Behavioral and neuroplastic changes in the blind: evidence for functionally relevant cross-modal interactions.

The study of blind individuals provides insight into the brain re-organization and behavioral compensations that occur following sensory deprivation. While behavioral studies have yielded conflicting results in terms of performance levels within the remaining senses, deafferentation of visual cortical areas through peripheral blindness results in clear neuroplastic changes. Most striking is the activation of occipital cortex in response to auditory and tactile stimulation. Indeed, parts of the "unimodal" visual cortex are recruited by other sensory modalities to process sensory information in a functionally relevant manner. In addition, a larger area of the sensorimotor cortex is devoted to the representation of the reading finger in blind Braille readers. The "visual" function of the deafferented occipital cortex is also altered, where transcranial magnetic stimulation-induced phosphenes can be elicited in only 20% of blind subjects. The neural mechanisms underlying these changes remain elusive but recent data showing rapid cross-modal plasticity in blindfolded, sighted subjects argue against the establishment of new connections to explain cross-modal interactions in the blind. Rather, latent pathways that participate in multisensory percepts in sighted subjects might be unmasked and may be potentiated in the event of complete loss of visual input. These issues have important implications for the development of visual prosthesis aimed at restoring some degree of vision in the blind.     

Morphometric Changes of the Corpus Callosum in Congenital Blindness

We examined the effects of visual deprivation at birth on the development of the corpus callosum in a large group of congenitally blind individuals. We acquired high-resolution T1-weighted MRI scans in 28 congenitally blind and 28 normal sighted subjects matched for age and gender. There was no overall group effect of visual deprivation on the total surface area of the corpus callosum. However, subdividing the corpus callosum into five subdivisions revealed significant regional changes in its three most posterior parts. Compared to the sighted controls, congenitally blind individuals showed a 12% reduction in the splenium, and a 20% increase in the isthmus and the posterior part of the body. A shape analysis further revealed that the bending angle of the corpus callosum was more convex in congenitally blind compared to the sighted control subjects. The observed morphometric changes in the corpus callosum are in line with the well-described cross-modal functional and structural neuroplastic changes in congenital blindness.     

Multivoxel Pattern Analysis Reveals Auditory Motion Information in MT+ of Both Congenitally Blind and Sighted Individuals

Cross-modal plasticity refers to the recruitment of cortical regions involved in the processing of one modality (e.g. vision) for processing other modalities (e.g. audition). The principles determining how and where cross-modal plasticity occurs remain poorly understood. Here, we investigate these principles by testing responses to auditory motion in visual motion area MT+ of congenitally blind and sighted individuals. Replicating previous reports, we find that MT+ as a whole shows a strong and selective responses to auditory motion in congenitally blind but not sighted individuals, suggesting that the emergence of this univariate response depends on experience. Importantly, however, multivoxel pattern analyses showed that MT+ contained information about different auditory motion conditions in both blind and sighted individuals. These results were specific to MT+ and not found in early visual cortex. Basic sensitivity to auditory motion in MT+ is thus experience-independent, which may be a basis for the region''s strong cross-modal recruitment in congenital blindness.     

Experience-Related Structural Changes of Degenerated Occipital White Matter in Late-Blind Humans – A Diffusion Tensor Imaging Study

Late-blind humans can learn to understand speech at ultra-fast syllable rates (ca. 20 syllables/s), a capability associated with hemodynamic activation of the central-visual system. Thus, the observed functional cross-modal recruitment of occipital cortex might facilitate ultra-fast speech processing in these individuals. To further elucidate the structural prerequisites of this skill, diffusion tensor imaging (DTI) was conducted in late-blind subjects differing in their capability of understanding ultra-fast speech. Fractional anisotropy (FA) was determined as a quantitative measure of the directionality of water diffusion, indicating fiber tract characteristics that might be influenced by blindness as well as the acquired perceptual skills. Analysis of the diffusion images revealed reduced FA in late-blind individuals relative to sighted controls at the level of the optic radiations at either side and the right-hemisphere dorsal thalamus (pulvinar). Moreover, late-blind subjects showed significant positive correlations between FA and the capacity of ultra-fast speech comprehension within right-hemisphere optic radiation and thalamus. Thus, experience-related structural alterations occurred in late-blind individuals within visual pathways that, presumably, are linked to higher order frontal language areas.     

