Human perceptual and metacognitive decision-making rely on distinct brain networks.

Perceptual decisions depend on the ability to exploit available sensory information in order to select the most adaptive option from a set of alternatives. Such decisions depend on the perceptual sensitivity of the organism, which is generally accompanied by a corresponding level of certainty about the choice made. Here, by use of corticocortical paired associative transcranial magnetic stimulation protocol (ccPAS) aimed at inducing plastic changes, we shaped perceptual sensitivity and metacognitive ability in a motion discrimination task depending on the targeted network, demonstrating their functional dissociation. Neurostimulation aimed at boosting V5/MT+-to-V1/V2 back-projections enhanced motion sensitivity without impacting metacognition, whereas boosting IPS/LIP-to-V1/V2 back-projections increased metacognitive efficiency without impacting motion sensitivity. This double-dissociation provides causal evidence of distinct networks for perceptual sensitivity and metacognitive ability in humans.

State-Dependent TMS Reveals Representation of Affective Body Movements in the Anterior Intraparietal Cortex.

In humans, recognition of others' actions involves a cortical network that comprises, among other cortical regions, the posterior superior temporal sulcus (pSTS), where biological motion is coded and the anterior intraparietal sulcus (aIPS), where movement information is elaborated in terms of meaningful goal-directed actions. This action observation system (AOS) is thought to encode neutral voluntary actions, and possibly some aspects of affective motor repertoire, but the role of the AOS' areas in processing affective kinematic information has never been examined. Here we investigated whether the AOS plays a role in representing dynamic emotional bodily expressions. In the first experiment, we assessed behavioral adaptation effects of observed affective movements. Participants watched series of happy or fearful whole-body point-light displays (PLDs) as adapters and were then asked to perform an explicit categorization of the emotion expressed in test PLDs. Participants were slower when categorizing any of the two emotions as long as it was congruent with the emotion in the adapter sequence. We interpreted this effect as adaptation to the emotional content of PLDs. In the second experiment, we combined this paradigm with TMS applied over either the right aIPS, pSTS, and the right half of the occipital pole (corresponding to Brodmann's area 17 and serving as control) to examine the neural locus of the adaptation effect. TMS over the aIPS (but not over the other sites) reversed the behavioral cost of adaptation, specifically for fearful contents. This demonstrates that aIPS contains an explicit representation of affective body movements.SIGNIFICANCE STATEMENT In humans, a network of areas, the action observation system, encodes voluntary actions. However, the role of these brain regions in processing affective kinematic information has not been investigated. Here we demonstrate that the aIPS contains a representation of affective body movements. First, in a behavioral experiment, we found an adaptation after-effect for emotional PLDs, indicating the existence of a neural representation selective for affective information in biological motion. To examine the neural locus of this effect, we then combined the adaptation paradigm with TMS. Stimulation of the aIPS (but not over pSTS and control site) reversed the behavioral cost of adaptation, specifically for fearful contents, demonstrating that aIPS contains a representation of affective body movements.

Common framework for "virtual lesion" and state-dependent TMS: The facilitatory/suppressive range model of online TMS effects on behavior.

The behavioral effects of Transcranial Magnetic Stimulation (TMS) are often nonlinear; factors such as stimulation intensity and brain state can modulate the impact of TMS on observable behavior in qualitatively different manner. Here we propose a theoretical framework to account for these effects. In this model, there are distinct intensity ranges for facilitatory and suppressive effects of TMS - low intensities facilitate neural activity and behavior whereas high intensities induce suppression. The key feature of the model is that these ranges are shifted by changes in neural excitability: consequently, a TMS intensity, which normally induces suppression, can have a facilitatory effect if the stimulated neurons are being inhibited by ongoing task-related processes or preconditioning. For example, adaptation reduces excitability of adapted neurons; the outcome is that TMS intensities which inhibit non-adapted neurons induce a facilitation on adapted neural representations, leading to reversal of adaptation effects. In conventional "virtual lesion" paradigms, similar effects occur because neurons not involved in task-related processes are inhibited by the ongoing task. The resulting reduction in excitability can turn high intensity "inhibitory" TMS to low intensity "facilitatory" TMS for these neurons, and as task-related neuronal representations are in the inhibitory range, the outcome is a reduction in signal-to-noise ratio and behavioral impairment.

The causal role of the occipital face area (OFA) and lateral occipital (LO) cortex in symmetry perception.

