[Blindness and visual rehabilitation]. / Cécité et réhabilitation visuelle.

Blindness and visual impairment are a major public health problem all over the world and in all societies. A large amount of basic science and clinical research aims to rehabilitate patients and help them become more independent. Various methods are explored from cell and molecular therapy to prosthetic interfaces. We review the various treatment alternatives, describing their results and their limitations.

A biophysical cortical column model to study the multi-component origin of the VSDI signal.

We propose a biological cortical column model, at an intermediate mesoscopic scale, in order to better understand and interpret biological sources of voltage-sensitive dye imaging signal (VSD signal). To perform a quantitative analysis of the relative contributions to the VSD signal, a detailed compartmental model was developed at a scale corresponding to one pixel of optical imaging. The generated model was used to solve the VSD direct problem, i.e. generate a VSD signal, given the neural substrate parameters and activities. Here, we confirm and quantify the fact that the VSD signal is the result of an average from multiple components. Not surprisingly, the compartments that mostly contribute to the signal are the upper layer dendrites of excitatory neurons. However, our model suggests that inhibitory cells, spiking activity and deep layers contributions are also significant and, more unexpected, are dynamically modulated with time and response strength.

Voltage-sensitive dye imaging: Technique review and models.

In this review, we present the voltage-sensitive dye imaging (VSDI) method. The possibility offered for in vivo (and in vitro) brain imaging is unprecedented in terms of spatial and temporal resolution. However, the unresolved multi-component origin of the optical signal encourages us to perform a detailed analysis of the method limitation and the existing models. We propose a biophysical model at a mesoscopic scale in order to understand and interpret this signal.

[A 3T fMRI study of cortical projection of visual scotomas: preliminary results]. / Etude en IRM fonctionnelle 3T de la projection corticale de scotomes rétiniens: résultats préliminaires.

AIM: We used functional magnetic resonance imaging (fMRI) to precisely measure both the localization and size of the cortical projections of artificial scotomas in healthy subjects as well as the size of a reversible retinal scotoma in a patient with central serous chorioretinopathy (CSCR). METHODS: Using a 3T MRI scanner, anatomical and functional data were acquired on two healthy subjects and a patient with CSCR. Retinotopic maps were first reconstructed using phase mapping techniques. Next, a block paradigm consisting of a grey background alternating with a full-field, flickering checkerboard was used to stimulate the complete central (19.5 degrees) visual field. A condition with artificial peri-foveal scotomas of different sizes and eccentricities was interleaved in healthy subjects. Differential maps were computed to obtain the cortical representation (size and location) of artificial scotomas. Full-field functional data were also acquired in the CSRC patient, at the acute stage and after recovery. RESULTS: Cortical projections of each scotoma were identified using differential maps and carefully characterized with quantitative analysis: the measured cortical positions of the inactivated cortical zones were compared with the known radius and eccentricity values in the scotomas in the visual field. We also compared the size of the inactivated cortical zones to the known size of scotomas. However, we found a consistent relationship between the size of the scotomas and their cortical projections, albeit with the absolute size smaller than expected from known cortical magnification factors. The cortical deactivation zone was also observed in the CRSC patient, which disappeared at recovery stage. CONCLUSIONS: Cortical retinotopic mapping can be performed successfully for both artificial and retinal scotomas. This study can serve as a basis for the future investigation of cortical plasticity in the visual cortex.

Input-output transformation in the visuo-oculomotor loop: comparison of real-time optical imaging recordings in V1 to ocular following responses upon center-surround stimulation.

In psychophysics and physiology, it is well established that lateral interactions are crucial mechanisms to constrain response normalization and contextual modulations. To study the cortical mechanisms involved in the contextual modulation of the behavioral contrast response function, we compared in behaving monkeys the Ocular Following Response (OFR) to V1 population activity measured using Optical Imaging of Voltage-Sensitive Dyes (VSD). If contrast response functions (CRF) to a simple local stimulus are similar in V1 and in the OFR, lateral interaction leads however to quite different modulation at those two levels. At the behavioural level, contrast response function is strongly suppressed by lateral interactions, and this suppression is stronger for higher contrasts. In V1, we showed a slow dynamic of facilitation for low contrasts integration and a fast suppression operating on high contrasts. These modulatory interactions influence differently the contrast response functions, interrupting the dynamic increase of contrast sensitivity in OFR, but not in V1 response. The temporal properties of those effects lead us to hypothesize that horizontal and feedback connectivity have differential effect on low and high contrasts integration in V1. V1 provides then an input to MT whose contextual dependency is not totally determined and must be refined before affecting the behavioural OFR.

[Retinotopic organization of the human visual cortex: a 3T fMRI study]. / Etude en IRM fonctionnelle 3T de l'organisation rétinotopique du cortex visuel.

UNLABELLED: INTRODUCTION. We used high-field (3T) functional magnetic resonance imaging (fMRI) to map the retinotopic organization of human cortical areas. METHODS: Retinotopic maps were reconstructed using existing mapping techniques. Stimuli were made of a rotating wedge stimulus, which provided angular coordinate maps, and an expanding or contracting ring, which provided eccentricity coordinate maps. Stimuli consisted of a grey background alternating with a flickering checkerboard. A Brucker 3T scanner equipped with a head coil and a custom optical system was used to acquire sets of echoplanar images of 20 occipital coronal slices within a RT of 2.111 ms and an 8 mm3 voxel resolution. Surface models of each subject's occipital lobes were constructed using the Brainvisa software from a sagittal T1-weighted image with a 1 mm3 voxel resolution. The cortical models were then inflated to obtain unfolded surfaces. Statistical analyses of the functional data were made under SPM99, and the response amplitudes were finally assigned to the cortical reconstructed surfaces. RESULTS: We identified boundaries between different early visual areas (V1, V2, V3) using eccentricity and polar angle retinotopic maps and detection of reversals in the representation of the polar angle. Both complete maps and reversals corresponding to the V1/V2 borders were clearly visible with a single recording session. Also, we were able to compare data from subjects across various fMRI acquisitions and found that there was a strong correlation between maps acquired at different sessions for the same subject. CONCLUSIONS: We developed a quick (<40 min) retinotopic cortical area mapping method at 3T, which makes it possible to study the cortical remapping in patients with retinal scotomas.

