Longitudinal stability of individual brain plasticity patterns in blindness.

The primary visual cortex (V1) in blindness 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 specific to task demands. This would suggest that reorganized V1 assumes a role like multiple-demand system regions. Alternatively, varying patterns of plasticity in blind V1 may be attributed to individual factors, with different blind individuals recruiting V1 preferentially for different functions. In support of this, we recently showed that V1 functional connectivity (FC) varies greatly across blind individuals. But do these represent stable individual patterns of plasticity, or are they driven more by instantaneous changes, like a multiple-demand system now inhabiting V1? Here, we tested whether individual FC patterns from the V1 of blind individuals are stable over time. We show that over two years, FC from the V1 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 V1 connectivity, this indicates that there may be a consistent role for V1 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.

Decoding Reach Direction in Early "Visual" Cortex of Congenitally Blind Individuals.

Motor actions, such as reaching or grasping, can be decoded from fMRI activity of early visual cortex (EVC) in sighted humans. This effect can depend on vision or visual imagery, or alternatively, could be driven by mechanisms independent of visual experience. Here, we show that the actions of reaching in different directions can be reliably decoded from fMRI activity of EVC in congenitally blind humans (both sexes). Thus, neither visual experience nor visual imagery is necessary for EVC to represent action-related information. We also demonstrate that, within EVC of blind humans, the accuracy of reach direction decoding is highest in areas typically representing foveal vision and gradually decreases in areas typically representing peripheral vision. We propose that this might indicate the existence of a predictive, hard-wired mechanism of aligning action and visual spaces. This mechanism might send action-related information primarily to the high-resolution foveal visual areas, which are critical for guiding and online correction of motor actions. Finally, we show that, beyond EVC, the decoding of reach direction in blind humans is most accurate in dorsal stream areas known to be critical for visuo-spatial and visuo-motor integration in the sighted. Thus, these areas can develop space and action representations even in the lifelong absence of vision. Overall, our findings in congenitally blind humans match previous research on the action system in the sighted, and suggest that the development of action representations in the human brain might be largely independent of visual experience.SIGNIFICANCE STATEMENT Early visual cortex (EVC) was traditionally thought to process only visual signals from the retina. Recent studies proved this account incomplete, and showed EVC involvement in many activities not directly related to incoming visual information, such as memory, sound, or action processing. Is EVC involved in these activities because of visual imagery? Here, we show robust reach direction representation in EVC of humans born blind. This demonstrates that EVC can represent actions independently of vision and visual imagery. Beyond EVC, we found that reach direction representation in blind humans is strongest in dorsal brain areas, critical for action processing in the sighted. This suggests that the development of action representations in the human brain is largely independent of visual experience.

Interoceptive training with real-time haptic versus visual heartbeat feedback.

The perception of signals from within the body, known as interoception, is increasingly recognized as a prerequisite for physical and mental health. This study is dedicated to the development of effective technological approaches for enhancing interoceptive abilities. We provide evidence of the effectiveness and practical feasibility of a novel real-time haptic heartbeat supplementation technology combining principles of biofeedback and sensory augmentation. In a randomized controlled study, we applied the developed naturalistic haptic feedback on a group of 30 adults, while another group of 30 adults received more traditional real-time visual heartbeat feedback. A single session of haptic, but not visual heartbeat feedback resulted in increased interoceptive accuracy and confidence, as measured by the heart rate discrimination task, and in a shift of attention toward the body. Participants rated the developed technology as more helpful and pleasant than the visual feedback, thus indicating high user satisfaction. The study highlights the importance of matching sensory characteristics of the feedback provided to the natural bodily prototype. Our work suggests that real-time haptic feedback might be a superior approach for strengthening the mind-body connection in interventions for physical and mental health.

Topographic maps and neural tuning for sensory substitution dimensions learned in adulthood in a congenital blind subject.

Topographic maps, a key principle of brain organization, emerge during development. It remains unclear, however, whether topographic maps can represent a new sensory experience learned in adulthood. MaMe, a congenitally blind individual, has been extensively trained in adulthood for perception of a 2D auditory-space (soundscape) where the y- and x-axes are represented by pitch and time, respectively. Using population receptive field mapping we found neural populations tuned topographically to pitch, not only in the auditory cortices but also in the parietal and occipito-temporal cortices. Topographic neural tuning to time was revealed in the parietal and occipito-temporal cortices. Some of these maps were found to represent both axes concurrently, enabling MaMe to represent unique locations in the soundscape space. This case study provides proof of concept for the existence of topographic maps tuned to the newly learned soundscape dimensions. These results suggest that topographic maps can be adapted or recycled in adulthood to represent novel sensory experiences.

