Bypassing input to V1 in visual awareness: A TMS-EROS investigation.

Early visual cortex (V1-V3) is believed to be critical for normal visual awareness by providing the necessary feedforward input. However, it remains unclear whether visual awareness can occur without further involvement of early visual cortex, such as re-entrant feedback. It has been challenging to determine the importance of feedback activity to these areas because of the difficulties in dissociating this activity from the initial feedforward activity. Here, we applied single-pulse transcranial magnetic stimulation (TMS) over the left posterior parietal cortex to elicit phosphenes in the absence of direct visual input to early visual cortex. Immediate neural activity after the TMS pulse was assessed using the event-related optical signal (EROS), which can measure activity under the TMS coil without artifacts. Our results show that: 1) The activity in posterior parietal cortex 50 ms after TMS was related to phosphene awareness, and 2) Activity related to awareness was observed in a small portion of V1 140 ms after TMS, but in contrast (3) Activity in V2 was a more robust correlate of awareness. Together, these results are consistent with interactive models proposing that sustained and recurrent loops of activity between cortical areas are necessary for visual awareness to emerge. In addition, we observed phosphene-related activations of the anteromedial cuneus and lateral occipital cortex, suggesting a functional network subserving awareness comprising these regions, the parietal cortex and early visual cortex.

Coherent activity within and between hemispheres: cortico-cortical connectivity revealed by rTMS of the right posterior parietal cortex.

Introduction: Low frequency (1 Hz) repetitive transcranial stimulation (rTMS) applied over right posterior parietal cortex (rPPC) has been shown to reduce cortical excitability both of the stimulated area and of the interconnected contralateral homologous areas. In the present study, we investigated the whole pattern of intra- and inter-hemispheric cortico-cortical connectivity changes induced by rTMS over rPPC. Methods: To do so, 14 healthy participants underwent resting state EEG recording before and after 30 min of rTMS at 1 Hz or sham stimulation over the rPPC (electrode position P6). Real stimulation was applied at 90% of motor threshold. Coherence values were computed on the electrodes nearby the stimulated site (i.e., P4, P8, and CP6) considering all possible inter- and intra-hemispheric combinations for the following frequency bands: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12Hz), low beta (12-20 Hz), high beta (20-30 Hz), and gamma (30-50 Hz). Results and discussion: Results revealed a significant increase in coherence in delta, theta, alpha and beta frequency bands between rPPC and the contralateral homologous sites. Moreover, an increase in coherence in theta, alpha, beta and gamma frequency bands was found between rPPC and right frontal sites, reflecting the activation of the fronto-parietal network within the right hemisphere. Summarizing, subthreshold rTMS over rPPC revealed cortico-cortical inter- and intra-hemispheric connectivity as measured by the increase in coherence among these areas. Moreover, the present results further confirm previous evidence indicating that the increase of coherence values is related to intra- and inter-hemispheric inhibitory effects of rTMS. These results can have implications for devising evidence-based rehabilitation protocols after stroke.

Mapping the routes of perception: Hemispheric asymmetries in signal propagation dynamics.

The visual system has long been considered equivalent across hemispheres. However, an increasing amount of data shows that functional differences may exist in this regard. We therefore tried to characterize the emergence of visual perception and the spatiotemporal dynamics resulting from the stimulation of visual cortices in order to detect possible interhemispheric asymmetries. Eighteen participants were tested. Each of them received 360 transcranial magnetic stimulation (TMS) pulses at phosphene threshold intensity over left and right early visual areas while electroencephalography was being recorded. After each single pulse, participants had to report the presence or absence of a phosphene. Local mean field power analysis of TMS-evoked potentials showed an effect of both site (left vs. right TMS) of stimulation and hemisphere (ipsilateral vs. contralateral to the TMS): while right TMS determined early stronger activations, left TMS determined later stronger activity in contralateral electrodes. The interhemispheric signal propagation index revealed differences in how TMS-evoked activity spreads: left TMS-induced activity diffused contralaterally more than right stimulation. With regard to phosphenes perception, distinct electrophysiological patterns were found to reflect similar perceptual experiences: left TMS-evoked phosphenes are associated with early occipito-parietal and frontal activity followed by late central activity; right TMS-evoked phosphenes determine only late, fronto-central, and parietal activations. Our results show that left and right occipital TMS elicits differential electrophysiological patterns in the brain, both per se and as a function of phosphene perception. These distinct activation patterns may suggest a different role of the two hemispheres in processing visual information and giving rise to perception.

