Resting-state functional connectivity in deaf and hearing individuals and its link to executive processing.

Sensory experience shapes brain structure and function, and it is likely to influence the organisation of functional networks of the brain, including those involved in cognitive processing. Here we investigated the influence of early deafness on the organisation of resting-state networks of the brain and its relation to executive processing. We compared resting-state connectivity between deaf and hearing individuals across 18 functional networks and 400 ROIs. Our results showed significant group differences in connectivity between seeds of the auditory network and most large-scale networks of the brain, in particular the somatomotor and salience/ventral attention networks. When we investigated group differences in resting-state fMRI and their link to behavioural performance in executive function tasks (working memory, inhibition and switching), differences between groups were found in the connectivity of association networks of the brain, such as the salience/ventral attention and default-mode networks. These findings indicate that sensory experience influences not only the organisation of sensory networks, but that it also has a measurable impact on the organisation of association networks supporting cognitive processing. Overall, our findings suggest that different developmental pathways and functional organisation can support executive processing in the adult brain.

Sensory experience modulates the reorganization of auditory regions for executive processing.

Crossmodal plasticity refers to the reorganization of sensory cortices in the absence of their typical main sensory input. Understanding this phenomenon provides insights into brain function and its potential for change and enhancement. Using functional MRI, we investigated how early deafness influences crossmodal plasticity and the organization of executive functions in the adult human brain. Deaf (n = 25; age: mean = 41.68, range = 19-66, SD = 14.38; 16 female, 9 male) and hearing (n = 20; age: mean = 37.50, range = 18-66, SD = 16.85; 15 female, 5 male) participants performed four visual tasks tapping into different components of executive processing: task switching, working memory, planning and inhibition. Our results show that deaf individuals specifically recruit 'auditory' regions during task switching. Neural activity in superior temporal regions, most significantly in the right hemisphere, are good predictors of behavioural performance during task switching in the group of deaf individuals, highlighting the functional relevance of the observed cortical reorganization. Our results show executive processing in typically sensory regions, suggesting that the development and ultimate role of brain regions are influenced by perceptual environmental experience.

Crossmodal reorganisation in deafness: Mechanisms for functional preservation and functional change.

The study of deafness and blindness has contributed unique knowledge to our understanding of the brain, showing that environmental experience critically shapes neural structure and function. Nevertheless, the most prevalent theories of crossmodal plasticity propose opposing views about the function of reorganised cortical regions. Some theories agree on functional preservation, where in the absence of early sensory stimulation, cortical regions respond to a different sensory modality, but perform the same function. Others propose that the absence of sensory stimulation from birth results in cortical regions changing their "typical" sensory processing function to higher-order cognition. Both deafness and blindness have provided vast evidence in support of each of these theories. Here we use examples from the study of deafness to explore organisational mechanisms that would allow functional preservation and functional change to co-exist either in the same or adjacent regions. We provide a set of predictions and testable hypotheses that support each of these accounts, and lay out some steps that could move us towards more specific theories of cortical reorganisation.

The effect of dopamine on the comprehension of spectrally-shifted noise-vocoded speech: a pilot study.

Objectives: Cochlear implantation has proven beneficial in restoring hearing. However, success is variable, and there is a need for a simple post-implantation therapy that could significantly increase implantation success. Dopamine has a general role in learning and in assigning value to environmental stimuli. We tested the effect of dopamine in the comprehension of spectrally-shifted noise-vocoded (SSNV) speech, which simulates, in hearing individuals, the signal delivered by a cochlear implant (CI).Design and study sample: Thirty-five participants (age = 38.0 ± 10.1 SD) recruited from the general population were divided into three groups. We tested SSNV speech comprehension in two experimental sessions. In one session, a metabolic precursor of dopamine (L-DOPA) was administered to participants in two of the groups; a placebo was administered in the other session.Results: A single dose of L-DOPA interacted with training to improve perception of SSNV speech, but did not significantly accelerate learning.Conclusions: These findings are a first step in exploring the use of dopamine to enhance speech understanding in CI patients. Replications of these results using SSNV in individuals with normal hearing, and also in CI users, are needed to determine whether these effects can translate into benefits in everyday language comprehension.

