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In JoVE (5)
- Dissecando o cérebro do primata não-humano no espaço estereotáxico
- Banking cérebro: Fazer oa maioria de espécimes sua Pesquisa
- A entrada para o cérebro: Dissecando o olho Primaz
- Sabendo o que conta: Estereologia Imparcial no cérebro de primatas não humanos
- A imunocoloração lote de Grande Escala da detecção de proteínas no cérebro do macaco inteiro
Other Publications (33)
- Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
- Neuroreport
- NeuroImage
- Visual Neuroscience
- Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
- Archives of Neurology
- Brain : a Journal of Neurology
- Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
- Journal of Chemical Neuroanatomy
- NeuroImage
- Journal of Integrative Neuroscience
- Proceedings of the National Academy of Sciences of the United States of America
- The Journal of Comparative Neurology
- Neuroreport
- Neuroreport
- Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
- Experimental Neurology
- Neuroreport
- Neuroreport
- Neuroscience Letters
- Brain Injury : [BI]
- Brain Research Bulletin
- NeuroImage
- Proceedings of the National Academy of Sciences of the United States of America
- Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
- Neuroreport
- Brain Research Bulletin
- The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
- NeuroImage
- NeuroImage
- Neuroreport
- Frontiers in Psychology
- Progress in Brain Research
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Articles by Maurice Ptito in JoVE
JoVE General
Dissecando o cérebro do primata não-humano no espaço estereotáxico
1Department of Physiology, University of Montreal, 2School of Optometry, University of Montreal, 3Département de chimie-biologie , Université du Québes à Trois-Rivières
O primata não-humano é uma importante espécie de translação para a nossa compreensão do processamento normal do cérebro. A organização anatômica do cérebro dos primatas podem fornecer importantes insights sobre condições normais e patológicas nos seres humanos.
JoVE General
Banking cérebro: Fazer oa maioria de espécimes sua Pesquisa
1Department of Physiology, University of Montreal, 2School of Optometry, University of Montreal
Bancário cérebro e amostragem sistemática de material biológico fornece a base para estereologia imparcial e maximiza o potencial de dados obtidos de cada espécime.
JoVE General
A entrada para o cérebro: Dissecando o olho Primaz
1Department of Physiology, University of Montreal, 2School of Optometry, University of Montreal, 3Departement de chimie-biologie, Universite du Quebec a Trois-Rivieres
O primata não-humano é uma importante espécie de translação para a nossa compreensão do desenvolvimento e envelhecimento. A organização anatômica da retina de primatas pode fornecer importantes insights sobre condições normais e patológicas nos seres humanos.
JoVE General
Sabendo o que conta: Estereologia Imparcial no cérebro de primatas não humanos
1Department of Physiology, University of Montreal, 2Ecole d’optometrie, University of Montreal, 3Stereology Resource Center
A organização anatômica do cérebro dos primatas podem fornecer importantes insights sobre condições normais e patológicas nos seres humanos. Estereologia imparcial é um método para estimar com precisão e eficiência o número de neurônios total (ou outro tipo de célula) em um espaço de referência dado
JoVE General
A imunocoloração lote de Grande Escala da detecção de proteínas no cérebro do macaco inteiro
1Cognitive Neuroscience Unit, Montreal Neurological Institute, 2Ècole d’Optomètrie, Universitè de Montrèal, 3Department of Psychology, McGill University
Grande escala imunodetecção de proteínas-alvo em todo o cérebro dos primatas é possível através do emprego de tecido romance incorporação e secção métodos combinados com o uso de aparelhos criativas para a coloração de vários lotes de livre flutuação seções em um determinado momento.
Other articles by Maurice Ptito on PubMed
Stereological Evaluation of Neurons and Glia in the Monkey Dorsal Lateral Geniculate Nucleus Following an Early Cerebral Hemispherectomy
The effects of an early, unilateral cerebral hemispherectomy on the cytoarchitecture of the dorsal lateral geniculate nucleus (dLGN) were quantitatively evaluated in the green monkey. The dLGN ipsilateral to the lesion showed a 73% reduction in size, more than 99% neuronal cell loss, 50% increase in glial cell density, but a 50% reduction in the total number of glial cells. The total number of neural and glial cells estimated for the dLGN contralateral to the ablation did not differ from control values. Despite evidence for substantial degeneration of the ipsilateral dLGN, cytochrome oxidase histochemistry revealed a small population of surviving cells that exhibited features of neuronal cells. More surviving cells were found in the parvocellular than in the magnocellular layers, and surviving parvocellular cells had the same size-frequency distribution as Nissl-stained neurons in an intact animal. These findings suggest that the intrinsic geniculate circuitry may be able to sustain the residual interneurons that can, in turn, contribute to maintaining retinal and brainstem afferents. The remaining neurons in the dLGN following hemispherectomy appear to be insufficient in number to be importantly implicated in the residual visual functions that have been reported in some hemispherectomized patients.
