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Sample records for age-related memory deficits

  1. Altered Hippocampal Transcript Profile Accompanies an Age-Related Spatial Memory Deficit in Mice

    ERIC Educational Resources Information Center

    Verbitsky, Miguel; Yonan, Amanda L.; Malleret, Gael; Kandel, Eric R.; Gilliam, T. Conrad; Pavlidis, Paul

    2004-01-01

    We have carried out a global survey of age-related changes in mRNA levels in the 57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged…

  2. Aging and associative recognition: A view from the DRYAD model of age-related memory deficits.

    PubMed

    Benjamin, Aaron S

    2016-02-01

    How do we best characterize the memory deficits that accompany aging? A popular hypothesis, articulated originally by Naveh-Benjamin (2000) and reviewed in the accompanying article by Smyth and Naveh-Benjamin (2016), suggests that older adults are selectively deficient in establishing associations between to-be-learned memoranda and as a result have deficits in memory for sources or contexts. An alternative proposal, called density of representations yields age-related deficits (DRYAD) and outlined in recent articles by Benjamin (2010) and colleagues (Benjamin, Diaz, Matzen, & Johnson, 2012), attributes disproportionate deficits in memory to a global, rather than a selective, deficit of memory. In an attempt to adjudicate between these competing positions, Smyth and Naveh-Benjamin (2016) discussed 2 sets of experimental data that they claim speak against the global deficit model. Here I review some general principles of how the global-deficit view is applied to experimental paradigms and demonstrate that even a simplified form of DRYAD can comfortably accommodate the critical findings cited by Smyth and Naveh-Benjamin. I also evaluate aspects of their results that may be problematic for DRYAD and describe ways in which DRYAD's account of associative recognition can be falsified. I end with a discussion of the complementary strengths and weaknesses of the 2 approaches and consider ways in which the associative deficit hypothesis and DRYAD might work more profitably together than apart.

  3. Changes in pattern completion – a key mechanism to explain age-related recognition memory deficits?

    PubMed Central

    Vieweg, Paula; Stangl, Matthias; Howard, Lorelei R.; Wolbers, Thomas

    2016-01-01

    Accurate memory retrieval from partial or degraded input requires the reactivation of memory traces, a hippocampal mechanism termed pattern completion. Age-related changes in hippocampal integrity have been hypothesized to shift the balance of memory processes in favor of the retrieval of already stored information (pattern completion), to the detriment of encoding new events (pattern separation). Using a novel behavioral paradigm, we investigated the impact of cognitive aging (1) on recognition performance across different levels of stimulus completeness, and (2) on potential response biases. Participants were required to identify previously learned scenes among new ones. Additionally, all stimuli were presented in gradually masked versions to alter stimulus completeness. Both young and older adults performed increasingly poorly as the scenes became less complete, and this decline in performance was more pronounced in elderly participants indicative of a pattern completion deficit. Intriguingly, when novel scenes were shown, only the older adults showed an increased tendency to identify these as familiar scenes. In line with theoretical models, we argue that this reflects an age-related bias towards pattern completion. PMID:25597525

  4. Age-related spatial working memory deficits in homing pigeons (Columba livia).

    PubMed

    Coppola, Vincent J; Hough, Gerald; Bingman, Verner P

    2014-12-01

    The hippocampus is particularly susceptible to age-related degeneration that, like hippocampal lesions, is thought to lead to age-related decline in spatial memory and navigation. Lesions to the avian hippocampal formation (HF) also result in impaired spatial memory and navigation, but the relationship between aging and HF-dependent spatial cognition is unknown. To investigate possible age-related decline in avian spatial cognition, the current study investigated spatial working memory performance in older homing pigeons (10+ years of age). Pigeons completed a behavioral procedure nearly identical to the delayed spatial, win-shift procedure in a modified radial arm maze that has been previously used to study spatial working memory in rats and pigeons. The results revealed that the older pigeons required a greater number of choices to task completion and were less accurate with their first 4 choices as compared to younger pigeons (1-2 years of age). In addition, older pigeons were more likely to adopt a stereotyped sampling strategy, which explained in part their impaired performance. To the best of our knowledge, this study is the first to demonstrate an age-related impairment of HF-dependent, spatial memory in birds. Implications and future directions of the findings are discussed.

  5. Reversal of aging-related emotional memory deficits by norepinephrine via regulating the stability of surface AMPA receptors.

    PubMed

    Luo, Yi; Zhou, Jun; Li, Ming-Xing; Wu, Peng-Fei; Hu, Zhuang-Li; Ni, Lan; Jin, You; Chen, Jian-Guo; Wang, Fang

    2015-04-01

    Aging-related emotional memory deficit is a well-known complication in Alzheimer's disease and normal aging. However, little is known about its molecular mechanism. To address this issue, we examined the role of norepinephrine (NE) and its relevant drug desipramine in the regulation of hippocampal long-term potentiation (LTP), surface expression of AMPA receptor, and associative fear memory in rats. We found that there was a defective regulation of NE content and AMPA receptor trafficking during fear conditioning, which were accompanied by impaired emotional memory and LTP in aged rats. Furthermore, we also found that the exogenous upregulation of NE ameliorated the impairment of LTP and emotional memory via enhancing AMPA receptor trafficking in aged rats, and the downregulation of NE impaired LTP in adult rats. Finally, acute treatment with NE or desipramine rescued the impaired emotional memory in aged rats. These results imply a pivotal role for NE in synaptic plasticity and associative fear memory in aging rats and suggest that desipramine is a potential candidate for treating aging-related emotional memory deficit.

  6. Tocotrienol rich fraction reverses age-related deficits in spatial learning and memory in aged rats.

    PubMed

    Taridi, Nursiati Mohamad; Abd Rani, Nazirah; Abd Latiff, Azian; Ngah, Wan Zurinah Wan; Mazlan, Musalmah

    2014-09-01

    Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.

  7. Proactive interference and concurrent inhibitory processes do not differentially affect item and associative recognition: Implication for the age-related associative memory deficit.

    PubMed

    Guez, Jonathan; Naveh-Benjamin, Moshe

    2016-09-01

    Previous studies have suggested an associative deficit hypothesis [Naveh-Benjamin, M. ( 2000 ). Adult age differences in memory performance: Tests of an associative deficit hypothesis. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1170-1187] to explain age-related episodic memory declines. The hypothesis attributes part of the deficient episodic memory performance in older adults to a difficulty in creating and retrieving cohesive episodes. In this article, we further evaluate this hypothesis by testing two alternative processes that potentially mediate associative memory deficits in older adults. Four experiments are presented that assess whether failure of inhibitory processes (proactive interference in Experiments 1 and 2), and concurrent inhibition (in Experiments 3 and 4) are mediating factors in age-related associative deficits. The results suggest that creating conditions that require the operation of inhibitory processes, or that interfere with such processes, cannot simulate associative memory deficit in older adults. Instead, such results support the idea that associative memory deficits reflect a unique binding failure in older adults. This failure seems to be independent of other cognitive processes, including inhibitory and other resource-demanding processes.

  8. Age-related associative deficits and the isolation effect.

    PubMed

    Badham, Stephen P; Maylor, Elizabeth A

    2013-01-01

    If all but one of the items in a list are similar (e.g., all black except one red), memory for the different item is enhanced (the isolation effect). Older adults generally show similar or smaller isolation effects compared to young adults, which has been attributed to age-related deficits in associative memory whereby older adults are less able to associate an isolated stimulus to its isolating feature. Experiment 1 examined the isolation effect for isolation based on spatial position, modality and color; in Experiment 2, the criterion for isolation was the associative relation between stimuli. The results consistently showed no differences between young and older participants in the magnitude of the isolation effect. Whilst age deficits in associative memory may act to reduce the isolation effect in older adults, age deficits in self-initiated processing and inhibitory functionality may counteract this reduction by enhancing the isolation effect in older adults.

  9. Age-related associative memory deficits in value-based remembering: The contribution of agenda-based regulation and strategy use.

    PubMed

    Ariel, Robert; Price, Jodi; Hertzog, Christopher

    2015-12-01

    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.

  10. 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

  11. Age-Related Differences in Learning Disabled and Skilled Readers' Working Memory.

    ERIC Educational Resources Information Center

    Swanson, H. Lee

    2003-01-01

    Examined whether age-related working memory deficits in learning disabled (LD) readers across four age groups (7, 10, 13, and 20) reflected retrieval efficiency or storage capacity problems. Found that LD readers' working memory performance was inferior to skilled readers' on verbal and visual-spatial working memory tasks across all ages.…

  12. Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system.

    PubMed

    Haider, Saida; Saleem, Sadia; Perveen, Tahira; Tabassum, Saiqa; Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Madiha, Syeda

    2014-06-01

    Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino-Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.

  13. 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.

  14. Stability of age-related deficits in the mnemonic similarity task across task variations.

    PubMed

    Stark, Shauna M; Stevenson, Rebecca; Wu, Claudia; Rutledge, Samantha; Stark, Craig E L

    2015-06-01

    Several studies in our lab and others have demonstrated age-related declines in mnemonic discrimination during a recognition memory paradigm using repeated items, similar lures, and novel foils. In particular, older adults exhibit a shift in lure discriminability, identifying similar lures as old items at a greater rate than young adults. This shift likely reflects deficits in pattern separation processing as a result of underlying changes in the dentate gyrus of the hippocampus. Here, we explored whether alterations in the task design could rescue the age-related impairment or whether it was ubiquitous as one might expect if the neurobiological mechanisms were truly disturbed by typical aging. Despite overt instructions to study item details during encoding, we replicated the age-related deficit in mnemonic discrimination. We established reliable effects with short lists of stimuli and with repeated testing. Altering the task design from a study/test to a continuous recognition paradigm replicated the age-related shift in lure discrimination as well. Modifying the task to an old/new response (rather than old/similar/new) showed the same effect and a d' analysis showed that lure items were more akin to target items in older adults. Finally, we varied the test instructions in order to promote gist or veridical responses in the old/new task. Even these overt veridical test instructions did not ameliorate older adults' lure discrimination problems. Together, these findings demonstrate the robust nature of this age-related deficit and support the hypothesis that typical aging results in neurobiological changes that underlie this impairment.

  15. Glial dysfunction causes age-related memory impairment in Drosophila.

    PubMed

    Yamazaki, Daisuke; Horiuchi, Junjiro; Ueno, Kohei; Ueno, Taro; Saeki, Shinjiro; Matsuno, Motomi; Naganos, Shintaro; Miyashita, Tomoyuki; Hirano, Yukinori; Nishikawa, Hiroyuki; Taoka, Masato; Yamauchi, Yoshio; Isobe, Toshiaki; Honda, Yoshiko; Kodama, Tohru; Masuda, Tomoko; Saitoe, Minoru

    2014-11-19

    Several aging phenotypes, including age-related memory impairment (AMI), are thought to be caused by cumulative oxidative damage. In Drosophila, age-related impairments in 1 hr memory can be suppressed by reducing activity of protein kinase A (PKA). However, the mechanism for this effect has been unclear. Here we show that decreasing PKA suppresses AMI by reducing activity of pyruvate carboxylase (PC), a glial metabolic enzyme whose amounts increase upon aging. Increased PC activity causes AMI through a mechanism independent of oxidative damage. Instead, increased PC activity is associated with decreases in D-serine, a glia-derived neuromodulator that regulates NMDA receptor activity. D-serine feeding suppresses both AMI and memory impairment caused by glial overexpression of dPC, indicating that an oxidative stress-independent dysregulation of glial modulation of neuronal activity contributes to AMI in Drosophila.

  16. DRYAD and ADH: Further comments on explaining age-related differences in memory.

    PubMed

    Naveh-Benjamin, Moshe; Smyth, Andrea C

    2016-02-01

    Recently, Smyth and Naveh-Benjamin (2016) questioned some of the main assumptions/hypotheses of DRYAD (or density of representations yields age-related deficits), a global-deficit model of aging and memory judgments (Benjamin, 2010; Benjamin et al., 2012). Smyth and Naveh-Benjamin (2016) provided empirical evidence that seems incompatible with DRYAD, but that fits the associative deficit hypothesis (ADH; Naveh-Benjamin, 2000), 1 specific-deficit theoretical view. In response, Aaron Benjamin (2016) offered a discussion of the complementary strengths and weaknesses of the DRYAD and the ADH, and the potential ways they might work together. We agree with many of his comments, but are not convinced that DRYAD is able to explain basic replicable empirical evidence of the type mentioned in Smyth and Naveh-Benjamin (2016). We discuss the reasons why we are not fully convinced by the demonstration of DRYAD's simulation of results presented in Benjamin (2016) and then present an implementation of ADH in a computationally based age-related impaired neuromodulation approach that was shown to simulate the basic empirical results of age-related associative memory deficits. We also discuss the issues of parsimony of theories and the appropriate type of representation, in the context of global versus specific deficits theoretical views. Finally, we show that the ADH's take on the distinction between items and associations has been adopted by some global computational models of memory. We believe that considerations of the above issues and others raised by Benjamin (2016) can lead to fruitful discussions that will benefit both theory development and existing knowledge of aging and memory.

  17. Age-related differences in working memory updating components.

    PubMed

    Linares, Rocío; Bajo, M Teresa; Pelegrina, Santiago

    2016-07-01

    The aim of this study was to investigate possible age-related changes throughout childhood and adolescence in different component processes of working memory updating (WMU): retrieval, transformation, and substitution. A set of numerical WMU tasks was administered to four age groups (8-, 11-, 14-, and 21-year-olds). To isolate the effect of each of the WMU components, participants performed different versions of a task that included different combinations of the WMU components. The results showed an expected overall decrease in response times and an increase in accuracy performance with age. Most important, specific age-related changes in the retrieval component were found, demonstrating that the effect of retrieval on accuracy was larger in children than in adolescents or young adults. These findings indicate that the availability of representations from outside the focus of attention may change with age. Thus, the retrieval component of updating could contribute to the age-related changes observed in the performance of many updating tasks.

  18. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline.

    PubMed

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-08-01

    A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline.

  19. Age-related Differences in Brain Activity during True and False Memory Retrieval

    PubMed Central

    Dennis, Nancy A.; Kim, Hongkeun; Cabeza, Roberto

    2010-01-01

    Compared to young adults, older adults show not only a reduction in true memories but also an increase in false memories. We investigated the neural bases of these age effects using functional magnetic resonance imaging and a false memory task that resembles the Deese–Roediger–McDermott (DRM) paradigm. Young and older participants were scanned during a word recognition task that included studied words and new words that were strongly associated with studied words (critical lures). During correct recognition of studied words (true memory), older adults showed weaker activity than young adults in the hippocampus but stronger activity than young adults in the retrosplenial cortex. The hippocampal reduction is consistent with age-related deficits in recollection, whereas the retrosplenial increase suggests compensatory recruitment of alternative recollection-related regions. During incorrect recognition of critical lures (false memory), older adults displayed stronger activity than young adults in the left lateral temporal cortex, a region involved in semantic processing and semantic gist. Taken together, the results suggest that older adults’ deficits in true memories reflect a decline in recollection processes mediated by the hippocampus, whereas their increased tendency to have false memories reflects their reliance on semantic gist mediated by the lateral temporal cortex. PMID:18303982

  20. Prefrontal cortical GABAergic dysfunction contributes to age-related working memory impairment.

    PubMed

    Bañuelos, Cristina; Beas, B Sofia; McQuail, Joseph A; Gilbert, Ryan J; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L

    2014-03-05

    Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions.

  1. Prefrontal Cortical GABAergic Dysfunction Contributes to Age-Related Working Memory Impairment

    PubMed Central

    Bañuelos, Cristina; Beas, B. Sofia; McQuail, Joseph A.; Gilbert, Ryan J.; Frazier, Charles J.; Setlow, Barry

    2014-01-01

    Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions. PMID:24599447

  2. Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates age-related deficits in water maze performance, especially in male rats.

    PubMed

    Kougias, Daniel G; Hankosky, Emily R; Gulley, Joshua M; Juraska, Janice M

    2017-03-01

    Beta-hydroxy-beta-methylbutyrate (HMB) is commonly supplemented to maintain muscle in elderly and clinical populations and has potential as a nootropic. Previously, we have shown that in both male and female rats, long-term HMB supplementation prevents age-related dendritic shrinkage within the medial prefrontal cortex (mPFC) and improves cognitive flexibility and working memory performance that are both age- and sex-specific. In this study, we further explore the cognitive effects by assessing visuospatial learning and memory with the Morris water maze. Female rats were ovariectomized at 11months of age to model human menopause. At 12months of age, male and female rats received relatively short- or long-term (1- or 7-month) dietary HMB (450mg/kg/dose) supplementation twice a day prior to testing. Spatial reference learning and memory was assessed across four days in the water maze with four trials daily and a probe trial on the last day. Consistent with previous work, there were age-related deficits in water maze performance in both sexes. However, these deficits were ameliorated in HMB-treated males during training and in both sexes during probe trial performance. Thus, HMB supplementation prevented the age-related decrement in water maze performance, especially in male rats.

  3. EPINEPHRINE AND GLUCOSE MODULATE TRAINING-RELATED CREB PHOSPHORYLATION IN OLD RATS: RELATIONSHIPS TO AGE-RELATED MEMORY IMPAIRMENTS

    PubMed Central

    Morris, Ken A.; Gold, Paul E.

    2012-01-01

    Epinephrine enhances memory in young adult rats, in part, by increasing blood glucose levels needed to modulate memory. In old rats, epinephrine is deficient at raising blood glucose levels and thus is only moderately effective at enhancing memory. In contrast, systemic glucose injections improve memory in old rats, with resulting memory performance equal to that of young rats. The diminished response of glucose to training in old rats may blunt downstream neurochemical and molecular mechanisms needed to upregulate memory processes. In the first experiment, young adult and old rats were trained on an inhibitory avoidance task with immediate post-training injections of aCSF or glucose into the dorsal hippocampus. Old rats had significant memory impairments compared to young rats 7 days after training. Intrahippocampal injections of glucose reversed age-related deficits, improving memory scores in old rats to values seen in young rats. A second experiment examined age-related changes in activation of the transcription factor CREB, which is widely implicated in memory formation and may act downstream of hormonal and metabolic signals. Activation was assessed in response to training with systemic injections of epinephrine and glucose at doses known to enhance memory. Young adult and old rats were trained on inhibitory avoidance with immediate post-training systemic injections of saline, epinephrine, or glucose. After training, old rats had significant impairments in CREB phosphorylation in area CA1 and the dentate gyrus region of the hippocampus, and in the basolateral and lateral amygdala. Epinephrine and glucose attenuated age-related deficits in CREB phosphorylation, but were more effective in the amygdala and hippocampus, respectively. Together, these results support the view that age-related changes in blood glucose responses to epinephrine contribute to memory impairments, which may be related to alterations in regional patterns of CREB phosphorylation. PMID

  4. Epinephrine and glucose modulate training-related CREB phosphorylation in old rats: relationships to age-related memory impairments.

    PubMed

    Morris, Ken A; Gold, Paul E

    2013-02-01

    Epinephrine enhances memory in young adult rats, in part, by increasing blood glucose levels needed to modulate memory. In old rats, epinephrine is deficient at raising blood glucose levels and thus is only moderately effective at enhancing memory. In contrast, systemic glucose injections improve memory in old rats, with resulting memory performance equal to that of young rats. The diminished response of glucose to training in old rats may blunt downstream neurochemical and molecular mechanisms needed to upregulate memory processes. In the first experiment, young adult and old rats were trained on an inhibitory avoidance task with immediate post-training injections of aCSF or glucose into the dorsal hippocampus. Old rats had significant memory impairments compared to young rats 7 days after training. Intrahippocampal injections of glucose reversed age-related deficits, improving memory scores in old rats to values seen in young rats. A second experiment examined age-related changes in activation of the transcription factor CREB, which is widely implicated in memory formation and may act downstream of hormonal and metabolic signals. Activation was assessed in response to training with systemic injections of epinephrine and glucose at doses known to enhance memory. Young adult and old rats were trained on inhibitory avoidance with immediate post-training systemic injections of saline, epinephrine, or glucose. After training, old rats had significant impairments in CREB phosphorylation in area CA1 and the dentate gyrus region of the hippocampus, and in the basolateral and lateral amygdala. Epinephrine and glucose attenuated age-related deficits in CREB phosphorylation, but were more effective in the amygdala and hippocampus, respectively. Together, these results support the view that age-related changes in blood glucose responses to epinephrine contribute to memory impairments, which may be related to alterations in regional patterns of CREB phosphorylation.

  5. Dynamical network model for age-related health deficits and mortality

    NASA Astrophysics Data System (ADS)

    Taneja, Swadhin; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-02-01

    How long people live depends on their health, and how it changes with age. Individual health can be tracked by the accumulation of age-related health deficits. The fraction of age-related deficits is a simple quantitative measure of human aging. This quantitative frailty index (F ) is as good as chronological age in predicting mortality. In this paper, we use a dynamical network model of deficits to explore the effects of interactions between deficits, deficit damage and repair processes, and the connection between the F and mortality. With our model, we qualitatively reproduce Gompertz's law of increasing human mortality with age, the broadening of the F distribution with age, the characteristic nonlinear increase of the F with age, and the increased mortality of high-frailty individuals. No explicit time-dependence in damage or repair rates is needed in our model. Instead, implicit time-dependence arises through deficit interactions—so that the average deficit damage rates increase, and deficit repair rates decrease, with age. We use a simple mortality criterion, where mortality occurs when the most connected node is damaged.

  6. Nutritional interventions protect against age-related deficits in behavior: from animals to humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on motor and cognitive tasks. Similar changes in behavior occur in humans with age, and the development of methods to retard or reverse these age-related neuronal and behavioral deficits could increase healthy aging and decrease health care costs. In the present s...

  7. fMRI and sleep correlates of the age-related impairment in motor memory consolidation.

    PubMed

    Fogel, Stuart M; Albouy, Genevieve; Vien, Catherine; Popovicci, Romana; King, Bradley R; Hoge, Rick; Jbabdi, Saad; Benali, Habib; Karni, Avi; Maquet, Pierre; Carrier, Julie; Doyon, Julien

    2014-08-01

    Behavioral studies indicate that older adults exhibit normal motor sequence learning (MSL), but paradoxically, show impaired consolidation of the new memory trace. However, the neural and physiological mechanisms underlying this impairment are entirely unknown. Here, we sought to identify, through functional magnetic resonance imaging during MSL and electroencephalographic (EEG) recordings during daytime sleep, the functional correlates and physiological characteristics of this age-related motor memory deficit. As predicted, older subjects did not exhibit sleep-dependent gains in performance (i.e., behavioral changes that reflect consolidation) and had reduced sleep spindles compared with young subjects. Brain imaging analyses also revealed that changes in activity across the retention interval in the putamen and related brain regions were associated with sleep spindles. This change in striatal activity was increased in young subjects, but reduced by comparison in older subjects. These findings suggest that the deficit in sleep-dependent motor memory consolidation in elderly individuals is related to a reduction in sleep spindle oscillations and to an associated decrease of activity in the cortico-striatal network.

  8. Modeling Age-Related Differences in Immediate Memory Using SIMPLE

    ERIC Educational Resources Information Center

    Surprenant, Aimee M.; Neath, Ian; Brown, Gordon D. A.

    2006-01-01

    In the SIMPLE model (Scale Invariant Memory and Perceptual Learning), performance on memory tasks is determined by the locations of items in multidimensional space, and better performance is associated with having fewer close neighbors. Unlike most previous simulations with SIMPLE, the ones reported here used measured, rather than assumed,…

  9. Age-related differences in inhibitory control and memory updating in boys with Asperger syndrome.

    PubMed

    Weiss, Elisabeth M; Gschaidbauer, Bianca; Kaufmann, Liane; Fink, Andreas; Schulter, Günter; Mittenecker, Erich; Papousek, Ilona

    2016-12-26

    Deficits in specific executive domains are highly prevalent in autism spectrum disorder; however, age-related improvements in executive functions (reflecting prefrontal maturational changes) have been reported even in individuals diagnosed with autism. The current study examined two components of cognitive flexibility (inhibition of prepotent responses and memory monitoring/updating) by using a random-motor-generation task (MPT) in a group of 23 boys with Asperger syndrome (AS) and 23 matched healthy controls. We found poorer inhibition and more repetitive responses in younger AS children solely, but comparable memory monitoring/updating skills across groups. Overall, our findings correspond well with previous studies and reveal that even in AS specific EFs may improve with age and, thus, call for a more differentiated view of executive (dys) function profiles in children diagnosed with AS. Tests such as the random-motor-generation task may help to disentangle more specific processes of executive deficits in autism spectrum disorder as compared to the more classical tests.

  10. Age-related changes to the neural correlates of working memory which emerge after midlife.

    PubMed

    Macpherson, Helen N; White, David J; Ellis, Kathryn A; Stough, Con; Camfield, David; Silberstein, Richard; Pipingas, Andrew

    2014-01-01

    Previous research has indicated that the neural processes which underlie working memory change with age. Both age-related increases and decreases to cortical activity have been reported. This study investigated which stages of working memory are most vulnerable to age-related changes after midlife. To do this we examined age-differences in the 13 Hz steady state visually evoked potential (SSVEP) associated with a spatial working memory delayed response task. Participants were 130 healthy adults separated into a midlife (40-60 years) and an older group (61-82 years). Relative to the midlife group, older adults demonstrated greater bilateral frontal activity during encoding and this pattern of activity was related to better working memory performance. In contrast, evidence of age-related under activation was identified over left frontal regions during retrieval. Findings from this study suggest that after midlife, under-activation of frontal regions during retrieval contributes to age-related decline in working memory performance.

  11. High cognitive reserve is associated with a reduced age-related deficit in spatial conflict resolution

    PubMed Central

    Puccioni, Olga; Vallesi, Antonino

    2012-01-01

    Several studies support the existence of a specific age-related difficulty in suppressing potentially distracting information. The aim of the present study is to investigate whether spatial conflict resolution is selectively affected by aging. The way aging affects individuals could be modulated by many factors determined by the socieconomic status: we investigated whether factors such as cognitive reserve (CR) and years of education may play a compensatory role against age-related deficits in the spatial domain. A spatial Stroop task with no feature repetitions was administered to a sample of 17 non-demented older adults (69–79 years-old) and 18 younger controls (18–34 years-old) matched for gender and years of education. The two age groups were also administered with measures of intelligence and CR. The overall spatial Stroop effect did not differ according to age, neither for speed nor for accuracy. The two age groups equally showed sequential effects for congruent trials: reduced response times (RTs) if another congruent trial preceded them, and accuracy at ceiling. For incongruent trials, older adults, but not younger controls, were influenced by congruency of trialn−1, since RTs increased with preceding congruent trials. Interestingly, such an age-related modulation negatively correlated with CR. These findings suggest that spatial conflict resolution in aging is predominantly affected by general slowing, rather than by a more specific deficit. However, a high level of CR seems to play a compensatory role for both factors. PMID:23248595

  12. Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48

    PubMed Central

    Pavlopoulos, Elias; Jones, Sidonie; Kosmidis, Stylianos; Close, Maggie; Kim, Carla; Kovalerchik, Olga; Small, Scott A.; Kandel, Eric R.

    2016-01-01

    To distinguish age-related memory loss more explicitly from Alzheimer’s disease (AD), we have explored its molecular underpinning in the dentate gyrus (DG), a subregion of the hippocampal formation thought to be targeted by aging. We carried out a gene expression study in human postmortem tissue harvested from both DG and entorhinal cortex (EC), a neighboring subregion unaffected by aging and known to be the site of onset of AD. Using expression in the EC for normalization, we identified 17 genes that manifested reliable age-related changes in the DG. The most significant change was an age-related decline in RbAp48, a histone-binding protein that modifies histone acetylation. To test whether the RbAp48 decline could be responsible for age-related memory loss, we turned to mice and found that, consistent with humans, RbAp48 was less abundant in the DG of old than in young mice. We next generated a transgenic mouse that expressed a dominant-negative inhibitor of RbAp48 in the adult forebrain. Inhibition of RbAp48 in young mice caused hippocampus-dependent memory deficits similar to those associated with aging, as measured by novel object recognition and Morris water maze tests. Functional magnetic resonance imaging studies showed that within the hippocampal formation, dysfunction was selectively observed in the DG, and this corresponded to a regionally selective decrease in histone acetylation. Up-regulation of RbAp48 in the DG of aged wild-type mice ameliorated age-related hippocampus-based memory loss and age-related abnormalities in histone acetylation. Together, these findings show that the DG is a hippocampal subregion targeted by aging, and identify molecular mechanisms of cognitive aging that could serve as valid targets for therapeutic intervention. PMID:23986399

  13. Mood, Memory and Movement: An Age-Related Neurodegenerative Complex?

    PubMed Central

    Granholm, Ann-Charlotte; Boger, Heather; Emborg, Marina E.

    2009-01-01

    The following review was constructed as a concept paper based on a recent workshop on neurodegenerative disease sponsored by the National Institute on Aging (NIA), the American Geriatric Society (AGS), and the John A. Hartford Foundation. The meeting was entitled “Thinking, moving and feeling: Common underlying mechanisms? 4th Annual Bedside-to-Bench Conference” and had the purpose to connect current basic and clinical findings on common brain-related alterations occurring with aging such as depression, movement disorders, and cognitive decline. Many prominent researchers expressed their opinion on aging and it was revealed that age-related brain dysfunction of any kind seems to share several risk factors and/or pathways. But can something be done to actively achieve “successful aging”? In this review, based largely on the workshop and current literature, we have summarized some of the current theories for depression, movement and cognitive impairment with aging, as well as potential preventive measures. We have also summarized the emerging need for relevant animal models and how these could be developed and utilized. PMID:20021382

  14. Age-related deficits of dual-task walking: the role of foot vision.

    PubMed

    Bock, Otmar; Beurskens, Rainer

    2011-02-01

    Previous studies found that age-related deficits of dual-task walking emerge with secondary tasks that require substantial visual processing, but are absent with tasks that require little or no visual processing. We evaluated whether this is so because visual tasks typically interfere with foot vision, on which older persons depend more heavily than young ones. Young (25±3 years) and older (69±5 years) subjects walked along a straight path and checked boxes on a handheld panel, separately or concurrently. The panel was either transparent or opaque, thus allowing or blocking vision of the feet, respectively. We quantified subjects' performance by spatial and temporal gait measures, and as the speed of checking. An analysis of variance revealed significant effects of age and of condition (single, dual) for several gait measures, as well as for checking speed. The dual-task costs (ǀdual-singleǀ/single) averaged 0.04±0.14 in younger and 0.33±0.30 in older subjects; this age difference was significant in a t-test (p<0.01). Most importantly, performance measures obtained with the transparent and with the opaque panel were not significantly different. In conclusion, our study confirms previous findings about age-related deficits of walking with a concurrent visual task, documents for the first time that these deficits influence the entire spatio-temporal gait structure, but provides no support for the notion that they reflect an increased dependence on foot vision.

  15. Age-Related Declines in Early Sensory Memory: Identification of Rapid Auditory and Visual Stimulus Sequences

    PubMed Central

    Fogerty, Daniel; Humes, Larry E.; Busey, Thomas A.

    2016-01-01

    Age-related temporal-processing declines of rapidly presented sequences may involve contributions of sensory memory. This study investigated recall for rapidly presented auditory (vowel) and visual (letter) sequences presented at six different stimulus onset asynchronies (SOA) that spanned threshold SOAs for sequence identification. Younger, middle-aged, and older adults participated in all tasks. Results were investigated at both equivalent performance levels (i.e., SOA threshold) and at identical physical stimulus values (i.e., SOAs). For four-item sequences, results demonstrated best performance for the first and last items in the auditory sequences, but only the first item for visual sequences. For two-item sequences, adults identified the second vowel or letter significantly better than the first. Overall, when temporal-order performance was equated for each individual by testing at SOA thresholds, recall accuracy for each position across the age groups was highly similar. These results suggest that modality-specific processing declines of older adults primarily determine temporal-order performance for rapid sequences. However, there is some evidence for a second amodal processing decline in older adults related to early sensory memory for final items in a sequence. This selective deficit was observed particularly for longer sequence lengths and was not accounted for by temporal masking. PMID:27199737

  16. Intrinsic Hippocampal Excitability Changes of Opposite Signs and Different Origins in CA1 and CA3 Pyramidal Neurons Underlie Aging-Related Cognitive Deficits

    PubMed Central

    Oh, M. Matthew; Simkin, Dina; Disterhoft, John F.

    2016-01-01

    Aging-related cognitive deficits have been attributed to dysfunction of neurons due to failures at synaptic or intrinsic loci, or both. Given the importance of the hippocampus for successful encoding of memory and that the main output of the hippocampus is via the CA1 pyramidal neurons, much of the research has been focused on identifying the aging-related changes of these CA1 pyramidal neurons. We and others have discovered that the postburst afterhyperpolarization (AHP) following a train of action potentials is greatly enlarged in CA1 pyramidal neurons of aged animals. This enlarged postburst AHP is a significant factor in reducing the intrinsic excitability of these neurons, and thus limiting their activity in the neural network during learning. Based on these data, it has largely been thought that aging-related cognitive deficits are attributable to reduced activity of pyramidal neurons. However, recent in vivo and ex vivo studies provide compelling evidence that aging-related deficits could also be due to a converse change in CA3 pyramidal neurons, which show increased activity with aging. In this review, we will incorporate these recent findings and posit that an interdependent dynamic dysfunctional change occurs within the hippocampal network, largely due to altered intrinsic excitability in CA1 and CA3 hippocampal pyramidal neurons, which ultimately leads to the aging-related cognitive deficits. PMID:27375440

  17. Age-related differences in sleep-based memory consolidation: A meta-analysis.

    PubMed

    Gui, Wen-Jun; Li, Hui-Jie; Guo, Yu-Hua; Peng, Peng; Lei, Xu; Yu, Jing

    2017-02-02

    A period of post-learning sleep benefits memory consolidation compared with an equal-length wake interval. However, whether this sleep-based memory consolidation changes as a function of age remains controversial. Here we report a meta-analysis that investigates the age differences in the sleep-based memory consolidation in two types of memory: declarative memory and procedural memory. The meta-analysis included 22 comparisons of the performance between young adults (N =640) and older adults (N =529) on behavioral tasks measuring sleep-based memory consolidation. Our results showed a significant overall sleep-based beneficial effect in young adults but not in older adults. However, further analyses suggested that the age differences were mainly manifested in sleep-based declarative memory consolidation but not in procedural memory consolidation. We discussed the possible underlying mechanisms for the age-related degradation in sleep-based memory consolidation. Further research is needed to determine the crucial components for sleep-related memory consolidation in older adults such as age-related changes in neurobiological and cardiovascular functions, which may play an important role in this context and have the potential to delineate the interrelationships between age-related changes in sleep and memory.

  18. Age-related memory impairments due to reduced blood glucose responses to epinephrine.

    PubMed

    Morris, Ken A; Chang, Qing; Mohler, Eric G; Gold, Paul E

    2010-12-01

    Increases in blood glucose levels are an important component of the mechanisms by which epinephrine enhances memory formation. The present experiments addressed the hypothesis that a dysfunction in the blood glucose response to circulating epinephrine contributes to age-related memory impairments. Doses of epinephrine and glucagon that significantly increased blood glucose levels in young adult rats were far less effective at doing so in 2-year-old rats. In young rats, epinephrine and glucose were about equally effective in enhancing memory and in prolonging post-training release of acetylcholine in the hippocampus. However, glucose was more effective than epinephrine in enhancing both memory and acetylcholine release in aged rats. These results suggest that an uncoupling between circulating epinephrine and glucose levels in old rats may lead to an age-related reduction in the provision of glucose to the brain during training. This in turn may contribute to age-related changes in memory and neural plasticity.

