Coppola, Vincent J; Hough, Gerald; Bingman, Verner P
The hippocampus is particularly susceptible to age-related degeneration that, like hippocampal lesions, is thought to lead to age-related decline in spatial memory and navigation. Lesions to the avian hippocampal formation (HF) also result in impaired spatial memory and navigation, but the relationship between aging and HF-dependent spatial cognition is unknown. To investigate possible age-related decline in avian spatial cognition, the current study investigated spatial working memory performance in older homing pigeons (10+ years of age). Pigeons completed a behavioral procedure nearly identical to the delayed spatial, win-shift procedure in a modified radial arm maze that has been previously used to study spatial working memory in rats and pigeons. The results revealed that the older pigeons required a greater number of choices to task completion and were less accurate with their first 4 choices as compared to younger pigeons (1-2 years of age). In addition, older pigeons were more likely to adopt a stereotyped sampling strategy, which explained in part their impaired performance. To the best of our knowledge, this study is the first to demonstrate an age-related impairment of HF-dependent, spatial memory in birds. Implications and future directions of the findings are discussed.
Verbitsky, Miguel; Yonan, Amanda L.; Malleret, Gael; Kandel, Eric R.; Gilliam, T. Conrad; Pavlidis, Paul
We have carried out a global survey of age-related changes in mRNA levels in the 57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged…
Taridi, Nursiati Mohamad; Abd Rani, Nazirah; Abd Latiff, Azian; Ngah, Wan Zurinah Wan; Mazlan, Musalmah
Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.
Belham, Flávia Schechtman; Satler, Corina; Garcia, Ana; Tomaz, Carlos; Gasbarri, Antonella; Rego, Artur; Tavares, Maria Clotilde H
Emotion, importantly displayed by facial expressions, is one of the most significant memory modulators. The interaction between memory and the different emotional valences change across lifespan, while young adults (YA) are expected to better recall negative events (Negativity Bias Hypothesis), older adults (OA) tend to focus on positive stimuli (Positivity Effect Hypothesis). This research work aims at verifying whether cortical electrical activity of these two age groups would also be differently influenced by emotional valences in a visuo-spatial working memory task. 27 YA (13 males) and 25 OA (14 males), all healthy volunteers, underwent electroencephalographic recordings (21 scalp electrodes montage), while performing the Spatial Delayed Recognition Span Task using a touch screen with different stimuli categories: neutral, positive and negative faces and geometric pictures. YA obtained higher scores than OA, and showed higher activation of theta and alpha bands in the frontal and midline regions, besides a more evident right-hemispheric asymmetry on alpha band when compared to OA. For both age groups, performance in the task was worse for positive faces than to negative and to neutral faces. Facial stimuli induced a better performance and higher alpha activation on the pre-frontal region for YA, and on the midline, occipital and left temporal regions for OA when compared to geometric figures. The superior performance of YA was expected due to the natural cognitive deficits connected to ageing, as was a better performance with facial stimuli due to the evolutionary importance of faces. These results were related to cortical activity on areas of importance for action-planning, decision making and sustained attention. Taken together, they are in accordance with the Negativity Bias but do not support the Positivity Effect. The methodology used was able to identify age-related differences in cortical activity during emotional mnemonic processing and may be
Belham, Flávia Schechtman; Satler, Corina; Garcia, Ana; Tomaz, Carlos; Gasbarri, Antonella; Rego, Artur; Tavares, Maria Clotilde H.
Emotion, importantly displayed by facial expressions, is one of the most significant memory modulators. The interaction between memory and the different emotional valences change across lifespan, while young adults (YA) are expected to better recall negative events (Negativity Bias Hypothesis), older adults (OA) tend to focus on positive stimuli (Positivity Effect Hypothesis). This research work aims at verifying whether cortical electrical activity of these two age groups would also be differently influenced by emotional valences in a visuo-spatial working memory task. 27 YA (13 males) and 25 OA (14 males), all healthy volunteers, underwent electroencephalographic recordings (21 scalp electrodes montage), while performing the Spatial Delayed Recognition Span Task using a touch screen with different stimuli categories: neutral, positive and negative faces and geometric pictures. YA obtained higher scores than OA, and showed higher activation of theta and alpha bands in the frontal and midline regions, besides a more evident right-hemispheric asymmetry on alpha band when compared to OA. For both age groups, performance in the task was worse for positive faces than to negative and to neutral faces. Facial stimuli induced a better performance and higher alpha activation on the pre-frontal region for YA, and on the midline, occipital and left temporal regions for OA when compared to geometric figures. The superior performance of YA was expected due to the natural cognitive deficits connected to ageing, as was a better performance with facial stimuli due to the evolutionary importance of faces. These results were related to cortical activity on areas of importance for action-planning, decision making and sustained attention. Taken together, they are in accordance with the Negativity Bias but do not support the Positivity Effect. The methodology used was able to identify age-related differences in cortical activity during emotional mnemonic processing and may be
Sinnott, Jan D.; And Others
As part of an experimental research program on lifespan naturalistic and laboratory memory for spatial representation, investigators examined interactions between the effects of visual and kinesthetic encoding and age on memory for space using a modification of the Sinnott (1987) human maze paradigm. It was hypothesized that an age effect favoring…
Salvin, Hannah E; McGreevy, Paul D; Sachdev, Perminder S; Valenzuela, Michael J
Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter circular pool was filled with a sand and powdered food reward mix to a depth of 10 cm. Dogs were given 4 habituation and 16 learning trials which alternated a food reward being half (control trials) or fully-buried (acquisition trials) in a fixed location. After a 90-min break, a probe trial was conducted. Cognitively normal, aged (> 8 years, n = 11) and young (1–4 years, n = 11), breed-matched dogs were compared. After correction for differences in control trials, average probe times were 2.97 and 10.81 s for young and aged dogs, respectively. In the probe trial, both groups spent significantly more time in the target quadrant but there was a trend for young dogs to cross a 1 m2 annulus zone around the buried reward more frequently (2.6 times) than aged dogs (1.5 times). Test–retest reliability in a subset of young dogs (n = 5) was high. On the basis of these findings, the Canine Sand Maze is presented as a quick, sensitive and nonaversive tool for assessing spatial learning and reference memory in dogs. PMID:21541168
Salvin, Hannah E.; McGreevy, Paul D.; Sachdev, Perminder S.; Valenzuela, Michael J.
Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter…
Ariel, Robert; Moffat, Scott D
Spatial cognitive performance is impaired in later adulthood but it is unclear whether the metacognitive processes involved in monitoring spatial cognitive performance are also compromised. Inaccurate monitoring could affect whether people choose to engage in tasks that require spatial thinking and also the strategies they use in spatial domains such as navigation. The current experiment examined potential age differences in monitoring spatial cognitive performance in a variety of spatial domains including visual-spatial working memory, spatial orientation, spatial visualization, navigation, and place learning. Younger and older adults completed a 2D mental rotation test, 3D mental rotation test, paper folding test, spatial memory span test, two virtual navigation tasks, and a cognitive mapping test. Participants also made metacognitive judgments of performance (confidence judgments, judgments of learning, or navigation time estimates) on each trial for all spatial tasks. Preference for allocentric or egocentric navigation strategies was also measured. Overall, performance was poorer and confidence in performance was lower for older adults than younger adults. In most spatial domains, the absolute and relative accuracy of metacognitive judgments was equivalent for both age groups. However, age differences in monitoring accuracy (specifically relative accuracy) emerged in spatial tasks involving navigation. Confidence in navigating for a target location also mediated age differences in allocentric navigation strategy use. These findings suggest that with the possible exception of navigation monitoring, spatial cognition may be spared from age-related decline even though spatial cognition itself is impaired in older age.
Létondor, Anne; Buaud, Benjamin; Vaysse, Carole; Richard, Emmanuel; Layé, Sophie; Pallet, Véronique; Alfos, Serge
Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore, we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ, and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT, and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging.
Swanson, H. Lee
Examined whether age-related working memory deficits in learning disabled (LD) readers across four age groups (7, 10, 13, and 20) reflected retrieval efficiency or storage capacity problems. Found that LD readers' working memory performance was inferior to skilled readers' on verbal and visual-spatial working memory tasks across all ages.…
Macpherson, Helen N; White, David J; Ellis, Kathryn A; Stough, Con; Camfield, David; Silberstein, Richard; Pipingas, Andrew
Previous research has indicated that the neural processes which underlie working memory change with age. Both age-related increases and decreases to cortical activity have been reported. This study investigated which stages of working memory are most vulnerable to age-related changes after midlife. To do this we examined age-differences in the 13 Hz steady state visually evoked potential (SSVEP) associated with a spatial working memory delayed response task. Participants were 130 healthy adults separated into a midlife (40-60 years) and an older group (61-82 years). Relative to the midlife group, older adults demonstrated greater bilateral frontal activity during encoding and this pattern of activity was related to better working memory performance. In contrast, evidence of age-related under activation was identified over left frontal regions during retrieval. Findings from this study suggest that after midlife, under-activation of frontal regions during retrieval contributes to age-related decline in working memory performance.
Yamazaki, Daisuke; Horiuchi, Junjiro; Ueno, Kohei; Ueno, Taro; Saeki, Shinjiro; Matsuno, Motomi; Naganos, Shintaro; Miyashita, Tomoyuki; Hirano, Yukinori; Nishikawa, Hiroyuki; Taoka, Masato; Yamauchi, Yoshio; Isobe, Toshiaki; Honda, Yoshiko; Kodama, Tohru; Masuda, Tomoko; Saitoe, Minoru
Several aging phenotypes, including age-related memory impairment (AMI), are thought to be caused by cumulative oxidative damage. In Drosophila, age-related impairments in 1 hr memory can be suppressed by reducing activity of protein kinase A (PKA). However, the mechanism for this effect has been unclear. Here we show that decreasing PKA suppresses AMI by reducing activity of pyruvate carboxylase (PC), a glial metabolic enzyme whose amounts increase upon aging. Increased PC activity causes AMI through a mechanism independent of oxidative damage. Instead, increased PC activity is associated with decreases in D-serine, a glia-derived neuromodulator that regulates NMDA receptor activity. D-serine feeding suppresses both AMI and memory impairment caused by glial overexpression of dPC, indicating that an oxidative stress-independent dysregulation of glial modulation of neuronal activity contributes to AMI in Drosophila.
Kojima-Yuasa, Akiko; Yamamoto, Tomiya; Yaku, Keisuke; Hirota, Shiori; Takenaka, Shigeo; Kawabe, Kouichi; Matsui-Yuasa, Isao
1'-Acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Alpinia galangal. Here, we examined the effect of ACA on learning and memory in senescence-accelerated mice prone 8 (SAMP8). In mice that were fed a control diet containing 0.02% ACA for 25 weeks, the learning ability in the Morris water maze test was significantly enhanced in comparison with mice that were fed the control diet alone. In the Y-maze test, SAMP8 mice showed decreased spontaneous alterations in comparison with senescence-accelerated resistant/1 (SAMR1) mice, a homologous control, which was improved by ACA pretreatment. Serum metabolite profiles were obtained by GC-MS analysis, and each metabolic profile was plotted on a 3D score plot. Based upon the diagram, it can be seen that the distribution areas for the three groups were completely separate. Furthermore, the contents of β-hydroxybutyric acid and palmitic acid in the serum of SAMP8-ACA mice were higher than those of SAMP8-control mice and SAMR1-control mice. We also found that SAMR1 mice did not show histological abnormalities, whereas histological damage in the CA1 region of the hippocampus in SAMP8-control mice was observed. However, SAMP8-ACA mice were observed in a similar manner as SAMR1 mice. These findings confirm that ACA increases the serum concentrations of β-hydroxybutyric acid and palmitic acid levels and thus these fuels might contribute to the maintenance of the cognitive performance of SAMP8 mice.
Linares, Rocío; Bajo, M Teresa; Pelegrina, Santiago
The aim of this study was to investigate possible age-related changes throughout childhood and adolescence in different component processes of working memory updating (WMU): retrieval, transformation, and substitution. A set of numerical WMU tasks was administered to four age groups (8-, 11-, 14-, and 21-year-olds). To isolate the effect of each of the WMU components, participants performed different versions of a task that included different combinations of the WMU components. The results showed an expected overall decrease in response times and an increase in accuracy performance with age. Most important, specific age-related changes in the retrieval component were found, demonstrating that the effect of retrieval on accuracy was larger in children than in adolescents or young adults. These findings indicate that the availability of representations from outside the focus of attention may change with age. Thus, the retrieval component of updating could contribute to the age-related changes observed in the performance of many updating tasks.
Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian
A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline.
Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee
To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180-220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required.
Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee
To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required. PMID:24454988
Surprenant, Aimee M.; Neath, Ian; Brown, Gordon D. A.
In the SIMPLE model (Scale Invariant Memory and Perceptual Learning), performance on memory tasks is determined by the locations of items in multidimensional space, and better performance is associated with having fewer close neighbors. Unlike most previous simulations with SIMPLE, the ones reported here used measured, rather than assumed,…
Granholm, Ann-Charlotte; Boger, Heather; Emborg, Marina E.
The following review was constructed as a concept paper based on a recent workshop on neurodegenerative disease sponsored by the National Institute on Aging (NIA), the American Geriatric Society (AGS), and the John A. Hartford Foundation. The meeting was entitled “Thinking, moving and feeling: Common underlying mechanisms? 4th Annual Bedside-to-Bench Conference” and had the purpose to connect current basic and clinical findings on common brain-related alterations occurring with aging such as depression, movement disorders, and cognitive decline. Many prominent researchers expressed their opinion on aging and it was revealed that age-related brain dysfunction of any kind seems to share several risk factors and/or pathways. But can something be done to actively achieve “successful aging”? In this review, based largely on the workshop and current literature, we have summarized some of the current theories for depression, movement and cognitive impairment with aging, as well as potential preventive measures. We have also summarized the emerging need for relevant animal models and how these could be developed and utilized. PMID:20021382
Gui, Wen-Jun; Li, Hui-Jie; Guo, Yu-Hua; Peng, Peng; Lei, Xu; Yu, Jing
A period of post-learning sleep benefits memory consolidation compared with an equal-length wake interval. However, whether this sleep-based memory consolidation changes as a function of age remains controversial. Here we report a meta-analysis that investigates the age differences in the sleep-based memory consolidation in two types of memory: declarative memory and procedural memory. The meta-analysis included 22 comparisons of the performance between young adults (N =640) and older adults (N =529) on behavioral tasks measuring sleep-based memory consolidation. Our results showed a significant overall sleep-based beneficial effect in young adults but not in older adults. However, further analyses suggested that the age differences were mainly manifested in sleep-based declarative memory consolidation but not in procedural memory consolidation. We discussed the possible underlying mechanisms for the age-related degradation in sleep-based memory consolidation. Further research is needed to determine the crucial components for sleep-related memory consolidation in older adults such as age-related changes in neurobiological and cardiovascular functions, which may play an important role in this context and have the potential to delineate the interrelationships between age-related changes in sleep and memory.
Morris, Ken A; Chang, Qing; Mohler, Eric G; Gold, Paul E
Increases in blood glucose levels are an important component of the mechanisms by which epinephrine enhances memory formation. The present experiments addressed the hypothesis that a dysfunction in the blood glucose response to circulating epinephrine contributes to age-related memory impairments. Doses of epinephrine and glucagon that significantly increased blood glucose levels in young adult rats were far less effective at doing so in 2-year-old rats. In young rats, epinephrine and glucose were about equally effective in enhancing memory and in prolonging post-training release of acetylcholine in the hippocampus. However, glucose was more effective than epinephrine in enhancing both memory and acetylcholine release in aged rats. These results suggest that an uncoupling between circulating epinephrine and glucose levels in old rats may lead to an age-related reduction in the provision of glucose to the brain during training. This in turn may contribute to age-related changes in memory and neural plasticity.
Bouazzaoui, Badiâa; Follenfant, Alice; Ric, François; Fay, Séverine; Croizet, Jean-Claude; Atzeni, Thierry; Taconnat, Laurence
Age-related stereotype concerns culturally shared beliefs about the inevitable decline of memory with age. In this study, stereotype priming and stereotype threat manipulations were used to explore the impact of age-related stereotype on metamemory beliefs and episodic memory performance. Ninety-two older participants who reported the same perceived memory functioning were divided into two groups: a threatened group and a non-threatened group (control). First, the threatened group was primed with an ageing stereotype questionnaire. Then, both groups were administered memory complaints and memory self-efficacy questionnaires to measure metamemory beliefs. Finally, both groups were administered the Logical Memory task to measure episodic memory, for the threatened group the instructions were manipulated to enhance the stereotype threat. Results indicated that the threatened individuals reported more memory complaints and less memory efficacy, and had lower scores than the control group on the logical memory task. A multiple mediation analysis revealed that the stereotype threat effect on the episodic memory performance was mediated by both memory complaints and memory self-efficacy. This study revealed that stereotype threat impacts belief in one's own memory functioning, which in turn impairs episodic memory performance.
Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.
Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis).…
Peich, Muy-Cheng; Husain, Masud; Bays, Paul M
Working memory declines with normal aging, but the nature of this impairment is debated. Studies based on detecting changes to arrays of visual objects have identified two possible components to age-related decline: a reduction in the number of items that can be stored, or a deficit in maintaining the associations (bindings) between individual object features. However, some investigations have reported intact binding with aging, and specific deficits arising only in Alzheimer's disease. Here, using a recently developed continuous measure of recall fidelity, we tested the precision with which adults of different ages could reproduce from memory the orientation and color of a probed array item. The results reveal a further component of cognitive decline: an age-related decrease in the resolution with which visual information can be maintained in working memory. This increase in recall variability with age was strongest under conditions of greater memory load. Moreover, analysis of the distribution of errors revealed that older participants were more likely to incorrectly report one of the unprobed items in memory, consistent with an age-related increase in misbinding. These results indicate a systematic decline with age in working memory resources that can be recruited to store visual information. The paradigm presented here provides a sensitive index of both memory resolution and feature binding, with the potential for assessing their modulation by interventions. The findings have implications for understanding the mechanisms underpinning working memory deficits in both health and disease.
Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone
Carney, J.M.; Starke-Reed, P.E.; Oliver, C.N.; Landum, R.W.; Cheng, M.S.; Wu, J.F.; Floyd, R.A. )
Oxygen free radicals and oxidative events have been implicated as playing a role in bringing about the changes in cellular function that occur during aging. Brain readily undergoes oxidative damage, so it is important to determine if aging-induced changes in brain may be associated with oxidative events. Previously we demonstrated that brain damage caused by an ischemia/reperfusion insult involved oxidative events. In addition, pretreatment with the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) diminished the increase in oxidized protein and the loss of glutamine synthetase (GS) activity that accompanied ischemia/reperfusion injury in brain. We report here that aged gerbils had a significantly higher level of oxidized protein as assessed by carbonyl residues and decreased GS and neutral protease activities as compared to young adult gerbils. We also found that chronic treatment with the spin-trapping compound PBN caused a decrease in the level of oxidized protein and an increase in both GS and neutral protease activity in aged Mongolian gerbil brain. In contrast to aged gerbils, PBN treatment of young adult gerbils had no significant effect on brain oxidized protein content or GS activity. Male gerbils, young adults (3 months of age) and retired breeders (15-18 months of age), were treated with PBN for 14 days with twice daily dosages of 32 mg/kg. If PBN administration was ceased after 2 weeks, the significantly decreased level of oxidized protein and increased GS and neutral protease activities in old gerbils changed in a monotonic fashion back to the levels observed in aged gerbils prior to PBN administration. We also report that old gerbils make more errors than young animals and that older gerbils treated with PBN made fewer errors in a radial arm maze test for temporal and spatial memory than the untreated aged controls.
Baudouin, Alexia; Vanneste, Sandrine; Pouthas, Viviane; Isingrini, Michel
The aim of the present research was to study age-related changes in duration reproduction by differentiating the working memory processes underlying this time estimation task. We compared performances of young and elderly adults in a duration reproduction task performed in simple and concurrent task conditions. Participants were also administered…
Saitoe, Minoru; Horiuchi, Junjiro; Tamura, Takuya; Ito, Naomi
Understanding the molecular mechanisms underlying age-related memory impairment (AMI) is important not only from a scientific viewpoint but also for the development of therapeutics that may eventually lead to the development of drugs to combat memory loss. AMI has been generally considered to be an overall or nonspecific decay of memory processes that results from dysfunction of neural networks. However, behavioral genetics to test this hypothesis have not been performed previously, due, in part, to the long lifespan of animal models. Using Drosophila, the first extensive behavioral-genetic characterization of AMI has been carried out. In Drosophila, memory acquired after a single olfactory conditioning paradigm has three distinct phases: short-term memory (STM), middle-term memory (MTM), and longer-lasting anesthesia-resistant memory (ARM). Significantly, AMI results from the specific decay of only one memory component, amnesiac-dependent MTM, and not other components. Since amnesiac encodes peptides that enhance adenylyl cyclase activity, these studies suggest the importance of the cAMP signaling pathway in AMI in Drosophila, a finding consistent with several models of AMI in mammals. Although many advances have been made in the study of pathways involved in aging, much remains to be elucidated on how these pathways affect memory formation to cause AMI. Due to its short lifespan, powerful genetics, and well-characterized and conserved pathways involved in memory and lifespan, Drosophila will be a useful model system for studying the molecular mechanisms underlying this process.
Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.
Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis). We investigated these 3 hypotheses by formally modeling the semantic recall patterns of 185 adults between 27 to 99 years of age in the animal fluency task (Thurstone, 1938). The results indicate that people switch between global frequency-based retrieval cues and local item-based retrieval cues to navigate their semantic memory. Contrary to the global slowing hypothesis that predicts no qualitative differences in dynamic search processes and the cluster-switching hypothesis that predicts reduced switching between retrieval cues, the results indicate that as people age, they tend to switch more often between local and global cues per item recalled, supporting the cue-maintenance hypothesis. Additional support for the cue-maintenance hypothesis is provided by a negative correlation between switching and digit span scores and between switching and total items recalled, which suggests that cognitive control may be involved in cue maintenance and the effective search of memory. Overall, the results are consistent with age-related decline in memory search being a consequence of reduced cognitive control, consistent with models suggesting that working memory is related to goal perseveration and the ability to inhibit distracting information. PMID:23586941
St Jacques, Peggy L; Rubin, David C; Cabeza, Roberto
Older adults recall less episodically rich autobiographical memories (AM), however, the neural basis of this effect is not clear. Using functional MRI, we examined the effects of age during search and elaboration phases of AM retrieval. Our results suggest that the age-related attenuation in the episodic richness of AMs is associated with difficulty in the strategic retrieval processes underlying recovery of information during elaboration. First, age effects on AM activity were more pronounced during elaboration than search, with older adults showing less sustained recruitment of the hippocampus and ventrolateral prefrontal cortex (VLPFC) for less episodically rich AMs. Second, there was an age-related reduction in the modulation of top-down coupling of the VLPFC on the hippocampus for episodically rich AMs. In sum, the present study shows that changes in the sustained response and coupling of the hippocampus and prefrontal cortex (PFC) underlie age-related reductions in episodic richness of the personal past.
Bañuelos, Cristina; Beas, B Sofia; McQuail, Joseph A; Gilbert, Ryan J; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L
Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions.
Bañuelos, Cristina; Beas, B. Sofia; McQuail, Joseph A.; Gilbert, Ryan J.; Frazier, Charles J.; Setlow, Barry
Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions. PMID:24599447
Sumida, Catherine A.; Holden, Heather M.; Van Etten, Emily J.; Wagner, Gabrielle M.; Hileman, Jacob D.
Our study examined age-related differences on a new memory test assessing memory for “who,” “when,” and “where,” and associations among these elements. Participants were required to remember a sequence of pictures of different faces paired with different places. Older adults remembered significantly fewer correct face–place pairs in the correct sequence compared with young adults. Correlation analyses with standardized neuropsychological tests provide preliminary evidence for construct validity. Our results offer insight into age-related changes in the ability to remember associations between people and places at different points in time using a portable test that can be administered rapidly in various settings. PMID:26670185
Age-related memory loss was a marginal issue in medical discussions during early modern times and until well into the second half of the 17th century. There are many possible explanations: the lack of similar traditions in antiquity and in the Middle Ages, insufficient physiological and morphological knowledge of the brain, and the underlying conflict between idealistic and materialistic perspectives on the functions of the soul and the conditions of these in old age. After these boundaries had been pushed back by the influence of Cartesianism and Iatromechanism, the problem of age-related memory loss was increasingly regarded as a physical illness and began to receive more attention. This trend first occurred in medicine, before spreading to the literary world, where the novel "Gulliver's Travels" is one clear and famous example.
Matsumoto, Yukihisa; Matsumoto, Chihiro S.; Takahashi, Toshihumi; Mizunami, Makoto
Age-related memory impairment (AMI) is a common feature and a debilitating phenotype of brain aging in many animals. However, the molecular mechanisms underlying AMI are still largely unknown. The cricket Gryllus bimaculatus is a useful experimental animal for studying age-related changes in learning and memory capability; because the cricket has relatively short life-cycle and a high capability of olfactory learning and memory. Moreover, the molecular mechanisms underlying memory formation in crickets have been examined in detail. In the present study, we trained male crickets of different ages by multiple-trial olfactory conditioning to determine whether AMI occurs in crickets. Crickets 3 weeks after the final molt (3-week-old crickets) exhibited levels of retention similar to those of 1-week-old crickets at 30 min or 2 h after training; however they showed significantly decreased levels of 1-day retention, indicating AMI in long-term memory (LTM) but not in anesthesia-resistant memory (ARM) in olfactory learning of crickets. Furthermore, 3-week-old crickets injected with a nitric oxide (NO) donor, a cyclic GMP (cGMP) analog or a cyclic AMP (cAMP) analog into the hemolymph before conditioning exhibited a normal level of LTM, the same level as that in 1-week-old crickets. The rescue effect by NO donor or cGMP analog injection was absent when the crickets were injected after the conditioning. For the first time, an NO donor and a cGMP analog were found to antagonize the age-related impairment of LTM formation, suggesting that deterioration of NO synthase (NOS) or molecules upstream of NOS activation is involved in brain-aging processes. PMID:27616985
Fakhri, Mohammad; Sikaroodi, Hajir; Maleki, Farid; Ali Oghabian, Mohammad; Ghanaati, Hosein
Purpose: To evaluate patterns of activation, convergence and divergence of three functional magnetic resonance imaging (fMRI) Working Memory (WM) tasks in two different age groups. We want to understand potential impact of task and subjects’ age on WM activations as well as most important areas with regard to WM functions. Materials and methods: Thirty-five healthy volunteers completed visual, verbal, and novel auditory WM tasks. The subjects were selected from age extremes to depict possible impact of normal aging. The General Linear Model was used to report significant activations and the effect of age group. Contrasts revealed differences in activation between tasks, and Combined Task Analysis was performed to determine common regions of activation across tasks. Results: Most of the observed differences between the tasks were seen in areas that were responsible for feature processing. Frontal regions were mainstay activation areas, regardless of the utilized stimulus. We found an age-related reduction in activity of visual (in visually-presented tasks) and auditory (in auditory task) cortices but an age-related increase in prefrontal cortex for all tasks. Conclusion: Regardless of the type of the task stimuli, frontal regions are the most important activation areas in WM processing. These areas are also main targets of age-related changes with regard to activation patterns. Our results also indicate that prefrontal overactivity in working memory might be a compensatory effort to mask age-related decline in sensory processing. PMID:22885811
Müller, Nils C. J.; Genzel, Lisa; Konrad, Boris N.; Pawlowski, Marcel; Neville, David; Fernández, Guillén; Steiger, Axel
The ability to consolidate procedural memories declines with increasing age. Prior knowledge enhances learning and memory consolidation of novel but related information in various domains. Here, we present evidence that prior motor experience–in our case piano skills–increases procedural learning and has a protective effect against age-related decline for the consolidation of novel but related manual movements. In our main experiment, we tested 128 participants with a sequential finger-tapping motor task during two sessions 24 hours apart. We observed enhanced online learning speed and offline memory consolidation for piano players. Enhanced memory consolidation was driven by a strong effect in older participants, whereas younger participants did not benefit significantly from prior piano experience. In a follow up independent control experiment, this compensatory effect of piano experience was not visible after a brief offline period of 30 minutes, hence requiring an extended consolidation window potentially involving sleep. Through a further control experiment, we rejected the possibility that the decreased effect in younger participants was caused by training saturation. We discuss our results in the context of the neurobiological schema approach and suggest that prior experience has the potential to rescue memory consolidation from age-related cognitive decline. PMID:27333186
Dennis, Nancy A.; Kim, Hongkeun; Cabeza, Roberto
Compared to young adults, older adults show not only a reduction in true memories but also an increase in false memories. We investigated the neural bases of these age effects using functional magnetic resonance imaging and a false memory task that resembles the Deese–Roediger–McDermott (DRM) paradigm. Young and older participants were scanned during a word recognition task that included studied words and new words that were strongly associated with studied words (critical lures). During correct recognition of studied words (true memory), older adults showed weaker activity than young adults in the hippocampus but stronger activity than young adults in the retrosplenial cortex. The hippocampal reduction is consistent with age-related deficits in recollection, whereas the retrosplenial increase suggests compensatory recruitment of alternative recollection-related regions. During incorrect recognition of critical lures (false memory), older adults displayed stronger activity than young adults in the left lateral temporal cortex, a region involved in semantic processing and semantic gist. Taken together, the results suggest that older adults’ deficits in true memories reflect a decline in recollection processes mediated by the hippocampus, whereas their increased tendency to have false memories reflects their reliance on semantic gist mediated by the lateral temporal cortex. PMID:18303982
Naveh-Benjamin, Moshe; Smyth, Andrea C
Recently, Smyth and Naveh-Benjamin (2016) questioned some of the main assumptions/hypotheses of DRYAD (or density of representations yields age-related deficits), a global-deficit model of aging and memory judgments (Benjamin, 2010; Benjamin et al., 2012). Smyth and Naveh-Benjamin (2016) provided empirical evidence that seems incompatible with DRYAD, but that fits the associative deficit hypothesis (ADH; Naveh-Benjamin, 2000), 1 specific-deficit theoretical view. In response, Aaron Benjamin (2016) offered a discussion of the complementary strengths and weaknesses of the DRYAD and the ADH, and the potential ways they might work together. We agree with many of his comments, but are not convinced that DRYAD is able to explain basic replicable empirical evidence of the type mentioned in Smyth and Naveh-Benjamin (2016). We discuss the reasons why we are not fully convinced by the demonstration of DRYAD's simulation of results presented in Benjamin (2016) and then present an implementation of ADH in a computationally based age-related impaired neuromodulation approach that was shown to simulate the basic empirical results of age-related associative memory deficits. We also discuss the issues of parsimony of theories and the appropriate type of representation, in the context of global versus specific deficits theoretical views. Finally, we show that the ADH's take on the distinction between items and associations has been adopted by some global computational models of memory. We believe that considerations of the above issues and others raised by Benjamin (2016) can lead to fruitful discussions that will benefit both theory development and existing knowledge of aging and memory.
Vieweg, Paula; Stangl, Matthias; Howard, Lorelei R.; Wolbers, Thomas
Accurate memory retrieval from partial or degraded input requires the reactivation of memory traces, a hippocampal mechanism termed pattern completion. Age-related changes in hippocampal integrity have been hypothesized to shift the balance of memory processes in favor of the retrieval of already stored information (pattern completion), to the detriment of encoding new events (pattern separation). Using a novel behavioral paradigm, we investigated the impact of cognitive aging (1) on recognition performance across different levels of stimulus completeness, and (2) on potential response biases. Participants were required to identify previously learned scenes among new ones. Additionally, all stimuli were presented in gradually masked versions to alter stimulus completeness. Both young and older adults performed increasingly poorly as the scenes became less complete, and this decline in performance was more pronounced in elderly participants indicative of a pattern completion deficit. Intriguingly, when novel scenes were shown, only the older adults showed an increased tendency to identify these as familiar scenes. In line with theoretical models, we argue that this reflects an age-related bias towards pattern completion. PMID:25597525
Puccioni, Olga; Vallesi, Antonino
Several studies support the existence of a specific age-related difficulty in suppressing potentially distracting information. The aim of the present study is to investigate whether spatial conflict resolution is selectively affected by aging. The way aging affects individuals could be modulated by many factors determined by the socieconomic status: we investigated whether factors such as cognitive reserve (CR) and years of education may play a compensatory role against age-related deficits in the spatial domain. A spatial Stroop task with no feature repetitions was administered to a sample of 17 non-demented older adults (69–79 years-old) and 18 younger controls (18–34 years-old) matched for gender and years of education. The two age groups were also administered with measures of intelligence and CR. The overall spatial Stroop effect did not differ according to age, neither for speed nor for accuracy. The two age groups equally showed sequential effects for congruent trials: reduced response times (RTs) if another congruent trial preceded them, and accuracy at ceiling. For incongruent trials, older adults, but not younger controls, were influenced by congruency of trialn−1, since RTs increased with preceding congruent trials. Interestingly, such an age-related modulation negatively correlated with CR. These findings suggest that spatial conflict resolution in aging is predominantly affected by general slowing, rather than by a more specific deficit. However, a high level of CR seems to play a compensatory role for both factors. PMID:23248595
Benjamin, Aaron S
How do we best characterize the memory deficits that accompany aging? A popular hypothesis, articulated originally by Naveh-Benjamin (2000) and reviewed in the accompanying article by Smyth and Naveh-Benjamin (2016), suggests that older adults are selectively deficient in establishing associations between to-be-learned memoranda and as a result have deficits in memory for sources or contexts. An alternative proposal, called density of representations yields age-related deficits (DRYAD) and outlined in recent articles by Benjamin (2010) and colleagues (Benjamin, Diaz, Matzen, & Johnson, 2012), attributes disproportionate deficits in memory to a global, rather than a selective, deficit of memory. In an attempt to adjudicate between these competing positions, Smyth and Naveh-Benjamin (2016) discussed 2 sets of experimental data that they claim speak against the global deficit model. Here I review some general principles of how the global-deficit view is applied to experimental paradigms and demonstrate that even a simplified form of DRYAD can comfortably accommodate the critical findings cited by Smyth and Naveh-Benjamin. I also evaluate aspects of their results that may be problematic for DRYAD and describe ways in which DRYAD's account of associative recognition can be falsified. I end with a discussion of the complementary strengths and weaknesses of the 2 approaches and consider ways in which the associative deficit hypothesis and DRYAD might work more profitably together than apart.
Albayram, Onder; Bilkei-Gorzo, Andras; Zimmer, Andreas
Previous studies have shown that cannabinoid 1 (CB1) receptor signaling dissociates between reward-associated and aversive memories. The influence of CB1 receptors on the aversion-driven spatial learning in the Morris water maze test is strongly age-dependent: mice with genetic deletion of CB1 receptors (Cnr1−/−) show superior learning when young but inferior learning when old compared to age-matched wild-type mice. Whether the reward-driven spatial learning is influenced in the same way by CB1 receptor signaling as the aversion-driven learning remains unclear. Thus, we examined the performance of Cn1−/− and their wild-type littermates at ages of 2-, 5-, and 12-months-old in the eight-arm radial maze test—a reward-motivated model of spatial learning. Interestingly, 2-months-old Cnr1−/− mice had a superior learning ability to wild-type mice. At the age of 5-months, Cnr1−/− mice showed the same performance as the wild-type littermates. However, 12-months-old Cnr1−/− mice showed significantly impaired performances in each parameter of the test. Accordingly, this study provides compelling support for our previous result that genetic deletion of CB1 receptor leads to early onset of age-related memory decline, similarly affecting both reward and aversion-driven learning. PMID:23227007
Fogel, Stuart M; Albouy, Genevieve; Vien, Catherine; Popovicci, Romana; King, Bradley R; Hoge, Rick; Jbabdi, Saad; Benali, Habib; Karni, Avi; Maquet, Pierre; Carrier, Julie; Doyon, Julien
Behavioral studies indicate that older adults exhibit normal motor sequence learning (MSL), but paradoxically, show impaired consolidation of the new memory trace. However, the neural and physiological mechanisms underlying this impairment are entirely unknown. Here, we sought to identify, through functional magnetic resonance imaging during MSL and electroencephalographic (EEG) recordings during daytime sleep, the functional correlates and physiological characteristics of this age-related motor memory deficit. As predicted, older subjects did not exhibit sleep-dependent gains in performance (i.e., behavioral changes that reflect consolidation) and had reduced sleep spindles compared with young subjects. Brain imaging analyses also revealed that changes in activity across the retention interval in the putamen and related brain regions were associated with sleep spindles. This change in striatal activity was increased in young subjects, but reduced by comparison in older subjects. These findings suggest that the deficit in sleep-dependent motor memory consolidation in elderly individuals is related to a reduction in sleep spindle oscillations and to an associated decrease of activity in the cortico-striatal network.
Zavagnin, Michela; De Beni, Rossana; Borella, Erika; Carretti, Barbara
The ability to remember past events and imagine future events (episodic future thinking-EFT) has been shown to decline with aging. However, only few studies have analyzed the cognitive mechanisms involved in EFT in both young and older adults. The present study examined the role of working memory and inhibition on age-related differences between young and older adults in EFT, in response to short sentences reflecting common events, some of which were repeated in both conditions (past and future). Thirty-seven young and 36 older adults completed an adapted version of the autobiographical interview, in which sentences were presented. Results showed that processing resources explained a significant part of the variance in the amount of details; in particular, inhibition explained the amount of external details produced in the future condition. In addition, using sentences, the older group did not differ from the young adults in terms of the proportion of internal details recalled in the past condition, whereas they produced a lower proportion of internal details in the future condition. The effect of using structured material was reinforced by repeating some sentences in the past. Further, only older adults rated the remembered episodes as more emotionally salient and relevant than the imagined ones. Age-related differences between young and older adults in EFT appear to depend on the type of material used, on basic mechanisms of cognition, and are characterized by both quantitative and qualitative differences.
Kuo, M C C; Liu, K P Y; Ting, K H; Chan, C C H
This study examined the age-related subsequent memory effect (SME) in perceptual and semantic encoding using event-related potentials (ERPs). Seventeen younger adults and 17 older adults studied a series of Chinese characters either perceptually (by inspecting orthographic components) or semantically (by determining whether the depicted object makes sounds). The two tasks had similar levels of difficulty. The participants made studied or unstudied judgments during the recognition phase. Younger adults performed better in both conditions, with significant SMEs detected in the time windows of P2, N3, P550, and late positive component (LPC). In the older group, SMEs were observed in the P2 and N3 latencies in both conditions but were only detected in the P550 in the semantic condition. Between-group analyses showed larger frontal and central SMEs in the younger sample in the LPC latency regardless of encoding type. Aging effect appears to be stronger on influencing perceptual than semantic encoding processes. The effects seem to be associated with a decline in updating and maintaining representations during perceptual encoding. The age-related decline in the encoding function may be due in part to changes in frontal lobe function.
Taillade, Mathieu; Sauzéon, Hélène; Arvind Pala, Prashant; Déjos, Marie; Larrue, Florian; Gross, Christian; N’Kaoua, Bernard
The aim of this study was to evaluate motor control activity (active vs. passive condition) with regards to wayfinding and spatial learning difficulties in large-scale spaces for older adults. We compared virtual reality (VR)-based wayfinding and spatial memory (survey and route knowledge) performances between 30 younger and 30 older adults. A significant effect of age was obtained on the wayfinding performances but not on the spatial memory performances. Specifically, the active condition deteriorated the survey measure in all of the participants and increased the age-related differences in the wayfinding performances. Importantly, the age-related differences in the wayfinding performances, after an active condition, were further mediated by the executive measures. All of the results relative to a detrimental effect of motor activity are discussed in terms of a dual task effect as well as executive decline associated with aging. PMID:23843992
Fogerty, Daniel; Humes, Larry E.; Busey, Thomas A.
Age-related temporal-processing declines of rapidly presented sequences may involve contributions of sensory memory. This study investigated recall for rapidly presented auditory (vowel) and visual (letter) sequences presented at six different stimulus onset asynchronies (SOA) that spanned threshold SOAs for sequence identification. Younger, middle-aged, and older adults participated in all tasks. Results were investigated at both equivalent performance levels (i.e., SOA threshold) and at identical physical stimulus values (i.e., SOAs). For four-item sequences, results demonstrated best performance for the first and last items in the auditory sequences, but only the first item for visual sequences. For two-item sequences, adults identified the second vowel or letter significantly better than the first. Overall, when temporal-order performance was equated for each individual by testing at SOA thresholds, recall accuracy for each position across the age groups was highly similar. These results suggest that modality-specific processing declines of older adults primarily determine temporal-order performance for rapid sequences. However, there is some evidence for a second amodal processing decline in older adults related to early sensory memory for final items in a sequence. This selective deficit was observed particularly for longer sequence lengths and was not accounted for by temporal masking. PMID:27199737
Weiss, Elisabeth M; Gschaidbauer, Bianca; Kaufmann, Liane; Fink, Andreas; Schulter, Günter; Mittenecker, Erich; Papousek, Ilona
Deficits in specific executive domains are highly prevalent in autism spectrum disorder; however, age-related improvements in executive functions (reflecting prefrontal maturational changes) have been reported even in individuals diagnosed with autism. The current study examined two components of cognitive flexibility (inhibition of prepotent responses and memory monitoring/updating) by using a random-motor-generation task (MPT) in a group of 23 boys with Asperger syndrome (AS) and 23 matched healthy controls. We found poorer inhibition and more repetitive responses in younger AS children solely, but comparable memory monitoring/updating skills across groups. Overall, our findings correspond well with previous studies and reveal that even in AS specific EFs may improve with age and, thus, call for a more differentiated view of executive (dys) function profiles in children diagnosed with AS. Tests such as the random-motor-generation task may help to disentangle more specific processes of executive deficits in autism spectrum disorder as compared to the more classical tests.
Terry, Alvin V.; Callahan, Patrick M.; Hall, Brandon; Webster, Scott J.
An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory
Morris, Ken A.; Gold, Paul E.
Epinephrine enhances memory in young adult rats, in part, by increasing blood glucose levels needed to modulate memory. In old rats, epinephrine is deficient at raising blood glucose levels and thus is only moderately effective at enhancing memory. In contrast, systemic glucose injections improve memory in old rats, with resulting memory performance equal to that of young rats. The diminished response of glucose to training in old rats may blunt downstream neurochemical and molecular mechanisms needed to upregulate memory processes. In the first experiment, young adult and old rats were trained on an inhibitory avoidance task with immediate post-training injections of aCSF or glucose into the dorsal hippocampus. Old rats had significant memory impairments compared to young rats 7 days after training. Intrahippocampal injections of glucose reversed age-related deficits, improving memory scores in old rats to values seen in young rats. A second experiment examined age-related changes in activation of the transcription factor CREB, which is widely implicated in memory formation and may act downstream of hormonal and metabolic signals. Activation was assessed in response to training with systemic injections of epinephrine and glucose at doses known to enhance memory. Young adult and old rats were trained on inhibitory avoidance with immediate post-training systemic injections of saline, epinephrine, or glucose. After training, old rats had significant impairments in CREB phosphorylation in area CA1 and the dentate gyrus region of the hippocampus, and in the basolateral and lateral amygdala. Epinephrine and glucose attenuated age-related deficits in CREB phosphorylation, but were more effective in the amygdala and hippocampus, respectively. Together, these results support the view that age-related changes in blood glucose responses to epinephrine contribute to memory impairments, which may be related to alterations in regional patterns of CREB phosphorylation. PMID
Morris, Ken A; Gold, Paul E
Epinephrine enhances memory in young adult rats, in part, by increasing blood glucose levels needed to modulate memory. In old rats, epinephrine is deficient at raising blood glucose levels and thus is only moderately effective at enhancing memory. In contrast, systemic glucose injections improve memory in old rats, with resulting memory performance equal to that of young rats. The diminished response of glucose to training in old rats may blunt downstream neurochemical and molecular mechanisms needed to upregulate memory processes. In the first experiment, young adult and old rats were trained on an inhibitory avoidance task with immediate post-training injections of aCSF or glucose into the dorsal hippocampus. Old rats had significant memory impairments compared to young rats 7 days after training. Intrahippocampal injections of glucose reversed age-related deficits, improving memory scores in old rats to values seen in young rats. A second experiment examined age-related changes in activation of the transcription factor CREB, which is widely implicated in memory formation and may act downstream of hormonal and metabolic signals. Activation was assessed in response to training with systemic injections of epinephrine and glucose at doses known to enhance memory. Young adult and old rats were trained on inhibitory avoidance with immediate post-training systemic injections of saline, epinephrine, or glucose. After training, old rats had significant impairments in CREB phosphorylation in area CA1 and the dentate gyrus region of the hippocampus, and in the basolateral and lateral amygdala. Epinephrine and glucose attenuated age-related deficits in CREB phosphorylation, but were more effective in the amygdala and hippocampus, respectively. Together, these results support the view that age-related changes in blood glucose responses to epinephrine contribute to memory impairments, which may be related to alterations in regional patterns of CREB phosphorylation.
Gatewood, Jessica D; Morgan, Melissa D; Eaton, Mollie; McNamara, Ilan M; Stevens, Lillian F; Macbeth, Abbe H; Meyer, Elizabeth A A; Lomas, Lisa M; Kozub, Frederick J; Lambert, Kelly G; Kinsley, Craig Howard
The current work examined spatial learning and memory (i.e., latencies to find a baited food well) in age-matched nulliparous, primiparous and multiparous (NULL, PRIM and MULT, zero, one or two pregnancies and lactations, respectively). We tested at 6, 12, 18 and 24 months of age in a dry land version of the Morris water maze (Main task), and at 12, 18 and 24 months in the same task in which the original location of the baited well was changed (Reversal task). We show that PRIM/MULT rats, compared to the age-matched NULL females, learned the spatial tasks significantly better and exhibited attenuated memory decline, up to 24 months of age. Furthermore, at the conclusion of behavioral testing, we investigated levels of these animals' hippocampal (CA1 and dentate gyrus) immunoreactive amyloid precursor protein (APP), a marker of neurodegeneration and age-related cognitive loss. MULTs had significantly reduced APP in both CA1 and DG, relative to PRIMs and NULLs, and PRIMs had a trend (p<0.06) toward a reduction in APP compared to NULLs in DG. Further, level of APP was negatively correlated with performance in the two tasks (viz., more APP, worse maze performance). Reproduction, therefore, with its attendant natural endocrine and postpartum sensory experiences, may facilitate lifelong learning and memory, and may mitigate markers of neural aging, in the rat. Combining natural hormonal exposure with subsequent substantial experience with stimuli from the offspring may preserve the aged parous female brain relative to that of NULL females.
Dragan, Michelle C; Leonard, Timothy K; Lozano, Andres M; McAndrews, Mary Pat; Ng, Karen; Ryan, Jennifer D; Tang-Wai, David F; Wynn, Jordana S; Hoffman, Kari L
Episodic memory - composed of memory for unique spatiotemporal experiences - is known to decline with aging, and even more severely in Alzheimer 's disease (AD). Memory for trial-unique objects in spatial scenes depends on the integrity of the hippocampus and interconnected structures that are among the first areas affected in AD. We reasoned that memory for objects-in-scenes would be impaired with aging, and that further impairments would be observed in AD. We asked younger adults, healthy older adults, older adults at-risk for developing cognitive impairments, and older adults with probable early AD to find changing items ('targets') within images of natural scenes, measuring repeated-trial changes in search efficiency and pupil diameter. Compared to younger adults, older adults took longer to detect target objects in repeated scenes, they required more fixations and those fixations were more dispersed. Whereas individuals with AD showed some benefit of memory in this task, they had substantially longer detection times, and more numerous, dispersed fixations on repeated scenes compared to age-matched older adults. Correspondingly, pupillary responses to novel and repeated scenes were diminished with aging and further in AD, and the memory-related changes were weaker with aging and absent in AD. Our results suggest that several nonverbal measures from memory-guided visual search tasks can index aging and Alzheimer's disease status, including pupillary dynamics. The task measurements are sensitive to the integrity of brain structures that are associated with Alzheimer's-related neurodegeneration, the task is well tolerated across a range of abilities, and thus, it may prove useful in early diagnostics and longitudinal tracking of memory decline.
Musel, Benoit; Hera, Ruxandra; Chokron, Sylvie; Alleysson, David; Chiquet, Christophe; Romanet, Jean-Paul; Guyader, Nathalie; Peyrin, Carole
Age-related macular degeneration (AMD) is characterized by a central vision loss. We explored the relationship between the retinal lesions in AMD patients and the processing of spatial frequencies in natural scene categorization. Since the lesion on the retina is central, we expected preservation of low spatial frequency (LSF) processing and the impairment of high spatial frequency (HSF) processing. We conducted two experiments that differed in the set of scene stimuli used and their exposure duration. Twelve AMD patients and 12 healthy age-matched participants in Experiment 1 and 10 different AMD patients and 10 healthy age-matched participants in Experiment 2 performed categorization tasks of natural scenes (Indoors vs. Outdoors) filtered in LSF and HSF. Experiment 1 revealed that AMD patients made more no-responses to categorize HSF than LSF scenes, irrespective of the scene category. In addition, AMD patients had longer reaction times to categorize HSF than LSF scenes only for indoors. Healthy participants' performance was not differentially affected by spatial frequency content of the scenes. In Experiment 2, AMD patients demonstrated the same pattern of errors as in Experiment 1. Furthermore, AMD patients had longer reaction times to categorize HSF than LSF scenes, irrespective of the scene category. Again, spatial frequency processing was equivalent for healthy participants. The present findings point to a specific deficit in the processing of HSF information contained in photographs of natural scenes in AMD patients. The processing of LSF information is relatively preserved. Moreover, the fact that the deficit is more important when categorizing HSF indoors, may lead to new perspectives for rehabilitation procedures in AMD.
Baudouin, Alexia; Clarys, David; Vanneste, Sandrine; Isingrini, Michel
The aim of the present study was to examine executive dysfunctioning and decreased processing speed as potential mediators of age-related differences in episodic memory. We compared the performances of young and elderly adults in a free-recall task. Participants were also given tests to measure executive functions and perceptual processing speed…
Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez
Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…
Pavlopoulos, Elias; Jones, Sidonie; Kosmidis, Stylianos; Close, Maggie; Kim, Carla; Kovalerchik, Olga; Small, Scott A.; Kandel, Eric R.