Symmetry is an important cue in face and object perception. Here we used fMRI-guided transcranial magnetic stimulation (TMS) to shed light on the role of the occipital face area (OFA), a key region in face processing, and the lateral occipital (LO) cortex, a key area in object processing, in symmetry detection. In the first experiment, we applied TMS over the rightOFA, its left homolog (leftOFA), rightLO, and vertex (baseline) while participants were discriminating between symmetric and asymmetric dot patterns. Stimulation of rightOFA and rightLO impaired performance, causally implicating these two regions in detection of symmetry in low-level dot configurations. TMS over rightLO but not rightOFA also significantly impaired detection of nonsymmetric shapes defined by collinear Gabor patches, demonstrating that rightOFA responds to symmetry but not to all cues mediating figure-ground segregation. The second experiment showed a causal role for rightOFA but not rightLO in facial symmetry detection. Overall, our results demonstrate that both the rightOFA and rightLO are sensitive to symmetry in dot patterns, whereas only rightOFA is causally involved in facial symmetry detection.

The role of the lateral occipital cortex in aesthetic appreciation of representational and abstract paintings: a TMS study.

Neuroimaging studies of aesthetic appreciation have shown that activity in the lateral occipital area (LO)-a key node in the object recognition pathway-is modulated by the extent to which visual artworks are liked or found beautiful. However, the available evidence is only correlational. Here we used transcranial magnetic stimulation (TMS) to investigate the putative causal role of LO in the aesthetic appreciation of paintings. In our first experiment, we found that interfering with LO activity during aesthetic appreciation selectively reduced evaluation of representational paintings, leaving appreciation of abstract paintings unaffected. A second experiment demonstrated that, although the perceived clearness of the images overall positively correlated with liking, the detrimental effect of LO TMS on aesthetic appreciation does not owe to TMS reducing perceived clearness. Taken together, our findings suggest that object-recognition mechanisms mediated by LO play a causal role in aesthetic appreciation of representational art.

Why is "blindsight" blind? A new perspective on primary visual cortex, recurrent activity and visual awareness.

The neuropsychological phenomenon of blindsight has been taken to suggest that the primary visual cortex (V1) plays a unique role in visual awareness, and that extrastriate activation needs to be fed back to V1 in order for the content of that activation to be consciously perceived. The aim of this review is to evaluate this theoretical framework and to revisit its key tenets. Firstly, is blindsight truly a dissociation of awareness and visual detection? Secondly, is there sufficient evidence to rule out the possibility that the loss of awareness resulting from a V1 lesion simply reflects reduced extrastriate responsiveness, rather than a unique role of V1 in conscious experience? Evaluation of these arguments and the empirical evidence leads to the conclusion that the loss of phenomenal awareness in blindsight may not be due to feedback activity in V1 being the hallmark awareness. On the basis of existing literature, an alternative explanation of blindsight is proposed. In this view, visual awareness is a "global" cognitive function as its hallmark is the availability of information to a large number of perceptual and cognitive systems; this requires inter-areal long-range synchronous oscillatory activity. For these oscillations to arise, a specific temporal profile of neuronal activity is required, which is established through recurrent feedback activity involving V1 and the extrastriate cortex. When V1 is lesioned, the loss of recurrent activity prevents inter-areal networks on the basis of oscillatory activity. However, as limited amount of input can reach extrastriate cortex and some extrastriate neuronal selectivity is preserved, computations involving comparison of neural firing rates within a cortical area remain possible. This enables "local" read-out from specific brain regions, allowing for the detection and discrimination of basic visual attributes. Thus blindsight is blind due to lack of "global" long-range synchrony, and it functions via "local" neural readout from extrastriate areas.

Neural basis of non-conscious visual working memory.

Recent research indicates that human observers can perform high-level cognitive tasks typically associated with working memory processes (e.g. learning of complex item sequences, reading, arithmetic or delayed visual discrimination) independently of conscious awareness of the relevant information. However, the neural basis of this phenomenon is not known. Here we show neuroimaging and neurostimulation evidence that the dorsolateral and anterior prefrontal cortex can operate on non-conscious information in a manner that goes beyond automatic forms of sensorimotor priming and which may support implicit working memory processes and higher-level cognitive function.

Distinct causal mechanisms of attentional guidance by working memory and repetition priming in early visual cortex.