  19. Ageing-related stereotypes in memory: When the beliefs come true.

    PubMed

    Bouazzaoui, Badiâa; Follenfant, Alice; Ric, François; Fay, Séverine; Croizet, Jean-Claude; Atzeni, Thierry; Taconnat, Laurence

    2016-01-01

    Age-related stereotype concerns culturally shared beliefs about the inevitable decline of memory with age. In this study, stereotype priming and stereotype threat manipulations were used to explore the impact of age-related stereotype on metamemory beliefs and episodic memory performance. Ninety-two older participants who reported the same perceived memory functioning were divided into two groups: a threatened group and a non-threatened group (control). First, the threatened group was primed with an ageing stereotype questionnaire. Then, both groups were administered memory complaints and memory self-efficacy questionnaires to measure metamemory beliefs. Finally, both groups were administered the Logical Memory task to measure episodic memory, for the threatened group the instructions were manipulated to enhance the stereotype threat. Results indicated that the threatened individuals reported more memory complaints and less memory efficacy, and had lower scores than the control group on the logical memory task. A multiple mediation analysis revealed that the stereotype threat effect on the episodic memory performance was mediated by both memory complaints and memory self-efficacy. This study revealed that stereotype threat impacts belief in one's own memory functioning, which in turn impairs episodic memory performance.

  20. 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).…

  1. Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit.

    PubMed

    Wang, Hongkai; Li, Chengren; Wang, Hanzhi; Mei, Feng; Liu, Zhi; Shen, Hai-Ying; Xiao, Lan

    2013-04-01

    Schizophrenia is a mental disease that mainly affects young individuals (15 to 35 years old) but its etiology remains largely undefined. Recently, accumulating evidence indicated that demyelination and/or dysfunction of oligodendrocytes is an important feature of its pathogenesis. We hypothesized that the vulnerability of young individuals to demyelination may contribute to the onset of schizophrenia. In the present study, three different age cohorts of mice, i.e. juvenile (3 weeks), young-adult (6 weeks) and middle-aged (8 months), were subjected to a 6-week diet containing 0.2% cuprizone (CPZ) to create an animal model of acute demyelination. Then, age-related vulnerability to CPZ-induced demyelination, behavioral outcomes, and myelination-related molecular biological changes were assessed. We demonstrated: (1) CPZ treatment led to more severe demyelination in juvenile and young-adult mice than in middle-aged mice in the corpus callosum, a region closely associated with the pathophysiology of schizophrenia; (2) the higher levels of demyelination in juvenile and young-adult mice were correlated with a greater reduction of myelin basic protein, more loss of CC-1-positive mature oligodendrocytes, and higher levels of astrocyte activation; and (3) CPZ treatment resulted in a more prominent exploratory behavior deficit in juvenile and young-adult mice than in middle-aged mice. Together, our data demonstrate an age-related vulnerability to demyelination with a concurrent behavioral deficit, providing supporting evidence for better understanding the susceptibility of the young to the onset of schizophrenia.

  2. Age-related deficits in selective attention during encoding increase demands on episodic reconstruction during context retrieval: An ERP study

    PubMed Central

    James, Taylor; Strunk, Jonathan; Arndt, Jason; Duarte, Audrey

    2017-01-01

    Previous event-related potential (ERP) and neuroimaging evidence suggests that directing attention toward single item-context associations compared to intra-item features at encoding improves context memory performance and reduces demands on strategic retrieval operations in young and older adults. In everyday situations, however, there are multiple event features competing for our attention. It is not currently known how selectively attending to one contextual feature while attempting to ignore another influences context memory performance and the processes that support successful retrieval in the young and old. We investigated this issue in the current ERP study. Young and older participants studied pictures of objects in the presence of two contextual features: a color and a scene, and their attention was directed to the object’s relationship with one of those contexts. Participants made context memory decisions for both attended and unattended contexts and rated their confidence in those decisions. Behavioral results showed that while both groups were generally successful in applying selective attention during context encoding, older adults were less confident in their context memory decisions for attended features and showed greater dependence in context memory accuracy for attended and unattended contextual features (i.e., hyper-binding). ERP results were largely consistent between age groups but older adults showed a more pronounced late posterior negativity (LPN) implicated in episodic reconstruction processes. We conclude that age-related suppression deficits during encoding result in reduced selectivity in context memory, thereby increasing subsequent demands on episodic reconstruction processes when sought after details are not readily retrieved. PMID:27094851

  3. The ties to unbind: age-related differences in feature (un)binding in working memory for emotional faces

    PubMed Central

    Pehlivanoglu, Didem; Jain, Shivangi; Ariel, Robert; Verhaeghen, Paul

    2014-01-01

    In the present study, we investigated age-related differences in the processing of emotional stimuli. Specifically, we were interested in whether older adults would show deficits in unbinding emotional expression (i.e., either no emotion, happiness, anger, or disgust) from bound stimuli (i.e., photographs of faces expressing these emotions), as a hyper-binding account of age-related differences in working memory would predict. Younger and older adults completed different N-Back tasks (side-by-side 0-Back, 1-Back, 2-Back) under three conditions: match/mismatch judgments based on either the identity of the face (identity condition), the face’s emotional expression (expression condition), or both identity and expression of the face (both condition). The two age groups performed more slowly and with lower accuracy in the expression condition than in the both condition, indicating the presence of an unbinding process. This unbinding effect was more pronounced in older adults than in younger adults, but only in the 2-Back task. Thus, older adults seemed to have a specific deficit in unbinding in working memory. Additionally, no age-related differences were found in accuracy in the 0-Back task, but such differences emerged in the 1-Back task, and were further magnified in the 2-Back task, indicating independent age-related differences in attention/STM and working memory. Pupil dilation data confirmed that the attention/STM version of the task (1-Back) is more effortful for older adults than younger adults. PMID:24795660

  4. Age-related individual variability in memory performance is associated with amygdala-hippocampal circuit function and emotional pattern separation.

    PubMed

    Leal, Stephanie L; Noche, Jessica A; Murray, Elizabeth A; Yassa, Michael A

    2017-01-01

    While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation. During false recognition, we found increased DG/CA3 activity in LP individuals, suggesting that hyperactivity may be associated with overgeneralization. We additionally observed a selective deficit in basolateral amygdala-lateral entorhinal cortex-DG/CA3 functional connectivity in LP individuals during pattern separation of negative information. During negative false recognition, LP individuals showed increased medial temporal lobe functional connectivity, consistent with overgeneralization. Overall, these results suggest a novel mechanistic account of individual differences in emotional memory alterations exhibited in aging.

  5. Age-related deficit in a bimanual joint position matching task is amplitude dependent

    PubMed Central

    Boisgontier, Matthieu P.; Swinnen, Stephan P.

    2015-01-01

    The cognitive load associated with joint position sense increases with age but does not necessarily result in impaired performance in a joint position matching task. It is still unclear which factors interact with age to predict matching performance. To test whether movement amplitude and direction are part of such predictors, young and older adults performed a bimanual wrist joint position matching task. Results revealed an age-related deficit when the target limb was positioned far from (25°) the neutral position, but not when close to (15°, 5°) the neutral joint position, irrespective of the direction. These results suggest that the difficulty associated with the comparison of two musculoskeletal states increases towards extreme joint amplitude and that older adults are more vulnerable to this increased difficulty. PMID:26347649

  6. Age-related changes in overcoming proactive interference in associative memory: The role of PFC-mediated executive control processes at retrieval.

    PubMed

    Dulas, Michael R; Duarte, Audrey

    2016-05-15

    Behavioral evidence has shown age-related impairments in overcoming proactive interference in memory, but it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require several executive control processes supported by the ventrolateral prefrontal cortex (VLPFC) and dorsolateral PFC (DLPFC). The present functional magnetic resonance imaging (fMRI) study investigated whether age-related changes in dissociable executive control processes underlie deficits in overcoming proactive interference in associative memory during retrieval. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that, as interference increased, memory performance decreased similarly across groups, with slight associative memory deficits in older adults. Imaging results demonstrated that, across groups, left mid-VLPFC showed increasing activity with increasing interference, though activity did not distinguish correct from incorrect associative memory responses, suggesting this region may not directly serve in successful resolution of proactive interference, per se. Under conditions of high interference, older adults showed reduced associative memory accuracy effects in the DLPFC and anterior PFC. These results suggest that age-related PFC dysfunction may not be ubiquitous. Executive processes supported by ventral regions that detect mnemonic interference may be less affected than processes supported by dorsal and anterior regions that directly resolve interference.

  7. Spatial Working Memory Deficits in Autism

    ERIC Educational Resources Information Center

    Steele, Shelly D.; Minshew, Nancy J.; Luna, Beatriz; Sweeney, John A.

    2007-01-01

    Previous studies have reported working memory deficits in autism, but this finding has been inconsistent. One possibility is that deficits in this domain may be present only when working memory load exceeds some limited capacity. High-functioning individuals with autism performed the CANTAB computerized test of spatial working memory. Individuals…

  8. Ameliorative effect of traditional Japanese medicine yokukansan on age-related impairments of working memory and reversal learning in rats.

    PubMed

    Mizoguchi, K; Shoji, H; Tanaka, Y; Tabira, T

    2011-03-17

    Aging is thought to impair prefrontal cortical (PFC) structure-sensitive cognitive functions and flexibility, such as working memory and reversal learning. A traditional Japanese medicine, yokukansan (YKS), is frequently used to treat age-related neurodegenerative disorders such as Alzheimer's disease in Japan, but its pharmacological properties have not been elucidated. The present study was designed to examine whether YKS improves age-related cognitive deficits using aged rats. YKS was administered to 21-month-old rats for 3 months. The ability to learn initially a reward rule for a T-maze discrimination task (initial learning) was examined in young control (4-month-old), aged control (24-month-old) and YKS-treated aged (24-month-old) rats. Subsequently, working memory and reversal learning were examined in delayed alternation and reversal discrimination T-maze tasks, respectively. Locomotor activity was also measured in new environments. Although performance accuracy in the initial learning procedure did not differ among any experimental groups, accuracy in the delayed alternation task was significantly decreased in aged rats compared to young rats. Aged rats also showed significant decreases in accuracy in the reversal discrimination task. YKS treatment significantly ameliorated the age-related decreases in accuracy in the delayed alternation and reversal discrimination tasks. The ameliorative effects of YKS on impaired delayed alternation performance were reduced by intracranial infusions of a dopamine D1 receptor antagonist, SCH 23390, into the prelimbic cortical region of the PFC, and the YKS effects on impaired reversal learning were done by the infusions into the orbitofrontal cortex (OFC). Locomotor activity did not change in any experimental group. Thus, YKS ameliorated age-related impairments of working memory and reversal learning, which might be mediated by a dopaminergic mechanism in the PFC structure. These investigations provide information

  9. Age-Related Changes in Duration Reproduction: Involvement of Working Memory Processes

    ERIC Educational Resources Information Center

    Baudouin, Alexia; Vanneste, Sandrine; Pouthas, Viviane; Isingrini, Michel

    2006-01-01

    The aim of the present research was to study age-related changes in duration reproduction by differentiating the working memory processes underlying this time estimation task. We compared performances of young and elderly adults in a duration reproduction task performed in simple and concurrent task conditions. Participants were also administered…

  10. Working and strategic memory deficits in schizophrenia

    NASA Technical Reports Server (NTRS)

    Stone, M.; Gabrieli, J. D.; Stebbins, G. T.; Sullivan, E. V.

    1998-01-01

    Working memory and its contribution to performance on strategic memory tests in schizophrenia were studied. Patients (n = 18) and control participants (n = 15), all men, received tests of immediate memory (forward digit span), working memory (listening, computation, and backward digit span), and long-term strategic (free recall, temporal order, and self-ordered pointing) and nonstrategic (recognition) memory. Schizophrenia patients performed worse on all tests. Education, verbal intelligence, and immediate memory capacity did not account for deficits in working memory in schizophrenia patients. Reduced working memory capacity accounted for group differences in strategic memory but not in recognition memory. Working memory impairment may be central to the profile of impaired cognitive performance in schizophrenia and is consistent with hypothesized frontal lobe dysfunction associated with this disease. Additional medial-temporal dysfunction may account for the recognition memory deficit.

  11. Drosophila as a novel animal model for studying the genetics of age-related memory impairment.

    PubMed

    Saitoe, Minoru; Horiuchi, Junjiro; Tamura, Takuya; Ito, Naomi

    2005-01-01

    Understanding the molecular mechanisms underlying age-related memory impairment (AMI) is important not only from a scientific viewpoint but also for the development of therapeutics that may eventually lead to the development of drugs to combat memory loss. AMI has been generally considered to be an overall or nonspecific decay of memory processes that results from dysfunction of neural networks. However, behavioral genetics to test this hypothesis have not been performed previously, due, in part, to the long lifespan of animal models. Using Drosophila, the first extensive behavioral-genetic characterization of AMI has been carried out. In Drosophila, memory acquired after a single olfactory conditioning paradigm has three distinct phases: short-term memory (STM), middle-term memory (MTM), and longer-lasting anesthesia-resistant memory (ARM). Significantly, AMI results from the specific decay of only one memory component, amnesiac-dependent MTM, and not other components. Since amnesiac encodes peptides that enhance adenylyl cyclase activity, these studies suggest the importance of the cAMP signaling pathway in AMI in Drosophila, a finding consistent with several models of AMI in mammals. Although many advances have been made in the study of pathways involved in aging, much remains to be elucidated on how these pathways affect memory formation to cause AMI. Due to its short lifespan, powerful genetics, and well-characterized and conserved pathways involved in memory and lifespan, Drosophila will be a useful model system for studying the molecular mechanisms underlying this process.

  12. 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

  13. Age-related effects on the neural correlates of autobiographical memory retrieval.

    PubMed

    St Jacques, Peggy L; Rubin, David C; Cabeza, Roberto

    2012-07-01

    Older adults recall less episodically rich autobiographical memories (AM), however, the neural basis of this effect is not clear. Using functional MRI, we examined the effects of age during search and elaboration phases of AM retrieval. Our results suggest that the age-related attenuation in the episodic richness of AMs is associated with difficulty in the strategic retrieval processes underlying recovery of information during elaboration. First, age effects on AM activity were more pronounced during elaboration than search, with older adults showing less sustained recruitment of the hippocampus and ventrolateral prefrontal cortex (VLPFC) for less episodically rich AMs. Second, there was an age-related reduction in the modulation of top-down coupling of the VLPFC on the hippocampus for episodically rich AMs. In sum, the present study shows that changes in the sustained response and coupling of the hippocampus and prefrontal cortex (PFC) underlie age-related reductions in episodic richness of the personal past.

  14. Who, when, and where? Age-related differences on a new memory test

    PubMed Central

    Sumida, Catherine A.; Holden, Heather M.; Van Etten, Emily J.; Wagner, Gabrielle M.; Hileman, Jacob D.

    2016-01-01

    Our study examined age-related differences on a new memory test assessing memory for “who,” “when,” and “where,” and associations among these elements. Participants were required to remember a sequence of pictures of different faces paired with different places. Older adults remembered significantly fewer correct face–place pairs in the correct sequence compared with young adults. Correlation analyses with standardized neuropsychological tests provide preliminary evidence for construct validity. Our results offer insight into age-related changes in the ability to remember associations between people and places at different points in time using a portable test that can be administered rapidly in various settings. PMID:26670185

  15. Gulliver meets Descartes: early modern concepts of age-related memory loss.

    PubMed

    Schäfer, Daniel

    2003-03-01

    Age-related memory loss was a marginal issue in medical discussions during early modern times and until well into the second half of the 17th century. There are many possible explanations: the lack of similar traditions in antiquity and in the Middle Ages, insufficient physiological and morphological knowledge of the brain, and the underlying conflict between idealistic and materialistic perspectives on the functions of the soul and the conditions of these in old age. After these boundaries had been pushed back by the influence of Cartesianism and Iatromechanism, the problem of age-related memory loss was increasingly regarded as a physical illness and began to receive more attention. This trend first occurred in medicine, before spreading to the literary world, where the novel "Gulliver's Travels" is one clear and famous example.

  16. Activation of NO-cGMP Signaling Rescues Age-Related Memory Impairment in Crickets

    PubMed Central

    Matsumoto, Yukihisa; Matsumoto, Chihiro S.; Takahashi, Toshihumi; Mizunami, Makoto

    2016-01-01

    Age-related memory impairment (AMI) is a common feature and a debilitating phenotype of brain aging in many animals. However, the molecular mechanisms underlying AMI are still largely unknown. The cricket Gryllus bimaculatus is a useful experimental animal for studying age-related changes in learning and memory capability; because the cricket has relatively short life-cycle and a high capability of olfactory learning and memory. Moreover, the molecular mechanisms underlying memory formation in crickets have been examined in detail. In the present study, we trained male crickets of different ages by multiple-trial olfactory conditioning to determine whether AMI occurs in crickets. Crickets 3 weeks after the final molt (3-week-old crickets) exhibited levels of retention similar to those of 1-week-old crickets at 30 min or 2 h after training; however they showed significantly decreased levels of 1-day retention, indicating AMI in long-term memory (LTM) but not in anesthesia-resistant memory (ARM) in olfactory learning of crickets. Furthermore, 3-week-old crickets injected with a nitric oxide (NO) donor, a cyclic GMP (cGMP) analog or a cyclic AMP (cAMP) analog into the hemolymph before conditioning exhibited a normal level of LTM, the same level as that in 1-week-old crickets. The rescue effect by NO donor or cGMP analog injection was absent when the crickets were injected after the conditioning. For the first time, an NO donor and a cGMP analog were found to antagonize the age-related impairment of LTM formation, suggesting that deterioration of NO synthase (NOS) or molecules upstream of NOS activation is involved in brain-aging processes. PMID:27616985

  17. Age-Related Frontal Hyperactivation Observed across Different Working Memory Tasks: An fMRI Study

    PubMed Central

    Fakhri, Mohammad; Sikaroodi, Hajir; Maleki, Farid; Ali Oghabian, Mohammad; Ghanaati, Hosein

    2012-01-01

    Purpose: To evaluate patterns of activation, convergence and divergence of three functional magnetic resonance imaging (fMRI) Working Memory (WM) tasks in two different age groups. We want to understand potential impact of task and subjects’ age on WM activations as well as most important areas with regard to WM functions. Materials and methods: Thirty-five healthy volunteers completed visual, verbal, and novel auditory WM tasks. The subjects were selected from age extremes to depict possible impact of normal aging. The General Linear Model was used to report significant activations and the effect of age group. Contrasts revealed differences in activation between tasks, and Combined Task Analysis was performed to determine common regions of activation across tasks. Results: Most of the observed differences between the tasks were seen in areas that were responsible for feature processing. Frontal regions were mainstay activation areas, regardless of the utilized stimulus. We found an age-related reduction in activity of visual (in visually-presented tasks) and auditory (in auditory task) cortices but an age-related increase in prefrontal cortex for all tasks. Conclusion: Regardless of the type of the task stimuli, frontal regions are the most important activation areas in WM processing. These areas are also main targets of age-related changes with regard to activation patterns. Our results also indicate that prefrontal overactivity in working memory might be a compensatory effort to mask age-related decline in sensory processing. PMID:22885811

  18. Age-related deficits in efficiency of low-level lateral inhibition

    PubMed Central

    Schlaghecken, Friederike; Birak, Kulbir S.; Maylor, Elizabeth A.

    2012-01-01

    Background: In a masked prime task using a 0 ms prime-target inter-stimulus-interval, responses on trials where prime and target match (compatible trials) are usually faster and more accurate than responses where prime and target mismatch (incompatible trials). This positive compatibility effect (PCE) comprises both behavioral benefits on compatible relative to neutral trials, and behavioral costs on incompatible relative to neutral trials. Comparing performance in 2- vs. 4-alternative-response versions of the task indicates that benefits are due to direct priming (i.e., pre-activation) of a motor response, whereas costs reflect an inhibition of the alternative response tendency. The present study employs this paradigm to test the hypothesis that normal aging is associated with a selective deficit in inhibitory function, affecting both low-level motor and higher-level executive control. Experiment and Results: Testing 20 young and 20 older healthy adults, we found that (1) overall, prime-induced benefits were of similar magnitude across age groups, but inhibition-based costs were smaller in older compared to young adults; (2) increasing the number of response alternatives caused the same pattern of unaltered benefits and reduced costs in both age groups; and (3) costs, but not benefits, in the 2-alternative condition were significantly predicted by scores on the digit symbol substitution task (DSST), independently of age and other background variables. Interpretation: Results demonstrate the possibility of isolating an inhibitory component in low-level perceptuo-motor control. Importantly, this component shows an age-related decline in the absence of a corresponding decline of visuo-motor excitability, and appears to be linked to performance on a higher-level processing speed task. We hypothesize that aging might affect the brain's ability to establish precise short-term lateral inhibitory links, and that even in young adults, the efficiency of such links is a

  19. 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

  20. Stuck in default mode: inefficient cross-frequency synchronization may lead to age-related short-term memory decline.

    PubMed

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando; Sauseng, Paul

    2015-04-01

    Aging-related decline in short-term memory capacity seems to be caused by deficient balancing of task-related and resting state brain networks activity; however, the exact neural mechanism underlying this deficit remains elusive. Here, we studied brain oscillatory activity in healthy young and old adults during visual information maintenance in a delayed match-to-sample task. Particular emphasis was on long range phase:amplitude coupling of frontal alpha (8-12 Hz) and posterior fast oscillatory activity (>30 Hz). It is argued that through posterior fast oscillatory activity nesting into the excitatory or the inhibitory phase of frontal alpha wave, long-range networks can be efficiently coupled or decoupled, respectively. On the basis of this mechanism, we show that healthy, elderly participants exhibit a lack of synchronization in task-relevant networks while maintaining synchronized regions of the resting state network. Lacking disconnection of this resting state network is predictive of aging-related short-term memory decline. These results support the idea of inefficient orchestration of competing brain networks in the aging human brain and identify the neural mechanism responsible for this control breakdown.

  1. Nap it or leave it in the elderly: A nap after practice relaxes age-related limitations in procedural memory consolidation.

    PubMed

    Korman, M; Dagan, Y; Karni, A

    2015-10-08

    Using a training protocol that effectively induces procedural memory consolidation (PMC) in young adults, we show that older adults are good learners, robustly improving their motor performance during training. However, performance declined over the day, and overnight 'offline' consolidation phase performance gains were under-expressed. A post-training nap countered these deficits. PMC processes are preserved but under-engaged in the elderly; sleep can relax some of the age-related constraints on long-term plasticity.

  2. Age-related differences on event-related potentials and brain rhythm oscillations during working memory activation.

    PubMed

    Missonnier, Pascal; Herrmann, François R; Rodriguez, Christelle; Deiber, Marie-Pierre; Millet, Phiippe; Fazio-costa, Lara; Gold, Gabriel; Giannakopoulos, Panteleimon

    2011-06-01

    Previous functional imaging studies have pointed to the compensatory recruitment of cortical circuits in old age in order to counterbalance the loss of neural efficiency and preserve cognitive performance. Recent electroencephalographic (EEG) analyses reported age-related deficits in the amplitude of an early positive-negative working memory (PN(wm)) component as well as changes in working memory (WM)-load related brain oscillations during the successful performance of the n-back task. To explore the age-related differences of EEG activation in the face of increasing WM demands, we assessed the PN(wm) component area, parietal alpha event-related synchronization (ERS) as well as frontal theta ERS in 32 young and 32 elderly healthy individuals who successfully performed a highly WM demanding 3-back task. PN(wm) area increased with higher memory loads (3- and 2-back > 0-back tasks) in younger subjects. Older subjects reached the maximal values for this EEG parameter during the less WM demanding 0-back task. They showed a rapid development of an alpha ERS that reached its maximal amplitude at around 800 ms after stimulus onset. In younger subjects, the late alpha ERS occurred between 1,200 and 2,000 ms and its amplitude was significantly higher compared with elders. Frontal theta ERS culmination peak decreased in a task-independent manner in older compared with younger cases. Only in younger individuals, there was a significant decrease in the phasic frontal theta ERS amplitude in the 2- and 3-back tasks compared with the detection and 0-back tasks. These observations suggest that older adults display a rapid mobilization of their neural generators within the parietal cortex to manage very low demanding WM tasks. Moreover, they are less able to activate frontal theta generators during attentional tasks compared with younger persons.

  3. Moringa oleifera mitigates memory impairment and neurodegeneration in animal model of age-related dementia.

    PubMed

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180-220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required.

  4. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    PubMed Central

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required. PMID:24454988

  5. Age-Related Deficits in the Processing of Fundamental Frequency Differences for the Intelligibility of Competing Voices

    PubMed Central

    2013-01-01

    A common complaint of older listeners is that they can hear speech, yet cannot understand it, especially when listening to speech in a background noise. When target and competing speech signals are concurrently presented, a difference in the fundamental frequency (ΔF0) between competing speech signals, which determines the pitch of voice, can be an important and commonly occurring cue to facilitate the separation of the target message from the interfering message, consequently improving intelligibility of the target message. To address the question of whether the older listeners have reduced ability to use ΔF0 and how the age-related deficits in the processing of ΔF0 are theoretically explained, this paper is divided into three parts. The first part of this article summarizes how the speech-communication difficulties that older listeners have are theoretically explained. In the second part, literatures on the perceptual benefits from ΔF0 and the age-related deficits on the use of ΔF0 are reviewed. As a final part, three theoretical models explaining the general processing of ΔF0 are compared to discuss which better explains the age-related deficits in the processing of ΔF0. PMID:24653895

  6. Measuring Working Memory Deficits in Aphasia

    ERIC Educational Resources Information Center

    Mayer, Jamie F.; Murray, Laura L.

    2012-01-01

    Purpose: Many adults with aphasia demonstrate concomitant deficits in working memory (WM), but such deficits are difficult to quantify because of a lack of validated measures as well as the complex interdependence between language and WM. We examined the feasibility, reliability, and internal consistency of an "n"-back task for…

  7. Episodic future thinking: the role of working memory and inhibition on age-related differences.

    PubMed

    Zavagnin, Michela; De Beni, Rossana; Borella, Erika; Carretti, Barbara

    2016-02-01

    The ability to remember past events and imagine future events (episodic future thinking-EFT) has been shown to decline with aging. However, only few studies have analyzed the cognitive mechanisms involved in EFT in both young and older adults. The present study examined the role of working memory and inhibition on age-related differences between young and older adults in EFT, in response to short sentences reflecting common events, some of which were repeated in both conditions (past and future). Thirty-seven young and 36 older adults completed an adapted version of the autobiographical interview, in which sentences were presented. Results showed that processing resources explained a significant part of the variance in the amount of details; in particular, inhibition explained the amount of external details produced in the future condition. In addition, using sentences, the older group did not differ from the young adults in terms of the proportion of internal details recalled in the past condition, whereas they produced a lower proportion of internal details in the future condition. The effect of using structured material was reinforced by repeating some sentences in the past. Further, only older adults rated the remembered episodes as more emotionally salient and relevant than the imagined ones. Age-related differences between young and older adults in EFT appear to depend on the type of material used, on basic mechanisms of cognition, and are characterized by both quantitative and qualitative differences.

  8. Age-related effects on perceptual and semantic encoding in memory.

    PubMed

    Kuo, M C C; Liu, K P Y; Ting, K H; Chan, C C H

    2014-03-07

    This study examined the age-related subsequent memory effect (SME) in perceptual and semantic encoding using event-related potentials (ERPs). Seventeen younger adults and 17 older adults studied a series of Chinese characters either perceptually (by inspecting orthographic components) or semantically (by determining whether the depicted object makes sounds). The two tasks had similar levels of difficulty. The participants made studied or unstudied judgments during the recognition phase. Younger adults performed better in both conditions, with significant SMEs detected in the time windows of P2, N3, P550, and late positive component (LPC). In the older group, SMEs were observed in the P2 and N3 latencies in both conditions but were only detected in the P550 in the semantic condition. Between-group analyses showed larger frontal and central SMEs in the younger sample in the LPC latency regardless of encoding type. Aging effect appears to be stronger on influencing perceptual than semantic encoding processes. The effects seem to be associated with a decline in updating and maintaining representations during perceptual encoding. The age-related decline in the encoding function may be due in part to changes in frontal lobe function.

  9. Age-related differences in cortical activity during a visuo-spatial working memory task with facial stimuli.

    PubMed

    Belham, Flávia Schechtman; Satler, Corina; Garcia, Ana; Tomaz, Carlos; Gasbarri, Antonella; Rego, Artur; Tavares, Maria Clotilde H

    2013-01-01

    Emotion, importantly displayed by facial expressions, is one of the most significant memory modulators. The interaction between memory and the different emotional valences change across lifespan, while young adults (YA) are expected to better recall negative events (Negativity Bias Hypothesis), older adults (OA) tend to focus on positive stimuli (Positivity Effect Hypothesis). This research work aims at verifying whether cortical electrical activity of these two age groups would also be differently influenced by emotional valences in a visuo-spatial working memory task. 27 YA (13 males) and 25 OA (14 males), all healthy volunteers, underwent electroencephalographic recordings (21 scalp electrodes montage), while performing the Spatial Delayed Recognition Span Task using a touch screen with different stimuli categories: neutral, positive and negative faces and geometric pictures. YA obtained higher scores than OA, and showed higher activation of theta and alpha bands in the frontal and midline regions, besides a more evident right-hemispheric asymmetry on alpha band when compared to OA. For both age groups, performance in the task was worse for positive faces than to negative and to neutral faces. Facial stimuli induced a better performance and higher alpha activation on the pre-frontal region for YA, and on the midline, occipital and left temporal regions for OA when compared to geometric figures. The superior performance of YA was expected due to the natural cognitive deficits connected to ageing, as was a better performance with facial stimuli due to the evolutionary importance of faces. These results were related to cortical activity on areas of importance for action-planning, decision making and sustained attention. Taken together, they are in accordance with the Negativity Bias but do not support the Positivity Effect. The methodology used was able to identify age-related differences in cortical activity during emotional mnemonic processing and may be

  10. Age-Related Differences in Cortical Activity during a Visuo-Spatial Working Memory Task with Facial Stimuli

    PubMed Central

    Belham, Flávia Schechtman; Satler, Corina; Garcia, Ana; Tomaz, Carlos; Gasbarri, Antonella; Rego, Artur; Tavares, Maria Clotilde H.

    2013-01-01

    Emotion, importantly displayed by facial expressions, is one of the most significant memory modulators. The interaction between memory and the different emotional valences change across lifespan, while young adults (YA) are expected to better recall negative events (Negativity Bias Hypothesis), older adults (OA) tend to focus on positive stimuli (Positivity Effect Hypothesis). This research work aims at verifying whether cortical electrical activity of these two age groups would also be differently influenced by emotional valences in a visuo-spatial working memory task. 27 YA (13 males) and 25 OA (14 males), all healthy volunteers, underwent electroencephalographic recordings (21 scalp electrodes montage), while performing the Spatial Delayed Recognition Span Task using a touch screen with different stimuli categories: neutral, positive and negative faces and geometric pictures. YA obtained higher scores than OA, and showed higher activation of theta and alpha bands in the frontal and midline regions, besides a more evident right-hemispheric asymmetry on alpha band when compared to OA. For both age groups, performance in the task was worse for positive faces than to negative and to neutral faces. Facial stimuli induced a better performance and higher alpha activation on the pre-frontal region for YA, and on the midline, occipital and left temporal regions for OA when compared to geometric figures. The superior performance of YA was expected due to the natural cognitive deficits connected to ageing, as was a better performance with facial stimuli due to the evolutionary importance of faces. These results were related to cortical activity on areas of importance for action-planning, decision making and sustained attention. Taken together, they are in accordance with the Negativity Bias but do not support the Positivity Effect. The methodology used was able to identify age-related differences in cortical activity during emotional mnemonic processing and may be

  11. Autobiographical and episodic memory deficits in mild traumatic brain injury.

    PubMed

    Wammes, Jeffrey D; Good, Tyler J; Fernandes, Myra A

    2017-02-01

    Those who have suffered a concussion, otherwise known as a mild traumatic brain injury (mTBI), often complain of lingering memory problems. However, there is little evidence in the behavioral literature reliably demonstrating memory deficits. Thus, in the present study, cognitive profiles including measures of general executive functioning and processing speed, as well as episodic and semantic memory were collected in younger and older adult participants with or without a remote (>1year prior to testing) mTBI. We first investigated whether there were observable episodic and autobiographical memory impairments associated with mTBI within an otherwise healthy young group. Next, because previous work had demonstrated some overlap in patterns of behavioral impairment in normally aging adults and younger adults with a history of mTBI (e.g. Ozen, Fernandes, Clark, & Roy, 2015), we sought to determine whether these groups displayed similar cognitive profiles. Lastly, we conducted an exploratory analysis to test whether having suffered an mTBI might exacerbate age-related cognitive decline. Results showed the expected age-related decline in episodic memory performance, coupled with a relative preservation of semantic memory in older adults. Importantly, this pattern was also present in younger adults with a history of remote mTBI. No differences were observed across older adult groups based on mTBI status. Logistic regression analyses, using each measure in our battery as a predictor, successfully classified mTBI status in younger participants with a high degree of specificity (79.5%). These results indicate that those who have had an mTBI demonstrate a distinct cognitive signature, characterized by impairment in episodic and autobiographical memory, coupled with a relative preservation of semantic memory.

  12. An expectation-based memory deficit in aging.

    PubMed

    Bollinger, Jacob; Rubens, Michael T; Masangkay, Edrick; Kalkstein, Jonathan; Gazzaley, Adam

    2011-05-01

    Memory performance can be enhanced by expectations regarding the appearance of ensuing stimuli. Here, we investigated the influence of stimulus-category expectation on memory performance in aging, and used fMRI to explore age-related alterations in associated neural mechanisms. Unlike younger adults, who demonstrated both working memory (WM) and long-term memory (LTM) performance benefits for face stimuli when this stimulus category was expected, older adults did not exhibit these memory benefits. Concordantly, older adults did not exhibit expectation-period activity modulation in visual association cortex (i.e., fusiform face area (FFA)), unlike younger adults. However, within the older population, individuals who demonstrated face-expectation memory benefits also exhibited expectation-period FFA activity modulation equivalent to younger adults. The older cohort also displayed diminished expectation-related functional connectivity between regions of the prefrontal cortex and the FFA, relative to younger adults, suggesting that network alterations underlie the absence of expectation-mediated cortical modulation and memory benefits. This deficit may have broader consequences for the effective utilization of predictive cues to guide attention and engender optimal cognitive performance in older individuals.

  13. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging

    PubMed Central

    Maimaiti, Shaniya; Anderson, Katie L.; DeMoll, Chris; Brewer, Lawrence D.; Rauh, Benjamin A.; Gant, John C.; Blalock, Eric M.; Porter, Nada M.