Graph Analysis of TMS-EEG Connectivity Reveals Hemispheric Differences following Occipital Stimulation.

(1) Background: Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) provides a unique opportunity to investigate brain connectivity. However, possible hemispheric asymmetries in signal propagation dynamics following occipital TMS have not been investigated. (2) Methods: Eighteen healthy participants underwent occipital single-pulse TMS at two different EEG sites, corresponding to early visual areas. We used a state-of-the-art Bayesian estimation approach to accurately estimate TMS-evoked potentials (TEPs) from EEG data, which has not been previously used in this context. To capture the rapid dynamics of information flow patterns, we implemented a self-tuning optimized Kalman (STOK) filter in conjunction with the information partial directed coherence (iPDC) measure, enabling us to derive time-varying connectivity matrices. Subsequently, graph analysis was conducted to assess key network properties, providing insight into the overall network organization of the brain network. (3) Results: Our findings revealed distinct lateralized effects on effective brain connectivity and graph networks after TMS stimulation, with left stimulation facilitating enhanced communication between contralateral frontal regions and right stimulation promoting increased intra-hemispheric ipsilateral connectivity, as evidenced by statistical test (p < 0.001). (4) Conclusions: The identified hemispheric differences in terms of connectivity provide novel insights into brain networks involved in visual information processing, revealing the hemispheric specificity of neural responses to occipital stimulation.

The spectral dynamics of visual awareness: An interplay of different frequencies?

The goal of this study was to investigate the neurophysiological correlates of visual awareness, with a specific focus on its event-related spectral perturbation (ERSP) features. To this aim, we tried to disentangle the proper neural correlates of consciousness (NCC) from other prerequisite and post-perceptual processing. To do so, we administered an orientation discrimination task, inducing a response bias through task instructions. EEG results showed that different frequency bands are involved in this kind of task, with different spectral and temporal dynamics. In particular, alpha and beta bands seem to be particularly engaged, especially in the aware-unaware contrast, showing a main power suppression for aware trials and replicating previous literature. Moreover, we demonstrated that the process of visual awareness is orchestrated by a complex interaction of different frequencies (i.e., theta, alpha, beta and gamma) being involved as prerequisites and post-perceptual processes.

Late Positivity Does Not Meet the Criteria to be Considered a Proper Neural Correlate of Perceptual Awareness.

Contrastive analysis has been widely employed in the search for the electrophysiological neural correlates of consciousness. However, despite its clear logic, it has been argued that it may not succeed in isolating neural processes solely involved in the emergence of perceptual awareness. In fact, data from contrastive analysis would be contaminated by potential confounding factors reflecting distinct, though related, processes either preceding or following the conscious perception. At present, the ERP components representing the proper correlates of perceptual awareness still remain to be identified among those correlating with awareness (i.e., Visual Awareness Negativity, VAN and Late Positivity, LP). In order to dissociate visual awareness from post-perceptual confounds specifically related to decision making, we manipulated the response criterion, which affects how a percept is translated into a decision. In particular, while performing an orientation discrimination task, participants were asked to shift their response criterion across sessions. As a consequence, the resulting modulation should concern the ERP component(s) not exclusively reflecting mechanisms regulating the subjective conscious experience itself but rather the processes accompanying it. Electrophysiological results showed that N1 and P3 were sensitive to the response criterion adopted by participants. Additionally, the more the participants shifted their response criterion, the bigger the ERP modulation was; this was consequently indicative of the critical role of these components in the decision-making processes regardless of awareness level. When considering data independently from the response criterion, the aware vs. unaware contrast showed that both VAN and LP were significant. Crucially, the LP component was also modulated by the interaction of awareness and response criterion, while VAN results to be unaffected. In agreement with previous literature, these findings provide evidence supporting the hypothesis that VAN tracks the emergence of visual awareness by encoding the conscious percept, whereas LP reflects the contribution from post-perceptual processes related to response requirements. This excludes a direct functional role of this later component in giving rise to perceptual awareness.

Spatiotemporal dynamics of attentional orienting and reorienting revealed by fast optical imaging in occipital and parietal cortices.