To distinguish age-related memory loss more explicitly from Alzheimer’s disease (AD), we have explored its molecular underpinning in the dentate gyrus (DG), a subregion of the hippocampal formation thought to be targeted by aging. We carried out a gene expression study in human postmortem tissue harvested from both DG and entorhinal cortex (EC), a neighboring subregion unaffected by aging and known to be the site of onset of AD. Using expression in the EC for normalization, we identified 17 genes that manifested reliable age-related changes in the DG. The most significant change was an age-related decline in RbAp48, a histone-binding protein that modifies histone acetylation. To test whether the RbAp48 decline could be responsible for age-related memory loss, we turned to mice and found that, consistent with humans, RbAp48 was less abundant in the DG of old than in young mice. We next generated a transgenic mouse that expressed a dominant-negative inhibitor of RbAp48 in the adult forebrain. Inhibition of RbAp48 in young mice caused hippocampus-dependent memory deficits similar to those associated with aging, as measured by novel object recognition and Morris water maze tests. Functional magnetic resonance imaging studies showed that within the hippocampal formation, dysfunction was selectively observed in the DG, and this corresponded to a regionally selective decrease in histone acetylation. Up-regulation of RbAp48 in the DG of aged wild-type mice ameliorated age-related hippocampus-based memory loss and age-related abnormalities in histone acetylation. Together, these findings show that the DG is a hippocampal subregion targeted by aging, and identify molecular mechanisms of cognitive aging that could serve as valid targets for therapeutic intervention. PMID:23986399
Callaghan, Eleanor; Holland, Carol; Kessler, Klaus
Background: Identifying age-related changes in cognition that contribute towards reduced driving performance is important for the development of interventions to improve older adults' driving and prolong the time that they can continue to drive. While driving, one is often required to switch from attending to events changing in time, to distribute attention spatially. Although there is extensive research into both spatial attention and temporal attention and how these change with age, the literature on switching between these modalities of attention is limited within any age group. Methods: Age groups (21-30, 40-49, 50-59, 60-69 and 70+ years) were compared on their ability to switch between detecting a target in a rapid serial visual presentation (RSVP) stream and detecting a target in a visual search display. To manipulate the cost of switching, the target in the RSVP stream was either the first item in the stream (Target 1st), towards the end of the stream (Target Mid), or absent from the stream (Distractor Only). Visual search response times and accuracy were recorded. Target 1st trials behaved as no-switch trials, as attending to the remaining stream was not necessary. Target Mid and Distractor Only trials behaved as switch trials, as attending to the stream to the end was required. Results: Visual search response times (RTs) were longer on "Target Mid" and "Distractor Only" trials in comparison to "Target 1st" trials, reflecting switch-costs. Larger switch-costs were found in both the 40-49 and 60-69 years group in comparison to the 21-30 years group when switching from the Target Mid condition. Discussion: Findings warrant further exploration as to whether there are age-related changes in the ability to switch between these modalities of attention while driving. If older adults display poor performance when switching between temporal and spatial attention while driving, then the development of an intervention to preserve and improve this ability would be
Callaghan, Eleanor; Holland, Carol; Kessler, Klaus
Background: Identifying age-related changes in cognition that contribute towards reduced driving performance is important for the development of interventions to improve older adults’ driving and prolong the time that they can continue to drive. While driving, one is often required to switch from attending to events changing in time, to distribute attention spatially. Although there is extensive research into both spatial attention and temporal attention and how these change with age, the literature on switching between these modalities of attention is limited within any age group. Methods: Age groups (21–30, 40–49, 50–59, 60–69 and 70+ years) were compared on their ability to switch between detecting a target in a rapid serial visual presentation (RSVP) stream and detecting a target in a visual search display. To manipulate the cost of switching, the target in the RSVP stream was either the first item in the stream (Target 1st), towards the end of the stream (Target Mid), or absent from the stream (Distractor Only). Visual search response times and accuracy were recorded. Target 1st trials behaved as no-switch trials, as attending to the remaining stream was not necessary. Target Mid and Distractor Only trials behaved as switch trials, as attending to the stream to the end was required. Results: Visual search response times (RTs) were longer on “Target Mid” and “Distractor Only” trials in comparison to “Target 1st” trials, reflecting switch-costs. Larger switch-costs were found in both the 40–49 and 60–69 years group in comparison to the 21–30 years group when switching from the Target Mid condition. Discussion: Findings warrant further exploration as to whether there are age-related changes in the ability to switch between these modalities of attention while driving. If older adults display poor performance when switching between temporal and spatial attention while driving, then the development of an intervention to preserve and
Riemer, Thomas G.; Schulte, Stefanie; Onken, Johanna; Heinz, Andreas; Rapp, Michael A.
Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years) and 25 older (aged 60–75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism. PMID:24772423
Kodali, Maheedhar; Parihar, Vipan K; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K
Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.
Luo, Yi; Zhou, Jun; Li, Ming-Xing; Wu, Peng-Fei; Hu, Zhuang-Li; Ni, Lan; Jin, You; Chen, Jian-Guo; Wang, Fang
Aging-related emotional memory deficit is a well-known complication in Alzheimer's disease and normal aging. However, little is known about its molecular mechanism. To address this issue, we examined the role of norepinephrine (NE) and its relevant drug desipramine in the regulation of hippocampal long-term potentiation (LTP), surface expression of AMPA receptor, and associative fear memory in rats. We found that there was a defective regulation of NE content and AMPA receptor trafficking during fear conditioning, which were accompanied by impaired emotional memory and LTP in aged rats. Furthermore, we also found that the exogenous upregulation of NE ameliorated the impairment of LTP and emotional memory via enhancing AMPA receptor trafficking in aged rats, and the downregulation of NE impaired LTP in adult rats. Finally, acute treatment with NE or desipramine rescued the impaired emotional memory in aged rats. These results imply a pivotal role for NE in synaptic plasticity and associative fear memory in aging rats and suggest that desipramine is a potential candidate for treating aging-related emotional memory deficit.
Street, Whitney N.; Wang, Ranxiao Frances
The perspective-taking task is one of the most common paradigms used to study the nature of spatial memory, and better performance for certain orientations is generally interpreted as evidence of spatial representations using these reference directions. However, performance advantages can also result from the relative ease in certain…
Kerster, Bryan E; Rhodes, Theo; Kello, Christopher T
Foraging and foraging-like processes are found in spatial navigation, memory, visual search, and many other search functions in human cognition and behavior. Foraging is commonly theorized using either random or correlated movements based on Lévy walks, or a series of decisions to remain or leave proximal areas known as "patches". Neither class of model makes use of spatial memory, but search performance may be enhanced when information about searched and unsearched locations is encoded. A video game was developed to test the role of human spatial memory in a canonical foraging task. Analyses of search trajectories from over 2000 human players yielded evidence that foraging movements were inherently clustered, and that clustering was facilitated by spatial memory cues and influenced by memory for spatial locations of targets found. A simple foraging model is presented in which spatial memory is used to integrate aspects of Lévy-based and patch-based foraging theories to perform a kind of area-restricted search, and thereby enhance performance as search unfolds. Using only two free parameters, the model accounts for a variety of findings that individually support competing theories, but together they argue for the integration of spatial memory into theories of foraging.
Lovatel, Gisele Agustini; Elsner, Viviane Rostirola; Bertoldi, Karine; Vanzella, Cláudia; Moysés, Felipe Dos Santos; Vizuete, Adriana; Spindler, Christiano; Cechinel, Laura Reck; Netto, Carlos Alexandre; Muotri, Alysson Renato; Siqueira, Ionara Rodrigues
It has been described that exercise can modulate both inflammatory response and epigenetic modifications, although the effect of exercise on these parameters during the normal brain aging process yet remains poorly understood. Here, we investigated the effect of aging and treadmill exercise on inflammatory and epigenetic parameters specifically pro and anti-inflammatory cytokines levels, activation of NF-kB and histone H4 acetylation levels in hippocampus from Wistar rats. Additionally, we evaluated aversive memory through inhibitory avoidance task. Rats of 3 and 20 months of age were assigned to non-exercised (sedentary) and exercised (running daily for 20 min for 2 weeks) groups. The effect of daily forced exercise in the treadmill was assessed. The levels of inflammatory and epigenetic parameters were determined 1h, 18 h, 3 days or 7 days after the last training session of exercise. It was observed an age-related decline on aversive memory, as well as aged rats showed increased hippocampal levels of inflammatory markers, such as TNFα, IL1-β and NF-kB and decreased IL-4 levels, an anti-inflammatory cytokine. Moreover, lower levels of global histone H4 acetylation were also observed in hippocampi from aged rats. Interestingly, there was a significant correlation between the biochemical markers and the inhibitory avoidance test performance. The forced exercise protocol ameliorated aging-related memory decline, decreased pro-inflammatory markers and increased histone H4 acetylation levels in hippocampi 20-months-old rats, while increased acutely IL-4 levels in hippocampi from young adult rats. Together, these results suggest that an imbalance of inflammatory markers might be involved to the aging-related aversive memory impairment. Additionally, our exercise protocol may reverse aging-related memory decline through improving cytokine profile.
Reichert, Johanna Louise; Kober, Silvia Erika; Witte, Matthias; Neuper, Christa; Wood, Guilherme
Both electrical brain activity during rest and memory functions change across the lifespan. Moreover, electrical brain activity is associated with memory functions. However, the interplay between all these effects has been investigated only scarcely. The present study investigated the extent to which the power of resting-state electroencephalographic (EEG) frequencies mediates the impact of aging on verbal and visuospatial memory. Seventy healthy participants with 22 to 83years of age completed a visuospatial and verbal learning and memory test and provided eyes-open and eyes-closed resting-state EEG data. Robust age-related effects on behavioral and EEG data were observed. Mediation analyses showed that the relative power of the theta (4-8Hz) frequency band in fronto-central locations partly explained the negative age-related effect on delayed recall in the verbal memory task. The relative power of the alpha II (10-12Hz) frequency band in mainly parietal locations partly explained the negative impact of age on immediate and delayed recall in the visuospatial task. Results indicate that spontaneous brain activity carries specific information about aging processes and predicts the level of competence in verbal and visuospatial memory tasks.
Theophilou, Georgios; Fogarty, Simon W.; Trevisan, Júlio; Strong, Rebecca J.; Heys, Kelly A.; Patel, Imran I.; Stringfellow, Helen F.; Martin-Hirsch, Pierre L.; Martin, Francis L.
Epidemiological evidence suggests that cancers attributable to exogenous carcinogenic agents may appear decades after initiating exposures. Environmental factors including lifestyle and/or diet have been implicated in the aetiology of breast cancer. Breast tissue undergoes continuous molecular and morphological changes from the time of thelarche to menopause and thereafter. These alterations are both cyclical and longitudinal, and can be influenced by several environmental factors including exposure to oestrogens. Research into the latent period leading to breast carcinogenesis has been mostly limited to when hyperplastic lesions are present. Investigations to identify a biomarker of commitment to disease in normal breast tissue are hindered by the molecular and histological diversity of disease-free breast tissue. Benign tissue from reduction mammoplasties provides an opportunity to study biochemical differences between women of similar ages as well as alterations with advancing age. Herein, synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy was used to examine the terminal ductal lobular epithelium (TDLU) and, intra- and inter-lobular epithelium to identify spatial and temporal changes within these areas. Principal component analysis (PCA) followed by linear discriminant analysis of mid-infrared spectra revealed unambiguous inter-individual as well as age-related differences in each histological compartment interrogated. Moreover, exploratory PCA of luminal and myoepithelial cells within the TDLU indicated the presence of specific cells, potentially stem cells. Understanding alterations within benign tissue may assist in the identification of alterations in latent pre-clinical stages of breast cancer.
Lindauer, Barbara K.; Paris, Scott G.
This paper focuses on a study which replicates and extends earlier work employing a recognition memory paradigm to investigate children's memory and developmental changes in dominant word associations. On the recognition test the implicit associative response can lead to better memory for the original items (this is the hit rate), and it can also…
Kaufman, Miron; Allen, P.
We develop and test a thermodynamic model of spatial memory. Our model is an application of statistical thermodynamics to cognitive science. It is related to applications of the statistical mechanics framework in parallel distributed processes research. Our macroscopic model allows us to evaluate an entropy associated with spatial memory tasks. We find that older adults exhibit higher levels of entropy than younger adults. Thurstone's Law of Categorical Judgment, according to which the discriminal processes along the psychological continuum produced by presentations of a single stimulus are normally distributed, is explained by using a Hooke spring model of spatial memory. We have also analyzed a nonlinear modification of the ideal spring model of spatial memory. This work is supported by NIH/NIA grant AG09282-06.
De Jaeger, Xavier; Courtey, Julie; Brus, Maïna; Artinian, Julien; Villain, Hélène; Bacquié, Elodie; Roullet, Pascal
Reconsolidation is necessary for the restabilization of reactivated memory traces. However, experimental parameters have been suggested as boundary conditions for this process. Here we investigated the role of a spatial memory trace's age, strength, and update on the reconsolidation process in mice. We first found that protein synthesis is…
Wong, Jessica T.; Cramer, Stefanie J.; Gallo, David A.
We investigated age-related reductions in episodic metamemory accuracy. Participants studied pictures and words in different colors, and then took forced-choice recollection tests. These tests required recollection of the earlier presentation color, holding familiarity of the response options constant. Metamemory accuracy was assessed for each participant by comparing recollection test accuracy to corresponding confidence judgments. We found that recollection test accuracy was greater in younger than older adults, and also for pictures than font color. Metamemory accuracy tracked each of these recollection differences, as well as individual differences in recollection test accuracy within each age group, suggesting that recollection ability affects metamemory accuracy. Critically, the age-related impairment in metamemory accuracy persisted even when the groups were matched on recollection test accuracy, suggesting that metamemory declines were not entirely due to differences in recollection frequency or quantity, but that differences in recollection quality and/or monitoring also played a role. We also found that age-related impairments in recollection and metamemory accuracy were equivalent for pictures and font colors. This result contrasted with previous false recognition findings, which predicted that older adults would be differentially impaired when monitoring memory for less distinctive memories. These and other results suggest that age-related reductions in metamemory accuracy are not entirely attributable to false recognition effects, but also depend heavily on deficient recollection and/or monitoring of specific details associated with studied stimuli. PMID:22449027
Ladage, L D; Roth, T C; Cerjanic, A M; Sinervo, B; Pravosudov, V V
In many animals, behaviours such as territoriality, mate guarding, navigation and food acquisition rely heavily on spatial memory abilities; this has been demonstrated in diverse taxa, from invertebrates to mammals. However, spatial memory ability in squamate reptiles has been seen as possible, at best, or non-existent, at worst. Of the few previous studies testing for spatial memory in squamates, some have found no evidence of spatial memory while two studies have found evidence of spatial memory in snakes, but have been criticized based on methodological issues. We used the Barnes maze, a common paradigm to test spatial memory abilities in mammals, to test for spatial memory abilities in the side-blotched lizard (Uta stansburiana). We found the existence of spatial memory in this species using this spatial task. Thus, our study supports the existence of spatial memory in this squamate reptile species and seeks to parsimoniously align this species with the diverse taxa that demonstrate spatial memory ability.
Chang, Qing; Gold, Paul E.
Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer’s Disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22–25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 μg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice. PMID:17644430
Pehlivanoglu, Didem; Jain, Shivangi; Ariel, Robert; Verhaeghen, Paul
In the present study, we investigated age-related differences in the processing of emotional stimuli. Specifically, we were interested in whether older adults would show deficits in unbinding emotional expression (i.e., either no emotion, happiness, anger, or disgust) from bound stimuli (i.e., photographs of faces expressing these emotions), as a hyper-binding account of age-related differences in working memory would predict. Younger and older adults completed different N-Back tasks (side-by-side 0-Back, 1-Back, 2-Back) under three conditions: match/mismatch judgments based on either the identity of the face (identity condition), the face’s emotional expression (expression condition), or both identity and expression of the face (both condition). The two age groups performed more slowly and with lower accuracy in the expression condition than in the both condition, indicating the presence of an unbinding process. This unbinding effect was more pronounced in older adults than in younger adults, but only in the 2-Back task. Thus, older adults seemed to have a specific deficit in unbinding in working memory. Additionally, no age-related differences were found in accuracy in the 0-Back task, but such differences emerged in the 1-Back task, and were further magnified in the 2-Back task, indicating independent age-related differences in attention/STM and working memory. Pupil dilation data confirmed that the attention/STM version of the task (1-Back) is more effortful for older adults than younger adults. PMID:24795660
Mizoguchi, K; Shoji, H; Tanaka, Y; Tabira, T
Aging is thought to impair prefrontal cortical (PFC) structure-sensitive cognitive functions and flexibility, such as working memory and reversal learning. A traditional Japanese medicine, yokukansan (YKS), is frequently used to treat age-related neurodegenerative disorders such as Alzheimer's disease in Japan, but its pharmacological properties have not been elucidated. The present study was designed to examine whether YKS improves age-related cognitive deficits using aged rats. YKS was administered to 21-month-old rats for 3 months. The ability to learn initially a reward rule for a T-maze discrimination task (initial learning) was examined in young control (4-month-old), aged control (24-month-old) and YKS-treated aged (24-month-old) rats. Subsequently, working memory and reversal learning were examined in delayed alternation and reversal discrimination T-maze tasks, respectively. Locomotor activity was also measured in new environments. Although performance accuracy in the initial learning procedure did not differ among any experimental groups, accuracy in the delayed alternation task was significantly decreased in aged rats compared to young rats. Aged rats also showed significant decreases in accuracy in the reversal discrimination task. YKS treatment significantly ameliorated the age-related decreases in accuracy in the delayed alternation and reversal discrimination tasks. The ameliorative effects of YKS on impaired delayed alternation performance were reduced by intracranial infusions of a dopamine D1 receptor antagonist, SCH 23390, into the prelimbic cortical region of the PFC, and the YKS effects on impaired reversal learning were done by the infusions into the orbitofrontal cortex (OFC). Locomotor activity did not change in any experimental group. Thus, YKS ameliorated age-related impairments of working memory and reversal learning, which might be mediated by a dopaminergic mechanism in the PFC structure. These investigations provide information
Greene, E; Naranjo, J N
The contribution of structures in the limbic diencephalon to spatial memory function was investigated. Rats with lesions of either the anteroventral thalamus, anteromedial thalamus, dorsomedial thalamus or mammillary bodies were compared in their ability to perform a delayed alternation task. The results indicate the ablation of the thalamic nuclei did not impair delayed-alternation memory, but there was impairment following damage to the mammillary bodies. Placement of the discrete lesions was verified using Nissl sections and by tracing the pattern of projections using a silver degeneration stain. The results suggest that individual thalamic nuclei are not essential in the storage and/or retrieval of spatial memory. The data are discussed in terms of spatial deficits resulting from damage to the hippocampus proper or to the pathways connecting it to other brain structures.
Isingrini, Michel; Angel, Lucie; Fay, Séverine; Taconnat, Laurence; Lemaire, Patrick; Bouazzaoui, Badiâa
We examined the hypothesis that age-related differences in the reliance on executive control may be better explained by variations of task demand than by a mechanism specifically linked to aging. To this end, we compared the relationship between the performance of young and older adults on two executive functioning tests and an updating working-memory task with different load levels. The results revealed a significant interaction between age, task demand, and individual executive capacities, indicating that executive resources were only involved at lower loads in older adults, and only at higher loads in young adults. Overall, the results are not consistent with the proposition that cognition places greater demand on executive control in older adults. However, they support the view that how much young and older adults rely on executive control to accomplish cognitive tasks depends on task demand. Finally, interestingly these results are consistent with the CRUNCH model accounting for age-related differences in brain activations. PMID:26700019
McNab, Fiona; Zeidman, Peter; Rutledge, Robb B; Smittenaar, Peter; Brown, Harriet R; Adams, Rick A; Dolan, Raymond J
A weakened ability to effectively resist distraction is a potential basis for reduced working memory capacity (WMC) associated with healthy aging. Exploiting data from 29,631 users of a smartphone game, we show that, as age increases, working memory (WM) performance is compromised more by distractors presented during WM maintenance than distractors presented during encoding. However, with increasing age, the ability to exclude distraction at encoding is a better predictor of WMC in the absence of distraction. A significantly greater contribution of distractor filtering at encoding represents a potential compensation for reduced WMC in older age.
Jackson, George R
Dementia is among the most feared complications of aging in the U.S. In this issue of Neuron, Yamazaki et al. (2014) present a tour de force mechanistic analysis of a "hit" from a proteomic screen carried out using a Drosophila mutation that affects memory.
Mattli, Florentina; Zollig, Jacqueline; West, Robert
The efficiency of prospective memory (PM) typically increases from childhood to young adulthood and then decreases in later adulthood. The current study used event-related brain potentials (ERPs) to examine the development of the neural correlates of processes associated with the detection of a PM cue, switching from the ongoing activity to the…
Leal, Stephanie L; Noche, Jessica A; Murray, Elizabeth A; Yassa, Michael A
While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation. During false recognition, we found increased DG/CA3 activity in LP individuals, suggesting that hyperactivity may be associated with overgeneralization. We additionally observed a selective deficit in basolateral amygdala-lateral entorhinal cortex-DG/CA3 functional connectivity in LP individuals during pattern separation of negative information. During negative false recognition, LP individuals showed increased medial temporal lobe functional connectivity, consistent with overgeneralization. Overall, these results suggest a novel mechanistic account of individual differences in emotional memory alterations exhibited in aging.
Seewald, P Michelle; De Jesus, Shannon Y; Graves, Lisa V; Moreno, Charles C; Mattson, Sarah N; Gilbert, Paul E
We developed a new test to examine incidental temporal order memory for a self-generated sequence of tasks one might complete in everyday life. Young and older adults were given 10 cards, each listing a task one might accomplish in a typical day. Participants were asked to self-generate a "to do" list by placing the 10 cards in a sequence representing the order in which they would accomplish the tasks, but were not informed of a subsequent memory test. We assessed immediate free recall, delayed free recall, and delayed cued recall for the order of the tasks in the sequence. Older adults were significantly impaired relative to young adults on immediate free recall, delayed free recall, and delayed cued recall. Correlation analyses with standardized neuropsychological tests provide preliminary evidence for construct validity for our test, which is portable and can be rapidly administered in clinical or laboratory settings.
Bucur, Barbara; Madden, David J.; Spaniol, Julia; Provenzale, James M.; Cabeza, Roberto; White, Leonard E.; Huettel, Scott A.
Previous research suggests that, in reaction time (RT) measures of episodic memory retrieval, the unique effects of adult age are relatively small compared to the effects aging shares with more elementary abilities such as perceptual speed. Little is known, however, regarding the mechanisms of perceptual speed. We used diffusion tensor imaging (DTI) to test the hypothesis that white matter integrity, as indexed by fractional anisotropy (FA), serves as one mechanism of perceptual slowing in episodic memory retrieval. Results indicated that declines in FA in the pericallosal frontal region and in the genu of the corpus callosum, but not in other regions, mediated the relationship between perceptual speed and episodic retrieval RT. This relation held, though to a different degree, for both hits and correct rejections. These findings suggest that white matter integrity in prefrontal regions is one mechanism underlying the relation between individual differences in perceptual speed and episodic retrieval. PMID:17383774
Bender, Andrew R; Raz, Naftali
Ability to form new associations between unrelated items is particularly sensitive to aging, but the reasons for such differential vulnerability are unclear. In this study, we examined the role of objective and subjective factors (working memory and beliefs about memory strategies) on differential relations of age with recognition of items and associations. Healthy adults (N = 100, age 21 to 79) studied word pairs, completed item and association recognition tests, and rated the effectiveness of shallow (e.g., repetition) and deep (e.g., imagery or sentence generation) encoding strategies. Advanced age was associated with reduced working memory (WM) capacity and poorer associative recognition. In addition, reduced WM capacity, beliefs in the utility of ineffective encoding strategies, and lack of endorsement of effective ones were independently associated with impaired associative memory. Thus, maladaptive beliefs about memory in conjunction with reduced cognitive resources account in part for differences in associative memory commonly attributed to aging.
Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G
Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity.
Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando; Sauseng, Paul
Aging-related decline in short-term memory capacity seems to be caused by deficient balancing of task-related and resting state brain networks activity; however, the exact neural mechanism underlying this deficit remains elusive. Here, we studied brain oscillatory activity in healthy young and old adults during visual information maintenance in a delayed match-to-sample task. Particular emphasis was on long range phase:amplitude coupling of frontal alpha (8-12 Hz) and posterior fast oscillatory activity (>30 Hz). It is argued that through posterior fast oscillatory activity nesting into the excitatory or the inhibitory phase of frontal alpha wave, long-range networks can be efficiently coupled or decoupled, respectively. On the basis of this mechanism, we show that healthy, elderly participants exhibit a lack of synchronization in task-relevant networks while maintaining synchronized regions of the resting state network. Lacking disconnection of this resting state network is predictive of aging-related short-term memory decline. These results support the idea of inefficient orchestration of competing brain networks in the aging human brain and identify the neural mechanism responsible for this control breakdown.
Tsai, Sheng-Feng; Chen, Pei-Chun; Calkins, Marcus J.; Wu, Shih-Ying; Kuo, Yu-Min
Age-related cognitive impairment has become one of the most common health threats in many countries. The biological substrate of cognition is the interconnection of neurons to form complex information processing networks. Experience-based alterations in the activities of these information processing networks lead to neuroadaptation, which is physically represented at the cellular level as synaptic plasticity. Although synaptic plasticity is known to be affected by aging, the underlying molecular mechanisms are not well described. Astrocytes, a glial cell type that is infrequently investigated in cognitive science, have emerged as energy suppliers which are necessary for meeting the abundant energy demand resulting from glutamatergic synaptic activity. Moreover, the concerted action of an astrocyte-neuron metabolic shuttle is essential for cognitive function; whereas, energetic incoordination between astrocytes and neurons may contribute to cognitive impairment. Whether altered function of the astrocyte-neuron metabolic shuttle links aging to reduced synaptic plasticity is unexplored. However, accumulated evidence documents significant beneficial effects of long-term, regular exercise on cognition and synaptic plasticity. Furthermore, exercise increases the effectiveness of astrocyte-neuron metabolic shuttle by upregulation of astrocytic lactate transporter levels. This review summarizes previous findings related to the neuronal activity-dependent astrocyte-neuron metabolic shuttle. Moreover, we discuss how aging and exercise may shape the astrocyte-neuron metabolic shuttle in cognition-associated brain areas. PMID:27047373
Brautigam, M R; Blommaert, F A; Verleye, G; Castermans, J; Jansen Steur, E N; Kleijnen, J
A growing number of people is subject to age-related cognitive impairment due to the proportional increase of the ageing population. Therefore, there is a growing interest in cognition-enhancing substances. The efficacy of an alcohol/water extract of Ginkgo biloba in elderly individuals with memory- and/or concentration complaints was tested in a randomized, double-blind, placebo-controlled study by using both subjective and objective parameters. After a wash-out period of 4 weeks 241 non-institutionalised patients in the age range 55-86 years were randomly allocated to receive either Ginkgo biloba alcohol/water extract in a high dose (HD), a low dose (LD) or a placebo (PL) for 24 weeks. Patients were assessed using a psychometric testbattery in the following order: Expended Mental Control Test (EMCT) measuring attention and concentration, Benton Test of Visual Retention-Revised (measures short term visual memory), Rey Test part 1 (measures short term memory and learning curve), Beck Depressive Inventory (BDI) measuring the presence and severeness of a depression in order to exclude depressive patients and Rey Test part 2 (measures long term memory: recognition). Furthermore, subjective perception of memory and concentration was measured. 197 patients completed the study (mean MMSE score: 26.29). In the subjective test, the EMCT, the Rey 1 and Rey 2 no significant differences in improvement in time between the groups were observed. In the Benton test increases of 18%, 26% and 11% (expressed as percentage of baseline scores) were observed in the HD, LD and PL respectively (MANOVA; p = 0.0076). No substantial correlation was observed between subjective perception of the severeness of memory complaints and the objective test results. No differences in the number of (gastrointestinal) side effects were observed between placebo and verum groups. These results indicate that the use of Ginkgo extracts in elderly individuals with cognitive impairment might be promising
Missonnier, Pascal; Herrmann, François R; Rodriguez, Christelle; Deiber, Marie-Pierre; Millet, Phiippe; Fazio-costa, Lara; Gold, Gabriel; Giannakopoulos, Panteleimon
Previous functional imaging studies have pointed to the compensatory recruitment of cortical circuits in old age in order to counterbalance the loss of neural efficiency and preserve cognitive performance. Recent electroencephalographic (EEG) analyses reported age-related deficits in the amplitude of an early positive-negative working memory (PN(wm)) component as well as changes in working memory (WM)-load related brain oscillations during the successful performance of the n-back task. To explore the age-related differences of EEG activation in the face of increasing WM demands, we assessed the PN(wm) component area, parietal alpha event-related synchronization (ERS) as well as frontal theta ERS in 32 young and 32 elderly healthy individuals who successfully performed a highly WM demanding 3-back task. PN(wm) area increased with higher memory loads (3- and 2-back > 0-back tasks) in younger subjects. Older subjects reached the maximal values for this EEG parameter during the less WM demanding 0-back task. They showed a rapid development of an alpha ERS that reached its maximal amplitude at around 800 ms after stimulus onset. In younger subjects, the late alpha ERS occurred between 1,200 and 2,000 ms and its amplitude was significantly higher compared with elders. Frontal theta ERS culmination peak decreased in a task-independent manner in older compared with younger cases. Only in younger individuals, there was a significant decrease in the phasic frontal theta ERS amplitude in the 2- and 3-back tasks compared with the detection and 0-back tasks. These observations suggest that older adults display a rapid mobilization of their neural generators within the parietal cortex to manage very low demanding WM tasks. Moreover, they are less able to activate frontal theta generators during attentional tasks compared with younger persons.
Tavassoli, Nader T.
Investigated spatial memory for written words as a behavioral consequence of verbal processing differences. Across three experiments with Chinese and U.S. college students, spatial memory for real and nonsense words was greater for Chinese logographs than for alphabetic English words. This spatial memory advantage was absent for pictures and…
Johnson, Marcia K; Kuhl, Brice A; Mitchell, Karen J; Ankudowich, Elizabeth; Durbin, Kelly A
Although older adults often show reduced episodic memory accuracy, their ratings of the subjective vividness of their memories often equal or even exceed those of young adults. Such findings suggest that young and older adults may differentially access and/or weight different kinds of information in making vividness judgments. We examined this idea using multivoxel pattern classification of fMRI data to measure category representations while participants saw and remembered pictures of objects and scenes. Consistent with our hypothesis, there were age-related differences in how category representations related to the subjective sense of vividness. During remembering, older adults' vividness ratings were more related, relative to young adults', to category representations in prefrontal cortex. In contrast, young adults' vividness ratings were more related, relative to older adults, to category representations in parietal cortex. In addition, category representations were more correlated among posterior regions in young than in older adults, whereas correlations between PFC and posterior regions did not differ between the 2 groups. Together, these results are consistent with the idea that young and older adults differentially weight different types of information in assessing subjective vividness of their memories.
Seckin, Ayse Nazli; Ozdemir, Hulya; Ceylan, Ayca; Artac, Hasibe
Children with Down syndrome (DS) have a high incidence of recurrent respiratory tract infections, leukaemia and autoimmune disorders, suggesting immune dysfunction. The present study evaluated the role of the CD19 complex and memory B cells in the pathogenesis of immunodeficiency in children with DS. The expression levels (median fluorescein intensity-MFI) of CD19, CD21 and CD81 molecules on the surface of B cells and memory B cell subsets were studied in 37 patients and 39 healthy controls. Twenty-nine of the DS group had congenital cardiac disease. The B cell count was significantly low in children with DS compared with healthy age-matched controls for all three age groups (under 2 years; 2-6 years and older than 6 years). The MFI of CD19 was reduced in all the age groups, whereas that of CD21 was increased in those older than 2 years with DS. The expression level of CD81 was significantly increased in those older than 6 years. Age-related changes were also detected in memory B cell subsets. The frequency of CD27(+)IgD(+)IgM(+) natural effector B cells was reduced in children with DS who had needed hospitalisation admission due to infections. The observed intrinsic defects in B cells may be responsible for the increased susceptibility of children with DS to severe respiratory tract infections.
Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando
Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM.
Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando
Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM. PMID
Vieillard, Sandrine; Gilet, Anne-Laure
There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplored the question of how aging may influence emotional responses to and memory for emotions conveyed by music. In the present study, eighteen older (60–84 years) and eighteen younger (19–24 years) listeners were asked to evaluate the strength of their experienced emotion on happy, peaceful, sad, and scary musical excerpts (Vieillard et al., 2008) while facial muscle activity was recorded. Participants then performed an incidental recognition task followed by a task in which they judged to what extent they experienced happiness, peacefulness, sadness, and fear when listening to music. Compared to younger adults, older adults (a) reported a stronger emotional reactivity for happiness than other emotion categories, (b) showed an increased zygomatic activity for scary stimuli, (c) were more likely to falsely recognize happy music, and (d) showed a decrease in their responsiveness to sad and scary music. These results are in line with previous findings and extend them to emotion experience and memory recognition, corroborating the view of age-related changes in emotional responses to music in a positive direction away from negativity. PMID:24137141
Vieillard, Sandrine; Gilet, Anne-Laure
There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplored the question of how aging may influence emotional responses to and memory for emotions conveyed by music. In the present study, eighteen older (60-84 years) and eighteen younger (19-24 years) listeners were asked to evaluate the strength of their experienced emotion on happy, peaceful, sad, and scary musical excerpts (Vieillard et al., 2008) while facial muscle activity was recorded. Participants then performed an incidental recognition task followed by a task in which they judged to what extent they experienced happiness, peacefulness, sadness, and fear when listening to music. Compared to younger adults, older adults (a) reported a stronger emotional reactivity for happiness than other emotion categories, (b) showed an increased zygomatic activity for scary stimuli, (c) were more likely to falsely recognize happy music, and (d) showed a decrease in their responsiveness to sad and scary music. These results are in line with previous findings and extend them to emotion experience and memory recognition, corroborating the view of age-related changes in emotional responses to music in a positive direction away from negativity.
Crystal, Jonathon D.; Babb, Stephanie J.
We investigated the time course of spatial-memory decay in rats using an eight-arm radial maze. It is well established that performance remains high with retention intervals as long as 4 h, but declines to chance with a 24-h retention interval (Beatty, W. W., & Shavalia, D. A. (1980b). Spatial memory in rats: time course of working memory and…
Ariel, Robert; Price, Jodi; Hertzog, Christopher
Value-based remembering in free-recall tasks may be spared from the typical age-related cognitive decline observed for episodic memory. However, it is unclear whether value-based remembering for associative information is also spared from age-related cognitive decline. The current experiments evaluated the contribution of agenda-based based regulation and strategy use during study to age differences and similarities in value-based remembering of associative information. Participants studied word pairs (Experiments 1-2) or single words (Experiment 2) slated with different point values by moving a mouse controlled cursor to different spatial locations to reveal either items for study or the point value associated with remembering each item. Some participants also provided strategy reports for each item. Younger and older adults allocated greater time to studying high- than low-valued information, reported using normatively effective encoding strategies to learn high-valued pairs, and avoided study of low-valued pairs. As a consequence, both age groups selectively remembered more high- than low-valued items. Despite nearly identical regulatory behavior, an associative memory deficit for older adults was present for high-valued pairs. Age differences in value-based remembering did not occur when the materials were word lists. Fluid intelligence also moderated the effectiveness of older adults' strategy use for high-valued pairs (Experiment 2). These results suggest that age differences in associative value-based remembering may be due to some older adults' gleaning less benefit from using normatively effective encoding strategies rather than age differences in metacognitive self-regulation per se.
Ariel, Robert; Price, Jodi; Hertzog, Christopher
Value-based remembering in free recall tasks may be spared from the typical age-related cognitive decline observed for episodic memory. However, it is unclear whether value-based remembering for associative information is also spared from age-related cognitive decline. The current experiments evaluated the contribution of agenda-based based regulation and strategy use during study to age differences and similarities in value-based remembering of associative information. Participants studied word pairs (Experiments 1-2) or single words (Experiment 2) slated with different point values by moving a mouse controlled cursor to different spatial locations to reveal either items for study or the point value associated with remembering each item. Some participants also provided strategy reports for each item. Younger and older adults allocated greater time to studying high than low valued information, reported using normatively effective encoding strategies to learn high-valued pairs, and avoided study of low-valued pairs. As a consequence, both age groups selectively remembered more high than low-valued items. Despite nearly identical regulatory behavior, an associative memory deficit for older adults was present for high valued pairs. Age differences in value-based remembering did not occur when the materials were word lists. Fluid intelligence also moderated the effectiveness of older adults’ strategy use for high valued pairs (Experiment 2). These results suggest that age differences in associative value-based remembering may be due to some older adults’ gleaning less benefit from using normatively effective encoding strategies rather than age differences in metacognitive self-regulation per se. PMID:26523692
Foster, Thomas C.; DeFazio, R. A.; Bizon, Jennifer L.
Episodic memory, especially memory for contextual or spatial information, is particularly vulnerable to age-related decline in humans and animal models of aging. The continuing improvement of virtual environment technology for testing humans signifies that widely used procedures employed in the animal literature for examining spatial memory could be developed for examining age-related cognitive decline in humans. The current review examines cross species considerations for implementing these tasks and translating findings across different levels of analysis. The specificity of brain systems as well as gaps in linking human and animal laboratory models is discussed. PMID:22988436
Meck, Warren H.; Williams, Christina L.; Cermak, Jennifer Marie; Blusztajn, Jan Krzysztof
In order to determine brain and behavioral sensitivity of nutrients that may serve as inductive signals during early development, we altered choline availability to rats during 7 time frames spanning embryonic day (ED) 6 through postnatal day (PD) 75 and examined spatial memory ability in the perinatally-treated adults. Two sensitive periods were identified, ED 12–17 and PD 16–30, during which choline supplementation facilitated spatial memory and produced increases in dendritic spine density in CA1 and dentate gyrus (DG) regions of the hippocampus while also changing the dendritic fields of DG granule cells. Moreover, choline supplementation during ED 12–17 only, prevented the memory decline normally observed in aged rats. These behavioral changes were strongly correlated with the acetylcholine (ACh) content of hippocampal slices following stimulated release. Our data demonstrate that the availability of choline during critical periods of brain development influences cognitive performance in adulthood and old age, and emphasize the importance of perinatal nutrition for successful cognitive aging. PMID:18958235
Oosterman, Joukje M; Morel, Sascha; Meijer, Lisette; Buvens, Cléo; Kessels, Roy P C; Postma, Albert
The present study was intended to compare age effects on visual and spatial working memory by using two versions of the same task that differed only in presentation mode. The working memory task contained both a simultaneous and a sequential presentation mode condition, reflecting, respectively, visual and spatial working memory processes. Young and older participants had to remember the locations of five equal objects under three different conditions: a baseline (immediate recall), a maintenance (including a delay of 5 seconds), and a manipulation (e.g., relocate all objects one column to the right) condition. Only older adults performed worse on the sequential compared to the simultaneous baseline condition and only this group revealed lower performance on the sequential delay compared to the simultaneous delay condition. However, in both groups the manipulation condition affected performance on the simultaneous and sequential presentation modes to the same extent. The findings of this study therefore partially support an age-related differentiation between visual and spatial working memory, with a stronger age effect on spatial than on visual working memory.
Steele, Shelly D.; Minshew, Nancy J.; Luna, Beatriz; Sweeney, John A.
Previous studies have reported working memory deficits in autism, but this finding has been inconsistent. One possibility is that deficits in this domain may be present only when working memory load exceeds some limited capacity. High-functioning individuals with autism performed the CANTAB computerized test of spatial working memory. Individuals…
Dulas, Michael R; Duarte, Audrey
Behavioral evidence has shown age-related impairments in overcoming proactive interference in memory, but it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require several executive control processes supported by the ventrolateral prefrontal cortex (VLPFC) and dorsolateral PFC (DLPFC). The present functional magnetic resonance imaging (fMRI) study investigated whether age-related changes in dissociable executive control processes underlie deficits in overcoming proactive interference in associative memory during retrieval. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that, as interference increased, memory performance decreased similarly across groups, with slight associative memory deficits in older adults. Imaging results demonstrated that, across groups, left mid-VLPFC showed increasing activity with increasing interference, though activity did not distinguish correct from incorrect associative memory responses, suggesting this region may not directly serve in successful resolution of proactive interference, per se. Under conditions of high interference, older adults showed reduced associative memory accuracy effects in the DLPFC and anterior PFC. These results suggest that age-related PFC dysfunction may not be ubiquitous. Executive processes supported by ventral regions that detect mnemonic interference may be less affected than processes supported by dorsal and anterior regions that directly resolve interference.
Vann, Seralynne D; Albasser, Mathieu M
Recognition and spatial memory are typically associated with the perirhinal cortex and hippocampal formation, respectively. Solely focusing on these structures for these specific mnemonic functions may, however, be limiting progress in the field. The distinction between these subdivisions of memory is becoming less defined as, for example, hippocampal cells traditionally considered to encode locations also encode place-object associations. There is increasing evidence for the involvement of overlapping networks of brain structures for aspects of both spatial and recognition memory. Future models of spatial and recognition memory will have to extend beyond the hippocampus and perirhinal cortex to incorporate a wider network of cortical and subcortical structures.
Ferretti, Valentina; Roullet, Pascal; Sargolini, Francesca; Rinaldi, Arianna; Perri, Valentina; Del Fabbro, Martina; Costantini, Vivian J A; Annese, Valentina; Scesa, Gianluigi; De Stefano, Maria Egle; Oliverio, Alberto; Mele, Andrea
Spatial memory formation is a dynamic process requiring a series of cellular and molecular steps, such as gene expression and protein translation, leading to morphological changes that have been envisaged as the structural bases for the engram. Despite the role suggested for medial temporal lobe plasticity in spatial memory, recent behavioral observations implicate specific components of the striatal complex in spatial information processing. However, the potential occurrence of neural plasticity within this structure after spatial learning has never been investigated. In this study we demonstrate that blockade of cAMP response element binding protein-induced transcription or inhibition of protein synthesis or extracellular proteolytic activity in the ventral striatum impairs long-term spatial memory. These findings demonstrate that, in the ventral striatum, similarly to what happens in the hippocampus, several key molecular events crucial for the expression of neural plasticity are required in the early stages of spatial memory formation.
Ferretti, Valentina; Roullet, Pascal; Sargolini, Francesca; Rinaldi, Arianna; Perri, Valentina; Del Fabbro, Martina; Costantini, Vivian J. A.; Annese, Valentina; Scesa, Gianluigi; De Stefano, Maria Egle; Oliverio, Alberto; Mele, Andrea
Spatial memory formation is a dynamic process requiring a series of cellular and molecular steps, such as gene expression and protein translation, leading to morphological changes that have been envisaged as the structural bases for the engram. Despite the role suggested for medial temporal lobe plasticity in spatial memory, recent behavioral observations implicate specific components of the striatal complex in spatial information processing. However, the potential occurrence of neural plasticity within this structure after spatial learning has never been investigated. In this study we demonstrate that blockade of cAMP response element binding protein–induced transcription or inhibition of protein synthesis or extracellular proteolytic activity in the ventral striatum impairs long-term spatial memory. These findings demonstrate that, in the ventral striatum, similarly to what happens in the hippocampus, several key molecular events crucial for the expression of neural plasticity are required in the early stages of spatial memory formation. PMID:20351272
Guez, Jonathan; Naveh-Benjamin, Moshe
Previous studies have suggested an associative deficit hypothesis [Naveh-Benjamin, M. ( 2000 ). Adult age differences in memory performance: Tests of an associative deficit hypothesis. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1170-1187] to explain age-related episodic memory declines. The hypothesis attributes part of the deficient episodic memory performance in older adults to a difficulty in creating and retrieving cohesive episodes. In this article, we further evaluate this hypothesis by testing two alternative processes that potentially mediate associative memory deficits in older adults. Four experiments are presented that assess whether failure of inhibitory processes (proactive interference in Experiments 1 and 2), and concurrent inhibition (in Experiments 3 and 4) are mediating factors in age-related associative deficits. The results suggest that creating conditions that require the operation of inhibitory processes, or that interfere with such processes, cannot simulate associative memory deficit in older adults. Instead, such results support the idea that associative memory deficits reflect a unique binding failure in older adults. This failure seems to be independent of other cognitive processes, including inhibitory and other resource-demanding processes.
Combined Administration of Levetiracetam and Valproic Acid Attenuates Age Related Hyperactivity of CA3 Place Cells, Reduces Place Field Area, and Increases Spatial Information Content in Aged Rat Hippocampus
Robitsek, RJ; Ratner, MH; Stewart, TM; Eichenbaum, H; Farb, DH
Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA. PMID:25941121
Combined administration of levetiracetam and valproic acid attenuates age-related hyperactivity of CA3 place cells, reduces place field area, and increases spatial information content in aged rat hippocampus.
Robitsek, Jonathan; Ratner, Marcia H; Stewart, Tara; Eichenbaum, Howard; Farb, David H
Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of functional inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA.
Jones, Bethany; Bukoski, Elizabeth; Nadel, Lynn; Fellous, Jean-Marc
There is strong evidence that reactivation of a memory returns it to a labile state, initiating a restabilization process termed reconsolidation, which allows for updating of the memory. In this study we investigated reactivation-dependent updating using a new positively motivated spatial task in rodents that was designed specifically to model a…
Koehl, Muriel; Ichas, François; De Giorgi, Francesca; Costet, Pierre; Abrous, Djoher Nora; Piazza, Pier Vincenzo
The dentate gyrus of the hippocampus is one of the few regions of the mammalian brain where new neurons are generated throughout adulthood. This adult neurogenesis has been proposed as a novel mechanism that mediates spatial memory. However, data showing a causal relationship between neurogenesis and spatial memory are controversial. Here, we developed an inducible transgenic strategy allowing specific ablation of adult-born hippocampal neurons. This resulted in an impairment of spatial relational memory, which supports a capacity for flexible, inferential memory expression. In contrast, less complex forms of spatial knowledge were unaltered. These findings demonstrate that adult-born neurons are necessary for complex forms of hippocampus-mediated learning. PMID:18509506
Korman, M; Dagan, Y; Karni, A
Using a training protocol that effectively induces procedural memory consolidation (PMC) in young adults, we show that older adults are good learners, robustly improving their motor performance during training. However, performance declined over the day, and overnight 'offline' consolidation phase performance gains were under-expressed. A post-training nap countered these deficits. PMC processes are preserved but under-engaged in the elderly; sleep can relax some of the age-related constraints on long-term plasticity.
Wenke, Jamie L.; Rose, Kristie L.; Spraggins, Jeffrey M.; Schey, Kevin L.
Purpose To spatially map human lens Aquaporin-0 (AQP0) protein modifications, including lipidation, truncation, and deamidation, from birth through middle age using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS). Methods Human lens sections were water-washed to facilitate detection of membrane protein AQP0. We acquired MALDI images from eight human lenses ranging in age from 2 months to 63 years. In situ tryptic digestion was used to generate peptides of AQP0 and peptide images were acquired on a 15T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Peptide extracts were analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and database searched to identify peptides observed in MALDI imaging experiments. Results Unmodified, truncated, and fatty acid–acylated forms of AQP0 were detected in protein imaging experiments. Full-length AQP0 was fatty acid acylated in the core and cortex of young (2- and 4-month) lenses. Acylated and unmodified AQP0 were C-terminally truncated in older lens cores. Deamidated tryptic peptides (+0.9847 Da) were mass resolved from unmodified peptides by FTICR MS. Peptide images revealed differential localization of un-, singly-, and doubly-deamidated AQP0 C-terminal peptide (239–263). Deamidation was present at 4 months and increases with age. Liquid chromatography–MS/MS results indicated N246 undergoes deamidation more rapidly than N259. Conclusions Results indicated AQP0 fatty acid acylation and deamidation occur during early development. Progressive age-related AQP0 processing, including deamidation and truncation, was mapped in human lenses as a function of age. The localization of these modified AQP0 forms suggests where AQP0 functions may change throughout lens development and aging. PMID:26574799
Older adults with age-related macular degeneration (AMD) are not immune to the other diseases of aging. Although AMD is the leading cause of low vision in older Americans, stroke is the leading cause of disability, and dementias affect another 2.5 million older Americans. Each condition alone can significantly impair a person's ability to…
Fagan, William F; Lewis, Mark A; Auger-Méthé, Marie; Avgar, Tal; Benhamou, Simon; Breed, Greg; LaDage, Lara; Schlägel, Ulrike E; Tang, Wen-wu; Papastamatiou, Yannis P; Forester, James; Mueller, Thomas
Memory is critical to understanding animal movement but has proven challenging to study. Advances in animal tracking technology, theoretical movement models and cognitive sciences have facilitated research in each of these fields, but also created a need for synthetic examination of the linkages between memory and animal movement. Here, we draw together research from several disciplines to understand the relationship between animal memory and movement processes. First, we frame the problem in terms of the characteristics, costs and benefits of memory as outlined in psychology and neuroscience. Next, we provide an overview of the theories and conceptual frameworks that have emerged from behavioural ecology and animal cognition. Third, we turn to movement ecology and summarise recent, rapid developments in the types and quantities of available movement data, and in the statistical measures applicable to such data. Fourth, we discuss the advantages and interrelationships of diverse modelling approaches that have been used to explore the memory-movement interface. Finally, we outline key research challenges for the memory and movement communities, focusing on data needs and mathematical and computational challenges. We conclude with a roadmap for future work in this area, outlining axes along which focused research should yield rapid progress.
Zhang, Hui; Mou, Weimin; McNamara, Timothy P.; Wang, Lin
Four experiments investigated the manner in which people use spatial reference directions to organize spatial memories of 2 conceptually nested layouts. Participants learned directions of 8 remote cities centered to Beijing or Edmonton, where the experiments occurred, using a map or using direct pointing. The map and the environment were aligned,…
Hess, Thomas M; Popham, Lauren E; Growney, Claire M
Background/Study Context: Previous research (Hess et al., 2013, Psychology and Aging, 28, 853-863) suggested that age-based positivity effects in memory were attenuated with social stimuli. This research examined the degree to which this generalized across arousal levels associated with social images. Variations in approach and avoidance responses to individual images were also examined, along with age differences in their relationship to memory performance.
Meneghetti, Chiara; Gyselinck, Valerie; Pazzaglia, Francesca; De Beni, Rossana
The present study investigates the relation between spatial ability and visuo-spatial and verbal working memory in spatial text processing. In two experiments, participants listened to a spatial text (Experiments 1 and 2) and a non-spatial text (Experiment 1), at the same time performing a spatial or a verbal concurrent task, or no secondary task.…
Cassilhas, Ricardo C; Tufik, Sergio; de Mello, Marco Túlio
There has long been discussion regarding the positive effects of physical exercise on brain activity. However, physical exercise has only recently begun to receive the attention of the scientific community, with major interest in its effects on the cognitive functions, spatial learning and memory, as a non-drug method of maintaining brain health and treating neurodegenerative and/or psychiatric conditions. In humans, several studies have shown the beneficial effects of aerobic and resistance exercises in adult and geriatric populations. More recently, studies employing animal models have attempted to elucidate the mechanisms underlying neuroplasticity related to physical exercise-induced spatial learning and memory improvement, even under neurodegenerative conditions. In an attempt to clarify these issues, the present review aims to discuss the role of physical exercise in the improvement of spatial learning and memory and the cellular and molecular mechanisms involved in neuroplasticity.
Fox, Jeffrey; Riccio, Mark; Hua, Fei; Bodenschatz, Eberhard; Gilmour, Robert
Beat-to-beat alternation of cardiac electrical properties (alternans) commonly occurs during rapid periodic pacing. Although alternans is generally associated with a resititution curve with slope >=1, recent studies by Gauthier and co-workers reported the absence of alternans in frog heart tissue with a restitution curve of slope >=1. These experimental findings were understood in terms of a memory model in which the duration D of an action potential depends on the preceding rest interval I as well as a memory variable M that accumulates during D and dissipates during I. We study the spatiotemporal dynamics of a spatially extended 1-d fiber using an ionic model that exhibits memory effects. We find that while a single cell can have a restitution slope >=1 and not show alternans (because of memory), the spatially extended system exhibits alternans. To understand the dynamical mechanism of this behavior, we study a coupled maps memory model both numerically and analytically. These results illustrate that spatial effects and memory effects can play a significant role in determining the dynamics of wave propagation in cardiac tissue.
Qiming Hou; Xin Sun; Kun Zhou; Lauterbach, C; Manocha, D
Recent GPU algorithms for constructing spatial hierarchies have achieved promising performance for moderately complex models by using the breadth-first search (BFS) construction order. While being able to exploit the massive parallelism on the GPU, the BFS order also consumes excessive GPU memory, which becomes a serious issue for interactive applications involving very complex models with more than a few million triangles. In this paper, we propose to use the partial breadth-first search (PBFS) construction order to control memory consumption while maximizing performance. We apply the PBFS order to two hierarchy construction algorithms. The first algorithm is for kd-trees that automatically balances between the level of parallelism and intermediate memory usage. With PBFS, peak memory consumption during construction can be efficiently controlled without costly CPU-GPU data transfer. We also develop memory allocation strategies to effectively limit memory fragmentation. The resulting algorithm scales well with GPU memory and constructs kd-trees of models with millions of triangles at interactive rates on GPUs with 1 GB memory. Compared with existing algorithms, our algorithm is an order of magnitude more scalable for a given GPU memory bound. The second algorithm is for out-of-core bounding volume hierarchy (BVH) construction for very large scenes based on the PBFS construction order. At each iteration, all constructed nodes are dumped to the CPU memory, and the GPU memory is freed for the next iteration's use. In this way, the algorithm is able to build trees that are too large to be stored in the GPU memory. Experiments show that our algorithm can construct BVHs for scenes with up to 20 M triangles, several times larger than previous GPU algorithms.
Cordon, Ingrid M.; Melinder, Annika M. D.; Goodman, Gail S.; Edelstein, Robin S.