Neural Networks Supporting Phoneme Monitoring Are Modulated by Phonology but Not Lexicality or Iconicity: Evidence From British and Swedish Sign Language.

Sign languages are natural languages in the visual domain. Because they lack a written form, they provide a sharper tool than spoken languages for investigating lexicality effects which may be confounded by orthographic processing. In a previous study, we showed that the neural networks supporting phoneme monitoring in deaf British Sign Language (BSL) users are modulated by phonology but not lexicality or iconicity. In the present study, we investigated whether this pattern generalizes to deaf Swedish Sign Language (SSL) users. British and SSLs have a largely overlapping phoneme inventory but are mutually unintelligible because lexical overlap is small. This is important because it means that even when signs lexicalized in BSL are unintelligible to users of SSL they are usually still phonologically acceptable. During fMRI scanning, deaf users of the two different sign languages monitored signs that were lexicalized in either one or both of those languages for phonologically contrastive elements. Neural activation patterns relating to different linguistic levels of processing were similar across SLs; in particular, we found no effect of lexicality, supporting the notion that apparent lexicality effects on sublexical processing of speech may be driven by orthographic strategies. As expected, we found an effect of phonology but not iconicity. Further, there was a difference in neural activation between the two groups in a motion-processing region of the left occipital cortex, possibly driven by cultural differences, such as education. Importantly, this difference was not modulated by the linguistic characteristics of the material, underscoring the robustness of the neural activation patterns relating to different linguistic levels of processing.

The Organization of Working Memory Networks is Shaped by Early Sensory Experience.

Early deafness results in crossmodal reorganization of the superior temporal cortex (STC). Here, we investigated the effect of deafness on cognitive processing. Specifically, we studied the reorganization, due to deafness and sign language (SL) knowledge, of linguistic and nonlinguistic visual working memory (WM). We conducted an fMRI experiment in groups that differed in their hearing status and SL knowledge: deaf native signers, and hearing native signers, hearing nonsigners. Participants performed a 2-back WM task and a control task. Stimuli were signs from British Sign Language (BSL) or moving nonsense objects in the form of point-light displays. We found characteristic WM activations in fronto-parietal regions in all groups. However, deaf participants also recruited bilateral posterior STC during the WM task, independently of the linguistic content of the stimuli, and showed less activation in fronto-parietal regions. Resting-state connectivity analysis showed increased connectivity between frontal regions and STC in deaf compared to hearing individuals. WM for signs did not elicit differential activations, suggesting that SL WM does not rely on modality-specific linguistic processing. These findings suggest that WM networks are reorganized due to early deafness, and that the organization of cognitive networks is shaped by the nature of the sensory inputs available during development.

Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions.

Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss.

Preexisting semantic representation improves working memory performance in the visuospatial domain.

Working memory (WM) for spoken language improves when the to-be-remembered items correspond to preexisting representations in long-term memory. We investigated whether this effect generalizes to the visuospatial domain by administering a visual n-back WM task to deaf signers and hearing signers, as well as to hearing nonsigners. Four different kinds of stimuli were presented: British Sign Language (BSL; familiar to the signers), Swedish Sign Language (SSL; unfamiliar), nonsigns, and nonlinguistic manual actions. The hearing signers performed better with BSL than with SSL, demonstrating a facilitatory effect of preexisting semantic representation. The deaf signers also performed better with BSL than with SSL, but only when WM load was high. No effect of preexisting phonological representation was detected. The deaf signers performed better than the hearing nonsigners with all sign-based materials, but this effect did not generalize to nonlinguistic manual actions. We argue that deaf signers, who are highly reliant on visual information for communication, develop expertise in processing sign-based items, even when those items do not have preexisting semantic or phonological representations. Preexisting semantic representation, however, enhances the quality of the gesture-based representations temporarily maintained in WM by this group, thereby releasing WM resources to deal with increased load. Hearing signers, on the other hand, may make strategic use of their speech-based representations for mnemonic purposes. The overall pattern of results is in line with flexible-resource models of WM.

Monitoring Different Phonological Parameters of Sign Language Engages the Same Cortical Language Network but Distinctive Perceptual Ones.