Cortical Areas Mediating Stereopsis in the Human Brain: a PET Study
Using PET, we investigated the neural substrates of stereodepth perception in humans. The presentation of Julesz-type random-dot stereograms (RDS) produced significant rCBF elevations in Brodmann areas (BA) 18, 19 and 7, all in the right hemisphere. Activation foci were also found in both middle temporal areas (MT). These results demonstrate that, as in primates, cortical area MT and extrastriate areas are central to stereovision and that a network of predominant right hemispheric regions is recruited to meet visuo-spatial processing demands associated with horizontal binocular disparity inputs.
Separate Neural Pathways for Contour and Biological-motion Cues in Motion-defined Animal Shapes
To determine whether contour and biological motion (BM) cues for motion-defined shapes are subserved by two separate mechanisms, we used PET to measure regional cerebral blood flow in nine human subjects. Subjects were scanned in the following four conditions: (1) contour-defined animals with natural movements (running), (2) motion-defined animals in which the contours were removed and dots were placed on the limbs and moving parts (BM; running); (3) drifting static animal shapes (contours); and (4) drifting dots. The results demonstrate that the perception of BM involves the superior frontal gyrus, the precuneus, the fusiform, the lingual and the medial temporal gyri, the inferior parietal lobe, the hippocampal and parahippocampal areas, and the cerebellum. In addition, the anterior cingulate cortex and the amygdala were significantly activated. The perception of contour-defined shapes produced significant elevation of rCBF in some areas similar to the BM condition, namely the fusiform, medial occipital, medial temporal, and lingual gyri. Only the occipital pole and the inferior temporal cortex were specifically activated by contour-defined shapes. These results are congruent with previous findings that the dorsal visual pathway is important for the perception of BM. They further support psychophysical results showing that contour and BM cues for motion-defined animal shapes are processed by independent channels.
Retinal Projections in the Cat: a Cholera Toxin B Subunit Study
The B fragment of cholera toxin (CTb) is a highly sensitive anterograde tracer for the labelling of retinal axons. It can reveal dense retinofugal projections to well-known retinorecipient nuclei along with sparse but distinct input to target areas that are not commonly recognized. Following a unilateral injection of CTb into the vitreous chamber of seven adult cats, we localized the toxin immunohistochemically in order to identify direct retinal projections in these animals. Consistent with previous findings, the strongest projections were observed in the superficial layers of the superior colliculus, the dorsal and ventral lateral geniculate nuclei, the pretectal nuclei, the accessory optic nuclei, and the suprachiasmatic nucleus of the hypothalamus. However, we also found labelled terminals in several other brain areas, including the zona incerta, the medial geniculate nucleus, the lateral posterior-pulvinar complex, the lateral habenular nucleus, and the anterior and lateral hypothalamic regions. The morphological characteristics of the retinal axon terminals in most of the identified novel target sites are described.
Retinal Projections to the Lateral Posterior-pulvinar Complex in Intact and Early Visual Cortex Lesioned Cats
In intact cats, it is generally considered that the lateral posterior-pulvinar complex (LP-pulvinar) does not receive direct retinal terminals, with the exception of the retino-recipient zone known as the geniculate wing. There is, however, some evidence that early lesions of the visual cortex can occasionally induce the formation of novel retinal projections to the LP nucleus. Given the importance of knowing the connectivity pattern of the LP-pulvinar complex in intact and lesioned animals, we used the B fragment of cholera toxin, a sensitive anterograde tracer, to reinvestigate the retinal projections to the LP-pulvinar in normal cats and in cats with early unilateral lesions of the visual cortex (areas 17 and 18). Immunohistochemical localization of the toxin was performed to show the distribution and morphology of retinofugal terminals. A direct bilateral but predominantly contralateral retinal projection reached the caudal portion of LPl and LPm in the form of patches located mainly along its dorsomedial surface and many scattered terminals. The distribution of retinal projections to LP-pulvinar in intact and operated cats did not differ. Contrary to what had been previously reported, we found no evidence for lesion-induced sprouting of retinal axons in these higher-order thalamic nuclei. Retinal input to the LP-pulvinar might modulate visual responses driven by primary visual cortex or superior colliculus.
Recovery of Anterograde Amnesia in a Case of Craniopharyngioma
Studies of the amnesic syndrome have indicated that telencephalic and diencephalic structures are critical components of the memory system. The exact role of the mammillary bodies (MBs) in human memory remains elusive, since few cases of selective MB damage have been reported.
