rFEF TMS, during OKN, made participants more accurate on trials when the dot was still, and it slowed eye movements. In separate blocks, participants fixated during OKS. This not only controlled for eye movements but also allowed the use of EEG to explore the FEF's role in visual motion discrimination. In these blocks, by contrast, leftward dot motion discrimination was impaired, associated with a disruption of the frontal-posterior balance in alpha-band oscillations. None of these effects occurred in a control site (M1) experiment. These results demonstrate multiple related yet dissociable causal roles of the right FEF during optokinetic stimulation.NEW & NOTEWORTHY This study demonstrates causal roles of the right frontal eye field (FEF) in motion discrimination and eye movement control during visual scene motion: previous work had only examined other stimuli and eye movements such as saccades. Using combined transcranial magnetic stimulation and EEG and a novel optokinetic stimulation motion-discrimination task, we find evidence for multiple related yet dissociable causal roles within the FEF: perceptual processing during optokinetic stimulation, generation of the optokinetic nystagmus, and the maintenance of alpha oscillations.

Shift in lateralization during illusory self-motion: EEG responses to visual flicker at 10 Hz and frequency-specific modulation by tACS.

Self-motion perception is a key aspect of higher vestibular processing, suggested to rely upon hemispheric lateralization and alpha-band oscillations. The first aim of this study was to test for any lateralization in the EEG alpha band during the illusory sense of self-movement (vection) induced by large optic flow stimuli. Visual stimuli flickered at alpha frequency (approx. 10 Hz) in order to produce steady state visually evoked potentials (SSVEPs), a robust EEG measure which allows probing the frequency-specific response of the cortex. The first main result was that differential lateralization of the alpha SSVEP response was found during vection compared with a matched random motion control condition, supporting the idea of lateralization of visual-vestibular function. Additionally, this effect was frequency-specific, not evident with lower frequency SSVEPs. The second aim of this study was to test for a causal role of the right hemisphere in producing this lateralization effect and to explore the possibility of selectively modulating the SSVEP response. Transcranial alternating current stimulation (tACS) was applied over the right hemisphere simultaneously with SSVEP recording, using a novel artefact removal strategy for combined tACS-EEG. The second main result was that tACS enhanced SSVEP amplitudes, and the effect of tACS was not confined to the right hemisphere. Subsequent control experiments showed the effect of tACS requires the flicker frequency and tACS frequency to be closely matched and tACS to be of sufficient intensity. Combined tACS-SSVEPs are a promising method for future investigation into the role of neural oscillations and for optimizing tACS.

Taking Attention Out of Context: Frontopolar Transcranial Magnetic Stimulation Abolishes the Formation of New Context Memories in Visual Search.

This study investigates the causal contribution of the left frontopolar cortex (FPC) to the processing of violated expectations from learned target-distractor spatial contingencies during visual search. The experiment consisted of two phases: learning and test. Participants searched for targets presented either among repeated or nonrepeated target-distractor configurations. Prior research showed that repeated encounters of identically arranged displays lead to memory about these arrays, which then can come to guide search (contextual cueing effect). The crucial manipulation was a change of the target location, in a nevertheless constant distractor layout, at the transition from learning to test. In addition to this change, we applied repetitive transcranial magnetic stimulation (rTMS) over the left lateral FPC, over a posterior control site, or no rTMS at all (baseline; between-group manipulation) to see how FPC rTMS influences the ability of observers to adapt context-based memories acquired in the training phase. The learning phase showed expedited search in repeated relative to nonrepeated displays, with this context-based facilitation being comparable across all experimental groups. For the test phase, the recovery of cueing was critically dependent on the stimulation site: Although there was evidence of context adaptation toward the end of the experiment in the occipital and no-rTMS conditions, observers with FPC rTMS showed no evidence of relearning at all after target location changes. This finding shows that FPC plays an important role in the regulation of prediction errors in statistical context learning, thus contributing to an update of the spatial target-distractor contingencies after target position changes in learned spatial arrays.

Subthalamic stimulation, oscillatory activity and connectivity reveal functional role of STN and network mechanisms during decision making under conflict.