Two studies were conducted to examine theoretical questions about children's and adults' memory for emotional visual stimuli. In Study 1, 7- to 9-year-olds and adults (N = 172) participated in the initial creation of the Developmental Affective Photo System (DAPS). Ratings of emotional valence, arousal, and complexity were obtained. In Study 2,…
Morris, Ken A.; Gold, Paul E.
This experiment examined whether age-related changes in CREB and pCREB contribute to the rapid forgetting seen in aged animals. Young (3-month-old) and aged (24-month-old) Fischer-344 rats received inhibitory avoidance training with a low (0.2 mA, 0.4 sec) or moderate (0.5 mA, 0.5 sec) footshock; memory was measured 7 days later. Other rats were euthanized 30 minutes after training, and CREB and pCREB expression levels were examined in the hippocampus, amygdala, and piriform cortex using immunohistochemistry. CREB levels decreased with age in the hippocampus and amygdala. After training with either shock level, young rats exhibited good memory and increases in pCREB levels in the hippocampus and amygdala. Aged rats exhibited good memory for the moderate but not the low shock but did not show increases in pCREB levels after either shock intensity. These results suggest that decreases in total CREB and in pCREB activation in the hippocampus and amygdala may contribute to rapid forgetting in aged rats. After moderate footshock, the stable memory in old rats together with absence of CREB activation suggests either that CREB was phosphorylated in a spatiotemporal pattern other than analyzed here or that the stronger training conditions engaged alternate mechanisms that promote long-lasting memory. PMID:22445851
Miller, Jonathan F.; Lazarus, Eben M.; Polyn, Sean M.; Kahana, Michael J.
In recalling a list of previously experienced items, participants are known to organize their responses on the basis of the items' semantic and temporal similarities. Here, we examine how spatial information influences the organization of responses in free recall. In Experiment 1, participants studied and subsequently recalled lists of landmarks.…
Klauer, Karl Christoph; Zhao, Zengmei
A visual short-term memory task was more strongly disrupted by visual than spatial interference, and a spatial memory task was simultaneously more strongly disrupted by spatial than visual interference. This double dissociation supports a fractionation of visuospatial short-term memory into separate visual and spatial components. In 6 experiments,…
Daugherty, Ana M; Ofen, Noa
The development of associative memory during childhood may be influenced by metacognitive factors. Here, one aspect of metamemory function--belief in strategy efficacy-was tested for a role in the effective use of encoding strategies. A sample of 61 children and adults (8-25 years of age) completed an associative recognition memory test and were assessed on belief in the efficacy of encoding strategies. Independent of age, belief ratings identified two factors: "deep" and "shallow" encoding strategies. Although the strategy factor structure was stable across age, adolescents and adults were more likely to prefer using a deep encoding strategy, whereas children were equally likely to prefer a shallow strategy. Belief ratings of deep encoding strategies increased with age and, critically, accounted for better associative recognition.
Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C
A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task that are sensitive to aging. Young and middle-age rats were trained on the five-choice serial reaction time task (5-CSRTT) and challenged with MK-801 (0.025, 0.05, and 0.1mg/kg or vehicle). Attention deficits were apparent in middle-age and performance of young and middle-age rats was enhanced for low doses of MK-801 (0.025 and 0.05). The beneficial effects on attention were reversed by the highest dose of MK-801. Older animals exhibited a delay-dependent impairment of episodic spatial memory examined on a delayed-matching to place water maze task. Similarly, a low dose of MK-801 (0.05mg/kg) impaired performance with increasing delay and aged animals were more susceptible to disruption by NMDAR blockade. Despite MK-801 impairment of episodic spatial memory, MK-801 had minimal effects on spatial reference memory. Our results confirm that NMDARs contribute to rapidly acquired and flexible spatial memory and support the idea that a decline in NMDAR function contributes to the age-related impairments in cognition.
Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C.
A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task that are sensitive to aging. Young and middle-age rats were trained on the five-choice serial reaction time task (5-CSRTT) and challenged with MK-801 (0.025, 0.05, and 0.1 mg/kg or vehicle). Attention deficits were apparent in middle-age and performance of young and middle-age rats was enhanced for low doses of MK-801 (0.025 and 0.05). The beneficial effects on attention were reversed by the highest dose of MK-801. Older animals exhibited a delay-dependent impairment of episodic spatial memory examined on a delayed-matching to place water maze task. Similarly, a low dose of MK-801 (0.05 mg/kg) impaired performance with increasing delay and aged animals were more susceptible to disruption by NMDAR blockade. Despite MK-801 impairment of episodic spatial memory, MK-801 had minimal effects on spatial reference memory. Our results confirm that NMDARs contribute to rapidly acquired and flexible spatial memory and support the idea that a decline in NMDAR function contributes to the age-related impairments in cognition. PMID:26234588
Tlauka, Michael; Clark, C. Richard; Liu, Ping; Conway, Marie
This study examined the temporal characteristics of event-related brain electrical activity associated with the processing of spatial memories derived from linguistic and tactile information. Participants learned a map by (1) reading a text description of the map, (2) touching a wooden topological representation of the map (hidden from view), or…
Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta
There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults' performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects.
Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta
There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults’ performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects. PMID:25426064
Uresti-Cabrera, Luis A.; Diaz, Rosalinda; Vaca-Palomares, Israel; Fernandez-Ruiz, Juan
Objective. To evaluate the effect of age-related cognitive changes in a visuomotor learning task that depends on strategic control and contrast it with the effect in a task principally depending on visuomotor recalibration. Methods. Participants performed a ball throwing task while donning either a reversing dove prism or a displacement wedge prism, which mainly depend on strategic control or visuomotor recalibration, respectively. Visuomotor performance was then analysed in relation to rule acquisition and reversal, recognition memory, visual memory, spatial planning, and spatial working memory with tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Results. The results confirmed previous works showing a detrimental effect of age on visuomotor learning. The analyses of the cognitive changes observed across age showed that both strategic control and visuomotor recalibration had significant negative correlations only with the number of errors in the spatial working memory task. However, when the effect of aging was controlled, the only significant correlation remaining was between the reversal adaptation magnitude and spatial working memory. Discussion. These results suggest that spatial working memory decline across aging could contribute to age-dependent deterioration in both visuomotor learning processes. However, spatial working memory integrity seems to affect strategic learning decline even after controlling for aging. PMID:26290623
Chiang, Hsueh-Sheng; Mudar, Raksha A.; Spence, Jeffrey S.; Pudhiyidath, Athula; Eroh, Justin; DeLaRosa, Bambi; Kraut, Michael A.; Hart, John
To investigate neural mechanisms that support semantic functions in aging, we recorded scalp EEG during an object retrieval task in 22 younger and 22 older adults. The task required determining if a particular object could be retrieved when two visual words representing object features were presented. Both age groups had comparable accuracy although response times were longer in older adults. In both groups a left fronto-temporal negative potential occurred at around 750 msec during object retrieval, consistent with previous findings (Brier et al., 2008). Only in older adults a later positive frontal potential was found peaking between 800 and 1000 msec during no retrieval. These findings suggest younger and older adults employ comparable neural mechanisms when features clearly facilitate retrieval of an object memory, but when features yield no retrieval, older adults use additional neural resources to engage in a more effortful and exhaustive search prior to making a decision. PMID:24911552
Robin, Jessica; Moscovitch, Morris
Episodic memory, future thinking, and memory for scenes have all been proposed to rely on the hippocampus, and evidence suggests that these all decline in healthy aging. Despite this age-related memory decline, studies examining the effects of context reinstatement on episodic memory have demonstrated that reinstating elements of the encoding context of an event leads to better memory retrieval in both younger and older adults. The current study was designed to test whether more familiar, real-world contexts, such as locations that participants visited often, would improve the detail richness and vividness of memory for scenes, autobiographical events, and imagination of future events in young and older adults. The predicted age-related decline in internal details across all 3 conditions was accompanied by persistent effects of contextual familiarity, in which a more familiar spatial context led to increased detail and vividness of remembered scenes, autobiographical events, and, to some extent, imagined future events. This study demonstrates that autobiographical memory, imagination of the future, and scene memory are similarly affected by aging, and all benefit from being associated with more familiar (real-world) contexts, illustrating the stability of contextual reinstatement effects on memory throughout the life span. (PsycINFO Database Record
DeMaster, Dana; Pathman, Thanujeni; Ghetti, Simona
The goal of the present study was to examine age-related differences in hippocampal and cortical contribution to episodic retrieval of spatial context in 3 age groups. Children ages 8-9 and 10-11 years old, and adults ages 18-25 (N=48) encoded black and white line drawings appearing either on the right side or the left side of a screen. Functional magnetic resonance imaging (fMRI) data were acquired while participants attempted to recall where each studied drawing had originally appeared. Correct recall of spatial source indicated successful episodic retrieval of spatial context. Activity in head and body of the hippocampus was associated with episodic retrieval in adults, but not in children. In children, individual differences in hippocampal activation for recognition predicted rates of correct spatial recall. Developmental differences were also found in regions in posterior parietal cortex, anterior prefrontal cortex, and insula. Overall, these results support the view that the development of episodic memory is supported by functional changes in the hippocampus as well as cortical regions.
Wang, Feng; Chen, Hong; Sun, Xiaojiang
At present, the mechanisms underlying cognitive disorders remain unclear. The senescence-accelerated mice (SAM) prone/8 (P8) has been proposed as a useful model for the study of aging, and SAM resistant/1 (R1) is its control as a normal aging strain. The purpose of this study was to investigate choline acetyltransferase (ChAT) expression in SAM brain. The age-related decline of learning and memory ability in P8 mice (4, 8 and 12 months old, n=10 for each group) was proved in Morris water maze test (MWM). After the behavioral test, protein and mRNA levels of ChAT were determined in the cerebral cortex, hippocampus and forebrain by means of immunostaining, Western blotting, and real time quantitative PCR (QPCR). Comparing with 4-month-old P8 and R1, 8- and 12-month-old P8 showed age-related cognitive impairment in MWM test. The latencies of the 4-month-old P8 in a hidden platform trial were significantly shorter, and the retention time was significantly longer than that of the older P8 groups. In addition, significantly low level of ChAT protein was observed in older P8 groups. Comparing with the 4-month-old P8, ChAT mRNA in the 12-month-old P8 declined significantly in all three regions of P8 brain. Pearson correlation test showed that the latencies in the MWM were positively correlated with the level of ChAT in P8. Such phenomenon could not be detected in normal aging R1 mice. These findings suggest that the decrease of ChAT in P8 mice was responsible for the age-related learning and memory impairments in some sense.
Peltz, Carrie Brumback; Gratton, Gabriele; Fabiani, Monica
Older adults exhibit great variability in their cognitive abilities, with some maintaining high levels of performance on executive control tasks and others showing significant deficits. Previous event-related potential (ERP) work has shown that some of these performance differences are correlated with persistence of the novelty/frontal P3 in older adults elicited by task-relevant events, presumably reflecting variability in the capacity to suppress orienting to unexpected but no longer novel events. In recent ERP work in young adults, we showed that the operation-span (OSPAN) task (a measure of attention control) is predictive of the ability of individuals to keep track of stimulus sequencing and to maintain running mental representations of task stimuli, as indexed by the parietally distributed P300 (or P3b). Both of these phenomena reflect aspects of frontal function (cognitive flexibility and attention control, respectively). To investigate these phenomena we sorted both younger and older adults into low- and high-working memory spans and low- and high-cognitive flexibility subgroups, and examined ERPs during an equal-probability choice reaction time task. For both age groups (a) participants with high OSPAN scores were better able to keep track of stimulus sequencing, as indicated by their smaller P3b to sequential changes; and (b) participants with lower cognitive flexibility had larger P3a than their high-scoring counterparts. However, these two phenomena did not interact suggesting that they manifest dissociable control mechanisms. Further, the fact that both effects are already visible in younger adults suggests that at least some of the brain mechanisms underlying individual differences in cognitive aging may already operate early in life. PMID:21887150
Fukumori, Kayoko; Okuda, Noboru; Yamaoka, Kosaku; Yanagisawa, Yasunobu
The ability to orient and navigate within a certain environment is essential for all animals, and spatial memory enables animals to remember the locations of such markers as predators, home, and food. Here we report that the migratory marine cardinalfish Apogon notatus has the potential to retain long-term spatial memory comparable to that of other animals. Female A. notatus establish a small territory on a shallow boulder bottom to pair and spawn with males. We carried out field research in two consecutive breeding seasons on territory settlement by individually marked females. Females maintained a territory at the same site throughout one breeding season. After overwintering in deep water, many of them (82.1%) returned to their breeding ground next spring and most occupied the same site as in the previous season, with only a 0.56 m shift on average. Our results suggest that female A. notatus have long-distance homing ability to pinpoint the exact location of their previous territory, and retain spatial memory for as long as 6 months.
Walrave, Laura; Vinken, Mathieu; Albertini, Giulia; De Bundel, Dimitri; Leybaert, Luc; Smolders, Ilse J.
Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs). We here investigated whether interfering with connexin43 (Cx43) HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19) into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory. PMID:28066184
Van de Weijer-Bergsma, Eva; Kroesbergen, Evelyn H; Van Luit, Johannes E H
The relative importance of visual-spatial and verbal working memory for mathematics performance and learning seems to vary with age, the novelty of the material, and the specific math domain that is investigated. In this study, the relations between verbal and visual-spatial working memory and performance in four math domains (i.e., addition, subtraction, multiplication, and division) at different ages during primary school are investigated. Children (N = 4337) from grades 2 through 6 participated. Visual-spatial and verbal working memory were assessed using online computerized tasks. Math performance was assessed at the start, middle, and end of the school year using a speeded arithmetic test. Multilevel Multigroup Latent Growth Modeling was used to model individual differences in level and growth in math performance, and examine the predictive value of working memory per grade, while controlling for effects of classroom membership. The results showed that as grade level progressed, the predictive value of visual-spatial working memory for individual differences in level of mathematics performance waned, while the predictive value of verbal working memory increased. Working memory did not predict individual differences between children in their rate of performance growth throughout the school year. These findings are discussed in relation to three, not mutually exclusive, explanations for such age-related findings.
Vorhees, Charles V.; Williams, Michael T.
Maneuvering safely through the environment is central to survival of almost all species. The ability to do this depends on learning and remembering locations. This capacity is encoded in the brain by two systems: one using cues outside the organism (distal cues), allocentric navigation, and one using self-movement, internal cues and nearby proximal cues, egocentric navigation. Allocentric navigation involves the hippocampus, entorhinal cortex, and surrounding structures; in humans this system encodes allocentric, semantic, and episodic memory. This form of memory is assessed in laboratory animals in many ways, but the dominant form of assessment is the Morris water maze (MWM). Egocentric navigation involves the dorsal striatum and connected structures; in humans this system encodes routes and integrated paths and, when overlearned, becomes procedural memory. In this article, several allocentric assessment methods for rodents are reviewed and compared with the MWM. MWM advantages (little training required, no food deprivation, ease of testing, rapid and reliable learning, insensitivity to differences in body weight and appetite, absence of nonperformers, control methods for proximal cue learning, and performance effects) and disadvantages (concern about stress, perhaps not as sensitive for working memory) are discussed. Evidence-based design improvements and testing methods are reviewed for both rats and mice. Experimental factors that apply generally to spatial navigation and to MWM specifically are considered. It is concluded that, on balance, the MWM has more advantages than disadvantages and compares favorably with other allocentric navigation tasks. PMID:25225309
Oosterman, Joukje M.; Morel, Sascha; Meijer, Lisette; Buvens, Cleo; Kessels, Roy P. C.; Postma, Albert
The present study was intended to compare age effects on visual and spatial working memory by using two versions of the same task that differed only in presentation mode. The working memory task contained both a simultaneous and a sequential presentation mode condition, reflecting, respectively, visual and spatial working memory processes. Young…
Wiholm, Clairy; Lowden, Arne; Kuster, Niels; Hillert, Lena; Arnetz, Bengt B; Akerstedt, Torbjörn; Moffat, Scott D
Radiofrequency (RF) emission during mobile phone use has been suggested to impair cognitive functions, that is, working memory. This study investigated the effects of a 2 1/2 h RF exposure (884 MHz) on spatial memory and learning, using a double-blind repeated measures design. The exposure was designed to mimic that experienced during a real-life mobile phone conversation. The design maximized the exposure to the left hemisphere. The average exposure was peak spatial specific absorption rate (psSAR10g) of 1.4 W/kg. The primary outcome measure was a "virtual" spatial navigation task modeled after the commonly used and validated Morris Water Maze. The distance traveled on each trial and the amount of improvement across trials (i.e., learning) were used as dependent variables. The participants were daily mobile phone users, with and without symptoms attributed to regular mobile phone use. Results revealed a main effect of RF exposure and a significant RF exposure by group effect on distance traveled during the trials. The symptomatic group improved their performance during RF exposure while there was no such effect in the non-symptomatic group. Until this new finding is further investigated, we can only speculate about the cause.
da Silva, Weber C N; Köhler, Cristiano C; Radiske, Andressa; Cammarota, Martín
We investigated the effect of the intra-CA1 administration of the D1/D5 receptor antagonist SCH23390 and the D1/D5 receptor agonist SKF38393 on spatial memory in the water maze. When given immediately, but not 3h after training, SCH23390 hindered long-term spatial memory formation without affecting non-spatial memory or the normal functionality of the hippocampus. On the contrary, post-training infusion of SKF38393 enhanced retention and facilitated the spontaneous recovery of the original spatial preference after reversal learning. Our findings demonstrate that hippocampal D1/D5 receptors play an essential role in spatial memory processing.
Oliveira-Santos, Luiz Gustavo R; Forester, James D; Piovezan, Ubiratan; Tomas, Walfrido M; Fernandez, Fernando A S
Memory is among the most important and neglected forces that shapes animal movement patterns. Research on the movement-memory interface is crucial to understand how animals use spatial learning to navigate across space because memory-based navigation is directly linked to animals' space use and home range behaviour; however, because memory cannot be measured directly, it is difficult to account for. Here, we incorporated spatial memory into step selection functions (SSF) to understand how resource selection and spatial memory affect space use of feral hogs (Sus scrofa). We used Biased Random Bridge kernel estimates linked to residence time as a surrogate for memory and tested four conceptually different dynamic maps of spatial memory. We applied this memory-based SSF to a data set of hog relocations to evaluate the importance of land cover type, time of day and spatial memory on the animals' space use. Our approach has shown how the incorporation of spatial memory into animal movement models can improve estimates of habitat selection. Memory-based SSF provided a feasible way to gain insight into how animals use spatial learning to guide their movement decisions. We found that while hogs selected forested areas and water bodies and avoided grasslands during the day (primarily at noon), they had a strong tendency to select previously visited areas, mainly those held in recent memory. Beyond actively updating their memory with recent experiences, hogs were able to discriminate among spatial memories encoded at different circadian phases of their activity. Even though hogs are thought to have long memory retention, they likely relied on recent experiences because the local food resources are quickly depleted and slowly renewed, yielding an uncertain spatial distribution of resources.
Won, Bo-Yeong; Jiang, Yuhong V.
Recent empirical and theoretical work has depicted a close relationship between visual attention and visual working memory. For example, rehearsal in spatial working memory depends on spatial attention, whereas adding a secondary spatial working memory task impairs attentional deployment in visual search. These findings have led to the proposal…
Fuchs, Fanny; Cosquer, Brigitte; Penazzi, Lorène; Mathis, Chantal; Kelche, Christian; Majchrzak, Monique; Barbelivien, Alexandra
In rats, some cognitive capabilities, like spatial learning and memory, are preserved from age-related decline by whole adult life enriched environment (EE) exposure. However, to which extent late EE contributes to such maintenance remains to be investigated. Here we assessed the impact of late housing condition (e.g., from the age of 18 months) on spatial learning and memory of aged rats (24 months) previously exposed or unexposed to EE from young adulthood. The results showed that late EE was not required for spatial memory maintenance in aged rats previously housed in EE. In contrast, late EE mitigates spatial memory deficit in aged rats previously unexposed to EE. These outcomes suggest that EE exposure up to middle age provides a "reserve"-like advantage which supports an enduring preservation of spatial capabilities in old age.
Kumar, Navnit; Priyadarshi, Brajesh
Working memory (WM) declines with age. However it seems unclear, whether age related decline is more pronounced on verbal WM or on visuo-spatial WM. The present study compares the effect of aging on verbal and visuo-spatial modality of WM on native Hindi healthy speakers, in the age range of 40-to-above 80 years. It was found that normal aging affect both the verbal and visual working memory in similar way. Both modality declines with a similar rate up to 50–60 years and after 60 years relative saturation in span take place. Although verbal WM span is higher than visuo-spatial WM span, but no significant difference between verbal and visuo-spatial WM span were observed. PMID:23946892
Spellman, Timothy; Rigotti, Mattia; Ahmari, Susanne E; Fusi, Stefano; Gogos, Joseph A; Gordon, Joshua A
Spatial working memory, the caching of behaviourally relevant spatial cues on a timescale of seconds, is a fundamental constituent of cognition. Although the prefrontal cortex and hippocampus are known to contribute jointly to successful spatial working memory, the anatomical pathway and temporal window for the interaction of these structures critical to spatial working memory has not yet been established. Here we find that direct hippocampal-prefrontal afferents are critical for encoding, but not for maintenance or retrieval, of spatial cues in mice. These cues are represented by the activity of individual prefrontal units in a manner that is dependent on hippocampal input only during the cue-encoding phase of a spatial working memory task. Successful encoding of these cues appears to be mediated by gamma-frequency synchrony between the two structures. These findings indicate a critical role for the direct hippocampal-prefrontal afferent pathway in the continuous updating of task-related spatial information during spatial working memory.
Avraamides, Marios N.; Kelly, Jonathan W.
Recent models in spatial cognition posit that distinct memory systems are responsible for maintaining transient and enduring spatial relations. The authors used perspective-taking performance to assess the presence of these enduring and transient spatial memories for locations encoded through verbal descriptions. Across 3 experiments, spatial…
Martinelli, Pénélope; Sperduti, Marco; Devauchelle, Anne-Dominique; Kalenzaga, Sandrine; Gallarda, Thierry; Lion, Stéphanie; Delhommeau, Marion; Anssens, Adèle; Amado, Isabelle; Meder, Jean François; Krebs, Marie-Odile; Oppenheim, Catherine; Piolino, Pascale
Age-related changes in autobiographical memory (AM) recall are characterized by a decline in episodic details, while semantic aspects are spared. This deleterious effect is supposed to be mediated by an inefficient recruitment of executive processes during AM retrieval. To date, contrasting evidence has been reported on the neural underpinning of this decline, and none of the previous studies has directly compared the episodic and semantic aspects of AM in elderly. We asked 20 young and 17 older participants to recall specific and general autobiographical events (i.e., episodic and semantic AM) elicited by personalized cues while recording their brain activity by means of fMRI. At the behavioral level, we confirmed that the richness of episodic AM retrieval is specifically impoverished in aging and that this decline is related to the reduction of executive functions. At the neural level, in both age groups, we showed the recruitment of a large network during episodic AM retrieval encompassing prefrontal, cortical midline and posterior regions, and medial temporal structures, including the hippocampus. This network was very similar, but less extended, during semantic AM retrieval. Nevertheless, a greater activity was evidenced in the dorsal anterior cingulate cortex (dACC) during episodic, compared to semantic AM retrieval in young participants, and a reversed pattern in the elderly. Moreover, activity in dACC during episodic AM retrieval was correlated with inhibition and richness of memories in both groups. Our findings shed light on the direct link between episodic AM retrieval, executive control, and their decline in aging, proposing a possible neuronal signature. They also suggest that increased activity in dACC during semantic AM retrieval in the elderly could be seen as a compensatory mechanism underpinning successful AM performance observed in aging. These results are discussed in the framework of recently proposed models of neural reorganization in aging
Coltman, Robin; Spain, Aisling; Tsenkina, Yanina; Fowler, Jill H; Smith, Jessica; Scullion, Gillian; Allerhand, Mike; Scott, Fiona; Kalaria, Rajesh N; Ihara, Masafumi; Daumas, Stephanie; Deary, Ian J; Wood, Emma; McCulloch, James; Horsburgh, Karen
The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing
Anooshian, L J; Wilson, K L
The present study examined developmental differences in the effect of route extensity on the memory for the locations of objects in a spatial array. Kindergarten and adult subjects were trained to remember the locations of 4 objects. During this training, objects were either connected by a combination of indirect, looped train tracks and direct train tracks (experimental subjects) or connected by entirely direct train-track routes (control subjects). Analyses of actual interobject distances, from subjects' reproductions of object locations on a response board (without train tracks), revealed that children, but not adults, distort distance in terms of the nature of travel observed between objects. Further testing revealed that differences in the amount of time taken for travel could not account for the results obtained with children.
Munneke, Jaap; Heslenfeld, Dirk J.; Theeuwes, Jan
The present study investigated how spatial working memory recruits early visual cortex. Participants were required to maintain a location in working memory while changes in blood oxygen level dependent (BOLD) signals were measured during the retention interval in which no visual stimulation was present. We show working memory effects during the…
Rinne, Teemu; Koistinen, Sonja; Talja, Suvi; Wikman, Patrik; Salonen, Oili
In the present study, we applied high-resolution functional magnetic resonance imaging (fMRI) of the human auditory cortex (AC) and adjacent areas to compare activations during spatial discrimination and spatial n-back memory tasks that were varied parametrically in difficulty. We found that activations in the anterior superior temporal gyrus (STG) were stronger during spatial discrimination than during spatial memory, while spatial memory was associated with stronger activations in the inferior parietal lobule (IPL). We also found that wide AC areas were strongly deactivated during the spatial memory tasks. The present AC activation patterns associated with spatial discrimination and spatial memory tasks were highly similar to those obtained in our previous study comparing AC activations during pitch discrimination and pitch memory (Rinne et al., 2009). Together our previous and present results indicate that discrimination and memory tasks activate anterior and posterior AC areas differently and that this anterior-posterior division is present both when these tasks are performed on spatially invariant (pitch discrimination vs. memory) or spatially varying (spatial discrimination vs. memory) sounds. These results also further strengthen the view that activations of human AC cannot be explained only by stimulus-level parameters (e.g., spatial vs. nonspatial stimuli) but that the activations observed with fMRI are strongly dependent on the characteristics of the behavioral task. Thus, our results suggest that in order to understand the functional structure of AC a more systematic investigation of task-related factors affecting AC activations is needed.
The analysis of spatial learning and memory in rodents is commonly used to investigate the mechanisms underlying certain forms of human cognition and to model their dysfunction in neuropsychiatric and neurodegenerative diseases. Proper interpretation of rodent behavior in terms of spatial memory and as a model of human cognitive functions is only possible if various navigation strategies and factors controlling the performance of the animal in a spatial task are taken into consideration. The aim of this review is to describe the experimental approaches that are being used for the study of spatial memory in rats and mice and the way that they can be interpreted in terms of general memory functions. After an introduction to the classification of memory into various categories and respective underlying neuroanatomical substrates, I explain the concept of spatial memory and its measurement in rats and mice by analysis of their navigation strategies. Subsequently, I describe the most common paradigms for spatial memory assessment with specific focus on methodological issues relevant for the correct interpretation of the results in terms of cognitive function. Finally, I present recent advances in the use of spatial memory tasks to investigate episodic-like memory in mice.
Beigneux, Katia; Plaie, Thierry; Isingrini, Michel
The aim of this study was to evaluate the effect of aging on the storage of visual and spatial working memory according to Logie's model of working memory (1995). In a first experiment young, elderly, and very old subjects carried out two tasks usually used to measure visual span (Visual Patterns Test) and spatial span (Corsi Block Tapping test).…
Motes, Michael A.; Hubbard, Timothy L.; Courtney, Jon R.; Rypma, Bart
Research has shown that spatial memory for moving targets is often biased in the direction of implied momentum and implied gravity, suggesting that representations of the subjective experiences of these physical principles contribute to such biases. The present study examined the association between these spatial memory biases. Observers viewed…
Rahman, Qazi; Bakare, Monsurat; Serinsu, Ceydan
Previous research has demonstrated a female advantage, albeit imperfectly, on tests of object location memory where object identity information is readily available. However, spatial and visual elements are often confounded in the experimental tasks used. Here spatial and visual memory performance was compared in 30 men and 30 women by presenting…
Rondina, Renante; Curtiss, Kaitlin; Meltzer, Jed A; Barense, Morgan D; Ryan, Jennifer D
Episodic memories are comprised of details of "where" and "when"; spatial and temporal relations, respectively. However, evidence from behavioural, neuropsychological, and neuroimaging studies has provided mixed interpretations about how memories for spatial and temporal relations are organised-they may be hierarchical, fully interactive, or independent. In the current study, we examined the interaction of memory for spatial and temporal relations. Using explicit reports and eye-tracking, we assessed younger and older adults' memory for spatial and temporal relations of objects that were presented singly across time in unique spatial locations. Explicit change detection of spatial relations was affected by a change in temporal relations, but explicit change detection of temporal relations was not affected by a change in spatial relations. Younger and older adults showed eye movement evidence of incidental memory for temporal relations, but only younger adults showed eye movement evidence of incidental memory for spatial relations. Together, these findings point towards a hierarchical organisation of relational memory. The implications of these findings are discussed in the context of the neural mechanisms that may support such a hierarchical organisation of memory.
Brown, Louise A
Working memory is vulnerable to age-related decline, but there is debate regarding the age-sensitivity of different forms of spatial-sequential working memory task, depending on their passive or active nature. The functional architecture of spatial working memory was therefore explored in younger (18-40 years) and older (64-85 years) adults, using passive and active recall tasks. Spatial working memory was assessed using a modified version of the Spatial Span subtest of the Wechsler Memory Scale - Third Edition (WMS-III; Wechsler, 1998). Across both age groups, the effects of interference (control, visual, or spatial), and recall type (forward and backward), were investigated. There was a clear effect of age group, with younger adults demonstrating a larger spatial working memory capacity than the older adults overall. There was also a specific effect of interference, with the spatial interference task (spatial tapping) reliably reducing performance relative to both the control and visual interference (dynamic visual noise) conditions in both age groups and both recall types. This suggests that younger and older adults have similar dependence upon active spatial rehearsal, and that both forward and backward recall require this processing capacity. Linear regression analyses were then carried out within each age group, to assess the predictors of performance in each recall format (forward and backward). Specifically the backward recall task was significantly predicted by age, within both the younger and older adult groups. This finding supports previous literature showing lifespan linear declines in spatial-sequential working memory, and in working memory tasks from other domains, but contrasts with previous evidence that backward spatial span is no more sensitive to aging than forward span. The study suggests that backward spatial span is indeed more processing-intensive than forward span, even when both tasks include a retention period, and that age predicts
Brown, Louise A.
Working memory is vulnerable to age-related decline, but there is debate regarding the age-sensitivity of different forms of spatial-sequential working memory task, depending on their passive or active nature. The functional architecture of spatial working memory was therefore explored in younger (18–40 years) and older (64–85 years) adults, using passive and active recall tasks. Spatial working memory was assessed using a modified version of the Spatial Span subtest of the Wechsler Memory Scale – Third Edition (WMS-III; Wechsler, 1998). Across both age groups, the effects of interference (control, visual, or spatial), and recall type (forward and backward), were investigated. There was a clear effect of age group, with younger adults demonstrating a larger spatial working memory capacity than the older adults overall. There was also a specific effect of interference, with the spatial interference task (spatial tapping) reliably reducing performance relative to both the control and visual interference (dynamic visual noise) conditions in both age groups and both recall types. This suggests that younger and older adults have similar dependence upon active spatial rehearsal, and that both forward and backward recall require this processing capacity. Linear regression analyses were then carried out within each age group, to assess the predictors of performance in each recall format (forward and backward). Specifically the backward recall task was significantly predicted by age, within both the younger and older adult groups. This finding supports previous literature showing lifespan linear declines in spatial-sequential working memory, and in working memory tasks from other domains, but contrasts with previous evidence that backward spatial span is no more sensitive to aging than forward span. The study suggests that backward spatial span is indeed more processing-intensive than forward span, even when both tasks include a retention period, and that age predicts
in press). Beyond language comprehension: Situation models as a form of autobiographical memory . In F. Schmalhofer & C. Perfetti (Eds.) Higher level...Technical Report 1221 Comprehension and Memory of Spatial and Temporal Event Components Gabriel A. Radvansky University of Notre Dame January 2008...SUBTITLE 5a. CONTRACT OR GRANT NUMBER Comprehension and memory of spatial and temporal event DASW01-02-K-0003 components 5b. PROGRAM ELEMENT NUMBER
Rosati, Alexandra G; Hare, Brian
Spatial cognition and memory are critical cognitive skills underlying foraging behaviors for all primates. While the emergence of these skills has been the focus of much research on human children, little is known about ontogenetic patterns shaping spatial cognition in other species. Comparative developmental studies of nonhuman apes can illuminate which aspects of human spatial development are shared with other primates, versus which aspects are unique to our lineage. Here we present three studies examining spatial memory development in our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (P. paniscus). We first compared memory in a naturalistic foraging task where apes had to recall the location of resources hidden in a large outdoor enclosure with a variety of landmarks (Studies 1 and 2). We then compared older apes using a matched memory choice paradigm (Study 3). We found that chimpanzees exhibited more accurate spatial memory than bonobos across contexts, supporting predictions from these species' different feeding ecologies. Furthermore, chimpanzees - but not bonobos - showed developmental improvements in spatial memory, indicating that bonobos exhibit cognitive paedomorphism (delays in developmental timing) in their spatial abilities relative to chimpanzees. Together, these results indicate that the development of spatial memory may differ even between closely related species. Moreover, changes in the spatial domain can emerge during nonhuman ape ontogeny, much like some changes seen in human children.
Rosati, Alexandra G; Rodriguez, Kerri; Hare, Brian
Evolutionary theories suggest that ecology is a major factor shaping cognition in primates. However, there have been few systematic tests of spatial memory abilities involving multiple primate species. Here, we examine spatial memory skills in four strepsirrhine primates that vary in level of frugivory: ruffed lemurs (Varecia sp.), ring-tailed lemurs (Lemur catta), mongoose lemurs (Eulemur mongoz), and Coquerel's sifakas (Propithecus coquereli). We compare these species across three studies targeting different aspects of spatial memory: recall after a long-delay, learning mechanisms supporting memory and recall of multiple locations in a complex environment. We find that ruffed lemurs, the most frugivorous species, consistently showed more robust spatial memory than the other species across tasks-especially in comparison with sifakas, the most folivorous species. We discuss these results in terms of the importance of considering both ecological and social factors as complementary explanations for the evolution of primate cognitive skills.
Nemes, V A; Whitaker, D; Heron, J; McKeefry, D J
Current models of short-term visual perceptual memory invoke mechanisms that are closely allied to low-level perceptual discrimination mechanisms. The purpose of this study was to investigate the extent to which human visual perceptual memory for spatial frequency is based upon multiple, spatially tuned channels similar to those found in the earliest stages of visual processing. To this end we measured how performance on a delayed spatial frequency discrimination paradigm was affected by the introduction of interfering or 'memory masking' stimuli of variable spatial frequency during the delay period. Masking stimuli were shown to induce shifts in the points of subjective equality (PSE) when their spatial frequencies were within a bandwidth of 1.2 octaves of the reference spatial frequency. When mask spatial frequencies differed by more than this value, there was no change in the PSE from baseline levels. This selective pattern of masking was observed for different spatial frequencies and demonstrates the existence of multiple, spatially tuned mechanisms in visual perceptual memory. Memory masking effects were also found to occur for horizontal separations of up to 6 deg between the masking and test stimuli and lacked any orientation selectivity. These findings add further support to the view that low-level sensory processing mechanisms form the basis for the retention of spatial frequency information in perceptual memory. However, the broad range of transfer of memory masking effects across spatial location and other dimensions indicates more long range, long duration interactions between spatial frequency channels that are likely to rely contributions from neural processes located in higher visual areas.
Weiss, Alison R; Bachevalier, Jocelyne
The contribution of the perirhinal cortex (PRh) to recognition memory is well characterized in adults, yet the same lesions have limited effect on recognition of spatial locations. Here, we assessed whether the same outcomes will follow when perirhinal lesions are performed in infancy. Monkeys with neonatal perirhinal (Neo-PRh) lesions and control animals were tested in three operant recognition tasks as they reached adulthood: Delayed Nonmatching-to-Sample (DNMS) and Object Memory Span (OMS), measuring object recognition, and Spatial Memory Span (SMS), measuring recognition of spatial locations. Although Neo-PRh lesions did not impact acquisition of the DNMS rule, they did impair performance when the delays were extended from 30s to 600s. In contrast, the same neonatal lesions had no impact on either the object or spatial memory span tasks, suggesting that the lesions impacted the maintenance of information across longer delays and not memory capacity. Finally, the magnitude of recognition memory impairment after the Neo-PRh lesions was similar to that previously observed after adult-onset perirhinal lesions, indicating minimal, or no, functional compensation after the early PRh lesions. Overall, the results indicate that the PRh is a cortical structure that is important for the normal development of mechanisms supporting object recognition memory. Its contribution may be relevant to the memory impairment observed with human cases of temporal lobe epilepsy without hippocampal sclerosis, but not to the memory impairment found in developmental amnesia cases. PMID:26593109
Meier, Timothy B; Nair, Veena A; Meyerand, Mary E; Birn, Rasmus M; Prabhakaran, Vivek
In this study, we investigated the neural correlates of age-related differences in the binding of verbal and spatial information utilizing event-related working memory tasks. Twenty-one right handed younger adults and twenty-one right handed older adults performed two versions of a dual task of verbal and spatial working memory. In the unbound dual task version letters and locations were presented simultaneously in separate locations, while in the bound dual task version each letter was paired with a specific location. In order to identify binding-specific differences, mixed-effects ANOVAs were run with the interaction of age and task as the effect of interest. Although older adults performed worse in the bound task than younger adults, there was no significant interaction between task and age on working memory performance. However, interactions of age and task were observed in brain activity analyses. Older adults did not display the greater unbound than bound task activity that younger adults did at the encoding phase in bilateral inferior parietal lobule, right putamen, and globus pallidus as well as at the maintenance phase in the cerebellum. We conclude that the binding of letters and locations in working memory is not as efficient in older adults as it is in younger adults, possibly due to the decline of cognitive control processes that are specific to working memory binding.
Ainge, James A.; Langston, Rosamund F.
Spatial memory is a well-characterized psychological function in both humans and rodents. The combined computations of a network of systems including place cells in the hippocampus, grid cells in the medial entorhinal cortex and head direction cells found in numerous structures in the brain have been suggested to form the neural instantiation of the cognitive map as first described by Tolman in 1948. However, while our understanding of the neural mechanisms underlying spatial representations in adults is relatively sophisticated, we know substantially less about how this network develops in young animals. In this article we briefly review studies examining the developmental timescale that these systems follow. Electrophysiological recordings from very young rats show that directional information is at adult levels at the outset of navigational experience. The systems supporting allocentric memory, however, take longer to mature. This is consistent with behavioral studies of young rats which show that spatial memory based on head direction develops very early but that allocentric spatial memory takes longer to mature. We go on to report new data demonstrating that memory for associations between objects and their spatial locations is slower to develop than memory for objects alone. This is again consistent with previous reports suggesting that adult like spatial representations have a protracted development in rats and also suggests that the systems involved in processing non-spatial stimuli come online earlier. PMID:22403529
Trofimiuk, Emil; Holownia, Adam; Braszko, Jan J
St. John's wort (Hypericum perforatum) is one of the leading psychotherapeutic phytomedicines. Beneficial effects of this herb in the treatment of mild to moderate depression are well known. In this study we tested a hypothesis that St. John's wort alleviates age-related memory impairments by increasing the levels of cyclic adenosine 3', 5'-monophosphate response element binding protein (CREB) and phosphorylated CREB (pCREB) in hippocampus. Middleaged rats (18 month-old) displayed a decline in the acquisition of spatial working memory (p < 0.001) in the Morris water maze (MWM). Chronic administration of Hypericum perforatum (HP) (350 mg/kg for 21 days), potently and significantly improved the processing of spatial information in the aged rats (p < 0.001). Also the herb increased the levels of pCREB in the aged rat's hippocampus (p < 0.01) as measured by western immunoblotting. Aging caused significant locomotor impairments as tested in the open field (p < 0.001) but not in the MWM test. However, these were unaffected by treatment with HP. Thus, this study indicates that St. John's wort effectively prevents aging-induced deterioration of spatial memory in 18 month-old rats, possibly by the activation of CREB regulated genes associated with memory formation. It appears that mechanism is probably inactive in young rats.
Postma, Albert; Jager, Gerry; Kessels, Roy P. C.; Koppeschaar, Hans P. F.; van Honk, Jack
In the present study, a systematic comparison of sex differences for several tests of spatial memory was conducted. Clear evidence for more accurate male performance was obtained for precise metric positional information in a wayfinding task and in an object location memory task. In contrast, no sex difference characterized topological information…
Crawford, L. Elizabeth; Landy, David; Salthouse, Timothy A.
Spatial memory research has attributed systematic bias in location estimates to a combination of a noisy memory trace with a prior structure that people impose on the space. Little is known about intraindividual stability and interindividual variation in these patterns of bias. In the current work, we align recent empirical and theoretical work on…
Mou, Weimin; Liu, Xianyun; McNamara, Timothy P.
Two experiments investigated whether the spatial reference directions that are used to specify objects' locations in memory can be solely determined by layout geometry. Participants studied a layout of objects from a single viewpoint while their eye movements were recorded. Subsequently, participants used memory to make judgments of relative…
Nelson, Charles A.; Monk, Christopher S.; Lin, Joseph; Carver, Leslie J.; Thomas, Kathleen M.; Truwit, Charles L.
Used functional magnetic resonance imaging (fMRI) to examine spatial working memory in 8- to 11-year-olds tested under 3 conditions. Found that subtracting activation of the motor condition from the memory condition revealed activity in dorsal aspects of the prefrontal cortex and in the posterior parietal and anterior cingulate cortex. Analysis of…
Robin, Jessica; Wynn, Jordana; Moscovitch, Morris
Events always unfold in a spatial context, leading to the claim that it serves as a scaffold for encoding and retrieving episodic memories. The ubiquitous co-occurrence of spatial context with events may induce participants to generate a spatial context when hearing scenarios of events in which it is absent. Spatial context should also serve as an…
Pearson, David G; Ball, Keira; Smith, Daniel T
There is little consensus regarding the specific processes responsible for encoding, maintenance, and retrieval of information in visuo-spatial working memory (VSWM). One influential theory is that VSWM may involve activation of the eye-movement (oculomotor) system. In this study we experimentally prevented healthy participants from planning or executing saccadic eye-movements during the encoding, maintenance, and retrieval stages of visual and spatial working memory tasks. Participants experienced a significant reduction in spatial memory span only when oculomotor preparation was prevented during encoding or maintenance. In contrast there was no reduction when oculomotor preparation was prevented only during retrieval. These results show that (a) involvement of the oculomotor system is necessary for optimal maintenance of directly-indicated locations in spatial working memory and (b) oculomotor preparation is not necessary during retrieval from spatial working memory. We propose that this study is the first to unambiguously demonstrate that the oculomotor system contributes to the maintenance of spatial locations in working memory independently from the involvement of covert attention.
Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan
A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…
Varner, Kaitlin M; Dopkins, Stephen; Philbeck, John W
The present research examined the effect of encoding from multiple viewpoints on scene recall in a group of younger (18-22 years) and older (65-80 years) adults. Participants completed a visual search task, during which they were given the opportunity to examine a room using two sets of windows that partitioned the room differently. Their choice of window set was recorded, to determine whether an association between these choices and spatial memory performance existed. Subsequently, participants were tested for spatial memory of the domain in which the search task was completed. Relative to younger adults, older adults demonstrated an increased tendency to use a single set of windows as well as decreased spatial memory for the domain. Window-set usage was associated with spatial memory, such that older adults who relied more heavily on a single set of windows also had better performance on the spatial memory task. These findings suggest that, in older adults, moderation in exploratory behavior may have a positive effect on memory for the domain of exploration.
McQuail, Joseph A; Beas, B Sofia; Kelly, Kyle B; Simpson, Kailey L; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L
Working memory, the ability to temporarily maintain representational knowledge, is a foundational cognitive process that can become compromised in aging and neuropsychiatric disease. NMDA receptor (NMDAR) activation in prefrontal cortex (PFC) is necessary for the pyramidal neuron activity believed to enable working memory; however, the distinct biophysical properties and localization of NMDARs containing NR2A and NR2B subunits suggest unique roles for NMDAR subtypes in PFC neural activity and working memory. Experiments herein show that working memory depends on NR2A- but not NR2B-NMDARs in PFC of rats and that NR2A-NMDARs mediate the majority of evoked NMDAR currents on layer 2/3 PFC pyramidal neurons. Moreover, attenuated expression of the NR2A but not the NR2B subunit in PFC associates with naturally occurring working memory impairment in aged rats. Finally, NMDAR currents and working memory are enhanced in aged rats by promoting activation of the NR2A-enriched synaptic pool of PFC NMDARs. These results implicate NR2A-NMDARs in normal working memory and suggest novel treatment strategies for improving working memory in cognitive disorders.
Nagel, Bonnie J.; Herting, Megan M.; Maxwell, Emily C.; Bruno, Richard; Fair, Damien
Adult functional magnetic resonance imaging (fMRI) literature suggests that a left-right hemispheric dissociation may exist between verbal and spatial working memory (WM), respectively. However, investigation of this type has been obscured by incomparable verbal and spatial WM tasks and/or visual inspection at arbitrary thresholds as means to…
Rosati, Alexandra G.; Hare, Brian
Spatial cognition and memory are critical cognitive skills underlying foraging behaviors for all primates. While the emergence of these skills has been the focus of much research on human children, little is known about ontogenetic patterns shaping spatial cognition in other species. Comparative developmental studies of nonhuman apes can…
Olive, Thierry; Kellogg, Ronald T.; Piolat, Annie
Two experiments examined whether text composition engages verbal, visual, and spatial working memory to different degrees. In Experiment 1, undergraduate students composed by longhand a persuasive text while performing a verbal, visual, or spatial concurrent task that was presented visually. In Experiment 2, participants performed a verbal or…
Lee, Sang Ah; Tucci, Valter; Sovrano, Valeria Anna; Vallortigara, Giorgio
Researchers in spatial cognition have debated for decades the specificity of the mechanisms through which spatial information is processed and stored. Interestingly, although rodents are the preferred animal model for studying spatial navigation, the behavioral methods traditionally used to assess spatial memory do not effectively test the predictions of specificity in their representation. To address such issues, the present study tested the ability of mice to use boundary geometry and features to remember a goal location across 2 types of tasks--a working memory task with a changing goal location, and a reference memory task with 1 rewarded goal location. We show for the first time that mice, like other animals, can successfully encode boundary geometry in a working memory spatial mapping task, just as they do in a reference memory task. Their use of a nongeometric featural cue (striped pattern), in contrast, was more limited in the working memory task, although it quickly improved in the reference memory task. We discuss the implications of these findings for future research on the neural and genetic underpinnings of spatial representations.
Burnham, Veronica; Sundby, Christopher; Laman-Maharg, Abigail; Thornton, Janice
Luteinizing hormone (LH) rises dramatically during and after menopause, and has been correlated with an increased incidence of Alzheimer's disease and decreased memory performance in humans and animal models. To test whether LH acts directly on the dorsal hippocampus to affect memory, ovariectomized female rats were infused with either the LH-homologue human chorionic gonadotropin (hCG) or the LH receptor antagonist deglycosylated-hCG (dg-hCG). Infusion of hCG into either the lateral ventricle or the dorsal hippocampus caused significant memory impairments in ovariectomized estradiol-treated females. Consistent with this, infusion of the LH antagonist dg-hCG into the dorsal hippocampus caused an amelioration of memory deficits in ovariectomized females. Furthermore, the gonadotropin-releasing hormone antagonist Antide, failed to act in the hippocampus to affect memory. These findings demonstrate a significant role for LH action in the dorsal hippocampus in spatial memory dysfunction.
Cassilhas, R C; Lee, K S; Fernandes, J; Oliveira, M G M; Tufik, S; Meeusen, R; de Mello, M T
A growing body of scientific evidence indicates that exercise has a positive impact on human health, including neurological health. Aerobic exercise, which is supposed to enhance cardiovascular functions and metabolism, also induces neurotrophic factors that affect hippocampal neurons, thereby improving spatial learning and memory. Alternatively, little is known about the effect of resistance exercise on hippocampus-dependent memory, although this type of exercise is increasingly recommended to improve muscle strength and bone density and to prevent age-related disabilities. Therefore, we evaluated the effects of resistance training on spatial memory and the signaling pathways of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1), comparing these effects with those of aerobic exercise. Adult male Wistar rats underwent 8 weeks of aerobic training on a treadmill (AERO group) or resistance training on a vertical ladder (RES group). Control and sham groups were also included. After the training period, both AERO and RES groups showed improved learning and spatial memory in a similar manner. However, both groups presented distinct signaling pathways. Although the AERO group showed increased level of IGF-1, BDNF, TrkB, and β-CaMKII (calcium/calmodulin-dependent kinase II) in the hippocampus, the RES group showed an induction of peripheral and hippocampal IGF-1 with concomitant activation of receptor for IGF-1 (IGF-1R) and AKT in the hippocampus. These distinct pathways culminated in an increase of synapsin 1 and synaptophysin expression in both groups. These findings demonstrated that both aerobic and resistance exercise can employ divergent molecular mechanisms but achieve similar results on learning and spatial memory.
Irrazabal, Natalia; Burin, Debora
During the comprehension of narrative texts, readers keep a mental representation of the location of protagonists and objects; a breach in spatial coherence is detected by longer online reading times (consistency effect). We addressed whether these spatial inferences involve verbal or spatial working memory in two experiments, combining the consistency paradigm with selective verbal and spatial working memory concurrent tasks. The first experiment found longer reading times with a concurrent spatial task under imagery instructions (t33 = 2.87, p = .021). The second experiment, under comprehension reading instructions, found effects of verbal interference on reading times and accuracy. With a verbal secondary task, reading times for the target sentence were shorter (t45 = 3.60, p = .004) and the error rate was significantly higher (t47 = 2.95, p = .005) than without interference. This pattern of results suggests that spatial inferences in narrative comprehension rely mainly on verbal resources, and spatial working memory resources are recruited when imagery is required.
Banta Lavenex, Pamela; Boujon, Valérie; Ndarugendamwo, Angélique; Lavenex, Pierre
Here, we aimed to determine the capacity of human short-term memory for allocentric spatial information in a real-world setting. Young adults were tested on their ability to learn, on a trial-unique basis, and remember over a 1-min interval the location(s) of 1, 3, 5, or 7 illuminating pads, among 23 pads distributed in a 4m×4m arena surrounded by curtains on three sides. Participants had to walk to and touch the pads with their foot to illuminate the goal locations. In contrast to the predictions from classical slot models of working memory capacity limited to a fixed number of items, i.e., Miller's magical number 7 or Cowan's magical number 4, we found that the number of visited locations to find the goals was consistently about 1.6 times the number of goals, whereas the number of correct choices before erring and the number of errorless trials varied with memory load even when memory load was below the hypothetical memory capacity. In contrast to resource models of visual working memory, we found no evidence that memory resources were evenly distributed among unlimited numbers of items to be remembered. Instead, we found that memory for even one individual location was imprecise, and that memory performance for one location could be used to predict memory performance for multiple locations. Our findings are consistent with a theoretical model suggesting that the precision of the memory for individual locations might determine the capacity of human short-term memory for spatial information.
Patai, Eva Zita; Buckley, Alice; Nobre, Anna Christina
A popular model of visual perception states that coarse information (carried by low spatial frequencies) along the dorsal stream is rapidly transmitted to prefrontal and medial temporal areas, activating contextual information from memory, which can in turn constrain detailed input carried by high spatial frequencies arriving at a slower rate along the ventral visual stream, thus facilitating the processing of ambiguous visual stimuli. We were interested in testing whether this model contributes to memory-guided orienting of attention. In particular, we asked whether global, low-spatial frequency (LSF) inputs play a dominant role in triggering contextual memories in order to facilitate the processing of the upcoming target stimulus. We explored this question over four experiments. The first experiment replicated the LSF advantage reported in perceptual discrimination tasks by showing that participants were faster and more accurate at matching a low spatial frequency version of a scene, compared to a high spatial frequency version, to its original counterpart in a forced-choice task. The subsequent three experiments tested the relative contributions of low versus high spatial frequencies during memory-guided covert spatial attention orienting tasks. Replicating the effects of memory-guided attention, pre-exposure to scenes associated with specific spatial memories for target locations (memory cues) led to higher perceptual discrimination and faster response times to identify targets embedded in the scenes. However, either high or low spatial frequency cues were equally effective; LSF signals did not selectively or preferentially contribute to the memory-driven attention benefits to performance. Our results challenge a generalized model that LSFs activate contextual memories, which in turn bias attention and facilitate perception.