Cross-modal Plasticity Revealed by Electrotactile Stimulation of the Tongue in the Congenitally Blind
In sensory substitution, information acquired with one sensory modality is used to accomplish a task which is normally subserved primarily by another sensory modality. We used PET to study cross-modal plasticity in the congenitally blind, using electrotactile stimulation of the tongue. Blind (n = 6) and sighted blindfolded controls (n = 5) were scanned before and after they were trained to use their tongue in a Snellen orientation detection task. Results showed that both groups of subjects learned the discrimination orientation task after seven 1 h training sessions. Before training, no significant changes in regional cerebral blood flow (rCBF) were observed in the occipital cortex in either group. In sharp contrast, activity in the occipital cortex increased after practice for the blind, but not for the sighted, providing evidence for training-induced plasticity in the blind. An inter-regional correlation analysis showed that task-related rCBF changes in left posterior parietal cortex were positively correlated with rCBF changes in the occipital area of the trained blind. These data reveal that cross-modal plasticity in the blind develops rapidly and that the occipital cortex is part of a functional neural network for tactile discrimination in conjunction with the posterior parietal cortex. Our data further show that the tongue can act as a portal to convey somatosensory information to visual cortex.
Distribution of Calcium Binding Proteins in Visual and Auditory Cortices of Hamsters
The morphology and distribution of neurons immunoreactive (ir) to parvalbumin (PV), calretinin (CR) and calbindin (CB) were studied in the primary visual (V1) and auditory (A1) cortices of hamsters. Cortical cell populations were labelled immunohistochemically using a glucose oxidase-diaminobenzidine-nickel combined revelation method. Quantitative analysis revealed significant differences between V1 and A1 in the density and distribution of their neuronal population. CBir cells exhibited several typologies in both cortical regions. Most cells were multipolar even though many of them had bitufted or bipolar morphologies. These cells were distributed in layers II/III and in layer V of both A1 and V1, but were more numerous in layer V of V1. CRir cells were of the fusiform type with long bipolar dendritic arbours. These were similarly distributed in both cortices with a peak in superficial layers II/III. PVir cells were also found in both cortices and had round or oval-shaped somata with multipolar processes. They were mostly located in layer V for V1 and in layers III/IV for A1. Visual and auditory primary cortices can thus be differentiated on the basis of their immunoreactivity to specific calcium binding proteins.
Regional Analysis of Neurofilament Protein Immunoreactivity in the Hamster's Cortex
The laminar distribution of several distinct populations of neurofilament protein containing neurons has been used as a criterion for the delineation of cortical areas in hamsters. SMI-32 is a monoclonal antibody that recognizes a non-phosphorylated epitope on the medium- and high-molecular weight subunits of neurofilament proteins. As in carnivores and primates, SMI-32 immunoreactivity in the hamster neocortex was present in cell bodies, proximal dendrites and axons of some medium and large pyramidal neurons located in cortical layers III, V and VI. A small population of labeled multipolar cells was also found in layer IV. Neurofilament protein immunoreactive neurons were found throughout isocortical areas. Very few labeled cells were encountered in supplemental motor area, insular cortex, medial portion of associative visual cortex and in parietal association cortex. Our data indicate that SMI-32 immunoreactive cells can be efficiently used to trace boundaries between neocortical areas in the hamster's brain. The regional distribution SMI-32 immunoreactivity in the hamster cortex corresponds quite closely with cortical areas as defined by their cytoarchitecture and myeloarchitecture. The primary sensory cortical areas contain the most intense of SMI-32 immunoreactivity and are also those with the highest density of myelinated axons. Very low SMI-32 immunoreactivity was found in orbital, insular, perirhinal, cingulate and infralimbic cortices, which are also poor in myelinated axons. This supports the association between SMI-32 immunoreactivity and myelin contents.
Pattern-motion Selectivity in the Human Pulvinar
On the basis of anatomical and physiological data obtained on animal models, we recently proposed that neurons in the main visual extrageniculate nuclei complex, the pulvinar, are actively involved in higher-order visual processing. Pulvinar neurons have been shown to integrate the component signals of a plaid pattern into a coherent global percept (pattern-motion selectivity). Using positron emission tomography (PET), we have investigated the possibility that the human pulvinar is also involved in plaid-defined higher-order motion integration. Plaid patterns were presented to normal observers in two conditions (coherent vs. transparent) created by varying the relative spatial frequency of the two gratings comprising the plaid. Regions of interest analysis revealed a significant activation of the pulvinar in the coherent condition supporting the notion that the human pulvinar nucleus is involved in higher-order motion processing. Plaid pattern activation was also observed in the medial temporal gyrus (area MT/V5), a motion area with strong anatomical connections to the pulvinar. These data provide the first direct evidence that the human pulvinar is involved in complex motion integration, as previously shown in animal models, and further support the existence of cortico-thalamo-cortical computational networks involved in higher-order visual processing.
