The functional characterization of callosal connections.

The brain operates through the synaptic interaction of distant neurons within flexible, often heterogeneous, distributed systems. Histological studies have detailed the connections between distant neurons, but their functional characterization deserves further exploration. Studies performed on the corpus callosum in animals and humans are unique in that they capitalize on results obtained from several neuroscience disciplines. Such data inspire a new interpretation of the function of callosal connections and delineate a novel road map, thus paving the way toward a general theory of cortico-cortical connectivity. Here we suggest that callosal axons can drive their post-synaptic targets preferentially when coupled to other inputs endowing the cortical network with a high degree of conditionality. This might depend on several factors, such as their pattern of convergence-divergence, the excitatory and inhibitory operation mode, the range of conduction velocities, the variety of homotopic and heterotopic projections and, finally, the state-dependency of their firing. We propose that, in addition to direct stimulation of post-synaptic targets, callosal axons often play a conditional driving or modulatory role, which depends on task contingencies, as documented by several recent studies.

Astrocytes close the mouse critical period for visual plasticity.

Brain postnatal development is characterized by critical periods of experience-dependent remodeling of neuronal circuits. Failure to end these periods results in neurodevelopmental disorders. The cellular processes defining critical-period timing remain unclear. Here, we show that in the mouse visual cortex, astrocytes control critical-period closure. We uncover the underlying pathway, which involves astrocytic regulation of the extracellular matrix, allowing interneuron maturation. Unconventional astrocyte connexin signaling hinders expression of extracellular matrix-degrading enzyme matrix metalloproteinase 9 (MMP9) through RhoA-guanosine triphosphatase activation. Thus, astrocytes not only influence the activity of single synapses but also are key elements in the experience-dependent wiring of brain circuits.

Beyond Rehabilitation of Acuity, Ocular Alignment, and Binocularity in Infantile Strabismus.

Infantile strabismus impairs the perception of all attributes of the visual scene. High spatial frequency components are no longer visible, leading to amblyopia. Binocularity is altered, leading to the loss of stereopsis. Spatial perception is impaired as well as detection of vertical orientation, the fastest movements, directions of movement, the highest contrasts and colors. Infantile strabismus also affects other vision-dependent processes such as control of postural stability. But presently, rehabilitative therapies for infantile strabismus by ophthalmologists, orthoptists and optometrists are restricted to preventing or curing amblyopia of the deviated eye, aligning the eyes and, whenever possible, preserving or restoring binocular vision during the critical period of development, i.e., before ~10 years of age. All the other impairments are thus ignored; whether they may recover after strabismus treatment even remains unknown. We argue here that medical and paramedical professionals may extend their present treatments of the perceptual losses associated with infantile strabismus. This hypothesis is based on findings from fundamental research on visual system organization of higher mammals in particular at the cortical level. In strabismic subjects (as in normal-seeing ones), information about all of the visual attributes converge, interact and are thus inter-dependent at multiple levels of encoding ranging from the single neuron to neuronal assemblies in visual cortex. Thus if the perception of one attribute is restored this may help to rehabilitate the perception of other attributes. Concomitantly, vision-dependent processes may also improve. This could occur spontaneously, but still should be assessed and validated. If not, medical and paramedical staff, in collaboration with neuroscientists, will have to break new ground in the field of therapies to help reorganize brain circuitry and promote more comprehensive functional recovery. Findings from fundamental research studies in both young and adult patients already support our hypothesis and are reviewed here. For example, presenting different contrasts to each eye of a strabismic patient during training sessions facilitates recovery of acuity in the amblyopic eye as well as of 3D perception. Recent data also demonstrate that visual recoveries in strabismic subjects improve postural stability. These findings form the basis for a roadmap for future research and clinical development to extend presently applied rehabilitative therapies for infantile strabismus.

Interhemispheric Connections between the Primary Visual Cortical Areas via the Anterior Commissure in Human Callosal Agenesis.

Aim: In humans, images in the median plane of the head either fall on both nasal hemi-retinas or on both temporal hemi-retinas. Interhemispheric connections allow cortical cells to have receptive fields on opposite sides. The major interhemispheric connection, the corpus callosum, is implicated in central stereopsis and disparity detection in front of the fixation plane. Yet individuals with agenesis of the corpus callosum may show normal stereopsis and disparity vergence. We set out to study a possible interhemispheric connection between primary visual cortical areas via the anterior commissure to explain this inconsistency because of the major role of these cortical areas in elaborating 3D visual perception. Methods: MRI, DTI and tractography of the brain of a 53-year old man with complete callosal agenesis and normal binocular single vision was undertaken. Tractography seed points were placed in both the right and the left V1 and V2. Nine individuals with both an intact corpus callosum and normal binocularity served as controls. Results: Interhemispheric tracts through the anterior commissure linking both V1 and V2 visual cortical areas bilaterally were indeed shown in the subject with callosal agenesis. All other individuals showed interhemispheric visual connections through the corpus callosum only. Conclusion: Callosal agenesis may result in anomalous interhemispheric connections of the primary visual areas via the anterior commissure. It is proposed here that these connections form as alternative to the normal callosal pathway and may participate in binocularity.