The visual cortical association field: a Gestalt concept or a psychophysiological entity?

The receptive field of a visual neurone is classically defined as the region of space (or retina) where a visual stimulus evokes a change in its firing activity. Intracellular recordings in cat area 17 show that the visually evoked synaptic integration field extends over a much larger area than that established on the basis of spike activity. Synaptic depolarizing (dominant excitation) responses decrease in strength for stimuli that are flashed at increasing distances away from the centre of the discharge field, while their onset latency increases. A detailed spatio-temporal analysis of these electrophysiological data shows that subthreshold synaptic responses observed in the 'silent' surround of cortical receptive fields result from the intracortical spread of activation waves carried by slowly conducting horizontal axons within primary visual cortex. They also predict that a perceptual facilitation may occur when feedforward activation produced by the motion signal in the retina travels in phase in the primary visual cortex with the visually induced spread of horizontal activation. A psychophysical correlate has been obtained in humans, showing that apparent motion produced by a sequence of co-linear Gabor patches, known to preferentially activate V1 orientation selective cells, are perceived by human observers as much faster than non co-linear sequences of the same physical speed.

Horizontal propagation of visual activity in the synaptic integration field of area 17 neurons.

The receptive field of a visual neuron is classically defined as the region of space (or retina) where a visual stimulus evokes a change in its firing activity. At the cortical level, a challenging issue concerns the roles of feedforward, local recurrent, intracortical, and cortico-cortical feedback connectivity in receptive field properties. Intracellular recordings in cat area 17 showed that the visually evoked synaptic integration field extends over a much larger area than that established on the basis of spike activity. Synaptic depolarizing responses to stimuli flashed at increasing distances from the center of the receptive field decreased in strength, whereas their onset latency increased. These findings suggest that subthreshold responses in the unresponsive region surrounding the classical discharge field result from the integration of visual activation waves spread by slowly conducting horizontal axons within primary visual cortex.

Synaptic integration fields and associative plasticity of visual cortical cells in vivo.

Two major constraints in connectivity decide the spatial extent of visual cortical receptive fields, both during development and adult functioning: 1) feedforward input, extrinsic to visual cortex, is organized in an orderly projection to form a point-to-point mapping of the retina onto the cortical mantle and constitutes the core of the minimal discharge field (MDF) after amplification by local intracortical circuits; and 2) a second type of connectivity consists of long distance horizontal intracortical connections which are thought to favor the binding of local visual operations occurring simultaneously in different parts of the visual field. We review here possible factors, intrinsic to the considered cortical cell, that may control the effectiveness of post-synaptic integration. Their expression during sensory recognition could depend on the spatio-temporal distribution of active inputs onto the target cell dendrite and on their interplay with non-linearities of the membrane properties. On the basis of intracellular recordings in cat area, 17, we have observed that peripheral responses (excitatory and inhibitory) could be boosted by coincident postsynaptic depolarization. This effect is lost if the response and the postsynaptic depolarization are mismatched by 1,000 ms, suggesting that temporal correlation of central and peripheral responses could regulate in a non-linear manner the gain of center-surround interactions. This temporal selectivity is compatible with up-regulation of composite potentials by the transient voltage-dependent activation of slowly inactivating conductances in visual cortical neurons. A direct consequence of these different considerations is that the receptive field (RF) of neurons in visual pathways should not be considered as a static hardwired window probing the outer environment, but as an active filter which may continuously adapt and be updated as a function of global context and past experience.

An intracellular study of space and time representation in primary visual cortical receptive fields.

In contrast with previous knowledge based on extracellular recordings, the recent development of intracellular techniques in vivo (sharp electrode or 'blind patch') ideally allows experimenters to analyze and dissect the contribution of feedforward and lateral connectivity in the functional expression of a synaptic 'integration field'. We will present recent data which demonstrate that the visual receptive field of cortical neurons described at the level of subthreshold synaptic events extends over much larger regions of the visual field than previously thought, and that the capacity of cells to amplify subthreshold responses depends on the immediate past history of their membrane potential. Our data suggest that visual cortical receptive fields should not be considered as a fixed entity but more as a dynamic field of integration and association. Two types of dynamics can be argued for: 1) the spatial structure of the minimal discharge field (defined by suprathreshold activation of the cell) can be profoundly reorganized at least during development and most probably during selective phases of learning under the control of activity-dependent mechanisms. Adaptive changes in visual responses are thought to reflect long-lasting potentiation and/or depression of synaptic efficacies conveying ON- and OFF-center information; and 2) during sensory processing, reconfiguration of synaptic weights may be achieved on a much faster time-scale and linked to nor-linear properties of the postsynaptic membrane as well as that of recruited networks. Association of information available in the central part of the receptive field (RF) and of input coming from the reputedly 'unresponsive' regions surrounding it, or arising simultaneously from different parts of the visual field, might be suppressive in certain cases and capable of boosting hidden responses in other cases, depending on the global stimulus configuration.