The mechanisms of visuospatial attention are mediated by two distinct fronto-parietal networks: a bilateral dorsal network (DAN), involved in the voluntary orientation of visuospatial attention, and a ventral network (VAN), lateralized to the right hemisphere, involved in the reorienting of attention to unexpected, but relevant, stimuli. The present study consisted of two aims: 1) to characterize the spatio-temporal dynamics of attention and 2) to examine the predictive interactions between and within the two attention systems along with visual areas, by using fast optical imaging combined with Granger causality. Data were collected from young healthy participants performing a discrimination task in a Posner-like paradigm. Functional analyses revealed bilateral dorsal parietal (i.e. dorsal regions included in the DAN) and visual recruitment during orienting, highlighting a recursive predictive interplay between specific dorsal parietal regions and visual cortex. Moreover, we found that both attention networks are active during reorienting, together with visual cortex, highlighting a mutual interaction among dorsal and visual areas, which, in turn, predicts subsequent ventral activity. For attentional reorienting our findings indicate that dorsal and visual areas encode disengagement of attention from the attended location and trigger reorientation to the unexpected location. Ventral network activity could instead reflect post-perceptual maintenance of the internal model to generate and keep updated task-related expectations.

Face Recognition Deficits in a Patient With Alzheimer's Disease: Amnesia or Agnosia? The Importance of Electrophysiological Markers for Differential Diagnosis.

Face recognition deficits are frequently reported in Alzheimer's disease (AD) and often attributed to memory impairment. However, it has been hypothesized that failure in identifying familiar people could also be due to deficits in higher-level perceptual processes, since there is evidence showing a reduced inversion effect for faces but not for cars in AD. To address the involvement of these higher processes, we investigated event-related potential (ERP) neural correlates of faces in a patient with AD showing a face recognition deficit. Eight healthy participants were tested as a control group. Participants performed different tasks following the stimulus presentation. In experiment 1, they should indicate whether the stimulus was either a face or a house or a scrambled image. In experiments 2 and 3, they should discriminate between upright and inverted faces (in experiment 2, stimuli were faces with neutral or fearful expressions, while in experiment 3, stimuli were famous or unfamiliar faces). Electrophysiological results reveal that the typical face-specific modulation of the N170 component, which is thought to reflect the structural encoding of faces, was not present in patient MCG, despite being affected by the emotional content of the face implicitly processed by MCG. Conversely, the N400 component, which is thought to reflect the recruitment of the memory trace of the face identity, was found to be implicitly modulated in MCG. These results may identify a possible role for gnosic processes in face recognition deficits in AD and suggest the importance of adopting an integrated approach to the AD diagnosis while considering electrophysiological markers.

Reliability in reporting perceptual experience: Behaviour and electrophysiology in hemianopic patients.

Patients with hemianopia can present with the so called blindsight phenomenon: the ability to perform above chance in the absence of acknowledged awareness. Proper awareness reports are, thus, crucial to distinguish pure forms of blindsight from forms of conscious, yet degraded, vision. It has, in fact, been recently shown that 1) dichotomous and graded measures to assess awareness can lead to different behavioural results in patients with hemianopia and that 2) different grades of perceptual clarity show different electrophysiological correlates in healthy participants. Here, in hemianopic patients, we assessed awareness by means of the four-point Perceptual Awareness Scale (PAS) and investigated its neural correlates with Event Related Potentials (ERPs). Results showed that patients, in most of the cases, can rate the clarity of their perceptual experience in a graded manner. Moreover, graded perceptual experiences correlated with the amplitude of deflections in ERPs. These results call for the need to assess perceptual awareness with graded measures and for the importance to use electrophysiological data to correlate behaviour with neural processing.

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.

Markers of TMS-evoked visual conscious experience in a patient with altitudinal hemianopia.

Transcranial magnetic stimulation (TMS) of the occipital and parietal cortices can induce phosphenes, i.e. visual sensations of light without light entering the eyes. In this paper, we adopted a TMS-EEG interactive co-registration approach with a patient (AM) showing altitudinal hemianopia. Occipital and parietal cortices in both hemispheres were stimulated while concurrently recording EEG signal. Results showed that, for all sites, neural activity differentially encoding for the presence vs. absence of a conscious experience could be found in a cluster of electrodes close to the stimulation site at an early (70ms) time-period after TMS. The present data indicate that both occipital and parietal sites are independent early gatekeepers of perceptual awareness, thus, in line with evidence in favor of early correlates of perceptual awareness. Moreover, these data support the valuable contribution of the TMS-EEG approach in patients with visual field defects to investigate the neural processes responsible for perceptual awareness.

