Early Blindness Research Articles

Congenital Anophthalmia and Binocular Neonatal Enucleation Differently Affect the Proteome of Primary and Secondary Visual Cortices in Mice.

In blind individuals, visually deprived occipital areas are activated by non-visual stimuli. The extent of this cross-modal activation depends on the age at onset of blindness. Cross-modal inputs have access to several anatomical pathways to reactivate deprived visual areas. Ectopic cross-modal subcortical connections have been shown in anophthalmic animals but not in animals deprived of sight at a later age. Direct and indirect cross-modal cortical connections toward visual areas could also be involved, yet the number of neurons implicated is similar between blind mice and sighted controls. Changes at the axon terminal, dendritic spine or synaptic level are therefore expected upon loss of visual inputs. Here, the proteome of V1, V2M and V2L from P0-enucleated, anophthalmic and sighted mice, sharing a common genetic background (C57BL/6J x ZRDCT/An), was investigated by 2-D DIGE and Western analyses to identify molecular adaptations to enucleation and/or anophthalmia. Few proteins were differentially expressed in enucleated or anophthalmic mice in comparison to sighted mice. The loss of sight affected three pathways: metabolism, synaptic transmission and morphogenesis. Most changes were detected in V1, followed by V2M. Overall, cross-modal adaptations could be promoted in both models of early blindness but not through the exact same molecular strategy. A lower metabolic activity observed in visual areas of blind mice suggests that even if cross-modal inputs reactivate visual areas, they could remain suboptimally processed.

Early Blindness Results in Developmental Plasticity for Auditory Motion Processing within Auditory and Occipital Cortex.

Early blind subjects exhibit superior abilities for processing auditory motion, which are accompanied by enhanced BOLD responses to auditory motion within hMT+ and reduced responses within right planum temporale (rPT). Here, by comparing BOLD responses to auditory motion in hMT+ and rPT within sighted controls, early blind, late blind, and sight-recovery individuals, we were able to separately examine the effects of developmental and adult visual deprivation on cortical plasticity within these two areas. We find that both the enhanced auditory motion responses in hMT+ and the reduced functionality in rPT are driven by the absence of visual experience early in life; neither loss nor recovery of vision later in life had a discernable influence on plasticity within these areas. Cortical plasticity as a result of blindness has generally be presumed to be mediated by competition across modalities within a given cortical region. The reduced functionality within rPT as a result of early visual loss implicates an additional mechanism for cross modal plasticity as a result of early blindness—competition across different cortical areas for functional role.

From auditory focus, to auditory influence, to multimodal experience in psychomusicological research.