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer’s disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca2+-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP. PMID:25659889

  14. How age-related strategy switching deficits affect wayfinding in complex environments.

    PubMed

    Harris, Mathew A; Wolbers, Thomas

    2014-05-01

    Although most research on navigation in aging focuses on allocentric processing deficits, impaired strategy switching may also contribute to navigational decline. Using a specifically designed task involving navigating a town-like virtual environment, we assessed the ability of young and old participants to switch from following learned routes to finding novel shortcuts. We found large age differences in the length of routes taken during testing and in use of shortcuts, as, while nearly all young participants switched from the egocentric route-following strategy to the allocentric wayfinding strategy, none of the older participants stably switched. Although secondary tasks confirmed that older participants were impaired both at strategy switching and allocentric processing, the difficulty in using shortcuts was selectively related to impaired strategy switching. This may in turn relate to dysfunction of the prefrontal-noradrenergic network responsible for coordinating switching behavior. We conclude that the large age difference in performance at the shortcutting task demonstrates for the first time, how strategy switching deficits can have a severe impact on navigation in aging.

  15. Alzheimer’s Disease and Age-Related Memory Decline (Preclinical)

    PubMed Central

    Terry, Alvin V.; Callahan, Patrick M.; Hall, Brandon; Webster, Scott J.

    2011-01-01

    An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory

  16. Modulation of Intestinal Microbiota by the Probiotic VSL#3 Resets Brain Gene Expression and Ameliorates the Age-Related Deficit in LTP

    PubMed Central

    Distrutti, Eleonora; O’Reilly, Julie-Ann; McDonald, Claire; Cipriani, Sabrina; Renga, Barbara; Lynch, Marina A.; Fiorucci, Stefano

    2014-01-01

    The intestinal microbiota is increasingly recognized as a complex signaling network that impacts on many systems beyond the enteric system modulating, among others, cognitive functions including learning, memory and decision-making processes. This has led to the concept of a microbiota-driven gut–brain axis, reflecting a bidirectional interaction between the central nervous system and the intestine. A deficit in synaptic plasticity is one of the many changes that occurs with age. Specifically, the archetypal model of plasticity, long-term potentiation (LTP), is reduced in hippocampus of middle-aged and aged rats. Because the intestinal microbiota might change with age, we have investigated whether the age-related deficit in LTP might be attenuated by changing the composition of intestinal microbiota with VSL#3, a probiotic mixture comprising 8 Gram-positive bacterial strains. Here, we report that treatment of aged rats with VSL#3 induced a robust change in the composition of intestinal microbiota with an increase in the abundance of Actinobacteria and Bacterioidetes, which was reduced in control-treated aged rats. VSL#3 administration modulated the expression of a large group of genes in brain tissue as assessed by whole gene expression, with evidence of a change in genes that impact on inflammatory and neuronal plasticity processes. The age-related deficit in LTP was attenuated in VSL#3-treated aged rats and this was accompanied by a modest decrease in markers of microglial activation and an increase in expression of BDNF and synapsin. The data support the notion that intestinal microbiota can be manipulated to positively impact on neuronal function. PMID:25202975

  17. Modulation of intestinal microbiota by the probiotic VSL#3 resets brain gene expression and ameliorates the age-related deficit in LTP.

    PubMed

    Distrutti, Eleonora; O'Reilly, Julie-Ann; McDonald, Claire; Cipriani, Sabrina; Renga, Barbara; Lynch, Marina A; Fiorucci, Stefano

    2014-01-01

    The intestinal microbiota is increasingly recognized as a complex signaling network that impacts on many systems beyond the enteric system modulating, among others, cognitive functions including learning, memory and decision-making processes. This has led to the concept of a microbiota-driven gut-brain axis, reflecting a bidirectional interaction between the central nervous system and the intestine. A deficit in synaptic plasticity is one of the many changes that occurs with age. Specifically, the archetypal model of plasticity, long-term potentiation (LTP), is reduced in hippocampus of middle-aged and aged rats. Because the intestinal microbiota might change with age, we have investigated whether the age-related deficit in LTP might be attenuated by changing the composition of intestinal microbiota with VSL#3, a probiotic mixture comprising 8 Gram-positive bacterial strains. Here, we report that treatment of aged rats with VSL#3 induced a robust change in the composition of intestinal microbiota with an increase in the abundance of Actinobacteria and Bacterioidetes, which was reduced in control-treated aged rats. VSL#3 administration modulated the expression of a large group of genes in brain tissue as assessed by whole gene expression, with evidence of a change in genes that impact on inflammatory and neuronal plasticity processes. The age-related deficit in LTP was attenuated in VSL#3-treated aged rats and this was accompanied by a modest decrease in markers of microglial activation and an increase in expression of BDNF and synapsin. The data support the notion that intestinal microbiota can be manipulated to positively impact on neuronal function.

  18. Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats.

    PubMed Central

    Geinisman, Y; de Toledo-Morrell, L; Morrell, F

    1986-01-01

    Most, but not all, aged rats exhibit a profound deficit in spatial memory when tested in a radial maze--a task known to depend on the integrity of the hippocampal formation. In this study, animals were divided into three groups based on their spatial memory capacity: young adult rats with good memory, aged rats with impaired memory, and aged rats with good memory. Memory-impaired aged animals showed a loss of perforated axospinous synapses in the dentate gyrus of the hippocampal formation in comparison with either young adults or aged rats with good memory. This finding suggests that the loss of perforated axospinous synapses in the hippocampal formation underlies the age-related deficit in spatial memory. Images PMID:3458260

  19. Activation of the medial septum reverses age-related hippocampal encoding deficits: a place field analysis.

    PubMed

    Sava, Simona; Markus, Etan J

    2008-02-20

    When a rat runs through a familiar environment, the hippocampus retrieves a previously stored spatial representation of the environment. When the environment is modified a new representation is seen, presumably corresponding to the hippocampus encoding the new information. The medial septum is hypothesized to modulate whether the hippocampus engages in retrieval or encoding. The cholinergic agonist carbachol was infused into the medial septum, and hippocampal CA1 place cells were recorded in freely moving rats. In a familiar environment, septal activation impaired the retrieval of a previously stored hippocampal place cell representation regardless of age. When the environment was changed, medial septal activation impaired the encoding process in young, but facilitated the encoding of the new information in aged rats. Moreover, the improved encoding was evident during a subsequent exposure to the modified environment 24 h later. The findings support the role the septum plays in modulating hippocampal retrieval/encoding states. Furthermore, our data indicate a mechanism of age-related cognitive impairment.

  20. Tocotrienol improves learning and memory deficit of aged rats

    PubMed Central

    Kaneai, Nozomi; Sumitani, Kazumi; Fukui, Koji; Koike, Taisuke; Takatsu, Hirokatsu; Urano, Shiro

    2016-01-01

    To define whether tocotrienol (T-3) improves cognitive deficit during aging, effect of T-3 on learning and memory functions of aged rats was assessed. It was found that T-3 markedly counteracts the decline in learning and memory function in aged rats. Quantitative analysis of T-3 content in the rat brain showed that the aged rats fed T-3 mixture-supplemented diet revealed the transport of α- and γ-T-3 to the brain. In contrast, normal young rats fed the same diet did not exhibit brain localization. Furthermore, the T-3 inhibited age-related decreases in the expression of certain blood brain barrier (BBB) proteins, including caludin-5, occludin and junctional adhesion molecule (JAM). It was found that the activation of the cellular proto-oncogene c-Src and extracellular signal-regulated protein kinase (ERK), in the mitogen-activated protein kinase (MAPK) cell signaling pathway for neuronal cell death, was markedly inhibited by T-3. These results may reveal that aging induces partial BBB disruption caused by oxidative stress, thereby enabling the transport of T-3 through the BBB to the central nervous system, whereupon neuronal protection may be mediated by inhibition of c-Src and/or ERK activation, resulting in an improvement in age-related cognitive deficits. PMID:27013777

  1. Recognition memory deficits in mild cognitive impairment.

    PubMed

    Algarabel, Salvador; Fuentes, Manuel; Escudero, Joaquín; Pitarque, Alfonso; Peset, Vicente; Mazón, José-Francisco; Meléndez, Juan-Carlos

    2012-09-01

    There is no agreement on the pattern of recognition memory deficits characteristic of patients diagnosed with mild cognitive impairment (MCI). Whereas lower performance in recollection is the hallmark of MCI, there is a strong controversy about possible deficits in familiarity estimates when using recognition memory tasks. The aim of this research is to shed light on the pattern of responding in recollection and familiarity in MCI. Five groups of participants were tested. The main participant samples were those formed by two MCI groups differing in age and an Alzheimer's disease group (AD), which were compared with two control groups. Whereas one of the control groups served to assess the performance of the MCI and AD people, the other one, composed of young healthy participants, served the purpose of evaluating the adequacy of the experimental tasks used in the evaluation of the different components of recognition memory. We used an associative recognition task as a direct index of recollection and a choice task on a pair of stimuli, one of which was perceptually similar to those studied in the associative recognition phase, as an index of familiarity. Our results indicate that recollection decreases with age and neurological status, and familiarity remains stable in the elderly control sample but it is deficient in MCI. This research shows that a unique encoding situation generated deficits in recollective and familiarity mechanisms in mild cognitive impaired individuals, providing evidence for the existence of deficits in both retrieval processes in recognition memory in a MCI stage.

  2. Age-related deficits in voluntary control over saccadic eye movements: consideration of electrical brain stimulation as a therapeutic strategy.

    PubMed

    Chen, Po Ling; Machado, Liana

    2016-05-01

    Sudden changes in our visual environment trigger reflexive eye movements, so automatically they often go unnoticed. Consequently, voluntary control over reflexive eye movements entails considerable effort. In relation to frontal-lobe deterioration, adult aging adversely impacts voluntary saccadic eye movement control in particular, which compromises effective performance of daily activities. Here, we review the nature of age-related changes in saccadic control, focusing primarily on the antisaccade task because of its assessment of 2 key age-sensitive control functions: reflexive saccade inhibition and voluntary saccade generation. With an ultimate view toward facilitating development of therapeutic strategies, we systematically review the neuroanatomy underpinning voluntary control over saccadic eye movements and natural mechanisms that kick in to compensate for age-related declines. We then explore the potential of noninvasive electrical brain stimulation to counteract aging deficits. Based on evidence that anodal transcranial direct current stimulation can confer a range of benefits specifically relevant to aging brains, we put forward this neuromodulation technique as a therapeutic strategy for improving voluntary saccadic eye movement control in older adults.

  3. Age-related change of neurochemical abnormality in attention-deficit hyperactivity disorder: a meta-analysis.

    PubMed

    Aoki, Yuta; Inokuchi, Ryota; Suwa, Hiroshi; Aoki, Ai

    2013-09-01

    Prevalence and symptoms of attention-deficit hyperactivity disorder (ADHD) change with advancing age. However, neurochemical background of such age-related change is yet to be elucidated. We therefore conducted a meta-analysis of 16 proton magnetic resonance spectroscopy studies comprising 270 individuals with ADHD and 235 controls. Standardized mean differences were calculated and used as an effect size. Sensitivity analyses and meta-regression to explore the effect of age on neurochemical abnormality were performed. A random effects model identified a significantly higher-than-normal N-acetylaspartate (NAA) in the medial prefrontal cortex (mPFC), but no significant differences of other metabolites in that area. No significant difference in metabolite levels was demonstrated in any other region. Sensitivity analysis of children with ADHD revealed significantly higher-than-normal NAA, whereas no significant difference was found in adults with ADHD. Meta-regression revealed significant correlation between advanced age and normal levels of NAA in the mPFC, suggesting that age-dependent abnormality of NAA level in the mPFC is a potential neural basis of age-related change of symptoms of ADHD.

  4. Executive Functioning and Processing Speed in Age-Related Differences in Memory: Contribution of a Coding Task

    ERIC Educational Resources Information Center

    Baudouin, Alexia; Clarys, David; Vanneste, Sandrine; Isingrini, Michel

    2009-01-01

    The aim of the present study was to examine executive dysfunctioning and decreased processing speed as potential mediators of age-related differences in episodic memory. We compared the performances of young and elderly adults in a free-recall task. Participants were also given tests to measure executive functions and perceptual processing speed…

  5. 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…

  6. Catechol-O-methyltransferase (COMT) Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    PubMed Central

    Riemer, Thomas G.; Schulte, Stefanie; Onken, Johanna; Heinz, Andreas; Rapp, Michael A.

    2014-01-01

    Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years) and 25 older (aged 60–75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism. PMID:24772423

  7. Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation.

    PubMed

    Kodali, Maheedhar; Parihar, Vipan K; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K

    2015-01-28

    Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.

  8. EPA/DHA and Vitamin A Supplementation Improves Spatial Memory and Alleviates the Age-related Decrease in Hippocampal RXRγ and Kinase Expression in Rats.

    PubMed

    Létondor, Anne; Buaud, Benjamin; Vaysse, Carole; Richard, Emmanuel; Layé, Sophie; Pallet, Véronique; Alfos, Serge

    2016-01-01

    Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore, we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ, and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT, and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging.

  9. Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome1

    PubMed Central

    Chang, Qing; Gold, Paul E.

    2008-01-01

    Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer’s Disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22–25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 μg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice. PMID:17644430

  10. Preterm Infant Hippocampal Volumes Correlate with Later Working Memory Deficits

    ERIC Educational Resources Information Center

    Beauchamp, Miriam H.; Thompson, Deanne K.; Howard, Kelly; Doyle, Lex W.; Egan, Gary F.; Inder, Terrie E.; Anderson, Peter J.

    2008-01-01

    Children born preterm exhibit working memory deficits. These deficits may be associated with structural brain changes observed in the neonatal period. In this study, the relationship between neonatal regional brain volumes and working memory deficits at age 2 years were investigated, with a particular interest in the dorsolateral prefrontal…

  11. Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus.

    PubMed

    Lovatel, Gisele Agustini; Elsner, Viviane Rostirola; Bertoldi, Karine; Vanzella, Cláudia; Moysés, Felipe Dos Santos; Vizuete, Adriana; Spindler, Christiano; Cechinel, Laura Reck; Netto, Carlos Alexandre; Muotri, Alysson Renato; Siqueira, Ionara Rodrigues

    2013-03-01

    It has been described that exercise can modulate both inflammatory response and epigenetic modifications, although the effect of exercise on these parameters during the normal brain aging process yet remains poorly understood. Here, we investigated the effect of aging and treadmill exercise on inflammatory and epigenetic parameters specifically pro and anti-inflammatory cytokines levels, activation of NF-kB and histone H4 acetylation levels in hippocampus from Wistar rats. Additionally, we evaluated aversive memory through inhibitory avoidance task. Rats of 3 and 20 months of age were assigned to non-exercised (sedentary) and exercised (running daily for 20 min for 2 weeks) groups. The effect of daily forced exercise in the treadmill was assessed. The levels of inflammatory and epigenetic parameters were determined 1h, 18 h, 3 days or 7 days after the last training session of exercise. It was observed an age-related decline on aversive memory, as well as aged rats showed increased hippocampal levels of inflammatory markers, such as TNFα, IL1-β and NF-kB and decreased IL-4 levels, an anti-inflammatory cytokine. Moreover, lower levels of global histone H4 acetylation were also observed in hippocampi from aged rats. Interestingly, there was a significant correlation between the biochemical markers and the inhibitory avoidance test performance. The forced exercise protocol ameliorated aging-related memory decline, decreased pro-inflammatory markers and increased histone H4 acetylation levels in hippocampi 20-months-old rats, while increased acutely IL-4 levels in hippocampi from young adult rats. Together, these results suggest that an imbalance of inflammatory markers might be involved to the aging-related aversive memory impairment. Additionally, our exercise protocol may reverse aging-related memory decline through improving cytokine profile.

  12. Age-related effects on verbal and visuospatial memory are mediated by theta and alpha II rhythms.

    PubMed

    Reichert, Johanna Louise; Kober, Silvia Erika; Witte, Matthias; Neuper, Christa; Wood, Guilherme

    2016-01-01

    Both electrical brain activity during rest and memory functions change across the lifespan. Moreover, electrical brain activity is associated with memory functions. However, the interplay between all these effects has been investigated only scarcely. The present study investigated the extent to which the power of resting-state electroencephalographic (EEG) frequencies mediates the impact of aging on verbal and visuospatial memory. Seventy healthy participants with 22 to 83years of age completed a visuospatial and verbal learning and memory test and provided eyes-open and eyes-closed resting-state EEG data. Robust age-related effects on behavioral and EEG data were observed. Mediation analyses showed that the relative power of the theta (4-8Hz) frequency band in fronto-central locations partly explained the negative age-related effect on delayed recall in the verbal memory task. The relative power of the alpha II (10-12Hz) frequency band in mainly parietal locations partly explained the negative impact of age on immediate and delayed recall in the visuospatial task. Results indicate that spontaneous brain activity carries specific information about aging processes and predicts the level of competence in verbal and visuospatial memory tasks.

  13. A Reevaluation of Age-Related Changes in Associative Memory Organization.

    ERIC Educational Resources Information Center

    Lindauer, Barbara K.; Paris, Scott G.

    This paper focuses on a study which replicates and extends earlier work employing a recognition memory paradigm to investigate children's memory and developmental changes in dominant word associations. On the recognition test the implicit associative response can lead to better memory for the original items (this is the hit rate), and it can also…

  14. Age-Related Reduction of the Confidence-Accuracy Relationship in Episodic Memory: Effects of Recollection Quality and Retrieval Monitoring

    PubMed Central

    Wong, Jessica T.; Cramer, Stefanie J.; Gallo, David A.

    2012-01-01

    We investigated age-related reductions in episodic metamemory accuracy. Participants studied pictures and words in different colors, and then took forced-choice recollection tests. These tests required recollection of the earlier presentation color, holding familiarity of the response options constant. Metamemory accuracy was assessed for each participant by comparing recollection test accuracy to corresponding confidence judgments. We found that recollection test accuracy was greater in younger than older adults, and also for pictures than font color. Metamemory accuracy tracked each of these recollection differences, as well as individual differences in recollection test accuracy within each age group, suggesting that recollection ability affects metamemory accuracy. Critically, the age-related impairment in metamemory accuracy persisted even when the groups were matched on recollection test accuracy, suggesting that metamemory declines were not entirely due to differences in recollection frequency or quantity, but that differences in recollection quality and/or monitoring also played a role. We also found that age-related impairments in recollection and metamemory accuracy were equivalent for pictures and font colors. This result contrasted with previous false recognition findings, which predicted that older adults would be differentially impaired when monitoring memory for less distinctive memories. These and other results suggest that age-related reductions in metamemory accuracy are not entirely attributable to false recognition effects, but also depend heavily on deficient recollection and/or monitoring of specific details associated with studied stimuli. PMID:22449027

  15. Prose memory deficits associated with schizophrenia.

    PubMed

    Lee, Tatia M C; Chan, Michelle W C; Chan, Chetwyn C H; Gao, Junling; Wang, Kai; Chen, Eric Y H

    2006-01-31

    Memory of contextual information is essential to one's quality of living. This study investigated if the different components of prose memory, across three recall conditions: first learning trial immediate recall, fifth learning trial immediate recall, and 30-min delayed recall, are differentially impaired in people with schizophrenia, relative to healthy controls. A total of 39 patients with schizophrenia and 39 matched healthy controls were recruited. Their prose memory, in terms of recall accuracy, temporal sequence, recognition accuracy and false positives, commission of distortions, and rates of learning, forgetting, and retention were tested and compared. After controlling for the level of intelligence and depression, the patients with schizophrenia were found to commit more distortions. Furthermore, they performed poorer on recall accuracy and temporal sequence accuracy only during the first initial immediate recall. On the other hand, the rates of forgetting/retention and recognition accuracy were comparable between the two groups. These findings suggest that people with schizophrenia could be benefited by repeated exposure to the materials to be remembered. These results may have important implications for rehabilitation of verbal declarative memory deficits in schizophrenia.

  16. Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits

    PubMed Central

    Bonasera, Stephen J.; Arikkath, Jyothi; Boska, Michael D.; Chaudoin, Tammy R.; DeKorver, Nicholas W.; Goulding, Evan H.; Hoke, Traci A.; Mojtahedzedah, Vahid; Reyelts, Crystal D.; Sajja, Balasrinivasa; Schenk, A. Katrin; Tecott, Laurence H.; Volden, Tiffany A.

    2016-01-01

    We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits. PMID:27689748

  17. Age-Related Differences in the Reliance on Executive Control in Working Memory: Role of Task Demand

    PubMed Central

    Isingrini, Michel; Angel, Lucie; Fay, Séverine; Taconnat, Laurence; Lemaire, Patrick; Bouazzaoui, Badiâa

    2015-01-01

    We examined the hypothesis that age-related differences in the reliance on executive control may be better explained by variations of task demand than by a mechanism specifically linked to aging. To this end, we compared the relationship between the performance of young and older adults on two executive functioning tests and an updating working-memory task with different load levels. The results revealed a significant interaction between age, task demand, and individual executive capacities, indicating that executive resources were only involved at lower loads in older adults, and only at higher loads in young adults. Overall, the results are not consistent with the proposition that cognition places greater demand on executive control in older adults. However, they support the view that how much young and older adults rely on executive control to accomplish cognitive tasks depends on task demand. Finally, interestingly these results are consistent with the CRUNCH model accounting for age-related differences in brain activations. PMID:26700019

  18. Age-related changes in working memory and the ability to ignore distraction.

    PubMed

    McNab, Fiona; Zeidman, Peter; Rutledge, Robb B; Smittenaar, Peter; Brown, Harriet R; Adams, Rick A; Dolan, Raymond J

    2015-05-19

    A weakened ability to effectively resist distraction is a potential basis for reduced working memory capacity (WMC) associated with healthy aging. Exploiting data from 29,631 users of a smartphone game, we show that, as age increases, working memory (WM) performance is compromised more by distractors presented during WM maintenance than distractors presented during encoding. However, with increasing age, the ability to exclude distraction at encoding is a better predictor of WMC in the absence of distraction. A significantly greater contribution of distractor filtering at encoding represents a potential compensation for reduced WMC in older age.

  19. Learn to forget: regulation of age-related memory impairment by neuronal-glial crosstalk.

    PubMed

    Jackson, George R

    2014-11-19

    Dementia is among the most feared complications of aging in the U.S. In this issue of Neuron, Yamazaki et al. (2014) present a tour de force mechanistic analysis of a "hit" from a proteomic screen carried out using a Drosophila mutation that affects memory.

  20. Age-Related Differences in the Temporal Dynamics of Prospective Memory Retrieval: A Lifespan Approach

    ERIC Educational Resources Information Center

    Mattli, Florentina; Zollig, Jacqueline; West, Robert

    2011-01-01

    The efficiency of prospective memory (PM) typically increases from childhood to young adulthood and then decreases in later adulthood. The current study used event-related brain potentials (ERPs) to examine the development of the neural correlates of processes associated with the detection of a PM cue, switching from the ongoing activity to the…

  1. Age-related differences on a new test of temporal order memory for everyday events.

    PubMed

    Seewald, P Michelle; De Jesus, Shannon Y; Graves, Lisa V; Moreno, Charles C; Mattson, Sarah N; Gilbert, Paul E

    2017-03-07

    We developed a new test to examine incidental temporal order memory for a self-generated sequence of tasks one might complete in everyday life. Young and older adults were given 10 cards, each listing a task one might accomplish in a typical day. Participants were asked to self-generate a "to do" list by placing the 10 cards in a sequence representing the order in which they would accomplish the tasks, but were not informed of a subsequent memory test. We assessed immediate free recall, delayed free recall, and delayed cued recall for the order of the tasks in the sequence. Older adults were significantly impaired relative to young adults on immediate free recall, delayed free recall, and delayed cued recall. Correlation analyses with standardized neuropsychological tests provide preliminary evidence for construct validity for our test, which is portable and can be rapidly administered in clinical or laboratory settings.

  2. Age-related slowing of memory retrieval: Contributions of perceptual speed and cerebral white matter integrity

    PubMed Central

    Bucur, Barbara; Madden, David J.; Spaniol, Julia; Provenzale, James M.; Cabeza, Roberto; White, Leonard E.; Huettel, Scott A.

    2007-01-01

    Previous research suggests that, in reaction time (RT) measures of episodic memory retrieval, the unique effects of adult age are relatively small compared to the effects aging shares with more elementary abilities such as perceptual speed. Little is known, however, regarding the mechanisms of perceptual speed. We used diffusion tensor imaging (DTI) to test the hypothesis that white matter integrity, as indexed by fractional anisotropy (FA), serves as one mechanism of perceptual slowing in episodic memory retrieval. Results indicated that declines in FA in the pericallosal frontal region and in the genu of the corpus callosum, but not in other regions, mediated the relationship between perceptual speed and episodic retrieval RT. This relation held, though to a different degree, for both hits and correct rejections. These findings suggest that white matter integrity in prefrontal regions is one mechanism underlying the relation between individual differences in perceptual speed and episodic retrieval. PMID:17383774

  3. Age-related differences in recognition memory for items and associations: contribution of individual differences in working memory and metamemory.

    PubMed

    Bender, Andrew R; Raz, Naftali

    2012-09-01

    Ability to form new associations between unrelated items is particularly sensitive to aging, but the reasons for such differential vulnerability are unclear. In this study, we examined the role of objective and subjective factors (working memory and beliefs about memory strategies) on differential relations of age with recognition of items and associations. Healthy adults (N = 100, age 21 to 79) studied word pairs, completed item and association recognition tests, and rated the effectiveness of shallow (e.g., repetition) and deep (e.g., imagery or sentence generation) encoding strategies. Advanced age was associated with reduced working memory (WM) capacity and poorer associative recognition. In addition, reduced WM capacity, beliefs in the utility of ineffective encoding strategies, and lack of endorsement of effective ones were independently associated with impaired associative memory. Thus, maladaptive beliefs about memory in conjunction with reduced cognitive resources account in part for differences in associative memory commonly attributed to aging.

  4. 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.

  5. Assessing the associative deficit of older adults in long-term and short-term/working memory.

    PubMed

    Chen, Tina; Naveh-Benjamin, Moshe

    2012-09-01

    Older adults exhibit a deficit in associative long-term memory relative to younger adults. However, the literature is inconclusive regarding whether this deficit is attenuated in short-term/working memory. To elucidate the issue, three experiments assessed younger and older adults' item and interitem associative memory and the effects of several variables that might potentially contribute to the inconsistent pattern of results in previous studies. In Experiment 1, participants were tested on item and associative recognition memory with both long-term and short-term retention intervals in a single, continuous recognition paradigm. There was an associative deficit for older adults in the short-term and long-term intervals. Using only short-term intervals, Experiment 2 utilized mixed and blocked test designs to examine the effect of test event salience. Blocking the test did not attenuate the age-related associative deficit seen in the mixed test blocks. Finally, an age-related associative deficit was found in Experiment 3, under both sequential and simultaneous presentation conditions. Even while accounting for some methodological issues, the associative deficit of older adults is evident in short-term/working memory.

  6. Exercise Counteracts Aging-Related Memory Impairment: A Potential Role for the Astrocytic Metabolic Shuttle

    PubMed Central

    Tsai, Sheng-Feng; Chen, Pei-Chun; Calkins, Marcus J.; Wu, Shih-Ying; Kuo, Yu-Min

    2016-01-01

    Age-related cognitive impairment has become one of the most common health threats in many countries. The biological substrate of cognition is the interconnection of neurons to form complex information processing networks. Experience-based alterations in the activities of these information processing networks lead to neuroadaptation, which is physically represented at the cellular level as synaptic plasticity. Although synaptic plasticity is known to be affected by aging, the underlying molecular mechanisms are not well described. Astrocytes, a glial cell type that is infrequently investigated in cognitive science, have emerged as energy suppliers which are necessary for meeting the abundant energy demand resulting from glutamatergic synaptic activity. Moreover, the concerted action of an astrocyte-neuron metabolic shuttle is essential for cognitive function; whereas, energetic incoordination between astrocytes and neurons may contribute to cognitive impairment. Whether altered function of the astrocyte-neuron metabolic shuttle links aging to reduced synaptic plasticity is unexplored. However, accumulated evidence documents significant beneficial effects of long-term, regular exercise on cognition and synaptic plasticity. Furthermore, exercise increases the effectiveness of astrocyte-neuron metabolic shuttle by upregulation of astrocytic lactate transporter levels. This review summarizes previous findings related to the neuronal activity-dependent astrocyte-neuron metabolic shuttle. Moreover, we discuss how aging and exercise may shape the astrocyte-neuron metabolic shuttle in cognition-associated brain areas. PMID:27047373

  7. Treatment of age-related memory complaints with Ginkgo biloba extract: a randomized double blind placebo-controlled study.

    PubMed

    Brautigam, M R; Blommaert, F A; Verleye, G; Castermans, J; Jansen Steur, E N; Kleijnen, J

    1998-12-01

    A growing number of people is subject to age-related cognitive impairment due to the proportional increase of the ageing population. Therefore, there is a growing interest in cognition-enhancing substances. The efficacy of an alcohol/water extract of Ginkgo biloba in elderly individuals with memory- and/or concentration complaints was tested in a randomized, double-blind, placebo-controlled study by using both subjective and objective parameters. After a wash-out period of 4 weeks 241 non-institutionalised patients in the age range 55-86 years were randomly allocated to receive either Ginkgo biloba alcohol/water extract in a high dose (HD), a low dose (LD) or a placebo (PL) for 24 weeks. Patients were assessed using a psychometric testbattery in the following order: Expended Mental Control Test (EMCT) measuring attention and concentration, Benton Test of Visual Retention-Revised (measures short term visual memory), Rey Test part 1 (measures short term memory and learning curve), Beck Depressive Inventory (BDI) measuring the presence and severeness of a depression in order to exclude depressive patients and Rey Test part 2 (measures long term memory: recognition). Furthermore, subjective perception of memory and concentration was measured. 197 patients completed the study (mean MMSE score: 26.29). In the subjective test, the EMCT, the Rey 1 and Rey 2 no significant differences in improvement in time between the groups were observed. In the Benton test increases of 18%, 26% and 11% (expressed as percentage of baseline scores) were observed in the HD, LD and PL respectively (MANOVA; p = 0.0076). No substantial correlation was observed between subjective perception of the severeness of memory complaints and the objective test results. No differences in the number of (gastrointestinal) side effects were observed between placebo and verum groups. These results indicate that the use of Ginkgo extracts in elderly individuals with cognitive impairment might be promising

  8. CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats

    PubMed Central

    Yu, Xiao-Wen; Curlik, Daniel M; Oh, M Matthew; Yin, Jerry CP; Disterhoft, John F

    2017-01-01

    The molecular mechanisms underlying age-related cognitive deficits are not yet fully elucidated. In aged animals, a decrease in the intrinsic excitability of CA1 pyramidal neurons is believed to contribute to age-related cognitive impairments. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents facilitates cognition, and increases intrinsic excitability. However, it has yet to be tested if increasing CREB expression also ameliorates age-related behavioral and biophysical deficits. To test this hypothesis, we virally overexpressed CREB in CA1 of dorsal hippocampus. Rats received CREB or control virus, before undergoing water maze training. CREB overexpression in aged animals ameliorated the long-term memory deficits observed in control animals. Concurrently, cells overexpressing CREB in aged animals had reduced post-burst afterhyperpolarizations, indicative of increased intrinsic excitability. These results identify CREB modulation as a potential therapy to treat age-related cognitive decline. DOI: http://dx.doi.org/10.7554/eLife.19358.001 PMID:28051768

  9. Sleep Restores Daytime Deficits in Procedural Memory in Children with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Prehn-Kristensen, Alexander; Molzow, Ina; Munz, Manuel; Wilhelm, Ines; Muller, Kathrin; Freytag, Damaris; Wiesner, Christian D.; Baving, Lioba

    2011-01-01

    Sleep supports the consolidation of declarative and procedural memory. While prefrontal cortex (PFC) activity supports the consolidation of declarative memory during sleep, opposite effects of PFC activity are reported with respect to the consolidation of procedural memory during sleep. Patients with attention-deficit/hyperactivity disorder (ADHD)…

  10. Pupillary responses and memory-guided visual search reveal age-related and Alzheimer's-related memory decline.

    PubMed

    Dragan, Michelle C; Leonard, Timothy K; Lozano, Andres M; McAndrews, Mary Pat; Ng, Karen; Ryan, Jennifer D; Tang-Wai, David F; Wynn, Jordana S; Hoffman, Kari L

    2017-03-30

    Episodic memory - composed of memory for unique spatiotemporal experiences - is known to decline with aging, and even more severely in Alzheimer 's disease (AD). Memory for trial-unique objects in spatial scenes depends on the integrity of the hippocampus and interconnected structures that are among the first areas affected in AD. We reasoned that memory for objects-in-scenes would be impaired with aging, and that further impairments would be observed in AD. We asked younger adults, healthy older adults, older adults at-risk for developing cognitive impairments, and older adults with probable early AD to find changing items ('targets') within images of natural scenes, measuring repeated-trial changes in search efficiency and pupil diameter. Compared to younger adults, older adults took longer to detect target objects in repeated scenes, they required more fixations and those fixations were more dispersed. Whereas individuals with AD showed some benefit of memory in this task, they had substantially longer detection times, and more numerous, dispersed fixations on repeated scenes compared to age-matched older adults. Correspondingly, pupillary responses to novel and repeated scenes were diminished with aging and further in AD, and the memory-related changes were weaker with aging and absent in AD. Our results suggest that several nonverbal measures from memory-guided visual search tasks can index aging and Alzheimer's disease status, including pupillary dynamics. The task measurements are sensitive to the integrity of brain structures that are associated with Alzheimer's-related neurodegeneration, the task is well tolerated across a range of abilities, and thus, it may prove useful in early diagnostics and longitudinal tracking of memory decline.

  11. Age-related differences in the neural basis of the subjective vividness of memories: evidence from multivoxel pattern classification.

    PubMed

    Johnson, Marcia K; Kuhl, Brice A; Mitchell, Karen J; Ankudowich, Elizabeth; Durbin, Kelly A

    2015-09-01

    Although older adults often show reduced episodic memory accuracy, their ratings of the subjective vividness of their memories often equal or even exceed those of young adults. Such findings suggest that young and older adults may differentially access and/or weight different kinds of information in making vividness judgments. We examined this idea using multivoxel pattern classification of fMRI data to measure category representations while participants saw and remembered pictures of objects and scenes. Consistent with our hypothesis, there were age-related differences in how category representations related to the subjective sense of vividness. During remembering, older adults' vividness ratings were more related, relative to young adults', to category representations in prefrontal cortex. In contrast, young adults' vividness ratings were more related, relative to older adults, to category representations in parietal cortex. In addition, category representations were more correlated among posterior regions in young than in older adults, whereas correlations between PFC and posterior regions did not differ between the 2 groups. Together, these results are consistent with the idea that young and older adults differentially weight different types of information in assessing subjective vividness of their memories.

  12. Age-related alterations of the CD19 complex and memory B cells in children with Down syndrome.

    PubMed

    Seckin, Ayse Nazli; Ozdemir, Hulya; Ceylan, Ayca; Artac, Hasibe

    2017-02-14

    Children with Down syndrome (DS) have a high incidence of recurrent respiratory tract infections, leukaemia and autoimmune disorders, suggesting immune dysfunction. The present study evaluated the role of the CD19 complex and memory B cells in the pathogenesis of immunodeficiency in children with DS. The expression levels (median fluorescein intensity-MFI) of CD19, CD21 and CD81 molecules on the surface of B cells and memory B cell subsets were studied in 37 patients and 39 healthy controls. Twenty-nine of the DS group had congenital cardiac disease. The B cell count was significantly low in children with DS compared with healthy age-matched controls for all three age groups (under 2 years; 2-6 years and older than 6 years). The MFI of CD19 was reduced in all the age groups, whereas that of CD21 was increased in those older than 2 years with DS. The expression level of CD81 was significantly increased in those older than 6 years. Age-related changes were also detected in memory B cell subsets. The frequency of CD27(+)IgD(+)IgM(+) natural effector B cells was reduced in children with DS who had needed hospitalisation admission due to infections. The observed intrinsic defects in B cells may be responsible for the increased susceptibility of children with DS to severe respiratory tract infections.