A Whole-Body Sensory-Motor Gradient is Revealed in the Medial Wall of the Parietal Lobe.

In 1954, Penfield and Jasper's findings based on electric stimulation of epileptic patients led them to hypothesize that a sensory representation of the body should be found in the precuneus. They termed this representation the "supplementary sensory" area and emphasized that the exact form of this homunculus could not be specified on the basis of their results. In the decades that followed, their prediction was neglected. The precuneus was found to be involved in numerous motor, cognitive and visual processes, but no work was done on its somatotopic organization. Here, we used a periodic experimental design in which 16 human subjects (eight women) moved 20 body parts to investigate the possible body part topography of the precuneus. We found an anterior-to-posterior, dorsal-to-ventral, toes-to-tongue gradient in a mirror orientation to the SMA. When inspecting body-part-specific functional connectivity, we found differential connectivity patterns for the different body parts to the primary and secondary motor areas and parietal and visual areas, and a shared connectivity to the extrastriate body area, another topographically organized area. We suggest that a whole-body gradient can be found in the precuneus and is connected to multiple brain areas with different connectivity for different body parts. Its exact role and relations to the other known functions of the precuneus such as self-processing, motor imagery, reaching, visuomotor and other body-mind functions should be investigated.SIGNIFICANCE STATEMENT Using fMRI, as well as sensitive spectral analysis, we found a new homunculus in the precuneus: an anterior-to-posterior, dorsal-to-ventral, toes-to-tongue somatotopic gradient in a mirror orientation to the SMA. When inspecting body-part-specific functional connectivity, we found differential connectivity patterns for the different body parts to the primary and secondary motor areas, parietal and visual areas, and a shared connectivity to the extrastriate body area, another topographically organized area. We suggest that a whole-body gradient can be found in the precuneus and is connected to multiple brain areas in a body-part-specific manner.

Positive and Negative Somatotopic BOLD Responses in Contralateral Versus Ipsilateral Penfield Homunculus.

One of the basic properties of sensory cortices is their topographical organization. Most imaging studies explored this organization using the positive blood oxygenation level-dependent (BOLD) signal. Here, we studied the topographical organization of both positive and negative BOLD in contralateral and ipsilateral primary somatosensory cortex (S1). Using phase-locking mapping methods, we verified the topographical organization of contralateral S1, and further showed that different body segments elicit pronounced negative BOLD responses in both hemispheres. In the contralateral hemisphere, we found a sharpening mechanism in which stimulation of a given body segment triggered a gradient of activation with a significant deactivation in more remote areas. In the ipsilateral cortex, deactivation was not only located in the homolog area of the stimulated parts but rather was widespread across many parts of S1. Additionally, analysis of resting-state functional magnetic resonance imaging signal showed a gradient of connectivity to the neighboring contralateral body parts as well as to the ipsilateral homologous area for each body part. Taken together, our results indicate a complex pattern of baseline and activity-dependent responses in the contralateral and ipsilateral sides. Both primary sensory areas were characterized by unique negative BOLD responses, suggesting that they are an important component in topographic organization of sensory cortices.

Discontinuity of cortical gradients reflects sensory impairment.

Topographic maps and their continuity constitute a fundamental principle of brain organization. In the somatosensory system, whole-body sensory impairment may be reflected either in cortical signal reduction or disorganization of the somatotopic map, such as disturbed continuity. Here we investigated the role of continuity in pathological states. We studied whole-body cortical representations in response to continuous sensory stimulation under functional MRI (fMRI) in two unique patient populations-patients with cervical sensory Brown-Séquard syndrome (injury to one side of the spinal cord) and patients before and after surgical repair of cervical disk protrusion-enabling us to compare whole-body representations in the same study subjects. We quantified the spatial gradient of cortical activation and evaluated the divergence from a continuous pattern. Gradient continuity was found to be disturbed at the primary somatosensory cortex (S1) and the supplementary motor area (SMA), in both patient populations: contralateral to the disturbed body side in the Brown-Séquard group and before repair in the surgical group, which was further improved after intervention. Results corresponding to the nondisturbed body side and after surgical repair were comparable with control subjects. No difference was found in the fMRI signal power between the different conditions in the two groups, as well as with respect to control subjects. These results suggest that decreased sensation in our patients is related to gradient discontinuity rather than signal reduction. Gradient continuity may be crucial for somatotopic and other topographical organization, and its disruption may characterize pathological processing.

