EEG frequency-tagging demonstrates increased left hemispheric involvement and crossmodal plasticity for face processing in congenitally deaf signers.

In humans, face-processing relies on a network of brain regions predominantly in the right occipito-temporal cortex. We tested congenitally deaf (CD) signers and matched hearing controls (HC) to investigate the experience dependence of the cortical organization of face processing. Specifically, we used EEG frequency-tagging to evaluate: (1) Face-Object Categorization, (2) Emotional Facial-Expression Discrimination and (3) Individual Face Discrimination. The EEG was recorded to visual stimuli presented at a rate of 6 Hz, with oddball stimuli at a rate of 1.2 Hz. In all three experiments and in both groups, significant face discriminative responses were found. Face-Object categorization was associated to a relative increased involvement of the left hemisphere in CD individuals compared to HC individuals. A similar trend was observed for Emotional Facial-Expression discrimination but not for Individual Face Discrimination. Source reconstruction suggested a greater activation of the auditory cortices in the CD group for Individual Face Discrimination. These findings suggest that the experience dependence of the relative contribution of the two hemispheres as well as crossmodal plasticity vary with different aspects of face processing.

Neural correlates of semantic and syntactic processing in German Sign Language.

The study of deaf and hearing native users of signed languages can offer unique insights into how biological constraints and environmental input interact to shape the neural bases of language processing. Here, we use functional magnetic resonance imaging (fMRI) to address two questions: (1) Do semantic and syntactic processing in a signed language rely on anatomically and functionally distinct neural substrates as it has been shown for spoken languages? and (2) Does hearing status affect the neural correlates of these two types of linguistic processing? Deaf and hearing native signers performed a sentence judgement task on German Sign Language (Deutsche Gebärdensprache: DGS) sentences which were correct or contained either syntactic or semantic violations. We hypothesized that processing of semantic and syntactic violations in DGS relies on distinct neural substrates as it has been shown for spoken languages. Moreover, we hypothesized that effects of hearing status are observed within auditory regions, as deaf native signers have been shown to activate auditory areas to a greater extent than hearing native signers when processing a signed language. Semantic processing activated low-level visual areas and the left inferior frontal gyrus (IFG), suggesting both modality-dependent and independent processing mechanisms. Syntactic processing elicited increased activation in the right supramarginal gyrus (SMG). Moreover, psychophysiological interaction (PPI) analyses revealed a cluster in left middle occipital regions showing increased functional coupling with the right SMG during syntactic relative to semantic processing, possibly indicating spatial processing mechanisms that are specific to signed syntax. Effects of hearing status were observed in the right superior temporal cortex (STC): deaf but not hearing native signers showed greater activation for semantic violations than for syntactic violations in this region. Taken together, the present findings suggest that the neural correlates of language processing are partly determined by biological constraints, but that they may additionally be influenced by the unique processing demands of the language modality and different sensory experiences.

Functional Preference for Object Sounds and Voices in the Brain of Early Blind and Sighted Individuals.

Sounds activate occipital regions in early blind individuals. However, how different sound categories map onto specific regions of the occipital cortex remains a matter of debate. We used fMRI to characterize brain responses of early blind and sighted individuals to familiar object sounds, human voices, and their respective low-level control sounds. In addition, sighted participants were tested while viewing pictures of faces, objects, and phase-scrambled control pictures. In both early blind and sighted, a double dissociation was evidenced in bilateral auditory cortices between responses to voices and object sounds: Voices elicited categorical responses in bilateral superior temporal sulci, whereas object sounds elicited categorical responses along the lateral fissure bilaterally, including the primary auditory cortex and planum temporale. Outside the auditory regions, object sounds also elicited categorical responses in the left lateral and in the ventral occipitotemporal regions in both groups. These regions also showed response preference for images of objects in the sighted group, thus suggesting a functional specialization that is independent of sensory input and visual experience. Between-group comparisons revealed that, only in the blind group, categorical responses to object sounds extended more posteriorly into the occipital cortex. Functional connectivity analyses evidenced a selective increase in the functional coupling between these reorganized regions and regions of the ventral occipitotemporal cortex in the blind group. In contrast, vocal sounds did not elicit preferential responses in the occipital cortex in either group. Nevertheless, enhanced voice-selective connectivity between the left temporal voice area and the right fusiform gyrus were found in the blind group. Altogether, these findings suggest that, in the absence of developmental vision, separate auditory categories are not equipotent in driving selective auditory recruitment of occipitotemporal regions and highlight the presence of domain-selective constraints on the expression of cross-modal plasticity.