  13. Emotional memory deficit and its psychophysiological correlate in family caregivers of patients with dementia.

    PubMed

    Palma, Kayla Araújo Ximenes Aguiar; Balardin, Joana Bisol; Vedana, Gustavo; de Lima Argimon, Irani Iracema; Luz, Clarice; Schröder, Nadja; Quevedo, João; Bromberg, Elke

    2011-01-01

    This study examined the cortisol secretion pattern and declarative memory performance of dementia caregivers. An illustrated story paradigm memory task was used to evaluate the effects of emotional arousal on memory and assess the caregivers' cognitive compensation capacity. Younger (n=19) and elderly (n=24) noncaregivers and elderly caregivers (n=14) took part in 2 experiments to elucidate the effects of aging (experiment 1) and chronic stress (experiment 2) on memory performance and cortisol levels. Each group was divided in 2 subgroups: one that was exposed to an emotionally neutral story, and one that was exposed to a similar, but emotionally arousing story. Participants completed a multiple-choice questionnaire in the test session. Salivary cortisol samples were collected at 8:00 AM, 4:00 PM, and 10:00 PM, 1 day after memory testing. Experiment 1 showed that, despite an age-related memory deficit, arousal manipulation produced a similar effect in both age groups. Experiment 2 showed that, in addition to the characteristic memory decline of aging, elderly caregivers did not benefit from emotionally arousing material as their noncaregiver counterparts did. This impairment correlated with elevated nighttime cortisol levels, indicating a potential worsening impact of caregiver burden on age-related cognitive decline.

  14. Age-independent and age-related deficits in visuospatial learning, sleep-wake states, thermoregulation and motor activity in PDAPP mice.

    PubMed

    Huitrón-Reséndiz, Salvador; Sánchez-Alavez, Manuel; Gallegos, Roger; Berg, Greta; Crawford, Elena; Giacchino, Jeannie L; Games, Dora; Henriksen, Steven J; Criado, José R

    2002-02-22

    Recent studies demonstrated that mice overexpressing the human mutant beta-amyloid precursor protein (hbetaAPP; PDAPP mice) show age-independent and age-related deficits in spatial learning. We used behavioral and electrophysiological techniques to determine in young and aged PDAPP mice whether deficits in spatial learning also involve alterations in sleep-wake states, thermoregulation and motor activity. Consistent with earlier studies, young PDAPP mice exhibited selective age-independent deficits using spatial, but not random and serial strategies in the circular maze. Aged PDAPP mice exhibited deficits using all search strategies. The core body temperature (Tb) in young and aged PDAPP mice was significantly lower than in age-matched non-transgenic (non-Tg) littermates. During the dark period, the motor activity (LMA) was significantly increased in young PDAPP mice, but not in aged PDAPP mice. During the light period, young PDAPP mice showed a reduction in the generation of rapid-eye-movement (REM) sleep. In contrast, aged PDAPP mice exhibited a reduction in the amount of time spent in W and an increase in SWS during the light period. Aged PDAPP mice also showed an increase in the amount of time spent in W and a reduction in REM sleep during the dark period. Our findings support previous reports indicating deficits in spatial learning in young and aged PDAPP mice. These data also suggest that PDAPP mice exhibit age-independent and age-related deficits in neural mechanisms regulating visuospatial learning, the total amount and the circadian distribution of sleep-wake states, thermoregulation and motor activity.

  15. Age-related changes in brain activity are specific for high order cognitive processes during successful encoding of information in working memory.

    PubMed

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

    2015-01-01

    Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM.

  16. Age-related changes in brain activity are specific for high order cognitive processes during successful encoding of information in working memory

    PubMed Central

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

    2015-01-01

    Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM. PMID

  17. Encoding, Memory, and Transcoding Deficits in Childhood Apraxia of Speech

    ERIC Educational Resources Information Center

    Shriberg, Lawrence D.; Lohmeier, Heather L.; Strand, Edythe A.; Jakielski, Kathy J.

    2012-01-01

    A central question in Childhood Apraxia of Speech (CAS) is whether the core phenotype is limited to transcoding (planning/programming) deficits or if speakers with CAS also have deficits in auditory-perceptual "encoding" (representational) and/or "memory" (storage and retrieval of representations) processes. We addressed this and other questions…

  18. Age-related differences in affective responses to and memory for emotions conveyed by music: a cross-sectional study

    PubMed Central

    Vieillard, Sandrine; Gilet, Anne-Laure

    2013-01-01

    There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplored the question of how aging may influence emotional responses to and memory for emotions conveyed by music. In the present study, eighteen older (60–84 years) and eighteen younger (19–24 years) listeners were asked to evaluate the strength of their experienced emotion on happy, peaceful, sad, and scary musical excerpts (Vieillard et al., 2008) while facial muscle activity was recorded. Participants then performed an incidental recognition task followed by a task in which they judged to what extent they experienced happiness, peacefulness, sadness, and fear when listening to music. Compared to younger adults, older adults (a) reported a stronger emotional reactivity for happiness than other emotion categories, (b) showed an increased zygomatic activity for scary stimuli, (c) were more likely to falsely recognize happy music, and (d) showed a decrease in their responsiveness to sad and scary music. These results are in line with previous findings and extend them to emotion experience and memory recognition, corroborating the view of age-related changes in emotional responses to music in a positive direction away from negativity. PMID:24137141

  19. Loss of CB1 receptors leads to differential age-related changes in reward-driven learning and memory

    PubMed Central

    Albayram, Onder; Bilkei-Gorzo, Andras; Zimmer, Andreas

    2012-01-01

    Previous studies have shown that cannabinoid 1 (CB1) receptor signaling dissociates between reward-associated and aversive memories. The influence of CB1 receptors on the aversion-driven spatial learning in the Morris water maze test is strongly age-dependent: mice with genetic deletion of CB1 receptors (Cnr1−/−) show superior learning when young but inferior learning when old compared to age-matched wild-type mice. Whether the reward-driven spatial learning is influenced in the same way by CB1 receptor signaling as the aversion-driven learning remains unclear. Thus, we examined the performance of Cn1−/− and their wild-type littermates at ages of 2-, 5-, and 12-months-old in the eight-arm radial maze test—a reward-motivated model of spatial learning. Interestingly, 2-months-old Cnr1−/− mice had a superior learning ability to wild-type mice. At the age of 5-months, Cnr1−/− mice showed the same performance as the wild-type littermates. However, 12-months-old Cnr1−/− mice showed significantly impaired performances in each parameter of the test. Accordingly, this study provides compelling support for our previous result that genetic deletion of CB1 receptor leads to early onset of age-related memory decline, similarly affecting both reward and aversion-driven learning. PMID:23227007

  20. Age-related differences in affective responses to and memory for emotions conveyed by music: a cross-sectional study.

    PubMed

    Vieillard, Sandrine; Gilet, Anne-Laure

    2013-01-01

    There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplored the question of how aging may influence emotional responses to and memory for emotions conveyed by music. In the present study, eighteen older (60-84 years) and eighteen younger (19-24 years) listeners were asked to evaluate the strength of their experienced emotion on happy, peaceful, sad, and scary musical excerpts (Vieillard et al., 2008) while facial muscle activity was recorded. Participants then performed an incidental recognition task followed by a task in which they judged to what extent they experienced happiness, peacefulness, sadness, and fear when listening to music. Compared to younger adults, older adults (a) reported a stronger emotional reactivity for happiness than other emotion categories, (b) showed an increased zygomatic activity for scary stimuli, (c) were more likely to falsely recognize happy music, and (d) showed a decrease in their responsiveness to sad and scary music. These results are in line with previous findings and extend them to emotion experience and memory recognition, corroborating the view of age-related changes in emotional responses to music in a positive direction away from negativity.

  1. Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits.

    PubMed

    Joseph, J A; Shukitt-Hale, B; Denisova, N A; Prior, R L; Cao, G; Martin, A; Taglialatela, G; Bickford, P C

    1998-10-01

    Recent research has indicated that increased vulnerability to oxidative stress may be the major factor involved in CNS functional declines in aging and age-related neurodegenerative diseases, and that antioxidants, e.g., vitamin E, may ameliorate or prevent these declines. Present studies examined whether long-term feeding of Fischer 344 rats, beginning when the rats were 6 months of age and continuing for 8 months, with diets supplemented with a fruit or vegetable extract identified as being high in antioxidant activity, could prevent the age-related induction of receptor-mediated signal transduction deficits that might have a behavioral component. Thus, the following parameters were examined: (1) oxotremorine-enhanced striatal dopamine release (OX-K+-ERDA), (2) cerebellar beta receptor augmentation of GABA responding, (3) striatal synaptosomal 45Ca2+ clearance, (4) carbachol-stimulated GTPase activity, and (5) Morris water maze performance. The rats were given control diets or those supplemented with strawberry extracts (SE), 9.5 gm/kg dried aqueous extract (DAE), spinach (SPN 6.4 gm/kg DAE), or vitamin E (500 IU/kg). Results indicated that SPN-fed rats demonstrated the greatest retardation of age-effects on all parameters except GTPase activity, on which SE had the greatest effect, whereas SE and vitamin E showed significant but equal protection against these age-induced deficits on the other parameters. For example, OX-K+-ERDA enhancement was four times greater in the SPN group than in controls. Thus, phytochemicals present in antioxidant-rich foods such as spinach may be beneficial in retarding functional age-related CNS and cognitive behavioral deficits and, perhaps, may have some benefit in neurodegenerative disease.

  2. Motherhood mitigates aging-related decrements in learning and memory and positively affects brain aging in the rat.

    PubMed

    Gatewood, Jessica D; Morgan, Melissa D; Eaton, Mollie; McNamara, Ilan M; Stevens, Lillian F; Macbeth, Abbe H; Meyer, Elizabeth A A; Lomas, Lisa M; Kozub, Frederick J; Lambert, Kelly G; Kinsley, Craig Howard

    2005-07-30

    The current work examined spatial learning and memory (i.e., latencies to find a baited food well) in age-matched nulliparous, primiparous and multiparous (NULL, PRIM and MULT, zero, one or two pregnancies and lactations, respectively). We tested at 6, 12, 18 and 24 months of age in a dry land version of the Morris water maze (Main task), and at 12, 18 and 24 months in the same task in which the original location of the baited well was changed (Reversal task). We show that PRIM/MULT rats, compared to the age-matched NULL females, learned the spatial tasks significantly better and exhibited attenuated memory decline, up to 24 months of age. Furthermore, at the conclusion of behavioral testing, we investigated levels of these animals' hippocampal (CA1 and dentate gyrus) immunoreactive amyloid precursor protein (APP), a marker of neurodegeneration and age-related cognitive loss. MULTs had significantly reduced APP in both CA1 and DG, relative to PRIMs and NULLs, and PRIMs had a trend (p<0.06) toward a reduction in APP compared to NULLs in DG. Further, level of APP was negatively correlated with performance in the two tasks (viz., more APP, worse maze performance). Reproduction, therefore, with its attendant natural endocrine and postpartum sensory experiences, may facilitate lifelong learning and memory, and may mitigate markers of neural aging, in the rat. Combining natural hormonal exposure with subsequent substantial experience with stimuli from the offspring may preserve the aged parous female brain relative to that of NULL females.

  3. Age-related deficit in behavioural extinction is counteracted by long-term ethanol consumption: correlation between 5-HIAA/5HT ratio in dorsal raphe nucleus and cognitive parameters.

    PubMed

    Oliveira-Silva, Ieda F; Pinto, Lucas; Pereira, Silvia R C; Ferraz, Vany P; Barbosa, Alfredo J A; Coelho, Vivian A A; Gualberto, Felipe F A S; Souza, Valeria F; Faleiro, Rosiane R M; Franco, Glaura C; Ribeiro, Angela M

    2007-06-18

    We investigated age-related changes in learning and memory performance and behavioural extinction in the water maze; and in endogenous levels of serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the neocortex, hippocampus, thalamus and dorsal raphe nucleus of Wistar rats. Another aim was to assess the correlation between behavioural and biochemical parameters, which were measured in rodents of two different ages: 5 months (adults) and 16 months (middle-aged). The middle-aged subjects succeeded in learning the behavioural task, albeit with significantly worse performance when compared to adult animals. Aging also had significant main effects on memory and extinction. An age-dependent decrease in 5-HIAA levels was observed in both hippocampus and dorsal raphe nucleus (DRN). The decrease in DRN 5-HIAA was paralleled by a decrease in 5-HIAA/5-HT ratio in this brain area, which was significantly correlated to the animals' spatial memory performance and behavioural extinction. In addition, using middle-aged rats, a 2x2 factorial study was carried out to examine the effects of food restriction and chronic ethanol consumption on rat's performance in a spatial behavioural task and on central serotonergic parameters. None of these two treatments had a significant effect on the behavioural and biochemical parameters assessed, with the exception of extinction index, which was significantly affected by ethanol consumption. Long-term ethanol ameliorated the impairment in behavioural flexibility caused by aging. In conclusion, long-term ethanol consumption may have a role in protecting against age-related deficit in behavioural extinction. Moreover, the present results also indicate that DRN serotonergic system is involved in spatial memory and behavioural extinction.

  4. Age-Related Declines in General Cognitive Abilities of Balb/C Mice and General Activity Are Associated with Disparities in Working Memory, Body Weight, and General Activity

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan

    2008-01-01

    A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…

  5. The Impact of Visual Memory Deficits on Academic Achievement in Children and Adolescents

    ERIC Educational Resources Information Center

    Larsen, Jessica Maria

    2011-01-01

    Memory assessment can often alert practitioners and educators to learning problems children may be experiencing. Results of a memory assessment may indicate that a child has a specific memory deficit in verbal memory, visual memory, or both. Deficits in visual or verbal modes of memory could potentially have adverse effects on academic…

  6. Glucocorticoid therapy-induced memory deficits: acute versus chronic effects.

    PubMed

    Coluccia, Daniel; Wolf, Oliver T; Kollias, Spyros; Roozendaal, Benno; Forster, Adrian; de Quervain, Dominique J-F

    2008-03-26

    Conditions with chronically elevated glucocorticoid levels are usually associated with declarative memory deficits. Considerable evidence suggests that long-term glucocorticoid exposure may cause cognitive impairment via cumulative and long-lasting influences on hippocampal function and morphology. However, because elevated glucocorticoid levels at the time of retention testing are also known to have direct impairing effects on memory retrieval, it is possible that such acute hormonal influences on retrieval processes contribute to the memory deficits found with chronic glucocorticoid exposure. To investigate this issue, we examined memory functions and hippocampal volume in 24 patients with rheumatoid arthritis who were treated either chronically (5.3 +/- 1.0 years, mean +/- SE) with low to moderate doses of prednisone (7.5 +/- 0.8 mg, mean +/- SE) or without glucocorticoids. In both groups, delayed recall of words learned 24 h earlier was assessed under conditions of either elevated or basal glucocorticoid levels in a double-blind, placebo-controlled crossover design. Although the findings in this patient population did not provide evidence for harmful effects of a history of chronic prednisone treatment on memory performance or hippocampal volume per se, acute prednisone administration 1 h before retention testing to either the steroid or nonsteroid group impaired word recall. Thus, these findings indicate that memory deficits observed under chronically elevated glucocorticoid levels result, at least in part, from acute and reversible glucocorticoid effects on memory retrieval.

  7. Working memory deficit in children with mathematical difficulties: a general or specific deficit?

    PubMed

    Andersson, Ulf; Lyxell, Björn

    2007-03-01

    This study examined whether children with mathematical difficulties (MDs) or comorbid mathematical and reading difficulties have a working memory deficit and whether the hypothesized working memory deficit includes the whole working memory system or only specific components. In the study, 31 10-year-olds with MDs and 37 10-year-olds with both mathematical and reading difficulties were compared with 47 age-matched and 50 younger controls (9-year-olds) on a number of working memory tasks. Compared with the age-matched controls, both groups of children with MDs performed worse on tasks tapping the central executive (e.g., visual matrix span) and the phonological loop (e.g., word span). More important, the MD group performed worse than the younger controls on the counting span task, whereas the group with comorbid mathematical and reading difficulties performed worse on the counting span task and the visual matrix span task. These findings provide support for the assumption that children with MDs have a working memory deficit. More specifically, children with MDs have a central executive deficit connected to concurrent processing and storage of numerical and visual information.

  8. Memory Inhibition, Aging, and the Executive Deficit Hypothesis

    ERIC Educational Resources Information Center

    Ortega, Almudena; Gomez-Ariza, Carlos J.; Roman, Patricia; Bajo, M. Teresa

    2012-01-01

    Although memory inhibition seems to underlie retrieval-induced forgetting (RIF), there is some controversy about the precise nature of this effect. Because normal RIF is observed in people with deficits in executive control (i.e., older adults), some have proposed that an automatic-like inhibitory process is responsible for the effect. On the…

  9. Impact of Education on Memory Deficits in Subclinical Depression

    PubMed Central

    McLaren, Molly E.; Szymkowicz, Sarah M.; Kirton, Joshua W.; Dotson, Vonetta M.

    2015-01-01

    Elevated depressive symptoms are associated with cognitive deficits, while higher education protects against cognitive decline. This study was conducted to test if education level moderates the relationship between depressive symptoms and cognitive function. Seventy-three healthy, dementia-free adults aged 18–81 completed neuropsychological tests, as well as depression and anxiety questionnaires. Controlling for age, sex, and state anxiety, we found a significant interaction of depressive symptoms and education for immediate and delayed verbal memory, such that those with a higher education level performed well regardless of depressive symptomatology, whereas those with lower education and high depressive symptoms had worse performance. No effects were found for executive functioning or processing speed. Results suggest that education protects against verbal memory deficits in individuals with elevated depressive symptoms. Further research on cognitive reserve in depression-related cognitive deficits and decline is needed to understand the mechanisms behind this phenomenon. PMID:26109434

  10. Impact of Education on Memory Deficits in Subclinical Depression.

    PubMed

    McLaren, Molly E; Szymkowicz, Sarah M; Kirton, Joshua W; Dotson, Vonetta M

    2015-08-01

    Elevated depressive symptoms are associated with cognitive deficits, while higher education protects against cognitive decline. This study was conducted to test if education level moderates the relationship between depressive symptoms and cognitive function. Seventy-three healthy, dementia-free adults aged 18-81 completed neuropsychological tests, as well as depression and anxiety questionnaires. Controlling for age, sex, and state anxiety, we found a significant interaction of depressive symptoms and education for immediate and delayed verbal memory, such that those with a higher education level performed well regardless of depressive symptomatology, whereas those with lower education and high depressive symptoms had worse performance. No effects were found for executive functioning or processing speed. Results suggest that education protects against verbal memory deficits in individuals with elevated depressive symptoms. Further research on cognitive reserve in depression-related cognitive deficits and decline is needed to understand the mechanisms behind this phenomenon.

  11. The neuroscience of positive memory deficits in depression

    PubMed Central

    Dillon, Daniel G.

    2015-01-01

    Adults with unipolar depression typically show poor episodic memory for positive material, but the neuroscientific mechanisms responsible for this deficit have not been characterized. I suggest a simple hypothesis: weak memory for positive material in depression reflects disrupted communication between the mesolimbic dopamine pathway and medial temporal lobe (MTL) memory systems during encoding. This proposal draws on basic research showing that dopamine release in the hippocampus is critical for the transition from early- to late-phase long-term potentiation (LTP) that marks the conversion of labile, short-term memories into stable, long-term memories. Neuroimaging and pharmacological data from healthy humans paint a similar picture: activation of the mesolimbic reward circuit enhances encoding and boosts retention. Unipolar depression is characterized by anhedonia–loss of pleasure–and reward circuit dysfunction, which is believed to reflect negative effects of stress on the mesolimbic dopamine pathway. Thus, I propose that the MTL is deprived of strengthening reward signals in depressed adults and memory for positive events suffers accordingly. Although other mechanisms are important, this hypothesis holds promise as an explanation for positive memory deficits in depression. PMID:26441703

  12. Age-Related Changes in Electrophysiological and Neuropsychological Indices of Working Memory, Attention Control, and Cognitive Flexibility

    PubMed Central

    Peltz, Carrie Brumback; Gratton, Gabriele; Fabiani, Monica

    2011-01-01

    Older adults exhibit great variability in their cognitive abilities, with some maintaining high levels of performance on executive control tasks and others showing significant deficits. Previous event-related potential (ERP) work has shown that some of these performance differences are correlated with persistence of the novelty/frontal P3 in older adults elicited by task-relevant events, presumably reflecting variability in the capacity to suppress orienting to unexpected but no longer novel events. In recent ERP work in young adults, we showed that the operation-span (OSPAN) task (a measure of attention control) is predictive of the ability of individuals to keep track of stimulus sequencing and to maintain running mental representations of task stimuli, as indexed by the parietally distributed P300 (or P3b). Both of these phenomena reflect aspects of frontal function (cognitive flexibility and attention control, respectively). To investigate these phenomena we sorted both younger and older adults into low- and high-working memory spans and low- and high-cognitive flexibility subgroups, and examined ERPs during an equal-probability choice reaction time task. For both age groups (a) participants with high OSPAN scores were better able to keep track of stimulus sequencing, as indicated by their smaller P3b to sequential changes; and (b) participants with lower cognitive flexibility had larger P3a than their high-scoring counterparts. However, these two phenomena did not interact suggesting that they manifest dissociable control mechanisms. Further, the fact that both effects are already visible in younger adults suggests that at least some of the brain mechanisms underlying individual differences in cognitive aging may already operate early in life. PMID:21887150

  13. Pathology associated memory deficits in Swedish mutant genome-based amyloid precursor protein transgenic mice.

    PubMed

    Hock, Brian J; Lattal, K Matthew; Kulnane, Laura Shapiro; Abel, Ted; Lamb, Bruce T

    2009-12-01

    To gain insight into the relationship between pathological alterations and memory deficits observed in Alzheimer's disease (AD), a number of amyloid precursor protein (APP) transgenic animal models have been generated containing familial AD mutations. The most commonly utilized method involves a cDNA-based approach, utilizing heterologous promoters to drive expression of specific APP isoforms. As a result of the assumptions inherent in the design of each model, the different cDNA-based transgenic mouse models have revealed different relationships between the biochemical, pathological and behavioral alterations observed in these models. Here we provide further characterization of a genomic-based, amyloid precursor protein yeast artificial chromosome transgenic mouse model of AD, R1.40, that makes few assumptions regarding disease pathogenesis to study the relationship between brain pathology and altered behavior. Aged R1.40 transgenic and control mice were tested for learning and memory in the Morris water maze and for working memory in the Y maze. Results from the water maze demonstrated intact learning in the both control and R1.40 mice, but impairments in the long-term retention of this information in the transgenic mice, but not controls. Interestingly, however, long-term memory deficits did not correlate with the presence of Abeta deposits within the group of animals examined. By contrast, age-related working memory impairments were also observed in the Y maze in the R1.40 mice, and these deficits correlated with the presence of Abeta deposits. Our results demonstrate unique behavioral alterations in the R1.40 mouse model of AD that are likely both dependent and independent of Abeta deposition.

  14. Visuospatial memory in dyslexia: evidence for strategic deficits.

    PubMed

    Bacon, Alison M; Parmentier, Fabrice B R; Barr, Polly

    2013-01-01

    Impairments in working memory are suggested to be one of the defining characteristics of dyslexia, and deficits in verbal recall are well documented. However, the situation regarding visuospatial memory is less clear. In a widely used measure, the Corsi blocks task, sequences of visuospatial locations can be recalled forwards, in the order presented (CF), or backwards, in reverse order (CB). Previous research has suggested that, while CF draws on spatial-sequential resources, CB may load executive and distinctly visual processes. While people with dyslexia typically show no deficit on CF, CB is rarely presented. We present three studies which indicate a consistent dyslexic deficit on CB that can be ameliorated by visual strategy instructions. Our data suggest that, without instruction, people with dyslexia are unable to adopt an effective CB strategy and this is consistent with a deficit in executive function. These results have implications for our understanding of visuospatial memory in dyslexia, and also in terms of the administration of the Corsi task to special populations.

  15. The Need for Standardized Assessment of Muscle Quality in Skeletal Muscle Function Deficit and Other Aging-Related Muscle Dysfunctions: A Symposium Report.

    PubMed

    Correa-de-Araujo, Rosaly; Harris-Love, Michael O; Miljkovic, Iva; Fragala, Maren S; Anthony, Brian W; Manini, Todd M

    2017-01-01

    A growing body of scientific literature suggests that not only changes in skeletal muscle mass, but also other factors underpinning muscle quality, play a role in the decline in skeletal muscle function and impaired mobility associated with aging. A symposium on muscle quality and the need for standardized assessment was held on April 28, 2016 at the International Conference on Frailty and Sarcopenia Research in Philadelphia, Pennsylvania. The purpose of this symposium was to provide a venue for basic science and clinical researchers and expert clinicians to discuss muscle quality in the context of skeletal muscle function deficit and other aging-related muscle dysfunctions. The present article provides an expanded introduction concerning the emerging definitions of muscle quality and a potential framework for scientific inquiry within the field. Changes in muscle tissue composition, based on excessive levels of inter- and intra-muscular adipose tissue and intramyocellular lipids, have been found to adversely impact metabolism and peak force generation. However, methods to easily and rapidly assess muscle tissue composition in multiple clinical settings and with minimal patient burden are needed. Diagnostic ultrasound and other assessment methods continue to be developed for characterizing muscle pathology, and enhanced sonography using sensors to provide user feedback and improve reliability is currently the subject of ongoing investigation and development. In addition, measures of relative muscle force such as specific force or grip strength adjusted for body size have been proposed as methods to assess changes in muscle quality. Furthermore, performance-based assessments of muscle power via timed tests of function and body size estimates, are associated with lower extremity muscle strength may be responsive to age-related changes in muscle quality. Future aims include reaching consensus on the definition and standardized assessments of muscle quality, and

  16. The Need for Standardized Assessment of Muscle Quality in Skeletal Muscle Function Deficit and Other Aging-Related Muscle Dysfunctions: A Symposium Report

    PubMed Central

    Correa-de-Araujo, Rosaly; Harris-Love, Michael O.; Miljkovic, Iva; Fragala, Maren S.; Anthony, Brian W.; Manini, Todd M.

    2017-01-01

    A growing body of scientific literature suggests that not only changes in skeletal muscle mass, but also other factors underpinning muscle quality, play a role in the decline in skeletal muscle function and impaired mobility associated with aging. A symposium on muscle quality and the need for standardized assessment was held on April 28, 2016 at the International Conference on Frailty and Sarcopenia Research in Philadelphia, Pennsylvania. The purpose of this symposium was to provide a venue for basic science and clinical researchers and expert clinicians to discuss muscle quality in the context of skeletal muscle function deficit and other aging-related muscle dysfunctions. The present article provides an expanded introduction concerning the emerging definitions of muscle quality and a potential framework for scientific inquiry within the field. Changes in muscle tissue composition, based on excessive levels of inter- and intra-muscular adipose tissue and intramyocellular lipids, have been found to adversely impact metabolism and peak force generation. However, methods to easily and rapidly assess muscle tissue composition in multiple clinical settings and with minimal patient burden are needed. Diagnostic ultrasound and other assessment methods continue to be developed for characterizing muscle pathology, and enhanced sonography using sensors to provide user feedback and improve reliability is currently the subject of ongoing investigation and development. In addition, measures of relative muscle force such as specific force or grip strength adjusted for body size have been proposed as methods to assess changes in muscle quality. Furthermore, performance-based assessments of muscle power via timed tests of function and body size estimates, are associated with lower extremity muscle strength may be responsive to age-related changes in muscle quality. Future aims include reaching consensus on the definition and standardized assessments of muscle quality, and

  17. Reference and working memory deficits in the 3xTg-AD mouse between 2 and 15-months of age: a cross-sectional study.

    PubMed

    Stevens, Leanne M; Brown, Richard E

    2015-02-01

    Impairments in working memory (WM) can predict the shift from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and the rate at which AD progresses with age. The 3xTg-AD mouse model develops both Aβ plaques and neurofibrillary tangles, the neuro-pathological hallmarks of AD, by 6 months of age, but no research has investigated the age-related changes in WM in these mice. Using a cross-sectional design, we tested male and female 3xTg-AD and wildtype control (B6129SF2/J) mice between 2 and 15 months of age for reference and working memory errors in the 8-arm radial maze. The 3xTg-AD mice had deficits in both working and reference memory across the ages tested, rather than showing the predicted age-related memory deficits. Male 3xTg-AD mice showed more working and reference memory errors than females, but there were no sex differences in wildtype control mice. These results indicate that the 3xTg-AD mouse replicates the impairments in WM found in patients with AD. However, these mice show memory deficits as early as two months of age, suggesting that the genes underlying reference and working memory in these mice cause deficits from an early age. The finding that males were affected more than females suggests that more attention should be paid to sex differences in transgenic AD mice.

  18. Electroencephalography Correlates of Spatial Working Memory Deficits in Attention-Deficit/Hyperactivity Disorder: Vigilance, Encoding, and Maintenance

    PubMed Central

    Delorme, Arnaud; Walshaw, Patricia D.; Cho, Alex L.; Bilder, Robert M.; McGough, James J.; McCracken, James T.; Makeig, Scott; Loo, Sandra K.

    2014-01-01

    In the current study we sought to dissociate the component processes of working memory (WM) (vigilance, encoding and maintenance) that may be differentially impaired in attention-deficit/ hyperactivity disorder (ADHD). We collected electroencephalographic (EEG) data from 52 children with ADHD and 47 typically developing (TD) children, ages 7–14 years, while they performed a spatial Sternberg working memory task. We used independent component analysis and time-frequency analysis to identify midoccipital alpha (8–12 Hz) to evaluate encoding processes and frontal midline theta (4–7 Hz) to evaluate maintenance processes. We tested for effects of task difficulty and cue processing to evaluate vigilance. Children with ADHD showed attenuated alpha band event-related desynchronization (ERD) during encoding. This effect was more pronounced when task difficulty was low (consistent with impaired vigilance) and was predictive of memory task performance and symptom severity. Correlated with alpha ERD during encoding were alpha power increases during the maintenance period (relative to baseline), suggesting a compensatory effort. Consistent with this interpretation, midfrontal theta power increases during maintenance were stronger in ADHD and in high-load memory conditions. Furthermore, children with ADHD exhibited a maturational lag in development of posterior alpha power whereas age-related changes in frontal theta power deviated from the TD pattern. Last, subjects with ADHD showed age-independent attenuation of evoked responses to warning cues, suggesting low vigilance. Combined, these three EEG measures predicted diagnosis with 70% accuracy. We conclude that the interplay of impaired vigilance and encoding in ADHD may compromise maintenance and lead to impaired WM performance in this group. PMID:24453310

  19. Electroencephalography correlates of spatial working memory deficits in attention-deficit/hyperactivity disorder: vigilance, encoding, and maintenance.

    PubMed

    Lenartowicz, Agatha; Delorme, Arnaud; Walshaw, Patricia D; Cho, Alex L; Bilder, Robert M; McGough, James J; McCracken, James T; Makeig, Scott; Loo, Sandra K

    2014-01-22

    In the current study we sought to dissociate the component processes of working memory (WM) (vigilance, encoding and maintenance) that may be differentially impaired in attention-deficit/ hyperactivity disorder (ADHD). We collected electroencephalographic (EEG) data from 52 children with ADHD and 47 typically developing (TD) children, ages 7-14 years, while they performed a spatial Sternberg working memory task. We used independent component analysis and time-frequency analysis to identify midoccipital alpha (8-12 Hz) to evaluate encoding processes and frontal midline theta (4-7 Hz) to evaluate maintenance processes. We tested for effects of task difficulty and cue processing to evaluate vigilance. Children with ADHD showed attenuated alpha band event-related desynchronization (ERD) during encoding. This effect was more pronounced when task difficulty was low (consistent with impaired vigilance) and was predictive of memory task performance and symptom severity. Correlated with alpha ERD during encoding were alpha power increases during the maintenance period (relative to baseline), suggesting a compensatory effort. Consistent with this interpretation, midfrontal theta power increases during maintenance were stronger in ADHD and in high-load memory conditions. Furthermore, children with ADHD exhibited a maturational lag in development of posterior alpha power whereas age-related changes in frontal theta power deviated from the TD pattern. Last, subjects with ADHD showed age-independent attenuation of evoked responses to warning cues, suggesting low vigilance. Combined, these three EEG measures predicted diagnosis with 70% accuracy. We conclude that the interplay of impaired vigilance and encoding in ADHD may compromise maintenance and lead to impaired WM performance in this group.

  20. Common Cognitive Deficits in Children with Attention-Deficit/Hyperactivity Disorder and Autism: Working Memory and Visual-Motor Integration

    ERIC Educational Resources Information Center

    Englund, Julia A.; Decker, Scott L.; Allen, Ryan A.; Roberts, Alycia M.

    2014-01-01

    Cognitive deficits in working memory (WM) are characteristic features of Attention-Deficit/Hyperactivity Disorder (ADHD) and autism. However, few studies have investigated cognitive deficits using a wide range of cognitive measures. We compared children with ADHD ("n" = 49) and autism ("n" = 33) with a demographically matched…

  1. Memory Loss, Dementia, and Stroke: Implications for Rehabilitation of Older Adults with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Warren, Mary

    2008-01-01

    Older adults with age-related macular degeneration (AMD) are not immune to the other diseases of aging. Although AMD is the leading cause of low vision in older Americans, stroke is the leading cause of disability, and dementias affect another 2.5 million older Americans. Each condition alone can significantly impair a person's ability to…

  2. Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis

    PubMed Central

    Baehr, Leslie M.; West, Daniel W.D.; Marcotte, George; Marshall, Andrea G.; De Sousa, Luis Gustavo; Baar, Keith; Bodine, Sue C.

    2016-01-01

    Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength. PMID:26826670

  3. Age-Related Visual and Kinesthetic Encoding Effects on Spatial Memory of a Maze-Like Floor Plan.

    ERIC Educational Resources Information Center

    Sinnott, Jan D.; And Others

    As part of an experimental research program on lifespan naturalistic and laboratory memory for spatial representation, investigators examined interactions between the effects of visual and kinesthetic encoding and age on memory for space using a modification of the Sinnott (1987) human maze paradigm. It was hypothesized that an age effect favoring…

  4. Age-Related Effects on Memory for Social Stimuli: The Role of Valence, Arousal, and Emotional Responses.

    PubMed

    Hess, Thomas M; Popham, Lauren E; Growney, Claire M

    2017-01-01

    Background/Study Context: Previous research (Hess et al., 2013, Psychology and Aging, 28, 853-863) suggested that age-based positivity effects in memory were attenuated with social stimuli. This research examined the degree to which this generalized across arousal levels associated with social images. Variations in approach and avoidance responses to individual images were also examined, along with age differences in their relationship to memory performance.