Reliability of TMS phosphene threshold estimation: Toward a standardized protocol.

BACKGROUND: Phosphenes induced by transcranial magnetic stimulation (TMS) are a subjectively described visual phenomenon employed in basic and clinical research as index of the excitability of retinotopically organized areas in the brain. OBJECTIVE: Phosphene threshold estimation is a preliminary step in many TMS experiments in visual cognition for setting the appropriate level of TMS doses; however, the lack of a direct comparison of the available methods for phosphene threshold estimation leaves unsolved the reliability of those methods in setting TMS doses. The present work aims at fulfilling this gap. METHODS: We compared the most common methods for phosphene threshold calculation, namely the Method of Constant Stimuli (MOCS), the Modified Binary Search (MOBS) and the Rapid Estimation of Phosphene Threshold (REPT). In two experiments we tested the reliability of PT estimation under each of the three methods, considering the day of administration, participants' expertise in phosphene perception and the sensitivity of each method to the initial values used for the threshold calculation. RESULTS: We found that MOCS and REPT have comparable reliability when estimating phosphene thresholds, while MOBS estimations appear less stable. CONCLUSIONS: Based on our results, researchers and clinicians can estimate phosphene threshold according to MOCS or REPT equally reliably, depending on their specific investigation goals. We suggest several important factors for consideration when calculating phosphene thresholds and describe strategies to adopt in experimental procedures.

Blind-Sight vs. Degraded-Sight: Different Measures Tell a Different Story.

Blindsight patients can detect, localize, and discriminate visual stimuli in their blind field, despite denying being able to see the stimuli. However, the literature documents the cases of blindsight patients who demonstrated a preserved degree of awareness in their impaired visual field. The aim of this study is to investigate the nature of visual processing within the impaired visual field and to ask whether it reflects pure unconscious behavior or conscious, yet degraded, vision. A hemianopic patient (SL) with a complete lesion to the left primary visual cortex was tested. SL was asked to discriminate several stimulus features (orientation, color, contrast, and motion) presented in her impaired visual field in a two-alternative forced-choice task. SL had to report her subjective experience: in the first experiment as "seen" or "guessed," whereas in the second experiment as the degree of clarity of her experience according to the perceptual awareness scale. In the first experiment, SL demonstrated a performance above-chance in the discrimination task for "guessed" trials, thus showing type 1 blindsight. In the second experiment, however, SL showed above-chance performance only when she reported a certain degree of awareness, thus showing that SL's preserved discrimination ability relies on conscious vision. These data show that graded measures to assess awareness, which can better tap on the complexity of conscious experience, need to be used in order to differentiate genuine forms of blindsight from degraded conscious vision.

Early Local Activity in Temporal Areas Reflects Graded Content of Visual Perception.

In visual cognitive neuroscience the debate on consciousness is focused on two major topics: the search for the neural correlates of the different properties of visual awareness and the controversy on the graded versus dichotomous nature of visual conscious experience. The aim of this study is to search for the possible neural correlates of different grades of visual awareness investigating the Event Related Potentials to reduced contrast visual stimuli whose perceptual clarity was rated on the four-point Perceptual Awareness Scale. Results revealed a left centro-parietal negative deflection (Visual Awareness Negativity; VAN) peaking at 280-320 ms from stimulus onset, related to the perceptual content of the stimulus, followed by a bilateral positive deflection (Late Positivity; LP) peaking at 510-550 ms over almost all electrodes, reflecting post-perceptual processes performed on such content. Interestingly, the amplitude of both deflections gradually increased as a function of visual awareness. Moreover, the intracranial generators of the phenomenal content (VAN) were found to be located in the left temporal lobe. The present data thus seem to suggest (1) that visual conscious experience is characterized by a gradual increase of perceived clarity at both behavioral and neural level and (2) that the actual content of perceptual experiences emerges from early local activation in temporal areas, without the need of later widespread frontal engagement.

