The Rate of Source Memory Decline across the Adult Life Span

ERIC Educational Resources Information Center

Cansino, Selene; Estrada-Manilla, Cinthya; Hernandez-Ramos, Evelia; Martinez-Galindo, Joyce Graciela; Torres-Trejo, Frine; Gomez-Fernandez, Tania; Ayala-Hernandez, Mariana; Osorio, David; Cedillo-Tinoco, Melisa; Garces-Flores, Lissete; Gomez-Melgarejo, Sandra; Beltran-Palacios, Karla; Guadalupe Garcia-Lazaro, Haydee; Garcia-Gutierrez, Fabiola; Cadena-Arenas, Yadira; Fernandez-Apan, Luisa; Bartschi, Andrea; Resendiz-Vera, Julieta; Rodriguez-Ortiz, Maria Dolores

2013-01-01

Previous studies have suggested that the ability to remember contextual information related to specific episodic experiences declines with advancing age; however, the exact moment in the adult life span when this deficit begins is still controversial. Source memory for spatial information was tested in a life span sample of 1,500 adults between…

Delayed-matching-to-place Task in a Dry Maze to Measure Spatial Working Memory in Mice.

PubMed

Feng, Xi; Krukowski, Karen; Jopson, Timothy; Rosi, Susanna

2017-07-05

The delayed-matching-to-place (DMP) dry maze test is a variant of DMP water maze (Steele and Morris, 1999; Faizi et al. , 2012) which measures spatial working/episodic-like learning and memory that depends on both hippocampal and cortical functions (Wang and Morris, 2010; Euston et al. , 2012). Using this test we can detect normal aging related spatial working memory decline, as well as trauma induced working memory deficits. Furthermore, we recently reported that fractionated whole brain irradiation does not affect working memory in mice (Feng et al. , 2016). Here we describe the experimental setup and procedures of this behavioral test.

Dopaminergic and cholinergic modulations of visual-spatial attention and working memory: insights from molecular genetic research and implications for adult cognitive development.

PubMed

Störmer, Viola S; Passow, Susanne; Biesenack, Julia; Li, Shu-Chen

2012-05-01

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.

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function.

PubMed

Kwon, Diana; Maillet, David; Pasvanis, Stamatoula; Ankudowich, Elizabeth; Grady, Cheryl L; Rajah, M Natasha

2016-06-01

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Exposure to radiation accelerates normal brain aging and produces deficits in spatial learning and memory

NASA Astrophysics Data System (ADS)

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

Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice.

PubMed

Kubo, Kin-ya; Yamada, Yukiko; Iinuma, Mitsuo; Iwaku, Fumihiko; Tamura, Yasuo; Watanabe, Kazuko; Nakamura, Hiroyuki; Onozuka, Minoru

2007-03-06

We examined the effect of occlusal disharmony in senescence-accelerated (SAMP8) mice on plasma corticosterone levels, hippocampal neuron number, and spatial performance in the water maze. The bite-raised condition was associated with an accelerated age-related decline in spatial memory, increased plasma corticosterone levels, and a decreased number of neurons in the hippocampal CA3 region. The findings suggest that the bite-raised condition in aged SAMP8 mice induces hippocampal neuron loss, thereby leading to senile memory deficits.

Delayed-matching-to-place Task in a Dry Maze to Measure Spatial Working Memory in Mice

PubMed Central

Feng, Xi; Krukowski, Karen; Jopson, Timothy; Rosi, Susanna

2017-01-01

The delayed-matching-to-place (DMP) dry maze test is a variant of DMP water maze (Steele and Morris, 1999; Faizi et al., 2012) which measures spatial working/episodic-like learning and memory that depends on both hippocampal and cortical functions (Wang and Morris, 2010; Euston et al., 2012). Using this test we can detect normal aging related spatial working memory decline, as well as trauma induced working memory deficits. Furthermore, we recently reported that fractionated whole brain irradiation does not affect working memory in mice (Feng et al., 2016). Here we describe the experimental setup and procedures of this behavioral test. PMID:28944261

Late Enrichment Maintains Accurate Recent and Remote Spatial Memory Only in Aged Rats That Were Unimpaired When Middle Aged

ERIC Educational Resources Information Center

Fuchs, Fanny; Herbeaux, Karine; Aufrere, Noémie; Kelche, Christian; Mathis, Chantal; Barbelivien, Alexandra; Majchrzak, Monique

2016-01-01

Exposure of rodents to a stimulating environment has beneficial effects on some cognitive functions that are impaired during physiological aging, and especially spatial reference memory. The present study investigated whether environmental enrichment rescues these functions in already declining subjects and/or protects them from subsequent…

Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.

PubMed

Schipper, Sandra; Aalbers, Marlien W; Rijkers, Kim; Lagiere, Melanie; Bogaarts, Jan G; Blokland, Arjan; Klinkenberg, Sylvia; Hoogland, Govert; Vles, Johan S H

2016-12-01

Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Course of Relational and Non-Relational Recognition Memory across the Adult Lifespan

ERIC Educational Resources Information Center

Soei, Eleonore; Daum, Irene

2008-01-01

Human recognition memory shows a decline during normal ageing, which is thought to be related to age-associated dysfunctions of mediotemporal lobe structures. Whether the hippocampus is critical for human general relational memory or for spatial relational memory only is still disputed. The human perirhinal cortex is thought to be critically…

A lower ratio of omega-6 to omega-3 fatty acids predicts better hippocampus-dependent spatial memory and cognitive status in older adults.

PubMed

Andruchow, Nadia D; Konishi, Kyoko; Shatenstein, Bryna; Bohbot, Véronique D

2017-10-01

Evidence from several cross-sectional studies indicates that an increase in omega-6 to omega-3 fatty acids (FAs) may negatively affect cognition in old age. The hippocampus is among the first neural structures affected by age and atrophy in this brain region is associated with cognitive decline. Therefore, we hypothesized that a lower omega-6:3 FA ratio would predict better hippocampus-dependent spatial memory, and a higher general cognitive status. Fifty-two healthy older adults completed a Food Frequency Questionnaire, the Montreal Cognitive Assessment test (MoCA; a test of global cognition) and virtual navigation tasks that assess navigational strategies and spatial memory. In this cross-sectional study, a lower ratio of omega-6 to omega-3 FA intake strongly predicted more accurate hippocampus-dependent spatial memory and faster learning on our virtual navigation tasks, as well as higher cognitive status overall. These results may help elucidate why certain dietary patterns with a lower omega-6:3 FA ratio, like the Mediterranean diet, are associated with reduced risk of cognitive decline. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The Aging Navigational System.

PubMed

Lester, Adam W; Moffat, Scott D; Wiener, Jan M; Barnes, Carol A; Wolbers, Thomas

2017-08-30

The discovery of neuronal systems dedicated to computing spatial information, composed of functionally distinct cell types such as place and grid cells, combined with an extensive body of human-based behavioral and neuroimaging research has provided us with a detailed understanding of the brain's navigation circuit. In this review, we discuss emerging evidence from rodents, non-human primates, and humans that demonstrates how cognitive aging affects the navigational computations supported by these systems. Critically, we show 1) that navigational deficits cannot solely be explained by general deficits in learning and memory, 2) that there is no uniform decline across different navigational computations, and 3) that navigational deficits might be sensitive markers for impending pathological decline. Following an introduction to the mechanisms underlying spatial navigation and how they relate to general processes of learning and memory, the review discusses how aging affects the perception and integration of spatial information, the creation and storage of memory traces for spatial information, and the use of spatial information during navigational behavior. The closing section highlights the clinical potential of behavioral and neural markers of spatial navigation, with a particular emphasis on neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of memory representation in the vigilance decrement.

PubMed

Caggiano, Daniel M; Parasuraman, Raja

2004-10-01

Working memory load is critically important for the overall level of performance on vigilance tasks. However, its role in a key aspect of vigilance-sensitivity decrement over time-is unclear. We used a dual-task procedure in which either a spatial or a nonspatial working memory task was performed simultaneously with a spatial vigilance task for 20 min. Sensitivity in the vigilance task declined over time when the concurrent task involved spatial working memory. In contrast, there was no sensitivity decrement with a nonspatial working memory task. The results provide the first evidence of a specific role for working memory representation in vigilance decrement. The findings are also consistent with a multiple resource theory in which separate resources for memory representation and cognitive control operations are differentially susceptible to depletion over time, depending on the demands of the task at hand.

Changes in hippocampal volume and neuron number co-occur with memory decline in old homing pigeons (Columba livia).

PubMed

Coppola, Vincent J; Kanyok, Nate; Schreiber, Austin J; Flaim, Mary E; Bingman, Verner P

2016-05-01

The mammalian hippocampus is particularly susceptible to age-related structural changes, which have been used to explain, in part, age-related memory decline. These changes are generally characterized by atrophy (e.g., a decrease in volume and number of synaptic contacts). Recent studies have reported age-related spatial memory deficits in older pigeons similar to those seen in older mammals. However, to date, little is known about any co-occurring changes in the aging avian hippocampal formation (HF). In the current study, it was found that the HF of older pigeons was actually larger and contained more neurons than the HF of younger pigeons, a finding that suggests that the pattern of structural changes during aging in the avian HF is different from that seen in the mammalian hippocampus. A working hypothesis for relating the observed structural changes with spatial-cognitive decline is offered. Copyright © 2016 Elsevier Inc. All rights reserved.

A simple spatial working memory and attention test on paired symbols shows developmental deficits in schizophrenia patients.

PubMed

Song, Wei; Zhang, Kai; Sun, Jinhua; Ma, Lina; Jesse, Forrest Fabian; Teng, Xiaochun; Zhou, Ying; Bao, Hechen; Chen, Shiqing; Wang, Shuai; Yang, Beimeng; Chu, Xixia; Ding, Wenhua; Du, Yasong; Cheng, Zaohuo; Wu, Bin; Chen, Shanguang; He, Guang; He, Lin; Chen, Xiaoping; Li, Weidong

2013-01-01

People with neuropsychiatric disorders such as schizophrenia often display deficits in spatial working memory and attention. Evaluating working memory and attention in schizophrenia patients is usually based on traditional tasks and the interviewer's judgment. We developed a simple Spatial Working Memory and Attention Test on Paired Symbols (SWAPS). It takes only several minutes to complete, comprising 101 trials for each subject. In this study, we tested 72 schizophrenia patients and 188 healthy volunteers in China. In a healthy control group with ages ranging from 12 to 60, the efficiency score (accuracy divided by reaction time) reached a peak in the 20-27 age range and then declined with increasing age. Importantly, schizophrenia patients failed to display this developmental trend in the same age range and adults had significant deficits compared to the control group. Our data suggests that this simple Spatial Working Memory and Attention Test on Paired Symbols can be a useful tool for studies of spatial working memory and attention in neuropsychiatric disorders.

An exploratory study of the effects of spatial working-memory load on prefrontal activation in low- and high-performing elderly.

PubMed

Vermeij, Anouk; van Beek, Arenda H E A; Reijs, Babette L R; Claassen, Jurgen A H R; Kessels, Roy P C

2014-01-01

Older adults show more bilateral prefrontal activation during cognitive performance than younger adults, who typically show unilateral activation. This over-recruitment has been interpreted as compensation for declining structure and function of the brain. Here we examined how the relationship between behavioral performance and prefrontal activation is modulated by different levels of working-memory load. Eighteen healthy older adults (70.8 ± 5.0 years; MMSE 29.3 ± 0.9) performed a spatial working-memory task (n-back). Oxygenated ([O2Hb]) and deoxygenated ([HHb]) hemoglobin concentration changes were registered by two functional Near-Infrared Spectroscopy (fNIRS) channels located over the left and right prefrontal cortex. Increased working-memory load resulted in worse performance compared to the control condition. [O2Hb] increased with rising working-memory load in both fNIRS channels. Based on the performance in the high working-memory load condition, the group was divided into low and high performers. A significant interaction effect of performance level and hemisphere on [O2Hb] increase was found, indicating that high performers were better able to keep the right prefrontal cortex engaged under high cognitive demand. Furthermore, in the low performers group, individuals with a larger decline in task performance from the control to the high working-memory load condition had a larger bilateral increase of [O2Hb]. The high performers did not show a correlation between performance decline and working-memory load related prefrontal activation changes. Thus, additional bilateral prefrontal activation in low performers did not necessarily result in better cognitive performance. Our study showed that bilateral prefrontal activation may not always be successfully compensatory. Individual behavioral performance should be taken into account to be able to distinguish successful and unsuccessful compensation or declined neural efficiency.

Impairments of spatial working memory and attention following acute psychosocial stress.

PubMed

Olver, James S; Pinney, Myra; Maruff, Paul; Norman, Trevor R

2015-04-01

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. Copyright © 2014 John Wiley & Sons, Ltd.

Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence

PubMed Central

Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C.

2015-01-01

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

Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence.

PubMed

Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C

2015-11-01

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS

PubMed Central

Rocca, Maria A.; Leavitt, Victoria M.; Dackovic, Jelena; Mesaros, Sarlota; Drulovic, Jelena; DeLuca, John; Filippi, Massimo

2014-01-01

Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time. Methods: Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression. Results: Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ηp2 = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.126) and memory (p = 0.037, ηp2 = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment. Conclusion: We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS. PMID:24748670

The role of memory representation in the vigilance decrement

PubMed Central

CAGGIANO, DANIEL M.; PARASURAMAN, RAJA

2005-01-01

Working memory load is critically important for the overall level of performance on vigilance tasks. However, its role in a key aspect of vigilance—sensitivity decrement over time—is unclear. We used a dual-task procedure in which either a spatial or a nonspatial working memory task was performed simultaneously with a spatial vigilance task for 20 min. Sensitivity in the vigilance task declined over time when the concurrent task involved spatial working memory. In contrast, there was no sensitivity decrement with a nonspatial working memory task. The results provide the first evidence of a specific role for working memory representation in vigilance decrement. The findings are also consistent with a multiple resource theory in which separate resources for memory representation and cognitive control operations are differentially susceptible to depletion over time, depending on the demands of the task at hand. PMID:15732706

Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression After Whole-Brain Irradiation

PubMed Central

Wong-Goodrich, Sarah J.E.; Pfau, Madeline L.; Flores, Catherine T.; Fraser, Jennifer A.; Williams, Christina L.; Jones, Lee W.

2010-01-01

Whole-brain irradiation (WBI) therapy produces progressive learning and memory deficits in patients with primary or secondary brain tumors. Exercise enhances memory and adult hippocampal neurogenesis in the intact brain, so we hypothesized that exercise may be an effective treatment to alleviate consequences of WBI. Previous studies using animal models to address this issue have yielded mixed results and have not examined potential molecular mechanisms. We investigated the short- and long-term effects of WBI on spatial learning and memory retention, and determined whether voluntary running after WBI aids recovery of brain and cognitive function. Forty adult female C57Bl/6 mice given a single dose of 5 Gy or sham WBI were trained 2.5 weeks and up to four months after WBI in a Barnes maze. Half of the mice received daily voluntary wheel access starting one month after sham- or WBI. Daily running following WBI prevented the marked decline in spatial memory retention observed months after irradiation. Bromodeoxyuridine (BrdU) immunolabeling and ELISA indicated that this behavioral rescue was accompanied by a partial restoration of newborn BrdU+/NeuN+ neurons in the dentate gyrus and increased hippocampal expression of brain-derived vascular endothelial growth factor and insulin-like growth factor, and occurred despite irradiation-induced elevations in hippocampal pro-inflammatory cytokines. WBI in adult mice produced a progressive memory decline consistent with what has been reported in cancer patients receiving WBI therapy. Our findings show that running can abrogate this memory decline and aid recovery of adult hippocampal plasticity, thus highlighting exercise as a potential therapeutic intervention. PMID:20884629

Team performance in networked supervisory control of unmanned air vehicles: effects of automation, working memory, and communication content.

PubMed

McKendrick, Ryan; Shaw, Tyler; de Visser, Ewart; Saqer, Haneen; Kidwell, Brian; Parasuraman, Raja

2014-05-01

Assess team performance within a net-worked supervisory control setting while manipulating automated decision aids and monitoring team communication and working memory ability. Networked systems such as multi-unmanned air vehicle (UAV) supervision have complex properties that make prediction of human-system performance difficult. Automated decision aid can provide valuable information to operators, individual abilities can limit or facilitate team performance, and team communication patterns can alter how effectively individuals work together. We hypothesized that reliable automation, higher working memory capacity, and increased communication rates of task-relevant information would offset performance decrements attributed to high task load. Two-person teams performed a simulated air defense task with two levels of task load and three levels of automated aid reliability. Teams communicated and received decision aid messages via chat window text messages. Task Load x Automation effects were significant across all performance measures. Reliable automation limited the decline in team performance with increasing task load. Average team spatial working memory was a stronger predictor than other measures of team working memory. Frequency of team rapport and enemy location communications positively related to team performance, and word count was negatively related to team performance. Reliable decision aiding mitigated team performance decline during increased task load during multi-UAV supervisory control. Team spatial working memory, communication of spatial information, and team rapport predicted team success. An automated decision aid can improve team performance under high task load. Assessment of spatial working memory and the communication of task-relevant information can help in operator and team selection in supervisory control systems.

Exposure to 56Fe irradiation accelerates normal brain aging and produces deficits in spatial learning and memory

NASA Astrophysics Data System (ADS)

Shukitt-Hale, Barbara; Casadesus, Gemma; Carey, Amanda N.; Rabin, Bernard M.; Joseph, James A.

Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles) such as 56Fe, 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. For example, an increased release of reactive oxygen species, and the subsequent oxidative stress and inflammatory damage caused to the central nervous system, is likely responsible for the deficits seen in aging and following irradiation. Therefore, dietary antioxidants, such as those found in fruits and vegetables, could be used as countermeasures to prevent the behavioral changes seen in these conditions. 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 56Fe high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts, particularly middle-aged ones, to perform critical tasks during long-term space travel beyond the magnetosphere.

Short term memory for single surface features and bindings in ageing: A replication study.

PubMed

Isella, Valeria; Molteni, Federica; Mapelli, Cristina; Ferrarese, Carlo

2015-06-01

In the present study we replicated a previous experiment investigating visuo-spatial short term memory binding in young and older healthy individuals, in the attempt to verify the pattern of impairment that can be observed in normal elderly for short term memory for single items vs short term memory for bindings. Assessing a larger sample size (25 young and 25 older subjects), using a more appropriate measure of accuracy for a change detection task (A'), and adding the evaluation of speed of performance, we confirmed that old normals show a decline in short term memory for bindings of shape and colour that is of comparable extent, and not major, to the decline in memory for single shapes and single colours. The absence of a specific deficit of short term memory for conjunctions of surface features seems to distinguish cognitive ageing from Alzheimer's Disease. Copyright © 2015 Elsevier Inc. All rights reserved.

The reduced serum free triiodothyronine and increased dorsal hippocampal SNAP-25 and Munc18-1 had existed in middle-aged CD-1 mice with mild spatial cognitive impairment.

PubMed

Cao, Lei; Jiang, Wei; Wang, Fang; Yang, Qi-Gang; Wang, Chao; Chen, Yong-Ping; Chen, Gui-Hai

2013-12-02

Changes of synaptic proteins in highlighted brain regions and decreased serum thyroid hormones (THs) have been implied in age-related learning and memory decline. Previously, we showed significant pairwise correlations among markedly impaired spatial learning and memory ability, decreased serum free triiodothyronine (FT3) and increased hippocampal SNAP-25 and Munc18-1 in old Kunming mice. However, whether these changes and the correlations occur in middle-age mice remains unclear. Since this age is one of the best stages to study age-related cognitive decline, we explored the spatial learning and memory ability, serum THs, cerebral SNAP-25 and Munc18-1 levels and their relationships of middle-aged mice in this study. The learning and memory abilities of 35 CD-1 mice (19 mice aged 6 months and 16 mice aged 12 months) were measured with a radial six-arm water maze (RAWM). The SNAP-25 and Munc18-1 levels were semi-quantified by Western blotting and the serum THs were detected by radioimmunoassay. The results showed the middle-aged mice had decreased serum FT3, increased dorsal hippocampal (DH) SNAP-25 and Munc18-1, and many or long number of errors and latency in both learning and memory phases of the RAWM. The Pearson's correlation test showed that the DH SANP-25 and Munc18-1 levels were positively correlated with the number of errors and latency in learning phases of the RAWM. Meanwhile, the DH SANP-25 and Munc18-1 levels negatively correlated with the serum FT3 level. These results suggested that reduced FT3 with increased DH SNAP-25 and Munc18-1 levels might be involved in the spatial learning ability decline in the middle-aged mice. © 2013 Elsevier B.V. All rights reserved.

A Special Extract of Bacopa monnieri (CDRI-08) Restores Learning and Memory by Upregulating Expression of the NMDA Receptor Subunit GluN2B in the Brain of Scopolamine-Induced Amnesic Mice

PubMed Central

Rai, Rakesh; Singh, Hemant K.; Prasad, S.

2015-01-01

In the present communication, we have investigated effects of the CDRI-08, a well characterized extract of Bacopa monnieri, on expression of the GluN2B subunit of NMDAR in various brain regions of the scopolamine-induced amnesic mice. Our behavioral data reveal that scopolamine-treated amnesic mice exhibit significant decline in the spatial memory compared to the normal control mice. Our RT-PCR and immunoblotting data revealed that the scopolamine treatment resulted in a significant downregulation of the NMDAR GluN2B subunit expression in prefrontal cortex and hippocampus. Our enzyme assay data revealed that scopolamine caused a significant increase in the acetylcholinesterase activity in both the brain regions. Further, oral administration of the CDRI-08 to scopolamine-treated amnesic mice restored the spatial memory which was found to be associated with significant upregulation of the GluN2B subunit expression and decline in the acetylcholinesterase activity in prefrontal cortex as well as hippocampus towards their levels in the normal control mice. Our study provides the evidence for the mechanism underlying role of the Bacopa monnieri extract (CDRI-08) in restoring spatial memory in amnesic mice, which may have therapeutic implications. PMID:26413117

Effects of pointing compared with naming and observing during encoding on item and source memory in young and older adults.

PubMed

Ouwehand, Kim; van Gog, Tamara; Paas, Fred

2016-10-01

Research showed that source memory functioning declines with ageing. Evidence suggests that encoding visual stimuli with manual pointing in addition to visual observation can have a positive effect on spatial memory compared with visual observation only. The present study investigated whether pointing at picture locations during encoding would lead to better spatial source memory than naming (Experiment 1) and visual observation only (Experiment 2) in young and older adults. Experiment 3 investigated whether response modality during the test phase would influence spatial source memory performance. Experiments 1 and 2 supported the hypothesis that pointing during encoding led to better source memory for picture locations than naming or observation only. Young adults outperformed older adults on the source memory but not the item memory task in both Experiments 1 and 2. In Experiments 1 and 2, participants manually responded in the test phase. Experiment 3 showed that if participants had to verbally respond in the test phase, the positive effect of pointing compared with naming during encoding disappeared. The results suggest that pointing at picture locations during encoding can enhance spatial source memory in both young and older adults, but only if the response modality is congruent in the test phase.

Poorer Visual Acuity Is Associated with Declines in Cognitive Performance Across Multiple Cognitive Domains: The Maine-Syracuse Longitudinal Study.

PubMed

Dearborn, Peter J; Elias, Merrill F; Sullivan, Kevin J; Sullivan, Cara E; Robbins, Michael A

2018-06-21

Prior studies have found associations between visual acuity (VA) and cognitive function. However, these studies used a limited range of cognitive measures and did not control for cardiovascular disease risk factors (CVD-RFs) and baseline function. The primary objective of this study was to analyze the associations of VA and cognitive performance using a thorough neuropsychological test battery. This study used community-dwelling sample data across the sixth (2001-2006) and seventh (2006-2010) waves of the Maine-Syracuse Longitudinal Study (n=655). Wave 6 VA as measured by the Snellen Eye Test was the primary predictor of wave 6 and wave 7 Global cognitive performance, Visual-Spatial Organization and Memory, Verbal Episodic Memory, Working Memory, Scanning and Tracking, and Executive Function. Additionally, VA was used to predict longitudinal changes in wave 7 cognitive performance (wave 6 performance adjusted). We analyzed these relationships with multiple linear and logistic regression models adjusted for age, sex, education, ethnicity, depressive symptoms, physical function deficits in addition to CVD-RFs, chronic kidney disease, homocysteine, continuous systolic blood pressure, and hypertension status. Adjusted for demographic covariates and CVD-RFs, poorer VA was associated with concurrent and approximate 5-year declines in Global cognitive function, Visual-Spatial Organization and Memory, and Verbal Episodic Memory. VA may be used in combination with other screening measures to determine risk for cognitive decline. (JINS, 2018, 24, 1-9).

Arginine vasopressin prevents against Abeta(25-35)-induced impairment of spatial learning and memory in rats.

PubMed

Pan, Yan-Fang; Chen, Xiao-Rong; Wu, Mei-Na; Ma, Cun-Gen; Qi, Jin-Shun

2010-04-01

Amyloid beta protein (Abeta) is thought to be responsible for loss of memory in Alzheimer's disease (AD). A significant decrease in [Arg(8)]-vasopressin (AVP) has been found in the AD brain and in plasma; however, it is unclear whether this decrease in AVP is involved in Abeta-induced impairment of spatial cognition and whether AVP can protect against Abeta-induced deficits in cognitive function. The present study examined the effects of intracerebroventricular (i.c.v.) injection of AVP on spatial learning and memory in the Morris water maze test and investigated the potential protective function of AVP against Abeta-induced impairment in spatial cognition. The results were as follows: (1) i.c.v. injection of 25 nmol Abeta(25-35) resulted in a significant decline in spatial learning and memory; (2) 1 nmol and 10 nmol, but not 0.1 nmol, AVP injections markedly improved learning and memory; (3) pretreatment with 1 nmol or 10 nmol, but not 0.1 nmol, AVP effectively reversed the impairment in spatial learning and memory induced by Abeta(25-35); and (4) none of the drugs, including Abeta(25-35) and different concentrations of AVP, affected the vision or swimming speed of the rats. These results indicate that Abeta(25-35) could significantly impair spatial learning and memory in rats, and pretreatment with AVP centrally can enhance spatial learning and effectively prevent the behavioral impairment induced by neurotoxic Abeta(25-35). Thus, the present study provides further insight into the mechanisms by which Abeta impairs spatial learning and memory, suggesting that up-regulation of central AVP might be beneficial in the prevention and treatment of AD. Copyright 2010 Elsevier Inc. All rights reserved.

Erythropoietin Attenuates the Memory Deficits in Aging Rats by Rescuing the Oxidative Stress and Inflammation and Promoting BDNF Releasing.

PubMed

Jia, Zhankui; Xue, Rui; Ma, Shengli; Xu, Jingjing; Guo, Si; Li, Songchao; Zhang, Erwei; Wang, Jun; Yang, Jinjian

2016-10-01

Aging is a natural process accompanied with many disorders, including the memory decline. The underlying mechanisms for the age-related memory decline are complicated. Previous work suggested that oxidative stress, inflammatory disturbance, and the neurotropic absence play important roles in the age-related disorders. Thus, to seek a drug to target those abnormalities might be a possible protective approach for aging. Here, we reported that supplements with exogenous erythropoietin (EPO) for 4 weeks could partially rescue the spatial and fear memory impairments in aged rats. The EPO treatment also suppresses the oxidative stress and inflammatory response. Most importantly, EPO supplement restores the mRNA and protein levels of brain-derived neurotrophic factor (BDNF), the critical neurotropic factor for synaptic plasticity and memory. Our study strongly suggests the potential usage of EPO in an anti-aging agent clinically.

White matter microstructure mediates the relationship between cardiorespiratory fitness and spatial working memory in older adults.

PubMed

Oberlin, Lauren E; Verstynen, Timothy D; Burzynska, Agnieszka Z; Voss, Michelle W; Prakash, Ruchika Shaurya; Chaddock-Heyman, Laura; Wong, Chelsea; Fanning, Jason; Awick, Elizabeth; Gothe, Neha; Phillips, Siobhan M; Mailey, Emily; Ehlers, Diane; Olson, Erin; Wojcicki, Thomas; McAuley, Edward; Kramer, Arthur F; Erickson, Kirk I

2016-05-01

White matter structure declines with advancing age and has been associated with a decline in memory and executive processes in older adulthood. Yet, recent research suggests that higher physical activity and fitness levels may be associated with less white matter degeneration in late life, although the tract-specificity of this relationship is not well understood. In addition, these prior studies infrequently associate measures of white matter microstructure to cognitive outcomes, so the behavioral importance of higher levels of white matter microstructural organization with greater fitness levels remains a matter of speculation. Here we tested whether cardiorespiratory fitness (VO2max) levels were associated with white matter microstructure and whether this relationship constituted an indirect pathway between cardiorespiratory fitness and spatial working memory in two large, cognitively and neurologically healthy older adult samples. Diffusion tensor imaging was used to determine white matter microstructure in two separate groups: Experiment 1, N=113 (mean age=66.61) and Experiment 2, N=154 (mean age=65.66). Using a voxel-based regression approach, we found that higher VO2max was associated with higher fractional anisotropy (FA), a measure of white matter microstructure, in a diverse network of white matter tracts, including the anterior corona radiata, anterior internal capsule, fornix, cingulum, and corpus callosum (PFDR-corrected<.05). This effect was consistent across both samples even after controlling for age, gender, and education. Further, a statistical mediation analysis revealed that white matter microstructure within these regions, among others, constituted a significant indirect path between VO2max and spatial working memory performance. These results suggest that greater aerobic fitness levels are associated with higher levels of white matter microstructural organization, which may, in turn, preserve spatial memory performance in older adulthood. Copyright © 2015 Elsevier Inc. All rights reserved.

Idea density measured in late life predicts subsequent cognitive trajectories: implications for the measurement of cognitive reserve.

PubMed

Farias, Sarah Tomaszewski; Chand, Vineeta; Bonnici, Lisa; Baynes, Kathleen; Harvey, Danielle; Mungas, Dan; Simon, Christa; Reed, Bruce

2012-11-01

The Nun Study showed that lower linguistic ability in young adulthood, measured by idea density (ID), increased the risk of dementia in late life. The present study examined whether ID measured in late life continues to predict the trajectory of cognitive change. ID was measured in 81 older adults who were followed longitudinally for an average of 4.3 years. Changes in global cognition and 4 specific neuropsychological domains (episodic memory, semantic memory, spatial abilities, and executive function) were examined as outcomes. Separate random effects models tested the effect of ID on longitudinal change in outcomes, adjusted for age and education. Lower ID was associated with greater subsequent decline in global cognition, semantic memory, episodic memory, and spatial abilities. When analysis was restricted to only participants without dementia at the time ID was collected, results were similar. Linguistic ability in young adulthood, as measured by ID, has been previously proposed as an index of neurocognitive development and/or cognitive reserve. The present study provides evidence that even when ID is measured in old age, it continues to be associated with subsequent cognitive decline and as such may continue to provide a marker of cognitive reserve.

Remembering to learn: independent place and journey coding mechanisms contribute to memory transfer.

PubMed

Bahar, Amir S; Shapiro, Matthew L

2012-02-08

The neural mechanisms that integrate new episodes with established memories are unknown. When rats explore an environment, CA1 cells fire in place fields that indicate locations. In goal-directed spatial memory tasks, some place fields differentiate behavioral histories ("journey-dependent" place fields) while others do not ("journey-independent" place fields). To investigate how these signals inform learning and memory for new and familiar episodes, we recorded CA1 and CA3 activity in rats trained to perform a "standard" spatial memory task in a plus maze and in two new task variants. A "switch" task exchanged the start and goal locations in the same environment; an "altered environment" task contained unfamiliar local and distal cues. In the switch task, performance was mildly impaired, new firing maps were stable, but the proportion and stability of journey-dependent place fields declined. In the altered environment, overall performance was strongly impaired, new firing maps were unstable, and stable proportions of journey-dependent place fields were maintained. In both tasks, memory errors were accompanied by a decline in journey codes. The different dynamics of place and journey coding suggest that they reflect separate mechanisms and contribute to distinct memory computations. Stable place fields may represent familiar relationships among environmental features that are required for consistent memory performance. Journey-dependent activity may correspond with goal-directed behavioral sequences that reflect expectancies that generalize across environments. The complementary signals could help link current events with established memories, so that familiarity with either a behavioral strategy or an environment can inform goal-directed learning.

REMEMBERING TO LEARN: INDEPENDENT PLACE AND JOURNEY CODING MECHANISMS CONTRIBUTE TO MEMORY TRANSFER

PubMed Central

Bahar, Amir S.; Shapiro, Matthew L.

2012-01-01

The neural mechanisms that integrate new episodes with established memories are unknown. When rats explore an environment, CA1 cells fire in place fields that indicate locations. In goal-directed spatial memory tasks, some place fields differentiate behavioral histories (journey-dependent place fields) while others do not (journey-independent place fields). To investigate how these signals inform learning and memory for new and familiar episodes, we recorded CA1 and CA3 activity in rats trained to perform a standard spatial memory task in a plus maze and in two new task variants. A switch task exchanged the start and goal locations in the same environment; an altered environment task contained unfamiliar local and distal cues. In the switch task, performance was mildly impaired, new firing maps were stable, but the proportion and stability of journey-dependent place fields declined. In the altered environment, overall performance was strongly impaired, new firing maps were unstable, and stable proportions of journey-dependent place fields were maintained. In both tasks, memory errors were accompanied by a decline in journey codes. The different dynamics of place and journey coding suggest that they reflect separate mechanisms and contribute to distinct memory computations. Stable place fields may represent familiar relationships among environmental features that are required for consistent memory performance. Journey-dependent activity may correspond with goal directed behavioral sequences that reflect expectancies that generalize across environments. The complementary signals could help link current events with established memories, so that familiarity with either a behavioral strategy or an environment can inform goal-directed learning. PMID:22323731

The cortisol awakening response and memory performance in older men and women.

PubMed

Almela, Mercedes; van der Meij, Leander; Hidalgo, Vanesa; Villada, Carolina; Salvador, Alicia

2012-12-01

The activity and regulation of the hypothalamus-pituitary-adrenal axis has been related to cognitive decline during aging. This study investigated whether the cortisol awakening response (CAR) is related to memory performance among older adults. The sample was composed of 88 participants (44 men and 44 women) from 55 to 77 years old. The memory assessment consisted of two tests measuring declarative memory (a paragraph recall test and a word list learning test) and two tests measuring working memory (a spatial span test and a spatial working memory test). Among those participants who showed the CAR on two consecutive days, we found that a greater CAR was related to poorer declarative memory performance in both men and women, and to better working memory performance only in men. The results of our study suggest that the relationship between CAR and memory performance is negative in men and women when memory performance is largely dependent on hippocampal functioning (i.e. declarative memory), and positive, but only in men, when memory performance is largely dependent on prefrontal cortex functioning (i.e. working memory). Copyright © 2012 Elsevier Ltd. All rights reserved.

Normative shifts of cortical mechanisms of encoding contribute to adult age differences in visual-spatial working memory.

PubMed

Störmer, Viola S; Li, Shu-Chen; Heekeren, Hauke R; Lindenberger, Ulman

2013-06-01

The capacity of visual-spatial working memory (WM) declines from early to late adulthood. Recent attempts at identifying neural correlates of WM capacity decline have focused on the maintenance phase of WM. Here, we investigate neural mechanisms during the encoding phase as another potential mechanism contributing to adult age differences in WM capacity. We used electroencephalography to track neural activity during encoding and maintenance on a millisecond timescale in 35 younger and 35 older adults performing a visual-spatial WM task. As predicted, we observed pronounced age differences in ERP indicators of WM encoding: Younger adults showed attentional selection during item encoding (N2pc component), but this selection mechanism was greatly attenuated in older adults. Conversely, older adults showed more pronounced signs of early perceptual stimulus processing (N1 component) than younger adults. The amplitude modulation of the N1 component predicted WM capacity in older adults, whereas the attentional amplitude modulation of the N2pc component predicted WM capacity in younger adults. Our findings suggest that adult age differences in mechanisms of WM encoding contribute to adult age differences in limits of visual-spatial WM capacity. Copyright © 2013 Elsevier Inc. All rights reserved.

Preserved memory-based orienting of attention with impaired explicit memory in healthy ageing

PubMed Central

Salvato, Gerardo; Patai, Eva Z.; Nobre, Anna C.

2016-01-01

It is increasingly recognised that spatial contextual long-term memory (LTM) prepares neural activity for guiding visuo-spatial attention in a proactive manner. In the current study, we investigated whether the decline in explicit memory observed in healthy ageing would compromise this mechanism. We compared the behavioural performance of younger and older participants on learning new contextual memories, on orienting visual attention based on these learnt contextual associations, and on explicit recall of contextual memories. We found a striking dissociation between older versus younger participants in the relationship between the ability to retrieve contextual memories versus the ability to use these to guide attention to enhance performance on a target-detection task. Older participants showed significant deficits in the explicit retrieval task, but their behavioural benefits from memory-based orienting of attention were equivalent to those in young participants. Furthermore, memory-based orienting correlated significantly with explicit contextual LTM in younger adults but not in older adults. These results suggest that explicit memory deficits in ageing might not compromise initial perception and encoding of events. Importantly, the results also shed light on the mechanisms of memory-guided attention, suggesting that explicit contextual memories are not necessary. PMID:26649914

Assessment of Attentional Workload while Driving by Eye-fixation-related Potentials

NASA Astrophysics Data System (ADS)

Takeda, Yuji; Yoshitsugu, Noritoshi; Itoh, Kazuya; Kanamori, Nobuhiro

How do drivers cope with the attentional workload of in-vehicle information technology? In the present study, we propose a new psychophysiological measure for assessing drivers' attention: eye-fixation-related potential (EFRP). EFRP is a kind of event-related brain potential measurable at the eye-movement situation that reflects how closely observers examine visual information at the eye-fixated position. In the experiment, the effects of verbal working memory load and spatial working memory load during simulated driving were examined by measuring the number of saccadic eye-movements and EFRP as the indices of drivers' attention. The results showed that the spatial working memory load affected both the number of saccadic eye-movements and the amplitude of the P100 component of EFRP, whereas the verbal working memory load affected only the number of saccadic eye-movements. This implies that drivers can perform time-sharing processing between driving and the verbal working memory task, but the decline of accuracy of visual processing during driving is inescapable when the spatial working memory load is given. The present study suggests that EFRP can provide a new index of drivers' attention, other than saccadic eye-movements.

Selective white matter pathology induces a specific impairment in spatial working memory.

PubMed

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

2011-12-01

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 parallel pathology and behavior in the same mice. Copyright © 2011. Published by Elsevier Inc.

Idea Density Measured in Late Life Predicts Subsequent Cognitive Trajectories: Implications for the Measurement of Cognitive Reserve

PubMed Central

Chand, Vineeta; Bonnici, Lisa; Baynes, Kathleen; Harvey, Danielle; Mungas, Dan; Simon, Christa; Reed, Bruce

2012-01-01

Objective. The Nun Study showed that lower linguistic ability in young adulthood, measured by idea density (ID), increased the risk of dementia in late life. The present study examined whether ID measured in late life continues to predict the trajectory of cognitive change. Method. ID was measured in 81 older adults who were followed longitudinally for an average of 4.3 years. Changes in global cognition and 4 specific neuropsychological domains (episodic memory, semantic memory, spatial abilities, and executive function) were examined as outcomes. Separate random effects models tested the effect of ID on longitudinal change in outcomes, adjusted for age and education. Results. Lower ID was associated with greater subsequent decline in global cognition, semantic memory, episodic memory, and spatial abilities. When analysis was restricted to only participants without dementia at the time ID was collected, results were similar. Discussion. Linguistic ability in young adulthood, as measured by ID, has been previously proposed as an index of neurocognitive development and/or cognitive reserve. The present study provides evidence that even when ID is measured in old age, it continues to be associated with subsequent cognitive decline and as such may continue to provide a marker of cognitive reserve. PMID:22357642

Effects of blueberries on inflammation, motor performance and cognitive function

USDA-ARS?s Scientific Manuscript database

Motor and cognitive function decrease with age, to include deficits in balance, coordination, gait, processing speed, executive function, memory, and spatial learning. These functional declines may be caused by long term increases in and susceptibility to oxidative stress and inflammation. Research ...

Early deficits in spatial memory and theta rhythm in experimental temporal lobe epilepsy.

PubMed

Chauvière, Laetitia; Rafrafi, Nadia; Thinus-Blanc, Catherine; Bartolomei, Fabrice; Esclapez, Monique; Bernard, Christophe

2009-04-29

Patients with temporal lobe epilepsy (TLE), the most common form of epilepsy in adults, often display cognitive deficits. The time course and underlying mechanisms of cognitive decline remain unknown during epileptogenesis (the process leading to epilepsy). Using the rat pilocarpine model of TLE, we performed a longitudinal study to assess spatial and nonspatial cognitive performance during epileptogenesis. In parallel, we monitored interictal-like activity (ILA) in the hippocampal CA1 region, as well as theta oscillations, a brain rhythm central to numerous cognitive processes. Here, we report that spatial memory was altered soon after pilocarpine-induced status epilepticus, i.e., already during the seizure-free, latent period. Spatial deficits correlated with a decrease in the power of theta oscillations but not with the frequency of ILA. Spatial deficits persisted when animals had spontaneous seizures (chronic stage) without further modification. In contrast, nonspatial memory performances remained unaffected throughout. We conclude that the reorganization of hippocampal circuitry that immediately follows the initial insult can affect theta oscillation mechanisms, in turn, resulting in deficits in hippocampus-dependent memory tasks. These deficits may be dissociated from the process that leads to epilepsy itself but could instead constitute, as ILA, early markers in at-risk patients and/or provide beneficial therapeutic targets.

Preserved memory-based orienting of attention with impaired explicit memory in healthy ageing.

PubMed

Salvato, Gerardo; Patai, Eva Z; Nobre, Anna C

2016-01-01

It is increasingly recognised that spatial contextual long-term memory (LTM) prepares neural activity for guiding visuo-spatial attention in a proactive manner. In the current study, we investigated whether the decline in explicit memory observed in healthy ageing would compromise this mechanism. We compared the behavioural performance of younger and older participants on learning new contextual memories, on orienting visual attention based on these learnt contextual associations, and on explicit recall of contextual memories. We found a striking dissociation between older versus younger participants in the relationship between the ability to retrieve contextual memories versus the ability to use these to guide attention to enhance performance on a target-detection task. Older participants showed significant deficits in the explicit retrieval task, but their behavioural benefits from memory-based orienting of attention were equivalent to those in young participants. Furthermore, memory-based orienting correlated significantly with explicit contextual LTM in younger adults but not in older adults. These results suggest that explicit memory deficits in ageing might not compromise initial perception and encoding of events. Importantly, the results also shed light on the mechanisms of memory-guided attention, suggesting that explicit contextual memories are not necessary. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Environmental impoverishment and aging alter object recognition, spatial learning, and dentate gyrus astrocytes.

PubMed

Diniz, Daniel G; Foro, César A R; Rego, Carla M D; Gloria, David A; de Oliveira, Fabio R R; Paes, Juliana M P; de Sousa, Aline A; Tokuhashi, Tatyana P; Trindade, Lucas S; Turiel, Maíra C P; Vasconcelos, Erick G R; Torres, João B; Cunnigham, Colm; Perry, Victor H; Vasconcelos, Pedro F da Costa; Diniz, Cristovam W P

2010-08-01

Environmental and age-related effects on learning and memory were analysed and compared with changes observed in astrocyte laminar distribution in the dentate gyrus. Aged (20 months) and young (6 months) adult female albino Swiss mice were housed from weaning either in impoverished conditions or in enriched conditions, and tested for episodic-like and water maze spatial memories. After these behavioral tests, brain hippocampal sections were immunolabeled for glial fibrillary acid protein to identify astrocytes. The effects of environmental enrichment on episodic-like memory were not dependent on age, and may protect water maze spatial learning and memory from declines induced by aging or impoverished environment. In the dentate gyrus, the number of astrocytes increased with both aging and enriched environment in the molecular layer, increased only with aging in the polymorphic layer, and was unchanged in the granular layer. We suggest that long-term experience-induced glial plasticity by enriched environment may represent at least part of the circuitry groundwork for improvements in behavioral performance in the aged mice brain.

Age-related differences in the use of spatial and categorical relationships in a visuo-spatial working memory task.

PubMed

Dai, Ruizhi; Thomas, Ayanna K; Taylor, Holly A

2018-01-30

Research examining object identity and location processing in visuo-spatial working memory (VSWM) has yielded inconsistent results on whether age differences exist in VSWM. The present study investigated whether these inconsistencies may stem from age-related differences in VSWM sub-processes, and whether processing of component VSWM information can be facilitated. In two experiments, younger and older adults studied 5 × 5 grids containing five objects in separate locations. In a continuous recognition paradigm, participants were tested on memory for object identity, location, or identity and location information combined. Spatial and categorical relationships were manipulated within grids to provide trial-level facilitation. In Experiment 1, randomizing trial types (location, identity, combination) assured that participants could not predict the information that would be queried. In Experiment 2, blocking trials by type encouraged strategic processing. Thus, we manipulated the nature of the task through object categorical relationship and spatial organization, and trial blocking. Our findings support age-related declines in VSWM. Additionally, grid organizations (categorical and spatial relationships), and trial blocking differentially affected younger and older adults. Younger adults used spatial organizations more effectively whereas older adults demonstrated an association bias. Our finding also suggests that older adults may be less efficient than younger adults in strategically engaging information processing.

Scopolamine-induced greater alterations in neurochemical profile and increased oxidative stress demonstrated a better model of dementia: A comparative study.

PubMed

Haider, Saida; Tabassum, Saiqa; Perveen, Tahira

2016-10-01

Cognitive decline is found to be a common feature of various neurological disorders like Alzheimer's disease (AD). In order to recapitulate AD associated cognitive deficits and to plan therapeutic strategies researchers have developed various preclinical dementia models to recapitulate different aspects of cognitive domains affected in AD brain. So, the present study was aimed to compare alterations in previously reported dementia models i.e. pharmacological (Scopolamine-induced and corticosterone-induced), Environmental (Aluminium-induced and noise-stress) and physiological (natural aging) models in rats in a single experimental study across three cognitive domains spatial, recognition, and associative memory and associated alterations in their oxidative status and neurochemical profile to select appropriate dementia model. All groups received their respective treatments for 14days after which behavioural analysis was performed including Open Field test to assess ambulatory activity, Novel Object Recognition test, Morris Water Maze test and Passive Avoidance test for the assessment of recognition, spatial and associative memory. After monitoring the behavioural activities, rats were decapitated and their brains and hippocampus samples were collected for analysis of oxidative status and neurochemical profile. Results showed significant decline in different aspects of memory function in all dementia models which was more significant in scopolamine-injected rats. A significant decline in levels of monoamines and acetylcholine was also observed. In addition, significant alterations were also seen in oxidative profile indicating that cognitive decline could be associated with increased oxidative stress. Therefore, present findings highlight that for planning therapeutic strategies against cognitive dysfunctions, scopolamine-induced dementia model is the most appropriate dementia model to reveal AD-related cognitive impairment profile. Copyright © 2016 Elsevier Inc. All rights reserved.

Individual variations in dose response for spatial memory learning among outbred wistar rats exposed from 5 to 20 cGy of (56) Fe particles.

PubMed

Wyrobek, Andrew J; Britten, Richard A

2016-06-01

Exposures of brain tissue to ionizing radiation can lead to persistent deficits in cognitive functions and behaviors. However, little is known about the quantitative relationships between exposure dose and neurological risks, especially for lower doses and among genetically diverse individuals. We investigated the dose relationship for spatial memory learning among genetically outbred male Wistar rats exposed to graded doses of (56) Fe particles (sham, 5, 10, 15, and 20 cGy; 1 GeV/n). Spatial memory learning was assessed on a Barnes maze using REL3 ratios measured at three months after exposure. Irradiated animals showed dose-dependent declines in spatial memory learning that were fit by a linear regression (P for slope <0.0002). The irradiated animals showed significantly impaired learning at 10 cGy exposures, no detectable learning between 10 and 15 cGy, and worsened performances between 15 and 20 cGy. The proportions of poor learners and the magnitude of their impairment were fit by linear regressions with doubling doses of ∼10 cGy. In contrast, there were no detectable deficits in learning among the good learners in this dose range. Our findings suggest that genetically diverse individuals can vary substantially in their spatial memory learning, and that exposures at low doses appear to preferentially impact poor learners. This hypothesis invites future investigations of the genetic and physiological mechanisms of inter-individual variations in brain function related to spatial memory learning after low-dose HZE radiation exposures and to determine whether it also applies to physical trauma to brain tissue and exposures to chemical neurotoxicants. Environ. Mol. Mutagen. 57:331-340, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hippocampus-dependent spatial memory impairment due to molar tooth loss is ameliorated by an enriched environment.

PubMed

Kondo, Hiroko; Kurahashi, Minori; Mori, Daisuke; Iinuma, Mitsuo; Tamura, Yasuo; Mizutani, Kenmei; Shimpo, Kan; Sonoda, Shigeru; Azuma, Kagaku; Kubo, Kin-ya

2016-01-01

Teeth are crucial, not only for mastication, but for overall nutrition and general health, including cognitive function. Aged mice with chronic stress due to tooth loss exhibit impaired hippocampus-dependent learning and memory. Exposure to an enriched environment restores the reduced hippocampal function. Here, we explored the effects of an enriched environment on learning deficits and hippocampal morphologic changes in aged senescence-accelerated mouse strain P8 (SAMP8) mice with tooth loss. Eight-month-old male aged SAMP8 mice with molar intact or with molars removed were housed in either a standard environment or enriched environment for 3 weeks. The Morris water maze was performed for spatial memory test. The newborn cell proliferation, survival, and differentiation in the hippocampus were analyzed using 5-Bromodeoxyuridine (BrdU) immunohistochemical method. The hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured. Mice with upper molars removed (molarless) exhibited a significant decline in the proliferation and survival of newborn cells in the dentate gyrus (DG) as well as in hippocampal BDNF levels. In addition, neuronal differentiation of newly generated cells was suppressed and hippocampus-dependent spatial memory was impaired. Exposure of molarless mice to an enriched environment attenuated the reductions in the hippocampal BDNF levels and neuronal differentiation, and partially improved the proliferation and survival of newborn cells, as well as the spatial memory ability. These findings indicated that an enriched environment could ameliorate the hippocampus-dependent spatial memory impairment induced by molar tooth loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

COGNITIVE IMPAIRMENT AND MORPHOLOGICAL CHANGES IN THE DORSAL HIPPOCAMPUS OF VERY OLD FEMALE RATS

PubMed Central

Morel, Gustavo R.; Andersen, Tomás; Pardo, Joaquín; Zuccolilli, Gustavo O.; Cambiaggi, Vanina L.; Hereñú, Claudia B.; Goya, Rodolfo G.

2015-01-01

The hippocampus, a medial temporal lobe structure necessary for the formation of spatial memory, is particularly affected by both normal and pathologic aging. In previous studies, we observed a significant age-related increase in dopaminergic neuron loss in the hypothalamus and the substantia nigra of female rats, which becomes more conspicuous at extreme ages. Here, we extend our studies by assessing spatial memory 4–6 months old (young), 26 months old (old) and 29–32 months old (senile) Sprague–Dawley female rats as well as the age-related histopathological changes in their dorsal hippocampus. Age changes in spatial memory performance were assessed with a modified version of the Barnes maze test. We employed two probe trials (PT), one and five days after training, respectively, in order to evaluate learning ability as well as short-term and longer-term spatial memory retention. A set of relevant hippocampal cell markers was also quantitated in the animals by means of an unbiased stereological approach. The results revealed that old rats perform better than senile rats in acquisition trials and young rats perform better than both aging groups. However, during short-term PT both aging groups showed a preserved spatial memory while in longer-term PT, spatial memory showed deterioration in both aged groups. Morphological analysis showed a marked decrease (94–97%) in doublecortin neuron number in the dentate gyrus in both aged groups and a reduction in glial fibrillary acidic protein-positive cell number in the stratum radiatum of aging rats. Astroglial process length and branching complexity decreased in the aged rats. We conclude that while target-seeking activity and learning ability decrease in aged females, spatial memory only declines in the longer-term tests. The reduction in neuroblast number and astroglial arborescence complexity in the dorsal hippocampus are likely to play a role in the cognitive deficits of aging rats. PMID:26141841

Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks.

PubMed

Bour, Alexandra; Grootendorst, Jeannette; Vogel, Elise; Kelche, Christian; Dodart, Jean-Cosme; Bales, Kelly; Moreau, Pierre-Henri; Sullivan, Patrick M; Mathis, Chantal

2008-11-21

Apolipoprotein (apo) E4, one of three human apoE (h-apoE) isoforms, has been identified as a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. However, the biological mechanisms involving apoE in learning and memory processes are unclear. A potential isoform-dependent role of apoE in cognitive processes was studied in human apoE targeted-replacement (TR) mice. These mice express either the human apoE3 or apoE4 gene under the control of endogenous murine apoE regulatory sequences, resulting in physiological expression of h-apoE in both a temporal and spatial pattern similar to humans. Male and female apoE3-TR, apoE4-TR, apoE-knockout and C57BL/6J mice (15-18 months) were tested with spatial memory and avoidance conditioning tasks. Compared to apoE3-TR mice, spatial memory in female apoE4-TR mice was impaired based on their poor performances in; (i) the probe test of the water-maze reference memory task, (ii) the water-maze working memory task and (iii) an active avoidance Y-maze task. Retention performance on a passive avoidance task was also impaired in apoE4-TR mice, but not in other genotypes. These deficits in both spatial and avoidance memory tasks may be related to the anatomical and functional abnormalities previously reported in the hippocampus and the amygdala of apoE4-TR mice. We conclude that the apoE4-TR mice provide an excellent model for understanding the mechanisms underlying apoE4-dependent susceptibility to cognitive decline.

Spatial recognition test: A novel cognition task for assessing topographical memory in mice.

PubMed

Havolli, Enes; Hill, Mark Dw; Godley, Annie; Goetghebeur, Pascal Jd

2017-06-01

Dysfunction in topographical memory is a core feature of several neurological disorders. There is a large unmet medical need to address learning and memory deficits as a whole in central nervous system disease. There are considerable efforts to identify pro-cognitive compounds but current methods are either lengthy or labour intensive. Our test used a two chamber apparatus and is based on the preference of rodents to explore novel environments. It was used firstly to assess topographical memory in mice at different retention intervals (RI) and secondly to investigate the effect of three drugs reported to be beneficial for cognitive decline associated with Alzheimer's disease, namely: donepezil, memantine and levetiracetam. Animals show good memory performance at all RIs tested under four hours. At the four-hour RI, animals show a significantly poorer memory performance which can be rescued using donepezil, memantine and levetiracetam. Using this test we established and validated a spatial recognition paradigm to address topographical memory in mice by showing a decremental time-induced forgetting response and reversing this decrease in performance using pharmacological tools. The spatial recognition test differs from more commonly used visuospatial laboratory tests in both throughput capability and potentially neuroanatomical substrate. This test has the potential to be used to assess cognitive performance in transgenic animals, disease models and to screen putative cognitive enhancers or depressors.

Serial-position effects for items and relations in short-term memory.

PubMed

Jones, Tim; Oberauer, Klaus

2013-04-01

Two experiments used immediate probed recall of words to investigate serial-position effects. Item memory was tested through probing with a semantic category. Relation memory was tested through probing with the word's spatial location of presentation. Input order and output order were deconfounded by presenting and probing items in different orders. Primacy and recency effects over input position were found for both item memory and relation memory. Both item and relation memory declined over output position. The finding of a U-shaped input position function for item memory rules out an explanation purely in terms of positional confusions (e.g., edge effects). Either these serial-position effects arise from variations in the intrinsic memory strength of the items, or they arise from variations in the strength of item-position bindings, together with retrieval by scanning.

Transfer after process-based object-location memory training in healthy older adults.

PubMed

Zimmermann, Kathrin; von Bastian, Claudia C; Röcke, Christina; Martin, Mike; Eschen, Anne

2016-11-01

A substantial part of age-related episodic memory decline has been attributed to the decreasing ability of older adults to encode and retrieve associations among simultaneously processed information units from long-term memory. In addition, this ability seems to share unique variance with reasoning. In this study, we therefore examined whether process-based training of the ability to learn and remember associations has the potential to induce transfer effects to untrained episodic memory and reasoning tasks in healthy older adults (60-75 years). For this purpose, the experimental group (n = 36) completed 30 sessions of process-based object-location memory training, while the active control group (n = 31) practiced visual perception on the same material. Near (spatial episodic memory), intermediate (verbal episodic memory), and far transfer effects (reasoning) were each assessed with multiple tasks at four measurements (before, midway through, immediately after, and 4 months after training). Linear mixed-effects models revealed transfer effects on spatial episodic memory and reasoning that were still observed 4 months after training. These results provide first empirical evidence that process-based training can enhance healthy older adults' associative memory performance and positively affect untrained episodic memory and reasoning abilities. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The beneficial effects of berry fruit on cognitive and neuronal function in aging

USDA-ARS?s Scientific Manuscript database

Research has demonstrated, in both human and animals, that cognition decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associated changes i...

Berry fruit can improve age-associated neuronal and cognitive deficits: from the laboratory to the clinic

USDA-ARS?s Scientific Manuscript database

Research has demonstrated, in both human and animals, that cognitive functioning decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associat...

The relationship between anthocyanins found in berry fruit, inflammation, and cognitive function in older adults

USDA-ARS?s Scientific Manuscript database

Research in both human and animals has demonstrated that cognitive function decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. These functional declines may be caused by long-term increases in and susceptibility to oxidative stress and infl...

Polyphenols found in berry fruit improve age-associated changes in cognitive function and brain inflammation

USDA-ARS?s Scientific Manuscript database

Research has demonstrated, in both human and animals, that cognitive functioning decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associat...

Neural Plastic Effects of Cognitive Training on Aging Brain

PubMed Central

Leung, Natalie T. Y.; Tam, Helena M. K.; Chu, Leung W.; Kwok, Timothy C. Y.; Chan, Felix; Lam, Linda C. W.; Woo, Jean; Lee, Tatia M. C.

2015-01-01

Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age. PMID:26417460

Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice.

PubMed

Pandey, Surya P; Singh, Hemant K; Prasad, S

2015-01-01

Bacopa monnieri extract has been implicated in the recovery of memory impairments due to various neurological disorders in animal models and humans. However, the precise molecular mechanism of the role of CDRI-08, a well characterized fraction of Bacopa monnieri extract, in recovery of the diabetes mellitus-induced memory impairments is not known. Here, we demonstrate that DM2 mice treated orally with lower dose of CDRI-08 (50- or 100 mg/kg BW) is able to significantly enhance spatial memory in STZ-DM2 mice and this is correlated with a significant decline in oxidative stress and up regulation of the AMPA receptor GluR2 subunit gene expression in the hippocampus. Treatment of DM2 mice with its higher dose (150 mg/kg BW or above) shows anti-diabetic effect in addition to its ability to recover the spatial memory impairment by reversing the DM2-induced elevated oxidative stress and decreased GluR2 subunit expression near to their values in normal and CDRI-08 treated control mice. Our results provide evidences towards molecular basis of the memory enhancing and anti diabetic role of the Bacopa monnieri extract in STZ-induced DM2 mice, which may have therapeutic implications.

Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice

PubMed Central

Pandey, Surya P.; Singh, Hemant K.; Prasad, S.

2015-01-01

Bacopa monnieri extract has been implicated in the recovery of memory impairments due to various neurological disorders in animal models and humans. However, the precise molecular mechanism of the role of CDRI-08, a well characterized fraction of Bacopa monnieri extract, in recovery of the diabetes mellitus-induced memory impairments is not known. Here, we demonstrate that DM2 mice treated orally with lower dose of CDRI-08 (50- or 100 mg/kg BW) is able to significantly enhance spatial memory in STZ-DM2 mice and this is correlated with a significant decline in oxidative stress and up regulation of the AMPA receptor GluR2 subunit gene expression in the hippocampus. Treatment of DM2 mice with its higher dose (150 mg/kg BW or above) shows anti-diabetic effect in addition to its ability to recover the spatial memory impairment by reversing the DM2-induced elevated oxidative stress and decreased GluR2 subunit expression near to their values in normal and CDRI-08 treated control mice. Our results provide evidences towards molecular basis of the memory enhancing and anti diabetic role of the Bacopa monnieri extract in STZ-induced DM2 mice, which may have therapeutic implications. PMID:26161865

Head west or left, east or right: interactions between memory systems in neurocognitive aging

PubMed Central

Pereira, Inês Tomás; Gallagher, Michela; Rapp, Peter R.

2018-01-01

Cognitive aging is accompanied by decline in multiple domains of memory. Here, we developed a T-maze task that required rats to learn competing hippocampal, and striatal navigation strategies in succession, across days. A final session increased demands on cognitive flexibility and required within-day switching between strategies, emphasizing capacities that engage the prefrontal cortex. Background characterization in young and aged rats used a water maze protocol optimized for individual differences in hippocampal integrity. Consistent with earlier work, young adults acquired place strategies in the T-maze faster than response, whereas the opposite was observed in aged rats with impaired spatial memory. The novel result was that aged animals with preserved spatial memory displayed a qualitatively distinct pattern, acquiring place and response strategies equally rapidly, without disruption when switching between them. Subsequent in situ hybridization for the plasticity-related immediate-early gene Arc revealed that while increasing demands on cognitive flexibility and within-day strategy switching potently engaged the prefrontal cortex in young adult and aged-impaired rats, Arc expression was insensitive in aged rats with normal spatial memory and superior switching abilities. Together, the results indicate that cognitive aging is an emergent property of the interactions between memory systems, and that successful cognitive outcomes reflect a distinct neuroadaptive process rather than a slower rate of aging. PMID:26281759

The neural correlates of age effects on verbal-spatial binding in working memory.

PubMed

Meier, Timothy B; Nair, Veena A; Meyerand, Mary E; Birn, Rasmus M; Prabhakaran, Vivek

2014-06-01

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. Copyright © 2014 Elsevier B.V. All rights reserved.

P3 amplitude attenuation secondary to increases in target-to-target interval (TTI) during spatial serial order recall: Implications for EEG models of working memory function.

PubMed

Hochberger, William C; Axelrod, Jenna L; Sarapas, Casey; Shankman, Stewart A; Hill, S Kristian

2018-06-08

Research suggests that increasing delays in stimulus read-out can trigger declines in serial order recall accuracy due to increases in cognitive demand imposed by the delay; however, the exact neural mechanisms associated with this decline are unclear. Changes in neural resource allocation present as the ideal target and can easily be monitored by examining changes in the amplitude of an ERP component known as the P3. Changes in P3 amplitude secondary to exogenous pacing of stimulus read-out via increased target-to-target intervals (TTI) during recall could reflect decreased neural resource allocation due to increased cognitive demand. This shift in resource allocation could result in working memory storage decay and the declines in serial order accuracy described by prior research. In order to examine this potential effect, participants were administered a spatial serial order processing task, with the recall series consisting of a series of correct ("match") or incorrect ("non-match" or "oddball") stimuli. Moreover, the recall series included either a brief (500ms) or extended (2000ms) delay between stimuli. Results were significant for the presence of a P3 response to non-match stimuli for both experimental conditions, and attenuation of P3 amplitude secondary to the increase in target-to-target interval (TTI). These findings suggest that extending the delay between target recognition could increase cognitive demand and trigger a decrease in neural resource allocation that results in a decay of working memory stores.