Lin, Chien-Heng; Chen, Chien-Min; Lou, Yu-Chiung
The abilities of both spatial orientation and spatial memory play very important roles in human navigation and spatial cognition. Since such abilities are difficult to strengthen through books or classroom instruction, there are no particular curricula or methods to assist in their development. Therefore, this study develops a spatial…
Nategh, Mohsen; Nikseresht, Sara; Khodagholi, Fariba; Motamedi, Fereshteh
Nucleus incertus (NI) is a pontine nucleus which releases mainly GABA and relaxin-3 in rats. Its suggested functions include response to stress, arousal, and modulation of hippocampal theta rhythm. Since the role of NI in learning and memory has not been well characterized, therefore the involvement of this nucleus in spatial learning and memory and the aftermath hippocampal levels of c-fos and pCREB were evaluated. NI was targeted by implanting cannula in male rats. For reference memory, NI was inactivated by lidocaine (0.4 μl, 4%) at three stages of acquisition, consolidation and retrieval in Morris water maze paradigm. For working memory, NI was inactivated in acquisition and retrieval phases. Injection of lidocaine prior to the first training session of reference memory significantly increased the distance moved, suggesting that inactivation of NI delays acquisition in this spatial task. Inactivation also interfered with the retrieval phase of spatial reference memory, as the time in target quadrant for lidocaine group was less, and the escape latency was higher compared to the control group. However, no difference was observed in the consolidation phase. In the working memory task, with inter-trial intervals of 75 min, the escape latency was higher when NI was inactivated in the retrieval phase. In addition, c-fos and pCREB/CREB levels decreased in NI-inhibited rats. This study suggests that nucleus incertus might participate in acquisition of spatial reference, and retrieval of both spatial reference and working memory. Further studies should investigate possible roles of NI in the hippocampal plasticity.
Won, Bo-Yeong; Jiang, Yuhong V
Recent empirical and theoretical work has depicted a close relationship between visual attention and visual working memory. For example, rehearsal in spatial working memory depends on spatial attention, whereas adding a secondary spatial working memory task impairs attentional deployment in visual search. These findings have led to the proposal that working memory is attention directed toward internal representations. Here, we show that the close relationship between these 2 constructs is limited to some but not all forms of spatial attention. In 5 experiments, participants held color arrays, dot locations, or a sequence of dots in working memory. During the memory retention interval, they performed a T-among-L visual search task. Crucially, the probable target location was cued either implicitly through location probability learning or explicitly with a central arrow or verbal instruction. Our results showed that whereas imposing a visual working memory load diminished the effectiveness of explicit cuing, it did not interfere with probability cuing. We conclude that spatial working memory shares similar mechanisms with explicit, goal-driven attention but is dissociated from implicitly learned attention.
Winocur, Gordon; Moscovitch, Morris; Rosenbaum, R Shayna; Sekeres, Melanie
The effect of aging on remote spatial memory was tested in a group of 2-year-old rats (VR-O) that, as young adults, were reared for 3 months in a complex 'village' environment. The VR-O rats exhibited significant savings in finding the locations of specific reward compartments within the village, relative to a group of old rats (VNR-O) experiencing the village for the first time. The VNR-O rats were also impaired, relative to naive young rats, in learning the reward locations. Probe tests indicated that the VR-O rats retained allocentric spatial memory for the environment and were not using sensory or other non-spatial cues to guide behaviour. Overall, the results indicate that the aged rats experienced a decline in the ability to learn and remember detailed spatial relationships and that the VR-O group's successful performance on the remote spatial memory test was guided by a form of schematic memory that captured the essential features of the village environment. The potential contribution of the hippocampus to the pattern of lost and spared learning and memory observed in the aged rats was discussed.
Lee, Annie; Archer, Jo; Wong, Caroline Kai Yun; Chen, Shen-Hsing Annabel; Qiu, Anqi
Paired associates learning (PAL) has been widely used in aging-related research, suggesting an age-related decline in associative learning. However, there are several cognitive processes (attention, spatial and recognition memory, strategy, and associative learning) involved in PAL. It is unclear which component contributes to the decline in PAL performance associated with age effects. The present study determines whether age effects on associative learning are independent of other cognitive processes involved in PAL. Using a validated computerized cognitive program (CANTAB), we examined cognitive performance of associative learning, spatial and recognition memory, attention and strategy use in 184 Singaporean Chinese adults aged from 21 to 80 years old. Linear regression revealed significant age-related decline in associative learning, spatial and recognition memory, and the level of strategy use. This age-related decline in associative learning remains even after adjusting for attention, spatial and recognition memory, and strategy use. These results show that age effects on associative learning are independent of other cognitive processes involved in PAL.
Cox, Simon R; Bastin, Mark E; Ferguson, Karen J; Allerhand, Mike; Royle, Natalie A; Maniega, Susanna Muñoz; Starr, John M; MacLullich, Alasdair M J; Wardlaw, Joanna M; Deary, Ian J; MacPherson, Sarah E
Functional neuroimaging studies report increased right prefrontal cortex (PFC) involvement during verbal memory tasks amongst low-scoring older individuals, compared to younger controls and their higher-scoring contemporaries. Some propose that this reflects inefficient use of neural resources through failure of the left PFC to inhibit non-task-related right PFC activity, via the anterior corpus callosum (CC). For others, it indicates partial compensation - that is, the right PFC cannot completely supplement the failing neural network, but contributes positively to performance. We propose that combining structural and diffusion brain MRI can be used to test predictions from these theories which have arisen from fMRI studies. We test these hypotheses in immediate and delayed verbal memory ability amongst 90 healthy older adults of mean age 73 years. Right hippocampus and left dorsolateral prefrontal cortex (DLPFC) volumes, and fractional anisotropy (FA) in the splenium made unique contributions to verbal memory ability in the whole group. There was no significant effect of anterior callosal white matter integrity on performance. Rather, segmented linear regression indicated that right DLPFC volume was a significantly stronger positive predictor of verbal memory for lower-scorers than higher-scorers, supporting a compensatory explanation for the differential involvement of the right frontal lobe in verbal memory tasks in older age.
Frick, Karyn M
A wealth of data collected in recent decades has demonstrated that ovarian sex-steroid hormones, particularly 17β-estradiol (E2), are important trophic factors that regulate the function of cognitive regions of the brain such as the hippocampus. The loss of hormone cycling at menopause is associated with cognitive decline and dementia in women, and the onset of memory decline in animal models. However, hormone therapy is not currently recommended to prevent or treat cognitive decline, in part because of its detrimental side effects. In this article, it is proposed that investigations of the rapid effects of E2 on hippocampal function be used to further the design of new drugs that mimic the beneficial effects of E2 on memory without the side effects of current therapies. A conceptual model is presented for elucidating the molecular and biochemical mechanisms through which sex-steroid hormones modulate memory, and a specific hypothesis is proposed to account for the rapid memory-enhancing effects of E2. Empirical support for this hypothesis is discussed as a means of stimulating the consideration of new directions for the development of hormone-based therapies to preserve memory function in menopausal women.
Crawford, L Elizabeth; Landy, David; Salthouse, Timothy A
Spatial memory research has attributed systematic bias in location estimates to a combination of a noisy memory trace with a prior structure that people impose on the space. Little is known about intraindividual stability and interindividual variation in these patterns of bias. In the current work, we align recent empirical and theoretical work on working memory capacity limits and spatial memory bias to generate the prediction that those with lower working memory capacity will show greater bias in memory of the location of a single item. Reanalyzing data from a large study of cognitive aging, we find support for this prediction. Fitting separate models to individuals' data revealed a surprising variety of strategies. Some were consistent with Bayesian models of spatial category use, however roughly half of participants biased estimates outward in a way not predicted by current models and others seemed to combine these strategies. These analyses highlight the importance of studying individuals when developing general models of cognition. (PsycINFO Database Record
Vendetti, Michael; Castel, Alan D; Holyoak, Keith J
People typically remember objects to which they have frequently been exposed, suggesting that memory is a by-product of perception. However, prior research has shown that people have exceptionally poor memory for the features of some objects (e.g., coins) to which they have been exposed over the course of many years. Here, we examined how people remember the spatial layout of the buttons on a frequently used elevator panel, to determine whether physical interaction (rather than simple exposure) would ensure the incidental encoding of spatial information. Participants who worked in an eight-story office building displayed very poor recall for the elevator panel but above-chance performance on a recognition test. Performance was related to how often and how recently the person had used the elevator. In contrast to their poor memory for the spatial layout of the elevator buttons, most people readily recalled small distinctive graffiti on the elevator walls. In a more implicit test, the majority were able to locate their office floor and the eighth floor button when asked to point toward these buttons when in the actual elevator, with the button labels covered. However, identification was very poor for other floors (including the first floor), suggesting that even frequent interaction with information does not always lead to accurate spatial memory. These findings have implications for understanding the complex relationships among attention, expertise, and memory.
Toepper, Max; Markowitsch, Hans J; Gebhardt, Helge; Beblo, Thomas; Bauer, Eva; Woermann, Friedrich G; Driessen, Martin; Sammer, Gebhard
Healthy aging is accompanied by a decline in spatial working memory that is related to functional cerebral changes within the spatial working memory network. In the last decade, important findings were presented concerning the location (e.g., prefrontal), kind (e.g., 'underactivation,' 'overactivation'), and meaning (e.g., functional deficits, compensation) of these changes. Less is known about how functional connections between specific brain regions are affected by age and how these changes are related to behavioral performance. To address these issues, we used functional magnetic resonance imaging to examine retrieval-related brain activation and functional connectivity in 18 younger individuals and 18 older individuals. We assessed working memory with a modified version of the Corsi Block-Tapping test, which requires the storage and reproduction of spatial target sequences. Analyses of group differences in brain activation and functional connectivity included comparisons between younger individuals, older individuals, older high-performers, and older low-performers. In addition, we conducted a functional connectivity analysis by using a seed region approach. In comparison to younger individuals, older individuals showed lower right-hemispheric dorsolateral prefrontal activation and lower functional connectivity between the right dorsolateral prefrontal cortex and the bilateral orbitofrontal cortex. Older high-performers showed higher right dorsolateral and anterior prefrontal cortex activation than older low-performers, as well as higher functional connectivity between these brain regions. The present results suggest age-related reductions of prefrontal activation during spatial working memory retrieval. Moreover, task-related functional connectivity appears to be lower in older adults. Performance accuracy in older adults is associated with right dorsolateral and anterior prefrontal cortex activation, and with the functional connection between these regions.
Mayer, Uwe; Watanabe, Shigeru; Bischof, Hans-Joachim
The aim of the present review is to show that spatial learning and memory is not a specialty of just a few avian species, and to describe the role of the avian hippocampus in spatial learning, memory and orientation. Based on our own research in zebra finches, we try to give an (not complete and probably biased) overview of this topic, and we also discuss the question of functional equivalence of hippocampus in birds and in mammals in that we question how far theories developed for mammalian hippocampus can also be applied to the avian hippocampal formation.
Bender, Andrew R.; Raz, Naftali
Advanced age and vascular risk are associated with declines in the volumes of multiple brain regions, especially the prefrontal cortex, and the hippocampus. Older adults, even unencumbered by declining health, perform less well than their younger counterparts in multiple cognitive domains, such as episodic memory, executive functions, and speed of…
Badham, Stephen P; Maylor, Elizabeth A
If all but one of the items in a list are similar (e.g., all black except one red), memory for the different item is enhanced (the isolation effect). Older adults generally show similar or smaller isolation effects compared to young adults, which has been attributed to age-related deficits in associative memory whereby older adults are less able to associate an isolated stimulus to its isolating feature. Experiment 1 examined the isolation effect for isolation based on spatial position, modality and color; in Experiment 2, the criterion for isolation was the associative relation between stimuli. The results consistently showed no differences between young and older participants in the magnitude of the isolation effect. Whilst age deficits in associative memory may act to reduce the isolation effect in older adults, age deficits in self-initiated processing and inhibitory functionality may counteract this reduction by enhancing the isolation effect in older adults.
Bannerman, Rachel L; Temminck, Elisha V; Sahraie, Arash
There is evidence that emotional stimuli capture spatial attention and that visual memory is enhanced for emotional content. Here we examine the relationship between emotional content of stimuli and interactions with spatial memory. To assess spatial memory, a modified version of the Corsi Blocks Task (CBT), utilising emotional stimuli, was employed. In the CBT a series of spatial positions are highlighted and the participant has to repeat these in the order in which they were produced. Results showed that presenting more meaningful stimuli, such as emotional faces (e.g. angry or happy) at the spatial locations in the CBT did not enhance spatial memory span relative to the presentation of neutral stimuli (e.g. neutral faces) or non-image stimuli signified by a change in the luminance of the blocks. In addition, saccadic eye movements performed during retention disrupted spatial memory for all items. This occurred irrespective of whether the item to be remembered was a face, a luminance-defined stimulus or whether the face carried emotional significance. The results were not related to the visibility of the test stimuli as participants recognised the emotion displayed by the faces significantly above chance and rated emotional faces as being more arousing than neutral faces. Changes in the type of emotional stimulus (e.g. fearful faces, emotional schematic faces, spiders or flowers) or encoding (short vs. long) duration did not alter the pattern of results. These findings demonstrate an important dissociation between spatial capture and memory. Although emotional content can modulate orienting behaviour, it appears to be of limited effect on spatial memory.
Haider, Saida; Saleem, Sadia; Perveen, Tahira; Tabassum, Saiqa; Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Madiha, Syeda
Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino-Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.
Narimoto, Tadamasa; Matsuura, Naomi; Takezawa, Tomohiro; Mitsuhashi, Yoshinori; Hiratani, Michio
The authors investigated whether impaired spatial short-term memory exhibited by children with nonverbal learning disabilities is due to a problem in the encoding process. Children with or without nonverbal learning disabilities performed a simple spatial test that required them to remember 3, 5, or 7 spatial items presented simultaneously in random positions (i.e., spatial configuration) and to decide if a target item was changed or all items including the target were in the same position. The results showed that, even when the spatial positions in the encoding and probe phases were similar, the mean proportion correct of children with nonverbal learning disabilities was 0.58 while that of children without nonverbal learning disabilities was 0.84. The authors argue with the results that children with nonverbal learning disabilities have difficulty encoding relational information between spatial items, and that this difficulty is responsible for their impaired spatial short-term memory.
LaDage, Lara D.; Roth, Timothy C.; Fox, Rebecca A.; Pravosudov, Vladimir V.
The adult hippocampus in birds and mammals undergoes neurogenesis and the resulting new neurons appear to integrate structurally and functionally into the existing neural architecture. However, the factors underlying the regulation of new neuron production is still under scrutiny. In recent years, the concept that spatial memory affects adult hippocampal neurogenesis has gained acceptance, although results attempting to causally link memory use to neurogenesis remain inconclusive, possibly owing to confounds of motor activity, task difficulty or training for the task. Here, we show that ecologically relevant, spatial memory-based experiences of food caching and retrieving directly affect hippocampal neurogenesis in mountain chickadees (Poecile gambeli). We found that restricting memory experiences in captivity caused significantly lower rates of neurogenesis, as determined by doublecortin expression, compared with captive individuals provided with such experiences. However, neurogenesis rates in both groups of captive birds were still greatly lower than those in free-ranging conspecifics. These findings show that ecologically relevant spatial memory experiences can directly modulate neurogenesis, separate from other confounds that may also independently affect neurogenesis. PMID:19939840
Mohan, T; de Supinski, B R; McKee, S A; Mueller, F; Yoo, A; Schulz, M
The growing processor/memory performance gap causes the performance of many codes to be limited by memory accesses. If known to exist in an application, strided memory accesses forming streams can be targeted by optimizations such as prefetching, relocation, remapping, and vector loads. Undetected, they can be a significant source of memory stalls in loops. Existing stream-detection mechanisms either require special hardware, which may not gather statistics for subsequent analysis, or are limited to compile-time detection of array accesses in loops. Formally, little treatment has been accorded to the subject; the concept of locality fails to capture the existence of streams in a program's memory accesses. The contributions of this paper are as follows. First, we define spatial regularity as a means to discuss the presence and effects of streams. Second, we develop measures to quantify spatial regularity, and we design and implement an on-line, parallel algorithm to detect streams - and hence regularity - in running applications. Third, we use examples from real codes and common benchmarks to illustrate how derived stream statistics can be used to guide the application of profile-driven optimizations. Overall, we demonstrate the benefits of our novel regularity metric as a low-cost instrument to detect potential for code optimizations affecting memory performance.
Shah, Darshna S; Prados, Jose; Gamble, Jasmin; De Lillo, Carlo; Gibson, Claire L
The present study assessed the spatial abilities of male and female human participants using different versions of the non-navigational Corsi block-tapping test (CBT) and a search task. Males performed significantly better than females on the standard manual version of the CBT; however, the standard CBT does not allow discrimination between spatial memory span and the role of spatial organisational factors (structure, path length and presence of crossings) in the sequences to recall. These organisational factors were assessed, therefore, in an experiment in which 7-block-sequences had to be recalled in a computerised version of the CBT. No sex differences in performance were observed on the computerised CBT, indicating that males do not make better use of spatial organisational principles. Accordingly, sex differences observed in the manual CBT are likely to rely upon differences in memory span between males and females. In the search task, participants could locate a goal by reference to a Euclidian space (the geometry of a virtual enclose) or to proximal non-geometric cues. Both male and female participants showed a preference for the non-geometric cues, which overshadowed learning about the geometric cues when the two sets were available simultaneously during the training stage. These results indicate that sex differences do exist in those tests which are dependent on memory span. Sex differences were absent, however, in spatial organisational skills or in the usage of Euclidian and egocentric strategies to solve problems relying on spatial ability.
Lanfranchi, Silvia; De Mori, Letizia; Mammarella, Irene C.; Carretti, Barbara; Vianello, Renzo
The aim of the present study was to compare visuospatial working memory performance in 18 individuals with Williams syndrome (WS) and 18 typically developing (TD) children matched for nonverbal mental age. Two aspects were considered: task presentation format (i.e., spatial-sequential or spatial-simultaneous), and level of attentional control…
Abrahamse, Elger; van Dijck, Jean-Philippe; Fias, Wim
Number-space associations are a robust observation, but their underlying mechanisms remain debated. Two major accounts have been identified. First, spatial codes may constitute an intrinsic part of number representations stored in the brain – a perspective most commonly referred to as the Mental Number Line account. Second, spatial codes may be generated at the level of working memory when number (or other) representations are coordinated in function of a specific task. The aim of the current paper is twofold. First, whereas a pure Mental Number Line account cannot capture the complexity of observations reported in the literature, we here explore if and how a pure working memory account can suffice. Second, we make explicit (more than in our earlier work) the potential building blocks of such a working memory account, thereby providing clear and concrete foci for empirical efforts to test the feasibility of the account. PMID:27445937
Tsujii, Takeo; Yamamoto, Eriko; Masuda, Sayako; Watanabe, Shigeru
This study longitudinally compared activity in the frontal cortex during a spatial working memory task between 5-year-old and 7-year-old children using near-infrared spectroscopy. Eight children participated in this study twice, once at 5 years and once at 7 years of age. Behavioral analysis showed that older children performed the working memory task more precisely and more rapidly than younger children. Near-infrared spectroscopy analysis showed that right hemisphere dominance was observed in older children, whereas no hemispheric difference was apparent in younger children. Children with strengthened lateralization showed improved performance from 5 to 7 years. We therefore offer the first demonstration of the developmental changes in frontal cortical activation during spatial working memory tasks during the preschool period.
Holden, Mark P.; Newcombe, Nora S.; Shipley, Thomas F.
Memories for spatial locations often show systematic errors toward the central value of the surrounding region. The Category Adjustment (CA) model suggests that this bias is due to a Bayesian combination of categorical and metric information, which offers an optimal solution under conditions of uncertainty (Huttenlocher, Hedges, & Duncan,…
Rossato, Janine I.; Medina, Jorge H.; Izquierdo, Ivan; Cammarota, Martin; Bevilaqua, Lia R. M.
Nonreinforced retrieval can cause extinction and/or reconsolidation, two processes that affect subsequent retrieval in opposite ways. Using the Morris water maze task we show that, in the rat, repeated nonreinforced expression of spatial memory causes extinction, which is unaffected by inhibition of protein synthesis within the CA1 region of the…
Anguera, Joaquin A.; Reuter-Lorenz, Patricia A.; Willingham, Daniel T.; Seidler, Rachael D.
Previous studies of motor learning have described the importance of cognitive processes during the early stages of learning; however, the precise nature of these processes and their neural correlates remains unclear. The present study investigated whether spatial working memory (SWM) contributes to visuomotor adaptation depending on the stage of…
Lavenex, Pierre; Lavenex, Pamela Banta
This experiment assesses spatial and nonspatial relational memory in freely moving 9-mo-old and adult (11-13-yr-old) macaque monkeys ("Macaca mulatta"). We tested the use of proximal landmarks, two different objects placed at the center of an open-field arena, as conditional cues allowing monkeys to predict the location of food rewards hidden in…
Thomas, Laura E.
Directed actions can play a causal role in cognition, shaping thought processes. What drives this cross-talk between action and thought? I investigated the hypothesis that representations in spatial working memory mediate interactions between directed actions and problem solving. Participants attempted to solve an insight problem while…
Galati, Alexia; Michael, Christina; Mello, Catherine; Greenauer, Nathan M.; Avraamides, Marios N.
We examined whether people spontaneously represent the partner's viewpoint in spatial memory when it is available in advance and whether they adapt their spontaneous descriptions accordingly. In 18 pairs, Directors studied arrays of objects while: (1) not knowing about having to describe the array to a Matcher, (2) knowing about the subsequent…
Méndez-Couz, M; Conejo, N M; Vallejo, G; Arias, J L
While the neuronal basis of spatial memory consolidation has been thoroughly studied, the substrates mediating the process of extinction remain largely unknown. This study aimed to evaluate the functional contribution of selected brain regions during the extinction of a previously acquired spatial memory task in the Morris water maze. For that purpose, we used adult male Wistar rats trained in a spatial reference memory task. Learning-related changes in c-Fos inmunoreactive cells after training were evaluated in cortical and subcortical regions. Results show that removal of the hidden platform in the water maze induced extinction of the previously reinforced escape behavior after 16 trials, without spontaneous recovery 24h later. Extinction was related with significantly higher numbers of c-Fos positive nuclei in amygdala nuclei and prefrontal cortex. On the other hand, the lateral mammillary bodies showed higher number of c-Fos positive cells than the control group. Therefore, in contrast with the results obtained in studies of classical conditioning, we show the involvement of diencephalic structures mediating this kind of learning. In summary, our findings suggest that medial prefrontal cortex, the amygdala complex and diencephalic structures like the lateral mammillary nuclei are relevant for the extinction of spatial memory.
Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul
Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.
Rossato, Janine I.; Bevilaqua, Lia R.M.; Medina, Jorge H.; Izquierdo, Iván; Cammarota, Martín
Nonreinforced retrieval can cause extinction and/or reconsolidation, two processes that affect subsequent retrieval in opposite ways. Using the Morris water maze task we show that, in the rat, repeated nonreinforced expression of spatial memory causes extinction, which is unaffected by inhibition of protein synthesis within the CA1 region of the dorsal hippocampus. However, if the number of nonreinforced retrieval trials is insufficient to induce long-lasting extinction, then a hippocampal protein synthesis-dependent reconsolidation process recovers the original memory. Inhibition of hippocampal protein synthesis after reversal learning sessions impairs retention of the reversed preference and blocks persistence of the original one, suggesting that reversal learning involves reconsolidation rather than extinction of the original memory. Our results suggest the existence of a hippocampal protein synthesis-dependent reconsolidation process that operates to recover or update retrieval-weakened memories from incomplete extinction. PMID:16882860
Lavenex, Pamela Banta; Bostelmann, Mathilde; Brandner, Catherine; Costanzo, Floriana; Fragnière, Emilie; Klencklen, Giuliana; Lavenex, Pierre; Menghini, Deny; Vicari, Stefano
Studies have shown that persons with Down syndrome (DS) exhibit relatively poor language capacities, and impaired verbal and visuoperceptual memory, whereas their visuospatial memory capacities appear comparatively spared. Individuals with DS recall better where an object was previously seen than what object was previously seen. However, most of the evidence concerning preserved visuospatial memory comes from tabletop or computerized experiments which are biased toward testing egocentric (viewpoint-dependent) spatial representations. Accordingly, allocentric (viewpoint-independent) spatial learning and memory capacities may not be necessary to perform these tasks. Thus, in order to more fully characterize the spatial capacities of individuals with DS, allocentric processes underlying real-world navigation must also be investigated. We tested 20 participants with DS and 16 mental age-matched, typically developing (TD) children in a real-world, allocentric spatial (AS) memory task. During local cue (LC) trials, participants had to locate three rewards marked by local color cues, among 12 locations distributed in a 4 m × 4 m arena. During AS trials, participants had to locate the same three rewards, in absence of LCs, based on their relations to distal environmental cues. All TD participants chose rewarded locations in LC and AS trials at above chance level. In contrast, although all but one of the participants with DS exhibited a preference for the rewarded locations in LC trials, only 50% of participants with DS chose the rewarded locations at above chance level in AS trials. As a group, participants with DS performed worse than TD children on all measures of task performance. These findings demonstrate that individuals with DS are impaired at using an AS representation to learn and remember discrete locations in a controlled environment, suggesting persistent and pervasive deficits in hippocampus-dependent memory in DS. PMID:25762946
Störmer, Viola S; Passow, Susanne; Biesenack, Julia; Li, Shu-Chen
Attention and working memory are fundamental for selecting and maintaining behaviorally relevant information. Not only do both processes closely intertwine at the cognitive level, but they implicate similar functional brain circuitries, namely the frontoparietal and the frontostriatal networks, which are innervated by cholinergic and dopaminergic pathways. Here we review the literature on cholinergic and dopaminergic modulations of visual-spatial attention and visual working memory processes to gain insights on aging-related changes in these processes. Some extant findings have suggested that the cholinergic system plays a role in the orienting of attention to enable the detection and discrimination of visual information, whereas the dopaminergic system has mainly been associated with working memory processes such as updating and stabilizing representations. However, since visual-spatial attention and working memory processes are not fully dissociable, there is also evidence of interacting cholinergic and dopaminergic modulations of both processes. We further review gene-cognition association studies that have shown that individual differences in visual-spatial attention and visual working memory are associated with acetylcholine- and dopamine-relevant genes. The efficiency of these 2 transmitter systems declines substantially during healthy aging. These declines, in part, contribute to age-related deficits in attention and working memory functions. We report novel data showing an effect of dopamine COMT gene on spatial updating processes in older but not in younger adults, indicating potential magnification of genetic effects in old age.
Jacobson, Aaron; Green, Erin; Haase, Lori; Szajer, Jacquelyn; Murphy, Claire
Age affects the human taste system at peripheral and central levels. Metabolic syndrome is a constellation of risk factors (e.g., abdominal obesity and hypertension) that co-occur, increase with age, and heighten risk for cardiovascular disease, diabetes, and cognitive decline. Little is known about how age, metabolic syndrome, and hunger state interact to influence how the brain processes information about taste. We investigated brain activation during the hedonic evaluation of a pleasant, nutritive stimulus (sucrose) within regions critical for taste, homeostatic energy regulation, and reward, as a function of the interactions among age, metabolic syndrome, and hunger condition. We scanned young and elderly adults, half with risk factors associated with metabolic syndrome twice: Once fasted overnight and once after a preload. Functional magnetic resonance imaging data indicated significant effects of age as well as interactive effects with metabolic syndrome and hunger condition. Age-related differences in activation were dependent on the hunger state in regions critical for homoeostatic energy regulation and basic as well as higher order sensory processing and integration. The effects of age and metabolic syndrome on activation in the insula, orbital frontal cortex, caudate, and the hypothalamus may have particularly important implications for taste processing, energy regulation, and dietary choices.
Hsu, Wei-Lun; Ma, Yun-Li; Hsieh, Ding-You; Liu, Yen-Chen; Lee, Eminy Hy
Signal transducer and activator of transcription-1 (STAT1) has an important role in inflammation and the innate immune response, but its role in the central nervous system is less well understood. Here, we examined the role of STAT1 in spatial learning and memory, and assessed the involvement of STAT1 in mediating the memory-impairing effect of amyloid-beta (Aβ). We found that water maze training downregulated STAT1 expression in the rat hippocampal CA1 area, and spatial learning and memory function was enhanced in Stat1-knockout mice. Conversely, overexpression of STAT1 impaired water maze performance. STAT1 strongly upregulated the expression of the extracellular matrix protein laminin β1 (LB1), which also impaired water maze performance in rats. Furthermore, Aβ impaired spatial learning and memory in association with a dose-dependent increase in STAT1 and LB1 expression, but knockdown of STAT1 and LB1 both reversed this effect of Aβ. This Aβ-induced increase in STAT1 and LB1 expression was also associated with a decrease in the expression of the N-methyl-D-aspartate receptor (NMDAR) subunits, NR1, and NR2B. Overexpression of NR1 or NR2B or exogenous application of NMDA reversed Aβ-induced learning and memory deficits as well as Aβ-induced STAT1 and LB1 expression. Our results demonstrate that STAT1 negatively regulates spatial learning and memory through transcriptional regulation of LB1 expression. We also identified a novel mechanism for Aβ pathogenesis through STAT1 induction. Notably, impairment of spatial learning and memory by this STAT1-mediated mechanism is independent of cAMP responsive element-binding protein signaling.
Riotte-Lambert, Louise; Benhamou, Simon; Chamaillé-Jammes, Simon
Home ranges (HRs) are a remarkably common form of animal space use, but we still lack an integrated view of the individual-level processes that can lead to their emergence and maintenance, particularly when individuals are in competition for resources. We built a spatially explicit mechanistic movement model to investigate how simple memory-based foraging rules may enable animals to establish HRs and to what extent this increases their foraging efficiency compared to individuals that do not base foraging decisions on memory. We showed that these simple rules enable individuals to perform better than individuals using the most efficient strategy that does not rely on memory and drive them to spatially segregate through avoidance of resource patches used by others. This striking result questions the common assumption that low HR overlaps are indicators of territorial behavior. Indeed, it appears that, by using an information-updating system, individuals can keep their environment relatively predictable without paying the cost of defending an exclusive space. However, memory-based foraging strategies leading to HR emergence seem unable to prevent the disruptive effects of the arrival of new individuals. This calls for further research on the mechanisms that can stabilize HR spatial organization in the long term.
Carlei, Christophe; Kerzel, Dirk
Hemispheric asymmetries were investigated by changing the horizontal position of stimuli that had to be remembered in a visuo-spatial short-term memory task. Observers looked at matrices containing a variable number of filled squares on the left or right side of the screen center. At stimulus offset, participants reproduced the positions of the filled squares in an empty response matrix. Stimulus and response matrices were presented in the same quadrant. We observed that memory performance was better when the matrices were shown on the left side of the screen. We distinguished between recall strategies that relied on visual or non-visual (verbal) cues and found that the effect of gaze position occurred more reliably in participants using visual recall strategies. Overall, the results show that there is a solid enhancement of visuo-spatial short-term memory when observers look to the left. In contrast, vertical position had no influence on performance. We suggest that unilateral gaze to the left activates centers in the right hemisphere contributing to visuo-spatial memory.
Lambert, Farfalla Ribordy; Lavenex, Pierre; Lavenex, Pamela Banta
Allocentric spatial memory, the memory for locations coded in relation to objects comprising our environment, is a fundamental component of episodic memory and is dependent on the integrity of the hippocampal formation in adulthood. Previous research from different laboratories reported that basic allocentric spatial memory abilities are reliably…
Loureiro, Michael; Lecourtier, Lucas; Engeln, Michel; Lopez, Joëlle; Cosquer, Brigitte; Geiger, Karin; Kelche, Christian; Cassel, Jean-Christophe; Pereira de Vasconcelos, Anne
Current views posit the dorsal hippocampus (DHipp) as contributing to spatial memory processes. Conversely, the ventral hippocampus (VHipp) modulates stress, emotions and affects. Arguments supporting this segregation include differences in (i) connectivity: the DHipp is connected with the entorhinal cortex which receives visuospatial neocortical inputs; the VHipp is connected with both the amygdala and hypothalamus, (ii) electrophysiological characteristics: there is a larger proportion of place cells in the DHipp than in the VHipp, and an increasing dorsoventral gradient in the size of place fields, suggesting less refined spatial coding in the VHipp, and (iii) consequences of lesions: spatial memory is altered after DHipp lesions, less dramatically, sometimes not, after VHipp lesions. Using reversible inactivation, we report in rats, that lidocaine infusions into the DHipp or VHipp right before a probe trial impair retrieval performance in a water-maze task. This impairment was found at two post-acquisition delays compatible with recent memory (1 and 5 days). Pre-training blockade of the VHipp did not prevent task acquisition and drug-free retrieval, on the contrary to pre-training blockade of DHipp, which altered performance in a subsequent drug-free probe trial. Complementary experiments excluded possible locomotor, sensorimotor, motivational or anxiety-related biases from data interpretation. Our conclusion is that a spatial memory can be acquired with the DHipp, less efficiently with the VHipp, and that the retrieval of such a memory and/or the expression of its representation engages the dorsoventral axis of the hippocampus when the task has been learnt with an entirely functional hippocampus.
Kobilo, Tali; Yuan, Chunyan; van Praag, Henriette
Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor δ agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and neurogenesis. Mice were injected with GW for 7 d or AICAR for 7 or 14 d. Two weeks thereafter mice were tested in the Morris water maze. AICAR (7 d) and GW improved spatial memory. Moreover, AICAR significantly, and GW modestly, elevated dentate gyrus neurogenesis. Thus, pharmacological activation of skeletal muscle may mediate cognitive effects. PMID:21245211
Smith, Alexandra E; Slivicki, Richard A; Hohmann, Andrea G; Crystal, Jonathon D
Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that have a negative impact on the quality of life of cancer survivors. Cognitive side effects occur across a variety of domains, including memory, executive function, and processing speed. Such impairments are exacerbated under cognitive challenges and a subgroup of patients experience long-term impairments. Episodic memory in rats can be examined using a source memory task. In the current study, rats received paclitaxel, a taxane-derived chemotherapeutic agent, and learning and memory functioning was examined using the source memory task. Treatment with paclitaxel did not impair spatial and episodic memory, and paclitaxel treated rats were not more susceptible to cognitive challenges. Under conditions in which memory was not impaired, paclitaxel treatment impaired learning of new rules, documenting a decreased sensitivity to changes in experimental contingencies. These findings provide new information on the nature of cancer chemotherapy-induced cognitive impairments, particularly regarding the incongruent vulnerability of episodic memory and new learning following treatment with paclitaxel.
Toepper, M; Gebhardt, H; Beblo, T; Thomas, C; Driessen, M; Bischoff, M; Blecker, C R; Vaitl, D; Sammer, G
Executive working memory operations are related to prefrontal regions in the healthy brain. Moreover, neuroimaging data provide evidence for a functional dissociation of ventrolateral and dorsolateral prefrontal cortex. Most authors either suggest a modality-specific or a function-specific prefrontal cortex organization. In the present study we particularly aimed at the identification of different prefrontal cerebral areas that are involved in executive inhibitory processes during spatial working memory encoding. In an fMRI study (functional magnetic resonance imaging) we examined the neural correlates of spatial working memory processing by varying the amount of executive demands of the task. Twenty healthy volunteers performed the Corsi Block-Tapping test (CBT) during fMRI. The CBT requires the storage and reproduction of spatial target sequences. In a second condition, we presented an adapted version of the Block-Suppression-Test (BST). The BST is based on the original CBT but additionally requires the active suppression of visual distraction within the target sequences. In comparison to the CBT performance, particularly the left dorsolateral prefrontal cortex (BA 9) showed more activity during the BST condition. Our results show that the left dorsolateral prefrontal cortex plays a crucial role for executive controlled inhibition of spatial distraction. Furthermore, our findings are in line with the processing model of a functional dorsolateral-ventrolateral prefrontal cortex organization.
Golbeck, Susan L.
Children's memory for spatial locations in a room designed to look like a grocery store was examined. In the first of two studies, 48 preschoolers completed a memory task for spatial locations problem and an incidental recall task in two room arrangements varying in logical organization. Memory for spatial locations was higher in a clustered and…
Plescia, Fulvio; Marino, Rosa A M; Navarra, Michele; Gambino, Giuditta; Brancato, Anna; Sardo, Pierangelo; Cannizzaro, Carla
This study aims at providing an insight into early handling procedures on learning and memory performance in adult female rats. Early handling procedures were started on post-natal day 2 until 21, and consisted in 15 min, daily separations of the dams from their litters. Assessment of declarative memory was carried out in the novel-object recognition task; spatial learning, reference- and working memory were evaluated in the Morris water maze (MWM). Our results indicate that early handling induced an enhancement in: (1) declarative memory, in the object recognition task, both at 1h and 24h intervals; (2) reference memory in the probe test and working memory and behavioral flexibility in the "single-trial and four-trial place learning paradigm" of the MWM. Short-term separation by increasing maternal care causes a dampening in HPA axis response in the pups. A modulated activation of the stress response may help to protect brain structures, involved in cognitive function. In conclusion, this study shows the long-term effects of a brief maternal separation in enhancing object recognition-, spatial reference- and working memory in female rats, remarking the impact of early environmental experiences and the consequent maternal care on the behavioral adaptive mechanisms in adulthood.
Alaei, Hojjatallah; Moloudi, Rohallah; Sarkaki, Ali Reza; Azizi-Malekabadi, Hamid; Hanninen, Osmo
Previous studies have shown that physical activity improves learning and memory. Present study was performed to determine the effects of acute, chronic and continuous exercise with different periods on spatial learning and memory recorded as the latency and length of swim path in the Morris water maze testing in subsequent 8 days. Four rat groups were included as follows: 1- Group C (controls which did not exercise). 2- Group A (30 days treadmill running before and 8 days during the Morris water maze testing period). 3- Group B (30 days exercise before the Morris water maze testing period only) and 4- Group D (8 days exercise only during the Morris water maze testing period). The results showed that chronic (30 days) and continuous (during 8 days of Morris water maze testing days) treadmill training produced a significant enhancement in spatial learning and memory which was indicated by decreases in path length and latency to reach the platform in the Morris water maze test (p < 0.05). The benefits in these tests were lost in three days, if the daily running session was abandoned. In group D with acute treadmill running (8 days exercise only) the difference between the Group A disappeared in one week and benefit seemed to be obtained in comparison with the controls without running program. In conclusion the chronic and daily running exercises promoted learning and memory in Morris water maze, but the benefits were lost in few days without daily running sessions in adult rats. Key pointsDaily running influence on spatial memory.The velocity of learning can be influenced by running activity.Path length is important parameter for measuring the speed of learning.
Schutte, Anne R.; Spencer, John P.
This study tested a dynamic field theory (DFT) of spatial working memory and an associated spatial precision hypothesis (SPH). Between 3 and 6 years of age, there is a qualitative shift in how children use reference axes to remember locations: 3-year-olds' spatial recall responses are biased toward reference axes after short memory delays, whereas…
Christoffersen, Gert R J; Simonyi, Agnes; Schachtman, Todd R; Clausen, Bettina; Clement, David; Bjerre, Vicky K; Mark, Louise T; Reinholdt, Mette; Schmith-Rasmussen, Kati; Zink, Lena V B
Metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in memory processing in some but not all learning tasks. The reason why this receptor is involved in some tasks but not in others remains to be determined. The present experiments using rats examined effects of the mGlu5-antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP)--applied systemically i.p. (1-10mg/kg) or bilaterally into the prelimbic cortex (1-10 microg)---on the ability of rats to explore and remember new stimuli. A cross-maze, open field, and object recognition task were used to evaluate exploration and memory and it was found that: (1) locomotion during exploration of spatial environments and exploration time at novel objects were reduced by i.p. but not by prelimbic administration of MPEP, (2) spatial short-term memory was impaired in cross-maze and object discrimination was reduced after both types of administration, (3) long-term retention of spatial conditioning in the cross-maze was inhibited after i.p. applications which (4) also inhibited spontaneous alternation performance during maze-exploration. Reduced exploratory locomotion and exploration time after i.p. injections may have contributed to the observed retention impairments. However, the fact that prelimbic administration of MPEP inhibited retention without reducing exploration shows that memory formation was also impacted directly by prelimbic mGlu5 in both spatial and non-spatial learning.
Tyurenkov, I N; Volotova, E V; Kurkin, D V
This work was aimed at evaluating the influence of gliatilin administration on the spatial memory in aged rats. Cognitive function and spatial memory in animals was evaluated using radial (8-beam) maze test. Errors of working spatial memory and reference memory were used as indicators of impaired cognitive function. It was found that aged (24-month) rats compared with younger (6-months) age group exhibited cognitive impairment, as manifested by deterioration of short- and long-term memory processes. Course administration of gliatilin in rats of the older age group at a dose of 100 mg/kg resulted in significant improvement of the working and reference spatial memory in aged rats.
Using Peripheral Processing and Spatial Memory to Facilitate Task Resumption Raj M. Ratwani1,2, Alyssa E. Andrews2, Malcolm McCurry1, J. Gregory...Trafton1,2, Matthew S. Peterson2 Naval Research Laboratory1 George Mason University2 Washington, D.C . Fairfax, VA...Participants. Thirty-three George Mason University undergraduate students participated for course credit. Materials. Thirty Microsoft Excel
Lavenex, Pierre; Lavenex, Pamela Banta
This experiment assesses spatial and nonspatial relational memory in freely moving 9-mo-old and adult (11-13-yr-old) macaque monkeys (Macaca mulatta). We tested the use of proximal landmarks, two different objects placed at the center of an open-field arena, as conditional cues allowing monkeys to predict the location of food rewards hidden in one of two sets of three distinct locations. Monkeys were tested in two different conditions: (1) when local visual cues marked the two sets of potentially baited locations, so that monkeys could use both local and spatial information to discriminate these locations from never-baited locations; and (2) when no local visual cues marked the two sets of potentially baited locations, so that monkeys had to rely on a spatial relational representation of the environment to discriminate these locations. No 9-mo-old or adult monkey associated the presence of the proximal landmarks, at the center of the arena, with the presence of food in one set of three distinct locations. All monkeys, however, discriminated the potentially baited locations in the presence of local visual cues, thus providing evidence of visual discrimination learning. More importantly, all 9-mo-old monkeys tested discriminated the potentially baited locations in absence of the local visual cues, thus exhibiting evidence of spatial relational learning. These findings indicate that spatial memory processes characterized by a relational representation of the environment are present as early as 9 mo of age in macaque monkeys.
Parslow, David M; Morris, Robin G; Fleminger, Simon; Rahman, Qazi; Abrahams, Sharon; Recce, Michael
An immersive virtual reality (IVR) system was used to investigate allocentric spatial memory in a patient (PR) who had selective hippocampal damage, and also in patients who had undergone unilateral temporal lobectomies (17 right TL and 19 left TL), their performance compared against normal control groups. A human analogue of the Olton [Olton (1979). Hippocampus, space, and memory. Behavioural Brain Science, 2, 315] spatial maze was developed, consisting of a virtual room, a central virtual circular table and an array of radially arranged up-turned 'shells.' The participant had to search these shells in turn in order to find a blue 'cube' that would then 'move' to another location and so on, until all the shells had been target locations. Within-search errors could be made when the participants returned to a previously visited location during a search, and between-search errors when they revisited previously successful, but now incorrect locations. PR made significantly more between-search errors than his control group, but showed no increase in within-search errors. The right TL group showed a similar pattern of impairment, but the left TL group showed no impairment. This finding implicates the right hippocampal formation in spatial memory functioning in a scenario in which the visual environment was controlled so as to eliminate extraneous visual cues.
Beatty, W W; Rush, J R
To assess the possible involvement of the monoaminergic neurotransmitters norepinephrine, dopamine and serotonin in the maintenance of spatial working memory rats were treated with antagonists 0 or 2 hr after completing the first 4 choices in an 8 arm maze. Haloperidol (0.25-1 mg/kg), when administered 2 hr after Choice 4, produced a small but consistent impairment in performance on retention tests given 5 hr after the first 4 choices. This deficit closely resembled natural forgetting in terms of the type of errors committed. By contrast, haloperidol in the same doses given 0 hr after Choice 4 or 3 hr before the first 4 choices did not affect retention. Likewise treatment with propranolol (10-20 mg/kg), phentolamine (5-20 mg/kg) or methysergide (5-15 mg/kg) did not impair spatial memory, regardless of when these drugs were injected within the session. Evidently dopaminergic neuronal systems are important in the maintenance of normal spatial working memory.
Esteban, Laura; Vivas, Ana B.; Fuentes, Luis J.; Estévez, Angeles F.
Working memory (WM) is essential to academic achievement. Any enhancement of WM abilities may improve children’s school performance. We tested the usefulness of the differential outcomes procedure (DOP) to enhance typically developing children’s performance on a spatial WM task. The DOP involves a conditional discriminative learning task in which a correct choice response to a specific stimulus-stimulus association is reinforced with a particular reinforcer (outcome). We adapted a spatial memory task to be used with the DOP. Participants had to learn and retain in their WM four target locations of eight possible locations where a shape could be presented. Two groups of 5- and 7-year-old children performed the low-attentional version of the spatial task, and an additional group of 7-year-old children performed the high-attentional version. The results showed that compared with the standard non-differential outcomes procedure (NOP), the DOP produced better memory-based performance in 5-year-old children with the low-attentional task and in 7-year-old children with the high-attentional task. Additionally, delay intervals impaired performance in the NOP but not in the DOP. These findings suggest that the DOP may be a useful complement to other WM intervention programs targeted to improve children´s academic performance at school. PMID:26596777
Kennard, John A.; Harrison, Fiona E.
The present study investigated the effects of a single intravenous (i.v.) dose of Vitamin C (ascorbate, ASC) on spatial memory in APP/PSEN1 mice, an Alzheimer's disease model. First, we confirmed the uptake time course in ASC-depleted gulo (−/−) mice, which cannot synthesize ASC. Differential tissue uptake was seen based on ASC transporter distribution. Liver (SVCT1 & SVCT2) ASC was elevated at 30, 60 and 120 min post-treatment (125 mg/kg, i.v.), whereas spleen (SVCT2) ASC increased at 60 and 120 min. There was no detectable change in cortical (SVCT2 at choroid plexus, and neurons) ASC within the 2-hour interval, although the cortex preferentially retained ASC. APP/PSEN1 and wild type (WT) mice at three ages (3, 9, or 20 months) were treated with ASC (125 mg/kg, i.v.) or saline 45 min before testing on the Modified Y-maze, a two-trial task of spatial memory. Memory declined with age and ASC treatment improved performance in 9 month-old APP/PSEN1 and WT mice. APP/PSEN1 mice displayed no behavioral impairment relative to WT controls. Although dopamine and metabolite DOPAC decreased in the nucleus accumbens with age, and improved spatial memory was correlated with increased dopamine in saline treated mice, acute ASC treatment did not alter monoamine levels in the nucleus accumbens. These data show that the Modified Y-maze is sensitive to age-related deficits, but not additional memory deficits due to amyloid pathology in APP/PSEN1 mice. They also suggest improvements in short-term spatial memory were not due to changes in the neuropathological features of AD or monoamine signaling. PMID:24508240
Ando, J; Ono, Y; Wright, M J
Working memory (WM) encompasses both short-term memory (storage) and executive functions that play an essential role in all forms of cognition. In this study, the genetic structure of storage and executive functions engaged in both a spatial and verbal WM span task is investigated using a twin sample. The sample consists of 143 monozygotic (MZ) and 93 dizygotic (DZ) Japanese twin pairs, ages 16 to 29 years. In 155 (87 MZ, 62 DZ) of these pairs, cognitive ability scores from the Kyodai Japanese IQ test are also obtained. The phenotypic relationship between WM and cognitive ability is confirmed (r = 0.26-0.44). Individual differences in WM storage and executive functions are found to be significantly influenced by genes, with heritability estimates all moderately high (43%-49%), and estimates for cognitive ability comparable to previous studies (65%). A large part of the genetic variance in storage and executive functions in both spatial and verbal modalities is due to a common genetic factor that accounts for 11% to 43% of the variance. In the reduced sample, this common genetic factor accounts for 64% and 26% of the variance in spatial and verbal cognitive ability, respectively. Additional genetic variance in WM (7%-30%) is due to modality specific factors (spatial and verbal) and a storage specific factor that may be particularly important for the verbal modality. None of the variance in cognitive ability is accounted for by the modality and storage genetic factors, suggesting these may be specific to WM.
Background Memory retrieval is not a passive process. Recent studies have shown that reactivated memory is destabilized and then restabilized through gene expression-dependent reconsolidation. Molecular studies on the regulation of memory stability after retrieval have focused almost exclusively on fear memory, especially on the restabilization process of the reactivated fear memory. We previously showed that, similarly with fear memories, reactivated spatial memory undergoes reconsolidation in the Morris water maze. However, the underlying molecular mechanisms by which reactivated spatial memory is destabilized and restabilized remain poorly understood. In this study, we investigated the molecular mechanism that regulates the stability of the reactivated spatial memory. Results We first showed that pharmacological inactivation of the N-methyl-D-aspartate glutamate receptor (NMDAR) in the hippocampus or genetic inhibition of cAMP-responsible element binding protein (CREB)-mediated transcription disrupted reactivated spatial memory. Finally, we showed that pharmacological inhibition of cannabinoid receptor 1 (CB1) and L-type voltage gated calcium channels (LVGCCs) in the hippocampus blocked the disruption of the reactivated spatial memory by the inhibition of protein synthesis. Conclusions Our findings indicated that the reactivated spatial memory is destabilized through the activation of CB1 and LVGCCs and then restabilized through the activation of NMDAR- and CREB-mediated transcription. We also suggest that the reactivated spatial memory undergoes destabilization and restabilization in the hippocampus, through similar molecular processes as those for reactivated contextual fear memories, which require CB1 and LVGCCs for destabilization and NMDAR and CREB for restabilization. PMID:21314917
Edwards, Stephen R; Hamlin, Adam S; Marks, Nicola; Coulson, Elizabeth J; Smith, Maree T
Evaluation of the efficacy of novel therapeutics for potential treatment of Alzheimer's disease (AD) requires an animal model that develops age-related cognitive deficits reproducibly between independent groups of investigators. Herein we assessed comparative temporal changes in spatial memory function in two commercially available transgenic mouse models of AD using the Morris water maze (MWM), incorporating both visible and hidden platform training. Individual cohorts of cDNA-based 'line 85'-derived double-transgenic mice coexpressing the 'Swedish' mutation of amyloid precursor protein (APPSwe) and the presenillin 1 (PS1) 'dE9' mutation were assessed in the MWM at mean ages of 3.6, 9.3 and 14.8 months. We found significant deficits in spatial memory retention in APPSwe/PS1dE9 mice aged 3.6 months and robust deficits in spatial memory acquisition and retention in APPSwe/PS1dE9 mice aged 9.3 months, with a further significant decline by age 14.8 months. β-Amyloid deposits were present in brain sections by 7.25 months of age. In contrast, MWM studies with individual cohorts (aged 4-21 months) of single-transgenic genomic-based APPSwe mice expressing APPSwe on a yeast artificial chromosomal (YAC) construct showed no significant deficits in spatial memory acquisition until 21 months of age. There were no significant deficits in spatial memory retention up to 21 months of age and β-amyloid deposits were not present in brain sections up to 24 months of age. These data, generated using comprehensive study designs, show that APPSwe/PS1dE9 but not APPSwe YAC mice appear to provide a suitably robust model of AD for efficacy assessment of novel AD treatments in development.