Altered Anatomical Network in Early Blindness Revealed by Diffusion Tensor Tractography

The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. Diffusion MRI studies have revealed the efficient small-world properties and modular structure of the anatomical network in normal subjects. However, no previous study has used diffusion MRI to reveal changes in the brain anatomical network in early blindness. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 17 early blind subjects and 17 age- and gender-matched sighted controls. We established the existence of structural connections between any pair of the 90 cortical and sub-cortical regions using deterministic tractography. Compared with controls, early blind subjects showed a decreased degree of connectivity, a reduced global efficiency, and an increased characteristic path length in their brain anatomical network, especially in the visual cortex. Moreover, we revealed some regions with motor or somatosensory function have increased connections with other brain regions in the early blind, which suggested experience-dependent compensatory plasticity. This study is the first to show alterations in the topological properties of the anatomical network in early blindness. From the results, we suggest that analyzing the brain''s anatomical network obtained using diffusion MRI data provides new insights into the understanding of the brain''s re-organization in the specific population with early visual deprivation.     

Sensitive period for a multimodal response in human visual motion area MT/MST

The middle temporal complex (MT/MST) is a brain region specialized for the perception of motion in the visual modality. However, this specialization is modified by visual experience: after long-standing blindness, MT/MST responds to sound. Recent evidence also suggests that the auditory response of MT/MST is selective for motion. The developmental time course of this plasticity is not known. To test for a sensitive period in MT/MST development, we used fMRI to compare MT/MST function in congenitally blind, late-blind, and sighted adults. MT/MST responded to sound in congenitally blind adults, but not in late-blind or sighted adults, and not in an individual who lost his vision between ages of 2 and 3 years. All blind adults had reduced functional connectivity between MT/MST and other visual regions. Functional connectivity was increased between MT/MST and lateral prefrontal areas in congenitally blind relative to sighted and late-blind adults. These data suggest that early blindness affects the function of feedback projections from prefrontal cortex to MT/MST. We conclude that there is a sensitive period for visual specialization in MT/MST. During typical development, early visual experience either maintains or creates a vision-dominated response. Once established, this response profile is not altered by long-standing blindness.     

The Ferrier lecture, 1989. Outlooks for blindsight: explicit methodologies for implicit processes

In primates the retina is connected with different targets in the brain via several parallel pathways, the largest of which is that going to the lateral geniculate nucleus of the thalamus and thence to the striate cortex, the geniculo-striate pathway. When this route is damaged in man, apparent blindness in a corresponding part of the visual field occurs, despite the integrity of the other parallel pathways. In animals, it has been demonstrated by conventional behavioural forced-choice techniques that extrastriate routes can sustain a variety of visual discriminations. Comparable discriminations are also possible in some human subjects with geniculo-striate damage when forced-choice 'guessing' techniques are used. 'Blind-sight' refers to those subjects who state that they are unaware of the visual stimuli, even when performing discriminations at high levels of proficiency. Extensions of this approach are reviewed, especially to spectral sensitivity and movement discrimination. But residual capacities can also be assessed without requiring guessing responses, thereby avoiding issues of differential response criteria and other practical difficulties. Effects of 'unseen' stimuli in the cortically blind field on the visible perception of concurrent stimuli in the intact field can be measured. Also, positive reactions of the autonomic nervous system, such as the galvanic skin response, can be recorded to visual stimuli presented in the blind field. Recent evidence demonstrates that the pupil in normal adult subjects is systematically sensitive to structural and chromatic features of visual stimuli. Pupillometry reveals specific changes and residual capacities in visual-field defects of adult patients with striate cortical damage. Thus non-verbal and sensitive methods are available that permit the comparative study of normal and residual visual capacity in human infants, adults and infra-human animals.     