New whole-body sensory-motor gradients revealed using phase-locked analysis and verified using multivoxel pattern analysis and functional connectivity.

Topographic organization is one of the main principles of organization in the human brain. Specifically, whole-brain topographic mapping using spectral analysis is responsible for one of the greatest advances in vision research. Thus, it is intriguing that although topography is a key feature also in the motor system, whole-body somatosensory-motor mapping using spectral analysis has not been conducted in humans outside M1/SMA. Here, using this method, we were able to map a homunculus in the globus pallidus, a key target area for deep brain stimulation, which has not been mapped noninvasively or in healthy subjects. The analysis clarifies contradictory and partial results regarding somatotopy in the caudal-cingulate zone and rostral-cingulate zone in the medial wall and in the putamen. Most of the results were confirmed at the single-subject level and were found to be compatible with results from animal studies. Using multivoxel pattern analysis, we could predict movements of individual body parts in these homunculi, thus confirming that they contain somatotopic information. Using functional connectivity, we demonstrate interhemispheric functional somatotopic connectivity of these homunculi, such that the somatotopy in one hemisphere could have been found given the connectivity pattern of the corresponding regions of interest in the other hemisphere. When inspecting the somatotopic and nonsomatotopic connectivity patterns, a similarity index indicated that the pattern of connected and nonconnected regions of interest across different homunculi is similar for different body parts and hemispheres. The results show that topographical gradients are even more widespread than previously assumed in the somatosensory-motor system. Spectral analysis can thus potentially serve as a gold standard for defining somatosensory-motor system areas for basic research and clinical applications.

The origins of metamodality in visual object area LO: Bodily topographical biases and increased functional connectivity to S1.

Recent evidence from blind participants suggests that visual areas are task-oriented and sensory modality input independent rather than sensory-specific to vision. Specifically, visual areas are thought to retain their functional selectivity when using non-visual inputs (touch or sound) even without having any visual experience. However, this theory is still controversial since it is not clear whether this also characterizes the sighted brain, and whether the reported results in the sighted reflect basic fundamental a-modal processes or are an epiphenomenon to a large extent. In the current study, we addressed these questions using a series of fMRI experiments aimed to explore visual cortex responses to passive touch on various body parts and the coupling between the parietal and visual cortices as manifested by functional connectivity. We show that passive touch robustly activated the object selective parts of the lateral-occipital (LO) cortex while deactivating almost all other occipital-retinotopic-areas. Furthermore, passive touch responses in the visual cortex were specific to hand and upper trunk stimulations. Psychophysiological interaction (PPI) analysis suggests that LO is functionally connected to the hand area in the primary somatosensory homunculus (S1), during hand and shoulder stimulations but not to any of the other body parts. We suggest that LO is a fundamental hub that serves as a node between visual-object selective areas and S1 hand representation, probably due to the critical evolutionary role of touch in object recognition and manipulation. These results might also point to a more general principle suggesting that recruitment or deactivation of the visual cortex by other sensory input depends on the ecological relevance of the information conveyed by this input to the task/computations carried out by each area or network. This is likely to rely on the unique and differential pattern of connectivity for each visual area with the rest of the brain.

Increased functional connectivity between language and visually deprived areas in late and partial blindness.

In the congenitally blind, language processing involves visual areas. In the case of normal visual development however, it remains unclear whether later visual loss induces interactions between the language and visual areas. This study compared the resting-state functional connectivity (FC) of retinotopic and language areas in two unique groups of late visually deprived subjects: (1) blind individuals suffering from retinitis pigmentosa (RP), (2) RP subjects without a visual periphery but with preserved central "tunnel vision", both of whom were contrasted with sighted controls. The results showed increased FC between Broca's area and the visually deprived areas in the peripheral V1 for individuals with tunnel vision, and both the peripheral and central V1 for blind individuals. These findings suggest that FC can develop in the adult brain between the visual and language systems in the completely and partially blind. These changes start in the deprived areas and increase in size (involving both foveal and peripheral V1) and strength (from negative to positive FC) as the disease and sensory deprivation progress. These observations support the claim that functional connectivity between remote systems that perform completely different tasks can change in the adult brain in cases of total and even partial visual deprivation.

Intensity-based masking: A tool to improve functional connectivity results of resting-state fMRI.