McConnell, Sarah E A; Alla, Juliet; Wheat, Elizabeth; Romeo, Russell D; McEwen, Bruce; Thornton, Janice E
Attempts to determine the influence of testicular hormones on learning and memory in males have yielded contradictory results. The present studies examined whether testicular hormones are important for maximal levels of spatial memory in young adult male rats. To minimize any effect of stress, we used the Object Location Task which is a spatial working memory task that does not involve food or water deprivation or aversive stimuli for motivation. In Experiment 1 sham gonadectomized male rats demonstrated robust spatial memory, but gonadectomized males showed diminished spatial memory. In Experiment 2 subcutaneous testosterone (T) capsules restored spatial memory performance in gonadectomized male rats, while rats with blank capsules demonstrated compromised spatial memory. In Experiment 3, gonadectomized male rats implanted with blank capsules again showed compromised spatial memory, while those with T, dihydrotestosterone (DHT), or estradiol (E) capsules demonstrated robust spatial memory, indicating that T's effects may be mediated by its conversion to E or to DHT. Gonadectomized male rats injected with Antide, a gonadotropin-releasing hormone receptor antagonist which lowers luteinizing hormone levels, also demonstrated spatial memory, comparable to that shown by T-, E-, or DHT-treated males. These data indicate that testicular androgens are important for maximal levels of spatial working memory in male rats, that testosterone may be converted to E and/or DHT to exert its effects, and that some of the effects of these steroid hormones may occur via negative feedback effects on LH.
Byrne, Patrick; Becker, Suzanna; Burgess, Neil
The authors model the neural mechanisms underlying spatial cognition, integrating neuronal systems and behavioral data, and address the relationships between long-term memory, short-term memory, and imagery, and between egocentric and allocentric and visual and ideothetic representations. Long-term spatial memory is modeled as attractor dynamics…
Place, Ryan; Lykken, Christy; Beer, Zachery; Suh, Junghyup; McHugh, Thomas J.; Tonegawa, Susumu; Eichenbaum, Howard; Sauvage, Magdalena M.
Recent studies focusing on the memory for temporal order have reported that CA1 plays a critical role in the memory for the sequences of events, in addition to its well-described role in spatial navigation. In contrast, CA3 was found to principally contribute to the memory for the association of items with spatial or contextual information in…
Bedard, Anne-Claude; Martinussen, Rhonda; Ickowicz, Abel; Tannock, Rosemary
Objective: To investigate the effect of methylphenidate (MPH) on visual-spatial memory, as measured by subtests of the Cambridge Neuropsychological Testing Automated Battery (CANTAB), in children with attention-deficit/hyperactivity disorder (ADHD). Visual-spatial memory is a core component of working memory that has been shown to be impaired in…
Ramirez, Gerardo; Gunderson, Elizabeth A; Levine, Susan C; Beilock, Sian L
Spatial ability is a strong predictor of students' pursuit of higher education in science and mathematics. However, very little is known about the affective factors that influence individual differences in spatial ability, particularly at a young age. We examine the role of spatial anxiety in young children's performance on a mental rotation task. We show that even at a young age, children report experiencing feelings of nervousness at the prospect of engaging in spatial activities. Moreover, we show that these feelings are associated with reduced mental rotation ability among students with high but not low working memory (WM). Interestingly, this WM × spatial anxiety interaction was only found among girls. We discuss these patterns of results in terms of the problem-solving strategies that boys versus girls use in solving mental rotation problems.
Gmeindl, Leon; Courtney, Susan M.
Objective To investigate whether spatial working memory (WM) is impaired in multiple sclerosis (MS), and, if it is, to localize impairment to specific cognitive subprocess(es). Method In Experiment 1, MS and control participants performed computerized memory-span and visuomotor tasks. WM subprocesses were taxed by manipulating (1) the requirement to remember serial order, (2) delay duration, and (3) the presence of irrelevant stimuli during target presentation. In Experiment 2, recall and recognition tests varied the difficulty of WM retrieval. In Experiment 3, an attention-cueing task tested the ability to voluntarily and rapidly reorient attention. Results Performance was worse for MS than for control participants in both spatial recall (Exp. 1 span: 95% CIMS = [5.11, 5.57], 95% CIControls = [5.58, 6.03], p = 0.003, 1-tailed; Exp. 2 span: 95% CIMS = [4.44, 5.54], 95% CIControls = [5.47, 6.57], p = 0.006, 1-tailed) and recognition (accuracy: 95% CIMS = [0.71, 0.81], 95% CIControls = [0.79, 0.88], p = 0.01, 1-tailed) tests. However, there was no evidence for deficits in spatiotemporal binding, maintenance, retrieval, distractor suppression, or visuomotor processing. In contrast, MS participants were abnormally slow to reorient attention (cueing effect (ms): 95% CIMS: [90, 169], 95% CIControls: [29, 107], p = 0.015, 1-tailed). Conclusions Results suggest that, whereas spatial WM is impaired in MS, once spatial information has been adequately encoded into WM, individuals with MS are, on average, able to maintain and retrieve this information. Impoverished encoding of spatial information, however, may be due to inefficient voluntary orienting of attention. PMID:22059650
Sprague, Thomas C; Ester, Edward F; Serences, John T
Summary Working memory (WM) enables the maintenance and manipulation of information relevant to behavioral goals. Variability in WM ability is strongly correlated with IQ  and WM function is impaired in many neurological and psychiatric disorders [2, 3], suggesting that this system is a core component of higher cognition. WM storage is thought to be mediated by patterns of activity in neural populations selective for specific properties (e.g., color, orientation, location, motion direction) of memoranda [4–13]. Accordingly, many models propose that differences in the amplitude of these population responses should be related to differences in memory performance [14, 15]. Here, we used functional magnetic resonance imaging (fMRI) and an image reconstruction technique based on a spatial encoding model  to visualize and quantify population-level memory representations supported by multivoxel patterns of activation within regions of occipital, parietal and frontal cortex while participants precisely remembered the location(s) of 0, 1, or 2 small stimuli. We successfully reconstructed images containing representations of the remembered – but not forgotten – locations within regions of occipital, parietal, and frontal cortex using delay-period activation patterns. Critically, the amplitude of representations of remembered locations and behavioral performance both decreased with increasing memory load. These results suggest that differences in visual WM performance between memory load conditions are mediated by changes in the fidelity of large-scale population response profiles distributed across multiple areas of human cortex. PMID:25201683
Langley, C M
Desert kangaroo rats (Dipodomys deserti) forage for seed distributed in patches in the desert environment and may remember patch locations. In Experiment 1, 7 desert kangaroo rats that had discovered the location of a plastic token in 1 box accurately dug for a token hidden in the same location in a 2nd identical box. Results of Experiment 2 indicated that the rats primarily remembered the spatial location of the token within the box in relation to extramaze objects and the walls of the experimental box. Female rats also remembered the chip's location in relation to objects inside the box, but males did not. Experiment 3 demonstrated that the rats' ability to locate the buried token did not depend on detection of the odor of the token. In the discussion I propose that spatial memory in kangaroo rats may have evolved as a result of an overall change in the ontogeny of the species rather than as a specialized adaptation for foraging efficiency.
Banta Lavenex, Pamela; Lavenex, Pierre
Studies of the role of the monkey hippocampus in spatial learning and memory, however few, have reliably produced inconsistent results. Whereas the role of the hippocampus in spatial learning and memory has been clearly established in rodents, studies in nonhuman primates have made a variety of claims that range from the involvement of the hippocampus in spatial memory only at relatively longer memory delays, to no role for the hippocampus in spatial memory at all. In contrast, we have shown that selective damage restricted to the hippocampus (CA regions) prevents the learning or use of allocentric, spatial relational representations of the environment in freely behaving adult monkeys tested in an open-field arena. In this commentary, we discuss a unifying framework that explains these apparently discrepant results regarding the role of the monkey hippocampus in spatial learning and memory. We describe clear and strict criteria to interpret the findings from previous studies and guide future investigations of spatial memory in monkeys. Specifically, we affirm that, as in the rodent, the primate hippocampus is critical for spatial relational learning and memory, and in a time-independent manner. We describe how claims to the contrary are the result of experimental designs that fail to recognize, and control for, egocentric (hippocampus-independent) and allocentric (hippocampus-dependent) spatial frames of reference. Finally, we conclude that the available data demonstrate unequivocally that the central role of the hippocampus in allocentric, spatial relational learning and memory is conserved among vertebrates, including nonhuman primates.
Alain, Claude; Shen, Dawei; Yu, He; Grady, Cheryl
Attending and responding to sound location generates increased activity in parietal cortex which may index auditory spatial working memory and/or goal-directed action. Here, we used an n-back task (Experiment 1) and an adaptation paradigm (Experiment 2) to distinguish memory-related activity from that associated with goal-directed action. In Experiment 1, participants indicated, in separate blocks of trials, whether the incoming stimulus was presented at the same location as in the previous trial (1-back) or two trials ago (2-back). Prior to a block of trials, participants were told to use their left or right index finger. Accuracy and reaction times were worse for the 2-back than for the 1-back condition. The analysis of functional magnetic resonance imaging data revealed greater sustained task-related activity in the inferior parietal lobule (IPL) and superior frontal sulcus during 2-back than 1-back after accounting for response-related activity elicited by the targets. Target detection and response execution were also associated with enhanced activity in the IPL bilaterally, though the activation was anterior to that associated with sustained task-related activity. In Experiment 2, we used an event-related design in which participants listened (no response required) to trials that comprised four sounds presented either at the same location or at four different locations. We found larger IPL activation for changes in sound location than for sounds presented at the same location. The IPL activation overlapped with that observed during the auditory spatial working memory task. Together, these results provide converging evidence supporting the role of parietal cortex in auditory spatial working memory which can be dissociated from response selection and execution. PMID:21833258
Ross, A P; Bartness, T J; Mielke, J G; Parent, M B
Over the past three decades there has been a substantial increase in the amount of fructose consumed by North Americans. Recent evidence from rodents indicates that hippocampal insulin signaling facilitates memory and excessive fructose consumption produces hippocampal insulin resistance. Based on this evidence, the present study tested the hypothesis that a high fructose diet would impair hippocampal-dependent memory. Adult male Sprague-Dawley rats (postnatal day 61) were fed either a control (0% fructose) or high fructose diet (60% of calories). Food intake and body mass were measured regularly. After 19 weeks, the rats were given 3 days of training (8 trials/day) in a spatial version of the water maze task, and retention performance was probed 48 h later. The high fructose diet did not affect acquisition of the task, but did impair performance on the retention test. Specifically, rats fed a high fructose diet displayed significantly longer latencies to reach the area where the platform had been located, made significantly fewer approaches to that area, and spent significantly less time in the target quadrant than did control diet rats. There was no difference in swim speed between the two groups. The retention deficits correlated significantly with fructose-induced elevations of plasma triglyceride concentrations. Consequently, the impaired spatial water maze retention performance seen with the high fructose diet may have been attributable, at least in part, to fructose-induced increases in plasma triglycerides.
Bottini, Roberto; Mattioni, Stefania; Collignon, Olivier
Several studies suggest that serial order in working memory (WM) is grounded on space. For a list of ordered items held in WM, items at the beginning of the list are associated with the left side of space and items at the end of the list with the right side. This suggests that maintaining items in verbal WM is performed in strong analogy to writing these items down on a physical whiteboard for later consultation (The Mental Whiteboard Hypothesis). What drives this spatial mapping of ordered series in WM remains poorly understood. In the present study we tested whether visual experience is instrumental in establishing the link between serial order in WM and spatial processing. We tested early blind (EB), late blind (LB) and sighted individuals in an auditory WM task. Replicating previous studies, left-key responses were faster for early items in the list whereas later items facilitated right-key responses in the sighted group. The same effect was observed in LB individuals. In contrast, EB participants did not show any association between space and serial position in WM. These results suggest that early visual experience plays a critical role in linking ordered items in WM and spatial representations. The analogical spatial structure of WM may depend in part on the actual experience of using spatially organized devices (e.g., notes, whiteboards) to offload WM. These practices are largely precluded to EB individuals, who instead rely to mnemonic devices that are less spatially organized (e.g., recordings, vocal notes). The way we habitually organize information in the external world may bias the way we organize information in our WM.
Smith, S T; Stackman, R W; Clark, A S
The effects of anabolic-androgenic steroid (AAS) compounds on spatial working memory were evaluated in male rats. Thirty days of administration of a high dose of three individual AAS compounds (17 alpha-methyltestosterone, methandrostenolone, or testosterone cypionate) had no effects on spatial memory or motivation as tested on a delayed non-match-to-sample radial arm maze task. Administration of these AAS compounds at doses within the human abuse range does not impair spatial working memory in rats.
Thangthaeng, Nopporn; Rutledge, Margaret; Wong, Jessica M.; Vann, Philip H.; Forster, Michael J.; Sumien, Nathalie
Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. However, beneficial actions of metformin in the central nervous system have not been clearly established. The current study examined the effect of chronic oral metformin treatment on motor and cognitive function when initiated in young, middle-aged, or old male mice. C57BL/6 mice aged 4, 11, or 22 months were randomly assigned to either a metformin group (2 mg/ml in drinking water) or a control group. The mice were monitored weekly for body weight, as well as food and water intake and a battery of behavioral tests for motor, cognitive and visual function was initiated after the first month of treatment. Liver, hippocampus and cortex were collected at the end of the study to assess redox homeostasis. Overall, metformin supplementation in male mice failed to affect blood glucose, body weights and redox homeostasis at any age. It also had no beneficial effect on age-related declines in psychomotor, cognitive or sensory functions. However, metformin treatment had a deleterious effect on spatial memory and visual acuity, and reduced SOD activity in brain regions. These data confirm that metformin treatment may be associated with deleterious effect resulting from the action of metformin on the central nervous system. PMID:28203479
Johnson, Sarah A.; Sacks, Patricia K.; Turner, Sean M.; Gaynor, Leslie S.; Ormerod, Brandi K.; Maurer, Andrew P.; Bizon, Jennifer L.; Burke, Sara N.
Hippocampal-dependent episodic memory and stimulus discrimination abilities are both compromised in the elderly. The reduced capacity to discriminate between similar stimuli likely contributes to multiple aspects of age-related cognitive impairment; however, the association of these behaviors within individuals has never been examined in an animal…
Milton, Russell; Babichev, Andrey; Dabaghian, Yuri
In the hippocampus, a network of place cells generates a cognitive map of space, in which each cell is responsive to a particular area of the environment - its place field. The peak response of each cell and the size of each place field have considerable variability. Experimental evidence suggests that place cells encode a topological map of space that serves as a basis of spatial memory and spatial awareness. Using a computational model based on Persistent Homology Theory we demonstrate that if the parameters of the place cells spiking activity fall inside of the physiological range, the network correctly encodes the topological features of the environment. We next introduce parameters of synaptic connectivity into the model and demonstrate that failures in synapses that detect coincident neuronal activity lead to spatial learning deficiencies similar to the ones that are observed in rodent models of neurodegenerative diseases. Moreover, we show that these learning deficiencies may be mitigated by increasing the number of active cells and/or by increasing their firing rate, suggesting the existence of a compensatory mechanism inherent to the cognitive map.
Ardiles, Álvaro O.; Tapia-Rojas, Cheril C.; Mandal, Madhuchhanda; Alexandre, Frédéric; Kirkwood, Alfredo; Inestrosa, Nibaldo C.; Palacios, Adrian G.
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder associated with progressive memory loss, severe dementia, and hallmark neuropathological markers, such as deposition of amyloid-β (Aβ) peptides in senile plaques and accumulation of hyperphosphorylated tau proteins in neurofibrillary tangles. Recent evidence obtained from transgenic mouse models suggests that soluble, nonfibrillar Aβ oligomers may induce synaptic failure early in AD. Despite their undoubted value, these transgenic models rely on genetic manipulations that represent the inherited and familial, but not the most abundant, sporadic form of AD. A nontransgenic animal model that still develops hallmarks of AD would be an important step toward understanding how sporadic AD is initiated. Here we show that starting between 12 and 36 mo of age, the rodent Octodon degus naturally develops neuropathological signs of AD, such as accumulation of Aβ oligomers and phosphorylated tau proteins. Moreover, age-related changes in Aβ oligomers and tau phosphorylation levels are correlated with decreases in spatial and object recognition memory, postsynaptic function, and synaptic plasticity. These findings validate O. degus as a suitable natural model for studying how sporadic AD may be initiated. PMID:22869717
Hassanpoor, Hossein; Fallah, Ali; Raza, Mohsin
Our knowledge about encoding and maintenance of spatial memory emphasizes the integrated functional role of the grid cells and the place cells of the hippocampus in the generation of theta rhythm in spatial memory formation. However, the role of astrocytes in these processes is often underestimated in their contribution to the required structural and functional characteristics of hippocampal neural network operative in spatial memory. We show that hippocampal astrocytes, by the secretion of gliotransmitters, such as glutamate, d-serine, and ATP and growth factors such as BDNF and by the expression of receptors and channels such as those of TNFα and aquaporin, have several diverse fuctions in spatial memory. We specifically focus on the role of astrocytes on five phases of spatial memory: (1) theta rhythm generation, (2) theta phase precession, (3) formation of spatial memory by mapping data of entorhinal grid cells into the place cells, (4) storage of spatial information, and (5) maintenance of spatial memory. Finally, by reviewing the literature, we propose specific mechanisms mentioned in the form of a hypothesis suggesting that astrocytes are important in spatial memory formation.
Sapiurka, Maya; Squire, Larry R; Clark, Robert E
In earlier work, patients with hippocampal damage successfully path integrated, apparently by maintaining spatial information in working memory. In contrast, rats with hippocampal damage were unable to path integrate, even when the paths were simple and working memory might have been expected to support performance. We considered possible ways to understand these findings. We tested rats with either hippocampal lesions or lesions of medial prefrontal cortex (mPFC) on three tasks of spatial or nonspatial memory: path integration, spatial alternation, and a nonspatial alternation task. Rats with mPFC lesions were impaired on both spatial and nonspatial alternation but performed normally on path integration. By contrast, rats with hippocampal lesions were impaired on path integration and spatial alternation but performed normally on nonspatial alternation. We propose that rodent neocortex is limited in its ability to construct a coherent spatial working memory of complex environments. Accordingly, in tasks such as path integration and spatial alternation, working memory cannot depend on neocortex alone. Rats may accomplish many spatial memory tasks by relying on long-term memory. Alternatively, they may accomplish these tasks within working memory through sustained coordination between hippocampus and other cortical brain regions such as mPFC, in the case of spatial alternation, or parietal cortex in the case of path integration. © 2016 Wiley Periodicals, Inc.
Besnard, S; Machado, M L; Vignaux, G; Boulouard, M; Coquerel, A; Bouet, V; Freret, T; Denise, P; Lelong-Boulouard, V
It has recently been shown that a lack of vestibular sensory information decreases spatial memory performance and induces biochemical changes in the hippocampus in rodents. After vestibular neurectomy, patients display spatial memory deficit and hippocampal atrophy. Our objectives were to explore: (a) spatial (Y maze, radial-arm maze), and non-spatial (object recognition) memory performance, (b) modulation of NMDA receptors within the hippocampus using radioligand binding, and (c) hippocampal atrophy, using MRI, in a rat model of bilateral labyrinthectomy realized in two operations. Chemical vestibular lesions (VLs) were induced in 24 animals by transtympanic injections of sodium arsanilate (30 mg/0.1 ml/ear), one side being lesioned 3 weeks after the other. The control group received transtympanic saline solution (0.1 ml/ear) (n = 24). Spatial memory performance (Y maze and radial maze) decreased after VL. Conversely, non-spatial memory performance (object recognition) was not affected by VL. No hippocampal atrophy was observed with MRI, but density of NMDA receptors were increased in the hippocampus after VL. These findings show that the lack of vestibular information induced specific deficits in spatial memory. Additionally, quantitative autoradiographic data suggest the involvement of the glutamatergic system in spatial memory processes related to vestibular information. When studying spatial memory performances in the presence of vestibular syndrome, two-step labyrinthectomy is a suitable procedure for distinguishing between the roles of the specific components of vestibular input loss and those of impaired locomotor activity.
Wang, Lu; Carr, Martha
In this review, a new model that is grounded in information-processing theory is proposed to account for gender differences in spatial ability. The proposed model assumes that the relative strength of working memory, as expressed by the ratio of visuospatial working memory to verbal working memory, influences the type of strategies used on spatial…
Ribordy, Farfalla; Jabes, Adeline; Lavenex, Pamela Banta; Lavenex, Pierre
Episodic memories for autobiographical events that happen in unique spatiotemporal contexts are central to defining who we are. Yet, before 2 years of age, children are unable to form or store episodic memories for recall later in life, a phenomenon known as infantile amnesia. Here, we studied the development of allocentric spatial memory, a…
Sekeres, Melanie J.; Neve, Rachael L.; Frankland, Paul W.; Josselyn, Sheena A.
Although the transcription factor CREB has been widely implicated in memory, whether it is sufficient to produce spatial memory under conditions that do not normally support memory formation in mammals is unknown. We found that locally and acutely increasing CREB levels in the dorsal hippocampus using viral vectors is sufficient to induce robust…
Lim, Sukbin; Goldman, Mark S
A hallmark of working memory is the ability to maintain graded representations of both the spatial location and amplitude of a memorized stimulus. Previous work has identified a neural correlate of spatial working memory in the persistent maintenance of spatially specific patterns of neural activity. How such activity is maintained by neocortical circuits remains unknown. Traditional models of working memory maintain analog representations of either the spatial location or the amplitude of a stimulus, but not both. Furthermore, although most previous models require local excitation and lateral inhibition to maintain spatially localized persistent activity stably, the substrate for lateral inhibitory feedback pathways is unclear. Here, we suggest an alternative model for spatial working memory that is capable of maintaining analog representations of both the spatial location and amplitude of a stimulus, and that does not rely on long-range feedback inhibition. The model consists of a functionally columnar network of recurrently connected excitatory and inhibitory neural populations. When excitation and inhibition are balanced in strength but offset in time, drifts in activity trigger spatially specific negative feedback that corrects memory decay. The resulting networks can temporally integrate inputs at any spatial location, are robust against many commonly considered perturbations in network parameters, and, when implemented in a spiking model, generate irregular neural firing characteristic of that observed experimentally during persistent activity. This work suggests balanced excitatory-inhibitory memory circuits implementing corrective negative feedback as a substrate for spatial working memory.
A hallmark of working memory is the ability to maintain graded representations of both the spatial location and amplitude of a memorized stimulus. Previous work has identified a neural correlate of spatial working memory in the persistent maintenance of spatially specific patterns of neural activity. How such activity is maintained by neocortical circuits remains unknown. Traditional models of working memory maintain analog representations of either the spatial location or the amplitude of a stimulus, but not both. Furthermore, although most previous models require local excitation and lateral inhibition to maintain spatially localized persistent activity stably, the substrate for lateral inhibitory feedback pathways is unclear. Here, we suggest an alternative model for spatial working memory that is capable of maintaining analog representations of both the spatial location and amplitude of a stimulus, and that does not rely on long-range feedback inhibition. The model consists of a functionally columnar network of recurrently connected excitatory and inhibitory neural populations. When excitation and inhibition are balanced in strength but offset in time, drifts in activity trigger spatially specific negative feedback that corrects memory decay. The resulting networks can temporally integrate inputs at any spatial location, are robust against many commonly considered perturbations in network parameters, and, when implemented in a spiking model, generate irregular neural firing characteristic of that observed experimentally during persistent activity. This work suggests balanced excitatory–inhibitory memory circuits implementing corrective negative feedback as a substrate for spatial working memory. PMID:24828633
Rensel, M A; Salwiczek, L; Roth, J; Schlinger, B A
Estradiol is known to impact cognitive function including spatial learning and memory, with studies focused largely on rodent models. Estrogens can be produced peripherally or centrally as neuroestrogens, and the specific role for neuroestrogens in memory processes remains unresolved. Many songbirds possess remarkable spatial memory capabilities and also express the estrogen synthetic enzyme aromatase abundantly in the hippocampus, suggesting that locally-produced estrogens may promote the acquisition or retrieval of spatial memories in these birds. We examined the effect of estradiol on spatial memory in three contexts in the zebra finch: retrieval after discrimination training, retrieval after familiarization but without discrimination training, and memory acquisition, using a combination of estradiol implants and oral dosing with the aromatase inhibitor fadrozole (FAD). Retrieval of spatial memory in both contexts was impaired when estradiol production was blocked. However, spatial memory acquisition was enhanced when estradiol production was inhibited whereas estradiol replacement impaired acquisition. These results provide evidence for a context-specific role of estradiol in songbird spatial memory, results that find accord with some mammalian studies but have not yet been observed in birds.
Guenzel, Friederike M; Wolf, Oliver T; Schwabe, Lars
Stress and stress hormones are known to affect learning and memory processes. However, although effects of stress on hippocampus-dependent declarative learning and memory are well-documented, relatively little attention has been paid to the impact of stress on striatum-dependent stimulus-response (S-R) learning and memory. Recent evidence indicates that glucocorticoid stress hormones shortly after learning enhance S-R memory consolidation, whereas stress prior to retention testing impairs S-R memory retrieval. Whether stress affects also the acquisition of S-R memories in humans remains unclear. For this reason, we examined here the effects of acute stress on S-R memory formation and contrasted these stress effects with those on hippocampus-dependent spatial memory. Healthy men and women underwent a stressor (socially evaluated cold pressor test, SECPT) or a control manipulation before they completed an S-R task and two spatial learning tasks. Memory was assessed one week later. Our data showed that stress impaired S-R memory performance in men but not in women. Conversely, spatial memory was impaired by stress in women but not in men. These findings provide further evidence that stress may alter learning and memory processes beyond the hippocampus. Moreover, our data underline that participants' sex may play a critical role in the impact of stress on multiple memory systems.
Morey, Candice C.; Miron, Monica D.
Among models of working memory, there is not yet a consensus about how to describe functions specific to storing verbal or visual-spatial memories. We presented aural-verbal and visual-spatial lists simultaneously and sometimes cued one type of information after presentation, comparing accuracy in conditions with and without informative…
Luna, David; Martínez, Héctor
The occurrence of spontaneous recovery in human spatial memory was assessed using a virtual environment. In Experiment 1, spatial memory was established by training participants to locate a hidden platform in a virtual water maze using a set of four distal landmarks. In Experiment 2, after learning about the location of a hidden platform, the…
Robin, Jessica; Moscovitch, Morris
Several recent studies have explored the effect of contextual familiarity on remembered and imagined events. The aim of this study was to examine the extent of this effect by comparing the effect of cuing spatial memories, episodic memories, and imagined future events with spatial contextual cues of varying levels of familiarity. We used…
Yerramsetti, Ashok; Marchette, Steven A.; Shelton, Amy L.
Orientation dependence in spatial memory has often been interpreted in terms of accessibility: Object locations are encoded relative to a reference orientation that affords the most accurate access to spatial memory. An open question, however, is whether people naturally use this "preferred" orientation whenever recalling the space. We…
Brunye, Tad T.; Taylor, Holly A.
Four dual-task experiments examined visuospatial, articulatory, and central executive working memory involvement during the development and application of spatial mental models. In Experiments 1 and 2 participants read route and survey spatial descriptions while undertaking one of four secondary tasks targeting working memory components.…
Shukitt-Hale, B.; Casadesus, G.; McEwen, J. J.; Rabin, B. M.; Joseph, J. A.
It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.
Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y
Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies.
Morey, Candice C; Mall, Jonathan T
Some evidence suggests that memory for serial order is domain-general. Evidence also points to asymmetries in interference between verbal and visual-spatial tasks. We confirm that concurrently remembering verbal and spatial serial lists provokes substantial interference compared with remembering a single list, but we further investigate the impact of this interference throughout the serial position curve, where asymmetries are indeed apparent. A concurrent verbal order memory task affects spatial memory performance throughout the serial positions of the list, but performing a spatial order task affects memory for the verbal serial list only for early list items; in the verbal task only, the final items are unaffected by a concurrent task. Adding suffixes eliminates this asymmetry, resulting in impairment throughout the list for both tasks. These results suggest that domain-general working memory resources may be supplemented with resources specific to the verbal domain, but perhaps not with equivalent spatial resources.
Wartman, Brianne C.; Gabel, Jennifer; Holahan, Matthew R.
One system consolidation model suggests that as time passes, ensembles of cortical neurons form strong connections to represent remote memories. In this model, the anterior cingulate cortex (ACC) serves as a cortical region that represents remote memories. However, there is debate as to whether remote spatial memories go through this systems consolidation process and come to rely on the ACC. The present experiment examined whether increasing the processing demand on the hippocampus, by sequential training on two spatial tasks, would more fully engage the ACC during retrieval of a remote spatial memory. In this scenario, inactivation of the ACC at a remote time point was hypothesized to produce a severe memory deficit if rats had been trained on two, sequential spatial tasks. Rats were trained on a water maze (WM) task only or a WM task followed by a radial arm maze task. A WM probe test was given recently or remotely to all rats. Prior to the probe test, rats received an injection of saline or muscimol into the ACC. A subtle deficit in probe performance was found at the remote time point in the group trained on only one spatial task and treated with muscimol. In the group trained on two spatial tasks and treated with muscimol, a subtle deficit in probe performance was noted at the recent time point and a substantial deficit in probe performance was observed at the remote time point. c-Fos labeling in the hippocampus revealed more labeling in the CA1 region in all remotely tested groups than recently tested groups. Findings suggest that spatial remote memories come to rely more fully on the ACC when hippocampal processing requirements are increased. Results also suggest continued involvement of the hippocampus in spatial memory retrieval along with a progressive strengthening of cortical connections as time progresses. PMID:25279556
Li, Lin; Sase, Ajinkya; Patil, Sudarshan; Sunyer, Berta; Höger, Harald; Smalla, Karl-Heinz; Stork, Oliver; Lubec, Gert
Protein phosphorylation and dephosphorylation events play a key role in memory formation and various protein kinases and phosphatases have been firmly associated with memory performance. Here, we determined expression changes of protein kinases and phosphatases following retrieval of spatial memory in CD1 mice in a Morris Water Maze task, using antibody microarrays and confirmatory Western blot. Comparing changes following single and consecutive retrieval, we identified stably and differentially expressed kinases, some of which have never been implicated before in memory functions. On the basis of these findings we define a small signaling network associated with spatial memory retrieval. Moreover, we describe differential regulation and correlation of expression levels with behavioral performance of polo-like kinase 1. Together with its recently observed genetic association to autism-spectrum disorders our data suggest a role of this kinase in balancing preservation and flexibility of learned behavior.
Budzinskaia, M V
The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy.
Kreitz, Carina; Furley, Philip; Memmert, Daniel; Simons, Daniel J
Working memory and attention are closely related constructs. Models of working memory often incorporate an attention component, and some even equate working memory and attentional control. Although some attention-related processes, including inhibitory control of response conflict and interference resolution, are strongly associated with working memory, for other aspects of attention the link is less clear. We examined the association between working-memory performance and attentional breadth, the ability to spread attention spatially. If the link between attention and working memory is broader than inhibitory and interference resolution processes, then working-memory performance might also be associated with other attentional abilities, including attentional breadth. We tested 123 participants on a variety of working-memory and attentional-breadth measures, finding a strong correlation between performances on these two types of tasks. This finding demonstrates that the link between working memory and attention extends beyond inhibitory processes.
Lithfous, Ségolène; Tromp, Delphine; Dufour, André; Pebayle, Thierry; Goutagny, Romain; Després, Olivier
The purpose of this study was to investigate the role of theta activity in cognitive mapping, and to determine whether age-associated decreased theta power may account for navigational difficulties in elderly individuals. Cerebral activity was recorded using electroencephalograph in young and older individuals performing a spatial memory task that required the creation of cognitive maps. Power spectra were computed in the frontal and parietal regions and correlated with recognition performance. We found that accuracy of cognitive mapping was positively correlated with left frontal theta activity during encoding in young adults but not in older individuals. Compared with young adults, older participants were impaired in the creation of cognitive maps and showed reduced theta and alpha activity at encoding. These results suggest that encoding processes are impaired in older individual, which may explain age-related cognitive mapping deficits.
Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision.
Allen, Kevin; Fuchs, Elke C; Jaschonek, Hannah; Bannerman, David M; Monyer, Hannah
Gap junctions containing connexin 36 electrically couple interneurons in many brain regions and synchronize their activity. We used connexin-36 knock-out mice (Cx36(-/-)) to study the importance of electrical coupling between interneurons for spatial coding in the hippocampus and for different forms of hippocampus-dependent spatial memory. Recordings in behaving mice revealed that the spatial selectivity of hippocampal pyramidal neurons was reduced and less stable in Cx36(-/-) mice. Altered network activity was reflected in slower theta oscillations in the mutants. Temporal coding, assessed by determining the presence and characteristics of theta phase precession, had different dynamics in Cx36(-/-) mice compared with controls. At the behavioral level, Cx36(-/-) mice displayed impaired short-term spatial memory but normal spatial reference memory. These results highlight the functional role of electrically coupled interneurons for spatial coding and cognition. Moreover, they suggest that the precise spatial selectivity of place cells is not essential for normal performance on spatial tasks assessing associative long-term memory.
Hulgard, Katrine; Ratcliffe, John M
Related species with different diets are predicted to rely on different cognitive strategies: those best suited for locating available and appropriate foods. Here we tested two predictions of the niche-specific cognitive strategies hypothesis in bats, which suggests that predatory species should rely more on object memory than on spatial memory for finding food and that the opposite is true of frugivorous and nectivorous species. Specifically, we predicted that: (1) predatory bats would readily learn to associate shapes with palatable prey and (2) once bats had made such associations, these would interfere with their subsequent learning of a spatial memory task. We trained free-flying Myotis nattereri to approach palatable and unpalatable insect prey suspended below polystyrene objects. Experimentally naïve bats learned to associate different objects with palatable and unpalatable prey but performed no better than chance in a subsequent spatial memory experiment. Because experimental sequence was predicted to be of consequence, we introduced a second group of bats first to the spatial memory experiment. These bats learned to associate prey position with palatability. Control trials indicated that bats made their decisions based on information acquired through echolocation. Previous studies have shown that bat species that eat mainly nectar and fruit rely heavily on spatial memory, reflecting the relative consistency of distribution of fruit and nectar compared with insects. Our results support the niche-specific cognitive strategies hypothesis and suggest that for gleaning and clutter-resistant aerial hawking bats, learning to associate shape with food interferes with subsequent spatial memory learning.
Starc, Martina; Anticevic, Alan; Repovš, Grega
Pupillometry provides an accessible option to track working memory processes with high temporal resolution. Several studies showed that pupil size increases with the number of items held in working memory; however, no study has explored whether pupil size also reflects the quality of working memory representations. To address this question, we used a spatial working memory task to investigate the relationship of pupil size with spatial precision of responses and indicators of reliance on generalized spatial categories. We asked 30 participants (15 female, aged 19-31) to remember the position of targets presented at various locations along a hidden radial grid. After a delay, participants indicated the remembered location with a high-precision joystick providing a parametric measure of trial-to-trial accuracy. We recorded participants' pupil dilations continuously during task performance. Results showed a significant relation between pupil dilation during preparation/early encoding and the precision of responses, possibly reflecting the attentional resources devoted to memory encoding. In contrast, pupil dilation at late maintenance and response predicted larger shifts of responses toward prototypical locations, possibly reflecting larger reliance on categorical representation. On an intraindividual level, smaller pupil dilations during encoding predicted larger dilations during late maintenance and response. On an interindividual level, participants relying more on categorical representation also produced larger precision errors. The results confirm the link between pupil size and the quality of spatial working memory representation. They suggest compensatory strategies of spatial working memory performance-loss of precise spatial representation likely increases reliance on generalized spatial categories.
Vergauwe, Evie; Barrouillet, Pierre; Camos, Valerie
Examinations of interference between visual and spatial materials in working memory have suggested domain- and process-based fractionations of visuo-spatial working memory. The present study examined the role of central time-based resource sharing in visuo-spatial working memory and assessed its role in obtained interference patterns. Visual and…
Chin, Vivien S; Van Skike, Candice E; Berry, Raymond B; Kirk, Roger E; Diaz-Granados, Jamie; Matthews, Douglas B
The effects of ethanol differ in adolescent and adult rats on a number of measures. The evidence of the effects of ethanol on spatial memory in adolescents and adults is equivocal. Whether adolescents are more or less sensitive to ethanol-induced impairment of spatial memory acquisition remains unclear; with regard to the effects of acute ethanol on spatial memory retrieval there is almost no research looking into any age difference. Thus, we examined the effects of acute ethanol on spatial memory in the Morris Watermaze in adolescents and adults. Allopregnanolone (ALLO) is a modulator of the GABA(A) receptor and has similar behavioral effects as ethanol. We sought to also determine the effects of allopreganolone on spatial memory in adolescent and adults. Male adolescent (post natal [PN]28-30) and adult (PN70-72) rats were trained in the Morris Watermaze for 6 days and acute doses of ethanol (saline, 1.5 and 2.0 g/kg) or ALLO (vehicle, 9 and 18 mg/kg) were administered on Day 7. A probe trial followed on Day 8. As expected, there were dose effects; higher doses of both ethanol and ALLO impaired spatial memory. However, in both the ethanol and ALLO conditions adolescents and adults had similar spatial memory impairments. The current results suggest that ethanol and ALLO both impair hippocampal-dependent spatial memory regardless of age in that once learning has occurred, ethanol or ALLO does not differentially impair the retrieval of spatial memory in adolescents and adults. Given the mixed results on the effect of ethanol on cognition in adolescent rats, additional research is needed to ascertain the factors critical for the reported differential results.
Voleti, Vinod B; Hubschman, Jean-Pierre
As with many organs, compromised function of the eye is accompanied with age and has become increasingly prevalent with the aging population. When decreased visual loss becomes significant, patients' ability to perform activities of daily living becomes compromised. This decrease in function is met with morbidity and mortality, as well as a large socioeconomic burden throughout the world. This review summarizes the most common age-related eye diseases, including cataract, glaucoma, diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration. Although our understanding of the genetic and biochemical pathways of these diseases is sill at its primitive stages, we have become able to help our patients improve the quality of life as they age.
AiQi 218 DIRECT ACCESS BY SPATIAL POSITION IN VISUAL MEMORY 1 1/1 SYNOPSIS OF PRINCIPAL FINDINGS(U) PENNSYLVANIA UNIV PPHILADELPHIA S STERNBERG ET...IRR04204 RR04206-01 11 TITLE (Include SecuriY Claw ficat,@n) Direct Access by Spatial Position in Visual Memory: 1. Synopsis of Principal Findings 12...034 -amJanuary 20. 1986 , ? ’ I~ Direct Access by Spatial Position In Visual Memory: 1. Synopsis of Principal gfdings 1. Introduction In recent years
Paleja, Meera; Girard, Todd A.; Christensen, Bruce K.
Spatial pattern separation (SPS) and spatial pattern completion (SPC) have played an increasingly important role in computational and rodent literatures as processes underlying associative memory. SPS and SPC are complementary processes, allowing the formation of unique representations and the reconstruction of complete spatial environments based…
Li, Xiaoou; Carlson, Laura A.; Mou, Weimin; Williams, Mark R.; Miller, Jared E.
A target object's location within a configuration of objects can be described by spatially relating it to a reference object that is selected from among its neighbors, with a preference for reference objects that are spatially close and aligned with the target. In the spatial memory literature, these properties of alignment and proximity are…
Heuer, Eric; Bachevalier, Jocelyne
Earlier studies in monkeys have reported mild impairment in recognition memory after nonselective neonatal hippocampal lesions. To assess whether the memory impairment could have resulted from damage to cortical areas adjacent to the hippocampus, we tested adult monkeys with neonatal focal hippocampal lesions and sham-operated controls in three recognition tasks: delayed nonmatching-to-sample, object memory span, and spatial memory span. Further, to rule out that normal performance on these tasks may relate to functional sparing following neonatal hippocampal lesions, we tested adult monkeys that had received the same focal hippocampal lesions in adulthood and their controls in the same three memory tasks. Both early and late onset focal hippocampal damage did not alter performance on any of the three tasks, suggesting that damage to cortical areas adjacent to the hippocampus was likely responsible for the recognition impairment reported by the earlier studies. In addition, given that animals with early and late onset hippocampal lesions showed object and spatial recognition impairment when tested in a visual paired comparison task, the data suggest that not all object and spatial recognition tasks are solved by hippocampal-dependent memory processes. The current data may not only help explain the neural substrate for the partial recognition memory impairment reported in cases of developmental amnesia, but they are also clinically relevant given that the object and spatial memory tasks used in monkeys are often translated to investigate memory functions in several populations of human infants and children in which dysfunction of the hippocampus is suspected.
Rauchs, Géraldine; Orban, Pierre; Schmidt, Christina; Albouy, Geneviève; Balteau, Evelyne; Degueldre, Christian; Schnackers, Caroline; Sterpenich, Virginie; Tinguely, Gilberte; Luxen, André; Maquet, Pierre; Peigneux, Philippe
It is known that sleep reshapes the neural representations that subtend the memories acquired while navigating in a virtual environment. However, navigation is not process-pure, as manifold learning components contribute to performance, notably the spatial and contextual memory constituents. In this context, it remains unclear whether post-training sleep globally promotes consolidation of all of the memory components embedded in virtual navigation, or rather favors the development of specific representations. Here, we investigated the effect of post-training sleep on the neural substrates of the consolidation of spatial and contextual memories acquired while navigating in a complex 3D, naturalistic virtual town. Using fMRI, we mapped regional cerebral activity during various tasks designed to tap either the spatial or the contextual memory component, or both, 72 h after encoding with or without sleep deprivation during the first post-training night. Behavioral performance was not dependent upon post-training sleep deprivation, neither in a natural setting that engages both spatial and contextual memory processes nor when looking more specifically at each of these memory representations. At the neuronal level however, analyses that focused on contextual memory revealed distinct correlations between performance and neuronal activity in frontal areas associated with recollection processes after post-training sleep, and in the parahippocampal gyrus associated with familiarity processes in sleep-deprived participants. Likewise, efficient spatial memory was associated with posterior cortical activity after sleep whereas it correlated with parahippocampal/medial temporal activity after sleep deprivation. Finally, variations in place-finding efficiency in a natural setting encompassing spatial and contextual elements were associated with caudate activity after post-training sleep, suggesting the automation of navigation. These data indicate that post-training sleep
Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert
Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein
Ribordy Lambert, Farfalla; Lavenex, Pierre; Banta Lavenex, Pamela
Allocentric spatial memory, "where" with respect to the surrounding environment, is one of the three fundamental components of episodic memory: what, where, when. Whereas basic allocentric spatial memory abilities are reliably observed in children after 2 years of age, coinciding with the offset of infantile amnesia, the resolution of allocentric spatial memory acquired over repeated trials improves from 2 to 4 years of age. Here, we first show that single-trial allocentric spatial memory performance improves in children from 3.5 to 7 years of age, during the typical period of childhood amnesia. Second, we show that large individual variation exists in children's performance at this age. Third, and most importantly, we show that improvements in single-trial allocentric spatial memory performance are due to an increasing ability to spatially and temporally separate locations and events. Such improvements in spatial and temporal processing abilities may contribute to the gradual offset of childhood amnesia.
Rotzer, S; Loenneker, T; Kucian, K; Martin, E; Klaver, P; von Aster, M
The underlying neural mechanisms of developmental dyscalculia (DD) are still far from being clearly understood. Even the behavioral processes that generate or influence this heterogeneous disorder are a matter of controversy. To date, the few studies examining functional brain activation in children with DD mainly focus on number and counting related tasks, whereas studies on more general cognitive domains that are involved in arithmetical development, such as working memory are virtually absent. There are several studies showing a close relationship between DD and spatial working memory [Camos, V. (2008). Low working memory capacity impedes both efficiency and learning of number transcoding in children. Journal of Experimental Child Psychology, 99(1), 37-57; McLean, J. F., & Hitch, G. J. (1999). Working memory impairments in children with specific arithmetic learning difficulties. Journal of Experimental Child Psychology, 74(3), 240-260; Rosselli, M., Matute, E., Pinto, N., & Ardila, A. (2006). Memory abilities in children with subtypes of dyscalculia. Developmental Neuropsychology, 30(3), 801-818; Siegel, L. S., & Ryan, E. B. (1989). The development of working memory in normally achieving and subtypes of learning disabled children. Child Development, 60(4), 973-980]. The relationship between these two mechanisms is still matter of debate, but this study follows the assumption that poor spatial working memory capacity may hinder the acquisition of spatial number representations in children with DD [Geary, D. C. (1993). Mathematical disabilities: Cognitive, neuropsychological, and genetic components. Psychological Bulletin, 114(2), 345-362; von Aster, M., & Shalev, R. S. (2007). Number development and developmental dyscalculia. Developmental Medicine and Child Neurology, 49(11), 868-873]. Using functional MRI the current study compares brain activity associated with spatial working memory processes in 8-10-year-old children with DD and normally achieving controls
Machado, M L; Lelong-Boulouard, V; Smith, P F; Freret, T; Philoxene, B; Denise, P; Besnard, S
It is now well established that vestibular information plays an important role in spatial memory processes. Although vestibular lesions induce anxiety in humans, this finding remains controversial in rodents. However, it is possible that anxiety-related behavior is associated with spatial memory impairments after vestibular lesions. We aimed to evaluate anxiety-like behavior and the effect of an anxiolytic treatment during a complex spatial memory task in a rat model of compensated bilateral vestibular lesions. Adult rats were divided into four groups, with or without vestibular lesions and, treated or untreated by diazepam. The vestibular lesion was performed by transtympanic injection of arsanilate and compared to transtympanic saline injection. Diazepam or saline was administered 1h before each test or learning session. Vestibular-lesioned rats exhibited anxiety-like behavior which was decreased with diazepam. Spatial memory performance was similar in control-treated and untreated groups, suggesting no effect on memory at the dose of diazepam used. Spatial memory performances were not modified by anxiolytic drug treatment in vestibular-lesioned rats compared to vestibular-lesioned rats without drug treatment. We conclude that bilateral vestibular lesions in rats induced anxiety-like behavior which was unrelated to spatial memory impairment and was probably specifically related to the loss of vestibular information.
Park, D C; Puglisi, J T; Sovacool, M
In the present study the spatial location of picture and word stimuli was varied across four quadrants of photographic slides. Young and old people received either pictures or words to study and were told to remember either just the item or the item and its location. Recognition memory for items and memory for spatial location were tested. A pictorial superiority effect occurred for both old and young people's item recognition. Additionally, instructions to study position decreased item memory and facilitated position memory in both age groups. Spatial memory was markedly superior for pictures compared with matched words for old and young adults. The results are interpreted within the Hasher and Zacks framework of automatic processing. The implications of the data for designing mnemonic aids for elderly persons are considered.
Mammarella, Irene C; Coltri, Silvia; Lucangeli, Daniela; Cornoldi, Cesare
We report the case of B.A., an 11-year-old child with a nonverbal (visuospatial) learning disability (NLD). Detailed psychometric and neuropsychological assessment on visuospatial working memory (VSWM) revealed specific simultaneous-spatial working memory impairment. A treatment targeting simultaneous-spatial working memory was given to B.A. for seven sessions (over one month); this resulted in improvement of simultaneous-spatial working memory, with the benefit that the training was maintained after six months. Discussion of clinical and theoretical implications is given, taking account of the distinctions that can be made between the different components of visuospatial working memory and different subtypes of NLD, thus allowing the tailoring of specific training to target the impaired VSWM component.
Wang, Wei; Tan, Tao; Tu, Man; He, Wenting; Dong, Zhifang; Han, Huili
Reports of the effects of pentobarbital on learning and memory are contradictory. Some studies have not shown any interference with learning and memory, whereas others have shown that pentobarbital impairs memory and that these impairments can last for long periods. However, it is unclear whether acute local microinjections of pentobarbital affect learning and memory, and if so, the potential mechanisms are also unclear. Here, we reported that the intra-hippocampal infusion of pentobarbital (8.0mM, 1μl per side) significantly impaired hippocampus-dependent spatial learning and memory retrieval. Moreover, in vitro electrophysiological recordings revealed that these behavioral changes were accompanied by impaired hippocampal CA1 long-term potentiation (LTP) and suppressed neuronal excitability as reflected by a decrease in the number of action potentials (APs). These results suggest that acute pentobarbital application causes spatial learning and memory deficits that might be attributable to the suppression of synaptic plasticity and neuronal excitability.
Bischof, Hans-Joachim; Lieshoff, Carsten; Watanabe, Shigeru
Spatial memory and hippocampal function have as yet been investigated mainly in pigeons and food storing songbirds. We show here that the zebra finch, a songbird not specialized in food storing and caching, is also able to learn a spatial memory task and uses a spatial map for finding food in a 'dry water maze'. Hippocampal lesions prevent learning and retention of this spatial task. The immediate early gene (IEG) products Zenk and Fos are expressed within the hippocampus when the bird is learning the task. Spatial learning cannot be assigned to any hippocampal subregion; IEG expression within the hippocampus is patchy and seems almost arbitrarily located. The IEG activation pattern in spatial memory experiments is compared with those in other learning experiments with zebra finches.
Glikmann-Johnston, Yifat; Saling, Michael M.; Reutens, David C.; Stout, Julie C.
Spatial cognition is fundamental for survival in the topographically complex environments inhabited by humans and other animals. The hippocampus, which has a central role in spatial cognition, is characterized by high concentration of serotonin (5-hydroxytryptamine; 5-HT) receptor binding sites, particularly of the 1A receptor (5-HT1A) subtype. This review highlights converging evidence for the role of hippocampal 5-HT1A receptors in spatial learning and memory. We consider studies showing that activation or blockade of the 5-HT1A receptors using agonists or antagonists, respectively, lead to changes in spatial learning and memory. For example, pharmacological manipulation to induce 5-HT release, or to block 5-HT uptake, have indicated that increased extracellular 5-HT concentrations maintain or improve memory performance. In contrast, reduced levels of 5-HT have been shown to impair spatial memory. Furthermore, the lack of 5-HT1A receptor subtype in single gene knockout mice is specifically associated with spatial memory impairments. These findings, along with evidence from recent cognitive imaging studies using positron emission tomography (PET) with 5-HT1A receptor ligands, and studies of individual genetic variance in 5-HT1A receptor availability, strongly suggests that 5-HT, mediated by the 5-HT1A receptor subtype, plays a key role in spatial learning and memory. PMID:26696889
Kelly, Jonathan W; McNamara, Timothy P
Previous research has uncovered three primary cues that influence spatial memory organization:egocentric experience, intrinsic structure (object defined), and extrinsic structure (environment defined). In the present experiments, we assessed the relative importance of these cues when all three were available during learning. Participants learned layouts from two perspectives in immersive virtual reality. In Experiment 1, axes defined by intrinsic and extrinsic structures were in conflict, and learning occurred from two perspectives, each aligned with either the intrinsic or the extrinsic structure. Spatial memories were organized around a reference direction selected from the first perspective, regardless of its alignment with intrinsic or extrinsic structures. In Experiment 2, axes defined by intrinsic and extrinsic structures were congruent, and spatial memories were organized around reference axes defined by those congruent structures, rather than by the initially experienced view. The findings are discussed in the context of spatial memory theory as it relates to real and virtual environments.
Sarkisyan, Gor; Hedlund, Peter B
The hippocampus has been implicated in aspects of spatial memory. Its ability to generate new neurons has been suggested to play a role in memory formation. Hippocampal serotonin (5-HT) neurotransmission has also been proposed as a contributor to memory processing. Studies have shown that the 5-HT(7) receptor is present in the hippocampus in relatively high abundance. Thus the aim of the present study was to investigate the possible role of the 5-HT(7) receptor in spatial memory using 5-HT(7) receptor-deficient mice (5-HT(7)(-/-)). A hippocampus-associated spatial memory deficit in 5-HT(7)(-/-) mice was demonstrated using a novel location/novel object test. A similar reduction in novel location exploration was observed in C57BL/6J mice treated with the selective 5-HT(7) receptor antagonist SB-269970. These findings prompted an extended analysis using the Barnes maze demonstrating that 5-HT(7)(-/-) mice were less efficient in accommodating to changes in spatial arrangement than 5-HT(7)(+/+) mice. 5-HT(7)(-/-) mice had specific impairments in memory compilation required for resolving spatial tasks, which resulted in impaired allocentric spatial memory whereas egocentric spatial memory remained intact after the mice were forced to switch back from striatum-dependent egocentric to hippocampus-dependent allocentric memory. To further investigate the physiological bases underlining these behaviors we compared hippocampal neurogenesis in 5-HT(7)(+/+) and 5-HT(7)(-/-) mice employing BrdU immunohistochemistry. The rate of cell proliferation in the dentate gyrus was identical in the two genotypes. From the current data we conclude that the 5-HT(7)(-/-) mice performed by remembering a simple sequence of actions that resulted in successfully locating a hidden target in a static environment.