The study of signed languages allows the dissociation of sensorimotor and cognitive neural components of the language signal. Here we investigated the neurocognitive processes underlying the monitoring of two phonological parameters of sign languages: handshape and location. Our goal was to determine if brain regions processing sensorimotor characteristics of different phonological parameters of sign languages were also involved in phonological processing, with their activity being modulated by the linguistic content of manual actions. We conducted an fMRI experiment using manual actions varying in phonological structure and semantics: (1) signs of a familiar sign language (British Sign Language), (2) signs of an unfamiliar sign language (Swedish Sign Language), and (3) invented nonsigns that violate the phonological rules of British Sign Language and Swedish Sign Language or consist of nonoccurring combinations of phonological parameters. Three groups of participants were tested: deaf native signers, deaf nonsigners, and hearing nonsigners. Results show that the linguistic processing of different phonological parameters of sign language is independent of the sensorimotor characteristics of the language signal. Handshape and location were processed by different perceptual and task-related brain networks but recruited the same language areas. The semantic content of the stimuli did not influence this process, but phonological structure did, with nonsigns being associated with longer RTs and stronger activations in an action observation network in all participants and in the supramarginal gyrus exclusively in deaf signers. These results suggest higher processing demands for stimuli that contravene the phonological rules of a signed language, independently of previous knowledge of signed languages. We suggest that the phonological characteristics of a language may arise as a consequence of more efficient neural processing for its perception and production.

Differential activity in Heschl's gyrus between deaf and hearing individuals is due to auditory deprivation rather than language modality.

Sensory cortices undergo crossmodal reorganisation as a consequence of sensory deprivation. Congenital deafness in humans represents a particular case with respect to other types of sensory deprivation, because cortical reorganisation is not only a consequence of auditory deprivation, but also of language-driven mechanisms. Visual crossmodal plasticity has been found in secondary auditory cortices of deaf individuals, but it is still unclear if reorganisation also takes place in primary auditory areas, and how this relates to language modality and auditory deprivation. Here, we dissociated the effects of language modality and auditory deprivation on crossmodal plasticity in Heschl's gyrus as a whole, and in cytoarchitectonic region Te1.0 (likely to contain the core auditory cortex). Using fMRI, we measured the BOLD response to viewing sign language in congenitally or early deaf individuals with and without sign language knowledge, and in hearing controls. Results show that differences between hearing and deaf individuals are due to a reduction in activation caused by visual stimulation in the hearing group, which is more significant in Te1.0 than in Heschl's gyrus as a whole. Furthermore, differences between deaf and hearing groups are due to auditory deprivation, and there is no evidence that the modality of language used by deaf individuals contributes to crossmodal plasticity in Heschl's gyrus.

Dissociating cognitive and sensory neural plasticity in human superior temporal cortex.

Disentangling the effects of sensory and cognitive factors on neural reorganization is fundamental for establishing the relationship between plasticity and functional specialization. Auditory deprivation in humans provides a unique insight into this problem, because the origin of the anatomical and functional changes observed in deaf individuals is not only sensory, but also cognitive, owing to the implementation of visual communication strategies such as sign language and speechreading. Here, we describe a functional magnetic resonance imaging study of individuals with different auditory deprivation and sign language experience. We find that sensory and cognitive experience cause plasticity in anatomically and functionally distinguishable substrates. This suggests that after plastic reorganization, cortical regions adapt to process a different type of input signal, but preserve the nature of the computation they perform, both at a sensory and cognitive level.

Similar digit-based working memory in deaf signers and hearing non-signers despite digit span differences.

Similar working memory (WM) for lexical items has been demonstrated for signers and non-signers while short-term memory (STM) is regularly poorer in deaf than hearing individuals. In the present study, we investigated digit-based WM and STM in Swedish and British deaf signers and hearing non-signers. To maintain good experimental control we used printed stimuli throughout and held response mode constant across groups. We showed that deaf signers have similar digit-based WM performance, despite shorter digit spans, compared to well-matched hearing non-signers. We found no difference between signers and non-signers on STM span for letters chosen to minimize phonological similarity or in the effects of recall direction. This set of findings indicates that similar WM for signers and non-signers can be generalized from lexical items to digits and suggests that poorer STM in deaf signers compared to hearing non-signers may be due to differences in phonological similarity across the language modalities of sign and speech.