Psychomusicology: Music, Mind and Brain Volume 26 is pleased to add to its growing collection of special issues the following special issue on Music as a Multimodal Experience coedited by Renee Timmers and Roni Granot. When research in music psychology began to escalate in the 1980s, its focus was primarily the auditory domain, building bridges between psychoacoustics and music perception, between music theory and music cognition, and between verbal and music memory. Perhaps this was all that researchers could do to encourage recognition of music as a legitimate stimulus deserving of attention in the psychology laboratory. In 1994, Volume 13 of Psychomusicology made a radical departure from this sound-only focus with its special issue on the Psychology of Film Music. For the first time, a collection of empirical articles explored a link between music and a nonauditory domain. That set of papers examined in a variety of contexts how music influenced the interpretation of motion images, be it closure in a film (Thompson, Russo, & Sinclair, 1994), meaning of a Hollywood blockbuster (Lipscomb & Kendall, 1994), the social interactions of wolves (Bolivar, Cohen, & Fentress, 1994), a short feature film (Bullerjahn & Guldenring, 1994), a music video (Iwamiya, 1994), or an abstract animation (Sirius & Clarke, 1994). A growing interest in music and film or media interactions since then has been captured in a book entitled the Psychology of Music in Multimedia (Tan, Cohen, Lipscomb, & Kendall, 2013). But here again, the focus has been typically on interpretation: how music changes the interpretation of visual media, and occasionally, how visual information changes the interpretation of the music (Boltz, 2013).In recent years the notion of musical embodiment has engaged the attention of many researchers (Leman, 2008, reviewed by Repp, 2009), although hints of this certainly came earlier, for example with Clarke's (2001, 2005) focus on affordances and motion, and long before in the little known work of Alexandar Truslit (cf. Haverkamp, 2013a; Repp, 1993). Research on synesthesia is also only now coming into its own (Ward, 2015; Ward & Mattingley, 2006). Ideas of musical embodiment on the one hand and synesthesia on the other go beyond interactions of music and the visual, and suggest that the experience of music extends outside the auditory realm from the outset, and that it is inherently multimodal. From this perspective, music is then even larger than was once thought, by virtue of multiple mediators. So I was delighted to learn from the journal's Associate Editor Renee Timmers of an International Conference on the Multimodal Experience of Music at Sheffield University in March, 2015 that she initiated under the auspices of the British Academy, through a collaboration of the University of Sheffield, Tel Aviv University, and The Hebrew University of Jerusalem. I was even more delighted when Renee suggested the possibility of a special issue for Psychomusicology based on the conference. Renee had just completed coediting an insightful book on expressiveness in human performance (Fabian, Timmers, & Schubert, 2014; for review see Ginsborg, 2015) and had guest coedited a special issue of Psychomusicology on the Emotion and Cognition of Music (Coutinho & Timmers, 2014). She had previously published in the area of crossmodal associations (Eitan & Timmers, 2010), and was about to begin a fellowship at the MARCS Institute of the University of Western Sydney examining the role of cross-modal information in interperformer synchronization. Clearly, the proposed special issue would be in good hands, especially when Roni Granot accepted Renee's invitation to serve as Guest Coeditor. Roni Granot had published research on several new aspects of the multimodal experience of music including cross-domain mappings of music in persons with congenital or early blindness (Eitan, Ornoy, & Granot, 2012), and on the ways listeners associate changes in musical variables with physical space and bodily motion (Eitan & Granot, 2006). …

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

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

Transcranial magnetic stimulation of the visual cortex in congenital blindness

Event Abstract Back to Event Transcranial magnetic stimulation of the visual cortex in congenital blindness Maurice Ptito1, 2* and Ron Kupers1, 2 1 Université de Montreal, School of Optometry, Canada 2 University of Copenhagen, Neuroscience and Pharmacology, Denmark Introduction: For human and non-human primates, vision is one of the most privileged sensory channels used to interact with the environment. The importance of vision is strongly embedded in the organization of the brain as about one third of its cortical surface is involved in visual functions. It is therefore not surprising that the absence of vision from birth, or the loss of vision later in life, has huge consequences, both anatomically and functionally. We have shown in previous studies that, although, the visual system is largely atrophied by the loss of vision at birth, it is nonetheless present and can be activated by a variety of non-visual stimuli such as touch, audition and even smell. We present here a series of behavioral and brain imaging studies showing that the congenitally blind brain is capable of cross-modal plasticity and sensory substitution. Methods and results We recently showed that the occipital lobe of blind individuals is reduced in volume (whole brain Voxel Based Morphometry-VBM) (Ptito et al., 2008), has an increased cortical thickness (FreeSurfer and CIVET) and shows a supra-metabolic activity as revealed by fluoro-desoxy-glucose (18FDG-PET) (Kupers and Ptito, 2014) (Figure 1A, B, C respectively). Moreover, other non-visual structures in the blind brain were affected by early visual deprivation such as the posterior part of the right hippocampus (Chebat et al., 2007) and the splenium of the corpus callosum (Tomaiuolo et al., 2014), both regions showing a volumetric reduction. Figure 1. Structural and metabolic changes in the congenitally blind brain We used, in a series of experiments, a sensory substitution device coined the Tongue Display Unit or TDU. This apparatus translates an image grabbed by a camera into electrotactile pulses administered to the tongue via a grid of electrodes (Figure 2A). Figure 2. The tongue Display Unit (TDU) Congenitally blind (CB) subjects equipped with the TDU can learn to discriminate the orientation of a bar, discriminate motion and shapes (Ptito et al., 2009, 2012; Matteau et al., 2010). To do so, they activate regions of the brain that are visual in nature namely the visual cortex and the ventral and dorsal streams as revealed with functional Resonance Imaging (Figure 1B) (reviewed in Kupers and Ptito, 2014). Moreover the TDU has been successfully used as a navigation tool. CB individuals were able to point to, recognize and avoid obstacles while walking in a corridor (Chebat et al., 2011). Tested in an fMRI scanner in a virtual route recognition task, CB participants recruited not only their visual cortex but also the parahippocampal region, areas usually activated during topographical learning and spatial representation in sighted subjects (Kupers et al., 2010). To test for the functional role of visual cortical areas in blind, we used trans-cranial magnetic stimulation (TMS). Short repetitive TMS bursts applied over the mid-occipital cortex of the blind interfere with repetition priming effects of a list of words presented several times. Moreover, rTMS over the motion cortical area, which is part of the dorsal visual stream (area hMT+), induces an increase in the reaction times to moving stimuli in blind subjects only. We tested for the subjective experience associated with the activation of the visual cortex. While control seeing-subjects experienced visual phosphenes, blind participants reported parasthesiae (tingling sensations) either on the tongue or the fingers (figure 3). Finally, using somesthesic evoked potentials following learning with the TDU, we were able to show that the information originating in area SI was transferred to the primary visual cortex of the blind through increased cortico-cortical projections. Figure 3. TMS of the occipital cortex of blind subjects can induce tactile sensations referred to the tongue (A) and fingers (B). Conclusions The results obtained from this series of studies have valuable information on the nature of the plastic processes that take place in early blindness and might lead to the development of a new multisensory device that will use non-visual modalities to funnel sensory information to the visual cortex of the blind and help them “see”. Figure 1 Figure 2 Figure 3 Acknowledgements The authors are indebted to these Foundations for their their generous support: The Harland Sanders Foundation (Canada), the Lundbeck Foundation (Denmark) and The Danish Medical Research Council FSS, Denmark).

