Longitudinal stability of individual brain plasticity patterns in blindness.

The primary visual cortex (V1) in individuals born blind is engaged in a wide spectrum of tasks and sensory modalities, including audition, touch, language, and memory. This widespread involvement raises questions regarding the constancy of its role and whether it might exhibit flexibility in its function over time, connecting to diverse network functions in response to task-specific demands. This would suggest that reorganized V1 takes on a role similar to cognitive multiple-demand system regions. Alternatively, it is possible that the varying patterns of plasticity observed in the blind V1 can be attributed to individual factors, whereby different blind individuals recruit V1 for different functions, highlighting the immense idiosyncrasy of plasticity. In support of this second account, we have recently shown that V1 functional connectivity varies greatly across blind individuals. But do these represent stable individual patterns of plasticity or merely instantaneous changes, for a multiple-demand system now inhabiting V1? Here we tested if individual connectivity patterns from the visual cortex of blind individuals are stable over time. We show that over two years, fMRI functional connectivity from the primary visual cortex is unique and highly stable in a small sample of repeatedly sampled congenitally blind individuals. Further, using multivoxel pattern analysis, we demonstrate that the unique reorganization patterns of these individuals allow decoding of participant identity. Together with recent evidence for substantial individual differences in visual cortex connectivity, this indicates there may be a consistent role for the visual cortex in blindness, which may differ for each individual. Further, it suggests that the variability in visual reorganization in blindness across individuals could be used to seek stable neuromarkers for sight rehabilitation and assistive approaches.

Spoken language processing activates the primary visual cortex.

Primary visual cortex (V1) is generally thought of as a low-level sensory area that primarily processes basic visual features. Although there is evidence for multisensory effects on its activity, these are typically found for the processing of simple sounds and their properties, for example spatially or temporally-congruent simple sounds. However, in congenitally blind individuals, V1 is involved in language processing, with no evidence of major changes in anatomical connectivity that could explain this seemingly drastic functional change. This is at odds with current accounts of neural plasticity, which emphasize the role of connectivity and conserved function in determining a neural tissue's role even after atypical early experiences. To reconcile what appears to be unprecedented functional reorganization with known accounts of plasticity limitations, we tested whether V1's multisensory roles include responses to spoken language in sighted individuals. Using fMRI, we found that V1 in normally sighted individuals was indeed activated by comprehensible spoken sentences as compared to an incomprehensible reversed speech control condition, and more strongly so in the left compared to the right hemisphere. Activation in V1 for language was also significant and comparable for abstract and concrete words, suggesting it was not driven by visual imagery. Last, this activation did not stem from increased attention to the auditory onset of words, nor was it correlated with attentional arousal ratings, making general attention accounts an unlikely explanation. Together these findings suggest that V1 responds to spoken language even in sighted individuals, reflecting the binding of multisensory high-level signals, potentially to predict visual input. This capability might be the basis for the strong V1 language activation observed in people born blind, re-affirming the notion that plasticity is guided by pre-existing connectivity and abilities in the typically developed brain.

The Role of Visual Experience in Individual Differences of Brain Connectivity.

Visual cortex organization is highly consistent across individuals. But to what degree does this consistency depend on life experience, in particular sensory experience? In this study, we asked whether visual cortex reorganization in congenital blindness results in connectivity patterns that are particularly variable across individuals, focusing on resting-state functional connectivity (RSFC) patterns from the primary visual cortex. We show that the absence of shared visual experience results in more variable RSFC patterns across blind individuals than sighted controls. Increased variability is specifically found in areas that show a group difference between the blind and sighted in their RSFC. These findings reveal a relationship between brain plasticity and individual variability; reorganization manifests variably across individuals. We further investigated the different patterns of reorganization in the blind, showing that the connectivity to frontal regions, proposed to have a role in the reorganization of the visual cortex of the blind toward higher cognitive roles, is highly variable. Further, we link some of the variability in visual-to-frontal connectivity to another environmental factor-duration of formal education. Together, these findings show a role of postnatal sensory and socioeconomic experience in imposing consistency on brain organization. By revealing the idiosyncratic nature of neural reorganization, these findings highlight the importance of considering individual differences in fitting sensory aids and restoration approaches for vision loss.SIGNIFICANCE STATEMENT The typical visual system is highly consistent across individuals. What are the origins of this consistency? Comparing the consistency of visual cortex connectivity between people born blind and sighted people, we showed that blindness results in higher variability, suggesting a key impact of postnatal individual experience on brain organization. Further, connectivity patterns that changed following blindness were particularly variable, resulting in diverse patterns of brain reorganization. Individual differences in reorganization were also directly affected by nonvisual experiences in the blind (years of formal education). Together, these findings show a role of sensory and socioeconomic experiences in creating individual differences in brain organization and endorse the use of individual profiles for rehabilitation and restoration of vision loss.