Human V6: functional characterisation and localisation.

Human visual area V6, in the parieto-occipital sulcus, is thought to have an important role in the extraction of optic flow for the monitoring and guidance of self-motion (egomotion) because it responds differentially to egomotion-compatible optic flow when compared to: (a) coherent but egomotion-incompatible flow (Cardin & Smith, 2010), and (b) incoherent motion (Pitzalis et al., 2010). It is not clear, however, whether V6 responds more strongly to egomotion-incompatible global motion than to incoherent motion. This is relevant not only for determining the functional properties of V6, but also in order to choose optimal stimuli for localising V6 accurately with fMRI. Localisation with retinotopic mapping is difficult and there is a need for a simple, reliable method. We conducted an event-related 3T fMRI experiment in which participants viewed a display of dots which either: a) followed a time-varying optic flow trajectory in a single, egomotion-compatible (EC) display; b) formed an egomotion-incompatible (EI) 3 × 3 array of optic flow patches; or c) moved randomly (RM). Results from V6 show an ordering of response magnitudes: EC > EI > RM. Neighbouring areas V3A and V7 responded more strongly to EC than to RM, but about equally to EC and EI. Our results suggest that although V6 may have a general role in the extraction of global motion, in clear contrast to neighbouring motion areas it is especially concerned with encoding EC stimuli. They suggest two strategies for localising V6: (1) contrasting EC and EI; or (2) contrasting EC and RM, which is more sensitive but carries a risk of including voxels from neighbouring regions that also show a EC > RM preference.

Adaptation to heading direction dissociates the roles of human MST and V6 in the processing of optic flow.

The extraction of optic flow cues is fundamental for successful locomotion. During forward motion, the focus of expansion (FoE), in conjunction with knowledge of eye position, indicates the direction in which the individual is heading. Therefore, it is expected that cortical brain regions that are involved in the estimation of heading will be sensitive to this feature. To characterize cortical sensitivity to the location of the FoE or, more generally, the center of flow (CoF) during visually simulated self-motion, we carried out a functional MRI (fMRI) adaptation experiment in several human visual cortical areas that are thought to be sensitive to optic flow parameters, namely, V3A, V6, MT/V5, and MST. In each trial, two optic flow patterns were sequentially presented, with the CoF located in either the same or different positions. With an adaptation design, an area sensitive to heading direction should respond more strongly to a pair of stimuli with different CoFs than to stimuli with the same CoF. Our results show such release from adaptation in areas MT/V5 and MST, and to a lesser extent V3A, suggesting the involvement of these areas in the processing of heading direction. The effect could not be explained either by differences in local motion or by attention capture. It was not observed to a significant extent in area V6 or in control area V1. The different patterns of responses observed in MST and V6, areas that are both involved in the processing of egomotion in macaques and humans, suggest distinct roles in the processing of visual cues for self-motion.

Sensitivity of human visual cortical area V6 to stereoscopic depth gradients associated with self-motion.

The principal visual cue to self-motion (egomotion) is optic flow, which is specified in terms of local 2D velocities in the retinal image without reference to depth cues. However, in general, points near the center of expansion of natural flow fields are distant, whereas those in the periphery are closer, creating gradients of horizontal binocular disparity. To assess whether the brain combines disparity gradients with optic flow when encoding egomotion, stereoscopic gradients were applied to expanding dot patterns presented to observers during functional MRI scanning. The gradients were radially symmetrical, disparity changing as a function of eccentricity. The depth cues were either consistent with egomotion (peripheral dots perceived as near and central dots perceived as far) or inconsistent (the reverse gradient, central dots near, peripheral dots far). The BOLD activity generated by these stimuli was compared in a range of predefined visual regions in 13 participants with good stereoacuity. Visual area V6, in the parieto-occipital sulcus, showed a unique pattern of results, responding well to all optic flow patterns but much more strongly when they were paired with consistent rather than inconsistent or zero-disparity gradients. Of the other areas examined, a region of the precuneus and parietoinsular vestibular cortex also differentiate between consistent and inconsistent gradients, but with weak or suppressive responses. V3A, V7, MT, and ventral intraparietal area responded more strongly in the presence of a depth gradient but were indifferent to its depth-flow congruence. The results suggest that depth and flow cues are integrated in V6 to improve estimation of egomotion.