  5. Memory deficits associated with khat (Catha edulis) use in rodents.

    PubMed

    Kimani, S T; Patel, N B; Kioy, P G

    2016-02-01

    Khat products and chewing practices are common in East Africa, Middle East for centuries with concomitant socio-economic and public health repercussions. We assessed memory deficits associated with khat use in rodents. Young male CBA mice, 5-7 weeks old (n = 20), weighing 25-35 g were used. Mice were treated with either 40, 120 or 360 mg/kg body weight (bw) methanolic khat extract, or 0.5 ml saline for 10 days. Spatial acquisition, reversal and reference memory were assessed using modified Morris Water maze (MMWM). Mice treated with 40 mg/kg khat extract had longer (t4 = 4.12 p = 0.015) and t4 = 2.28 p = 0.065) escape latency on first and second day during reversal relative to the baseline. Under 120 mg/kg khat dose, the escape latency was shorter (t4 = -2.49 p = 0.05) vs (t3 = -2.5 p = 0.05) on third and fourth day. Further, treatment with 360 mg/kg khat extract resulted in significantly longer time (49.13, 33.5, 40.2 and 35.75) vs. (23.5 s), compared to baseline. Mice treated with khat or control preferred the target quadrant post acquisition while differential pattern was seen during reversal phase. Mice treated with 40 or 120 mg/kg khat showed significant preference for target quadrant. Substantial time (19.9) was spent in the old target compared to the new (16.9 s) by animals treated with highest dose however, the difference was not significant. There is a biological plausibility that chronic khat use may induce memory deficits and impair cognitive flexibility. The differential patterns of memory deficits may reflect the differences in dose effect as well as time dependent impairment.

  6. Memory deficit in patients with schizophrenia and posttraumatic stress disorder: relational vs item-specific memory

    PubMed Central

    Jung, Wookyoung; Lee, Seung-Hwan

    2016-01-01

    It has been well established that patients with schizophrenia have impairments in cognitive functioning and also that patients who experienced traumatic events suffer from cognitive deficits. Of the cognitive deficits revealed in schizophrenia or posttraumatic stress disorder (PTSD) patients, the current article provides a brief review of deficit in episodic memory, which is highly predictive of patients’ quality of life and global functioning. In particular, we have focused on studies that compared relational and item-specific memory performance in schizophrenia and PTSD, because measures of relational and item-specific memory are considered the most promising constructs for immediate tangible development of clinical trial paradigm. The behavioral findings of schizophrenia are based on the tasks developed by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative and the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) Consortium. The findings we reviewed consistently showed that schizophrenia and PTSD are closely associated with more severe impairments in relational memory compared to item-specific memory. Candidate brain regions involved in relational memory impairment in schizophrenia and PTSD are also discussed. PMID:27274250

  7. Memory tests in subgroups of adult attention deficit hyperactivity disorder reveals simultaneous capacity deficit.

    PubMed

    Dige, Niels; Maahr, Eija; Backenroth-Ohsako, Gunnel

    2008-04-01

    Neuropsychological tests were used to evaluate different memory systems in the three subgroups of adult Attention Deficit Hyperactivity Disorder (ADHD) (n=105) using analysis of means, factor analysis, and GLM analysis with covariance of gender, estimated IQ, and level of anxiety and depression measured with the Hospital anxiety and depression scale. A higher IQ level was found in the neuropsychological background tests for the predominantly inattentive subtype (ADD). In the memory tests the dual-task memory/simultaneous capacity tests "Brown-Peterson" Consonant Trigram and Benton Visual Retention Test (BVRT) were the most sensitive and were severely reduced in all three subgroups, but only the BVRT revealed a difference between the three ADHD groups. In learning and delayed recall measured with Rey Auditory Verbal learning test and modified Diagnosticum für Cerebralschädigung (mDCS), the Attention Deficit Disorder subgroup had the best learning and delayed capacity of the three groups. A good agreement was found between the interviewed DSM-IV-TR criteria, Conners CAARS S:S scale, and Wender WURS 25-item scales. Despite the difference in number of ADHD criteria for the three ADHD subgroups, the results in the neuropsychological memory tests indicate a severe reduction in all three subgroups of adult ADHD in simultaneous capacity.

  8. Memory Deficit Recovery after Chronic Vanadium Exposure in Mice.

    PubMed

    Folarin, Oluwabusayo; Olopade, Funmilayo; Onwuka, Silas; Olopade, James

    2016-01-01

    Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old) were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal.

  9. The Canine Sand Maze: An Appetitive Spatial Memory Paradigm Sensitive to Age-Related Change in Dogs

    ERIC Educational Resources Information Center

    Salvin, Hannah E.; McGreevy, Paul D.; Sachdev, Perminder S.; Valenzuela, Michael J.

    2011-01-01

    Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter…

  10. Children's and Adults' Memory for Emotional Pictures: Examining Age-Related Patterns Using the Developmental Affective Photo System

    ERIC Educational Resources Information Center

    Cordon, Ingrid M.; Melinder, Annika M. D.; Goodman, Gail S.; Edelstein, Robin S.

    2013-01-01

    Two studies were conducted to examine theoretical questions about children's and adults' memory for emotional visual stimuli. In Study 1, 7- to 9-year-olds and adults (N = 172) participated in the initial creation of the Developmental Affective Photo System (DAPS). Ratings of emotional valence, arousal, and complexity were obtained. In Study 2,…

  11. 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.

  12. AGE-RELATED IMPAIRMENTS IN MEMORY AND IN CREB AND pCREB EXPRESSION IN HIPPOCAMPUS AND AMYGDALA FOLLOWING INHIBITORY AVOIDANCE TRAINING

    PubMed Central

    Morris, Ken A.; Gold, Paul E.

    2012-01-01

    This experiment examined whether age-related changes in CREB and pCREB contribute to the rapid forgetting seen in aged animals. Young (3-month-old) and aged (24-month-old) Fischer-344 rats received inhibitory avoidance training with a low (0.2 mA, 0.4 sec) or moderate (0.5 mA, 0.5 sec) footshock; memory was measured 7 days later. Other rats were euthanized 30 minutes after training, and CREB and pCREB expression levels were examined in the hippocampus, amygdala, and piriform cortex using immunohistochemistry. CREB levels decreased with age in the hippocampus and amygdala. After training with either shock level, young rats exhibited good memory and increases in pCREB levels in the hippocampus and amygdala. Aged rats exhibited good memory for the moderate but not the low shock but did not show increases in pCREB levels after either shock intensity. These results suggest that decreases in total CREB and in pCREB activation in the hippocampus and amygdala may contribute to rapid forgetting in aged rats. After moderate footshock, the stable memory in old rats together with absence of CREB activation suggests either that CREB was phosphorylated in a spatiotemporal pattern other than analyzed here or that the stronger training conditions engaged alternate mechanisms that promote long-lasting memory. PMID:22445851

  13. That's a good one! Belief in efficacy of mnemonic strategies contributes to age-related increase in associative memory.

    PubMed

    Daugherty, Ana M; Ofen, Noa

    2015-08-01

    The development of associative memory during childhood may be influenced by metacognitive factors. Here, one aspect of metamemory function--belief in strategy efficacy-was tested for a role in the effective use of encoding strategies. A sample of 61 children and adults (8-25 years of age) completed an associative recognition memory test and were assessed on belief in the efficacy of encoding strategies. Independent of age, belief ratings identified two factors: "deep" and "shallow" encoding strategies. Although the strategy factor structure was stable across age, adolescents and adults were more likely to prefer using a deep encoding strategy, whereas children were equally likely to prefer a shallow strategy. Belief ratings of deep encoding strategies increased with age and, critically, accounted for better associative recognition.

  14. Developmental Periods of Choline Sensitivity Provide an Ontogenetic Mechanism for Regulating Memory Capacity and Age-Related Dementia

    PubMed Central

    Meck, Warren H.; Williams, Christina L.; Cermak, Jennifer Marie; Blusztajn, Jan Krzysztof

    2008-01-01

    In order to determine brain and behavioral sensitivity of nutrients that may serve as inductive signals during early development, we altered choline availability to rats during 7 time frames spanning embryonic day (ED) 6 through postnatal day (PD) 75 and examined spatial memory ability in the perinatally-treated adults. Two sensitive periods were identified, ED 12–17 and PD 16–30, during which choline supplementation facilitated spatial memory and produced increases in dendritic spine density in CA1 and dentate gyrus (DG) regions of the hippocampus while also changing the dendritic fields of DG granule cells. Moreover, choline supplementation during ED 12–17 only, prevented the memory decline normally observed in aged rats. These behavioral changes were strongly correlated with the acetylcholine (ACh) content of hippocampal slices following stimulated release. Our data demonstrate that the availability of choline during critical periods of brain development influences cognitive performance in adulthood and old age, and emphasize the importance of perinatal nutrition for successful cognitive aging. PMID:18958235

  15. Allocentric spatial learning and memory deficits in Down syndrome

    PubMed Central

    Lavenex, Pamela Banta; Bostelmann, Mathilde; Brandner, Catherine; Costanzo, Floriana; Fragnière, Emilie; Klencklen, Giuliana; Lavenex, Pierre; Menghini, Deny; Vicari, Stefano

    2015-01-01

    Studies have shown that persons with Down syndrome (DS) exhibit relatively poor language capacities, and impaired verbal and visuoperceptual memory, whereas their visuospatial memory capacities appear comparatively spared. Individuals with DS recall better where an object was previously seen than what object was previously seen. However, most of the evidence concerning preserved visuospatial memory comes from tabletop or computerized experiments which are biased toward testing egocentric (viewpoint-dependent) spatial representations. Accordingly, allocentric (viewpoint-independent) spatial learning and memory capacities may not be necessary to perform these tasks. Thus, in order to more fully characterize the spatial capacities of individuals with DS, allocentric processes underlying real-world navigation must also be investigated. We tested 20 participants with DS and 16 mental age-matched, typically developing (TD) children in a real-world, allocentric spatial (AS) memory task. During local cue (LC) trials, participants had to locate three rewards marked by local color cues, among 12 locations distributed in a 4 m × 4 m arena. During AS trials, participants had to locate the same three rewards, in absence of LCs, based on their relations to distal environmental cues. All TD participants chose rewarded locations in LC and AS trials at above chance level. In contrast, although all but one of the participants with DS exhibited a preference for the rewarded locations in LC trials, only 50% of participants with DS chose the rewarded locations at above chance level in AS trials. As a group, participants with DS performed worse than TD children on all measures of task performance. These findings demonstrate that individuals with DS are impaired at using an AS representation to learn and remember discrete locations in a controlled environment, suggesting persistent and pervasive deficits in hippocampus-dependent memory in DS. PMID:25762946

  16. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    PubMed

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults' performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects.

  17. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    PubMed Central

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults’ performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects. PMID:25426064

  18. Attention and memory deficits in breast cancer survivors: implications for nursing practice and research.

    PubMed

    Frank, Jennifer Sandson; Vance, David E; Jukkala, Angela; Meneses, Karen M

    2014-10-01

    Breast cancer survivors (BCSs) commonly report deficits in attention and memory, cognitive functions crucial for daily optimal functioning. Perceived deficits are reported before, during, and after adjuvant therapy and affect quality of life throughout survivorship. Deficits of attention and memory are particularly disruptive for BCSs working or attending school who report that subtle impairment diminishes their confidence and their performance at all levels of occupation. Chemotherapy and endocrine therapy contribute to attention and memory deficits, but research findings have not fully established the extent or timing of that influence. Fortunately, potential interventions for attention and memory deficits in BCSs are promising. These include cognitive remediation therapies aimed at training for specific areas of deficit, cognitive behavioral therapies aimed at developing compensatory strategies for areas of deficit, complementary therapies, and pharmacologic therapies.

  19. Age-related changes in feature-based object memory retrieval as measured by event-related potentials

    PubMed Central

    Chiang, Hsueh-Sheng; Mudar, Raksha A.; Spence, Jeffrey S.; Pudhiyidath, Athula; Eroh, Justin; DeLaRosa, Bambi; Kraut, Michael A.; Hart, John

    2014-01-01

    To investigate neural mechanisms that support semantic functions in aging, we recorded scalp EEG during an object retrieval task in 22 younger and 22 older adults. The task required determining if a particular object could be retrieved when two visual words representing object features were presented. Both age groups had comparable accuracy although response times were longer in older adults. In both groups a left fronto-temporal negative potential occurred at around 750 msec during object retrieval, consistent with previous findings (Brier et al., 2008). Only in older adults a later positive frontal potential was found peaking between 800 and 1000 msec during no retrieval. These findings suggest younger and older adults employ comparable neural mechanisms when features clearly facilitate retrieval of an object memory, but when features yield no retrieval, older adults use additional neural resources to engage in a more effortful and exhaustive search prior to making a decision. PMID:24911552

  20. The Canine Sand Maze: an Appetitive Spatial Memory Paradigm Sensitive to Age-Related Change in Dogs

    PubMed Central

    Salvin, Hannah E; McGreevy, Paul D; Sachdev, Perminder S; Valenzuela, Michael J

    2011-01-01

    Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter circular pool was filled with a sand and powdered food reward mix to a depth of 10 cm. Dogs were given 4 habituation and 16 learning trials which alternated a food reward being half (control trials) or fully-buried (acquisition trials) in a fixed location. After a 90-min break, a probe trial was conducted. Cognitively normal, aged (> 8 years, n  =  11) and young (1–4 years, n  =  11), breed-matched dogs were compared. After correction for differences in control trials, average probe times were 2.97 and 10.81 s for young and aged dogs, respectively. In the probe trial, both groups spent significantly more time in the target quadrant but there was a trend for young dogs to cross a 1 m2 annulus zone around the buried reward more frequently (2.6 times) than aged dogs (1.5 times). Test–retest reliability in a subset of young dogs (n  =  5) was high. On the basis of these findings, the Canine Sand Maze is presented as a quick, sensitive and nonaversive tool for assessing spatial learning and reference memory in dogs. PMID:21541168

  1. Working Memory Deficits in Boys with Attention-Deficit/Hyperactivity Disorder (ADHD): The Contribution of Central Executive and Subsystem Processes

    ERIC Educational Resources Information Center

    Rapport, Mark D.; Alderson, R. Matt; Kofler, Michael J.; Sarver, Dustin E.; Bolden, Jennifer; Sims, Valerie

    2008-01-01

    The current study investigated contradictory findings from recent experimental and meta-analytic studies concerning working memory deficits in ADHD. Working memory refers to the cognitive ability to temporarily store and mentally manipulate limited amounts of information for use in guiding behavior. Phonological (verbal) and visuospatial…

  2. A flavanoid component of chocolate quickly reverses an imposed memory deficit.

    PubMed

    Knezevic, Bogdan; Komatsuzaki, Yoshimasa; de Freitas, Emily; Lukowiak, Ken

    2016-03-01

    The ability to remember is influenced by environmental and lifestyle factors, such as stress and diet. A flavanol contained in chocolate, epicatechin (Epi), has been shown to enhance long-term memory (LTM) formation in Lymnaea. Combining two stressors (low-calcium pond water and crowding) blocks learning and all forms of memory; that is, this combination of environmentally relevant stressors creates a memory-unfriendly state. We tested the hypothesis that Epi will immediately reverse the memory-unfriendly state, i.e. that snails in the memory-deficit state when trained in Epi will immediately become competent to learn and form memory. We found that Epi not only reverses the memory-deficit state but also further enhances LTM formation. Thus, a naturally occurring bioactive plant compound can overcome a memory-unfriendly state. This supports the idea that bioactive substances may mitigate memory-making deficits that, for example, occur with ageing.

  3. Acute memory deficits in chemotherapy-treated adults.

    PubMed

    Lindner, Oana C; Mayes, Andrew; McCabe, Martin G; Talmi, Deborah

    2017-03-13

    Data from research on amnesia and epilepsy are equivocal with regards to the dissociation, shown in animal models, between rapid and slow long-term memory consolidation. Cancer treatments have lasting disruptive effects on memory and on brain structures associated with memory, but their acute effects on synaptic consolidation are unknown. We investigated the hypothesis that cancer treatment selectively impairs slow synaptic consolidation. Cancer patients and their matched controls were administered a novel list-learning task modelled on the Rey Auditory Verbal Learning Test. Learning, forgetting, and retrieval were tested before, and one day after patients' first chemotherapy treatment. Due to difficulties recruiting cancer patients at that sensitive time, we were only able to study 10 patients and their matched controls. Patients exhibited treatment-dependent accelerated forgetting over 24 hours compared to their own pre-treatment performance and to the performance of control participants, in agreement with our hypothesis. The number of intrusions increased after treatment, suggesting retrieval deficits. Future research with larger samples should adapt our methods to distinguish between consolidation and retrieval causes for treatment-dependent accelerated forgetting. The presence of significant accelerated forgetting in our small sample is indicative of a potentially large acute effect of chemotherapy treatment on forgetting, with potentially clinically relevant implications.

  4. True Memory, False Memory, and Subjective Recollection Deficits after Focal Parietal Lobe Lesions

    PubMed Central

    Drowos, David B.; Berryhill, Marian; André, Jessica M.; Olson, Ingrid R.

    2010-01-01

    Objective There is mounting evidence that the posterior parietal cortex (PPC) plays an important role in episodic memory. We previously found that patients with PPC damage exhibit retrieval-related episodic memory deficits. Our objective was to assess whether parietal lobe damage affects episodic memory on a different task: the Deese-Roediger-McDermott (DRM) false-memory paradigm. Method Two patients with bilateral PPC damage and matched controls were tested. In Experiment 1, the task was to remember words; in Experiment 2 the task was to remember pictures of common objects. Prior studies have shown that normal participants have high levels of false memory to words, low levels to pictures. Results The patients exhibited significantly lower levels of false memory to words. The patients' false memories were accompanied by reduced levels of recollection, as tested by a Remember/Know procedure. It is unlikely that a failure of gist processing accounts for these results, as patients accurately remembered thematic elements of short vignettes, but failed to remember details. These results support the view that portions of the PPC play a critical role in objective and subjective aspects of recollection. PMID:20604621

  5. Inhibiting corticosterone synthesis during fear memory formation exacerbates cued fear extinction memory deficits within the single prolonged stress model.

    PubMed

    Keller, Samantha M; Schreiber, William B; Stanfield, Briana R; Knox, Dayan

    2015-01-01

    Using the single prolonged stress (SPS) animal model of post-traumatic stress disorder (PTSD), previous studies suggest that enhanced glucocorticoid receptor (GR) expression leads to cued fear extinction retention deficits. However, it is unknown how the endogenous ligand of GRs, corticosterone (CORT), may contribute to extinction retention deficits in the SPS model. Given that CORT synthesis during fear learning is critical for fear memory consolidation and SPS enhances GR expression, CORT synthesis during fear memory formation could strengthen fear memory in SPS rats by enhancing GR activation during fear learning. In turn, this could lead to cued fear extinction retention deficits. We tested the hypothesis that CORT synthesis during fear learning leads to cued fear extinction retention deficits in SPS rats by administering the CORT synthesis inhibitor metyrapone to SPS and control rats prior to fear conditioning, and observed the effect this had on extinction memory. Inhibiting CORT synthesis during fear memory formation in control rats tended to decrease cued freezing, though this effect never reached statistical significance. Contrary to our hypothesis, inhibiting CORT synthesis during fear memory formation disrupted extinction retention in SPS rats. This finding suggests that even though SPS exposure leads to cued fear extinction memory deficits, CORT synthesis during fear memory formation enhances extinction retention in SPS rats. This suggests that stress-induced CORT synthesis in previously stressed rats can be beneficial.

  6. Impaired strategic monitoring as the locus of a focal prospective memory deficit.

    PubMed

    West, Robert; McNerney, M Windy; Krauss, Iseli

    2007-04-01

    In this study we examine the locus of a prospective memory deficit in an individual with multiple sclerosis. Extensive psychometric and neuropsychological testing revealed above average to superior general intelligence, retrospective and autobiographical memory, short-term/working memory and executive functions. In contrast, the individual demonstrated poor prospective memory on a variety of measures incorporating naturalistic, self-report, and laboratory methods. This deficit appeared to arise from a disruption of processes underlying strategic monitoring. These data clearly demonstrate that impaired prospective memory can exist in the presence of an otherwise intact neuropsychological profile.

  7. Memory loss versus memory distortion: the role of encoding and retrieval deficits in Korsakoff patients' false memories.

    PubMed

    Van Damme, Ilse; d'Ydewalle, Gery

    2009-05-01

    Recent studies with the Deese/Roediger-McDermott (DRM) paradigm have revealed that Korsakoff patients show reduced levels of false recognition and different patterns of false recall compared to controls. The present experiment examined whether this could be attributed to an encoding deficit, or rather to problems with explicitly retrieving thematic information at test. In a variation on the DRM paradigm, both patients and controls were presented with associative as well as categorised word lists, with the order of recall and recognition tests manipulated between-subjects. The results point to an important role for the automatic/controlled retrieval distinction: Korsakoff patients' false memory was only diminished compared to controls' when automatic or short-term memory processes could not be used to fulfil the task at hand. Hence, the patients' explicit retrieval deficit appears to be crucial in explaining past and present data. Results are discussed in terms of fuzzy-trace and activation-monitoring theories.

  8. 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…

  9. Google Calendar: a new memory aid to compensate for prospective memory deficits following acquired brain injury.

    PubMed

    McDonald, A; Haslam, C; Yates, P; Gurr, B; Leeder, G; Sayers, A

    2011-12-01

    Prospective memory impairment is common following acquired brain injury (ABI) and intervention has proved challenging. The current treatment of choice involves using external memory aids as a method of compensation, with those incorporating active reminders proving most successful. In this paper we report findings of an investigation into the effectiveness of a novel external memory aid, Google Calendar. This aid incorporates active reminders and overcomes some of the limitations associated with existing aids. Twelve participants with ABI took part in the study incorporating a randomised control crossover within-subjects design, consisting of a 5-week baseline phase, followed by two 5-week intervention phases where either Google Calendar or a standard diary were used. Participants identified activities to target during the study and a family member monitored their success. Google Calendar was more effective than the diary in enhancing prospective memory performance. It also proved more popular, on account of its active reminders which helped trigger the retrieval of intentions, whilst reducing the need for monitoring. While further research is required to substantiate these initial findings, it is recommended that clinicians familiarise themselves with using Google Calendar, as it appears to offer additional potential in the management of prospective memory deficits following ABI.

  10. Effects of histamine on MK-801-induced memory deficits in radial maze performance in rats.

    PubMed

    Chen, Z; Zhao, Q; Sugimoto, Y; Fujii, Y; Kamei, C

    1999-08-21

    The effects of histamine on the spatial memory deficits induced by MK-801 were investigated using the eight-arm radial maze paradigm in rats. Intracerebroventricular (i.c.v.) injection of histamine or thioperamide, and intraperitoneal (i.p.) injection of histidine improved the spatial memory deficits induced by MK-801. Similar results were obtained with 2-thiazolylethylamine. In contrast, 4-methylhistamine showed no significant effect. Based on these observations, it seems likely that the protective effect of histamine on MK-801-induced spatial memory deficit is mediated by H(1)-receptors.

  11. Deconstructing Spatial Working Memory and Attention Deficits in Multiple Sclerosis

    PubMed Central

    Gmeindl, Leon; Courtney, Susan M.

    2011-01-01

    Objective To investigate whether spatial working memory (WM) is impaired in multiple sclerosis (MS), and, if it is, to localize impairment to specific cognitive subprocess(es). Method In Experiment 1, MS and control participants performed computerized memory-span and visuomotor tasks. WM subprocesses were taxed by manipulating (1) the requirement to remember serial order, (2) delay duration, and (3) the presence of irrelevant stimuli during target presentation. In Experiment 2, recall and recognition tests varied the difficulty of WM retrieval. In Experiment 3, an attention-cueing task tested the ability to voluntarily and rapidly reorient attention. Results Performance was worse for MS than for control participants in both spatial recall (Exp. 1 span: 95% CIMS = [5.11, 5.57], 95% CIControls = [5.58, 6.03], p = 0.003, 1-tailed; Exp. 2 span: 95% CIMS = [4.44, 5.54], 95% CIControls = [5.47, 6.57], p = 0.006, 1-tailed) and recognition (accuracy: 95% CIMS = [0.71, 0.81], 95% CIControls = [0.79, 0.88], p = 0.01, 1-tailed) tests. However, there was no evidence for deficits in spatiotemporal binding, maintenance, retrieval, distractor suppression, or visuomotor processing. In contrast, MS participants were abnormally slow to reorient attention (cueing effect (ms): 95% CIMS: [90, 169], 95% CIControls: [29, 107], p = 0.015, 1-tailed). Conclusions Results suggest that, whereas spatial WM is impaired in MS, once spatial information has been adequately encoded into WM, individuals with MS are, on average, able to maintain and retrieve this information. Impoverished encoding of spatial information, however, may be due to inefficient voluntary orienting of attention. PMID:22059650

  12. Spatial learning and memory deficits induced by exposure to iron-56-particle radiation

    NASA Technical Reports Server (NTRS)

    Shukitt-Hale, B.; Casadesus, G.; McEwen, J. J.; Rabin, B. M.; Joseph, J. A.

    2000-01-01

    It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

  13. Age-Related Changes in the Functional Network Underlying Specific and General Autobiographical Memory Retrieval: A Pivotal Role for the Anterior Cingulate Cortex

    PubMed Central

    Martinelli, Pénélope; Sperduti, Marco; Devauchelle, Anne-Dominique; Kalenzaga, Sandrine; Gallarda, Thierry; Lion, Stéphanie; Delhommeau, Marion; Anssens, Adèle; Amado, Isabelle; Meder, Jean François; Krebs, Marie-Odile; Oppenheim, Catherine; Piolino, Pascale

    2013-01-01

    Age-related changes in autobiographical memory (AM) recall are characterized by a decline in episodic details, while semantic aspects are spared. This deleterious effect is supposed to be mediated by an inefficient recruitment of executive processes during AM retrieval. To date, contrasting evidence has been reported on the neural underpinning of this decline, and none of the previous studies has directly compared the episodic and semantic aspects of AM in elderly. We asked 20 young and 17 older participants to recall specific and general autobiographical events (i.e., episodic and semantic AM) elicited by personalized cues while recording their brain activity by means of fMRI. At the behavioral level, we confirmed that the richness of episodic AM retrieval is specifically impoverished in aging and that this decline is related to the reduction of executive functions. At the neural level, in both age groups, we showed the recruitment of a large network during episodic AM retrieval encompassing prefrontal, cortical midline and posterior regions, and medial temporal structures, including the hippocampus. This network was very similar, but less extended, during semantic AM retrieval. Nevertheless, a greater activity was evidenced in the dorsal anterior cingulate cortex (dACC) during episodic, compared to semantic AM retrieval in young participants, and a reversed pattern in the elderly. Moreover, activity in dACC during episodic AM retrieval was correlated with inhibition and richness of memories in both groups. Our findings shed light on the direct link between episodic AM retrieval, executive control, and their decline in aging, proposing a possible neuronal signature. They also suggest that increased activity in dACC during semantic AM retrieval in the elderly could be seen as a compensatory mechanism underpinning successful AM performance observed in aging. These results are discussed in the framework of recently proposed models of neural reorganization in aging

  14. Hyperactivity in Boys with Attention-Deficit/Hyperactivity Disorder (ADHD): A Ubiquitous Core Symptom or Manifestation of Working Memory Deficits?

    ERIC Educational Resources Information Center

    Rapport, Mark D.; Bolden, Jennifer; Kofler, Michael J.; Sarver, Dustin E.; Raiker, Joseph S.; Alderson, R. Matt

    2009-01-01

    Hyperactivity is currently considered a core and ubiquitous feature of attention-deficit/hyperactivity disorder (ADHD); however, an alternative model challenges this premise and hypothesizes a functional relationship between working memory (WM) and activity level. The current study investigated whether children's activity level is functionally…

  15. An age-related numerical and functional deficit in CD19(+) CD24(hi) CD38(hi) B cells is associated with an increase in systemic autoimmunity.

    PubMed

    Duggal, Niharika A; Upton, Jane; Phillips, Anna C; Sapey, Elizabeth; Lord, Janet M

    2013-10-01

    Autoimmunity increases with aging indicative of reduced immune tolerance, but the mechanisms involved are poorly defined. In recent years, subsets of B cells with immunoregulatory properties have been identified in murine models of autoimmune disorders, and these cells downregulate immune responses via secretion of IL10. In humans, immature transitional B cells with a CD19(+) CD24(hi) CD38(hi) phenotype have been reported to regulate immune responses via IL10 production. We found the frequency and numbers of CD19(+) CD24(hi) CD38(hi) cells were reduced in the PBMC pool with age. IL10 expression and secretion following activation via either CD40, or Toll-like receptors was also impaired in CD19(+) CD24(hi) CD38(hi) B cells from healthy older donors. When investigating the mechanisms involved, we found that CD19(+) CD24(hi) CD38(hi) B-cell function was compromised by age-related effects on both T cells and B cells: specifically, CD40 ligand expression was lower in CD4 T cells from older donors following CD3 stimulation, and signalling through CD40 was impaired in CD19(+) CD24(hi) CD38(hi) B cells from elders as evidenced by reduced phosphorylation (Y705) and activation of STAT3. However, there was no age-associated change in expression of costimulatory molecules CD80 and CD86 on CD19(+) CD24(hi) CD38(hi) cells, suggesting IL10-dependent immune suppression is impaired, but contact-dependent suppressive capacity is intact with age. Finally, we found a negative correlation between CD19(+) CD24(hi) CD38(hi) B-cell IL10 production and autoantibody (Rheumatoid factor) levels in older adults. We therefore propose that an age-related decline in CD19(+) CD24(hi) CD38(hi) B cell number and function may contribute towards the increased autoimmunity and reduced immune tolerance seen with aging.

  16. Shared Etiology of Phonological Memory and Vocabulary Deficits in School-Age Children

    ERIC Educational Resources Information Center

    Peterson, Robin L.; Pennington, Bruce F.; Samuelsson, Stefan; Byrne, Brian; Olson, Richard K.

    2013-01-01

    Purpose: The goal of this study was to investigate the etiologic basis for the association between deficits in phonological memory (PM) and vocabulary in school-age children. Method: Children with deficits in PM or vocabulary were identified within the International Longitudinal Twin Study (ILTS; Samuelsson et al., 2005). The ILTS includes 1,045…

  17. Assessment of Working Memory in Children with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Messina, Lucinete de Freitas; Tiedemann, Klaus Bruno; de Andrade, Enio Roberto; Primi, Ricardo

    2006-01-01

    Objective: This research investigated the cognitive abilities and the working memory in children and youngsters with three different types of attention-deficit/hyperactivity disorder (ADHD): (a) mainly with attention-deficit, (b) hyperactive and impulsive, and (c) combined. Method: A computerized test called Infant Cognitive Abilities Test, which…

  18. A Meta-Analysis of Working Memory Impairments in Children with Attention-Deficit/hyperactivity Disorder.

    ERIC Educational Resources Information Center

    Martinussen, Rhonda; Hayden, Jill; Hogg-Johnson, Sheilah; Tannock, Rosemary

    2005-01-01

    Objective: To determine the empirical evidence for deficits in working memory (WM) processes in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: Exploratory meta-analytic procedures were used to investigate whether children with ADHD exhibit WM impairments. Twenty-six empirical research studies published from…

  19. Explaining Semantic Short-Term Memory Deficits: Evidence for the Critical Role of Semantic Control

    ERIC Educational Resources Information Center

    Hoffman, Paul; Jefferies, Elizabeth; Lambon Ralph, Matthew A.

    2011-01-01

    Patients with apparently selective short-term memory (STM) deficits for semantic information have played an important role in developing multi-store theories of STM and challenge the idea that verbal STM is supported by maintaining activation in the language system. We propose that semantic STM deficits are not as selective as previously thought…

  20. Clinical Correlates of Working Memory Deficits in Youth With and Without ADHD: A Controlled Study

    PubMed Central

    Fried, Ronna; Chan, James; Feinberg, Leah; Pope, Amanda; Woodworth, K. Yvonne; Faraone, Stephen V.; Biederman, Joseph

    2016-01-01

    Objective Both working memory (WM) (a brain system that provides temporary storage and manipulation of the information) and attention-deficit/hyperactivity disorder (ADHD) have been associated with educational deficits. Since WM deficits are prevalent in children with ADHD, the main aim of the present study was to examine whether educational deficits are driven by working memory deficits or driven by the effect of ADHD itself. Method Participants were referred youth with (N=276) and without (N=241) ADHD ascertained from pediatric and psychiatric sources. Assessment included measures of psychiatric, psychosocial, educational, and cognitive functioning. Education deficits were defined as grade retention or placement in special classes, and were assessed using interviews and written rating scales. Working memory was assessed using the WISC-R Freedom from Distractibility (FFD) factor based on digit span, arithmetic and coding. Results Significantly more youth with ADHD had WM deficits than controls (31.9% vs. 13.7%, p< 0.05). In ADHD children, WM deficits were significantly (p<0.01) associated with an increased risk for grade retention and placement in special classes as well as lower scores on reading and math achievement tests, relative to ADHD children without WM deficits. In contrast, no other differences were noted in other areas of functioning. Although WM deficits also had some adverse impact on educational and cognitive correlates in non ADHD controls, these differences failed to attain statistical significance. Conclusion WM deficits significantly and selectively increase the risk for academic deficits and cognitive dysfunction in children with ADHD beyond those conferred by ADHD. Screening for WM deficits may help identify children with ADHD at high risk for academic and cognitive dysfunction. PMID:26902180

  1. An age-related numerical and functional deficit in CD19+CD24hiCD38hi B cells is associated with an increase in systemic autoimmunity

    PubMed Central

    Duggal, Niharika A; Upton, Jane; Phillips, Anna C; Sapey, Elizabeth; Lord, Janet M

    2013-01-01

    Autoimmunity increases with aging indicative of reduced immune tolerance, but the mechanisms involved are poorly defined. In recent years, subsets of B cells with immunoregulatory properties have been identified in murine models of autoimmune disorders, and these cells downregulate immune responses via secretion of IL10. In humans, immature transitional B cells with a CD19+CD24hiCD38hi phenotype have been reported to regulate immune responses via IL10 production. We found the frequency and numbers of CD19+CD24hiCD38hi cells were reduced in the PBMC pool with age. IL10 expression and secretion following activation via either CD40, or Toll-like receptors was also impaired in CD19+CD24hiCD38hi B cells from healthy older donors. When investigating the mechanisms involved, we found that CD19+CD24hiCD38hi B-cell function was compromised by age-related effects on both T cells and B cells: specifically, CD40 ligand expression was lower in CD4 T cells from older donors following CD3 stimulation, and signalling through CD40 was impaired in CD19+CD24hiCD38hi B cells from elders as evidenced by reduced phosphorylation (Y705) and activation of STAT3. However, there was no age-associated change in expression of costimulatory molecules CD80 and CD86 on CD19+CD24hiCD38hi cells, suggesting IL10-dependent immune suppression is impaired, but contact-dependent suppressive capacity is intact with age. Finally, we found a negative correlation between CD19+CD24hiCD38hi B-cell IL10 production and autoantibody (Rheumatoid factor) levels in older adults. We therefore propose that an age-related decline in CD19+CD24hiCD38hi B cell number and function may contribute towards the increased autoimmunity and reduced immune tolerance seen with aging. PMID:23755918

  2. White matter injury and microglia/macrophage polarization are strongly linked with age-related long-term deficits in neurological function after stroke.