Are reaching and grasping effector-independent? Similarities and differences in reaching and grasping kinematics between the hand and foot.

While reaching and grasping are highly prevalent manual actions, neuroimaging studies provide evidence that their neural representations may be shared between different body parts, i.e., effectors. If these actions are guided by effector-independent mechanisms, similar kinematics should be observed when the action is performed by the hand or by a cortically remote and less experienced effector, such as the foot. We tested this hypothesis with two characteristic components of action: the initial ballistic stage of reaching, and the preshaping of the digits during grasping based on object size. We examined if these kinematic features reflect effector-independent mechanisms by asking participants to reach toward and to grasp objects of different widths with their hand and foot. First, during both reaching and grasping, the velocity profile up to peak velocity matched between the hand and the foot, indicating a shared ballistic acceleration phase. Second, maximum grip aperture and time of maximum grip aperture of grasping increased with object size for both effectors, indicating encoding of object size during transport. Differences between the hand and foot were found in the deceleration phase and time of maximum grip aperture, likely due to biomechanical differences and the participants' inexperience with foot actions. These findings provide evidence for effector-independent visuomotor mechanisms of reaching and grasping that generalize across body parts.

Evidence for an effector-independent action system from people born without hands.

Many parts of the visuomotor system guide daily hand actions, like reaching for and grasping objects. Do these regions depend exclusively on the hand as a specific body part whose movement they guide, or are they organized for the reaching task per se, for any body part used as an effector? To address this question, we conducted a neuroimaging study with people born without upper limbs-individuals with dysplasia-who use the feet to act, as they and typically developed controls performed reaching and grasping actions with their dominant effector. Individuals with dysplasia have no prior experience acting with hands, allowing us to control for hand motor imagery when acting with another effector (i.e., foot). Primary sensorimotor cortices showed selectivity for the hand in controls and foot in individuals with dysplasia. Importantly, we found a preference based on action type (reaching/grasping) regardless of the effector used in the association sensorimotor cortex, in the left intraparietal sulcus and dorsal premotor cortex, as well as in the basal ganglia and anterior cerebellum. These areas also showed differential response patterns between action types for both groups. Intermediate areas along a posterior-anterior gradient in the left dorsal premotor cortex gradually transitioned from selectivity based on the body part to selectivity based on the action type. These findings indicate that some visuomotor association areas are organized based on abstract action functions independent of specific sensorimotor parameters, paralleling sensory feature-independence in visual and auditory cortices in people born blind and deaf. Together, they suggest association cortices across action and perception may support specific computations, abstracted from low-level sensorimotor elements.

Publisher Correction: Creative exploration as a scale-invariant search on a meaning landscape.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Large-Scale Organization of the Hand Action Observation Network in Individuals Born Without Hands.

The human high-level visual cortex comprises regions specialized for the processing of distinct types of stimuli, such as objects, animals, and human actions. How does this specialization emerge? Here, we investigated the role of effector-specific visuomotor coupling experience in shaping the organization of the action observation network (AON) as a window on this question. Observed body movements are frequently coupled with corresponding motor codes, e.g., during monitoring one's own movements and imitation, resulting in bidirectionally connected circuits between areas involved in body movements observation (e.g., of the hand) and the motor codes involved in their execution. If the organization of the AON is shaped by this effector-specific visuomotor coupling, then, it should not form for body movements that do not belong to individuals' motor repertoire. To test this prediction, we used fMRI to investigate the spatial arrangement and functional properties of the hand and foot action observation circuits in individuals born without upper limbs. Multivoxel pattern decoding, pattern similarity, and univariate analyses revealed an intact hand AON in the individuals born without upper limbs. This suggests that the organization of the AON does not require effector-specific visuomotor coupling.

