Spatial memory impairments in amnestic mild cognitive impairment in a virtual radial arm maze

Lee, Jun-Young; Kho, S. H.; Yoo, Hye Bin; Park, Soowon; Choi, Jung Seok; Kwon, Jun Soo; Ryeol, Kyung; Jung, Hee Yeon

doi:10.2147/ndt.s58185

Cited by 41 publications

(37 citation statements)

References 44 publications

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“…Fetal alcohol syndrome impaired both human (Uecker and Nadel, 1996) and rat (Reyes et al, 1989) performance of a RAM. A virtual RAM exists (Astur et al, 2004, Lee et al, 2014), that activates both hippocampal and frontal cortices (Astur et al, 2005). More importantly, people with hippocampal damage are impaired in the virtual RAM (Goodrich-Hunsaker and Hopkins, 2010) as occurs in rodents.…”

Section: Cross-species Cognitive Assessmentmentioning

confidence: 99%

Developing treatments for cognitive deficits in schizophrenia: The challenge of translation

Young

Geyer

2014

J Psychopharmacol

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Schizophrenia is a life-long debilitating mental disorder affecting tens of millions of people worldwide. The serendipitous discovery of antipsychotics focused pharmaceutical research on developing a better antipsychotic. Our understanding of the disorder has advanced however, with the knowledge that cognitive enhancers are required for patients in order to improve their everyday lives. Whilst antipsychotics treat psychosis, they do not enhance cognition and hence are not antischizophrenics. Developing pro-cognitive therapeutics has been extremely difficult however, especially when no approved treatment exists. In lieu of stumbling on an efficacious treatment, developing targeted compounds can be facilitated by understanding the neural mechanisms underlying altered cognitive functioning in patients. Equally importantly, these cognitive domains will need to be measured similarly in animals and humans so that novel targets can be tested prior to conducting expensive clinical trials. To date, the limited similarity of testing across species has resulted in a translational bottleneck. In this review, we emphasize that schizophrenia is a disorder characterized by abnormal cognitive behavior. Quantifying these abnormalities using tasks having cross-species validity would enable the quantification of comparable processes in rodents. This approach would increase the likelihood that the neural substrates underlying relevant behaviors will be conserved across species. Hence, we detail cross-species tasks which can be used to test the effects of manipulations relevant to schizophrenia and putative therapeutics. Such tasks offer the hope of providing a bridge between non-clinical and clinical testing that will eventually lead to treatments developed specifically for patients with deficient cognition.

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Section: Cross-species Cognitive Assessmentmentioning

confidence: 99%

Developing treatments for cognitive deficits in schizophrenia: The challenge of translation

Young

Geyer

2014

J Psychopharmacol

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“…Virtual environments have been used to mimic the tasks designed to examine behavioral phenotypes in a variety of species (e.g., mice, rats, cats, rabbits, and nonhuman primates) and provide a way to translate basic research to the human population (Dolins, Klimowicz, Kelley, & Menzel, 2014;MacLeod et al, 2010;Shore, Stanford, MacInnes, Klein, & Brown, 2001;van Gerven, Schneider, Wuitchik, & Skelton, 2012;Yuan, Daugherty, & Raz, 2014). For example, numerous maze tasks have been successfully created on a virtual platform to make direct comparisons between animal models and humans (Braun et al, 2012;Lee et al, 2014;MacLeod et al, 2010;Shore et al, 2001;van Gerven et al, 2012;Yuan et al, 2014).…”

mentioning

confidence: 99%

Translating dyslexia across species

et al. 2016

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Direct relationships between induced mutation in the DCDC2 candidate dyslexia susceptibility gene in mice and changes in behavioral measures of visual spatial learning have been reported. We were interested in determining whether performance on a visual-spatial learning and memory task could be translated across species (study 1) and whether children with reading impairment showed a similar impairment to animal models of the disorder (study 2). Study 1 included 37 participants who completed six trials of four different virtual Hebb-Williams maze configurations. A 2 × 4 × 6 mixed factorial repeated measures ANOVA indicated consistency in performance between humans and mice on these tasks, enabling us to translate across species. Study 2 included a total of 91 participants (age range = 8-13 years). Eighteen participants were identified with reading disorder by performance on the Woodcock-Johnson III Tests of Achievement. Participants completed six trials of five separate virtual Hebb-Williams maze configurations. A 2 × 5 × 6 mixed factorial ANCOVA (gender as covariate) indicated that individuals with reading impairment demonstrated impaired visuo-spatial performance on this task. Overall, results from this study suggest that we are able to translate behavioral deficits observed in genetic animal models of dyslexia to humans with reading impairment. Future studies will utilize the virtual environment to further explore the underlying basis for this impairment.

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“…Changes in spatial behaviour are well-documented in patients with Alzheimer's disease (Graham 2015). For example, formal assessment of navigation strategies in patients indicates an early decline in path integration and allocentric memory processes in tasks analogues to the watermaze and the radial maze (Laczó et al 2010;Lee et al 2014;Mokrisova et al 2016). In addition, foraging for rewards in an open field arena has revealed deficits in allocentric memory in patients with Down syndrome, who are at increased risk of developing dementia (Lavenex et al 2015).…”

Section: Introductionmentioning

confidence: 99%

A rapidly acquired foraging-based working memory task, sensitive to hippocampal lesions, reveals age-dependent and age-independent behavioural changes in a mouse model of amyloid pathology

Evans

Hvoslef-Eide

Thomas

et al. 2018

Neurobiology of Learning and Memory

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Three experiments examined the ability of mice to forage efficiently for liquid rewards in pots located in an open field arena. Search behaviour was unconstrained other than by the walls of the arena. All mice acquired the task within 4 days of training, with one trial per day. Experiment 1 tested the hypothesis that hippocampal lesions would disrupt foraging behaviour using extramaze cues. Mice with hippocampal lesions showed normal latency to initiate foraging and to complete the task relative to sham-operated mice. However, lesioned mice showed increased perseverative responding (sensitization) to recently rewarded locations, increased total working memory errors and an increased propensity to search near previously rewarded locations. In Experiment 2, the extramaze cues were obscured and each pot was identified by a unique pattern. Under these conditions, mice with hippocampal lesions showed comparable working memory errors to control mice. However, lesioned mice continued to display increased perseverative responding and altered search strategies. Experiment 3 tested the hypothesis that age-related accumulation of amyloid would disrupt foraging behaviour in transgenic PDAPP mice expressing the V717F amyloid precursor protein (APP) mutation. Consistent with previous findings, PDAPP mice showed both age-dependent and age-independent behavioural changes. More specifically, 14-16 month-old PDAPP mice showed a deficit in perseverative responding and working memory errors. In contrast, changes in search behaviour, such as systematic circling, were present throughout development. The latter indicates that APP overexpression contributed to some features of the PDAPP behavioural phenotype, whereas working memory and flexible responding was sensitive to ageing and β-amyloid burden. In conclusion, the present study provided novel insight into the role of the hippocampus and the effects of APP overexpression on memory and search behaviour in an open-field foraging task.

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Spatial memory impairments in amnestic mild cognitive impairment in a virtual radial arm maze

Cited by 41 publications

References 44 publications

Developing treatments for cognitive deficits in schizophrenia: The challenge of translation

Developing treatments for cognitive deficits in schizophrenia: The challenge of translation

Translating dyslexia across species

A rapidly acquired foraging-based working memory task, sensitive to hippocampal lesions, reveals age-dependent and age-independent behavioural changes in a mouse model of amyloid pathology

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