Human attention may be guided by representations held in working memory (WM) and also by priming from implicit memory. Neurophysiological data suggest that WM and priming may be associated with distinct neural mechanisms, but this prior evidence is only correlative. Furthermore, the role of the visual cortex in attention biases from memory remains unclear, because most previous studies conflated memory and selection processes. Here, we manipulated memory and attention in an orthogonal fashion and used an interventional approach to demonstrate the functional significance of WM and priming states in visual cortex for attentional biasing. Observers searched for a Landolt target that was preceded by a nonpredictive color cue that either had to be held in WM for a later recognition test or merely attended (priming counterpart). The application of transcranial magnetic stimulation (TMS) over the occipital cortex modulated the impact of memory on search. Critically, the direction of this modulation depended on the memory state. In the WM condition, the application of TMS on validly cued trials (when the cue surrounded the sought target) enhanced search accuracy relative to the invalid trials (when the cue surrounded a distracter); the opposite pattern was observed in the priming condition. That the effects of occipital TMS on selection were contingent on memory context demonstrates that WM and priming represent distinct states in the early visual cortex that play a causal role in memory-based guidance of attention.

How visual short-term memory maintenance modulates the encoding of external input: evidence from concurrent visual adaptation and TMS.

The impact of memory representations on the encoding of visual input has been the subject of much debate. Here we investigated this issue by examining how visual short-term memory (VSTM) maintenance of orientation information modulates the strength of the tilt aftereffect (TAE) induced by a concurrent visual adapter. We reasoned that if VSTM maintenance facilitates visual processing of stimuli that match the VSTM content, then the magnitude of the TAE should be enhanced when the orientations of the memory item and the adapter are identical. In contrast, if VSTM content inhibits visual processing, then the TAE induced by the adapter should be reduced. Our results are consistent with the latter hypothesis, and a TMS study demonstrated that the reduction of the TAE by VSTM maintenance of orientation information occurs in the early visual cortex. VSTM maintenance of shape information also reduced the TAE magnitude, but to a smaller extent than maintenance of orientation information. A TMS experiment did not implicate the early visual cortex in this phenomenon. In summary, our results indicate that VSTM maintenance under these circumstances inhibits the encoding of concurrent visual input, and that this inhibition occurs at various levels of the visual cortex.

Processing of featural and configural aspects of faces is lateralized in dorsolateral prefrontal cortex: a TMS study.

Facial recognition relies on distinct and parallel types of processing: featural processing focuses on the individual components of a face (e.g., the shape or the size of the eyes), whereas configural (or "relational") processing considers the spatial interrelationships among the single facial components (e.g., distance of the mouth from the nose). Previous neuroimaging evidence has suggested that featural and configural processes may rely on different brain circuits. By using rTMS, here we show for the first time a double dissociation in dorsolateral prefrontal cortex for different aspects of face processing: in particular, TMS over the left middle frontal gyrus (BA8) selectively disrupted featural processing, whereas TMS over the right inferior frontal gyrus (BA44) selectively interfered with configural processing of faces. By establishing a causal link between activation in left and right prefrontal areas and different modes of face processing, our data extend previous neuroimaging evidence and may have important implications in the study of face-processing deficits, such as those manifested in prosopagnosia and autistic spectrum disorders.

How visual short-term memory maintenance modulates subsequent visual aftereffects.

Prolonged viewing of a visual stimulus can result in sensory adaptation, giving rise to perceptual phenomena such as the tilt aftereffect (TAE). However, it is not known if short-term memory maintenance induces such effects. We examined how visual short-term memory (VSTM) maintenance modulates the strength of the TAE induced by subsequent visual adaptation. We reasoned that if VSTM maintenance induces aftereffects on subsequent encoding of visual information, then it should either enhance or reduce the TAE induced by a subsequent visual adapter, depending on the congruency of the memory cue and the adapter. Our results were consistent with this hypothesis and thus indicate that the effects of VSTM maintenance can outlast the maintenance period.

Seeing mathematics: perceptual experience and brain activity in acquired synesthesia.

We studied the patient JP who has exceptional abilities to draw complex geometrical images by hand and a form of acquired synesthesia for mathematical formulas and objects, which he perceives as geometrical figures. JP sees all smooth curvatures as discrete lines, similarly regardless of scale. We carried out two preliminary investigations to establish the perceptual nature of synesthetic experience and to investigate the neural basis of this phenomenon. In a functional magnetic resonance imaging (fMRI) study, image-inducing formulas produced larger fMRI responses than non-image inducing formulas in the left temporal, parietal and frontal lobes. Thus our main finding is that the activation associated with his experience of complex geometrical images emerging from mathematical formulas is restricted to the left hemisphere.