Bigdeli, Imanollah; Asia, Masomeh Nikfarjam- Haft; Miladi-Gorji, Hossein; Fadaei, Atefeh
Objective(s): There is controversial evidence about the effect of methamphetamine (METH) on spatial memory. We tested the time- dependent effects of METH on spatial short-term (working) and long-term (reference) memory in METH –sensitized and withdrawn rats in the Morris water maze. Materials and Methods: Rats were sensitized to METH (2 mg/kg, daily/5 days, SC). Rats were trained in water maze (4 trials/day/for 5 days). Probe test was performed 24 hr after training. Two days after probe test, working memory training (2 trials/day/for 5 days) was conducted. Acquisition–retention interval was 75 min. The treatment was continued per day 30 and 120 min before the test. Two groups of METH –sensitized rats were trained in reference memory after a longer period of withdrawal (30 days). Results: Sensitized rats exhibited significantly longer escape latencies on the training, spent significantly less time in the target zone (all, P<0.05), and their working memory impaired 30 min after injection. While, METH has no effect on the spatial learning process 120 min after injection, and rats spent significantly less time in the target zone (P<0.05), as well it has no effect on working memory. Also, impairment of reference memory persisted after prolonged abstinence. Conclusion: Our findings indicated that METH impaired spatial learning and memory 30 min after injection, but spared spatial learning, either acquisition or retention of spatial working, but partially impaired retention of spatial reference memory following 120 min after injection in sensitized rats, which persisted even after prolonged abstinence. PMID:25945235
Carr, Joshua K.; Fournier, Neil M.; Lehmann, Hugo
We examined whether increasing retrieval difficulty in a spatial memory task would promote the recruitment of the anterior cingulate cortex (ACC) similar to what is typically observed during remote memory retrieval. Rats were trained on the hidden platform version of the Morris Water Task and tested three or 30 d later. Retrieval difficulty was…
Zhang, Ming; Storm, Daniel R; Wang, Hongbing
When certain memory becomes obsolete, effective suppression of the previously established memory is essential for animals to adapt to the changing environment. At the cellular level, reversal of synaptic potentiation may be important for neurons to acquire new information and to prevent synaptic saturation. Here, we investigated the function of Ca(2+)-stimulated cAMP signaling in the regulation of bidirectional synaptic plasticity and spatial memory formation in double knock-out mice (DKO) lacking both type 1 and 8 adenylyl cyclases (ACs). In anesthetized animals, the DKO mutants showed defective long-term potentiation (LTP) after a single high-frequency stimulation (HFS) or two spaced HFSs at 100 Hz. However, DKO mice showed normal LTP after a single HFS at 200 Hz or two compressed HFSs at 100 Hz. Interestingly, reversal of synaptic potentiation as well as de novo synaptic depression was impaired in DKO mice. In the Morris water maze, DKO mice showed defective acquisition and memory retention, although the deficits could be attenuated by overtraining or compressed trainings with a shorter intertrial interval. In the reversal platform test, DKO animals were impaired in both relearning and old memory suppression. Furthermore, the extinction of the old spatial memory was not efficient in DKO mice. These data demonstrate that Ca(2+)-stimulated AC activity is important not only for LTP and spatial memory formation but also for the suppression of both previously established synaptic potentiation and old spatial memory.
Nadel, Lynn; Uecker, Anne
Thirty Native American children (mean age=10.3 years), 15 identified with fetal alcohol syndrome (FAS) and 15 controls, were asked to recall places and objects in a task previously shown to be sensitive to memory skills in individuals with and without mental retardation. Children with FAS demonstrated a spatial but not an object memory impairment.…
Ekstrom, Arne D.; Bookheimer, Susan Y.
Imaging, electrophysiological studies, and lesion work have shown that the medial temporal lobe (MTL) is important for episodic memory; however, it is unclear whether different MTL regions support the spatial, temporal, and item elements of episodic memory. In this study we used fMRI to examine retrieval performance emphasizing different aspects…
Shelton, Amy L.; Marchette, Steven A.
Testing spatial memory within the same environment used for learning produces interference between one's immediate representation of current position and the to-be-retrieved position. In a series of 3 experiments, we show that "current position" and its influence on memory performance can be driven by conceptual factors in an ambiguous…
Liu, Hu; Wang, Ting; Dai, Wei; Jiang, Zheng; Li, Yuan-hai; Liu, Xue-sheng
Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase kinase-3β (GSK-3β) activity affects memory. Constitutively active GSK-3β is required for memory retrieval, and propofol has been shown to inhibit GSK-3β. Thus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3β activity. Adult Sprague-Dawley rats were trained on a Morris water maze task (eight acquisition trials in one session) and subjected under the influence of a subhypnotic dose of propofol to a 24-hour probe trial memory retrieval test. The results showed that rats receiving pretest propofol (25 mg/kg) spent significantly less time in the target quadrant but showed no change in locomotor activity compared with those in the control group. Memory retrieval was accompanied by reduced phosphorylation of the serine-9 residue of GSK-3β in the hippocampus, whereas phosphorylation of the tyrosine-216 residue was unaffected. However, propofol blocked this retrieval-associated serine-9 phosphorylation. These findings suggest that subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3β signaling in the hippocampus. PMID:28197192
Liu, Hu; Wang, Ting; Dai, Wei; Jiang, Zheng; Li, Yuan-Hai; Liu, Xue-Sheng
Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase kinase-3β (GSK-3β) activity affects memory. Constitutively active GSK-3β is required for memory retrieval, and propofol has been shown to inhibit GSK-3β. Thus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3β activity. Adult Sprague-Dawley rats were trained on a Morris water maze task (eight acquisition trials in one session) and subjected under the influence of a subhypnotic dose of propofol to a 24-hour probe trial memory retrieval test. The results showed that rats receiving pretest propofol (25 mg/kg) spent significantly less time in the target quadrant but showed no change in locomotor activity compared with those in the control group. Memory retrieval was accompanied by reduced phosphorylation of the serine-9 residue of GSK-3β in the hippocampus, whereas phosphorylation of the tyrosine-216 residue was unaffected. However, propofol blocked this retrieval-associated serine-9 phosphorylation. These findings suggest that subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3β signaling in the hippocampus.
Talamini, Lucia M; Nieuwenhuis, Ingrid L C; Takashima, Atsuko; Jensen, Ole
The last decade has brought forth convincing evidence for a role of sleep in non-declarative memory. A similar function of sleep in episodic memory is supported by various correlational studies, but direct evidence is limited. Here we show that cued recall of face-location associations is significantly higher following a 12-h retention interval containing sleep than following an equally long period of waking. Furthermore, retention is significantly higher over a 24-h sleep-wake interval than over an equally long wake-sleep interval. This difference occurs because retention during sleep was significantly better when sleep followed learning directly, rather than after a day of waking. These data demonstrate a beneficial effect of sleep on memory that cannot be explained solely as a consequence of reduced interference. Rather, our findings suggest a competitive consolidation process, in which the fate of a memory depends, at least in part, on its relative stability at sleep onset: Strong memories tend to be preserved, while weaker memories erode still further. An important aspect of memory consolidation may thus result from the removal of irrelevant memory "debris."
Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H
Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887
Morgan, Celia J. A.; Dodds, Chris M.; Furby, Hannah; Pepper, Fiona; Fam, Johnson; Freeman, Tom P.; Hughes, Emer; Doeller, Christian; King, John; Howes, Oliver; Stone, James M.
Ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist, is rising in popularity as a drug of abuse. Preliminary evidence suggests that chronic, heavy ketamine use may have profound effects on spatial memory but the mechanism of these deficits is as yet unclear. This study aimed to examine the neural mechanism by which heavy ketamine use impairs spatial memory processing. In a sample of 11 frequent ketamine users and 15 poly-drug controls, matched for IQ, age, years in education. We used fMRI utilizing an ROI approach to examine the neural activity of three regions known to support successful navigation; the hippocampus, parahippocampal gyrus, and the caudate nucleus during a virtual reality task of spatial memory. Frequent ketamine users displayed spatial memory deficits, accompanied by and related to, reduced activation in both the right hippocampus and left parahippocampal gyrus during navigation from memory, and in the left caudate during memory updating, compared to controls. Ketamine users also exhibited schizotypal and dissociative symptoms that were related to hippocampal activation. Impairments in spatial memory observed in ketamine users are related to changes in medial temporal lobe activation. Disrupted medial temporal lobe function may be a consequence of chronic ketamine abuse and may relate to schizophrenia-like symptomatology observed in ketamine users. PMID:25538631
Méndez-Couz, Marta; Conejo, Nélida M; Vallejo, Guillermo; Arias, Jorge L
Several studies suggest a prefrontal cortex involvement during the acquisition and consolidation of spatial memory, suggesting an active modulating role at late stages of acquisition processes. Recently, we have reported that the prelimbic and infralimbic areas of the prefrontal cortex, among other structures, are also specifically involved in the late phases of spatial memory extinction. This study aimed to evaluate whether the inactivation of the prelimbic area of the prefrontal cortex impaired spatial memory extinction. For this purpose, male Wistar rats were implanted bilaterally with cannulae into the prelimbic region of the prefrontal cortex. Animals were trained during 5 consecutive days in a hidden platform task and tested for reference spatial memory immediately after the last training session. One day after completing the training task, bilateral infusion of the GABAA receptor agonist Muscimol was performed before the extinction protocol was carried out. Additionally, cytochrome c oxidase histochemistry was applied to map the metabolic brain activity related to the spatial memory extinction under prelimbic cortex inactivation. Results show that animals acquired the reference memory task in the water maze, and the extinction task was successfully completed without significant impairment. However, analysis of the functional brain networks involved by cytochrome oxidase activity interregional correlations showed changes in brain networks between the group treated with Muscimol as compared to the saline-treated group, supporting the involvement of the mammillary bodies at a the late stage in the memory extinction process.
Thurm, Franka; Schuck, Nicolas W; Fauser, Mareike; Doeller, Christian F; Stankevich, Yuliya; Evens, Ricarda; Riedel, Oliver; Storch, Alexander; Lueken, Ulrike; Li, Shu-Chen
Striatal dopamine depletion is a key pathophysiological feature of Parkinson's disease (PD) causing motor and nonmotor symptoms. Research on nonmotor symptoms has mainly focused on frontostriatal functions. However, dopamine pathways ascending from the ventral tegmental area also innervate hippocampal structures and modulate hippocampal-dependent functions, such as spatial memory. Using a virtual spatial navigation task, we investigated dopaminergic modulation of spatial memory in PD patients in a crossover medication ON/OFF design. We examined medication effects on striatal- and hippocampal-dependent spatial memory by either replacing a location cue in the environment or enlarging its spatial boundary. Key results indicate that in contrast to prior evidence for younger adults, PD patients, like their age-matched controls, rely more on striatal cue-based than hippocampal spatial learning. Medication facilitated striatal-dependent cue-location learning, whereas medication benefit in hippocampal boundary-related spatial memory depended on prior experience with the task. Medication effects on spatial memory were comparable to and independent of benefits on motor symptoms. These findings shed new light on dopaminergic modulation of hippocampal-striatal functions in PD.
Ludvig, Nandor; Tang, Hai M; Baptiste, Shirn L; Stefanov, Dimitre G; Kral, John G
This study investigated the possible influence of the Subdural Pharmacotherapy Device (SPD) on spatial memory in 3 adult, male bonnet macaques (Macaca radiata). The device was implanted in and above the subdural/subarachnoid space and cranium overlaying the right parietal/frontal cortex: a circuitry involved in spatial memory processing. A large test chamber, equipped with four baited and four non-baited food-ports at different locations, was used: reaches into empty food ports were counted as spatial memory errors. In this study of within-subject design, before SPD implantation (control) the animals made mean 373.3 ± 114.9 (mean ± SEM) errors in the first spatial memory test session. This value dropped to 47.7 ± 18.4 by the 8th session. After SPD implantation and alternating cycles of transmeningeal saline delivery and local cerebrospinal fluid (CSF) drainage in the implanted cortex the spatial memory error count, with the same port locations, was 33.0 ± 12.2 during the first spatial memory test session, further decreasing to 5.7 ± 3.5 by the 8th post-implantation session (P<0.001 for trend). Replacing transmeningeal saline delivery with similar delivery of the GABAA receptor agonist muscimol (1.0mM) by the SPD did not affect the animals' spatial memory performance, which in fact included at least one completely error-free session per animal over time. The study showed that complication-free implantation and use of the SPD over the parietal and frontal cortices for months leave spatial memory processes intact in nonhuman primates.
Banta Lavenex, Pamela; Lecci, Sandro; Prêtre, Vincent; Brandner, Catherine; Mazza, Christian; Pasquier, Jérôme; Lavenex, Pierre
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.
Méndez-Couz, M; Conejo, N M; González-Pardo, H; Arias, J L
The standard model of memory system consolidation supports the temporal reorganization of brain circuits underlying long-term memory storage, including interactions between the dorsal hippocampus and extra-hippocampal structures. In addition, several brain regions have been suggested to be involved in the retrieval of spatial memory. In particular, several authors reported a possible role of the ventral portion of the hippocampus together with the thalamus or the striatum in the persistence of this type of memory. Accordingly, the present study aimed to evaluate the contribution of different cortical and subcortical brain regions, and neural networks involved in spatial memory retrieval. For this purpose, we used cytochrome c oxidase quantitative histochemistry as a reliable method to measure brain oxidative metabolism. Animals were trained in a hidden platform task and tested for memory retention immediately after the last training session; one week after completing the task, they were also tested in a memory retrieval probe. Results showed that retrieval of the previously learned task was associated with increased levels of oxidative metabolism in the prefrontal cortex, the dorsal and ventral striatum, the anterodorsal thalamic nucleus and the dentate gyrus of the dorsal and ventral hippocampus. The analysis of functional interactions between brain regions suggest that the dorsal and ventral dentate gyrus could be involved in spatial memory retrieval. In addition, the results highlight the key role of the extended hippocampal system, thalamus and striatum in this process. Our study agrees with previous ones reporting interactions between the dorsal hippocampus and the prefrontal cortex during spatial memory retrieval. Furthermore, novel activation patterns of brain networks involving the aforementioned regions were found. These functional brain networks could underlie spatial memory retrieval evaluated in the Morris water maze task.
McEvoy, L K; Smith, M E; Gevins, A
Working memory (WM), the ability to briefly retain and manipulate information in mind, is central to intelligent behavior. Here we take advantage of the high temporal resolution of electrophysiological measures to obtain a millisecond timescale view of the activity induced in distributed cortical networks by tasks that impose significant WM demands. We examined how these networks are affected by the type and amount of information to be remembered, and by the amount of task practice. Evoked potentials (EPs) were obtained from eight subjects performing spatial and verbal versions of a visual n-back WM task (n = 1, 2, 3) on each of three testing days. In well-trained subjects, WM tasks elicited transient responses reflecting different subcomponents of task processing, including transient (lasting 0.02-0.3 s) task-sensitive and load-sensitive EPs, as well as sustained responses (lasting 1-1.5 s), including the prestimulus Contingent Negative Variation (CNV), and post-stimulus frontal and parietal Slow Waves. The transient responses, with the exception of the P300, differed between the verbal and spatial task versions, and between trials with different response requirements. The P300 and the Slow Waves were not affected by task version but were affected by increased WM load. These results suggest that WM emerges from the formation of a dynamic cortical network linking task-specific processes with non-specific, capacity-limited, higher-order attentional processes. Practice effects on the EPs suggested that practice led to the development of a more effective cognitive strategy for dealing with lower-order aspects of task processing, but did not diminish demands made on higher order processes. Thus a simple WM task is shown to be composed of numerous elementary subsecond neural processes whose characteristics vary with type and amount of information being remembered, and amount of practice.
Sawangjit, Anuck; Kelemen, Eduard; Born, Jan; Inostroza, Marion
Social memory refers to the fundamental ability of social species to recognize their conspecifics in quite different contexts. Sleep has been shown to benefit consolidation, especially of hippocampus-dependent episodic memory whereas effects of sleep on social memory are less well studied. Here, we examined the effect of sleep on memory for conspecifics in rats. To discriminate interactions between the consolidation of social memory and of spatial context during sleep, adult Long Evans rats performed on a social discrimination task in a radial arm maze. The Learning phase comprised three 10-min sampling sessions in which the rats explored a juvenile rat presented at a different arm of the maze in each session. Then the rats were allowed to sleep (n = 18) or stayed awake (n = 18) for 120 min. During the following 10-min Test phase, the familiar juvenile rat (of the Learning phase) was presented along with a novel juvenile rat, each rat at an opposite arm of the maze. Significant social recognition memory, as indicated by preferential exploration of the novel over the familiar conspecific, occurred only after post-learning sleep, but not after wakefulness. Sleep, compared with wakefulness, significantly enhanced social recognition during the first minute of the Test phase. However, memory expression depended on the spatial configuration: Significant social recognition memory emerged only after sleep when the rat encountered the novel conspecific at a place different from that of the familiar juvenile in the last sampling session before sleep. Though unspecific retrieval-related effects cannot entirely be excluded, our findings suggest that sleep, rather than independently enhancing social and spatial aspects of memory, consolidates social memory by acting on an episodic representation that binds the memory of the conspecific together with the spatial context in which it was recently encountered.
Sawangjit, Anuck; Kelemen, Eduard; Born, Jan; Inostroza, Marion
Social memory refers to the fundamental ability of social species to recognize their conspecifics in quite different contexts. Sleep has been shown to benefit consolidation, especially of hippocampus-dependent episodic memory whereas effects of sleep on social memory are less well studied. Here, we examined the effect of sleep on memory for conspecifics in rats. To discriminate interactions between the consolidation of social memory and of spatial context during sleep, adult Long Evans rats performed on a social discrimination task in a radial arm maze. The Learning phase comprised three 10-min sampling sessions in which the rats explored a juvenile rat presented at a different arm of the maze in each session. Then the rats were allowed to sleep (n = 18) or stayed awake (n = 18) for 120 min. During the following 10-min Test phase, the familiar juvenile rat (of the Learning phase) was presented along with a novel juvenile rat, each rat at an opposite arm of the maze. Significant social recognition memory, as indicated by preferential exploration of the novel over the familiar conspecific, occurred only after post-learning sleep, but not after wakefulness. Sleep, compared with wakefulness, significantly enhanced social recognition during the first minute of the Test phase. However, memory expression depended on the spatial configuration: Significant social recognition memory emerged only after sleep when the rat encountered the novel conspecific at a place different from that of the familiar juvenile in the last sampling session before sleep. Though unspecific retrieval-related effects cannot entirely be excluded, our findings suggest that sleep, rather than independently enhancing social and spatial aspects of memory, consolidates social memory by acting on an episodic representation that binds the memory of the conspecific together with the spatial context in which it was recently encountered. PMID:28270755
Delorme, Arnaud; Walshaw, Patricia D.; Cho, Alex L.; Bilder, Robert M.; McGough, James J.; McCracken, James T.; Makeig, Scott; Loo, Sandra K.
In the current study we sought to dissociate the component processes of working memory (WM) (vigilance, encoding and maintenance) that may be differentially impaired in attention-deficit/ hyperactivity disorder (ADHD). We collected electroencephalographic (EEG) data from 52 children with ADHD and 47 typically developing (TD) children, ages 7–14 years, while they performed a spatial Sternberg working memory task. We used independent component analysis and time-frequency analysis to identify midoccipital alpha (8–12 Hz) to evaluate encoding processes and frontal midline theta (4–7 Hz) to evaluate maintenance processes. We tested for effects of task difficulty and cue processing to evaluate vigilance. Children with ADHD showed attenuated alpha band event-related desynchronization (ERD) during encoding. This effect was more pronounced when task difficulty was low (consistent with impaired vigilance) and was predictive of memory task performance and symptom severity. Correlated with alpha ERD during encoding were alpha power increases during the maintenance period (relative to baseline), suggesting a compensatory effort. Consistent with this interpretation, midfrontal theta power increases during maintenance were stronger in ADHD and in high-load memory conditions. Furthermore, children with ADHD exhibited a maturational lag in development of posterior alpha power whereas age-related changes in frontal theta power deviated from the TD pattern. Last, subjects with ADHD showed age-independent attenuation of evoked responses to warning cues, suggesting low vigilance. Combined, these three EEG measures predicted diagnosis with 70% accuracy. We conclude that the interplay of impaired vigilance and encoding in ADHD may compromise maintenance and lead to impaired WM performance in this group. PMID:24453310
Lenartowicz, Agatha; Delorme, Arnaud; Walshaw, Patricia D; Cho, Alex L; Bilder, Robert M; McGough, James J; McCracken, James T; Makeig, Scott; Loo, Sandra K
In the current study we sought to dissociate the component processes of working memory (WM) (vigilance, encoding and maintenance) that may be differentially impaired in attention-deficit/ hyperactivity disorder (ADHD). We collected electroencephalographic (EEG) data from 52 children with ADHD and 47 typically developing (TD) children, ages 7-14 years, while they performed a spatial Sternberg working memory task. We used independent component analysis and time-frequency analysis to identify midoccipital alpha (8-12 Hz) to evaluate encoding processes and frontal midline theta (4-7 Hz) to evaluate maintenance processes. We tested for effects of task difficulty and cue processing to evaluate vigilance. Children with ADHD showed attenuated alpha band event-related desynchronization (ERD) during encoding. This effect was more pronounced when task difficulty was low (consistent with impaired vigilance) and was predictive of memory task performance and symptom severity. Correlated with alpha ERD during encoding were alpha power increases during the maintenance period (relative to baseline), suggesting a compensatory effort. Consistent with this interpretation, midfrontal theta power increases during maintenance were stronger in ADHD and in high-load memory conditions. Furthermore, children with ADHD exhibited a maturational lag in development of posterior alpha power whereas age-related changes in frontal theta power deviated from the TD pattern. Last, subjects with ADHD showed age-independent attenuation of evoked responses to warning cues, suggesting low vigilance. Combined, these three EEG measures predicted diagnosis with 70% accuracy. We conclude that the interplay of impaired vigilance and encoding in ADHD may compromise maintenance and lead to impaired WM performance in this group.
Dzieciol, Anna M.; Gadian, David G.; Jentschke, Sebastian; Doeller, Christian F.; Burgess, Neil; Mishkin, Mortimer
The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with “moderate” hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. SIGNIFICANCE STATEMENT In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on
Voyer, Daniel; Voyer, Susan D; Saint-Aubin, Jean
Visual-spatial working memory measures are widely used in clinical and experimental settings. Furthermore, it has been argued that the male advantage in spatial abilities can be explained by a sex difference in visual-spatial working memory. Therefore, sex differences in visual-spatial working memory have important implication for research, theory, and practice, but they have yet to be quantified. The present meta-analysis quantified the magnitude of sex differences in visual-spatial working memory and examined variables that might moderate them. The analysis used a set of 180 effect sizes from healthy males and females drawn from 98 samples ranging in mean age from 3 to 86 years. Multilevel meta-analysis was used on the overall data set to account for non-independent effect sizes. The data also were analyzed in separate task subgroups by means of multilevel and mixed-effects models. Results showed a small but significant male advantage (mean d = 0.155, 95 % confidence interval = 0.087-0.223). All the tasks produced a male advantage, except for memory for location, where a female advantage emerged. Age of the participants was a significant moderator, indicating that sex differences in visual-spatial working memory appeared first in the 13-17 years age group. Removing memory for location tasks from the sample affected the pattern of significant moderators. The present results indicate a male advantage in visual-spatial working memory, although age and specific task modulate the magnitude and direction of the effects. Implications for clinical applications, cognitive model building, and experimental research are discussed.
Lee, Choong-Hee; Ryu, Jungwon; Lee, Sang-Hun; Kim, Hakjin; Lee, Inah
The hippocampus plays critical roles in both object-based event memory and spatial navigation, but it is largely unknown whether the left and right hippocampi play functionally equivalent roles in these cognitive domains. To examine the hemispheric symmetry of human hippocampal functions, we used an fMRI scanner to measure BOLD activity while subjects performed tasks requiring both object-based event memory and spatial navigation in a virtual environment. Specifically, the subjects were required to form object-place paired associate memory after visiting four buildings containing discrete objects in a virtual plus maze. The four buildings were visually identical, and the subjects used distal visual cues (i.e., scenes) to differentiate the buildings. During testing, the subjects were required to identify one of the buildings when cued with a previously associated object, and when shifted to a random place, the subject was expected to navigate to the previously chosen building. We observed that the BOLD activity foci changed from the left hippocampus to the right hippocampus as task demand changed from identifying a previously seen object (object-cueing period) to searching for its paired-associate place (object-cued place recognition period). Furthermore, the efficient retrieval of object-place paired associate memory (object-cued place recognition period) was correlated with the BOLD response of the left hippocampus, whereas the efficient retrieval of relatively pure spatial memory (spatial memory period) was correlated with the right hippocampal BOLD response. These findings suggest that the left and right hippocampi in humans might process qualitatively different information for remembering episodic events in space. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.
Lee, Choong‐Hee; Ryu, Jungwon; Lee, Sang‐Hun; Kim, Hakjin
ABSTRACT The hippocampus plays critical roles in both object‐based event memory and spatial navigation, but it is largely unknown whether the left and right hippocampi play functionally equivalent roles in these cognitive domains. To examine the hemispheric symmetry of human hippocampal functions, we used an fMRI scanner to measure BOLD activity while subjects performed tasks requiring both object‐based event memory and spatial navigation in a virtual environment. Specifically, the subjects were required to form object‐place paired associate memory after visiting four buildings containing discrete objects in a virtual plus maze. The four buildings were visually identical, and the subjects used distal visual cues (i.e., scenes) to differentiate the buildings. During testing, the subjects were required to identify one of the buildings when cued with a previously associated object, and when shifted to a random place, the subject was expected to navigate to the previously chosen building. We observed that the BOLD activity foci changed from the left hippocampus to the right hippocampus as task demand changed from identifying a previously seen object (object‐cueing period) to searching for its paired‐associate place (object‐cued place recognition period). Furthermore, the efficient retrieval of object‐place paired associate memory (object‐cued place recognition period) was correlated with the BOLD response of the left hippocampus, whereas the efficient retrieval of relatively pure spatial memory (spatial memory period) was correlated with the right hippocampal BOLD response. These findings suggest that the left and right hippocampi in humans might process qualitatively different information for remembering episodic events in space. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27009679
Working memory capacity increases throughout childhood and adolescence, which is important for the development of a wide range of cognitive abilities, including complex reasoning. The spatial-span task, in which subjects retain information about the order and position of a number of objects, is a sensitive task to measure development of spatial working memory. This review considers results from previous neuroimaging studies investigating the neural correlates of this development. Older children and adolescents, with higher capacity, have been found to have higher brain activity in the intraparietal cortex and in the posterior part of the superior frontal sulcus, during the performance of working memory tasks. The structural maturation of white matter has been investigated by diffusion tensor magnetic resonance imaging (DTI). This has revealed several regions in the frontal lobes in which white matter maturation is correlated with the development of working memory. Among these is a superior fronto-parietal white matter region, located close to the grey matter regions that are implicated in the development of working memory. Furthermore, the degree of white matter maturation is positively correlated with the degree of cortical activation in the frontal and parietal regions. This suggests that during childhood and adolescence, there is development of networks related to specific cognitive functions, such as visuo-spatial working memory. These networks not only consist of cortical areas but also the white matter tracts connecting them. For visuo-spatial working memory, this network could consist of the superior frontal and intraparietal cortex.
Scriba, M F; Gasparini, J; Jacquin, L; Mettke-Hofmann, C; Rattenborg, N C; Roulin, A
Poor environmental conditions experienced during early development can have negative long-term consequences on fitness. Animals can compensate for negative developmental effects through phenotypic plasticity by diverting resources from non-vital to vital traits such as spatial memory to enhance foraging efficiency. We tested in young feral pigeons (Columba livia) how diets of different nutritional value during development affect the capacity to retrieve food hidden in a spatially complex environment, a process we refer to as 'spatial memory'. Parents were fed with either high- or low-quality food from egg laying until young fledged, after which all young pigeons received the same high-quality diet until memory performance was tested at 6 months of age. The pigeons were trained to learn a food location out of 18 possible locations in one session, and then their memory of this location was tested 24 h later. Birds reared with the low-quality diet made fewer errors in the memory test. These results demonstrate that food quality during development has long-lasting effects on memory, with a moderate nutritional deficit improving spatial memory performance in a foraging context. It might be that under poor feeding conditions resources are redirected from non-vital to vital traits, or pigeons raised with low-quality food might be better in using environmental cues such as the position of the sun to find where food was hidden.
Lee, Ogyoung; Redford, Melissa A.
The goal of the present study was to test the effects of working memory on speech production. Twenty American-English speaking adults produced syntactically complex sentences in tasks that taxed either verbal or spatial working memory. Sentences spoken under load were produced with more errors, fewer prosodic breaks, and at faster rates than sentence produced in the control conditions, but other acoustic correlates of rhythm and intonation did not change. Verbal and spatial working memory had very similar effects on production, suggesting that the different span tasks used to tax working memory merely shifted speakers’ attention away from the act of speaking. This finding runs contra the hypothesis of incremental phonological/phonetic encoding, which predicts the manipulation of information in verbal working memory during speech production. PMID:26448563
Kaufman, Miron; Allen, Philip
The molar neural network model of P. Allen, M. Kaufman, A. F. Smith, R. E. Popper, Psychology and Aging 13, 501 (1998) and Experimental Aging Research, 24, 307 (1998) is extended to incorporate reaction times. In our model the entropy associated with a particular task determines the reaction time. We use this molar neural model to directly analyze experimental data on episodic (spatial) memory and semantic (lexical) memory tasks. In particular we are interested in the effect of aging on the two types of memory. We find that there is no difference in performance levels for lexical memory tasks between younger and older adults. In the case spatial memory tasks we find that aging has a detrimental effect on the performance level. This work is supported by NIH/NIA grant AG09282-06.
Cheung, Lily K; Eaton, Angie
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease.
Saab, Bechara J; Georgiou, John; Nath, Arup; Lee, Frank J S; Wang, Min; Michalon, Aubin; Liu, Fang; Mansuy, Isabelle M; Roder, John C
The molecular underpinnings of exploration and its link to learning and memory remain poorly understood. Here we show that inducible, modest overexpression of neuronal calcium sensor 1 (Ncs1) selectively in the adult murine dentate gyrus (DG) promotes a specific form of exploratory behavior. The mice also display a selective facilitation of long-term potentiation (LTP) in the medial perforant path and a selective enhancement in rapid-acquisition spatial memory, phenotypes that are reversed by direct application of a cell-permeant peptide (DNIP) designed to interfere with NCS-1 binding to the dopamine type-2 receptor (D2R). Moreover, the DNIP and the D2R-selective antagonist L-741,626 attenuated exploratory behavior, DG LTP, and spatial memory in control mice. These data demonstrate a role for NCS-1 and D2R in DG plasticity and provide insight for understanding how the DG contributes to the origin of exploration and spatial memory acquisition.
Perfilova, V N; Zhakupova, G A; Lashchenova, L I; Lebedeva, S A; Tyurenkov, I N
Spatial memory was studied in 2-month-old offspring of rats subjected to different types of experimental preeclampsia (replacement of drinking water with 1.8% NaCl from day 1 to 21 of gestation or intraperitoneal administration of non-selective NO-synthase inhibitor L-NAME to pregnant rats in a daily dose of 25 mg/kg for 7 days on gestation days 14-20). Spatial memory was evaluated in an elevated 8-arm radial maze. Both types of experimental preeclampsia impaired spatial (long-term and short-term) memory and can be used in the development of drugs correcting negative effects of this pregnancy complication on memory.
Bitencourt, Rafael M; Guerra de Souza, Ana C; Bicca, Maíra A; Pamplona, Fabrício A; de Mello, Nelson; Passos, Giselle F; Medeiros, Rodrigo; Takahashi, Reinaldo N; Calixto, João B; Prediger, Rui D
Previous studies have demonstrated that targeting bradykinin receptors is a promising strategy to counteract the cognitive impairment related with aging and Alzheimer's disease (AD). The hippocampus is critical for cognition, and abnormalities in this brain region are linked to the decline in mental ability. Nevertheless, the impact of bradykinin signaling on hippocampal function is unknown. Therefore, we sought to determine the role of hippocampal bradykinin receptors B1R and B2R on the cognitive decline of middle-aged rats. Twelve-month-old rats exhibited impaired ability to acquire and retrieve spatial information in the Morris water maze task. A single intra-hippocampal injection of the selective B1R antagonist des-Arg(9)-[Leu(8)]-bradykinin (DALBK, 3 nmol), but not the selective B2R antagonist D-Arg-[Hyp(3),Thi(5),D-Tic(7),Oic(8)]-BK (Hoe 140, 3 nmol), reversed the spatial learning and memory deficits on these animals. However, both drugs did not affect the cognitive function in 3-month-old rats, suggesting absence of nootropic properties. Molecular biology analysis revealed an up-regulation of B1R expression in the hippocampal CA1 sub-region and in the pre-frontal cortex of 12-month-old rats, whereas no changes in the B2R expression were observed in middle-aged rats. These findings provide new evidence that inappropriate hippocampal B1R expression and activation exert a critical role on the spatial learning and memory deficits in middle-aged rats. Therefore, selective B1R antagonists, especially orally active non-peptide antagonists, may represent drugs of potential interest to counteract the age-related cognitive decline.
Mammarella, Irene Cristina; Lucangeli, Daniela; Cornoldi, Cesare
Visuospatial working memory and its involvement in arithmetic were examined in two groups of 7- to 11-year-olds: one comprising children described by teachers as displaying symptoms of nonverbal learning difficulties (N = 21), the other a control group without learning disabilities (N = 21). The two groups were matched for verbal abilities, age, gender, and sociocultural level. The children were presented with a visuospatial working memory battery of recognition tests involving visual, spatial-sequential and spatial-simultaneous processes, and two arithmetic tasks (number ordering and written calculations). The two groups were found to differ on some spatial tasks but not in the visual working memory tasks. On the arithmetic tasks, the children with nonverbal learning difficulties made more errors than controls in calculation and were slower in number ordering. A discriminant function analysis confirmed the crucial role of spatial-sequential working memory in distinguishing between the two groups. Results are discussed with reference to spatial working memory and arithmetic difficulties in nonverbal learning disabilities. Implications for the relationship between visuospatial working memory and arithmetic are also considered.
Allan, K; Allan, J L
To help maintain a positive energy balance in ancestral human habitats, evolution appears to have designed a functional bias in spatial memory that enhances our ability to remember the location of high-calorie foodstuffs. Here, we investigated whether this functional bias has obesogenic consequences for individuals living in a modern urban environment. Spatial memory, dietary intentions, and perceived desirability, for high-calorie snacks and lower-calorie fruits and vegetables were measured using a computer-based task in 41 women (age: 18-35, body mass index: 18.5-30.0). Using multiple linear regression, we analyzed whether enhanced spatial memory for high-calorie snacks versus fruits and vegetables predicted BMI, controlling for dietary intention strength and perceived food desirability. We observed that enhanced spatial memory for high-calorie snacks (both independently, and relative to that for fruits and vegetables), significantly predicted higher BMI. The evolved function of high-calorie bias in human spatial memory, to promote positive energy balance, would therefore appear to be intact. But our data reveal that this function may contribute to higher, less healthy BMI in individuals in whom the memory bias is most marked. Our findings reveal a novel cognitive marker of vulnerability to weight gain that, once the proximal mechanisms are understood, may offer new possibilities for weight control interventions.
Rensel, Michelle A; Ellis, Jesse M S; Harvey, Brigit; Schlinger, Barney A
Estrogens significantly impact spatial memory function in mammalian species. Songbirds express the estrogen synthetic enzyme aromatase at relatively high levels in the hippocampus and there is evidence from zebra finches that estrogens facilitate performance on spatial learning and/or memory tasks. It is unknown, however, whether estrogens influence hippocampal function in songbirds that naturally exhibit memory-intensive behaviors, such as cache recovery observed in many corvid species. To address this question, we examined the impact of estradiol on spatial memory in non-breeding Western scrub-jays, a species that routinely participates in food caching and retrieval in nature and in captivity. We also asked if there were sex differences in performance or responses to estradiol. Utilizing a combination of an aromatase inhibitor, fadrozole, with estradiol implants, we found that while overall cache recovery rates were unaffected by estradiol, several other indices of spatial memory, including searching efficiency and efficiency to retrieve the first item, were impaired in the presence of estradiol. In addition, males and females differed in some performance measures, although these differences appeared to be a consequence of the nature of the task as neither sex consistently out-performed the other. Overall, our data suggest that a sustained estradiol elevation in a food-caching bird impairs some, but not all, aspects of spatial memory on an innate behavioral task, at times in a sex-specific manner.
Wareing, Michelle; Fisk, John E; Murphy, Philip; Montgomery, Catharine
Verbal working memory and executive deficits have been observed in ecstasy users. The present study sought to establish whether these also extended to visuo-spatial working memory. Thirty-six current ecstasy users, 12 former users (abstinent for at least 6 months) and 31 individuals that had never used ecstasy were tested on a maintenance plus type visuo-spatial working memory task. The task required participants to recall a sequence of specially marked cells in a four-by-four matrix display while at the same time performing a concurrent visual judgement task. Both the current and former user groups registered impairments relative to nonusers. These remained significant following statistical controls for a range of potentially confounding variables including the use of various other drugs during the 3 months prior to testing. Users were unimpaired on a simple spatial span measure suggesting that the deficits observed reflected the executive aspects of the spatial working memory task. Also consistent with executive involvement, statistical controls for measures of verbal working memory performance (computation span) removed half of the ecstasy-related variance in spatial working memory. The possibility that the pattern of results obtained might reflect some general impairment in information processing efficiency is discussed.
Pooters, Tine; Van der Jeugd, Ann; Callaerts-Vegh, Zsuzsanna; D'Hooge, Rudi
Spatial learning and memory in rodents represent close equivalents of human episodic declarative memory, which is especially sensitive to cerebral aging, neurodegeneration, and various neuropsychiatric disorders. Many tests and protocols are available for use in laboratory rodents, but Morris water maze and radial-arm maze remain the most widely used as well as the most valid and reliable spatial tests. Telencephalic neurocircuitry that plays functional roles in spatial learning and memory includes hippocampus, dorsal striatum and medial prefrontal cortex. Prefrontal-hippocampal circuitry comprises the major associative system in the rodent brain, and is critical for navigation in physical space, whereas interconnections between prefrontal cortex and dorsal striatum are probably more important for motivational or goal-directed aspects of spatial learning. Two major forms of synaptic plasticity, namely long-term potentiation, a lasting increase in synaptic strength between simultaneously activated neurons, and long-term depression, a decrease in synaptic strength, have been found to occur in hippocampus, dorsal striatum and medial prefrontal cortex. These and other phenomena of synaptic plasticity are probably crucial for the involvement of telencephalic neurocircuitry in spatial learning and memory. They also seem to play a role in the pathophysiology of two brain pathologies with episodic declarative memory impairments as core symptoms, namely Alzheimer's disease and schizophrenia. Further research emphasis on rodent telencephalic neurocircuitry could be relevant to more valid and reliable preclinical research on these most devastating brain disorders. This article is part of a Special Issue entitled SI: Brain and Memory.
Jang, Saebyeol; Dilger, Ryan N.; Johnson, Rodney W.
A dysregulated overexpression of inflammatory mediators by microglia may facilitate cognitive aging and neurodegeneration. Considerable evidence suggests the flavonoid luteolin has antiinflammatory effects, but its ability to inhibit microglia, reduce inflammatory mediators, and improve hippocampal-dependent learning and memory in aged mice is unknown. In initial studies, pretreatment of BV-2 microglia with luteolin inhibited the induction of inflammatory genes and the release of inflammatory mediators after lipopolysaccharide (LPS) stimulation. Supernatants from LPS-stimulated microglia caused discernible death in Neuro.2a cells. However, treating microglia with luteolin prior to LPS reduced neuronal cell death caused by conditioned supernatants, indicating luteolin was neuroprotective. In subsequent studies, adult (3–6 mo) and aged (22–24 mo) mice were fed control or luteolin (20 mg/d)-supplemented diet for 4 wk and spatial working memory was assessed as were several inflammatory markers in the hippocampus. Aged mice fed control diet exhibited deficits in spatial working memory and expression of inflammatory markers in the hippocampus indicative of increased microglial cell activity. Luteolin consumption improved spatial working memory and restored expression of inflammatory markers in the hippocampus compared with that of young adults. Luteolin did not affect either spatial working memory or inflammatory markers in young adults. Taken together, the current findings suggest dietary luteolin enhanced spatial working memory by mitigating microglial-associated inflammation in the hippocampus. Therefore, luteolin consumption may be beneficial in preventing or treating conditions involving increased microglial cell activity and inflammation. PMID:20685893
Fremouw, Thane; Fessler, Christy L; Ferguson, Robert J; Burguete, Yamil
Clinical studies suggest that chemotherapy is associated with long-term cognitive impairment in some patients. A number of underlying mechanisms have been proposed, however, the etiology of chemotherapy-related cognitive dysfunction remains relatively unknown. As part of a multifaceted approach, animal models of chemotherapy-induced cognitive impairment are being developed. Thus far, the majority of animal studies have utilized a rat model, however, mice may prove particularly beneficial in studying genetic risk factors for developing chemotherapy-induced cognitive impairment. Various chemotherapy agents, including cytosine arabinoside (Ara-C), have been found to impair remote spatial memory in rats in the Morris water maze. The present study evaluated the effects of Ara-C on remote (30 d) spatial memory in mice. In addition, the possibility that time relative to chemotherapy treatment may modulate the effect of chemotherapy on spatial learning and/or recent (1 d) memory was explored. Male C57BL/6J mice received either Ara-C (275 mg/kg i.p. daily for 5 days) or saline. Spatial learning and memory was assessed using the Morris water maze. Half the mice performed a remote (30 d) memory version of the task and the other half performed a recent (1 d) memory version of the task. The experiment was designed such that the probe trial for the recent memory version occurred on the same day relative to chemotherapy treatment as the remote memory version. Despite significant toxic effects as assessed by weight loss, Ara-C treated mice performed as well as control mice during acquisition, recent memory, and remote memory portions of the task. As are some humans, C57BL/6J mice may be resistant to at least some aspects of chemotherapy induced cognitive decline.
Vanzella, Cláudia; Sanches, Eduardo Farias; Odorcyk, Felipe Kawa; Nicola, Fabrício; Kolling, Janaína; Longoni, Aline; Dos Santos, Tiago Marcon; Wyse, Angela Terezinha de Souza; Netto, Carlos Alexandre
Regular physical activity has shown to improve the quality of life and to prevent age-related memory deficits. Memory processing requires proper regulation of several enzymes such as sodium-potassium adenosine triphosphatase (Na(+), K(+)-ATPase) and acetylcholinesterase (AChE), which have a pivotal role in neuronal transmission. The present study investigated the effects of a treadmill running protocol in young (3 months), mature (6 months) and aged (22 months) Wistar rats, on: (a) cognitive function, as assessed in the Water maze spatial tasks; (b) Na(+), K(+)-ATPase and AChE activities in the hippocampus following cognitive training alone or treadmill running combined with cognitive training. Animals of all ages were assigned to naïve (with no behavioral or exercise training), sedentary (non-exercised, with cognitive training) and exercised (20 min of daily running sessions, 3 times per week for 4 weeks and with cognitive training) groups. Cognition was assessed by reference and working memory tasks run in the Morris Water maze; 24 h after last session of behavioral testing, hippocampi were collected for biochemical analysis. Results demonstrated that: (a) a moderate treadmill running exercise prevented spatial learning and memory deficits in aged rats; (b) training in the Water maze increased both Na(+), K(+)-ATPase and AChE activities in the hippocampus of mature and aged rats; (c) aged exercised rats displayed an even further increase of Na(+), K(+)-ATPase activity in the hippocampus, (d) enzyme activity correlated with memory performance in aged rats. It is suggested that exercise prevents spatial memory deficits in aged rats probably through the activation of Na(+), K(+)-ATPase in the hippocampus.
Murray, Andrew J; Sauer, Jonas-Frederic; Riedel, Gernot; McClure, Christina; Ansel, Laura; Cheyne, Lesley; Bartos, Marlene; Wisden, William; Wulff, Peer
Parvalbumin-positive GABAergic interneurons in cortical circuits are hypothesized to control cognitive function. To test this idea directly, we functionally removed parvalbumin-positive interneurons selectively from hippocampal CA1 in mice. We found that parvalbumin-positive interneurons are dispensable for spatial reference, but are essential for spatial working memory.
Rahman, Qazi; Newland, Cherie; Smyth, Beatrice Mary
Prior research has demonstrated robust sex and sexual orientation-related differences in object location memory in humans. Here we show that this sexual variation may depend on the spatial position of target objects and the task-specific nature of the spatial array. We tested the recovery of object locations in three object arrays (object…
Park, Denise Cortis; And Others
Tested recognition memory for items and spatial location by varying picture and word stimuli across four slide quadrants. Results showed a pictorial superiority effect for item recognition and a greater ability to remember the spatial location of pictures versus words for both old and young adults (N=95). (WAS)
Guerard, Katherine; Tremblay, Sebastien
The authors revisited evidence in favor of modularity and of functional equivalence between the processing of verbal and spatial information in short-term memory. This was done by investigating the patterns of intrusions, omissions, transpositions, and fill-ins in verbal and spatial serial recall and order reconstruction tasks under control,…
Madl, Tamas; Chen, Ke; Montaldi, Daniela; Trappl, Robert
Spatial memory refers to the part of the memory system that encodes, stores, recognizes and recalls spatial information about the environment and the agent's orientation within it. Such information is required to be able to navigate to goal locations, and is vitally important for any embodied agent, or model thereof, for reaching goals in a spatially extended environment. In this paper, a number of computationally implemented cognitive models of spatial memory are reviewed and compared. Three categories of models are considered: symbolic models, neural network models, and models that are part of a systems-level cognitive architecture. Representative models from each category are described and compared in a number of dimensions along which simulation models can differ (level of modeling, types of representation, structural accuracy, generality and abstraction, environment complexity), including their possible mapping to the underlying neural substrate. Neural mappings are rarely explicated in the context of behaviorally validated models, but they could be useful to cognitive modeling research by providing a new approach for investigating a model's plausibility. Finally, suggested experimental neuroscience methods are described for verifying the biological plausibility of computational cognitive models of spatial memory, and open questions for the field of spatial memory modeling are outlined.
Bellani, Rudy; Luecken, Linda J; Conrad, Cheryl D
We tested the hypothesis that peripubertal anxiety levels are predictive of the detrimental effects of chronic stress on hippocampal-dependent spatial memory. The anxiety levels of peripubertal male Sprague-Dawley rats (43 days old) were characterized using open field and elevated plus mazes, followed by chronic restraint stress for 6 h/day/21 days beginning in young adulthood (75 days). Following chronic stress treatment, rats were tested on the spatial Y-maze using two inter-trial interval levels of difficulty (4 h: 1 day post-chronic stress; 1 min: 2 days post-chronic stress). As expected, all groups displayed intact spatial memory in the less difficult 1 min version of the Y-maze. However, in the 4 h version of the Y-maze, chronically stressed high anxiety rats showed impaired spatial memory, while chronically stressed low anxiety and control (low and high anxiety) rats displayed intact spatial memory. Moreover, a month after chronic stress ended, high anxiety rats had significantly higher basal corticosterone levels than low anxiety rats (control and stress). These results indicate that peripubertal anxiety and chronic stress interact to influence hippocampal-dependent spatial memory in adulthood.
Heuer, Eric; Bachevalier, Jocelyne
Earlier studies in monkeys have reported mild impairment in recognition memory following nonselective neonatal hippocampal lesions (Bachevalier, Beauregard, & Alvarado, 1999; Rehbein, Killiany, & Mahut, 2005). To assess whether the memory impairment could have resulted from damage to cortical areas adjacent to the hippocampus, we tested adult monkeys with neonatal focal hippocampal lesions and sham-operated controls in three recognition tasks: delayed nonmatching-to-sample, object memory span, and spatial memory span. Further, to rule out that normal performance on these tasks may relate to functional sparing following neonatal hippocampal lesions, we tested adult monkeys that had received the same focal hippocampal lesions in adulthood and their controls in the same three memory tasks. Both early and late onset focal hippocampal damage did not alter performance on any of the three tasks, suggesting that damage to cortical areas adjacent to the hippocampus was likely responsible for the recognition impairment reported by the earlier studies. In addition, given that animals with early and late onset hippocampal lesions showed object and spatial recognition impairment when tested in a visual paired comparison task (Zeamer, Meunier, & Bachevalier, Submitted; Zeamer, Heuer & Bachevalier, 2010), the data suggest that not all object and spatial recognition tasks are solved by hippocampal-dependent memory processes. The current data may not only help explain the neural substrate for the partial recognition memory impairment reported in cases of developmental amnesia (Adlam, Malloy, Mishkin, & Vargha-Khadem, 2009), but they are also clinically relevant given that the object and spatial memory tasks used in monkeys are often translated to investigate memory functions in several populations of human infants and children in which dysfunction of the hippocampus is suspected. PMID:21341885
Barnhart, Christopher D; Yang, Dongren; Lein, Pamela J
Mouse models have been indispensable for elucidating normal and pathological processes that influence learning and memory. A widely used method for assessing these cognitive processes in mice is the Morris water maze, a classic test for examining spatial learning and memory. However, Morris water maze studies with mice have principally been performed using adult animals, which preclude studies of critical neurodevelopmental periods when the cellular and molecular substrates of learning and memory are formed. While weanling rats have been successfully trained in the Morris water maze, there have been few attempts to test weanling mice in this behavioral paradigm even though mice offer significant experimental advantages because of the availability of many genetically modified strains. Here, we present experimental evidence that weanling mice can be trained in the Morris water maze beginning on postnatal day 24. Maze-trained weanling mice exhibit significant improvements in spatial learning over the training period and results of the probe trial indicate the development of spatial memory. There were no sex differences in the animals' performance in these tasks. In addition, molecular biomarkers of synaptic plasticity are upregulated in maze-trained mice at the transcript level. These findings demonstrate that the Morris water maze can be used to assess spatial learning and memory in weanling mice, providing a potentially powerful experimental approach for examining the influence of genes, environmental factors and their interactions on the development of learning and memory.
Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence
Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9-10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported.
Moroni, Fabio; Nobili, Lino; Iaria, Giuseppe; Sartori, Ivana; Marzano, Cristina; Tempesta, Daniela; Proserpio, Paola; Lo Russo, Giorgio; Gozzo, Francesca; Cipolli, Carlo; De Gennaro, Luigi; Ferrara, Michele
The hypothesis that sleep is instrumental in the process of memory consolidation is currently largely accepted. Hippocampal formation is involved in the acquisition of declarative memories and particularly of spatial memories. Nevertheless, although largely investigated in rodents, the relations between spatial memory and hippocampal EEG activity have been scarcely studied in humans. Aimed to evaluate the effects of spatial learning on human hippocampal sleep EEG activity, we recorded hippocampal Stereo-EEG (SEEG) in a group of refractory epilepsy patients undergoing presurgical clinical evaluation, after a training on a spatial navigation task. We observed that hippocampal high-delta (2-4 Hz range) activity increases during the first NREM episode after learning compared to the baseline night. Moreover, the amount of hippocampal NREM high-delta power was correlated with task performance at retest. The effect involved only the hippocampal EEG frequencies inasmuch no differences were observed at the neocortical electrodes and in the traditional polysomnographic measures. The present findings support the crucial role of hippocampal slow EEG frequencies during sleep in the memory consolidation processes. More generally, together with previous results, they suggest that slow frequency rhythms are a fundamental characteristic of human hippocampal EEG during both sleep and wakefulness, and are related to the consolidation of different types of memories.