Cross-modal Plasticity in Early Blindness
The brain shows a remarkable capacity to reorganize itself following early sensory deprivation or neonatal brain damage. Using two models of deprivation, we will show that the brain does indeed adjust to the loss of either the visual cortex (which receives most of the retinal inputs through the lateral geniculate bodies of the thalamus) or the eyes (which provide the major input to the visual cortex) through cross-modal plastic processes. Hamsters, deprived of their visual system at birth, develop novel and permanent retinal projections to the auditory thalamus. These projections form functional synapses and project to the auditory cortex. When trained on a visual discrimination task, the "rewired" hamsters perform as well as normal hamsters. Lesions of the auditory cortex produce cortical blindness. Congenitally blind human subjects, trained to discriminate the orientation of a stimulus applied to the tongue via an electrotactile device, show activation of their visual cortex, whereas trained blindfolded controls show only activation of the somatosensory cortex representing the tongue. We propose that in blind subjects, there is an unmasking of existing cortico-cortical (parieto-occipital) connections, enabling transfer of somatosensory information to visual cortex.
Transcranial Magnetic Stimulation of the Visual Cortex Induces Somatotopically Organized Qualia in Blind Subjects
After loss of a particular sensory channel, the deprived cortex can be activated by inputs from other sensory modalities. It is not known whether activation of the rewired cortex evokes subjective experiences characteristic of that cortex or consistent with the rerouted sensory information. In a previous study, blind subjects were trained to perform visual tasks with a tongue display unit, a sensory substitution device that translates visual displays into electrotactile tongue stimulation. This cross-modal sensory stimulation activated their visual cortices. We now extend this finding by using transcranial magnetic stimulation to examine the perceptual correlates of training-induced plastic responses. We find that blind subjects proficient with the use of the tongue display unit report somatopically organized tactile sensations that are referred to the tongue when transcranial magnetic stimulation is applied over the occipital cortex. No such sensations were evoked in trained, blindfolded, seeing control subjects who performed the sensory substitution task equally well. These data show that the perceptual correlate of activity in a given cortical area reflects the characteristics of its novel sensory input source.
Development of the Commissure of the Superior Colliculus in the Hamster
The development of the corpus callosum (CC) and the anterior commissure (CA) is well known in a wide variety of species. No study, however, has described the development of the commissure of the superior colliculus (CSC) from embryonic state to adulthood in mammals. In this study, by using the lipophylic tracer DiI, we investigated the ontogeny of this mesencephalic commissure in the hamster at various ages. The development of axonal terminals, growth cone morphologies, and axons branching were described for the superior colliculus (SC) contralateral to the tracer injection. The first CSC axons cross the midline at embryonic day 11 (E-11) and grow further into the intermediate layers of the contralateral SC between E-12 and E-14. There is little axon growth therein between E-14 and the day of birth (P-0). Growth cones at the tip of these axons adopt complex morphologies at E-12 and progressively simplify until P-0. Pioneer axons are clearly visible between E-14 and P-1. These are followed by other axons progressively more numerous between P-0 and P-5. Axons do not show any branching until P-2. Between P-3 and P-9, the axons progressively arborize in the intermediate layers. Some axons reach the superficial layers at P-5, and they become more numerous around P-11, and only a few axons remain therein by P-21. Myelinated axons appear at P11 and are very dense at P-21. Our results indicate that the CSC follows developmental schemes similar to those of the CC and the AC but that initial axon midline crossing occurs earlier.
Alterations in Right Posterior Hippocampus in Early Blind Individuals
This study compares hippocampal volumes of early blind and sex/age-matched sighted controls through volumetric and localization analyses. Early blind individuals showed a significantly smaller right posterior hippocampus compared with controls. No differences in total hippocampal volumes were found between groups and there were no within-group differences for left versus right hippocampus. Sex, age and total brain grey matter volume had no effect on hippocampal volumes. Although extensive navigational training results in structural enhancement of the hippocampus for the sighted, the reduction of the posterior hippocampus in early blind individuals suggests the implication of this region in visual spatial memory.
Tactile-'visual' Acuity of the Tongue in Early Blind Individuals
This study compares the 'tactile-visual' acuity of the tongue for 15 early blind participants with that of 24 age-matched and sex-matched sighted controls. Snellen's tumbling E test was used to assess 'visual' acuity using the tongue display unit. The tongue display unit is a sensory substitution device that converts a visual stimulus grabbed by a camera into electro-tactile pulses delivered to the tongue via a grid made out of electrodes. No overall significant difference was found in thresholds between early blind (1/206) and sighted control (1/237) participants. We found, however, a larger proportion of early blind in the two highest visual acuity categories (1/150 and 1/90). These results extend earlier findings that it is possible to measure visual acuity in the blind individuals using the tongue. Moreover, our data demonstrate that a subgroup of early blind participants is more efficient than controls in conveying visual information through the tongue.