Edible Bird's Nest Prevents Menopause-Related Memory and Cognitive Decline in Rats via Increased Hippocampal Sirtuin-1 Expression

PubMed Central

He, Peiyuan; Qi, Jiemen; Tang, Shiying; Song, Chengjun; Ismail, Maznah

2017-01-01

Menopause causes cognitive and memory dysfunction due to impaired neuronal plasticity in the hippocampus. Sirtuin-1 (SIRT1) downregulation in the hippocampus is implicated in the underlying molecular mechanism. Edible bird's nest (EBN) is traditionally used to improve general wellbeing, and in this study, we evaluated its effects on SIRT1 expression in the hippocampus and implications on ovariectomy-induced memory and cognitive decline in rats. Ovariectomized female Sprague-Dawley rats were fed with normal pellet alone or normal pellet + EBN (6, 3, or 1.5%), compared with estrogen therapy (0.2 mg/kg/day). After 12 weeks of intervention, Morris water maze (four-day trial and one probe trial) was conducted, and serum estrogen levels, toxicity markers (alanine transaminase, alkaline phosphatase, urea, and creatinine), and hippocampal SIRT1 immunohistochemistry were estimated after sacrifice. The results indicated that EBN and estrogen enhanced spatial learning and memory and increased serum estrogen and hippocampal SIRT1 expression. In addition, the EBN groups did not show as much toxicity to the liver as the estrogen group. The data suggested that EBN treatment for 12 weeks could improve cognition and memory in ovariectomized female rats and may be an effective alternative to estrogen therapy for menopause-induced aging-related memory loss. PMID:29104731

Coccomyxa Gloeobotrydiformis Improves Learning and Memory in Intrinsic Aging Rats.

PubMed

Sun, Luning; Jin, Ying; Dong, Liming; Sui, Hai-Juan; Sumi, Ryo; Jahan, Rabita; Hu, Dahai; Li, Zhi

2015-01-01

Declining in learning and memory is one of the most common and prominent problems during the aging process. Neurotransmitter changes, oxidative stress, mitochondrial dysfunction and abnormal signal transduction were considered to participate in this process. In the present study, we examined the effects of Coccomyxa gloeobotrydiformis (CGD) on learning and memory ability of intrinsic aging rats. As a result, CGD treated (50 mg/kg·d or 100 mg/kg ·d for a duration of 8 weeks) 22-month-old male rats, which have shown significant improvement on learning and spatial memory ability compared with control, which was evidently revealed in both the hidden platform tasks and probe trials. The following immunohistochemistry and Western blot experiments suggested that CGD could increase the content of Ach and thereby improve the function of the cholinergic neurons in the hippocampus, and therefore also improving learning and memory ability of the aged rats by acting as an anti-inflammatory agent. The effects of CGD on learning and memory might also have an association with the ERK/CREB signalling. The results above suggest that the naturally made drug CGD may have several great benefit as a multi-target drug in the process of prevention and/or treatment of age-dependent cognitive decline and aging process.

Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice.

PubMed

Gu, Yeunhwa; Huang, Chien-Sheng; Inoue, Tota; Yamashita, Takenori; Ishida, Torao; Kang, Ki-Mun; Nakao, Atsunori

2010-05-01

Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.

Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer's disease mice.

PubMed

Perusini, Jennifer N; Cajigas, Stephanie A; Cohensedgh, Omid; Lim, Sean C; Pavlova, Ina P; Donaldson, Zoe R; Denny, Christine A

2017-10-01

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. APPswe/PS1dE9 (APP/PS1) mice have been developed as an AD model and are characterized by plaque formation at 4-6 months of age. Here, we sought to better understand AD-related cognitive decline by characterizing various types of memory. In order to better understand how memory declines with AD, APP/PS1 mice were bred with ArcCreER T2 mice. In this line, neural ensembles activated during memory encoding can be indelibly tagged and directly compared with neural ensembles activated during memory retrieval (i.e., memory traces/engrams). We first administered a battery of tests examining depressive- and anxiety-like behaviors, as well as spatial, social, and cognitive memory to APP/PS1 × ArcCreER T2 × channelrhodopsin (ChR2)-enhanced yellow fluorescent protein (EYFP) mice. Dentate gyrus (DG) neural ensembles were then optogenetically stimulated in these mice to improve memory impairment. AD mice had the most extensive differences in fear memory, as assessed by contextual fear conditioning (CFC), which was accompanied by impaired DG memory traces. Optogenetic stimulation of DG neural ensembles representing a CFC memory increased memory retrieval in the appropriate context in AD mice when compared with control (Ctrl) mice. Moreover, optogenetic stimulation facilitated reactivation of the neural ensembles that were previously activated during memory encoding. These data suggest that activating previously learned DG memory traces can rescue cognitive impairments and point to DG manipulation as a potential target to treat memory loss commonly seen in AD. © 2017 Wiley Periodicals, Inc.

[Impairment of spatial learning and memory and changes of oxidative stress in hippocampus from Type 1 diabetic mice].

PubMed

Wang, Chun; Lü, Gaoyou; Li, Yan; Zhao, Shidi; Huang, Li

2018-05-28

To investigate the relevance between spatial learning and memory impairment and the changes of inducible nitric oxide synthase (iNOS) activity, superoxide dismutase (SOD) activity and malondiadehyde (MDA) content in hippocampus from Type 1 diabetic mice.
 Methods: Sixty male mice were randomly assigned into a control group (NC group, 20 mice) and a Type 1 diabetic group (DM group, 40 mice). Type 1 diabetic mouse models were established by a large dose intraperitoneal injection of streptozotocin (100 mg/kg). The spatial learning and memory abilities of mice were assessed by Morris water maze (MWM) test. After MWM test, we chose 20 mice (diabetic encephalopathy mice) with the worst spatial learning and memory abilities from diabetic model group, and detected the iNOS activity, SOD activity and MDA content in hippocampus in both groups.
 Results: Compared with the NC group, the escape latency was significantly extended and platform crossings were significantly declined in diabetic mice (P<0.01). Furthermore, the activity of iNOS and the content of MDA were markedly increased, and the activity of SOD was significantly decreased in hippocampus of diabetic encephalopathy mice (P<0.01).
 Conclusion: The established Type 1 diabetic mice show symptoms of cognitive dysfunction, which might be related to the increase of oxidative stress in hippocampus.

Can Training in a Real-Time Strategy Videogame Attenuate Cognitive Decline in Older Adults?

PubMed Central

Basak, Chandramallika; Boot, Walter R.; Voss, Michelle W.; Kramer, Arthur F.

2014-01-01

Declines in various cognitive abilities, particularly executive control functions, are observed in older adults. An important goal of cognitive training is to slow or reverse these age-related declines. However, opinion is divided in the literature regarding whether cognitive training can engender transfer to a variety of cognitive skills in older adults. Yet, recent research indicates that videogame training of young adults may engender broad transfer to skills of visual attention. In the current study, we used a real-time strategy videogame to attempt to train executive functions in older adults, such as working memory, task switching, short-term memory, inhibition, and reasoning. Older adults were either trained in a real-time strategy videogame for 23.5 hours (RON, n=20) or not (CONTROLS, n=20). A battery of cognitive tasks, including tasks of executive control and visuo-spatial skills, were assessed before, during, and after video game training. The trainees improved significantly in the measures of game performance. They also improved significantly more than the controls in a subset of the cognitive tasks, such as task switching, working memory, visual short term memory, and mental rotation. Trends in improvement were also observed, for the video game trainees, in inhibition and reasoning. Individual differences in changes in game performance were correlated with improvements in task-switching. The study has implications for the enhancement of executive control processes of older adults. PMID:19140648

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation.

PubMed

Irish, Muireann; Lawlor, Brian A; Coen, Robert F; O'Mara, Shane M

2011-08-04

Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.

Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: Relationship with spatial impairment

PubMed Central

Bañuelos, C.; LaSarge, C. L.; McQuail, J. A.; Hartman, J. J.; Gilbert, R. J.; Ormerod, B. K.; Bizon, J. L.

2013-01-01

Both cholinergic and GABAergic projections from the rostral basal forebrain have been implicated in hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in co-distributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase (ChAT) immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 (GAD67) immunopositive) neurons, and total (NeuN immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline. PMID:22817834

Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models of Alzheimer's disease.

PubMed

Edwards, Stephen R; Hamlin, Adam S; Marks, Nicola; Coulson, Elizabeth J; Smith, Maree T

2014-10-01

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. © 2014 Wiley Publishing Asia Pty Ltd.

Group differences in anterior hippocampal volume and in the retrieval of spatial and temporal context memory in healthy young versus older adults.

PubMed

Rajah, M Natasha; Kromas, Michelle; Han, Jung Eun; Pruessner, Jens C

2010-12-01

The ability to retrieve temporal and spatial context information from memory declines with healthy aging. The hippocampus (HC) has been shown to be associated with successful encoding and retrieval of spatio-temporal context, versus item recognition information (Davachi, Mitchell, & Wagner, 2003; Nadel, Samsonovich, Ryan, & Moscovitch, 2000; Ross & Slotnick, 2008). Aging has been linked to volume reduction in the HC (Bouchard, Malykhin, Martin, Hanstock, Emery, Fisher, & Camicioli, 2008; Malykhin, Bouchard, Camicioli, & Coupland, 2008; Raz et al., 2005). As such, age-associated reductions in anterior HC volume may contribute to the context memory deficits observed in older adults. In the current MRI study we investigated whether item recognition, spatial context and temporal context memory performance would be predicted by regional volumes in HC head (HH), body (HB) and tail (HT) volumes, using within group multiple regression analyses in a sample of 19 healthy young (mean age 24.3) and 20 older adults (mean age 67.7). We further examined between age-group differences in the volumes of the same HC sub-regions. Multiple regression analyses revealed that in younger adults both spatial and temporal context retrieval performance was predicted by anterior HC volume. Older age was associated with significant volume reductions in HH and HB, but not HT; and with reduced ability to retrieve spatial and temporal contextual details from episodic memory. However, HC volumes did not predict context retrieval performance in older adults. We conclude that individual differences in anterior, not posterior, HC volumes predict context memory performance in young adults. With age there may be a posterior-to-anterior shift from using HC-related processes, due to HC volume loss, to employing the prefrontal cortex to aid in the performance of cognitively demanding context memory tasks. However, due to concomitant changes in the prefrontal system with age, there are limits to compensation in the aging brain. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Influence of schooling and age on cognitive performance in healthy older adults

PubMed Central

Bento-Torres, N.V.O.; Bento-Torres, J.; Tomás, A.M.; Costa, V.O.; Corrêa, P.G.R.; Costa, C.N.M.; Jardim, N.Y.V.; Picanço-Diniz, C.W.

2017-01-01

Few studies have examined the influence of a low level of schooling on age-related cognitive decline in countries with wide social and economic inequalities by using the Cambridge Automated Neuropsychological Test Battery (CANTAB). The aim of the present study was to assess the influence of schooling on age-related cognitive decline using unbiased cognitive tests. CANTAB allows cognitive assessment across cultures and education levels with reduced interference of the examiner during data acquisition. Using two-way ANOVA, we assessed the influences of age and education on test scores of old adults (61–84 years of age). CANTAB tests included: Visual Sustained Attention, Reaction Time, Spatial Working Memory, Learning and Episodic Memory. All subjects had a minimum visual acuity of 20/30 (Snellen Test), no previous or current history of traumatic brain/head trauma, stroke, language impairment, chronic alcoholism, neurological diseases, memory problems or depressive symptoms, and normal scores on the Mini Mental State Examination (MMSE). Subjects were grouped according to education level (1 to 7 and ≥8 years of schooling) and age (60–69 and ≥70 years). Low schooling level was associated with significantly lower performance on visual sustained attention, learning and episodic memory, reaction time, and spatial working memory. Although reaction time was influenced by age, no significant results on post hoc analysis were detected. Our findings showed a significantly worse cognitive performance in volunteers with lower levels of schooling and suggested that formal education in early life must be included in the preventive public health agenda. In addition, we suggest that CANTAB may be useful to detect subtle cognitive changes in healthy aging. PMID:28355353

Genetic Variance in Processing Speed Drives Variation in Aging of Spatial and Memory Abilities

ERIC Educational Resources Information Center

Finkel, Deborah; Reynolds, Chandra A.; McArdle, John J.; Hamagami, Fumiaki; Pedersen, Nancy L.

2009-01-01

Previous analyses have identified a genetic contribution to the correlation between declines with age in processing speed and higher cognitive abilities. The goal of the current analysis was to apply the biometric dual change score model to consider the possibility of temporal dynamics underlying the genetic covariance between aging trajectories…

[Predictors of verbal memory decline following temporal lobe surgery].

PubMed

de Vanssay-Maigne, A; Boutin, M; Baudoin-Chial, S

2008-05-01

Verbal memory decline can occur after temporal lobe surgery, especially when the left dominant hemisphere is involved. This potential functional risk must be evaluated before surgery. Among all factors that have been identified by several studies, the side of surgery (left dominant) and high baseline memory performance have been found to be predictive of verbal memory decline. Other factors such as etiology, sex, age at surgery, age at seizure onset, and duration may influence memory decline, but the results are not clear. Our purpose was to identify, in our population of patients and among all risk factors, those that may be predictive of verbal memory decline. Logistic regression was used to examine the effect of each factor on the postoperative verbal memory index (WMS-R) in 101 patients who underwent a right (n=49) or left (n=52) anterior temporal lobe resection. In the group as a whole, 22 % of the patients demonstrated verbal memory decline of more than one standard deviation. The verbal memory decline was significantly related to surgery on the left side and a high level of verbal memory performance. These factors were significant predictors of decline. The other factors (etiology, sex, age at surgery, age at seizure onset, and duration) were not found to be predictive of this decline. Our analysis demonstrates that the patients who are most at risk of undergoing verbal memory deterioration are those who undergo left-sided temporal resection and have good memory scores preoperatively. The contradictions found in the literature about the other factors could be explained by the diversity of the tests and criteria used to assess memory decline.

The role of cognitive and visual abilities as predictors in the Multifactorial Model of Driving Safety.

PubMed

Anstey, Kaarin J; Horswill, Mark S; Wood, Joanne M; Hatherly, Christopher

2012-03-01

The current study evaluated part of the Multifactorial Model of Driving Safety to elucidate the relative importance of cognitive function and a limited range of standard measures of visual function in relation to the Capacity to Drive Safely. Capacity to Drive Safely was operationalized using three validated screening measures for older drivers. These included an adaptation of the well validated Useful Field of View (UFOV) and two newer measures, namely a Hazard Perception Test (HPT), and a Hazard Change Detection Task (HCDT). Community dwelling drivers (n=297) aged 65-96 were assessed using a battery of measures of cognitive and visual function. Factor analysis of these predictor variables yielded factors including Executive/Speed, Vision (measured by visual acuity and contrast sensitivity), Spatial, Visual Closure, and Working Memory. Cognitive and Vision factors explained 83-95% of age-related variance in the Capacity to Drive Safely. Spatial and Working Memory were associated with UFOV, HPT and HCDT, Executive/Speed was associated with UFOV and HCDT and Vision was associated with HPT. The Capacity to Drive Safely declines with chronological age, and this decline is associated with age-related declines in several higher order cognitive abilities involving manipulation and storage of visuospatial information under speeded conditions. There are also age-independent effects of cognitive function and vision that determine driving safety. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats.

PubMed

Rushaidhi, M; Zhang, H; Liu, P

2013-03-27

Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Age Is Associated with Reduced Sharp-Wave Ripple Frequency and Altered Patterns of Neuronal Variability

PubMed Central

Wiegand, Jean-Paul L.; Gray, Daniel T.; Schimanski, Lesley A.; Lipa, Peter; Barnes, C. A.

2016-01-01

Spatial and episodic memory performance declines with age, and the neural basis for this decline is not well understood. Sharp-wave ripples are brief (∼70 ms) high-frequency oscillatory events generated in the hippocampus and are associated with the consolidation of spatial memories. Given the connection between ripple oscillations and memory consolidation, we investigated whether the structure of ripple oscillations and ripple-triggered patterns of single-unit activity are altered in aged rats. Local field and single-unit activity surrounding sharp-wave ripple events were examined in the CA1 region of the hippocampus of old (n = 5) and young (n = 6) F344 rats during periods of rest preceding and following performance on a place-dependent eyeblink-conditioning task. Neural responses in aged rats differed from responses in young rats in several ways. First, compared with young rats, the rate of ripple occurrence (ripple density) is reduced in aged rats during postbehavior rest. Second, mean ripple frequency during prebehavior and postbehavior rest is lower in aged animals (aged: 132 Hz; young: 146 Hz). Third, single neurons in aged animals responded more consistently from ripple to ripple. Fourth, variability in interspike intervals was greater in aged rats. Finally, neurons were tuned to a narrower range of phases of the ripple oscillation relative to young animals. Together, these results suggest that the CA1 network in aged animals has a reduced “vocabulary” of available representational states. SIGNIFICANCE STATEMENT The hippocampus is a structure that is critical for the formation of episodic memories. Sharp-wave ripple events generated in the hippocampus have been implicated in memory consolidation processes critical to memory stabilization. We examine here whether these ripple oscillations are altered over the course of the life span, which could contribute to hippocampus-dependent memory deficits that occur during aging. This experiment used young and aged memory-impaired rats to examine age-related changes in ripple architecture, ripple-triggered spike variance, and spike-phase coherence. We found that there are, indeed, significant changes in characteristics of ripples in older animals that could impact consolidation processes and memory stabilization in the aged brain. PMID:27194342

Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression.

PubMed

Lim, Patrick H; Wert, Stephanie L; Tunc-Ozcan, Elif; Marr, Robert; Ferreira, Adriana; Redei, Eva E

2018-02-25

Aging and major depressive disorder are risk factors for dementia, including Alzheimer's Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs. This deficit, measured as duration of freezing in the fear provoking-context was not related to activity differences between the strains prior to fear conditioning. Hippocampal expression of AD-related genes, such as amyloid precursor protein, amyloid beta 42, beta secretase, synucleins, total and dephosphorylated tau, and synaptophysin, did not differ between WLIs and WMIs in either age group. However, hippocampal transcript levels of catalase (Cat) and hippocampal and frontal cortex expression of insulin-like growth factor 2 (Igf2) and Igf2 receptor (Igf2r) paralleled fear memory differences between middle-aged WLIs and WMIs. This data suggests that chronic depression-like behavior that is present in this genetic model is a risk factor for early spatial memory decline in females. The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model. Copyright © 2018 Elsevier B.V. All rights reserved.

T-Tau is Associated with Objective Memory Decline Over Two Years in Persons Seeking Help for Subjective Cognitive Decline: A Report from the Gothenburg-Oslo MCI Study.

PubMed

Hessen, Erik; Nordlund, Arto; Stålhammar, Jacob; Eckerström, Marie; Bjerke, Maria; Eckerström, Carl; Göthlin, Mattias; Fladby, Tormod; Reinvang, Ivar; Wallin, Anders

2015-01-01

There is a need to find very early markers for pre-clinical Alzheimer's disease as interventions early in the disease process are thought to be most effective. The present study aimed to address the potential relation between cerebrospinal fluid (CSF) biomarkers and reduced cognitive function in a relatively young cohort of memory clinic patients with subjective cognitive decline. 122 patients (mean age 63 years) with subjective cognitive decline were recruited from two university memory clinics and followed for two years. The main finding was that the subgroup with objective memory decline during the study period had significantly higher T-tau at baseline than the group with improved memory. Baseline CSF variables showed a trend toward more pathological values in the patients with memory decline compared to those who improved or remained stable. The baseline memory score of those who declined was significantly better than the baseline score of those who improved over two years. The general trend for the whole group was improved memory and executive test scores. There were no differences in cognitive scores based on CSF quartiles at baseline, nor were there differences in cognitive outcome for patients with early amnestic mild cognitive impairment versus average cognitive function at baseline. The main finding that T-tau rather than amyloid-β was associated with memory decline do not support the prevailing opinion about the chain of events assumed to take place in Alzheimer's disease. In addition, memory decline was not associated with poor baseline memory score. Thus, a memory cut-off indicating low baseline memory would not would have identified the declining group.

Memory improvements in elderly women following 16 weeks treatment with a combined multivitamin, mineral and herbal supplement: A randomized controlled trial.

PubMed

Macpherson, Helen; Ellis, Kathryn A; Sali, Avni; Pipingas, Andrew

2012-03-01

There is potential for multivitamin supplementation to improve cognition in the elderly. This randomized, double-blind, placebo-controlled trial was conducted to investigate the effects of 16 weeks multivitamin supplementation (Swisse Women's 50+ Ultivite ®) on cognition in elderly women. Participants in this study were 56 community dwelling, elderly women, with subjective complaints of memory loss. Cognition was assessed using a computerized battery of memory and attention tasks designed to be sensitive to age-related declines to fluid intelligence, and a measure of verbal recall. Biochemical measures of selected nutrients, homocysteine, markers of inflammation, oxidative stress, and blood safety parameters were also collected. All cognitive and haematological parameters were assessed at baseline and 16 weeks post-treatment. The multivitamin improved speed of response on a measure of spatial working memory, however benefits to other cognitive processes were not observed. Multivitamin supplementation decreased levels of homocysteine and increased levels of vitamin B(6) and B(12), with a trend for vitamin E to increase. There were no hepatotoxic effects of the multivitamin formula indicating this supplement was safe for everyday usage in the elderly. Sixteen weeks ssupplementation with a combined multivitamin, mineral and herbal formula may benefit working memory in elderly women at risk of cognitive decline.

Down-Regulation of Neuregulin1/ErbB4 Signaling in the Hippocampus Is Critical for Learning and Memory.

PubMed

Tian, Jia; Geng, Fei; Gao, Feng; Chen, Yi-Hua; Liu, Ji-Hong; Wu, Jian-Lin; Lan, Yu-Jie; Zeng, Yuan-Ning; Li, Xiao-Wen; Yang, Jian-Ming; Gao, Tian-Ming

2017-08-01

Hippocampal function is important for learning and memory, and dysfunction of the hippocampus has been linked to the pathophysiology of neuropsychiatric diseases such as schizophrenia. Neuregulin1 (NRG1) and ErbB4, two susceptibility genes for schizophrenia, reportedly modulate long-term potentiation (LTP) at hippocampal Schaffer collateral (SC)-CA1 synapses. However, little is known regarding the contribution of hippocampal NRG1/ErbB4 signaling to learning and memory function. Here, quantitative real-time PCR and Western blotting were used to assess the mRNA and protein levels of NRG1 and ErbB4. Pharmacological and genetic approaches were used to manipulate NRG1/ErbB4 signaling, following which learning and memory behaviors were evaluated using the Morris water maze, Y-maze test, and the novel object recognition test. Spatial learning was found to reduce hippocampal NRG1 and ErbB4 expression. The blockade of NRG1/ErbB4 signaling in hippocampal CA1, either by neutralizing endogenous NRG1 or inhibiting/ablating ErbB4 receptor activity, enhanced hippocampus-dependent spatial learning, spatial working memory, and novel object recognition memory. Accordingly, administration of exogenous NRG1 impaired those functions. More importantly, the specific ablation of ErbB4 in parvalbumin interneurons also improved learning and memory performance. The manipulation of NRG1/ErbB4 signaling in the present study revealed that NRG1/ErbB4 activity in the hippocampus is critical for learning and memory. These findings might provide novel insights on the pathophysiological mechanisms of schizophrenia and a new target for the treatment of Alzheimer's disease, which is characterized by a progressive decline in cognitive function.

A reduction in hippocampal GABAA receptor alpha5 subunits disrupts the memory for location of objects in mice.

PubMed

Prut, L; Prenosil, G; Willadt, S; Vogt, K; Fritschy, J-M; Crestani, F

2010-07-01

The memory for location of objects, which binds information about objects to discrete positions or spatial contexts of occurrence, is a form of episodic memory particularly sensitive to hippocampal damage. Its early decline is symptomatic for elderly dementia. Substances that selectively reduce alpha5-GABA(A) receptor function are currently developed as potential cognition enhancers for Alzheimer's syndrome and other dementia, consistent with genetic studies implicating these receptors that are highly expressed in hippocampus in learning performance. Here we explored the consequences of reduced GABA(A)alpha5-subunit contents, as occurring in alpha5(H105R) knock-in mice, on the memory for location of objects. This required the behavioral characterization of alpha5(H105R) and wild-type animals in various tasks examining learning and memory retrieval strategies for objects, locations, contexts and their combinations. In mutants, decreased amounts of alpha5-subunits and retained long-term potentiation in hippocampus were confirmed. They exhibited hyperactivity with conserved circadian rhythm in familiar actimeters, and normal exploration and emotional reactivity in novel places, allocentric spatial guidance, and motor pattern learning acquisition, inhibition and flexibility in T- and eight-arm mazes. Processing of object, position and context memories and object-guided response learning were spared. Genotype difference in object-in-place memory retrieval and in encoding and response learning strategies for object-location combinations manifested as a bias favoring object-based recognition and guidance strategies over spatial processing of objects in the mutants. These findings identify in alpha5(H105R) mice a behavioral-cognitive phenotype affecting basal locomotion and the memory for location of objects indicative of hippocampal dysfunction resulting from moderately decreased alpha5-subunit contents.

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation

PubMed Central

2011-01-01

Background Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. Results The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. Conclusions As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time. PMID:21816065

A virtual reality task based on animal research – spatial learning and memory in patients after the first episode of schizophrenia

PubMed Central

Fajnerová, Iveta; Rodriguez, Mabel; Levčík, David; Konrádová, Lucie; Mikoláš, Pavol; Brom, Cyril; Stuchlík, Aleš; Vlček, Kamil; Horáček, Jiří

2014-01-01

Objectives: Cognitive deficit is considered to be a characteristic feature of schizophrenia disorder. A similar cognitive dysfunction was demonstrated in animal models of schizophrenia. However, the poor comparability of methods used to assess cognition in animals and humans could be responsible for low predictive validity of current animal models. In order to assess spatial abilities in schizophrenia and compare our results with the data obtained in animal models, we designed a virtual analog of the Morris water maze (MWM), the virtual Four Goals Navigation (vFGN) task. Methods: Twenty-nine patients after the first psychotic episode with schizophrenia symptoms and a matched group of healthy volunteers performed the vFGN task. They were required to find and remember four hidden goal positions in an enclosed virtual arena. The task consisted of two parts. The Reference memory (RM) session with a stable goal position was designed to test spatial learning. The Delayed-matching-to-place (DMP) session presented a modified working memory protocol designed to test the ability to remember a sequence of three hidden goal positions. Results: Data obtained in the RM session show impaired spatial learning in schizophrenia patients compared to the healthy controls in pointing and navigation accuracy. The DMP session showed impaired spatial memory in schizophrenia during the recall of spatial sequence and a similar deficit in spatial bias in the probe trials. The pointing accuracy and the quadrant preference showed higher sensitivity toward the cognitive deficit than the navigation accuracy. Direct navigation to the goal was affected by sex and age of the tested subjects. The age affected spatial performance only in healthy controls. Conclusions: Despite some limitations of the study, our results correspond well with the previous studies in animal models of schizophrenia and support the decline of spatial cognition in schizophrenia, indicating the usefulness of the vFGN task in comparative research. PMID:24904329

Testing a dynamic-field account of interactions between spatial attention and spatial working memory.

PubMed

Johnson, Jeffrey S; Spencer, John P

2016-05-01

Studies examining the relationship between spatial attention and spatial working memory (SWM) have shown that discrimination responses are faster for targets appearing at locations that are being maintained in SWM, and that location memory is impaired when attention is withdrawn during the delay. These observations support the proposal that sustained attention is required for successful retention in SWM: If attention is withdrawn, memory representations are likely to fail, increasing errors. In the present study, this proposal was reexamined in light of a neural-process model of SWM. On the basis of the model's functioning, we propose an alternative explanation for the observed decline in SWM performance when a secondary task is performed during retention: SWM representations drift systematically toward the location of targets appearing during the delay. To test this explanation, participants completed a color discrimination task during the delay interval of a spatial-recall task. In the critical shifting-attention condition, the color stimulus could appear either toward or away from the midline reference axis, relative to the memorized location. We hypothesized that if shifting attention during the delay leads to the failure of SWM representations, there should be an increase in the variance of recall errors, but no change in directional errors, regardless of the direction of the shift. Conversely, if shifting attention induces drift of SWM representations-as predicted by the model-systematic changes in the patterns of spatial-recall errors should occur that would depend on the direction of the shift. The results were consistent with the latter possibility-recall errors were biased toward the locations of discrimination targets appearing during the delay.

Testing a Dynamic Field Account of Interactions between Spatial Attention and Spatial Working Memory

PubMed Central

Johnson, Jeffrey S.; Spencer, John P.

2016-01-01

Studies examining the relationship between spatial attention and spatial working memory (SWM) have shown that discrimination responses are faster for targets appearing at locations that are being maintained in SWM, and that location memory is impaired when attention is withdrawn during the delay. These observations support the proposal that sustained attention is required for successful retention in SWM: if attention is withdrawn, memory representations are likely to fail, increasing errors. In the present study, this proposal is reexamined in light of a neural process model of SWM. On the basis of the model's functioning, we propose an alternative explanation for the observed decline in SWM performance when a secondary task is performed during retention: SWM representations drift systematically toward the location of targets appearing during the delay. To test this explanation, participants completed a color-discrimination task during the delay interval of a spatial recall task. In the critical shifting attention condition, the color stimulus could appear either toward or away from the memorized location relative to a midline reference axis. We hypothesized that if shifting attention during the delay leads to the failure of SWM representations, there should be an increase in the variance of recall errors but no change in directional error, regardless of the direction of the shift. Conversely, if shifting attention induces drift of SWM representations—as predicted by the model—there should be systematic changes in the pattern of spatial recall errors depending on the direction of the shift. Results were consistent with the latter possibility—recall errors were biased toward the location of discrimination targets appearing during the delay. PMID:26810574

Long-term acarbose administration alleviating the impairment of spatial learning and memory in the SAMP8 mice was associated with alleviated reduction of insulin system and acetylated H4K8.

PubMed

Yan, Wen-Wen; Chen, Gui-Hai; Wang, Fang; Tong, Jing-Jing; Tao, Fei

2015-04-07

Age-associated memory impairment (AAMI) not only reduces the quality of life for the elderly but also increases the costs of healthcare for society. Methods that can regulate glucose metabolism, insulin/insulin-like growth factor 1 (IGF-1) system and acetylated histone H4 lysine 8 (H4K8ac), one of the most well-researched facets of histone acetylation modification associating with cognition, tend to ameliorate the AAMI. Here, we used SAMP8 mice, the excellent animal model of aging and AAMI, to study the effect of long-term treatment with acarbose, an inhibitor of a-glucosidase, on AAMI and explore whether blood glucose, insulin/IGF-1 system and H4K8ac are associated with potential effects. The treatment group received acarbose (20mg/kg/d, dissolved in drinking water) at the age of 3-month until 9-month old before the behavioral test, and the controls only received water. Compared to the young controls (3-month-old, n=11), the old group (9-month-old, n=8) had declined abilities of spatial learning and memory and levels of serum insulin, hippocampal insulin receptors (InsRs) and H4K8ac. Interestingly, the acarbose group (9-month-old, n=9) showed better abilities of spatial learning and memory and higher levels of insulin, InsRs and H4K8ac relative to the old controls. Good performance of spatial learning and memory was positively correlated with the elevated insulin, InsRs and H4K8ac. All these results suggested that long-term administration of acarbose could alleviate the age-related impairment of spatial learning and memory in the SAMP8 mice, and the alleviated reduction of an insulin system and H4K8ac might be associated with the alleviation. Copyright © 2015 Elsevier B.V. All rights reserved.

Age-related changes in the three-way correlation between anterior hippocampus volume, whole-brain patterns of encoding activity and subsequent context retrieval.

PubMed

Maillet, David; Rajah, M Natasha

2011-10-28

Age-related declines in memory for context have been linked to volume loss in the hippocampal head (HH) with age. However, it remains unclear how this volumetric decline correlates with age-related changes in whole-brain activity during context encoding, and subsequent context retrieval. In the current study we examine this. We collected functional magnetic resonance imaging data in young and older adults during the encoding of item, spatial context and temporal context. HH volume and subsequent retrieval performance was measured in all participants. In young adults only there was a positive three-way correlation between larger HH volumes, better memory retrieval, and increased activity in right hippocampus, right ventrolateral prefrontal cortex (VLPFC) and midline brain regions during episodic encoding. In contrast, older adults exhibited a positive three-way association between HH volume, generalized activity in bilateral hippocampus and dorsolateral PFC across all encoding tasks, and subsequent spatial context retrieval. Young adults also engaged this network, but only during the most difficult temporal context encoding task and activity in this network correlated with subsequent temporal context retrieval. We conclude that age-related volumetric reductions in HH disrupted the structure-function association between the hippocampus and activity in the first general encoding network recruited by young adults. Instead, older adults recruited those brain regions young adults only engaged for the most difficult temporal task, at lower difficulty levels. This altered pattern of association correlated with spatial context retrieval in older adults, but was not sufficient to maintain context memory abilities overall. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Age-related similarities and differences in monitoring spatial cognition.

PubMed

Ariel, Robert; Moffat, Scott D

2018-05-01

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.

Prenatal complex rhythmic music sound stimulation facilitates postnatal spatial learning but transiently impairs memory in the domestic chick.

PubMed

Kauser, H; Roy, S; Pal, A; Sreenivas, V; Mathur, R; Wadhwa, S; Jain, S

2011-01-01

Early experience has a profound influence on brain development, and the modulation of prenatal perceptual learning by external environmental stimuli has been shown in birds, rodents and mammals. In the present study, the effect of prenatal complex rhythmic music sound stimulation on postnatal spatial learning, memory and isolation stress was observed. Auditory stimulation with either music or species-specific sounds or no stimulation (control) was provided to separate sets of fertilized eggs from day 10 of incubation. Following hatching, the chicks at age 24, 72 and 120 h were tested on a T-maze for spatial learning and the memory of the learnt task was assessed 24 h after training. In the posthatch chicks at all ages, the plasma corticosterone levels were estimated following 10 min of isolation. The chicks of all ages in the three groups took less (p < 0.001) time to navigate the maze over the three trials thereby showing an improvement with training. In both sound-stimulated groups, the total time taken to reach the target decreased significantly (p < 0.01) in comparison to the unstimulated control group, indicating the facilitation of spatial learning. However, this decline was more at 24 h than at later posthatch ages. When tested for memory after 24 h of training, only the music-stimulated chicks at posthatch age 24 h took a significantly longer (p < 0.001) time to traverse the maze, suggesting a temporary impairment in their retention of the learnt task. In both sound-stimulated groups at 24 h, the plasma corticosterone levels were significantly decreased (p < 0.001) and increased thereafter at 72 h (p < 0.001) and 120 h which may contribute to the differential response in spatial learning. Thus, prenatal auditory stimulation with either species-specific or complex rhythmic music sounds facilitates spatial learning, though the music stimulation transiently impairs postnatal memory. 2011 S. Karger AG, Basel.

Age-Related Memory Impairment Associated With Decreased Endogenous Estradiol in the Hippocampus of Female Rats.

PubMed

Chamniansawat, Siriporn; Sawatdiyaphanon, Chattraporn

It is widely known that not only the gonadal estradiol (E2) but also hippocampal E2 plays an essential role in memory process. However, the role of hippocampal E2-enhanced memory mechanism during aging is largely unknown. The aim of the present study was to investigate the effect of age on E2 concentration, the expression level of its receptors, and key steroidogenic enzymes in hippocampus. We also investigated the effect of microglia activation on E2 synthesis in hippocampal neurons. The results showed that serum E2 was higher in 19-month-old (aged) rats, which exhibited spatial memory decline in the Morris water maze (MWM) test when compared to the younger rats. Hence, serum E2 may not be associated with the reduced spatial memory performance in aging. In contrast, the level of E2 and the expressions of its receptors were significantly decreased in hippocampus of aged female rat compared to younger females. Furthermore, the expressions of key hippocampal steroidogenic enzymes, steroidogenic acute regulatory protein (StAR), and cytochrome P450 (P450) also significantly decreased with age, which resulted in lower hippocampal E2 levels. In addition, we found that the microglia of aged brain highly expressed interleukin 6 (IL-6), which directly inhibited E2 synthesis in hippocampal neurons via suppression of P450 synthesis. Taken together, we summarized that the microglia-derived IL-6 inhibited hippocampal E2 synthesis in aged rats which, in turn, contributed to the deficit of spatial memory performance.

Everyday Experiences of Memory Problems and Control: The Adaptive Role of Selective Optimization with Compensation in the Context of Memory Decline

PubMed Central

Hahn, Elizabeth A.; Lachman, Margie E.

2014-01-01

The present study examined the role of long-term working memory decline in the relationship between everyday experiences of memory problems and perceived control, and we also considered whether the use of accommodative strategies [selective optimization with compensation (SOC)] would be adaptive. The study included Boston-area participants (n=103) from the Midlife in the United States study (MIDUS) who completed two working memory assessments over ten years and weekly diaries following Time 2. In adjusted multi-level analyses, greater memory decline and lower general perceived control were associated with more everyday memory problems. Low perceived control reported in a weekly diary was associated with more everyday memory problems among those with greater memory decline and low SOC strategy use (Est.=−0.28, SE=0.13, p=.036). These results suggest that the use of SOC strategies in the context of declining memory may help to buffer the negative effects of low perceived control on everyday memory. PMID:24597768

Everyday experiences of memory problems and control: the adaptive role of selective optimization with compensation in the context of memory decline.

PubMed

Hahn, Elizabeth A; Lachman, Margie E

2015-01-01

The present study examined the role of long-term working memory decline in the relationship between everyday experiences of memory problems and perceived control, and we also considered whether the use of accommodative strategies [selective optimization with compensation (SOC)] would be adaptive. The study included Boston-area participants (n = 103) from the Midlife in the United States study (MIDUS) who completed two working memory assessments over 10 years and weekly diaries following Time 2. In adjusted multi-level analyses, greater memory decline and lower general perceived control were associated with more everyday memory problems. Low perceived control reported in a weekly diary was associated with more everyday memory problems among those with greater memory decline and low SOC strategy use (Est. = -0.28, SE= 0.13, p = .036). These results suggest that the use of SOC strategies in the context of declining memory may help to buffer the negative effects of low perceived control on everyday memory.

Repeated cognitive stimulation alleviates memory impairments in an Alzheimer's disease mouse model.

PubMed

Martinez-Coria, Hilda; Yeung, Stephen T; Ager, Rahasson R; Rodriguez-Ortiz, Carlos J; Baglietto-Vargas, David; LaFerla, Frank M

2015-08-01

Alzheimer's disease is a neurodegenerative disease associated with progressive memory and cognitive decline. Previous studies have identified the benefits of cognitive enrichment on reducing disease pathology. Additionally, epidemiological and clinical data suggest that repeated exercise, and cognitive and social enrichment, can improve and/or delay the cognitive deficiencies associated with aging and neurodegenerative diseases. In the present study, 3xTg-AD mice were exposed to a rigorous training routine beginning at 3 months of age, which consisted of repeated training in the Morris water maze spatial recognition task every 3 months, ending at 18 months of age. At the conclusion of the final Morris water maze training session, animals subsequently underwent testing in another hippocampus-dependent spatial task, the Barnes maze task, and on the more cortical-dependent novel object recognition memory task. Our data show that periodic cognitive enrichment throughout aging, via multiple learning episodes in the Morris water maze task, can improve the memory performance of aged 3xTg-AD mice in a separate spatial recognition task, and in a preference memory task, when compared to naïve aged matched 3xTg-AD mice. Furthermore, we observed that the cognitive enrichment properties of Morris water maze exposer, was detectable in repeatedly trained animals as early as 6 months of age. These findings suggest early repeated cognitive enrichment can mitigate the diverse cognitive deficits observed in Alzheimer's disease. Published by Elsevier Inc.

Amyloid β Deposition and Suspected Non-Alzheimer Pathophysiology and Cognitive Decline Patterns for 12 Years in Oldest Old Participants Without Dementia.

PubMed

Zhao, Yujing; Tudorascu, Dana L; Lopez, Oscar L; Cohen, Ann D; Mathis, Chester A; Aizenstein, Howard J; Price, Julie C; Kuller, Lewis H; Kamboh, M Ilyas; DeKosky, Steven T; Klunk, William E; Snitz, Beth E

2018-01-01

The prevalence of pathologic conditions of the brain associated with Alzheimer disease increases strongly with age. Little is known about the distribution and clinical significance of preclinical biomarker staging in the oldest old, when most individuals without dementia are likely to have positive biomarkers. To compare the patterns of long-term cognitive decline in multiple domains by preclinical biomarker status in the oldest old without dementia. A longitudinal observational study with a mean (SD) of 12.2 (2.2) years (range 7.2-15.1 years) of follow-up was conducted in an academic medical center from August 24, 2000, to January 14, 2016, including and extending observations from the Ginkgo Evaluation of Memory study. A total of 197 adults who had completed the Ginkgo Evaluation of Memory study, were free of dementia, and were able to undergo magnetic resonance imaging were eligible for a neuroimaging study in 2009. Of these patients, 175 were included in the present analyses; 140 (80%) were cognitively normal and 35 (20%) had mild cognitive impairment. Biomarker groups included amyloid β negative (Aβ-)/neurodegeneration negative (ND-), amyloid β positive (Aβ+)/ND-, Aβ-/neurodegeneration positive (ND+), and Aβ+/ND+ based on Pittsburgh Compound B retention and hippocampal volume in 2009. Participants completed baseline neuropsychological testing from 2000 to 2002 and annual testing from 2004 to 2016. Domains included memory, executive function, language, visual-spatial reasoning, and attention and psychomotor speed. Slopes of decline were evaluated with linear mixed models adjusted for age, sex, and years of education. Of the 175 participants (71 women and 104 men), at imaging, mean (SD) age was 86.0 (2.9) years (range, 82-95 years). A total of 42 participants (24.0%) were Aβ-/ND-, 32 (18.3%) were Aβ+/ND-, 35 (20.0%) were Aβ-/ND+, and 66 (37.7%) were Aβ+/ND+. On all cognitive measures, the Aβ+/ND+ group showed the steepest decline. Compared with the Aβ-/ND- group, the amyloid deposition alone (Aβ+/ND-) group showed faster decline on tests of verbal and visual memory (-0.3513; 95% CI, -0.5269 to -0.1756), executive function (0.0158; 95% CI, 0.0013-0.0303), and language (-0.1934; 95% CI, -0.3520 to -0.0348). The Aβ-/ND+ group showed faster visual memory decline than the Aβ-/ND- reference group (-0.3007; 95% CI, -0.4736 to -0.1279). In the oldest old without dementia, presence of either or both Aβ and hippocampal atrophy is typical (>75%). Isolated hippocampal volume atrophy is associated only with greater decline in memory. However, isolated Aβ is associated with decline in memory plus language and executive functions. These findings suggest different underlying pathophysiologic processes in the Aβ+/ND- and Aβ-/ND+ groups.

A Larger Social Network Enhances Novel Object Location Memory and Reduces Hippocampal Microgliosis in Aged Mice.

PubMed

Smith, Bryon M; Yao, Xinyue; Chen, Kelly S; Kirby, Elizabeth D

2018-01-01

The mammalian hippocampus shows marked decline in function with aging across many species, including humans and laboratory rodent models. This decline frequently manifests in memory impairments that occur even in the absence of dementia pathology. In humans, a number of factors correlate with preserved hippocampal memory in aging, such as exercise, cognitive stimulation and number of social ties. While interventional studies and animal models clearly indicate that exercise and cognitive stimulation lead to hippocampal preservation, there is relatively little research on whether a decline in social ties leads to cognitive decline or vice versa. Even in animal studies of environmental enrichment in aging, the focus typically falls on physical enrichment such as a rotating cast of toys, rather than the role of social interactions. The present studies investigated the hypothesis that a greater number of social ties in aging mice would lead to improved hippocampal function. Aged, female C57/Bl6 mice were housed for 3 months in pairs or large groups (7 mice per cage). Group-housed mice showed greater novel object location memory and stronger preference for a spatial navigation strategy in the Barnes maze, though no difference in escape latency, compared to pair-housed mice. Group-housed mice did not differ from pair-housed mice in basal corticosterone levels or adult hippocampal neurogenesis. Group-housed mice did, however, show reduced numbers of Iba1/CD68+ microglia in the hippocampus. These findings suggest that group housing led to better memory function and reduced markers of neuroinflammation in aged mice. More broadly, they support a causative link between social ties and hippocampal function, suggesting that merely having a larger social network can positively influence the aging brain. Future research should address the molecular mechanisms by which a greater number of social ties alters hippocampal function.

A Larger Social Network Enhances Novel Object Location Memory and Reduces Hippocampal Microgliosis in Aged Mice

PubMed Central

Smith, Bryon M.; Yao, Xinyue; Chen, Kelly S.; Kirby, Elizabeth D.

2018-01-01

The mammalian hippocampus shows marked decline in function with aging across many species, including humans and laboratory rodent models. This decline frequently manifests in memory impairments that occur even in the absence of dementia pathology. In humans, a number of factors correlate with preserved hippocampal memory in aging, such as exercise, cognitive stimulation and number of social ties. While interventional studies and animal models clearly indicate that exercise and cognitive stimulation lead to hippocampal preservation, there is relatively little research on whether a decline in social ties leads to cognitive decline or vice versa. Even in animal studies of environmental enrichment in aging, the focus typically falls on physical enrichment such as a rotating cast of toys, rather than the role of social interactions. The present studies investigated the hypothesis that a greater number of social ties in aging mice would lead to improved hippocampal function. Aged, female C57/Bl6 mice were housed for 3 months in pairs or large groups (7 mice per cage). Group-housed mice showed greater novel object location memory and stronger preference for a spatial navigation strategy in the Barnes maze, though no difference in escape latency, compared to pair-housed mice. Group-housed mice did not differ from pair-housed mice in basal corticosterone levels or adult hippocampal neurogenesis. Group-housed mice did, however, show reduced numbers of Iba1/CD68+ microglia in the hippocampus. These findings suggest that group housing led to better memory function and reduced markers of neuroinflammation in aged mice. More broadly, they support a causative link between social ties and hippocampal function, suggesting that merely having a larger social network can positively influence the aging brain. Future research should address the molecular mechanisms by which a greater number of social ties alters hippocampal function. PMID:29904345

Autobiographical memory decline in Alzheimer’s Disease

PubMed Central

EL HAJ, Mohamad; Antoine, Pascal; Nandrino, Jean-Louis; Kapogiannis, Dimitrios

2016-01-01

Autobiographical memory, or memory for personal experiences, allows individuals to define themselves and construct a meaningful life story. Decline of this ability, as observed in Alzheimer’s Disease (AD), results in an impaired sense of self and identity. We present a critical review of theories and findings regarding cognitive and neuroanatomical underpinnings of autobiographical memory and its decline in AD and highlight studies on its clinical rehabilitation. We propose that autobiographical recall in AD is mainly characterized by loss of associated episodic information, which leads to de-contextualisation of autobiographical memories and a shift from reliving past events to a general sense of familiarity. This decline refers to retrograde, but also anterograde amnesia that affects newly acquired memories besides remote ones. One consequence of autobiographical memory decline in AD is decreased access to memories that shape self-consciousness, self-knowledge, and self-images, leading to a diminished sense of self and identity. The link between autobiographical decline and compromised sense of self in AD can also manifest itself as low correspondence and coherence between past memories and current goals and beliefs. By linking cognitive, neuroanatomical, and clinical aspects of autobiographical decline in AD, our review provides a theoretical foundation, which may lead to better rehabilitation strategies. PMID:26876367

Autobiographical memory decline in Alzheimer’s disease, a theoretical and clinical overview

PubMed Central

El Haj, Mohamad; Antoine, Pascal; Nandrino, Jean Louis; Kapogiannis, Dimitrios

2017-01-01

Autobiographical memory, or memory for personal experiences, allows individuals to define themselves and construct a meaningful life story. Decline of this ability, as observed in Alzheimer’s disease (AD), results in an impaired sense of self and identity. In our model (AMAD: Autobiographical Memory in Alzheimer’s Disease), we present a critical review of theories and findings regarding cognitive and neuroanatomical underpinnings of autobiographical memory and its decline in AD and highlight studies on its clinical rehabilitation. We propose that autobiographical recall in AD is mainly characterized by loss of associated episodic information, which leads to de-contextualization of autobiographical memories and a shift from reliving past events to a general sense of familiarity. This decline refers to retrograde, but also anterograde amnesia that affects newly acquired memories besides remote ones. One consequence of autobiographical memory decline in AD is decreased access to memories that shape self-consciousness, self-knowledge, and self-images, leading to a diminished sense of self and identity. The link between autobiographical decline and compromised sense of self in AD can also manifest itself as low correspondence and coherence between past memories and current goals and beliefs. By linking cognitive, neuroanatomical, and clinical aspects of autobiographical decline in AD, our review provides a theoretical foundation, which may lead to better rehabilitation strategies. PMID:26169474

Estrogen receptor β-selective phytoestrogenic formulation prevents physical and neurological changes in a preclinical model of human menopause.

PubMed

Zhao, Liqin; Mao, Zisu; Schneider, Lon S; Brinton, Roberta D

2011-10-01

As an alternative to estrogen therapy, the efficacy of an estrogen receptor β-selective phytoestrogenic (phyto-β-SERM) formulation to regulate climacteric symptoms and decline in brain responses associated with ovarian hormone loss in menopause was assessed. A phyto-β-SERM formulation-containing diet was compared with a commercial soy extract diet and a phytoestrogen-free base/control diet in an ovariectomized (OVX) mouse model of human menopause. Two treatment studies were conducted: (1) a 2-month study assessed the effects of experimental diets on tail skin temperature as a model of menopausal hot flashes, and (2) a 9-month study assessed the long-term impact of the diets on overall health, hair thinning/loss, spatial working memory, and associated protein expression in the hippocampus. The phyto-β-SERM diet prevented OVX-induced menopause-like changes including the rise in skin temperature, hair thinning/loss, deficit in spatial memory function, and reversed OVX-induced decline in the expression of hippocampal proteins involved in neural plasticity and β-amyloid degradation/clearance. The soy extract diet had no effect or exacerbated OVX-induced changes. Overall, the phyto-β-SERM diet induced physical and neurological responses comparable with ovary-intact mice, suggesting the therapeutic potential of the phyto-β-SERM formulation for the prevention/alleviation of climacteric symptoms and decline in brain responses induced by ovarian hormone loss, which provides the basis for further work in postmenopausal women.

Young APOE[subscript 4] Targeted Replacement Mice Exhibit Poor Spatial Learning and Memory, with Reduced Dendritic Spine Density in the Medial Entorhinal Cortex

ERIC Educational Resources Information Center

Rodriguez, Gustavo A.; Burns, Mark P.; Weeber, Edwin J.; Rebeck, G. William

2013-01-01

The apolipoprotein E4 ("APOE-[epsilon]4") allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, and may predispose individuals to Alzheimer's-related cognitive decline by affecting normal brain function early in life. To investigate the impact of human APOE alleles on cognitive performance in mice, we trained…

Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study.

PubMed

Palta, Priya; Carlson, Michelle C; Crum, Rosa M; Colantuoni, Elizabeth; Sharrett, A Richey; Yasar, Sevil; Nahin, Richard L; DeKosky, Steven T; Snitz, Beth; Lopez, Oscar; Williamson, Jeff D; Furberg, Curt D; Rapp, Stephen R; Golden, Sherita Hill

2017-12-12

Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Event memory and moving in a well-known environment.

PubMed

Tamplin, Andrea K; Krawietz, Sabine A; Radvansky, Gabriel A; Copeland, David E

2013-11-01

Research in narrative comprehension has repeatedly shown that when people read about characters moving in well-known environments, the accessibility of object information follows a spatial gradient. That is, the accessibility of objects is best when they are in the same room as the protagonist, and it becomes worse the farther away they are see, e.g., Morrow, Greenspan, & Bower, (Journal of Memory and Language, 26, 165-187, 1987). In the present study, we assessed this finding using an interactive environment in which we had people memorize a map and navigate a virtual simulation of the area. During navigation, people were probed with pairs of object names and indicated whether both objects were in the same room. In contrast to the narrative studies described above, several experiments showed no evidence of a clear spatial gradient. Instead, memory for objects in currently occupied locations (e.g., the location room) was more accessible, especially after a small delay, but no clear decline was evident in the accessibility of information in memory with increased distance. Also, memory for objects along the pathway of movement (i.e., rooms that a person only passed through) showed a transitory suppression effect that was present immediately after movement, but attenuated over time. These results were interpreted in light of the event horizon model of event cognition.

The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women.

PubMed

Fournier, L R; Ryan Borchers, T A; Robison, L M; Wiediger, M; Park, J S; Chew, B P; McGuire, M K; Sclar, D A; Skaer, T L; Beerman, K A

2007-01-01

The decline in estrogen concentrations in women after menopause can contribute to health related changes including impairments in cognition, especially memory. Because of the health concerns related to hormone replacement therapy (HRT), alternative approaches to treat menopausal symptoms, such as nutritional supplements and/or diet containing isoflavones, are of interest. This study investigated whether soy isoflavones (soy milk and supplement) could improve cognitive functioning in healthy, postmenopausal women. PARTICIPANTS, INTERVENTION AND DESIGN: A total of 79 postmenopausal women, 48-65 years of age, completed a double-blind, placebo-controlled trial in which they were randomly assigned to one of three experimental groups: cow's milk and a placebo supplement (control); soy milk and placebo supplement (soy milk, 72 mg isoflavones/day); or cow's milk and isoflavone supplement (isoflavone supplement, 70 mg isoflavones/day). Cognitive functioning was assessed using various cognitive tasks before the intervention (baseline) and after the intervention (test). In contrast to predictions, soy isoflavones did not improve selective attention (Stroop task), visual long-term memory (pattern recognition), short-term visuospatial memory (Benton Visual Retention Test), or visuo-spatial working memory (color match task). Also, the soy milk group showed a decline in verbal working memory (Digit Ordering Task) compared to the soy supplement and control groups. Soy isoflavones consumed as a food or supplement over a 16-week period did not improve or appreciably affect cognitive functioning in healthy, postmenopausal women.

Use of Preoperative Functional MRI to Predict Verbal Memory Decline After Temporal Lobe Epilepsy Surgery

PubMed Central

Binder, Jeffrey R.; Sabsevitz, David S.; Swanson, Sara J.; Hammeke, Thomas A.; Raghavan, Manoj; Mueller, Wade M.

2010-01-01

Purpose Verbal memory decline is a frequent complication of left anterior temporal lobectomy (L-ATL). The goal of this study was to determine whether preoperative language mapping using functional magnetic resonance imaging (fMRI) is useful for predicting which patients are likely to experience verbal memory decline after L-ATL. Methods Sixty L-ATL patients underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language and memory lateralization, and pre- and postoperative neuropsychological testing. Demographic, historical, neuropsychological, and imaging variables were examined for their ability to predict pre- to postoperative memory change. Results Verbal memory decline occurred in over 30% of patients. Good preoperative performance, late age at onset of epilepsy, left dominance on fMRI, and left dominance on the Wada test were each predictive of memory decline. Preoperative performance and age at onset together accounted for roughly 50% of the variance in memory outcome (p < .001), and fMRI explained an additional 10% of this variance (p ≤ .003). Neither Wada memory asymmetry nor Wada language asymmetry added additional predictive power beyond these noninvasive measures. Discussion Preoperative fMRI is useful for identifying patients at high risk for verbal memory decline prior to L-ATL surgery. Lateralization of language is correlated with lateralization of verbal memory, whereas Wada memory testing is either insufficiently reliable or insufficiently material-specific to accurately localize verbal memory processes. PMID:18435753

Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis.

PubMed

Hescham, Sarah; Temel, Yasin; Schipper, Sandra; Lagiere, Mélanie; Schönfeld, Lisa-Maria; Blokland, Arjan; Jahanshahi, Ali

2017-03-01

Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.

Cognitive performance of detoxified alcoholic Korsakoff syndrome patients remains stable over two years.

PubMed

Fujiwara, Esther; Brand, Matthias; Borsutzky, Sabine; Steingass, Hans-P; Markowitsch, Hans J

2008-07-01

Excessive alcohol consumption is assumed to promote cognitive decline, eventually increasing the risk of dementia. However, little is known about the time course of cognitive functions in patients with chronic alcoholic Korsakoff syndrome (KS). Therefore, we assessed neuropsychological performance in 20 detoxified chronic KS inpatients at time 1 (T1) with a follow-up after two years (T2). The neuropsychological tests assessed verbal and visual short- and long-term memory, working memory, basic executive functions, language, general knowledge, and visual-spatial abilities. Surveys with caregivers and medical records provided information about current and previous disease-related parameters, drinking history, additional pathologies, as well as psychosocial and cognitive therapy within the two-year period. At both sessions, the majority of the KS patients' results were inferior to those of normal subjects. Comparing T1 and T2 revealed no significant decline in any of the investigated functions. Instead, general knowledge, visual long-term memory, and verbal fluency improved slightly after two years, though they still remained within pathological range. Comparing most improved and most deteriorated patients, better outcome occurred more frequently in men than women and was associated with higher premorbid education and fewer detoxifications in the past. In this sample of detoxified KS patients there was no indication of accelerated cognitive decline or onset of dementia-like symptoms over two years.

Age Is Associated with Reduced Sharp-Wave Ripple Frequency and Altered Patterns of Neuronal Variability.

PubMed

Wiegand, Jean-Paul L; Gray, Daniel T; Schimanski, Lesley A; Lipa, Peter; Barnes, C A; Cowen, Stephen L

2016-05-18

Spatial and episodic memory performance declines with age, and the neural basis for this decline is not well understood. Sharp-wave ripples are brief (∼70 ms) high-frequency oscillatory events generated in the hippocampus and are associated with the consolidation of spatial memories. Given the connection between ripple oscillations and memory consolidation, we investigated whether the structure of ripple oscillations and ripple-triggered patterns of single-unit activity are altered in aged rats. Local field and single-unit activity surrounding sharp-wave ripple events were examined in the CA1 region of the hippocampus of old (n = 5) and young (n = 6) F344 rats during periods of rest preceding and following performance on a place-dependent eyeblink-conditioning task. Neural responses in aged rats differed from responses in young rats in several ways. First, compared with young rats, the rate of ripple occurrence (ripple density) is reduced in aged rats during postbehavior rest. Second, mean ripple frequency during prebehavior and postbehavior rest is lower in aged animals (aged: 132 Hz; young: 146 Hz). Third, single neurons in aged animals responded more consistently from ripple to ripple. Fourth, variability in interspike intervals was greater in aged rats. Finally, neurons were tuned to a narrower range of phases of the ripple oscillation relative to young animals. Together, these results suggest that the CA1 network in aged animals has a reduced "vocabulary" of available representational states. The hippocampus is a structure that is critical for the formation of episodic memories. Sharp-wave ripple events generated in the hippocampus have been implicated in memory consolidation processes critical to memory stabilization. We examine here whether these ripple oscillations are altered over the course of the life span, which could contribute to hippocampus-dependent memory deficits that occur during aging. This experiment used young and aged memory-impaired rats to examine age-related changes in ripple architecture, ripple-triggered spike variance, and spike-phase coherence. We found that there are, indeed, significant changes in characteristics of ripples in older animals that could impact consolidation processes and memory stabilization in the aged brain. Copyright © 2016 the authors 0270-6474/16/365650-11$15.00/0.

Accelerated behavioural development changes fine-scale search behaviour and spatial memory in honey bees (Apis mellifera L.).

PubMed

Ushitani, Tomokazu; Perry, Clint J; Cheng, Ken; Barron, Andrew B

2016-02-01

Normally, worker honey bees (Apis mellifera) begin foraging when more than 2 weeks old as adults, but if individual bees or the colony is stressed, bees often begin foraging precociously. Here, we examined whether bees that accelerated their behavioural development to begin foraging precociously differed from normal-aged foragers in cognitive performance. We used a social manipulation to generate precocious foragers from small experimental colonies and tested their performance in a free-flight visual reversal learning task, and a test of spatial memory. To assess spatial memory, bees were trained to learn the location of a small sucrose feeder within an array of three landmarks. In tests, the feeder and one landmark were removed and the search behaviour of the bees was recorded. Performance of precocious and normal-aged foragers did not differ in a visual reversal learning task, but the two groups showed a clear difference in spatial memory. Flight behaviour suggested normal-aged foragers were better able to infer the position of the removed landmark and feeder relative to the remaining landmarks than precocious foragers. Previous studies have documented the cognitive decline of old foragers, but this is the first suggestion of a cognitive deficit in young foragers. These data imply that worker honey bees continue their cognitive development during the adult stage. These findings may also help to explain why precocious foragers perform quite poorly as foragers and have a higher than normal loss rate. © 2016. Published by The Company of Biologists Ltd.

Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation

PubMed Central

Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F.

2014-01-01

Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. PMID:25451612

Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

PubMed

Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

2015-02-01

Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

Treadmill Exercise Ameliorates Spatial Learning and Memory Deficits Through Improving the Clearance of Peripheral and Central Amyloid-Beta Levels.

PubMed

Khodadadi, Davar; Gharakhanlou, Reza; Naghdi, Naser; Salimi, Mona; Azimi, Mohammad; Shahed, Atabak; Heysieattalab, Soomaayeh

2018-06-11

Aggregated amyloid beta (Aβ) peptides are believed to play a decisive role in the pathology of Alzheimer's disease (AD). Previous evidence suggested that exercise contributes to the improvement of cognitive decline and slows down pathogenesis of AD; however, the exact mechanisms for this have not been fully understood. Here, we evaluated the effect of a 4-week moderate treadmill exercise on spatial memory via central and peripheral Aβ clearance mechanisms following developed AD-like neuropathology induced by intra-hippocampal Aβ 1-42 injection in male Wistar rats. We found Aβ 1-42 -treated animals showed spatial learning and memory impairment which was accompanied by increased levels of amyloid plaque load and soluble Aβ 1-42 (sAβ 1-42 ), decreased mRNA and protein expression of neprilysin (NEP), insulin degrading enzyme (IDE) and low-density lipoprotein receptor-related protein-1 (LRP-1) in the hippocampus. Aβ 1-42 -treated animals also exhibited a higher level of sAβ 1-42 and a lower level of soluble LRP-1 (sLRP-1) in plasma, as well as a decreased level of LRP-1 mRNA and protein content in the liver. However, exercise training improved the spatial learning and memory deficits, reduced both plaque load and sAβ 1-42 levels, and up-regulated expression of NEP, IDE, and LRP-1 in the hippocampus of Aβ 1-42 -treated animals. Aβ 1-42 -treated animals subjected to treadmill exercise also revealed decreased levels of sAβ 1-42 and increased levels of sLRP-1 in plasma, as well as increased levels of LRP-1 mRNA and protein in the liver. In conclusion, our findings suggest that exercise-induced improvement in both of central and peripheral Aβ clearance are likely involved in ameliorating spatial learning and memory deficits in an animal model of AD. Future studies need to determine their relative contribution.

Cyclooxygenase inhibition targets neurons to prevent early behavioural decline in Alzheimer’s disease model mice

PubMed Central

Woodling, Nathaniel S.; Colas, Damien; Wang, Qian; Minhas, Paras; Panchal, Maharshi; Liang, Xibin; Mhatre, Siddhita D.; Brown, Holden; Ko, Novie; Zagol-Ikapitte, Irene; van der Hart, Marieke; Khroyan, Taline V.; Chuluun, Bayarsaikhan; Priyam, Prachi G.; Milne, Ginger L.; Rassoulpour, Arash; Boutaud, Olivier; Manning-Boğ, Amy B.; Heller, H. Craig

2016-01-01

Abstract Identifying preventive targets for Alzheimer’s disease is a central challenge of modern medicine. Non-steroidal anti-inflammatory drugs, which inhibit the cyclooxygenase enzymes COX-1 and COX-2, reduce the risk of developing Alzheimer’s disease in normal ageing populations. This preventive effect coincides with an extended preclinical phase that spans years to decades before onset of cognitive decline. In the brain, COX-2 is induced in neurons in response to excitatory synaptic activity and in glial cells in response to inflammation. To identify mechanisms underlying prevention of cognitive decline by anti-inflammatory drugs, we first identified an early object memory deficit in APP Swe -PS1 ΔE9 mice that preceded previously identified spatial memory deficits in this model. We modelled prevention of this memory deficit with ibuprofen, and found that ibuprofen prevented memory impairment without producing any measurable changes in amyloid-β accumulation or glial inflammation. Instead, ibuprofen modulated hippocampal gene expression in pathways involved in neuronal plasticity and increased levels of norepinephrine and dopamine. The gene most highly downregulated by ibuprofen was neuronal tryptophan 2,3-dioxygenase ( Tdo2 ), which encodes an enzyme that metabolizes tryptophan to kynurenine. TDO2 expression was increased by neuronal COX-2 activity, and overexpression of hippocampal TDO2 produced behavioural deficits. Moreover, pharmacological TDO2 inhibition prevented behavioural deficits in APP Swe -PS1 ΔE9 mice. Taken together, these data demonstrate broad effects of cyclooxygenase inhibition on multiple neuronal pathways that counteract the neurotoxic effects of early accumulating amyloid-β oligomers. PMID:27190010

Genetic and environmental contributions to the associations between intraindividual variability in reaction time and cognitive function.