Screening for mutations in RPGR and RP2 genes in Jordanian families with X-linked retinitis pigmentosa.

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous disease causing progressive degeneration of retinal photoreceptor cells. X-linked RP (XLRP), in which photoreceptor degeneration begins in early childhood and complete blindness often occurs by the fourth decade of life, constitutes the most severe form of this disease. Two genes commonly associated with XLRP have previously been cloned: retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (RP2). We sought to identify mutations in these genes in Jordanian families suffering from this disease. Five unrelated Jordanian families with confirmed XLRP were screened for such mutations using direct sequencing. Three mutations were identified in the ORF15 exon of RPGR. The silent g.ORF15+470G>A substitution and the g.ORF15+1822insA insertion in the 3ꞌ-untranslated region were found in both normal and affected male family members at comparable frequencies, and thus were considered normal variants. The third mutation, g.ORF15+588G>A, in which alanine is substituted by threonine, was found in all affected men and one unaffected man in the two families harboring this variant. Thus, this mutation may be pathogenic, but with incomplete penetrance. No RP2 mutations were found among the examined families. Mutation screening of RP patients is essential to understand the mechanism behind this disease and develop treatments. A complete family history is required to identify its inheritance pattern and provide genetic counseling for patients and their families.

Pituitary morphovolumetric changes in Alström syndrome

Alström syndrome (AS) is a rare monogenic ciliopathy characterized by cone-code dystrophy, leading to early blindness, and obesity. Early endocrinological dysfunctions, especially growth hormone deficiency and hypogonadism, are detected in about half of AS patients. This MRI study investigates the presence of pituitary gland abnormalities in a large cohort of AS patients. Pituitary morphological changes (gland flattening with partial or total empty sella) were evaluated on midsagittal high-resolution T1-weighted images of 32 AS patients (mean-age 23.2±9.4 years; range: 6-45, 15 females) and 21 unrelated healthy subjects (mean age 23.2±11.2 years; range: 6-43; 10 females). Among AS patients, 11/32 (34%) had total empty sella and 6/32 (19%) partial empty sella, while 3/21 (14%) of controls had partial empty sella and none presented with total empty sella (P<0.005). AS patients harboring a total or partial empty sella did not differ from those with normal pituitary gland for gender (P=0.98), BMI (P=0.10) or visual impairment (P=0.21), while the presence of empty sella was associated with an older age (P=0.007) being especially frequent above the age of 30. Total or partial empty sella appears commonly during the course of AS. Pituitary gland flattening might represent the morphological underpinning of subtle endocrinologic dysfunctions and raises the need to further investigate the pituitary function in this rare ciliopathy.