Pinwheel-dipole configuration in cat early visual cortex.

In the early visual cortex, information is processed within functional maps whose layouts are thought to underlie visual perception. However, the precise organization of these functional maps as well as their interrelationships remain unsettled. Here, we show that spatial frequency representation in cat early visual cortex exhibits singularities around which the map organizes like an electric dipole potential. These singularities are precisely co-located with singularities of the orientation map: the pinwheel centers. To show this, we used high resolution intrinsic optical imaging in cat areas 17 and 18. First, we show that a majority of pinwheel centers exhibit in their neighborhood both semi-global maximum and minimum in the spatial frequency map (i.e. extreme values of the spatial frequency in a hypercolumn). This contradicts pioneering studies suggesting that pinwheel centers are placed at the locus of a single spatial frequency extremum. Based on an analogy with electromagnetism, we proposed a mathematical model for a dipolar structure, accurately fitting optical imaging data. We conclude that a majority of orientation pinwheel centers form spatial frequency dipoles in cat early visual cortex. Given the functional specificities of neurons at singularities in the visual cortex, it is argued that the dipolar organization of spatial frequency around pinwheel centers could be fundamental for visual processing.

Spatial and temporal analyses of posture in strabismic children.

PURPOSE: To analyse postural performances of strabismic children, both in the spatial and the temporal domains, by wavelet transformation, comparing both stable and unstable situations. METHODS: Twenty-six strabismic children aged from 4 to 11 years old and 26 age-matched normal children participated in the study. Postural performances were evaluated using the Framiral® platform. Posture was recorded in the following conditions: eyes open fixating a target and eyes closed on stable and unstable platforms. RESULTS: For both strabismic and non-strabismic children, the surface and the mean velocity of the center of pressure (CoP) were significantly larger in the eyes closed on unstable platform condition, but this was much more pronounced in case of strabismus. Spectral power index and cancelling time were also found to be altered in strabismic children compared to non-strabismic children. CONCLUSIONS: This data demonstrates poor postural stability for both groups on an unstable platform with the eyes closed. However, strabismic children had significantly worse performance than non-strabismic children. Strabismic children also engage more energy to stabilize their posture by using visuo-vestibular sensory inputs to compensate their altered vision due to strabismus, in comparison to non-strabismic children.

Origins of strabismus and loss of binocular vision.

Strabismus is a frequent ocular disorder that develops early in life in humans. As a general rule, it is characterized by a misalignment of the visual axes which most often appears during the critical period of visual development. However other characteristics of strabismus may vary greatly among subjects, for example, being convergent or divergent, horizontal or vertical, with variable angles of deviation. Binocular vision may also vary greatly. Our main goal here is to develop the idea that such "polymorphy" reflects a wide variety in the possible origins of strabismus. We propose that strabismus must be considered as possibly resulting from abnormal genetic and/or acquired factors, anatomical and/or functional abnormalities, in the sensory and/or the motor systems, both peripherally and/or in the brain itself. We shall particularly develop the possible "central" origins of strabismus. Indeed, we are convinced that it is time now to open this "black box" in order to move forward. All of this will be developed on the basis of both presently available data in literature (including most recent data) and our own experience. Both data in biology and medicine will be referred to. Our conclusions will hopefully help ophthalmologists to better understand strabismus and to develop new therapeutic strategies in the future. Presently, physicians eliminate or limit the negative effects of such pathology both on the development of the visual system and visual perception through the use of optical correction and, in some cases, extraocular muscle surgery. To better circumscribe the problem of the origins of strabismus, including at a cerebral level, may improve its management, in particular with respect to binocular vision, through innovating tools by treating the pathology at the source.

Comparative analysis of orientation maps in areas 17 and 18 of the cat primary visual cortex following adaptation.

Object orientations in the visual field are columned into specific orientation domains in the primary visual cortex [area 17 (A17) and area 18 (A18)] of cats. At the single-cell level, adapting A17 neurons to a non-preferred orientation (adaptor) shifts their preferred orientation either towards the adaptor (attractive shift) or away from it (repulsive shift). As A17 and A18 are reciprocally connected, we sought to determine how changes in preferred orientations in A18 neurons are correlated with changes recorded in A17 anesthetised cats. To this end, we simultaneously traced populations of neurons in A17 and A18, using intrinsic optical imaging, before and after long (12 min) and short (3 min) adaptations. The comparison of A17 and A18 maps pre-adaptation and post-adaptation showed that variance in shift amplitudes is greater in A18 than A17 for short adaptations. Our results indicate a rapid reconfiguration of functional maps that may spread to many cortical areas.

Organization and origin of spatial frequency maps in cat visual cortex.

