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.

Inefficient white matter activity in Schizophrenia evoked during intra and inter-hemispheric communication.

Intensive cognitive tasks induce inefficient regional and network responses in schizophrenia (SCZ). fMRI-based studies have naturally focused on gray matter, but appropriately titrated visuo-motor integration tasks reliably activate inter- and intra-hemispheric white matter pathways. Such tasks can assess network inefficiency without demanding intensive cognitive effort. Here, we provide the first application of this framework to the study of white matter functional responses in SCZ. Event-related fMRI data were acquired from 28 patients (nine females, mean age 43.3, ±11.7) and 28 age- and gender-comparable controls (nine females, mean age 42.1 ± 10.1), using the Poffenberger paradigm, a rapid visual detection task used to induce intra- (ipsi-lateral visual and motor cortex) or inter-hemispheric (contra-lateral visual and motor cortex) transfer. fMRI data were pre- and post-processed to reliably isolate activations in white matter, using probabilistic tractography-based white matter tracts. For intra- and inter-hemispheric transfer conditions, SCZ evinced hyper-activations in longitudinal and transverse white matter tracts, with hyper-activation in sub-regions of the corpus callosum primarily observed during inter-hemispheric transfer. Evidence for the functional inefficiency of white matter was observed in conjunction with small (~50 ms) but significant increases in response times. Functional inefficiencies in SCZ are (1) observable in white matter, with the degree of inefficiency contextually related to task-conditions, and (2) are evoked by simple detection tasks without intense cognitive processing. These cumulative results while expanding our understanding of this dys-connection syndrome, also extend the search of biomarkers beyond the traditional realm of fMRI studies of gray matter.

The functional characterization of callosal connections.

The brain operates through the synaptic interaction of distant neurons within flexible, often heterogeneous, distributed systems. Histological studies have detailed the connections between distant neurons, but their functional characterization deserves further exploration. Studies performed on the corpus callosum in animals and humans are unique in that they capitalize on results obtained from several neuroscience disciplines. Such data inspire a new interpretation of the function of callosal connections and delineate a novel road map, thus paving the way toward a general theory of cortico-cortical connectivity. Here we suggest that callosal axons can drive their post-synaptic targets preferentially when coupled to other inputs endowing the cortical network with a high degree of conditionality. This might depend on several factors, such as their pattern of convergence-divergence, the excitatory and inhibitory operation mode, the range of conduction velocities, the variety of homotopic and heterotopic projections and, finally, the state-dependency of their firing. We propose that, in addition to direct stimulation of post-synaptic targets, callosal axons often play a conditional driving or modulatory role, which depends on task contingencies, as documented by several recent studies.

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.

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.

Split-Brain: What We Know Now and Why This is Important for Understanding Consciousness.

Recently, the discussion regarding the consequences of cutting the corpus callosum ("split-brain") has regained momentum (Corballis, Corballis, Berlucchi, & Marzi, Brain, 141(6), e46, 2018; Pinto et al., Brain, 140(5), 1231-1237, 2017a; Pinto, Lamme, & de Haan, Brain, 140(11), e68, 2017; Volz & Gazzaniga, Brain, 140(7), 2051-2060, 2017; Volz, Hillyard, Miller, & Gazzaniga, Brain, 141(3), e15, 2018). This collective review paper aims to summarize the empirical common ground, to delineate the different interpretations, and to identify the remaining questions. In short, callosotomy leads to a broad breakdown of functional integration ranging from perception to attention. However, the breakdown is not absolute as several processes, such as action control, seem to remain unified. Disagreement exists about the responsible mechanisms for this remaining unity. The main issue concerns the first-person perspective of a split-brain patient. Does a split-brain harbor a split consciousness or is consciousness unified? The current consensus is that the body of evidence is insufficient to answer this question, and different suggestions are made with respect to how future studies might address this paucity. In addition, it is suggested that the answers might not be a simple yes or no but that intermediate conceptualizations need to be considered.

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.

Visually evoked responses from the blind field of hemianopic patients.

