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.

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.

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.

Only minimal differences between individuals with congenital aphantasia and those with typical imagery on neuropsychological tasks that involve imagery.

Aphantasia describes the experience of individuals who self-report a lack of voluntary visual imagery. It is not yet known whether individuals with aphantasia show deficits in cognitive and neuropsychological tasks thought to relate to aspects of visual imagery, including Spatial Span, One Touch Stocking of Cambridge, Pattern Recognition Memory, Verbal Recognition Memory and Mental Rotation. Twenty individuals with congenital aphantasia (VVIQ < 25) were identified and matched on measures of age and IQ to twenty individuals with typical imagery (VVIQ > 35). A group difference was found in the One Touch Stocking of Cambridge task for response time, but not accuracy, when the number of imagined moves that participants had to hold in their heads to complete the task increased. Similarly, a group difference in response time was apparent in the mental rotation task, but only in the subgroup of aphantasic participants who reported a severe deficit in visual imagery (VVIQ score of 16). These results suggest that the cognitive profile of people without imagery does not greatly differ from those with typical imagery when examined by group. In addition, the severity of aphantasia (and VVIQ criterion) may be an important factor to consider when investigating differences in imagery experience. Overall, this study raises questions about whether or not aphantasia represents a difference in cognitive function or in conscious experience.

The chronometry of symmetry detection in the lateral occipital (LO) cortex.

The lateral occipital cortex (LO) has been shown to code the presence of both vertical and horizontal visual symmetry in dot patterns. However, the specific time window at which LO is causally involved in symmetry encoding has not been investigated. This was assessed using a chronometric transcranial magnetic stimulation (TMS) approach. Participants were presented with a series of dot configurations and instructed to judge whether they were symmetric along the vertical axis or not while receiving a double pulse of TMS over either the right LO (rLO) or the vertex (baseline) at different time windows (ranging from 50 ms to 290 ms from stimulus onset). We found that TMS delivered over the rLO significantly decreased participants' accuracy in discriminating symmetric from non-symmetric patterns when TMS was applied between 130 ms and 250 ms from stimulus onset, suggesting that LO is causally involved in symmetry perception within this time window. These findings confirm and extend prior neuroimaging and ERP evidence by demonstrating not only that LO is causally involved in symmetry encoding but also that its contribution occurs in a relatively large temporal window, at least in tasks requiring fast discrimination of mirror symmetry in briefly (75 ms) presented patterns as in our study.

State-dependent TMS effects in the visual cortex after visual adaptation: A combined TMS-EEG study.

OBJECTIVE: The impact of transcranial magnetic stimulation (TMS) has been shown to depend on the initial brain state of the stimulated cortical region. This observation has led to the development of paradigms that aim to enhance the specificity of TMS effects by using visual/luminance adaptation to modulate brain state prior to the application of TMS. However, the neural basis of interactions between TMS and adaptation is unknown. Here, we examined these interactions by using electroencephalography (EEG) to measure the impact of TMS over the visual cortex after luminance adaptation. METHODS: Single-pulses of neuronavigated TMS (nTMS) were applied at two different intensities over the left visual cortex after adaptation to either high or low luminance. We then analyzed the effects of adaptation on the global and local cortical excitability. RESULTS: The analysis revealed a significant interaction between the TMS-evoked responses and the adaptation condition. In particular, when nTMS was applied with high intensity, the evoked responses were larger after adaptation to high than low luminance. CONCLUSION: This result provides the first neural evidence on the interaction between TMS with visual adaptation. SIGNIFICANCE: TMS can activate neurons differentially as a function of their adaptation state.

Nonlinear interaction between stimulation intensity and initial brain state: Evidence for the facilitatory/suppressive range model of online TMS effects.

The effects of online Transcranial Magnetic Stimulation (TMS) can qualitatively vary as a function of brain state. For example, TMS intensities which normally impair performance can have a facilitatory effect if the targeted neuronal representations are in a suppressed state. These phenomena have been explained in terms of the existence of distinct facilitatory and suppressive ranges as a function of TMS intensity which are shifted by changes in neural excitability. We tested this model by applying TMS at a low (60 % of phosphene threshold) or high (120 % of phosphene threshold) intensity during a priming paradigm. Our results show that state-dependent TMS effects vary qualitatively as a function of TMS intensity. Whereas the application of TMS at 120 % of participants' phosphene threshold impaired performance on fully congruent trials (in effect, reducing the benefit of priming), TMS applied at a lower intensity (60 % of phosphene threshold), facilitated performance on congruent trials. These results demonstrate that behavioral effects of TMS reflect a nonlinear interaction between initial activation state and TMS intensity. They also provide support for the existence of facilitatory/suppressive ranges of TMS effects which shift when neural excitability changes.

Different neural representations for detection of symmetry in dot-patterns and in faces: A state-dependent TMS study.