Auditory motion in the sighted and blind: Early visual deprivation triggers a large-scale imbalance between auditory and "visual" brain regions.

How early blindness reorganizes the brain circuitry that supports auditory motion processing remains controversial. We used fMRI to characterize brain responses to in-depth, laterally moving, and static sounds in early blind and sighted individuals. Whole-brain univariate analyses revealed that the right posterior middle temporal gyrus and superior occipital gyrus selectively responded to both in-depth and laterally moving sounds only in the blind. These regions overlapped with regions selective for visual motion (hMT+/V5 and V3A) that were independently localized in the sighted. In the early blind, the right planum temporale showed enhanced functional connectivity with right occipito-temporal regions during auditory motion processing and a concomitant reduced functional connectivity with parietal and frontal regions. Whole-brain searchlight multivariate analyses demonstrated higher auditory motion decoding in the right posterior middle temporal gyrus in the blind compared to the sighted, while decoding accuracy was enhanced in the auditory cortex bilaterally in the sighted compared to the blind. Analyses targeting individually defined visual area hMT+/V5 however indicated that auditory motion information could be reliably decoded within this area even in the sighted group. Taken together, the present findings demonstrate that early visual deprivation triggers a large-scale imbalance between auditory and "visual" brain regions that typically support the processing of motion information.

Tracking the evolution of crossmodal plasticity and visual functions before and after sight restoration.

Visual deprivation leads to massive reorganization in both the structure and function of the occipital cortex, raising crucial challenges for sight restoration. We tracked the behavioral, structural, and neurofunctional changes occurring in an early and severely visually impaired patient before and 1.5 and 7 mo after sight restoration with magnetic resonance imaging. Robust presurgical auditory responses were found in occipital cortex despite residual preoperative vision. In primary visual cortex, crossmodal auditory responses overlapped with visual responses and remained elevated even 7 mo after surgery. However, these crossmodal responses decreased in extrastriate occipital regions after surgery, together with improved behavioral vision and with increases in both gray matter density and neural activation in low-level visual regions. Selective responses in high-level visual regions involved in motion and face processing were observable even before surgery and did not evolve after surgery. Taken together, these findings demonstrate that structural and functional reorganization of occipital regions are present in an individual with a long-standing history of severe visual impairment and that such reorganizations can be partially reversed by visual restoration in adulthood.

Impact of blindness onset on the functional organization and the connectivity of the occipital cortex.

Contrasting the impact of congenital versus late-onset acquired blindness provides a unique model to probe how experience at different developmental periods shapes the functional organization of the occipital cortex. We used functional magnetic resonance imaging to characterize brain activations of congenitally blind, late-onset blind and two groups of sighted control individuals while they processed either the pitch or the spatial attributes of sounds. Whereas both blind groups recruited occipital regions for sound processing, activity in bilateral cuneus was only apparent in the congenitally blind, highlighting the existence of region-specific critical periods for crossmodal plasticity. Most importantly, the preferential activation of the right dorsal stream (middle occipital gyrus and cuneus) for the spatial processing of sounds was only observed in the congenitally blind. This demonstrates that vision has to be lost during an early sensitive period in order to transfer its functional specialization for space processing toward a non-visual modality. We then used a combination of dynamic causal modelling with Bayesian model selection to demonstrate that auditory-driven activity in primary visual cortex is better explained by direct connections with primary auditory cortex in the congenitally blind whereas it relies more on feedback inputs from parietal regions in the late-onset blind group. Taken together, these results demonstrate the crucial role of the developmental period of visual deprivation in (re)shaping the functional architecture and the connectivity of the occipital cortex. Such findings are clinically important now that a growing number of medical interventions may restore vision after a period of visual deprivation.

