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.

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.

Role of corpus callosum in unconscious vision.

The existence of unconscious visually triggered behavior in patients with cortical blindness (e.g., homonymous hemianopia) has been amply demonstrated and the neural bases of this phenomenon have been thoroughly studied. However, a crosstalk between the two hemispheres as a possible mechanism of unconscious or partially conscious vision has not been so far considered. Thus, the aim of this study was to assess the relationship between structural and functional properties of the corpus callosum (CC), as shown by probabilistic tractography (PT), behavioral detection/discrimination performance and level of perceptual awareness in the blind field of patients with hemianopia. Twelve patients were tested in two tasks with black-and-white visual square-wave gratings, one task of movement and the other of orientation. The stimuli were lateralized to one hemifield either intact or blind. A PT analysis was carried out on MRI data to extract fiber properties along the CC (genu, body, and splenium). Compared with a control group of participants without brain damage, patients showed lower FA values in all three CC sections studied. For the intact hemifield we found a significant correlation between PT values and visual detection/discrimination accuracy. For the blind hemifield the level of perceptual awareness correlated with PT values for all three CC sections in the movement task. Importantly, significant differences in all three CC sections were found also between patients with above-vs. chance detection/discrimination performance while differences in the genu were found between patients with and without perceptual awareness. Overall, our study provides evidence that the properties of CC fibers are related to the presence of unconscious stimulus detection/discrimination and to hints of perceptual awareness for stimulus presentation to the blind hemifield. These results underline the importance of information exchange between the damaged and the healthy hemisphere for possible partial or full recovery from hemianopia.

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.

Olfaction and gustation in blindness: a state of the art of the literature.

To date, there are quite a few studies assessing olfaction and gustation in blindness, with great variability in sample size, participants' age, blindness onset and smell and taste evaluation methods. Indeed, the evaluation of olfactory and gustatory performance can differ depending on several factors, including cultural differences. Therefore, here we analysed through a narrative review, all the works reporting a smell and taste assessment in blind individuals during the last 130 years, trying to summarize and address the knowledge in this field.

A Practical Framework for Academics to Implement Public Engagement Interventions and Measure Their Impact.

Academic institutions have shown an increased interest in the so-called third mission to offer an impactful contribution to society. Indeed, public engagement programs ensure knowledge transfer and help to inspire positive public discourse. We aimed to propose a comprehensive framework for academic institutions planning to implement a public engagement intervention and to suggest potential indicators to measure its impact. To inform the framework development, we searched the literature on public engagement, the third mission, and design theory in electronic databases and additional sources (e.g., academic recommendations) and partnered with a communication agency offering non-academic advice. In line with this framework, we designed a public engagement intervention to foster scientific literacy in Italian youth, actively involving them in the development of the intervention. Our framework is composed of four phases (planning/design, implementation, immediate impact assessment, and medium- and long-term assessment). Impact indicators were subdivided into outcome variables that were immediately describable (e.g., changed understanding and awareness of the target population) and measurable only in the medium or long run (e.g., adoption of the intervention by other institutions). The framework is expected to maximize the impact of public engagement interventions and ultimately lead to better reciprocal listening and mutual understanding between academia and the public.

Visuo-spatial attention to the blind hemifield of hemianopic patients: Can it survive the impairment of visual awareness?

The general aim of this study was to assess the effect produced by visuo-spatial attention on both behavioural performance and brain activation in hemianopic patients following visual stimulus presentation to the blind hemifield. To do that, we tested five hemianopic patients and six age-matched healthy controls in an MRI scanner during the execution of a Posner-like paradigm using a predictive central cue. Participants were instructed to covertly orient attention toward the blind or sighted hemifield in different blocks while discriminating the orientation of a visual grating. In patients, we found significantly faster reaction times (RT) in valid and neutral than invalid trials not only in the sighted but also in the blind hemifield, despite the impairment of consciousness and performance at chance. As to the fMRI signal, in valid trials we observed the activation of ipsilesional visual areas (mainly lingual gyrus - area 19) during the orientation of attention toward the blind hemifield. Importantly, this activation was similar in patients and controls. In order to assess the related functional network, we performed a psychophysiological interactions (PPI) analysis that revealed an increased functional connectivity (FC) in patients with respect to controls between the ipsilesional lingual gyrus and ipsilateral fronto-parietal as well as contralesional parietal regions. Moreover, the shift of attention from the blind to the sighted hemifield revealed stronger FC between the contralesional visual areas V3/V4 and ipsilateral parietal regions in patients than controls. These results indicate a higher cognitive effort in patients when paying attention to the blind hemifiled or when shifting attention from the blind to the sighted hemfield, possibly as an attempt to compensate for the visual loss. Taken together, these results show that hemianopic patients can covertly orient attention toward the blind hemifield with a top-down mechanism by activating a functional network mainly including fronto-parietal regions belonging to the dorsal attentional network.