Seed-based functional connectivity (FC) of resting-state functional MRI data is a widely used methodology, enabling the identification of functional brain networks in health and disease. Based on signal correlations across the brain, FC measures are highly sensitive to noise. A somewhat neglected source of noise is the fMRI signal attenuation found in cortical regions in close vicinity to sinuses and air cavities, mainly in the orbitofrontal, anterior frontal and inferior temporal cortices. BOLD signal recorded at these regions suffers from dropout due to susceptibility artifacts, resulting in an attenuated signal with reduced signal-to-noise ratio in as many as 10% of cortical voxels. Nevertheless, signal attenuation is largely overlooked during FC analysis. Here we first demonstrate that signal attenuation can significantly influence FC measures by introducing false functional correlations and diminishing existing correlations between brain regions. We then propose a method for the detection and removal of the attenuated signal ("intensity-based masking") by fitting a Gaussian-based model to the signal intensity distribution and calculating an intensity threshold tailored per subject. Finally, we apply our method on real-world data, showing that it diminishes false correlations caused by signal dropout, and significantly improves the ability to detect functional networks in single subjects. Furthermore, we show that our method increases inter-subject similarity in FC, enabling reliable distinction of different functional networks. We propose to include the intensity-based masking method as a common practice in the pre-processing of seed-based functional connectivity analysis, and provide software tools for the computation of intensity-based masks on fMRI data. Hum Brain Mapp 37:2407-2418, 2016. © 2016 Wiley Periodicals, Inc.

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.

Flexibility and Stability in Sensory Processing Revealed Using Visual-to-Auditory Sensory Substitution.

The classical view of sensory processing involves independent processing in sensory cortices and multisensory integration in associative areas. This hierarchical structure has been challenged by evidence of multisensory responses in sensory areas, and dynamic weighting of sensory inputs in associative areas, thus far reported independently. Here, we used a visual-to-auditory sensory substitution algorithm (SSA) to manipulate the information conveyed by sensory inputs while keeping the stimuli intact. During scan sessions before and after SSA learning, subjects were presented with visual images and auditory soundscapes. The findings reveal 2 dynamic processes. First, crossmodal attenuation of sensory cortices changed direction after SSA learning from visual attenuations of the auditory cortex to auditory attenuations of the visual cortex. Secondly, associative areas changed their sensory response profile from strongest response for visual to that for auditory. The interaction between these phenomena may play an important role in multisensory processing. Consistent features were also found in the sensory dominance in sensory areas and audiovisual convergence in associative area Middle Temporal Gyrus. These 2 factors allow for both stability and a fast, dynamic tuning of the system when required.

Negative blood oxygenation level dependent homunculus and somatotopic information in primary motor cortex and supplementary motor area.

A crucial attribute in movement encoding is an adequate balance between suppression of unwanted muscles and activation of required ones. We studied movement encoding across the primary motor cortex (M1) and supplementary motor area (SMA) by inspecting the positive and negative blood oxygenation level-dependent (BOLD) signals in these regions. Using periodic and event-related experiments incorporating the bilateral/axial movements of 20 body parts, we report detailed mototopic imaging maps in M1 and SMA. These maps were obtained using phase-locked analysis. In addition to the positive BOLD, significant negative BOLD was detected in M1 but not in the SMA. The negative BOLD spatial pattern was neither located at the ipsilateral somatotopic location nor randomly distributed. Rather, it was organized somatotopically across the entire homunculus and inversely to the positive BOLD, creating a negative BOLD homunculus. The neuronal source of negative BOLD is unclear. M1 provides a unique system to test whether the origin of negative BOLD is neuronal, because different arteries supply blood to different regions in the homunculus, ruling out blood-stealing explanations. Finally, multivoxel pattern analysis showed that positive BOLD in M1 and SMA and negative BOLD in M1 contain somatotopic information, enabling prediction of the moving body part from inside and outside its somatotopic location. We suggest that the neuronal processes underlying negative BOLD participate in somatotopic encoding in M1 but not in the SMA. This dissociation may emerge because of differences in the activity of these motor areas associated with movement suppression.

Highly compromised auditory spatial perception in aided congenitally hearing-impaired and rapid improvement with tactile technology.

Spatial understanding is a multisensory construct while hearing is the only natural sense enabling the simultaneous perception of the entire 3D space. To test whether such spatial understanding is dependent on auditory experience, we study congenitally hearing-impaired users of assistive devices. We apply an in-house technology, which, inspired by the auditory system, performs intensity-weighting to represent external spatial positions and motion on the fingertips. We see highly impaired auditory spatial capabilities for tracking moving sources, which based on the "critical periods" theory emphasizes the role of nature in sensory development. Meanwhile, for tactile and audio-tactile spatial motion perception, the hearing-impaired show performance similar to typically hearing individuals. The immediate availability of 360° external space representation through touch, despite the lack of such experience during the lifetime, points to the significant role of nurture in spatial perception development, and to its amodal character. The findings show promise toward advancing multisensory solutions for rehabilitation.