Neuroplasticity: Unexpected Consequences of Early Blindness

A pair of recent studies shows that congenital blindness can have significant consequences for the functioning of the visual system after sight restoration, particularly if that restoration is delayed.

Theory-of-mind in individuals with Alström syndrome is related to executive functions, and verbal ability.

Objective: This study focuses on cognitive prerequisites for the development of theory-of-mind (ToM), the ability to impute mental states to self and others in young adults with Alström syndrome (AS). AS is a rare and quite recently described recessively inherited ciliopathic disorder which causes progressive sensorineural hearing loss and juvenile blindness, as well as many other organ dysfunctions. Two cognitive abilities were considered; Phonological working memory (WM) and executive functions (EF), both of importance in speech development.Methods: Ten individuals (18–37 years) diagnosed with AS, and 20 individuals with no known impairment matched for age, gender, and educational level participated. Sensory functions were measured. Information about motor functions and communicative skills was obtained from responses to a questionnaire. ToM was assessed using Happés strange stories, verbal ability by a vocabulary test, phonological WM by means of an auditory presented non-word serial recall task and EF by tests of updating and inhibition.Results: The AS group performed at a significantly lower level than the control group in both the ToM task and the EF tasks. A significant correlation was observed between recall of non-words and EF in the AS group. Updating, but not inhibition, correlated significantly with verbal ability, whereas both updating and inhibition were significantly related to the ability to initiate and sustain communication. Poorer performance in the ToM and EF tasks were related to language perseverance and motor mannerisms.Conclusion: The AS group displayed a delayed ToM as well as reduced phonological WM, EF, and verbal ability. A significant association between ToM and EF, suggests a compensatory role of EF. This association may reflect the importance of EF to perceive and process input from the social environment when the social interaction is challenged by dual sensory loss. We argue that limitations in EF capacity in individuals with AS, to some extent, may be related to early blindness and progressive hearing loss, but maybe also to gene specific abnormalities.

Frequency-tuned auditory motion responses within hMT+ as a result of early blindness

Frequency-tuned auditory motion responses within hMT+ as a result of early blindness

Dimerization Domain of Retinal Membrane Guanylyl Cyclase 1 (RetGC1) Is an Essential Part of Guanylyl Cyclase-activating Protein (GCAP) Binding Interface

The photoreceptor-specific proteins guanylyl cyclase-activating proteins (GCAPs) bind and regulate retinal membrane guanylyl cyclase 1 (RetGC1) but not natriuretic peptide receptor A (NPRA). Study of RetGC1 regulation in vitro and its association with fluorescently tagged GCAP in transfected cells showed that R822P substitution in the cyclase dimerization domain causing congenital early onset blindness disrupted RetGC1 ability to bind GCAP but did not eliminate its affinity for another photoreceptor-specific protein, retinal degeneration 3 (RD3). Likewise, the presence of the NPRA dimerization domain in RetGC1/NPRA chimera specifically disabled binding of GCAPs but not of RD3. In subsequent mapping using hybrid dimerization domains in RetGC1/NPRA chimera, multiple RetGC1-specific residues contributed to GCAP binding by the cyclase, but the region around Met(823) was the most crucial. Either positively or negatively charged residues in that position completely blocked GCAP1 and GCAP2 but not RD3 binding similarly to the disease-causing mutation in the neighboring Arg(822). The specificity of GCAP binding imparted by RetGC1 dimerization domain was not directly related to promoting dimerization of the cyclase. The probability of coiled coil dimer formation computed for RetGC1/NPRA chimeras, even those incapable of binding GCAP, remained high, and functional complementation tests showed that the RetGC1 active site, which requires dimerization of the cyclase, was formed even when Met(823) or Arg(822) was mutated. These results directly demonstrate that the interface for GCAP binding on RetGC1 requires not only the kinase homology region but also directly involves the dimerization domain and especially its portion containing Arg(822) and Met(823).

The effects of lifelong blindness on murine neuroanatomy and gene expression.