Noninvasive Brain Stimulation: Multiple Effects on Cognition.

Noninvasive brain stimulation (NIBS) techniques are widely used tools for the study and rehabilitation of cognitive functions. Different NIBS approaches aim to enhance or impair different cognitive processes. The methodological focus for achieving this has been on stimulation protocols that are considered either inhibitory or facilitatory. However, despite more than three decades of use, their application is based on incomplete and overly simplistic conceptualizations of mechanisms of action. Such misconception limits the usefulness of these approaches in the basic science and clinical domains. In this review, we challenge this view by arguing that stimulation protocols themselves are neither inhibitory nor facilitatory. Instead, we suggest that all induced effects reflect complex interactions of internal and external factors. Given these considerations, we present a novel model in which we conceptualize NIBS effects as an interaction between brain activity and the characteristics of the external stimulus. This interactive model can explain various phenomena in the brain stimulation literature that have been considered unexpected or paradoxical. We argue that these effects no longer seem paradoxical when considered from the viewpoint of state dependency.

Where in the brain do internally generated and externally presented visual information interact?

Conscious experiences normally result from the flow of external input into our sensory systems. However, we can also create conscious percepts independently of sensory stimulation. These internally generated percepts are referred to as mental images, and they have many similarities with real visual percepts. Consequently, mental imagery is often referred to as "seeing in the mind's eye". While the neural basis of imagery has been widely studied, the interaction between internal and external sources of visual information has received little interest. Here we examined this question by using fMRI to record brain activity of healthy human volunteers while they were performing visual imagery that was distracted with a concurrent presentation of a visual stimulus. Multivariate pattern analysis (MVPA) was used to identify the brain basis of this interaction. Visual imagery was reflected in several brain areas in ventral temporal, lateral occipitotemporal, and posterior frontal cortices, with a left-hemisphere dominance. The key finding was that imagery content representations in the left lateral occipitotemporal cortex were disrupted when a visual distractor was presented during imagery. Our results thus demonstrate that the representations of internal and external visual information interact in brain areas associated with the encoding of visual objects and shapes.

Improved motion perception and impaired spatial suppression following disruption of cortical area MT/V5.

As stimulus size increases, motion direction of high-contrast patterns becomes increasingly harder to perceive. This counterintuitive behavioral result, termed "spatial suppression," is hypothesized to reflect center-surround antagonism-a receptive field property ubiquitous in sensory systems. Prior research proposed that spatial suppression of motion signals is a direct correlate of center-surround antagonism within cortical area MT. Here, we investigated whether human MT/V5 is indeed causally involved in spatial suppression of motion signals. The key assumption is that a disruption of neural mechanisms that play a critical role in spatial suppression could allow these normally suppressed motion signals to reach perceptual awareness. Thus, our hypothesis was that a disruption of MT/V5 should weaken spatial suppression and, consequently, improve motion perception of large, moving patterns. To disrupt MT/V5, we used offline 1 Hz transcranial magnetic stimulation (TMS)-a method that temporarily attenuates normal functioning of the targeted cortex. Early visual areas were also targeted as a control site. The results supported our hypotheses and showed that disruption of MT/V5 improved motion discrimination of large, moving stimuli, presumably by weakening surround suppression strength. This effect was specific to MT/V5 stimulation and contralaterally presented stimuli. Evidently, the critical neural constraints limiting motion perception of large, high-contrast stimuli involve MT/V5. Additionally, our findings mimic spatial suppression deficits that are observed in several patient populations and implicate impaired MT/V5 processes as likely neural correlates for the reported perceptual abnormalities in the elderly, patients with schizophrenia and those with a history of depression.

Stochastic resonance effects reveal the neural mechanisms of transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a popular method for studying causal relationships between neural activity and behavior. However, its mode of action remains controversial, and so far there is no framework to explain its wide range of facilitatory and inhibitory behavioral effects. While some theoretical accounts suggest that TMS suppresses neuronal processing, other competing accounts propose that the effects of TMS result from the addition of noise to neuronal processing. Here we exploited the stochastic resonance phenomenon to distinguish these theoretical accounts and determine how TMS affects neuronal processing. Specifically, we showed that online TMS can induce stochastic resonance in the human brain. At low intensity, TMS facilitated the detection of weak motion signals, but with higher TMS intensities and stronger motion signals, we found only impairment in detection. These findings suggest that TMS acts by adding noise to neuronal processing, at least in an online TMS protocol. Importantly, such stochastic resonance effects may also explain why TMS parameters that under normal circumstances impair behavior can induce behavioral facilitations when the stimulated area is in an adapted or suppressed state.