Inhibitory control is an important executive function that is necessary to suppress premature actions and to block interference from irrelevant stimuli. Current experimental studies and models highlight proactive and reactive mechanisms and claim several cortical and subcortical structures to be involved in response inhibition. However, the involved structures, network mechanisms and the behavioral relevance of the underlying neural activity remain debated. We report cortical EEG and invasive subthalamic local field potential recordings from a fully implanted sensing neurostimulator in Parkinson's patients during a stimulus- and response conflict task with and without deep brain stimulation (DBS). DBS made reaction times faster overall while leaving the effects of conflict intact: this lack of any effect on conflict may have been inherent to our task encouraging a high level of proactive inhibition. Drift diffusion modelling hints that DBS influences decision thresholds and drift rates are modulated by stimulus conflict. Both cortical EEG and subthalamic (STN) LFP oscillations reflected reaction times (RT). With these results, we provide a different interpretation of previously conflict-related oscillations in the STN and suggest that the STN implements a general task-specific decision threshold. The timecourse and topography of subthalamic-cortical oscillatory connectivity suggest the involvement of motor, frontal midline and posterior regions in a larger network with complementary functionality, oscillatory mechanisms and structures. While beta oscillations are functionally associated with motor cortical-subthalamic connectivity, low frequency oscillations reveal a subthalamic-frontal-posterior network. With our results, we suggest that proactive as well as reactive mechanisms and structures are involved in implementing a task-related dynamic inhibitory signal. We propose that motor and executive control networks with complementary oscillatory mechanisms are tonically active, react to stimuli and release inhibition at the response when uncertainty is resolved and return to their default state afterwards.

The role of the dorsal medial frontal cortex in central processing limitation: a transcranial magnetic stimulation study.

When humans perform two tasks simultaneously, responses to the second task are increasingly delayed as the interval between the two tasks decreases (psychological refractory period). This delay of the second task is thought to reflect a central processing limitation at the response selection stage. However, the neural mechanisms underlying this central processing limitation remain unclear. Using transcranial magnetic stimulation (TMS), we examined the role of the dorsal medial frontal cortex (dMFC) in a dual-task paradigm in which participants performed an auditory task 1 and a visual task 2. We found that dMFC TMS, relative to control conditions, reduced the psychological refractory period for task 2 processing, whereas we observed no dMFC TMS effects on task 1 processing. This suggests a causal role of the dMFC in coordinating response selection processes at the central bottleneck.

Occipital TMS at phosphene detection threshold captures attention automatically.

Strong stimuli may capture attention automatically, suggesting that attentional selection is determined primarily by physical stimulus properties. The mechanisms underlying capture remain controversial, in particular, whether feedforward subcortical processes are its main source. Also, it remains unclear whether only physical stimulus properties determine capture strength. Here, we demonstrate strong capture in the absence of feedforward input to subcortical structures such as the superior colliculus, by using transcranial magnetic stimulation (TMS) over occipital visual cortex as an attention cue. This implies that the feedforward sweep through subcortex is not necessary for capture to occur but rather provides an additional source of capture. Furthermore, seen cues captured attention more strongly than (physically identical) unseen cues, suggesting that the momentary state of the nervous system modulates attentional selection. In summary, we demonstrate the existence of several sources of attentional capture, and that both physical stimulus properties and the state of the nervous system influence capture.

Dissociable networks control conflict during perception and response selection: a transcranial magnetic stimulation Study.

Current models of conflict processing propose that cognitive control resolves conflict in the flanker task by enhancing task-relevant stimulus processing at a perceptual level. However, because conflicts occur at both a perceptual and a response selection level in that task, we tested the hypothesis of conflict-specific control networks for perceptual and response selection conflicts using transcranial magnetic stimulation (TMS). TMS of the presupplementary motor area selectively disrupted the processing of response selection conflict, whereas TMS of the posterior intraparietal sulcus/inferior parietal lobule interfered with perceptual conflict processing. In more detail, the presupplementary motor area seems to resolve response selection conflict mainly when no conflicts have occurred in the previous trial. In contrast, the posterior intraparietal sulcus/inferior parietal lobule may resolve perceptual conflicts selectively when a conflict has occurred in the previous trial. The current data show the need for revising models of cognitive control by providing evidence for the existence of conflict-specific control networks resolving conflict at different processing levels.

A paradoxical role for inhibition in initiation.

Subliminal stimuli, of which subjects are unaware, affect movements made to subsequent visible cues. Sumner and colleagues in this issue of Neuron show that restricted supplementary motor and eye field lesions compromise voluntary control of action because they disrupt the normal unconscious and automatic inhibition of alternative movements partially activated by subliminal stimuli.