Central Nervous System Changes Related to the Reduction of Visual Input in a Naturally Blind Fish (Astyanax hubbsi)

Tectal anatomy and physiology of the blind cave characin, Astyanaxhubbsi, have been compared with that of its sighted ancestorAstyanax mexicanus (the river fish) and with goldfish. Normaland experimental neuroanatomic methods have revealed that, withthe exception of a greatly reduced retinotectal projection,connectivity and structure of cave fish tecta are similar tothose described in sighted species. It appears that the rudimentaryretinotectal input is nonfunctional, since no tectal evokedresponses could be elicited with electrical or visual stimulationof the optic cyst, and all attempts to visually condition cavefish were unsuccessful. Attempts have also been made to record somatosensory, auditoryand lateral line activity in the tecta of the blind and sightedfish. A sparse somatic representation was found in the deeperportion of the sighted fish tecta which contrasts with a dense,well-organized one in the cave fish. No tectal responses werefound to auditory or lateral line stimuli. CNS plasticity is discussed in relation to studies of fish,amphibians, reptiles, birds and mammals, in which a reductionof sensory input by any one of a number of means has resultedin alterations of structure and function.     

Superior Orthonasal but Not Retronasal Olfactory Skills in Congenital Blindness

Sight is undoubtedly important for finding and appreciating food, and cooking. Blind individuals are strongly impaired in finding food, limiting the variety of flavours they are exposed to. We have shown before that compared to sighted controls, congenitally blind individuals have enhanced olfactory but reduced taste perception. In this study we tested the hypothesis that congenitally blind subjects have enhanced orthonasal but not retronasal olfactory skills. Twelve congenitally blind and 14 sighted control subjects, matched in age, gender and body mass index, were asked to identify odours using grocery-available food powders. Results showed that blind subjects were significantly faster and tended to be better at identifying odours presented orthonasally. This was not the case when odorants were presented retronasally. We also found a significant group x route interaction, showing that although both groups performed better for retronasally compared to orthonasally presented odours, this gain was less pronounced for blind subjects. Finally, our data revealed that blind subjects were more familiar with the orthonasal odorants and used the retronasal odorants less often for cooking than their sighted counterparts. These results confirm that orthonasal but not retronasal olfactory perception is enhanced in congenital blindness, a result that is concordant with the reduced food variety exposure in this group.     

Element Distribution in Visual System,the Optic Chiasma,Lateral Geniculate Body,and Superior Colliculus

To elucidate compositional changes of the visual system with aging, the authors investigated age-related changes of elements in the optic chiasma, lateral geniculate body, and superior colliculus, relationships among their elements, relationships among their brain regions from a viewpoint of elements, and gender differences in their elements by direct chemical analysis. After ordinary dissection at Nara Medical University was finished, the optic chiasmas, lateral geniculate bodies, and superior colliculi were resected from identical cerebra of the subjects. The subjects consisted of 14 men and 10 women, ranging in age from 75 to 96 years (average age = 85.6 ± 5.9 years). After ashing with nitric acid and perchloric acid, element contents were determined by inductively coupled plasma-atomic emission spectrometry. As the result, the average content of P was significantly higher in the optic chiasma and superior colliculus compared with the lateral geniculate body. Regarding age-related changes of elements, no significant changes with aging were found in seven elements of the optic chiasma, lateral geniculate body, and superior colliculus in the subjects more than 75 years of age. The findings that with regard to the relationships among elements, there were extremely significant direct correlations between Ca and Zn contents and significant inverse correlations between Mg and Na contents were obtained in common in all of the optic chiasma, lateral geniculate body, and superior colliculus. It was examined whether there were significant correlations among the optic chiasma, lateral geniculate body, and superior colliculus in the seven elements and the following results were obtained: There were significant direct correlations between the optic chiasma and lateral geniculate body in both the P and Mg contents; there was a significant direct correlation between the optic chiasma and superior colliculus in the Fe content; and a significant direct correlation was found between the lateral geniculate body and superior colliculus in the Mg content. Regarding the gender differences in elements, it was found that both the Ca and Zn contents of the lateral geniculate body were significantly higher in women than in men.     

