Deficits In Visual Learning Research Articles

Verbal learning, working memory, and attention/vigilance may be candidate phenotypes of bipolar II depression in Chinese Han nationality

ObjectivesBipolar II depression (BD-II) is a subtype of bipolar disorder with recurrent depressive, manic, and frequent depressive episodes as the main clinical manifestations. This study aimed to compare the cognitive function of patients with BD-II with those of healthy siblings and controls to explore the internal phenotype of BD-II in the field of cognitive function. Methods66 BD-II patients, 58 healthy siblings, and 55 healthy controls were assessed with the Trail Making Test (TMT), Digit Symbol Coding Test (DSCT), Category Fluency, Hopkins Verbal Learning Test-Revised (HVLTR), Brief Visuospatial Memory Test-Revised (BVMT-R), Wechsler Memory Scale 3rd ed. Spatial Span Subtest (WMS-III SS), Neuropsychological Assessment Battery Mazes (NABM), Continuous Performance Test, and Identical Pairs (CPT-IP). ResultsPatients with BD-II showed cognitive deficits in visual learning, reasoning and problem solving, verbal learning, attention/vigilance, working memory, and speed of processing. Healthy siblings showed cognitive deficits in reasoning and problem solving, verbal learning, attention/vigilance, working memory, and speed of processing. Substantial differences were observed among the three groups in reasoning and problem solving. ConclusionsVerbal learning, working memory, and attention/vigilance may be potential endophenotypes that can be used to identify BD-II among Han Chinese in the early stage.

Deficits in Seizure Threshold and Other Behaviors in Adult Mice without Gross Neuroanatomic Injury after Late Gestation Transient Prenatal Hypoxia

Intrauterine hypoxia is a common cause of brain injury in children resulting in a broad spectrum of long-term neurodevelopmental sequela, including life-long disabilities that can occur even in the absence of severe neuroanatomic damage. Postnatal hypoxia-ischemia rodent models are commonly used to understand the effects of ischemia and transient hypoxia on the developing brain. Postnatal models, however, have some limitations. First, they do not test the impact of placental pathologies on outcomes from hypoxia. Second, they primarily recapitulate severe injury because they provoke substantial cell death, which is not seen in children with mild hypoxic injury. Lastly, they do not model preterm hypoxic injury. Prenatal models of hypoxia in mice may allow us to address some of these limitations to expand our understanding of developmental brain injury. The published rodent models of prenatal hypoxia employ multiple days of hypoxic exposure or complicated surgical procedures, making these models challenging to perform consistently in mice. Furthermore, large animal models suggest that transient prenatal hypoxia without ischemia is sufficient to lead to significant functional impairment to the developing brain. However, these large animal studies are resource-intensive and not readily amenable to mechanistic molecular studies. Therefore, here we characterized the effect of late gestation (embryonic day 17.5) transient prenatal hypoxia (5% inspired oxygen) on long-term anatomical and neurodevelopmental outcomes in mice. Late gestation transient prenatal hypoxia increased hypoxia-inducible factor 1 alpha protein levels (a marker of hypoxic exposure) in the fetal brain. Hypoxia exposure predisposed animals to decreased weight at postnatal day 2, which normalized by day 8. However, hypoxia did not affect gestational age at birth, litter size at birth, or pup survival. No differences in fetal brain cell death or long-term gray or white matter changes resulted from hypoxia. Animals exposed to prenatal hypoxia did have several long-term functional consequences, including sex-dichotomous changes. Hypoxia exposure was associated with a decreased seizure threshold and abnormalities in hindlimb strength and repetitive behaviors in males and females. Males exposed to hypoxia had increased anxiety-related deficits, whereas females had deficits in social interaction. Neither sex developed any motor or visual learning deficits. This study demonstrates that late gestation transient prenatal hypoxia in mice is a simple, clinically relevant paradigm for studying putative environmental and genetic modulators of the long-term effects of hypoxia on the developing brain.

Mouse Nr2f1 haploinsufficiency unveils new pathological mechanisms of a human optic atrophy syndrome

Optic nerve atrophy represents the most common form of hereditary optic neuropathies leading to vision impairment. The recently described Bosch‐Boonstra‐Schaaf optic atrophy (BBSOA) syndrome denotes an autosomal dominant genetic form of neuropathy caused by mutations or deletions in the NR2F1 gene. Herein, we describe a mouse model recapitulating key features of BBSOA patients—optic nerve atrophy, optic disc anomalies, and visual deficits—thus representing the only available mouse model for this syndrome. Notably, Nr2f1‐deficient optic nerves develop an imbalance between oligodendrocytes and astrocytes leading to postnatal hypomyelination and astrogliosis. Adult heterozygous mice display a slower optic axonal conduction velocity from the retina to high‐order visual centers together with associative visual learning deficits. Importantly, some of these clinical features, such the optic nerve hypomyelination, could be rescued by chemical drug treatment in early postnatal life. Overall, our data shed new insights into the cellular mechanisms of optic nerve atrophy in BBSOA patients and open a promising avenue for future therapeutic approaches.