PubMed

Finkel, Deborah; Pedersen, Nancy L

2014-01-01

Intraindividual variability (IIV) in reaction time has been related to cognitive decline, but questions remain about the nature of this relationship. Mean and range in movement and decision time for simple reaction time were available from 241 individuals aged 51-86 years at the fifth testing wave of the Swedish Adoption/Twin Study of Aging. Cognitive performance on four factors was also available: verbal, spatial, memory, and speed. Analyses indicated that range in reaction time could be used as an indicator of IIV. Heritability estimates were 35% for mean reaction and 20% for range in reaction. Multivariate analysis indicated that the genetic variance on the memory, speed, and spatial factors is shared with genetic variance for mean or range in reaction time. IIV shares significant genetic variance with fluid ability in late adulthood, over and above and genetic variance shared with mean reaction time.

Tau hyperphosphorylation and P-CREB reduction are involved in acrylamide-induced spatial memory impairment: Suppression by curcumin.

PubMed

Yan, Dandan; Yao, Jianling; Liu, Ying; Zhang, Xing; Wang, Yiqi; Chen, Xiaoyi; Liu, Liegang; Shi, Nian; Yan, Hong

2018-04-26

Acrylamide (ACR) is an axonal toxicant that produces peripheral neuropathy in laboratory animals and humans. Epidemiological study found that diet ACR exposure was associated with a mild cognitive decline in men. However, limited information is available as regards its potential and underlying mechanism to cause memory alterations. Curcumin is a polyphenol with neuroprotective and cognitive-enhancing properties. In this study, we aimed to investigate the mechanism of ACR-induced spatial memory impairment and the beneficial effect of curcumin. ACR exposure at 10 mg/kg/d for 7 weeks caused slight gait abnormality and spatial memory deficits, which was associated with an activation of glial cells, a reduction of phosphorylated cAMP response elements binding protein (P-CREB) and an aggregation of hyperphosphorylated tau including p-tau (Ser 262 ), AT8 (p-tau Ser 202 /Thr 205 ) and PHF1 (p-tau Ser 396/404 ) in the hippocampus and cortex. ACR markedly regulate the expression of glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase-5 (cdk5) to accelerate tau hyperphosphorylation. ACR inhibited the protein phosphatase 2A (PP2A) and lysosomal protease cathepsin D to decrease the p-tau dephosphorylation and degradation. The P-CREB and brain derived neurotrophic factor (BDNF) were significantly decreased by ACR. The upstream signalings of P-CREB, extracellular signal-related kinase (ERK) and Akt were markedly inhibited. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) -eukaryotic initiation factor-2α (eIF2α) - activating transcription factor 4 (ATF4) signaling which negatively regulate memory processes by suppressing CREB was activated by ACR. Curcumin alleviated ACR-induced spatial memory impairment through reversing tau abnormalities and P-CREB reduction in the hippocampus. These results offered deeper insight into the mechanisms of and presented a potential new treatment for ACR-induced neurotoxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

Sex-based memory advantages and cognitive aging: a challenge to the cognitive reserve construct?

PubMed

Caselli, Richard J; Dueck, Amylou C; Locke, Dona E C; Baxter, Leslie C; Woodruff, Bryan K; Geda, Yonas E

2015-02-01

Education and related proxies for cognitive reserve (CR) are confounded by associations with environmental factors that correlate with cerebrovascular disease possibly explaining discrepancies between studies examining their relationships to cognitive aging and dementia. In contrast, sex-related memory differences may be a better proxy. Since they arise developmentally, they are less likely to reflect environmental confounds. Women outperform men on verbal and men generally outperform women on visuospatial memory tasks. Furthermore, memory declines during the preclinical stage of AD, when it is clinically indistinguishable from normal aging. To determine whether CR mitigates age-related memory decline, we examined the effects of gender and APOE genotype on longitudinal memory performances. Memory decline was assessed in a cohort of healthy men and women enriched for APOE ɛ4 who completed two verbal [Rey Auditory Verbal Learning Test (AVLT), Buschke Selective Reminding Test (SRT)] and two visuospatial [Rey-Osterrieth Complex Figure Test (CFT), and Benton Visual Retention Test (VRT)] memory tests, as well as in a separate larger and older cohort [National Alzheimer's Coordinating Center (NACC)] who completed a verbal memory test (Logical Memory). Age-related memory decline was accelerated in APOE ɛ4 carriers on all verbal memory measures (AVLT, p=.03; SRT p<.001; logical memory p<.001) and on the VRT p=.006. Baseline sex associated differences were retained over time, but no sex differences in rate of decline were found for any measure in either cohort. Sex-based memory advantage does not mitigate age-related memory decline in either APOE ɛ4 carriers or non-carriers.

Cognitive and motor aging in female chimpanzees.

PubMed

Lacreuse, Agnès; Russell, Jamie L; Hopkins, William D; Herndon, James G

2014-03-01

We present the first longitudinal data on cognitive and motor aging in the chimpanzee (Pan troglodytes). Thirty-eight adult female chimpanzees (10-54 years old) were studied. The apes were tested longitudinally for 3 years in a modified Primate Cognition Test Battery, which comprised 12 tests of physical and social cognition. The chimpanzees were also administered a fine motor task requiring them to remove a steel nut from rods of various complexity. There was little evidence for an age-related decline in tasks of Physical Cognition: for most tasks, performance was either stable or improved with repeated testing across age groups. An exception was Spatial Memory, for which 4 individuals more than 50 years old experienced a significant performance decline across the 3 years of testing. Poorer performance with age was found in 2 tasks of Social Cognition, an attention-getting task and a gaze-following task. A slight motor impairment was also observed, with old chimpanzees improving less than younger animals with repeated testing on the simplest rod. Hormonal status effects were restricted to spatial memory, with non-cycling females outperforming cycling females independently of age. Unexpectedly, older chimpanzees were better than younger individuals in understanding causality relationships based on sound. Copyright © 2014 Elsevier Inc. All rights reserved.

Transparent Meta-Analysis: Does Aging Spare Prospective Memory with Focal vs. Non-Focal Cues?

PubMed Central

Uttl, Bob

2011-01-01

Background Prospective memory (ProM) is the ability to become aware of a previously-formed plan at the right time and place. For over twenty years, researchers have been debating whether prospective memory declines with aging or whether it is spared by aging and, most recently, whether aging spares prospective memory with focal vs. non-focal cues. Two recent meta-analyses examining these claims did not include all relevant studies and ignored prevalent ceiling effects, age confounds, and did not distinguish between prospective memory subdomains (e.g., ProM proper, vigilance, habitual ProM) (see Uttl, 2008, PLoS ONE). The present meta-analysis focuses on the following questions: Does prospective memory decline with aging? Does prospective memory with focal vs. non-focal cues decline with aging? Does the size of age-related declines with focal vs. non-focal cues vary across ProM subdomains? And are age-related declines in ProM smaller than age-related declines in retrospective memory? Methods and Findings A meta-analysis of event-cued ProM using data visualization and modeling, robust count methods, and conventional meta-analysis techniques revealed that first, the size of age-related declines in ProM with both focal and non-focal cues are large. Second, age-related declines in ProM with focal cues are larger in ProM proper and smaller in vigilance. Third, age-related declines in ProM proper with focal cues are as large as age-related declines in recall measures of retrospective memory. Conclusions The results are consistent with Craik's (1983) proposal that age-related declines on ProM tasks are generally large, support the distinction between ProM proper vs. vigilance, and directly contradict widespread claims that ProM, with or without focal cues, is spared by aging. PMID:21304905

Posteromedial hyperactivation during episodic recognition among people with memory decline: findings from the WRAP study.

PubMed

Nicholas, Christopher R; Okonkwo, Ozioma C; Bendlin, Barbara B; Oh, Jennifer M; Asthana, Sanjay; Rowley, Howard A; Hermann, Bruce; Sager, Mark A; Johnson, Sterling C

2015-12-01

Episodic memory decline is one of the earliest preclinical symptoms of AD, and has been associated with an upregulation in the BOLD response in the prodromal stage (e.g. MCI) of AD. In a previous study, we observed upregulation in cognitively normal (CN) subjects with subclinical episodic memory decline compared to non-decliners. In light of this finding, we sought to determine if a separate cohort of Decliners will show increased brain activation compared to Stable subjects during episodic memory processing, and determine whether the BOLD effect was influenced by cerebral blood flow (CBF) or gray matter volume (GMV). Individuals were classified as a "Decliner" if scores on the Rey Auditory Verbal Learning Test (RAVLT) consistently fell ≥ 1.5 SD below expected intra- or inter-individual levels. FMRI was used to compare activation during a facial recognition memory task in 90 Stable (age = 59.1) and 34 Decliner (age = 62.1, SD = 5.9) CN middle-aged adults and 10 MCI patients (age = 72.1, SD = 9.4). Arterial spin labeling and anatomical T1 MRI were used to measure resting CBF and GMV, respectively. Stables and Decliners performed similarly on the episodic recognition memory task and significantly better than MCI patients. Compared to Stables, Decliners showed increased BOLD signal in the left precuneus on the episodic memory task that was not explained by CBF or GMV, familial AD risk factors, or neuropsychological measures. These findings suggest that subtle changes in the BOLD signal reflecting altered neural function may be a relatively early phenomenon associated with memory decline.

Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

PubMed

Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

2014-09-01

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.

Posteromedial hyperactivation during episodic recognition among people with memory decline: findings from the WRAP study

PubMed Central

Nicholas, Christopher R.; Okonkwo, Ozioma C.; Bendlin, Barbara B.; Oh, Jennifer M.; Asthana, Sanjay; Rowley, Howard A.; Hermann, Bruce; Sager, Mark A.

2014-01-01

Episodic memory decline is one of the earliest preclinical symptoms of AD, and has been associated with an upregulation in the BOLD response in the prodromal stage (e.g. MCI) of AD. In a previous study, we observed upregulation in cognitively normal (CN) subjects with subclinical episodic memory decline compared to non-decliners. In light of this finding, we sought to determine if a separate cohort of Decliners will show increased brain activation compared to Stable subjects during episodic memory processing, and determine whether the BOLD effect was influenced by cerebral blood flow (CBF) or gray matter volume (GMV). Individuals were classified as a “Decliner” if scores on the Rey Auditory Verbal Learning Test (RAVLT) consistently fell≥1.5 SD below expected intra- or inter-individual levels. FMRI was used to compare activation during a facial recognition memory task in 90 Stable (age=59.1) and 34 Decliner (age=62.1, SD=5.9) CN middle-aged adults and 10 MCI patients (age=72.1, SD= 9.4). Arterial spin labeling and anatomical T1 MRI were used to measure resting CBF and GMV, respectively. Stables and Decliners performed similarly on the episodic recognition memory task and significantly better than MCI patients. Compared to Stables, Decliners showed increased BOLD signal in the left precuneus on the episodic memory task that was not explained by CBF or GMV, familial AD risk factors, or neuropsychological measures. These findings suggest that subtle changes in the BOLD signal reflecting altered neural function may be a relatively early phenomenon associated with memory decline. PMID:25332108

Cholesteryl ester transfer protein genotype modifies the effect of apolipoprotein ε4 on memory decline in older adults.

PubMed

Sundermann, Erin Elizabeth; Wang, Cuiling; Katz, Mindy; Zimmerman, Molly E; Derby, Carol A; Hall, Charles B; Ozelius, Laurie J; Lipton, Richard B

2016-05-01

Apolipoprotein ε4 (ApoE4) is a strong genetic risk factor for sporadic Alzheimer's disease and memory decline in older adults. A single-nucleotide polymorphism in the cholesteryl ester transfer protein (CETP) gene (isoleucine to valine; V405) is associated with slower memory decline and a lower risk of Alzheimer's disease. As both genes regulate cholesterol, we hypothesized that the favorable CETPV405 allele may buffer the effect of ApoE4 on memory decline in older adults. Using linear regression, we examined the interactive effect of ApoE4 by CETPV405 on memory decline among 909 community-dwelling, nondemented, older adults (≥70 years) from the Einstein Aging Study. Episodic memory was measured using the picture version of the Free and Cued Selective Reminding Test with immediate recall (pFCSRT+IR). There was a significant ApoE × CETP interaction on decline in pFCSRT+IR scores (p = 0.01). ApoE4 carriers experienced faster decline than noncarriers among CETPI405I homozygotes (p = 0.007) and in CETPI405V heterozygotes (p = 0.015) but not in CETPV405V homozygotes (p = 0.614). Results suggest that the CETPV405 allele buffers ApoE4-associated memory decline in a gene dose-dependent manner. Copyright © 2016 Elsevier Inc. All rights reserved.

Remaking memories: Reconsolidation updates positively motivated spatial memory in rats

PubMed Central

Jones, Bethany; Bukoski, Elizabeth; Nadel, Lynn; Fellous, Jean-Marc

2012-01-01

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 human list-learning paradigm. On Day 1, rats were trained to run to three feeders (List 1) for rewards. On Day 2, rats were trained to run to three different feeders (List 2) in either the same (Reminder condition) or a different (No Reminder condition) experimental context than on Day 1. On Day 3, rats were cued to recall List 1. Rats in the Reminder condition made significantly more visits to List 2 feeders (intrusions) during List 1 recall than rats in the No Reminder condition, indicating that the reminder triggered reactivation and allowed integration of List 2 items into List 1. This reminder effect was selective for the reactivated List 1 memory, as no intrusions occurred when List 2 was recalled on Day 3. No intrusions occurred when retrieval took place in a different context from the one used at encoding, indicating that the expression of the updated memory is dependent upon the retrieval context. Finally, the level of intrusions was highest when retrieval took place immediately after List 2 learning, and generally declined when retrieval occurred 1–4 h later, indicating that the List 2 memory competed with short-term retrieval of List 1. These results demonstrate the dynamic nature of memory over time and the impact of environmental context at different stages of memory processing. PMID:22345494

Remaking memories: reconsolidation updates positively motivated spatial memory in rats.

PubMed

Jones, Bethany; Bukoski, Elizabeth; Nadel, Lynn; Fellous, Jean-Marc

2012-02-17

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 human list-learning paradigm. On Day 1, rats were trained to run to three feeders (List 1) for rewards. On Day 2, rats were trained to run to three different feeders (List 2) in either the same (Reminder condition) or a different (No Reminder condition) experimental context than on Day 1. On Day 3, rats were cued to recall List 1. Rats in the Reminder condition made significantly more visits to List 2 feeders (intrusions) during List 1 recall than rats in the No Reminder condition, indicating that the reminder triggered reactivation and allowed integration of List 2 items into List 1. This reminder effect was selective for the reactivated List 1 memory, as no intrusions occurred when List 2 was recalled on Day 3. No intrusions occurred when retrieval took place in a different context from the one used at encoding, indicating that the expression of the updated memory is dependent upon the retrieval context. Finally, the level of intrusions was highest when retrieval took place immediately after List 2 learning, and generally declined when retrieval occurred 1-4 h later, indicating that the List 2 memory competed with short-term retrieval of List 1. These results demonstrate the dynamic nature of memory over time and the impact of environmental context at different stages of memory processing.

Working Memory Encoding and False Memory in Schizophrenia and Bipolar Disorder in a Spatial Delayed Response Task

PubMed Central

Mayer, Jutta S.; Park, Sohee

2014-01-01

Working memory (WM) impairment is a core feature of schizophrenia, but the contributions of different WM components are not yet specified. Here, we investigated the potential role of inefficient encoding in reduced WM performance in patients with schizophrenia (PSZ). Twenty-eight PSZ, 16 patients with bipolar disorder (PBP), 16 unaffected and unmedicated relatives of PSZ (REL), and 29 demographically matched healthy controls (HC) performed a spatial delayed response task with either low or high WM demands. The demands on attentional selection were also manipulated by presenting distractor stimuli during encoding in some of the trials. After each trial, participants rated their level of response confidence. This allowed us to analyze different types of WM responses. WM was severely impaired in PSZ compared to HC; this reduction was mainly due to an increase in the amount of false memory responses (incorrect responses that were given with high confidence) rather than an increase in the amount of incorrect and not-confident responses. Although PBP showed WM impairments, they did not have increased false memory errors. In contrast, reduced WM in REL was also accompanied by an increase in false memory errors. The presentation of distractors led to a decline in WM performance, which was comparable across groups indicating that attentional selection was intact in PSZ. These findings suggest that inefficient WM encoding is responsible for impaired WM in schizophrenia and point to differential mechanisms underlying WM impairments in PSZ and PBP. PMID:22708888

Age-related differences in associative memory: Empirical evidence and theoretical perspectives.

PubMed

Naveh-Benjamin, Moshe; Mayr, Ulrich

2018-02-01

Systematic research and anecdotal evidence both indicate declines in episodic memory in older adults in good health without dementia-related disorders. Several hypotheses have been proposed to explain these age-related changes in episodic memory, some of which attribute such declines to a deterioration in associative memory. The current special issue of Psychology and Aging on Age-Related Differences in Associative Memory includes 16 articles by top researchers in the area of memory and aging. Their contributions provide a wealth of empirical work that addresses different aspects of aging and associative memory, including different mediators and predictors of age-related declines in binding and associative memory, cognitive, noncognitive, genetic, and neuro-related ones. The contributions also address the processing phases where these declines manifest themselves and look at ways to ameliorate these age-related declines. Furthermore, the contributions in this issue draw on different theoretical perspectives to explain age-related changes in associative memory and provide a wealth of varying methodologies to assess older and younger adults' performance. Finally, although most of the studies focus on normative/healthy aging, some of them contain insights that are potentially applicable to disorders and pathologies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Daily Stress Magnifies the Association between Cognitive Decline and Everyday Memory Problems: An Integration of Longitudinal and Diary Methods

PubMed Central

Rickenbach, Elizabeth H.; Almeida, David M.; Seeman, Teresa E.; Lachman, Margie E.

2014-01-01

We examined whether long-term fluid cognitive decline was associated with memory problems in everyday life, and whether stress plays a moderating role. We expected that the association between cognitive decline and everyday memory problems would be magnified in the context of self-reported and physiological stress. Data are from the Boston Longitudinal Study, a subsample of the Midlife in the United States study. Participants in the current study (n=112) completed a battery of tests measuring fluid cognitive functioning at Time 1 (T1) and 2 (T2) over ten years. At T2, participants completed weekly diaries of self-reported daily stressors and everyday memory problems for twelve consecutive weeks. Also at T2, participants provided four saliva samples over the course of one day to assess physiological stress using diurnal cortisol profiles [cortisol awakening response (CAR) and diurnal cortisol slope (DCS)]. Self-reported daily stressors and a less healthy DCS were associated with more everyday memory problems, and participants with greater cognitive decline reported more memory problems compared to those with less or no decline. Self-reported daily stressors and CAR moderated the relationship of cognitive decline and memory problems. As expected, more cognitive decline was associated with greater increases in memory problems on weeks when individuals reported more daily stressors and for individuals with a less healthy CAR. The current findings can inform interventions aimed to identify factors, such as daily stress, that contribute to daily functioning in the context of cognitive decline. PMID:25365691

Spatial discrimination deficits as a function of mnemonic interference in aged adults with and without memory impairment.

PubMed

Reagh, Zachariah M; Roberts, Jared M; Ly, Maria; DiProspero, Natalie; Murray, Elizabeth; Yassa, Michael A

2014-03-01

It is well established that aging is associated with declines in episodic memory. In recent years, an emphasis has emerged on the development of behavioral tasks and the identification of biomarkers that are predictive of cognitive decline in healthy as well as pathological aging. Here, we describe a memory task designed to assess the accuracy of discrimination ability for the locations of objects. Object locations were initially encoded incidentally, and appeared in a single space against a 5 × 7 grid. During retrieval, subjects viewed repeated object-location pairings, displacements of 1, 2, 3, or 4 grid spaces, and maximal corner-to-opposite-corner displacements. Subjects were tasked with judging objects in this second viewing as having retained their original location, or having moved. Performance on a task such as this is thought to rely on the capacity of the individual to perform hippocampus-mediated pattern separation. We report a performance deficit associated with a physically healthy aged group compared to young adults specific to trials with low mnemonic interference. Additionally, for aged adults, performance on the task was correlated with performance on the delayed recall portion of the Rey Auditory Verbal Learning Test (RAVLT), a neuropsychological test sensitive to hippocampal dysfunction. In line with prior work, dividing the aged group into unimpaired and impaired subgroups based on RAVLT Delayed Recall scores yielded clearly distinguishable patterns of performance, with the former subgroup performing comparably to young adults, and the latter subgroup showing generally impaired memory performance even with minimal interference. This study builds on existing tasks used in the field, and contributes a novel paradigm for differentiation of healthy from possible pathological aging, and may thus provide an avenue for early detection of age-related cognitive decline. Copyright © 2013 Wiley Periodicals, Inc.

Assessing the mental frame syncing in the elderly: a virtual reality protocol.

PubMed

Serino, Silvia; Cipresso, Pietro; Gaggioli, Andrea; Riva, Giuseppe

2014-01-01

Decline in spatial memory in the elderly is often underestimated, and it is crucial to fully investigate the cognitive underpinnings of early spatial impairment. A virtual reality-based procedure was developed to assess deficit in the "mental frame syncing", namely the cognitive ability that allows an effective orientation by synchronizing the allocentric view-point independent representation with the allocentric view-point dependent representation. A pilot study was carried out to evaluate abilities in the mental frame syncing in a sample of 16 elderly participants. Preliminary results indicated that the general cognitive functioning was associated with the ability in the synchronization between these two allocentric references frames.

Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

ERIC Educational Resources Information Center

Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

2013-01-01

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).…

Using an Alzheimer Disease Polygenic Risk Score to Predict Memory Decline in Black and White Americans Over 14 Years of Follow-up.

PubMed

Marden, Jessica R; Mayeda, Elizabeth R; Walter, Stefan; Vivot, Alexandre; Tchetgen Tchetgen, Eric J; Kawachi, Ichiro; Glymour, M Maria

2016-01-01

Evidence on whether genetic predictors of Alzheimer disease (AD) also predict memory decline is inconsistent, and limited data are available for African ancestry populations. For 8253 non-Hispanic white (NHW) and non-Hispanic black (NHB) Health and Retirement Study participants with memory scores measured 1 to 8 times between 1998 and 2012 (average baseline age=62), we calculated weighted polygenic risk scores [AD Genetic Risk Score (AD-GRS)] using the top 22 AD-associated loci, and an alternative score excluding apolipoprotein E (APOE) (AD-GRSexAPOE). We used generalized linear models with AD-GRS-by-age and AD-GRS-by-age interactions (age centered at 70) to predict memory decline. Average NHB decline was 26% faster than NHW decline (P<0.001). Among NHW, 10% higher AD-GRS predicted faster memory decline (linear β=-0.058 unit decrease over 10 y; 95% confidence interval,-0.074 to -0.043). AD-GRSexAPOE also predicted faster decline for NHW, although less strongly. Among NHB, AD-GRS predicted faster memory decline (linear β=-0.050; 95% confidence interval, -0.106 to 0.006), but AD-GRSexAPOE did not. Our nonsignificant estimate among NHB may reflect insufficient statistical power or a misspecified AD-GRS among NHB as an overwhelming majority of genome-wide association studies are conducted in NHW. A polygenic score based on previously identified AD loci predicts memory loss in US blacks and whites.

Young and Older Adults’ Beliefs about Effective Ways to Mitigate Age-Related Memory Decline

PubMed Central

Horhota, Michelle; Lineweaver, Tara; Ositelu, Monique; Summers, Kristi; Hertzog, Christopher

2013-01-01

This study investigated whether young and older adults vary in their beliefs about the impact of various mitigating factors on age-related memory decline. Eighty young (ages 18–23) and eighty older (ages 60–82) participants reported their beliefs about their own memory abilities and the strategies that they use in their everyday lives to attempt to control their memory. Participants also reported their beliefs about memory change with age for hypothetical target individuals who were described as using (or not using) various means to mitigate memory decline. There were no age differences in personal beliefs about control over current or future memory ability. However, the two age groups differed in the types of strategies they used in their everyday life to control their memory. Young adults were more likely to use internal memory strategies, whereas older adults were more likely to focus on cognitive exercise and maintaining physical health as ways to optimize their memory ability. There were no age differences in rated memory change across the life span in hypothetical individuals. Both young and older adults perceived strategies related to improving physical and cognitive health as effective means of mitigating memory loss with age, whereas internal memory strategies were perceived as less effective means for controlling age-related memory decline. PMID:22082012

Aβ-related memory decline in APOE ε4 noncarriers: Implications for Alzheimer disease.

PubMed

Lim, Yen Ying; Laws, Simon M; Villemagne, Victor L; Pietrzak, Robert H; Porter, Tenielle; Ames, David; Fowler, Christopher; Rainey-Smith, Stephanie; Snyder, Peter J; Martins, Ralph N; Salvado, Olivier; Bourgeat, Pierrick; Rowe, Christopher C; Masters, Colin L; Maruff, Paul

2016-04-26

As the absence of Aβ-related memory decline in APOE ε4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ε4 carriers and noncarriers who were cognitively normal (CN). CN older adults (n = 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments. Relative to Aβ- CN ε4 noncarriers, both Aβ+ CN ε4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of progression to a clinical classification of mild cognitive impairment. Memory decline was greater in Aβ+ CN ε4 carriers than in Aβ+ CN ε4 noncarriers. No cognitive decline was evident in Aβ- CN ε4 carriers. In CN older adults, Aβ+ is associated with memory decline in ε4 noncarriers; however, the rate of this decline is much slower than that observed in ε4 carriers. These data indicate that the processes by which ε4 carriage increases the rate of Aβ-related cognitive decline occur in the preclinical stage of Alzheimer disease. © 2016 American Academy of Neurology.

Modeling Longitudinal Changes in Older Adults’ Memory for Spoken Discourse: Findings from the ACTIVE Cohort

PubMed Central

Payne, Brennan R.; Gross, Alden L.; Parisi, Jeanine M.; Sisco, Shannon M.; Stine-Morrow, Elizabeth A. L.; Marsiske, Michael; Rebok, George W.

2014-01-01

Episodic memory shows substantial declines with advancing age, but research on longitudinal trajectories of spoken discourse memory (SDM) in older adulthood is limited. Using parallel process latent growth curve models, we examined 10 years of longitudinal data from the no-contact control group (N = 698) of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) randomized controlled trial in order to test (a) the degree to which SDM declines with advancing age, (b) predictors of these age-related declines, and (c) the within-person relationship between longitudinal changes in SDM and longitudinal changes in fluid reasoning and verbal ability over 10 years, independent of age. Individuals who were younger, White, had more years of formal education, were male, and had better global cognitive function and episodic memory performance at baseline demonstrated greater levels of SDM on average. However, only age at baseline uniquely predicted longitudinal changes in SDM, such that declines accelerated with greater age. Independent of age, within-person decline in reasoning ability over the 10-year study period was substantially correlated with decline in SDM (r = .87). An analogous association with SDM did not hold for verbal ability. The findings suggest that longitudinal declines in fluid cognition are associated with reduced spoken language comprehension. Unlike findings from memory for written prose, preserved verbal ability may not protect against developmental declines in memory for speech. PMID:24304364

EFFECTS OF MEDIAL SEPTAL LESION ON HIPPOCAMPAL EXTRACELLULAR GLUTAMATE AND GABA LEVELS DURING SPATIAL ALTERNATION TESTING.

PubMed

Mataradze, S; Naneishvili, T; Sephashvili, M; Mikeladze, D; Dashniani, M

2016-10-01

The present study investigated spatial working memory assessed in spontaneous alternation (SA) task and hippocampal glutamate and GABA release prior to, during, and after SA test in sham-operated and electrolytic medial septal (MS) lesioned rats. Also, have been investigated the effects of MS lesion on KCl-stimulated release of glutamate and GABA in the hippocampus. Behavioral study showed that electrolytic lesion of MS significantly impaired SA performance. Although both groups of animals had an insignificant rise in their respective hippocampal glutamate efflux during the SA, the rise of MS lesioned animals was blunted when compared with control animals. Hippocampal GABA levels did not change during behavioral testing in both groups. Most of control animals showed increase in KCl-stimulated glutamate release. By contrast, only one MS lesioned rat showed increase in glutamate release in response to KCl stimulation. Most of control and MS lesioned rats were non-responders in GABA release in response to KCl stimulation. Decreased glutamate release (upon stimulation) in the MS lesioned rats may contribute to spatial working memory impairment in these animals. We propose that SA testing coupled with in vivo microdialysis sampling represents a suitable approach to revealing the neurochemical correlates of hippocampal-dependent memory function, and thus could be a useful tool for better understanding of the neurochemical basis of cognitive decline associated with various disorders and neurodegenerative diseases.

Functional brain imaging of episodic memory decline in ageing.

PubMed

Nyberg, L

2017-01-01

The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation. © 2016 The Association for the Publication of the Journal of Internal Medicine.

Water maze experience and prenatal choline supplementation differentially promote long-term hippocampal recovery from seizures in adulthood

PubMed Central

Wong-Goodrich, Sarah J.E.; Glenn, Melissa J.; Mellott, Tiffany J.; Liu, Yi B.; Blusztajn, Jan K.; Williams, Christina L.

2010-01-01

Status epilepticus (SE) in adulthood dramatically alters the hippocampus and produces spatial learning and memory deficits. Some factors, like environmental enrichment and exercise, may promote functional recovery from SE. Prenatal choline supplementation (SUP) also protects against spatial memory deficits observed shortly after SE in adulthood, and we have previously reported that SUP attenuates the neuropathological response to SE in the adult hippocampus just 16 days after SE. It is unknown whether SUP can ameliorate longer-term cognitive and neuropathological consequences of SE, whether repeatedly engaging the injured hippocampus in a cognitive task might facilitate recovery from SE, and whether our prophylactic prenatal dietary treatment would enable the injured hippocampus to more effectively benefit from cognitive rehabilitation. To address these issues, adult offspring from rat dams that received either a control (CON) or SUP diet on embryonic days 12–17 first received training on a place learning water maze task (WM) and were then administered saline or kainic acid (KA) to induce SE. Rats then either remained in their home cage, or received three additional WM sessions at 3, 6.5, and 10 weeks after SE to test spatial learning and memory retention. Eleven weeks after SE, the brains were analyzed for several hippocampal markers known to be altered by SE. SUP attenuated SE-induced spatial learning deficits and completely rescued spatial memory retention by 10 weeks post-SE. Repeated WM experience prevented SE-induced declines in glutamic acid decarboxylase (GAD) and dentate gyrus neurogenesis, and attenuated increased glial fibrilary acidic protein (GFAP) levels. Remarkably, SUP alone was similarly protective to an even greater extent, and SUP rats that were water maze trained after SE showed reduced hilar migration of newborn neurons. These findings suggest that prophylactic SUP is protective against the long-term cognitive and neuropathological effects of KA-induced SE, and that rehabilitative cognitive enrichment may be partially beneficial. PMID:20232399

A Novel 1,4-Dihydropyridine Derivative Improves Spatial Learning and Memory and Modifies Brain Protein Expression in Wild Type and Transgenic APPSweDI Mice.

PubMed

Jansone, Baiba; Kadish, Inga; van Groen, Thomas; Beitnere, Ulrika; Moore, Doyle Ray; Plotniece, Aiva; Pajuste, Karlis; Klusa, Vija

2015-01-01

Ca2+ blockers, particularly those capable of crossing the blood-brain barrier (BBB), have been suggested as a possible treatment or disease modifying agents for neurodegenerative disorders, e.g., Alzheimer's disease. The present study investigated the effects of a novel 4-(N-dodecyl) pyridinium group-containing 1,4-dihydropyridine derivative (AP-12) on cognition and synaptic protein expression in the brain. Treatment of AP-12 was investigated in wild type C57BL/6J mice and transgenic Alzheimer's disease model mice (Tg APPSweDI) using behavioral tests and immunohistochemistry, as well as mass spectrometry to assess the blood-brain barrier (BBB) penetration. The data demonstrated the ability of AP-12 to cross the BBB, improve spatial learning and memory in both mice strains, induce anxiolytic action in transgenic mice, and increase expression of hippocampal and cortical proteins (GAD67, Homer-1) related to synaptic plasticity. The compound AP-12 can be seen as a prototype molecule for use in the design of novel drugs useful to halt progression of clinical symptoms (more specifically, anxiety and decline in memory) of neurodegenerative diseases, particularly Alzheimer's disease.

Apigenin attenuates isoflurane-induced cognitive dysfunction via epigenetic regulation and neuroinflammation in aged rats.

PubMed

Chen, Lin; Xie, Wenji; Xie, Wenqin; Zhuang, Weiqiang; Jiang, Changcheng; Liu, Naizhen

2017-11-01

Post operational cognitive dysfunction (POCD) occurs in patients after anesthesia and surgery. Abnormal histone acetylation and neuroinflammation are key factors in the pathogenesis of cognitive impairment. Apigenin not only has an anti-inflammatory activity but also modifies histone acetylation. We aimed to investigate whether apigenin can attenuate isoflurane exposure-induced cognitive decline by regulating histone acetylation and inflammatory signaling. Spatial learning and memory were assessed by Morris water maze test. Levels of histone acetylation, BDNF and downstream signaling, and inflammatory components were analyzed. Isoflurane exposure in aged rats lead to impaired spatial learning and memory. These rats exhibited dysregulated histone H3K9 and H4K12 acetylation, which was accompanied by reduced BDNF expression and suppressed BDNF downstream signaling pathway. Apigenin restored histone acetylation and BDNF signaling. Apigenin also suppressed isoflurane exposure induced upregulation of proinflammatory cytokines and NFκB signaling pathway. Memory impairment induced by isoflurane exposure is associated with dysregulated histone acetylation in the hippocampus, which affects BDNF expression and hence BDNF downstream signaling pathway. Apigenin recovers cognitive function by restoring histone acetylation and suppressing neuroinflammation. Copyright © 2017 Elsevier B.V. All rights reserved.

Memory complaints and APOE-epsilon4 accelerate cognitive decline in cognitively normal elderly.

PubMed

Dik, M G; Jonker, C; Comijs, H C; Bouter, L M; Twisk, J W; van Kamp, G J; Deeg, D J

2001-12-26

To investigate to what extent subjective memory complaints and APOE-epsilon4 allele carriage predict future cognitive decline in cognitively intact elderly persons, by evaluating both their separate and combined effects. We selected 1,168 subjects from the population-based Longitudinal Aging Study Amsterdam who were 62 to 85 years of age and had no obvious cognitive impairment at baseline (Mini-Mental State Examination [MMSE] score, > or =27). Memory complaints and APOE phenotypes were assessed at baseline. MMSE, the Auditory Verbal Learning Test (memory: immediate recall and delayed recall), and the Alphabet Coding Task-15 (information processing speed) were used to study cognitive decline. Follow-up data were collected after 3 and 6 years. Data were analyzed with generalized estimating equations, adjusted for age, sex, education, and depression. Baseline memory complaints were reported by 25.5% of the cognitively intact elderly persons. Overall, 25.3% of the subjects were carriers of at least one APOE-epsilon4 allele. Memory complaints were associated with a greater rate of decline in all cognitive measures, except immediate recall. In addition, APOE-epsilon4 allele carriers had a greater rate of cognitive decline shown by MMSE scores and slower information processing speeds after 6 years. The effects of both memory complaints and APOE-epsilon4 allele carriage were additive: subjects with both factors had a two times higher cognitive decline than did subjects without both factors. Both memory complaints and APOE-epsilon4 allele carriage predict cognitive decline at an early stage. This finding highlights the importance of subjective memory complaints, which are important even at an early stage when objective tests are still unable to detect cognitive deficits and are especially important for elderly carriers of the APOE-epsilon4 allele because they have an additional risk.

Association of Source of Memory Complaints and Increased Risk of Cognitive Impairment and Cognitive Decline: A Community-Based Study.

PubMed

Qi, Xue-Mei; Gu, Lin; Tang, Hui-Dong; Chen, Sheng-Di; Ma, Jian-Fang

2018-04-20

Memory complaint is common in the elderly. Recently, it was shown that self-report memory complaint was predictive of cognitive decline. This study aimed to investigate the predictive value of the source of memory complaints on the risk of cognitive impairment and cognitive decline in a community-based cohort. Data on memory complaints and cognitive function were collected among 1840 Chinese participants (aged ≥55 years old) in an urban community at baseline interview and 5-year follow-up. Incident cognitive impairment was identified based on education-adjusted Mini-Mental State Examination score. Logistic regression model was used to estimate the association between the source of memory complaints and risk of cognitive impairment conversion and cognitive decline, after adjusting for covariates. A total of 1840 participants were included into this study including 1713 normal participants and 127 cognitive impairment participants in 2009. Among 1713 normal participants in 2009, 130 participants were converted to cognitive impairment after 5 years of follow-up. In 2014, 606 participants were identified as cognitive decline. Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment (odds ratio [OR] = 1.60, 95% confidence interval [CI]: 1.04-2.48) and cognitive decline (OR = 1.30, 95% CI: 1.01-1.68). Furthermore, this association was more significant in males (OR = 2.10, 95% CI: 1.04-4.24 for cognitive impairment and OR = 1.87, 95% CI: 1.20-2.99 for cognitive decline) and in higher education level (OR = 1.79, 95% CI: 1.02-3.15 for cognitive impairment and OR = 1.40, 95% CI: 1.02-1.91 for cognitive decline). Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment conversion and cognitive decline, especially in persons with male gender and high educational background.

Recognition of Famous Names Predicts Episodic Memory Decline in Cognitively Intact Elders

PubMed Central

Seidenberg, Michael; Kay, Christina; Woodard, John L.; Nielson, Kristy A.; Smith, J. Carson; Kandah, Cassandra; Guidotti Breting, Leslie M.; Novitski, Julia; Lancaster, Melissa; Matthews, Monica; Hantke, Nathan; Butts, Alissa; Rao, Stephen M.

2013-01-01

Objective: Semantic memory impairment is common in both Mild Cognitive Impairment (MCI) and early Alzheimer’s disease (AD), and the ability to recognize familiar people is particularly vulnerable. A time-limited temporal gradient (TG) in which well known people from decades earlier are better recalled than those learned recently is also reported in both AD and MCI. In this study, we hypothesized that the TG pattern on a famous name recognition task (FNRT) administered to cognitively intact elders would predict future episodic memory decline, and would also show a significant correlation with hippocampal volume. Methods: 78 healthy elders (ages 65-90) with normal cognition and episodic memory at baseline were administered a FNRT. Follow-up episodic memory testing 18 months later produced two groups: Declining (≥ 1 SD reduction in episodic memory) and Stable (< 1 SD). Results: The Declining group (N=27) recognized fewer recent famous names than the Stable group (N=51), while recognition for remote names was comparable. Baseline MRI volumes for both the left and right hippocampus was significantly smaller in the Declining group than the Stable group. Smaller baseline hippocampal volume was also significantly correlated with poorer performance for recent, but not remote famous names. Logistic regression analyses indicated that baseline TG performance was a significant predictor of group status (Declining versus Stable) independent of chronological age and APOE ε4 inheritance. Conclusions: Famous name recognition may serve as an early pre-clinical cognitive marker of episodic memory decline in older individuals. PMID:23688215

Curcuma comosa improves learning and memory function on ovariectomized rats in a long-term Morris water maze test

PubMed Central

Su, Jian; Sripanidkulchai, Kittisak; Wyss, J. Michael; Sripanidkulchai, Bungorn

2010-01-01

Aim of the study Curcuma comosa extract and some purified compounds from this plant have been reported to have estrogenic-like effects, and estrogen improves learning in some animals and potentially in postmenopausal women; therefore, this study tested the hypothesis that Curcuma comosa and estrogen have similar beneficial effects on spatial learning and memory. Materials and methods Curcuma comosa hexane extract, containing 0.165 mg of (4E,6E)-1,7-diphenylhepta-4,6-dien-3-one per mg of the crude extract, was orally administered to ovariectomized Wistar rats at the doses of 250 or 500 mg/kg body weight. 17β-estradiol (10 μg/kg body weight, subcutaneously) was used as a positive control. Thirty days after the initiation of treatment, animals were tested in a Morris water maze for spatial learning and memory. They were re-tested every 30 days and a final probe trial was run on day 119. Results Compared to control rats, OVX rats displayed significant memory impairment for locating the platform in the water maze from day 67 after the surgery, onward. In contrast, OVX rats treated with either Curcuma comosa or estrogen were significantly protected from this decline in cognitive function. Further, the protection of cognitive effects by Curcuma comosa was larger at higher dose. Conclusions These results suggest that long-term treatment with Curcuma comosa has beneficial effects on learning and memory function in rats. PMID:20420894

Verbal memory after temporal lobe epilepsy surgery in children: Do only mesial structures matter?

PubMed

Law, Nicole; Benifla, Mony; Rutka, James; Smith, Mary Lou

2017-02-01

Previous findings have been mixed regarding verbal memory outcome after left temporal lobectomy in children, and there are few studies comparing verbal memory change after lateral versus mesial temporal lobe resections. We compared verbal memory outcome associated with sparing or including the mesial structures in children who underwent left or right temporal lobe resection. We also investigated predictors of postsurgical verbal memory change. We retrospectively assessed verbal memory change approximately 1 year after unilateral temporal lobe epilepsy surgery using a list learning task. Participants included 23 children who underwent temporal lobe surgery with sparing of the mesial structures (13 left), and 40 children who had a temporal lobectomy that included resection of mesial structures (22 left). Children who underwent resection from the left lateral and mesial temporal lobe were the only group to show decline in verbal memory. Furthermore, when we considered language representation in the left temporal resection group, patients with left language representation and spared mesial structures showed essentially no change in verbal memory from preoperative to follow-up, whereas those with left language representation and excised mesial structures showed a decline. Postoperative seizure status had no effect on verbal memory change in children after left temporal lobe surgery. Finally, we found that patients with intact preoperative verbal memory experienced a significant decline compared to those with below average preoperative verbal memory. Our findings provide evidence of significant risk factors for verbal memory decline in children, specific to left mesial temporal lobe epilepsy. Children who undergo left temporal lobe surgery that includes mesial structures may be most vulnerable for verbal memory decline, especially when language representation is localized to the left hemisphere and when preoperative verbal memory is intact. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Young and older adults' beliefs about effective ways to mitigate age-related memory decline.

PubMed

Horhota, Michelle; Lineweaver, Tara; Ositelu, Monique; Summers, Kristi; Hertzog, Christopher

2012-06-01

This study investigated whether young and older adults vary in their beliefs about the impact of various mitigating factors on age-related memory decline. Eighty young (ages 18-23) and 80 older (ages 60-82) participants reported their beliefs about their own memory abilities and the strategies that they use in their everyday lives to attempt to control their memory. Participants also reported their beliefs about memory change with age for hypothetical target individuals who were described as using (or not using) various means to mitigate memory decline. There were no age differences in personal beliefs about control over current or future memory ability. However, the two age groups differed in the types of strategies they used in their everyday life to control their memory. Young adults were more likely to use internal memory strategies, whereas older adults were more likely to focus on cognitive exercise and maintaining physical health as ways to optimize their memory ability. There were no age differences in rated memory change across the life span in hypothetical individuals. Both young and older adults perceived strategies related to improving physical and cognitive health as effective means of mitigating memory loss with age, whereas internal memory strategies were perceived as less effective means for controlling age-related memory decline. PsycINFO Database Record (c) 2012 APA, all rights reserved

Posterior cortical atrophy variant of Alzheimer's dementia-A case report.

PubMed

Mukku, Shiva Shanker Reddy; Chintala, Haripriya; Nagaraj, Chandana; Mangalore, Sandhya; Sivakumar, Palanimuthu T; Varghese, Mathew

2018-05-17

Alzheimer's dementia (AD) is the commonest type of dementia presenting with initial episodic memory decline followed by involvement of other cognitive domains. Posterior cortical atrophy (PCA) is one of the variants of Alzheimer's dementia (AD) characterized by the atypical presentation of relatively persevered memory in the initial stage. PCA is an uncommon early onset dementia affecting adults between 50 and 65 years. It presents predominantly with visuo-spatial and visuo-perceptual deficits. PCA is a phenotype with varied etiology most common being Alzheimer's disease. The complex and atypical presentation with preserved memory and insight in patients with PCA poses challenge to clinicians in diagnosing at initial stages. There is also paucity of research on prevalence, course, prognosis and management of PCA. In this article we describe a middle aged gentlemen presenting with clinical features suggestive of PCA. We also discussed relevant literature. Copyright © 2018 Elsevier B.V. All rights reserved.

The effects of age, illustrations, and task variables on the performance of procedural assembly tasks.

PubMed

Morrell, R W; Park, D C

1993-09-01

Older adults may be disadvantaged in the performance of procedural assembly tasks because of age-related declines in working memory operations. It was hypothesized that adding illustrations to instructional text may lessen age-related performance differences by minimizing processing demands on working memory in the elderly. In the present study, younger and older adults constructed a series of 3-dimensional objects from 3 types of instructions (text only, illustration only, or text and illustrations). Results indicated that instructions consisting of text and illustrations reduced errors in construction for both age groups compared with the other formats. Younger adults, however, outperformed older adults under all instructional format conditions. Measures of spatial and verbal working memory and text comprehension ability accounted for substantial age-related variance across the different format conditions but did not fully account for the age differences observed.

The complex interaction between anxiety and cognition: insight from spatial and verbal working memory

PubMed Central

Vytal, Katherine E.; Cornwell, Brian R.; Letkiewicz, Allison M.; Arkin, Nicole E.; Grillon, Christian

2013-01-01

Anxiety can be distracting, disruptive, and incapacitating. Despite problems with empirical replication of this phenomenon, one fruitful avenue of study has emerged from working memory (WM) experiments where a translational method of anxiety induction (risk of shock) has been shown to disrupt spatial and verbal WM performance. Performance declines when resources (e.g., spatial attention, executive function) devoted to goal-directed behaviors are consumed by anxiety. Importantly, it has been shown that anxiety-related impairments in verbal WM depend on task difficulty, suggesting that cognitive load may be an important consideration in the interaction between anxiety and cognition. Here we use both spatial and verbal WM paradigms to probe the effect of cognitive load on anxiety-induced WM impairment across task modality. Subjects performed a series of spatial and verbal n-back tasks of increasing difficulty (1, 2, and 3-back) while they were safe or at risk for shock. Startle reflex was used to probe anxiety. Results demonstrate that induced-anxiety differentially impacts verbal and spatial WM, such that low and medium-load verbal WM is more susceptible to anxiety-related disruption relative to high-load, and spatial WM is disrupted regardless of task difficulty. Anxiety impacts both verbal and spatial processes, as described by correlations between anxiety and performance impairment, albeit the effect on spatial WM is consistent across load. Demanding WM tasks may exert top-down control over higher-order cortical resources engaged by anxious apprehension, however high-load spatial WM may continue to experience additional competition from anxiety-related changes in spatial attention, resulting in impaired performance. By describing this disruption across task modalities, these findings inform current theories of emotion–cognition interactions and may facilitate development of clinical interventions that seek to target cognitive impairments associated with anxiety. PMID:23542914

Association of Crossword Puzzle Participation with Memory Decline in Persons Who Develop Dementia

PubMed Central

Pillai, Jagan A.; Hall, Charles B.; Dickson, Dennis W.; Buschke, Herman; Lipton, Richard B.; Verghese, Joe

2013-01-01

Participation in cognitively stimulating leisure activities such as crossword puzzles may delay onset of the memory decline in the preclinical stages of dementia, possibly via its effect on improving cognitive reserve. We followed 488 initially cognitively intact community residing individuals with clinical and cognitive assessments every 12–18 months in the Bronx Aging Study. We assessed the influence of crossword puzzle participation on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. Crossword puzzle participation at baseline delayed onset of accelerated memory decline by 2.54 years. Inclusion of education or participation in other cognitively stimulating activities did not significantly add to the fit of the model beyond the effect of puzzles. Our findings show that late life crossword puzzle participation, independent of education, was associated with delayed onset of memory decline in persons who developed dementia. Given the wide availability and accessibility of crossword puzzles, their role in preventing cognitive decline should be validated in future clinical trials. PMID:22040899

Age-related differences in associative memory: the role of sensory decline.

PubMed

Naveh-Benjamin, Moshe; Kilb, Angela

2014-09-01

Numerous studies show age-related decline in episodic memory. One of the explanations for this decline points to older adults' deficit in associative memory, reflecting the difficulties they have in binding features of episodes into cohesive entities and retrieving these bindings. Here, we evaluate the degree to which this deficit may be mediated by sensory loss associated with increased age. In 2 experiments, young adults studied word pairs that were degraded at encoding either visually (Experiment 1) or auditorily (Experiment 2). We then tested their memory for both the component words and the associations with recognition tests. For both experiments, young adults under nondegraded conditions showed an advantage in associative over item memory, relative to a group of older adults. In contrast, under perceptually degraded conditions younger adults performed similarly to the older adults who were tested under nondegraded conditions. More specifically, under perceptual degradation, young adults' associative memory declined and their component memory improved somewhat, resulting in an associative deficit, similar to that shown by older adults. This evidence is consistent with a sensory acuity decline in old age being one mediator in the associative deficit of older adults. These results broaden our understanding of age-related memory changes and how sensory and cognitive processes interact to shape these changes. The theoretical implications of these results are discussed with respect to mechanisms underlying age-related changes in episodic memory and resource tradeoffs in the encoding of component and associative memory. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Delayed memory effects after intense stress in Special Forces candidates: exploring path processes between cortisol secretion and memory recall.

PubMed

Taverniers, John; Taylor, Marcus K; Smeets, Tom

2013-05-01

The aim of this paper is twofold. First, it explores delayed effects of high endogenously evoked cortisol concentrations on visuo-spatial declarative memory. Subsequently, it applies multiple mediation (MM) analyses to reveal path processes between stress and cognitive performance in a sample of 24 male Special Forces (SF) candidates (mean age = 27.0 years, SD = 4.1). The SF candidates were randomly assigned to a control (n = 12) or an intense stress group (n = 12), and cortisol secretion for the intense stress condition was triggered by a brusque 60 min prisoner of war exercise. Stress exposure provoked robust increases in cortisol concentrations and a significant decline in immediate recall performance, measured with the Rey-Osterrieth Complex Figure (ROCF). The relative retrieval differences in regard to the ROCF persisted even after a recovery period of 24 h, as both groups showed similar levels of memory decline over 24 h. Next, the study applied a MM design that involved distribution-independent asymptotic and resampling strategies to extend traditional bivariate analyses. MM results showed that ROCF performance was mediated by increases in cortisol concentrations. Considering the studied variables, the current analysis was the first to provide statistical support for the generally accepted thesis that cortisol secretion in itself, rather than subjective strain or the experimental treatment, affects cognitive performance. The revelation of such path processes is important because it establishes process identification and may refine existing paradigms.

Depressive Mood and Testosterone Related to Declarative Verbal Memory Decline in Middle-Aged Caregivers of Children with Eating Disorders.

PubMed

Romero-Martínez, Ángel; Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

2016-03-04

Caring for children diagnosed with a chronic psychological disorder such as an eating disorder (ED) can be used as a model of chronic stress. This kind of stress has been reported to have deleterious effects on caregivers' cognition, particularly in verbal declarative memory of women caregivers. Moreover, high depressive mood and variations in testosterone (T) levels moderate this cognitive decline. The purpose of this study was to characterize whether caregivers of individuals with EDs (n = 27) show declarative memory impairments compared to non-caregivers caregivers (n = 27), using for this purpose a standardized memory test (Rey's Auditory Verbal Learning Test). Its purpose was also to examine the role of depressive mood and T in memory decline. Results showed that ED caregivers presented high depressive mood, which was associated to worse verbal memory performance, especially in the case of women. In addition, all caregivers showed high T levels. Nonetheless, only in the case of women caregivers did T show a curvilinear relationship with verbal memory performance, meaning that the increases of T were associated to the improvement in verbal memory performance, but only up to a certain point, as after such point T continued to increase and memory performance decreased. Thus, chronic stress due to caregiving was associated to disturbances in mood and T levels, which in turn was associated to verbal memory decline. These findings should be taken into account in the implementation of intervention programs for helping ED caregivers cope with caregiving situations and to prevent the risk of a pronounced verbal memory decline.

Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease.

PubMed

Carrasquillo, Minerva M; Crook, Julia E; Pedraza, Otto; Thomas, Colleen S; Pankratz, V Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G; Ma, Li; Bisceglio, Gina D; Roberts, Rosebud O; Lucas, John A; Smith, Glenn E; Ivnik, Robert J; Machulda, Mary M; Graff-Radford, Neill R; Petersen, Ronald C; Younkin, Steven G; Ertekin-Taner, Nilüfer

2015-01-01

We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Differences in quantitative methods for measuring subjective cognitive decline - results from a prospective memory clinic study.

PubMed

Vogel, Asmus; Salem, Lise Cronberg; Andersen, Birgitte Bo; Waldemar, Gunhild

2016-09-01

Cognitive complaints occur frequently in elderly people and may be a risk factor for dementia and cognitive decline. Results from studies on subjective cognitive decline are difficult to compare due to variability in assessment methods, and little is known about how different methods influence reports of cognitive decline. The Subjective Memory Complaints Scale (SMC) and The Memory Complaint Questionnaire (MAC-Q) were applied in 121 mixed memory clinic patients with mild cognitive symptoms (mean MMSE = 26.8, SD 2.7). The scales were applied independently and raters were blinded to results from the other scale. Scales were not used for diagnostic classification. Cognitive performances and depressive symptoms were also rated. We studied the association between the two measures and investigated the scales' relation to depressive symptoms, age, and cognitive status. SMC and MAC-Q were significantly associated (r = 0.44, N = 121, p = 0.015) and both scales had a wide range of scores. In this mixed cohort of patients, younger age was associated with higher SMC scores. There were no significant correlations between cognitive test performances and scales measuring subjective decline. Depression scores were significantly correlated to both scales measuring subjective decline. Linear regression models showed that age did not have a significant contribution to the variance in subjective memory beyond that of depressive symptoms. Measures for subjective cognitive decline are not interchangeable when used in memory clinics and the application of different scales in previous studies is an important factor as to why studies show variability in the association between subjective cognitive decline and background data and/or clinical results. Careful consideration should be taken as to which questions are relevant and have validity when operationalizing subjective cognitive decline.

ESTROGENS AND AGE-RELATED MEMORY DECLINE IN RODENTS: WHAT HAVE WE LEARNED AND WHERE DO WE GO FROM HERE?

PubMed Central

Frick, Karyn M.

2009-01-01

The question of whether ovarian hormone therapy can prevent or reduce age-related memory decline in menopausal women has been the subject of much recent debate. Although numerous studies have demonstrated a beneficial effect of estrogen and/or progestin therapy for certain types of memory in menopausal women, recent clinical trials suggest that such therapy actually increases the risk of cognitive decline and dementia. Because rodent models have been frequently used to examine the effects of age and/or ovarian hormone deficiency on mnemonic function, rodent models of age-related hormone and memory decline may be useful in helping to resolve this issue. This review will focus on evidence suggesting that estradiol modulates memory, particularly hippocampal-dependent memory, in young and aging female rats and mice. Various factors affecting the mnemonic response to estradiol in aging females will be highlighted to illustrate the complications inherent to studies of estrogen therapy in aging females. Avenues for future development of estradiol-based therapies will also be discussed, and it is argued that an approach to drug development based on identifying the molecular mechanisms underlying estrogenic modulation of memory may lead to promising future treatments for reducing age-related mnemonic decline. PMID:18835561

Age-related decline of precision and binding in visual working memory.

PubMed

Peich, Muy-Cheng; Husain, Masud; Bays, Paul M

2013-09-01

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.

Age-Related Decline of Precision and Binding in Visual Working Memory

PubMed Central

2013-01-01

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. PMID:23978008

Sleep-dependent memory consolidation in healthy aging and mild cognitive impairment.

PubMed

Pace-Schott, Edward F; Spencer, Rebecca M C

2015-01-01

Sleep quality and architecture as well as sleep's homeostatic and circadian controls change with healthy aging. Changes include reductions in slow-wave sleep's (SWS) percent and spectral power in the sleep electroencephalogram (EEG), number and amplitude of sleep spindles, rapid eye movement (REM) density and the amplitude of circadian rhythms, as well as a phase advance (moved earlier in time) of the brain's circadian clock. With mild cognitive impairment (MCI) there are further reductions of sleep quality, SWS, spindles, and percent REM, all of which further diminish, along with a profound disruption of circadian rhythmicity, with the conversion to Alzheimer's disease (AD). Sleep disorders may represent risk factors for dementias (e.g., REM Behavior Disorder presages Parkinson's disease) and sleep disorders are themselves extremely prevalent in neurodegenerative diseases. Working memory , formation of new episodic memories, and processing speed all decline with healthy aging whereas semantic, recognition, and emotional declarative memory are spared. In MCI, episodic and working memory further decline along with declines in semantic memory. In young adults, sleep-dependent memory consolidation (SDC) is widely observed for both declarative and procedural memory tasks. However, with healthy aging, although SDC for declarative memory is preserved, certain procedural tasks, such as motor-sequence learning, do not show SDC. In younger adults, fragmentation of sleep can reduce SDC, and a normative increase in sleep fragmentation may account for reduced SDC with healthy aging. Whereas sleep disorders such as insomnia, obstructive sleep apnea, and narcolepsy can impair SDC in the absence of neurodegenerative changes, the incidence of sleep disorders increases both with normal aging and, further, with neurodegenerative disease. Specific features of sleep architecture, such as sleep spindles and SWS are strongly linked to SDC. Diminution of these features with healthy aging and their further decline with MCI may account for concomitant declines in SDC. Notably these same sleep features further markedly decline, in concert with declining cognitive function, with the progression to AD. Therefore, progressive changes in sleep quality, architecture, and neural regulation may constitute a contributing factor to cognitive decline that is seen both with healthy aging and, to a much greater extent, with neurodegenerative disease.

Requiring collaboration: Hippocampal-prefrontal networks needed in spatial working memory and ageing. A multivariate analysis approach.

PubMed

Zancada-Menendez, C; Alvarez-Suarez, P; Sampedro-Piquero, P; Cuesta, M; Begega, A

2017-04-01

Ageing is characterized by a decline in the processes of retention and storage of spatial information. We have examined the behavioural performance of adult rats (3months old) and aged rats (18months old) in a spatial complex task (delayed match to sample). The spatial task was performed in the Morris water maze and consisted of three sessions per day over a period of three consecutive days. Each session consisted of two trials (one sample and retention) and inter-session intervals of 5min. Behavioural results showed that the spatial task was difficult for middle aged group. This worse execution could be associated with impairments of processing speed and spatial information retention. We examined the changes in the neuronal metabolic activity of different brain regions through cytochrome C oxidase histochemistry. Then, we performed MANOVA and Discriminant Function Analyses to determine the functional profile of the brain networks that are involved in the spatial learning of the adult and middle-aged groups. This multivariate analysis showed two principal functional networks that necessarily participate in this spatial learning. The first network was composed of the supramammillary nucleus, medial mammillary nucleus, CA3, and CA1. The second one included the anterior cingulate, prelimbic, and infralimbic areas of the prefrontal cortex, dentate gyrus, and amygdala complex (basolateral l and central subregions). There was a reduction in the hippocampal-supramammilar network in both learning groups, whilst there was an overactivation in the executive network, especially in the aged group. This response could be due to a higher requirement of the executive control in a complex spatial memory task in older animals. Copyright © 2017 Elsevier Inc. All rights reserved.

Terminal decline of episodic memory and perceptual speed in a biracial population.

PubMed

Wilson, Robert S; Rajan, Kumar B; Barnes, Lisa L; Jansen, Willemijn; Amofa, Priscilla; Weuve, Jennifer; Evans, Denis A

2018-05-01

We compared trajectories of terminal cognitive decline in older Black (n = 3372) and White (n = 1756) persons from a defined population who completed tests of episodic memory and perceptual speed at 3-year intervals for up to 18 years. During a mean of 9.9 years of observation, 1608 Black persons and 902 White persons died. Preterminal decline of episodic memory did not differ by race. Terminal episodic memory decline began earlier in Black persons (mean of 4.3 years before death) than in White persons (mean = 3.9 years) and progressed more slowly. By contrast, terminal decline of perceptual speed began earlier in White persons (mean = 5.0 years) than in Black persons (mean = 4.5 years). Rate of perceptual speed decline was more rapid in White persons than in Black persons in both the preterminal and terminal periods. The results indicate that terminal cognitive decline occurs in Black persons but suggest that the rate of cognitive decline during the terminal period is less rapid in Black persons than in White persons.

Epigenetic alterations in the suprachiasmatic nucleus and hippocampus contribute to age-related cognitive decline

PubMed Central

Deibel, Scott H.; Zelinski, Erin L.; Keeley, Robin J.; Kovalchuk, Olga; McDonald, Robert J.

2015-01-01

Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151

Age differences in spatial working memory contributions to visuomotor adaptation and transfer.

PubMed

Langan, Jeanne; Seidler, Rachael D

2011-11-20

Throughout our life span we encounter challenges that require us to adapt to the demands of our changing environment; this entails learning new skills. Two primary components of motor skill learning are motor acquisition, the initial process of learning the skill, and motor transfer, when learning a new skill is benefitted by the overlap with a previously learned one. Older adults typically exhibit declines in motor acquisition compared to young adults, but remarkably, do not demonstrate deficits in motor transfer [10]. Our recent work demonstrates that a failure to engage spatial working memory (SWM) is associated with skill learning deficits in older adults [16]. Here, we investigate the role that SWM plays in both motor learning and transfer in young and older adults. Both age groups exhibited performance savings, or positive transfer, at transfer of learning for some performance variables. Measures of spatial working memory performance and reaction time correlated with both motor learning and transfer for young adults. Young adults recruited overlapping brain regions in prefrontal, premotor, parietal and occipital cortex for performance of a SWM and a visuomotor adaptation task, most notably during motor learning, replicating our prior findings [12]. Neural overlap between the SWM task and visuomotor adaptation for the older adults was limited to parietal cortex, with minimal changes from motor learning to transfer. Combined, these results suggest that age differences in engagement of cognitive strategies have a differential impact on motor learning and transfer. Copyright © 2011 Elsevier B.V. All rights reserved.

Age differences in spatial working memory contributions to visuomotor adaptation and transfer

PubMed Central

Langan, Jeanne; Seidler, Rachael. D.

2011-01-01

Throughout our life span we encounter challenges that require us to adapt to the demands of our changing environment; this entails learning new skills. Two primary components of motor skill learning are motor acquisition, the initial process of learning the skill, and motor transfer, when learning a new skill is benefitted by the overlap with a previously learned one. Older adults typically exhibit declines in motor acquisition compared to young adults, but remarkably, do not demonstrate deficits in motor transfer (Seidler, 2007). Our recent work demonstrates that a failure to engage spatial working memory (SWM) is associated with skill learning deficits in older adults (Anguera et al., 2011). Here, we investigate the role that SWM plays in both motor learning and transfer in young and older adults. Both age groups exhibited performance savings, or positive transfer, at transfer of learning for some performance variables. Measures of spatial working memory performance and reaction time correlated with both motor learning and transfer for young adults. Young adults recruited overlapping brain regions in prefrontal, premotor, parietal and occipital cortex for performance of a SWM and a visuomotor adaptation task, most notably during motor learning, replicating our prior findings (Anguera et al., 2010). Neural overlap between the SWM task and visuomotor adaptation for the older adults was limited to parietal cortex, with minimal changes from motor learning to transfer. Combined, these results suggest that age differences in engagement of cognitive strategies have a differential impact on motor learning and transfer. PMID:21784106

Attenuation of cadmium-induced decline in spatial, habituation and recognition memory by long-term administration of almond and walnut supplementation: Role of cholinergic function.