TMS of the right angular gyrus modulates priming of pop-out in visual search: combined TMS-ERP evidence.

During priming of pop-out, performance at discriminating a pop-out feature target in visual search is affected by whether the target on the previous trial was defined by the same feature as on the upcoming trial. Recent studies suggest that priming of pop-out relies on attentional processes. With the use of simultaneous, combined transcranial magnetic stimulation and event-related potential recording (TMS-ERP), we tested for any critical role of the right angular gyrus (rANG) and left and right frontal eye fields (FEFs)-key attentional sites-in modulating both performance and the ERPs evoked by such visual events. Intertrial TMS trains were applied while participants discriminated the orientation of a color pop-out element in a visual search array. rANG TMS disrupted priming of pop-out, reducing reaction time costs on switch trials and speeding responses when the color of the pop-out target switched. rANG TMS caused a negativity in the ERP elicited in response to the visual stimulus array, starting 210 ms after stimulus onset. Both behavioral and ERP effects were apparent only after rANG TMS, on switch trials, and when the target in the visual search array was presented in the left visual field, with no effects after left or right FEF TMS. These results provide evidence for an attentional reorienting mechanism, which originates in the rANG and is modulated by the implicit memory of the previous trial. The rANG plays a causal role on switch trials during priming of pop-out by interacting with visual processing, particularly in the ipsilateral hemisphere representing the contralateral hemifield.

Self-initiation Inhibits the Postural and Electrophysiological Responses to Optic Flow and Button Pressing.

As we move through our environment, our visual system is presented with optic flow, a potentially important cue for perception, navigation and postural control. How does the brain anticipate the optic flow that arises as a consequence of our own movement? Converging evidence suggests that stimuli are processed differently by the brain if occurring as a consequence of self-initiated actions, compared to when externally generated. However, this has mainly been demonstrated with auditory stimuli. It is not clear how this occurs with optic flow. We measured behavioural, neurophysiological and head motion responses of 29 healthy participants to radially expanding, vection-inducing optic flow stimuli, simulating forward transitional motion, which were either initiated by the participant's own button-press ("self-initiated flow") or by the computer ("passive flow"). Self-initiation led to a prominent and left-lateralized inhibition of the flow-evoked posterior event-related alpha desynchronization (ERD), and a stabilisation of postural responses. Neither effect was present in control button-press-only trials, without optic flow. Additionally, self-initiation also produced a large event-related potential (ERP) negativity between 130-170 ms after optic flow onset. Furthermore, participants' visual induced motion sickness (VIMS) and vection intensity ratings correlated positively across the group - although many participants felt vection in the absence of any VIMS, none reported the opposite combination. Finally, we found that the simple act of making a button press leads to a detectable head movement even when using a chin rest. Taken together, our results indicate that the visual system is capable of predicting optic flow when self-initiated, to affect behaviour.

The influence of TMS of the rTPJ on attentional control and mentalizing.

Mentalizing is the powerful cognitive ability to understand others. By attributing mental states to others, we become able to explain and predict their behavior. The right temporoparietal junction (rTPJ) plays a key role in processing models of mental states. Yet, a different line of research suggests that the rTPJ is crucially involved in attentional control, prompting debates on its cognitive function. In this pre-registered neuro-navigated event-related TMS study, we tested for the rTPJ's specificity in mentalizing and attentional control. We interfered with its activity in a recently developed spatial cueing paradigm in which another's mental states were apparently task-relevant, allowing direct comparison of TMS effects on attention and mentalizing. We contrasted effects with a nearby control TMS site. Our confirmatory analysis showed no evidence for an involvement of the rTPJ in mentalizing or attentional control, presumably due to an observed large inter-individual variability of TMS effects on context and validity. To follow up this finding, we conducted exploratory analyses which revealed that rTPJ TMS had an influence on both attentional control and mentalizing. TMS effects on attention and mentalizing co-varied across participants: participants responding most to rTPJ TMS on mentalizing were also those for whom rTPJ TMS increased the attentional effect the most. This provides further evidence against total absolute segregation between mentalizing and attention within the rTPJ. Rather, our results suggest a common cognitive mechanism in both domains for which the rTPJ is necessary, paving the way for future research to cross-validate and extend these findings.