Kaufman, Scott Barry
Sex differences in spatial ability are well documented, but poorly understood. In order to see whether working memory is an important factor in these differences, 50 males and 50 females performed tests of three-dimensional mental rotation and spatial visualization, along with tests of spatial and verbal working memory. Substantial differences…
Arthur, Joeanna C; Philbeck, John W; Kleene, Nicholas J; Chichka, David
Angular path integration refers to the ability to maintain an estimate of self-location after a rotational displacement by integrating internally-generated (idiothetic) self-motion signals over time. Previous work has found that non-sensory inputs, namely spatial memory, can play a powerful role in angular path integration (Arthur et al., 2007, 2009). Here we investigated the conditions under which spatial memory facilitates angular path integration. We hypothesized that the benefit of spatial memory is particularly likely in spatial updating tasks in which one's self-location estimate is referenced to external space. To test this idea, we administered passive, non-visual body rotations (ranging 40°-140°) about the yaw axis and asked participants to use verbal reports or open-loop manual pointing to indicate the magnitude of the rotation. Prior to some trials, previews of the surrounding environment were given. We found that when participants adopted an egocentric frame of reference, the previously-observed benefit of previews on within-subject response precision was not manifested, regardless of whether remembered spatial frameworks were derived from vision or spatial language. We conclude that the powerful effect of spatial memory is dependent on one's frame of reference during self-motion updating.
While neurons in the lateral prefrontal cortex (PFC) encode spatial information during the performance of working memory tasks, they are also known to participate in subjective behavior such as spatial attention and action selection. In the present study, we analyzed the activity of primate PFC neurons during the performance of a free choice memory-guided saccade task in which the monkeys needed to choose a saccade direction by themselves. In trials when the receptive field location was subsequently chosen by the animal, PFC neurons with spatially selective visual response started to show greater activation before cue onset. This result suggests that the fluctuation of firing before cue presentation prematurely biased the representation of a certain spatial location and eventually encouraged the subsequent choice of that location. In addition, modulation of the activity by the animal's choice was observed only in neurons with high sustainability of activation and was also dependent on the spatial configuration of the visual cues. These findings were consistent with known characteristics of PFC neurons in information maintenance in spatial working memory function. These results suggest that precue fluctuation of spatial representation was shared and enhanced through the working memory network in the PFC and could finally influence the animal's free choice of saccade direction. The present study revealed that the PFC plays an important role in decision making in a free choice condition and that the dynamics of decision making are constrained by the network architecture embedded in this cortical area. PMID:26490287
Mochizuki, Kei; Funahashi, Shintaro
While neurons in the lateral prefrontal cortex (PFC) encode spatial information during the performance of working memory tasks, they are also known to participate in subjective behavior such as spatial attention and action selection. In the present study, we analyzed the activity of primate PFC neurons during the performance of a free choice memory-guided saccade task in which the monkeys needed to choose a saccade direction by themselves. In trials when the receptive field location was subsequently chosen by the animal, PFC neurons with spatially selective visual response started to show greater activation before cue onset. This result suggests that the fluctuation of firing before cue presentation prematurely biased the representation of a certain spatial location and eventually encouraged the subsequent choice of that location. In addition, modulation of the activity by the animal's choice was observed only in neurons with high sustainability of activation and was also dependent on the spatial configuration of the visual cues. These findings were consistent with known characteristics of PFC neurons in information maintenance in spatial working memory function. These results suggest that precue fluctuation of spatial representation was shared and enhanced through the working memory network in the PFC and could finally influence the animal's free choice of saccade direction. The present study revealed that the PFC plays an important role in decision making in a free choice condition and that the dynamics of decision making are constrained by the network architecture embedded in this cortical area.
Guan, Zhiwei; Peng, Xuwen; Fang, Jidong
Loss of sleep may result in memory impairment. However, little is known about the biochemical basis for memory deficits induced by sleep deprivation. Extracellular signal-regulated kinase (ERK) is involved in memory consolidation in different tasks. Phosphorylation of ERK is necessary for its activation and is an important step in mediating neuronal responses to synaptic activities. The aim of the present study was to determine the effects of total sleep deprivation (TSD) on memory and ERK phosphorylation in the brain. Rats were trained in Morris water maze to find a hidden platform (a spatial task) or a visible platform (a nonspatial task) after 6 h TSD or spontaneous sleep. TSD had no effect on spatial learning, but significantly impaired spatial memory tested 24 h after training. Nonspatial learning and memory were not impaired by TSD. Phospho-ERK levels in the hippocampus were significantly reduced after 6 h TSD compared to the controls and returned to the control levels after 2 h recovery sleep. Total ERK1 and ERK2 were slightly increased after 6 h TSD and returned to the control levels after 2 h recovery sleep. These alterations were not observed in the cortex after TSD. Protein phosphotase-1 and mitogen-activated protein kinase phosphatase-2, which dephosphorylates phospho-ERK, were also measured, but they were not altered by TSD. The impairments of both spatial memory and ERK phosphorylation indicate that the hippocampus is vulnerable to sleep loss. These results are consistent with the idea that decreased ERK activation in the hippocampus is involved in sleep deprivation-induced spatial memory impairment.
Juan, M-Carmen; Mendez-Lopez, Magdalena; Perez-Hernandez, Elena; Albiol-Perez, Sergio
Short-term memory can be defined as the capacity for holding a small amount of information in mind in an active state for a short period of time. Although some instruments have been developed to study spatial short-term memory in real environments, there are no instruments that are specifically designed to assess visuospatial short-term memory in an attractive way to children. In this paper, we present the ARSM (Augmented Reality Spatial Memory) task, the first Augmented Reality task that involves a user's movement to assess spatial short-term memory in healthy children. The experimental procedure of the ARSM task was designed to assess the children's skill to retain visuospatial information. They were individually asked to remember the real place where augmented reality objects were located. The children (N = 76) were divided into two groups: preschool (5-6 year olds) and primary school (7-8 year olds). We found a significant improvement in ARSM task performance in the older group. The correlations between scores for the ARSM task and traditional procedures were significant. These traditional procedures were the Dot Matrix subtest for the assessment of visuospatial short-term memory of the computerized AWMA-2 battery and a parent's questionnaire about a child's everyday spatial memory. Hence, we suggest that the ARSM task has high verisimilitude with spatial short-term memory skills in real life. In addition, we evaluated the ARSM task's usability and perceived satisfaction. The study revealed that the younger children were more satisfied with the ARSM task. This novel instrument could be useful in detecting visuospatial short-term difficulties that affect specific developmental navigational disorders and/or school academic achievement.
Juan, M.-Carmen; Mendez-Lopez, Magdalena; Perez-Hernandez, Elena; Albiol-Perez, Sergio
Short-term memory can be defined as the capacity for holding a small amount of information in mind in an active state for a short period of time. Although some instruments have been developed to study spatial short-term memory in real environments, there are no instruments that are specifically designed to assess visuospatial short-term memory in an attractive way to children. In this paper, we present the ARSM (Augmented Reality Spatial Memory) task, the first Augmented Reality task that involves a user's movement to assess spatial short-term memory in healthy children. The experimental procedure of the ARSM task was designed to assess the children's skill to retain visuospatial information. They were individually asked to remember the real place where augmented reality objects were located. The children (N = 76) were divided into two groups: preschool (5–6 year olds) and primary school (7–8 year olds). We found a significant improvement in ARSM task performance in the older group. The correlations between scores for the ARSM task and traditional procedures were significant. These traditional procedures were the Dot Matrix subtest for the assessment of visuospatial short-term memory of the computerized AWMA-2 battery and a parent's questionnaire about a child's everyday spatial memory. Hence, we suggest that the ARSM task has high verisimilitude with spatial short-term memory skills in real life. In addition, we evaluated the ARSM task's usability and perceived satisfaction. The study revealed that the younger children were more satisfied with the ARSM task. This novel instrument could be useful in detecting visuospatial short-term difficulties that affect specific developmental navigational disorders and/or school academic achievement. PMID:25438146
Conrad, Cheryl D
The purpose of this review is to evaluate the effects of chronic stress on hippocampal-dependent function, based primarily upon studies using young, adult male rodents and spatial navigation tasks. Despite this restriction, variability amongst the findings was evident and how or even whether chronic stress influenced spatial ability depended upon the type of task, the dependent variable measured and how the task was implemented, the type and duration of the stressors, housing conditions of the animals that include accessibility to food and cage mates, and duration from the end of the stress to the start of behavioral assessment. Nonetheless, patterns emerged as follows: For spatial memory, chronic stress impairs spatial reference memory and has transient effects on spatial working memory. For spatial learning, however, chronic stress effects appear to be task-specific: chronic stress impairs spatial learning on appetitively motivated tasks, such as the radial arm maze or holeboard, tasks that evoke relatively mild to low arousal components from fear. But under testing conditions that evoke moderate to strong arousal components from fear, such as during radial arm water maze testing, chronic stress appears to have minimal impairing effects or may even facilitate spatial learning. Chronic stress clearly impacts nearly every brain region and thus, how chronic stress alters hippocampal spatial ability likely depends upon the engagement of other brain structures during behavioral training and testing.
Bonnì, Sonia; Perri, Roberta; Fadda, Lucia; Tomaiuolo, Francesco; Koch, Giacomo; Caltagirone, Carlo; Carlesimo, Giovanni Augusto
We report the neuropsychological and MRI investigation of a patient (GP) who developed a selective impairment of spatial short-term memory (STM) following damage to the dorso-mesial areas of the right frontal lobe. We assessed in this patient spatial STM with an experimental procedure that evaluated immediate and 5-20 s delayed recall of verbal, visual and spatial stimuli. The patient scored significantly worse than normal controls on tests that required delayed recall of spatial data. This could not be ascribed to a deficit of spatial episodic long-term memory because amnesic patients performed normally on these tests. Conversely, the patient scored in the normal range on tests of immediate recall of verbal, visual and spatial data and tests of delayed recall of verbal and visual data. Comparison with a previously described patient who had a selective deficit in immediate spatial recall and an ischemic lesion that affected frontal and parietal dorso-mesial areas in the right hemisphere (Carlesimo GA, Perri R, Turriziani P, Tomaiuolo F, Caltagirone C. Remembering what but not where: independence of spatial and visual working memory in the human brain. Cortex. 2001 Sep; 37(4):519-34) suggests that the right parietal areas are involved in the short-term storage of spatial information and that the dorso-mesial regions of the right frontal underlie mechanisms for the delayed maintenance of the same data.
Kobilo, Tali; Yuan, Chunyan; van Praag, Henriette
Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor [delta] agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and…
Solman, Grayden J F; Kingstone, Alan
Humans are remarkably capable of finding desired objects in the world, despite the scale and complexity of naturalistic environments. Broadly, this ability is supported by an interplay between exploratory search and guidance from episodic memory for previously observed target locations. Here we examined how the environment itself may influence this interplay. In particular, we examined how partitions in the environment-like buildings, rooms, and furniture-can impact memory during repeated search. We report that the presence of partitions in a display, independent of item configuration, reliably improves episodic memory for item locations. Repeated search through partitioned displays was faster overall and was characterized by more rapid ballistic orienting in later repetitions. Explicit recall was also both faster and more accurate when displays were partitioned. Finally, we found that search paths were more regular and systematic when displays were partitioned. Given the ubiquity of partitions in real-world environments, these results provide important insights into the mechanisms of naturalistic search and its relation to memory.
Chen, Di; Liu, Fang; Wan, Jian-Bo; Lai, Chao-Qiang; Shen, Li-Rong
Royal jelly (RJ) produced by worker honeybees is the sole food for the queen bee throughout her life as well as the larvae of worker bees for the first 3 days after hatching. Supplementation of RJ in the diet has been shown to increase spatial memory in rodents. However, the key constituents in RJ responsible for improvement of cognitive function are unknown. Our objective was to determine if the major royal jelly proteins (MRJPs) extracted from RJ can improve the spatial memory of aged rats. The spatial memory assay using the Morris water maze test was administered once to rats after a 14-week feeding. Metabolomics analysis based on quadrupole time-of-flight mass spectrometry was conducted to examine the differences in compounds from urine. Aged male rats fed MRJPs showed improved spatial memory up to 48.5% when compared to the control male aged rats fed distilled water. The metabolite pattern of the MRJPs-fed aged rats was regressed to that of the young rats. Compounds altered by MRJPs were mapped to nicotinate and nicotinamide metabolism, cysteine taurine metabolism, and energy metabolism pathways. In summary, MRJPs may improve spatial memory and possess the potential for prevention of cognitive impairment via the cysteine and taurine metabolism and energy metabolism pathways in aged rats.
Libby, Laura A; Hannula, Deborah E; Ranganath, Charan
Several models have proposed that different medial temporal lobe (MTL) regions represent different kinds of information in the service of long-term memory. For instance, it has been proposed that perirhinal cortex (PRC), parahippocampal cortex (PHC), and hippocampus differentially support long-term memory for item information, spatial context, and item-context relations present during an event, respectively. Recent evidence has indicated that, in addition to long-term memory, MTL subregions may similarly contribute to processes that support the retention of complex spatial arrangements of objects across short delays. Here, we used functional magnetic resonance imaging and multivoxel pattern similarity analysis to investigate the extent to which human MTL regions independently code for object and spatial information, as well as the conjunction of this information, during working memory encoding and active maintenance. Voxel activity patterns in PRC, temporopolar cortex, and amygdala carried information about individual objects, whereas activity patterns in the PHC and posterior hippocampus carried information about the configuration of spatial locations that was to be remembered. Additionally, the integrity of multivoxel patterns in the right anterior hippocampus across encoding and delay periods was predictive of accurate short-term memory for object-location relationships. These results are consistent with parallel processing of item and spatial context information by PRC and PHC, respectively, and the binding of item and context by the hippocampus.
Hannula, Deborah E.; Ranganath, Charan
Several models have proposed that different medial temporal lobe (MTL) regions represent different kinds of information in the service of long-term memory. For instance, it has been proposed that perirhinal cortex (PRC), parahippocampal cortex (PHC), and hippocampus differentially support long-term memory for item information, spatial context, and item–context relations present during an event, respectively. Recent evidence has indicated that, in addition to long-term memory, MTL subregions may similarly contribute to processes that support the retention of complex spatial arrangements of objects across short delays. Here, we used functional magnetic resonance imaging and multivoxel pattern similarity analysis to investigate the extent to which human MTL regions independently code for object and spatial information, as well as the conjunction of this information, during working memory encoding and active maintenance. Voxel activity patterns in PRC, temporopolar cortex, and amygdala carried information about individual objects, whereas activity patterns in the PHC and posterior hippocampus carried information about the configuration of spatial locations that was to be remembered. Additionally, the integrity of multivoxel patterns in the right anterior hippocampus across encoding and delay periods was predictive of accurate short-term memory for object–location relationships. These results are consistent with parallel processing of item and spatial context information by PRC and PHC, respectively, and the binding of item and context by the hippocampus. PMID:25339737
Lee, Andy C H; Brodersen, Kay H; Rudebeck, Sarah R
Although the role of the hippocampus in spatial cognition is well accepted, it is unclear whether its involvement is restricted to the mnemonic domain or also extends to perception. We used fMRI to scan neurologically healthy participants during a scene oddity judgment task that placed no explicit demand on long-term memory. Crucially, a surprise recognition test was administered after scanning so that each trial could be categorized not only according to oddity accuracy but also according to subsequent memory. Univariate analyses showed significant hippocampal activity in association with correct oddity judgment, whereas greater parahippocampal place area (PPA) activity was observed during incorrect oddity trials, both irrespective of subsequent recognition performance. Consistent with this, multivariate pattern analyses revealed that a linear support vector machine was able to distinguish correct from incorrect oddity trials on the basis of activity in voxels within the hippocampus or PPA. Although no significant regions of activity were identified by univariate analyses in association with memory performance, a classifier was able to predict subsequent memory using voxels in either the hippocampus or PPA. Our findings are consistent with the idea that the hippocampus is important for processes beyond long-term declarative memory and that this structure may also play a role in complex spatial perception.
Kelly, Jonathan W.; McNamara, Timothy P.
Four experiments investigated the role of reference frames during the acquisition and development of spatial knowledge, when learning occurs incrementally across views. In two experiments, participants learned overlapping spatial layouts. Layout 1 was first studied in isolation, and Layout 2 was later studied in the presence of Layout 1. The…
Spritzer, Mark D.; Daviau, Emily D.; Coneeny, Meagan K.; Engelman, Shannon M.; Prince, W. Tyler; Rodriguez-Wisdom, Karlye N.
A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting seven days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects. PMID:21295035
Badcock, Johanna C; Michiel, Patricia T; Rock, Danny
Working memory may be conceptualized as a multi-component system involving the active maintenance and manipulation of stored information in the service of planning/guiding behaviour. Impaired spatial working memory is a robust finding in schizophrenia patients which has been related to an impairment in frontostriatal connectivity. The purpose of this study was to examine the specificity of this impairment by comparing the mnemonic and executive aspects of working memory performance in schizophrenia and bipolar disorder with psychotic features, focusing particularly on the functional dynamics between task components. Twenty-four patients with schizophrenia, 14 patients with bipolar I disorder (manic phase) and 33 healthy control subjects were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB): including the spatial working memory (between search errors and strategy scores) spatial span (storage capacity) and spatial planning (Stockings of Cambridge: accuracy and latency) tasks. Both patient groups were impaired on the spatial span task, which requires the maintenance and retrieval of stored information. In contrast, only schizophrenia patients showed a significant deficit in between search errors, which requires both maintenance and manipulation of information in working memory. That is, they exhibited both a mnemonic and an executive dysfunction. Spatial span was particularly important to accurate planning ability in bipolar patients. In contrast, in patients with schizophrenia poor spatial working memory was a significant predictor of planning impairments, consistent with failures in goal selection, evaluation and/or execution. Furthermore, initial planning time was positively correlated with the latency to complete a planning sequence. This pattern of slow cognitive processing in schizophrenia patients only, resembled that reported previously in patients with basal ganglia disorders. These findings are discussed in terms of a possible
Parslow, David M; Rose, David; Brooks, Barbara; Fleminger, Simon; Gray, Jeffrey A; Giampietro, Vincent; Brammer, Michael J; Williams, Steven; Gasston, David; Andrew, Christopher; Vythelingum, Goparlen N; Loannou, Glafkos; Simmons, Andrew; Morris, Robin G
Hippocampal activation was investigated, comparing allocentric and egocentric spatial memory. Healthy participants were immersed in a virtual reality circular arena, with pattern-rendered walls. In a viewpoint-independent task, they moved toward a pole, which was then removed. They were relocated to another position and had to move to the prior location of the pole. For viewpoint-dependent memory, the participants were not moved to a new starting point, but the patterns were rotated to prevent them from indicating the final position. Hippocampal and parahippocampal activation were found in the viewpoint-independent memory encoding phase. Viewpoint-dependent memory did not result in such activation. These results suggest differential activation of the hippocampal formation during allocentric encoding, in partial support of the spatial mapping hypothesis as applied to humans.
Tian, Qing; Zhang, Jun-Xia; Zhang, Yao; Wu, Feng; Tang, Qian; Wang, Cheng; Shi, Zhi-Yong; Zhang, Jing-Hui; Liu, Sang; Wang, Yue; Zhang, Qi; Wang, Jian-Zhi
To explore the role of protein kinase A (PKA) in regulating tau phosphorylation and spatial memory, we injected forskolin, an activator of PKA, at different concentrations into the rat brains. We found that forskolin at concentrations up to 80 microM enhanced tau phosphorylation and was associated with prominent spatial memory impairment. Higher concentrations of forskolin, up to 200 microM, were associated with reduced phosphorylation levels of tau and no memory deficits. Forskolin elevated cAMP and activated PKA in a dose-dependent manner. When infused at 200 microM, forskolin also resulted in the activation and overexpression of protein phosphatase-2A (PP-2A) and attenuated the okadaic acid-induced PP-2A inhibition. These data suggest that the upregulation of PKA by forskolin to a certain level may activate PP-2A but that the latter can ameliorate the PKA-induced tau phosphorylation and memory impairment in the rats.
Shukitt-Hale, B.; Casadesus, G.; Carey, A.; Rabin, B. M.; Joseph, J. A.
Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles), produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism; oxidative stress damage to the central nervous system caused by an increased release of reactive oxygen species is likely responsible for the deficits seen in aging and following irradiation. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a "map" provided by the configuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Supported by NASA Grants NAG9-1190 and NAG9-1529
Jarrold, Christopher; Phillips, Caroline; Baddeley, Alan D
A main aim of this study was to test the claim that individuals with Williams syndrome have selectively impaired memory for spatial as opposed to visual information. The performance of 16 individuals with Williams syndrome (six males, 10 females; mean age 18y 7mo [SD 7y 6mo], range 9y 1mo-30y 7mo) on tests of short-term memory for item and…
Akhlaghpour, Hessameddin; Wiskerke, Joost; Choi, Jung Yoon; Taliaferro, Joshua P; Au, Jennifer; Witten, Ilana B
Several lines of evidence suggest that the striatum has an important role in spatial working memory. The neural dynamics in the striatum have been described in tasks with short delay periods (1–4 s), but remain largely uncharacterized for tasks with longer delay periods. We collected and analyzed single unit recordings from the dorsomedial striatum of rats performing a spatial working memory task with delays up to 10 s. We found that neurons were activated sequentially, with the sequences spanning the entire delay period. Surprisingly, this sequential activity was dissociated from stimulus encoding activity, which was present in the same neurons, but preferentially appeared towards the onset of the delay period. These observations contrast with descriptions of sequential dynamics during similar tasks in other brains areas, and clarify the contribution of the striatum to spatial working memory. DOI: http://dx.doi.org/10.7554/eLife.19507.001 PMID:27636864
Czarnolewski, Mark Y; Eliot, John
Test scores of 119 students, attending either a public four-year college or a technical school, were related to their proportionality and detail drawing scores on the Memory for Designs Test. In regression models, the ETS Maze Tracing, Eliot-Price Mental Rotations, and Bender-Gestalt tests were consistent predictors of proportionality scores, with the latter two tests uniquely related to these. The ETS Shapes Memory Test and the Form Board Test were the strongest predictors for detail accuracy scores. The Shapes test predicted proportionality when the CTY Visual Memory Test BB was excluded. The models then provided support for the hypothesis that drawing designs from memory, a critical skill in drawing, regardless of whether one focuses on accuracy for proportionality scores or for detail scores, is jointly related to the measures of recognition, production, and traditional spatial ability measures. This study identified multifaceted skills in drawing from memory.
Gan, Qifeng; Seoud, Lama; Ben Tahar, Houssem; Langlois, J. M. Pierre
Spatial Averaging Filters (SAF) are extensively used in image processing for image smoothing and denoising. Their latest implementations have already achieved constant time computational complexity regardless of kernel size. However, all the existing O(1) algorithms require additional memory for temporary data storage. In order to minimize memory usage in embedded systems, we introduce a new two-dimensional recursive SAF. It uses previous resultant pixel values along both rows and columns to calculate the current one. It can achieve constant time computational complexity without using any additional memory usage. Experimental comparisons with previous SAF implementations shows that the proposed 2D-Recursive SAF does not require any additional memory while offering a computational time similar to the most efficient existing SAF algorithm. These features make it especially suitable for embedded systems with limited memory capacity.
Iwanaga, Makoto; Ito, Takako
The purpose of the present study was to examine the disturbance effect of music on performances of memory tasks. Subjects performed a verbal memory task and a spatial memory task in 4 sound conditions, including the presence of vocal music, instrumental music, a natural sound (murmurings of a stream), and no music. 47 undergraduate volunteers were randomly assigned to perform tasks under each condition. Perceived disturbance was highest under the vocal music condition regardless of the type of task. A disturbance in performance by music was observed only with the verbal memory task under the vocal and the instrumental music conditions. These findings were discussed from the perspectives of the working memory hypothesis and the changing state model.
Khabour, Omar F; Alzoubi, Karem H; Alomari, Mahmoud A; Alzubi, Mohammad A
Previous literature suggests that learning and memory formation can be influenced by diet and exercise. In the current study, we investigated the combined effects of forced swimming exercise (FSE) and every other day fasting (EODF) on spatial memory formation and on the levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of Wistar male rats. The radial arm water maze (RAWM) paradigm was used to assess changes in learning and memory formation, whereas ELISA assay was used to measure BDNF protein levels. The FSE and/or EODF were simultaneously instituted for 6 weeks. Results show that FSE improved learning, short-term as well as long-term memory formation, and significantly increased BDNF protein in the hippocampus (p<0.05). However, EODF had no effect on either spatial learning and memory formation or the levels of hippocamapal BDNF protein (p>0.05). In addition, EODF did not modulate beneficial effect of swimming exercise on cognitive function (p>0.05). Thus exercise enhanced, while EODF did not affect spatial learning and memory formation.
Khabour, Omar F; Alzoubi, Karem H; Alomari, Mahmoud A; Alzubi, Mohammad A
Substantial data suggest that cognitive function can be influenced by many lifestyle activities associated with changes in energy metabolism such as exercise and diet. In the current study, we investigated the combined effects of voluntary exercise (access to running wheels) and dietary restriction (every other day fasting, EODF) on spatial memory formation and on the levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of Wistar male rats. Spatial learning and memory formation was assessed using the radial arm water maze (RAWM) paradigm, while BDNF protein was measured using ELISA test. Voluntary exercise and/or EODF were instituted for 6 weeks. Voluntary exercise alone significantly enhanced short-term, intermediate-term, and long-term memory formation, and increased BDNF protein levels in the hippocampus. EODF enhanced mean running wheel activity by approximately twofold. However, EODF did not modulate the effects of exercise on memory formation and expression of BDNF. In addition, EODF alone had no effect on memory and BDNF protein in the hippocampus. In conclusion, results of this study indicate that exercise enhanced while EODF had neutral effect on both spatial memory formation and hippocampus BDNF levels.
Belnik, A P; Ostrovskaya, R U; Poletaeva, I I
The effect of original nootropic preparation Noopept on learning and long-term memory was studied with BALB/c mice. Scopolamine (1 mg/kg) impaired long-term memory trace, while Noopept (0.5 mg/kg) had no significant effect. Noopept completely prevented the development of cognitive disorders induced by scopolamine (blockade of muscarinic cholinergic receptors). Our results confirmed the presence of choline-positive effect in dipeptide piracetam analogue Noopept on retrieval of learned skill of finding a submerged platform (spatial memory). We conclude that the effectiveness of this drug should be evaluated in patients with Alzheimer's disease.
Ramos, J M
In animal models of human amnesia, using lesion methods, it has been difficult to establish the role played by the hippocampus in the formation of long-term spatial knowledge. For example, lesions sustained after acquisition have generally produced a flat retrograde amnesia for spatial information. These results have not made it possible to dissociate the participation of the hippocampus in retrieval/performance processes from its participation in consolidation/retention. The present study was designed to investigate if electrolytic hippocampal lesions made before training lead to a deficit in the long-term retention of spatial knowledge when the rats show equal performance levels during the acquisition. Results show that lesioned rats learn a place response just as well as the control rats when, during the training, an intramaze cue orients the animal in its navigation towards the goal arm. One day after reaching criterion, lesioned and control rats remember the task perfectly during a transfer test in which the intramaze signal used previously is not present. However, 24 days later, the hippocampal animals manifest a profound deficit in the retention of the spatial information. When the spatial task learned during the acquisition phase requires only the use of a guidance strategy, control and lesioned animals show the same level of performance during the training phase and the same degree of retention during the retraining phase 24 days after criterion. Taken together, these results suggest that the hippocampus plays a crucial role in long-term retention of allocentric spatial information.
Iñiguez, Sergio D; Charntikov, Sergios; Baella, Shelley A; Herbert, Matthew S; Bolaños-Guzmán, Carlos A; Crawford, Cynthia A
In this study, we examined the ability of post-training injections of cocaine to facilitate spatial memory performance using the Morris water maze (MWM). We also investigated the role that hippocampal protein kinase A (PKA) and extracellular signal-regulated kinase 1/2 (ERK) signaling may play in cocaine-mediated spatial memory consolidation processes. Male and female C57BL/6 mice were first trained in a MWM task (eight consecutive trials) then injected with cocaine (0, 1.25, 2.5, 5, or 20 mg/kg), and memory for the platform location was retested after a 24 h delay. Cocaine had a dose-dependent effect on spatial memory performance because only the mice receiving 2.5 mg/kg cocaine displayed a significant reduction in latency to locate the platform. No sex differences in MWM performance were observed; however, females showed higher hippocampal levels of PKA when compared with males. A second experiment demonstrated that 2.5 mg/kg cocaine enhanced MWM performance only when administered within 2, but not 4 h after spatial training. We also found that cocaine (2.5 mg/kg) increased ERK2 phosphorylation within the hippocampus and one of its downstream targets (ribosomal S6 kinase), a mechanism that may be responsible, at least in part, for the enhanced cocaine-mediated spatial memory performance. Overall, these data demonstrate that a low dose of cocaine (2.5 mg/kg) administered within 2 h after training facilitates MWM spatial memory performance in C57BL/6 mice.
Thomson, Lisa M; Sutherland, Robert J
Sickness behaviors are a set of adaptive responses to infection that include lethargy, anorexia, and, of direct relevance to this work, learning and memory impairments. The proinflammatory cytokine, interleukin-1 beta (IL-1beta) has been proposed as the primary peripheral mediator of these sickness behaviors, though few studies have investigated the effects of peripheral IL-1beta on learning and memory. We used three different versions of the Morris water task (Morris water task), a spatial learning and memory task, to separately assess the effects of peripheral IL-1beta on acquisition, consolidation, and retention of spatial location information. Using a dose that induced anorexia, assessed as a significant reduction in body weight, we observed no performance impairments in the IL-1beta-treated rats across the different versions of the task, suggesting that peripheral IL-1beta alone is insufficient to induce spatial learning and memory impairments in the rat. The observed dissociation of anorexia and cognitive dysfunction suggests that, either spatial learning and memory are not principal components of the sickness response, or cognitive dysfunction requires different or additional peripheral mediator(s).
Lee, Sang Ah; Tucci, Valter; Vallortigara, Giorgio
Research across the cognitive and brain sciences has begun to elucidate some of the processes that guide navigation and spatial memory. Boundary geometry and featural landmarks are two distinct classes of environmental cues that have dissociable neural correlates in spatial representation and follow different patterns of learning. Consequently, spatial navigation depends both on the type of cue available and on the type of learning provided. We investigated this interaction between spatial representation and memory by administering two different tasks (working memory, reference memory) using two different environmental cues (rectangular geometry, striped landmark) in mouse models of human genetic disorders: Prader-Willi syndrome (PWScr(m+/p-) mice, n = 12) and Beta-catenin mutation (Thr653Lys-substituted mice, n = 12). This exploratory study provides suggestive evidence that these models exhibit different abilities and impairments in navigating by boundary geometry and featural landmarks, depending on the type of memory task administered. We discuss these data in light of the specific deficits in cognitive and brain function in these human syndromes and their animal model counterparts.
Shea, Chloe J A; Carhuatanta, Kimberly A K; Wagner, Jessica; Bechmann, Naomi; Moore, Raquel; Herman, James P; Jankord, Ryan
The effects of chronic stress on learning are highly variable across individuals. This variability stems from gene-environment interactions. However, the mechanisms by which stress affects genetic predictors of learning are unclear. Thus, we aim to determine whether the genetic pathways that predict spatial memory performance are altered by previous exposure to chronic stress. Sixty-two BXD recombinant inbred strains of mice, as well as parent strains C57BL/6J and DBA/2J, were randomly assigned as behavioral control or to a chronic variable stress paradigm and then underwent behavioral testing to assess spatial memory and learning performance using the Morris water maze. Quantitative trait loci (QTL) mapping was completed for average escape latency times for both control and stress animals. Loci on chromosomes 5 and 10 were found in both control and stress environmental populations; eight additional loci were found to be unique to either the control or stress environment. In sum, results indicate that certain genetic loci predict spatial memory performance regardless of prior stress exposure, while exposure to stress also reveals unique genetic predictors of training during the memory task. Thus, we find that genetic predictors contributing to spatial learning and memory are susceptible to the presence of chronic stress.
Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanan; Leksomboon, Ratana; Chaichun, Amnart; Wigmore, Peter; Welbat, Jariya Umka
Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis.
Zhu, Xiaolin; Sun, Wei; Li, Xinwang; Tan, Shuping; Zhang, Xiangyang
Drug addiction is associated with memory processes. We simultaneously measured conditioned place preference (CPP) and locomotor sensitization to investigate the influence of spatial memory retrieval on morphine reward and psychomotor excitement. According to their performance in space probe trial involving the Morris water maze mice were assigned to high (including morphine and saline subgroups, H-Mor and H-Sal) and low spatial memory retrieval ability groups (L-Mor and L-Sal). Morphine (10mg/kg) produced significant CPP in L-Mor and H-Mor mice, although, L-Mor mice showed a significantly greater response to morphine. During the development period of behavior sensitization, no significant group-by-day interaction was found. However, locomotor activities of L-Mor mice were also significantly higher than H-Mor mice during the expression period of behavior sensitization. Our findings suggested that the spatial memory retrieval ability of mice influences morphine CPP, as well as behavioral sensitization. Thus, spatial memory might be implicated in drug addiction.
Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanan; Leksomboon, Ratana; Chaichun, Amnart; Wigmore, Peter; Umka Welbat, Jariya
Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis. PMID:26445061
Lee, Sang Ah; Tucci, Valter; Vallortigara, Giorgio
Research across the cognitive and brain sciences has begun to elucidate some of the processes that guide navigation and spatial memory. Boundary geometry and featural landmarks are two distinct classes of environmental cues that have dissociable neural correlates in spatial representation and follow different patterns of learning. Consequently, spatial navigation depends both on the type of cue available and on the type of learning provided. We investigated this interaction between spatial representation and memory by administering two different tasks (working memory, reference memory) using two different environmental cues (rectangular geometry, striped landmark) in mouse models of human genetic disorders: Prader-Willi syndrome (PWScrm+/p− mice, n = 12) and Beta-catenin mutation (Thr653Lys-substituted mice, n = 12). This exploratory study provides suggestive evidence that these models exhibit different abilities and impairments in navigating by boundary geometry and featural landmarks, depending on the type of memory task administered. We discuss these data in light of the specific deficits in cognitive and brain function in these human syndromes and their animal model counterparts. PMID:28208764
Ramos, Juan M J
Two experiments examined the effects of perirhinal cortex and hippocampal neurotoxic lesions on the retention of allocentric information. Perirhinal (Expt. 1) and hippocampal rats (Expt. 2) were trained on an allocentric task until they reached a performance equal to that of the control groups. Results showed that 24 days after acquisition, during a retraining period, only the hippocampal rats presented a deficit in retention. These results suggest that the perirhinal cortex and the hippocampus can be functionally dissociated in terms of their participation in the formation of long-term spatial memory. Also, the allocentric spatial memory functions of the hippocampus seem not to depend on their afferent connections with the perirhinal cortex.
Spiers, Mary V; Sakamoto, Maiko; Elliott, Richard J; Baumann, Steve
The grocery shopping Virtual Reality Spatial Object-Location Test (VRSOLT) was developed to examine sex differences in spatial object-location memory in a 3D virtual environment that simulates the real world. Forty college students (20 males, 20 females) were tested on the VRSOLT as well as mental rotation and 2D object-location memory tasks. Both convergent and divergent validity was demonstrated. Males showed an advantage on mental rotation, and results of the VRSOLT grocery store test replicated the female object-location advantage seen in 2D tests. A strategy of systematically navigating the environment may aid female encoding for object location.
Wang, Qing M.; Meng, Zhaoxiang; Yin, Zhenglu
Objective To investigate whether gait dysfunction is a predictor of severe spatial learning and memory impairment in aged mice. Methods A total of 100 12-month-old male mice that had no obvious abnormal motor ability and whose Morris water maze performances were not significantly different from those of two-month-old male mice were selected for the study. The selected aged mice were then divided into abnormal or normal gait groups according to the results from the quantitative gait assessment. Gaits of aged mice were defined as abnormal when the values of quantitative gait parameters were two standard deviations (SD) lower or higher than those of 2-month-old male mice. Gait parameters included stride length, variability of stride length, base of support, cadence, and average speed. After nine months, mice exhibiting severe spatial learning and memory impairment were separated from mice with mild or no cognitive dysfunction. The rate of severe spatial learning and memory impairment in the abnormal and normal gait groups was tested by a chi-square test and the correlation between gait dysfunction and decline in cognitive function was tested using a diagnostic test. Results The 12-month-old aged mice were divided into a normal gait group (n = 75) and an abnormal gait group (n = 25). Nine months later, three mice in the normal gait group and two mice in the abnormal gait group had died. The remaining mice were subjected to the Morris water maze again, and 17 out of 23 mice in the abnormal gait group had developed severe spatial learning and memory impairment, including six with stride length deficits, 15 with coefficient of variation (CV) in stride length, two with base of support (BOS) deficits, five with cadence dysfunction, and six with average speed deficits. In contrast, only 15 out of 72 mice in the normal gait group developed severe spatial learning and memory impairment. The rate of severe spatial learning and memory impairment was significantly higher in
Navawongse, Rapeechai; Eichenbaum, Howard
Hippocampal neurons encode events within the context in which they occurred, a fundamental feature of episodic memory. Here we explored the sources of event and context information represented by hippocampal neurons during the retrieval of object associations in rats. Temporary inactivation of the medial prefrontal cortex differentially reduced the selectivity of rule-based object associations represented by hippocampal neuronal firing patterns but did not affect spatial firing patterns. By contrast, inactivation of the medial entorhinal cortex resulted in a pervasive reorganization of hippocampal mappings of spatial context and events. These results suggest distinct and cooperative prefrontal and medial temporal mechanisms in memory representation. PMID:23325238
Clark, Kelsey L; Noudoost, Behrad; Moore, Tirin
Spatial attention is known to gate entry into visual short-term memory, and some evidence suggests that spatial signals may also play a role in binding features or protecting object representations during memory maintenance. To examine the persistence of spatial signals during object short-term memory, the activity of neurons in the frontal eye field (FEF) of macaque monkeys was recorded during an object-based delayed match-to-sample task. In this task, monkeys were trained to remember an object image over a brief delay, regardless of the locations of the sample or target presentation. FEF neurons exhibited visual, delay, and target period activity, including selectivity for sample location and target location. Delay period activity represented the sample location throughout the delay, despite the irrelevance of spatial information for successful task completion. Furthermore, neurons continued to encode sample position in a variant of the task in which the matching stimulus never appeared in their response field, confirming that FEF maintains sample location independent of subsequent behavioral relevance. FEF neurons also exhibited target-position-dependent anticipatory activity immediately before target onset, suggesting that monkeys predicted target position within blocks. These results show that FEF neurons maintain spatial information during short-term memory, even when that information is irrelevant for task performance.
Richmond, Jenny L; Zhao, Jenna L; Burns, Mary A
Episodic memory involves binding components of an event (who, what, when, and where) into a relational representation. The ability to encode information about the relative locations of objects (i.e., spatial relational memory) is a key component of episodic memory. Here we used eye tracking to test whether infants and toddlers learn about the spatial relations among objects. In Experiment 1, 9-, 18-, and 27-month olds were familiarized with an array of three objects. Following familiarization, they saw test arrays in which two of the objects had been replaced with novel ones (object switch condition) and arrays in which two of the objects had switched positions (location switch condition). Both 18- and 27-month olds looked significantly longer than would be predicted by chance at the objects that had switched spatial locations; however, 9-month olds did not. In Experiment 2, we showed that, given sufficient familiarization time, 9-month olds were also capable of detecting disruptions to the spatial relations among an array of objects. These results have important implications for our understanding of spatial relational memory development.
Nakai, Megumi; Iizuka, Michiro; Matsui, Nobuaki; Hosogi, Kazuko; Imai, Akiko; Abe, Noriaki; Shiraishi, Hisashi; Hirata, Ayumu; Yagi, Yusuke; Jobu, Kohei; Yokota, Junko; Kato, Eishin; Hosoda, Shinya; Yoshioka, Saburo; Harada, Kenichi; Kubo, Miwa; Fukuyama, Yoshiyasu; Miyamura, Mitsuhiko
Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.
Ribordy, Farfalla; Jabès, Adeline; Banta Lavenex, Pamela; Lavenex, Pierre
Episodic memories for autobiographical events that happen in unique spatiotemporal contexts are central to defining who we are. Yet, before 2 years of age, children are unable to form or store episodic memories for recall later in life, a phenomenon known as infantile amnesia. Here, we studied the development of allocentric spatial memory, a fundamental component of episodic memory, in two versions of a real-world memory task requiring 18 month- to 5-year-old children to search for rewards hidden beneath cups distributed in an open-field arena. Whereas children 25-42-months-old were not capable of discriminating three reward locations among 18 possible locations in absence of local cues marking these locations, children older than 43 months found the reward locations reliably. These results support previous findings suggesting that allocentric spatial memory, if present, is only rudimentary in children under 3.5 years of age. However, when tested with only one reward location among four possible locations, children 25-39-months-old found the reward reliably in absence of local cues, whereas 18-23-month-olds did not. Our findings thus show that the ability to form a basic allocentric representation of the environment is present by 2 years of age, and its emergence coincides temporally with the offset of infantile amnesia. However, the ability of children to distinguish and remember closely related spatial locations improves from 2 to 3.5 years of age, a developmental period marked by persistent deficits in long-term episodic memory known as childhood amnesia. These findings support the hypothesis that the differential maturation of distinct hippocampal circuits contributes to the emergence of specific memory processes during early childhood.
Boon, Paul J.; Belopolsky, Artem V.; Theeuwes, Jan
Visual-spatial working memory (VSWM) helps us to maintain and manipulate visual information in the absence of sensory input. It has been proposed that VSWM is an emergent property of the oculomotor system. In the present study we investigated the role of the oculomotor system in updating of spatial working memory representations across saccades. Participants had to maintain a location in memory while making a saccade to a different location. During the saccade the target was displaced, which went unnoticed by the participants. After executing the saccade, participants had to indicate the memorized location. If memory updating fully relies on cancellation driven by extraretinal oculomotor signals, the displacement should have no effect on the perceived location of the memorized stimulus. However, if postsaccadic retinal information about the location of the saccade target is used, the perceived location will be shifted according to the target displacement. As it has been suggested that maintenance of accurate spatial representations across saccades is especially important for action control, we used different ways of reporting the location held in memory; a match-to-sample task, a mouse click or by making another saccade. The results showed a small systematic target displacement bias in all response modalities. Parametric manipulation of the distance between the to-be-memorized stimulus and saccade target revealed that target displacement bias increased over time and changed its spatial profile from being initially centered on locations around the saccade target to becoming spatially global. Taken together results suggest that we neither rely exclusively on extraretinal nor on retinal information in updating working memory representations across saccades. The relative contribution of retinal signals is not fixed but depends on both the time available to integrate these signals as well as the distance between the saccade target and the remembered location. PMID
Vilela, Thais Ceresér; Muller, Alexandre Pastoris; Damiani, Adriani Paganini; Macan, Tamires Pavei; da Silva, Sabrina; Canteiro, Paula Bortoluzzi; de Sena Casagrande, Alisson; Pedroso, Giulia Dos Santos; Nesi, Renata Tiscoski; de Andrade, Vanessa Moraes; de Pinho, Ricardo Aurino
Aging is associated with impaired cognition and memory and increased susceptibility to neurodegenerative disorders. Physical exercise is neuroprotective; however, the major evidence of this effect involves studies of only aerobic training in young animals. The benefits of other exercise protocols such as strength training in aged animals remains unknown. Here, we investigated the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats. Aging Wistar rats performed aerobic or strength training for 50 min 3 to 4 days/week for 8 weeks. Spatial memory and neurotrophic and glutamatergic signaling in the hippocampus of aged rats were evaluated after aerobic or strength training. Both aerobic and strength training improved cognition during the performance of a spatial memory task. Remarkably, the improvement in spatial memory was accompanied by an increase in synaptic plasticity proteins within the hippocampus after exercise training, with some differences in the intracellular functions of those proteins between the two exercise protocols. Moreover, neurotrophic signaling (CREB, BDNF, and the P75(NTR) receptor) increased after training for both exercise protocols, and aerobic exercise specifically increased glutamatergic proteins (NMDA receptor and PSD-95). We also observed a decrease in DNA damage after aerobic training. In contrast, strength training increased levels of PKCα and the proinflammatory factors TNF-α and IL-1β. Overall, our results show that both aerobic and strength training improved spatial memory in aging rats through inducing distinct molecular mechanisms of neuroplasticity. Our findings extend the idea that exercise protocols can be used to improve cognition during aging.
Martin, G N; Chaudry, A
Sensory influences on working memory (WM) performance were investigated in 86 healthy adults. Participants were exposed to an ambient pleasant odor (lemon), unpleasant odor (machine oil) or no odor during completion of three WM tests from the Wechsler Memory Scale-III: the letter-number sequencing, spatial span and digit span tests. A significant main effect of odor was found for spatial span but no other task: scores were significantly lower in the unpleasant odor condition than the pleasant odor condition. Significant odor × sex interactions were found for the spatial span, digit span and letter-number sequencing tasks: men's spatial span scores were lower in the unpleasant odor condition than in the control condition, and women's scores were significantly better in the pleasant odor condition than in the unpleasant odor condition. The results suggest that ambient odor may impair or facilitate specific types of WM depending on the task, sex of the participant and affective characteristics of the odor.
Piccardi, L; Bianchini, F; Nori, R; Marano, A; Iachini, F; Lasala, L; Guariglia, C
Spatial information processing is influenced by the space in which an individual acts and the nature of the stimulus. This distinction is also present in spatial memory, where stimuli are processed differently because of their nature and the space in which they are released. The aim of the present study was to compare college students' performance on spatial location and pathway memory tasks in two different domains (reaching and walking). Reaching space refers to the portion of space within "grasping distance" and walking space to that beyond arm's reach. Research results indicate that it is easier to remember a pathway in the walking than the reaching domain and to remember single spatial locations in the reaching domain. Women are more able to perform the task in the walking domain than the reaching domain and men perform equally well in both domains.
Mertes, Christine; Wascher, Edmund; Schneider, Daniel
The effect of healthy aging on cognitive control of irrelevant visual information was investigated by using event-related potentials. Participants performed a spatial cuing task where an irrelevant color cue that was either contingent (color search) or noncontingent (shape search) on the attentional set was presented before a target with different stimulus-onset asynchronies. In the contingent condition, attentional capture appeared independent of age and persisted over the stimulus-onset asynchronies but was markedly pronounced for elderly people. Accordingly, event-related potential analyses revealed that both older and younger adults initially selected the irrelevant cue when it was contingent on the attentional set and transferred spatial cue information into working memory. However, only younger adults revealed inhibitory mechanisms to compensate for attentional capture. It is proposed that this age-related lack of reactive inhibition leads to stickiness in visual processing whenever information is contingent on the attentional set, unveiling older adults' "Achilles' heel" in cognitive control.
Kougias, Daniel G; Hankosky, Emily R; Gulley, Joshua M; Juraska, Janice M
Beta-hydroxy-beta-methylbutyrate (HMB) is commonly supplemented to maintain muscle in elderly and clinical populations and has potential as a nootropic. Previously, we have shown that in both male and female rats, long-term HMB supplementation prevents age-related dendritic shrinkage within the medial prefrontal cortex (mPFC) and improves cognitive flexibility and working memory performance that are both age- and sex-specific. In this study, we further explore the cognitive effects by assessing visuospatial learning and memory with the Morris water maze. Female rats were ovariectomized at 11months of age to model human menopause. At 12months of age, male and female rats received relatively short- or long-term (1- or 7-month) dietary HMB (450mg/kg/dose) supplementation twice a day prior to testing. Spatial reference learning and memory was assessed across four days in the water maze with four trials daily and a probe trial on the last day. Consistent with previous work, there were age-related deficits in water maze performance in both sexes. However, these deficits were ameliorated in HMB-treated males during training and in both sexes during probe trial performance. Thus, HMB supplementation prevented the age-related decrement in water maze performance, especially in male rats.
Kelly, Jonathan W.; Avraamides, Marios N.
Two experiments investigated whether visual cues influence spatial reference frame selection for locations learned through touch. Participants experienced visual cues emphasizing specific environmental axes and later learned objects through touch. Visual cues were manipulated and haptic learning conditions were held constant. Imagined perspective…
Zanos, Panos; Bhat, Shambhu; Terrillion, Chantelle E; Smith, Robert J; Tonelli, Leonardo H; Gould, Todd D
Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively. Hippocampal expression of Cacna1c mRNA was measured by quantitative polymerase chain reaction. Ageing was associated with object recognition and contextual/emotional memory deficits, and a significant increase in hippocampal Cacna1c mRNA expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA expression in both young and old animals. However, haploinsufficient mice did not manifest an age-related increase in expression of this gene. Behaviourally, Cacna1c haploinsufficiency prevented object recognition deficits during ageing in both male and female mice. A significant correlation between higher Cacna1c levels and decreased object recognition performance was observed in both sexes. Also, a sex-dependent protective role of decreased Cacna1c levels in contextual/emotional memory loss has been observed, specifically in male mice. These data provide evidence for an association between increased hippocampal Cacna1c expression and age-related cognitive decline. Additionally, they indicate an interaction between the Cacna1c gene and sex in the modulation of age-related contextual memory declines.
Darling, S; Della Sala, S; Logie, R H; Cantagallo, A
There is increasing evidence to support the idea that visuo-spatial working memory can be segregated into separate cognitive subsystems. However, the nature of these systems remains unclear. In this paper we report data from two brain injured patients suggesting that information about visual appearance is retained in a different subsystem from information about spatial location, and that this differential processing can be observed when the style of presentation (sequential or simultaneous) is controlled.
Myatchin, I; Lemiere, J; Danckaerts, M; Lagae, L
Working memory (WM) dysfunction and increased within-subject variability are known issues in attention deficit/hyperactivity disorder (ADHD) patients. Little is known about the electrophysiological characteristics of this variability. We evaluated behavioral and electrophysiological within-subject variability taking developmental aspects into account in a group of ADHD patients. Multichannel (n = 31) event-related potentials (ERP) were measured during a visuo-spatial backmatching task; 44 children (8-16 years old) were tested: 22 children with ADHD, combined (n = 17) and inattentive (n = 5) type, and 22 age- and intelligence-matched control children. One-backmatching (BM1) and two-backmatching (BM2) tasks were performed. Classical behavioral parameters and target and nontarget ERP were compared between groups. In addition, motor response variability and ERP amplitude variability were studied. Age-related changes in both motor response and ERP amplitude variability were analyzed in each group. Attention deficit/hyperactivity disorder children made more commission errors, which was more pronounced in the difficult (BM2) task. No difference between groups was found in ERP amplitude and in motor response variability. However, ADHD patients had higher ERP amplitude variability, which was again more pronounced in the difficult WM task. A delayed maturation of amplitude variability was seen in ADHD patients with a slower than in controls decrease in variability with age. This amplitude variability was correlated with the number of commissions, but in an opposite way for ADHD and control children. Our findings indicate an impaired visuo-spatial WM processing in ADHD children with greater ERP amplitude variability compared to controls. Our results also support the view of a delayed cortical development of visuo-spatial WM circuits in this disorder.