Mammalian neocortical development is regulated by neural patterning mechanisms, with distinct sensory and motor areas arising through the process of arealization. This development occurs alongside developing central or peripheral sensory systems. Specifically, the parcellation of neocortex into specific areas of distinct cytoarchitecture, connectivity and function during development is reliant upon both cortically intrinsic mechanisms, such as gene expression, and extrinsic processes, such as input from the sensory receptors. This developmental program shifts from patterning to maintenance as the animal ages and is believed to be active throughout life, where the brain’s organization is stable yet plastic. In this study, we characterize the long-term effects of early removal of visual input via bilateral enucleation at birth. To understand the long-term effects of early blindness we conducted anatomical and molecular assays 18 months after enucleation, near the end of lifespan in the mouse. Bilateral enucleation early in life leads to long-term, stable size reductions of the thalamic lateral geniculate nucleus (LGN) and the primary visual cortex (V1) alongside a increase in individual whisker barrel size. Neocortical gene expression in the aging brain has not been previously identified; we document cortical expression of multiple regionalization genes. Expression patterns of Ephrin A5, COUP-TFI, and RZRβ and patterns of intraneocortical connectivity (INC) are altered in the neocortices of aging blind mice. Sensory inputs from different modalities during development likely play a major role in the development of cortical areal and thalamic nuclear boundaries. We suggest that early patterning by prenatal retinal activity combined with persistent gene expression within the thalamus and cortex is sufficient to establish and preserve a small but present LGN and V1 into late adulthood.

Characterization of Leber Congenital Amaurosis-associated NMNAT1 Mutants

Leber congenital amaurosis 9 (LCA9) is an autosomal recessive retinal degeneration condition caused by mutations in the NAD(+) biosynthetic enzyme NMNAT1. This condition leads to early blindness but no other consistent deficits have been reported in patients with NMNAT1 mutations despite its central role in metabolism and ubiquitous expression. To study how these mutations affect NMNAT1 function and ultimately lead to the retinal degeneration phenotype, we performed detailed analysis of LCA-associated NMNAT1 mutants, including the expression, nuclear localization, enzymatic activity, secondary structure, oligomerization, and promotion of axonal and cellular integrity in response to injury. In many assays, most mutants produced results similar to wild type NMNAT1. Indeed, NAD(+) synthetic activity is unlikely to be a primary mechanism underlying retinal degeneration as most LCA-associated NMNAT1 mutants had normal enzymatic activity. In contrast, the secondary structure of many NMNAT1 mutants was relatively less stable as they lost enzymatic activity after heat shock, whereas wild type NMNAT1 retains significant activity after this stress. These results suggest that LCA-associated NMNAT1 mutants are more vulnerable to stressful conditions that lead to protein unfolding, a potential contributor to the retinal degeneration observed in this syndrome.

Aspects of learning from the perspective of people with Alström syndrome

Purpose: The aim of the study was to explore aspects of learning, from a lifelong perspective, in individuals with Alström syndrome (AS). AS is an autosomal recessive disorder causing early blindness, progressive sensorineural hearing loss, cardiomyopathy, endocrine disorders, metabolic dysfunction, and abbreviated lifespan. Method: Eleven individuals with AS participated. The study had a qualitative explorative design, giving voice to the participants’ perspectives on their situation. Data were collected using semi-structured interviews, which were subjected to conventional (inductive) qualitative content analysis. Results: The analysis revealed in the participants a quest for independence and an image of themselves as capable people willing to learn, but in constant need of support to continue learning throughout their lives to be as independent as possible. Conclusion: Based on the levels of functioning, i.e. personal resources, revealed in the interviews, supervisors, caregivers, and teachers are encouraged to allow people with AS to be their own advocates, as they know best how, what, and with whom they learn, and what type of sensory material – tactile, auditory, visual, or a combination – is most helpful.Implications for RehabilitationIndividuals with AS strive for independence, and to be independent they need to continue to learn throughout their lives.Individuals with AS know best how they learn, and should be asked what modalities are the most effective for them.The tactile modality for learning will continue throughout life and should be emphasized early in the individual’s education and rehabilitation.

Alström Syndrome: Mutation Spectrum of ALMS1.