A common right fronto-parietal network for numerosity and duration processing: an fMRI study.

Numerosity and duration processing have been modeled by a functional mechanism taking the form of an accumulator working under two different operative modes. Separate investigations of their cerebral substrates have revealed partly similar patterns of activation, mainly in parietal and frontal areas. However, the precise cerebral implementation of the accumulator model within these areas has not yet been directly assessed. In this study, we asked participants to categorize the numerosity of flashed dot sequences or the duration of single dot displays, and we used functional magnetic resonance imaging (fMRI) to examine the common neural correlates of these processes. The results reveal a large right-lateralized fronto-parietal network, including the intraparietal sulcus (IPS) and areas in the precentral, middle and superior frontal gyri, which is activated by both numerosity and duration processing. Complementary psychophysiological interaction (PPI) analyses show a functional connectivity between the right IPS and the frontal areas in both tasks, whereas the right IPS was functionally connected to the left IPS and the right precentral area in the numerosity categorization task only. We propose that the right IPS underlies a common magnitude processing system for both numerosity and duration, possibly corresponding to the encoding and accumulation stages of the accumulator model, whereas the frontal areas are involved in subsequent working-memory storage and decision-making processes.

Plasticity of the dorsal "spatial" stream in visually deprived individuals.

Studies on visually deprived individuals provide one of the most striking demonstrations that the brain is highly plastic and is able to rewire as a function of the sensory input it receives from the environment. In the current paper, we focus on spatial abilities that are typically related to the dorsal visual pathway (i.e., spatial/motion processing). Bringing together evidence from cataract-reversal individuals, early- and late-blind individuals and sight-recovery cases of long-standing blindness, we suggest that the dorsal "spatial" pathway is mostly plastic early in life and is then more resistant to subsequent experience once it is set, highlighting some limits of neuroplasticity.

Extensive visual training in adulthood significantly reduces the face inversion effect.

The poorer recognition performance for inverted as compared to upright faces is one of the most well-known and robust behavioral effects observed in the field of face perception. Here we investigated whether extensive training at individualizing a large set of inverted faces in adulthood could significantly reduce this inversion effect for novel faces. This issue is important because inverted faces are as complex as upright faces but they are not visually experienced during development. Moreover, inverted faces violate the biological constraints, present at birth, for preferential looking (i.e., a larger number of elements in the top part than the bottom part of the stimulus). Eight adult observers were trained for 2 weeks (16 hr) to individualize 30 inverted face identities presented under different depth-rotated views. Following training, all participants showed a significant reduction of their inversion effect for novel face identities presented in a challenging four-alternatives delayed matching task. This reduction of the face inversion effect was observed in comparison to the magnitude of the same observers' effect before training, and to the magnitude of the face inversion effect of a group of untrained participants. These observations indicate that extensive training in adulthood can lead to a significant reduction of the inversion effect that generalizes to novel faces, suggesting a larger degree of flexibility of the adult face processing system than previously thought.

Functional selectivity in sensory-deprived cortices.

In a recent study, Lomber, Meredith, and Kral (2010) investigated crossmodal reorganization in congenitally deaf cats. They demonstrated that specific regions of the auditory cortex are responsible for distinct supranormal visual performances following early auditory deprivation. These exciting results are considered in light of recently increasing research suggesting that crossmodal plasticity associated with early sensory deprivation follows organizational principles that maintain the functional specialization of the colonized brain regions.

Steady state evoked potentials indicate changes in nonlinear neural mechanisms of vision in sight recovery individuals.

