Exploration of the visual system : Part 2. In vivo analysis methods : virtual-reality optomotor system, fundus examination and fluorescent angiography

The mouse has emerged as an animal model for many diseases. At IRO, we have used this animal to understand the development of many eye diseases and treatment of some of them. Precise evaluation of vision is a prerequisite for both these approaches. In this unit we describe three ways to measure vision: testing the optokinetic response, and evaluating the fundus by direct observation and by fluorescent angiography.

Automatic top-down processing explains common left occipito-temporal responses to visual words and objects.

Previous studies have demonstrated that a region in the left ventral occipito-temporal (LvOT) cortex is highly selective to the visual forms of written words and objects relative to closely matched visual stimuli. Here, we investigated why LvOT activation is not higher for reading than picture naming even though written words and pictures of objects have grossly different visual forms. To compare neuronal responses for words and pictures within the same LvOT area, we used functional magnetic resonance imaging adaptation and instructed participants to name target stimuli that followed briefly presented masked primes that were either presented in the same stimulus type as the target (word-word, picture-picture) or a different stimulus type (picture-word, word-picture). We found that activation throughout posterior and anterior parts of LvOT was reduced when the prime had the same name/response as the target irrespective of whether the prime-target relationship was within or between stimulus type. As posterior LvOT is a visual form processing area, and there was no visual form similarity between different stimulus types, we suggest that our results indicate automatic top-down influences from pictures to words and words to pictures. This novel perspective motivates further investigation of the functional properties of this intriguing region.

Long-term fluctuation of relative afferent pupillary defect in subjects with normal visual function.

PURPOSE: To determine whether the relative afferent pupillary defect (RAPD) remains constant over time in normal subjects. METHODS: Seventeen normal subjects were tested with infrared pupillography and automated perimetry in four sessions over 3 years. The changes in RAPD and visual field asymmetry between testing sessions were compared. RESULTS: The range of RAPD was 0.0 to 0.3 log unit, and the difference in the mean deviation between the eyes on automated static perimetry was 0 to 3 dB. Eight subjects repeatedly had an RAPD in the same eye. There was no correlation between the RAPD and the visual field asymmetry at the same visit. Changes in the magnitude of the RAPD between any two sessions were typically small (median, 0.08 log unit; 25th percentile, 0.04 log unit; 75th percentile, 0.15 log unit). CONCLUSIONS: Some normal subjects may show a persistent but small RAPD in the absence of detectable pathologic disease. Therefore, an isolated RAPD in the range of 0.3 log unit that is not associated with any other significant historical or clinical finding should probably be considered benign.

Accurate performance of a rat model of schizophrenia in the water maze depends on visual cue availability and stability: a distortion in cognitive mapping abilities?

Rats were treated postnatally (PND 5-16) with BSO (l-buthionine-(S,R)-sulfoximine) in an animal model of schizophrenia based on transient glutathione deficit. The BSO treated rats were impaired in patrolling a maze or a homing table when adult, yet demonstrated preserved escape learning, place discrimination and reversal in a water maze task [37]. In the present work, BSO rats' performance in the water maze was assessed in conditions controlling for the available visual cues. First, in a completely curtained environment with two salient controlled cues, BSO rats showed little accuracy compared to control rats. Secondly, pre-trained BSO rats were impaired in reaching the familiar spatial position when curtains partially occluded different portions of the room environment in successive sessions. The apparently preserved place learning in a classical water maze task thus appears to require the stability and the richness of visual landmarks from the surrounding environment. In other words, the accuracy of BSO rats in place and reversal learning is impaired in a minimal cue condition or when the visual panorama changes between trials. However, if the panorama remains rich and stable between trials, BSO rats are equally efficient in reaching a familiar position or in learning a new one. This suggests that the BSO accurate performance in the water maze does not satisfy all the criteria for a cognitive map based navigation on the integration of polymodal cues. It supports the general hypothesis of a binding deficit in BSO rats.

Visual binding abilities in the initial and advanced stages of schizophrenia

OBJECTIVE: The study tests the hypothesis that intramodal visual binding is disturbed in schizophrenia and should be detectable in all illness stages as a stable trait marker. METHOD: Three groups of patients (rehospitalized chronic schizophrenic, first admitted schizophrenic and schizotypal patients believed to be suffering from a pre-schizophrenic prodrome) and a group of normal control subjects were tested on three tasks targeting visual 'binding' abilities (Muller-Lyer's illusion and two figure detection tasks) in addition to control parameters such as reaction time, visual selective attention, Raven's test and two conventional cortical tasks of spatial working memory (SWM) and a global local test. RESULTS: Chronic patients had a decreased performance on the binding tests. Unexpectedly, the prodromal group exhibited an enhanced Gestalt extraction on these tests compared both to schizophrenic patients and to healthy subjects. Furthermore, chronic schizophrenia was associated with a poor performance on cortical tests of SWM, global local and on Raven. This association appears to be mediated by or linked to the chronicity of the illness. CONCLUSION: The study confirms a variety of neurocognitive deficits in schizophrenia which, however, in this sample seem to be linked to chronicity of illness. However, certain aspects of visual processing concerned with Gestalt extraction deserve attention as potential vulnerability- or prodrome- indicators. The initial hypothesis of the study is rejected.