Kida, Kumiko; Tsuji, Tadataka; Tanaka, Susumu; Kogo, Mikihiko
Sufficient oral microelements such as zinc and fully chewing of foods are required to maintain cognitive function despite aging. No knowledge exists about the combination of factors such as zinc deficiency and reduced mastication on learning and memory. Here we show that tooth extraction only in 8-week-old mice did not change the density of glial fibrillary acidic protein-labeled astrocytes in the hippocampus or spatial memory parameters. However, tooth extraction followed by zinc deprivation strongly impaired spatial memory and led to an increase in astrocytic density in the hippocampal CA1 region. The impaired spatial performance in the zinc-deficient only (ZD) mice also coincided well with the increase in the astrocytic density in the hippocampal CA1 region. After switching both zinc-deficient groups to a normal diet with sufficient zinc, spatial memory recovered, and more time was spent in the quadrant with the goal in the probe test in the mice with tooth extraction followed by zinc deprivation (EZD) compared to the ZD mice. Interestingly, we found no differences in astrocytic density in the CA1 region among all groups at 22 weeks of age. Furthermore, the escape latency in a visible probe test at all times was longer in zinc-deficient groups than the others and demonstrated a negative correlation with body weight. No significant differences in escape latency were observed in the visible probe test among the ZD, EZD, and normal-fed control at 4 weeks (CT4w) groups in which body weight was standardized to that of the EZD group, or in the daily reduction in latency between the normal-fed control and CT4w groups. Our data showed that zinc-deficient feeding during a young age impairs spatial memory performance and leads to an increase in astrocytic density in the hippocampal CA1 region and that zinc-sufficient feeding is followed by recovery of the impaired spatial memory along with changes in astrocytic density. The combination of the two factors, zinc deficiency
Paul, Carrillo-Mora; Magda, Giordano; Abel, Santamaría
The assessment of learning and memory in animal models has been widely employed in scientific research for a long time. Among these models, those representing diseases with primary processes of affected memory - such as amnesia, dementia, brain aging, etc. - studies dealing with the toxic effects of specific drugs, and other exploring neurodevelopment, trauma, epilepsy and neuropsychiatric disorders, are often called on to employ these tools. There is a diversity of experimental methods assessing animal learning and memory skills. Overall, mazes are the devices mostly used today to test memory in rodents; there are several types of them, but their real usefulness, advantages and applications remain to be fully established and depend on the particular variant selected by the experimenter. The aims of the present article are first, to briefly review the accumulated knowledge in regard to spatial memory tasks; second, to bring the reader information on the different types of rodent mazes available to test spatial memory; and third, to elucidate the usefulness and limitations of each of these devices.
Katus, Tobias; Andersen, Søren K; Müller, Matthias M
Orienting attention to locations in mnemonic representations engages processes that functionally and anatomically overlap the neural circuitry guiding prospective shifts of spatial attention. The attention-based rehearsal account predicts that the requirement to withdraw attention from a memorized location impairs memory accuracy. In a dual-task study, we simultaneously presented retro-cues and pre-cues to guide spatial attention in short-term memory (STM) and perception, respectively. The spatial direction of each cue was independent of the other. The locations indicated by the combined cues could be compatible (same hand) or incompatible (opposite hands). Incompatible directional cues decreased lateralized activity in brain potentials evoked by visual cues, indicating interference in the generation of prospective attention shifts. The detection of external stimuli at the prospectively cued location was impaired when the memorized location was part of the perceptually ignored hand. The disruption of attention-based rehearsal by means of incompatible pre-cues reduced memory accuracy and affected encoding of tactile test stimuli at the retrospectively cued hand. These findings highlight the functional significance of spatial attention for spatial STM. The bidirectional interactions between both tasks demonstrate that spatial attention is a shared neural resource of a capacity-limited system that regulates information processing in internal and external stimulus representations.
Munger, Ronald G; Cutler, Adele; Quach, Anna; Bowles, Austin; Corcoran, Christopher; Tschanz, JoAnn T; Norton, Maria C; Welsh-Bohmer, Kathleen A
Background: Healthy dietary patterns may protect against age-related cognitive decline, but results of studies have been inconsistent. Objective: We examined associations between Dietary Approaches to Stop Hypertension (DASH)– and Mediterranean-style dietary patterns and age-related cognitive change in a prospective, population-based study. Design: Participants included 3831 men and women ≥65 y of age who were residents of Cache County, UT, in 1995. Cognitive function was assessed by using the Modified Mini-Mental State Examination (3MS) ≤4 times over 11 y. Diet-adherence scores were computed by summing across the energy-adjusted rank-order of individual food and nutrient components and categorizing participants into quintiles of the distribution of the diet accordance score. Mixed-effects repeated-measures models were used to examine 3MS scores over time across increasing quintiles of dietary accordance scores and individual food components that comprised each score. Results: The range of rank-order DASH and Mediterranean diet scores was 1661–25,596 and 2407–26,947, respectively. Higher DASH and Mediterranean diet scores were associated with higher average 3MS scores. People in quintile 5 of DASH averaged 0.97 points higher than those in quintile 1 (P = 0.001). The corresponding difference for Mediterranean quintiles was 0.94 (P = 0.001). These differences were consistent over 11 y. Higher intakes of whole grains and nuts and legumes were also associated with higher average 3MS scores [mean quintile 5 compared with 1 differences: 1.19 (P < 0.001), 1.22 (P < 0.001), respectively]. Conclusions: Higher levels of accordance with both the DASH and Mediterranean dietary patterns were associated with consistently higher levels of cognitive function in elderly men and women over an 11-y period. Whole grains and nuts and legumes were positively associated with higher cognitive functions and may be core neuroprotective foods common to various healthy plant
Wheelan, Nicola; Webster, Scott P.; Kenyon, Christopher J.; Caughey, Sarah; Walker, Brian R.; Holmes, Megan C.; Seckl, Jonathan R.; Yau, Joyce L.W.
High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals. PMID:25497454
Wheelan, Nicola; Webster, Scott P; Kenyon, Christopher J; Caughey, Sarah; Walker, Brian R; Holmes, Megan C; Seckl, Jonathan R; Yau, Joyce L W
High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals.
Goldstein, Kim E; Hazlett, Erin A; Savage, Kimberley R; Berlin, Heather A; Hamilton, Holly K; Zelmanova, Yuliya; Look, Amy E; Koenigsberg, Harold W; Mitsis, Effie M; Tang, Cheuk Y; McNamara, Margaret; Siever, Larry J; Cohen, Barry H; New, Antonia S
Schizotypal personality disorder (SPD) individuals and borderline personality disorder (BPD) individuals have been reported to show neuropsychological impairments and abnormalities in brain structure. However, relationships between neuropsychological function and brain structure in these groups are not well understood. This study compared visual-spatial working memory (SWM) and its associations with dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) gray matter volume in 18 unmedicated SPD patients with no BPD traits, 18 unmedicated BPD patients with no SPD traits, and 16 healthy controls (HC). Results showed impaired SWM in SPD but not BPD, compared with HC. Moreover, among the HC group, but not SPD patients, better SWM performance was associated with larger VLPFC (BA44/45) gray matter volume (Fisher's Z p-values <0.05). Findings suggest spatial working memory impairments may be a core neuropsychological deficit specific to SPD patients and highlight the role of VLPFC subcomponents in normal and dysfunctional memory performance.
Hritcu, Lucian; Cioanca, Oana; Hancianu, Monica
Lavender is reported to be an effective medical plant in treating inflammation, depression, stress and mild anxiety in Europe and the USA. The present study investigated the effects of two different lavender essential oils from Lavandula angustifolia ssp. angustifolia Mill. (Lamiaceae) and Lavandula hybrida Rev. (Lamiaceae) on neurological capacity of male Wistar rats subjected to scopolamine (0.7mg/kg)-induced dementia rat model. Chronic exposures to lavender essential oils (daily, for 7 continuous days) significantly reduced anxiety-like behavior and inhibited depression in elevated plus-maze and forced swimming tests, suggesting anxiolytic and antidepressant activity. Also, spatial memory performance in Y-maze and radial arm-maze tasks was improved, suggesting positive effects on memory formation. Taken together, multiple exposures to lavender essential oils could effectively reverse spatial memory deficits induced by dysfunction of the cholinergic system in the rat brain and might provide an opportunity for management neurological abnormalities in dementia conditions.
Meneghetti, Chiara; De Beni, Rossana; Gyselinck, Valérie; Pazzaglia, Francesca
The study investigates the relationships between working memory (WM), amount of learning, and strategies used in spatial description. WM involvement and strategies reported were assumed to change, depending on whether the text learning was extensive or limited. Two experiments were carried out using dual-task paradigm: participants listened to spatial text three times and concurrently one group performed a spatial concurrent task, one group a verbal task (to measure WM involvement), and one group no secondary task. In Experiment 1, participants listened three consecutive times then performed recall tasks (one verbal - verification test; one spatial - graphical representation). In Experiment 2, recall tasks were performed after first and third listening. The strategies used were ascertained through a questionnaire. Results showed that the verification test was impaired by the verbal concurrent task after listening three times (Experiment 1) and after first listening (Experiment 2). The graphical representation performance was impaired by verbal and spatial concurrent tasks, detected only after listening three times, not after a single time (Experiments 1 and 2). The strategies most used were visuo-spatial; their relationship with WM changes as a function of number of times of listening. Overall, the results showed that extensive learning allows construction of a spatial mental representation that is modulated by WM and strategies.
Mou, Weimin; Xiao, Chengli; McNamara, Timothy P.
Two experiments investigated participants' spatial memory of a briefly viewed layout. Participants saw an array of five objects on a table and, after a short delay, indicated whether the target object indicated by the experimenter had been moved. Experiment 1 showed that change detection was more accurate when non-target objects were stationary…
Lalonde, Jasmin; Chaudhuri, Avi
Discrimination thresholds were obtained using a delayed spatial frequency discrimination task. In Experiment 1, we found that presentation of a mask 3 s before onset of a reference Gabor patch caused a selective, spatial frequency dependent interference in a subsequent discrimination task. However, a 10 s interval abolished this masking effect. In Experiment 2, the mask was associated with a second spatial frequency discrimination task so that a representation of the mask had to be coded into short-term perceptual memory. This experiment was performed to assess whether absence of masking in the 10 s condition of Experiment 1 might be due to decay of the mask information in the perceptual or the memory representational domain. The presence of this second discrimination task now caused similar interference effects on the primary discrimination task at both the 3 s and 10 s interstimulus intervals (ISI) conditions. Finally, to test the robustness of the masking effect, the nature of the secondary masking task was changed from a spatial frequency discrimination task to an orientation discrimination task in Experiment 3. The masking effect was now abolished in both the 3 and 10 s ISI conditions. Together, the results from these experiments are consistent with the idea of a two-level perceptual memory mechanism. The results also suggest that stimulus representations during a perceptual discrimination task are shared between the perceptual and memory representation domains in a task-dependent manner.
Rodríguez, Fernando; López, J Carlos; Vargas, J Pedro; Gómez, Yolanda; Broglio, Cristina; Salas, Cosme
The hippocampus of mammals and birds is critical for spatial memory. Neuroanatomical evidence indicates that the medial cortex (MC) of reptiles and the lateral pallium (LP) of ray-finned fishes could be homologous to the hippocampus of mammals and birds. In this work, we studied the effects of lesions to the MC of turtles and to the LP of goldfish in spatial memory. Lesioned animals were trained in place, and cue maze tasks and crucial probe and transfer tests were performed. In experiment 1, MC-lesioned turtles in the place task failed to locate the goal during trials in which new start positions were used, whereas sham animals navigated directly to the goal independently of start location. In contrast, no deficit was observed in cue learning. In experiment 2, LP lesion produced a dramatic impairment in goldfish trained in the place task, whereas medial and dorsal pallium lesions did not decrease accuracy. In addition, none of these pallial lesions produced deficits in cue learning. These results indicate that lesions to the MC of turtles and to the LP of goldfish, like hippocampal lesions in mammals and birds, selectively impair map-like memory representations of the environmental space. Thus, the forebrain structures of reptiles and teleost fish neuroanatomically equivalent to the mammalian and avian hippocampus also share a central role in spatial cognition. Present results suggest that the presence of a hippocampus-dependent spatial memory system is a primitive feature of the vertebrate forebrain that has been conserved through evolution.
Ortmann, Margaret R.; Schutte, Anne R.
Early in development, there is a transition in spatial working memory (SWM). When remembering a location in a homogeneous space (e.g., in a sandbox), young children are biased toward the midline symmetry axis of the space. Over development, a transition occurs that leads to older children being biased away from midline. The dynamic field theory…
Wallentin, Mikkel; Kristensen, Line Burholt; Olsen, Jacob Hedeager; Nielsen, Andreas Hojlund
The brain's frontal eye fields (FEF), responsible for eye movement control, are known to be involved in spatial working memory (WM). In a previous fMRI experiment (Wallentin, Roepstorff & Burgess, Neuropsychologia, 2008) it was found that FEF activation was primarily related to the formation of an object-centered, rather than egocentric, spatial…
Schroeder, Anna; Hudson, Matthew; Du, Xin; Wu, Yee Wen Candace; Nakamura, Jay; van den Buuse, Maarten; Jones, Nigel C; Hill, Rachel A
Previous work suggests that estradiol regulates the expression of hippocampal parvalbumin as well as hippocampus-dependent spatial memory in mice. Parvalbumin interneurons generate neuronal oscillatory activity in the gamma frequency range (30-80Hz) and gamma oscillations are closely linked with higher cognitive functions. Raloxifene, a selective estrogen receptor modulator, shows beneficial effects on human cognitive performance, and has few peripheral side effects unlike estradiol, but the biological mechanisms which underpin these benefits are not clear. This study aimed to investigate whether estradiol and raloxifene modulate hippocampal gamma-band oscillations during spatial memory performance. Prepubescent female mice were ovariectomized (OVX) and implanted with a subcutaneous pellet of either estradiol (E2), raloxifene or placebo. During adulthood, local field potentials were recorded from the dorsal hippocampus while mice were performing the Y-maze hippocampus-dependent spatial memory task. Ovariectomy caused deficits in spatial memory, accompanied by a significant reduction in hippocampal gamma oscillations, specifically during decision making. Estradiol as well as raloxifene rescued both behavioural and electrophysiological deficits. These data have significant implications for disorders of cognitive impairment where altered gamma oscillations are apparent, such as schizophrenia.
Vestergaard, Martin; Madsen, Kathrine Skak; Baare, William F. C.; Skimminge, Arnold; Ejersbo, Lisser Rye; Ramsoy, Thomas Z.; Gerlach, Christian; Akeson, Per; Paulson, Olaf B.; Jernigan, Terry L.
During childhood and adolescence, ongoing white matter maturation in the fronto-parietal cortices and connecting fiber tracts is measurable with diffusion-weighted imaging. Important questions remain, however, about the links between these changes and developing cognitive functions. Spatial working memory (SWM) performance improves significantly…
Mahmoudi, Ali; Hosseini-Sharifabad, Ali; Monsef-Esfahani, Hamid R; Yazdinejad, Ali R; Khanavi, Mahnaz; Roghani, Ali; Beyer, Cordian; Sharifzadeh, Mohammad
Time-dependent effects of ethanolic extract of Boswellia papyrifera, administered systemically, on spatial memory retention in the Morris water maze were investigated in male rats. A total extract of Boswellia papyrifera (300 mg/kg) was administered every eight hours to three groups of rats by gavage for 1, 2 and 4 weeks. In a separate set of experiments, three doses of a fraction of the extract, called the boswellic acids (100, 200 and 300 mg/kg) were administered by gavage to three groups of rats three times a day for 2 weeks. Following these applications, animals were trained for 4 days. Behavioral testing for evaluation of spatial memory retention was performed 48 h after completion of training. Boswellia papyrifera extracts and boswellic acids caused a significant reduction in escape latency and distance traveled but had no influence on swimming speed. These findings provide evidence that Boswellia papyrifera extracts affect spatial memory retention irrespective of the treatment period. In addition our data show that systemic administration of the boswellic acids fraction enhanced spatial memory retention in a dose-dependent manner. These improving effects may be due to some extent to the interactions of these products with inflammatory mediators, neurotransmitter signaling cascades or protein kinase pathways in the brain.
Ramos, Juan M. J.
In a previous study we showed a temporally graded retrograde amnesia after hippocampal lesions when rats learned a spatial reference memory task in which two types of signals simultaneously indicated the goal arm (shape of the experimental room and extramaze landmarks). To investigate the effect that the navigational demands of the task have on…
Vuckovich, Joseph A.; Semel, Mara E.; Baxter, Mark G.
A recent study suggests that lesions to all major areas of the cholinergic basal forebrain in the rat (medial septum, horizontal limb of the diagonal band of Broca, and nucleus basalis magnocellularis) impair a spatial working memory task. However, this experiment used a surgical technique that may have damaged cerebellar Purkinje cells. The…
Wuhr, Peter; Biebl, Rupert
This study investigates the impact of working memory (WM) load on response conflicts arising from spatial (non) correspondence between irrelevant stimulus location and response location (Simon effect). The dominant view attributes the Simon effect to automatic processes of location-based response priming. The automaticity view predicts…
Wong, Ling M.; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.
Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with…
Yamazaki, Kaoruko; Wakabayashi, Noriyuki; Kobayashi, Takuya; Suzuki, Tetsuya
The mechanism by which tooth loss accelerates spatial memory impairment is unknown. The purpose of this study was to test the hypothesis that tooth loss affects trkB-mRNA levels and leads to an accelerated decrease in the hippocampal cell density in rats. A radial maze was used to evaluate the spatial memory of male Wistar rats that were categorized based on the number of extracted molar teeth. Number of hippocampal pyramidal cells and the trkB-mRNA expressions in the amygdala, perirhinal cortex, thalamus, and the hippocampal CA1, CA3, and CA4 areas, were evaluated using molecular biological techniques. Seven weeks after tooth extraction, maze performance was significantly lower in each tooth loss group than in the control group, and the number of extracted teeth was inversely proportional to the induction of the trkB-mRNA and the hippocampal cell density. The average weight of rats increased by controlled feeding throughout the experiment without showing a significant difference between the control and experimental groups. The results indicated that, in rats, the spatial memory-linked trkB-mRNA was reduced in association with the tooth loss; this supports the hypothesis and suggests that teeth have a role in the prevention of spatial memory impairment.
Holden, Mark P.; Curby, Kim M.; Newcombe, Nora S.; Shipley, Thomas F.
Memories for spatial locations often show systematic errors toward the central value of the surrounding region. This bias has been explained using a Bayesian model in which fine-grained and categorical information are combined (Huttenlocher, Hedges, & Duncan, 1991). However, experiments testing this model have largely used locations contained in…
Li, Taijun; Ren, Bowen; Wang, Dahui; Liu, Guobin
Knowledge about the long-term influences of climate change on the amount of potential carbon (C) sequestration in forest ecosystems, including age-related dynamics, remains unclear. This study used two similar age-sequences of black locust forests (Robinia pseudoacacia L.) in the semi-arid and semi-humid zones of China’s Loess Plateau to assess the variation in C stocks and age-related dynamics. Our results demonstrated that black locust forests of the semi-humid zone stored significantly more C than did forests in the semi-arid zone, across the chronosequence (p < 0.001). The C carrying capacity of the plantations was measured at 166.4 Mg C ha−1 (1 Mg = 106 g) in the semi-humid zone, while the semi-arid zone had a capacity of only 79.4 Mg C ha−1. Soil organic C (SOC) increased continuously with stand age in the semi-arid zone (R2 = 0.84, p = 0.010). However, in the semi-humid zone, SOC declined sharply by 47.8% after the initial stage (5 to 10 y). The C stock in trees increased continuously with stand age in the semi-humid zone (R2 = 0.83, p = 0.011), yet in the semi-arid zone, it decreased dramatically from 43.0 Mg C ha−1 to 28.4 Mg C ha−1 during the old forest stage (38 to 56 y). The shift from being a net C sink to a net C source occurred at the initial stage in the semi-humid zone versus at the old forest stage in the semi-arid zone after reforestation. Surprisingly, with the exception of the initial and later stages (55 y), the patterns of C allocation among trees, soils, understory and litter were not statistically different between the two climate zones. Our results suggest that climate factors can alter the potential amount and age-related dynamics of forest C sequestration. PMID:25799100
Li, Taijun; Ren, Bowen; Wang, Dahui; Liu, Guobin
Knowledge about the long-term influences of climate change on the amount of potential carbon (C) sequestration in forest ecosystems, including age-related dynamics, remains unclear. This study used two similar age-sequences of black locust forests (Robinia pseudoacacia L.) in the semi-arid and semi-humid zones of China's Loess Plateau to assess the variation in C stocks and age-related dynamics. Our results demonstrated that black locust forests of the semi-humid zone stored significantly more C than did forests in the semi-arid zone, across the chronosequence (p < 0.001). The C carrying capacity of the plantations was measured at 166.4 Mg C ha-1 (1 Mg = 106 g) in the semi-humid zone, while the semi-arid zone had a capacity of only 79.4 Mg C ha-1. Soil organic C (SOC) increased continuously with stand age in the semi-arid zone (R2 = 0.84, p = 0.010). However, in the semi-humid zone, SOC declined sharply by 47.8% after the initial stage (5 to 10 y). The C stock in trees increased continuously with stand age in the semi-humid zone (R2 = 0.83, p = 0.011), yet in the semi-arid zone, it decreased dramatically from 43.0 Mg C ha-1 to 28.4 Mg C ha-1 during the old forest stage (38 to 56 y). The shift from being a net C sink to a net C source occurred at the initial stage in the semi-humid zone versus at the old forest stage in the semi-arid zone after reforestation. Surprisingly, with the exception of the initial and later stages (55 y), the patterns of C allocation among trees, soils, understory and litter were not statistically different between the two climate zones. Our results suggest that climate factors can alter the potential amount and age-related dynamics of forest C sequestration.
Burke, Hanna M; Robinson, Cristina M; Wentz, Bethany; McKay, Jerel; Dexter, Kyle W; Pisansky, Julia M; Talbot, Jeffery N; Zoladz, Phillip R
It has been suggested that cognitive impairments exhibited by people with post-traumatic stress disorder (PTSD) result from intrusive, flashback memories transiently interfering with ongoing cognitive processing. Researchers have further speculated that females are more susceptible to developing PTSD because they form stronger traumatic memories than males, hence females may be more sensitive to the negative effects of intrusive memories on cognition. We have examined how the reminder of a naturalistic stress experience would affect rat spatial memory and if sex was a contributing factor to such effects. Male and female Sprague-Dawley rats were exposed, without contact, to an adult female cat for 30 min. Five weeks later, the rats were trained to locate a hidden platform in the radial-arm water maze and given a single long-term memory test trial 24 h later. Before long-term memory testing, the rats were given a 30-min reminder of the cat exposure experienced 5 weeks earlier. The results indicated that the stress reminder impaired spatial memory in the female rats only. Control manipulations revealed that this effect was not attributable to the original cat exposure adversely impacting learning that occurred 5 weeks later, or to merely exposing rats to a novel environment or predator-related cues immediately before testing. These findings provide evidence that the reminder of a naturalistic stressful experience can impair cognitive processing in rats; moreover, since female rats were more susceptible to the memory-impairing effects of the stress reminder, the findings could lend insight into the existing sex differences in susceptibility to PTSD.
Moscovitch, Morris; Rosenbaum, R Shayna; Gilboa, Asaf; Addis, Donna Rose; Westmacott, Robyn; Grady, Cheryl; McAndrews, Mary Pat; Levine, Brian; Black, Sandra; Winocur, Gordon; Nadel, Lynn
We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re-experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra-hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time-limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory. PMID
Beaudet, Gregory; Bouet, Valentine; Jozet-Alves, Christelle; Schumann-Bard, Pascale; Dauphin, François; Paizanis, Eleni; Boulouard, Michel; Freret, Thomas
Elderly persons often face biological, psychological or social changes over time that may cause discomfort or morbidity. While some cognitive domains remain stable over time, others undergo a decline. Spatial navigation is a complex cognitive function essential for independence, safety and quality of life. While egocentric (body-centered) navigation is quite preserved during aging, allocentric (externally-centered) navigation—based on a cognitive map using distant landmarks—declines with age. Recent preclinical studies showed that serotonergic 5-HT7 receptors are localized in brain regions associated with allocentric spatial navigation processing. Behavioral assessments with pharmacological or genetic tools have confirmed the role of 5-HT7 receptors in allocentric navigation. Moreover, few data suggested a selective age-related decrease in the expression of 5-HT7 receptors in pivotal brain structures implicated in allocentric navigation such as the hippocampal CA3 region. We aim to provide a short overview of the potential role of 5-HT7 receptors in spatial navigation, and to argue for their interests as therapeutic targets against age-related cognitive decline. PMID:25642173
Beaudet, Gregory; Bouet, Valentine; Jozet-Alves, Christelle; Schumann-Bard, Pascale; Dauphin, François; Paizanis, Eleni; Boulouard, Michel; Freret, Thomas
Elderly persons often face biological, psychological or social changes over time that may cause discomfort or morbidity. While some cognitive domains remain stable over time, others undergo a decline. Spatial navigation is a complex cognitive function essential for independence, safety and quality of life. While egocentric (body-centered) navigation is quite preserved during aging, allocentric (externally-centered) navigation-based on a cognitive map using distant landmarks-declines with age. Recent preclinical studies showed that serotonergic 5-HT7 receptors are localized in brain regions associated with allocentric spatial navigation processing. Behavioral assessments with pharmacological or genetic tools have confirmed the role of 5-HT7 receptors in allocentric navigation. Moreover, few data suggested a selective age-related decrease in the expression of 5-HT7 receptors in pivotal brain structures implicated in allocentric navigation such as the hippocampal CA3 region. We aim to provide a short overview of the potential role of 5-HT7 receptors in spatial navigation, and to argue for their interests as therapeutic targets against age-related cognitive decline.
Leszczyński, Marcin; Wykowska, Agnieszka; Perez-Osorio, Jairo; Müller, Hermann J
Recalling information from visual short-term memory (VSTM) involves the same neural mechanisms as attending to an actually perceived scene. In particular, retrieval from VSTM has been associated with orienting of visual attention towards a location within a spatially-organized memory representation. However, an open question concerns whether spatial attention is also recruited during VSTM retrieval even when performing the task does not require access to spatial coordinates of items in the memorized scene. The present study combined a visual search task with a modified, delayed central probe protocol, together with EEG analysis, to answer this question. We found a temporal contralateral negativity (TCN) elicited by a centrally presented go-signal which was spatially uninformative and featurally unrelated to the search target and informed participants only about a response key that they had to press to indicate a prepared target-present vs. -absent decision. This lateralization during VSTM retrieval (TCN) provides strong evidence of a shift of attention towards the target location in the memory representation, which occurred despite the fact that the present task required no spatial (or featural) information from the search to be encoded, maintained, and retrieved to produce the correct response and that the go-signal did not itself specify any information relating to the location and defining feature of the target.
Perez-Osorio, Jairo; Müller, Hermann J.
Recalling information from visual short-term memory (VSTM) involves the same neural mechanisms as attending to an actually perceived scene. In particular, retrieval from VSTM has been associated with orienting of visual attention towards a location within a spatially-organized memory representation. However, an open question concerns whether spatial attention is also recruited during VSTM retrieval even when performing the task does not require access to spatial coordinates of items in the memorized scene. The present study combined a visual search task with a modified, delayed central probe protocol, together with EEG analysis, to answer this question. We found a temporal contralateral negativity (TCN) elicited by a centrally presented go-signal which was spatially uninformative and featurally unrelated to the search target and informed participants only about a response key that they had to press to indicate a prepared target-present vs. -absent decision. This lateralization during VSTM retrieval (TCN) provides strong evidence of a shift of attention towards the target location in the memory representation, which occurred despite the fact that the present task required no spatial (or featural) information from the search to be encoded, maintained, and retrieved to produce the correct response and that the go-signal did not itself specify any information relating to the location and defining feature of the target. PMID:24386295
Mammarella, Irene C.; Meneghetti, Chiara; Pazzaglia, Francesca; Cornoldi, Cesare
The present study investigated the difficulties encountered by children with non-verbal learning disability (NLD) and reading disability (RD) when processing spatial information derived from descriptions, based on the assumption that both groups should find it more difficult than matched controls, but for different reasons, i.e., due to a memory encoding difficulty in cases of RD and to spatial information comprehension problems in cases of NLD. Spatial descriptions from both survey and route perspectives were presented to 9–12-year-old children divided into three groups: NLD (N = 12); RD (N = 12), and typically developing controls (TD; N = 15); then participants completed a sentence verification task and a memory for locations task. The sentence verification task was presented in two conditions: in one the children could refer to the text while answering the questions (i.e., text present condition), and in the other the text was withdrawn (i.e., text absent condition). Results showed that the RD group benefited from the text present condition, but was impaired to the same extent as the NLD group in the text absent condition, suggesting that the NLD children’s difficulty is due mainly to their poor comprehension of spatial descriptions, while the RD children’s difficulty is due more to a memory encoding problem. These results are discussed in terms of their implications in the neuropsychological profiles of children with NLD or RD, and the processes involved in spatial descriptions. PMID:25610417
Tyler, Anna L; Mahoney, J Matthew; Richard, Gregory R; Holmes, Gregory L; Lenck-Santini, Pierre-Pascal; Scott, Rod C
Status epilepticus (SE) is a common neurological emergency, which has been associated with subsequent cognitive impairments. Neuronal death in hippocampal CA1 is thought to be an important mechanism of these impairments. However, it is also possible that functional interactions between surviving neurons are important. In this study we recorded in vivo single-unit activity in the CA1 hippocampal region of rats while they performed a spatial memory task. From these data we constructed functional networks describing pyramidal cell interactions. To build the networks, we used maximum entropy algorithms previously applied only to in vitro data. We show that several months following SE pyramidal neurons display excessive neuronal synchrony and less neuronal reactivation during rest compared with those in healthy controls. Both effects predict rat performance in a spatial memory task. These results provide a physiological mechanism for SE-induced cognitive impairment and highlight the importance of the systems-level perspective in investigating spatial cognition.
Chow, Carmen; Epp, Jonathan R; Lieblich, Stephanie E; Barha, Cindy K; Galea, Liisa A M
Adult hippocampal neurogenesis is often associated with hippocampus-dependent learning and memory. Throughout a new neuron's development, it is differentially sensitive to factors that can influence its survival and functionality. Previous research shows that spatial training that occurred 6-10 days after an injection of the DNA synthesis marker, bromodeoxyuridine (BrdU), increased cell survival in male rats. Because sex differences in spatial cognition and hippocampal neurogenesis have been reported, it is unclear whether spatial training would influence hippocampal neurogenesis in the same way in males and females. Therefore, this study examined sex differences in hippocampal neurogenesis following training in a spatial task. Male and female rats were trained in the spatial or cued version of the Morris water maze 6-10 days after one injection of BrdU (200mg/kg). Twenty days following BrdU injection, all animals were given a probe trial and perfused. Males performed better in the spatial, but not cue, task than females. Spatial training increased BrdU-labeled cells relative to cue training only in males, but both males and females showed greater activation of new cells (BrdU co-labeled with immediate early gene product zif268) after spatial training compared to cue training. Furthermore, performance during spatial training was positively correlated with cell activation in females but not males. This study shows that while spatial training differentially regulates hippocampal neurogenesis in males and females, the activity of new neurons in response to spatial memory retrieval is similar. These findings highlight the importance of sex on neural plasticity and cognition.
Shinomori, Keizo; Schefrin, Brooke E.; Werner, John S.
Wavelength discrimination functions (420 to 620–650 nm) were measured for four younger (mean 30.9 years) and four older (mean 72.5 years) observers. Stimuli consisted of individually determined isoluminant monochromatic lights (10 Td) presented in each half of a 2° circular bipartite field with use of a Maxwellian-view optical system. A spatial two-alternative forced-choice method was used in combination with a staircase procedure to determine discrimination thresholds across the spectrum. Small but consistent elevations in discrimination thresholds were found for older compared with younger observers. Because the retinal illuminance of the stimuli was equated across all observers, these age-related losses in discrimination are attributable to neural changes. Analyses of these data reveal a significant change in Weber fraction across adulthood for a chromatically opponent pathway receiving primarily antagonistic signals from middle-wavelength-sensitive and long-wavelength-sensitive cones but not for a short-wavelength-sensitive cone pathway. PMID:11205976
Maillet, David; Schacter, Daniel L.
The majority of studies that have investigated the effects of healthy aging on cognition have focused on age-related differences in voluntary and deliberately engaged cognitive processes. Yet many forms of cognition occur spontaneously, without any deliberate attempt at engaging them. In this article we review studies that have assessed age-related differences in four such types of spontaneous thought processes: mind-wandering, involuntary autobiographical memory, intrusive thoughts, and spontaneous prospective memory retrieval. These studies suggest that older adults exhibit a reduction in frequency of both mind-wandering and involuntary autobiographical memory, whereas findings regarding intrusive thoughts have been more mixed. Additionally, there is some preliminary evidence that spontaneous prospective memory retrieval may be relatively preserved in aging. We consider the roles of age-related differences in cognitive resources, motivation, current concerns and emotional regulation in accounting for these findings. We also consider age-related differences in the neural correlates of spontaneous cognitive processes. PMID:26617263
Basu, Amrita; McFarlane, Hewlet G; Kopchick, John J
Growth hormone (GH) has a significant influence on cognitive performance in humans and other mammals. To understand the influence of altered GH action on cognition, we assessed spatial learning and memory using a Barnes maze (BM) comparing twelve-month old, male, bovine GH (bGH) and GH receptor antagonist (GHA) transgenic mice and their corresponding wild type (WT) littermates. During the acquisition training period in the BM, bGH mice showed increased latency, traveled longer path lengths and made more errors to reach the target than WT mice indicating significantly poorer learning. Short-term memory (STM) and long-term memory (LTM) trials showed significantly suppressed memory retention in bGH mice when compared to the WT group. Conversely, GHA mice showed significantly better learning parameters (latency, path length and errors) and increased use of an efficient search strategy than WT mice. Our study indicates a negative impact of GH excess and a beneficial effect of the inhibition of GH action on spatial learning and memory and, therefore, cognitive performance in male mice. Further research to elucidate GH's role in brain function will facilitate identifying therapeutic applications of GH or GHA for neuropathological and neurodegenerative conditions.
Olver, James S; Pinney, Myra; Maruff, Paul; Norman, Trevor R
Few studies have investigated the effect of an acute psychosocial stress paradigm on impaired attention and working memory in humans. Further, the duration of any stress-related cognitive impairment remains unclear. The aim of this study was to examine the effect of an acute psychosocial stress paradigm, the Trier Social Stress, on cognitive function in healthy volunteers. Twenty-three healthy male and female subjects were exposed to an acute psychosocial stress task. Physiological measures (salivary cortisol, heart rate and blood pressure) and subjective stress ratings were measured at baseline, in anticipation of stress, immediately post-stress and after a period of rest. A neuropsychological test battery including spatial working memory and verbal memory was administered at each time point. Acute psychosocial stress produced significant increases in cardiovascular and subjective measures in the anticipatory and post-stress period, which recovered to baseline after rest. Salivary cortisol steadily declined over the testing period. Acute psychosocial stress impaired delayed verbal recall, attention and spatial working memory. Attention remained impaired, and delayed verbal recall continued to decline after rest. Acute psychosocial stress is associated with an impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in attention and memory.
Wiener, J M; Ehbauer, N N; Mallot, H A
For large numbers of targets, path planning is a complex and computationally expensive task. Humans, however, usually solve such tasks quickly and efficiently. We present experiments studying human path planning performance and the cognitive processes and heuristics involved. Twenty-five places were arranged on a regular grid in a large room. Participants were repeatedly asked to solve traveling salesman problems (TSP), i.e., to find the shortest closed loop connecting a start location with multiple target locations. In Experiment 1, we tested whether humans employed the nearest neighbor (NN) strategy when solving the TSP. Results showed that subjects outperform the NN-strategy, suggesting that it is not sufficient to explain human route planning behavior. As a second possible strategy we tested a hierarchical planning heuristic in Experiment 2, demonstrating that participants first plan a coarse route on the region level that is refined during navigation. To test for the relevance of spatial working memory (SWM) and spatial long-term memory (LTM) for planning performance and the planning heuristics applied, we varied the memory demands between conditions in Experiment 2. In one condition the target locations were directly marked, such that no memory was required; a second condition required participants to memorize the target locations during path planning (SWM); in a third condition, additionally, the locations of targets had to retrieved from LTM (SWM and LTM). Results showed that navigation performance decreased with increasing memory demands while the dependence on the hierarchical planning heuristic increased.
Churchwell, John C; Kesner, Raymond P
Memory processes may be independent, compete, operate in parallel, or interact. In accordance with this view, behavioral studies suggest that the hippocampus (HPC) and prefrontal cortex (PFC) may act as an integrated circuit during performance of tasks that require working memory over longer delays, whereas during short delays the HPC and PFC may operate in parallel or have completely dissociable functions. In the present investigation we tested rats in a spatial delayed non-match to sample working memory task using short and long time delays to evaluate the hypothesis that intermediate CA1 region of the HPC (iCA1) and medial PFC (mPFC) interact and operate in parallel under different temporal working memory constraints. In order to assess the functional role of these structures, we used an inactivation strategy in which each subject received bilateral chronic cannula implantation of the iCA1 and mPFC, allowing us to perform bilateral, contralateral, ipsilateral, and combined bilateral inactivation of structures and structure pairs within each subject. This novel approach allowed us to test for circuit-level systems interactions, as well as independent parallel processing, while we simultaneously parametrically manipulated the temporal dimension of the task. The current results suggest that, at longer delays, iCA1 and mPFC interact to coordinate retrospective and prospective memory processes in anticipation of obtaining a remote goal, whereas at short delays either structure may independently represent spatial information sufficient to successfully complete the task.
Hashemi Nosrat Abadi, T; Vaghef, L; Babri, S; Mahmood-Alilo, M; Beirami, M
Chronic ethanol consumption is often accompanied by numerous cognitive deficits and may lead to long-lasting impairments in spatial learning and memory. The aim of the present study was to evaluate the therapeutic potential of regular treadmill exercise on hippocampal-dependent memory in ethanol-treated rats. Spatial memory was tested in a Morris Water Maze task. Adult male Wistar rats were exposed to ethanol (4 g/kg, 20% v/v for 4 weeks) and effects of three exercise protocols (pre-ethanol, post-ethanol and pre-to-post-ethanol treatment) were examined. Results showed that ethanol exposure resulted in longer escape latencies during the acquisition phase of the Morris Water Maze task. Moreover, all three exercise protocols significantly decreased the latency to locate the hidden platform. During the probe trial, ethanol led to decreased time spent in the target quadrant. In contrast, performance on the probe trial was significantly better in the rats that had done the post- and pre-to-post-ethanol, but not pre-ethanol, exercises. These findings suggest that treadmill running can attenuate the adverse effects of chronic ethanol exposure on spatial memory, and may serve as a non-pharmacological alcohol abuse treatment.
Sun, Huaying; Mao, Yu; Wang, Jianhong; Ma, Yuanye
The beta-adrenergic system has been suggested to be involved in novelty detection and memory modulation. The present study aimed to investigate the role of beta-adrenergic receptors on novelty-based spatial recognition memory and exploratory behavior in mice using Y-maze test and open-field respectively. Mice were injected with three doses of beta-adrenergic receptor antagonist, propranolol (2, 10 and 20 mg/kg) or saline at three different time points (15 min prior to training, immediately after training and 15 min before test). The results showed that higher doses of propranolol (10 and 20 mg/kg) given before the training trial impaired spatial recognition memory while those injected at other two time points did not. A detailed analysis of exploratory behavior in open-field showed that lower dose (2 mg/kg) of propranolol reduced exploratory behavior of mice. Our findings indicate that higher dose of propranolol can impair acquisition of spatial information in the Y-maze without altering locomotion, suggesting that the beta-adrenergic system may be involved in modulating memory processes at the time of learning.
Patarroyo, William E; García-Perez, Milady; Lamprea, Marisol; Múnera, Alejandro; Troncoso, Julieta
This research was aimed at establishing how the absence of active whisking in rats affects acquisition and recovery of spatial memory. The mystacial vibrissae were irreversibly paralyzed by cutting the facial nerve's mandibular and buccal branches bilaterally in the facial nerve lesion group (N=14); control animals were submitted to sham-surgery (N=15). Sham-operated (N=11) and facial nerve-lesioned (N=10) animals were trained (one session, eight acquisition trials) and tested 24h later in a circular Barnes maze. It was found that facial nerve lesioned-animals adequately acquired the spatial task, but had impaired recovery of it when tested 24h after training as compared to control ones. Plasma corticosterone levels were measured after memory testing in four randomly chosen animals of each trained group and after a single training trial in the maze in additional facial nerve-lesioned (N=4) and sham-operated animals (N=4). Significant differences respecting the elevation of corticosterone concentration after either a single training trial or memory testing indicated that stress response was enhanced in facial nerve-lesioned animals as compared to control ones. Increased corticosterone levels during training and testing might have elicited the observed whisker paralysis-induced spatial memory retrieval impairment.
Chen, Yan-Chu; Hsu, Wei-Lun; Ma, Yun-Li; Tai, Derek J C; Lee, Eminy H Y
cAMP-responsive element binding protein (CREB) phosphorylation and signaling plays an important role in long-term memory formation, but other posttranslational modifications of CREB are less known. Here, we found that CREB1Δ, the short isoform of CREB, could be sumoylated by the small ubiquitin-like modifier (SUMO) E3 ligase protein inhibitor of activated STAT1 (PIAS1) at Lys271 and Lys290 and PIAS1 SUMOylation of CREB1Δ increased the expression level of CREB1Δ. CREB1Δ could also be sumoylated by other PIAS family proteins, but not by the E3 ligases RanBP2 and Pc2 or by the E2 ligase Ubc9. Furthermore, water maze training increased the level of endogenous CREB SUMOylation in rat CA1 neurons determined by in vitro SUMOylation assay, but this effect was not observed in other brain areas. Moreover, transduction of Lenti-CREBWT to rat CA1 area facilitated, whereas transduction of Lenti-CREB double sumo-mutant (CREBK271RK290R) impaired, spatial learning and memory performance. Transduction of Lenti-CREBWT-SUMO1 fusion vector to rat CA1 area showed a more significant effect in enhancing spatial learning and memory and CREB SUMOylation. Lenti-CREBWT transduction increased, whereas Lenti-CREBK271RK290R transduction decreased, CREB DNA binding to the brain-derived neurotrophic factor (bdnf) promoter and decreased bdnf mRNA expression. Knock-down of PIAS1 expression in CA1 area by PIAS1 siRNA transfection impaired spatial learning and memory and decreased endogenous CREB SUMOylation. In addition, CREB SUMOylation was CREB phosphorylation dependent and lasted longer. Therefore, CREB phosphorylation may be responsible for signal transduction during the early phase of long-term memory formation, whereas CREB SUMOylation sustains long-term memory.
Slotnick, Scott D; Thakral, Preston P
Long-term memory can be based on general familiarity or detailed recollection. Although familiarity is thought to be a continuous/graded process, the nature of recollection is currently under debate. In the present functional MRI spatial source memory study, we evaluated the pattern of activity in the hippocampus to assess whether this region operates in a threshold/all-or-none or a continuous manner during recollection. During the study phase, abstract shapes were presented to the left or right of fixation. During the test phase, old and new shapes were presented at fixation, and participants classified each shape as old-left, old-right, or new, followed by a sure-unsure confidence rating. Accurate spatial memory for old-left shapes produced a single activation in the left hippocampus. The corresponding event-related activation profile revealed a threshold above which old-left-sure responses produced positive activity for old-left but not old-right shapes. This hippocampal activation profile was used to generate a source memory receiver operating characteristic that was adequately fit by a threshold model of recollection but was not adequately fit by a continuous model of recollection. By contrast, there was no evidence of a threshold in the behavioral response profile, which is consistent with previous behavioral source memory receiver operating characteristic results indicating that recollection is a continuous process. The present results indicate that the hippocampus can operate in a threshold manner during spatial source memory and further suggest that this discrete signal is transformed into a continuous process through the operation of other brain regions that also contribute to behavioral performance.
Voytek, Bradley; Kramer, Mark A; Case, John; Lepage, Kyle Q; Tempesta, Zechari R; Knight, Robert T; Gazzaley, Adam
Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15-53 years) and scalp EEG data from healthy younger (20-30 years) and older (60-70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <-1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. Significance statement: Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise-induced deficits in
Working memory is a dynamic neural system that includes processes for temporarily maintaining and processing information. Working memory plays a significant role in a variety of cognitive functions, such as thinking, reasoning, decision-making, and language comprehension. Although the prefrontal cortex (PFC) is known to play an important role in working memory, several lines of evidence indicate that the thalamic mediodorsal nucleus (MD) also participates in this process. While monkeys perform spatial working memory tasks, MD neurons exhibit directionally selective delay-period activity, which is considered to be a neural correlate for the temporary maintenance of information in PFC neurons. Studies have also shown that, while most MD neurons maintain prospective motor information, some maintain retrospective sensory information. Thus, the MD plays a greater role in prospective motor aspects of working memory processes than the PFC, which participates more in retrospective aspects. For the performance of spatial working memory tasks, the information provided by a sensory cue needs to be transformed into motor information to give an appropriate response. A population vector analysis using neural activities revealed that, although the transformation of sensory-to-motor information occurred during the delay period in both the PFC and the MD, PFC activities maintained sensory information until the late phase of the delay period, while MD activities initially represented sensory information but then started to represent motor information in the earlier phase of the delay period. These results indicate that long-range neural interactions supported by reciprocal connections between the MD and the PFC could play an important role in the transformation of maintained information in working memory processes.
Katshu, Mohammad Zia Ul Haq; d'Avossa, Giovanni
While sensory processes are tuned to particular features, such as an object's specific location, color or orientation, visual working memory (vWM) is assumed to store information using representations, which generalize over a feature dimension. Additionally, current vWM models presume that different features or objects are stored independently. On the other hand, configurational effects, when observed, are supposed to mainly reflect encoding strategies. We show that the location of the target, relative to the display center and boundaries, and overall memory load influenced recall precision, indicating that, like sensory processes, capacity limited vWM resources are spatially tuned. When recalling one of three memory items the target distance from the display center was overestimated, similar to the error when only one item was memorized, but its distance from the memory items' average position was underestimated, showing that not only individual memory items' position, but also the global configuration of the memory array may be stored. Finally, presenting the non-target items at recall, consequently providing landmarks and configurational information, improved precision and accuracy of target recall. Similarly, when the non-target items were translated at recall, relative to their position in the initial display, a parallel displacement of the recalled target was observed. These findings suggest that fine-grained spatial information in vWM is represented in local maps whose resolution varies with distance from landmarks, such as the display center, while coarse representations are used to store the memory array configuration. Both these representations are updated at the time of recall. PMID:25259601
Croston, Rebecca; Branch, Carrie L; Kozlovsky, Dovid Y; Roth, Timothy C; LaDage, Lara D; Freas, Cody A; Pravosudov, Vladimir V
Harsh environments and severe winters have been hypothesized to favor improvement of the cognitive abilities necessary for successful foraging. Geographic variation in winter climate, then, is likely associated with differences in selection pressures on cognitive ability, which could lead to evolutionary changes in cognition and its neural mechanisms, assuming that variation in these traits is heritable. Here, we focus on two species of food-caching chickadees (genus Poecile), which rely on stored food for survival over winter and require the use of spatial memory to recover their stores. These species also exhibit extensive climate-related population level variation in spatial memory and the hippocampus, including volume, the total number and size of neurons, and adults' rates of neurogenesis. Such variation could be driven by several mechanisms within the context of natural selection, including independent, population-specific selection (local adaptation), environment experience-based plasticity, developmental differences, and/or epigenetic differences. Extensive data on cognition, brain morphology, and behavior in multiple populations of these two species of chickadees along longitudinal, latitudinal, and elevational gradients in winter climate are most consistent with the hypothesis that natural selection drives the evolution of local adaptations associated with spatial memory differences among populations. Conversely, there is little support for the hypotheses that environment-induced plasticity or developmental differences are the main causes of population differences across climatic gradients. Available data on epigenetic modifications of memory ability are also inconsistent with the observed patterns of population variation, with birds living in more stressful and harsher environments having better spatial memory associated with a larger hippocampus and a larger number of hippocampal neurons. Overall, the existing data are most consistent with the
Majkutewicz, Irena; Kurowska, Ewelina; Podlacha, Magdalena; Myślińska, Dorota; Grembecka, Beata; Ruciński, Jan; Plucińska, Karolina; Jerzemowska, Grażyna; Wrona, Danuta
Intracerebroventricular (ICV) injection of streptozotocin (STZ) is a widely-accepted animal model of sporadic Alzheimer's disease (sAD). The present study evaluated the ability of dimethyl fumarate (DMF), an agent with antioxidant and anti-inflammatory properties, to prevent spatial memory impairments and hippocampal neurodegeneration mediated by ICV injection of STZ in 4-month-old rats. Rodent chow containing DMF (0.4%) or standard rodent chow was made available on day 0. Rat body weight and food intake were measured daily for whole the experiment (21days). STZ or vehicle (SHAM) ICV injections were performed on days 2 and 4. Spatial reference and working memory were evaluated using the Morris water maze on days 14-21. Cells containing Fluoro-Jade B (neurodegeneration marker), IL-6, IL-10 were quantified in the hippocampus and choline acetyltransferase (ChAT) in the basal forebrain. The disruption of spatial memory and a high density of hippocampal CA1-3 cells labeled with Fluoro-Jade B or containing IL-6 or IL-10 were observed in the STZ group but not in the STZ+DMF group, as compared to the SHAM or SHAM+DMF groups. STZ vs. STZ+DMF differences were found: worse reference memory acquisition, fewer ChAT-positive neurons in the medial septum (Ch1), more Fluoro-Jade-positive CA1 hippocampal cells in STZ rats. DMF therapy in a rodent model of sAD prevented the disruption of spatial reference and working memory, loss of Ch1 cholinergic cells and hippocampal neurodegeneration as well as the induction of IL-6 and IL-10 in CA1. These beneficial cognitive and molecular effects validate the anti-inflammatory and neuroprotective properties of DMF in the hippocampus.
Thangarajan, Rajesh; Rai, Kiranmai. S.; Gopalakrishnan, Sivakumar; Perumal, Vivek
Background Gestational infections induced inflammation (GIII) is a cause of various postnatal neurological deficits in developing countries. Such intra uterine insults could result in persistent learning-memory disabilities. There are no studies elucidating the efficacy of adolescence exercise on spatial learning- memory abilities of young adult rats pre-exposed to inflammatory insult during fetal life. Aims and Objectives The present study addresses the efficacy of physical (running) exercise during adolescent period in attenuating spatial memory deficits induced by exposure to GIII in rats. Materials and Methods Pregnant Wistar dams were randomly divided into control and lipopolysaccharide (LPS) groups, injected intra peritoneally (i.p) with saline (0.5ml) or lipopolysaccharide (LPS) (0.5mg/kg) on alternate days from gestation day 14 (GD 14) till delivery. After parturition, pups were divided into 3 groups (n=6/group) a) Sham control and LPS group divided into 2 subgroups- b) LPS and c) LPS exercise group. Running exercise was given only to LPS exercise group during postnatal days (PNDs) 30 to 60 (15min/day). Spatial learning and memory performance was assessed by Morris water maze test (MWM), on postnatal day 61 to 67 in all groups. Results Young rats pre-exposed to GIII and subjected to running exercise through juvenile period displayed significant decrease in latency to reach escape platform and spent significant duration in target quadrant in MWM test, compared to age matched LPS group. Results of the current study demonstrated that exercise through juvenile/adolescent period effectively mitigates gestational inflammation-induced cognitive deficits in young adult rats. Conclusion Inflammation during gestation impairs offspring’s spatial memory and learning abilities. Whereas, early postnatal physical exercise attenuates, to higher extent, cognitive impairment resulted from exposure to LPS induced inflammation during intrauterine growth period. PMID:26266117
Roskos-Ewoldsen, Beverly; Black, Sheila R.; Mccown, Steven M.
Age-related differences in cognitive processes were used to understand age-related declines in creativity. According to the Geneplore model (Finke, Ward, & Smith, 1992), there are two phases of creativity--generating an idea and exploring the implications of the idea--each with different underlying cognitive processes. These two phases are…
Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 . Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...
Alexander, Gerianne M; Packard, Mark G; Peterson, Bradley S
Memory for object location relative both to veridical center (left versus right visual hemispace) and to eccentricity (central versus peripheral objects) was measured in 26 males and 25 females using the Silverman and Eals Location Memory Task. A subset of participants (17 males and 13 females) also completed a measure of implicit learning, the mirror-tracing task. No sex differences were observed in memory for object identities. Further, in both sexes, memory for object locations was better for peripherally located objects than for centrally located objects. In contrast to these similarities in female and male task performance, females but not males showed better recovery of object locations in the right compared to the left visual hemispace. Moreover, memory for object locations in the right hemispace was associated with mirror-tracing performance in women but not in men. Together, these data suggest that the processing of object features and object identification in the left cerebral hemisphere may include processing of spatial information that may contribute to superior object location memory in females relative to males.
Brunec, Iva K; Ozubko, Jason D; Barense, Morgan D; Moscovitch, Morris
Time and space represent two key aspects of episodic