Rubber hands feel touch, but not in blind individuals

Psychology and neuroscience have a long-standing tradition of studying blind individuals to investigate how visual experience shapes perception of the external world. Here, we study how blind people experience their own body by exposing them to a multisensory body illusion: the somatic rubber hand illusion. In this illusion, healthy blindfolded participants experience that they are touching their own right hand with their left index finger, when in fact they are touching a rubber hand with their left index finger while the experimenter touches their right hand in a synchronized manner (Ehrsson et al. 2005). We compared the strength of this illusion in a group of blind individuals (n = 10), all of whom had experienced severe visual impairment or complete blindness from birth, and a group of age-matched blindfolded sighted participants (n = 12). The illusion was quantified subjectively using questionnaires and behaviorally by asking participants to point to the felt location of the right hand. The results showed that the sighted participants experienced a strong illusion, whereas the blind participants experienced no illusion at all, a difference that was evident in both tests employed. A further experiment testing the participants' basic ability to localize the right hand in space without vision (proprioception) revealed no difference between the two groups. Taken together, these results suggest that blind individuals with impaired visual development have a more veridical percept of self-touch and a less flexible and dynamic representation of their own body in space compared to sighted individuals. We speculate that the multisensory brain systems that re-map somatosensory signals onto external reference frames are less developed in blind individuals and therefore do not allow efficient fusion of tactile and proprioceptive signals from the two upper limbs into a single illusory experience of self-touch as in sighted individuals.     

Extra-visual functional and structural connection abnormalities in Leber's hereditary optic neuropathy

We assessed abnormalities within the principal brain resting state networks (RSNs) in patients with Leber's hereditary optic neuropathy (LHON) to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT) MRI data. Neuro-ophthalmologic assessment, DT MRI and RS fMRI data were acquired from 13 LHON patients and 13 healthy controls. RS fMRI data were analyzed using independent component analysis and SPM5. A DT MRI connectivity-based parcellation analysis was performed using the primary visual and auditory cortices, bilaterally, as seed regions. Compared to controls, LHON patients had a significant increase of RS fluctuations in the primary visual and auditory cortices, bilaterally. They also showed decreased RS fluctuations in the right lateral occipital cortex and right temporal occipital fusiform cortex. Abnormalities of RS fluctuations were correlated significantly with retinal damage and disease duration. The DT MRI connectivity-based parcellation identified a higher number of clusters in the right auditory cortex in LHON vs. controls. Differences of cluster-centroid profiles were found between the two groups for all the four seeds analyzed. For three of these areas, a correspondence was found between abnormalities of functional and structural connectivities. These results suggest that functional and structural abnormalities extend beyond the visual network in LHON patients. Such abnormalities also involve the auditory network, thus corroborating the notion of a cross-modal plasticity between these sensory modalities in patients with severe visual deficits.     

The effect of M-cholinolytics on the lability of rabbit visual analyzer structures]

The influence of M-cholinolytics (amizyl, glipine, cyclozyl and 4-oxypiperidylbenzylate) in 0.01--10 mg/kg doses on EEG and photic driving in structures of the visual analyser was studied in experiments on twenty intact rabbits with chronically implanted electrodes in the optic chiasm, the optic tract, the lateral geniculate body and the visual cortex. All M-cholinolitics in the doses studied produced synchronization of the EEG. Photic stimulation against the background of small doses of M-cholinolytics (0.01--0.5 mg/kg) did not lead to any disturbances of photic driving. With increased doses of cholinolitics up to 1--5 mg/kg only low frequencies (1--5 imp/sec) produced driving in the lateral geniculate body and the visual cortex, while in the optic tract the driving remained at the initial level. Administration of drugs in a 10 mg/kg dose resulted in complete depression of the driving response in the lateral geniculate body and visual cortex, while in the optic tract the driving was retained.     