Visual and verbal learning and memory in cystinosis

Cystinosis is a rare genetic lysosomal storage disorder characterized by the accumulation of cystine in lysosomes. Many organ systems are vulnerable to this cystine accumulation including the CNS. A past study demonstrated that children with cystinosis have deficits in visual learning and memory while their verbal learning and memory and global intellectual function are spared (Spilkin, Ballantyne, & Trauner, 2009). However, no related study has been performed to assess the dissociation between visual and verbal learning and memory in adults with cystinosis who have had the benefit of longterm treatment with the cystine-depleting agent, cysteamine. In this study we assessed visual and verbal learning and memory in 15 adults with cystinosis, with a mean age of 30.2 years. The results indicate that adults with cystinosis have no significant deficits in either verbal or visual learning and memory. However, the individuals did perform better on the verbal assessment. The results suggest that if early and continued treatment is given to individuals with cystinosis there is a relative sparing of visual learning and memory that might have otherwise declined. This emphasizes the essential nature of the proper clinical management of cystinosis.

Cognitive deficits in subjects at risk for psychosis, first-episode and chronic schizophrenia patients

Background: Identifying the types and characteristics of cognitive deficits before the onset of schizophrenia and during its subsequent course could improve early detection and contribute to our understanding of the evolution of the core behavioral deficits underlying this disorder. Methods: This study used the Measurement and Treatment Research to Improve Cognition In Schizophrenia (MATRICS) battery to identify cognitive deficits and their progression during the course of schizophrenia from genetic high risk (HRF) subjects, subjects with prodromal symptoms (prodromal), and patients with first episode (FSCZ) and multi-episode (CSCZ) schizophrenia, compared to controls, in a Chinese Han population of 267 subjects. Results: There were statistically significant cognitive deficits which first appeared in prodromal subjects which were also present in FSCZ and CSCZ. There were no statistically significant differences between controls and HRF on any cognitive measure. Deficits in Visual Learning, Speed of Processing, and Overall Cognition were significantly correlated with some symptom measures on PANSS or SIPS. There were no statistically significant differences in cognitive deficits between FSCZ and CSCZ, and on most measures the patients with schizophrenia did not show a progression to more severe cognitive deficits than the prodromal subjects. Conclusions: In this sample of Chinese subjects, prodromal subjects showed significant cognitive deficits which were similar in most domains to those found in patients with schizophrenia. Whether the pattern of cognitive deficits on the MATRICS battery found in prodromal subjects will help predict conversion to diagnosed schizophrenia or other psychotic disorders would help determine how useful this profile of cognitive deficits is as a potential endophenotype for schizophrenia.

RBFOX3/NeuN is dispensable for visual function.

RBFOX3/NeuN is a neuronal splicing regulator involved in neural circuitry balance, as well as neurogenesis and synaptogenesis. Rbfox3 is expressed in neurons; however, in the retina, expression is restricted to cells in the ganglion cell layer and some cells of the inner nuclear layer. Rbfox3 is expressed in a layer-specific manner in the retina, which implies a functional role, however, the role of RBFOX3 in the retina is unknown. Rbfox3 homozygous knockout (Rbfox3-/-) mice exhibit deficits in visual learning; therefore, understanding the role of RBFOX3 in the retina is critical for interpreting behavioral results. We found Rbfox3 expression was developmentally regulated in the retina and specifically expressed in ganglion cells, amacrine cells and horizontal cells of the retina. We demonstrate deletion of Rbfox3 resulted in a reduction in the thickness of the inner plexiform layer of the retina, where synapses are formed. Number of ganglion cells and amacrine cells is normal with loss of Rbfox3. Innervation of retinal ganglion cells into their targeted brain regions is normal in Rbfox3-/- mice. Importantly, Rbfox3-/- mice displayed normal non-image and image forming functions. Taken together, our results suggest RBFOX3 is dispensable for visual function.

Schizophrenia, smoking status, and performance on the matrics Cognitive Consensus Battery.