Alterations of the Visual Pathways in Congenital Blindness
We used whole brain MRI voxel-based morphometry (VBM) to study the anatomical organization of the visual system in congenitally blind (CB) adults. Eleven CB without a history of visual perception were compared with 21 age- and sex-matched normal-sighted controls (NS). CB showed significant atrophy of the geniculo-striate system, encompassing the optic nerves, the optic chiasm, the optic radiations and the primary visual cortex (BA17). The volume decrease in BA17 reached 25% in both hemispheres. The pulvinar and its projections to the associative visual areas were also dramatically altered, BA18/19 and the middle temporal cortex (MT) showing volume reductions of up to 20%. Additional significant white matter alterations were observed in the inferior longitudinal tract and in the posterior part of the corpus callosum, which links the visual areas of both hemispheres. Our data indicate that the afferent projections to the visual cortex in CB are largely atrophied. Despite the massive volume reductions in the occipital lobes, there is compelling evidence from the literature (reviewed in Noppeney 2007; Ptito and Kupers 2005) that blind subjects activate their visual cortex when performing tasks that involve somatosensory or auditory inputs, suggesting a reorganization of the neural pathways that transmit sensory information to the visual cortex.
Protein Kinase A Modulates Retinal Ganglion Cell Growth During Development
During development, retinal ganglion cells (RGCs) extend their axons toward their thalamic and mesencephalic targets. Their navigation is largely directed by guidance cues present in their environment. Since cAMP is an important second messenger that mediates the neural response to guidance molecules and its intracellular levels seem to decrease significantly following birth, we tested whether modulation of the cAMP/protein kinase A (PKA) pathway would affect the normal development of RGC axons. At postnatal day 1, hamsters received a unilateral intraocular injection of either 0.9% saline solution, 12 mM of the membrane-permeable cAMP analogue (dibutyryl cAMP; db-cAMP), or 10 microM of the PKA inhibitor KT5720. Intraocular elevation of cAMP significantly accelerated RGC axonal growth while inhibition of PKA activity decreased it. Moreover, when highly purified RGC cultures were treated with forskolin (an activator of adenylate cyclase) or cAMP analogues (db-cAMP and Sp-cAMP), neurite length, growth cone (GC) surface area and GC filopodia number were significantly increased. This indicates that intraocular elevation of cAMP acts directly on RGCs. Since these effects were prevented by PKA inhibitors, it demonstrates that cAMP also exerts its action via the PKA pathway. Taken together, these results suggest that the cAMP/PKA cascade is essential for the normal development of retinothalamic projections.
Neuronal Reduction in Frontal Cortex of Primates After Prenatal Alcohol Exposure
Children with fetal alcohol spectrum disorders (FASD) show behavioral and intellectual impairments that indicate frontal lobe dysfunction, but the extent of damage to this region has not been clarified by brain imaging studies. This study uses the St Kitts vervet monkey, a species that voluntarily consumes beverage alcohol, to examine the effects of prenatal ethanol exposure. Pregnant vervets were allowed to drink the equivalent of 3-5 standard drinks four times a week during the third trimester. Using unbiased stereology, we estimated neuronal reduction and found significantly fewer cells in the frontal lobes of FASD offspring as well as an increased density of interstitial white matter neurons. These cytoarchitectonic effects are consistent with the behavioral and cognitive changes observed in FASD.
Recruitment of the Middle Temporal Area by Tactile Motion in Congenital Blindness
We used positron emission tomography to investigate whether tactile motion discrimination activates the dorsal visual stream in congenitally blind (CB) participants compared with sighted controls. The tactile stimuli consisted of either static dots, dots moving coherently in one of two possible directions, or in random directions. Although CB and sighted controls performed equally well on the motion discrimination task, only CB showed increased activation in the right middle temporal area. In addition, CB also activated other visual areas including the cuneus and extrastriate area V3. These results indicate that the dorsal visual pathway is activated by tactile motion stimuli in CB, therefore providing additional support for the cross-modal plasticity hypothesis.
Partial Recovery of Hemiparesis Following Hemispherectomy in Infant Monkeys
Hemiparesis, unilateral weakness or partial paralysis, is a common outcome following hemispherectomy in humans. We use the non-human primate as an invaluable translational model for our understanding of developmental plasticity in response to hemispherectomy. Three infant vervet monkeys (Chlorocebus sabeus) underwent hemispherectomy at a median age of 9 weeks and two additional monkeys at 48 months. Gross motor assessment was conducted in a large open field that contained a horizontal bar spanning the width of the cage. Subjects were assessed yearly following surgery in infantile lesions for a period of 3 years. Adult-lesioned subjects were assessed 40 months following surgery. Shortly after surgery both infant and adult-lesioned subjects were unable to move the contralateral side of their body, but all subjects were able to walk within 6 months following surgery. At each time point the lower limb gait was normal in infant-lesioned subjects with no apparent limp or dragging, however the upper limb demonstrated significant impairment. Horizontal bar crossing was significantly impaired during the first 24 months following surgery. Adult-lesioned subjects also displayed upper limb movement impairments similar to infant-lesioned subjects. In addition the adult-lesioned subjects displayed a noticeable lower limb limp, which was not observed in the infant-lesioned group. Both groups at each time point showed a propensity for ipsiversive turning. The upper limb gait impairment and horizontal bar crossing of lesioned subjects are reminiscent of hemiparesis seen in hemisperectomized humans with the young-lesioned subjects showing a greater propensity for recovery.