Humans with a transient phase of congenital pattern vision deprivation have been observed to feature prevailing deficits, particularly in higher order visual functions. However, the neural correlates of these prevalent visual impairments remain unclear. To probe different visual processing stages, we measured steady state visual evoked potentials (SSVEPs) generated by luminance flicker stimuli at 6.1 Hz, with superimposed horizontal periodic motion at 2.1 Hz or 2.4 Hz. SSVEP responses at the fundamental and second harmonic of luminance flicker frequency, and at their intermodulation frequencies with motion information, were analyzed. Three groups were tested: (1) 15 individuals who had suffered a lack of pattern vision from birth due to the presence of bilateral total congenital cataracts (CC group), which were surgically removed between 4 months and 22 years of age, (2) 13 individuals with reversed developmental i.e., later developing cataracts (DC group), and (3) normally sighted control participants (SC group; n = 13) matched in age and sex to the CC individuals. SSVEPs at the second harmonic frequency (i.e., 12.2 Hz) and at the intermodulation frequencies (8.2 Hz, and 8.5 Hz) were attenuated in the CC group. In contrast, fundamental frequency responses (i.e., at 6.1 Hz) were not significantly altered in the CC group compared to the control groups (SC and DC groups). Based on previous evidence on the role of striate vs. extrastriate generators of fundamental vs. second harmonics of SSVEPs, these results provide evidence for a stronger experience dependence of extrastriate than striate cortical processing, and furthermore, suggest a sensitive period for the development of putative nonlinear neural mechanisms hypothesized to mediate visual feature binding.

Mode-dependent and mode-independent representations of numerosity in the right intraparietal sulcus.

In humans, areas around the intraparietal sulcus (IPS) have been found to play a crucial role in coding nonsymbolic numerosities (i.e., number of elements in a collection). In the parietal cortex of monkeys, some populations of neurons were found to respond selectively to sequentially- or simultaneously-presented numerosities, whereas other populations showed similar activation in both modes of presentation. However, whether such mode-dependent and -independent representations of numerosity also exist in humans is still unknown. Here, we used fMRI to identify the areas involved in numerosity processing while participants classified linear arrays of dots (simultaneous stimuli) or flashed dot sequences (sequential stimuli). The processing of simultaneous numerosities induced activations bilaterally in several areas of the IPS, whereas activations during the processing of sequential numerosities were restricted to the right hemisphere. A conjunction analysis showed that only the right IPS and precentral gyrus showed overlapping activations during the judgement of sequential and simultaneous stimuli. Voxelwise correlations confirmed the highly similar pattern of activation found in these regions during both tasks. This pattern was weaker or absent in mode-dependent regions, like the right inferior frontal cortex and the lateral occipital complex. Finally, a close look at the right IPS revealed an anterior-to-posterior gradient of activation with selective activation for sequential and simultaneous stimuli in the anterior and posterior areas, respectively, and overlapping activations in-between. This study provides the first direct evidence that, in humans, the right IPS contains both mode-dependent and mode-independent representations of numerosity.

Risk of herpes zoster in the Japanese population with immunocompromising and chronic disease conditions: Results from a claims database cohort study, from 2005 to 2014.

Older adults, women and patients with immunocompromised (IC) or chronic medical conditions have a higher incidence of herpes zoster (HZ) and are at higher risk of developing HZ-associated complications such as postherpetic neuralgia. The incidence rates of HZ in various IC and chronic conditions have been previously reported in a retrospective cohort study using claims data from Japanese adults. Here, we report further analyses from this cohort using univariate and multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) associated with different IC and chronic conditions. After adjusting for multiple covariates (age, sex and other coexisting medical conditions), the risk of HZ was higher in women (HR, 1.14 [95% CI, 1.11-1.17]), irrespective of age and increased with increasing age, being substantially higher in patients aged 65 years or older (HR, 3.28 [95% CI, 3.07-3.49]) when compared with those aged 18-29 years. The highest HRs were observed for the following specific IC conditions; hematopoietic stem cell transplant recipients (HR, 9.85 [95% CI, 6.80-14.28]), hematological malignancy (HR, 3.22 [95% CI, 2.54-4.09]), systemic lupus erythematosus (HR, 2.46 [95% CI, 1.45-4.15]) and inflammatory bowel disease (HR, 1.59 [95% CI, 1.14-2.21]). For most other IC and chronic medical conditions, a higher risk was also apparent though of a smaller magnitude (HRs ranging from 1.2 to <1.5). These results corroborate our previous findings and demonstrate an increased risk of HZ associated with different IC and chronic conditions.

A Brief Period of Postnatal Visual Deprivation Alters the Balance between Auditory and Visual Attention.