Cognitive deficits and high rates of nicotine dependence are consistently documented in the schizophrenia literature. However, there is currently no consensus about how regular smoking influences cognition in schizophrenia or which cognitive domains are most affected by chronic smoking. Previous studies have also failed to disambiguate the effects of chronic nicotine from those of acute exposure. The current study uses a novel approach to testing nicotine addicted patients at a time-point between acute enhancement and withdrawal and implements the MATRICS Cognitive Consensus Battery (MCCB) to compare the overall cognitive performance of regular smokers (n=40) and nonsmokers (n=36) with schizophrenia. Controlling for age, gender, and education, smokers with schizophrenia were significantly more impaired on a visual learning task, the Brief Visuospatial Memory Test-Revised (BVMT-R), than their nonsmoking peers. Among smokers, smoking behavior (i.e., exhaled carbon monoxide levels of smokers) predicted BVMT-R T score; greater smoking was associated with more impaired visual learning. Negative symptom severity was not predictive of greater visual learning deficits in smokers or nonsmokers. Future longitudinal research will be required to determine if there is a dose-response relationship between chronic nicotine and visual learning impairment in patients at various stages of psychotic illness.

Therapeutic benefits of methylene blue on cognitive impairment during chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion, a risk factor for mild cognitive impairment and Alzheimer's disease, affects mitochondrial respiration and memory consolidation. Therefore, drugs that improve mitochondrial function may be appropriate cognitive treatments for cerebral hypoperfusion. Methylene blue (MB) crosses the blood-brain barrier and at low doses serves as an electron cycler in the mitochondrial electron transport chain. Previous studies implicate MB in both memory enhancement and neuroprotection. We treated rats that underwent permanent bilateral carotid occlusion (2VO) or sham surgery with daily 4 mg/kg USP MB or saline for one month. Animals went through a battery of behavioral tests, including open field, visual water maze, and odor-recognition tasks. 2VO rats showed worse performance in the visual water task without showing differences in general motor activity, visually guided swimming ability or odor recognition. Daily MB attenuated the deficits in visual learning and memory that resulted from cerebrovascular insufficiency. During training on three different discrimination problems in the visual water task, all animals were able to reach a criterion of 8/10 correct trials, but 2VO animals took longer to learn each problem and showed lower performance in a challenging memory probe. However, animals that received daily post-session MB performed significantly better than saline-treated subjects both during training and during the memory probe. This is the first study to demonstrate that MB attenuates learning and memory deficits caused by carotid occlusion. The results suggest that MB may be beneficial for conditions involving chronic cerebral hypoperfusion, such as mild cognitive impairment, vascular dementia, and Alzheimer's disease.

Increased reaction time predicts visual learning deficits in Parkinson's disease

To determine whether the process involved in movement preparation of patients in the early stages of Parkinson's disease (PD) shares attentional resources with visual learning, we tested 23 patients with PD and 13 healthy controls with two different tasks. The first was a motor task where subjects were required to move as soon as possible to randomly presented targets by minimizing reaction time. The second was a visual learning task where targets were presented in a preset order and subjects were asked to learn the sequence order by attending to the display without moving. Patients with PD showed higher reaction and movement times, while visual learning was reduced compared with controls. For patients with PD, reaction times, but not movement times, displayed an inverse significant correlation with the scores of visual learning. We conclude that visual declarative learning and movement preparation might share similar attentional and working memory resources. (c) 2010 Movement Disorder Society.

Visual Learning Deficits in Nonresected Patients with Right Temporal Lobe Epilepsy

A visual learning test Diagnostikum für Zerebralschäden (DCS) was revised and applied to three matched patient groups defined by interictal and ictal EEG findings: 24 patients with left temporal lobe epilepsy (LTE), 19 patients with right temporal lobe epilepsy (RTE) and 34 patients with a bitemporal epileptic involvement (BTE). Fifty seven healthy subjects served as controls. Performance on a measure of sustained attention and visual construction was also assessed. Results were as follows: (1) In contrast to controls and LTE patients, patients with right temporal epileptic involvement (RTE/BTE) showed a significantly reduced immediate recall as well as a reduced learning capacity and mean learning performance. (2) Patients made significantly more errors than controls, with RTE patients exhibiting the most visuo-spatial errors. (3) RTE/BTE patients additionally showed impaired performances on visuoconstruction, but when visual construction scores were used as covariate, they did not diminish the strong group effects upon learning. (4) Attentional deficits were independent from memory deficits and rather reflected the bitemporal extention of epilepsy. As a conclusion, the data suggest an impairment of visual-spatial consolidation processes in patients with right temporal lobe epilepsy.