Localizing 3D motion through the fingertips: Following in the footsteps of elephants.

Each sense serves a different specific function in spatial perception, and they all form a joint multisensory spatial representation. For instance, hearing enables localization in the entire 3D external space, while touch traditionally only allows localization of objects on the body (i.e., within the peripersonal space alone). We use an in-house touch-motion algorithm (TMA) to evaluate individuals' capability to understand externalized 3D information through touch, a skill that was not acquired during an individual's development or in evolution. Four experiments demonstrate quick learning and high accuracy in localization of motion using vibrotactile inputs on fingertips and successful audio-tactile integration in background noise. Subjective responses in some participants imply spatial experiences through visualization and perception of tactile "moving" sources beyond reach. We discuss our findings with respect to developing new skills in an adult brain, including combining a newly acquired "sense" with an existing one and computation-based brain organization.

Perceiving depth beyond sight: Evaluating intrinsic and learned cues via a proof of concept sensory substitution method in the visually impaired and sighted.

This study explores spatial perception of depth by employing a novel proof of concept sensory substitution algorithm. The algorithm taps into existing cognitive scaffolds such as language and cross modal correspondences by naming objects in the scene while representing their elevation and depth by manipulation of the auditory properties for each axis. While the representation of verticality utilized a previously tested correspondence with pitch, the representation of depth employed an ecologically inspired manipulation, based on the loss of gain and filtration of higher frequency sounds over distance. The study, involving 40 participants, seven of which were blind (5) or visually impaired (2), investigates the intrinsicness of an ecologically inspired mapping of auditory cues for depth by comparing it to an interchanged condition where the mappings of the two axes are swapped. All participants successfully learned to use the algorithm following a very brief period of training, with the blind and visually impaired participants showing similar levels of success for learning to use the algorithm as did their sighted counterparts. A significant difference was found at baseline between the two conditions, indicating the intuitiveness of the original ecologically inspired mapping. Despite this, participants were able to achieve similar success rates following the training in both conditions. The findings indicate that both intrinsic and learned cues come into play with respect to depth perception. Moreover, they suggest that by employing perceptual learning, novel sensory mappings can be trained in adulthood. Regarding the blind and visually impaired, the results also support the convergence view, which claims that with training, their spatial abilities can converge with those of the sighted. Finally, we discuss how the algorithm can open new avenues for accessibility technologies, virtual reality, and other practical applications.

Hearing temperatures: employing machine learning for elucidating the cross-modal perception of thermal properties through audition.

People can use their sense of hearing for discerning thermal properties, though they are for the most part unaware that they can do so. While people unequivocally claim that they cannot perceive the temperature of pouring water through the auditory properties of hearing it being poured, our research further strengthens the understanding that they can. This multimodal ability is implicitly acquired in humans, likely through perceptual learning over the lifetime of exposure to the differences in the physical attributes of pouring water. In this study, we explore people's perception of this intriguing cross modal correspondence, and investigate the psychophysical foundations of this complex ecological mapping by employing machine learning. Our results show that not only can the auditory properties of pouring water be classified by humans in practice, the physical characteristics underlying this phenomenon can also be classified by a pre-trained deep neural network.

Enhancing interoceptive sensibility through exteroceptive-interoceptive sensory substitution.

Exploring a novel approach to mental health technology, this study illuminates the intricate interplay between exteroception (the perception of the external world), and interoception (the perception of the internal world). Drawing on principles of sensory substitution, we investigated how interoceptive signals, particularly respiration, could be conveyed through exteroceptive modalities, namely vision and hearing. To this end, we developed a unique, immersive multisensory environment that translates respiratory signals in real-time into dynamic visual and auditory stimuli. The system was evaluated by employing a battery of various psychological assessments, with the findings indicating a significant increase in participants' interoceptive sensibility and an enhancement of the state of flow, signifying immersive and positive engagement with the experience. Furthermore, a correlation between these two variables emerged, revealing a bidirectional enhancement between the state of flow and interoceptive sensibility. Our research is the first to present a sensory substitution approach for substituting between interoceptive and exteroceptive senses, and specifically as a transformative method for mental health interventions, paving the way for future research.

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.