What cortical areas are responsible for blindsight in hemianopic patients?

The presence of above-chance unconscious behavioral responses following stimulus presentation to the blind hemifield of hemianopic patients (blindsight) is a well-known phenomenon. What is still lacking is a systematic study of the neuroanatomical bases of two distinct aspects of blindsight: the unconscious above chance performance and the phenomenological aspects that may be associated. Here, we tested 17 hemianopic patients in two tasks i.e. movement and orientation discrimination of a visual grating presented to the sighted or blind hemifield. We classified patients in four groups on the basis of the presence of above chance unconscious discrimination without or with perceptual awareness reports for stimulus presentation to the blind hemifield. A fifth group was represented by patients with interruption of the Optic Radiation. In the various groups we carried out analyses of lesion extent of various cortical areas, probabilistic tractography as well as assessment of the cortical thickness of the intact hemisphere. All patients had lesions mainly, but not only, in the occipital lobe and the statistical comparison of their extent provided clues as to the critical anatomical substrate of unconscious above-chance performance and of perceptual awareness reports, respectively. In fact, the two areas that turned out to be critical for above-chance performance in the discrimination of moving versus non-moving visual stimuli were the Precuneus and the Posterior Cingulate Gyrus while for perceptual awareness reports the crucial areas were Intracalcarine, Supracalcarine, Cuneus, and the Posterior Cingulate Gyrus. Interestingly, the proportion of perceptual awareness reports was higher in patients with a spared right hemisphere. As to probabilistic tractography, all pathways examined yielded higher positive values for patients with perceptual awareness reports. Finally, the cortical thickness of the intact hemisphere was greater in patients showing above-chance performance than in those at chance. This effect is likely to be a result of neuroplastic compensatory mechanisms.

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.

Neural bases of unconscious orienting of attention in hemianopic patients: Hemispheric differences.

The aim of this research was to study the behavioral and neurophysiological correlates of visual attention orientation to unseen stimuli presented to the blind hemifield of hemianopic patients, and the existence of hemispheric differences for this kind of unconscious attention. Behaviorally, by using a Posner paradigm, we found a significant attention effect in speed of response to unseen stimuli similar to that observed in the sighted hemifield and in healthy participants for visible stimuli. Moreover, event-related potential (ERP) and oscillatory attention-related activity were present following stimulus presentation to the blind hemifield. Importantly, in patients this pattern of activity was different as a function of the side of the brain lesion: Left damaged patients showed attention-related ERP and oscillatory activity broadly similar to that found in healthy participants. In contrast, right damaged patients showed a radically different pattern. These data confirm and extend to neurophysiological mechanisms the existence of unconscious visual orienting and are in keeping with a right hemisphere dominance for both unconscious and conscious attention.

Neural bases of visual processing of moving and stationary stimuli presented to the blind hemifield of hemianopic patients.

Unilateral damage to post-chiasmatic visual pathways or cortical areas results in the loss of vision in the contralateral hemifield, known as hemianopia. Some patients, however, may retain the ability to perform an above chance unconscious detection or discrimination of visual stimuli presented to the blind hemifield, known as "blindsight". An important finding in blindsight research is that it can often be elicited by moving stimuli. Therefore, in the present study, we wanted to test whether moving stimuli might yield blindsight phenomena in patients with cortical lesions resulting in hemianopia, in a discrimination task where stimulus movement is orthogonal to the feature of interest. This could represent an important strategy for rehabilitation because it might improve discrimination ability of stimulus features different but related to movement, e.g. line orientation. We tested eight hemianopic patients and eight age-matched healthy controls in an orientation discrimination task with moving or static visual stimuli. During performance of the task we carried out fMRI scanning and tractography. Behaviourally, we did not find a reliable main effect of motion on orientation discrimination; however, an important result was that in different patients blindsight could occur only with moving or stationary stimuli or with both. As to brain imaging results, following presentation of moving stimuli to the blind hemifield, a widespread fronto-parietal bilateral network was recruited including areas of the dorsal stream and in particular bilateral motion area hMT + whose activation positively correlated with behavioural performance. This bilateral network was not activated in controls suggesting that it represents a compensatory functional change following brain damage. Moreover, there was a higher activation of ipsilesional area hMT+ in patients who performed above chance in the moving condition. By contrast, in patients who performed above chance in the static condition, we found a higher activation of contralesional area V1 and extrastriate visual areas. Finally, we found a linear relationship between structural integrity of the ipsilesional pathway connecting lateral geniculate nucleus (LGN) with motion area hMT+ and both behavioural performance and ipsilesional hMT + activation. These results support the role of LGN in modulating performance as well as BOLD amplitude in the absence of visual awareness in ipsilesional area hMT+ during an orientation discrimination task with moving stimuli.