Spatial and visual learning deficits in Alzheimer's and Parkinson's disease

Experimental paradigms adopted from animal models were used to compare the neuropsychological mechanisms underlying the dementias of Alzheimer's and Parkinson's diseases. Two tasks were selected because characteristic profiles of impairment in nonhuman primates are seen following selective lesions of frontal cortex, temporal cortex, and fornix. The tasks consisted of a spatial and a visual learning problem, each with two components: (1) original learning and (2) reversal of the original learning. The Alzheimer's patients were significantly impaired on original learning and reversal learning in the visual modality compared with demented Parkinson's patients, even though both groups were equated for severity of dementia. On the spatial tasks, both the Alzheimer's and the demented Parkinson's patients were impaired on reversal learning but not on original learning. The profile of deficits on the visual tasks may serve to differentiate Alzheimer's from Parkinson's dementia and may reflect selective orbitofrontal system lesions in the former.

Event-related potentials in children with specific visual cognitive disability

Event-related potentials (ERPs) elicited by novel and well memorozed non-verbal visual patterns were recorded over the right and left hemispheres from ten children with Specific Visual Cognitive Disability (SVCD) and ten matched Control subjects (C). ERPs of SVCD children were generally longer in latency (particularly N2) and decreased in amplitude (particularly P3) relative to the ERPs of Cs. No hemisphere differences were observed in the SVCD group, while the latency on N2 in the C group tended to be slightly shorter and the amplitude of P3 was significantly larger over the right than over the left hemisphere. The results are discussed in terms of deficits in visual learning and visual pattern analysis. The different hemispheric pattern in SVCD children as compared to Cs is suggested to be a symptom secondary to basic visual cognitive deficits.

Glutamate and specific perceptual input interact to cause retarded learning in chicks

Intracranial glutamate administered to newly hatched chickens has previously been demonstrated to cause permanent deficits in visual learning. A study was therefore undertaken to determine whether this effect was in any way related to the visual input occurring concomitantly. It was found that for slowed visual learning to be induced the chick needed to see intersecting lines, angles or circles for 3 hr after glutamate administration on the second day of life. Stationary or moving parallel lines were not effective. Slowed visual learning appeared to result from an interaction between glutamate and the neural activity resulting from exposure to patterned input and not the processes required for learning about the patterns. These results are discussed in context of the neurophysiology of the visual system. It is proposed that glutamate causes slowed visual learning by interfering with early forebrain development of higher visual areas which results from precise and specific changes in neural connectivity occurring in response to perceptual input. Experiments utilizing ouabain indicated that the action of glutamate was predominantly extracellular. Glutamate may affect neural interconnections as a consequence of its putative neurotransmitter actions.

Deficits in visual learning produced by posterior temporal lesions in cats.

Eight cats with lesions in the posterior temporal (PT) cortex, seven cats with lesions in the basolateral amygdala (BLA), and eight intact controls were observed on eight tests of visual discrimination learning and of spontaneous responses to salient visual stimuli. The effects of the two lesions were somewhat dissociable. The PT lesions were accompanied by a severe deficit in pattern discrimination learning but no loss in visual tracking or orientation to the silhouette of a threatening cat. The BLA lesions produced a milder and less consistent loss in pattern discrimination but serious defects in tracking and reponse to the cat silhouette. Both operated groups performed well on the visual cliff. The deficit from PT lesions appeared independent of damage to the geniculocortical system. The parallel of symptoms from PT lesions in cats and inferotemporal lesions in monkeys is discussed.

Deficits in visual learning by cats with lesions of the visual cortex

Cats were trained for food reward in a divided straight maze or in a V-maze on a light-dark discrimination and on a series of horizontal-vertical stripe discriminations. Errors were scored by both door-push and alley-entrance criteria. After lesions of the visual cortex, cats could relearn or initially learn the light-dark discrimination but were not successfully trained to shift from brightness to pattern cues when learning the series of horizontal-vertical stripe discriminations, using a modified method of limits procedure. Both unoperated cats and cats with lesions of the visual cortex committed alley-entrance errors when learning the light-dark discrimination.

Similar deficits in visual learning by cats with lesions of the frontal cortex or of the superior colliculus

Similar deficits in visual learning by cats with lesions of the frontal cortex or of the superior colliculus

Visual-learning deficits following cerebellar damage in rats.

Allan Memorial Institute, McGill University, Montreal, Quebec, CanadaExperiments with rats suggest that: (a) cerebellar damage hinders learningbut not performance in some visual-learning tasks under conditions of highmotivation; and (b) the location and size of the cerebellar lesions are im-portant variables for showing this effect. It is speculated that the intactcerebellum may act to modulate motor arousal and prevent overfacilita-tion of inappropriate responses during learning.

Visual receptive fields in the superior colliculus of the cat.

Visual receptive fields in the superior colliculus of the cat.