Dolphin peripheral visual pathway in chronic unilateral ocular atrophy: Complete decussation apparent

Components of the peripheral visual pathway were examined in two bottlenose dolphins, Tursiops truncatus, each with unilateral ocular degeneration and scarring of 3 or more years' duration. In both animals, the optic nerve associated with the blind eye right eye in Tg419 and left eye in Tt038 had a translucent, gel-like appearance upon gross examination. This translucency was also evident in the optic tract contralateral to the affected eye. In Tg419, myelinated axons of varying diameters were apparent in the left optic nerve, whereas the right optic nerve, serving the blind eye, appeared to be devoid of axons. In Tt038, myelinated axons were associated with the right optic nerve (serving the functional eye) and left optic tract but were essentially absent in the left optic nerve and right optic tract. Examined by light microscopy in serial horizontal sections, the optic chiasm of Tt038 was arranged along its central plane in segregated, alternating pathways for the decussation of right and left optic nerve fibers. Ventral to this plane, the chiasm was comprised of fibers from the left optic nerve, whereas dorsal to the central plane, fibers derived from the right optic nerve. Because of this architectural arrangement, the right and left optic nerves grossly appeared to overlap as they crossed the optic chiasm with the right optic nerve coursing dorsally to the left optic nerve. At the light and electron microscopic levels, the optic nerves and tracts lacking axons were well vascularized and dominated by glial cell bodies and glial processes, an expression of the marked glial scarring associated with postinjury axonal degeneration. The apparent absence of axons in one of the optic tract pairs (right in Tt038 and left in Tg419) supports the concept of complete decussation of right and left optic nerve fibers at the optic chiasm in the bottlenose dolphin. © 1994 Wiley-Liss, Inc.     

Enriched Environment Protects the Optic Nerve from Early Diabetes-Induced Damage in Adult Rats

Diabetic retinopathy is a leading cause of reduced visual acuity and acquired blindness. Axoglial alterations of the distal (close to the chiasm) optic nerve (ON) could be the first structural change of the visual pathway in streptozotocin (STZ)-induced diabetes in rats. We analyzed the effect of environmental enrichment on axoglial alterations of the ON provoked by experimental diabetes. For this purpose, three days after vehicle or STZ injection, animals were housed in enriched environment (EE) or remained in a standard environment (SE) for 6 weeks. Anterograde transport, retinal morphology, optic nerve axons (toluidine blue staining and phosphorylated neurofilament heavy immunoreactivity), microglia/macrophages (ionized calcium binding adaptor molecule 1 (Iba-1) immunoreactivity), astrocyte reactivity (glial fibrillary acid protein-immunostaining), myelin (myelin basic protein immunoreactivity), ultrastructure, and brain derived neurotrophic factor (BDNF) levels were assessed in non-diabetic and diabetic animals housed in SE or EE. No differences in retinal morphology or retinal ganglion cell number were observed among groups. EE housing which did not affect the STZ-induced weight loss and hyperglycemia, prevented a decrease in the anterograde transport from the retina to the superior colliculus, ON axon number, and phosphorylated neurofilament heavy immunoreactivity. Moreover, EE housing prevented an increase in Iba-1 immunoreactivity, and astrocyte reactivity, as well as ultrastructural myelin alterations in the ON distal portion at early stages of diabetes. In addition, EE housing avoided a decrease in BDNF levels induced by experimental diabetes. These results suggest that EE induced neuroprotection in the diabetic visual pathway.     

Beyond Motor Scheme: A Supramodal Distributed Representation in the Action-Observation Network

The representation of actions within the action-observation network is thought to rely on a distributed functional organization. Furthermore, recent findings indicate that the action-observation network encodes not merely the observed motor act, but rather a representation that is independent from a specific sensory modality or sensory experience. In the present study, we wished to determine to what extent this distributed and ‘more abstract’ representation of action is truly supramodal, i.e. shares a common coding across sensory modalities. To this aim, a pattern recognition approach was employed to analyze neural responses in sighted and congenitally blind subjects during visual and/or auditory presentation of hand-made actions. Multivoxel pattern analyses-based classifiers discriminated action from non-action stimuli across sensory conditions (visual and auditory) and experimental groups (blind and sighted). Moreover, these classifiers labeled as ‘action’ the pattern of neural responses evoked during actual motor execution. Interestingly, discriminative information for the action/non action classification was located in a bilateral, but left-prevalent, network that strongly overlaps with brain regions known to form the action-observation network and the human mirror system. The ability to identify action features with a multivoxel pattern analyses-based classifier in both sighted and blind individuals and independently from the sensory modality conveying the stimuli clearly supports the hypothesis of a supramodal, distributed functional representation of actions, mainly within the action-observation network.     