V5/MT+ modulates spatio-temporal integration differently across and within hemifields: Causal evidence from TMS.

It is unclear how the brain reaches the correct balance between temporal and spatial processing necessary to perceive motion across space. Here, we tested whether visual motion area V5/MT + plays a causal role in Ternus illusion. Ternus displays can be perceived as showing either group motion or element motion and are empirically useful for dissociating temporal and spatial grouping across visual fields. Online single-pulse TMS was applied to observers during the presentation of Ternus displays, either within or across hemifields, over left V5/MT + or, respectively, a control site in the left somatosensory cortex, or an additional 'Sham' control condition. In the cross-hemifields condition, observers perceived more element motion with TMS over left V5/MT + than in either control condition. By contrast, in the within-hemifield condition, observers reported more group motion after left V5/MT + TMS. Our findings demonstrate a causal role of left V5/MT+ in the spatio-temporal grouping of Ternus apparent motion, and in maintaining the balance of spatio-temporal processing both within and across individual hemifields.

The neural signature of phosphene perception.

Artificial percepts (phosphenes) can be induced by applying transcranial magnetic stimulation (TMS) over human visual cortex. Although phosphenes have been used to study visual awareness, the neural mechanisms generating them have not yet been delineated. We directly tested the two leading hypotheses of how phosphenes arise. These hypotheses correspond to the two competing views of the neural genesis of awareness: the early, feedforward view and the late, recurrent feedback model. We combined online TMS and EEG recordings to investigate whether the electrophysiological correlates of conscious phosphene perception are detectable early after TMS onset as an immediate local effect of TMS, or only at longer latencies, after interactions of TMS-induced activity with other visual areas. Stimulation was applied at the intensity threshold at which participants saw a phosphene on half of the trials, and brain activity was recorded simultaneously with electroencephalography. Phosphene perception was associated with a differential pattern of TMS-evoked brain potentials that started 160-200 ms after stimulation and encompassed a wide array of posterior areas. This pattern was differentiated from the TMS-evoked potential after stimulation of a control site. These findings suggest that conscious phosphene perception is not a local phenomenon, but arises only after extensive recurrent processing.

Mobile steady-state evoked potential recording: Dissociable neural effects of real-world navigation and visual stimulation.

BACKGROUND: The ability to record brain activity in humans during movement, and in real world environments, is an important step towards understanding cognition. Electroencephalography (EEG) is well suited to mobile applications but suffers from the problem of artefacts introduced into the signal during movement. Steady state visually evoked potentials (SSVEPs) give an excellent signal-to-noise ratio and averaging a sufficient number of trials will eventually remove any noise not phase locked to the visual flicker. NEW METHOD: Here we present a method for producing SSVEPs of real world environments using modified LCD shutter glasses, which are commonly used for 3D TV, by adapting the glass to flicker at neurophysiologically relevant frequencies (alpha band). Participants viewed a room whilst standing and walking. Either the left or right side of the room was illuminated, to test if it is possible to recover the resulting SSVEPs when walking, as well as to probe the effect of walking on neural activity. Additionally, by using a signal generator to produce "simulated SSVEPs" on the scalp we can demonstrate that this method is able to accurately recover evoked neural responses during walking. RESULTS: The amplitude of SSVEPs over right parietal cortex was reduced by walking. Furthermore, the waveform and phase of the SSVEPs is highly preserved between walking and standing, but was sensitive to whether the left or right side of the room was illuminated. CONCLUSIONS: This method allows probing neural responses during natural movements within real environments, potentially at a wide range of frequencies.

Reducing variability of perceptual decision making with offline theta-burst TMS of dorsal medial frontal cortex.

BACKGROUND: Recent evidence suggests that the dorsal medial frontal cortex (dMFC) may make an important contribution to perceptual decision-making, and not only to motor control. OBJECTIVE/HYPOTHESIS: By fitting psychometric functions to behavioural data after TMS we tested whether the dMFC is critical specifically for the precision and/or bias of perceptual judgements. Additionally we aimed to disentangle potential roles of the dMFC in dealing with perceptual versus response switching. METHODS: A subjective visual vertical task (SVV) was used in which participants weight visual (and other, e.g., vestibular) information to establish whether a line is oriented vertically. To ensure a high perceptual demand (putatively necessary to demonstrate a dMFC involvement) SVV lines were presented inside pop-out targets within a visual search array. Distinct features of perceptual performance were analysed before as compared to following theta-burst TMS stimulation of the dMFC, a control site, or no stimulation, in three groups, each of 20 healthy participants. RESULTS: dMFC stimulation improved the precision of verticality judgments. Moreover, dMFC stimulation improved accuracy, selectively when response switches occurred with perceptual repeats. CONCLUSION: These findings point to a causal role of the dMFC in establishing the precision of perceptual decision making, demonstrably dissociable from an additional role in motor control in attentionally demanding contexts.