Is a short and transient period of visual deprivation early in life sufficient to induce lifelong changes in how we attend to, and integrate, simple visual and auditory information [1, 2]? This question is of crucial importance given the recent demonstration in both animals and humans that a period of blindness early in life permanently affects the brain networks dedicated to visual, auditory, and multisensory processing [1-16]. To address this issue, we compared a group of adults who had been treated for congenital bilateral cataracts during early infancy with a group of normally sighted controls on a task requiring simple detection of lateralized visual and auditory targets, presented alone or in combination. Redundancy gains obtained from the audiovisual conditions were similar between groups and surpassed the reaction time distribution predicted by Miller's race model. However, in comparison to controls, cataract-reversal patients were faster at processing simple auditory targets and showed differences in how they shifted attention across modalities. Specifically, they were faster at switching attention from visual to auditory inputs than in the reverse situation, while an opposite pattern was observed for controls. Overall, these results reveal that the absence of visual input during the first months of life does not prevent the development of audiovisual integration but enhances the salience of simple auditory inputs, leading to a different crossmodal distribution of attentional resources between auditory and visual stimuli.

Long-Lasting Crossmodal Cortical Reorganization Triggered by Brief Postnatal Visual Deprivation.

Animal and human studies have demonstrated that transient visual deprivation early in life, even for a very short period, permanently alters the response properties of neurons in the visual cortex and leads to corresponding behavioral visual deficits. While it is acknowledged that early-onset and longstanding blindness leads the occipital cortex to respond to non-visual stimulation, it remains unknown whether a short and transient period of postnatal visual deprivation is sufficient to trigger crossmodal reorganization that persists after years of visual experience. In the present study, we characterized brain responses to auditory stimuli in 11 adults who had been deprived of all patterned vision at birth by congenital cataracts in both eyes until they were treated at 9 to 238 days of age. When compared to controls with typical visual experience, the cataract-reversal group showed enhanced auditory-driven activity in focal visual regions. A combination of dynamic causal modeling with Bayesian model selection indicated that this auditory-driven activity in the occipital cortex was better explained by direct cortico-cortical connections with the primary auditory cortex than by subcortical connections. Thus, a short and transient period of visual deprivation early in life leads to enduring large-scale crossmodal reorganization of the brain circuitry typically dedicated to vision.

Embodied numbers: the role of vision in the development of number-space interactions.

The strong association between numbers and space is found in the well-documented SNARC effect (Spatial Numerical Association of Response Codes), where responses on small/large numbers are faster in the left/right side of space, respectively. However, little is known about the developmental process through which numbers are mapped onto external physical space. Here we show that early blind individuals, but not late blind or sighted, demonstrate a reversed SNARC effect when performing a numerical comparison task with hands crossed over the body midline. Importantly, this reversed SNARC effect was not observed in any group of participants in a control parity judgment task. The present study therefore demonstrates that early visual experience drives the development of an external coordinate system for the visuo-spatial representation of numbers and further supports the idea that different types of spatial information are engaged in specific numerical tasks.

Attentional shifts induced by uninformative number symbols modulate neural activity in human occipital cortex.

Number processing interacts with space encoding in a wide variety of experimental paradigms. Most intriguingly, the passive viewing of uninformative number symbols can shift visuo-spatial attention to different target locations according to the number magnitude, i.e., small/large numbers facilitate processing of left/right targets, respectively. The brain architecture dedicated to these attention shifts associated with numbers remains unknown. Evoked potential recordings indicate that both early and late stages are involved in this spatio-numerical interaction, but the neuro-functional anatomy needs to be specified. Here we use, for the first time, functional magnetic resonance imaging (fMRI) to investigate attentional orienting following uninformative Arabic digits. We show that BOLD response in occipital visual regions is modulated by the congruency between digit magnitude (small/large) and target side (left/right). Additionally, we report higher BOLD responses following large (8, 9) compared to small (1, 2) digits in two bilateral parietal regions, yielding a significant effect of digit magnitude. We propose and discuss the view that encoding of semantic representations related to number symbols in parietal cortex leads to shifts in visuo-spatial attention and enhances visual processing in the occipital cortex according to number-space congruency rules.