    PubMed

    Suenaga, Jun; Hu, Xiaoming; Pu, Hongjian; Shi, Yejie; Hassan, Sulaiman Habib; Xu, Mingyue; Leak, Rehana K; Stetler, R Anne; Gao, Yanqin; Chen, Jun

    2015-10-01

    Most of the successes in experimental models of stroke have not translated well to the clinic. One potential reason for this failure is that stroke mainly afflicts the elderly and the majority of experimental stroke studies rely on data gathered from young adult animals. Therefore, in the present study we established a reliable, reproducible model of stroke with low mortality in aged (18month) male mice and contrasted their pathophysiological changes with those in young (2month) animals. To this end, mice were subjected to permanent tandem occlusion of the left distal middle cerebral artery (dMCAO) with ipsilateral common carotid artery occlusion (CCAO). Cerebral blood flow (CBF) was evaluated repeatedly during and after stroke. Reduction of CBF was more dramatic and sustained in aged mice. Aged mice exhibited more severe long-term sensorimotor deficits, as manifested by deterioration of performance in the Rotarod and hanging wire tests up to 35d after stroke. Aged mice also exhibited significantly worse long-term cognitive deficits after stroke, as measured by the Morris water maze test. Consistent with these behavioral observations, brain infarct size and neuronal tissue loss after dMCAO were significantly larger in aged mice at 2d and 14d, respectively. The young versus aged difference in neuronal tissue loss, however, did not persist until 35d after dMCAO. In contrast to the transient difference in neuronal tissue loss, we found significant and long lasting deterioration of white matter in aged animals, as revealed by the loss of myelin basic protein (MBP) staining in the striatum at 35d after dMCAO. We further examined the expression of M1 (CD16/CD32) and M2 (CD206) markers in Iba-1(+) microglia by double immunofluorescent staining. In both young and aged mice, the expression of M2 markers peaked around 7d after stroke whereas the expression of M1 markers peaked around 14d after stroke, suggesting a progressive M2-to-M1 phenotype shift in both groups. However

  3. Decreased theta power at encoding and cognitive mapping deficits in elderly individuals during a spatial memory task.

    PubMed

    Lithfous, Ségolène; Tromp, Delphine; Dufour, André; Pebayle, Thierry; Goutagny, Romain; Després, Olivier

    2015-10-01

    The purpose of this study was to investigate the role of theta activity in cognitive mapping, and to determine whether age-associated decreased theta power may account for navigational difficulties in elderly individuals. Cerebral activity was recorded using electroencephalograph in young and older individuals performing a spatial memory task that required the creation of cognitive maps. Power spectra were computed in the frontal and parietal regions and correlated with recognition performance. We found that accuracy of cognitive mapping was positively correlated with left frontal theta activity during encoding in young adults but not in older individuals. Compared with young adults, older participants were impaired in the creation of cognitive maps and showed reduced theta and alpha activity at encoding. These results suggest that encoding processes are impaired in older individual, which may explain age-related cognitive mapping deficits.

  4. Learning and Memory Impairments in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Andersen, Per N.; Egeland, Jens; Øie, Merete

    2013-01-01

    There are relatively few studies on learning and delayed memory with attention-deficit/hyperactivity disorder (ADHD). The objective of the present study was to examine acquisition, free delayed memory, and recognition skills in medication naive children and adolescents aged 8-16 years with ADHD combined subtype (36 participants) and inattentive…

  5. Developmental Trends in Memory and Metamemory in Children with Attention Deficit Disorder.

    ERIC Educational Resources Information Center

    Voelker, Sylvia L.

    1989-01-01

    The study investigated the development of memory strategy knowledge and spontaneous use of strategy by 6- to 12-year-old boys with attention deficit disorder and hyperactivity (ADD-H). Although there was no difference between experimental and control groups in metamemory knowledge, the ADD-H subjects were less likely to use memory strategies.…

  6. Memory Modality Differences in Children with Attention Deficit Hyperactive Disorder with and without Learning Disabilities.

    ERIC Educational Resources Information Center

    Webster, Raymond E.; And Others

    1996-01-01

    Assesses information processing and memory functioning in 50 children diagnosed with Attention Deficit Hyperactive Disorder (ADHD) with and without learning disabilities (LD). Both groups struggled with auditory ordered recall. The ADHD/LD group demonstrated more problems transferring information into short-term and long-term memory stores than…

  7. Implicit and Explicit Memory Performance in Children with Attention Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Aloisi, Bruno A.; McKone, Elinor; Heubeck, Bernd G.

    2004-01-01

    The present investigation examined implicit and explicit memory in 20 children diagnosed with attention deficit/hyperactivity disorder (AD/HD) and 20 matched controls. Consistent with previous research, children with AD/HD performed more poorly than controls on an explicit test of long-term memory for pictures. New results were that (a) there was…

  8. A Comprehensive Investigation of Memory Impairment in Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder

    ERIC Educational Resources Information Center

    Rhodes, Sinead M.; Park, Joanne; Seth, Sarah; Coghill, David R.

    2012-01-01

    Background: We conducted a comprehensive and systematic assessment of memory functioning in drug-naive boys with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). Methods: Boys performed verbal and spatial working memory (WM) component (storage and central executive) and verbal and spatial storage load tasks,…

  9. Visual Working Memory and Number Sense: Testing the Double Deficit Hypothesis in Mathematics

    ERIC Educational Resources Information Center

    Toll, Sylke W. M.; Kroesbergen, Evelyn H.; Van Luit, Johannes E. H.

    2016-01-01

    Background: Evidence exists that there are two main underlying cognitive factors in mathematical difficulties: working memory and number sense. It is suggested that real math difficulties appear when both working memory and number sense are weak, here referred to as the double deficit (DD) hypothesis. Aims: The aim of this study was to test the DD…

  10. Emerging Depression Is Associated with Face Memory Deficits in Adolescent Girls

    ERIC Educational Resources Information Center

    Guyer, Amanda E.; Choate, Victoria R.; Grimm, Kevin J.; Pine, Daniel S.; Keenan, Kate

    2011-01-01

    Objective: To examine the association between memory for previously encoded emotional faces and depression symptoms assessed over 4 years in adolescent girls. Investigating the interface between memory deficits and depression in adolescent girls may provide clues about depression pathophysiology. Method: Participants were 213 girls recruited from…

  11. Disordered Connectivity Associated with Memory Deficits in Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Chan, Agnes S.; Han, Yvonne M. Y.; Sze, Sophia L.; Cheung, Mei-chun; Leung, Winnie Wing-man; Chan, Raymond C. K.; To, Cho Yee

    2011-01-01

    The present study examined the memory performance and cortical connectivity of children with ASD, and investigated whether the memory deficits exhibited by these children were associated with the cortical connectivity. Twenty-one children with ASD and 21 children with normal development (NC), aged 5-14 years, participated in the study. Each child…

  12. A Specific Deficit in Visuospatial Simultaneous Working Memory in Down Syndrome

    ERIC Educational Resources Information Center

    Lanfranchi, S.; Carretti, B.; Spano, G.; Cornoldi, C.

    2009-01-01

    Background: Recent studies have demonstrated that individuals with Down syndrome (DS) present both central and verbal working memory deficits compared with controls matched for mental age, whereas evidence on visuospatial working memory (VSWM) has remained ambiguous. The present paper uses a battery of VSWM tasks to test the hypothesis that…

  13. The effects of emotional arousal and gender on the associative memory deficit of older adults.

    PubMed

    Naveh-Benjamin, Moshe; Maddox, Geoffrey B; Jones, Peter; Old, Susan; Kilb, Angela

    2012-05-01

    In this study we assessed the potential moderating roles of stimulus type (emotionally arousing) and participants' characteristics (gender) in older adults' associative memory deficit. In two experiments, young and older participants studied lists that included neutral and emotionally arousing word pairs (positive and negative) and completed recognition tests for the words and their associations. In Experiment 1, the majority of the word pairs were composed of two nouns, whereas in Experiment 2 they were composed of adjective-noun pairs. The results extend evidence for older adults' associative deficit and suggest that older and younger adults' item memory is improved for emotionally arousing words. However, associative memory for the word pairs did not benefit (and even showed a slight decline) from emotionally arousing words, which was the case for both younger and older adults. In addition, in these experiments, gender appeared to moderate the associative deficit of older adults, with older males but not females demonstrating this deficit.

  14. Memory deficits and industrial toxicant exposure: a comparative study of hard metal, solvent and asbestos workers.

    PubMed

    Jordan, C M; Whitman, R D; Harbut, M

    1997-06-01

    Memory functioning was examined in ex-factory workers with hard metal disease, resulting from exposure to alloys utilizing cobalt. Since these workers are also exposed to organic solvents and may suffer from chronic hypoxia as a result of their pulmonary disorder, solvent and asbestos workers, as well as an unexposed matched sample, served as controls. Results demonstrated deficits in the allocation of attentional resources and in short-term verbal memory. A pattern of findings across several tests suggested that repetition or delay is important for adequate memory performance in individuals exposed to hard metal, implicating a deficit in encoding or slowed consolidation.

  15. Age-related decline in Kv3.1b expression in the mouse auditory brainstem correlates with functional deficits in the medial olivocochlear efferent system.

    PubMed

    Zettel, Martha L; Zhu, Xiaoxia; O'Neill, William E; Frisina, Robert D

    2007-06-01

    Kv3.1b channel protein is widely distributed in the mammalian auditory brainstem, but studies have focused mainly on regions critical for temporal processing, including the medial nucleus of the trapezoid body (MNTB) and anteroventral cochlear nucleus (AVCN). Because temporal processing declines with age, this study was undertaken to determine if the expression of Kv3.1b likewise declines, and if changes are specific to these nuclei. Immunocytochemistry using an anti-Kv3.1b antibody was performed, and the relative optical density of cells and neuropil was determined from CBA/CaJ mice of four age groups. Declines in expression in AVCN, MNTB, and lateral superior olive (35, 26, and 23%) were found, but changes were limited to neuropil. Interestingly, cellular optical density declines were found in superior paraolivary nucleus, ventral nucleus of the trapezoid body, and lateral nucleus of the trapezoid body (24, 29, and 26%), which comprise the medial olivocochlear (MOC) feedback system. All declines occurred by middle age (15 months old). No age-related changes were found in the remaining regions of cochlear nucleus or in the inferior colliculus. Contralateral suppression of distortion-product otoacoustic emission amplitudes of age-matched littermates also declined by middle age, suggesting a correlation between Kv3.1 expression and MOC function. In search of more direct evidence for such a correlation, Kv3.1b knockout mice were examined. Knockouts show poor MOC function as compared to +/+ and +/- genotypes. Thus, Kv3.1b expression declines in MOC neurons by middle age, and these changes appear to correlate with functional declines in efferent activity in both middle-aged CBA mice and Kv3.1b knockout mice.

  16. Visual short-term memory deficits in REM sleep behaviour disorder mirror those in Parkinson's disease.

    PubMed

    Rolinski, Michal; Zokaei, Nahid; Baig, Fahd; Giehl, Kathrin; Quinnell, Timothy; Zaiwalla, Zenobia; Mackay, Clare E; Husain, Masud; Hu, Michele T M

    2016-01-01

    Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson's disease. Here we examined visual short-term memory deficits--long associated with Parkinson's disease--in patients with REM sleep behaviour disorder without Parkinson's disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson's disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson's disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson's disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson's disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of 'prodromal' Parkinson's disease that might be useful in tracking disease progression and for disease-modifying intervention trials.

  17. Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain.

    PubMed

    Mattfeld, Aaron T; Whitfield-Gabrieli, Susan; Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Fried, Ronna; Gabrieli, John D E

    2016-01-01

    Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI). Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity.

  18. Traumatic stress is linked to a deficit in associative episodic memory.

    PubMed

    Guez, Jonathan; Naveh-Benjamin, Moshe; Yankovsky, Yan; Cohen, Jonathan; Shiber, Asher; Shalev, Hadar

    2011-06-01

    Individuals with posttraumatic stress disorder (PTSD) are haunted by persistent memories of the trauma, but ironically are impaired in memories of daily life. The current set of 4 experiments compared new learning and memory of emotionally neutral content in 2 groups of patients and aged- and education-matched controls: 20 patients diagnosed with chronic posttraumatic stress disorder (C-PTSD) and 20 patients diagnosed with acute stress disorder (ASD). In all experiments, participants studied a list of stimuli pairs (words or pictures) and were then tested for their memory of the items, or for the association between items in each pair. Results indicated that both types of patients showed associative memory impairment compared to a control group, although their item memory performance was relatively intact. Potential mechanisms underlying such associative memory deficits in posttraumatic patients are discussed.

  19. Cerebellar Damage Produces Selective Deficits in Verbal Working Memory

    ERIC Educational Resources Information Center

    Ravizza, Susan M.; Mccormick, Cristin A.; Schlerf, John E.; Justus, Timothy; Ivry, Richard B.; Fiez, Julie A.

    2006-01-01

    The cerebellum is often active in imaging studies of verbal working memory, consistent with a putative role in articulatory rehearsal. While patients with cerebellar damage occasionally exhibit a mild impairment on standard neuropsychological tests of working memory, these tests are not diagnostic for exploring these processes in detail. The…

  20. Alzheimer's disease and memory-monitoring impairment: Alzheimer's patients show a monitoring deficit that is greater than their accuracy deficit.

    PubMed

    Dodson, Chad S; Spaniol, Maggie; O'Connor, Maureen K; Deason, Rebecca G; Ally, Brandon A; Budson, Andrew E

    2011-07-01

    We assessed the ability of two groups of patients with mild Alzheimer's disease (AD) and two groups of older adults to monitor the likely accuracy of recognition judgments and source identification judgments about who spoke something earlier. Alzheimer's patients showed worse performance on both memory judgments and were less able to monitor with confidence ratings the likely accuracy of both kinds of memory judgments, as compared to a group of older adults who experienced the identical study and test conditions. Critically, however, when memory performance was made comparable between the AD patients and the older adults (e.g., by giving AD patients extra exposures to the study materials), AD patients were still greatly impaired at monitoring the likely accuracy of their recognition and source judgments. This result indicates that the monitoring impairment in AD patients is actually worse than their memory impairment, as otherwise there would have been no differences between the two groups in monitoring performance when there were no differences in accuracy. We discuss the brain correlates of this memory-monitoring deficit and also propose a Remembrance-Evaluation model of memory-monitoring.

  1. Arctigenin isolated from the seeds of Arctium lappa ameliorates memory deficits in mice.

    PubMed

    Lee, In-Ah; Joh, Eun-Ha; Kim, Dong-Hyun

    2011-09-01

    The seeds of Arctium lappa L. (AL, family Asteraceae), the main constituents of which are arctiin and arctigenin, have been used as an herbal medicine or functional food to treat inflammatory diseases. These main constituents were shown to inhibit acetylcholinesterase (AChE) activity. Arctigenin more potently inhibited AChE activity than arctiin. Arctigenin at doses of 30 and 60 mg/kg (p. o.) potently reversed scopolamine-induced memory deficits by 62 % and 73 %, respectively, in a passive avoidance test. This finding is comparable with that of tacrine (10 mg/kg p. o.). Arctigenin also significantly reversed scopolamine-induced memory deficits in the Y-maze and Morris water maze tests. On the basis of these findings, arctigenin may ameliorate memory deficits by inhibiting AChE.

  2. Progression of logopenic variant primary progressive aphasia to apraxia and semantic memory deficits

    PubMed Central

    2013-01-01

    Background Due to the nature of neurodegenerative disorders, patients with primary progressive aphasia develop cognitive impairment other than aphasia as the disorder progresses. The progression of logopenic variant primary progressive aphasia (lvPPA), however, has not been well described. In particular, praxic disorders and semantic memory deficits have rarely been reported. Case presentations We report three patients in the initial stage of lvPPA who subsequently developed apraxia in the middle stage and developed clinically evident semantic memory deficits in the advanced stages. Conclusions The present case series suggests that some patients with lvPPA develop an atypical type of dementia with apraxia and semantic memory deficits, suggesting that these cases should be classified as a type of early-onset Alzheimer’s disease. PMID:24176108

  3. Working memory deficits in adults with ADHD: is there evidence for subtype differences?

    PubMed Central

    Schweitzer, Julie B; Hanford, Russell B; Medoff, Deborah R

    2006-01-01

    Background Working memory performance is important for maintaining functioning in cognitive, academic and social activities. Previous research suggests there are prevalent working memory deficits in children with attention deficit hyperactivity disorder (ADHD). There is now a growing body of literature characterizing working memory functioning according to ADHD subtypes in children. The expression of working memory deficits in adults with ADHD and how they vary according to subtype, however, remains to be more fully documented. Methods This study assessed differences in working memory functioning between Normal Control (NC) adults (N = 18); patients with ADHD, Combined (ADHD-CT) Type ADHD (N = 17); and ADHD, Inattentive (ADHD-IA) Type (N = 16) using subtests from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-III and the Paced Auditory Serial Addition Task (PASAT). Results The ADHD groups displayed significant weaknesses in contrast to the NC group on working memory tests requiring rapid processing and active stimulus manipulation. This included the Letter-Number-Sequencing test of the Wechsler scales, PASAT omission errors and the longest sequence of consecutive correct answers on the PASAT. No overall ADHD group subtype differences emerged; however differences between the ADHD groups and the NC group varied depending on the measure and the gender of the participants. Gender differences in performance were evident on some measures of working memory, regardless of group, with males performing better than females. Conclusion In general, the data support a dimensional interpretation of working memory deficits experienced by the ADHD-CT and ADHD-IA subtypes, rather than an absolute difference between subtypes. Future studies should test the effects of processing speed and load on subtype performance and how those variables interact with gender in adults with ADHD. PMID:17173676

  4. Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

    PubMed

    Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

    2015-04-01

    Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress.

  5. Hippocampal formation alterations differently contribute to autobiographic memory deficits in mild cognitive impairment and Alzheimer's disease.

    PubMed

    Hirjak, Dusan; Wolf, Robert C; Remmele, Barbara; Seidl, Ulrich; Thomann, Anne K; Kubera, Katharina M; Schröder, Johannes; Maier-Hein, Klaus H; Thomann, Philipp A

    2017-03-09

    Autobiographical memory (AM) is part of declarative memory and includes both semantic and episodic aspects. AM deficits are among the major complaints of patients with Alzheimer's disease (AD) even in early or preclinical stages. Previous MRI studies in AD patients have showed that deficits in semantic and episodic AM are associated with hippocampal alterations. However, the question which specific hippocampal subfields and adjacent extrahippocampal structures contribute to deficits of AM in individuals with mild cognitive impairment (MCI) and AD patients has not been investigated so far. Hundred and seven participants (38 AD patients, 38 MCI individuals and 31 healthy controls [HC]) underwent MRI at 3 Tesla. AM was assessed with a semi-structured interview (E-AGI). FreeSurfer 5.3 was used for hippocampal parcellation. Semantic and episodic AM scores were related to the volume of 5 hippocampal subfields and cortical thickness in the parahippocampal and entorhinal cortex. Both semantic and episodic AM deficits were associated with bilateral hippocampal alterations. These associations referred mainly to CA1, CA2-3, presubiculum, and subiculum atrophy. Episodic, but not semantic AM loss was associated with cortical thickness reduction of the bilateral parahippocampal and enthorinal cortex. In MCI individuals, episodic, but not semantic AM deficits were associated with alterations of the CA1, presubiculum and subiculum. Our findings support the crucial role of CA1, presubiculum, and subiculum in episodic memory. The present results implicate that in MCI individuals, semantic and episodic AM deficits are subserved by distinct neuronal systems.

  6. Chromaffin cell grafts to rat cerebral cortex reverse lesion-induced memory deficits.

    PubMed

    Welner, S A; Koty, Z C; Boksa, P

    1990-09-10

    Adrenal chromaffin cells were isolated from donor adult rats and transplanted to the cerebral cortex of bilaterally nucleus basalis magnocellularis-lesioned rats. Chromaffin cell grafts to lesioned animals completely reversed the spatial memory deficit seen in lesioned alone animals on a T-maze alternation task. Although chromaffin cell grafts have been used previously to reverse motor abnormalities arising from defective nigro-striatal aminergic transmission, the present report is the first evidence that chromaffin cell transplants can reverse deficits in memory function. Grafts also enhanced cortical acetylcholinesterase staining.

  7. Global Processing Training to Improve Visuospatial Memory Deficits after Right-Brain Stroke

    PubMed Central

    Chen, Peii; Hartman, Ashley J.; Priscilla Galarza, C.; DeLuca, John

    2012-01-01

    Visuospatial stimuli are normally perceived from the global structure to local details. A right-brain stroke often disrupts this perceptual organization, resulting in piecemeal encoding and thus poor visuospatial memory. Using a randomized controlled design, the present study examined whether promoting the global-to-local encoding improves retrieval accuracy in right-brain-damaged stroke survivors with visuospatial memory deficits. Eleven participants received a single session of the Global Processing Training (global-to-local encoding) or the Rote Repetition Training (no encoding strategy) to learn the Rey–Osterrieth Complex Figure. The result demonstrated that the Global Processing Training significantly improved visuospatial memory deficits after a right-brain stroke. On the other hand, rote practice without a step-by-step guidance limited the degree of memory improvement. The treatment effect was observed both immediately after the training procedure and 24 h post-training. Overall, the present findings are consistent with the long-standing principle in cognitive rehabilitation that an effective treatment is based on specific training aimed at improving specific neurocognitive deficits. Importantly, visuospatial memory deficits after a right-brain stroke may improve with treatments that promote global processing at encoding. PMID:23070314

  8. Physical exercise can reverse the deficit in fear memory induced by maternal deprivation.

    PubMed

    Mello, Pâmela Billig; Benetti, Fernando; Cammarota, Martín; Izquierdo, Iván

    2009-10-01

    Maternal deprivation during the first 10 days of life induces significant behavioral alterations in rodents which persist through adulthood. Physical exercise reduces the cognitive deficits associated with pharmacologic and pathological conditions. Here we investigated whether forced physical exercise alters memory deficits caused by postnatal maternal deprivation. Male rats were divided into four groups: (1) control, (2) deprived, (3) exercised, and (4) deprived+exercised. In groups 2 and 4, pups were deprived from their mothers for 3h/day during the first 10 days post-birth. In groups 3 and 4, from postnatal day 45 (PND-45) on, animals were submitted to forced treadmill exercise. At adulthood, animals were submitted to four different behavioral tasks: open field, Morris water maze (MWM), object recognition (OR) and inhibitory avoidance (IA). Maternal deprivation had no effect on open field behavior, but disrupted memory in the three other tasks. Physical exercise alone had no effect, except for a slight enhancement of MWM learning. Importantly, physical exercise reversed the deficit of IA and reduced the deficit of spatial memory but not that of OR seen in deprived animals. It is possible that physical exercise may counteract the influence of maternal deprivation on neurohumoral or hormonal memory modulatory systems related to stress. Indeed, the decreasing order of the effect of exercise on the memory disturbances induced by deprivation roughly follows the descending degree of stress associated with each task (IA>MWM>OR). Maternal deprivation is known to hinder hormonal mechanisms involved in coping with stress.

  9. Oxytocin is implicated in social memory deficits induced by early sensory deprivation in mice.

    PubMed

    Zhang, Jin-Bao; Chen, Ling; Lv, Zhu-Man; Niu, Xue-Yuan; Shao, Can-Can; Zhang, Chan; Pruski, Michal; Huang, Ying; Qi, Cong-Cong; Song, Ning-Ning; Lang, Bing; Ding, Yu-Qiang

    2016-12-13

    Early-life sensory input plays a crucial role in brain development. Although deprivation of orofacial sensory input at perinatal stages disrupts the establishment of the barrel cortex and relevant callosal connections, its long-term effect on adult behavior remains elusive. In this study, we investigated the behavioral phenotypes in adult mice with unilateral transection of the infraorbital nerve (ION) at postnatal day 3 (P3). Although ION-transected mice had normal locomotor activity, motor coordination, olfaction, anxiety-like behaviors, novel object memory, preference for social novelty and sociability, they presented deficits in social memory and spatial memory compared with control mice. In addition, the social memory deficit was associated with reduced oxytocin (OXT) levels in the hypothalamus and could be partially restored by intranasal administration of OXT. Thus, early sensory deprivation does result in behavioral alterations in mice, some of which may be associated with the disruption of oxytocin signaling.

  10. Association between Early Attention-Deficit/Hyperactivity Symptoms and Current Verbal and Visuo-Spatial Short-Term Memory

    ERIC Educational Resources Information Center

    Gau, Susan Shur-Fen; Chiang, Huey-Ling

    2013-01-01

    Deficits in short-term memory are common in adolescents with attention-deficit/hyperactivity disorder (ADHD), but their current ADHD symptoms cannot well predict their short-term performance. Taking a developmental perspective, we wanted to clarify the association between ADHD symptoms at early childhood and short-term memory in late childhood and…

  11. Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers.

    PubMed

    Swartzwelder, H Scott; Acheson, Shawn K; Miller, Kelsey M; Sexton, Hannah G; Liu, Wen; Crews, Fulton T; Risher, Mary-Louise

    2015-01-01

    The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30) received exposure to AIE (5g/kg, i.g.) or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR) test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.

  12. Higher body mass index is associated with episodic memory deficits in young adults

    PubMed Central

    Cheke, Lucy G.; Simons, Jon S.; Clayton, Nicola S.

    2016-01-01

    Obesity has become an international health crisis. There is accumulating evidence that excess bodyweight is associated with changes to the structure and function of the brain and with a number of cognitive deficits. In particular, research suggests that obesity is associated with hippocampal and frontal lobe dysfunction, which would be predicted to impact memory. However, evidence for such memory impairment is currently limited. We hypothesised that higher body mass index (BMI) would be associated with reduced performance on a test of episodic memory that assesses not only content, but also context and feature integration. A total of 50 participants aged 18–35 years, with BMIs ranging from 18 to 51, were tested on a novel what–where–when style episodic memory test: the “Treasure-Hunt Task”. This test requires recollection of object, location, and temporal order information within the same paradigm, as well as testing the ability to integrate these features into a single event recollection. Higher BMI was associated with significantly lower performance on the what–where–when (WWW) memory task and all individual elements: object identification, location memory, and temporal order memory. After controlling for age, sex, and years in education, the effect of BMI on the individual what, where, and when tasks remained, while the WWW dropped below significance. This finding of episodic memory deficits in obesity is of concern given the emerging evidence for a role for episodic cognition in appetite regulation. PMID:26447832

  13. Deficits in Long-Term Recognition Memory Reveal Dissociated Subtypes in Congenital Prosopagnosia

    PubMed Central

    Stollhoff, Rainer; Jost, Jürgen; Elze, Tobias; Kennerknecht, Ingo

    2011-01-01

    The study investigates long-term recognition memory in congenital prosopagnosia (CP), a lifelong impairment in face identification that is present from birth. Previous investigations of processing deficits in CP have mostly relied on short-term recognition tests to estimate the scope and severity of individual deficits. We firstly report on a controlled test of long-term (one year) recognition memory for faces and objects conducted with a large group of participants with CP. Long-term recognition memory is significantly impaired in eight CP participants (CPs). In all but one case, this deficit was selective to faces and didn't extend to intra-class recognition of object stimuli. In a test of famous face recognition, long-term recognition deficits were less pronounced, even after accounting for differences in media consumption between controls and CPs. Secondly, we combined test results on long-term and short-term recognition of faces and objects, and found a large heterogeneity in severity and scope of individual deficits. Analysis of the observed heterogeneity revealed a dissociation of CP into subtypes with a homogeneous phenotypical profile. Thirdly, we found that among CPs self-assessment of real-life difficulties, based on a standardized questionnaire, and experimentally assessed face recognition deficits are strongly correlated. Our results demonstrate that controlled tests of long-term recognition memory are needed to fully assess face recognition deficits in CP. Based on controlled and comprehensive experimental testing, CP can be dissociated into subtypes with a homogeneous phenotypical profile. The CP subtypes identified align with those found in prosopagnosia caused by cortical lesions; they can be interpreted with respect to a hierarchical neural system for face perception. PMID:21283572

  14. Deficits in long-term recognition memory reveal dissociated subtypes in congenital prosopagnosia.

    PubMed

    Stollhoff, Rainer; Jost, Jürgen; Elze, Tobias; Kennerknecht, Ingo

    2011-01-25

    The study investigates long-term recognition memory in congenital prosopagnosia (CP), a lifelong impairment in face identification that is present from birth. Previous investigations of processing deficits in CP have mostly relied on short-term recognition tests to estimate the scope and severity of individual deficits. We firstly report on a controlled test of long-term (one year) recognition memory for faces and objects conducted with a large group of participants with CP. Long-term recognition memory is significantly impaired in eight CP participants (CPs). In all but one case, this deficit was selective to faces and didn't extend to intra-class recognition of object stimuli. In a test of famous face recognition, long-term recognition deficits were less pronounced, even after accounting for differences in media consumption between controls and CPs. Secondly, we combined test results on long-term and short-term recognition of faces and objects, and found a large heterogeneity in severity and scope of individual deficits. Analysis of the observed heterogeneity revealed a dissociation of CP into subtypes with a homogeneous phenotypical profile. Thirdly, we found that among CPs self-assessment of real-life difficulties, based on a standardized questionnaire, and experimentally assessed face recognition deficits are strongly correlated. Our results demonstrate that controlled tests of long-term recognition memory are needed to fully assess face recognition deficits in CP. Based on controlled and comprehensive experimental testing, CP can be dissociated into subtypes with a homogeneous phenotypical profile. The CP subtypes identified align with those found in prosopagnosia caused by cortical lesions; they can be interpreted with respect to a hierarchical neural system for face perception.

  15. Forced Treadmill Exercise Prevents Spatial Memory Deficits in Aged Rats Probably Through the Activation of Na(+), K(+)-ATPase in the Hippocampus.

    PubMed

    Vanzella, Cláudia; Sanches, Eduardo Farias; Odorcyk, Felipe Kawa; Nicola, Fabrício; Kolling, Janaína; Longoni, Aline; Dos Santos, Tiago Marcon; Wyse, Angela Terezinha de Souza; Netto, Carlos Alexandre

    2017-02-16

    Regular physical activity has shown to improve the quality of life and to prevent age-related memory deficits. Memory processing requires proper regulation of several enzymes such as sodium-potassium adenosine triphosphatase (Na(+), K(+)-ATPase) and acetylcholinesterase (AChE), which have a pivotal role in neuronal transmission. The present study investigated the effects of a treadmill running protocol in young (3 months), mature (6 months) and aged (22 months) Wistar rats, on: (a) cognitive function, as assessed in the Water maze spatial tasks; (b) Na(+), K(+)-ATPase and AChE activities in the hippocampus following cognitive training alone or treadmill running combined with cognitive training. Animals of all ages were assigned to naïve (with no behavioral or exercise training), sedentary (non-exercised, with cognitive training) and exercised (20 min of daily running sessions, 3 times per week for 4 weeks and with cognitive training) groups. Cognition was assessed by reference and working memory tasks run in the Morris Water maze; 24 h after last session of behavioral testing, hippocampi were collected for biochemical analysis. Results demonstrated that: (a) a moderate treadmill running exercise prevented spatial learning and memory deficits in aged rats; (b) training in the Water maze increased both Na(+), K(+)-ATPase and AChE activities in the hippocampus of mature and aged rats; (c) aged exercised rats displayed an even further increase of Na(+), K(+)-ATPase activity in the hippocampus, (d) enzyme activity correlated with memory performance in aged rats. It is suggested that exercise prevents spatial memory deficits in aged rats probably through the activation of Na(+), K(+)-ATPase in the hippocampus.

  16. Age-Related Changes in 1/f Neural Electrophysiological Noise.

    PubMed

    Voytek, Bradley; Kramer, Mark A; Case, John; Lepage, Kyle Q; Tempesta, Zechari R; Knight, Robert T; Gazzaley, Adam

    2015-09-23

    Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15-53 years) and scalp EEG data from healthy younger (20-30 years) and older (60-70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <-1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. Significance statement: Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise-induced deficits in

  17. Nicotine improves AF64A-induced spatial memory deficits in Morris water maze in rats.

    PubMed

    Yamada, Kazuo; Furukawa, Satoshi; Iwasaki, Tsuneo; Ichitani, Yukio

    2010-01-18

    Ethylcholine mustard aziridinium ion (AF64A) is a neurotoxic derivative of choline that produces not only long-term presynaptic cholinergic deficits, but also various memory deficits in rats similar to some characteristics observed in Alzheimer's disease patients. This study investigated whether nicotine (NCT) administration attenuated spatial learning deficits induced by intracerebroventricular AF64A treatment. AF64A (6 nmol/6 microl)-or saline (SAL)-treated rats were trained in Morris water maze task. NCT (0.025-0.25mg/kg) was subcutaneously injected 5 min before the training every day. The results showed that moderate dose (0.10mg/kg) of NCT attenuated AF64A-induced prolongation of escape latency. Furthermore, NCT dose-dependently recovered the AF64A-induced decrease of time spent in the target quadrant in the probe test. These results suggest that NCT improves AF64A-induced spatial memory deficits, and thus it is a potential therapeutic agent for the treatment of memory deficits in dementia.

  18. Inhibitor of Phosphodiestearse-4 improves memory deficits, oxidative stress, neuroinflammation and neuropathological alterations in mouse models of dementia of Alzheimer's Type.

    PubMed

    Kumar, Amit; Singh, Nirmal

    2017-04-01

    The study investigates the potential of Rolipram a phosphodiesterase-4 inhibitor in cognitive deficits induced by streptozotocin (STZ, 3mg/kg intracerebroventricularly) and natural ageing in mice. Morris water maze (MWM) test was employed to evaluate learning and memory of the animals. Extent of oxidative stress was measured by estimating the levels of brain glutathione (GSH) and thiobarbituric acid reactive species (TBARS). Brain acetylcholinestrase (AChE) activity was also estimated. The brain activity of myeloperoxidase (MPO) was measured as a marker of inflammation. STZ and ageing results in marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ treated mice and aged mice exhibited a marked accentuation of AChE activity, TBARS and MPO activity along with fall in GSH level. Further the stained micrographs of STZ treated mice and aged mice indicate pathological changes, severe neutrophilic infiltration and amyloid deposition. Rolipram treatment significantly attenuated STZ induced and age related memory deficits, biochemical and histopathological alterations. The findings demonstrate the potential of Rolipram in memory dysfunctions which may probably be attributed to its anti-cholinesterase, anti-amyloid, anti-oxidative and anti-inflammatory effects. The study concludes that PDE-4 can be explored as a potential therapeutic target in dementia.

  19. NR2A-Containing NMDARs in the Prefrontal Cortex Are Required for Working Memory and Associated with Age-Related Cognitive Decline.

    PubMed

    McQuail, Joseph A; Beas, B Sofia; Kelly, Kyle B; Simpson, Kailey L; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L

    2016-12-14

    Working memory, the ability to temporarily maintain representational knowledge, is a foundational cognitive process that can become compromised in aging and neuropsychiatric disease. NMDA receptor (NMDAR) activation in prefrontal cortex (PFC) is necessary for the pyramidal neuron activity believed to enable working memory; however, the distinct biophysical properties and localization of NMDARs containing NR2A and NR2B subunits suggest unique roles for NMDAR subtypes in PFC neural activity and working memory. Experiments herein show that working memory depends on NR2A- but not NR2B-NMDARs in PFC of rats and that NR2A-NMDARs mediate the majority of evoked NMDAR currents on layer 2/3 PFC pyramidal neurons. Moreover, attenuated expression of the NR2A but not the NR2B subunit in PFC associates with naturally occurring working memory impairment in aged rats. Finally, NMDAR currents and working memory are enhanced in aged rats by promoting activation of the NR2A-enriched synaptic pool of PFC NMDARs. These results implicate NR2A-NMDARs in normal working memory and suggest novel treatment strategies for improving working memory in cognitive disorders.

