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.

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.

Blindsight is sensitive to stimulus numerosity and configuration: evidence from the redundant signal effect.

One important, yet relatively unexplored question is whether blindsight, i.e., unconscious visually guided behavior in hemianopic patients, is endowed with basic perceptual properties such as detecting stimulus numerosity and overall configuration. Rather than a forced-choice procedure in which patients are supposed to guess about stimuli presented to the blind hemifield, we used a redundant signal effect paradigm, i.e., the speeding of simple reaction time (RT) when presenting multiple versus single similar stimuli. The presence of an effect of numerosity for the (unseen) stimuli presented to the blind field was indirectly assessed by measuring RT to bilateral versus unilateral stimuli presented to the intact hemifield. Chronic hemianopic patients were tested with unilateral or bilateral black dots, both of which could be either single or quadruple. The latter could either have a fixed spatial configuration representing a diamond or be randomly spatially assembled on every trial. Both configurations covered the same extent of visual field and had the overall same luminance. We found that a numerosity effect as a result of increasing the number of stimuli in the blind field was indeed present but only with the diamond configuration. This is a convincing evidence that this form of blindsight does not depend upon stimulus numerosity per se but is likely to be related to the presence of structured and memorized rather than meaningless changing stimuli.

Speeded manual responses to unseen visual stimuli in hemianopic patients: what kind of blindsight?

Blindsight, i.e., unconscious visually guided behaviour triggered by stimuli presented to a cortically blind hemifield, has been typically found either by using direct (forced choice) or indirect (interhemispheric) methods. However, one would expect to find blindsight also in fast responses to suddenly appearing visual stimuli, a reminiscence of evolutionary ancient adaptive behaviour. In this study we provide preliminary evidence of this form of blindsight by using a conservative method for assessing blindsight based on a comparison between the cumulative probability functions (CPFs) of simple reaction times to blind and intact field stimuli. Furthermore, in two patients with blindsight we provided evidence that their above-chance unconscious responses were likely to be triggered by the intact hemisphere.

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.

Differential impairment of interhemispheric transmission in bipolar disease.

There is abundant evidence that the cerebral white matter and in particular the corpus callosum show several structural abnormalities in both schizophrenia (SCZ) and bipolar disease (BD). However, which cognitive functions are impaired as a result of these anomalies is still unclear. Previous behavioural tests of interhemispheric crosstalk have shown a differential impairment in SCZ with interhemispheric transmission time, as tested with the Poffenberger paradigm, essentially normal but with an abnormally enhanced interhemispheric summation effect, as tested with the redundant signal effect. The present study was inspired by this discrepancy and by the more general question of a possible overlap between the pathophysiology of SCZ and BD. We tested both SCZ and BD patients in the Poffenberger paradigm and redundant signal effect and found a similar dissociation, namely a normal interhemispheric transfer time and an abnormal redundant signal effect. The only difference between the two groups was a selective slowing of speed of response of the dominant right hand in the SCZ group suggesting an impairment of left hemisphere functions. These results cast further light on the question of common and differential impairments of basic psychological functions in the two diseases.

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.

The effect of TMS on visual motion sensitivity: an increase in neural noise or a decrease in signal strength?

The underlying mechanisms of action of transcranial magnetic stimulation (TMS) are still a matter of debate. TMS may impair a subject's performance by increasing neural noise, suppressing the neural signal, or both. Here, we delivered a single pulse of TMS (spTMS) to V5/MT during a motion direction discrimination task while concurrently manipulating the level of noise in the motion stimulus. Our results indicate that spTMS essentially acts by suppressing the strength of the relevant visual signal. We suggest that TMS may induce a pattern of neural activity that complements the ongoing activation elicited by the sensory signal in a manner that partially impoverishes that signal.

Collicular vision guides nonconscious behavior.