PubMed

Batool, Zehra; Agha, Faiza; Ahmad, Saara; Liaquat, Laraib; Tabassum, Saiqa; Khaliq, Saima; Anis, Lubna; Sajid, Irfan; Emad, Shaista; Perveen, Tahira; Haider, Saida

2017-01-01

Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity. Cadmium was administered at the dose of 50 mg/kg/week. Whereas, almond and walnut was supplemented at the dose of 400 mg/kg/day along with cadmium administration to separate set of rats. At the end of experiment, memory function was assessed by Morris water maze, open field test and novel object recognition test. Results of the present study showed that cadmium administration significantly reduced memory retention. Reduced acetylcholine levels and elevated acetyl cholinesterase activity were also observed in frontal cortex and hippocampus of cadmium treated rats. Malondialdehyde levels were also significantly increased following the administration of cadmium. Daily supplementation of almond and walnut for 28 days significantly attenuated cadmium-induced memory impairment in rats. Results of the present study are discussed in term of cholinergic activity in cadmium-induced memory loss and its attenuation by nuts supplementation in rats.

Exendin-4, a glucagon-like peptide 1 receptor agonist, protects against amyloid-β peptide-induced impairment of spatial learning and memory in rats.

PubMed

Jia, Xiao-Tao; Ye-Tian; Yuan-Li; Zhang, Ge-Juan; Liu, Zhi-Qin; Di, Zheng-Li; Ying, Xiao-Ping; Fang, Yan; Song, Er-Fei; Qi, Jin-Shun; Pan, Yan-Fang

2016-05-15

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share specific molecular mechanisms, and agents with proven efficacy in one may be useful against the other. The glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 has similar properties to GLP-1 and is currently in clinical use for T2DM treatment. Thus, this study was designed to characterize the effects of exendin-4 on the impairment of learning and memory induced by amyloid protein (Aβ) and its probable molecular underlying mechanisms. The results showed that (1) intracerebroventricular (i.c.v.) injection of Aβ1-42 resulted in a significant decline of spatial learning and memory of rats in water maze tests; (2) pretreatment with exendin-4 effectively and dose-dependently protected against the Aβ1-42-induced impairment of spatial learning and memory; (3) exendin-4 treatment significantly decreased the expression of Bax and cleaved caspase-3 and increased the expression of Bcl2 in Aβ1-42-induced Alzheimer's rats. The vision and swimming speed of the rats among all groups in the visible platform tests did not show any difference. These findings indicate that systemic pretreatment with exendin-4 can effectively prevent the behavioral impairment induced by neurotoxic Aβ1-42, and the underlying protective mechanism of exendin-4 may be involved in the Bcl2, Bax and caspase-3 pathways. Thus, the application of exendin-4 or the activation of its signaling pathways may be a promising strategy to ameliorate the degenerative processes observed in AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Retrospective attention in short-term memory has a lasting effect on long-term memory across age.

PubMed

Strunk, Jonathan; Morgan, Lauren; Reaves, Sarah; Verhaeghen, Paul; Duarte, Audrey

2018-04-13

Declines in both short- and long-term memory are typical of healthy aging. Recent findings suggest that retrodictive attentional cues ("retro-cues") that indicate the location of to-be-probed items in short-term memory (STM) have a lasting impact on long-term memory (LTM) performance in young adults. Whether older adults can also use retro-cues to facilitate both STM and LTM is unknown. Young and older adults performed a visual STM task in which spatially informative retro-cues or non-informative neutral-cues were presented during STM maintenance of real-world objects. We tested participants' memory at both STM and LTM delays for objects that were previously cued with retrodictive or neutral cues during STM order to measure the lasting impact of retrospective attention on LTM. Older adults showed reduced STM and LTM capacity compared to young adults. However, they showed similar magnitude retro-cue memory benefits as young adults at both STM and LTM delays. To the best of our knowledge, this is the first study to investigate whether retro-cues in STM facilitate the encoding of objects into LTM such that they are more likely to be subsequently retrieved by older adults. Our results support the idea that retrospective attention can be an effective means by which older adults can improve their short and long-term memory performance, even in the context of reduced memory capacity.

Working Memory Systems in the Rat.

PubMed

Bratch, Alexander; Kann, Spencer; Cain, Joshua A; Wu, Jie-En; Rivera-Reyes, Nilda; Dalecki, Stefan; Arman, Diana; Dunn, Austin; Cooper, Shiloh; Corbin, Hannah E; Doyle, Amanda R; Pizzo, Matthew J; Smith, Alexandra E; Crystal, Jonathon D

2016-02-08

A fundamental feature of memory in humans is the ability to simultaneously work with multiple types of information using independent memory systems. Working memory is conceptualized as two independent memory systems under executive control [1, 2]. Although there is a long history of using the term "working memory" to describe short-term memory in animals, it is not known whether multiple, independent memory systems exist in nonhumans. Here, we used two established short-term memory approaches to test the hypothesis that spatial and olfactory memory operate as independent working memory resources in the rat. In the olfactory memory task, rats chose a novel odor from a gradually incrementing set of old odors [3]. In the spatial memory task, rats searched for a depleting food source at multiple locations [4]. We presented rats with information to hold in memory in one domain (e.g., olfactory) while adding a memory load in the other domain (e.g., spatial). Control conditions equated the retention interval delay without adding a second memory load. In a further experiment, we used proactive interference [5-7] in the spatial domain to compromise spatial memory and evaluated the impact of adding an olfactory memory load. Olfactory and spatial memory are resistant to interference from the addition of a memory load in the other domain. Our data suggest that olfactory and spatial memory draw on independent working memory systems in the rat. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of the Effect of Moringa peregrina Extract on Learning and Memory: Role of Oxidative Stress.

PubMed

Alzoubi, Karem H; Rawashdeh, Nasab Q; Khabour, Omar F; El-Elimat, Tamam; Albataineh, Hanan; Al-Zghool, Hamzeh M; Alali, Feras Q

2017-12-01

Oxidative stress interferes with the functional roles of the hippocampus and results in cognitive decline. Antioxidant supplementation has a cognitive enhancing activity through protecting hippocampus brain cells from the damaging effects of the reactive oxygen species. The dried methanolic extract of the aboveground parts of Moringa peregrina (Forssk.) Fiori (Moringaceae) was hypothesized to have memory-enhancing activity via its antioxidative properties. HPLC and LC-MS methods were used for qualitative analysis of the marker compounds. Six major compounds of the methanolic extract of M. peregrina were identified, namely, rutin, myricetin, α-amyrin, β-amyrin, lupeol acetate, and β-sitosterol. Male Wistar rats were administered via oral gavage three dose levels (50, 100, and 500 mg/kg) of M. peregrina methanolic extract for 2 months. The radial arm water maze (RAWM) was used to test spatial learning and memory. In addition, ELISA was used to analyze the levels of brain-derived neurotrophic factor (BDNF) and to assess the level of some oxidative stress markers. M. peregrina (150 mg/kg) resulted in short- and long-term memory enhancement (P < 0.05). Moreover, M. peregrina administration elevated BDNF levels in the hippocampus (P < 0.05) and caused favorable changes in oxidative stress biomarkers. In particular, an increase in glutathione (GSH), a decrease in oxidized glutathione (GSSG), and an increase in the antioxidant enzyme glutathione peroxidase (GPx) levels in the hippocampus were elicited after treatment with M. peregrina. Taken together, our data show that oral administration of M. peregrina enhances both short- and long-term memory functions via combating oxidative stress and increasing BDNF levels in the hippocampus. Consuming this safe plant may thus help promote spatial learning and improve memory.

Visuomotor adaptability in older adults with mild cognitive decline.

PubMed

Schaffert, Jeffrey; Lee, Chi-Mei; Neill, Rebecca; Bo, Jin

2017-02-01

The current study examined the augmentation of error feedback on visuomotor adaptability in older adults with varying degrees of cognitive decline (assessed by the Montreal Cognitive Assessment; MoCA). Twenty-three participants performed a center-out computerized visuomotor adaptation task when the visual feedback of their hand movement error was presented in a regular (ratio=1:1) or enhanced (ratio=1:2) error feedback schedule. Results showed that older adults with lower scores on the MoCA had less adaptability than those with higher MoCA scores during the regular feedback schedule. However, participants demonstrated similar adaptability during the enhanced feedback schedule, regardless of their cognitive ability. Furthermore, individuals with lower MoCA scores showed larger after-effects in spatial control during the enhanced schedule compared to the regular schedule, whereas individuals with higher MoCA scores displayed the opposite pattern. Additional neuro-cognitive assessments revealed that spatial working memory and processing speed were positively related to motor adaptability during the regular scheduled but negatively related to adaptability during the enhanced schedule. We argue that individuals with mild cognitive decline employed different adaptation strategies when encountering enhanced visual feedback, suggesting older adults with mild cognitive impairment (MCI) may benefit from enhanced visual error feedback during sensorimotor adaptation. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased PKA signaling disrupts recognition memory and spatial memory: role in Huntington's disease.

PubMed

Giralt, Albert; Saavedra, Ana; Carretón, Olga; Xifró, Xavier; Alberch, Jordi; Pérez-Navarro, Esther

2011-11-01

Huntington's disease (HD) patients and mouse models show learning and memory impairment even before the onset of motor symptoms. However, the molecular events involved in this cognitive decline are still poorly understood. Here, using three different paradigms, the novel object recognition test, the T-maze spontaneous alternation task and the Morris water maze, we detected severe cognitive deficits in the R6/1 mouse model of HD before the onset of motor symptoms. When we examined the putative molecular pathways involved in these alterations, we observed hippocampal cAMP-dependent protein kinase (PKA) hyper-activation in naïve R6/1 mice compared with wild-type (WT) mice, whereas extracellular signal-regulated kinase 1/2 and calcineurin activities were not modified. Increased PKA activity resulted in hyper-phosphorylation of its substrates N-methyl-D-aspartate receptor subunit 1, Ras-guanine nucleotide releasing factor-1 and striatal-enriched protein tyrosine phosphatase, but not cAMP-responsive element binding protein or the microtubule-associated protein tau. In correlation with the over-activation of the PKA pathway, we found a down-regulation of the protein levels of some phosphodiesterase (PDE) 4 family members. Similar molecular changes were found in the hippocampus of R6/2 mice and HD patients. Furthermore, chronic treatment of WT mice with the PDE4 inhibitor rolipram up-regulated PKA activity, and induced learning and memory deficits similar to those seen in R6 mice, but had no effect on R6/1 mice cognitive impairment. Importantly, hippocampal PKA inhibition by infusion of Rp-cAMPS restored long-term memory in R6/2 mice. Thus, our results suggest that occlusion of PKA-dependent processes is one of the molecular mechanisms underlying cognitive decline in R6 animals.

Effects of Ibuprofen on Cognition and NMDA Receptor Subunit Expression Across Aging

PubMed Central

Loza, Alejandra Márquez; Elias, Valerie; Wong, Carmen P.; Ho, Emily; Bermudez, Michelle; Magnusson, Kathy R.

2017-01-01

Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-D-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26 months) were fed ibuprofen (375 ppm) in NIH31 diet or diet alone for 6 weeks prior to testing. Behavioral testing using the Morris water maze showed that older mice performed significantly worse than younger in spatial long-term memory, reversal, and short-term memory tasks. Ibuprofen enhanced overall performance in the short-term memory task, but this appeared to be more related to improved executive function than memory. Ibuprofen induced significant decreases over all ages in the mRNA densities for GluN2B subunit, all GluN1 splice variants, and GluN1-1 splice forms in the frontal cortex and in protein expression of GluN2A, GluN2B and GluN1 C2′ cassettes in the hippocampus. GluN1-3 splice form mRNA and C2′ cassette protein were significantly increased across ages in frontal lobes of ibuprofen-treated mice. Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation. PMID:28057539

Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4.

PubMed

Olofsson, Jonas K; Josefsson, Maria; Ekström, Ingrid; Wilson, Donald; Nyberg, Lars; Nordin, Steven; Nordin Adolfsson, Annelie; Adolfsson, Rolf; Nilsson, Lars-Göran; Larsson, Maria

2016-05-01

The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memory and olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45-90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10-20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by >1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator. Copyright © 2016. Published by Elsevier Ltd.

Cognitive and neuropsychological underpinnings of relational and conjunctive working memory binding across age.

PubMed

van Geldorp, Bonnie; Parra, Mario A; Kessels, Roy P C

2015-01-01

The ability to form associations (i.e., binding) is critical for memory formation. Recent studies suggest that aging specifically affects relational binding (associating separate features) but not conjunctive binding (integrating features within an object). Possibly, this dissociation may be driven by the spatial nature of the studies so far. Alternatively, relational binding may simply require more attentional resources. We assessed relational and conjunctive binding in three age groups and we included an interfering task (i.e., an articulatory suppression task). Binding was examined in a working memory (WM) task using non-spatial features: shape and colour. Thirty-one young adults (mean age = 22.35), 30 middle-aged adults (mean age = 54.80) and 30 older adults (mean age = 70.27) performed the task. Results show an effect of type of binding and an effect of age but no interaction between type of binding and age. The interaction between type of binding and interference was significant. These results indicate that aging affects relational binding and conjunctive binding similarly. However, relational binding is more susceptible to interference than conjunctive binding, which suggests that relational binding may require more attentional resources. We suggest that a general decline in WM resources associated with frontal dysfunction underlies age-related deficits in WM binding.

An evaluation of memory accuracy in food hoarding marsh tits Poecile palustris--how accurate are they compared to humans?

PubMed

Brodin, Anders; Urhan, A Utku

2013-07-01

Laboratory studies of scatter hoarding birds have become a model system for spatial memory studies. Considering that such birds are known to have a good spatial memory, recovery success in lab studies seems low. In parids (titmice and chickadees) typically ranging between 25 and 60% if five seeds are cached in 50-128 available caching sites. Since these birds store many thousands of food items in nature in one autumn one might expect that they should easily retrieve five seeds in a laboratory where they know the environment with its caching sites in detail. We designed a laboratory set up to be as similar as possible with previous studies and trained wild caught marsh tits Poecile palustris to store and retrieve in this set up. Our results agree closely with earlier studies, of the first ten looks around 40% were correct when the birds had stored five seeds in 100 available sites both 5 and 24h after storing. The cumulative success curve suggests high success during the first 15 looks where after it declines. Humans performed much better, in the first five looks most subjects were 100% correct. We discuss possible reasons for why the birds were not doing better. Copyright © 2013 Elsevier B.V. All rights reserved.

Neurocognitive Predictors of Academic Outcomes among Childhood Leukemia Survivors

PubMed Central

(Ki) Moore, Ida M.; Lupo, Philip J.; Insel, Kathleen; Harris, Lynnette L.; Pasvogel, Alice; Koerner, Kari M.; Adkins, Kristin B.; Taylor, Olga A.; Hockenberry, Marilyn J.

2015-01-01

Background Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and survival approaches 90%. ALL survivors are more likely than healthy peers or siblings to experience academic underachievement yet little is known about neurocognitive predictors of academic outcomes. Objective Objectives were to compare neurocognitive abilities to age-adjusted standardized norms; to examine change over time in neurocognitive abilities; and to establish neurocognitive predictors of academic outcomes. Methods Seventy-one children were followed over the course of therapy. Cognitive abilities were assessed during Induction when the child was in remission (Baseline) and annually for 3 years (Year 1, Year 2, Year 3). Reading and mathematics abilities were assessed at Year 3. Results Fine motor dexterity was significantly below age-adjusted norms at all data points, but showed improvement over time. Baseline visual-motor integration was within the normal range but significantly declined by Year 3, and mean scores at Years 2 and 3 were significantly below age-adjusted norms. Verbal short-term memory was significantly below age-adjusted norms at all assessments. Visual-motor integration predicted reading and mathematic abilities. Verbal short-term memory predicted reading abilities, and visual short-term memory predicted mathematic abilities. Conclusions CNS-directed therapy is associated with specific neurocognitive problems. Visual spatial skills, verbal and visual short term memory predict academic outcomes. Implications for practice Early assessment of visual spatial perception and short-term memory can identify children at risk for academic problems. Children who are at risk for academic problems could benefit from a school based Individual Educational Program and/or educational intervention. PMID:26166361

Decomposing the relationship between cognitive functioning and self-referent memory beliefs in older adulthood: What’s memory got to do with it?

PubMed Central

Payne, Brennan R.; Gross, Alden L.; Hill, Patrick L.; Parisi, Jeanine M.; Rebok, George W.; Stine-Morrow, Elizabeth A. L.

2018-01-01

With advancing age, episodic memory performance shows marked declines along with concurrent reports of lower subjective memory beliefs. Given that normative age-related declines in episodic memory co-occur with declines in other cognitive domains, we examined the relationship between memory beliefs and multiple domains of cognitive functioning. Confirmatory bi-factor structural equation models were used to parse the shared and independent variance among factors representing episodic memory, psychomotor speed, and executive reasoning in one large cohort study (Senior Odyssey, N = 462), and replicated using another large cohort of healthy older adults (ACTIVE, N = 2,802). Accounting for a general fluid cognitive functioning factor (comprised of the shared variance among measures of episodic memory, speed, and reasoning) attenuated the relationship between objective memory performance and subjective memory beliefs in both samples. Moreover, the general cognitive functioning factor was the strongest predictor of memory beliefs in both samples. These findings are consistent with the notion that dispositional memory beliefs may reflect perceptions of cognition more broadly. This may be one reason why memory beliefs have broad predictive validity for interventions that target fluid cognitive ability. PMID:27685541

Decomposing the relationship between cognitive functioning and self-referent memory beliefs in older adulthood: what's memory got to do with it?

PubMed

Payne, Brennan R; Gross, Alden L; Hill, Patrick L; Parisi, Jeanine M; Rebok, George W; Stine-Morrow, Elizabeth A L

2017-07-01

With advancing age, episodic memory performance shows marked declines along with concurrent reports of lower subjective memory beliefs. Given that normative age-related declines in episodic memory co-occur with declines in other cognitive domains, we examined the relationship between memory beliefs and multiple domains of cognitive functioning. Confirmatory bi-factor structural equation models were used to parse the shared and independent variance among factors representing episodic memory, psychomotor speed, and executive reasoning in one large cohort study (Senior Odyssey, N = 462), and replicated using another large cohort of healthy older adults (ACTIVE, N = 2802). Accounting for a general fluid cognitive functioning factor (comprised of the shared variance among measures of episodic memory, speed, and reasoning) attenuated the relationship between objective memory performance and subjective memory beliefs in both samples. Moreover, the general cognitive functioning factor was the strongest predictor of memory beliefs in both samples. These findings are consistent with the notion that dispositional memory beliefs may reflect perceptions of cognition more broadly. This may be one reason why memory beliefs have broad predictive validity for interventions that target fluid cognitive ability.

Neurogranin as a predictor of memory and executive function decline in MCI patients.

PubMed

Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan

2018-03-06

To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.

Apolipoprotein E (APOE) ε4 and episodic memory decline in Alzheimer's disease: A review.

PubMed

El Haj, Mohamad; Antoine, Pascal; Amouyel, Philippe; Lambert, Jean-Charles; Pasquier, Florence; Kapogiannis, Dimitrios

2016-05-01

A growing body of research has examined the relationship between episodic memory decline, the cognitive hallmark of Alzheimer's disease (AD), and the presence of Apolipoprotein E ε4 (APOE ε4) allele, a major genetic risk factor for the disease. Our review attempts to summarize and critically evaluate this literature. We performed a systematic search for studies assessing episodic memory in AD patients who were genotyped for APOE ε4 and identified fourteen papers. Although most of these papers reported significant relationships between APOE ε4 and episodic memory decline in AD, some papers did not confirm this relationship. Our review links this controversy to the conflicting literature about the effects of APOE ε4 on general cognitive functioning in AD. We identify several shortcoming and limitations of the research on the relationship between APOE ε4 and episodic memory in AD, such as small sample sizes, non-representative populations, lack of comparison of early-onset vs. late-onset disease, and lack of comparison among different genotypes that include APOE ε4 (i.e., zero, one, or two ε4 alleles). Another major shortcoming of the reviewed literature was the lack of comprehensive evaluation of episodic memory decline, since episodic memory was solely evaluated with regard to encoding and retrieval, omitting evaluation of core episodic features that decline in AD, such as context recall (e.g., how, where, and when an episodic event has occurred) and subjective experience of remembering (e.g., reliving, emotion and feeling during episodic recollection). Future research taking these limitations into consideration could illuminate the nature of the relationship between APOE ε4 and episodic memory decline in AD. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of age on a real-world What-Where-When memory task

PubMed Central

Mazurek, Adèle; Bhoopathy, Raja Meenakshi; Read, Jenny C. A.; Gallagher, Peter; Smulders, Tom V.

2015-01-01

Many cognitive abilities decline with aging, making it difficult to detect pathological changes against a background of natural changes in cognition. Most of the tests to assess cognitive decline are artificial tasks that have little resemblance to the problems faced by people in everyday life. This means both that people may have little practice doing such tasks (potentially contributing to the decline in performance) and that the tasks may not be good predictors of real-world cognitive problems. In this study, we test the performance of young people (18–25 years) and older people (60+-year-olds) on a novel, more ecologically valid test of episodic memory: the real-world What-Where-When (WWW) memory test. We also compare them on a battery of other cognitive tests, including working memory, psychomotor speed, executive function, and episodic memory. Older people show the expected age-related declines on the test battery. In the WWW memory task, older people were more likely to fail to remember any WWW combination than younger people were, although they did not significantly differ in their overall WWW score due to some older people performing as well as or better than most younger people. WWW memory performance was significantly predicted by other measures of episodic memory, such as the single-trial learning and long-term retention in the Rey Auditory Verbal Learning task and Combined Object Location Memory in the Object Relocation task. Self-reported memory complaints also predicted performance on the WWW task. These findings confirm that our real-world WWW memory task is a valid measure of episodic memory, with high ecological validity, which may be useful as a predictor of everyday memory abilities. The task will require a bit more development to improve its sensitivity to cognitive declines in aging and to potentially distinguish between mentally healthy older adults and those with early signs of cognitive pathologies. PMID:26042030

Early-life Infection is a Vulnerability Factor for Aging-Related Glial Alterations and Cognitive Decline

PubMed Central

Bilbo, Staci D.

2010-01-01

There is significant individual variability in cognitive decline during aging, suggesting the existence of “vulnerability factors” for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or E. coli, and then tested for learning & memory at 2 or 16 month of age, using 2 fear conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16 month. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHC II on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity. PMID:20388544

Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline.

PubMed

Bilbo, Staci D

2010-07-01

There is significant individual variability in cognitive decline during aging, suggesting the existence of "vulnerability factors" for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or Escherichia coli, and then tested for learning and memory at 2 or 16months of age, using two fear-conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16months. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHCII on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity.

Effect of retirement on cognitive function: the Whitehall II cohort study.

PubMed

Xue, Baowen; Cadar, Dorina; Fleischmann, Maria; Stansfeld, Stephen; Carr, Ewan; Kivimäki, Mika; McMunn, Anne; Head, Jenny

2017-12-26

According to the 'use it or lose it' hypothesis, a lack of mentally challenging activities might exacerbate the loss of cognitive function. On this basis, retirement has been suggested to increase the risk of cognitive decline, but evidence from studies with long follow-up is lacking. We tested this hypothesis in a cohort of 3433 civil servants who participated in the Whitehall II Study, including repeated measurements of cognitive functioning up to 14 years before and 14 years after retirement. Piecewise models, centred at the year of retirement, were used to compare trajectories of verbal memory, abstract reasoning, phonemic verbal fluency, and semantic verbal fluency before and after retirement. We found that all domains of cognition declined over time. Declines in verbal memory were 38% faster after retirement compared to before, after taking account of age-related decline. In analyses stratified by employment grade, higher employment grade was protective against verbal memory decline while people were still working, but this 'protective effect' was lost when individuals retired, resulting in a similar rate of decline post-retirement across employment grades. We did not find a significant impact of retirement on the other cognitive domains. In conclusion, these findings are consistent with the hypothesis that retirement accelerates the decline in verbal memory function. This study points to the benefits of cognitively stimulating activities associated with employment that could benefit older people's memory.

Cadmium Increases the Sensitivity of Adolescent Female Mice to Nicotine-Related Behavioral Deficits

PubMed Central

Adeniyi, Philip Adeyemi; Olatunji, Babawale Peter; Ishola, Azeez Olakunle; Ajonijebu, Duyilemi Chris; Ogundele, Olalekan Michael

2014-01-01

This study investigates spatial and nonspatial working memory, anxiety related behavior, and motor activities in cadmium and/or nicotine exposed female adolescent mice. P28 female adolescent mice (albino strain) were divided into four groups of five (n = 5) mice each. A set of mice (Nic) received subcutaneous nicotine (2.0 mg/kg) while a separate set (Cd) was treated with 2.0 mg/kg cadmium (subcutaneous). For the combined treatments of cadmium and nicotine, we administered 2.0 mg/kg Nicotine and 2.0 mg/kg of Cd. Subsequently, a separate group of animals (n = 5; control) received normal saline. The total duration of treatment for all groups was 28 days (P28–P56). At P56, the treatment was discontinued, after which the animals were examined in behavioural tests. Nicotine and cadmium increased the metabolism and food intake in the female adolescent mice. This also corresponded to an increase in weight when compared with the control. However, a combined nicotine-cadmium treatment induced a decline in weight of the animals versus the control. Also, nicotine administration increased the motor function, while cadmium and nicotine-cadmium treatment caused a decline in motor activity. Both nicotine and cadmium induced a reduction in memory index; however, nicotine-cadmium treatment induced the most significant decrease in nonspatial working memory. PMID:25477708

Memory function and supportive technology

PubMed Central

Charness, Neil; Best, Ryan; Souders, Dustin

2013-01-01

Episodic and working memory processes show pronounced age-related decline, with other memory processes such as semantic, procedural, and metamemory less affected. Older adults tend to complain the most about prospective and retrospective memory failures. We introduce a framework for deciding how to mitigate memory decline using augmentation and substitution and discuss techniques that change the user, through mnemonics training, and change the tool or environment, by providing environmental support. We provide examples of low-tech and high-tech memory supports and discuss constraints on the utility of high-tech systems including effectiveness of devices, attitudes toward memory aids, and reliability of systems. PMID:24379752

Neuroprotective effects of oleuropein against cognitive dysfunction induced by colchicine in hippocampal CA1 area in rats.

PubMed

Pourkhodadad, Soheila; Alirezaei, Masoud; Moghaddasi, Mehrnoush; Ahmadvand, Hassan; Karami, Manizheh; Delfan, Bahram; Khanipour, Zahra

2016-09-01

Alzheimer's disease is a progressive neurodegenerative disorder with decline in memory. The role of oxidative stress is well known in the pathogenesis of the disease. The purpose of this study was to evaluate pretreatment effects of oleuropein on oxidative status and cognitive dysfunction induced by colchicine in the hippocampal CA1 area. Male Wistar rats were pretreated orally once daily for 10 days with oleuropein at doses of 10, 15 and 20 mg/kg. Thereafter, colchicine (15 μg/rat) was administered into the CA1 area of the hippocampus to induce cognitive dysfunction. The Morris water maze was used to assess learning and memory. Biochemical parameters such as glutathione peroxidase and catalase activities, nitric oxide and malondialdehyde concentrations were measured to evaluate the antioxidant status in the rat hippocampus. Our results indicated that colchicine significantly impaired spatial memory and induced oxidative stress; in contrast, oleuropein pretreatment significantly improved learning and memory retention, and attenuated the oxidative damage. The results clearly indicate that oleuropein has neuroprotective effects against colchicine-induced cognitive dysfunction and oxidative damage in rats.

Sexual Activity and Cognitive Decline in Older Adults.

PubMed

Allen, Mark S

2018-05-16

This prospective study tested whether sexual activity and emotional closeness during partnered sexual activity relate to cognitive decline (episodic memory performance) in older adulthood. In total, 6016 adults aged 50 and over (2672 men, 3344 women; M age = 66.0 ± 8.8 years) completed an episodic memory task and self-report questions related to health, sexual activity, and emotional closeness. Two years later, participants again completed the episodic memory task. After controlling for demographic and health-related lifestyle factors, more frequent sexual activity and greater emotional closeness during partnered sexual activity were associated with better memory performance. The association between sexual activity and memory performance was stronger among older participants in the sample. Memory performance worsened over 2 years, but change in memory performance was unrelated to sexual activity or emotional closeness during partnered sexual activity. These findings build on experimental research that has found sexual activity enhances episodic memory in non-human animals. Further research using longer timeframes and alternative measures of cognitive decline is recommended.

[Cognitive and functional decline in the stage previous to the diagnosis of Alzheimers disease].

PubMed

García-Sánchez, C; Estévez-González, A; Boltes, A; Otermín, P; López-Góngora, M; Gironell, A; Kulisevsky, J

2003-12-01

The decline in the phase prior to diagnosis of Alzheimers disease (AD) is not well known, although this knowledge is necessary to evaluate the efficiency of new drugs that can influence in disease course prior to diagnosis. To contribute to better knowledge of the decline prior to diagnosis, we have investigated the cognitive and functional deterioration for 2-3 years before the probable AD diagnosis was established. We compared results obtained by 17 control subjects and 27 patients at the time of diagnosis of a probable AD with results obtained 2-3 years before (interval of 27.7 4 months). We compared memory functions (logical, recognition, learning and autobiographical memory), naming, visual and visuospatial gnosis, visuoconstructive praxis, verbal fluency and the Mini-Mental State Examination (MMSE), Informant Questionnaire and Blessed's Scale scores. Performance of control subjects did not change. AD patients showed a significant decline in scores, except for verbal fluency. In order of importance, cognitive decline was more marked in scores of learning memory, visuospatial gnosis, autobiographical memory and visuoconstructive praxis. Decline prior to diagnosis of AD is characterized by an important learning memory impairment. Deterioration of visuospatial gnosis and visuoconstructive praxis is greater than deterioration of MMSE and Informant Questionnaire scores.

FDG metabolism associated with tau-amyloid interaction predicts memory decline

PubMed Central

Hanseeuw, Bernard J.; Betensky, Rebecca A.; Schultz, Aaron P.; Papp, Kate V.; Mormino, Elizabeth C.; Sepulcre, Jorge; Bark, John S.; Cosio, Danielle M.; LaPoint, Molly; Chhatwal, Jasmeer P.; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith

2017-01-01

Objective To evaluate in normal older adults and preclinical Alzheimer’s disease (AD) the impact of amyloid and regional tauopathy on cerebral glucose metabolism and subsequent memory decline. Methods We acquired positron emission tomography using F18 Flortaucipir (tau), C11 Pittsburgh Compound B (amyloid) and F18 Fluorodeoxyglucose in 90 clinically normal elderly of the Harvard Aging Brain Study. Results Posterior cingulate metabolism decreased when both amyloid and neocortical tau were high and predicted subsequent memory decline in a larger sample of normal elderly. In contrast, frontal hypometabolism related to the common age-related entorhinal tauopathy, but this dysfunction was independent of amyloid, and did not predict significant memory decline. Neocortical tauopathy was positively associated with metabolism in individuals with sub-threshold amyloid, suggesting that glucose metabolism increases before decreasing in the course of preclinical AD. Interpretation Our study identified a synergistic effect of amyloid and tau deposits and demonstrated for the first time in normal elderly its link to AD-like hypometabolism and to AD-like memory decline. The amyloid effect was seen with tau in neocortex, but not with tau in entorhinal cortex, which is the common site of age-related tauopathy. Entorhinal tau was associated with frontal hypometabolism, but this dysfunction was not associated with memory loss. PMID:28253546

Enhanced Cognition and Hypoglutamatergic Signaling in a Growth Hormone Receptor Knockout Mouse Model of Successful Aging.

PubMed

Hascup, Kevin N; Lynn, Mary K; Fitzgerald, Patrick J; Randall, Shari; Kopchick, John J; Boger, Heather A; Bartke, Andrzej; Hascup, Erin R

2017-03-01

Growth hormone receptor knockout (GHR-KO) mice are long lived with improved health span, making this an excellent model system for understanding biochemical mechanisms important to cognitive reserve. The purpose of the present study was to elucidate differences in cognition and glutamatergic dynamics between aged (20- to 24-month-old) GHR-KO and littermate controls. Glutamate plays a critical role in hippocampal learning and memory and is implicated in several neurodegenerative disorders, including Alzheimer's disease. Spatial learning and memory were assessed using the Morris water maze (MWM), whereas independent dentate gyrus (DG), CA3, and CA1 basal glutamate, release, and uptake measurements were conducted in isoflurane anesthetized mice utilizing an enzyme-based microelectrode array (MEA) coupled with constant potential amperometry. These MEAs have high temporal and low spatial resolution while causing minimal damage to the surrounding parenchyma. Littermate controls performed worse on the memory portion of the MWM behavioral task and had elevated DG, CA3, and CA1 basal glutamate and stimulus-evoked release compared with age-matched GHR-KO mice. CA3 basal glutamate negatively correlated with MWM performance. These results support glutamatergic regulation in learning and memory and may have implications for therapeutic targets to delay the onset of, or reduce cognitive decline, in Alzheimer's disease. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The organisation of spatial and temporal relations in memory.

PubMed

Rondina, Renante; Curtiss, Kaitlin; Meltzer, Jed A; Barense, Morgan D; Ryan, Jennifer D

2017-04-01

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.

Brain volume change and cognitive trajectories in aging.

PubMed

Fletcher, Evan; Gavett, Brandon; Harvey, Danielle; Farias, Sarah Tomaszewski; Olichney, John; Beckett, Laurel; DeCarli, Charles; Mungas, Dan

2018-05-01

Examine how longitudinal cognitive trajectories relate to brain baseline measures and change in lobar volumes in a racially/ethnically and cognitively diverse sample of older adults. Participants were 460 older adults enrolled in a longitudinal aging study. Cognitive outcomes were measures of episodic memory, semantic memory, executive function, and spatial ability derived from the Spanish and English Neuropsychological Assessment Scales (SENAS). Latent variable multilevel modeling of the four cognitive outcomes as parallel longitudinal processes identified intercepts for each outcome and a second order global change factor explaining covariance among the highly correlated slopes. We examined how baseline brain volumes (lobar gray matter, hippocampus, and white matter hyperintensity) and change in brain volumes (lobar gray matter) were associated with cognitive intercepts and global cognitive change. Lobar volumes were dissociated into global and specific components using latent variable methods. Cognitive change was most strongly associated with brain gray matter volume change, with strong independent effects of global gray matter change and specific temporal lobe gray matter change. Baseline white matter hyperintensity and hippocampal volumes had significant incremental effects on cognitive decline beyond gray matter change. Baseline lobar gray matter was related to cognitive decline, but did not contribute beyond gray matter change. Cognitive decline was strongly influenced by gray matter volume change and, especially, temporal lobe change. The strong influence of temporal lobe gray matter change on cognitive decline may reflect involvement of temporal lobe structures that are critical for late life cognitive health but also are vulnerable to diseases of aging. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Repeated application of Modafinil and Levodopa reveals a drug-independent precise timing of spatial working memory modulation.

PubMed

Bezu, M; Shanmugasundaram, B; Lubec, G; Korz, V

2016-10-01

Cognition enhancing drugs often target the dopaminergic system, which is involved in learning and memory, including working memory that in turn involves mainly the prefrontal cortex and the hippocampus. In most animal models for modulations of working memory animals are pre-trained to a certain criterion and treated then acutely to test drugs effects on working memory. Thus, little is known regarding subchronic or chronic application of cognition enhancing drugs and working memory performance. Therefore we trained male rats over six days in a rewarded alternation test in a T-maze. Rats received daily injections of either modafinil or Levodopa (L-Dopa) at a lower and a higher dose 30min before training. Levodopa but not modafinil increased working memory performance during early training significantly at day 3 when compared to vehicle controls. Both drugs induced dose dependent differences in working memory with significantly better performance at low doses compared to high doses for modafinil, in contrast to L-Dopa where high dose treated rats performed better than low dose rats. Strikingly, these effects appeared only at day 3 for both drugs, followed by a decline in behavioral performance. Thus, a critical drug independent time window for dopaminergic effects upon working memory could be revealed. Evaluating the underlying mechanisms contributes to the understanding of temporal effects of dopamine on working memory performance. Copyright © 2016 Elsevier B.V. All rights reserved.

No age deficits in the ability to use attention to improve visual working memory.

PubMed

Souza, Alessandra S

2016-08-01

Maintenance of information in mind to the moment-to-moment cognition is accomplished by working memory (WM). WM capacity is reduced in old age, but the nature of this decline is yet not clear. The current study examined the hypothesis that the decline in visual WM performance with age is related to a reduced ability to use attention to control the contents of WM. Young (M = 26 years) and old (M = 71 years) adults performed a color reproduction task in which the precise color of a set of dots had to be maintained in mind over a brief interval and later reproduced using a continuous color wheel. Attention was manipulated by presenting a spatial cue before the onset of the memory array (a precue) or during the maintenance phase (retro-cue). The cue indicated with 100% certainty the item to be tested at the end of the trial. A precue allows the selective encoding of only the relevant item to WM, whereas a retro-cue allows WM contents to be updated by refreshing the relevant (cued) item and removing nonrelevant (noncued) items. Aging was associated with a lower capacity in the baseline (no-cue) condition. Precues and (to a smaller extent) retro-cues improved WM performance (in terms of probability of recall and memory precision). Critically, the benefits of cueing were of similar magnitude in young and older adults showing that the ability to use attention to selectively encode and update the contents of WM is preserved with aging. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Happiness increases verbal and spatial working memory capacity where sadness does not: Emotion, working memory and executive control.

PubMed

Storbeck, Justin; Maswood, Raeya

2016-08-01

The effects of emotion on working memory and executive control are often studied in isolation. Positive mood enhances verbal and impairs spatial working memory, whereas negative mood enhances spatial and impairs verbal working memory. Moreover, positive mood enhances executive control, whereas negative mood has little influence. We examined how emotion influences verbal and spatial working memory capacity, which requires executive control to coordinate between holding information in working memory and completing a secondary task. We predicted that positive mood would improve both verbal and spatial working memory capacity because of its influence on executive control. Positive, negative and neutral moods were induced followed by completing a verbal (Experiment 1) or spatial (Experiment 2) working memory operation span task to assess working memory capacity. Positive mood enhanced working memory capacity irrespective of the working memory domain, whereas negative mood had no influence on performance. Thus, positive mood was more successful holding information in working memory while processing task-irrelevant information, suggesting that the influence mood has on executive control supersedes the independent effects mood has on domain-specific working memory.

Spatial Working Memory Interferes with Explicit, but Not Probabilistic Cuing of Spatial Attention

ERIC Educational Resources Information Center

Won, Bo-Yeong; Jiang, Yuhong V.

2015-01-01

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…

Differential alteration of hippocampal function and plasticity in females and males of the APPxPS1 mouse model of Alzheimer's disease.

PubMed

Richetin, Kevin; Petsophonsakul, Petnoi; Roybon, Laurent; Guiard, Bruno P; Rampon, Claire

2017-09-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and impaired cognitive functions. The higher incidence of AD among women indicates that sex is one of the main risk factor for developing the disease. Using the transgenic amyloid precursor protein × presenilin 1 (APPxPS1) mouse model of AD, we investigated sex inequality with regards to memory capacities and hippocampal plasticity. We report that spatial memory is strongly affected in APPxPS1 females while remarkably spared in males, at all ages tested. Given the contribution of adult neurogenesis to hippocampal-dependent memory processes, we examined whether impaired neurogenesis could account for age-related decline of memory functions in APPxPS1 mice. We show that not only limited numbers of new neurons are generated in these mice, but also, that new granule cells display reduced capacity for synaptic connectivity, a default that is exacerbated in females. Moreover, high densities of hypertrophic astrocytes are observed in the dentate gyrus of APPxPS1 females specifically. By revealing sex-dependent hippocampal alterations, our data may provide causal explanation to APPxPS1 females' memory deficits. Copyright © 2017 Elsevier Inc. All rights reserved.

Habitual attention in older and young adults.

PubMed

Jiang, Yuhong V; Koutstaal, Wilma; Twedell, Emily L

2016-12-01

Age-related decline is pervasive in tasks that require explicit learning and memory, but such reduced function is not universally observed in tasks involving incidental learning. It is unknown if habitual attention, involving incidental probabilistic learning, is preserved in older adults. Previous research on habitual attention investigated contextual cuing in young and older adults, yet contextual cuing relies not only on spatial attention but also on context processing. Here we isolated habitual attention from context processing in young and older adults. Using a challenging visual search task in which the probability of finding targets was greater in 1 of 4 visual quadrants in all contexts, we examined the acquisition, persistence, and spatial-reference frame of habitual attention. Although older adults showed slower visual search times and steeper search slopes (more time per additional item in the search display), like young adults they rapidly acquired a strong, persistent search habit toward the high-probability quadrant. In addition, habitual attention was strongly viewer-centered in both young and older adults. The demonstration of preserved viewer-centered habitual attention in older adults suggests that it may be used to counter declines in controlled attention. This, in turn, suggests the importance, for older adults, of maintaining habit-related spatial arrangements. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer's Disease.

PubMed

Miranda, Andre M; Herman, Mathieu; Cheng, Rong; Nahmani, Eden; Barrett, Geoffrey; Micevska, Elizabeta; Fontaine, Gaelle; Potier, Marie-Claude; Head, Elizabeth; Schmitt, Frederick A; Lott, Ira T; Jiménez-Velázquez, Ivonne Z; Antonarakis, Stylianos E; Di Paolo, Gilbert; Lee, Joseph H; Hussaini, S Abid; Marquer, Catherine

2018-06-05

The phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer's disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory. We show that increased SYNJ1 levels in autopsy brains from adults with Down syndrome (DS/AD) are inversely correlated with synaptophysin levels, a direct readout of synaptic integrity. We further report age-dependent cognitive decline in a mouse model overexpressing murine Synj1 to the levels observed in human sporadic AD, triggered through hippocampal hyperexcitability and defects in the spatial reproducibility of place fields. Taken together, our findings suggest that SYNJ1 contributes to memory deficits in the aging hippocampus in all forms of AD. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Does widowhood affect memory performance of older persons?

PubMed

Aartsen, Marja J; Van Tilburg, Theo; Smits, Carolien H M; Comijs, Hannie C; Knipscheer, Kees C P M

2005-02-01

The loss of a spouse has been found to have a negative effect on physical and mental health and leads to increased mortality. Whether conjugal bereavement also affects memory functioning has largely been unexamined. The present study investigates the effect of widowhood on memory functioning in older persons. The sample consisted of 474 married women and 690 married men aged 60-85 years in 1992, followed up in 1995 and 1998. During the study 135 (28%) of the women and 69 (10%) of the men lost their spouse. Linear regression analysis was used to examine whether widowed men and women differed from those who had not been widowed in rate of memory change over 6 years. Cross-domain latent-change models were subsequently used to evaluate the extent to which changes in memory are related to changes in other domains of functioning that may be affected by widowhood. Older adults who lost a spouse during follow-up showed a greater decline in memory over 6 years than those who remained married. A higher level of depressive symptoms at baseline was related to lower levels of memory functioning and a greater decline. Memory decline was unrelated to changes in depressive symptoms and physical health. Loss of the spouse is related to a greater decline in memory in older adults. The absence of an association with physical functioning and the weak association with mental functioning suggest that losing a spouse has an independent effect on memory functioning.

Age-related memory decline is associated with vascular and microglial degeneration in aged rats.

PubMed

Zhang, Rong; Kadar, Tamar; Sirimanne, Ernest; MacGibbon, Alastair; Guan, Jian

2012-12-01

The hippocampus processes memory is an early target of aging-related biological and structural lesions, leading to memory decline. With absent neurodegeneration in the hippocampus, which identified in rodent model of normal aging the pathology underlying age-related memory impairment is not complete. The effective glial-vascular networks are the key for maintaining neuronal functions. The changes of glial cells and cerebral capillaries with age may contribute to memory decline. Thus we examined age associated changes in neurons, glial phenotypes and microvasculature in the hippocampus of aged rats with memory decline. Young adult (6 months) and aged (35 months) male rats (Fisher/Norway-Brown) were used. To evaluate memory, four days of acquisition phase of Morris water maze tasks were carried out in both age groups and followed by a probe trial 2 h after the acquisition. The brains were then collected for analysis using immunochemistry. The aged rats showed a delayed latency (p<0.001) and longer swimming path (p<0.001) to locate a hidden platform. They also spent less time in and made delayed and fewer entries into the correct quadrant during the probe trial. Without seen neuronal degeneration, the aged rats with memory impairments have displayed dopamine depletion, profound vascular and microglial degeneration with reduced vascular endothelial growth factor and elevated GFAP expression in the hippocampus. The data indicate the memory decline with age is associated with neuronal dysfunction, possibly due to impaired glial-vascular-neuronal networks, but not neuronal degeneration. Glial and vascular degeneration found in aged rats may represent early event of aging pathology prior to neuronal degeneration. Copyright © 2012 Elsevier B.V. All rights reserved.

H3K9me3 Inhibition Improves Memory, Promotes Spine Formation, and Increases BDNF Levels in the Aged Hippocampus

PubMed Central

Prieto, G. Aleph; Petrosyan, Arpine; Loertscher, Brad M.; Dieskau, André P.; Overman, Larry E.; Cotman, Carl W.

2016-01-01

An increasing number of studies show that an altered epigenetic landscape may cause impairments in regulation of learning and memory-related genes within the aged hippocampus, eventually resulting in cognitive deficits in the aged brain. One such epigenetic repressive mark is trimethylation of H3K9 (H3K9me3), which is typically implicated in gene silencing. Here, we identify, for the first time, an essential role for H3K9me3 and its histone methyl transferase (SUV39H1) in mediating hippocampal memory functions. Pharmacological inhibition of SUV39H1 using a novel and selective inhibitor decreased levels of H3K9me3 in the hippocampus of aged mice, and improved performance in the objection location memory and fear conditioning tasks and in a complex spatial environment learning task. The inhibition of SUV39H1 induced an increase in spine density of thin and stubby but not mushroom spines in the hippocampus of aged animals and increased surface GluR1 levels in hippocampal synaptosomes, a key index of spine plasticity. Furthermore, there were changes at BDNF exon I gene promoter, in concert with overall BDNF levels in the hippocampus of drug-treated animals compared with control animals. Together, these data demonstrate that SUV39H1 inhibition and the concomitant H3K9me3 downregulation mediate gene transcription in the hippocampus and reverse age-dependent deficits in hippocampal memory. SIGNIFICANCE STATEMENT Cognitive decline is a debilitating condition associated with not only neurodegenerative diseases but also aging in general. However, effective treatments have been slow to emerge so far. In this study, we demonstrate that epigenetic regulation of key synaptic proteins may be an underlying, yet reversible, cause of this decline. Our findings suggest that histone 3 trimethylation is a probable target for pharmacological intervention that can counteract cognitive decline in the aging brain. Finally, we provide support to the hypothesis that, by manipulating the enzyme that regulates H3K9me3 (using a newly developed specific inhibitor of SUV39H1), it is possible to alter the chromatin state of subjects and restore memory and synaptic function in the aging brain. PMID:27013689

The (Spatial) Memory Game: Testing the Relationship Between Spatial Language, Object Knowledge, and Spatial Cognition.

PubMed

Gudde, Harmen B; Griffiths, Debra; Coventry, Kenny R

2018-02-19

The memory game paradigm is a behavioral procedure to explore the relationship between language, spatial memory, and object knowledge. Using two different versions of the paradigm, spatial language use and memory for object location are tested under different, experimentally manipulated conditions. This allows us to tease apart proposed models explaining the influence of object knowledge on spatial language (e.g., spatial demonstratives), and spatial memory, as well as understanding the parameters that affect demonstrative choice and spatial memory more broadly. Key to the development of the method was the need to collect data on language use (e.g., spatial demonstratives: "this/that") and spatial memory data under strictly controlled conditions, while retaining a degree of ecological validity. The language version (section 3.1) of the memory game tests how conditions affect language use. Participants refer verbally to objects placed at different locations (e.g., using spatial demonstratives: "this/that red circle"). Different parameters can be experimentally manipulated: the distance from the participant, the position of a conspecific, and for example whether the participant owns, knows, or sees the object while referring to it. The same parameters can be manipulated in the memory version of the memory game (section 3.2). This version tests the effects of the different conditions on object-location memory. Following object placement, participants get 10 seconds to memorize the object's location. After the object and location cues are removed, participants verbally direct the experimenter to move a stick to indicate where the object was. The difference between the memorized and the actual location shows the direction and strength of the memory error, allowing comparisons between the influences of the respective parameters.

Association of subjective memory complaints with subsequent cognitive decline in community-dwelling elderly individuals with baseline cognitive impairment.

PubMed

Schofield, P W; Marder, K; Dooneief, G; Jacobs, D M; Sano, M; Stern, Y

1997-05-01

The validity of subjective memory complaints has been questioned by clinical studies that have shown little relationship between memory complaints and objective memory performance. These studies often have been cross-sectional in design, have excluded individuals with cognitive impairment, or have lacked a comparison group. The authors conducted a study that attempted to avoid these limitations. Memory complaints of 364 nondemented, community-dwelling elderly individuals were recorded as present or absent at the baseline evaluation. After 1 year, 169 subjects were reevaluated. Standardized neurologic and neuropsychological evaluations were used at each assessment to classify subjects as normal or cognitively impaired. At baseline, 31% of the normal subjects and 47% of those with cognitive impairment had memory complaints. Subjects with memory complaints had higher Hamilton depression scale scores than subjects without memory complaints but equivalent scores on a measure of total recall. At follow-up, multivariate analyses showed that subjects with baseline memory complaints had significantly greater decline in memory and cognition than subjects without memory complaints. Secondary analyses showed this effect to be confined to subjects with baseline cognitive impairment. Memory complaints may lack validity in subjects with normal cognition, but in nondemented individuals with cognitive impairment, memory complaints may predict subsequent cognitive decline.

Cognitive Aging Research: What Does It Say about Cognition? Aging?

ERIC Educational Resources Information Center

Glucksberg, Sam

Cognitive aging research needs to clarify whether or not there are functional or ability declines with aging and, if so, to understand and mediate these declines. Recent research which has demonstrated declines in cognitive functioning with age has involved episodic memory and rehearsal-independent forms of such memory. It is not known how much of…

Verbal memory outcome in patients with normal preoperative verbal memory and left mesial temporal sclerosis.

PubMed

LoGalbo, Anthony; Sawrie, Stephen; Roth, David L; Kuzniecky, Ruben; Knowlton, Robert; Faught, Edward; Martin, Roy

2005-05-01

Previous studies have shown that structural integrity (i.e., presence/absence of mesial temporal sclerosis (MTS)) of the left mesial temporal lobe is associated with verbal memory outcome following left anterior temporal lobectomy (ATL). However, the functional integrity of the left temporal lobe, as exemplified by preoperative verbal memory performance, has also been associated with verbal memory outcome following surgery. We investigated the risk of verbal memory loss in patients with known structural abnormality (i.e., left mesial temporal sclerosis by MRI) and normal preoperative verbal memory performance who undergo left ATL. Seventeen patients with left temporal lobe epilepsy, MRI-based exclusive left MTS, and normal preoperative verbal memory were identified. Normal verbal memory was defined as performance on both Acquisition (learning across trials 1-5) and Retrieval (long delayed free recall) portions of the California Verbal Learning Test (CVLT) above a T score of 40 (>16%ile). Postoperative verbal memory outcome was established by incorporating standardized regression-based (SRB) change scores. Postoperative declines across both CVLT Retrieval T scores and Acquisition T scores (average 20% and average 15% declines from baseline scores, respectively) were measured for the group. The average CVLT Retrieval SRB change score was -2.5, and the average CVLT Acquisition SRB change score was -1.0. A larger proportion of patients demonstrated postoperative declines on Retrieval scores than Acquisition scores (64.7% vs 17.6%, respectively). Even in the presence of left MTS, patients exhibiting normal presurgical verbal memory are at risk for verbal memory declines following ATL. These results suggest that the functional integrity of the left mesial temporal lobe may play an important role in the verbal memory outcome in this patient group.

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

PubMed

Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

2016-01-01

Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Fluoride and Arsenic Exposure Impairs Learning and Memory and Decreases mGluR5 Expression in the Hippocampus and Cortex in Rats

PubMed Central

Jiang, Shoufang; Su, Jing; Yao, Sanqiao; Zhang, Yanshu; Cao, Fuyuan; Wang, Fei; Wang, Huihui; Li, Jun; Xi, Shuhua

2014-01-01

Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs) expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L), sodium arsenite (70 mg/L), and a sodium fluoride (120 mg/L) and sodium arsenite (70 mg/L) combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of glutamate level and mGluR5 expression in cortex and hippocampus. PMID:24759735

Spatial memory tasks in rodents: what do they model?

PubMed

Morellini, Fabio

2013-10-01

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.

Stereological Investigation of the Effects of Treadmill Running Exercise on the Hippocampal Neurons in Middle-Aged APP/PS1 Transgenic Mice.

PubMed

Chao, Fenglei; Jiang, Lin; Zhang, Yi; Zhou, Chunni; Zhang, Lei; Tang, Jing; Liang, Xin; Qi, Yingqiang; Zhu, Yanqing; Ma, Jing; Tang, Yong

2018-01-01

The risk of cognitive decline during Alzheimer's disease (AD) can be reduced if physical activity is maintained; however, the specific neural events underlying this beneficial effect are still uncertain. To quantitatively investigate the neural events underlying the effect of running exercise on middle-aged AD subjects, 12-month-old male APP/PS1 mice were randomly assigned to a control group or running group, and age-matched non-transgenic littermates were used as a wild-type group. AD running group mice were subjected to a treadmill running protocol (regular and moderate intensity) for four months. Spatial learning and memory abilities were assessed using the Morris water maze. Hippocampal amyloid plaques were observed using Thioflavin S staining and immunohistochemistry. Hippocampal volume, number of neurons, and number of newborn cells (BrdU+ cells) in the hippocampus were estimated using stereological techniques, and newborn neurons were observed using double-labelling immunofluorescence. Marked neuronal loss in both the CA1 field and dentate gyrus (DG) and deficits in both the neurogenesis and survival of new neurons in the DG of middle-aged APP/PS1 mice were observed. Running exercise could improve the spatial learning and memory abilities, reduce amyloid plaques in the hippocampi, delay neuronal loss, induce neurogenesis, and promote the survival of newborn neurons in the DG of middle-aged APP/PS1 mice. Exercise-induced protection of neurons and adult neurogenesis within the DG might be part of the important structural basis of the improved spatial learning and memory abilities observed in AD mice.

Long term impairment of cognitive functions and alterations of NMDAR subunits after continuous microwave exposure.

PubMed

Wang, Hui; Tan, Shengzhi; Xu, Xinping; Zhao, Li; Zhang, Jing; Yao, Binwei; Gao, Yabing; Zhou, Hongmei; Peng, Ruiyun

2017-11-01

The long term effects of continuous microwave exposure cannot be ignored for the simulation of the real environment and increasing concerns about the negative cognitive effects of microwave exposure. In this study, 220 male Wistar rats were exposed by a 2.856GHz radiation source with the average power density of 0, 2.5, 5 and 10mW/cm 2 for 6min/day, 5days/week and up to 6weeks. The MWM task, the EEG analysis, the hippocampus structure observation and the western blot were applied until the 12months after microwave exposure to detect the spatial learning and memory abilities, the cortical electrical activity, changes of hippocampal structure and the NMDAR subunits expressions. Results found that the rats in the 10mW/cm 2 group showed the decline of spatial learning and memory abilities and EEG disorders (the decrease of EEG frequencies, and increase of EEG amplitudes and delta wave powers). Moreover, changes of basic structure and ultrastructure of hippocampus also found in the 10 and 5mW/cm 2 groups. The decrease of NR 2A, 2B and p-NR2B might contribute to the impairment of cognitive functions. Our findings suggested that the continuous microwave exposure could cause the dose-dependent long term impairment of spatial learning and memory, the abnormalities of EEG and the hippocampal structure injuries. The decrease of NMDAR key subunits and phosphorylation of NR 2B might contribute to the cognitive impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

Personality and Cognitive Decline in Older Adults: Data From a Longitudinal Sample and Meta-Analysis

PubMed Central

Terracciano, Antonio; Stephan, Yannick; Sutin, Angelina R.

2016-01-01

Objectives: Personality traits are associated with risk of dementia; less is known about their association with the trajectory of cognitive functioning. This research examines the association between the 5 major dimensions of personality and cognitive function and decline in older adulthood and includes a meta-analysis of published studies. Method: Personality traits, objective and subjective memory, and cognitive status were collected in a large national sample (N = 13,987) with a 4-year follow-up period. For each trait, the meta-analysis pooled results from up to 5 prospective studies to examine personality and change in global cognition. Results: Higher Neuroticism was associated with worse performance on all cognitive measures and greater decline in memory, whereas higher Conscientiousness and Openness were associated with better memory performance concurrently and less decline over time. All traits were associated with subjective memory. Higher Conscientiousness and lower Extraversion were associated with better cognitive status and less decline. Although modest, these associations were generally larger than that of hypertension, diabetes, history of psychological treatment, obesity, smoking, and physical inactivity. The meta-analysis supported the association between Neuroticism and Conscientiousness and cognitive decline. Discussion: Personality is associated with cognitive decline in older adults, with effects comparable to established clinical and lifestyle risk factors. PMID:25583598

Spatial Memory for Chinese and English.

ERIC Educational Resources Information Center

Tavassoli, Nader T.

2002-01-01

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…

Comparison of semantic and episodic memory BOLD fMRI activation in predicting cognitive decline in older adults.

PubMed

Hantke, Nathan; Nielson, Kristy A; Woodard, John L; Breting, Leslie M Guidotti; Butts, Alissa; Seidenberg, Michael; Carson Smith, J; Durgerian, Sally; Lancaster, Melissa; Matthews, Monica; Sugarman, Michael A; Rao, Stephen M

2013-01-01

Previous studies suggest that task-activated functional magnetic resonance imaging (fMRI) can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively "Stable" or "Declining" based on ≥ 1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with Apolipoprotein E (APOE) ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R(2) = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R(2) = .285; C index = .787), whereas the addition of EM did not (R(2) = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer's disease.

Hippocampal and Cognitive Function, Exercise, and Ovarian Cancer: A Pilot Study

DTIC Science & Technology

2015-08-01

the hippocampus and subsequently offset memory decline. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF... hippocampus and subsequently offset memory decline. 2 KEYWORDS: Physical activity interventions, ovarian cancer treatment, chemotherapy-induced...chemotherapy complaint in a single cancer: problems with memory in patients with ovarian cancer. We focus on this problem for three reasons: 1

Anticholinergic drug use is associated with episodic memory decline in older adults without dementia.

PubMed

Papenberg, Goran; Bäckman, Lars; Fratiglioni, Laura; Laukka, Erika J; Fastbom, Johan; Johnell, Kristina

2017-07-01

Anticholinergic drug use is common in older adults and has been related to increased dementia risk. This suggests that users of these drugs may experience accelerated cognitive decline. So far, however, longitudinal data on this topic are absent and the available evidence is inconclusive with respect to effects on specific cognitive domains due to suboptimal control of confounding variables. We investigated whether anticholinergic medication use is associated with cognitive decline over 6 years in a population-based study of older adults (aged 60-90; n = 1473) without dementia. We found that users (n = 29) declined more on episodic memory over 6 years compared to nonusers (n = 1418). These results were independent of age, sex, education, overall drug intake, physical activity, depression, cardiovascular risk burden, and cardiovascular disease. By contrast, anticholinergic drug use was unrelated to performance in processing speed, semantic memory, short-term memory, verbal fluency, and global cognition (the Mini-Mental-State Examination). Our results suggest that effects of anticholinergics may be particularly detrimental to episodic memory in older adults, which supports the assertion that the cholinergic system plays an important role in episodic memory formation. Copyright © 2017 Elsevier Inc. All rights reserved.

Longitudinal association between hippocampus atrophy and episodic-memory decline.

PubMed

Gorbach, Tetiana; Pudas, Sara; Lundquist, Anders; Orädd, Greger; Josefsson, Maria; Salami, Alireza; de Luna, Xavier; Nyberg, Lars

2017-03-01

There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Motor Skills Enhance Procedural Memory Formation and Protect against Age-Related Decline

PubMed Central

Müller, Nils C. J.; Genzel, Lisa; Konrad, Boris N.; Pawlowski, Marcel; Neville, David; Fernández, Guillén; Steiger, Axel

2016-01-01

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

Hippocampal-prefrontal input supports spatial encoding in working memory.

PubMed

Spellman, Timothy; Rigotti, Mattia; Ahmari, Susanne E; Fusi, Stefano; Gogos, Joseph A; Gordon, Joshua A

2015-06-18

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.

Sex effects on spatial learning but not on spatial memory retrieval in healthy young adults.

PubMed

Piber, Dominique; Nowacki, Jan; Mueller, Sven C; Wingenfeld, Katja; Otte, Christian

2018-01-15

Sex differences have been found in spatial learning and spatial memory, with several studies indicating that males outperform females. We tested in the virtual Morris Water Maze (vMWM) task, whether sex differences in spatial cognitive processes are attributable to differences in spatial learning or spatial memory retrieval in a large student sample. We tested 90 healthy students (45 women and 45 men) with a mean age of 23.5 years (SD=3.5). Spatial learning and spatial memory retrieval were measured by using the vMWM task, during which participants had to search a virtual pool for a hidden platform, facilitated by visual cues surrounding the pool. Several learning trials assessed spatial learning, while a separate probe trial assessed spatial memory retrieval. We found a significant sex effect during spatial learning, with males showing shorter latency and shorter path length, as compared to females (all p<0.001). Yet, there was no significant sex effect in spatial memory retrieval (p=0.615). Furthermore, post-hoc analyses revealed significant sex differences in spatial search strategies (p<0.05), but no difference in the number of platform crossings (p=0.375). Our results indicate that in healthy young adults, males show faster spatial learning in a virtual environment, as compared to females. Interestingly, we found no significant sex differences during spatial memory retrieval. Our study raises the question, whether men and women use different learning strategies, which nevertheless result in equal performances of spatial memory retrieval. Copyright © 2017 Elsevier B.V. All rights reserved.

BDNF and TNF-α polymorphisms in memory.

PubMed

Yogeetha, B S; Haupt, L M; McKenzie, K; Sutherland, H G; Okolicsyani, R K; Lea, R A; Maher, B H; Chan, R C K; Shum, D H K; Griffiths, L R

2013-09-01

Here, we investigate the genetic basis of human memory in healthy individuals and the potential role of two polymorphisms, previously implicated in memory function. We have explored aspects of retrospective and prospective memory including semantic, short term, working and long-term memory in conjunction with brain derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-α). The memory scores for healthy individuals in the population were obtained for each memory type and the population was genotyped via restriction fragment length polymorphism for the BDNF rs6265 (Val66Met) SNP and via pyrosequencing for the TNF-α rs113325588 SNP. Using univariate ANOVA, a significant association of the BDNF polymorphism with visual and spatial memory retention and a significant association of the TNF-α polymorphism was observed with spatial memory retention. In addition, a significant interactive effect between BDNF and TNF-α polymorphisms was observed in spatial memory retention. In practice visual memory involves spatial information and the two memory systems work together, however our data demonstrate that individuals with the Val/Val BDNF genotype have poorer visual memory but higher spatial memory retention, indicating a level of interaction between TNF-α and BDNF in spatial memory retention. This is the first study to use genetic analysis to determine the interaction between BDNF and TNF-α in relation to memory in normal adults and provides important information regarding the effect of genetic determinants and gene interactions on human memory.

Spatial working memory load affects counting but not subitizing in enumeration.

PubMed

Shimomura, Tomonari; Kumada, Takatsune

2011-08-01

The present study investigated whether subitizing reflects capacity limitations associated with two types of working memory tasks. Under a dual-task situation, participants performed an enumeration task in conjunction with either a spatial (Experiment 1) or a nonspatial visual (Experiment 2) working memory task. Experiment 1 showed that spatial working memory load affected the slope of a counting function but did not affect subitizing performance or subitizing range. Experiment 2 showed that nonspatial visual working memory load affected neither enumeration efficiency nor subitizing range. Furthermore, in both spatial and nonspatial memory tasks, neither subitizing efficiency nor subitizing range was affected by amount of imposed memory load. In all the experiments, working memory load failed to influence slope, subitizing range, or overall reaction time. These findings suggest that subitizing is performed without either spatial or nonspatial working memory. A possible mechanism of subitizing with independent capacity of working memory is discussed.