It remains controversial whether and how spatial frequency (SF) is represented tangentially in cat visual cortex. Several models were proposed, but there is no consensus. Worse still, some data indicate that the SF organization previously revealed by optical imaging techniques simply reflects non-stimulus-specific responses. Instead, stimulus-specific responses arise from the homogeneous distribution of geniculo-cortical afferents representing X and Y pathways. To clarify this, we developed a new imaging method allowing rapid stimulation with a wide range of SFs covering more than 6 octaves with only 0.2 octave resolution. A benefit of this method is to avoid error of high-pass filtering methods which systematically under-represent dominant selectivity features near pinwheel centers. We show unequivocally that SF is organized into maps in cat area 17 (A17) and area 18 (A18). The SF organization in each area displays a global anteroposterior SF gradient and local patches. Its layout is constrained to that of the orientation map, and it is suggested that both maps share a common functional architecture. A17 and A18 are bound at the transition zone by another SF gradient involving the geniculo-cortical and the callosal pathways. A model based on principal component analysis shows that SF maps integrate three different SF-dependent channels. Two of these reflect the segregated excitatory input from X and Y geniculate cells to A17 and A18. The third one conveys a specific combination of excitatory and suppressive inputs to the visual cortex. In a manner coherent with anatomical and electrophysiological data, it is interpreted as originating from a subtype of Y geniculate cells.

Postural control in children with strabismus: effect of eye surgery.

The purpose of this study was to examine the postural control in children with strabismus before and after eye surgery. Control of posture is a complex multi-sensorial process relying on visual, vestibular and proprioceptive systems. Reduced influence of one of such systems leads to postural adaptation due to a compensation of one of the other systems [3]. Nine children with strabismus (4-8 years old) participated in the study. Ophthalmologic, orthoptic, vestibular and postural tests were done before and twice (2 and 8 weeks) after eye surgery. Postural stability was measured by a platform (TechnoConcept): two components of the optic flux were used for stimulation (contraction and expansion) and two conditions were tested eyes open and eyes closed. The surface area of the center of pressure (CoP), the variance of speed of the CoP and the frequency spectrum of the platform oscillations by fast Fourier transformation were analysed. Before surgery, similar to typically developing children, postural stability was better in the eyes open condition. The frequency analysis revealed that for the low frequency band more energy was spent in the antero-posterior direction compared to the medio-lateral one while the opposite occurred for the middle and the high frequency bands. After surgery, the eye deviation was reduced in all children and their postural stability also improved. However, the energy of the high frequency band in the medio-lateral direction increased significantly. These findings suggest that eye surgery influences somatosensory properties of extra-ocular muscles leading to improvement of postural control and that binocular visual perception could influence the whole body.

Asymmetrical interhemispheric connections develop in cat visual cortex after early unilateral convergent strabismus: anatomy, physiology, and mechanisms.

In the mammalian primary visual cortex, the corpus callosum contributes to the unification of the visual hemifields that project to the two hemispheres. Its development depends on visual experience. When this is abnormal, callosal connections must undergo dramatic anatomical and physiological changes. However, data concerning these changes are sparse and incomplete. Thus, little is known about the impact of abnormal postnatal visual experience on the development of callosal connections and their role in unifying representation of the two hemifields. Here, the effects of early unilateral convergent strabismus (a model of abnormal visual experience) were fully characterized with respect to the development of the callosal connections in cat visual cortex, an experimental model for humans. Electrophysiological responses and 3D reconstruction of single callosal axons show that abnormally asymmetrical callosal connections develop after unilateral convergent strabismus, resulting from an extension of axonal branches of specific orders in the hemisphere ipsilateral to the deviated eye and a decreased number of nodes and terminals in the other (ipsilateral to the non-deviated eye). Furthermore this asymmetrical organization prevents the establishment of a unifying representation of the two visual hemifields. As a general rule, we suggest that crossed and uncrossed retino-geniculo-cortical pathways contribute successively to the development of the callosal maps in visual cortex.

Interhemispheric synchrony in visual cortex and abnormal postnatal visual experience.

The question of whether neural synchrony may be preserved in adult mammalian visual cortex despite abnormal postnatal visual experience was investigated by combining anatomical and computational approaches. Single callosal axons in visual cortex of early monocularly deprived (MD) adult cats were labeled anterogradely with biocytin in vivo and reconstructed in 3D. Spike propagation was then orthodromically simulated within each of these axons with NEURON software. Data were systematically compared to those previously obtained in normally reared (NR) adult cats with comparable approaches. The architecture of the callosal axons in MD animals differed significantly from the NR group, with longer branches and first nodes located deeper below the cortex. But, surprisingly, simulation of spike propagation demonstrated that transmission latencies of most spikes remained inferior to 2 ms, like the NR group. These results indicate that synchrony of neural activity may be preserved in adult visual cortex despite abnormal postnatal visual experience. According to the temporal binding hypothesis, this also indicates that the necessary timing for visual perception is present despite anatomical abnormalities in visual cortex.