Hemianopia is a visual field defect characterized by decreased vision or blindness in the contralesional visual field of both eyes. The presence of well documented above-chance unconscious behavioural responses to visual stimuli presented to the blind hemifield (blindsight) has stimulated a great deal of research on the neural basis of this important phenomenon. The present study is concerned with electrophysiological responses from the blind field. Since previous studies found that transient Visual Evoked Potentials (VEPs) are not entirely suitable for this purpose here we propose to use Steady-State VEPs (SSVEPs). A positive result would have important implications for the understanding of the neural bases of conscious vision. We carried out a passive SSVEP stimulation with healthy participants and hemianopic patients. Stimuli consisted of four black-and-white sinusoidal Gabor gratings presented one in each visual field quadrant and flickering one at a time at a 12Hz rate. To assess response reliability a Signal-to-Noise Ratio analysis was conducted together with further analyses in time and frequency domains to make comparisons between groups (healthy participants and patients), side of brain lesion (left and right) and visual fields (sighted and blind). The important overall result was that stimulus presentation to the blind hemifield yielded highly reliable responses with time and frequency features broadly similar to those found for cortical extrastriate areas in healthy controls. Moreover, in the intact hemifield of hemianopics and in healthy controls there was evidence of a role of prefrontal structures in perceptual awareness. Finally, the presence of different patterns of brain reorganization depended upon the side of lesion.

Erratum to: Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness.

The original version of this article unfortunately contained a mistake. The family name of Paolo Brambilla was incorrectly spelled as Bambilla.

Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness.

Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer. Yet the role of uni-manual responses and/or right hand dominance in modulating brain activations during such basic tasks is unclear. Here we investigated how uni-manual responses with either hand modulated activations during a basic visuo-motor task (the established Poffenberger paradigm) alternating between inter- and within-hemispheric transfer conditions. In a large sample of strongly right-handed adults (n = 49), we used a factorial combination of transfer condition [Inter vs. Within] and response hand [Dominant(Right) vs. Non-Dominant (Left)] to discover fMRI-based activations in gray matter, and in narrowly defined white matter tracts. These tracts were identified using a priori probabilistic white matter atlases. Uni-manual responses with the right hand strongly modulated activations in gray matter, and notably in white matter. Furthermore, when responding with the left hand, activations during inter-hemispheric transfer were strongly predicted by the degree of right-hand dominance, with increased right-handedness predicting decreased fMRI activation. Finally, increasing age within the middle-aged sample was associated with a decrease in activations. These results provide novel evidence of complex relationships between uni-manual responses in right-handed subjects, and activations during within- and inter-hemispheric transfer suggest that the organization of the motor system exerts sophisticated functional effects. Moreover, our evidence of activation in white matter tracts is consistent with prior studies, confirming fMRI-detectable white matter activations which are systematically modulated by experimental condition.

Intact hemisphere and corpus callosum compensate for visuomotor functions after early visual cortex damage.

Unilateral damage to the primary visual cortex (V1) leads to clinical blindness in the opposite visual hemifield, yet nonconscious ability to transform unseen visual input into motor output can be retained, a condition known as "blindsight." Here we combined psychophysics, functional magnetic resonance imaging, and tractography to investigate the functional and structural properties that enable the developing brain to partly overcome the effects of early V1 lesion in one blindsight patient. Visual stimuli appeared in either the intact or blind hemifield and simple responses were given with either the left or right hand, thereby creating conditions where visual input and motor output involve the same or opposite hemisphere. When the V1-damaged hemisphere was challenged by incoming visual stimuli, or controlled manual responses to these unseen stimuli, the corpus callosum (CC) dynamically recruited areas in the visual dorsal stream and premotor cortex of the intact hemisphere to compensate for altered visuomotor functions. These compensatory changes in functional brain activity were paralleled by increased connections in posterior regions of the CC, where fibers connecting homologous areas of the parietal cortex course.

Lights from the Dark: Neural Responses from a Blind Visual Hemifield.