Following destruction or deafferentation of primary visual cortex (area V1, striate cortex), clinical blindness ensues, but residual visual functions may, nevertheless, persist without perceptual consciousness (a condition termed blindsight). The study of patients with such lesions thus offers a unique opportunity to investigate what visual capacities are mediated by the extrastriate pathways that bypass V1. Here we provide evidence for a crucial role of the collicular-extrastriate pathway in nonconscious visuomotor integration by showing that, in the absence of V1, the superior colliculus (SC) is essential to translate visual signals that cannot be consciously perceived into motor outputs. We found that a gray stimulus presented in the blind field of a patient with unilateral V1 loss, although not consciously seen, can influence his behavioral and pupillary responses to consciously perceived stimuli in the intact field (implicit bilateral summation). Notably, this effect was accompanied by selective activations in the SC and in occipito-temporal extrastriate areas. However, when instead of gray stimuli we presented purple stimuli, which predominantly draw on S-cones and are thus invisible to the SC, any evidence of implicit visuomotor integration disappeared and activations in the SC dropped significantly. The present findings show that the SC acts as an interface between sensory and motor processing in the human brain, thereby providing a contribution to visually guided behavior that may remain functionally and anatomically segregated from the geniculo-striate pathway and entirely outside conscious visual experience.

The neural mechanisms of the effects of transcranial magnetic stimulation on perception.

Transcranial magnetic stimulation (TMS) is a technique used to study perceptual, motor, and cognitive functions in the human brain. Its effects have been likened to a "virtual brain lesion," but a direct test of this assumption is lacking. To verify this hypothesis, we measured psychophysically the interaction between the neural activity induced by a visual motion-direction discrimination task and that induced by TMS. The visual stimulus featured two elements: a visual signal (dots that moved coherently in one direction) and visual noise (dots that moved randomly in many directions). Three hypotheses were tested to explain the impairment in performance as a result of TMS: 1) a decrease in signal strength; 2) an induction of randomly distributed neural noise with an accompanying decrement in system sensitivity; and 3) a suppression of relevant information processing and addition of neural noise. We provide evidence in favor of the second hypothesis by showing that TMS basically acts by adding neural noise to the perceptual process.

Is simple reaction time affected by visual illusions?

A number of studies have shown that while perceptual judgment is deceived by pictorial illusions, grasping and other kinds of motor behaviour are not. This is in keeping with the existence of two different cortical systems: a ventral stream subserving vision-for-perception and a dorsal stream subserving vision-for-action. The former is sensitive to illusions, the latter is not. Given this dissociation of functions, one wonders whether simple visuomotor reaction time (RT) follows the ventral or the dorsal rule in perceiving illusory figures. Answering this question might contribute to a better understanding of the different functions of the two systems. We carried out two experiments, one with the Ponzo and the other with the Ebbinghaus-Titchener illusion and found that RT is sensitive to both illusions with faster responses to stimuli appearing illusorily bigger than the others. These results show that motor action is subserved by the ventral system when that action directly reports the presence or onset of a target rather than when that action requires a spatial adjustment that reflects the physical features of the target.

Laterality effects in schizophrenia and bipolar disorder.

There are numerous reports in the literature of lateralised structural cerebral abnormalities and alterations of the corpus callosum in the major psychoses. In the light of these findings the purpose of this study was to directly compare hemispheric differences and callosal interhemispheric transmission (IT) in schizophrenia and bipolar disorder. To do that we tested schizophrenic (SCZ), bipolar disorder (BD) patients and controls in a simple manual reaction time (RT) task with lateralised visual stimuli (Poffenberger paradigm) which enables one to test both laterality effects and IT time. We found an overall slowing of responses with the right hand in schizophrenics but not in bipolar patients, who, like controls, showed no hand differences. This selective slowing down of the right hand is likely to be related to abnormalities of intrahemispheric cortico-cortical connections in the left hemisphere. In contrast, IT time was similar in SCZ and BD patients and did not differ with respect to controls. Two are the novel findings of the present study: first both SZC and BD share a normal IT of visuomotor information despite the presence of callosal abnormalities. Second, an impairment of intrahemispheric left hemispheric processing is present only in SCZ patients. This represents a potentially important clue to a further understanding of the pathogenetic differences between the two major psychoses.

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.

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.

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.