The occipital face area (OFA) has been shown to code the presence of symmetry in faces and in vertically symmetric dot patterns. However, it is not clear whether symmetry processing of face and non-face stimuli involve overlapping neural mechanisms in OFA. This was assessed using state-dependent TMS by employing a priming paradigm. Specifically, we examined whether prior presentation of low-level symmetry affects the impact of TMS on discrimination of symmetry in subsequently presented faces - indicating that the same neural mechanisms encode symmetry in both face and non-face stimuli. Participants performed a symmetry discrimination task on a series of faces, each of which was preceded by either a vertically symmetric, a horizontally symmetric or a non-symmetric dot configuration (prime) while receiving stimulation over either the right OFA, the right Lateral Occipital Cortex (rLO) or over a control site (Vertex). Vertically symmetric dot patterns primed symmetry discrimination in faces. The key finding was that the priming effect was not affected by TMS applied over OFA; stimulation of this site (but not of rLO) impaired the discrimination of facial symmetry regardless of prime type. Overall, these results suggest that distinct neural representations in OFA are involved in symmetry detection in face and non-face stimuli.

On the "blindness" of blindsight: What is the evidence for phenomenal awareness in the absence of primary visual cortex (V1)?

Blindsight has been central to theories of phenomenal awareness; that a lesion to primary visual cortex (V1) abolishes all phenomenal awareness while unconscious visual functions can remain has led to the view that this region plays a crucial role in generating visual consciousness. However, since the early 20th century, there have been reports, many of which controversial, of phenomenal awareness in patients with V1 lesions. These reports include selective sparing of motion awareness, hemianopic completion and visual aftereffects. More recently, there have been successful attempts of inducing visual qualia with noninvasive brain stimulation. Here we critically review this evidence and discuss their implications to theoretical understanding of phenomenal awareness.

Strengthening functionally specific neural pathways with transcranial brain stimulation.

Cortico-cortical paired associative stimulation (ccPAS) is a recently established offline dual-coil transcranial magnetic stimulation (TMS) protocol [1-3] based on the Hebbian principle of associative plasticity and designed to transiently enhance synaptic efficiency in neural pathways linking two interconnected (targeted) brain regions [4,5]. Here, we present a new 'function-tuning ccPAS' paradigm in which, by pairing ccPAS with the presentation of a specific visual feature, for example a specific motion direction, we can selectively target and enhance the synaptic efficiency of functionally specific, but spatially overlapping, pathways. We report that ccPAS applied in a state-dependent manner and at a low intensity selectively enhanced detection of the specific motion direction primed during the combined visual-TMS manipulations. This paradigm significantly enhances the specificity of TMS-induced plasticity, by allowing the targeting of cortico-cortical pathways associated with specific functions.

TMS over right OFA affects individuation of faces but not of exemplars of objects.

In addition to its well-documented role in processing of faces, the occipital face area in the right hemisphere (rOFA) may also play a role in identifying specific individuals within a class of objects. Here we explored this issue by using fMRI-guided TMS. In a first experiment, participants had to judge whether two sequentially presented images of faces or objects represented exactly the same exemplar or two different exemplars of the same class, while receiving online TMS over either the rOFA, the right lateral occipital cortex (rLO) or the Vertex (control). We found that, relative to Vertex, stimulation of rOFA impaired individuation of faces only, with no effect on objects; in contrast, TMS over rLO reduced individuation of objects but not of faces. In a second control experiment participants judged whether a picture representing a fragment of a stimulus belonged or not to the subsequently presented image of a whole stimulus (part-whole matching task). Our results showed that rOFA stimulation selectively disrupted performance with faces, whereas performance with objects (but not with faces) was selectively affected by TMS over rLO. Overall, our findings suggest that rOFA does not contribute to discriminate between exemplars of non-face objects.

On the Mechanisms of Transcranial Magnetic Stimulation (TMS): How Brain State and Baseline Performance Level Determine Behavioral Effects of TMS.

The behavioral effects of Transcranial Magnetic Stimulation (TMS) can change qualitatively when stimulation is preceded by initial state manipulations such as priming or adaptation. In addition, baseline performance level of the participant has been shown to play a role in modulating the impact of TMS. Here we examined the link between these two factors. This was done using data from a previous study using a TMS-priming paradigm, in which, at group level, TMS selectively facilitated targets incongruent with the prime while having no statistically significant effects on other prime-target congruencies. Correlation and linear mixed-effects analyses indicated that, for all prime-target congruencies, a significant linear relationship between baseline performance and the magnitude of the induced TMS effect was present: low levels of baseline performance were associated with TMS-induced facilitations and high baseline performance with impairments. Thus as performance level increased, TMS effects turned from facilitation to impairment. The key finding was that priming shifted the transition from facilitatory to disruptive effects for targets incongruent with the prime, such that TMS-induced facilitations were obtained until a higher level of performance than for other prime-target congruencies. Given that brain state manipulations such as priming operate via modulations of neural excitability, this result is consistent with the view that neural excitability, coupled with non-linear neural effects, underlie behavioral effects of TMS.