Neural representation of visual concepts in people born blind.

How do we represent information without sensory features? How are abstract concepts like "freedom", devoid of external perceptible referents, represented in the brain? Here, to address the role of sensory information in the neural representation of concepts, we used fMRI to investigate how people born blind process concepts whose referents are imperceptible to them because of their visual nature ("rainbow", "red"). Activity for these concepts was compared to that of sensorially-perceptible referents ("rain"), classical abstract concepts ("justice") and concrete concepts ("cup"), providing a gradient between fully concrete and fully abstract concepts in the blind. We find that anterior temporal lobe (ATL) responses track concept perceptibility and objecthood: preference for imperceptible object concepts was found in dorsal ATL, for abstract (non-object, non-referential) concepts in lateral ATL, and for perceptible concepts in medial ATL. These findings point to a new division-of-labor among aspects of ATL in representing conceptual properties that are abstract in different ways.

Creative exploration as a scale-invariant search on a meaning landscape.

Can knowledge accumulated in systems biology on mechanisms governing cell behavior help us to elucidate cognitive processes, such as human creative search? To address this, we focus on the property of scale invariance, which allows sensory systems to adapt to environmental signals spanning orders of magnitude. For example, bacteria search for nutrients, by responding to relative changes in nutrient concentration rather than absolute levels, via a sensory mechanism termed fold-change detection (FCD). Scale invariance is prevalent in cognition, yet the specific mechanisms are mostly unknown. Here, we screen many possible dynamic equation topologies, to find that an FCD model best describes creative search dynamics. The model further predicts robustness to variations in meaning perception, in agreement with behavioral data. We thus suggest FCD as a specific mechanism for scale invariant search, connecting sensory processes of cells and cognitive processes in human.

Plasticity based on compensatory effector use in the association but not primary sensorimotor cortex of people born without hands.

What forces direct brain organization and its plasticity? When brain regions are deprived of their input, which regions reorganize based on compensation for the disability and experience, and which regions show topographically constrained plasticity? People born without hands activate their primary sensorimotor hand region while moving body parts used to compensate for this disability (e.g., their feet). This was taken to suggest a neural organization based on functions, such as performing manual-like dexterous actions, rather than on body parts, in primary sensorimotor cortex. We tested the selectivity for the compensatory body parts in the primary and association sensorimotor cortex of people born without hands (dysplasic individuals). Despite clear compensatory foot use, the primary sensorimotor hand area in the dysplasic subjects showed preference for adjacent body parts that are not compensatorily used as effectors. This suggests that function-based organization, proposed for congenital blindness and deafness, does not apply to the primary sensorimotor cortex deprivation in dysplasia. These findings stress the roles of neuroanatomical constraints like topographical proximity and connectivity in determining the functional development of primary cortex even in extreme, congenital deprivation. In contrast, increased and selective foot movement preference was found in dysplasics' association cortex in the inferior parietal lobule. This suggests that the typical motor selectivity of this region for manual actions may correspond to high-level action representations that are effector-invariant. These findings reveal limitations to compensatory plasticity and experience in modifying brain organization of early topographical cortex compared with association cortices driven by function-based organization.

Brain Plasticity: When the Feet and Mouth Replace the Hand.

Cortex plasticity after hand amputation is considered harmful, causing phantom limb pain. A new study shows that cortical overtake can occur instead in a compensatory manner in people born with one hand, for multiple body parts used to overcome disability.

Sensorimotor-independent development of hands and tools selectivity in the visual cortex.