[GLIATILIN CORRECTION OF WORKING AND REFERENCE SPATIAL MEMORY IMPAIRMENT IN AGED RATS].

PubMed

Tyurenkov, I N; Volotova, E V; Kurkin, D V

2015-01-01

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.

A Comparison of Two FMRI Methods for Predicting Verbal Memory Decline After Left Temporal Lobectomy: Language Lateralization vs. Hippocampal Activation Asymmetry

PubMed Central

Binder, Jeffrey R.; Swanson, Sara J.; Sabsevitz, David S.; Hammeke, Thomas A.; Raghavan, Manoj; Mueller, Wade M.

2010-01-01

Purpose Language lateralization measured by preoperative fMRI was shown recently to be predictive of verbal memory outcome in patients undergoing left anterior temporal lobe (L-ATL) resection. The aim of this study was to determine whether language lateralization or hippocampal activation asymmetry is a better predictor of memory outcome in this setting. Methods Thirty L-ATL patients underwent preoperative language fMRI, preoperative hippocampal fMRI using a scene encoding task, and pre- and postoperative neuropsychological testing. A group of 37 right ATL surgery patients who underwent the same testing procedures was included for comparison. Results Verbal memory decline occurred in roughly half of the L-ATL patients. Preoperative language lateralization was correlated with postoperative verbal memory change. Hippocampal activation asymmetry was strongly related to side of seizure focus and to Wada memory asymmetry but was unrelated to verbal memory outcome. Discussion Preoperative hippocampal activation asymmetry elicited by a scene encoding task is not predictive of verbal memory outcome. Risk of verbal memory decline is likely to be related to lateralization of material-specific verbal memory networks, which are more closely correlated with language lateralization than with overall asymmetry of episodic memory processes. PMID:19817807

Fractionating spatial memory with glutamate receptor subunit-knockout mice.

PubMed

Bannerman, David M

2009-12-01

In recent years, the contribution that different glutamate receptor subtypes and subunits make to spatial learning and memory has been studied extensively using genetically modified mice in which key proteins are knocked out. This has revealed dissociations between different aspects of spatial memory that were not previously apparent from lesion studies. For example, studies with GluA1 AMPAR [AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor] subunit-knockout mice have revealed the presence of a GluA1-dependent, non-associative short-term memory mechanism that is important for performance on spatial working memory tasks, and a GluA1-independent, long-term associative memory mechanism which underlies performance on spatial reference memory tasks. Within this framework we have also studied the contributions of different GluN2-containing NMDARs [NMDA (N-methyl-D-aspartate) receptors] to spatial memory. Studies with GluN2 NMDAR mutants have revealed different contributions from GluN2A- and GluN2B-containing NMDARs to spatial learning. Furthermore, comparison of forebrain- and hippocampus-specific GluN2B-knockout mice has demonstrated that both hippocampal and extra-hippocampal NMDARs make important contributions to spatial memory performance.

Slime mold uses an externalized spatial "memory" to navigate in complex environments.

PubMed

Reid, Chris R; Latty, Tanya; Dussutour, Audrey; Beekman, Madeleine

2012-10-23

Spatial memory enhances an organism's navigational ability. Memory typically resides within the brain, but what if an organism has no brain? We show that the brainless slime mold Physarum polycephalum constructs a form of spatial memory by avoiding areas it has previously explored. This mechanism allows the slime mold to solve the U-shaped trap problem--a classic test of autonomous navigational ability commonly used in robotics--requiring the slime mold to reach a chemoattractive goal behind a U-shaped barrier. Drawn into the trap, the organism must rely on other methods than gradient-following to escape and reach the goal. Our data show that spatial memory enhances the organism's ability to navigate in complex environments. We provide a unique demonstration of a spatial memory system in a nonneuronal organism, supporting the theory that an externalized spatial memory may be the functional precursor to the internal memory of higher organisms.

Spatial working memory interferes with explicit, but not probabilistic cuing of spatial attention.

PubMed

Won, Bo-Yeong; Jiang, Yuhong V

2015-05-01

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. (c) 2015 APA, all rights reserved).

Spatial working memory interferes with explicit, but not probabilistic cuing of spatial attention

PubMed Central

Won, Bo-Yeong; Jiang, Yuhong V.

2014-01-01

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 two constructs is limited to some but not all forms of spatial attention. In five 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. PMID:25401460

Longitudinal evaluation of criteria for subjective cognitive decline and preclinical Alzheimer's disease in a memory clinic sample.

PubMed

Eckerström, Marie; Göthlin, Mattias; Rolstad, Sindre; Hessen, Erik; Eckerström, Carl; Nordlund, Arto; Johansson, Boo; Svensson, Johan; Jonsson, Michael; Sacuiu, Simona; Wallin, Anders

2017-01-01

Subjective cognitive decline (SCD) and biomarker-based "at-risk" concepts such as "preclinical" Alzheimer's disease (AD) have been developed to predict AD dementia before objective cognitive impairment is detectable. We longitudinally evaluated cognitive outcome when using these classifications. Memory clinic patients ( n  = 235) were classified as SCD ( n  = 122): subtle cognitive decline ( n  = 36) and mild cognitive impairment ( n  = 77) and subsequently subclassified into SCDplus and National Institute on Aging-Alzheimer's Association (NIA-AA) stages 0 to 3. Mean (standard deviation) follow-up time was 48 (35) months. Proportion declining cognitively and prognostic accuracy for cognitive decline was calculated for all classifications. Among SCDplus patients, 43% to 48% declined cognitively. Among NIA-AA stage 1 to 3 patients, 50% to 100% declined cognitively. The highest positive likelihood ratios (+LRs) for subsequent cognitive decline (+LR 6.3), dementia (+LR 3.4), and AD dementia (+LR 6.5) were found for NIA-AA stage 2. In a memory clinic setting, NIA-AA stage 2 seems to be the most successful classification in predicting objective cognitive decline, dementia, and AD dementia.

[Application of spatial working memory task fMRI in evaluation of primary insomnia patient's cognitive dysfunction].

PubMed

Dou, Shewei; Wang, Enfeng; Zhang, Hongju; Tong, Li; Zhang, Xiaoqi; Shi, Dapeng; Cheng, Jingliang; Li, Yongli

2015-06-02

To explore abnormal brain activation of spatial working memory in primary insomnia and its potential neuromechanism. we recruited 30 cases primary insomnia (PI) patients and 30 cases age, gender matched healthy control (HC) subjects from July 2013 to December 2013, the diagnosis of primary insomnia matched the diagnosis criterion of DSM-IV and Classification and diagnostic criteria of mental disorders in China third edition (CCMD-3). All the subjects attended the tests of PSQI, HAMA, HAMD and index of spatial working memory. And then, we collected the data of routine MRI and spatial working memory task fMRI on 3.0 T MRI scanner. After that, we used SPM8 and REST1.8 to analyze the fMRI data, compared difference of PSQI, HAMA, HAMD, index of spatial working memory and brain activation of spatial working memory between PI group and HC group. There were significant difference between PI group and HC group in PSQI, HAMA, HAMD and index of spatial working memory (P < 0.05). In the spatial working memory related activate brain region, compared with HC group, left temporal lobe, occipital lobe and right frontal lobe activation increased and bilateral parahippocampalis, temporal cortex, frontal cortex and superior parietal lobule activation reduced in PI group. Spatial working memory task fMRI revealed the pathological mechanisms of cognitive dysfunction of clinical spatial working memory and emotional disorder in primary insomnia patients.

TBI-Induced Formation of Toxic Tau and Its Biochemical Similarities to Tau in AD Brains

DTIC Science & Technology

2016-10-01

onto wild-type mice markedly reduces 1) memory including contextual fear memory and spatial memory, and 2) long-term potentiation, a type of...TERMS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s disease 16. SECURITY CLASSIFICATION OF: 17...mechanism leading to TBI and AD. 2 KEYWORDS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s

Six-month atrophy in MTL structures is associated with subsequent memory decline in elderly controls

PubMed Central

Murphy, E.A.; Holland, D.; Donohue, M.; McEvoy, L.K.; Hagler, D.J.; Dale, A.M.; Brewer, J. B.

2010-01-01

Neurodegeneration precedes the onset of dementias such as Alzheimer’s by several years. Recent advances in volumetric imaging allow quantification of subtle neuroanatomical change over time periods as short as six months. This study investigates whether neuroanatomical change in medial temporal lobe subregions is associated with later memory decline in elderly controls. Using high-resolution, T1-weighted magnetic resonance images acquired at baseline and six months follow-up, change in cortical thickness and subcortical volumes was measured in 142 healthy elderly subjects (aged 59 – 90 years) from the ADNI cohort. Regression analysis was used to identify whether change in fourteen subregions, selected a priori, was associated with declining performance on memory tests from baseline to two years follow-up. Percent thickness change in the right fusiform and inferior temporal cortices and expansion of the right inferior lateral ventricle were found to be significant predictors of subsequent decline on memory-specific neuropsychological measures. These results demonstrate that six-month regional neurodegeneration can be quantified in the healthy elderly and might help identify those at risk for subsequent cognitive decline. PMID:20633660

Impaired fasting blood glucose is associated to cognitive impairment and cerebral atrophy in middle-aged non-human primates

PubMed Central

Djelti, Fathia; Dhenain, Marc; Terrien, Jérémy; Picq, Jean-Luc; Hardy, Isabelle; Champeval, Delphine; Perret, Martine; Schenker, Esther; Epelbaum, Jacques; Aujard, Fabienne

2017-01-01

Age-associated cognitive impairment is a major health and social issue because of increasing aged population. Cognitive decline is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. In middle-aged healthy humans, fasting blood glucose levels in the upper normal range are associated with memory impairment and cerebral atrophy. Due to a close evolutional similarity to Man, non-human primates may be useful to investigate the relationships between glucose homeostasis, cognitive deficits and structural brain alterations. In the grey mouse lemur, Microcebus murinus, spatial memory deficits have been associated with age and cerebral atrophy but the origin of these alterations have not been clearly identified. Herein, we showed that, on 28 female grey mouse lemurs (age range 2.4-6.1 years-old), age correlated with impaired fasting blood glucose (rs=0.37) but not with impaired glucose tolerance or insulin resistance. In middle-aged animals (4.1-6.1 years-old), fasting blood glucose was inversely and closely linked with spatial memory performance (rs=0.56) and hippocampus (rs=−0.62) or septum (rs=−0.55) volumes. These findings corroborate observations in humans and further support the grey mouse lemur as a natural model to unravel mechanisms which link impaired glucose homeostasis, brain atrophy and cognitive processes. PMID:28039490

Impaired fasting blood glucose is associated to cognitive impairment and cerebral atrophy in middle-aged non-human primates.

PubMed

Djelti, Fathia; Dhenain, Marc; Terrien, Jérémy; Picq, Jean-Luc; Hardy, Isabelle; Champeval, Delphine; Perret, Martine; Schenker, Esther; Epelbaum, Jacques; Aujard, Fabienne

2016-12-28

Age-associated cognitive impairment is a major health and social issue because of increasing aged population. Cognitive decline is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. In middle-aged healthy humans, fasting blood glucose levels in the upper normal range are associated with memory impairment and cerebral atrophy. Due to a close evolutional similarity to Man, non-human primates may be useful to investigate the relationships between glucose homeostasis, cognitive deficits and structural brain alterations. In the grey mouse lemur, Microcebus murinus , spatial memory deficits have been associated with age and cerebral atrophy but the origin of these alterations have not been clearly identified. Herein, we showed that, on 28 female grey mouse lemurs (age range 2.4-6.1 years-old), age correlated with impaired fasting blood glucose (r s =0.37) but not with impaired glucose tolerance or insulin resistance. In middle-aged animals (4.1-6.1 years-old), fasting blood glucose was inversely and closely linked with spatial memory performance (r s =0.56) and hippocampus (r s =-0.62) or septum (r s =-0.55) volumes. These findings corroborate observations in humans and further support the grey mouse lemur as a natural model to unravel mechanisms which link impaired glucose homeostasis, brain atrophy and cognitive processes.

Relationship between intraoperative regional cerebral oxygen saturation trends and cognitive decline after total knee replacement: a post-hoc analysis

PubMed Central

2014-01-01

Background Bilateral regional brain oxygen saturation (rSO2) trends, reflecting intraoperative brain oxygen imbalance, could warn of brain dysfunction. Various types of cognitive impairment, such as memory decline, alterations in executive function or subjective complaints, have been described three months after surgery. Our aim was to explore the potential utility of rSO2 values as a warning sign for the development of different types of decline in postoperative psychological function. Methods Observational post-hoc analysis of data for the patient sample (n = 125) of a previously conducted clinical trial in patients over the age of 65 years undergoing total knee replacement under spinal anesthesia. Demographic, hemodynamic and bilateral rSO2 intraoperative values were recorded. An absolute rSO2 value of <50% or a reduction of >20% or >25% below baseline were chosen as relevant cutoffs. Composite function test scores were created from baseline to three months for each patient and adjusted for the mean (SD) score changes for a control group (n = 55). Tests were used to assess visual-motor coordination and executive function (VM-EF) (Wechsler Digit Symbol-Coding and Visual Reproduction, Trail Making Test) and memory (Auditory Verbal Learning, Wechsler Memory Scale); scales were used to assess psychological symptoms. Results We observed no differences in baseline rSO2 values; rSO2 decreased significantly in all patients during surgery (P < 0.0001). Seventy-five patients (60%) had no sign of cognitive decline or psychological symptoms. Twenty-one patients (16.8%) had memory decline, 3 (2.4%) had VM-EF decline, and 33 (26.4%) had psychological symptoms. Left and right rSO2 values were asymmetric in patients who had memory decline (mean [SD] left-right ratio of 95.03 [8.51] vs 101.29 [6.7] for patients with no changes, P = 0.0012). The mean right-left difference in rSO2 was also significant in these patients (-2.87% [4.73%], lower on the right, P = 0.0034). Conclusions Detection of a trend to asymmetry in rSO2 values can warn of possible postoperative onset of memory decline. Psychological symptoms and memory decline were common three months after knee replacement in our patients over the age of 65 years. PMID:25061427

Relationship between intraoperative regional cerebral oxygen saturation trends and cognitive decline after total knee replacement: a post-hoc analysis.

PubMed

Salazar, Fátima; Doñate, Marta; Boget, Teresa; Bogdanovich, Ana; Basora, Misericordia; Torres, Ferran; Gracia, Isabel; Fàbregas, Neus

2014-01-01

Bilateral regional brain oxygen saturation (rSO2) trends, reflecting intraoperative brain oxygen imbalance, could warn of brain dysfunction. Various types of cognitive impairment, such as memory decline, alterations in executive function or subjective complaints, have been described three months after surgery. Our aim was to explore the potential utility of rSO2 values as a warning sign for the development of different types of decline in postoperative psychological function. Observational post-hoc analysis of data for the patient sample (n = 125) of a previously conducted clinical trial in patients over the age of 65 years undergoing total knee replacement under spinal anesthesia. Demographic, hemodynamic and bilateral rSO2 intraoperative values were recorded. An absolute rSO2 value of <50% or a reduction of >20% or >25% below baseline were chosen as relevant cutoffs. Composite function test scores were created from baseline to three months for each patient and adjusted for the mean (SD) score changes for a control group (n = 55). Tests were used to assess visual-motor coordination and executive function (VM-EF) (Wechsler Digit Symbol-Coding and Visual Reproduction, Trail Making Test) and memory (Auditory Verbal Learning, Wechsler Memory Scale); scales were used to assess psychological symptoms. We observed no differences in baseline rSO2 values; rSO2 decreased significantly in all patients during surgery (P < 0.0001). Seventy-five patients (60%) had no sign of cognitive decline or psychological symptoms. Twenty-one patients (16.8%) had memory decline, 3 (2.4%) had VM-EF decline, and 33 (26.4%) had psychological symptoms. Left and right rSO2 values were asymmetric in patients who had memory decline (mean [SD] left-right ratio of 95.03 [8.51] vs 101.29 [6.7] for patients with no changes, P = 0.0012). The mean right-left difference in rSO2 was also significant in these patients (-2.87% [4.73%], lower on the right, P = 0.0034). Detection of a trend to asymmetry in rSO2 values can warn of possible postoperative onset of memory decline. Psychological symptoms and memory decline were common three months after knee replacement in our patients over the age of 65 years.

Distinct roles of hippocampus and medial prefrontal cortex in spatial and nonspatial memory.

PubMed

Sapiurka, Maya; Squire, Larry R; Clark, Robert E

2016-12-01

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. © 2016 Wiley Periodicals, Inc.

Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease

PubMed Central

Wang, Fen; Gordon, Brian A.; Ryman, Davis C.; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M.; Cairns, Nigel J.; Marcus, Daniel S.; McDade, Eric; Ringman, John M.; Graff-Radford, Neill R.; Ghetti, Bernardino; Farlow, Martin R.; Sperling, Reisa; Salloway, Steve; Schofield, Peter R.; Masters, Colin L.; Martins, Ralph N.; Rossor, Martin N.; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A.S.; Morris, John C.; Bateman, Randall J.

2015-01-01

Objective: To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Methods: Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89–4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. Results: In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Conclusions: Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. PMID:26245925

Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease.

PubMed

Wang, Fen; Gordon, Brian A; Ryman, Davis C; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M; Cairns, Nigel J; Marcus, Daniel S; McDade, Eric; Ringman, John M; Graff-Radford, Neill R; Ghetti, Bernardino; Farlow, Martin R; Sperling, Reisa; Salloway, Steve; Schofield, Peter R; Masters, Colin L; Martins, Ralph N; Rossor, Martin N; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A S; Morris, John C; Benzinger, Tammie L S; Bateman, Randall J

2015-09-01

To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. © 2015 American Academy of Neurology.

Verbal Memory Declines More Rapidly with Age in HIV Infected versus Uninfected Adults

PubMed Central

Seider, Talia R.; Luo, Xi; Gongvatana, Assawin; Devlin, Kathryn N.; de la Monte, Suzanne M.; Chasman, Jesse D.; Yan, Peisi; Tashima, Karen T.; Navia, Bradford; Cohen, Ronald A.

2015-01-01

Objectives In the current era of effective antiretroviral treatment, the number of older adults living with HIV is rapidly increasing. This study investigated the combined influence of age and HIV infection on longitudinal changes in verbal and visuospatial learning and memory. Methods In this longitudinal, case-control design, 54 HIV seropositive and 30 seronegative individuals aged 40–74 received neurocognitive assessments at baseline visits and again one year later. Assessment included tests of verbal and visuospatial learning and memory. Linear regression was used to predict baseline performance and longitudinal change on each test using HIV serostatus, age, and their interaction as predictors. MANOVA was used to assess the effects of these predictors on overall baseline performance and overall longitudinal change. Results The interaction of HIV and age significantly predicted longitudinal change in verbal memory performance, as did HIV status, indicating that although the seropositive group declined more than the seronegative group overall, the rate of decline depended on age such that greater age was associated with a greater decline in this group. The regression models for visuospatial learning and memory were significant at baseline, but did not predict change over time. HIV status significantly predicted overall baseline performance and overall longitudinal change. Conclusions This is the first longitudinal study focused on the effects of age and HIV on memory. Findings suggest that age and HIV interact to produce larger declines in verbal memory over time. Further research is needed to gain a greater understanding of the effects of HIV on the aging brain. PMID:24645772

Mineralocorticoid receptor stimulation effects on spatial memory in healthy young adults: A study using the virtual Morris Water Maze task.

PubMed

Piber, Dominique; Schultebraucks, Katharina; Mueller, Sven C; Deuter, Christian Eric; Wingenfeld, Katja; Otte, Christian

2016-12-01

Stress hormones such as cortisol are known to influence a wide range of cognitive functions, including hippocampal based spatial memory. In the brain, cortisol acts via two different receptors: the glucocorticoid (GR) and the mineralocorticoid receptor (MR). As the MR has a high density in the hippocampus, we examined the effects of pharmacological MR stimulation on spatial memory. Eighty healthy participants (40 women, 40 men, mean age=23.9years±SD=3.3) completed the virtual Morris Water Maze (vMWM) task to test spatial encoding and spatial memory retrieval after receiving 0.4mg fludrocortisone, a MR agonist, or placebo. There was no effect of MR stimulation on spatial encoding during the vMWM task. However, participants who received fludrocortisone exhibited improved spatial memory retrieval performance. There was neither a main effect of sex nor a sex-by-treatment interaction. In young healthy participants, MR stimulation improved hippocampal based spatial memory retrieval in a virtual Morris Water Maze task. Our study not only confirms the importance of MR function in spatial memory, but suggests beneficial effects of acute MR stimulation on spatial memory retrieval in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Fractionation of visuo-spatial memory processes in bipolar depression: a cognitive scaffolding account.

PubMed

Gallagher, P; Gray, J M; Kessels, R P C

2015-02-01

Previous studies of neurocognitive performance in bipolar disorder (BD) have demonstrated impairments in visuo-spatial memory. The aim of the present study was to use an object-location memory (OLM) paradigm to assess specific, dissociable processes in visuo-spatial memory and examine their relationship with broader neurocognitive performance. Fifty participants (25 patients with BD in a current depressive episode and 25 matched healthy controls) completed the OLM paradigm which assessed three different aspects of visuo-spatial memory: positional memory, object-location binding, and a combined process. Secondary neurocognitive measures of visuo-spatial memory, verbal memory, attention and executive function were also administered. BD patients were significantly impaired on all three OLM processes, with the largest effect in exact positional memory (d = 1.18, p < 0.0001). General deficits were also found across the secondary neurocognitive measures. Using hierarchical regression, verbal learning was found to explain significant variance on the OLM measures where object-identity was present (the object-location binding and combined processes) and accounted for the group difference. The group difference in precise positional memory remained intact. This study demonstrates that patients with bipolar depression manifest deficits in visuo-spatial memory, with substantial impairment in fine-grain, positional memory. The differential profile of processes underpinning the visuo-spatial memory impairment suggests a form of 'cognitive scaffolding', whereby performance on some measures can be supported by verbal memory. These results have important implications for our understanding of the functional cognitive architecture of mood disorder.

Verbal memory decline from hippocampal depth electrodes in temporal lobe surgery for epilepsy.

PubMed

Ljung, Hanna; Nordlund, Arto; Strandberg, Maria; Bengzon, Johan; Källén, Kristina

2017-12-01

To explore whether patients with refractory mesial temporal lobe epilepsy risk aggravated verbal memory loss from intracranial electroencephalography (EEG) recording with longitudinal hippocampal electrodes in the language-dominant hemisphere. A long-term neuropsychological follow-up (mean 61.5 months, range 22-111 months) was performed in 40 patients after ictal registration with left hippocampal depth electrodes (study group, n = 16) or no invasive EEG, only extracranial registration (reference group, n = 24). The groups were equal with respect to education, age at seizure onset, epilepsy duration, and prevalence of pharmacoresistant temporal lobe epilepsy (TLE; 75%) versus seizure freedom (25%). Retrospective neuropsychological data from preoperative surgical workup (T1) and prospective follow-up neuropsychological data (T2) were compared. A ≥1 SD intrapatient decline was considered as clinically relevant deterioration of verbal memory. Significant decline in verbal memory was seen in 56% of the patients in the study group compared to 21% in the reference group. At T1, there were no statistical between-group differences in memory performance. At T2, between-group comparison showed significantly greater verbal memory decline for the study group (Claeson Dahl Learning and Retention Test, Verbal Learning: p = 0.05; Rey Auditory Verbal Learning Test, Total Learning: p = 0.04; Claeson Dahl Learning and Retention Test, Verbal Retention: p = 0.04). An odds ratio (OR) of 7.1 (90% confidence interval [CI] 1.3-37.7) for verbal memory decline was seen if right temporal lobe resection (R TLR) had been performed between T1 and T2. The difference between groups remained unchanged when patients who had undergone R TLR were excluded from the analysis, with a remaining aggravated significant decline in verbal memory performance for the study group compared to the reference group. Our results suggest a risk of verbal memory deterioration after the use of depth electrodes along the longitudinal axis of the hippocampus. Until this issue is further investigated, caution regarding depth electrodes in the language-dominant hemisphere hippocampus seems advisable. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Improvement of Allocentric Spatial Memory Resolution in Children from 2 to 4 Years of Age

ERIC Educational Resources Information Center

Lambert, Farfalla Ribordy; Lavenex, Pierre; Lavenex, Pamela Banta

2015-01-01

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…

Visual and Spatial Working Memory Are Not that Dissociated after All: A Time-Based Resource-Sharing Account

ERIC Educational Resources Information Center

Vergauwe, Evie; Barrouillet, Pierre; Camos, Valerie

2009-01-01

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…

Spatial memory enhances the evacuation efficiency of virtual pedestrians under poor visibility condition

NASA Astrophysics Data System (ADS)

Ma, Yi; Lee, Eric Wai Ming; Shi, Meng; Kwok Kit Yuen, Richard

2018-03-01

Spatial memory is a critical navigation support tool for disoriented evacuees during evacuation under adverse environmental conditions such as dark or smoky conditions. Owing to the complexity of memory, it is challenging to understand the effect of spatial memory on pedestrian evacuation quantitatively. In this study, we propose a simple method to quantitatively represent the evacueeʼs spatial memory about the emergency exit, model the evacuation of pedestrians under the guidance of the spatial memory, and investigate the effect of the evacueeʼs spatial memory on the evacuation from theoretical and physical perspectives. The result shows that (i) a good memory can significantly assist the evacuation of pedestrians under poor visibility conditions, and the evacuation can always succeed when the degree of the memory exceeds a threshold (\\varphi > 0.5); (ii) the effect of memory is superior to that of “follow-the-crowd” under the same environmental conditions; (iii) in the case of multiple exits, the difference in the degree of the memory between evacuees has a significant effect (the greater the difference, the faster the evacuation) for the evacuation under poor visibility conditions. Our study provides a new quantitative insight into the effect of spatial memory on crowd evacuation under poor visibility conditions. Project supported by the Research Grants Council of the Hong Kong Special Administrative Region, China (Grant No. 11203615).

False memory for context and true memory for context similarly activate the parahippocampal cortex.

PubMed

Karanian, Jessica M; Slotnick, Scott D

2017-06-01

The role of the parahippocampal cortex is currently a topic of debate. One view posits that the parahippocampal cortex specifically processes spatial layouts and sensory details (i.e., the visual-spatial processing view). In contrast, the other view posits that the parahippocampal cortex more generally processes spatial and non-spatial contexts (i.e., the general contextual processing view). A large number of studies have found that true memories activate the parahippocampal cortex to a greater degree than false memories, which would appear to support the visual-spatial processing view as true memories are typically associated with greater visual-spatial detail than false memories. However, in previous studies, contextual details were also greater for true memories than false memories. Thus, such differential activity in the parahippocampal cortex may have reflected differences in contextual processing, which would challenge the visual-spatial processing view. In the present functional magnetic resonance imaging (fMRI) study, we employed a source memory paradigm to investigate the functional role of the parahippocampal cortex during true memory and false memory for contextual information to distinguish between the visual-spatial processing view and the general contextual processing view. During encoding, abstract shapes were presented to the left or right of fixation. During retrieval, old shapes were presented at fixation and participants indicated whether each shape was previously on the "left" or "right" followed by an "unsure", "sure", or "very sure" confidence rating. The conjunction of confident true memories for context and confident false memories for context produced activity in the parahippocampal cortex, which indicates that this region is associated with contextual processing. Furthermore, the direct contrast of true memory and false memory produced activity in the visual cortex but did not produce activity in the parahippocampal cortex. The present evidence suggests that the parahippocampal cortex is associated with general contextual processing rather than only being associated with visual-spatial processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility

PubMed Central

Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan

2011-01-01

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement. PMID:21521768

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility.

PubMed

Matzel, Louis D; Light, Kenneth R; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C; Kolata, Stefan

2011-01-01

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement.

Intra-hippocampal D-cycloserine rescues decreased social memory, spatial learning reversal, and synaptophysin levels in aged rats.

PubMed

Portero-Tresserra, Marta; Martí-Nicolovius, Margarita; Tarrés-Gatius, Mireia; Candalija, Ana; Guillazo-Blanch, Gemma; Vale-Martínez, Anna

2018-05-01

Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associated to neurodegenerative disorders and cognitive deficits observed in normal aging. The aim of the present study was to explore whether DCS would reverse age-dependent memory deficits and decreases in NMDA receptor subunits (GluN1, GluN2A, and GluN2B) and the presynaptic protein synaptophysin in Wistar rats. We investigated the effects of pre-training infusions of DCS (10 μg/hemisphere) in the ventral hippocampus on two hippocampal-dependent learning tasks, the social transmission of food preference (STFP), and the Morris water maze (MWM). The results revealed that infusions of DCS administered before the acquisition sessions rescued deficits in the STFP retention and MWM reversal learning in old rats. DCS also significantly increased the hippocampal levels of synaptophysin in old rats, which correlated with STFP and MWM performance in all tests. Moreover, although the levels of the GluN1 subunit correlated with the MWM acquisition and reversal, DCS did not enhance the expression of such synaptic protein. The present behavioral results support the role of DCS as a cognitive enhancer and suggest that enhancing the function of NMDARs and synaptic plasticity in the hippocampus may be related to improvement in social memory and spatial learning reversal in aged animals.

Biomarker progressions explain higher variability in stage-specific cognitive decline than baseline values in Alzheimer disease.

PubMed

Dodge, Hiroko H; Zhu, Jian; Harvey, Danielle; Saito, Naomi; Silbert, Lisa C; Kaye, Jeffrey A; Koeppe, Robert A; Albin, Roger L

2014-11-01

It is unknown which commonly used Alzheimer disease (AD) biomarker values-baseline or progression-best predict longitudinal cognitive decline. 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients. For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Long-term memory of hierarchical relationships in free-living greylag geese.

PubMed

Weiss, Brigitte M; Scheiber, Isabella B R

2013-01-01

Animals may memorise spatial and social information for many months and even years. Here, we investigated long-term memory of hierarchically ordered relationships, where the position of a reward depended on the relationship of a stimulus relative to other stimuli in the hierarchy. Seventeen greylag geese (Anser anser) had been trained on discriminations between successive pairs of five or seven implicitly ordered colours, where the higher ranking colour in each pair was rewarded. Geese were re-tested on the task 2, 6 and 12 months after learning the dyadic colour relationships. They chose the correct colour above chance at all three points in time, whereby performance was better in colour pairs at the beginning or end of the colour series. Nonetheless, they also performed above chance on internal colour pairs, which is indicative of long-term memory for quantitative differences in associative strength and/or for relational information. There were no indications for a decline in performance over time, indicating that geese may remember dyadic relationships for at least 6 months and probably well over 1 year. Furthermore, performance in the memory task was unrelated to the individuals' sex and their performance while initially learning the dyadic colour relationships. We discuss possible functions of this long-term memory in the social domain.

Caffeine suppresses exercise-enhanced long-term and location memory in middle-aged rats: Involvement of hippocampal Akt and CREB signaling.

PubMed

Cechella, José L; Leite, Marlon R; da Rocha, Juliana T; Dobrachinski, Fernando; Gai, Bibiana M; Soares, Félix A A; Bresciani, Guilherme; Royes, Luiz F F; Zeni, Gilson

2014-11-05

The cognitive function decline is closely related with brain changes generated by age. The ability of caffeine and exercise to prevent memory impairment has been reported in animal models and humans. The purpose of the present study was to investigate whether swimming exercise and caffeine administration enhance memory in middle-aged Wistar rats. Male Wistar rats (18months) received caffeine at a dose of 30mg/kg, 5days per week by a period of 4weeks. Animals were subjected to swimming training with a workload (3% of body weight, 20min per day for 4weeks). After 4weeks, the object recognition test (ORT) and the object location test (OLT) were performed. The results of this study demonstrated that caffeine suppressed exercise-enhanced long-term (ORT) and spatial (OLT) memory in middle-aged and this effect may be related to a decrease in hippocampal p-CREB signaling. This study also provided evidence that the effects of this protocol on memory were not accompanied by alterations in the levels of activated Akt. The [(3)H] glutamate uptake was reduced in hippocampus of rats administered with caffeine and submitted to swimming protocol. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Memory functions in chronic pain: examining contributions of attention and age to test performance.

PubMed

Oosterman, Joukje M; Derksen, Laura C; van Wijck, Albert J M; Veldhuijzen, Dieuwke S; Kessels, Roy P C

2011-01-01

Previous studies have revealed that memory performance is diminished in chronic pain patients. Few studies, however, have assessed multiple components of memory in a single sample. It is currently also unknown whether attentional problems, which are commonly observed in chronic pain, mediate the decline in memory. Finally, previous studies have focused on middle-aged adults, and a possible detrimental effect of aging on memory performance in chronic pain patients has been commonly disregarded. This study, therefore, aimed at describing the pattern of semantic, working, and visual and verbal episodic memory performance in participants with chronic pain, while testing for possible contributions of attention and age to task performance. Thirty-four participants with chronic pain and 32 pain-free participants completed tests of episodic, semantic, and working memory to assess memory performance and a test of attention. Participants with chronic pain performed worse on tests of working memory and verbal episodic memory. A decline in attention explained some, but not all, group differences in memory performance. Finally, no additional effect of age on the diminished task performance in participants with chronic pain was observed. Taken together, the results indicate that chronic pain significantly affects memory performance. Part of this effect may be caused by underlying attentional dysfunction, although this could not fully explain the observed memory decline. An increase in age in combination with the presence of chronic pain did not additionally affect memory performance.

Personality and Cognitive Decline in Older Adults: Data From a Longitudinal Sample and Meta-Analysis.

PubMed

Luchetti, Martina; Terracciano, Antonio; Stephan, Yannick; Sutin, Angelina R

2016-07-01

Personality traits are associated with risk of dementia; less is known about their association with the trajectory of cognitive functioning. This research examines the association between the 5 major dimensions of personality and cognitive function and decline in older adulthood and includes a meta-analysis of published studies. Personality traits, objective and subjective memory, and cognitive status were collected in a large national sample (N = 13,987) with a 4-year follow-up period. For each trait, the meta-analysis pooled results from up to 5 prospective studies to examine personality and change in global cognition. Higher Neuroticism was associated with worse performance on all cognitive measures and greater decline in memory, whereas higher Conscientiousness and Openness were associated with better memory performance concurrently and less decline over time. All traits were associated with subjective memory. Higher Conscientiousness and lower Extraversion were associated with better cognitive status and less decline. Although modest, these associations were generally larger than that of hypertension, diabetes, history of psychological treatment, obesity, smoking, and physical inactivity. The meta-analysis supported the association between Neuroticism and Conscientiousness and cognitive decline. Personality is associated with cognitive decline in older adults, with effects comparable to established clinical and lifestyle risk factors. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention

PubMed Central

Boots, Elizabeth A.; Schultz, Stephanie A.; Clark, Lindsay R.; Racine, Annie M.; Darst, Burcu F.; Koscik, Rebecca L.; Carlsson, Cynthia M.; Gallagher, Catherine L.; Hogan, Kirk J.; Bendlin, Barbara B.; Asthana, Sanjay; Sager, Mark A.; Hermann, Bruce P.; Christian, Bradley T.; Dubal, Dena B.; Engelman, Corinne D.; Johnson, Sterling C.

2017-01-01

Objective: To examine the influence of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on longitudinal cognitive trajectories in a large, cognitively healthy cohort enriched for Alzheimer disease (AD) risk and to understand whether β-amyloid (Aβ) burden plays a moderating role in this relationship. Methods: One thousand twenty-three adults (baseline age 54.94 ± 6.41 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent BDNF genotyping and cognitive assessment at up to 5 time points (average follow-up 6.92 ± 3.22 years). A subset (n = 140) underwent 11C-Pittsburgh compound B (PiB) scanning. Covariate-adjusted mixed-effects regression models were used to elucidate the effect of BDNF on cognitive trajectories in 4 cognitive domains, including verbal learning and memory, speed and flexibility, working memory, and immediate memory. Secondary mixed-effects regression models were conducted to examine whether Aβ burden, indexed by composite PiB load, modified any observed BDNF-related cognitive trajectories. Results: Compared to BDNF Val/Val homozygotes, Met carriers showed steeper decline in verbal learning and memory (p = 0.002) and speed and flexibility (p = 0.017). In addition, Aβ burden moderated the relationship between BDNF and verbal learning and memory such that Met carriers with greater Aβ burden showed even steeper cognitive decline (p = 0.033). Conclusions: In a middle-aged cohort with AD risk, carriage of the BDNF Met allele was associated with steeper decline in episodic memory and executive function. This decline was exacerbated by greater Aβ burden. These results suggest that the BDNF Val66Met polymorphism may play an important role in cognitive decline and could be considered as a target for novel AD therapeutics. PMID:28468845

Cognitive activities delay onset of memory decline in persons who develop dementia

PubMed Central

Hall, C B.; Lipton, R B.; Sliwinski, M; Katz, M J.; Derby, C A.; Verghese, J

2009-01-01

Background: Persons destined to develop dementia experience an accelerated rate of decline in cognitive ability, particularly in memory. Early life education and participation in cognitively stimulating leisure activities later in life are 2 factors thought to reflect cognitive reserve, which may delay the onset of the memory decline in the preclinical stages of dementia. Methods: We followed 488 initially cognitively intact community residing individuals with epidemiologic, clinical, and cognitive assessments every 12 to 18 months in the Bronx Aging Study. We assessed the influence of self-reported participation in cognitively stimulating leisure activities on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. Results: Each additional self-reported day of cognitive activity at baseline delayed the onset of accelerated memory decline by 0.18 years. Higher baseline levels of cognitive activity were associated with more rapid memory decline after that onset. Inclusion of education did not significantly add to the fit of the model beyond the effect of cognitive activities. Conclusions: Our findings show that late life cognitive activities influence cognitive reserve independently of education. The effect of early life education on cognitive reserve may be mediated by cognitive activity later in life. Alternatively, early life education may be a determinant of cognitive reserve, and individuals with more education may choose to participate in cognitive activities without influencing reserve. Future studies should examine the efficacy of increasing participation in cognitive activities to prevent or delay dementia. GLOSSARY AD = Alzheimer disease; BL = baseline; CAS = Cognitive Activity Scale; CI = confidence interval; DSM = Diagnostic and Statistical Manual of Mental Disorders; dx = diagnosis; NIA = National Institute on Aging; SRT = Selective Reminding Test; WAIS VIQ = Wechsler Adult Intelligence Scale Verbal IQ. PMID:19652139

BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention.

PubMed

Boots, Elizabeth A; Schultz, Stephanie A; Clark, Lindsay R; Racine, Annie M; Darst, Burcu F; Koscik, Rebecca L; Carlsson, Cynthia M; Gallagher, Catherine L; Hogan, Kirk J; Bendlin, Barbara B; Asthana, Sanjay; Sager, Mark A; Hermann, Bruce P; Christian, Bradley T; Dubal, Dena B; Engelman, Corinne D; Johnson, Sterling C; Okonkwo, Ozioma C

2017-05-30

To examine the influence of the brain-derived neurotrophic factor ( BDNF ) Val66Met polymorphism on longitudinal cognitive trajectories in a large, cognitively healthy cohort enriched for Alzheimer disease (AD) risk and to understand whether β-amyloid (Aβ) burden plays a moderating role in this relationship. One thousand twenty-three adults (baseline age 54.94 ± 6.41 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent BDNF genotyping and cognitive assessment at up to 5 time points (average follow-up 6.92 ± 3.22 years). A subset (n = 140) underwent 11 C-Pittsburgh compound B (PiB) scanning. Covariate-adjusted mixed-effects regression models were used to elucidate the effect of BDNF on cognitive trajectories in 4 cognitive domains, including verbal learning and memory, speed and flexibility, working memory, and immediate memory. Secondary mixed-effects regression models were conducted to examine whether Aβ burden, indexed by composite PiB load, modified any observed BDNF -related cognitive trajectories. Compared to BDNF Val/Val homozygotes, Met carriers showed steeper decline in verbal learning and memory ( p = 0.002) and speed and flexibility ( p = 0.017). In addition, Aβ burden moderated the relationship between BDNF and verbal learning and memory such that Met carriers with greater Aβ burden showed even steeper cognitive decline ( p = 0.033). In a middle-aged cohort with AD risk, carriage of the BDNF Met allele was associated with steeper decline in episodic memory and executive function. This decline was exacerbated by greater Aβ burden. These results suggest that the BDNF Val66Met polymorphism may play an important role in cognitive decline and could be considered as a target for novel AD therapeutics. © 2017 American Academy of Neurology.

Is attention based on spatial contextual memory preferentially guided by low spatial frequency signals?

PubMed

Patai, Eva Zita; Buckley, Alice; Nobre, Anna Christina

2013-01-01

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.

Is Attention Based on Spatial Contextual Memory Preferentially Guided by Low Spatial Frequency Signals?

PubMed Central

Patai, Eva Zita; Buckley, Alice; Nobre, Anna Christina

2013-01-01

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. PMID:23776509

Formation of spatial and nonspatial memory in different condensed versions of short-term learning in Morris water maze.

PubMed

Zots, M A; Ivashkina, O I; Ivanova, A A; Anokhin, K V

2014-03-01

We studied the formation of spatial and nonspatial memory in mice during learning in three different condensed versions of Morris water maze task. Learning in combined version caused the formation of both spatial and nonspatial memory, whereas learning in condensed versions (spatial and nonspatial) led to memory formation specific for the version.

Spatial memory in foraging games.

PubMed

Kerster, Bryan E; Rhodes, Theo; Kello, Christopher T

2016-03-01

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. Copyright © 2015 Elsevier B.V. All rights reserved.

What versus where: Investigating how autobiographical memory retrieval differs when accessed with thematic versus spatial information.

PubMed

Sheldon, Signy; Chu, Sonja

2017-09-01

Autobiographical memory research has investigated how cueing distinct aspects of a past event can trigger different recollective experiences. This research has stimulated theories about how autobiographical knowledge is accessed and organized. Here, we test the idea that thematic information organizes multiple autobiographical events whereas spatial information organizes individual past episodes by investigating how retrieval guided by these two forms of information differs. We used a novel autobiographical fluency task in which participants accessed multiple memory exemplars to event theme and spatial (location) cues followed by a narrative description task in which they described the memories generated to these cues. Participants recalled significantly more memory exemplars to event theme than to spatial cues; however, spatial cues prompted faster access to past memories. Results from the narrative description task revealed that memories retrieved via event theme cues compared to spatial cues had a higher number of overall details, but those recalled to the spatial cues were recollected with a greater concentration on episodic details than those retrieved via event theme cues. These results provide evidence that thematic information organizes and integrates multiple memories whereas spatial information prompts the retrieval of specific episodic content from a past event.

Slime mold uses an externalized spatial “memory” to navigate in complex environments

PubMed Central

Reid, Chris R.; Latty, Tanya; Dussutour, Audrey; Beekman, Madeleine

2012-01-01

Spatial memory enhances an organism’s navigational ability. Memory typically resides within the brain, but what if an organism has no brain? We show that the brainless slime mold Physarum polycephalum constructs a form of spatial memory by avoiding areas it has previously explored. This mechanism allows the slime mold to solve the U-shaped trap problem—a classic test of autonomous navigational ability commonly used in robotics—requiring the slime mold to reach a chemoattractive goal behind a U-shaped barrier. Drawn into the trap, the organism must rely on other methods than gradient-following to escape and reach the goal. Our data show that spatial memory enhances the organism’s ability to navigate in complex environments. We provide a unique demonstration of a spatial memory system in a nonneuronal organism, supporting the theory that an externalized spatial memory may be the functional precursor to the internal memory of higher organisms. PMID:23045640

Time gradient for post-test vulnerability to scopolamine-induced amnesia following the initial acquisition session of a spatial reference memory task in mice.

PubMed

Toumane, A; Durkin, T P

1993-09-01

The time course for vulnerability to the amnestic effects of the cholinergic antagonist, scopolamine, during the postacquisition period has been investigated. We have examined the effects of post-test injections of scopolamine (1 mg/kg ip) given at different times from 30 s for up to 6 h following the end of the first acquisition session of a concurrent spatial discrimination (reference memory) protocol in an 8-arm radial maze on subsequent long-term (24 h) retention performance in C57BL/6 mice. Results show that the immediate (30 s) post-test injection of scopolamine-HCl on Day 1 produces marked perturbation (amnesia) of long-term retention as attested to by significant deficits in various indices of spatial discrimination performance gain on Day 2 as compared to control subjects injected either with scopolamine-MBr or saline. The severity of this scopolamine-induced amnesia declines only slightly as a function of the treatment period 30 s-3 h post-test. However, no evidence for amnesia is observed if scopolamine-HCl injections are delayed for 6 h postsession. This important latter observation attests to the absence of any significant proactive effects of scopolamine on the ability of mice to perform the retention test via possible long-term effects on attention, motivation, or locomotor performance. These results thus constitute evidence for the existence of a limited (30 s-3 h) time gradient for vulnerability of the early memory trace to disruption by scopolamine. The present results are discussed in relation to our previous direct neurochemical observations describing the differential time courses of intervention of the ascending septohippocampal and nBM-cortical cholinergic pathways in the postlearning period. In particular, the presently observed time window concerning post-test vulnerability to scopolamine-induced amnesia corresponds more closely to the time course of the acute activation of the nBM-cortical cholinergic pathway, induced by testing with the same spatial memory protocol as used in the present study in mice.

Short-term memory deficits correlate with hippocampal-thalamic functional connectivity alterations following acute sleep restriction.

PubMed

Chengyang, Li; Daqing, Huang; Jianlin, Qi; Haisheng, Chang; Qingqing, Meng; Jin, Wang; Jiajia, Liu; Enmao, Ye; Yongcong, Shao; Xi, Zhang

2017-08-01

Acute sleep restriction heavily influences cognitive function, affecting executive processes such as attention, response inhibition, and memory. Previous neuroimaging studies have suggested a link between hippocampal activity and short-term memory function. However, the specific contribution of the hippocampus to the decline of short-term memory following sleep restriction has yet to be established. In the current study, we utilized resting-state functional magnetic resonance imaging (fMRI) to examine the association between hippocampal functional connectivity (FC) and the decline of short-term memory following total sleep deprivation (TSD). Twenty healthy adult males aged 20.9 ± 2.3 years (age range, 18-24 years) were enrolled in a within-subject crossover study. Short-term memory and FC were assessed using a Delay-matching short-term memory test and a resting-state fMRI scan before and after TSD. Seed-based correlation analysis was performed using fMRI data for the left and right hippocampus to identify differences in hippocampal FC following TSD. Subjects demonstrated reduced alertness and a decline in short-term memory performance following TSD. Moreover, fMRI analysis identified reduced hippocampal FC with the superior frontal gyrus (SFG), temporal regions, and supplementary motor area. In addition, an increase in FC between the hippocampus and bilateral thalamus was observed, the extent of which correlated with short-term memory performance following TSD. Our findings indicate that the disruption of hippocampal-cortical connectivity is linked to the decline in short-term memory observed after acute sleep restriction. Such results provide further evidence that support the cognitive impairment model of sleep deprivation.

Neuroimaging markers associated with maintenance of optimal memory performance in late-life.

PubMed

Dekhtyar, Maria; Papp, Kathryn V; Buckley, Rachel; Jacobs, Heidi I L; Schultz, Aaron P; Johnson, Keith A; Sperling, Reisa A; Rentz, Dorene M

2017-06-01

Age-related memory decline has been well-documented; however, some individuals reach their 8th-10th decade while maintaining strong memory performance. To determine which demographic and biomarker factors differentiated top memory performers (aged 75+, top 20% for memory) from their peers and whether top memory performance was maintained over 3 years. Clinically normal adults (n=125, CDR=0; age: 79.5±3.57 years) from the Harvard Aging Brain Study underwent cognitive testing and neuroimaging (amyloid PET, MRI) at baseline and 3-year follow-up. Participants were grouped into Optimal (n=25) vs. Typical (n=100) performers using performance on 3 challenging memory measures. Non-parametric tests were used to compare groups. There were no differences in age, sex, or education between Optimal vs. Typical performers. The Optimal group performed better in Processing Speed (p=0.016) and Executive Functioning (p<0.001). Optimal performers had larger hippocampal volumes at baseline compared with Typical Performers (p=0.027) but no differences in amyloid burden (p=0.442). Twenty-three of the 25 Optimal performers had longitudinal data and16 maintained top memory performance while 7 declined. Non-Maintainers additionally declined in Executive Functioning but not Processing Speed. Longitudinally, there were no hippocampal volume differences between Maintainers and Non-Maintainers, however Non-Maintainers exhibited higher amyloid burden at baseline in contrast with Maintainers (p=0.008). Excellent memory performance in late life does not guarantee protection against cognitive decline. Those who maintain an optimal memory into the 8th and 9th decades may have lower levels of AD pathology. Copyright © 2017. Published by Elsevier Ltd.

Topological Schemas of Memory Spaces.

PubMed

Babichev, Andrey; Dabaghian, Yuri A

2018-01-01

Hippocampal cognitive map-a neuronal representation of the spatial environment-is widely discussed in the computational neuroscience literature for decades. However, more recent studies point out that hippocampus plays a major role in producing yet another cognitive framework-the memory space-that incorporates not only spatial, but also non-spatial memories. Unlike the cognitive maps, the memory spaces, broadly understood as "networks of interconnections among the representations of events," have not yet been studied from a theoretical perspective. Here we propose a mathematical approach that allows modeling memory spaces constructively, as epiphenomena of neuronal spiking activity and thus to interlink several important notions of cognitive neurophysiology. First, we suggest that memory spaces have a topological nature-a hypothesis that allows treating both spatial and non-spatial aspects of hippocampal function on equal footing. We then model the hippocampal memory spaces in different environments and demonstrate that the resulting constructions naturally incorporate the corresponding cognitive maps and provide a wider context for interpreting spatial information. Lastly, we propose a formal description of the memory consolidation process that connects memory spaces to the Morris' cognitive schemas-heuristic representations of the acquired memories, used to explain the dynamics of learning and memory consolidation in a given environment. The proposed approach allows evaluating these constructs as the most compact representations of the memory space's structure.

Topological Schemas of Memory Spaces

PubMed Central

Babichev, Andrey; Dabaghian, Yuri A.

2018-01-01

Hippocampal cognitive map—a neuronal representation of the spatial environment—is widely discussed in the computational neuroscience literature for decades. However, more recent studies point out that hippocampus plays a major role in producing yet another cognitive framework—the memory space—that incorporates not only spatial, but also non-spatial memories. Unlike the cognitive maps, the memory spaces, broadly understood as “networks of interconnections among the representations of events,” have not yet been studied from a theoretical perspective. Here we propose a mathematical approach that allows modeling memory spaces constructively, as epiphenomena of neuronal spiking activity and thus to interlink several important notions of cognitive neurophysiology. First, we suggest that memory spaces have a topological nature—a hypothesis that allows treating both spatial and non-spatial aspects of hippocampal function on equal footing. We then model the hippocampal memory spaces in different environments and demonstrate that the resulting constructions naturally incorporate the corresponding cognitive maps and provide a wider context for interpreting spatial information. Lastly, we propose a formal description of the memory consolidation process that connects memory spaces to the Morris' cognitive schemas-heuristic representations of the acquired memories, used to explain the dynamics of learning and memory consolidation in a given environment. The proposed approach allows evaluating these constructs as the most compact representations of the memory space's structure. PMID:29740306

Epigenetic regulation of neuronal immediate early genes is associated with decline in their expression and memory consolidation in scopolamine-induced amnesic mice.

PubMed

Srivas, Sweta; Thakur, Mahendra K

2017-09-01

Recently, we reported a correlation of scopolamine mediated decline in memory consolidation with increase in the expression of DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in the mouse hippocampus. Memory consolidation is a protein synthesis-dependent process which involves the expression of synaptic plasticity genes, particularly neuronal immediate early genes (IEGs). However, the mechanism of regulation of these genes during decline in memory is poorly understood. Therefore, we have studied the epigenetic regulation of expression of neuronal IEGs in scopolamine-induced amnesic mice. Scopolamine significantly impaired memory consolidation as tested by radial arm maze, and the expression of neuronal IEGs was downregulated in the hippocampus as revealed by qRT-PCR and Western blotting. Further, methylated DNA immunoprecipitation (MeDIP) analysis showed increase in DNA methylation, while chromatin immunoprecipitation (ChIP) revealed decrease in H3K9/14 acetylation at the promoter of neuronal IEGs. Taken together, the present study shows that increased DNA methylation and decreased histone acetylation at the promoter of neuronal IEGs are associated with decline in their expression and memory consolidation during scopolamine-induced amnesia. These findings suggest that the epigenetic regulation through altered DNA methylation and histone acetylation might be explored further to develop potential therapeutic interventions for amnesia.

Building a better hormone therapy?: How understanding the rapid effects of sex steroid hormones could lead to new therapeutics for age-related memory decline

PubMed Central

Frick, Karyn M.

2012-01-01

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. PMID:22289043

Visual and spatial working memory are not that dissociated after all: a time-based resource-sharing account.

PubMed

Vergauwe, Evie; Barrouillet, Pierre; Camos, Valérie

2009-07-01

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 spatial storage were combined with both visual and spatial on-line processing components in computer-paced working memory span tasks (Experiment 1) and in a selective interference paradigm (Experiment 2). The cognitive load of the processing components was manipulated to investigate its impact on concurrent maintenance for both within-domain and between-domain combinations of processing and storage components. In contrast to both domain- and process-based fractionations of visuo-spatial working memory, the results revealed that recall performance was determined by the cognitive load induced by the processing of items, rather than by the domain to which those items pertained. These findings are interpreted as evidence for a time-based resource-sharing mechanism in visuo-spatial working memory.

Memory-For-Designs Test: Comparison of Performance of Young and Old Adults.

ERIC Educational Resources Information Center

Dustman, Robert E.; Beck, Edward C.

1980-01-01

No significant decline in performance occurred before age 50. Decline in Memory-For-Designs Test performance after age 60 is sufficient to suggest caution in the use of the test for evaluation of brain damage in the older patient. (Author)

A cross-sectional study of hormone treatment and hippocampal volume in postmenopausal women: Evidence for a limited window of opportunity

PubMed Central

Erickson, Kirk I.; Voss, Michelle W.; Prakash, Ruchika S.; Chaddock, Laura; Kramer, Arthur F.

2010-01-01

The influence of hormone treatment on brain and cognition in postmenopausal women has been a controversial topic. Contradictory patterns of results have prompted speculation that a critical period, or a limited window of opportunity, exists for hormone treatment to protect against cognitive and neural decline in older women. Consistent with this hypothesis, studies in both humans and rodents indicate that the latency between the time of menopause and the initiation of hormone treatment is an important factor in determining whether hormone treatment will prevent or exacerbate cognitive impairment. In this cross-sectional study of 102 postmenopausal women, we examined whether hippocampal, amygdala, or caudate nucleus volumes and spatial memory performance were related to the interval between menopause and the initiation of hormone treatment. Consistent with a critical period hypothesis, we found that shorter intervals between menopause and the initiation of hormone treatment, as determined by self-report, were associated with larger hippocampal volumes compared with longer intervals between menopause and treatment initiation. Initiation of hormone treatment at the time of menopause was also associated with larger hippocampal volumes when compared to peers who had never used hormone treatment. Furthermore, these effects were independent from potentially confounding factors such as age, years of education, the duration of hormone treatment, current or past use of hormone therapy, the type of therapy, and the age at menopause. Larger hippocampal volumes in women who initiated hormone treatment at the time of menopause failed to translate to improved spatial memory performance. There was no relationship between the timing of hormone initiation, spatial memory performance, and amygdala or caudate nucleus volume. Our results provide support for the idea that there is a limited window of opportunity at the time of menopause for hormone treatment to influence hippocampal volume, yet the degree to which these effects translate to improved memory performance is uncertain. PMID:20063947

Hippocampal activation during retrieval of spatial context from episodic and semantic memory.

PubMed

Hoscheidt, Siobhan M; Nadel, Lynn; Payne, Jessica; Ryan, Lee

2010-10-15

The hippocampus, a region implicated in the processing of spatial information and episodic memory, is central to the debate concerning the relationship between episodic and semantic memory. Studies of medial temporal lobe amnesic patients provide evidence that the hippocampus is critical for the retrieval of episodic but not semantic memory. On the other hand, recent neuroimaging studies of intact individuals report hippocampal activation during retrieval of both autobiographical memories and semantic information that includes historical facts, famous faces, and categorical information, suggesting that episodic and semantic memory may engage the hippocampus during memory retrieval in similar ways. Few studies have matched episodic and semantic tasks for the degree to which they include spatial content, even though spatial content may be what drives hippocampal activation during semantic retrieval. To examine this issue, we conducted a functional magnetic resonance imaging (fMRI) study in which retrieval of spatial and nonspatial information was compared during an episodic and semantic recognition task. Results show that the hippocampus (1) participates preferentially in the retrieval of episodic memories; (2) is also engaged by retrieval of semantic memories, particularly those that include spatial information. These data suggest that sharp dissociations between episodic and semantic memory may be overly simplistic and that the hippocampus plays a role in the retrieval of spatial content whether drawn from a memory of one's own life experiences or real-world semantic knowledge. Published by Elsevier B.V.

On the role of working memory in spatial contextual cueing.

PubMed

Travis, Susan L; Mattingley, Jason B; Dux, Paul E

2013-01-01

The human visual system receives more information than can be consciously processed. To overcome this capacity limit, we employ attentional mechanisms to prioritize task-relevant (target) information over less relevant (distractor) information. Regularities in the environment can facilitate the allocation of attention, as demonstrated by the spatial contextual cueing paradigm. When observers are exposed repeatedly to a scene and invariant distractor information, learning from earlier exposures enhances the search for the target. Here, we investigated whether spatial contextual cueing draws on spatial working memory resources and, if so, at what level of processing working memory load has its effect. Participants performed 2 tasks concurrently: a visual search task, in which the spatial configuration of some search arrays occasionally repeated, and a spatial working memory task. Increases in working memory load significantly impaired contextual learning. These findings indicate that spatial contextual cueing utilizes working memory resources.

Anxiety-like behavior as an early endophenotype in the TgF344-AD rat model of Alzheimer's disease.

PubMed

Pentkowski, Nathan S; Berkowitz, Laura E; Thompson, Shannon M; Drake, Emma N; Olguin, Carlos R; Clark, Benjamin J

2018-01-01

Alzheimer's disease (AD) is characterized by progressive cognitive decline and the presence of aggregates of amyloid beta (plaques) and hyperphosphorylated tau (tangles). Early diagnosis through neuropsychological testing is difficult due to comorbidity of symptoms between AD and other types of dementia. As a result, there is a need to identify the range of behavioral phenotypes expressed in AD. In the present study, we utilized a transgenic rat (TgF344-AD) model that bears the mutated amyloid precursor protein as well as presenilin-1 genes, resulting in progressive plaque and tangle pathogenesis throughout the cortex. We tested young adult male and female TgF344-AD rats in a spatial memory task in the Morris water maze and for anxiety-like behavior in the elevated plus-maze. Results indicated that regardless of sex, TgF344-AD rats exhibited increased anxiety-like behavior in the elevated plus-maze, which occurred without significant deficits in the spatial memory. Together, these results indicate that enhanced anxiety-like behavior represents an early-stage behavioral marker in the TgF344-AD rat model. Copyright © 2017 Elsevier Inc. All rights reserved.

Pre- and long-term postoperative courses of hippocampus-associated memory impairment in epilepsy patients with antibody-associated limbic encephalitis and selective amygdalohippocampectomy.

PubMed

Hansen, Niels; Ernst, Leon; Rüber, Theodor; Widman, Guido; Becker, Albert J; Elger, Christian E; Helmstaedter, Christoph

2018-02-01

Limbic encephalitis (LE) is defined by mesiotemporal lobe structure abnormalities, seizures, memory, and psychiatric disturbances. This study aimed to identify the long-term clinical and neuropsychological outcome of selective amygdalohippocampectomy (sAH) in drug-resistant patients with temporal lobe epilepsy due to known or later diagnosed subacute LE not responding to immunotherapy associated with neuronal autoantibodies. In seven patients with temporal lobe epilepsy due to antibody positive LE (glutamic acid decarboxylase (GAD65): n=5; voltage-gated potassium channel complex (VGKC), N-methyl d-aspartate receptor (NMDAR): n=1; Ma-2/Ta: n=1) sAH (6 left, 1 right) was performed. Those patients underwent repeated electroencephalography (EEG) recordings, magnetic resonance imaging (MRI) volumetry of the amygdala and hippocampus, and neuropsychological examinations and were followed up for 6-7years on average. Verbal memory and figural memory were affected in 57% of patients at baseline and 71% at the last follow-up. At the last follow-up, 14% of the patients had declined in verbal memory and figural memory. We observed improved memory in 43% of patients regarding figural memory, but not in a single patient regarding verbal memory. Repeated evaluations across the individual courses reveal cognitive and MRI dynamics that appear to be unrelated to surgery and drug treatment. Three of the seven patients with LE with different antibodies (NMDAR: n=1, Ma-2/Ta: n=1 and GAD65: n=1) achieved persistent seizure freedom along with no accelerated memory decline after surgery. Two of the five GAD65-antibody patients positive with LE showed progressive memory decline and a long-term tendency to contralateral hippocampus atrophy. While memory demonstrated some decline in the long run, what is most important is that a progressive decline in memory is seldom found after sAH in patients with LE. Moreover, the dynamics in performance and MRI before and after surgery reveal disease dynamics independent of surgery. Selective amygdalohippocampectomy can lead to seizure freedom, but should be considered as a last resort treatment option for drug-resistant patients with temporal lobe epilepsy due to LE. Particular caution is recommended in patients with GAD65-LE. Copyright © 2017 Elsevier Inc. All rights reserved.

Blood Glucose, Diet-Based Glycemic Load and Cognitive Aging Among Dementia-Free Older Adults

PubMed Central

Andel, Ross; McEvoy, Cathy; Dahl Aslan, Anna K.; Finkel, Deborah; Pedersen, Nancy L.

2015-01-01

Background. Although evidence indicates that Type II Diabetes is related to abnormal brain aging, the influence of elevated blood glucose on long-term cognitive change is unclear. In addition, the relationship between diet-based glycemic load and cognitive aging has not been extensively studied. The focus of this study was to investigate the influence of diet-based glycemic load and blood glucose on cognitive aging in older adults followed for up to 16 years. Methods. Eight-hundred and thirty-eight cognitively healthy adults aged ≥50 years (M = 63.1, SD = 8.3) from the Swedish Adoption/Twin Study of Aging were studied. Mixed effects growth models were utilized to assess overall performance and change in general cognitive functioning, perceptual speed, memory, verbal ability, and spatial ability as a function of baseline blood glucose and diet-based glycemic load. Results. High blood glucose was related to poorer overall performance on perceptual speed as well as greater rates of decline in general cognitive ability, perceptual speed, verbal ability, and spatial ability. Diet-based glycemic load was related to poorer overall performance in perceptual speed and spatial ability. Conclusion. Diet-based glycemic load and, in particular, elevated blood glucose appear important for cognitive performance/cognitive aging. Blood glucose control (perhaps through low glycemic load diets) may be an important target in the detection and prevention of age-related cognitive decline. PMID:25149688

Brain Network Changes and Memory Decline in Aging

PubMed Central

Beason-Held, Lori L.; Hohman, Timothy J.; Venkatraman, Vijay; An, Yang; Resnick, Susan M.