  20. Efficiency of the Prefrontal Cortex during Working Memory in Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Sheridan, Margaret A.; Hinshaw, Stephen; D'Esposito, Mark

    2007-01-01

    Objective: Previous research has demonstrated that during task conditions requiring an increase in inhibitory function or working memory, children and adults with attention-deficit/hyperactivity disorder (ADHD) exhibit greater and more varied prefrontal cortical(PFC) activation compared to age-matched control participants. This pattern may reflect…

  1. The Nature of Episodic Memory Deficits in MCI with and without Vascular Burden

    ERIC Educational Resources Information Center

    Villeneuve, Sylvia; Massoud, Fadi; Bocti, Christian; Gauthier, Serge; Belleville, Sylvie

    2011-01-01

    This study measured episodic memory deficits in individuals with mild cognitive impairment (MCI) as a function of their vascular burden. Vascular burden was determined clinically by computing the number of vascular risk factors and diseases and neuroradiologically by assessing the presence and severity of white matter lesions (WML). Strategic…

  2. Congenital Amusia: A Short-Term Memory Deficit for Non-Verbal, but Not Verbal Sounds

    ERIC Educational Resources Information Center

    Tillmann, Barbara; Schulze, Katrin; Foxton, Jessica M.

    2009-01-01

    Congenital amusia refers to a lifelong disorder of music processing and is linked to pitch-processing deficits. The present study investigated congenital amusics' short-term memory for tones, musical timbres and words. Sequences of five events (tones, timbres or words) were presented in pairs and participants had to indicate whether the sequences…

  3. Functional Deficits in Phonological Working Memory in Children with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Schuchardt, Kirsten; Maehler, Claudia; Hasselhorn, Marcus

    2011-01-01

    Recent studies indicate that children with intellectual disabilities have functional limitations primarily in the phonological loop of working memory (Baddeley, 1986). These findings are indicative of a specific structural deficit. Building on this research, the present study examines whether it is possible to identify specific phonological…

  4. Memory Deficits Are Associated with Impaired Ability to Modulate Neuronal Excitability in Middle-Aged Mice

    ERIC Educational Resources Information Center

    Kaczorowski, Catherine C.; Disterhoft, John F.

    2009-01-01

    Normal aging disrupts hippocampal neuroplasticity and learning and memory. Aging deficits were exposed in a subset (30%) of middle-aged mice that performed below criterion on a hippocampal-dependent contextual fear conditioning task. Basal neuronal excitability was comparable in middle-aged and young mice, but learning-related modulation of the…

  5. Working Memory in Down Syndrome: Is There a Dual Task Deficit?

    ERIC Educational Resources Information Center

    Lanfranchi, S.; Baddeley, A.; Gathercole, S.; Vianello, R.

    2012-01-01

    Background: Recent studies have shown that individuals with Down syndrome (DS) are poorer than controls in performing verbal and visuospatial dual tasks. The present study aims at better investigating the dual task deficit in working memory in individuals with DS. Method: Forty-five individuals with DS and 45 typically developing children matched…

  6. Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

    ERIC Educational Resources Information Center

    Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit

    2012-01-01

    Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…

  7. Naringin and Rutin Alleviates Episodic Memory Deficits in Two Differentially Challenged Object Recognition Tasks

    PubMed Central

    Ramalingayya, Grandhi Venkata; Nampoothiri, Madhavan; Nayak, Pawan G.; Kishore, Anoop; Shenoy, Rekha R.; Mallikarjuna Rao, Chamallamudi; Nandakumar, Krishnadas

    2016-01-01

    Background: Cognitive decline or dementia is a debilitating problem of neurological disorders such as Alzheimer's and Parkinson's disease, including special conditions like chemobrain. Dietary flavonoids proved to be efficacious in delaying the incidence of neurodegenerative diseases. Two such flavonoids, naringin (NAR) and rutin (RUT) were reported to have neuroprotective potential with beneficial effects on spatial and emotional memories in particular. However, the efficacy of these flavonoids is poorly understood on episodic memory, which comprises an important form of autobiographical memory. Objective: This study objective is to evaluate NAR and RUT to reverse time-delay-induced long-term and scopolamine-induced short-term episodic memory deficits in Wistar rats. Materials and Methods: We have evaluated both short-term and long-term episodic memory forms using novel object recognition task. Open field paradigm was used to assess locomotor activity for any confounding influence on memory assessment. Donepezil was used as positive control and was effective in both models at 1 mg/kg, i.p. Results: Animals treated with NAR and RUT at 50 and 100 mg/kg, p.o. spent significantly more time exploring novel object compared to familiar one, whereas control animals spent almost equal time with both objects in choice trial. NAR and RUT dose-dependently increased recognition and discriminative indices in time-induced long-term as well as scopolamine-induced short-term episodic memory deficit models without interfering with the locomotor activity. Conclusion: We conclude that, NAR and RUT averted both short- and long-term episodic memory deficits in Wistar rats, which may be potential interventions for neurodegenerative diseases as well as chemobrain condition. SUMMARY Incidence of Alzheimer's disease is increasing globally and the current therapy is only symptomatic. Curative treatment is a major lacuna. NAR and RUT are natural flavonoids proven for their pleiotropic

  8. Working Memory Deficits in Children with Specific Learning Disorders

    ERIC Educational Resources Information Center

    Schuchardt, Kirsten; Maehler, Claudia; Hasselhorn, Marcus

    2008-01-01

    This article examines working memory functioning in children with specific developmental disorders of scholastic skills as defined by ICD-10. Ninety-seven second to fourth graders with a minimum IQ of 80 are compared using a 2 x 2 factorial (dyscalculia vs. no dyscalculia; dyslexia vs. no dyslexia) design. An extensive test battery assesses the…

  9. Episodic memory in transient global amnesia: encoding, storage, or retrieval deficit?

    PubMed Central

    Eustache, F.; Desgranges, B.; Laville, P.; Guillery, B.; Lalevee, C.; Schaeffer, S.; de la Sayette, V.; Iglesias, S.; Baron, J.; Viader, F.

    1999-01-01

    OBJECTIVES—To assess episodic memory (especially anterograde amnesia) during the acute phase of transient global amnesia to differentiate an encoding, a storage, or a retrieval deficit.
METHODS—In three patients, whose amnestic episode fulfilled all current criteria for transient global amnesia, a neuropsychological protocol was administered which included a word learning task derived from the Grober and Buschke's procedure.
RESULTS—In one patient, the results suggested an encoding deficit, and in two others, a storage deficit.
CONCLUSIONS—The encoding/storage impairment concerning anterograde amnesia documented in our patients stands in clear contrast with the impairment in retrieval which must underly the retrograde amnesia that also characterises transient global amnesia. This dissociation in turn favours the idea of a functional independence among the cognitive mechanisms that subserve episodic memory.

 PMID:10071092

  10. Blockade of hippocampal bradykinin B1 receptors improves spatial learning and memory deficits in middle-aged rats.

    PubMed

    Bitencourt, Rafael M; Guerra de Souza, Ana C; Bicca, Maíra A; Pamplona, Fabrício A; de Mello, Nelson; Passos, Giselle F; Medeiros, Rodrigo; Takahashi, Reinaldo N; Calixto, João B; Prediger, Rui D

    2017-01-01

    Previous studies have demonstrated that targeting bradykinin receptors is a promising strategy to counteract the cognitive impairment related with aging and Alzheimer's disease (AD). The hippocampus is critical for cognition, and abnormalities in this brain region are linked to the decline in mental ability. Nevertheless, the impact of bradykinin signaling on hippocampal function is unknown. Therefore, we sought to determine the role of hippocampal bradykinin receptors B1R and B2R on the cognitive decline of middle-aged rats. Twelve-month-old rats exhibited impaired ability to acquire and retrieve spatial information in the Morris water maze task. A single intra-hippocampal injection of the selective B1R antagonist des-Arg(9)-[Leu(8)]-bradykinin (DALBK, 3 nmol), but not the selective B2R antagonist D-Arg-[Hyp(3),Thi(5),D-Tic(7),Oic(8)]-BK (Hoe 140, 3 nmol), reversed the spatial learning and memory deficits on these animals. However, both drugs did not affect the cognitive function in 3-month-old rats, suggesting absence of nootropic properties. Molecular biology analysis revealed an up-regulation of B1R expression in the hippocampal CA1 sub-region and in the pre-frontal cortex of 12-month-old rats, whereas no changes in the B2R expression were observed in middle-aged rats. These findings provide new evidence that inappropriate hippocampal B1R expression and activation exert a critical role on the spatial learning and memory deficits in middle-aged rats. Therefore, selective B1R antagonists, especially orally active non-peptide antagonists, may represent drugs of potential interest to counteract the age-related cognitive decline.

  11. Antiretroviral Non-Adherence is Associated With a Retrieval Profile of Deficits in Verbal Episodic Memory.

    PubMed

    Obermeit, Lisa C; Morgan, Erin E; Casaletto, Kaitlin B; Grant, Igor; Woods, Steven Paul

    2015-01-01

    HIV-associated deficits in verbal episodic memory are commonly associated with antiretroviral non-adherence; however, the specific aspects of memory functioning (e.g., encoding, consolidation, or retrieval) that underlie this established relationship are not well understood. This study evaluated verbal memory profiles of 202 HIV+ participants who underwent a 30-day electronic monitoring of antiretroviral adherence. At the group level, non-adherence was significantly associated with lower scores on immediate and delayed passage recall and word list learning. Retention and recognition of passages and word lists were not related to adherence. Participants were then classified as having either a normal verbal memory profile, a "subcortical" retrieval profile (i.e., impaired free recall with relatively spared recognition), or a "cortical" encoding profile (e.g., cued recall intrusions) based on the Massman et al. ( 1990 ) algorithm for the California Verbal Learning Test. HIV+ participants with a classic retrieval deficit had significantly greater odds of being non-adherent than participants with a normal or encoding profile. These findings suggest that adherence to prescribed antiretroviral regimens may be particularly vulnerable to disruption in HIV+ individuals due to deficits in the complex process of efficiently accessing verbal episodic information with minimal cues. A stronger relationship between non-adherence and passage (vs. word list) recall was also found and may reflect the importance of contextual features in remembering to take medications. Targeted interventions for enhancing and supporting episodic memory retrieval processes may improve antiretroviral adherence and overall health outcomes among persons living with HIV.

  12. Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents.

    PubMed

    Kimani, S; Sinei, K; Bukachi, F; Tshala-Katumbay, D; Maitai, C

    2014-03-01

    Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 μl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F(2, 19) = 4.57 p < 0.05), higher working memory errors (WME) (F(2, 19) = 5.09, p < 0.05) and longer RAM navigation time (F(2, 19) = 3.91, p < 0.05) for NaOCN relative to NaCN and saline treatments. The long-term working memory was significantly impaired by cyanide with fewer correct arm entries (F(2, 19) = 7.45, p < 0.01) and increased working memory errors (F(2, 19) = 9.35 p < 0.05) in NaCN relative to NaOCN or vehicle treated animals. Reference memory was not affected by either cyanide or cyanate. Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate.

  13. Dysfunctions of cerebral networks precede recognition memory deficits in early Parkinson's disease.

    PubMed

    Ibarretxe-Bilbao, Naroa; Zarei, Mojtaba; Junque, Carme; Marti, Maria Jose; Segura, Barbara; Vendrell, Pere; Valldeoriola, Francesc; Bargallo, Nuria; Tolosa, Eduardo

    2011-07-15

    We aimed to investigate changes in the verbal recognition memory network in patients with early Parkinson's disease (PD) without overt recognition memory alteration. Verbal recognition memory was assessed in 24 PD patients in early stages of the disease and a control group of 24 healthy subjects during fMRI data acquisition. Participants were presented with a list of 35 words before imaging, and later during fMRI scanning they were required to recognize these previously presented words. Both model-based (FEAT) and model-free (MELODIC) analyses of the fMRI data were carried out with FSL software. Memory was also assessed by means of Rey's Auditory Verbal Learning Test (RAVLT). PD patients showed no difference in the fMRI recognition memory task and recognition memory assessed by the RAVLT compared to healthy controls. Model-based analysis did not show significant differences between groups. On the other hand, model-free analysis identified components that fitted the task-model and were common to all the participants, as well as components that differed between PD and healthy controls. PD patients showed decreased task-related activations in areas involved in the recognition memory network and decreased task-related deactivations in the default mode network in comparison with controls. In conclusion, model-free fMRI analysis detected alterations in functional cerebral networks involved in a verbal memory task in PD patients without evident recognition memory deficit.

  14. Selectivity of verbal memory deficit in schizophrenic patients and their relatives.

    PubMed

    Toulopoulou, Timothea; Morris, Robin G; Rabe-Hesketh, Sophia; Murray, Robin M

    2003-01-01

    Some of the relatives of people with schizophrenia show impairments of memory and executive function. It is not known, however, whether within these domains there is a class of processes that is especially impaired. Seventy schizophrenic or schizoaffective patients, 115 of their relatives and 66 normal controls underwent a series of assessments evaluating modality specific recall/learning, and aspects of executive functioning, including, planning ability, spatial working memory, strategy formation and rapid mental flexibility. The pattern of performance across cognitive processes was assessed using z-scores that allow direct comparison between tests with different raw score metrics. Selectivity of deficit was evaluated by subtracting the z-score of each cognitive process from the mean of the z-scores of those remaining. Patients performed out worse than controls on most measures, with verbal immediate recall and visual memory/learning the most impaired. Their relatives showed lower scores than controls on verbal and visual memory/learning and strategy formation; verbal memory and strategy formation remained impaired after eliminating those relatives with a psychiatric diagnosis. Consistent with the findings in their schizophrenic kin, healthy relatives also showed disproportionate impairments in verbal immediate recall. Our finding of a selective deficit in verbal memory among relatives suggests that such impairment constitutes a familial, probably genetic, risk factor for schizophrenia.

  15. Visuo-spatial working memory deficits in current and former users of MDMA ('ecstasy').

    PubMed

    Wareing, Michelle; Fisk, John E; Murphy, Philip; Montgomery, Catharine

    2005-03-01

    Verbal working memory and executive deficits have been observed in ecstasy users. The present study sought to establish whether these also extended to visuo-spatial working memory. Thirty-six current ecstasy users, 12 former users (abstinent for at least 6 months) and 31 individuals that had never used ecstasy were tested on a maintenance plus type visuo-spatial working memory task. The task required participants to recall a sequence of specially marked cells in a four-by-four matrix display while at the same time performing a concurrent visual judgement task. Both the current and former user groups registered impairments relative to nonusers. These remained significant following statistical controls for a range of potentially confounding variables including the use of various other drugs during the 3 months prior to testing. Users were unimpaired on a simple spatial span measure suggesting that the deficits observed reflected the executive aspects of the spatial working memory task. Also consistent with executive involvement, statistical controls for measures of verbal working memory performance (computation span) removed half of the ecstasy-related variance in spatial working memory. The possibility that the pattern of results obtained might reflect some general impairment in information processing efficiency is discussed.

  16. LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice.

    PubMed

    Sun, Jun-Jun; Ren, Qing-Guo; Xu, Lin; Zhang, Zhi-Jun

    2015-09-18

    More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain containing NOGO receptor interacting protein 1) has been identified as an inhibitor of oligodendrocyte differentiation and myelination. Using the experimental autoimmune encephalomyelitis (EAE) mouse model, we assessed cognitive function at early and late stages of EAE, determined brain expression of myelin basic protein (MBP) and investigated whether the LINGO-1 antibody could restore deficits in learning and memory and ameliorate any loss of MBP. We found that deficits in learning and memory occurred in late EAE and identified decreased expression of MBP in the parahippocampal cortex (PHC) and fimbria-fornix. Moreover, the LINGO-1 antibody significantly improved learning and memory in EAE and partially restored MBP in PHC. Furthermore, the LINGO-1 antibody activated the AKT/mTOR signaling pathway regulating myelin growth. Our results suggest that demyelination in the PHC and fimbria-fornix might contribute to cognitive deficits and the LINGO-1 antibody could ameliorate these deficits by promoting myelin growth in the PHC. Our research demonstrates that LINGO-1 antagonism may be an effective approach to the treatment of the cognitive impairment of multiple sclerosis patients.

  17. 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.

  18. Visual short-term memory binding deficit in familial Alzheimer's disease

    PubMed Central

    Liang, Yuying; Pertzov, Yoni; Nicholas, Jennifer M.; Henley, Susie M.D.; Crutch, Sebastian; Woodward, Felix; Leung, Kelvin; Fox, Nick C.; Husain, Masud

    2016-01-01

    Long-term episodic memory deficits in Alzheimer's disease (AD) are well characterised but, until recently, short-term memory (STM) function has attracted far less attention. We employed a recently-developed, delayed reproduction task which requires participants to reproduce precisely the remembered location of items they had seen only seconds previously. This paradigm provides not only a continuous measure of localization error in memory, but also an index of relational binding by determining the frequency with which an object is misplaced to the location of one of the other items held in memory. Such binding errors in STM have previously been found on this task to be sensitive to medial temporal lobe (MTL) damage in focal lesion cases. Twenty individuals with pathological mutations in presenilin 1 or amyloid precursor protein genes for familial Alzheimer's disease (FAD) were tested together with 62 healthy controls. Participants were assessed using the delayed reproduction memory task, a standard neuropsychological battery and structural MRI. Overall, FAD mutation carriers were worse than controls for object identity as well as in gross localization memory performance. Moreover, they showed greater misbinding of object identity and location than healthy controls. Thus they would often mislocalize a correctly-identified item to the location of one of the other items held in memory. Significantly, asymptomatic gene carriers – who performed similarly to healthy controls on standard neuropsychological tests – had a specific impairment in object-location binding, despite intact memory for object identity and location. Consistent with the hypothesis that the hippocampus is critically involved in relational binding regardless of memory duration, decreased hippocampal volume across FAD participants was significantly associated with deficits in object-location binding but not with recall precision for object identity or localization. Object-location binding may

  19. Compensation or inhibitory failure? Testing hypotheses of age-related right frontal lobe involvement in verbal memory ability using structural and diffusion MRI.

    PubMed

    Cox, Simon R; Bastin, Mark E; Ferguson, Karen J; Allerhand, Mike; Royle, Natalie A; Maniega, Susanna Muñoz; Starr, John M; MacLullich, Alasdair M J; Wardlaw, Joanna M; Deary, Ian J; MacPherson, Sarah E

    2015-02-01

    Functional neuroimaging studies report increased right prefrontal cortex (PFC) involvement during verbal memory tasks amongst low-scoring older individuals, compared to younger controls and their higher-scoring contemporaries. Some propose that this reflects inefficient use of neural resources through failure of the left PFC to inhibit non-task-related right PFC activity, via the anterior corpus callosum (CC). For others, it indicates partial compensation - that is, the right PFC cannot completely supplement the failing neural network, but contributes positively to performance. We propose that combining structural and diffusion brain MRI can be used to test predictions from these theories which have arisen from fMRI studies. We test these hypotheses in immediate and delayed verbal memory ability amongst 90 healthy older adults of mean age 73 years. Right hippocampus and left dorsolateral prefrontal cortex (DLPFC) volumes, and fractional anisotropy (FA) in the splenium made unique contributions to verbal memory ability in the whole group. There was no significant effect of anterior callosal white matter integrity on performance. Rather, segmented linear regression indicated that right DLPFC volume was a significantly stronger positive predictor of verbal memory for lower-scorers than higher-scorers, supporting a compensatory explanation for the differential involvement of the right frontal lobe in verbal memory tasks in older age.

  20. 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

    Frick, Karyn M

    2012-02-01

    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.

  1. Theory of Mind Deficit versus Faulty Procedural Memory in Autism Spectrum Disorders

    PubMed Central

    Romero-Munguía, Miguel Ángel

    2013-01-01

    Individuals with autism spectrum disorders (ASD) have impairments in social interaction, communicative capacity, and behavioral flexibility (core triad). Three major cognitive theories (theory of mind deficit, weak central coherence, and executive dysfunction) seem to explain many of these impairments. Currently, however, the empathizing-systemizing (a newer version of the theory of mind deficit account) and mnesic imbalance theories are the only ones that attempt to explain all these core triadic symptoms of ASD On the other hand, theory of mind deficit in empathizing-systemizing theory is the most influential account for ASD, but its counterpart in the mnesic imbalance theory, faulty procedural memory, seems to occur earlier in development; consequently, this might be a better solution to the problem of the etiology of ASD, if it truly meets the precedence criterion. Hence, in the present paper I review the reasoning in favor of the theory of mind deficit but with a new interpretation based on the mnesic imbalance theory, which posits that faulty procedural memory causes deficits in several cognitive skills, resulting in poor performance in theory of mind tasks. PMID:23862063

  2. Protective effect of ascorbic acid and Ginkgo biloba against learning and memory deficits caused by fluoride.

    PubMed

    Jetti, Raghu; Raghuveer, C V; Mallikarjuna, Rao C

    2016-01-01

    Fluoride is present in the ground water, World Health Organization permitted level of fluoride in the ground water is 0.5 ppm. Tooth pastes, mouth washes, tea and sea fish are the sources of fluoride. Exposure to these multiple sources results in several adverse effects in addition to the fluorosis. The present study aimed to test the effect of vitamin C and Ginkgo biloba against the behavioural deficits caused by fluoride. Rats were divided into five groups with six animals in each group (n = 6). Control group received ordinary tap water with 0.5 ppm of fluoride, the remaining groups received 100 ppm of fluoride for 30 days prior to fluoride exposure. Two groups of animals received 100 mg/kg body weight of vitamin C and G. biloba for 15 days prior to fluoride exposure. After 45 days, behavioural studies (T-Maze, passive avoidance) were conducted on the experimental animals. The results of the present study showed no behavioural deficits in the control group of animals however, the rats that received fluoride water exhibited impairment in their spatial learning and memory deficits. The deficits are not marked in the vitamin C and G. biloba groups. To conclude chronic exposure to high levels of fluoride causes severe impairment in the spatial learning and memory, these deficits can be ameliorated with the vitamin C and G. biloba.

  3. Explaining semantic short-term memory deficits: Evidence for the critical role of semantic control

    PubMed Central

    Hoffman, Paul; Jefferies, Elizabeth; Lambon Ralph, Matthew A.

    2011-01-01

    Patients with apparently selective short-term memory (STM) deficits for semantic information have played an important role in developing multi-store theories of STM and challenge the idea that verbal STM is supported by maintaining activation in the language system. We propose that semantic STM deficits are not as selective as previously thought and can occur as a result of mild disruption to semantic control processes, i.e., mechanisms that bias semantic processing towards task-relevant aspects of knowledge and away from irrelevant information. We tested three semantic STM patients with tasks that tapped four aspects of semantic control: (i) resolving ambiguity between word meanings, (ii) sensitivity to cues, (iii) ignoring irrelevant information and (iv) detecting weak semantic associations. All were impaired in conditions requiring more semantic control, irrespective of the STM demands of the task, suggesting a mild, but task-general, deficit in regulating semantic knowledge. This mild deficit has a disproportionate effect on STM tasks because they have high intrinsic control demands: in STM tasks, control is required to keep information active when it is no longer available in the environment and to manage competition between items held in memory simultaneously. By re-interpreting the core deficit in semantic STM patients in this way, we are able to explain their apparently selective impairment without the need for a specialised STM store. Instead, we argue that semantic STM patients occupy the mildest end of spectrum of semantic control disorders. PMID:21195105

  4. Theory of Mind Deficit versus Faulty Procedural Memory in Autism Spectrum Disorders.

    PubMed

    Romero-Munguía, Miguel Ángel

    2013-01-01

    Individuals with autism spectrum disorders (ASD) have impairments in social interaction, communicative capacity, and behavioral flexibility (core triad). Three major cognitive theories (theory of mind deficit, weak central coherence, and executive dysfunction) seem to explain many of these impairments. Currently, however, the empathizing-systemizing (a newer version of the theory of mind deficit account) and mnesic imbalance theories are the only ones that attempt to explain all these core triadic symptoms of ASD On the other hand, theory of mind deficit in empathizing-systemizing theory is the most influential account for ASD, but its counterpart in the mnesic imbalance theory, faulty procedural memory, seems to occur earlier in development; consequently, this might be a better solution to the problem of the etiology of ASD, if it truly meets the precedence criterion. Hence, in the present paper I review the reasoning in favor of the theory of mind deficit but with a new interpretation based on the mnesic imbalance theory, which posits that faulty procedural memory causes deficits in several cognitive skills, resulting in poor performance in theory of mind tasks.

  5. Relations between Short-term Memory Deficits, Semantic Processing, and Executive Function

    PubMed Central

    Allen, Corinne M.; Martin, Randi C.; Martin, Nadine

    2012-01-01

    Background Previous research has suggested separable short-term memory (STM) buffers for the maintenance of phonological and lexical-semantic information, as some patients with aphasia show better ability to retain semantic than phonological information and others show the reverse. Recently, researchers have proposed that deficits to the maintenance of semantic information in STM are related to executive control abilities. Aims The present study investigated the relationship of executive function abilities with semantic and phonological short-term memory (STM) and semantic processing in such patients, as some previous research has suggested that semantic STM deficits and semantic processing abilities are critically related to specific or general executive function deficits. Method and Procedures 20 patients with aphasia and STM deficits were tested on measures of short-term retention, semantic processing, and both complex and simple executive function tasks. Outcome and Results In correlational analyses, we found no relation between semantic STM and performance on simple or complex executive function tasks. In contrast, phonological STM was related to executive function performance in tasks that had a verbal component, suggesting that performance in some executive function tasks depends on maintaining or rehearsing phonological codes. Although semantic STM was not related to executive function ability, performance on semantic processing tasks was related to executive function, perhaps due to similar executive task requirements in both semantic processing and executive function tasks. Conclusions Implications for treatment and interpretations of executive deficits are discussed. PMID:22736889

  6. Posttraining Epinephrine Reverses Memory Deficits Produced by Traumatic Brain Injury in Rats

    PubMed Central

    Lorón-Sánchez, Alejandro; Torras-Garcia, Meritxell; Coll-Andreu, Margalida; Costa-Miserachs, David; Portell-Cortés, Isabel

    2016-01-01

    The aim of this research is to evaluate whether posttraining systemic epinephrine is able to improve object recognition memory in rats with memory deficits produced by traumatic brain injury. Forty-nine two-month-old naïve male Wistar rats were submitted to surgical procedures to induce traumatic brain injury (TBI) or were sham-operated. Rats were trained in an object recognition task and, immediately after training, received an intraperitoneal injection of distilled water (Sham-Veh and TBI-Veh group) or 0.01 mg/kg epinephrine (TBI-Epi group) or no injection (TBI-0 and Sham-0 groups). Retention was tested 3 h and 24 h after acquisition. The results showed that brain injury produced severe memory deficits and that posttraining administration of epinephrine was able to reverse them. Systemic administration of distilled water also had an enhancing effect, but of a lower magnitude. These data indicate that posttraining epinephrine and, to a lesser extent, vehicle injection reduce memory deficits associated with TBI, probably through induction of a low-to-moderate emotional arousal. PMID:27127685

  7. CRF₂ receptor-deficiency reduces recognition memory deficits and vulnerability to stress induced by cocaine withdrawal.

    PubMed

    Morisot, Nadège; Le Moine, Catherine; Millan, Mark J; Contarino, Angelo

    2014-12-01

    Psychostimulant drug abuse, dependence and withdrawal are associated with cognitive dysfunction and impact stress-sensitive systems. The corticotropin-releasing factor (CRF) system orchestrates stress responses via CRF1 and CRF2 receptors and is implicated in substance use disorders. However, CRF2 role in psychostimulant drug-induced cognitive dysfunction remains to be elucidated. In the present study, wild-type and CRF2-/- mice are injected with cocaine and memory assessed by the novel object recognition (NOR) task throughout relatively long periods of drug withdrawal. Following recovery from the drug-induced memory deficits, the mice are stressed prior to the NOR task and brain gene expression evaluated by in situ hybridization. Cocaine impairs NOR memory in wild-type and CRF2-/- mice. However, following cocaine withdrawal NOR memory deficits last less time in CRF2-/- than in wild-type mice. Furthermore, a relatively mild stressor induces the re-emergence of NOR deficits in long-term cocaine-withdrawn wild-type but not CRF2-/- mice. Cocaine-withdrawn mice show a genotype-independent higher c-fos expression in the NOR memory-relevant perirhinal cortex than drug-naïve mice. However neither genotype nor drug withdrawal affect the expression of tyrosine hydroxylase in the ventral tegmental area or the locus coeruleus and CRF in the central nucleus of the amygdala or the paraventricular nucleus of the hypothalamus, brain regions implicated in stress and drug responses. These data indicate a new role for the CRF2 receptor in cognitive deficits induced by cocaine withdrawal, both as regards to their duration and their re-induction by stress. Interestingly, prototypical brain stress systems other than CRF do not appear to be involved.

  8. Auraptene consolidates memory, reverses scopolamine-disrupted memory in passive avoidance task, and ameliorates retention deficits in mice

    PubMed Central

    Tabrizian, Kaveh; Yaghoobi, Najmeh Sadat; Iranshahi, Mehrdad; Shahraki, Jafar; Rezaee, Ramin; Hashemzaei, Mahmoud

    2015-01-01

    Objective(s): Auraptene (7-geranyloxycoumarin) (AUR), from Citrus species has shown anti-inflammatory, neuroprotective, and acetylcholinesterase (AChE) and beta-secretase inhibitory effects. Scopolamine is a nonselective muscarinic receptor antagonist which causes short-term memory impairments and is used for inducing animal model of Alzheimer’s disease (AD). This research aimed to investigate the effect of AUR on scopolamine-induced avoidance memory retention deficits in step-through task in mice. Materials and Methods: The effect of four-day pre-training injections of AUR (50, 75, and 100 mg/kg, subcutaneous (SC)) and scopolamine (1 mg/kg, IP), and their co-administration on avoidance memory retention in step-through passive avoidance task, was investigated by measuring the latency to enter to the dark chamber. Results: Pre-training administration of AUR caused significant increase in step-through latency in comparison with control group, 48, 96, and 168 hr after training trial. The findings of this study showed that scopolamine (1 mg/kg, IP, for four consecutive days) impaired passive avoidance memory retention compared to saline-treated animals. Step-through passive avoidance task results showed that AUR markedly reversed scopolamine-induced avoidance memory retention impairments, 24 and 168 hr after training trial in step-through task. Conclusion: Results from co-administration of AUR and scopolamine showed that AUR reversed scopolamine-induced passive avoidance memory retention impairments. PMID:26730337

  9. Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze.

    PubMed

    Sebastian, Veronica; Diallo, Aissatou; Ling, Douglas S F; Serrano, Peter A

    2013-01-01

    Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

  10. Oral administration of grape seed polyphenol extract restores memory deficits in chronic cerebral hypoperfusion rats.

    PubMed

    Chen, Chen; Zheng, Yake; Wu, Tianwen; Wu, Chuanjie; Cheng, Xuan

    2017-04-01

    Chronic cerebral hypoperfusion (CCH) has been recognized as an important cause of both vascular dementia and Alzheimer's disease (AD), the two most prominent neurodegenerative diseases causing memory impairment in the elderly. However, an effective therapy for CCH-induced memory impairment has not yet been established. Grape seed polyphenol extract (GSPE) has powerful antioxidant properties and protects neurons and glia during ischemic injury, but its potential use in the prevention of CCH-induced memory impairment has not yet been investigated. Here, CCH-related memory impairment was modeled in rats using permanent bilateral occlusion of the common carotid artery. A Morris water maze task was used to evaluate memory, the levels of acetylcholinesterase, choline acetyltransferase, acetylcholine were used to evaluate cholinergic function, and oxidative stress was assessed by measuring the enzyme activity of superoxide dismutase, glutathione peroxidase, malonic dialdehyde, and catalase. We found that oral administration of GSPE for 1 month can rescue memory deficits. We also found that GSPE restores cholinergic neuronal function and represses oxidative damage in the hippocampus of CCH rats. We propose that GSPE protects memory in CCH rats by reducing ischemia-induced oxidative stress and cholinergic dysfunction. These findings provide a novel application of GSPE in CCH-related memory impairments.

  11. Inattention, working memory, and academic achievement in adolescents referred for attention deficit/hyperactivity disorder (ADHD).

    PubMed

    Rogers, Maria; Hwang, Heungsun; Toplak, Maggie; Weiss, Margaret; Tannock, Rosemary

    2011-01-01

    This study investigated the role of inattention and working memory in predicting academic achievement in 145 adolescents aged 13 to 18 referred for attention deficit/hyperactivity disorder (ADHD). Path analysis was used to examine whether auditory-verbal and visual-spatial working memory would mediate the relationships between classroom inattention symptoms and achievement outcomes. Results provide support for the mediational model. Behavioral inattention significantly predicted both auditory-verbal and visual-spatial working memory performance. Auditory-verbal working memory was strongly associated with adolescents' achievement in reading and mathematics, while visual-spatial working memory was only associated with achievement in mathematics. The path from inattention symptoms to reading was partially mediated by the working memory variables, but the path from inattention to mathematics was not mediated by working memory. The proposed model demonstrated a good fit to the data and explained a substantial amount of variance in the adolescents' achievement outcomes. These findings imply that working memory is a risk factor for academic failure for adolescents with attentional problems.

  12. 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…

  13. Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice

    PubMed Central

    Beglopoulos, V.; Tulloch, J.; Roe, A. D.; Daumas, S.; Ferrington, L.; Watson, R.; Fan, Z.; Hyman, B. T.; Kelly, P. A. T.; Bard, F.; Morris, R. G. M.

    2016-01-01

    Earlier diagnosis and treatment of Alzheimer's disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory task normally and displaying normal brain glucose uptake, they display faster forgetting after a long delay following performance to a criterion, together with a strong impairment of brain glucose uptake at the time of attempted memory retrieval. Preliminary observations suggest that these deficits, likely caused by an impairment in systems consolidation, could be rescued by immunotherapy with an anti-β-amyloid antibody. Our data suggest a biomarker strategy for the early detection of β-amyloid-related abnormalities. PMID:27249364

  14. Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice.

    PubMed

    Beglopoulos, V; Tulloch, J; Roe, A D; Daumas, S; Ferrington, L; Watson, R; Fan, Z; Hyman, B T; Kelly, P A T; Bard, F; Morris, R G M

    2016-06-01

    Earlier diagnosis and treatment of Alzheimer's disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory task normally and displaying normal brain glucose uptake, they display faster forgetting after a long delay following performance to a criterion, together with a strong impairment of brain glucose uptake at the time of attempted memory retrieval. Preliminary observations suggest that these deficits, likely caused by an impairment in systems consolidation, could be rescued by immunotherapy with an anti-β-amyloid antibody. Our data suggest a biomarker strategy for the early detection of β-amyloid-related abnormalities.