The Visual Dysphagia Questionnaire: Piloting a New Tool for Assessing Food Consistency-Dependent Dysphagia in Eosinophilic Esophagitis

Background and Aims: The international EEsAI study group is currently developing the first activity index specific for Eosinophilic Esophagitis (EoE). None of the existing dysphagia questionnaires takes into account the consistency of the ingested food that considerably impacts the symptom presentation. Goal: To develop an EoE-specific questionnaire assessing dysphagia associated with different food consistencies. Methods: Based on patient chart reviews, an expert panel (EEsAI study group) identified internationally standardized food prototypes typically associated with EoE-related dysphagia. Food consistencies were correlated with EoE-related dysphagia, also considering potential food avoidance. This Visual Dysphagia Questionnaire (VDQ) was then tested, as a pilot, in 10 EoE patients. Results: The following 9 food consistency prototypes were identified: water, soft foods (pudding, jelly), grits, toast bread, French fries, dry rice, ground meat, raw fibrous foods (eg. apple, carrot), solid meat. Dysphagia was ranked on a 5-point Likert scale (0=no difficulties, 5=very severe difficulties, food will not pass). Severity of dysphagia in the 10 EoE patients was related to the eosinophil load and presence of esophageal strictures. Conclusions: The VDQ will be the first EoE-specific tool for assessing dysphagia related to internationally defined food consistencies. It performed well in a pilot study and will now be further evaluated in a cohort study including 100 adult and 100 pediatric EoE patients.

Impaired early visual response modulations to spatial information in chronic schizophrenia.

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia.

Functional mapping of the human visual cortex with intravoxel incoherent motion MRI.

Functional imaging with intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) is demonstrated. Images were acquired at 3 Tesla using a standard Stejskal-Tanner diffusion-weighted echo-planar imaging sequence with multiple b-values. Cerebro-spinal fluid signal, which is highly incoherent, was suppressed with an inversion recovery preparation pulse. IVIM microvascular perfusion parameters were calculated according to a two-compartment (vascular and non-vascular) diffusion model. The results obtained in 8 healthy human volunteers during visual stimulation are presented. The IVIM blood flow related parameter fD* increased 170% during stimulation in the visual cortex, and 70% in the underlying white matter.

Deteriorated visual backward masking in the shine-through effect in adolescents with psychosis.

Visual backward masking is a reliable and widely used tool in schizophrenia research. Whereas many studies have shown masking deficits in adult patients, there are only very few studies with adolescents with psychosis-and with controversial results. Masking deficits of adolescents are of primary interest because they are not caused by long-term suffering from the disease and severe medication. We investigated 15 adolescents with psychosis and 19 age-matched controls in the shine-through backward masking paradigm for which strong performance deficits were shown previously in adult schizophrenic patients and their relatives. Adolescents with psychosis were strongly impaired in the shine-through effect compared to controls. This result adds further evidence that backward masking is an endophenotype of schizophrenia.

Visual stimulus-dependent changes in interhemispheric EEG coherence in humans.

We analyzed the coherence of electroencephalographic (EEG) signals recorded symmetrically from the two hemispheres, while subjects (n = 9) were viewing visual stimuli. Considering the many common features of the callosal connectivity in mammals, we expected that, as in our animal studies, interhemispheric coherence (ICoh) would increase only with bilateral iso-oriented gratings located close to the vertical meridian of the visual field, or extending across it. Indeed, a single grating that extended across the vertical meridian significantly increased the EEG ICoh in normal adult subjects. These ICoh responses were obtained from occipital and parietal derivations and were restricted to the gamma frequency band. They were detectable with different EEG references and were robust across and within subjects. Other unilateral and bilateral stimuli, including identical gratings that were effective in anesthetized animals, did not affect ICoh in humans. This fact suggests the existence of regulatory influences, possibly of a top-down kind, on the pattern of callosal activation in conscious human subjects. In addition to establishing the validity of EEG coherence analysis for assaying cortico-cortical connectivity, this study extends to the human brain the finding that visual stimuli cause interhemispheric synchronization, particularly in frequencies of the gamma band. It also indicates that the synchronization is carried out by cortico-cortical connection and suggests similarities in the organization of visual callosal connections in animals and in man.