Traumatic Brain Injury and Olfactory Deficits: the Tale of Two Smell Tests!
Olfactory functions are not systematically evaluated following traumatic brain injury (TBI). This study aimed at comparing two smell tests that are used in a clinical setting.
Beyond Visual, Aural and Haptic Movement Perception: HMT+ is Activated by Electrotactile Motion Stimulation of the Tongue in Sighted and in Congenitally Blind Individuals
The motion-sensitive middle temporal cortex (hMT+ complex) responds also to non-visual motion stimulation conveyed through the tactile and auditory modalities, both in sighted and in congenitally blind individuals. This indicates that hMT+ is truly responsive to motion-related information regardless of visual experience and the sensory modality through which such information is carried to the brain. Here we determined whether the hMT+ complex responds to motion perception per se, that is, motion not perceived through the visual, haptic or aural modalities. Using functional magnetic resonance imaging (fMRI), we investigated brain responses in eight congenitally blind and nine sighted volunteers who had been trained to use the tongue display unit (TDU), a sensory substitution device which converts visual information into electrotactile pulses delivered to the tongue, to resolve a tactile motion discrimination task. Stimuli consisted of either static dots, dots moving coherently or dots moving in random directions. Both groups learned the task at the same rate and activated the hMT+ complex during tactile motion discrimination, although at different anatomical locations. Furthermore, the congenitally blind subjects showed additional activations within the dorsal extrastriate cortical pathway. These results extend previous data in support of the supramodal functional organization of hMT+ complex by showing that this cortical area processes motion-related information per se, that is, motion stimuli that are not visual in nature and that are administered to body structures that, in humans, are not primarily devoted to movement perception or spatial location, such as the tongue. In line with previous studies, the differential activations between sighted and congenitally blind individuals indicate that lack of vision leads to functional rearrangements of these supramodal cortical areas.
Orientationally Invariant Indices of Axon Diameter and Density from Diffusion MRI
This paper proposes and tests a technique for imaging orientationally invariant indices of axon diameter and density in white matter using diffusion magnetic resonance imaging. Such indices potentially provide more specific markers of white matter microstructure than standard indices from diffusion tensor imaging. Orientational invariance allows for combination with tractography and presents new opportunities for mapping brain connectivity and quantifying disease processes. The technique uses a four-compartment tissue model combined with an optimized multishell high-angular-resolution pulsed-gradient-spin-echo acquisition. We test the method in simulation, on fixed monkey brains using a preclinical scanner and on live human brains using a clinical 3T scanner. The human data take about one hour to acquire. The simulation experiments show that both monkey and human protocols distinguish distributions of axon diameters that occur naturally in white matter. We compare the axon diameter index with the mean axon diameter weighted by axon volume. The index differs from this mean and is protocol dependent, but correlation is good for the monkey protocol and weaker, but discernible, for the human protocol where greater diffusivity and lower gradient strength limit sensitivity to only the largest axons. Maps of axon diameter and density indices from the monkey and human data in the corpus callosum and corticospinal tract reflect known trends from histology. The results show orientationally invariant sensitivity to natural axon diameter distributions for the first time with both specialist and clinical hardware. This demonstration motivates further refinement, validation, and evaluation of the precise nature of the indices and the influence of potential confounds.
Neural Correlates of Virtual Route Recognition in Congenital Blindness
Despite the importance of vision for spatial navigation, blind subjects retain the ability to represent spatial information and to move independently in space to localize and reach targets. However, the neural correlates of navigation in subjects lacking vision remain elusive. We therefore used functional MRI (fMRI) to explore the cortical network underlying successful navigation in blind subjects. We first trained congenitally blind and blindfolded sighted control subjects to perform a virtual navigation task with the tongue display unit (TDU), a tactile-to-vision sensory substitution device that translates a visual image into electrotactile stimulation applied to the tongue. After training, participants repeated the navigation task during fMRI. Although both groups successfully learned to use the TDU in the virtual navigation task, the brain activation patterns showed substantial differences. Blind but not blindfolded sighted control subjects activated the parahippocampus and visual cortex during navigation, areas that are recruited during topographical learning and spatial representation in sighted subjects. When the navigation task was performed under full vision in a second group of sighted participants, the activation pattern strongly resembled the one obtained in the blind when using the TDU. This suggests that in the absence of vision, cross-modal plasticity permits the recruitment of the same cortical network used for spatial navigation tasks in sighted subjects.