2016-01-01

One theory of age-related cognitive decline proposes that changes within the default mode network (DMN) of the brain impact the ability to successfully perform cognitive operations. To investigate this theory, we examined functional covariance within brain networks using regional cerebral blood flow data, measured by 15O-water PET, from 99 participants (mean baseline age 68.6 ±7.5) in the Baltimore Longitudinal Study of Aging collected over a 7.4 year period. The sample was divided in tertiles based on longitudinal performance on a verbal recognition memory task administered during scanning, and functional covariance was compared between the upper (improvers) and lower (decliners) tertile groups. The DMN and verbal memory networks (VMN) were then examined during the verbal memory scan condition. For each network, group differences in node-to-network coherence and individual node-to-node covariance relationships were assessed at baseline and in change over time. Compared with improvers, decliners showed differences in node-to-network coherence and in node-to-node relationships in the DMN but not the VMN during verbal memory. These DMN differences reflected greater covariance with better task performance at baseline and both increasing and declining covariance with declining task performance over time for decliners. When examined during the resting state alone, the direction of change in DMN covariance was similar to that seen during task performance, but node-to-node relationships differed from those observed during the task condition. These results suggest that disengagement of DMN components during task performance is not essential for successful cognitive performance as previously proposed. Instead, a proper balance in network processes may be needed to support optimal task performance. PMID:27319002

Aging and the shape of cognitive change before death: terminal decline or terminal drop?

PubMed

MacDonald, Stuart W S; Hultsch, David F; Dixon, Roger A

2011-05-01

Relative to typical age-related cognitive decrements, the terms "terminal decline" and "terminal drop" refer to the phenomenon of increased cognitive decline in proximity to death. Given that these terms are not necessarily synonymous, we examined the important theoretical distinction between the two alternative trajectories or shapes of changes they imply. We used 12-year (5-wave) data from the Victoria Longitudinal Study to directly test whether pre-death cognitive decrements follow a terminal decline (generally gradual) or a terminal drop (more abrupt) shape. Pre-death trajectories of cognitive decline for n=265 decedents (Mage = 72.67 years, SD = 6.44) were examined separately for 5 key cognitive constructs (verbal speed, working memory, episodic memory, semantic memory, and crystallized ability). Several classes of linear mixed models evaluated whether cognitive decline increased per additional year closer to death. Findings indicated that the shape of pre-death cognitive change was predominantly characterized by decline that is steeper as compared with typical aging-related change, but still best described as slow and steady decline, especially as compared with precipitous drop. The present findings suggest that terminal decline and terminal drop trajectories may not be mutually exclusive but could rather reflect distinct developmental trajectories within the same individual.

Patterns of brain atrophy associated with episodic memory and semantic fluency decline in aging.

PubMed

Pelletier, Amandine; Bernard, Charlotte; Dilharreguy, Bixente; Helmer, Catherine; Le Goff, Melanie; Chanraud, Sandra; Dartigues, Jean-François; Allard, Michèle; Amieva, Hélène; Catheline, Gwénaëlle

2017-03-09

The cerebral substratum of age-related cognitive decline was evaluated in an elderly-cohort followed for 12 years (n=306). Participants, free of dementia, received neuropsychological assessments every two years and an MRI exam at baseline and four years later. Cognitive decline was evaluated on two broadly used tests to detect dementia: the Free and Cued Selective Reminding Test (FCSRT), a verbal episodic memory task, and the Isaacs Set Test (IST), a semantic fluency task. Using voxel-based approach, the relationship between cognitive decline with 1/ baseline grey matter volumes and 2/ grey matter volume loss between the two scans was explored. Baseline volumes analysis revealed that FCSRT and IST declines were both associated with lower volumes of the medial temporal region. Volumes loss analysis confirmed that both declines are related to medial temporal lobe atrophy and revealed that FCSRT decline was specifically associated with atrophy of the posterior cingulate cortex whereas IST decline was specifically related to temporal pole atrophy. These results suggest that cognitive decline across aging is firstly related to structural modifications of the medial temporal lobe, followed by an atrophy in the posterior midline structures for episodic memory and an atrophy of the temporal pole for semantic fluency.

Balanced Cortical Microcircuitry for Spatial Working Memory Based on Corrective Feedback Control

PubMed Central

2014-01-01

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

Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: evidence for a dual-process memory model.

PubMed

Sanderson, David J; Good, Mark A; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H; Rawlins, J Nicholas P; Bannerman, David M

2009-06-01

The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of GluA1-dependent synaptic plasticity for short-term memory of recently visited places, but not for the ability to form long-term associations between a particular spatial location and an outcome. This hypothesis is in concordance with the theory that short-term and long-term memory depend on dissociable psychological processes. In this study we tested GluA1-/- mice on both short-term and long-term spatial memory using a simple novelty preference task. Mice were given a series of repeated exposures to a particular spatial location (the arm of a Y-maze) before their preference for a novel spatial location (the unvisited arm of the maze) over the familiar spatial location was assessed. GluA1-/- mice were impaired if the interval between the trials was short (1 min), but showed enhanced spatial memory if the interval between the trials was long (24 h). This enhancement was caused by the interval between the exposure trials rather than the interval prior to the test, thus demonstrating enhanced learning and not simply enhanced performance or expression of memory. This seemingly paradoxical enhancement of hippocampus-dependent spatial learning may be caused by GluA1 gene deletion reducing the detrimental effects of short-term memory on subsequent long-term learning. Thus, these results support a dual-process model of memory in which short-term and long-term memory are separate and sometimes competitive processes.

How Does the Sparse Memory "Engram" Neurons Encode the Memory of a Spatial-Temporal Event?

PubMed

Guan, Ji-Song; Jiang, Jun; Xie, Hong; Liu, Kai-Yuan

2016-01-01

Episodic memory in human brain is not a fixed 2-D picture but a highly dynamic movie serial, integrating information at both the temporal and the spatial domains. Recent studies in neuroscience reveal that memory storage and recall are closely related to the activities in discrete memory engram (trace) neurons within the dentate gyrus region of hippocampus and the layer 2/3 of neocortex. More strikingly, optogenetic reactivation of those memory trace neurons is able to trigger the recall of naturally encoded memory. It is still unknown how the discrete memory traces encode and reactivate the memory. Considering a particular memory normally represents a natural event, which consists of information at both the temporal and spatial domains, it is unknown how the discrete trace neurons could reconstitute such enriched information in the brain. Furthermore, as the optogenetic-stimuli induced recall of memory did not depend on firing pattern of the memory traces, it is most likely that the spatial activation pattern, but not the temporal activation pattern of the discrete memory trace neurons encodes the memory in the brain. How does the neural circuit convert the activities in the spatial domain into the temporal domain to reconstitute memory of a natural event? By reviewing the literature, here we present how the memory engram (trace) neurons are selected and consolidated in the brain. Then, we will discuss the main challenges in the memory trace theory. In the end, we will provide a plausible model of memory trace cell network, underlying the conversion of neural activities between the spatial domain and the temporal domain. We will also discuss on how the activation of sparse memory trace neurons might trigger the replay of neural activities in specific temporal patterns.

Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging.

PubMed

Márquez Loza, Alejandra; Elias, Valerie; Wong, Carmen P; Ho, Emily; Bermudez, Michelle; Magnusson, Kathy R

2017-03-06

Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-d-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26months) were fed ibuprofen (375ppm) in NIH31 diet or diet alone for 6weeks prior to testing. Behavioral testing using the Morris water maze showed that older mice performed significantly worse than younger in spatial long-term memory, reversal, and short-term memory tasks. Ibuprofen enhanced overall performance in the short-term memory task, but this appeared to be more related to improved executive function than memory. Ibuprofen induced significant decreases over all ages in the mRNA densities for GluN2B subunit, all GluN1 splice variants, and GluN1-1 splice forms in the frontal cortex and in protein expression of GluN2A, GluN2B and GluN1 C2' cassettes in the hippocampus. GluN1-3 splice form mRNA and C2' cassette protein were significantly increased across ages in frontal lobes of ibuprofen-treated mice. Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Learning to remember: cognitive training-induced attenuation of age-related memory decline depends on sex and cognitive demand, and can transfer to untrained cognitive domains.

PubMed

Talboom, Joshua S; West, Stephen G; Engler-Chiurazzi, Elizabeth B; Enders, Craig K; Crain, Ian; Bimonte-Nelson, Heather A

2014-12-01

Aging is associated with progressive changes in learning and memory. A potential approach to attenuate age-related cognitive decline is cognitive training. In this study, adult male and female rats were given either repeated exposure to a T-maze, or no exposure to any maze, and then tested on a final battery of cognitive tasks. Two groups of each sex were tested from 6 to 18 months old on the same T-maze; Group one received a version testing spatial reference memory, and Group two received only the procedural testing components with minimal cognitive demand. Groups three and four of each sex had no maze exposure until the final battery, and were comprised of aged or young rats, respectively. The final maze battery included the practiced T-maze plus two novel tasks, one with a similar, and one with a different, memory type to the practice task. Group five of each sex was not maze tested, serving as an aged control for the effects of maze testing on neurotrophin protein levels in cognitive brain regions. Results showed that adult intermittent cognitive training enhanced performance on the practice task when aged in both sexes, that cognitive training benefits transferred to novel tasks only in females, and that cognitive demand was necessary for these effects, since rats receiving only the procedural testing components showed no improvement on the final maze battery. Further, for both sexes, rats that showed faster learning when young demonstrated better memory when aged. Age-related increases in neurotrophin concentrations in several brain regions were revealed, which were related to performance on the training task only in females. This longitudinal study supports the tenet that cognitive training can help one remember later in life, with broader enhancements and associations with neurotrophins in females. Published by Elsevier Inc.

Learning to remember: Cognitive training-induced attenuation of age-related memory decline depends on sex and cognitive demand, and can transfer to untrained cognitive domains

PubMed Central

Talboom, Joshua S.; West, Stephen G.; Engler-Chiurazzi, Elizabeth B.; Enders, Craig K.; Crain, Ian; Bimonte-Nelson, Heather A.

2014-01-01

Aging is associated with progressive changes in learning and memory. A potential approach to attenuate age-related cognitive decline is cognitive training. In this study, adult male and female rats were given either repeated exposure to a T-maze, or no exposure to any maze, and then tested on a final battery of cognitive tasks. Two groups of each sex were tested from 6-18 months old on the same T-maze; one group received a version testing spatial reference memory, and the other group received only the procedural testing components with minimal cognitive demand. Groups three and four of each sex had no maze exposure until the final battery, and were comprised of aged or young rats. The final maze battery included the practiced T-maze plus two novel tasks, one with a similar, and one with a different, memory type to the practice task. The fifth group of each sex was not maze tested, serving as an aged control for the effects of maze testing on neurotrophin protein levels in cognitive brain regions. Results showed that adult intermittent cognitive training enhanced performance on the practice task when aged in both sexes, that cognitive training benefits transferred to novel tasks only in females, and that cognitive demand was necessary for these effects since rats receiving only the procedural testing components showed no improvement on the final maze battery. Further, for both sexes, rats that showed faster learning when young demonstrated better memory when aged. Age-related increases in neurotrophin concentrations in several brain regions were revealed, which was related to performance on the training task only in females. This longitudinal study supports the tenet that cognitive training can help one remember later in life, with broader enhancements and associations with neurotrophins in females. PMID:25104561

The interaction between hippocampal GABA-B and cannabinoid receptors upon spatial change and object novelty discrimination memory function.

PubMed

Nasehi, Mohammad; Alaghmandan-Motlagh, Niyousha; Ebrahimi-Ghiri, Mohaddeseh; Nami, Mohammad; Zarrindast, Mohammad-Reza

2017-10-01

Previous studies have postulated functional links between GABA and cannabinoid systems in the hippocampus. The aim of the present study was to investigate any possible interaction between these systems in spatial change and object novelty discrimination memory consolidation in the dorsal hippocampus (CA1 region) of NMRI mice. Assessment of the spatial change and object novelty discrimination memory function was carried out in a non-associative task. The experiment comprised mice exposure to an open field containing five objects followed by the examination of their reactivity to object displacement (spatial change) and object substitution (object novelty) after three sessions of habituation. Our results showed that the post-training intraperitoneal administration of the higher dose of ACPA (0.02 mg/kg) impaired both spatial change and novelty discrimination memory functions. Meanwhile, the higher dose of GABA-B receptor agonist, baclofen, impaired the spatial change memory by itself. Moreover, the post-training intra-CA1 microinjection of a subthreshold dose of baclofen increased the ACPA effect on spatial change and novelty discrimination memory at a lower and higher dose, respectively. On the other hand, the lower and higher but not mid-level doses of GABA-B receptor antagonist, phaclofen, could reverse memory deficits induced by ACPA. However, phaclofen at its mid-level dose impaired the novelty discrimination memory and whereas the higher dose impaired the spatial change memory. Based on our findings, GABA-B receptors in the CA1 region appear to modulate the ACPA-induced cannabinoid CB1 signaling upon spatial change and novelty discrimination memory functions.

Baseline Neurocognitive Performance and Clearance for Athletes to Return to Contact.

PubMed

Asken, Breton M; Clugston, James R; Snyder, Aliyah R; Bauer, Russell M

2017-01-01

 Computerized neurocognitive assessments are commonly used to manage sport-related concussion. Variations in baseline performance may influence neurocognitive performance after injury as well as the amount of time needed for an athlete to be cleared for return to sport participation.  To investigate the relationship between mean baseline Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) scores and postconcussion reliable decline as well as the association between postconcussion cognitive decline and days missed after injury.  Cross-sectional study.  University concussion databank.  A total of 84 collegiate athletes who sustained a concussion between 2008 and 2015 were studied. For each ImPACT composite score (verbal memory, visual memory, visual motor speed, reaction time), athletes were grouped based on the presence or absence of reliable decline and on the presence of reliable decline in 0, 1, 2, 3, or 4 cognitive domains.  Outcome measures were baseline ImPACT composite scores and days missed due to concussion.  Athletes with a reliable decline in visual memory scored higher on baseline visual memory than did athletes with no decline or an improvement (t 82 = -2.348, P = .021, d = 0.65). When comparing athletes who displayed a reliable decline with those who showed no change or an improvement in any composite score, days missed did not differ. The number of composite scores with a reliable decline demonstrated no main effect on days missed (P = .530).  Athletes who exhibited cognitive decline in most or all of the composite scores did not miss more days after injury than athletes with a decline in fewer or none of the composite scores. Athletes should be educated regarding the lack of association between baseline neurocognitive scores and the presence or absence of a reliable decline after concussion, as well as the fact that, on average, individuals with a reliable decline across multiple domains did not miss more time after concussion.

Multiple Systems of Spatial Memory: Evidence from Described Scenes

ERIC Educational Resources Information Center

Avraamides, Marios N.; Kelly, Jonathan W.

2010-01-01

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…

Abnormal Neural Network of Primary Insomnia: Evidence from Spatial Working Memory Task fMRI.

PubMed

Li, Yongli; Liu, Liya; Wang, Enfeng; Zhang, Hongju; Dou, Shewei; Tong, Li; Cheng, Jingliang; Chen, Chuanliang; Shi, Dapeng

2016-01-01

Contemporary functional MRI (fMRI) methods can provide a wealth of information about the neural mechanisms associated with primary insomnia (PI), which centrally involve neural network circuits related to spatial working memory. A total of 30 participants diagnosed with PI and without atypical brain anatomy were selected along with 30 age- and gender-matched healthy controls. Subjects were administered the Pittsburgh Sleep Quality Index (PSQI), Hamilton Rating Scale for Depression and clinical assessments of spatial working memory, followed by an MRI scan and fMRI in spatial memory task state. Statistically significant differences between PSQI and spatial working memory were observed between PI patients and controls (p < 0.01). Activation of neural networks related to spatial memory task state in the PI group was observed at the left temporal lobe, left occipital lobe and right frontal lobe. Lower levels of activation were observed in the left parahippocampal gyrus, right parahippocampal gyrus, bilateral temporal cortex, frontal cortex and superior parietal lobule. Participants with PI exhibited characteristic abnormalities in the neural network connectivity related to spatial working memory. These results may be indicative of an underlying pathological mechanism related to spatial working memory deterioration in PI, analogous to recently described mechanisms in other mental health disorders. © 2016 S. Karger AG, Basel.

Visual-spatial abilities relate to mathematics achievement in children with heavy prenatal alcohol exposure

PubMed Central

Crocker, N.; Riley, E.P.; Mattson, S.N.

2014-01-01

Objective The current study examined the relationship between mathematics and attention, working memory, and visual memory in children with heavy prenatal alcohol exposure and controls. Method Fifty-six children (29 AE, 27 CON) were administered measures of global mathematics achievement (WRAT-3 Arithmetic & WISC-III Written Arithmetic), attention, (WISC-III Digit Span forward and Spatial Span forward), working memory (WISC-III Digit Span backward and Spatial Span backward), and visual memory (CANTAB Spatial Recognition Memory and Pattern Recognition Memory). The contribution of cognitive domains to mathematics achievement was analyzed using linear regression techniques. Attention, working memory and visual memory data were entered together on step 1 followed by group on step 2, and the interaction terms on step 3. Results Model 1 accounted for a significant amount of variance in both mathematics achievement measures, however, model fit improved with the addition of group on step 2. Significant predictors of mathematics achievement were Spatial Span forward and backward and Spatial Recognition Memory. Conclusions These findings suggest that deficits in spatial processing may be related to math impairments seen in FASD. In addition, prenatal alcohol exposure was associated with deficits in mathematics achievement, above and beyond the contribution of general cognitive abilities. PMID:25000323

Visual-spatial abilities relate to mathematics achievement in children with heavy prenatal alcohol exposure.

PubMed

Crocker, Nicole; Riley, Edward P; Mattson, Sarah N

2015-01-01

The current study examined the relationship between mathematics and attention, working memory, and visual memory in children with heavy prenatal alcohol exposure and controls. Subjects were 56 children (29 AE, 27 CON) who were administered measures of global mathematics achievement (WRAT-3 Arithmetic & WISC-III Written Arithmetic), attention, (WISC-III Digit Span forward and Spatial Span forward), working memory (WISC-III Digit Span backward and Spatial Span backward), and visual memory (CANTAB Spatial Recognition Memory and Pattern Recognition Memory). The contribution of cognitive domains to mathematics achievement was analyzed using linear regression techniques. Attention, working memory, and visual memory data were entered together on Step 1 followed by group on Step 2, and the interaction terms on Step 3. Model 1 accounted for a significant amount of variance in both mathematics achievement measures; however, model fit improved with the addition of group on Step 2. Significant predictors of mathematics achievement were Spatial Span forward and backward and Spatial Recognition Memory. These findings suggest that deficits in spatial processing may be related to math impairments seen in FASD. In addition, prenatal alcohol exposure was associated with deficits in mathematics achievement, above and beyond the contribution of general cognitive abilities. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Recombinant growth differentiation factor 11 influences short-term memory and enhances Sox2 expression in middle-aged mice.

PubMed

Zhang, Min; Jadavji, Nafisa M; Yoo, Hyung-Suk; Smith, Patrice D

2018-04-02

Previous evidence suggests that a significant decline in cognitive ability begins during middle-age and continues to deteriorate with increase in age. Recent work has demonstrated the potential rejuvenation impact of growth differentiation factor-11 (GDF-11) in aged mice. We carried out experiments to evaluate the impact of a single dose of recombinant (rGDF-11) on short-term visual and spatial memory in middle-aged male mice. On the novel object recognition task, we observed middle-aged mice treated rGDF-11 showed improved performance on the novel object recognition task. However, middle-aged mice did not show increased expression of phosphorylated-Smad2/3, a downstream effector of GDF-11. We noted however that the expression of the transcription factor, Sox2 was increased within the dentate gyrus. Our data suggest that a single injection of rGDF-11 contributes to improvements in cognitive function of middle-aged animals, which may be critical in the preservation of short-term memory capacity in old age. Copyright © 2017 Elsevier B.V. All rights reserved.

Urtica dioica extract attenuates depressive like behavior and associative memory dysfunction in dexamethasone induced diabetic mice.

PubMed

Patel, Sita Sharan; Udayabanu, Malairaman

2014-03-01

Evidences suggest that glucocorticoids results in depression and is a risk factor for type 2 diabetes. Further diabetes induces oxidative stress and hippocampal dysfunction resulting in cognitive decline. Traditionally Urtica dioica has been used for diabetes mellitus and cognitive dysfunction. The present study investigated the effect of the hydroalcoholic extract of Urtica dioica leaves (50 and 100 mg/kg, p.o.) in dexamethasone (1 mg/kg, i.m.) induced diabetes and its associated complications such as depressive like behavior and cognitive dysfunction. We observed that mice administered with chronic dexamethasone resulted in hypercortisolemia, oxidative stress, depressive like behavior, cognitive impairment, hyperglycemia with reduced body weight, increased water intake and decreased hippocampal glucose transporter-4 (GLUT4) mRNA expression. Urtica dioica significantly reduced hyperglycemia, plasma corticosterone, oxidative stress and depressive like behavior as well as improved associative memory and hippocampal GLUT4 mRNA expression comparable to rosiglitazone (5 mg/kg, p.o.). Further, Urtica dioica insignificantly improved spatial memory and serum insulin. In conclusion, Urtica dioica reversed dexamethasone induced hyperglycemia and its associated complications such as depressive like behavior and cognitive dysfunction.

The hyperforin derivative IDN5706 occludes spatial memory impairments and neuropathological changes in a double transgenic Alzheimer's mouse model.

PubMed

Cerpa, W; Hancke, J L; Morazzoni, P; Bombardelli, E; Riva, Antonella; Marin, P P; Inestrosa, Nibaldo C

2010-03-01

The use of natural compounds is an interesting stratagem in the search of drugs with therapeutic potential for the treatment of Alzheimer's disease (AD). We report here the effect of the hyperforin derivative (IDN5706, tetrahydrohyperforin), a semi-synthetic derivative of the St. John's Wort, on the brain neuropathology, learning and memory in a double transgenic (APPswe, PS-1dE9) mouse model of AD. Results indicate that, IDN5706 alleviates memory decline induced by amyloid-beta (Abeta) deposits as indicated by the Morris water maze paradigm. Moreover, the analysis of Abeta deposits by immunodetection and thioflavin-S staining of brain sections, only reveals a decrease in the frequency of the larger-size Abeta deposits, suggesting that IDN5706 affected the turnover of amyloid plaques. Immunohistochemical analysis, using GFAP and n-Tyrosine indicated that the hyperforin derivative prevents the inflammatory astrocytic reaction and the oxidative damage triggered by high Abeta deposit levels. We conclude that the hyperforin derivative, IDN5706, has therapeutic potential for prevention and treatment of AD.

Walking through doorways causes forgetting: Further explorations.

PubMed

Radvansky, Gabriel A; Krawietz, Sabine A; Tamplin, Andrea K

2011-08-01

Previous research using virtual environments has revealed a location-updating effect in which there is a decline in memory when people move from one location to another. Here we assess whether this effect reflects the influence of the experienced context, in terms of the degree of immersion of a person in an environment, as suggested by some work in spatial cognition, or by a shift in context. In Experiment 1, the degree of immersion was reduced by using smaller displays. In comparison, in Experiment 2 an actual, rather than a virtual, environment was used, to maximize immersion. Location-updating effects were observed under both of these conditions. In Experiment 3, the original encoding context was reinstated by having a person return to the original room in which objects were first encoded. However, inconsistent with an encoding specificity account, memory did not improve by reinstating this context. Finally, we did a further analysis of the results of this and previous experiments to assess the differential influence of foregrounding and retrieval interference. Overall, these data are interpreted in terms of the event horizon model of event cognition and memory.

Roles of Arterial Stiffness and Blood Pressure in Hypertension-Associated Cognitive Decline in Healthy Adults.

PubMed

Hajjar, Ihab; Goldstein, Felicia C; Martin, Greg S; Quyyumi, Arshed A

2016-01-01

Although there is strong evidence that hypertension leads to cognitive decline, especially in the executive domain, the relationship between blood pressure and cognition has been conflicted. Hypertension is characterized by blood pressure elevation and increased arterial stiffness. We aimed at investigating whether arterial stiffness would be superior to blood pressure in predicting cognitive decline and explaining the hypertension-executive decline association. A randomly selected asymptomatic population (n=591, age=49.2 years, 70% women, 27% black, and education=18 years) underwent annual vascular and cognitive assessments. Cognition was assessed using computerized versions commonly used cognitive tests, and principal component analysis was used for deriving cognitive scores for executive function, memory, and working memory. Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV). Higher PWV, but not blood pressure, was associated with a steeper decline in executive (P=0.0002), memory (P=0.05), and working memory (P=0.02) scores after adjusting for demographics, education, and baseline cognitive performance. This remained true after adjusting for hypertension. Hypertension was associated with greater decline in executive score (P=0.0029) and those with combined hypertension and elevated PWV (>7 m/s) had the greatest decline in executive score (P value hypertension×PWV=0.02). PWV explained the association between hypertension and executive function (P value for hypertension=0.0029 versus 0.24 when adjusting for PWV). In healthy adults, increased arterial stiffness is superior to blood pressure in predicting cognitive decline in all domains and in explaining the hypertension-executive function association. Arterial stiffness, especially in hypertension, may be a target in the prevention of cognitive decline. © 2015 American Heart Association, Inc.

Fish Intake, Genetic Predisposition to Alzheimer Disease, and Decline in Global Cognition and Memory in 5 Cohorts of Older Persons.

PubMed

Samieri, Cécilia; Morris, Martha-Clare; Bennett, David A; Berr, Claudine; Amouyel, Philippe; Dartigues, Jean-François; Tzourio, Christophe; Chasman, Daniel I; Grodstein, Francine

2018-05-01

Fish are a primary source of long-chain omega-3 fatty acids, which may help delay cognitive aging. We pooled participants from the French Three-City study and 4 US cohorts (Nurses' Health Study, Women's Health Study, Chicago Health and Aging Project, and Rush Memory and Aging Project) for whom diet and cognitive data were available (n = 23,688 white persons, aged ≥65 years, 88% female, baseline year range of 1992-1999, and median follow-up range of 3.9-9.1 years) to investigate the relationship of fish intake to cognitive decline and examine interactions with genes related to Alzheimer disease. We estimated cohort-specific associations between fish and change in composite scores of global cognition and episodic memory using linear mixed models, and we pooled results using inverse-variance weighted meta-analysis. In multivariate analyses, higher fish intake was associated with slower decline in both global cognition and memory (P for trend ≤ 0.031). Consuming ≥4 servings/week versus <1 serving/week of fish was associated with a lower rate of memory decline: 0.018 (95% confidence interval: 0.004, 0.032) standard units, an effect estimate equivalent to that found for 4 years of age. For global cognition, no comparisons of higher versus low fish intake reached statistical significance. In this meta-analysis, higher fish intake was associated with a lower rate of memory decline. We found no evidence of effect modification by genes associated with Alzheimer disease.

Longitudinal deficits to attention, executive, and working memory in subtypes of mild cognitive impairment.

PubMed

Saunders, Nichole L J; Summers, Mathew J

2011-03-01

Mild cognitive impairment (MCI) has emerged as a classification for a prodromal phase of cognitive decline that may precede the emergence of Alzheimer's disease (AD). Recent research suggests that attention, executive, and working memory deficits may appear much earlier in the progression of AD than traditionally conceptualized, and may be more consistently associated with the later development of AD than memory processing deficits. The present study longitudinally tracked attention, executive and working memory functions in subtypes of MCI. In a longitudinal study, 52 amnestic MCI (a-MCI), 29 nonamnestic MCI (na-MCI), and 25 age- and education-matched controls undertook neuropsychological assessment of visual and verbal memory, attentional processing, executive functioning, working memory capacity, and semantic language at 10 month intervals. Analysis by repeated measures ANOVA indicate that the a-MCI and na-MCI groups displayed a decline in simple sustained attention (ηp² = .054) with a significant decline on a task of divided attention (ηp² = .053) being evident in the a-MCI group. Stable deficits were found on other measures of attention, working memory and executive function in the a-MCI and na-MCI groups. The a-MCI group displayed stable impairments to visual and verbal memory. The results indicate that a-MCI and na-MCI display a stable pattern of deficits to attention, working memory, and executive function. The decline in simple sustained attention in a-MCI and n-MCI groups and to divided attention in a-MCI may be early indicators of possible transition to dementia from MCI. However, further research is required to determine this. (c) 2011 APA, all rights reserved

Verbal makes it positive, spatial makes it negative: working memory biases judgments, attention, and moods.

PubMed

Storbeck, Justin; Watson, Philip

2014-12-01

Prior research has suggested that emotion and working memory domains are integrated, such that positive affect enhances verbal working memory, whereas negative affect enhances spatial working memory (Gray, 2004; Storbeck, 2012). Simon (1967) postulated that one feature of emotion and cognition integration would be reciprocal connectedness (i.e., emotion influences cognition and cognition influences emotion). We explored whether affective judgments and attention to affective qualities are biased by the activation of verbal and spatial working memory mind-sets. For all experiments, participants completed a 2-back verbal or spatial working memory task followed by an endorsement task (Experiments 1 & 2), word-pair selection task (Exp. 3), or attentional dot-probe task (Exp. 4). Participants who had an activated verbal, compared with spatial, working memory mind-set were more likely to endorse pictures (Exp. 1) and words (Exp. 2) as being more positive and to select the more positive word pair out of a set of word pairs that went 'together best' (Exp. 3). Additionally, people who completed the verbal working memory task took longer to disengage from positive stimuli, whereas those who completed the spatial working memory task took longer to disengage from negative stimuli (Exp. 4). Interestingly, across the 4 experiments, we observed higher levels of self-reported negative affect for people who completed the spatial working memory task, which was consistent with their endorsement and attentional bias toward negative stimuli. Therefore, emotion and working memory may have a reciprocal connectedness allowing for bidirectional influence.

Inhibition of Connexin43 Hemichannels Impairs Spatial Short-Term Memory without Affecting Spatial Working Memory.

PubMed

Walrave, Laura; Vinken, Mathieu; Albertini, Giulia; De Bundel, Dimitri; Leybaert, Luc; Smolders, Ilse J

2016-01-01

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.

Oculomotor preparation as a rehearsal mechanism in spatial working memory.

PubMed

Pearson, David G; Ball, Keira; Smith, Daniel T

2014-09-01

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. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Distinctiveness as a function of spatial expansion in verbal working memory: comment on Kreitz, Furley, Memmert, and Simons (2015).

PubMed

Guida, Alessandro; van Dijck, Jean-Philippe; Abrahamse, Elger

2017-05-01

In a recent study, Kreitz et al. (Psychological Research 79:1034-1041, 2015) reported on a relationship between verbal working memory capacity and visuo-spatial attentional breadth. The authors hinted at attentional control to be the major link underlying this relationship. We put forward an alternative explanation by framing it within the context of a recent theory on serial order in memory: verbal item sequences entering in working memory are coded by adding a spatial context that can be derived from reading/writing habits. The observation by Kreitz et al. (Psychological Research 79:1034-1041, 2015) enriches this framework by suggesting that a larger visuo-spatial attentional breadth allows for internal coding of the verbal items in a more (spatially) distinct manner-thereby increasing working memory performance. As such, Kreitz et al. (Psychological Research 79:1034-1041, 2015) is the first study revealing a functional link between visuo-spatial attentional breadth and verbal working memory size, which strengthens spatial accounts of serial order coding in working memory.

Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months.

PubMed

Thai, Christine; Lim, Yen Ying; Villemagne, Victor L; Laws, Simon M; Ames, David; Ellis, Kathryn A; Rainey-Smith, Stephanie R; Martins, Ralph N; Masters, Colin L; Rowe, Christopher C; Maruff, Paul

2015-01-01

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.

Methylphenidate Improves Visual-Spatial Memory in Children with Attention-Deficit- hyperactivity Disorder

ERIC Educational Resources Information Center

Bedard, Anne-Claude; Martinussen, Rhonda; Ickowicz, Abel; Tannock, Rosemary

2004-01-01

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…

Remembering the Past and Imagining the Future: A Neural Model of Spatial Memory and Imagery

ERIC Educational Resources Information Center

Byrne, Patrick; Becker, Suzanna; Burgess, Neil

2007-01-01

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…

Differential Age Effects on Spatial and Visual Working Memory

ERIC Educational Resources Information Center

Oosterman, Joukje M.; Morel, Sascha; Meijer, Lisette; Buvens, Cleo; Kessels, Roy P. C.; Postma, Albert

2011-01-01

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…

Mechanisms of Age-Related Decline in Memory Search Across the Adult Life Span

PubMed Central

Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

2013-01-01

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

Balanced cortical microcircuitry for spatial working memory based on corrective feedback control.

PubMed

Lim, Sukbin; Goldman, Mark S

2014-05-14

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. Copyright © 2014 the authors 0270-6474/14/346790-17$15.00/0.

The role of aging in intra-item and item-context binding processes in visual working memory.

PubMed

Peterson, Dwight J; Naveh-Benjamin, Moshe

2016-11-01

Aging is accompanied by declines in both working memory and long-term episodic memory processes. Specifically, important age-related memory deficits are characterized by performance impairments exhibited by older relative to younger adults when binding distinct components into a single integrated representation, despite relatively intact memory for the individual components. While robust patterns of age-related binding deficits are prevalent in studies of long-term episodic memory, observations of such deficits in visual working memory (VWM) may depend on the specific type of binding process being examined. For instance, a number of studies indicate that processes involved in item-context binding of items to occupied spatial locations within visual working memory are impaired in older relative to younger adults. Other findings suggest that intra-item binding of visual surface features (e.g., color, shape), compared to memory for single features, within visual working memory, remains relatively intact. Here, we examined each of these binding processes in younger and older adults under both optimal conditions (i.e., no concurrent load) and concurrent load (e.g., articulatory suppression, backward counting). Experiment 1 revealed an age-related intra-item binding deficit for surface features under no concurrent load but not when articulatory suppression was required. In contrast, in Experiments 2 and 3, we observed an age-related item-context binding deficit regardless of the level of concurrent load. These findings reveal that the influence of concurrent load on distinct binding processes within VWM, potentially those supported by rehearsal, is an important factor mediating the presence or absence of age-related binding deficits within VWM. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Short-term memory for spatial configurations in the tactile modality: a comparison with vision.

PubMed

Picard, Delphine; Monnier, Catherine

2009-11-01

This study investigates the role of acquisition constraints on the short-term retention of spatial configurations in the tactile modality in comparison with vision. It tests whether the sequential processing of information inherent to the tactile modality could account for limitation in short-term memory span for tactual-spatial information. In addition, this study investigates developmental aspects of short-term memory for tactual- and visual-spatial configurations. A total of 144 child and adult participants were assessed for their memory span in three different conditions: tactual, visual, and visual with a limited field of view. The results showed lower tactual-spatial memory span than visual-spatial, regardless of age. However, differences in memory span observed between the tactile and visual modalities vanished when the visual processing of information occurred within a limited field. These results provide evidence for an impact of acquisition constraints on the retention of spatial information in the tactile modality in both childhood and adulthood.

Memory Decline in Peri- and Post-menopausal Women: The Potential of Mind–Body Medicine to Improve Cognitive Performance

PubMed Central

Sliwinski, Jim R; Johnson, Aimee K; Elkins, Gary R

2014-01-01

Cognitive decline is a frequent complaint during the menopause transition and among post-menopausal women. Changes in memory correspond with diminished estrogen production. Further, many peri- and post-menopausal women report sleep concerns, depression, and hot flashes, and these factors may contribute to cognitive decline. Hormone therapy can increase estrogen but is contraindicated for many women. Mind–body medicine has been shown to have beneficial effects on sleep, mood, and hot flashes, among post-menopausal women. Further, mind–body medicine holds potential in addressing symptoms of cognitive decline post-menopause. This study proposes an initial framework for how mind–body interventions may improve cognitive performance and inform future research seeking to identify the common and specific factors associated with mind–body medicine for addressing memory decline in peri- and post-menopausal women. It is our hope that this article will eventually lead to a more holistic and integrative approach to the treatment of cognitive deficits in peri- and post-menopausal women. PMID:25125972

Outsourcing Memory in Response to an Aging Population.

PubMed

Ross, Michael; Schryer, Emily

2015-11-01

With baby boomers entering old age and longevity increasing, policymakers have focused on the physical, social, and health needs of older persons. We urge policymakers to consider cognitive aging as well, particularly normal, age-related memory decline. Psychological scientists attribute memory decline mainly to cognitive overload stemming from age-related reductions in sensory capacities, speed of cognitive processing, and the ability to filter out irrelevant information. Even in the absence of decline, however, memory is imperfect and forgetting can be especially consequential for older adults. For example, forgetting to take prescription medicines is an age-related problem largely because older adults tend to ingest many more prescription drugs. We propose that policymakers focus on increasing environmental support for memory that can reduce the burden on cognitive resources and thus improve recall. In providing environmental support, policymakers need to pay careful attention to potential age-related changes in physical and cognitive capacity, as well as behavior. © The Author(s) 2015.

Aging and the Shape of Cognitive Change Before Death: Terminal Decline Or Terminal Drop?

PubMed Central

Hultsch, David F.; Dixon, Roger A.

2011-01-01

Objectives. Relative to typical age-related cognitive decrements, the terms “terminal decline” and “terminal drop” refer to the phenomenon of increased cognitive decline in proximity to death. Given that these terms are not necessarily synonymous, we examined the important theoretical distinction between the two alternative trajectories or shapes of changes they imply. Methods. We used 12-year (5-wave) data from the Victoria Longitudinal Study to directly test whether pre-death cognitive decrements follow a terminal decline (generally gradual) or a terminal drop (more abrupt) shape. Pre-death trajectories of cognitive decline for n = 265 decedents (Mage = 72.67 years, SD = 6.44) were examined separately for 5 key cognitive constructs (verbal speed, working memory, episodic memory, semantic memory, and crystallized ability). Results. Several classes of linear mixed models evaluated whether cognitive decline increased per additional year closer to death. Findings indicated that the shape of pre-death cognitive change was predominantly characterized by decline that is steeper as compared with typical aging-related change, but still best described as slow and steady decline, especially as compared with precipitous drop. Discussion. The present findings suggest that terminal decline and terminal drop trajectories may not be mutually exclusive but could rather reflect distinct developmental trajectories within the same individual. PMID:21300703

Spatial transposition gradients in visual working memory.

PubMed

Rerko, Laura; Oberauer, Klaus; Lin, Hsuan-Yu

2014-01-01

In list memory, access to individual items reflects limits of temporal distinctiveness. This is reflected in the finding that neighbouring list items tend to be confused most often. This article investigates the analogous effect of spatial proximity in a visual working-memory task. Items were presented in different locations varying in spatial distance. A retro-cue indicated the location of the item relevant for the subsequent memory test. In two recognition experiments, probes matching spatially close neighbours of the relevant item led to more false alarms than probes matching distant neighbours or non-neighbouring memory items. In two probed-recall experiments, one with simultaneous, the other with sequential memory item presentation, items closer to the cued location were more frequently chosen for recall than more distant items. These results reflect a spatial transposition gradient analogous to the temporal transposition gradient in serial recall and challenge fixed-capacity models of visual working memory (WM).

Spatial memory deficit and neurodegeneration induced by the direct injection of okadaic acid into the hippocampus in rats.

PubMed

He, J; Yamada, K; Zou, L B; Nabeshima, T

2001-01-01

We investigated the effects of okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, on spatial memory and neuronal survival in rats. Rats were initially trained on a spatial memory task in an eight arm radial maze. Spatial reference and working memory was impaired 1 day after the unilateral microinjection of OA into the dorsal hippocampus. The impairment was transient, and had disappeared by the following day. In contrast, neurodegeneration induced by OA was persistent and extended to the contralateral side 13 days after the injection. These results suggest that OA causes spatial memory impairment and neurodegeneration when injected directly into the hippocampus. Our findings also indicate dissociation between memory impairment and neurodegeneration induced by OA.

The spatial learning and memory performance in methamphetamine–sensitized and withdrawn rats

PubMed Central

Bigdeli, Imanollah; Asia, Masomeh Nikfarjam- Haft; Miladi-Gorji, Hossein; Fadaei, Atefeh

2015-01-01

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

The optimal timing of stimulation to induce long-lasting positive effects on episodic memory in physiological aging.

PubMed

Manenti, Rosa; Sandrini, Marco; Brambilla, Michela; Cotelli, Maria

2016-09-15

Episodic memory displays the largest degree of age-related decline. A noninvasive brain stimulation technique that can be used to modulate memory in physiological aging is transcranial Direct Current Stimulation (tDCS). However, an aspect that has not been adequately investigated in previous studies is the optimal timing of stimulation to induce long-lasting positive effects on episodic memory function. Our previous studies showed episodic memory enhancement in older adults when anodal tDCS was applied over the left lateral prefrontal cortex during encoding or after memory consolidation with or without a contextual reminder. Here we directly compared the two studies to explore which of the tDCS protocols would induce longer-lasting positive effects on episodic memory function in older adults. In addition, we aimed to determine whether subjective memory complaints would be related to the changes in memory performance (forgetting) induced by tDCS, a relevant issue in aging research since individuals with subjective memory complaints seem to be at higher risk of later memory decline. The results showed that anodal tDCS applied after consolidation with a contextual reminder induced longer-lasting positive effects on episodic memory, conceivably through reconsolidation, than anodal tDCS during encoding. Furthermore, we reported, providing new data, a moderate negative correlation between subjective memory complaints and forgetting when anodal tDCS was applied after consolidation with a contextual reminder. This study sheds light on the best-suited timing of stimulation to induce long-lasting positive effects on memory function and might help the clinicians to select the most effective tDCS protocol to prevent memory decline. Copyright © 2016 Elsevier B.V. All rights reserved.

Protective effect of betulinic acid against intracerebroventricular streptozotocin induced cognitive impairment and neuronal damage in rats: Possible neurotransmitters and neuroinflammatory mechanism.

PubMed

Kaundal, Madhu; Deshmukh, Rahul; Akhtar, Mohd

2018-06-01

The purpose of the study was to explore the therapeutic potential of Betulinic acid (BA) in streptozotocin (STZ) induced memory damage in experimental rats. STZ (3mg/kg bilaterally) as intracerebroventrical (icv) route was administered on day 1 and 3 in rats. Donepezil (5mg/kg/day po), used as standard, and BA (5, 10 and 15mg/kg/day po) were administered after 1h of 1st STZ infusion up to 21days. Object recognition task (ORT) for non-spatial, Morris water maze (MWM) for spatial and locomotor activity were performed to evaluate behavioral changes in rats. On 22nd day, animals were decapitated and hippocampus was separated to perform biochemical (AChE, LPO, GSH, nitrite), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (NTs) (dopamine, norepinephrine and serotonin) analysis. STZ infusion significantly impaired memory as observed in MWM and ORT, increased oxidative stress, pro-inflammatory cytokine's level and altered NTs level. Moreover, BA demonstrated a neuroprotective effect in a dose-dependent manner. BA dose dependently (5, 10 and 15mg/kg) significantly restore STZ induced memory changes and pathological abnormalities in rat brain. The findings of the current study suggests that BA protect rat brain from STZ induced neuronal damage via acting through multiple mechanisms and would be used to curb cognitive decline associated with neurodegenerative disorders especially AD. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Expectations about Memory Change Across the Life Span Are Impacted By Aging Stereotypes

PubMed Central

Lineweaver, Tara T.; Berger, Andrea K.; Hertzog, Christopher

2008-01-01

This study examined whether expectations about memory change with age vary for different personality types. Four adjectives from each of Hummert’s age-stereotype trait sets were selected to create 11 adjective clusters varying in both valence (positive versus negative) and relevance to memory functioning. Three hundred and seventy three participants in three age groups rated the memory abilities of target adults, defined by the adjective clusters, across the adult life span. Consistent with past studies, participants believed in age-related memory decline. However, participants rated target adults with positive personality traits as having better memory ability and less age-related memory decline than target adults with negative personality traits. This effect was larger when the traits were relevant to memory than when they were not. Finally, older participants were more strongly influenced by both the valence and the relevance of the personality descriptions than younger participants. PMID:19290748

Job strain and cognitive decline: a prospective study of the framingham offspring cohort.

PubMed

Agbenyikey, W; Karasek, R; Cifuentes, M; Wolf, P A; Seshadri, S; Taylor, J A; Beiser, A S; Au, R

2015-04-01

Workplace stress is known to be related with many behavioral and disease outcomes. However, little is known about its prospective relationship with measures of cognitive decline. To investigate the association of job strain, psychological demands and job control on cognitive decline. Participants from Framingham Offspring cohort (n=1429), were assessed on job strain, and received neuropsychological assessment approximately 15 years and 21 years afterwards. High job strain and low control were associated with decline in verbal learning and memory. Job strain was associated with decline in word recognition skills. Active job and passive job predicted decline in verbal learning and memory relative to low strain jobs in the younger subgroup. Active job and demands were positively associated with abstract reasoning skills. Job strain and job control may influence decline in cognitive performance.

A test of the reward-value hypothesis.

PubMed

Smith, Alexandra E; Dalecki, Stefan J; Crystal, Jonathon D

2017-03-01

Rats retain source memory (memory for the origin of information) over a retention interval of at least 1 week, whereas their spatial working memory (radial maze locations) decays within approximately 1 day. We have argued that different forgetting functions dissociate memory systems. However, the two tasks, in our previous work, used different reward values. The source memory task used multiple pellets of a preferred food flavor (chocolate), whereas the spatial working memory task provided access to a single pellet of standard chow-flavored food at each location. Thus, according to the reward-value hypothesis, enhanced performance in the source memory task stems from enhanced encoding/memory of a preferred reward. We tested the reward-value hypothesis by using a standard 8-arm radial maze task to compare spatial working memory accuracy of rats rewarded with either multiple chocolate or chow pellets at each location using a between-subjects design. The reward-value hypothesis predicts superior accuracy for high-valued rewards. We documented equivalent spatial memory accuracy for high- and low-value rewards. Importantly, a 24-h retention interval produced equivalent spatial working memory accuracy for both flavors. These data are inconsistent with the reward-value hypothesis and suggest that reward value does not explain our earlier findings that source memory survives unusually long retention intervals.

Effect of chronic and acute low-frequency repetitive transcranial magnetic stimulation on spatial memory in rats.

PubMed

Li, Wei; Yang, Yuye; Ye, Qing; Yang, Bo; Wang, Zhengrong

2007-03-15

Repetitive transcranial magnetic stimulation (rTMS) is a novel, non-invasive neurological and psychiatric tool. The low-frequency (1 Hz or less) rTMS is likely to play a particular role in its mechanism of action with different effects in comparison with high-frequency (>1 Hz) rTMS. There is limited information regarding the effect of low-frequency rTMS on spatial memory. In our study, each male Wistar rat was daily given 300 stimuli (1.0 T, 200 micros) at a rate of 0.5 Hz or sham stimulation. We investigated the effects of chronic and acute rTMS on reference/working memory process in Morris water maze test with the hypothesis that the effect would differ by chronic or acute condition. Chronic low-frequency rTMS impaired the retrieval of spatial short- and long-term spatial reference memory but not acquisition process and working memory, whereas acute low-frequency rTMS predominantly induced no deficits in acquisition or short-term spatial reference memory as well as working memory except for long-term reference memory. In summary, chronic 0.5 Hz rTMS disrupts spatial short- and long-term reference memory function, but acute rTMS differently affects reference memory. Chronic low-frequency rTMS may be used to modulate reference memory. Treatment protocols using low-frequency rTMS in neurological and psychiatric disorders need to take into account the potential effect of chronic low-frequency rTMS on memory and other cognitive functions.

Investigating the Effects of Veridicality on Age Differences in Verbal Working Memory

ERIC Educational Resources Information Center

Shake, Matthew C.; Perschke, Meghan K.

2013-01-01

In the typical loaded verbal working memory (WM) span task (e.g., Daneman & Carpenter, 1980), participants judge the veridicality of a series of sentences while simultaneously storing the sentence final word for later recall. Performance declines as the number of sentences is increased; aging exacerbates this decline. The present study examined…

A Virtual Water Maze Revisited: Two-Year Changes in Navigation Performance and their Neural Correlates in Healthy Adults

PubMed Central

Daugherty, Ana M.; Raz, Naftali

2016-01-01

Age-related declines in spatial navigation are associated with deficits in procedural and episodic memory and deterioration of their neural substrates. For the lack of longitudinal evidence, the pace and magnitude of these declines and their neural mediators remain unclear. Here we examined virtual navigation in healthy adults (N=213, age 18–77 years) tested twice, two years apart, with complementary indices of navigation performance (path length and complexity) measured over six learning trials at each occasion. Slopes of skill acquisition curves and longitudinal change therein were estimated in structural equation modeling, together with change in regional brain volumes and iron content (R2* relaxometry). Although performance on the first trial did not differ between occasions separated by two years, the slope of path length improvement over trials was shallower and end-of-session performance worse at follow-up. Advanced age, higher pulse pressure, smaller cerebellar and caudate volumes, and greater caudate iron content were associated with longer search paths, i.e. poorer navigation performance. In contrast, path complexity diminished faster over trials at follow-up, albeit less so in older adults. Improvement in path complexity after two years was predicted by lower baseline hippocampal iron content and larger parahippocampal volume. Thus, navigation path length behaves as an index of perceptual-motor skill that is vulnerable to age-related decline, whereas path complexity may reflect cognitive mapping in episodic memory that improves with repeated testing, although not enough to overcome age-related deficits. PMID:27659539

A virtual water maze revisited: Two-year changes in navigation performance and their neural correlates in healthy adults.

PubMed

Daugherty, Ana M; Raz, Naftali

2017-02-01

Age-related declines in spatial navigation are associated with deficits in procedural and episodic memory and deterioration of their neural substrates. For the lack of longitudinal evidence, the pace and magnitude of these declines and their neural mediators remain unclear. Here we examined virtual navigation in healthy adults (N=213, age 18-77 years) tested twice, two years apart, with complementary indices of navigation performance (path length and complexity) measured over six learning trials at each occasion. Slopes of skill acquisition curves and longitudinal change therein were estimated in structural equation modeling, together with change in regional brain volumes and iron content (R2* relaxometry). Although performance on the first trial did not differ between occasions separated by two years, the slope of path length improvement over trials was shallower and end-of-session performance worse at follow-up. Advanced age, higher pulse pressure, smaller cerebellar and caudate volumes, and greater caudate iron content were associated with longer search paths, i.e. poorer navigation performance. In contrast, path complexity diminished faster over trials at follow-up, albeit less so in older adults. Improvement in path complexity after two years was predicted by lower baseline hippocampal iron content and larger parahippocampal volume. Thus, navigation path length behaves as an index of perceptual-motor skill that is vulnerable to age-related decline, whereas path complexity may reflect cognitive mapping in episodic memory that improves with repeated testing, although not enough to overcome age-related deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

Age-related Associative Memory Deficits in Value-based Remembering: The Contribution of Agenda-based Regulation and Strategy Use

PubMed Central

Ariel, Robert; Price, Jodi; Hertzog, Christopher

2015-01-01

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

Midlife stress alters memory and mood-related behaviors in old age: Role of locally activated glucocorticoids.

PubMed

Wheelan, Nicola; Kenyon, Christopher J; Harris, Anjanette P; Cairns, Carolynn; Al Dujaili, Emad; Seckl, Jonathan R; Yau, Joyce L W

2018-03-01

Chronic exposure to stress during midlife associates with subsequent age-related cognitive decline and may increase the vulnerability to develop psychiatric conditions. Increased hypothalamic-pituitary-adrenal (HPA) axis activity has been implicated in pathogenesis though any causative role for glucocorticoids is unestablished. This study investigated the contribution of local glucocorticoid regeneration by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), in persisting midlife stress-induced behavioral effects in mice. Middle-aged (10 months old) 11β-HSD1-deficient mice and wild-type congenic controls were randomly assigned to 28 days of chronic unpredictable stress or left undisturbed (non-stressed). All mice underwent behavioral testing at the end of the stress/non-stress period and again 6-7 months later. Chronic stress impaired spatial memory in middle-aged wild-type mice. The effects, involving a wide spectrum of behavioral modalities, persisted for 6-7 months after cessation of stress into early senescence. Enduring effects after midlife stress included impaired spatial memory, enhanced contextual fear memory, impaired fear extinction, heightened anxiety, depressive-like behavior, as well as reduced hippocampal glucocorticoid receptor mRNA expression. In contrast, 11β-HSD1 deficient mice resisted both immediate and enduring effects of chronic stress, despite similar stress-induced increases in systemic glucocorticoid activity during midlife stress. In conclusion, chronic stress in midlife exerts persisting effects leading to cognitive and affective dysfunction in old age via mechanisms that depend, at least in part, on brain glucocorticoids generated locally by 11β-HSD1. This finding supports selective 11β-HSD1 inhibition as a novel therapeutic target to ameliorate the long-term consequences of stress-related psychiatric disorders in midlife. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Risk to verbal memory following anterior temporal lobectomy in patients with severe left-sided hippocampal sclerosis.

PubMed

Martin, Roy C; Kretzmer, Tracy; Palmer, Cheryl; Sawrie, Stephen; Knowlton, Robert; Faught, Edward; Morawetz, Richard; Kuzniecky, Ruben

2002-12-01

Previous investigations indicate low risk for memory loss following anterior temporal lobectomy (ATL) in patients with severe hippocampal sclerosis (HS) compared with patients with mild HS. However, these conclusions have been established primarily with group-level analyses. To investigate individual base rate risk for verbal memory loss following ATL in patients who have pathologically verified mild, moderate, or severe HS. One hundred fifteen patients with unilateral temporal lobe epilepsy (68 with left-sided and 47 with right-sided epilepsy) were included. Acquisition, retrieval, and recognition components of verbal memory, as measured by the California Verbal Learning Test, were assessed before and after ATL. Postoperatively, the degree of neuronal loss and reactive gliosis of the hippocampus was assessed via a 3-tiered rating system establishing mild, moderate, and severe pathologic features. Patients with preoperative magnetic resonance imaging-based evidence of lesions outside the mesial temporal area (side of surgical resection) were excluded. Neither seizure laterality nor severity of HS was associated with preoperative verbal memory performance. Postoperatively, the left-sided ATL group demonstrated significant decline across the acquisition (P<.01), retrival (P<.001), and recognition (P<.001) verbal memory components compared with the right-sided ATL group. Patients who underwent left-sided ATL and had mild HS displayed the largest magnitude and percentage proportion of postoperative decline across all verbal memory components. However, 28 (48%) of the 58 patients who underwent left-sided ATL and who had moderate and severe HS displayed statistically reliable declines on retrieval aspects of verbal memory. Most patients undergoing right-sided ATL, regardless of the extent of hippocampal pathologic features, displayed no postoperative memory change. Substantial individual heterogeneity of memory outcome exists across groups of patients undergoing ATL, with various degrees of pathologically verified HS. Patients undergoing left-sided ATL who have mild HS seem at greatest risk for broad-spectrum verbal memory decline. However, when examining outcome on a patient-by-patient basis, many patients undergoing left-sided ATL who have moderate to severe HS were also vulnerable to verbal memory loss. This risk seems selective to a retrieval-based aspect of verbal memory.

Biphasic effect of citral, a flavoring and scenting agent, on spatial learning and memory in rats.

PubMed

Yang, Zheqiong; Xi, Jinlei; Li, Jihong; Qu, Wen

2009-10-01

Although some central effects of citral have been reported, cognitive effects on spatial memory have not been investigated. The evidence showed that citral can regulate the synthesis of retinoic acid (RA), which exerts a vital function in the development and maintenance of spatial memory. In this study, we applied Morris water maze to test the effect of citral on animals' spatial learning and memory. To elucidate the mechanism of this effect, we also measured the retinoic acid concentration in rats' hippocampus by high performance liquid chromatography (HPLC). Our data implied biphasic effects of citral. The low dose (0.1 mg/kg) of citral improved the spatial learning capability, and enhanced the spatial reference memory of rats, whereas the high dose (1.0 mg/kg) was like to produce the opposite effects. Meanwhile, the low dose of citral increased the hippocampal retinoic acid concentration, while the high dose decreased it. Due to the quick elimination and non-bioaccumulation in the body, effects of citral on spatial memory in this study seemed to be indirect actions. The change in hippocampal retinoic acid concentration induced by different doses of citral might be responsible for the biphasic effect of citral on spatial learning and memory.

Evidence for age-associated cognitive decline from Internet game scores.

PubMed

Geyer, Jason; Insel, Philip; Farzin, Faraz; Sternberg, Daniel; Hardy, Joseph L; Scanlon, Michael; Mungas, Dan; Kramer, Joel; Mackin, R Scott; Weiner, Michael W

2015-06-01

Lumosity's Memory Match (LMM) is an online game requiring visual working memory. Change in LMM scores may be associated with individual differences in age-related changes in working memory. Effects of age and time on LMM learning and forgetting rates were estimated using data from 1890 game sessions for users aged 40 to 79 years. There were significant effects of age on baseline LMM scores (β = -.31, standard error or SE = .02, P < .0001) and lower learning rates (β = -.0066, SE = .0008, P < .0001). A sample size of 202 subjects/arm was estimated for a 1-year study for subjects in the lower quartile of game performance. Online memory games have the potential to identify age-related decline in cognition and to identify subjects at risk for cognitive decline with smaller sample sizes and lower cost than traditional recruitment methods.

Gap junctions between interneurons are required for normal spatial coding in the hippocampus and short-term spatial memory

PubMed Central

Allen, Kevin; Fuchs, Elke C.; Jaschonek, Hannah; Bannerman, David M.; Monyer, Hannah

2011-01-01

Gap junctions containing connexin-36 (Cx36) electrically couple interneurons in many brain regions and synchronize their activity. We used Cx36 knockout 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 to 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. PMID:21525295

Reversible Hippocampal Lesions Disrupt Water Maze Performance during Both Recent and Remote Memory Tests

ERIC Educational Resources Information Center

Broadbent, Nicola J.; Squire, Larry R.; Clark, Robert E.

2006-01-01

Conventional lesion methods have shown that damage to the rodent hippocampus can impair previously acquired spatial memory in tasks such as the water maze. In contrast, work with reversible lesion methods using a different spatial task has found remote memory to be spared. To determine whether the finding of spared remote spatial memory depends on…

Developmental Differences in the Influence of Distractors on Maintenance in Spatial Working Memory

ERIC Educational Resources Information Center

Schutte, Anne R.; Keiser, Brian A.; Beattie, Heidi L.

2017-01-01

This study examined whether attention to a location plays a role in the maintenance of locations in spatial working memory in young children as it does in adults. This study was the first to investigate whether distractors presented during the delay of a spatial working-memory task influenced young children's memory responses. Across 2…

Impact of Spatial and Verbal Short-Term Memory Load on Auditory Spatial Attention Gradients.

PubMed

Golob, Edward J; Winston, Jenna; Mock, Jeffrey R

2017-01-01

Short-term memory load can impair attentional control, but prior work shows that the extent of the effect ranges from being very general to very specific. One factor for the mixed results may be reliance on point estimates of memory load effects on attention. Here we used auditory attention gradients as an analog measure to map-out the impact of short-term memory load over space. Verbal or spatial information was maintained during an auditory spatial attention task and compared to no-load. Stimuli were presented from five virtual locations in the frontal azimuth plane, and subjects focused on the midline. Reaction times progressively increased for lateral stimuli, indicating an attention gradient. Spatial load further slowed responses at lateral locations, particularly in the left hemispace, but had little effect at midline. Verbal memory load had no (Experiment 1), or a minimal (Experiment 2) influence on reaction times. Spatial and verbal load increased switch costs between memory encoding and attention tasks relative to the no load condition. The findings show that short-term memory influences the distribution of auditory attention over space; and that the specific pattern depends on the type of information in short-term memory.

Impact of Spatial and Verbal Short-Term Memory Load on Auditory Spatial Attention Gradients

PubMed Central

Golob, Edward J.; Winston, Jenna; Mock, Jeffrey R.

2017-01-01

Short-term memory load can impair attentional control, but prior work shows that the extent of the effect ranges from being very general to very specific. One factor for the mixed results may be reliance on point estimates of memory load effects on attention. Here we used auditory attention gradients as an analog measure to map-out the impact of short-term memory load over space. Verbal or spatial information was maintained during an auditory spatial attention task and compared to no-load. Stimuli were presented from five virtual locations in the frontal azimuth plane, and subjects focused on the midline. Reaction times progressively increased for lateral stimuli, indicating an attention gradient. Spatial load further slowed responses at lateral locations, particularly in the left hemispace, but had little effect at midline. Verbal memory load had no (Experiment 1), or a minimal (Experiment 2) influence on reaction times. Spatial and verbal load increased switch costs between memory encoding and attention tasks relative to the no load condition. The findings show that short-term memory influences the distribution of auditory attention over space; and that the specific pattern depends on the type of information in short-term memory. PMID:29218024

Cued memory decline in biomarker-defined preclinical Alzheimer disease.

PubMed

Papp, Kathryn V; Rentz, Dorene M; Mormino, Elizabeth C; Schultz, Aaron P; Amariglio, Rebecca E; Quiroz, Yakeel; Johnson, Keith A; Sperling, Reisa A

2017-04-11

To determine whether a decline in cued recall is observable in the preclinical stage of Alzheimer disease (AD) in clinically normal older adults with elevated β-amyloid (Aβ) burden on PET imaging. Clinically normal older adults underwent baseline neuroimaging (PET to assess Aβ +/- status and MRI) and annual neuropsychological testing. Cox proportional hazards models were used to assess the relative risk of cued memory decline (drop of 1, 2, 3, or 4 points on the total score of the Free and Cued Selective Reminding Test) in relation to neuroimaging measures, functional status, age, sex, and education. A total of 276 older adults (Clinical Dementia Rating = 0, mean Mini-Mental State Examination score = 29 ± 1.06) were followed up for a mean of 3.6 ± 1.2 years. Despite the infrequency of cued memory decline (only 19% of participants scored ≤46/48 in total recall by year 3), Aβ + participants were 3.55 times (95% confidence interval = 1.77-7.12) more likely to exhibit decline in total recall (≤46/48) compared with their Aβ - peers. Furthermore, Aβ + participants who scored ≤46/48 had smaller hippocampal volumes ( t = 3.37, p = 0.001) and evidence of early functional decline, i.e., greater risk of progression to global Clinical Dementia Rating of 0.5 (χ 2 = 14.30, p < 0.001), compared with their Aβ + peers with intact total recall. Cued memory decline in healthy older adults may be particularly indicative of Aβ-related decline during the preclinical stage of AD and useful for identifying Aβ + clinically normal individuals at greatest risk of short-term clinical progression. © 2017 American Academy of Neurology.

Cued memory decline in biomarker-defined preclinical Alzheimer disease

PubMed Central

Rentz, Dorene M.; Mormino, Elizabeth C.; Schultz, Aaron P.; Amariglio, Rebecca E.; Quiroz, Yakeel; Johnson, Keith A.; Sperling, Reisa A.

2017-01-01

Objective: To determine whether a decline in cued recall is observable in the preclinical stage of Alzheimer disease (AD) in clinically normal older adults with elevated β-amyloid (Aβ) burden on PET imaging. Methods: Clinically normal older adults underwent baseline neuroimaging (PET to assess Aβ+/− status and MRI) and annual neuropsychological testing. Cox proportional hazards models were used to assess the relative risk of cued memory decline (drop of 1, 2, 3, or 4 points on the total score of the Free and Cued Selective Reminding Test) in relation to neuroimaging measures, functional status, age, sex, and education. Results: A total of 276 older adults (Clinical Dementia Rating = 0, mean Mini-Mental State Examination score = 29 ± 1.06) were followed up for a mean of 3.6 ± 1.2 years. Despite the infrequency of cued memory decline (only 19% of participants scored ≤46/48 in total recall by year 3), Aβ+ participants were 3.55 times (95% confidence interval = 1.77–7.12) more likely to exhibit decline in total recall (≤46/48) compared with their Aβ− peers. Furthermore, Aβ+ participants who scored ≤46/48 had smaller hippocampal volumes (t = 3.37, p = 0.001) and evidence of early functional decline, i.e., greater risk of progression to global Clinical Dementia Rating of 0.5 (χ2 = 14.30, p < 0.001), compared with their Aβ+ peers with intact total recall. Conclusions: Cued memory decline in healthy older adults may be particularly indicative of Aβ-related decline during the preclinical stage of AD and useful for identifying Aβ+ clinically normal individuals at greatest risk of short-term clinical progression. PMID:28283594

Tests of the Dynamic Field Theory and The Spatial Precision Hypothesis: Capturing a Qualitative Developmental Transition in Spatial Working Memory

ERIC Educational Resources Information Center

Schutte, Anne R.; Spencer, John P.

2009-01-01

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…

Aging and the Effects of Exploratory Behavior on Spatial Memory.