Retinal axon pathfinding in the optic chiasm: divergence of crossed and uncrossed fibers

In the developing mammalian visual system, retinal fibers grow through the optic chiasm, where one population crosses to the opposite side of the brain and the other does not. Evidence from labeling growing retinal axons with the carbocyanine dye Dil in mouse embryos indicates that the two subpopulations diverge at a zone along the midline of the optic chiasm. At the border of this zone, crossed fibers grow directly across, whereas uncrossed fibers turn back, developing highly complex terminations with bifurcating and wide-ranging growth cones. When one eye is removed at early stages, uncrossed fibers from the remaining eye stall at the chiasm midline. These results suggest that crossed and uncrossed retinal fibers respond differently to cues along the midline of the chiasm and that the uncrossed fibers from one eye grow along crossed fibers from the other eye, both guidance mechanisms contributing to the establishment of the bilateral pattern of visual projections in mammalian brain.     

Visual specialization and brain evolution in primates.

Several theories have been proposed to explain the evolution of species differences in brain size, but no consensus has emerged. One unresolved question is whether brain size differences are a result of neural specializations or of biological constraints affecting the whole brain. Here I show that, among primates, brain size variation is associated with visual specialization. Primates with large brains for their body size have relatively expanded visual brain areas, including the primary visual cortex and lateral geniculate nucleus. Within the visual system, it is, in particular, one functionally specialized pathway upon which selection has acted: evolutionary changes in the number of neurons in parvocellular, but not magnocellular, layers of the lateral geniculate nucleus are correlated with changes in both brain size and ecological variables (diet and social group size). Given the known functions of the parvocellular pathway, these results suggest that the relatively large brains of frugivorous species are products of selection on the ability to perceive and select fruits using specific visual cues such as colour. The separate correlation between group size and visual brain evolution, on the other hand, may indicate the visual basis of social information processing in the primate brain.     

Visual deprivation modifies oscillatory activity in visual and auditory centers

Loss of vision may enhance the capabilities of auditory perception, but the mechanisms mediating these changes remain elusive. Here, visual deprivation in rats resulted in altered oscillatory activities, which appeared to be the result of a common mechanism underlying neuronal assembly formation in visual and auditory centers. The power of high-frequency β and γ oscillations in V1 (the primary visual cortex) and β oscillations in the LGN (lateral geniculate nucleus) was increased after one week of visual deprivation. Meanwhile, the power of β oscillations in A1 (the primary auditory cortex) and the power of β and γ oscillations in the MGB (medial geniculate body) were also enhanced in the absence of visual input. Furthermore, nerve tracing revealed a bidirectional nerve fiber connection between V1 and A1 cortices, which might be involved in transmitting auditory information to the visual cortex, contributing to enhanced auditory perception after visual deprivation. These results may facilitate the better understanding of multisensory cross-modal plasticity.     

Does Shape Discrimination by the Mouth Activate the Parietal and Occipital Lobes? – Near-Infrared Spectroscopy Study

A cross-modal association between somatosensory tactile sensation and parietal and occipital activities during Braille reading was initially discovered in tests with blind subjects, with sighted and blindfolded healthy subjects used as controls. However, the neural background of oral stereognosis remains unclear. In the present study, we investigated whether the parietal and occipital cortices are activated during shape discrimination by the mouth using functional near-infrared spectroscopy (fNIRS). Following presentation of the test piece shape, a sham discrimination trial without the test pieces induced posterior parietal lobe (BA7), extrastriate cortex (BA18, BA19), and striate cortex (BA17) activation as compared with the rest session, while shape discrimination of the test pieces markedly activated those areas as compared with the rest session. Furthermore, shape discrimination of the test pieces specifically activated the posterior parietal cortex (precuneus/BA7), extrastriate cortex (BA18, 19), and striate cortex (BA17), as compared with sham sessions without a test piece. We concluded that oral tactile sensation is recognized through tactile/visual cross-modal substrates in the parietal and occipital cortices during shape discrimination by the mouth.