Reduced Soma Size of the M-neurons in the Lateral Geniculate Nucleus Following Foetal Alcohol Exposure in Non-human Primates
Visual impairment is commonly reported as a consequence of heavy prenatal ethanol exposure in humans. Children generally display characteristic cranio-facial dysmorphology and represent typical severe cases of foetal alcohol syndrome. Binge-like rodent model systems have concluded that third trimester equivalent ethanol exposure results in widespread apoptosis in the visual system from the retina to the visual cortex. Neither clinical nor animal studies address the consequences of more moderate prenatal ethanol exposure on the visual system. The current study uses a naturalistic and voluntary consumption approach in non-human primates (Chlorocebus sabeus) in order to more closely model prenatal ethanol consumption patterns in humans. Pregnant vervet monkeys voluntarily drank on average 2.418 +/- 0.296 g etoh/kg/day four times a week during the third trimester. Using unbiased stereology, we estimated the neuronal and glial population of the parvocellular (P) and magnocellular (M) layers of the lateral geniculate nucleus (LGN) following foetal alcohol exposure (FAE) in infant subjects. Layer volume and total number of neurons and glia in the LGN of the FAE subjects were not significantly different from age-matched control subjects. The M neuronal soma size of FAE subjects, however, was significantly reduced to resemble the size of the P-neurons. These results suggest that alterations at the level of morphology and anatomy of the M-neurons may lead to behavioural deficits associated with the integrity of the dorsal visual pathway.
Tactile Maze Solving in Congenitally Blind Individuals
Vision is undoubtedly important for navigation although not essential as blind individuals outperform their blindfolded seeing counterparts in a variety of navigational tasks. It is believed that the blind's superior performance is because of their efficient use of proprioceptive signals and environmental cues such as temperature and echolocation. We hypothesize that by limiting these cues, blind individuals will lose their advantage compared with controls in spatial navigation tasks. We therefore evaluated the performance of blind and sighted individuals in small-scale, tactile multiple T mazes. Our results show that blindfolded sighted controls outperformed blind participants in the route-learning tasks. This suggests that, contrary to indoor large-scale spaces, navigational skills inside small-scale spaces benefit from visual experience.
Odor Perception and Odor Awareness in Congenital Blindness
It is generally acknowledged that people blind from birth develop supra-normal sensory abilities in order to compensate for their visual deficit. While extensive research has been done on the somatosensory and auditory modalities of the blind, information about their sense of smell remains scant. The goal of this study was therefore to compare odor perception and odor awareness in a group of 11 congenitally blind and 14 sighted control subjects. We measured odor detection threshold, odor discrimination and odor identification using the Sniffin'Sticks test. Participants also filled in the Odor Awareness Scale (OAS) to assess consciousness of olfactory sensations. Our data showed that blind subjects had a lower odor detection threshold compared to the sighted. However, no group differences were found for odor discrimination and odor identification. Interestingly, the OAS revealed that blind participants scored higher for odor awareness. The largest group differences were found for items of the OAS that measure responses to body odors and fragrances. We conclude that blind subjects rely more on their sense of smell than the sighted in order to assess their environment and to recognize places and other people.
Concerted Action of CB1 Cannabinoid Receptor and Deleted in Colorectal Cancer in Axon Guidance
Endocannabinoids (eCBs) are retrograde neurotransmitters that modulate the function of many types of synapses. The presence of eCBs, their CB1 receptor (CB1R), and metabolizing enzymes at embryonic and early postnatal periods have been linked to developmental processes such as neuronal proliferation, differentiation, and migration, axon guidance, and synaptogenesis. Here, we demonstrate the presence of a functional eCB system in the developing visual system and the role of CB1R during axon growth and retinothalamic development. Pharmacological treatment of retinal explants and primary cortical neuron cultures with ACEA, a selective CB1R agonist, induced a collapse of the growth cone (GC). Furthermore the application of AM251, a CB1R inverse agonist, to the neuronal cultures increased the surface area of GC. In vivo, intraocular injection of ACEA diminished retinal projection growth, while AM251 promoted growth and caused aberrant projections. In addition, compared with their wild-type littermates, CB1R-deficient adult mice revealed a lower level of eye-specific segregation of retinal projections in the dorsal lateral geniculate nucleus. Finally, we found that pharmacological modulation of CB1R affected the trafficking of Deleted in colorectal cancer (DCC) receptor to the plasma membrane in a PKA-dependent manner. Moreover, pharmacological inhibition or genetic inactivation of DCC abolished the CB1R-induced reorganization of the GC. Overall, these findings establish a mechanism by which the CB1R influences GC behavior and nervous system development in concerted action with DCC.