The visual occipito-temporal cortex is composed of several distinct regions specialized in the identification of different object kinds such as tools and bodies. Its organization appears to reflect not only the visual characteristics of the inputs but also the behavior that can be achieved with them. For example, there are spatially overlapping responses for viewing hands and tools, which is likely due to their common role in object-directed actions. How dependent is occipito-temporal cortex organization on object manipulation and motor experience? To investigate this question, we studied five individuals born without hands (individuals with upper limb dysplasia), who use tools with their feet. Using fMRI, we found the typical selective hand-tool overlap (HTO) not only in typically developed control participants but also in four of the five dysplasics. Functional connectivity of the HTO in the dysplasics also showed a largely similar pattern as in the controls. The preservation of functional organization in the dysplasics suggests that occipito-temporal cortex specialization is driven largely by inherited connectivity constraints that do not require sensorimotor experience. These findings complement discoveries of intact functional organization of the occipito-temporal cortex in people born blind, supporting an organization largely independent of any one specific sensory or motor experience.

Topographical functional connectivity patterns exist in the congenitally, prelingually deaf.

Congenital deafness causes large changes in the auditory cortex structure and function, such that without early childhood cochlear-implant, profoundly deaf children do not develop intact, high-level, auditory functions. But how is auditory cortex organization affected by congenital, prelingual, and long standing deafness? Does the large-scale topographical organization of the auditory cortex develop in people deaf from birth? And is it retained despite cross-modal plasticity? We identified, using fMRI, topographic tonotopy-based functional connectivity (FC) structure in humans in the core auditory cortex, its extending tonotopic gradients in the belt and even beyond that. These regions show similar FC structure in the congenitally deaf throughout the auditory cortex, including in the language areas. The topographic FC pattern can be identified reliably in the vast majority of the deaf, at the single subject level, despite the absence of hearing-aid use and poor oral language skills. These findings suggest that large-scale tonotopic-based FC does not require sensory experience to develop, and is retained despite life-long auditory deprivation and cross-modal plasticity. Furthermore, as the topographic FC is retained to varying degrees among the deaf subjects, it may serve to predict the potential for auditory rehabilitation using cochlear implants in individual subjects.

Origins of task-specific sensory-independent organization in the visual and auditory brain: neuroscience evidence, open questions and clinical implications.

Evidence of task-specific sensory-independent (TSSI) plasticity from blind and deaf populations has led to a better understanding of brain organization. However, the principles determining the origins of this plasticity remain unclear. We review recent data suggesting that a combination of the connectivity bias and sensitivity to task-distinctive features might account for TSSI plasticity in the sensory cortices as a whole, from the higher-order occipital/temporal cortices to the primary sensory cortices. We discuss current theories and evidence, open questions and related predictions. Finally, given the rapid progress in visual and auditory restoration techniques, we address the crucial need to develop effective rehabilitation approaches for sensory recovery.

Functional connectivity of visual cortex in the blind follows retinotopic organization principles.

Is visual input during critical periods of development crucial for the emergence of the fundamental topographical mapping of the visual cortex? And would this structure be retained throughout life-long blindness or would it fade as a result of plastic, use-based reorganization? We used functional connectivity magnetic resonance imaging based on intrinsic blood oxygen level-dependent fluctuations to investigate whether significant traces of topographical mapping of the visual scene in the form of retinotopic organization, could be found in congenitally blind adults. A group of 11 fully and congenitally blind subjects and 18 sighted controls were studied. The blind demonstrated an intact functional connectivity network structural organization of the three main retinotopic mapping axes: eccentricity (centre-periphery), laterality (left-right), and elevation (upper-lower) throughout the retinotopic cortex extending to high-level ventral and dorsal streams, including characteristic eccentricity biases in face- and house-selective areas. Functional connectivity-based topographic organization in the visual cortex was indistinguishable from the normally sighted retinotopic functional connectivity structure as indicated by clustering analysis, and was found even in participants who did not have a typical retinal development in utero (microphthalmics). While the internal structural organization of the visual cortex was strikingly similar, the blind exhibited profound differences in functional connectivity to other (non-visual) brain regions as compared to the sighted, which were specific to portions of V1. Central V1 was more connected to language areas but peripheral V1 to spatial attention and control networks. These findings suggest that current accounts of critical periods and experience-dependent development should be revisited even for primary sensory areas, in that the connectivity basis for visual cortex large-scale topographical organization can develop without any visual experience and be retained through life-long experience-dependent plasticity. Furthermore, retinotopic divisions of labour, such as that between the visual cortex regions normally representing the fovea and periphery, also form the basis for topographically-unique plastic changes in the blind.