PubMed

Varner, Kaitlin M; Dopkins, Stephen; Philbeck, John W

2016-03-01

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. © The Author(s) 2016.

The Multifold Relationship Between Memory and Decision Making: An Individual-differences Study

PubMed Central

Del Missier, Fabio; Mäntylä, Timo; Hansson, Patrik; Bruine de Bruin, Wändi; Parker, Andrew M.; Nilsson, Lars-Göran

2014-01-01

Several judgment and decision-making tasks are assumed to involve memory functions, but significant knowledge gaps on the memory processes underlying these tasks remain. In a study on 568 adults between 25 to 80 years, hypotheses were tested on the specific relationships between individual differences in working memory, episodic memory, and semantic memory, respectively, and six main components of decision-making competence. In line with the hypotheses, working memory was positively related with the more cognitively-demanding tasks (Resistance to Framing, Applying Decision Rules, and Under/Overconfidence), whereas episodic memory was positively associated with a more experience-based judgment task (Recognizing Social Norms). Furthermore, semantic memory was positively related with two more knowledge-based decision-making tasks (Consistency in Risk Perception and Resistance to Sunk Costs). Finally, the age-related decline observed in some of the decision-making tasks was (partially or totally) mediated by the age-related decline in working memory or episodic memory. These findings are discussed in relation to the functional roles fulfilled by different memory processes in judgment and decision-making tasks. PMID:23565790

Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex

PubMed Central

Ku, Shih-pi; Nakamura, Nozomu H.; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M.

2017-01-01

The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc, which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval. PMID:28790897

Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex.

PubMed

Ku, Shih-Pi; Nakamura, Nozomu H; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M

2017-01-01

The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc , which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval.

Hi-Corrector: a fast, scalable and memory-efficient package for normalizing large-scale Hi-C data.

PubMed

Li, Wenyuan; Gong, Ke; Li, Qingjiao; Alber, Frank; Zhou, Xianghong Jasmine

2015-03-15

Genome-wide proximity ligation assays, e.g. Hi-C and its variant TCC, have recently become important tools to study spatial genome organization. Removing biases from chromatin contact matrices generated by such techniques is a critical preprocessing step of subsequent analyses. The continuing decline of sequencing costs has led to an ever-improving resolution of the Hi-C data, resulting in very large matrices of chromatin contacts. Such large-size matrices, however, pose a great challenge on the memory usage and speed of its normalization. Therefore, there is an urgent need for fast and memory-efficient methods for normalization of Hi-C data. We developed Hi-Corrector, an easy-to-use, open source implementation of the Hi-C data normalization algorithm. Its salient features are (i) scalability-the software is capable of normalizing Hi-C data of any size in reasonable times; (ii) memory efficiency-the sequential version can run on any single computer with very limited memory, no matter how little; (iii) fast speed-the parallel version can run very fast on multiple computing nodes with limited local memory. The sequential version is implemented in ANSI C and can be easily compiled on any system; the parallel version is implemented in ANSI C with the MPI library (a standardized and portable parallel environment designed for solving large-scale scientific problems). The package is freely available at http://zhoulab.usc.edu/Hi-Corrector/. © The Author 2014. Published by Oxford University Press.

Short-term inhibition of 11β-hydroxysteroid dehydrogenase type 1 reversibly improves spatial memory but persistently impairs contextual fear memory in aged mice

PubMed Central

Wheelan, Nicola; Webster, Scott P.; Kenyon, Christopher J.; Caughey, Sarah; Walker, Brian R.; Holmes, Megan C.; Seckl, Jonathan R.; Yau, Joyce L.W.

2015-01-01

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

Short-term inhibition of 11β-hydroxysteroid dehydrogenase type 1 reversibly improves spatial memory but persistently impairs contextual fear memory in aged mice.

PubMed

Wheelan, Nicola; Webster, Scott P; Kenyon, Christopher J; Caughey, Sarah; Walker, Brian R; Holmes, Megan C; Seckl, Jonathan R; Yau, Joyce L W

2015-04-01

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dorsal CA1 interneurons contribute to acute stress-induced spatial memory deficits.

PubMed

Yu, Jing-Ying; Fang, Ping; Wang, Chi; Wang, Xing-Xing; Li, Kun; Gong, Qian; Luo, Ben-Yan; Wang, Xiao-Dong

2018-06-01

Exposure to severely stressful experiences disrupts the activity of neuronal circuits and impairs declarative memory. GABAergic interneurons coordinate neuronal network activity, but their involvement in stress-evoked memory loss remains to be elucidated. Here, we provide evidence that interneurons in area CA1 of the dorsal hippocampus partially modulate acute stress-induced memory deficits. In adult male mice, both acute forced swim stress and restraint stress impaired hippocampus-dependent spatial memory and increased the density of c-fos-positive interneurons in the dorsal CA1. Selective activation of dorsal CA1 interneurons by chemogenetics disrupted memory performance in the spatial object recognition task. In comparison, anxiety-related behavior, spatial working memory and novel object recognition memory remained intact when dorsal CA1 interneurons were overactivated. Moreover, chemogenetic activation of dorsal CA1 interneurons suppressed the activity of adjacent pyramidal neurons, whereas a single exposure to forced swim stress but not restraint stress increased the activity of CA1 pyramidal neurons. However, chemogenetic inhibition of dorsal CA1 interneurons led to spatial memory impairments and failed to attenuate acute stress-induced memory loss. These findings suggest that acute stress may overactivate interneurons in the dorsal CA1, which reduces the activity of pyramidal neurons and in turn disrupts long-term memory. Copyright © 2018 Elsevier Ltd. All rights reserved.

Thermodynamic Model of Spatial Memory

NASA Astrophysics Data System (ADS)

Kaufman, Miron; Allen, P.

1998-03-01

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.

Central executive involvement in children's spatial memory.

PubMed

Ang, Su Yin; Lee, Kerry

2008-11-01

Previous research with adults found that spatial short-term and working memory tasks impose similar demands on executive resources. We administered spatial short-term and working memory tasks to 8- and 11-year-olds in three separate experiments. In Experiments 1 and 2 an executive suppression task (random number generation) was found to impair performances on a short-term memory task (Corsi blocks), a working memory task (letter rotation), and a spatial visualisation task (paper folding). In Experiment 3 an articulatory suppression task only impaired performance on the working memory task. These results suggest that short-term and working memory performances are dependent on executive resources. The degree to which the short-term memory task was dependent on executive resources was expected to be related to the amount of experience children have had with such tasks. Yet we found no significant age-related suppression effects. This was attributed to differences in employment of cognitive strategies by the older children.

Sex differences in visual-spatial working memory: A meta-analysis.

PubMed

Voyer, Daniel; Voyer, Susan D; Saint-Aubin, Jean

2017-04-01

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.

Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation

PubMed Central

Dzieciol, Anna M.; Gadian, David G.; Jentschke, Sebastian; Doeller, Christian F.; Burgess, Neil; Mishkin, Mortimer

2015-01-01

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 hippocampal integrity in humans is not well documented. We investigated spatial recall using a virtual environment in two groups of patients with hippocampal damage (moderate/severe) and a normal control group. The results showed that patients with severe hippocampal damage are impaired in learning and recalling allocentric spatial information. Furthermore, hippocampal volume reduction impaired allocentric navigation beyond what can be predicted by memory quotient as a widely used measure of general memory function. PMID:26490854

Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation.

PubMed

Guderian, Sebastian; Dzieciol, Anna M; Gadian, David G; Jentschke, Sebastian; Doeller, Christian F; Burgess, Neil; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-10-21

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. 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 hippocampal integrity in humans is not well documented. We investigated spatial recall using a virtual environment in two groups of patients with hippocampal damage (moderate/severe) and a normal control group. The results showed that patients with severe hippocampal damage are impaired in learning and recalling allocentric spatial information. Furthermore, hippocampal volume reduction impaired allocentric navigation beyond what can be predicted by memory quotient as a widely used measure of general memory function. Copyright © 2015 Guderian et al.

How Does the Sparse Memory “Engram” Neurons Encode the Memory of a Spatial–Temporal Event?

PubMed Central

Guan, Ji-Song; Jiang, Jun; Xie, Hong; Liu, Kai-Yuan

2016-01-01

Episodic memory in human brain is not a fixed 2-D picture but a highly dynamic movie serial, integrating information at both the temporal and the spatial domains. Recent studies in neuroscience reveal that memory storage and recall are closely related to the activities in discrete memory engram (trace) neurons within the dentate gyrus region of hippocampus and the layer 2/3 of neocortex. More strikingly, optogenetic reactivation of those memory trace neurons is able to trigger the recall of naturally encoded memory. It is still unknown how the discrete memory traces encode and reactivate the memory. Considering a particular memory normally represents a natural event, which consists of information at both the temporal and spatial domains, it is unknown how the discrete trace neurons could reconstitute such enriched information in the brain. Furthermore, as the optogenetic-stimuli induced recall of memory did not depend on firing pattern of the memory traces, it is most likely that the spatial activation pattern, but not the temporal activation pattern of the discrete memory trace neurons encodes the memory in the brain. How does the neural circuit convert the activities in the spatial domain into the temporal domain to reconstitute memory of a natural event? By reviewing the literature, here we present how the memory engram (trace) neurons are selected and consolidated in the brain. Then, we will discuss the main challenges in the memory trace theory. In the end, we will provide a plausible model of memory trace cell network, underlying the conversion of neural activities between the spatial domain and the temporal domain. We will also discuss on how the activation of sparse memory trace neurons might trigger the replay of neural activities in specific temporal patterns. PMID:27601979

Sports training enhances visuo-spatial cognition regardless of open-closed typology

PubMed Central

Hsieh, Shu-Shih; Chen, Kuan-Fu; Chang, Yu-Kai

2017-01-01

The aim of this study was to investigate the effects of open and closed sport participation on visuo-spatial attention and memory performance among young adults. Forty-eight young adults—16 open-skill athletes, 16 closed-skill athletes, and 16 non-athletes controls—were recruited for the study. Both behavioral performance and event-related potential (ERP) measurement were assessed when participants performed non-delayed and delayed match-to-sample task that tested visuo-spatial attention and memory processing. Results demonstrated that regardless of training typology, the athlete groups exhibited shorter reaction times in both the visuo-spatial attention and memory conditions than the control group with no existence of speed-accuracy trade-off. Similarly, a larger P3 amplitudes were observed in both athlete groups than in the control group for the visuo-spatial memory condition. These findings suggest that sports training, regardless of typology, are associated with superior visuo-spatial attention and memory performance, and more efficient neural resource allocation in memory processing. PMID:28560098

Sex Differences in Mental Rotation and Spatial Visualization Ability: Can They Be Accounted for by Differences in Working Memory Capacity?

ERIC Educational Resources Information Center

Kaufman, Scott Barry

2007-01-01

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…

NMDA Signaling in CA1 Mediates Selectively the Spatial Component of Episodic Memory

ERIC Educational Resources Information Center

Place, Ryan; Lykken, Christy; Beer, Zachery; Suh, Junghyup; McHugh, Thomas J.; Tonegawa, Susumu; Eichenbaum, Howard; Sauvage, Magdalena M.

2012-01-01

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…

β-Amyloid binding in elderly subjects with declining or stable episodic memory function measured with PET and [¹¹C]AZD2184.

PubMed

Mattsson, Patrik; Forsberg, Anton; Persson, Jonas; Nyberg, Lars; Nilsson, Lars-Göran; Halldin, Christer; Farde, Lars

2015-09-01

Cognitive decline has been suggested as an early marker for later onset of Alzheimer's disease. We therefore explored the relationship between decline in episodic memory and β-amyloid using positron emission tomography (PET) and [(11)C]AZD2184, a radioligand with potential to detect low levels of amyloid deposits. Healthy elderly subjects with declining (n = 10) or stable (n = 10) episodic memory over 15 years were recruited from the population-based Betula study and examined with PET. Brain radioactivity was measured after intravenous administration of [(11)C]AZD2184. The binding potential BP ND was calculated using linear graphical analysis with the cerebellum as reference region. The binding of [(11)C]AZD2184 in total grey matter was generally low in the declining group, whereas some binding could be observed in the stable group. Mean BP ND was significantly higher in the stable group compared to the declining group (p = 0.019). An observation was that the three subjects with the highest BP ND were ApoE ε4 allele carriers. We conclude that cognitive decline in the general population does not seem to stand by itself as an early predictor for amyloid deposits.

Job Strain and Cognitive Decline: A Prospective Study of the Framingham Offspring Cohort

PubMed Central

Agbenyikey, W; Karasek, R; Cifuentes, M; Wolf, PA; Seshadri, S; Taylor, JA; Beiser, AS; Au, R

2017-01-01

Background Workplace stress is known to be related with many behavioral and disease outcomes. However, little is known about its prospective relationship with measures of cognitive decline. Objective To investigate the association of job strain, psychological demands and job control on cognitive decline. Methods Participants from Framingham Offspring cohort (n=1429), were assessed on job strain, and received neuropsychological assessment approximately 15 years and 21 years afterwards. Results High job strain and low control were associated with decline in verbal learning and memory. Job strain was associated with decline in word recognition skills. Active job and passive job predicted decline in verbal learning and memory relative to low strain jobs in the younger subgroup. Active job and demands were positively associated with abstract reasoning skills. Conclusions Job strain and job control may infuence decline in cognitive performance. PMID:25890602

Developmental gender differences in children in a virtual spatial memory task.

PubMed

León, Irene; Cimadevilla, José Manuel; Tascón, Laura

2014-07-01

Behavioral achievements are the product of brain maturation. During postnatal development, the medial temporal lobe completes its maturation, and children acquire new memory abilities. In recent years, virtual reality-based tasks have been introduced in the neuropsychology field to assess different cognitive functions. In this work, desktop virtual reality tasks are combined with classic psychometric tests to assess spatial abilities in 4- to 10-year-old children. Fifty boys and 50 girls 4-10-years of age participated in this study. Spatial reference memory and spatial working memory were assessed using a desktop virtual reality-based task. Other classic psychometric tests were also included in this work (e.g., the Corsi Block Tapping Test, digit tests, 10/36 Spatial Recall Test). In general terms, 4- and 5-year-old groups showed poorer performance than the older groups. However, 5-year-old children showed basic spatial navigation abilities with little difficulty. In addition, boys outperformed girls from the 6-8-year-old groups. Gender differences only emerged in the reference-memory version of the spatial task, whereas both sexes displayed similar performances in the working-memory version. There was general improvement in the performance of different tasks in children older than 5 years. However, results also suggest that brain regions involved in allocentric memory are functional even at the age of 5. In addition, the brain structures underlying reference memory mature later in girls than those required for the working memory.

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

PubMed

Banta Lavenex, Pamela; Lecci, Sandro; Prêtre, Vincent; Brandner, Catherine; Mazza, Christian; Pasquier, Jérôme; Lavenex, Pierre

2011-05-16

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. Copyright © 2011 Elsevier B.V. All rights reserved.

Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies

PubMed Central

Arvanitakis, Z.; Yu, L.; Boyle, P. A.; Leurgans, S. E.; Bennett, D. A.

2012-01-01

Lewy bodies are common in the ageing brain and often co-occur with Alzheimer’s disease pathology. There is little known regarding the independent role of Lewy body pathology in cognition impairment, decline and fluctuations in community-dwelling older persons. We examined the contribution of Lewy body pathology to dementia, global cognition, cognitive domains, cognitive decline and fluctuations in 872 autopsied subjects (mean age = 87.9 years) from the Rush Religious Order Study (n = 491) and Memory and Aging Project (n = 381) longitudinal community-based clinical–pathological studies. Dementia was based on a clinical evaluation; annual cognitive performance tests were used to create a measure of global cognition and five cognitive domains. Lewy body type was determined by using α-synuclein immunostained sections of substantia nigra, limbic and neocortical regions. Statistical models included multiple regression models for dementia and cognition and mixed effects models for decline. Cognitive fluctuations were estimated by comparing standard deviations of individual residuals from mean trajectories of decline in those with and without Lewy bodies. All models controlled for age, sex, education, Alzheimer’s disease pathology and infarcts. One hundred and fifty-seven subjects (18%) exhibited Lewy body pathology (76 neocortical-type, 54 limbic-type and 27 nigra-predominant). One hundred and three (66%) subjects with Lewy body pathology had a pathologic diagnosis of Alzheimer’s disease. Neocortical-type, but not nigral-predominant or limbic-type Lewy body pathology was related to an increased odds of dementia (odds ratio = 3.21; 95% confidence interval = 1.78–5.81) and lower cognition (P < 0.001) including episodic memory function (P < 0.001) proximate to death. Neocortical-type Lewy body pathology was also related to a faster decline in global cognition (P < 0.001), decline in all five specific cognitive domains (all P-values < 0.001), and to fluctuations in decline of working and semantic memory (P-values < 0.001). Limbic-type Lewy body pathology was related to lower and faster decline in visuospatial skills (P = 0.042). The relationship of Lewy body pathology to cognition and dementia was not modified by Alzheimer’s disease pathology. Neocortical-type Lewy body pathology is associated with increased odds of dementia; lower and more rapid decline in all cognitive domains including episodic memory and fluctuations in decline in semantic and working memory. Limbic-type Lewy body pathology is specifically associated with lower and more rapid decline in visuospatial skills. The effect of Lewy body pathology on cognition appears to be independent of Alzheimer’s disease pathology. PMID:23065790

Functional neuroimaging and behavioral correlates of capacity decline in visual short-term memory after sleep deprivation.

PubMed

Chee, Michael W L; Chuah, Y M Lisa

2007-05-29

Sleep deprivation (SD) impairs short-term memory, but it is unclear whether this is because of reduced storage capacity or processes contributing to appropriate information encoding. We evaluated 30 individuals twice, once after a night of normal sleep and again after 24 h of SD. In each session, we evaluated visual memory capacity by presenting arrays of one to eight colored squares. Additionally, we measured cortical responses to varying visual array sizes without engaging memory. The magnitude of intraparietal sulcus activation and memory capacity after normal sleep were highly correlated. SD elicited a pattern of activation in both tasks, indicating that deficits in visual processing and visual attention accompany and could account for loss of short-term memory capacity. Additionally, a comparison between better and poorer performers showed that preservation of precuneus and temporoparietal junction deactivation with increasing memory load corresponds to less performance decline when one is sleep-deprived.

Cognitive Changes Across the Menopause Transition: A Longitudinal Evaluation of the Impact of Age and Ovarian Status on Spatial Memory

PubMed Central

Koebele, Stephanie V.; Mennenga, Sarah E.; Hiroi, Ryoko; Quihuis, Alicia M.; Hewitt, Lauren T.; Poisson, Mallori L.; George, Christina; Mayer, Loretta P.; Dyer, Cheryl A.; Aiken, Leona S.; Demers, Laurence M.; Carson, Catherine; Bimonte-Nelson, Heather A.

2017-01-01

Cognitive changes that occur during mid-life and beyond are linked to both aging and the menopause transition. Studies in women suggest that the age at menopause onset can impact cognitive status later in life; yet, little is known about memory changes that occur during the transitional period to the post-menopausal state. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of perimenopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the trajectory of cognitive change across time with normal aging and aging with transitional menopause via VCD-induced follicular depletion, as well as to evaluate whether age at the onset of follicular depletion plays a role in cognitive outcomes. Animals experiencing the onset of menopause at a younger age exhibited impaired spatial memory early in the transition to a follicle-deplete state. Additionally, at the mid- and post- follicular depletion time points, VCD-induced follicular depletion amplified an age effect on memory. Overall, these findings suggest that the age at the onset of menopause is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study illustrates how age at menopause onset might impact cognition in menopausal women, and provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition period. Hormone therapy during this critical juncture might be especially efficacious at attenuating age- and menopause- related cognitive decline, producing healthy brain aging profiles in women who retain their ovaries throughout their lifespan. PMID:27793768

Cognitive changes across the menopause transition: A longitudinal evaluation of the impact of age and ovarian status on spatial memory.

PubMed

Koebele, Stephanie V; Mennenga, Sarah E; Hiroi, Ryoko; Quihuis, Alicia M; Hewitt, Lauren T; Poisson, Mallori L; George, Christina; Mayer, Loretta P; Dyer, Cheryl A; Aiken, Leona S; Demers, Laurence M; Carson, Catherine; Bimonte-Nelson, Heather A

2017-01-01

Cognitive changes that occur during mid-life and beyond are linked to both aging and the menopause transition. Studies in women suggest that the age at menopause onset can impact cognitive status later in life; yet, little is known about memory changes that occur during the transitional period to the postmenopausal state. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of perimenopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the trajectory of cognitive change across time with normal aging and aging with transitional menopause via VCD-induced follicular depletion, as well as to evaluate whether age at the onset of follicular depletion plays a role in cognitive outcomes. Animals experiencing the onset of menopause at a younger age exhibited impaired spatial memory early in the transition to a follicle-deplete state. Additionally, at the mid- and post- follicular depletion time points, VCD-induced follicular depletion amplified an age effect on memory. Overall, these findings suggest that age at the onset of menopause is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study illustrates how age at menopause onset might impact cognition in menopausal women, and provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition period. Hormone therapy during this critical juncture might be especially efficacious at attenuating age- and menopause- related cognitive decline, producing healthy brain aging profiles in women who retain their ovaries throughout their lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

Activation of Gαq Signaling Enhances Memory Consolidation and Slows Cognitive Decline.

PubMed

Arey, Rachel N; Stein, Geneva M; Kaletsky, Rachel; Kauffman, Amanda; Murphy, Coleen T

2018-05-02

Perhaps the most devastating decline with age is the loss of memory. Therefore, identifying mechanisms to restore memory function with age is critical. Using C. elegans associative learning and memory assays, we identified a gain-of-function G αq signaling pathway mutant that forms a long-term (cAMP response element binding protein [CREB]-dependent) memory following one conditioned stimulus-unconditioned stimulus (CS-US) pairing, which usually requires seven CS-US pairings. Increased CREB activity in AIM interneurons reduces the threshold for memory consolidation through transcription of a set of previously identified "long-term memory" genes. Enhanced G αq signaling in the AWC sensory neuron is both necessary and sufficient for improved memory and increased AIM CREB activity, and activation of G αq specifically in aged animals rescues the ability to form memory. Activation of G αq in AWC sensory neurons non-cell autonomously induces consolidation after one CS-US pairing, enabling both cognitive function maintenance with age and restoration of memory function in animals with impaired memory performance without decreased longevity. Copyright © 2018 Elsevier Inc. All rights reserved.

Online assessment of risk factors for dementia and cognitive function in healthy adults.

PubMed

Huntley, J; Corbett, A; Wesnes, K; Brooker, H; Stenton, R; Hampshire, A; Ballard, C

2018-02-01

Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation. Managing these risk factors in late midlife and older age may help reduce the risk of dementia; however, it is unclear whether these factors also relate to cognitive performance in older individuals without dementia. Data from 14 201 non-demented individuals aged >50 years who enrolled in the online PROTECT study were used to examine the relationship between cognitive function and known modifiable risk factors for dementia. Multivariate regression analyses were conducted on 4 cognitive outcomes assessing verbal and spatial working memory, visual episodic memory, and verbal reasoning. Increasing age was associated with reduced performance across all tasks. Higher educational achievement, the presence of a close confiding relationship, and moderate alcohol intake were associated with benefits across all 4 cognitive tasks, and exercise was associated with better performance on verbal reasoning and verbal working memory tasks. A diagnosis of depression was negatively associated with performance on visual episodic memory and working memory tasks, whereas being underweight negatively affected performance on all tasks apart from verbal working memory. A history of stroke was negatively associated with verbal reasoning and working memory performance. Known modifiable risk factors for dementia are associated with cognitive performance in non-demented individuals in late midlife and older age. This provides further support for public health interventions that seek to manage these risk factors across the lifespan. Copyright © 2017 John Wiley & Sons, Ltd.

Differential association of left and right hippocampal volumes with verbal episodic and spatial memory in older adults.

PubMed

Ezzati, Ali; Katz, Mindy J; Zammit, Andrea R; Lipton, Michael L; Zimmerman, Molly E; Sliwinski, Martin J; Lipton, Richard B

2016-12-01

The hippocampus plays a critical role in verbal and spatial memory, thus any pathological damage to this formation may lead to cognitive impairment. It is suggested that right and left hippocampi are affected differentially in healthy or pathologic aging. The purpose of this study was to test the hypothesis that verbal episodic memory performance is associated with left hippocampal volume (HV) while spatial memory is associated with right HV. 115 non-demented adults over age 70 were drawn from the Einstein Aging Study. Verbal memory was measured using the free recall score from the Free and Cued Selective Reminding Test - immediate recall (FCSRT-IR), logical memory immediate and delayed subtests (LM-I and LM-II) from the Wechsler Memory Scale-Revised (WMS-R). Spatial Memory was measured using a computerized dot memory paradigm that has been validated for use in older adults. All participants underwent 3T MRI with subsequent automatized measurement of the volume of each hippocampus. The sample had a mean age of 78.7 years (SD=5.0); 57% were women, and 52% were white. Participants had a mean of 14.3 years (SD=3.5) of education. In regression models, two tests of verbal memory (FCSRT-IR free recall and LM-II) were positively associated with left HV, but not with right HV. Performance on the spatial memory task was associated with right HV, but not left HV. Our findings support the hypothesis that the left hippocampus plays a critical role in episodic verbal memory, while right hippocampus might be more important for spatial memory processing among non-demented older adults. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spatial contrast sensitivity - Effects of age, test-retest, and psychophysical method

NASA Technical Reports Server (NTRS)

Higgins, Kent E.; Jaffe, Myles J.; Caruso, Rafael C.; Demonasterio, Francisco M.

1988-01-01

Two different psychophysical methods were used to test the spatial contrast sensitivity in normal subjects from five age groups. The method of adjustment showed a decline in sensitivity with increasing age at all spatial frequencies, while the forced-choice procedure showed an age-related decline predominantly at high spatial frequencies. It is suggested that a neural component is responsible for this decline.

Hippocampal 5-HT1A Receptor and Spatial Learning and Memory

PubMed Central

Glikmann-Johnston, Yifat; Saling, Michael M.; Reutens, David C.; Stout, Julie C.

2015-01-01

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

The role of the hippocampus in navigation is memory

PubMed Central

2017-01-01

There is considerable research on the neurobiological mechanisms within the hippocampal system that support spatial navigation. In this article I review the literature on navigational strategies in humans and animals, observations on hippocampal function in navigation, and studies of hippocampal neural activity in animals and humans performing different navigational tasks and tests of memory. Whereas the hippocampus is essential to spatial navigation via a cognitive map, its role derives from the relational organization and flexibility of cognitive maps and not from a selective role in the spatial domain. Correspondingly, hippocampal networks map multiple navigational strategies, as well as other spatial and nonspatial memories and knowledge domains that share an emphasis on relational organization. These observations suggest that the hippocampal system is not dedicated to spatial cognition and navigation, but organizes experiences in memory, for which spatial mapping and navigation are both a metaphor for and a prominent application of relational memory organization. PMID:28148640

Adolescent Self-Organization Predicts Midlife Memory in a Prospective Birth Cohort Study

PubMed Central

2013-01-01

Childhood and adolescent mental health have a lasting impact on adult life chances, with strong implications for subsequent health, including cognitive aging. Using the British 1946 birth cohort, the authors tested associations between adolescent conduct problems, emotional problems and aspects of self-organization, and verbal memory at 43 years and rate of decline in verbal memory from 43 to 60–64 years. After controlling for childhood intelligence, adolescent self-organization was positively associated with verbal memory at 43 years, mainly through educational attainment, although not with rate of memory decline. Associations between adolescent conduct and emotional problems and future memory were of negligible magnitude. It has been suggested that interventions to improve self-organization may save a wide range of societal costs; this study also suggests that this might also benefit cognitive function in later life. PMID:24364401

Visual function and cognitive speed of processing mediate age-related decline in memory span and fluid intelligence

PubMed Central

Clay, Olivio J.; Edwards, Jerri D.; Ross, Lesley A.; Okonkwo, Ozioma; Wadley, Virginia G.; Roth, David L.; Ball, Karlene K.

2010-01-01

Objectives: To evaluate the relationship between sensory and cognitive decline, particularly with respect to speed of processing, memory span, and fluid intelligence. Additionally, the common cause, sensory degradation and speed of processing hypotheses were compared. Methods: Structural equation modeling was used to investigate the complex relationships among age-related decrements in these areas. Results: Cross-sectional data analyses included 842 older adult participants (M = 73 years). After accounting for age-related declines in vision and processing speed, the direct associations between age and memory span and between age and fluid intelligence were nonsignificant. Older age was associated with visual decline, which was associated with slower speed of processing, which in turn was associated with greater cognitive deficits. Discussion: The findings support both the sensory degradation and speed of processing accounts of age-related cognitive decline. Further, the findings highlight positive aspects of normal cognitive aging in that older age may not be associated with a loss of fluid intelligence if visual sensory functioning and processing speed can be maintained. PMID:19436063

Contextual Cueing: Implicit Learning and Memory of Visual Context Guides Spatial Attention.

ERIC Educational Resources Information Center

Chun, Marvin M.; Jiang, Yuhong

1998-01-01

Six experiments involving a total of 112 college students demonstrate that a robust memory for visual context exists to guide spatial attention. Results show how implicit learning and memory of visual context can guide spatial attention toward task-relevant aspects of a scene. (SLD)

A Principal Components Analysis of Dynamic Spatial Memory Biases

ERIC Educational Resources Information Center

Motes, Michael A.; Hubbard, Timothy L.; Courtney, Jon R.; Rypma, Bart

2008-01-01

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…

Egocentric and nonegocentric coding in memory for spatial layout: Evidence from scene recognition

PubMed Central

2005-01-01

Much contemporary research has suggested that memories for spatial layout are stored with a preferred orientation. The present paper examines whether spatial memories are also stored with a preferred viewpoint position. Participants viewed images of an arrangement of objects taken from a single viewpoint, and were subsequently tested on their ability to recognize the arrangement from novel viewpoints that had been translated in either the lateral or depth dimension. Lateral and forward displacements of the viewpoint resulted in increasing response latencies and errors. Backward displacement showed no such effect, nor did lateral translation that resulted in a centered “canonical” view of the arrangement. These results further constrain the specificity of spatial memory, while also providing some evidence that nonegocentric spatial information is coded in memory. PMID:16933759

A test of the reward-contrast hypothesis.

PubMed

Dalecki, Stefan J; Panoz-Brown, Danielle E; Crystal, Jonathon D

2017-12-01

Source memory, a facet of episodic memory, is the memory of the origin of information. Whereas source memory in rats is sustained for at least a week, spatial memory degraded after approximately a day. Different forgetting functions may suggest that two memory systems (source memory and spatial memory) are dissociated. However, in previous work, the two tasks used baiting conditions consisting of chocolate and chow flavors; notably, the source memory task used the relatively better flavor. Thus, according to the reward-contrast hypothesis, when chocolate and chow were presented within the same context (i.e., within a single radial maze trial), the chocolate location was more memorable than the chow location because of contrast. We tested the reward-contrast hypothesis using baiting configurations designed to produce reward-contrast. The reward-contrast hypothesis predicts that under these conditions, spatial memory will survive a 24-h retention interval. We documented elimination of spatial memory performance after a 24-h retention interval using a reward-contrast baiting pattern. These data suggest that reward contrast does not explain our earlier findings that source memory survives unusually long retention intervals. Copyright © 2017 Elsevier B.V. All rights reserved.

Thrombin-induced microglial activation impairs hippocampal neurogenesis and spatial memory ability in mice.

PubMed

Yang, Yuan; Zhang, Meikui; Kang, Xiaoni; Jiang, Chen; Zhang, Huan; Wang, Pei; Li, Jingjing

2015-09-26

To investigate the effects of microglia/macrophages activation induced by intrastriatal thrombin injection on dentate gyrus neurogenesis and spatial memory ability in mice. The male C57BL/6 mice were divided into 4 groups of 10: sham, intracerebral hemorrhage (ICH), ICH + hirudin (thrombin inhibitor), and ICH + indometacin (Indo, an anti-inflammation drug). ICH model was created by intrastriatal thrombin (1U) injection. BrdU (50 mg/kg) was administrated on the same day after surgery for 6 consecutive days. Motor functions were evaluated with rotarod and beam walking tests. The spatial memory deficit was measured with Morris water maze (MWM). Cell quantification was performed for doublecortin (DCX, immature neuron), BrdU (S-phase proliferating cell population) and CD68 (activated microglia/macrophage) immune-reactive cells. Microglia/macrophages activation induced by intrastriatal thrombin injection reduced hippocampal neurogenesis and impaired spatial memory ability, but did not affect the motor function at 3 and 5 days post-injury. Both hirudin and indometacin reduced microglia/macrophages activation, enhanced hippocampal neurogenesis, and improved spatial memory ability in mice. Microglia/macrophages activation induced by intrastriatal thrombin injection might be responsible for the spatial memory deficit. Targeting both thrombin and inflammation systems in acute phase of ICH might be important in alleviating the significant spatial memory deficits.

Enhanced Long-Term and Impaired Short-Term Spatial Memory in GluA1 AMPA Receptor Subunit Knockout Mice: Evidence for a Dual-Process Memory Model

ERIC Educational Resources Information Center

Sanderson, David J.; Good, Mark A.; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H.; Rawlins, J. Nicholas P.; Bannerman, David M.

2009-01-01

The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of…

Oculomotor selection underlies feature retention in visual working memory.

PubMed

Hanning, Nina M; Jonikaitis, Donatas; Deubel, Heiner; Szinte, Martin

2016-02-01

Oculomotor selection, spatial task relevance, and visual working memory (WM) are described as three processes highly intertwined and sustained by similar cortical structures. However, because task-relevant locations always constitute potential saccade targets, no study so far has been able to distinguish between oculomotor selection and spatial task relevance. We designed an experiment that allowed us to dissociate in humans the contribution of task relevance, oculomotor selection, and oculomotor execution to the retention of feature representations in WM. We report that task relevance and oculomotor selection lead to dissociable effects on feature WM maintenance. In a first task, in which an object's location was encoded as a saccade target, its feature representations were successfully maintained in WM, whereas they declined at nonsaccade target locations. Likewise, we observed a similar WM benefit at the target of saccades that were prepared but never executed. In a second task, when an object's location was marked as task relevant but constituted a nonsaccade target (a location to avoid), feature representations maintained at that location did not benefit. Combined, our results demonstrate that oculomotor selection is consistently associated with WM, whereas task relevance is not. This provides evidence for an overlapping circuitry serving saccade target selection and feature-based WM that can be dissociated from processes encoding task-relevant locations. Copyright © 2016 the American Physiological Society.

The relation between navigation strategy and associative memory: An individual differences approach.

PubMed

Ngo, Chi T; Weisberg, Steven M; Newcombe, Nora S; Olson, Ingrid R

2016-04-01

Although the hippocampus is implicated in both spatial navigation and associative memory, very little is known about whether individual differences in the 2 domains covary. People who prefer to navigate using a hippocampal-dependent place strategy may show better performance on associative memory tasks than those who prefer a caudate-dependent response strategy (Bohbot, Gupta, Banner, & Dahmani, 2011), but not all studies suggest such an effect (Woollett & Maguire, 2009, 2012). Here we tested nonexpert young adults and found that preference for a place strategy positively correlated with spatial (object-location) associative memory performance but did not correlate with nonspatial (face-name) associative memory performance. Importantly, these correlations differed from each other, indicating that the relation between navigation strategy and associative memory is specific to the spatial domain. In addition, the 2 associative memory tasks significantly correlated, suggesting that object-location memory taps into processes relevant to both hippocampal-dependent navigation and nonspatial associative memory. Our findings also suggest that individual differences in spatial associative memory may account for some of the variance in navigation strategies. (c) 2016 APA, all rights reserved).

Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats

PubMed Central

Cippitelli, Andrea; Zook, Michelle; Bell, Lauren; Damadzic, Ruslan; Eskay, Robert L.; Schwandt, Melanie; Heilig, Markus

2010-01-01

Excessive alcohol use leads to neurodegeneration in several brain structures including the hippocampal dentate gyrus and the entorhinal cortex. Cognitive deficits that result are among the most insidious and debilitating consequences of alcoholism. The object exploration task (OET) provides a sensitive measurement of spatial memory impairment induced by hippocampal and cortical damage. In this study, we examine whether the observed neurotoxicity produced by a 4-day binge ethanol treatment results in long-term memory impairment by observing the time course of reactions to spatial change (object configuration) and non-spatial change (object recognition). Wistar rats were assessed for their abilities to detect spatial configuration in the OET at 1 week and 10 weeks following the ethanol treatment, in which ethanol groups received 9–15 g/kg/day and achieved blood alcohol levels over 300 mg/dl. At 1 week, results indicated that the binge alcohol treatment produced impairment in both spatial memory and non-spatial object recognition performance. Unlike the controls, ethanol treated rats did not increase the duration or number of contacts with the displaced object in the spatial memory task, nor did they increase the duration of contacts with the novel object in the object recognition task. After 10 weeks, spatial memory remained impaired in the ethanol treated rats but object recognition ability was recovered. Our data suggest that episodes of binge-like alcohol exposure result in long-term and possibly permanent impairments in memory for the configuration of objects during exploration, whereas the ability to detect non-spatial changes is only temporarily affected. PMID:20849966

Exposure to low doses (20 cGy) of Hze results in spatial memory impairment in rats.

NASA Astrophysics Data System (ADS)

Britten, Richard; Johnson, Angela; Davis, Leslie; Green-Mitchell, Shamina; Chabriol, Olivia; Sanford, Larry; Drake, Richard

INTRODUCTION. Current models predict that the astronauts on a mission to a deep space destination, such as Mars, will be exposed to 25 cGy of Galactic cosmic radiation (GCR). The long-term consequence of exposure to such doses is largely unknown, but given that 1.3 Gy of X-rays has been reported to lead to long-term cognitive deficits (Shore et al, 1976) and that CGR have an RBE of 2-5, it is likely that the predicted 25 cGy of GCR will lead to defects in the cognitive ability of the astronauts during and after the mission. Our studies are designed to help define the GCR dose that will lead to defects in complex working memory, and also to elucidate the mechanisms whereby hadronic radiation diminishes neurocognitive function. The identification of such processes would provide an opportunity for post-mission surveillance, and hopefully will lead to intervention strategies that will ameliorate or attenuate GCR-induced neurocognitive deficits. MATERIALS METHODS. Four-week old male Wistar rats were exposed to either X-rays or 1 GeV 56Fe. At three or six months post exposure the performance of the rats in the Barnes' Maze (Spatial memory) was established. The duration and frequency of REM sleep was also monitored to determine if the neurocognitive deficits arose due to reduced memory consolidation as a result of diminished REM sleep. We used a novel, but maturing technique, called MALDI-MS imaging (or MALDI-MSI), to identify specific regions of the brain where the neuroproteome differs in rats that have developed spatial memory impairments. RESULTS. 11.5 Gy of X-rays led to reduced performance in the Barnes's maze. In contrast, exposure to 20 cGy of Hze (1 GeV 56Fe) resulted in a significant impairment of spatial memory performance as measured in the Barnes' Maze, which was manifested by an increase in relative escape latency REL over a 5 day testing period. Such an increase in REL could arise from the rats becoming less able, or perhaps less willing, to locate the Escape hole over the 5 days of training. There was a suggestion that there may be some recovery in spatial memory performance by 6 months post exposure. Our preliminary data on Hze-induced exposure on sleep, suggests that within 4 weeks of Hze exposure there is a change in sleep latency, raising the possibility that some of the observed decline in neurocognitive performance may arise due to perturbed sleep patterns. We have used MALDI-IMS to determine the Hze-induced changes in the neuroproteome with a high degree of spatial resolution. Using this technique we have found that a peptide with a m/z of 14207 is differentially elevated in the Thalamus of irradiated rats that have good spatial memory. MALDI-MSI thus appears to be a powerful tool that can be used to identify radiation-induced changes in ancillary brain regions that correlate with neurocognitive impairment, and will ultimately be useful for identifying proteins whose expression changes in parallel with Hze-induced neurocognitive deficits. SUMMARY. We have found that mission-relevant Hze doses (20 cGy) lead to significant neu-rocognitive defects. Clearly such low doses of Hze are unlikely to lead to a significant loss of neuronal cells, and have not been reported to lead to gliosis etc. We take this as further evi-dence that neurocognitive impairment is not solely dependent upon radiation-induced changes in neurogenesis and neuronal cell death. FUNDING: The authors gratefully acknowledge grant support from NASA (NNJ06HD89D).

Abnormal interactions of verbal- and spatial-memory networks in young people at familial high-risk for schizophrenia.

PubMed

Li, Xiaobo; Thermenos, Heidi W; Wu, Ziyan; Momura, Yoko; Wu, Kai; Keshavan, Matcheri; Seidman, Lawrence; DeLisi, Lynn E

2016-10-01

Working memory impairment (especially in verbal and spatial domains) is the core neurocognitive impairment in schizophrenia and the familial high-risk (FHR) population. Inconsistent results have been reported in clinical and neuroimaging studies examining the verbal- and spatial-memory deficits in the FHR subjects, due to sample differences and lack of understanding on interactions of the brain regions for processing verbal- and spatial-working memory. Functional MRI data acquired during a verbal- vs. spatial-memory task were included from 51 young adults [26 FHR and 25 controls]. Group comparisons were conducted in brain activation patterns responding to 1) verbal-memory condition (A), 2) spatial-memory condition (B), 3) verbal higher than spatial (A-B), 4) spatial higher than verbal (B-A), 5) conjunction of brain regions that were activated during both A and B (A∧B). Group difference of the laterality index (LI) in inferior frontal lobe for condition A was also assessed. Compared to controls, the FHR group exhibited significantly decreased brain activity in left inferior frontal during A, and significantly stronger involvement of ACC, PCC, paracentral gyrus for the contrast of A-B. The LI showed a trend of reduced left-higher-than-right pattern for verbal-memory processing in the HR group. Our findings suggest that in the entire functional brain network for working-memory processing, verbal information processing associated brain pathways are significantly altered in people at familial high risk for developing schizophrenia. Future studies will need to examine whether these alterations may indicate vulnerability for predicting the onset of Schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Spatial attention interacts with serial-order retrieval from verbal working memory.

PubMed

van Dijck, Jean-Philippe; Abrahamse, Elger L; Majerus, Steve; Fias, Wim

2013-09-01

The ability to maintain the serial order of events is recognized as a major function of working memory. Although general models of working memory postulate a close link between working memory and attention, such a link has so far not been proposed specifically for serial-order working memory. The present study provided the first empirical demonstration of a direct link between serial order in verbal working memory and spatial selective attention. We show that the retrieval of later items of a sequence stored in working memory-compared with that of earlier items-produces covert attentional shifts toward the right. This observation suggests the conceptually surprising notion that serial-order working memory, even for nonspatially defined verbal items, draws on spatial attention.

Unilateral lesion of dorsal hippocampus in adult rats impairs contralateral long-term potentiation in vivo and spatial memory in the early postoperative phase.

PubMed

Li, Hongjie; Wu, Xiaoyan; Bai, Yanrui; Huang, Yan; He, Wenting; Dong, Zhifang

2012-05-01

It is well documented that bilateral hippocampal lesions or unilateral hippocampal lesion at birth causes impairment of contralateral LTP and long-term memory. However, effects of unilateral hippocampal lesion in adults on contralateral in vivo LTP and memory are not clear. We here examined the influence of unilateral electrolytic dorsal hippocampal lesion in adult rats on contralateral LTP in vivo and spatial memory during different postoperative phases. We found that acute unilateral hippocampal lesion had no effect on contralateral LTP. However, contralateral LTP was impaired at 1 week after lesion, and was restored to the control level at postoperative week 4. Similarly, spatial memory was also impaired at postoperative week 1, and was restored at postoperative week 4. In addition, the rats at postoperative week 1 showed stronger spatial exploratory behavior in a novel open-field environment. The sham operation had no effects on contralateral LTP, spatial memory and exploration at either postoperative week 1 or week 4. These results suggest that unilateral dorsal hippocampal lesion in adult rats causes transient contralateral LTP impairment and spatial memory deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

Memory for pictures, words, and spatial location in older adults: evidence for pictorial superiority.

PubMed

Park, D C; Puglisi, J T; Sovacool, M

1983-09-01

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.

17β-Estradiol regulates histone alterations associated with memory consolidation and increases Bdnf promoter acetylation in middle-aged female mice

PubMed Central

Fortress, Ashley M.; Kim, Jaekyoon; Poole, Rachel L.; Gould, Thomas J.

2014-01-01

Histone acetylation is essential for hippocampal memory formation in young adult rodents. Although dysfunctional histone acetylation has been associated with age-related memory decline in male rodents, little is known about whether histone acetylation is altered by aging in female rodents. In young female mice, the ability of 17β-estradiol (E2) to enhance object recognition memory consolidation requires histone H3 acetylation in the dorsal hippocampus. However, the extent to which histone acetylation is regulated by E2 in middle-aged females is unknown. The mnemonic benefits of E2 in aging females appear to be greatest in middle age, and so pinpointing the molecular mechanisms through which E2 enhances memory at this age could lead to the development of safer and more effective treatments for maintaining memory function without the side effects of current therapies. Here, we show that dorsal hippocampal infusion of E2 rapidly enhanced object recognition and spatial memory, and increased histone H3 acetylation in the dorsal hippocampus, while also significantly reducing levels of histone deacetylase (HDAC2 and HDAC3) proteins. E2 specifically increased histone H3 acetylation at Bdnf promoters pII and pIV in the dorsal hippocampus of both young and middle-aged mice, despite age-related decreases in pI and pIV acetylation. Furthermore, levels of mature BDNF and pro-BDNF proteins in the dorsal hippocampus were increased by E2 in middle-aged females. Together, these data suggest that the middle-aged female dorsal hippocampus remains epigenetically responsive to E2, and that E2 may enhance memory in middle-aged females via epigenetic regulation of Bdnf. PMID:25128537

Age effects on explicit and implicit memory

PubMed Central

Ward, Emma V.; Berry, Christopher J.; Shanks, David R.

2013-01-01

It is well-documented that explicit memory (e.g., recognition) declines with age. In contrast, many argue that implicit memory (e.g., priming) is preserved in healthy aging. For example, priming on tasks such as perceptual identification is often not statistically different in groups of young and older adults. Such observations are commonly taken as evidence for distinct explicit and implicit learning/memory systems. In this article we discuss several lines of evidence that challenge this view. We describe how patterns of differential age-related decline may arise from differences in the ways in which the two forms of memory are commonly measured, and review recent research suggesting that under improved measurement methods, implicit memory is not age-invariant. Formal computational models are of considerable utility in revealing the nature of underlying systems. We report the results of applying single and multiple-systems models to data on age effects in implicit and explicit memory. Model comparison clearly favors the single-system view. Implications for the memory systems debate are discussed. PMID:24065942

Processing Speed, Inhibitory Control, and Working Memory: Three Important Factors to Account for Age-Related Cognitive Decline

ERIC Educational Resources Information Center

Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez

2008-01-01

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…

Cognitive changes in people with temporal lobe epilepsy over a 13-year period.

PubMed

Mameniškienė, Rūta; Rimšienė, Justė; Puronaitė, Roma

2016-10-01

The aims of our study were to evaluate cognitive decline in people with temporal lobe epilepsy over a period of 13years and to determine what clinical and treatment characteristics may have been associated with these. Thirty-three individuals with temporal lobe epilepsy underwent the same neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions using the same cognitive test battery as one used 13years ago. Long-term verbal and nonverbal memory was tested four weeks later. Results were compared with those carried out 13years earlier. There was no significant change in verbal and verbal-logical memory tests; however, nonverbal memory worsened significantly. Long-term verbal memory declined for 21.9% of participants, long-term verbal-logical memory for 34.4%, and long-term nonverbal memory for 56.3%. Worsening of working verbal and verbal-logical memory was associated with longer epilepsy duration and lower levels of patients' education; worsening of verbal delayed recall and long-term verbal-logical memory was associated with higher seizure frequency. Decline in long-term nonverbal memory had significant association with a longer duration of epilepsy. The worsening of reaction and attention inversely correlated with the symptoms of depression. Over a 13-year period, cognitive functions did not change significantly. Good seizure control and reduced symptoms of depression in this sample of people with temporal lobe epilepsy were associated with better cognitive functioning. The predictors of change of cognitive functions could be complex and require further study. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial Memory in the Progeny of Rats Subjected to Different Types of Experimental Preeclampsia.

PubMed

Perfilova, V N; Zhakupova, G A; Lashchenova, L I; Lebedeva, S A; Tyurenkov, I N

2016-09-01

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.

Fluoride and arsenic exposure affects spatial memory and activates the ERK/CREB signaling pathway in offspring rats.

PubMed

Zhu, Yu-Peng; Xi, Shu-Hua; Li, Ming-Yan; Ding, Ting-Ting; Liu, Nan; Cao, Fu-Yuan; Zeng, Yang; Liu, Xiao-Jing; Tong, Jun-Wang; Jiang, Shou-Fang

2017-03-01

Fluoride and arsenic are inorganic contaminants that occur in the natural environment. Chronic fluoride and/or arsenic exposure can induce developmental neurotoxicity and negatively influence intelligence in children, although the underlying molecular mechanisms are poorly understood. This study explored the effects of fluoride and arsenic exposure in drinking water on spatial learning, memory and key protein expression in the ERK/CREB signaling pathway in hippocampal and cerebral cortex tissue in rat offspring. Pregnant rats were divided into four groups. Control rats drank tap water, while rats in the three exposure groups drank water with sodium fluoride (100mg/L), sodium arsenite (75mg/L), and a sodium fluoride (100mg/L) and sodium arsenite (75mg/L) combination during gestation and lactation. After weaning, rat pups drank the same solution as their mothers. Spatial learning and memory ability of pups at postnatal day 21 (PND21) and postnatal day 42 (PND42) were measured using a Morris water maze. ERK, phospho-ERK (p-ERK), CREB and phospho-CREB (p-CREB) protein expression in the hippocampus and cerebral cortex was detected using Western blot. Compared with the control pups, escape latencies increased in PND42 pups exposed to arsenic and co-exposed to fluoride and arsenic, and the short-term and long-term spatial memory ability declined in pups exposed to fluoride and arsenic, both alone and in combination. Compared with controls, ERK and p-ERK levels decreased in the hippocampus and cerebral cortex in pups exposed to combined fluoride and arsenic. CREB protein expression in the cerebral cortex decreased in pups exposed to fluoride, arsenic, and the fluoride and arsenic combination. p-CREB protein expression in both the hippocampus and cerebral cortex was decreased in pups exposed to fluoride and arsenic in combination compared to the control group. There were negative correlation between the proteins expression and escape latency periods in pups. These data indicate that exposure to fluoride and arsenic in early life stage changes ERK, p-ERK, CREB and p-CREB protein expression in the hippocampus and cerebral cortex of rat offspring at PND21 and PND 42, which may contribute to impaired neurodevelopment following exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Fine-grained versus categorical: Pupil size differentiates between strategies for spatial working memory performance.

PubMed

Starc, Martina; Anticevic, Alan; Repovš, Grega

2017-05-01

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. © 2017 Society for Psychophysiological Research.

No functional role of attention-based rehearsal in maintenance of spatial working memory representations.

PubMed

Belopolsky, Artem V; Theeuwes, Jan

2009-10-01

The present study systematically examined the role of attention in maintenance of spatial representations in working memory as proposed by the attention-based rehearsal hypothesis [Awh, E., Jonides, J., & Reuter-Lorenz, P. A. (1998). Rehearsal in spatial working memory. Journal of Experimental Psychology--Human Perception and Performance, 24(3), 780-790]. Three main issues were examined. First, Experiments 1-3 demonstrated that inhibition and not facilitation of visual processing is often observed at the memorized location during the retention interval. This inhibition was caused by keeping a location in memory and not by the exogenous nature of the memory cue. Second, Experiment 4 showed that inhibition of the memorized location does not lead to any significant impairment in memory accuracy. Finally, Experiment 5 connected current results to the previous findings and demonstrated facilitation of processing at the memorized location. Importantly, facilitation of processing did not lead to more accurate memory performance. The present results challenge the functional role of attention in maintenance of spatial working memory representations.

Spatial and temporal episodic memory retrieval recruit dissociable functional networks in the human brain.

PubMed

Ekstrom, Arne D; Bookheimer, Susan Y

2007-10-01

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 of episodic memory in the context of a spatial navigation paradigm. Subjects played a taxi-driver game ("yellowcab"), in which they freely searched for passengers and delivered them to specific landmark stores. Subjects then underwent fMRI scanning as they retrieved landmarks, spatial, and temporal associations from their navigational experience in three separate runs. Consistent with previous findings on item memory, perirhinal cortex activated most strongly during landmark retrieval compared with spatial or temporal source information retrieval. Both hippocampus and parahippocampal cortex activated significantly during retrieval of landmarks, spatial associations, and temporal order. We found, however, a significant dissociation between hippocampal and parahippocampal cortex activations, with spatial retrieval leading to greater parahippocampal activation compared with hippocampus and temporal order retrieval leading to greater hippocampal activation compared with parahippocampal cortex. Our results, coupled with previous findings, demonstrate that the hippocampus and parahippocampal cortex are preferentially recruited during temporal order and spatial association retrieval--key components of episodic "source" memory.

No Sex Differences in Spatial Location Memory for Abstract Designs

ERIC Educational Resources Information Center

Rahman, Qazi; Bakare, Monsurat; Serinsu, Ceydan

2011-01-01

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…

Accessibility versus Accuracy in Retrieving Spatial Memory: Evidence for Suboptimal Assumed Headings

ERIC Educational Resources Information Center

Yerramsetti, Ashok; Marchette, Steven A.; Shelton, Amy L.

2013-01-01

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…

Ginkgo biloba for Preventing Cognitive Decline in Older Adults

PubMed Central

Snitz, Beth E.; O'Meara, Ellen S.; Carlson, Michelle C.; Arnold, Alice M.; Ives, Diane G.; Rapp, Stephen R.; Saxton, Judith; Lopez, Oscar L.; Dunn, Leslie O.; Sink, Kaycee M.; DeKosky, Steven T.

2010-01-01

Context The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning. Objective To determine whether G biloba slows the rates of global or domain-specific cognitive decline in older adults. Design, Setting, and Participants The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years. Intervention Twice-daily dose of 120-mg extract of G biloba (n=1545) or identical-appearing placebo (n=1524). Main Outcome Measures Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests. Results Annual rates of decline in z scores did not differ between G biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P=.71; for ADAS-Cog, P=.97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P>.05). Conclusion Compared with placebo, the use of G biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment. Trial Registration clinicaltrials.gov Identifier: NCT00010803 PMID:20040554

Individual Differences in Spatial Text Processing: High Spatial Ability Can Compensate for Spatial Working Memory Interference

ERIC Educational Resources Information Center

Meneghetti, Chiara; Gyselinck, Valerie; Pazzaglia, Francesca; De Beni, Rossana

2009-01-01

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.…

Prenatal Stress Impairs Spatial Learning and Memory Associated with Lower mRNA Level of the CAMKII and CREB in the Adult Female Rat Hippocampus.

PubMed

Sun, Hongli; Wu, Haibin; Liu, Jianping; Wen, Jun; Zhu, Zhongliang; Li, Hui

2017-05-01

Prenatal stress (PS) results in various behavioral and emotional alterations observed in later life. In particular, PS impairs spatial learning and memory processes but the underlying mechanism involved in this pathogenesis still remains unknown. Here, we reported that PS lowered the body weight in offspring rats, particularly in female rats, and impaired spatial learning and memory of female offspring rats in the Morris water maze. Correspondingly, the decreased CaMKII and CREB mRNA in the hippocampus were detected in prenatally stressed female offspring, which partially explained the effect of PS on the spatial learning and memory. Our findings suggested that CaMKII and CREB may be involved in spatial learning and memory processes in the prenatally stressed adult female offspring.

Long-Term Moderate Exercise Rescues Age-Related Decline in Hippocampal Neuronal Complexity and Memory.

PubMed

Tsai, Sheng-Feng; Ku, Nai-Wen; Wang, Tzu-Feng; Yang, Yan-Hsiang; Shih, Yao-Hsiang; Wu, Shih-Ying; Lee, Chu-Wan; Yu, Megan; Yang, Ting-Ting; Kuo, Yu-Min

2018-05-07

Aging impairs hippocampal neuroplasticity and hippocampus-related learning and memory. In contrast, exercise training is known to improve hippocampal neuronal function. However, whether exercise is capable of restoring memory function in old animals is less clear. Here, we investigated the effects of exercise on the hippocampal neuroplasticity and memory functions during aging. Young (3 months), middle-aged (9-12 months), and old (18 months) mice underwent moderate-intensity treadmill running training for 6 weeks, and their hippocampus-related learning and memory, and the plasticity of their CA1 neurons was evaluated. The memory performance (Morris water maze and novel object recognition tests), and dendritic complexity (branch and length) and spine density of their hippocampal CA1 neurons decreased as their age increased. The induction and maintenance of high-frequency stimulation-induced long-term potentiation in the CA1 area and the expressions of neuroplasticity-related proteins were not affected by age. Treadmill running increased CA1 neuron long-term potentiation and dendritic complexity in all three age groups, and it restored the learning and memory ability in middle-aged and old mice. Furthermore, treadmill running upregulated the hippocampal expressions of brain-derived neurotrophic factor and monocarboxylate transporter-4 in middle-aged mice, glutamine synthetase in old mice, and full-length TrkB in middle-aged and old mice. The hippocampus-related memory function declines from middle age, but long-term moderate-intensity running effectively increased hippocampal neuroplasticity and memory in mice of different ages, even when the memory impairment had progressed to an advanced stage. Thus, long-term, moderate intensity exercise training might be a way of delaying and treating aging-related memory decline. © 2018 S. Karger AG, Basel.

Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model

PubMed Central

Lockrow, Jason; Prakasam, Annamalai; Huang, Peng; Bimonte-Nelson, Heather; Sambamurti, Kumar; Granholm, Ann-Charlotte

2009-01-01

Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated oxidative stress in Ts65Dn mice, and assessed the efficacy of long-term antioxidant supplementation on memory and basal forebrain pathology. We report that oxidative stress was elevated in the adult Ts65Dn brain, and that supplementation with the antioxidant vitamin E effectively reduced these markers. Also, Ts65Dn mice receiving vitamin E exhibited improved performance on a spatial working memory task and showed an attenuation of cholinergic neuron pathology in the basal forebrain. This study provides evidence that vitamin E delays onset of cognitive and morphological abnormalities in a mouse model of DS, and may represent a safe and effective treatment early in the progression of DS neuropathology. PMID:19135442

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

DOE PAGES

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.; ...

2017-02-08

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

Inactivation of the dorsal hippocampus or the medial prefrontal cortex impairs retrieval but has differential effect on spatial memory reconsolidation.

PubMed

Rossato, Janine I; Köhler, Cristiano A; Radiske, Andressa; Bevilaqua, Lia R M; Cammarota, Martín

2015-11-01

Active memories can incorporate new information through reconsolidation. However, the notion that memory retrieval is necessary for reconsolidation has been recently challenged. Non-reinforced retrieval induces hippocampus and medial prefrontal cortex (mPFC)-dependent reconsolidation of spatial memory in the Morris water maze (MWM). We found that the effect of protein synthesis inhibition on this process is abolished when retrieval of the learned spatial preference is hindered through mPFC inactivation but not when it is blocked by deactivation of dorsal CA1. Our results do not fully agree with the hypothesis that retrieval is unneeded for reconsolidation. Instead, they support the idea that a hierarchic interaction between the hippocampus and the mPFC controls spatial memory in the MWM, and indicate that this cortex is sufficient to retrieve the information essential to reconsolidate the spatial memory trace, even when the hippocampus is inactivated. Copyright © 2015 Elsevier Inc. All rights reserved.

Spatial But Not Oculomotor Information Biases Perceptual Memory: Evidence From Face Perception and Cognitive Modeling.

PubMed

Wantz, Andrea L; Lobmaier, Janek S; Mast, Fred W; Senn, Walter

2017-08-01

Recent research put forward the hypothesis that eye movements are integrated in memory representations and are reactivated when later recalled. However, "looking back to nothing" during recall might be a consequence of spatial memory retrieval. Here, we aimed at distinguishing between the effect of spatial and oculomotor information on perceptual memory. Participants' task was to judge whether a morph looked rather like the first or second previously presented face. Crucially, faces and morphs were presented in a way that the morph reactivated oculomotor and/or spatial information associated with one of the previously encoded faces. Perceptual face memory was largely influenced by these manipulations. We considered a simple computational model with an excellent match (4.3% error) that expresses these biases as a linear combination of recency, saccade, and location. Surprisingly, saccades did not play a role. The results suggest that spatial and temporal rather than oculomotor information biases perceptual face memory. Copyright © 2016 Cognitive Science Society, Inc.

Spatial sequences, but not verbal sequences, are vulnerable to general interference during retention in working memory.

PubMed

Morey, Candice C; Miron, Monica D

2016-12-01

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 retro-cues. This design isolates interference due specifically to maintenance, which appears most clearly in the uncued trials, from interference due to encoding, which occurs in all dual-task trials. When recall accuracy was comparable between tasks, we found that spatial memory was worse in uncued than in retro-cued trials, whereas verbal memory was not. Our findings bolster proposals that maintenance of spatial serial order, like maintenance of visual materials more broadly, relies on general rather than specialized resources, while maintenance of verbal sequences may rely on domain-specific resources. We argue that this asymmetry should be explicitly incorporated into models of working memory. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Semantic memory and depressive symptoms in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.

PubMed

Lehrner, J; Coutinho, G; Mattos, P; Moser, D; Pflüger, M; Gleiss, A; Auff, E; Dal-Bianco, P; Pusswald, G; Stögmann, E

2017-07-01

Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment. 323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated. Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS. We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.

27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation

PubMed Central

Mateos, Laura; Maioli, Silvia; Ali, Zeina; Gulyás, Balázs; Winblad, Bengt; Savitcheva, Irina

2017-01-01

Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)–mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders. PMID:28213512

Fasting insulin levels and cognitive decline in older women without diabetes.

PubMed

van Oijen, Marieke; Okereke, Olivia I; Kang, Jae Hee; Pollak, Michael N; Hu, Frank B; Hankinson, Susan E; Grodstein, Francine

2008-01-01

Type 2 diabetes has been associated with an increased risk of dementia. To assess possible independent effects of insulin, we investigated the relation of insulin levels to cognitive decline in nondiabetic women. Fasting plasma insulin levels were measured in mid-life in 1,416 nondiabetic Nurses' Health Study participants, who also completed cognitive testing that began 10 years later (current age: 70-75 years). Over 4 years, 3 assessments of general cognition, verbal memory, category fluency and attention were administered. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) performance, the global score (average of all tests) and verbal memory (average of verbal recall tests). Linear mixed-effects models were used to calculate the association between insulin and cognitive decline. Higher insulin levels were associated with a faster decline on the TICS and verbal memory. For analysis, batch-specific quartiles of insulin levels were constructed. Compared to the lowest quartile, adjusted differences in the annual rates of decline (with 95% CI values in parentheses) for the second, third and fourth quartiles were: TICS, -0.06 (-0.16, 0.03), -0.14 (-0.24, -0.04), and -0.09 (-0.19, 0.01) points (p trend = 0.04); verbal memory, -0.01 (-0.04, 0.02), -0.05 (-0.08, -0.02), and -0.02 (-0.05, 0.01) units (p trend = 0.02). These associations remained after multivariable adjustment. Our study provides evidence for a potential role of higher fasting insulin levels in cognitive decline, possibly independent of diabetes. (c) 2008 S. Karger AG, Basel

Patients' perceptions of memory functioning before and after surgical intervention to treat medically refractory epilepsy.