The Left Fusiform Gyrus Hosts Trisensory Representations of Manipulable Objects
During object manipulation the brain integrates the visual, auditory, and haptic experience of an object into a unified percept. Previous brain imaging studies have implicated for instance the dorsal part of the lateral occipital complex in visuo-tactile and the posterior superior temporal sulcus in audio-visual integration of object-related inputs (Amedi et al., 2005). Yet it is still unclear which brain regions represent object-specific information of all three sensory modalities. To address this question, we performed two complementary functional magnetic resonance imaging experiments. In the first experiment, we identified brain regions which were consistently activated by unimodal visual, auditory, and haptic processing of manipulable objects relative to non-object control stimuli presented in the same modality. In the second experiment, we assessed regional brain activations when participants had to match object-related information that was presented simultaneously in two or all three modalities. Only a well-defined region in left fusiform gyrus (FG) showed an object-specific activation during unisensory processing in the visual, auditory, and tactile modalities. The same region was also consistently activated during multisensory matching of object-related information across all three senses. Taken together, our results suggest that this region is central to the recognition of manipulable objects. A putative role of this FG region is to unify object-specific information provided by the visual, auditory, and tactile modalities into trisensory object representations.
Distribution of Collateral Fibers in the Monkey Cervical Spinal Cord Detected with Diffusion-weighted Magnetic Resonance Imaging
Diffusion anisotropy monitored with diffusion-weighted magnetic resonance imaging (DWMRI) is a sensitive marker to monitor developmental or pathological microstructural changes in spinal cord. The white matter is often treated as a unidirectional axonal bundle but collateral fibers branching off the main spinal pathways contradicts this assumption and affects the diffusion anisotropy. It is the aim of this study to investigate to what extent collateral fibers are apparent in diffusion tensor data and if collaterals can be detected as individual fiber directions using crossing fiber detection techniques. We calculate the diffusion tensor and the persistent angular structure (PAS), a multi-fiber reconstruction technique, from high quality post mortem data of a perfusion-fixed vervet monkey cervical spinal cord sample and simulated crossing fiber data. Our results show that (i) cylindrical geometry in the white matter of the spinal cord is an invalid assumption due to collateral fibers. We also demonstrate that (ii) collateral fibers can be resolved as distinct peaks in the water diffusion propagator in white matter using multi-fiber models. Finally, we show that (iii) crossing fibers are mainly located laterally and increase towards the cervical enlargement.
Navigation with a Sensory Substitution Device in Congenitally Blind Individuals
Vision allows for obstacle detection and avoidance. The compensatory mechanisms involved in maintaining these functions in blind people using their remaining intact senses are poorly understood. We investigated the ability of congenitally blind participants to detect and avoid obstacles using the tongue display unit, a sensory substitution device that uses the tongue as a portal to the brain. We found that congenitally blind were better than sighted control participants in detecting and avoiding obstacles using the tongue display unit. Obstacles size and avoidance strategy had a significant effect on performance: large obstacles were better detected than small ones and step-around obstacles were better avoided than step-over ones. These data extend our earlier findings that when using a sensory substitution device, blind participants outperform sighted controls not only in a virtual navigation task but also during effective navigation within a human-sized obstacle course.
The Nature of Consciousness in the Visually Deprived Brain
Vision plays a central role in how we represent and interact with the world around us. The primacy of vision is structurally imbedded in cortical organization as about one-third of the cortical surface in primates is involved in visual processes. Consequently, the loss of vision, either at birth or later in life, affects brain organization and the way the world is perceived and acted upon. In this paper, we address a number of issues on the nature of consciousness in people deprived of vision. Do brains from sighted and blind individuals differ, and how? How does the brain of someone who has never had any visual perception form an image of the external world? What is the subjective correlate of activity in the visual cortex of a subject who has never seen in life? More in general, what can we learn about the functional development of the human brain in physiological conditions by studying blindness? We discuss findings from animal research as well from recent psychophysical and functional brain imaging studies in sighted and blind individuals that shed some new light on the answers to these questions.
Insights from Darkness: What the Study of Blindness Has Taught Us About Brain Structure and Function
Vision plays a central role in how we represent and interact with the world around us. Roughly, one-third of the cortical surface in primates is involved in visual processes. The loss of vision, either at birth or later in life, must therefore have profound consequences on brain organization and on the way the world is perceived and acted upon. In this chapter, we formulate a number of critical questions. Do blind individuals indeed develop supra-normal capacities for the remaining senses in order to compensate for their loss of vision? Do brains from sighted and blind individuals differ, and how? How does the brain of someone who has never had any visual perception form an image of the external world? We discuss findings from animal research as well from recent psychophysical and functional brain imaging studies in sighted and blind individuals that shed some new light on the answers to these questions.
