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.

Learning-induced plasticity in human audition: Objects, time, and space.

The human auditory system is comprised of specialized but interacting anatomic and functional pathways encoding object, spatial, and temporal information. We review how learning-induced plasticity manifests along these pathways and to what extent there are common mechanisms subserving such plasticity. A first series of experiments establishes a temporal hierarchy along which sounds of objects are discriminated along basic to fine-grained categorical boundaries and learned representations. A widespread network of temporal and (pre)frontal brain regions contributes to object discrimination via recursive processing. Learning-induced plasticity typically manifested as repetition suppression within a common set of brain regions. A second series considered how the temporal sequence of sound sources is represented. We show that lateralized responsiveness during the initial encoding phase of pairs of auditory spatial stimuli is critical for their accurate ordered perception. Finally, we consider how spatial representations are formed and modified through training-induced learning. A population-based model of spatial processing is supported wherein temporal and parietal structures interact in the encoding of relative and absolute spatial information over the initial ∼300ms post-stimulus onset. Collectively, these data provide insights into the functional organization of human audition and open directions for new developments in targeted diagnostic and neurorehabilitation strategies.

Generating controlled image sets in cognitive neuroscience research.

The investigation of perceptual and cognitive functions with non-invasive brain imaging methods critically depends on the careful selection of stimuli for use in experiments. For example, it must be verified that any observed effects follow from the parameter of interest (e.g. semantic category) rather than other low-level physical features (e.g. luminance, or spectral properties). Otherwise, interpretation of results is confounded. Often, researchers circumvent this issue by including additional control conditions or tasks, both of which are flawed and also prolong experiments. Here, we present some new approaches for controlling classes of stimuli intended for use in cognitive neuroscience, however these methods can be readily extrapolated to other applications and stimulus modalities. Our approach is comprised of two levels. The first level aims at equalizing individual stimuli in terms of their mean luminance. Each data point in the stimulus is adjusted to a standardized value based on a standard value across the stimulus battery. The second level analyzes two populations of stimuli along their spectral properties (i.e. spatial frequency) using a dissimilarity metric that equals the root mean square of the distance between two populations of objects as a function of spatial frequency along x- and y-dimensions of the image. Randomized permutations are used to obtain a minimal value between the populations to minimize, in a completely data-driven manner, the spectral differences between image sets. While another paper in this issue applies these methods in the case of acoustic stimuli (Aeschlimann et al., Brain Topogr 2008), we illustrate this approach here in detail for complex visual stimuli.

Binding under Conflict Conditions: State-Space Analysis of Multivariate EEG Synchronization.

Real-world objects are often endowed with features that violate Gestalt principles. In our experiment, we examined the neural correlates of binding under conflict conditions in terms of the binding-by-synchronization hypothesis. We presented an ambiguous stimulus ("diamond illusion") to 12 observers. The display consisted of four oblique gratings drifting within circular apertures. Its interpretation fluctuates between bound ("diamond") and unbound (component gratings) percepts. To model a situation in which Gestalt-driven analysis contradicts the perceptually explicit bound interpretation, we modified the original diamond (OD) stimulus by speeding up one grating. Using OD and modified diamond (MD) stimuli, we managed to dissociate the neural correlates of Gestalt-related (OD vs. MD) and perception-related (bound vs. unbound) factors. Their interaction was expected to reveal the neural networks synchronized specifically in the conflict situation. The synchronization topography of EEG was analyzed with the multivariate S-estimator technique. We found that good Gestalt (OD vs. MD) was associated with a higher posterior synchronization in the beta-gamma band. The effect of perception manifested itself as reciprocal modulations over the posterior and anterior regions (theta/beta-gamma bands). Specifically, higher posterior and lower anterior synchronization supported the bound percept, and the opposite was true for the unbound percept. The interaction showed that binding under challenging perceptual conditions is sustained by enhanced parietal synchronization. We argue that this distributed pattern of synchronization relates to the processes of multistage integration ranging from early grouping operations in the visual areas to maintaining representations in the frontal networks of sensory memory.

Effects of anxiety on visuospatial pattern discrimination and decision-making processes: what can we learn from brain dynamics ?

Detection and discrimination of visuospatial input involve at least extracting, selecting and encoding relevant information and decision-making processes allowing selecting a response. These two operations are altered, respectively, by attentional mechanisms that change discrimination capacities, and by beliefs concerning the likelihood of uncertain events. Information processing is tuned by the attentional level that acts like a filter on perception, while decision-making processes are weighed by subjective probability of risk. In addition, it has been shown that anxiety could affect the detection of unexpected events through the modification of the level of arousal. Consequently, purpose of this study concerns whether and how decision-making and brain dynamics are affected by anxiety. To investigate these questions, the performance of women with either a high (12) or a low (12) STAI-T (State-Trait Anxiety Inventory, Spielberger, 1983) was examined in a decision-making visuospatial task where subjects have to recognize a target visual pattern from non-target patterns. The target pattern was a schematic image of furniture arranged in such a way as to give the impression of a living room. Non-target patterns were created by either the compression or the dilatation of the distances between objects. Target and non-target patterns were always presented in the same configuration. Preliminary behavioral results show no group difference in reaction time. In addition, visuo-spatial abilities were analyzed trough the signal detection theory for quantifying perceptual decisions in the presence of uncertainty (Green and Swets, 1966). This theory treats detection of a stimulus as a decision-making process determined by the nature of the stimulus and cognitive factors. Astonishingly, no difference in d' (corresponding to the distance between means of the distributions) and c (corresponds to the likelihood ratio) indexes was observed. Comparison of Event-related potentials (ERP) reveals that brain dynamics differ according to anxiety. It shows differences in component latencies, particularly a delay in anxious subjects over posterior electrode sites. However, these differences are compensated during later components by shorter latencies in anxious subjects compared to non-anxious one. These inverted effects seem indicate that the absence of difference in reaction time rely on a compensation of attentional level that tunes cortical activation in anxious subjects, but they have to hammer away to maintain performance.

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.

As the world turns: short-term human spatial memory in egocentric and allocentric coordinates

We aimed to determine whether human subjects' reliance on different sources of spatial information encoded in different frames of reference (i.e., egocentric versus allocentric) affects their performance, decision time and memory capacity in a short-term spatial memory task performed in the real world. Subjects were asked to play the Memory game (a.k.a. the Concentration game) without an opponent, in four different conditions that controlled for the subjects' reliance on egocentric and/or allocentric frames of reference for the elaboration of a spatial representation of the image locations enabling maximal efficiency. We report experimental data from young adult men and women, and describe a mathematical model to estimate human short-term spatial memory capacity. We found that short-term spatial memory capacity was greatest when an egocentric spatial frame of reference enabled subjects to encode and remember the image locations. However, when egocentric information was not reliable, short-term spatial memory capacity was greater and decision time shorter when an allocentric representation of the image locations with respect to distant objects in the surrounding environment was available, as compared to when only a spatial representation encoding the relationships between the individual images, independent of the surrounding environment, was available. Our findings thus further demonstrate that changes in viewpoint produced by the movement of images placed in front of a stationary subject is not equivalent to the movement of the subject around stationary images. We discuss possible limitations of classical neuropsychological and virtual reality experiments of spatial memory, which typically restrict the sensory information normally available to human subjects in the real world.

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.