PubMed

Lineweaver, Tara T; Naugle, Richard I; Cafaro, Alyce M; Bingaman, William; Lüders, Hans O

2004-12-01

One risk associated with epilepsy surgery is memory loss, but perhaps more important is how patients perceive changes in their memories. This longitudinal study evaluated changes in memory self-reports and investigated how self-reports relate to changes on objective memory measures in temporal or extratemporal epilepsy patients who underwent surgery. Objective memory (Wechsler Memory Scale-Revised) and subjective memory self-reports (Memory Assessment Clinics Self-Rating Scale) were individually assessed for 136 patients approximately 6 months before and 6 months after surgery. A measure of depressive affect (Beck Depression Inventory-2nd Edition) was used to control variance attributable to emotional distress. Despite a lack of significant correlational relationships between objective and subjective memory for the entire sample, significant correlations between objective memory scores and self-reports did emerge for a subset of patients who evidenced memory decline. Differences also were found in the subjective memory ratings of temporal lobe versus extratemporal patients. Temporal lobe patients rated their memories more negatively than did extratemporal patients and were more likely to report significant improvements in their memory after surgery. In general, patients were not accurate when rating their memories compared to other adults. However, patients with significant declines in their memories were sensitive to actual changes in their memories over time relative to their own personal baselines.

Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats.

PubMed

Cippitelli, Andrea; Zook, Michelle; Bell, Lauren; Damadzic, Ruslan; Eskay, Robert L; Schwandt, Melanie; Heilig, Markus

2010-11-01

Excessive alcohol use leads to neurodegeneration in several brain structures including the hippocampal dentate gyrus and the entorhinal cortex. Cognitive deficits that result are among the most insidious and debilitating consequences of alcoholism. The object exploration task (OET) provides a sensitive measurement of spatial memory impairment induced by hippocampal and cortical damage. In this study, we examine whether the observed neurotoxicity produced by a 4-day binge ethanol treatment results in long-term memory impairment by observing the time course of reactions to spatial change (object configuration) and non-spatial change (object recognition). Wistar rats were assessed for their abilities to detect spatial configuration in the OET at 1 week and 10 weeks following the ethanol treatment, in which ethanol groups received 9-15 g/kg/day and achieved blood alcohol levels over 300 mg/dl. At 1 week, results indicated that the binge alcohol treatment produced impairment in both spatial memory and non-spatial object recognition performance. Unlike the controls, ethanol treated rats did not increase the duration or number of contacts with the displaced object in the spatial memory task, nor did they increase the duration of contacts with the novel object in the object recognition task. After 10 weeks, spatial memory remained impaired in the ethanol treated rats but object recognition ability was recovered. Our data suggest that episodes of binge-like alcohol exposure result in long-term and possibly permanent impairments in memory for the configuration of objects during exploration, whereas the ability to detect non-spatial changes is only temporarily affected. Copyright © 2010 Elsevier Inc. All rights reserved.

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning.

PubMed

Hamson, Dwayne K; Roes, Meighen M; Galea, Liisa A M

2016-06-13

Sex differences in neurological disease exist in incidence, severity, progression, and symptoms and may ultimately influence treatment. Cognitive disturbances are frequent in neuropsychiatric disease with men showing greater cognitive impairment in schizophrenia, but women showing more severe dementia and cognitive decline with Alzheimer's disease. Although there are no overall differences in intelligence between the sexes, men, and women demonstrate slight but consistent differences in a number of cognitive domains. These include a male advantage, on average, in some types of spatial abilities and a female advantage on some measures of verbal fluency and memory. Sex differences in traits or behaviors generally indicate the involvement of sex hormones, such as androgens and estrogens. We review the literature on whether adult levels of testosterone and estradiol influence spatial ability in both males and females from rodent models to humans. We also include information on estrogens and their ability to modulate verbal memory in men and women. Estrone and progestins are common components of hormone therapies, and we also review the existing literature concerning their effects on cognition. We also review the sex differences in the hippocampus and prefrontal cortex as they relate to cognitive performance in both rodents and humans. There has been greater recognition in the scientific literature that it is important to study both sexes and also to analyze study findings with sex as a variable. Only by examining these sex differences can we progress to finding treatments that will improve the cognitive health of both men and women. © 2016 American Physiological Society. Compr Physiol 6:1295-1337, 2016. Copyright © 2016 John Wiley & Sons, Inc.

Control of information in working memory: Encoding and removal of distractors in the complex-span paradigm.

PubMed

Oberauer, Klaus; Lewandowsky, Stephan

2016-11-01

The article reports four experiments with complex-span tasks in which encoding of memory items alternates with processing of distractors. The experiments test two assumptions of a computational model of complex span, SOB-CS: (1) distractor processing impairs memory because distractors are encoded into working memory, thereby interfering with memoranda; and (2) free time following distractors is used to remove them from working memory by unbinding their representations from list context. Experiment 1 shows that distractors are erroneously chosen for recall more often than not-presented stimuli, demonstrating that distractors are encoded into memory. Distractor intrusions declined with longer free time, as predicted by distractor removal. Experiment 2 shows these effects even when distractors precede the memory list, ruling out an account based on selective rehearsal of memoranda during free time. Experiments 3 and 4 test the notion that distractors decay over time. Both experiments show that, contrary to the notion of distractor decay, the chance of a distractor intruding at test does not decline with increasing time since encoding of that distractor. Experiment 4 provides additional evidence against the prediction from distractor decay that distractor intrusions decline over an unfilled retention interval. Taken together, the results support SOB-CS and rule out alternative explanations. Data and simulation code are available on Open Science Framework: osf.io/3ewh7. Copyright © 2016 Elsevier B.V. All rights reserved.

Changes in verbal learning and memory in schizophrenia and non-psychotic controls in midlife: A nine-year follow-up in the Northern Finland Birth Cohort study 1966.

PubMed

Rannikko, Irina; Haapea, Marianne; Miettunen, Jouko; Veijola, Juha; Murray, Graham K; Barnett, Jennifer H; Husa, Anja P; Jones, Peter B; Isohanni, Matti; Jääskeläinen, Erika

2015-08-30

Findings on longitudinal change of cognitive performance in schizophrenia are extremely variable in the case of verbal learning and memory, and it is still unclear which dimensions of verbal learning and memory exhibit possible deterioration over the long-term. Our aim was to compare the change in verbal learning and memory in individuals with schizophrenia 10-20 years after the illness onset and healthy controls during a nine-year follow-up in a general population sample. Our sample included 41 schizophrenia spectrum subjects and 73 controls from the Northern Finland Birth Cohort study 1966. The California Verbal Learning Test (CVLT) was used to estimate the degree of change in verbal learning and memory during a nine-year follow-up from age 34-years to 43- years. Both cases and controls deteriorated. There was statistically significant decline in two out of 20 CVLT items among cases and in 13 out of 20 CVLT items among controls. With the exception of two variables, the decline in verbal learning and memory over nine years was not significantly larger in cases. We conclude that during midlife verbal learning and memory in schizophrenia mostly declines in a normative fashion with aging at the same rate as the general population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Histopathologic subtype of hippocampal sclerosis and episodic memory performance before and after temporal lobectomy for epilepsy.

PubMed

Saghafi, Shahram; Ferguson, Lisa; Hogue, Olivia; Gales, Jordan M; Prayson, Richard; Busch, Robyn M

2018-04-01

The International League Against Epilepsy (ILAE) proposed a classification system for hippocampal sclerosis (HS) based on location and extent of hippocampal neuron loss. The literature debates the usefulness of this classification system when studying memory in people with temporal lobe epilepsy (TLE) and determining memory outcome after temporal lobe resection (TLR). This study further explores the relationship between HS ILAE subtypes and episodic memory performance in patients with TLE and examines memory outcomes after TLR. This retrospective study identified 213 patients with TLE who underwent TLR and had histopathological evidence of HS (HS ILAE type 1a = 92; type 1b = 103; type 2 = 18). Patients completed the Wechsler Memory Scale-3rd Edition prior to surgery, and 78% of patients had postoperative scores available. Linear regressions examined differences in preoperative memory scores as a function of pathology classification, controlling for potential confounders. Fisher's exact tests were used to compare pathology subtypes on the magnitude of preoperative memory impairment and the proportion of patients who experienced clinically meaningful postoperative memory decline. Individuals with HS ILAE type 2 demonstrated better preoperative verbal memory performance than patients with HS ILAE type 1; however, individual data revealed verbal and visual episodic memory impairments in many patients with HS ILAE type 2. The base rate of postoperative memory decline was similar among all 3 pathology groups. This is the largest reported overall sample and the largest subset of patients with HS ILAE type 2. Group data suggest that patients with HS ILAE type 2 perform better on preoperative memory measures, but individually there were no differences in the magnitude of memory impairment. Following surgery, there were no statistically significant differences between groups in the proportion of patients who declined. Future research should focus on quantitative measurements of hippocampal neuronal loss, and multicenter collaboration is encouraged. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Aging-related episodic memory decline: are emotions the key?

PubMed Central

Kinugawa, Kiyoka; Schumm, Sophie; Pollina, Monica; Depre, Marion; Jungbluth, Carolin; Doulazmi, Mohamed; Sebban, Claude; Zlomuzica, Armin; Pietrowsky, Reinhard; Pause, Bettina; Mariani, Jean; Dere, Ekrem

2013-01-01

Episodic memory refers to the recollection of personal experiences that contain information on what has happened and also where and when these events took place. Episodic memory function is extremely sensitive to cerebral aging and neurodegerative diseases. We examined episodic memory performance with a novel test in young (N = 17, age: 21–45), middle-aged (N = 16, age: 48–62) and aged but otherwise healthy participants (N = 8, age: 71–83) along with measurements of trait and state anxiety. As expected we found significantly impaired episodic memory performance in the aged group as compared to the young group. The aged group also showed impaired working memory performance as well as significantly decreased levels of trait anxiety. No significant correlation between the total episodic memory and trait or state anxiety scores was found. The present results show an age-dependent episodic memory decline along with lower trait anxiety in the aged group. Yet, it still remains to be determined whether this difference in anxiety is related to the impaired episodic memory performance in the aged group. PMID:23378831

Modeling Learning and Memory Using Verbal Learning Tests: Results From ACTIVE

PubMed Central

Gross, Alden L.

2013-01-01

Objective. To investigate the influence of memory training on initial recall and learning. Method. The Advanced Cognitive Training for Independent and Vital Elderly study of community-dwelling adults older than age 65 (n = 1,401). We decomposed trial-level recall in the Auditory Verbal Learning Test (AVLT) and Hopkins Verbal Learning Test (HVLT) into initial recall and learning across trials using latent growth models. Results. Trial-level increases in words recalled in the AVLT and HVLT at each follow-up visit followed an approximately logarithmic shape. Over the 5-year study period, memory training was associated with slower decline in Trial 1 AVLT recall (Cohen’s d = 0.35, p = .03) and steep pre- and posttraining acceleration in learning (d = 1.56, p < .001). Findings were replicated using the HVLT (decline in initial recall, d = 0.60, p = .01; pre- and posttraining acceleration in learning, d = 3.10, p < .001). Because of the immediate training boost, the memory-trained group had a higher level of recall than the control group through the end of the 5-year study period despite faster decline in learning. Discussion. This study contributes to the understanding of the mechanisms by which training benefits memory and expands current knowledge by reporting long-term changes in initial recall and learning, as measured from growth models and by characterization of the impact of memory training on these components. Results reveal that memory training delays the worsening of memory span and boosts learning. PMID:22929389

Controlling memory impairment in elderly adults using virtual reality memory training: a randomized controlled pilot study.

PubMed

Optale, Gabriele; Urgesi, Cosimo; Busato, Valentina; Marin, Silvia; Piron, Lamberto; Priftis, Konstantinos; Gamberini, Luciano; Capodieci, Salvatore; Bordin, Adalberto

2010-05-01

Memory decline is a prevalent aspect of aging but may also be the first sign of cognitive pathology. Virtual reality (VR) using immersion and interaction may provide new approaches to the treatment of memory deficits in elderly individuals. The authors implemented a VR training intervention to try to lessen cognitive decline and improve memory functions. The authors randomly assigned 36 elderly residents of a rest care facility (median age 80 years) who were impaired on the Verbal Story Recall Test either to the experimental group (EG) or the control group (CG). The EG underwent 6 months of VR memory training (VRMT) that involved auditory stimulation and VR experiences in path finding. The initial training phase lasted 3 months (3 auditory and 3 VR sessions every 2 weeks), and there was a booster training phase during the following 3 months (1 auditory and 1 VR session per week). The CG underwent equivalent face-to-face training sessions using music therapy. Both groups participated in social and creative and assisted-mobility activities. Neuropsychological and functional evaluations were performed at baseline, after the initial training phase, and after the booster training phase. The EG showed significant improvements in memory tests, especially in long-term recall with an effect size of 0.7 and in several other aspects of cognition. In contrast, the CG showed progressive decline. The authors suggest that VRMT may improve memory function in elderly adults by enhancing focused attention.

Modeling learning and memory using verbal learning tests: results from ACTIVE.

PubMed

Gross, Alden L; Rebok, George W; Brandt, Jason; Tommet, Doug; Marsiske, Michael; Jones, Richard N

2013-03-01

To investigate the influence of memory training on initial recall and learning. The Advanced Cognitive Training for Independent and Vital Elderly study of community-dwelling adults older than age 65 (n = 1,401). We decomposed trial-level recall in the Auditory Verbal Learning Test (AVLT) and Hopkins Verbal Learning Test (HVLT) into initial recall and learning across trials using latent growth models. Trial-level increases in words recalled in the AVLT and HVLT at each follow-up visit followed an approximately logarithmic shape. Over the 5-year study period, memory training was associated with slower decline in Trial 1 AVLT recall (Cohen's d = 0.35, p = .03) and steep pre- and posttraining acceleration in learning (d = 1.56, p < .001). Findings were replicated using the HVLT (decline in initial recall, d = 0.60, p = .01; pre- and posttraining acceleration in learning, d = 3.10, p < .001). Because of the immediate training boost, the memory-trained group had a higher level of recall than the control group through the end of the 5-year study period despite faster decline in learning. This study contributes to the understanding of the mechanisms by which training benefits memory and expands current knowledge by reporting long-term changes in initial recall and learning, as measured from growth models and by characterization of the impact of memory training on these components. Results reveal that memory training delays the worsening of memory span and boosts learning.

Fast but fleeting: adaptive motor learning processes associated with aging and cognitive decline.

PubMed

Trewartha, Kevin M; Garcia, Angeles; Wolpert, Daniel M; Flanagan, J Randall

2014-10-01

Motor learning has been shown to depend on multiple interacting learning processes. For example, learning to adapt when moving grasped objects with novel dynamics involves a fast process that adapts and decays quickly-and that has been linked to explicit memory-and a slower process that adapts and decays more gradually. Each process is characterized by a learning rate that controls how strongly motor memory is updated based on experienced errors and a retention factor determining the movement-to-movement decay in motor memory. Here we examined whether fast and slow motor learning processes involved in learning novel dynamics differ between younger and older adults. In addition, we investigated how age-related decline in explicit memory performance influences learning and retention parameters. Although the groups adapted equally well, they did so with markedly different underlying processes. Whereas the groups had similar fast processes, they had different slow processes. Specifically, the older adults exhibited decreased retention in their slow process compared with younger adults. Within the older group, who exhibited considerable variation in explicit memory performance, we found that poor explicit memory was associated with reduced retention in the fast process, as well as the slow process. These findings suggest that explicit memory resources are a determining factor in impairments in the both the fast and slow processes for motor learning but that aging effects on the slow process are independent of explicit memory declines. Copyright © 2014 the authors 0270-6474/14/3413411-11$15.00/0.

The Ups and Downs of Memory

ERIC Educational Resources Information Center

Erdelyi, Matthew Hugh

2010-01-01

Ever since the classic work of Ebbinghaus (1885/1964), the default view in scientific psychology has been that memory declines over time. Less well-known clinical and laboratory traditions suggest, however, that memory can also increase over time. Ballard (1913) demonstrated that, actually, memory simultaneously increases and decreases over time…

Amyloid-β, anxiety, and cognitive decline in preclinical Alzheimer disease: a multicenter, prospective cohort study.

PubMed

Pietrzak, Robert H; Lim, Yen Ying; Neumeister, Alexander; Ames, David; Ellis, Kathryn A; Harrington, Karra; Lautenschlager, Nicola T; Restrepo, Carolina; Martins, Ralph N; Masters, Colin L; Villemagne, Victor L; Rowe, Christopher C; Maruff, Paul

2015-03-01

Alzheimer disease (AD) is now known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. Although the presence of abnormal levels of amyloid-β (Aβ) is associated with higher rates of progression to clinically classified mild cognitive impairment or dementia, little research has evaluated potentially modifiable moderators of Aβ-related cognitive decline, such as anxiety and depressive symptoms. To evaluate the association between Aβ status and cognitive changes, and the role of anxiety and depressive symptoms in moderating Aβ-related cognitive changes in the preclinical phase of AD. In this multicenter, prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments, we studied 333 healthy, older adults at hospital-based research clinics. Carbon 11-labeled Pittsburgh Compound B (PiB)-, florbetapir F 18-, or flutemetamol F 18-derived measures of Aβ, Hospital Anxiety and Depression Scale scores, and comprehensive neuropsychological evaluation that yielded measures of global cognition, verbal memory, visual memory, attention, language, executive function, and visuospatial ability. A positive Aβ (Aβ+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function, and elevated anxiety symptoms moderated these associations. Compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+, high-anxiety group, with Cohen d values of 0.78 (95% CI, 0.33-1.23) for global cognition, 0.54 (95% CI, 0.10-0.98) for verbal memory, 0.51 (95% CI, 0.07-0.96) for language, and 0.39 (95% CI, 0.05-0.83) for executive function. These effects were independent of age, educational level, IQ, APOE genotype, subjective memory complaints, vascular risk factors, and depressive symptoms; furthermore, depressive symptoms and subjective memory complaints did not moderate the association between Aβ and cognitive decline. These results provide additional support for the deleterious effect of elevated Aβ levels on cognitive function in preclinical AD. They further suggest that elevated anxiety symptoms moderate the effect of Aβ on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. Given that there is currently no standard antiamyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD.

Spatial Sequences, but Not Verbal Sequences, Are Vulnerable to General Interference during Retention in Working Memory

ERIC Educational Resources Information Center

Morey, Candice C.; Miron, Monica D.

2016-01-01

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…

Spontaneous Recovery of Human Spatial Memory in a Virtual Water Maze

ERIC Educational Resources Information Center

Luna, David; Martínez, Héctor

2015-01-01

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…

Spatial Working Memory Effects in Early Visual Cortex

ERIC Educational Resources Information Center

Munneke, Jaap; Heslenfeld, Dirk J.; Theeuwes, Jan

2010-01-01

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…

Cardiorespiratory Fitness Is Associated With Cognitive Performance in Older But Not Younger Adults.

PubMed

Hayes, Scott M; Forman, Daniel E; Verfaellie, Mieke

2016-05-01

Aging is associated with declines in executive function and episodic memory. Cardiorespiratory fitness (CRF) has been associated with enhanced executive function in older adults (OA), but the relationship with episodic memory remains unclear. The purpose of the study was to examine the relationship between CRF and cognition in young and OA and whether CRF mitigates age-related cognitive decline. Participants completed exercise testing to evaluate CRF (peak VO2) and neuropsychological testing to assess cognition. In OA, peak VO2 was positively related to executive function, as well as to accuracy on an experimental face-name memory task and visual episodic memory. In young adults (YA), a relationship between peak VO2 and cognition was not evident. High-fit OA performed as well as YA on executive function measures. On episodic memory measures, YA performed better than high-fit OA, who in turn performed better than low-fit OA. CRF is positively associated with executive function and episodic memory in OA and attenuates age-related cognitive decline. We provide preliminary support for the age-dependence hypothesis, which posits that cognition and CRF relationships may be most readily observed during lifetime periods of significant neurocognitive development. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

The Role of Occupational Complexity in Trajectories of Cognitive Aging Before and After Retirement

PubMed Central

Finkel, Deborah; Andel, Ross; Gatz, Margaret; Pedersen, Nancy L.

2009-01-01

We examined the association between complexity of the main lifetime occupation and changes in cognitive ability in later life. Data on complexity of work with data, people, and things and on four cognitive factors (verbal, spatial, memory, and speed) were available from 462 individuals in the longitudinal Swedish Adoption/Twin Study of Aging. Mean age at the first measurement wave was 64.3 (s.d. = 7.2) and 65% of the sample had at least 3 waves of data. Occupational complexity with people and data were both correlated with cognitive performance. Individuals with more complex work demonstrated higher mean performance on the verbal, spatial, and speed factors. Latent growth curve analyses indicated that, after correcting for education, only complexity with people was associated with differences in cognitive performance and rate of cognitive change. Continued engagement as a result of occupational complexity with people helped to facilitate verbal function before retirement, while a previous high level of complexity of work with people was associated with faster decline after retirement on the spatial factor. PMID:19739912

Age-Related Differences and Cognitive Correlates of Self-Reported and Direct Navigation Performance: The Effect of Real and Virtual Test Conditions Manipulation

PubMed Central

Taillade, Mathieu; N'Kaoua, Bernard; Sauzéon, Hélène

2016-01-01

The present study investigated the effect of aging on direct navigation measures and self-reported ones according to the real-virtual test manipulation. Navigation (wayfinding tasks) and spatial memory (paper-pencil tasks) performances, obtained either in real-world or in virtual-laboratory test conditions, were compared between young (n = 32) and older (n = 32) adults who had self-rated their everyday navigation behavior (SBSOD scale). Real age-related differences were observed in navigation tasks as well as in paper-pencil tasks, which investigated spatial learning relative to the distinction between survey-route knowledge. The manipulation of test conditions (real vs. virtual) did not change these age-related differences, which are mostly explained by age-related decline in both spatial abilities and executive functioning (measured with neuropsychological tests). In contrast, elderly adults did not differ from young adults in their self-reporting relative to everyday navigation, suggesting some underestimation of navigation difficulties by elderly adults. Also, spatial abilities in young participants had a mediating effect on the relations between actual and self-reported navigation performance, but not for older participants. So, it is assumed that the older adults carried out the navigation task with fewer available spatial abilities compared to young adults, resulting in inaccurate self-estimates. PMID:26834666

Age-Related Differences and Cognitive Correlates of Self-Reported and Direct Navigation Performance: The Effect of Real and Virtual Test Conditions Manipulation.

PubMed

Taillade, Mathieu; N'Kaoua, Bernard; Sauzéon, Hélène

2015-01-01

The present study investigated the effect of aging on direct navigation measures and self-reported ones according to the real-virtual test manipulation. Navigation (wayfinding tasks) and spatial memory (paper-pencil tasks) performances, obtained either in real-world or in virtual-laboratory test conditions, were compared between young (n = 32) and older (n = 32) adults who had self-rated their everyday navigation behavior (SBSOD scale). Real age-related differences were observed in navigation tasks as well as in paper-pencil tasks, which investigated spatial learning relative to the distinction between survey-route knowledge. The manipulation of test conditions (real vs. virtual) did not change these age-related differences, which are mostly explained by age-related decline in both spatial abilities and executive functioning (measured with neuropsychological tests). In contrast, elderly adults did not differ from young adults in their self-reporting relative to everyday navigation, suggesting some underestimation of navigation difficulties by elderly adults. Also, spatial abilities in young participants had a mediating effect on the relations between actual and self-reported navigation performance, but not for older participants. So, it is assumed that the older adults carried out the navigation task with fewer available spatial abilities compared to young adults, resulting in inaccurate self-estimates.

Smad4 SUMOylation is essential for memory formation through upregulation of the skeletal myopathy gene TPM2.

PubMed

Hsu, Wei L; Ma, Yun L; Liu, Yen C; Lee, Eminy H Y

2017-11-28

Smad4 is a critical effector of TGF-β signaling that regulates a variety of cellular functions. However, its role in the brain has rarely been studied. Here, we examined the molecular mechanisms underlying the post-translational regulation of Smad4 function by SUMOylation, and its role in spatial memory formation. In the hippocampus, Smad4 is SUMOylated by the E3 ligase PIAS1 at Lys-113 and Lys-159. Both spatial training and NMDA injection enhanced Smad4 SUMOylation. Inhibition of Smad4 SUMOylation impaired spatial learning and memory in rats by downregulating TPM2, a gene associated with skeletal myopathies. Similarly, knockdown of TPM2 expression impaired spatial learning and memory, while TPM2 mRNA and protein expression increased after spatial training. Among the TPM2 mutations associated with skeletal myopathies, the TPM2E122K mutation was found to reduce TPM2 expression and impair spatial learning and memory in rats. We have identified a novel role of Smad4 SUMOylation and TPM2 in learning and memory formation. These results suggest that patients with skeletal myopathies who carry the TPM2E122K mutation may also have deficits in learning and memory functions.

Coordinated prefrontal-hippocampal activity and navigation strategy-related prefrontal firing during spatial memory formation.

PubMed

Negrón-Oyarzo, Ignacio; Espinosa, Nelson; Aguilar, Marcelo; Fuenzalida, Marco; Aboitiz, Francisco; Fuentealba, Pablo

2018-06-18

Learning the location of relevant places in the environment is crucial for survival. Such capacity is supported by a distributed network comprising the prefrontal cortex and hippocampus, yet it is not fully understood how these structures cooperate during spatial reference memory formation. Hence, we examined neural activity in the prefrontal-hippocampal circuit in mice during acquisition of spatial reference memory. We found that interregional oscillatory coupling increased with learning, specifically in the slow-gamma frequency (20 to 40 Hz) band during spatial navigation. In addition, mice used both spatial and nonspatial strategies to navigate and solve the task, yet prefrontal neuronal spiking and oscillatory phase coupling were selectively enhanced in the spatial navigation strategy. Lastly, a representation of the behavioral goal emerged in prefrontal spiking patterns exclusively in the spatial navigation strategy. These results suggest that reference memory formation is supported by enhanced cortical connectivity and evolving prefrontal spiking representations of behavioral goals.

Spatial navigation, episodic memory, episodic future thinking, and theory of mind in children with autism spectrum disorder: evidence for impairments in mental simulation?

PubMed Central

Lind, Sophie E.; Bowler, Dermot M.; Raber, Jacob

2014-01-01

This study explored spatial navigation alongside several other cognitive abilities that are thought to share common underlying neurocognitive mechanisms (e.g., the capacity for self-projection, scene construction, or mental simulation), and which we hypothesized may be impaired in autism spectrum disorder (ASD). Twenty intellectually high-functioning children with ASD (with a mean age of ~8 years) were compared to 20 sex, age, IQ, and language ability matched typically developing children on a series of tasks to assess spatial navigation, episodic memory, episodic future thinking (also known as episodic foresight or prospection), theory of mind (ToM), relational memory, and central coherence. This is the first study to explore these abilities concurrently within the same sample. Spatial navigation was assessed using the “memory island” task, which involves finding objects within a realistic, computer simulated, three-dimensional environment. Episodic memory and episodic future thinking were assessed using a past and future event description task. ToM was assessed using the “animations” task, in which children were asked to describe the interactions between two animated triangles. Relational memory was assessed using a recognition task involving memory for items (line drawings), patterned backgrounds, or combinations of items and backgrounds. Central coherence was assessed by exploring differences in performance across segmented and unsegmented versions of block design. Children with ASD were found to show impairments in spatial navigation, episodic memory, episodic future thinking, and central coherence, but not ToM or relational memory. Among children with ASD, spatial navigation was found to be significantly negatively related to the number of repetitive behaviors. In other words, children who showed more repetitive behaviors showed poorer spatial navigation. The theoretical and practical implications of the results are discussed. PMID:25538661

Spatial navigation, episodic memory, episodic future thinking, and theory of mind in children with autism spectrum disorder: evidence for impairments in mental simulation?

PubMed

Lind, Sophie E; Bowler, Dermot M; Raber, Jacob

2014-01-01

This study explored spatial navigation alongside several other cognitive abilities that are thought to share common underlying neurocognitive mechanisms (e.g., the capacity for self-projection, scene construction, or mental simulation), and which we hypothesized may be impaired in autism spectrum disorder (ASD). Twenty intellectually high-functioning children with ASD (with a mean age of ~8 years) were compared to 20 sex, age, IQ, and language ability matched typically developing children on a series of tasks to assess spatial navigation, episodic memory, episodic future thinking (also known as episodic foresight or prospection), theory of mind (ToM), relational memory, and central coherence. This is the first study to explore these abilities concurrently within the same sample. Spatial navigation was assessed using the "memory island" task, which involves finding objects within a realistic, computer simulated, three-dimensional environment. Episodic memory and episodic future thinking were assessed using a past and future event description task. ToM was assessed using the "animations" task, in which children were asked to describe the interactions between two animated triangles. Relational memory was assessed using a recognition task involving memory for items (line drawings), patterned backgrounds, or combinations of items and backgrounds. Central coherence was assessed by exploring differences in performance across segmented and unsegmented versions of block design. Children with ASD were found to show impairments in spatial navigation, episodic memory, episodic future thinking, and central coherence, but not ToM or relational memory. Among children with ASD, spatial navigation was found to be significantly negatively related to the number of repetitive behaviors. In other words, children who showed more repetitive behaviors showed poorer spatial navigation. The theoretical and practical implications of the results are discussed.

Gait Rather Than Cognition Predicts Decline in Specific Cognitive Domains in Early Parkinson's Disease.

PubMed

Morris, Rosie; Lord, Sue; Lawson, Rachael A; Coleman, Shirley; Galna, Brook; Duncan, Gordon W; Khoo, Tien K; Yarnall, Alison J; Burn, David J; Rochester, Lynn

2017-11-09

Dementia is significant in Parkinson's disease (PD) with personal and socioeconomic impact. Early identification of risk is of upmost importance to optimize management. Gait precedes and predicts cognitive decline and dementia in older adults. We aimed to evaluate gait characteristics as predictors of cognitive decline in newly diagnosed PD. One hundred and nineteen participants recruited at diagnosis were assessed at baseline, 18 and 36 months. Baseline gait was characterized by variables that mapped to five domains: pace, rhythm, variability, asymmetry, and postural control. Cognitive assessment included attention, fluctuating attention, executive function, visual memory, and visuospatial function. Mixed-effects models tested independent gait predictors of cognitive decline. Gait characteristics of pace, variability, and postural control predicted decline in fluctuating attention and visual memory, whereas baseline neuropsychological assessment performance did not predict decline. This provides novel evidence for gait as a clinical biomarker for PD cognitive decline in early disease. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging.

PubMed

Maass, Anne; Lockhart, Samuel N; Harrison, Theresa M; Bell, Rachel K; Mellinger, Taylor; Swinnerton, Kaitlin; Baker, Suzanne L; Rabinovici, Gil D; Jagust, William J

2018-01-17

The medial temporal lobe (MTL) is an early site of tau accumulation and MTL dysfunction may underlie episodic-memory decline in aging and dementia. Postmortem data indicate that tau pathology in the transentorhinal cortex is common by age 60, whereas spread to neocortical regions and worsening of cognition is associated with β-amyloid (Aβ). We used [ 18 F]AV-1451 and [ 11 C]PiB positron emission tomography, structural MRI, and neuropsychological assessment to investigate how in vivo tau accumulation in temporal lobe regions, Aβ, and MTL atrophy contribute to episodic memory in cognitively normal older adults ( n = 83; age, 77 ± 6 years; 58% female). Stepwise regressions identified tau in MTL regions known to be affected in old age as the best predictor of episodic-memory performance independent of Aβ status. There was no interactive effect of MTL tau with Aβ on memory. Higher MTL tau was related to higher age in the subjects without evidence of Aβ. Among temporal lobe subregions, episodic memory was most strongly related to tau-tracer uptake in the parahippocampal gyrus, particularly the posterior entorhinal cortex, which in our parcellation includes the transentorhinal cortex. In subjects with longitudinal MRI and cognitive data ( n = 57), entorhinal atrophy mirrored patterns of tau pathology and their relationship with memory decline. Our data are consistent with neuropathological studies and further suggest that entorhinal tau pathology underlies memory decline in old age even without Aβ. SIGNIFICANCE STATEMENT Tau tangles and β-amyloid (Aβ) plaques are key lesions in Alzheimer's disease (AD) but both pathologies also occur in cognitively normal older people. Neuropathological data indicate that tau tangles in the medial temporal lobe (MTL) underlie episodic-memory impairments in AD dementia. However, it remains unclear whether MTL tau pathology also accounts for memory impairments often seen in elderly people and how Aβ affects this relationship. Using tau-specific and Aβ-specific positron emission tomography tracers, we show that in vivo MTL tau pathology is associated with episodic-memory performance and MTL atrophy in cognitively normal adults, independent of Aβ. Our data point to MTL tau pathology, particularly in the entorhinal cortex, as a substrate of age-related episodic-memory loss. Copyright © 2018 the authors 0270-6474/18/380530-14$15.00/0.

Validation of the human odor span task: effects of nicotine.

PubMed

MacQueen, David A; Drobes, David J

2017-10-01

Amongst non-smokers, nicotine generally enhances performance on tasks of attention, with limited effect on working memory. In contrast, nicotine has been shown to produce robust enhancements of working memory in non-humans. To address this gap, the present study investigated the effects of nicotine on the performance of non-smokers on a cognitive battery which included a working memory task reverse-translated from use with rodents (the odor span task, OST). Nicotine has been reported to enhance OST performance in rats and the present study assessed whether this effect generalizes to human performance. Thirty non-smokers were tested on three occasions after consuming either placebo, 2 mg, or 4 mg nicotine gum. On each occasion, participants completed a battery of clinical and experimental tasks of working memory and attention. Nicotine was associated with dose-dependent enhancements in sustained attention, as evidenced by increased hit accuracy on the rapid visual information processing (RVIP) task. However, nicotine failed to produce main effects on OST performance or on alternative measures of working memory (digit span, spatial span, letter-number sequencing, 2-back) or attention (digits forward, 0-back). Interestingly, enhancement of RVIP performance occurred concomitant to significant reductions in self-reported attention/concentration. Human OST performance was significantly related to N-back performance, and as in rodents, OST accuracy declined with increasing memory load. Given the similarity of human and rodent OST performance under baseline conditions and the strong association between OST and visual 0-back accuracy, the OST may be particular useful in the study of conditions characterized by inattention.

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.

PubMed

Daulatzai, Mak Adam

2016-10-01

Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory

PubMed Central

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

2005-01-01

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:16011544

Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory.

PubMed

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

2005-07-01

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.

Emotion’s Influence on Memory for Spatial and Temporal Context

PubMed Central

Schmidt, Katherine; Patnaik, Pooja; Kensinger, Elizabeth A.

2010-01-01

Individuals report remembering emotional items vividly. It is debated whether this report reflects enhanced memory accuracy or a bias to believe emotional memories are vivid. We hypothesized emotion would enhance memory accuracy, improving memory for contextual details. The hallmark of episodic memory is that items are remembered in a spatial and temporal context, so we examined whether an item’s valence (positive, negative) or arousal (high, low) would influence its ability to be remembered with those contextual details. Across two experiments, high-arousal items were remembered with spatial and temporal context more often than low-arousal items. Item valence did not influence memory for those details, although positive high-arousal items were recognized or recalled more often than negative items. These data suggest that emotion does not just bias participants to believe they have a vivid memory; rather, the arousal elicited by an event can benefit memory for some types of contextual details. PMID:21379376

Emotional state and local versus global spatial memory.

PubMed

Brunyé, Tad T; Mahoney, Caroline R; Augustyn, Jason S; Taylor, Holly A

2009-02-01

The present work investigated the effects of participant emotional state on global versus local memory for map-based information. Participants were placed into one of four emotion induction groups, crossing high and low arousal with positive and negative valence, or a control group. They then studied a university campus map and completed two memory tests, free recall and spatial statement verification. Converging evidence from these two tasks demonstrated that arousal amplifies symbolic distance effects and leads to a globally-focused spatial mental representation, partially at the expense of local knowledge. These results were found for both positively- and negatively-valenced affective states. The present study is the first investigation of emotional effects on spatial memory, and has implications for theories of emotion and spatial cognition.

Effect of acute pesticide exposure on bee spatial working memory using an analogue of the radial-arm maze

NASA Astrophysics Data System (ADS)

Samuelson, Elizabeth E. W.; Chen-Wishart, Zachary P.; Gill, Richard J.; Leadbeater, Ellouise

2016-12-01

Pesticides, including neonicotinoids, typically target pest insects by being neurotoxic. Inadvertent exposure to foraging insect pollinators is usually sub-lethal, but may affect cognition. One cognitive trait, spatial working memory, may be important in avoiding previously-visited flowers and other spatial tasks such as navigation. To test this, we investigated the effect of acute thiamethoxam exposure on spatial working memory in the bumblebee Bombus terrestris, using an adaptation of the radial-arm maze (RAM). We first demonstrated that bumblebees use spatial working memory to solve the RAM by showing that untreated bees performed significantly better than would be expected if choices were random or governed by stereotyped visitation rules. We then exposed bees to either a high sub-lethal positive control thiamethoxam dose (2.5 ng-1 bee), or one of two low doses (0.377 or 0.091 ng-1) based on estimated field-realistic exposure. The high dose caused bees to make more and earlier spatial memory errors and take longer to complete the task than unexposed bees. For the low doses, the negative effects were smaller but statistically significant, and dependent on bee size. The spatial working memory impairment shown here has the potential to harm bees exposed to thiamethoxam, through possible impacts on foraging efficiency or homing.

Selective deficit in spatial memory strategies contrast to intact response strategies in patients with schizophrenia spectrum disorders tested in a virtual navigation task.

PubMed

Wilkins, Leanne K; Girard, Todd A; Konishi, Kyoko; King, Matthew; Herdman, Katherine A; King, Jelena; Christensen, Bruce; Bohbot, Veronique D

2013-11-01

Spatial memory is impaired among persons with schizophrenia (SCZ). However, different strategies may be used to solve most spatial memory and navigation tasks. This study investigated the hypothesis that participants with schizophrenia-spectrum disorders (SSD) would demonstrate differential impairment during acquisition and retrieval of target locations when using a hippocampal-dependent spatial strategy, but not a response strategy, which is more associated with caudate function. Healthy control (CON) and SSD participants were tested using the 4-on-8 virtual maze (4/8VM), a virtual navigation task designed to differentiate between participants' use of spatial and response strategies. Consistent with our predictions, SSD participants demonstrated a differential deficit such that those who navigated using a spatial strategy made more errors and took longer to locate targets. In contrast, SSD participants who spontaneously used a response strategy performed as well as CON participants. The differential pattern of spatial-memory impairment in SSD provides only indirect support for underlying hippocampal dysfunction. These findings emphasize the importance of considering individual strategies when investigating SSD-related memory and navigation performance. Future cognitive intervention protocols may harness SSD participants' intact ability to navigate using a response strategy and/or train the deficient ability to navigate using a spatial strategy to improve navigation and memory abilities in participants with SSD. Copyright © 2013 Wiley Periodicals, Inc.

Effects of verbal and nonverbal interference on spatial and object visual working memory.

PubMed

Postle, Bradley R; Desposito, Mark; Corkin, Suzanne

2005-03-01

We tested the hypothesis that a verbal coding mechanism is necessarily engaged by object, but not spatial, visual working memory tasks. We employed a dual-task procedure that paired n-back working memory tasks with domain-specific distractor trials inserted into each interstimulus interval of the n-back tasks. In two experiments, object n-back performance demonstrated greater sensitivity to verbal distraction, whereas spatial n-back performance demonstrated greater sensitivity to motion distraction. Visual object and spatial working memory may differ fundamentally in that the mnemonic representation of featural characteristics of objects incorporates a verbal (perhaps semantic) code, whereas the mnemonic representation of the location of objects does not. Thus, the processes supporting working memory for these two types of information may differ in more ways than those dictated by the "what/where" organization of the visual system, a fact more easily reconciled with a component process than a memory systems account of working memory function.

Spatial working memory capacity predicts bias in estimates of location.

PubMed

Crawford, L Elizabeth; Landy, David; Salthouse, Timothy A

2016-09-01

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 (c) 2016 APA, all rights reserved).

Spatial Working Memory Capacity Predicts Bias in Estimates of Location

PubMed Central

Crawford, L. Elizabeth; Landy, David H.; Salthouse, Timothy A.

2016-01-01

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 intra-individual stability and inter-individual 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. PMID:26900708

Effects of verbal and nonverbal interference on spatial and object visual working memory

PubMed Central

POSTLE, BRADLEY R.; D’ESPOSITO, MARK; CORKIN, SUZANNE

2005-01-01

We tested the hypothesis that a verbal coding mechanism is necessarily engaged by object, but not spatial, visual working memory tasks. We employed a dual-task procedure that paired n-back working memory tasks with domain-specific distractor trials inserted into each interstimulus interval of the n-back tasks. In two experiments, object n-back performance demonstrated greater sensitivity to verbal distraction, whereas spatial n-back performance demonstrated greater sensitivity to motion distraction. Visual object and spatial working memory may differ fundamentally in that the mnemonic representation of featural characteristics of objects incorporates a verbal (perhaps semantic) code, whereas the mnemonic representation of the location of objects does not. Thus, the processes supporting working memory for these two types of information may differ in more ways than those dictated by the “what/where” organization of the visual system, a fact more easily reconciled with a component process than a memory systems account of working memory function. PMID:16028575

Characteristic of cognitive decline in Parkinson's disease: a 1-year follow-up.

PubMed

McKinlay, Audrey; Grace, Randolph C

2011-10-01

The aim of this study was to track the evolution of cognitive decline in Parkinson's disease (PD) patients 1 year after baseline testing. Thirty-three PD patients, divided according to three previously determined subgroups based on their initial cognitive performance, and a healthy comparison group were reassessed after a 1-year interval. Participants were assessed in the following five domains: Executive Function, Problem Solving, Working Memory/Attention, Memory, and Visuospatial Ability. The PD groups differed on the domains of Executive Function, Problem Solving, and Working Memory, with the most severe deficits being evident for the group that had previously shown the greatest level of impairment. Increased cognitive problems were also associated with decreased functioning in activities of daily living. The most severely impaired group had evidence of global cognitive decline, possibly reflecting a stage of preclinical dementia.

Differential verbal, visual, and spatial working memory in written language production.

PubMed

Raulerson, Bascom A; Donovan, Michael J; Whiteford, Alison P; Kellogg, Ronald T

2010-02-01

The contributions of verbal, visual, and spatial working memory to written language production were investigated. Participants composed definitions for nouns while concurrently performing a task which required updating, storing, and retrieving information coded either verbally, visually, or spatially. The present study extended past findings by showing the linguistic encoding of planned conceptual content makes its largest demand on verbal working memory for both low and high frequency nouns. Kellogg, Olive, and Piolat in 2007 found that concrete nouns place substantial demands on visual working memory when imaging the nouns' referents during planning, whereas abstract nouns make no demand. The current study further showed that this pattern was not an artifact of visual working memory being sensitive to manipulation of just any lexical property of the noun prompts. In contrast to past results, writing made a small but detectible demand on spatial working memory.

Practice of aerobic sports is associated with better spatial memory in adults and older men.

PubMed

Sánchez-Horcajo, Rubén; Llamas-Alonso, Juan; Cimadevilla, José Manuel

2015-01-01

BACKGROUND/STUDY CONTEXT: Cognitive abilities experience diverse age-related changes. Memory complaints are common in aging. The practice of sports is known to benefit brain functioning, improving memory among other abilities. Introduction of virtual reality tasks makes it possible to easily assess cognitive functions such as spatial memory, a hippocampus-dependent cognitive ability. In this study, the authors applied a virtual reality-based task to study spatial reference memory in two groups of men, sportsmen (n=28) and sedentary (n=28), across three different age groups: 50-59, 60-69, and 70-77 years. The data showed that sportsmen outperformed sedentary participants. In addition, there was also a significant effect of the factor age. Hence, older men (70-77 years old) displayed a poorer performance in comparison with the other age groups. These results support the beneficial effect of habitual physical activity in spatial memory.

Developing Spatial Orientation and Spatial Memory with a Treasure Hunting Game

ERIC Educational Resources Information Center

Lin, Chien-Heng; Chen, Chien-Min; Lou, Yu-Chiung

2014-01-01

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…

Primacy Performance of Normal and Retarded Children: Stimulus Familiarity or Spatial Memory?

ERIC Educational Resources Information Center

Swanson, Lee

1978-01-01

Explores the effect of stimulus familiarity on the spatial primacy performance of normal and retarded children. Assumes that serial recall tasks reflect spatial memory rather than verbal rehearsal. (BD)

White Matter Abnormalities Correlating with Memory and Depression in Heroin Users under Methadone Maintenance Treatment

PubMed Central

Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chien-Chih; Huang, Chu-Chung; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Wang, Ya-Ling; Cheng, Yu-Fan; Lin, Ching-Po

2012-01-01

Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM) disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI), and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT. PMID:22496768

The Effects of Spatial Contextual Familiarity on Remembered Scenes, Episodic Memories, and Imagined Future Events

ERIC Educational Resources Information Center

Robin, Jessica; Moscovitch, Morris

2014-01-01

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…

Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition

PubMed Central

Miller, Adam M. P.; Vedder, Lindsey C.; Law, L. Matthew; Smith, David M.

2014-01-01

Spatial navigation requires memory representations of landmarks and other navigation cues. The retrosplenial cortex (RSC) is anatomically positioned between limbic areas important for memory formation, such as the hippocampus (HPC) and the anterior thalamus, and cortical regions along the dorsal stream known to contribute importantly to long-term spatial representation, such as the posterior parietal cortex. Damage to the RSC severely impairs allocentric representations of the environment, including the ability to derive navigational information from landmarks. The specific deficits seen in tests of human and rodent navigation suggest that the RSC supports allocentric representation by processing the stable features of the environment and the spatial relationships among them. In addition to spatial cognition, the RSC plays a key role in contextual and episodic memory. The RSC also contributes importantly to the acquisition and consolidation of long-term spatial and contextual memory through its interactions with the HPC. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the HPC and as a target of the hippocampal-dependent systems consolidation of long-term memory. PMID:25140141

Remaking Memories: Reconsolidation Updates Positively Motivated Spatial Memory in Rats

ERIC Educational Resources Information Center

Jones, Bethany; Bukoski, Elizabeth; Nadel, Lynn; Fellous, Jean-Marc

2012-01-01

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…

Verbal and visual-spatial working memory and mathematical ability in different domains throughout primary school.

PubMed

Van de Weijer-Bergsma, Eva; Kroesbergen, Evelyn H; Van Luit, Johannes E H

2015-04-01

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.

The Structure of Working Memory Abilities across the Adult Life Span

PubMed Central

Hale, Sandra; Rose, Nathan S.; Myerson, Joel; Strube, Michael J; Sommers, Mitchell; Tye-Murray, Nancy; Spehar, Brent

2010-01-01

The present study addresses three questions regarding age differences in working memory: (1) whether performance on complex span tasks decreases as a function of age at a faster rate than performance on simple span tasks; (2) whether spatial working memory decreases at a faster rate than verbal working memory; and (3) whether the structure of working memory abilities is different for different age groups. Adults, ages 20–89 (n=388), performed three simple and three complex verbal span tasks and three simple and three complex spatial memory tasks. Performance on the spatial tasks decreased at faster rates as a function of age than performance on the verbal tasks, but within each domain, performance on complex and simple span tasks decreased at the same rates. Confirmatory factor analyses revealed that domain-differentiated models yielded better fits than models involving domain-general constructs, providing further evidence of the need to distinguish verbal and spatial working memory abilities. Regardless of which domain-differentiated model was examined, and despite the faster rates of decrease in the spatial domain, age group comparisons revealed that the factor structure of working memory abilities was highly similar in younger and older adults and showed no evidence of age-related dedifferentiation. PMID:21299306

Electrolytic lesions of dorsal CA3 impair episodic-like memory in rats.

PubMed

Li, Jay-Shake; Chao, Yuen-Shin

2008-02-01

Episodic memory is the ability to recollect one's past experiences occurring in an unique spatial and temporal context. In non-human animals, it is expressed in the ability to combine "what", "where" and "when" factors to form an integrated memory system. During the search for its neural substrates, the hippocampus has attracted a lot of attentions. Yet, it is not yet possible to induce a pure episodic-like memory deficit in animal studies without being confounded by impairments in the spatial cognition. Here, we present a lesion study evidencing direct links between the hippocampus CA3 region and the episodic-like memory in rats. In a spontaneous object exploration task, lesioned rats showed no interaction between the temporal and spatial elements in their memory associated with the objects. In separate tests carried out subsequently, the same animals still expressed abilities to process spatial, temporal, and object recognition memory. In conclusions, our results support the idea that the hippocampus CA3 has a particular status in the neural mechanism of the episodic-like memory system. It is responsible for combining information from different modules of cognitive processes.

High and low schizotypal female subjects do not differ in spatial memory abilities in a virtual reality task.

PubMed

García-Montes, José Manuel; Noguera, Carmen; Alvarez, Dolores; Ruiz, Marina; Cimadevilla Redondo, José Manuel

2014-01-01

Schizotypy is a psychological construct related to schizophrenia. The exact relationship between both entities is not clear. In recent years, schizophrenia has been associated with hippocampal abnormalities and spatial memory problems. The aim of this study was to determine possible links between high schizotypy (HS) and low schizotypy (LS) and spatial abilities, using virtual reality tasks. We hypothesised that the HS group would exhibit a lower performance in spatial memory tasks than the LS group. Two groups of female students were formed according to their score on the ESQUIZO-Q-A questionnaire. HS and LS subjects were tested on two different tasks: the Boxes Room task, a spatial memory task sensitive to hippocampal alterations and a spatial recognition task. Data showed that both groups mastered both tasks. Groups differed in personality features but not in spatial performance. These results provide valuable information about the schizotypy-schizophrenia connections. Schizotypal subjects are not impaired on spatial cognition and, accordingly, the schizotypy-schizophrenia relationship is not straightforward.

Functional connectivity of hippocampal and prefrontal networks during episodic and spatial memory based on real-world environments.

PubMed

Robin, Jessica; Hirshhorn, Marnie; Rosenbaum, R Shayna; Winocur, Gordon; Moscovitch, Morris; Grady, Cheryl L

2015-01-01

Several recent studies have compared episodic and spatial memory in neuroimaging paradigms in order to understand better the contribution of the hippocampus to each of these tasks. In the present study, we build on previous findings showing common neural activation in default network areas during episodic and spatial memory tasks based on familiar, real-world environments (Hirshhorn et al. (2012) Neuropsychologia 50:3094-3106). Following previous demonstrations of the presence of functionally connected sub-networks within the default network, we performed seed-based functional connectivity analyses to determine how, depending on the task, the hippocampus and prefrontal cortex differentially couple with one another and with distinct whole-brain networks. We found evidence for a medial prefrontal-parietal network and a medial temporal lobe network, which were functionally connected to the prefrontal and hippocampal seeds, respectively, regardless of the nature of the memory task. However, these two networks were functionally connected with one another during the episodic memory task, but not during spatial memory tasks. Replicating previous reports of fractionation of the default network into stable sub-networks, this study also shows how these sub-networks may flexibly couple and uncouple with one another based on task demands. These findings support the hypothesis that episodic memory and spatial memory share a common medial temporal lobe-based neural substrate, with episodic memory recruiting additional prefrontal sub-networks. © 2014 Wiley Periodicals, Inc.

Cultural differences in rated typicality and perceived causes of memory changes in adulthood.

PubMed

Bottiroli, Sara; Cavallini, Elena; Fastame, Maria Chiara; Hertzog, Christopher

2013-01-01

This study examined cultural differences in stereotypes and attributions regarding aging and memory. Two subcultures belonging to the same country, Italy, were compared on general beliefs about memory. Sardinians live longer than other areas of Italy, which is a publically shared fact that informs stereotypes about that subculture. An innovative instrument evaluating simultaneously aging stereotypes and attributions about memory and memory change in adulthood was administered to 52 Sardinian participants and 52 Milanese individuals divided into three age groups: young (20-30), young-old (60-70), and old-old (71-85) adults. Both Milanese and Sardinians reported that memory decline across the life span is more typical than a pattern of stability or improvement. However, Sardinians viewed stability and improvement in memory as more typical than did the Milanese. Interestingly, cultural differences emerged in attributions about memory improvement. Although all Sardinian age groups rated nutrition and heredity as relevant causes in determining the memory decline, Sardinians' rated typicality of life-span memory improvement correlated strongly with causal attributions to a wide number of factors, including nutrition and heredity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effects of testosterone on spatial learning and memory in adult male rats

PubMed Central

Spritzer, Mark D.; Daviau, Emily D.; Coneeny, Meagan K.; Engelman, Shannon M.; Prince, W. Tyler; Rodriguez-Wisdom, Karlye N.

2011-01-01

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

The Spatial Scaffold: The Effects of Spatial Context on Memory for Events

ERIC Educational Resources Information Center

Robin, Jessica; Wynn, Jordana; Moscovitch, Morris

2016-01-01

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…

Changes in the Hippocampal Proteome Associated with Spatial Memory Impairment after Exposure to Low (20 cGy) Doses of 1 GeV/n 56Fe Radiation.

PubMed

Britten, Richard A; Jewell, Jessica S; Davis, Leslie K; Miller, Vania D; Hadley, Melissa M; Semmes, O John; Lonart, György; Dutta, Sucharita M

2017-03-01

Exposure to low (∼20 cGy) doses of high-energy charged (HZE) particles, such as 1 GeV/n 56 Fe, results in impaired hippocampal-dependent learning and memory (e.g., novel object recognition and spatial memory) in rodents. While these findings raise the possibility that astronauts on deep-space missions may develop cognitive deficits, not all rats develop HZE-induced cognitive impairments, even after exposure to high (200 cGy) HZE doses. The reasons for this differential sensitivity in some animals that develop HZE-induced cognitive failure remain speculative. We employed a robust quantitative mass spectrometry-based workflow, which links early-stage discovery to next-stage quantitative verification, to identify differentially active proteins/pathways in rats that developed spatial memory impairment at three months after exposure to 20 cGy of 1 GeV/n 56 Fe (20/impaired), and in those rats that managed to maintain normal cognitive performance (20/functional). Quantitative data were obtained on 665-828 hippocampal proteins in the various cohorts of rats studied, of which 580 were expressed in all groups. A total of 107 proteins were upregulated in the irradiated rats irrespective of their spatial memory performance status, which included proteins involved in oxidative damage response, calcium transport and signaling. Thirty percent (37/107) of these "radiation biomarkers" formed a functional interactome of the proteasome and the COP9 signalosome. These data suggest that there is persistent oxidative stress, ongoing autophagy and altered synaptic plasticity in the irradiated hippocampus, irrespective of the spatial memory performance status, suggesting that the ultimate phenotype may be determined by how well the hippocampal neurons compensate to the ongoing oxidative stress and associated side effects. There were 67 proteins with expression that correlated with impaired spatial memory performance. Several of the "impaired biomarkers" have been implicated in poor spatial memory performance, neurodegeneration, neuronal loss or neuronal susceptibility to apoptosis, or neuronal synaptic or structural plasticity. Therefore, in addition to the baseline oxidative stress and altered adenosine metabolism observed in all irradiated rats, the 20/impaired rats expressed proteins that led to poor spatial memory performance, enhanced neuronal loss and apoptosis, changes in synaptic plasticity and dendritic remodeling. A total of 46 proteins, which were differentially upregulated in the sham-irradiated and 20/functional rat cohorts, can thus be considered as markers of good spatial memory, while another 95 proteins are associated with the maintenance of good spatial memory in the 20/functional rats. The loss or downregulation of these "good spatial memory" proteins would most likely exacerbate the situation in the 20/impaired rats, having a major impact on their neurocognitive status, given that many of those proteins play an important role in neuronal homeostasis and function. Our large-scale comprehensive proteomic analysis has provided some insight into the processes that are altered after exposure, and the collective data suggests that there are multiple problems with the functionality of the neurons and astrocytes in the irradiated hippocampi, which appear to be further exacerbated in the rats that have impaired spatial memory performance or partially compensated for in the rats with good spatial memory.

Nucleus incertus inactivation impairs spatial learning and memory in rats.

PubMed

Nategh, Mohsen; Nikseresht, Sara; Khodagholi, Fariba; Motamedi, Fereshteh

2015-02-01

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. Copyright © 2014 Elsevier Inc. All rights reserved.

Age-Related Differences in Memory and Executive Functions in Healthy "APOE"[epsilon]4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure

ERIC Educational Resources Information Center

Bender, Andrew R.; Raz, Naftali

2012-01-01

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…

Visual distraction and visuo-spatial memory: a sandwich effect.

PubMed

Tremblay, Sébastien; Nicholls, Alastair P; Parmentier, Fabrice B R; Jones, Dylan M

2005-01-01

The functional characteristics of visuo-spatial serial memory and its sensitivity to irrelevant visual information are examined in the present study, through the investigation of the sandwich effect (e.g., Hitch, 1975). The memory task was one of serial recall for the position of a sequence of seven spatially and temporally separated dots. The presence of irrelevant dots interpolated with to-be-remembered dots affected performance over most serial positions (Experiment 1) but that effect was significantly reduced when the interpolated dots were distinct from the to-be-remembered dots by colour and shape (Experiment 2). Parallels are made between verbal and spatial serial memory, and the reduction of the sandwich effect is discussed in terms of the contribution of perceptual organisation and attentional factors in short-term memory.

The Role of Aging in Intra-Item and Item-Context Binding Processes in Visual Working Memory

ERIC Educational Resources Information Center

Peterson, Dwight J.; Naveh-Benjamin, Moshe

2016-01-01

Aging is accompanied by declines in both working memory and long-term episodic memory processes. Specifically, important age-related memory deficits are characterized by performance impairments exhibited by older relative to younger adults when binding distinct components into a single integrated representation, despite relatively intact memory…

Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation.

PubMed

Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

2015-03-01

Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured spatial learning and memory, the time of normal rats was shortened by GEN treatment compared to the vehicle group, but only in the early stages of testing. In the glucose-loaded group, GEN treatment improved performance as mazes were advanced. In the open-field test, GEN treatment delayed habituation to the new environment in normal rats, and increased the exploratory behaviors of glucose-loaded rats. There were no significant differences observed for emotionality or fear-motivated learning and memory. Together, these results indicate that GEN treatment improved spatial learning and memory only in the early stages of testing in the normal state, but improved spatial learning and memory when glucose levels increased during memory consolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

Persistent increased PKMζ in long-term and remote spatial memory.

PubMed

Hsieh, Changchi; Tsokas, Panayiotis; Serrano, Peter; Hernández, A Iván; Tian, Dezhi; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2017-02-01

PKMζ is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKMζ protein sustain the kinase's action in LTP, the molecular mechanism for the persistent action of PKMζ during long-term memory has not been characterized. PKMζ inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1day to 1month after training. Therefore, if the mechanisms of PKMζ's persistent action in LTP maintenance and long-term memory were similar, persistent increases in PKMζ would last for the duration of the memory, far longer than most other learning-induced gene products. Here we find that spatial conditioning by aversive active place avoidance or appetitive radial arm maze induces PKMζ increases in dorsal hippocampus that persist from 1day to 1month, coinciding with the strength and duration of memory retention. Suppressing the increase by intrahippocampal injections of PKMζ-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKMζ sustains the kinase's action during long-term and remote spatial memory maintenance. Copyright © 2016. Published by Elsevier Inc.

What we remember affects how we see: spatial working memory steers saccade programming.

PubMed

Wong, Jason H; Peterson, Matthew S

2013-02-01

Relationships between visual attention, saccade programming, and visual working memory have been hypothesized for over a decade. Awh, Jonides, and Reuter-Lorenz (Journal of Experimental Psychology: Human Perception and Performance 24(3):780-90, 1998) and Awh et al. (Psychological Science 10(5):433-437, 1999) proposed that rehearsing a location in memory also leads to enhanced attentional processing at that location. In regard to eye movements, Belopolsky and Theeuwes (Attention, Perception & Psychophysics 71(3):620-631, 2009) found that holding a location in working memory affects saccade programming, albeit negatively. In three experiments, we attempted to replicate the findings of Belopolsky and Theeuwes (Attention, Perception & Psychophysics 71(3):620-631, 2009) and determine whether the spatial memory effect can occur in other saccade-cuing paradigms, including endogenous central arrow cues and exogenous irrelevant singletons. In the first experiment, our results were the opposite of those in Belopolsky and Theeuwes (Attention, Perception & Psychophysics 71(3):620-631, 2009), in that we found facilitation (shorter saccade latencies) instead of inhibition when the saccade target matched the region in spatial working memory. In Experiment 2, we sought to determine whether the spatial working memory effect would generalize to other endogenous cuing tasks, such as a central arrow that pointed to one of six possible peripheral locations. As in Experiment 1, we found that saccade programming was facilitated when the cued location coincided with the saccade target. In Experiment 3, we explored how spatial memory interacts with other types of cues, such as a peripheral color singleton target or irrelevant onset. In both cases, the eyes were more likely to go to either singleton when it coincided with the location held in spatial working memory. On the basis of these results, we conclude that spatial working memory and saccade programming are likely to share common overlapping circuitry.

Interaction between hippocampal serotonin and cannabinoid systems in reactivity to spatial and object novelty detection.

PubMed

Nasehi, Mohammad; Rostam-Nezhad, Elnaz; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

2017-01-15

Functional interaction between cannabinoid and serotonin neuronal systems have been reported in different tasks related to memory assessment. The present study investigated the effect of serotonin 5-HT4 agents into the dorsal hippocampus (the CA1 region) on spatial and object novelty detection deficits induced by activation of cannabinoid CB1 receptors (CB1Rs) using arachidonylcyclopropylamide (ACPA) in a non-associative behavioral task designed to forecast the ability of rodents to encode spatial and non-spatial relationships between distinct stimuli. Post-training, intra-CA1 microinjection of 5-HT4 receptor agonist RS67333 or 5-HT4 receptor antagonist RS23597 both at the dose of 0.016μg/mouse impaired spatial memory, while cannabinoid CB1R antagonist AM251 (0.1μg/mouse) facilitated object novelty memory. Also, post-training, intraperitoneal administration of CB1R agonist ACPA (0.005-0.05mg/kg) impaired both memories. However, a subthreshold dose of RS67333 restored ACPA response on both memories. Moreover, a subthreshold dose of RS23597 potentiated ACPA (0.01mg/kg) and reversed ACPA (0.05mg/kg) responses on spatial memory, while it potentiated ACPA response at the dose of 0.005 or 0.05mg/kg on object novelty memory. Furthermore, effective dose of AM251 restored ACPA response at the higher dose. AM251 blocked response induced by combination of RS67333 or RS23597 and the higher dose of ACPA on both memories. Our results highlight that hippocampal 5-HT4 receptors differently affect cannabinoid signaling in spatial and object novelty memories. The inactivation of CB1 receptors blocks the effect of 5-HT4 agents into the CA1 region on memory deficits induced by activation of CB1Rs via ACPA. Copyright © 2016. Published by Elsevier B.V.

Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease.

PubMed

Cordella, Alberto; Krashia, Paraskevi; Nobili, Annalisa; Pignataro, Annabella; La Barbera, Livia; Viscomi, Maria Teresa; Valzania, Alessandro; Keller, Flavio; Ammassari-Teule, Martine; Mercuri, Nicola Biagio; Berretta, Nicola; D'Amelio, Marcello

2018-08-01

The functional loop involving the ventral tegmental area (VTA), dorsal hippocampus and nucleus accumbens (NAc) plays a pivotal role in the formation of spatial memory and persistent memory traces. In particular, the dopaminergic innervation from the VTA to the hippocampus is critical for hippocampal-related memory function and alterations in the midbrain dopaminergic system are frequently reported in Alzheimer's disease (AD), contributing to age-related decline in memory and non-cognitive functions. However, much less is known about the hippocampus-NAc connectivity in AD. Here, we evaluated the functioning of the hippocampus-to-NAc core connectivity in the Tg2576 mouse model of AD that shows a selective and progressive degeneration of VTA dopaminergic neurons. We show that reduced dopaminergic innervation in the Tg2576 hippocampus results in reduced synaptic plasticity and excitability of dorsal subiculum pyramidal neurons. Importantly, the glutamatergic transmission from the hippocampus to the NAc core is also impaired. Chemogenetic depolarisation of Tg2576 subicular pyramidal neurons with an excitatory Designer Receptor Exclusively Activated by Designer Drugs, or systemic administration of the DA precursor levodopa, can both rescue the deficits in Tg2576 mice. Our data suggest that the dopaminergic signalling in the hippocampus is essential for the proper functioning of the hippocampus-NAc excitatory synaptic transmission. Copyright © 2018 Elsevier Inc. All rights reserved.