Alström Syndrome (ALMS), a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically characterized by multisystem involvement including early cone-rod retinal dystrophy and blindness, hearing loss, childhood obesity, type 2 diabetes mellitus, cardiomyopathy, fibrosis, and multiple organ failure. The precise function of ALMS1 remains elusive, but roles in endosomal and ciliary transport and cell cycle regulation have been shown. The aim of our study was to further define the spectrum of ALMS1 mutations in patients with clinical features of ALMS. Mutational analysis in a world-wide cohort of 204 families identified 109 novel mutations, extending the number of known ALMS1 mutations to 239 and highlighting the allelic heterogeneity of this disorder. This study represents the most comprehensive mutation analysis in patients with ALMS, identifying the largest number of novel mutations in a single study worldwide. Here, we also provide an overview of all ALMS1 mutations identified to date.

Functional plasticity of the visual system in multiple sclerosis.

OPINION article Front. Neurol., 08 April 2015Sec. Multiple Sclerosis and Neuroimmunology Volume 6 - 2015 | https://doi.org/10.3389/fneur.2015.00079

Subcortical functional reorganization due to early blindness.

Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses.

Congenital blindness affects diencephalic but not mesencephalic structures in the human brain.

While there is ample evidence that the structure and function of visual cortical areas are affected by early visual deprivation, little is known of how early blindness modifies subcortical relay and association thalamic nuclei, as well as mesencephalic structures. Therefore, in the present multicenter study, we used MRI to measure volume of the superior and inferior colliculi, as well as of the thalamic nuclei relaying sensory and motor information to the neocortex, parcellated according to atlas-based thalamo-cortical connections, in 29 individuals with congenital blindness of peripheral origin (17 M, age 35.7 ± 14.3 years) and 29 sighted subjects (17 M, age 31.9 ± 9.0). Blind participants showed an overall volume reduction in the left (p = 0.008) and right (p = 0.007) thalami, as compared to the sighted individuals. Specifically, the lateral geniculate (i.e., primary visual thalamic relay nucleus) was 40% reduced (left: p = 4 × 10(-6), right: p < 1 × 10(-6)), consistent with findings from animal studies. In addition, associated thalamic nuclei that project to temporal (left: p = 0.005, right: p = 0.005), prefrontal (left: p = 0.010, right: p = 0.014), occipital (left: p = 0.005, right: p = 0.023), and right premotor (p = 0.024) cortical regions were also significantly reduced in the congenitally blind group. Conversely, volumes of the relay nuclei directly involved in auditory, motor, and somatosensory processing were not affected by visual deprivation. In contrast, no difference in volume was observed in either the superior or the inferior colliculus between the two groups. Our findings indicate that visual loss since birth leads to selective volumetric changes within diencephalic, but not mesencephalic, structures. Both changes in reciprocal cortico-thalamic connections or modifications in the intrinsic connectivity between relay and association nuclei of the thalamus may contribute to explain these alterations in thalamic volumes. Sparing of the superior colliculi is in line with their composite, multisensory projections, and with their not exclusive visual nature.

Anatomical and functional plasticity in early blind individuals and the mixture of experts architecture.

As described elsewhere in this special issue, recent advances in neuroimaging over the last decade have led to a rapid expansion in our knowledge of anatomical and functional correlations within the normal and abnormal human brain. Here, we review how early blindness has been used as a model system for examining the role of visual experience in the development of anatomical connections and functional responses. We discuss how lack of power in group comparisons may provide a potential explanation for why extensive anatomical changes in cortico-cortical connectivity are not observed. Finally we suggest a framework—cortical specialization via hierarchical mixtures of experts—which offers some promise in reconciling a wide range of functional and anatomical data.

Schizophrenia and cortical blindness: protective effects and implications for language.

The repeatedly noted absence of case-reports of individuals with schizophrenia and congenital/early developed blindness has led several authors to argue that the latter can confer protective effects against the former. In this work, we present a number of relevant case-reports from different syndromes that show comorbidity of congenital and early blindness with schizophrenia. On the basis of these reports, we argue that a distinction between different types of blindness in terms of the origin of the visual deficit, cortical or peripheral, is crucial for understanding the observed patterns of comorbidity. We discuss the genetic underpinnings and the brain structures involved in schizophrenia and blindness, with insights from language processing, laying emphasis on the three structures that particularly stand out: the occipital cortex, the lateral geniculate nucleus (LGN), and the pulvinar. Last, we build on previous literature on the nature of the protective effects in order to offer novel insights into the nature of the protection mechanism from the perspective of the brain structures involved in each type of blindness.