Why the assessment of causality in brain-behavior relations requires brain stimulation.

A central aim in cognitive neuroscience is to explain how neural activity gives rise to perception and behavior; the causal link of paramount interest is thus from brain to behavior. Functional neuroimaging studies, however, tend to provide information in the opposite direction by informing us how manipulation of behavior may affect neural activity. Although this may provide valuable insights into neuronal properties, one cannot use such evidence to make inferences about the behavioral significance of the observed activations; if A causes B, it does not necessarily follow that B causes A. In contrast, brain stimulation techniques enable us to directly modulate brain activity as the source of behavior and thus establish causal links.

Visual feature binding: the critical time windows of V1/V2 and parietal activity.

Interactions between the posterior parietal cortex and the early visual cortex have been proposed to play a central role in the binding of visual features into coherent objects. Here we investigated the importance of these interactions by contrasting the time windows at which the early visual cortex (V1/V2) and the angular gyrus (AG) play a causal role in visual feature binding. Transcranial magnetic stimulation was applied over these areas at different latencies during a visual task requiring binding. The contribution of V1/V2 was critical for feature detection 90-120 ms after the onset of the stimulus. When visual binding was required, an additional late time window (lasting until 240 ms after stimulus onset) was observed. The contribution of AG was found to be necessary for visual binding between 90 ms and 180 ms, overlapping with the "early" feature detection stage in V1/V2 and peaking around 180 ms. That the late V1/V2 time window overlaps and even extends beyond the peak time window of AG is consistent with the view that reentrant processing between higher areas and early visual cortex is necessary for visual binding.

Causal evidence for subliminal percept-to-memory interference in early visual cortex.

There has been recent interest in the neural correlates of visual short-term memory (VSTM) interference by irrelevant perceptual input. These studies, however, presented distracters that were subjected to conscious scrutiny by participants thus strongly involving attentional control mechanisms. In order to minimize the role of attentional control and to investigate interference occurring at the level of sensory representations, we developed a paradigm in which a subliminal visual distracter is presented during the delay period of a visual short-term memory task requiring the maintenance of stimulus orientation. This subliminal distracter could be either congruent or incongruent with the orientation of the memory item. Behavioral results showed that the intervening distracter affected the fidelity of VSTM when it was incongruent with the memory cue. We then assessed the causal role of the early visual cortex in this interaction by using transcranial magnetic stimulation (TMS). We found that occipital TMS impaired the fidelity VSTM content in the absence of the memory mask. Interestingly, TMS facilitated VSTM performance in the presence of a subliminal memory mask that was incongruent with the memory content. Signal detection analyses indicated that TMS did not modulate perceptual sensitivity of the masked distracter. That the impact of TMS on the precision of VSTM was dissociated by the presence vs. absence of a subliminal perceptual distracter and its congruency with the VSTM content provides causal evidence for the view that competitive interactions between memory and perception can occur at the earliest cortical stages of visual processing.

Cross-adaptation combined with TMS reveals a functional overlap between vision and imagery in the early visual cortex.

The extent to which the generation of mental images draws on the neuronal representations involved in visual perception has been the subject of much debate. To investigate this overlap, we assessed whether adaptation to visual stimuli affects the ability to generate visual mental images; such cross-adaptation would indicate shared neural representations between visual perception and imagery. Mental imagery was tested using a modified version of the clock task, in which subjects are presented with a digital time (e.g. "2.15") and are asked to generate a mental image of the clock hands displaying this time on an empty clock face. Participants were adapted to oriented lines either on the upper or lower side of the clock face prior to the mental image generation. The results showed that mental imagery was impaired when the mental image had to be generated in the adapted region of visual space (Experiment 1). In Experiment 2, we used TMS to determine whether this adaptation effect occurs in the early visual cortex (EVC; V1/V2). Relative to control conditions (No TMS and Vertex TMS), EVC TMS facilitated mental imagery generation when the mental image spatially overlapped with the adapter. Our results thus show that neuronal representations in the EVC which encode (and are suppressed by) visual input play a causal role in visual mental imagery.