Top-down modulations in the visual form pathway revealed with dynamic causal modeling.

Perception entails interactions between activated brain visual areas and the records of previous sensations, allowing for processes like figure-ground segregation and object recognition. The aim of this study was to characterize top-down effects that originate in the visual cortex and that are involved in the generation and perception of form. We performed a functional magnetic resonance imaging experiment, where subjects viewed 3 groups of stimuli comprising oriented lines with different levels of recognizable high-order structure (none, collinearity, and meaning). Our results showed that recognizable stimuli cause larger activations in anterior visual and frontal areas. In contrast, when stimuli are random or unrecognizable, activations are greater in posterior visual areas, following a hierarchical organization where areas V1/V2 were less active with "collinearity" and the middle occipital cortex was less active with "meaning." An effective connectivity analysis using dynamic causal modeling showed that high-order visual form engages higher visual areas that generate top-down signals, from multiple levels of the visual hierarchy. These results are consistent with a model in which if a stimulus has recognizable attributes, such as collinearity and meaning, the areas specialized for processing these attributes send top-down messages to the lower levels to facilitate more efficient encoding of visual form.

Sensitivity of human visual and vestibular cortical regions to egomotion-compatible visual stimulation.

The analysis and representation of visual cues to self-motion (egomotion) is primarily associated with cortical areas MST, VIP, and (recently) cingulate sulcus visual area (CSv). Various other areas, including visual areas V6 and V6A, and vestibular areas parietoinsular vestibular cortex (PIVC), putative area 2v (p2v), and 3aNv, are also potentially suited to processing egomotion (in some cases based on multisensory cues), but it is not known whether they are in fact involved in this process. In a functional magnetic resonance imaging (fMRI) experiment, we presented human participants with 2 types of random dot kinematograms. Both contained coherent motion but one simulated egomotion while the other did not. An area in the parieto-occipital sulcus that may correspond to V6, PIVC, and p2v were all differentially responsive to egomotion-compatible visual stimuli, suggesting that they may be involved in encoding egomotion. More generally, we show that the use of such stimuli provides a simple and reliable fMRI localizer for human PIVC and p2v, which hitherto required galvanic or caloric stimulation to be identified.

Potentiation of the osmosensitive taurine release and cell volume regulation by cytosolic Ca2+ rise in cultured cerebellar astrocytes.

Hyposmolarity (-30%) in cultured cerebellar astrocytes raised cytosolic Ca2+ concentration ([Ca2+]i) from 160 to 400 nM and activated the osmosensitive taurine release (OTR) pathway. Although OTR is essentially [Ca2+]i-independent, further increase in [Ca2+]i by ionomycin strongly enhanced OTR, with a more robust effect at low and mild osmolarity reductions. Ionomycin did not affect isosmotic taurine efflux. OTR was decreased by tyrphostin A25 and increased by ortho-vanadate, suggesting a modulation by tyrosine kinase or phosphorylation state. Inhibition of phosphatidylinositol-3-kinase activity by wortmannin markedly decreased OTR and the ionomycin increase. Conversely, OTR and the ionomycin effect were independent of ERK1/ERK2 activation. OTR and its potentiation by ionomycin differed in their sensitivity to CaM and CaMK blockers and in the requirement of an intact cytoskeleton for the ionomycin effect, but not for normal OTR. Changes in the actin cytoskeleton organization elicited by hyposmolarity were not observed in ionomycin-treated cells, which may permit the operation of CaM/CaMK pathways involved in the OTR potentiation by [Ca2+]i rise. OTR potentiation by [Ca2+]i requires the previous or simultaneous activation/operation of the taurine release mechanism and is not modifying its set point, but rather increasing the effectiveness of the pathway, resulting in a more efficient volume regulation. This may have a beneficial effect in pathological situations with concurrent swelling and [Ca2+]i elevation in astrocytes.