The neural basis of visual symmetry and its role in mid- and high-level visual processing.

Symmetry is an important and prominent feature of the visual world. It has been studied as a basis for image segmentation and perceptual organization, but it also plays a role in higher level processes, such as face and object perception. Over the past decade, there has been progress in the study of the neural mechanisms of symmetry perception in humans and other animals. There is extended activity in the ventral stream, including the lateral occipital complex (LOC) and VO1; this activity starts in V3 and it occurs independently of the task (automatic response). Additionally, when the task requires processing of symmetry, the activation may emerge for objects that are symmetrical, even though they do not project a symmetrical image. There is also some evidence of hemispheric lateralization, especially for the LOC. We review the studies on the cortical basis of visual symmetry processing and its links to encoding of other aspects of the visual world, such as faces and objects.

Visual working memory performance in aphantasia.

Aphantasia, i.e., the congenital inability to experience voluntary mental imagery, offers a new model for studying the functional role of mental imagery in (visual) cognition. However, until now, there have been no studies investigating whether aphantasia can be linked to specific impairments in cognitive functioning. Here, we assess visual working memory performance in an aphantasic individual. We find that she performs significantly worse than controls on the most difficult (i.e., requiring the highest degree of precision) visual working memory trials. Surprisingly, her performance on a task designed to involve mental imagery did not differ from controls', although she lacked metacognitive insight into her performance. Together, these results indicate that although a lack of mental imagery can be compensated for under some conditions, mental imagery has a functional role in other areas of visual cognition, one of which is high-precision working memory.

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.

Initial activation state, stimulation intensity and timing of stimulation interact in producing behavioral effects of TMS.

Behavioral effects of transcranial magnetic stimulation (TMS) have been shown to depend on various factors, such as neural activation state, stimulation intensity, and timing of stimulation. Here we examined whether these factors interact, by applying TMS at either sub- or suprathreshold intensity (relative to phosphene threshold, PT) and at different time points during a state-dependent TMS paradigm. The state manipulation involved a behavioral task in which a visual prime (color grating) was followed by a target stimulus which could be either congruent, incongruent or partially congruent with the color and orientation of the prime. In Experiment 1, single-pulse TMS was applied over the early visual cortex (V1/V2) or Vertex (baseline) at the onset of the target stimulus - timing often used in state-dependent TMS studies. With both subthreshold and suprathreshold stimulation, TMS facilitated the detection of incongruent stimuli while not significantly affecting other stimulus types. In Experiment 2, TMS was applied at 100ms after target onset -a time window in which V1/V2 is responding to visual input. Only TMS applied at suprathreshold intensity facilitated the detection of incongruent stimuli, with no effect with subthreshold stimulation. The need for higher stimulation intensity is likely to reflect reduced susceptibility to TMS of neurons responding to visual stimulation. Furthermore, the finding that in Experiment 2 only suprathreshold TMS induced a behavioral facilitation on incongruent targets (whereas facilitations in the absence of priming have been reported with subthreshold TMS) indicates that priming, by reducing neural excitability to incongruent targets, shifts the facilitatory/inhibitory range of TMS effects.

Not all visual symmetry is equal: Partially distinct neural bases for vertical and horizontal symmetry.

Visual mirror symmetry plays an important role in visual perception in both human and animal vision; its importance is reflected in the fact that it can be extracted automatically during early stages of visual processing. However, how this extraction is implemented at the cortical level remains an open question. Given the importance of symmetry in visual perception, one possibility is that there is a network which extracts all types of symmetry irrespective of axis of orientation; alternatively, symmetry along different axes might be encoded by different brain regions, implying that there is no single neural mechanism for symmetry processing. Here we used fMRI-guided transcranial magnetic stimulation (TMS) to compare the neural basis of the two main types of symmetry found in the natural world, vertical and horizontal symmetry. TMS was applied over either right Lateral Occipital Cortex (LO), right Occipital Face Area (OFA) or Vertex while participants were asked to detect symmetry in low-level dot configurations. Whereas detection of vertical symmetry was impaired by TMS over both LO and OFA, detection of horizontal symmetry was delayed by stimulation of LO only. Thus, different types of visual symmetry rely on partially distinct cortical networks.

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.

Working Memory Maintenance: Sustained Firing or Synaptic Mechanisms?

According to conventional views, holding information in working memory (WM) involves elevated and persistent neuronal firing. This has been challenged by models in which WM maintenance is implemented by activity-silent synaptic mechanisms. A new study suggests that both have a role, consistent with cognitive models positing several states of WM. However, do these states reflect the operation of attention or awareness?