Here we present evidence that a hemianopic patient with a lesion of the left primary visual cortex (V1) showed an unconscious above-chance orientation discrimination with moving rather than static visual gratings presented to the blind hemifield. The patient did not report any perceptual experience of the stimulus features except for a feeling that something appeared in the blind hemifield. Interestingly, in the lesioned left hemisphere, following stimulus presentation to the blind hemifield, we found an event-related potential (ERP) N1 component at a post-stimulus onset latency of 180-260 ms and a source generator in the left BA 19. In contrast, we did not find evidence of the early visual components C1 and P1 and of the later component P300. A positive component (P2a) was recorded between 250 and 320 ms after stimulus onset frontally in both hemispheres. Finally, in the time range 320-440 ms there was a negative peak in right posterior electrodes that was present only for the moving condition. In sum, there were two noteworthy results: Behaviorally, we found evidence of above chance unconscious (blindsight) orientation discrimination with moving but not static stimuli. Physiologically, in contrast to previous studies, we found reliable ERP components elicited by stimuli presented to the blind hemifield at various electrode locations and latencies that are likely to index either the perceptual report of the patient (N1 and P2a) or, the above-chance unconscious performance with moving stimuli as is the case of the posterior ERP negative component. This late component can be considered as the neural correlate of a kind of blindsight enabling feature discrimination only when stimuli are moving and that is subserved by the intact right hemisphere through interhemispheric transfer.

Gestalt Perceptual Organization of Visual Stimuli Captures Attention Automatically: Electrophysiological Evidence.

The visual system leverages organizational regularities of perceptual elements to create meaningful representations of the world. One clear example of such function, which has been formalized in the Gestalt psychology principles, is the perceptual grouping of simple visual elements (e.g., lines and arcs) into unitary objects (e.g., forms and shapes). The present study sought to characterize automatic attentional capture and related cognitive processing of Gestalt-like visual stimuli at the psychophysiological level by using event-related potentials (ERPs). We measured ERPs during a simple visual reaction time task with bilateral presentations of physically matched elements with or without a Gestalt organization. Results showed that Gestalt (vs. non-Gestalt) stimuli are characterized by a larger N2pc together with enhanced ERP amplitudes of non-lateralized components (N1, N2, P3) starting around 150 ms post-stimulus onset. Thus, we conclude that Gestalt stimuli capture attention automatically and entail characteristic psychophysiological signatures at both early and late processing stages. Highlights We studied the neural signatures of the automatic processes of visual attention elicited by Gestalt stimuli. We found that a reliable early correlate of attentional capture turned out to be the N2pc component. Perceptual and cognitive processing of Gestalt stimuli is associated with larger N1, N2, and P3.

The superior colliculus is sensitive to gestalt-like stimulus configuration in hemispherectomy patients.

Patients with cortical blindness following a lesion to the primary visual cortex (V1) may retain nonconscious visual abilities (blindsight). One intriguing, though largely unexplored question, is whether nonconscious vision in the blind hemifield of hemianopic patients can be sensitive to higher-order perceptual organization, and which V1-independent structure underlies such effect. To answer this question, we tested two rare hemianopic patients who had undergone hemispherectomy, and in whom the only post-chiasmatic visual structure left intact in the same side of the otherwise damaged hemisphere was the superior colliculus (SC). By using a variant of the redundant target effect (RTE), we presented single dots, patterns composed by the same dots organized in quadruple gestalt-like configurations, or patterns of four dots arranged in random configurations, either singly to the intact visual hemifield or bilaterally to both hemifields. As reported in a number of prior studies on blindsight patients, we found that bilateral stimulation yielded faster reaction times (RTs) than single stimulation of the intact field for all conditions (i.e., there was an implicit RTE). In addition to this effect, both patients showed a further speeding up of RTs when the gestalt-like, but not the random shape, quadruple patterns were projected to their blind hemifield during bilateral stimulation. Because other retino-recipient subcortical and cortical structures in the damaged hemisphere are absent, the SC on the lesioned side seems solely responsible for such an effect. The present results provide initial support to the notion that nonconscious vision might be sensitive to perceptual organization and stimulus configuration through the pivotal contribution of the SC, which can enhance the processing of gestalt-like or structured stimuli over meaningless or randomly assembled ones and translate them into facilitatory motor outputs.