Visual cortex extrastriate body-selective area activation in congenitally blind people "seeing" by using sounds.

Vision is by far the most prevalent sense for experiencing others' body shapes, postures, actions, and intentions, and its congenital absence may dramatically hamper body-shape representation in the brain. We investigated whether the absence of visual experience and limited exposure to others' body shapes could still lead to body-shape selectivity. We taught congenitally fully-blind adults to perceive full-body shapes conveyed through a sensory-substitution algorithm topographically translating images into soundscapes [1]. Despite the limited experience of the congenitally blind with external body shapes (via touch of close-by bodies and for ~10 hr via soundscapes), once the blind could retrieve body shapes via soundscapes, they robustly activated the visual cortex, specifically the extrastriate body area (EBA; [2]). Furthermore, body selectivity versus textures, objects, and faces in both the blind and sighted control groups was not found in the temporal (auditory) or parietal (somatosensory) cortex but only in the visual EBA. Finally, resting-state data showed that the blind EBA is functionally connected to the temporal cortex temporal-parietal junction/superior temporal sulcus Theory-of-Mind areas [3]. Thus, the EBA preference is present without visual experience and with little exposure to external body-shape information, supporting the view that the brain has a sensory-independent, task-selective supramodal organization rather than a sensory-specific organization.

Reading with sounds: sensory substitution selectively activates the visual word form area in the blind.

Using a visual-to-auditory sensory-substitution algorithm, congenitally fully blind adults were taught to read and recognize complex images using "soundscapes"--sounds topographically representing images. fMRI was used to examine key questions regarding the visual word form area (VWFA): its selectivity for letters over other visual categories without visual experience, its feature tolerance for reading in a novel sensory modality, and its plasticity for scripts learned in adulthood. The blind activated the VWFA specifically and selectively during the processing of letter soundscapes relative to both textures and visually complex object categories and relative to mental imagery and semantic-content controls. Further, VWFA recruitment for reading soundscapes emerged after 2 hr of training in a blind adult on a novel script. Therefore, the VWFA shows category selectivity regardless of input sensory modality, visual experience, and long-term familiarity or expertise with the script. The VWFA may perform a flexible task-specific rather than sensory-specific computation, possibly linking letter shapes to phonology.

'Visual' acuity of the congenitally blind using visual-to-auditory sensory substitution.

Sensory Substitution Devices (SSDs) convey visual information through sounds or touch, thus theoretically enabling a form of visual rehabilitation in the blind. However, for clinical use, these devices must provide fine-detailed visual information which was not yet shown for this or other means of visual restoration. To test the possible functional acuity conveyed by such devices, we used the Snellen acuity test conveyed through a high-resolution visual-to-auditory SSD (The vOICe). We show that congenitally fully blind adults can exceed the World Health Organization (WHO) blindness acuity threshold using SSDs, reaching the highest acuity reported yet with any visual rehabilitation approach. This demonstrates the potential capacity of SSDs as inexpensive, non-invasive visual rehabilitation aids, alone or when supplementing visual prostheses.

The large-scale organization of "visual" streams emerges without visual experience.

A key question in sensory perception is the role of experience in shaping the functional architecture of the sensory neural systems. Here we studied dependence on visual experience in shaping the most fundamental division of labor in vision, namely between the ventral "what" and the dorsal "where and how" processing streams. We scanned 11 fully congenitally blind (CB) and 9 sighted individuals performing location versus form identification tasks following brief training on a sensory substitution device used for artificial vision. We show that the dorsal/ventral visual pathway division of labor can be revealed in the adult CB when perceiving sounds that convey the relevant visual information. This suggests that the most important large-scale organization of the visual system into the 2 streams can develop even without any visual experience and can be attributed at least partially to innately determined constraints and later to cross-modal plasticity. These results support the view that the brain is organized into task-specific but sensory modality-independent operators.