Egocentric processing in the roll plane and dorsal parietal cortex: A TMS-ERP study of the subjective visual vertical.

The intraparietal sulcus within the dorsal right posterior parietal cortex is associated with spatial orientation and attention in relation to egocentric reference frames, such as left or right hemifield. It remains unclear whether it plays a causal role in the human in the roll plane (i.e. when visual stimuli are tilted clockwise or anticlockwise) which this is an important aspect of egocentric visual processing with clinical relevance in vestibular disorders. The subjective visual vertical (SVV) task measures the deviation between an individual's subjective vertical perception and the veridical vertical, involves the integration of visual, and vestibular information, and relies on a distributed network of multisensory regions that shows right lateralization and inter-areal inhibition. This study used combined TMS-EEG to investigate the role of the human dorsal parietal cortex in verticality perception using the SVV task in darkness. Participants were sorted according to their baseline bias at this task i.e. those with either a slight counterclockwise versus clockwise bias when judging a line to be truly vertical. Right parietal TMS facilitated verticality perception, reducing the difference between groups. ERPs suggested that the behavioral TMS effect occurred through normalizing individual SVV biases, evident frontally and late in the trial, and which was abolished after right parietal TMS. Effects were site and task specific, shown with a homologous left hemisphere control, and a landmark task performed on the same stimuli. These results support a right lateralization of visual-vestibular cognition and a distinct representation of the roll plane for egocentric processing in dorsal parietal cortex.

Subsecond changes in top down control exerted by human medial frontal cortex during conflict and action selection: a combined transcranial magnetic stimulation electroencephalography study.

Action selection requires choosing one of all the possible conflicting action plans that are available. There is currently a debate as to whether the dorsal medial frontal cortex (dMFC) merely detects or actively resolves response conflict. We used combined on-line transcranial magnetic stimulation and electroencephalographic recording (TMS-EEG) to test whether human dMFC plays a critical causal role in conflict resolution, and whether the mechanism for such a function is via interactions with primary motor cortex. In an Eriksen flanker task, subjects discriminated the direction of the centermost arrow in an array of five, responding with the left or right hand. The lateralized readiness potential (LRP), a measure of relative levels of activity in left and right motor cortices, was also recorded. Reaction times and error rates were higher on incongruent than congruent trials, and incongruent trials produced a positive LRP deflection reflecting initial partial activation of the incorrect response. On one-half of trials, repetitive TMS was applied to left dMFC starting 100 ms before visual stimulus onset and ending 100 ms afterward. TMS disrupted performance by selectively increasing error rates on contralateral (right hand) incongruent trials. TMS also only modulated the LRP on incongruent trials, causing an increased positive deflection (associated with preparation of the incorrect response) starting 180 ms after visual stimulus onset. TMS of a control site did not interfere with behavior or motor cortical activity. dMFC has a direct causal role in resolving conflict during action selection, and the mechanism involves the top-down modulation of primary motor cortical activity.

Combining TMS and EEG to study cognitive function and cortico-cortico interactions.

There has long been an interest in exploring the functional dynamics of the brain's connectivity during cognitive processing, and some recent methodological developments now allow us to test important long-standing hypotheses. This review focuses on the recent development of combined online transcranial magnetic stimulation and electroencephalography (TMS-EEG) and on new studies that have employed this combination to study causal interactions between neural areas involved in perception and cognition.

Imaging causal interactions during sensorimotor processing.

We review three ways in which transcranial magnetic stimulation (TMS) has been used to investigate causal interactions between different brain areas: (1) combined with functional imaging; (2) combined with EEG; and (3) applied successively over two brain areas. We discuss the theoretical advantages of each technique, illustrated by examples from the literature, and highlight the potential of these approaches to provide novel insights into the neural bases of action control.