The influence of posterior parietal cortex on extrastriate visual activity: A concurrent TMS and fast optical imaging study.

The posterior parietal cortex (PPC) is a critical node in attentional and saccadic eye movement networks of the cerebral cortex, exerting top-down control over activity in visual cortex. Here, we sought to further elucidate the properties of PPC feedback by providing a time-resolved map of functional connectivity between parietal and occipital cortex using single-pulse TMS to stimulate the left PPC while concurrently recording fast optical imaging data from bilateral occipital cortex. Magnetic stimulation of the PPC induced transient ipsilateral occipital activations (BA 18) 24-48ms post-TMS. Concurrent TMS and fast optical imaging results demonstrate a clear influence of PPC stimulation on activity within human extrastriate visual cortex and further extend this time- and space-resolved method for examining functional connectivity.

Assessing the effects of physical and perceived luminance contrast on RT and TMS-induced percepts.

Simple reaction times (RTs) are inversely related to the luminance of a visual region, with RT increasing as luminance decreases, and decreasing as luminance increases. A potential discrepancy in the link between luminance and RT, however, stems from the perception of luminance itself. Here, we tested whether RT is modulated by a measureable amount of light (luminance) or perceptual amount of light (brightness), as two test regions having the same luminance can be perceived as having different brightness. The current study investigates the effects of brightness using probes and artificial percepts, i.e., transcranial magnetic stimulation (TMS)-induced light and dark percepts. In Experiment 1, participants performed a RT task to light and dark probes presented over two backgrounds, one exhibiting a physical luminance and the other exhibiting perceptual brightness. Experiment 2 tested whether perceptual brightness could influence RT and frequency of artificial percepts. We found that while brightness contrast modulated RT to the dark probes, the frequency of artificial percepts was susceptible to both physical and perceived changes in luminance. These data suggest that some behavioral responses can be influenced by an illusion of brightness, wherein there is no actual change in luminance, as well as the perception of TMS-induced percepts.

Shining new light on dark percepts: visual sensations induced by TMS.

Phosphenes induced by transcranial magnetic stimulation (TMS) are sensations of light, whereas a missing region in the visual field induced by TMS is generally referred to as a scotoma. It is believed that phosphenes are caused by neural excitation, while scotomas are due to neural inhibition. In light of the recent literature it might, however, be surmised that both phenomena are the result of neural noise injected into the cortex by TMS and that the likelihood of perceiving the two kinds of percepts depends on the state of the cortex at the time of stimulation. In the present study, TMS was applied over the left occipital cortex under different background conditions (Experiments 1-2) and using different TMS intensities (Experiment 3). Behavioral responses indicate the visual system processes luminance in a standardized manner, as lighter percepts were reacted to faster than darker percepts; this effect, however, did not extend to percept size. Our results suggest that phenomenological characteristics of artificial visual percepts are in line with the proposed effects of TMS as the induction of random neural noise interfering with the neural dynamics (the state of the cortex) at the time of stimulation.

Waves of awareness for occipital and parietal phosphenes perception.

Transcranial magnetic stimulation (TMS) of the occipital cortex is known to induce visual sensations, i.e. phosphenes, which appear as flashes of light in the absence of an external stimulus. Recent studies have shown that TMS can produce phosphenes also when the intraparietal sulcus (IPS) is stimulated. The main question addressed in this paper is whether parietal phosphenes are generated directly by local mechanisms or emerge through indirect activation of other visual areas. Electroencephalographic (EEG) signals were recorded while stimulating left occipital or parietal cortices inducing phosphene perception in healthy participants and in a hemianopic patient who suffered from complete destruction of the early visual cortex of the left hemisphere. Results in healthy participants showed that the onset of phosphene perception induced by occipital TMS correlated with differential cortical activity in temporal sites while the onset of phosphene perception induced by parietal TMS correlated with differential cortical activity in the stimulated parietal site. Moreover, IPS-TMS of the lesioned hemisphere of the hemianopic patient with a complete lesion to V1 showed again that the onset of phosphene perception correlated with differential cortical activity in the stimulated parietal site. The present data seem thus to suggest that temporal and parietal cortices can serve as different local early gatekeepers of perceptual awareness and that activity in the occipital cortex, although being relevant for perception in general, is not part of the neural bases of the perceptual awareness of phosphenes.