Functional interactions in patients with hemianopia: A graph theory-based connectivity study of resting fMRI signal.

The assessment of task-independent functional connectivity (FC) after a lesion causing hemianopia remains an uncovered topic and represents a crucial point to better understand the neural basis of blindsight (i.e. unconscious visually triggered behavior) and visual awareness. In this light, we evaluated functional connectivity (FC) in 10 hemianopic patients and 10 healthy controls in a resting state paradigm. The main aim of this study is twofold: first of all we focused on the description and assessment of density and intensity of functional connectivity and network topology with and without a lesion affecting the visual pathway, and then we extracted and statistically compared network metrics, focusing on functional segregation, integration and specialization. Moreover, a study of 3-cycle triangles with prominent connectivity was conducted to analyze functional segregation calculated as the area of each triangle created connecting three neighboring nodes. To achieve these purposes we applied a graph theory-based approach, starting from Pearson correlation coefficients extracted from pairs of regions of interest. In these analyses we focused on the FC extracted by the whole brain as well as by four resting state networks: The Visual (VN), Salience (SN), Attention (AN) and Default Mode Network (DMN), to assess brain functional reorganization following the injury. The results showed a general decrease in density and intensity of functional connections, that leads to a less compact structure characterized by decrease in functional integration, segregation and in the number of interconnected hubs in both the Visual Network and the whole brain, despite an increase in long-range inter-modules connections (occipito-frontal connections). Indeed, the VN was the most affected network, characterized by a decrease in intra- and inter-network connections and by a less compact topology, with less interconnected nodes. Surprisingly, we observed a higher functional integration in the DMN and in the AN regardless of the lesion extent, that may indicate a functional reorganization of the brain following the injury, trying to compensate for the general reduced connectivity. Finally we observed an increase in functional specialization (lower between-network connectivity) and in inter-networks functional segregation, which is reflected in a less compact network topology, highly organized in functional clusters. These descriptive findings provide new insight on the spontaneous brain activity in hemianopic patients by showing an alteration in the intrinsic architecture of a large-scale brain system that goes beyond the impairment of a single RSN.

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.

The EEG signature of sensory evidence accumulation during decision formation closely tracks subjective perceptual experience.

How neural representations of low-level visual information are accessed by higher-order processes to inform decisions and give rise to conscious experience is a longstanding question. Research on perceptual decision making has revealed a late event-related EEG potential (the Centro-Parietal Positivity, CPP) to be a correlate of the accumulation of sensory evidence. We tested how this evidence accumulation signal relates to externally presented (physical) and internally experienced (subjective) sensory evidence. Our results show that the known relationship between the physical strength of the external evidence and the evidence accumulation signal (reflected in the CPP amplitude) is mediated by the level of subjective experience of stimulus strength. This shows that the CPP closely tracks the subjective perceptual evidence, over and above the physically presented evidence. We conclude that a remarkably close relationship exists between the evidence accumulation process (i.e. CPP) and subjective perceptual experience, suggesting that neural decision processes and components of conscious experience are tightly linked.

Neural Correlates of Visuospatial Attention to Unseen Stimuli in Hemianopic Patients. A Steady-State Visual Evoked Potential Study.

The relationship between attention and awareness is a topic of great interest in cognitive neuroscience. Some studies in healthy participants and hemianopic patients have shown dissociation between these two processes. In contrast, others confirmed the classic notion that the two processes are mutually exclusive. To try and cast further light on this fascinating dilemma, in the present study we have investigated the neural mechanisms of visual spatial attention when perceptual awareness is totally lacking. To do that, we monitored with steady-state visual evoked potentials (SSVEPs) the neurophysiological correlates of endogenous spatial attention to unseen stimuli presented to the blind field of hemianopic patients. Behaviourally, stimulus detection (a brief change in the orientation of a gabor grating) was absent in the blind hemifield while in the sighted field there was a lower, but non-significant, performance in hit rate with respect to a healthy control group. Importantly, however, in both blind and sighted hemifield of hemianopics (as well as in healthy participants) SSVEP recordings showed an attentional effect with higher frequency power in the attended than unattended condition. The scalp distribution of this effect was broadly in keeping with the location of the dorsal system of endogenous spatial attention. In conclusion, the present results provide evidence that the neural correlates of spatial attention are present regardless of visual awareness and this is in accord with the general hypothesis of a possible dissociation between attention and awareness.