  15. Histamine reverses a memory deficit induced in rats by early postnatal maternal deprivation.

    PubMed

    Benetti, Fernando; da Silveira, Clarice Kras Borges; da Silva, Weber Cláudio; Cammarota, Martín; Izquierdo, Iván

    2012-01-01

    Early partial maternal deprivation causes long-lasting neurochemical, behavioral and brain structural effects. In rats, it causes a deficit in memory consolidation visible in adult life. Some of these deficits can be reversed by donepezil and galantamine, which suggests that they may result from an impairment of brain cholinergic transmission. One such deficit, representative of all others, is an impairment of memory consolidation, clearly observable in a one-trial inhibitory avoidance task. Recent data suggest a role of brain histaminergic systems in the regulation of behavior, particularly inhibitory avoidance learning. Here we investigate whether histamine itself, its analog SKF-91844, or various receptor-selective histamine agonists and antagonists given into the CA1 region of the hippocampus immediately post-training can affect retention of one-trial inhibitory avoidance in rats submitted to early postnatal maternal deprivation. We found that histamine, SKF-91844 and the H2 receptor agonist, dimaprit enhance consolidation on their own and reverse the consolidation deficit induced by maternal deprivation. The enhancing effect of histamine was blocked by the H2 receptor antagonist, ranitidine, but not by the H1 receptor antagonist pyrilamine or by the H3 antagonist thioperamide given into CA1 at doses known to have other behavioral actions, without altering locomotor and exploratory activity or the anxiety state of the animals. The present results suggest that the memory deficit induced by early postnatal maternal deprivation in rats may in part be due to an impairment of histamine mediated mechanisms in the CA1 region of the rat hippocampus.

  16. Xanthoceraside attenuates learning and memory deficits via improving insulin signaling in STZ-induced AD rats.

    PubMed

    Liu, Peng; Zou, Libo; Jiao, Qing; Chi, Tianyan; Ji, Xuefei; Qi, Yue; Xu, Qian; Wang, Lihua

    2013-05-24

    Xanthoceraside, a triterpenoid saponin extracted from the fruit husks of Xanthoceras sorbifolia Bunge, has been shown to reverse the cognitive deficits observed in several Alzheimer's disease (AD) animal models. Increasing evidence suggests the involvement of the insulin signaling pathway in neurodegenerative disorders such as AD. Thus, we used an AD animal model of cognitive impairment induced by the intracerebroventricular (ICV) injection of streptozotocin (STZ) to test the effects of xanthoceraside on behavioral impairments and insulin signaling mechanisms. In our present study, memory impairment was assessed using the Morris water maze test. The expression of IR, IGF-1R and Raf-1/ERK/CREB was tested by western blotting. The STZ group showed memory deficits in the Morris water maze test and significant decreases in IR and IGF-1R protein levels in the hippocampus. Xanthoceraside treatment significantly rescued memory deficits, as well as IR and IGF-1R protein expression levels. STZ inhibited the Ras/ERK signaling cascade and decreased the phosphorylation of CREB; these effects were also attenuated by xanthoceraside treatment. These results suggest the potential use of xanthoceraside for the treatment of neurodegenerative disorders in which brain insulin signaling may be involved.

  17. GLYX-13 (rapastinel) ameliorates subchronic phencyclidine- and ketamine-induced declarative memory deficits in mice.

    PubMed

    Rajagopal, Lakshmi; Burgdorf, Jeffrey S; Moskal, Joseph R; Meltzer, Herbert Y

    2016-02-15

    GLYX-13 (rapastinel), a tetrapeptide (Thr-Pro-Pro-Thr-amide), has been reported to have fast acting antidepressant properties in man based upon its N-methyl-D-aspartate receptor (NMDAR) glycine site functional partial agonism. Ketamine, a non-competitive NMDAR antagonist, also reported to have fast acting antidepressant properties, produces cognitive impairment in rodents and man, whereas rapastinel has been reported to have cognitive enhancing properties in rodents, without impairing cognition in man, albeit clinical testing has been limited. The goal of this study was to compare the cognitive impairing effects of rapastinel and ketamine in novel object recognition (NOR), a measure of declarative memory, in male C57BL/6J mice treated with phencyclidine (PCP), another NMDAR noncompetitive antagonist known to severely impair cognition, in both rodents and man. C57BL/6J mice given a single dose or subchronic ketamine (30 mg/kg.i.p.) showed acute or persistent deficits in NOR, respectively. Acute i.v. rapastinel (1.0 mg/kg), did not induce NOR deficit. Pre-treatment with rapastinel significantly prevented acute ketamine-induced NOR deficit. Rapastinel (1.0 mg/kg, but not 0.3 mg/kg, iv) significantly reversed both subchronic ketamine- and subchronic PCP-induced NOR deficits. Rapastinel also potentiated the atypical antipsychotic drug with antidepressant properties, lurasidone, to restore NOR in subchronic ketamine-treated mice. These findings indicate that rapastinel, unlike ketamine, does not induce a declarative memory deficit in mice, and can prevent or reverse the ketamine-induced NOR deficit. Further study is required to determine if these differences translate during clinical use of ketamine and rapastinel as fast acting antidepressant drugs and if rapastinel could have non-ionotropic effects as an add-on therapy with antipsychotic/antidepressant medications.

  18. GLYX-13 (rapastinel) ameliorates subchronic phencyclidine- and ketamine-induced declarative memory deficits in mice

    PubMed Central

    Rajagopal, Lakshmi; Burgdorf, Jeffrey S.; Moskal, Joseph R.; Meltzer, Herbert Y.

    2016-01-01

    GLYX-13 (rapastinel), a tetrapeptide (Thr-Pro-Pro-Thr-amide), has been reported to have fast acting antidepressant properties in man based upon its N-methyl-d-aspartate receptor (NMDAR) glycine site functional partial agonism. Ketamine, a non-competitive NMDAR antagonist, also reported to have fast acting antidepressant properties, produces cognitive impairment in rodents and man, whereas rapastinel has been reported to have cognitive enhancing properties in rodents, without impairing cognition in man, albeit clinical testing has been limited. The goal of this study was to compare the cognitive impairing effects of rapastinel and ketamine in novel object recognition (NOR), a measure of declarative memory, in male C57BL/6J mice treated with phencyclidine (PCP), another NMDAR noncompetitive antagonist known to severely impair cognition, in both rodents and man. C57BL/6J mice given a single dose or subchronic ketamine (30 mg/kg. i.p.) showed acute or persistent deficits in NOR, respectively. Acute i.v. rapastinel (1.0 mg/kg), did not induce NOR deficit. Pre-treatment with rapastinel significantly prevented acute ketamine-induced NOR deficit. Rapastinel (1.0 mg/kg, but not 0.3 mg/kg, iv) significantly reversed both subchronic ketamine- and subchronic PCP-induced NOR deficits. Rapastinel also potentiated the atypical antipsychotic drug with antidepressant properties, lurasidone, to restore NOR in subchronic ketamine-treated mice. These findings indicate that rapastinel, unlike ketamine, does not induce a declarative memory deficit in mice, and can prevent or reverse the ketamine-induced NOR deficit. Further study is required to determine if these differences translate during clinical use of ketamine and rapastinel as fast acting antidepressant drugs and if rapastinel could have non-ionotropic effects as an add-on therapy with antipsychotic/antidepressant medications. PMID:26632337

  19. Binge drinking during adolescence and young adulthood is associated with deficits in verbal episodic memory.

    PubMed

    Carbia, Carina; Cadaveira, Fernando; Caamaño-Isorna, Francisco; Rodríguez-Holguín, Socorro; Corral, Montse

    2017-01-01

    Binge drinking (BD), a harmful pattern of alcohol consumption, is common during adolescence. Young adults with alcohol use disorders exhibit hippocampal alterations and episodic memory deficits. However, it is not known how these difficulties progress in community BD adolescents. Our objective was to analyze the relationship between BD trajectory and verbal episodic memory during the developmental period spanning from adolescence and to early adulthood. An initial sample of 155 male and female first-year university students with no other risk factors were followed over six years. Participants were classified as stable non-BDs, stable BDs and ex-BDs according to the third AUDIT item. At baseline, participants comprised 36 ♂/ 40 ♀ non-BDs (18.58 years), 40 ♂/ 39 ♀ BDs (18.87 years), and at the third follow-up, they comprised 8 ♂/ 8 ♀ stable non-BDs (25.49 years), 2 ♂/ 2 ♀ stable BDs (25.40) and 8 ♂/ 12 ♀ ex-BDs (24.97 years). Episodic memory was assessed four times with the Logical Memory subtest (WMS-III) and the Rey Auditory Verbal Learning Test (RAVLT). Generalized linear mixed models were applied. The results showed that, relative to non-BDs, stable BDs presented difficulties in immediate and delayed recall in the Logical Memory subtest. These difficulties remained stable over time. The short-term ex-BDs continued to display difficulties in immediate and delayed recall in the Logical Memory subtest, but long-term ex-BDs did not. The effects were not influenced by age of alcohol onset, frequency of cannabis use, tobacco use or psychopathological distress. In conclusion, BD during adolescence and young adulthood is associated with episodic memory deficits. Abandoning the BD pattern may lead to partial recovery. These findings are consistent with the vulnerability of the adolescent hippocampus to the neurotoxic effects of alcohol.

  20. Binge drinking during adolescence and young adulthood is associated with deficits in verbal episodic memory

    PubMed Central

    Cadaveira, Fernando; Caamaño-Isorna, Francisco; Rodríguez-Holguín, Socorro

    2017-01-01

    Binge drinking (BD), a harmful pattern of alcohol consumption, is common during adolescence. Young adults with alcohol use disorders exhibit hippocampal alterations and episodic memory deficits. However, it is not known how these difficulties progress in community BD adolescents. Our objective was to analyze the relationship between BD trajectory and verbal episodic memory during the developmental period spanning from adolescence and to early adulthood. An initial sample of 155 male and female first-year university students with no other risk factors were followed over six years. Participants were classified as stable non-BDs, stable BDs and ex-BDs according to the third AUDIT item. At baseline, participants comprised 36 ♂/ 40 ♀ non-BDs (18.58 years), 40 ♂/ 39 ♀ BDs (18.87 years), and at the third follow-up, they comprised 8 ♂/ 8 ♀ stable non-BDs (25.49 years), 2 ♂/ 2 ♀ stable BDs (25.40) and 8 ♂/ 12 ♀ ex-BDs (24.97 years). Episodic memory was assessed four times with the Logical Memory subtest (WMS-III) and the Rey Auditory Verbal Learning Test (RAVLT). Generalized linear mixed models were applied. The results showed that, relative to non-BDs, stable BDs presented difficulties in immediate and delayed recall in the Logical Memory subtest. These difficulties remained stable over time. The short-term ex-BDs continued to display difficulties in immediate and delayed recall in the Logical Memory subtest, but long-term ex-BDs did not. The effects were not influenced by age of alcohol onset, frequency of cannabis use, tobacco use or psychopathological distress. In conclusion, BD during adolescence and young adulthood is associated with episodic memory deficits. Abandoning the BD pattern may lead to partial recovery. These findings are consistent with the vulnerability of the adolescent hippocampus to the neurotoxic effects of alcohol. PMID:28152062

  1. [Age related macular degeneration].

    PubMed

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  2. Is the frontal dysexecutive syndrome due to a working memory deficit? Evidence from patients with stroke.

    PubMed

    Roussel, Martine; Dujardin, Kathy; Hénon, Hilde; Godefroy, Olivier

    2012-07-01

    Although frontal dysexecutive disorders are frequently considered to be due to working memory deficit, this has not been systematically examined and very little evidence is available for impairment of working memory in frontal damage. The objective of this study was to examine the components of working memory, their anatomy and the relations with executive functions in patients with stroke involving the frontal or posterior cortex. The study population consisted of 29 patients (frontal: n=17; posterior: n=12) and 29 matched controls. Phonological loop (letter and word spans, phonological store; rehearsal process), visuospatial sketchpad (visuospatial span) and the central executive (working memory span, dual task and updating process) were examined. The group comparison analysis showed impairment in the frontal group of: (i) verbal spans (P<0.03); (ii) with a deficit of the rehearsal process (P=0.006); (iii) visuospatial span (P=0.04); (iv) working memory span (P=0.001) that disappeared after controlling for verbal span and (v) running memory (P=0.05) unrelated to updating conditions. The clinical anatomical correlation study showed that impairment of the central executive depended on frontal and posterior lesion. Cognitive dysexecutive disorders were observed in 11/20 patients with central executive deficit and an inverse dissociation was observed in two patients. Receiver operating characteristic curve analysis indicated that cognitive dysexecutive disorders had the highest ability to discriminate frontal lesions (area under curve=0.844, 95% confidence interval: 0.74-0.95; P=0.0001; central executive impairment: area under curve=0.732, 95% confidence interval: 0.57-0.82; P=0.006). This study reveals that frontal lesions induce mild impairment of short-term memory associated with a deficit of the rehearsal process supporting the role of the frontal lobe in this process; the central executive depends on lesions in the frontal lobe and posterior regions accounting

  3. Nitric oxide modulates apomorphine-induced recognition memory deficits in rats.

    PubMed

    Gourgiotis, Ioannis; Kampouri, Nikoletta G; Koulouri, Vasiliki; Lempesis, Ioannis G; Prasinou, Maria D; Georgiadou, Georgia; Pitsikas, Nikolaos

    2012-10-01

    Nitric oxide (NO) is an important intracellular messenger in the brain. The implication of NO in schizophrenia is well documented although it is not yet clear whether net over or underproduction of NO is typical of this disease. In line with this, either NO donors or NO synthase (NOS) inhibitors were found to abolish psychotomimetic effects, including cognition deficits, produced by N-methyl-D-aspartate (NMDA) receptor hypofunction. In addition, there is poor experimental evidence concerning the efficacy of NO to modulate memory deficits produced by dopamine (DA) dysfunction. The present study was designed to investigate the ability of NO modulators (NO donors and NOS inhibitors to reverse recognition memory impairments produced by the DA D(1)/D(2) mixed receptor agonist apomorphine in rats. For these studies, the novel object recognition test (NORT) was used as the memory test. Apomorphine (0.05, 0.1, 0.5 and 1.0 mg/kg), dose-dependently, disrupted performance in this recognition memory procedure in rats. The NO donors molsidomine (2.0 and 4.0 mg/kg) and SNP (0.3 and 1.0 mg/kg), reversed the impairing effects of apomorphine (1.0 mg/kg) in the NORT. Administration of the NOS inhibitors L-NAME (1.0 and 3.0 mg/kg) or 7-NI (1.0 and 3.0 mg/kg) produced similar results. The present findings indicate a) that apomorphine dose-dependently impaired recognition memory and b) that a cognitive deficit produced by DA dysfunction is sensitive to NO.

  4. Inflammation During Gestation Induced Spatial Memory and Learning Deficits: Attenuated by Physical Exercise in Juvenile Rats

    PubMed Central

    Thangarajan, Rajesh; Rai, Kiranmai. S.; Gopalakrishnan, Sivakumar; Perumal, Vivek

    2015-01-01

    Background Gestational infections induced inflammation (GIII) is a cause of various postnatal neurological deficits in developing countries. Such intra uterine insults could result in persistent learning-memory disabilities. There are no studies elucidating the efficacy of adolescence exercise on spatial learning- memory abilities of young adult rats pre-exposed to inflammatory insult during fetal life. Aims and Objectives The present study addresses the efficacy of physical (running) exercise during adolescent period in attenuating spatial memory deficits induced by exposure to GIII in rats. Materials and Methods Pregnant Wistar dams were randomly divided into control and lipopolysaccharide (LPS) groups, injected intra peritoneally (i.p) with saline (0.5ml) or lipopolysaccharide (LPS) (0.5mg/kg) on alternate days from gestation day 14 (GD 14) till delivery. After parturition, pups were divided into 3 groups (n=6/group) a) Sham control and LPS group divided into 2 subgroups- b) LPS and c) LPS exercise group. Running exercise was given only to LPS exercise group during postnatal days (PNDs) 30 to 60 (15min/day). Spatial learning and memory performance was assessed by Morris water maze test (MWM), on postnatal day 61 to 67 in all groups. Results Young rats pre-exposed to GIII and subjected to running exercise through juvenile period displayed significant decrease in latency to reach escape platform and spent significant duration in target quadrant in MWM test, compared to age matched LPS group. Results of the current study demonstrated that exercise through juvenile/adolescent period effectively mitigates gestational inflammation-induced cognitive deficits in young adult rats. Conclusion Inflammation during gestation impairs offspring’s spatial memory and learning abilities. Whereas, early postnatal physical exercise attenuates, to higher extent, cognitive impairment resulted from exposure to LPS induced inflammation during intrauterine growth period. PMID:26266117

  5. Antiretroviral Non-Adherence is Associated with a Retrieval Profile of Deficits in Verbal Episodic Memory

    PubMed Central

    Obermeit, Lisa C.; Morgan, Erin E.; Casaletto, Kaitlin B.; Grant, Igor; Woods, Steven Paul

    2015-01-01

    Objective HIV-associated deficits in verbal episodic memory are commonly associated with antiretroviral non-adherence; however, the specific aspects of memory functioning (e.g., encoding, consolidation, or retrieval) that underlie this established relationship are not well understood. Method This study evaluated verbal memory profiles of 202 HIV+ participants who underwent a 30-day electronic monitoring of antiretroviral adherence. Results At the group level, non-adherence was significantly associated with lower scores on immediate and delayed passage recall and word list learning. Retention and recognition of passages and word lists were not related to adherence. Participants were then classified as having either a normal verbal memory profile, a “subcortical” retrieval profile (i.e., impaired free recall with relatively spared recognition), or a “cortical” encoding profile (e.g., cued recall intrusions) based on the Massman et al. (1990) algorithm for the California Verbal Learning Test. HIV+ participants with a classic retrieval deficit had significantly greater odds of being non-adherent than participants with a normal or encoding profile. Conclusions These findings suggest that adherence to prescribed antiretroviral regimens may be particularly vulnerable to disruption in HIV+ individuals due to deficits in the complex process of efficiently accessing verbal episodic information with minimal cues. A stronger relationship between non-adherence and passage (vs. word list) recall was also found and may reflect the importance of contextual features in remembering to take medications. Targeted interventions for enhancing and supporting episodic memory retrieval processes may improve antiretroviral adherence and overall health outcomes among persons living with HIV. PMID:25781903

  6. Age-Related Changes in Gustatory, Homeostatic, Reward, and Memory Processing of Sweet Taste in the Metabolic Syndrome: An fMRI Study.

    PubMed

    Jacobson, Aaron; Green, Erin; Haase, Lori; Szajer, Jacquelyn; Murphy, Claire

    2017-01-01

    Age affects the human taste system at peripheral and central levels. Metabolic syndrome is a constellation of risk factors (e.g., abdominal obesity and hypertension) that co-occur, increase with age, and heighten risk for cardiovascular disease, diabetes, and cognitive decline. Little is known about how age, metabolic syndrome, and hunger state interact to influence how the brain processes information about taste. We investigated brain activation during the hedonic evaluation of a pleasant, nutritive stimulus (sucrose) within regions critical for taste, homeostatic energy regulation, and reward, as a function of the interactions among age, metabolic syndrome, and hunger condition. We scanned young and elderly adults, half with risk factors associated with metabolic syndrome twice: Once fasted overnight and once after a preload. Functional magnetic resonance imaging data indicated significant effects of age as well as interactive effects with metabolic syndrome and hunger condition. Age-related differences in activation were dependent on the hunger state in regions critical for homoeostatic energy regulation and basic as well as higher order sensory processing and integration. The effects of age and metabolic syndrome on activation in the insula, orbital frontal cortex, caudate, and the hypothalamus may have particularly important implications for taste processing, energy regulation, and dietary choices.

  7. Bangle (Zingiber purpureum) Improves Spatial Learning, Reduces Deficits in Memory, and Promotes Neurogenesis in the Dentate Gyrus of Senescence-Accelerated Mouse P8.

    PubMed

    Nakai, Megumi; Iizuka, Michiro; Matsui, Nobuaki; Hosogi, Kazuko; Imai, Akiko; Abe, Noriaki; Shiraishi, Hisashi; Hirata, Ayumu; Yagi, Yusuke; Jobu, Kohei; Yokota, Junko; Kato, Eishin; Hosoda, Shinya; Yoshioka, Saburo; Harada, Kenichi; Kubo, Miwa; Fukuyama, Yoshiyasu; Miyamura, Mitsuhiko

    2016-05-01

    Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.

  8. Syntactic Versus Memory Accounts of the Sentence Comprehension Deficits of Specific Language Impairment: Looking Back, Looking Ahead

    ERIC Educational Resources Information Center

    Montgomery, James W.; Gillam, Ronald B.; Evans, Julia L.

    2016-01-01

    Purpose: Compared with same-age typically developing peers, school-age children with specific language impairment (SLI) exhibit significant deficits in spoken sentence comprehension. They also demonstrate a range of memory limitations. Whether these 2 deficit areas are related is unclear. The present review article aims to (a) review 2 main…

  9. Neural correlates of visuospatial working memory in attention-deficit/hyperactivity disorder and healthy controls.

    PubMed

    van Ewijk, Hanneke; Weeda, Wouter D; Heslenfeld, Dirk J; Luman, Marjolein; Hartman, Catharina A; Hoekstra, Pieter J; Faraone, Stephen V; Franke, Barbara; Buitelaar, Jan K; Oosterlaan, Jaap

    2015-08-30

    Impaired visuospatial working memory (VSWM) is suggested to be a core neurocognitive deficit in attention-deficit/hyperactivity disorder (ADHD), yet the underlying neural activation patterns are poorly understood. Furthermore, it is unclear to what extent age and gender effects may play a role in VSWM-related brain abnormalities in ADHD. Functional magnetic resonance imaging (fMRI) data were collected from 109 individuals with ADHD (60% male) and 103 controls (53% male), aged 8-25 years, during a spatial span working memory task. VSWM-related brain activation was found in a widespread network, which was more widespread compared with N-back tasks used in the previous literature. Higher brain activation was associated with higher age and male gender. In comparison with controls, individuals with ADHD showed greater activation in the left inferior frontal gyrus (IFG) and the lateral frontal pole during memory load increase, effects explained by reduced activation on the low memory load in the IFG pars triangularis and increased activation during high load in the IFG pars opercularis. Age and gender effects did not differ between controls and individuals with ADHD. Results indicate that individuals with ADHD have difficulty in efficiently and sufficiently recruiting left inferior frontal brain regions with increasing task difficulty.

  10. 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

  11. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

    PubMed Central

    Havekes, Robbert; Park, Alan J; Tudor, Jennifer C; Luczak, Vincent G; Hansen, Rolf T; Ferri, Sarah L; Bruinenberg, Vibeke M; Poplawski, Shane G; Day, Jonathan P; Aton, Sara J; Radwańska, Kasia; Meerlo, Peter; Houslay, Miles D; Baillie, George S; Abel, Ted

    2016-01-01

    Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density. DOI: http://dx.doi.org/10.7554/eLife.13424.001 PMID:27549340

  12. Effects of intracerebroventricular injection of histamine on memory deficits induced by hippocampal lesions in rats.

    PubMed

    Kamei, C; Chen, Z; Nakamura, S; Sugimoto, Y

    1997-05-01

    The influence of bilateral hippocampal lesions on active avoidance response was studied in rats, as well as the effect of intracerebroventricular (i.c.v.) injection of histamine on memory deficits caused by hippocampectomy. Retardation of learning acquisition was produced by lesioning of the bilateral dorsal hippocampus in active avoidance response. Memory retention was also impaired by hippocampectomy. Although locomotor activity and rearing behavior measured by open-field test increased after hippocampal lesions, there was no relation between impairment of learning and increase in exploratory behavior. I.c.v. injection of histamine and i.p. injection of histidine resulted in an improvement of memory deficits (not only learning acquisition but also memory retrieval) induced by hippocampal lesions in rats. Histamine contents of the hippocampus and hypothalamus decreased after hippocampectomy, and a decrease in histamine contents of both areas was restored by histamine (i.c.v.) and histidine (i.p.) injection. In addition, a close relationship was found between decrease in response latency of avoidance response and an increase in histamine content of the hippocampus and hypothalamus after histamine injection.

  13. How Word Reading Skill Impacts Text Memory: The Centrality Deficit and How Domain Knowledge Can Compensate

    PubMed Central

    Miller, Amanda C.; Keenan, Janice M.

    2010-01-01

    We examined text memory in children with word reading deficits to determine how these difficulties impact representations of text meaning. We show that even though children with poor word decoding recall more central than peripheral information, they show a significantly bigger deficit relative to controls on central than on peripheral information. We call this the centrality deficit and argue that it is the consequence of insufficient cognitive resources for connecting ideas together due to these children's resources being diverted from comprehension to word decoding. We investigated a possible compensatory mechanism for making these connections. Because a text representation is a synthesis of text information and a reader's prior knowledge, we hypothesized that having knowledge of the passage topic might reduce or eliminate the centrality deficit. Our results support this knowledge compensation hypothesis: the centrality deficit was evident when poor readers did not have prior knowledge, but was eliminated when they did. This presents an exciting avenue to pursue for possible remediation of reading comprehension in children with word identification difficulties. PMID:19475514

  14. Improvement in γ-hydroxybutyrate-induced contextual fear memory deficit by systemic administration of NCS-382

    PubMed Central

    Ishiwari, Keita

    2016-01-01

    Low, nonsedative doses of γ-hydroxybutyric acid (GHB) produce short-term anterograde amnesia in humans and memory impairments in experimental animals. We have previously shown that acute systemic treatment of GHB in adolescent female rats impairs the acquisition, but not the expression, of contextual fear memory while sparing both the acquisition and the expression of auditory cued fear memory. In the brain, GHB binds to specific GHB-binding sites as well as to γ-aminobutyric acid type B (GABAB) receptors. Although many of the behavioral effects of GHB at high doses have been attributed to its effects on the GABAB receptor, it is unclear which receptor mediates its relatively low-dose memory-impairing effects. The present study examined the ability of the putative GHB receptor antagonist NCS-382 to block the disrupting effects of GHB on fear memory in adolescent rat. Groups of rats received either a single dose of NCS-382 (3–10 mg/kg, intraperitoneally) or vehicle, followed by an injection of either GHB (100 mg/kg, intraperitoneally) or saline. All rats were trained in the fear paradigm, and tested for contextual fear memory and auditory cued fear memory. NCS-382 dose-dependently reversed deficits in the acquisition of contextual fear memory induced by GHB in adolescent rats, with 5 mg/kg of NCS-382 maximally increasing freezing to the context compared with the group administered GHB alone. When animals were tested for cued fear memory, treatment groups did not differ in freezing responses to the tone. These results suggest that low-dose amnesic effects of GHB are mediated by GHB receptors. PMID:27105320

  15. Visual short-term memory deficits associated with GBA mutation and Parkinson's disease.

    PubMed

    Zokaei, Nahid; McNeill, Alisdair; Proukakis, Christos; Beavan, Michelle; Jarman, Paul; Korlipara, Prasad; Hughes, Derralynn; Mehta, Atul; Hu, Michele T M; Schapira, Anthony H V; Husain, Masud

    2014-08-01

    Individuals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene are at significantly high risk of developing Parkinson's disease with cognitive deficit. We examined whether visual short-term memory impairments, long associated with patients with Parkinson's disease, are also present in GBA-positive individuals-both with and without Parkinson's disease. Precision of visual working memory was measured using a serial order task in which participants observed four bars, each of a different colour and orientation, presented sequentially at screen centre. Afterwards, they were asked to adjust a coloured probe bar's orientation to match the orientation of the bar of the same colour in the sequence. An additional attentional 'filtering' condition tested patients' ability to selectively encode one of the four bars while ignoring the others. A sensorimotor task using the same stimuli controlled for perceptual and motor factors. There was a significant deficit in memory precision in GBA-positive individuals-with or without Parkinson's disease-as well as GBA-negative patients with Parkinson's disease, compared to healthy controls. Worst recall was observed in GBA-positive cases with Parkinson's disease. Although all groups were impaired in visual short-term memory, there was a double dissociation between sources of error associated with GBA mutation and Parkinson's disease. The deficit observed in GBA-positive individuals, regardless of whether they had Parkinson's disease, was explained by a systematic increase in interference from features of other items in memory: misbinding errors. In contrast, impairments in patients with Parkinson's disease, regardless of GBA status, was explained by increased random responses. Individuals who were GBA-positive and also had Parkinson's disease suffered from both types of error, demonstrating the worst performance. These findings provide evidence for dissociable signature deficits within the domain of visual short

  16. Clove oil reverses learning and memory deficits in scopolamine-treated mice.

    PubMed

    Halder, Sumita; Mehta, Ashish Krishan; Kar, Rajarshi; Mustafa, Mohammad; Mediratta, Pramod Kumari; Sharma, Krishna Kishore

    2011-05-01

    The present study was performed to examine the effect of Eugenia caryophyllata (Myrtaceae) on learning and memory, and also evaluate whether it can modulate oxidative stress in mice. Passive avoidance step-down task and elevated plus-maze were used to assess learning and memory in scopolamine-treated mice. Oxidative stress parameters were also assessed in brain samples by estimating the malondialdehyde (MDA) and reduced glutathione (GSH) levels at the end of the study. Scopolamine (0.3 mg/kg, i. p.) produced impairment of acquisition memory as evidenced by a decrease in step-down latency and an increase in transfer latency on day 1, and also impairment of retention of memory on day 2. Pretreatment with clove oil (0.05 mL/kg and 0.1 mL/kg) for 3 weeks significantly reversed the increase in acquisition latency and all the doses (0.025, 0.05, 0.1 mL/kg, i. p.) reversed the increase in retention latency induced by scopolamine (0.3 mg/kg, i. p.) in elevated plus-maze. However, 0.05 mL/kg clove oil attenuated memory deficits in the passive avoidance step-down task. Brain samples showed a significant decrease in MDA levels in the group treated with clove oil (0.05 and 0.025 mL/kg). GSH levels were also increased in clove oil-treated mice though the results were not significant. Thus, it can be concluded that clove oil can reverse the short-term and long-term memory deficits induced by scopolamine (0.3 mg/kg, i. p.) and this effect can, to some extent, be attributed to decreased oxidative stress.

  17. Older individuals with HIV infection have greater memory deficits than younger individuals

    PubMed Central

    Tan, IL; Smith, BR; Hammond, E; Vronbrock-Roosa, H; Creighton, JA; Selnes, OA; McArthur, JC; Sacktor, N

    2013-01-01

    Objectives The prevalence of HIV-associated neurocognitive disorder (HAND) remains persistently high in the era of combination anti-retroviral therapy (cART). We aimed to characterize the pattern of neurocognitive dysfunction in older subjects with HAND, in particular amnestic versus non-amnestic impairment. Methods 106 subjects from the Johns Hopkins University NIMH Clinical Outcomes cohort underwent standardized neuropsychological (NP) testing between November 2006 and June 2010. We examined performance in seven cognitive domains (memory, attention, speed of processing, visuospatial, language, motor and executive). Older subjects were defined as age > 50 years at the time of NP testing. Subjects were diagnosed with HAND according to established criteria, and dichotomized into amnestic cognitive impairment or non-amnestic cognitive impairment, with deficit defined as z-scores < −1.5 for the verbal and non-verbal memory domains. Results There were 32 older subjects with a mean age (SD) of 54.2 (2.8) years, and 74 younger subjects, 43.7 (4.3) years. Older age was associated with a 4.8 fold higher odds of memory deficits, adjusted for potential confounders (p=0.035) identified a priori. With age modeled as a continuous covariate, every 1-year increase in age was associated with a 1.11 fold higher odds of memory deficit (p=0.05). Conclusion There was a higher proportion of amnestic cognitive impairment among older subjects than younger subjects with HIV infection. Neurodegenerative processes other than those directly due to HIV may be increasingly important as individuals with chronic HIV infection and HAND survive into older age. PMID:24078559

  18. The Effects of Incentives on Visual-Spatial Working Memory in Children with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Shiels, Keri; Hawk, Larry W., Jr.; Lysczek, Cynthia L.; Tannock, Rosemary; Pelham, William E., Jr.; Spencer, Sarah V.; Gangloff, Brian P.; Waschbusch, Daniel A.

    2008-01-01

    Working memory is one of several putative core neurocognitive processes in attention-deficit/hyperactivity disorder (ADHD). The present work seeks to determine whether visual-spatial working memory is sensitive to motivational incentives, a laboratory analogue of behavioral treatment. Participants were 21 children (ages 7-10) with a diagnosis of…

  19. Serial Order Reconstruction in Down Syndrome: Evidence for a Selective Deficit in Verbal Short-Term Memory

    ERIC Educational Resources Information Center

    Brock, Jon; Jarrold, Christopher

    2005-01-01

    Background: Individuals with Down syndrome consistently perform less well than appropriately matched comparison groups on tests of verbal short-term memory, despite performing relatively well on non-verbal short-term memory tasks. However, it is not clear whether these findings constitute evidence for a selective deficit in verbal short-term…

  20. Chronic administration of quercetin prevent spatial learning and memory deficits provoked by chronic stress in rats.

    PubMed

    Mohammadi, Hadis Said; Goudarzi, Iran; Lashkarbolouki, Taghi; Abrari, Kataneh; Elahdadi Salmani, Mahmoud

    2014-08-15

    There are several reports that cognitive impairment is observed in stress related disorders and chronic stress impairs learning and memory. However, very few studies have looked into the possible ways of preventing this stress-induced deficit. This research study was conducted to evaluate the effects of quercetin, a natural flavonoid, with strong antioxidant and free radical scavenger properties, on chronic stress induced learning and memory deficits and oxidative stress in hippocampus. For chronic stress, rats were restrained daily for 6h/day (from 9:00 to 15:00) for 21 days in well-ventilated plexiglass tubes without access to food and water. The animals were injected with quercetin or vehicle 60 min before restraint stress over a period of 21 days. Then, rats trained with six trials per day for 6 consecutive days in the water maze. On day 28, a probe test was done to measure memory retention. In addition, oxidative stress markers in the hippocampus were evaluated. Results of this study demonstrated that chronic stress exposure rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency and average proximity in probe trial test. Quercetin (50mg/kg) treatment during restraint stress (21 days) markedly decreased escape latency and increased time spent in target quadrant during Morris water maze task. In comparison to vehicle treated group, chronic-stress group had significantly higher malondialdehyde (MDA) levels, significantly higher superoxide dismutase (SOD) activity and significantly lower glutathione peroxidase (GPx) activity in the hippocampus. Quercetin treatment caused a significant decrease in the hippocampus MDA levels and improves SOD and GPx activities in stressed animals. Finally, quercetin significantly decreased plasma corticosterone levels in stressed animals. Based on results of this study, chronic stress has detrimental effects on learning and memory and quercetin treatment

  1. Bacopa monnieri ameliorates memory deficits in olfactory bulbectomized mice: possible involvement of glutamatergic and cholinergic systems.

    PubMed

    Le, Xoan Thi; Pham, Hang Thi Nguyet; Do, Phuong Thi; Fujiwara, Hironori; Tanaka, Ken; Li, Feng; Van Nguyen, Tai; Nguyen, Khoi Minh; Matsumoto, Kinzo

    2013-10-01

    This study investigated the effects of alcoholic extract of Bacopa monnieri (L.) Wettst. (BM) on cognitive deficits using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its action. OBX mice were treated daily with BM (50 mg/kg, p.o.) or a reference drug, tacrine (2.5 mg/kg, i.p.), 1 week before and continuously 3 days after OBX. Cognitive performance of the animals was analyzed by the novel object recognition test, modified Y maze test, and fear conditioning test. Brain tissues of OBX animals were used for neurochemical and immunohistochemical studies. OBX impaired non-spatial short-term memory, spatial working memory, and long-term fair memory. BM administration ameliorated these memory disturbances. The effect of BM on short-term memory deficits was abolished by a muscarinic receptor antagonist, scopolamine. OBX downregulated phosphorylation of synaptic plasticity-related signaling proteins: NR1 subunit of N-methyl-D-aspartate receptor, glutamate receptor 1 (GluR1), and calmodulin-dependent kinase II but not cyclic AMP-responsive element binding protein (CREB), and reduced brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. OBX also reduced choline acetyltransferase in the hippocampus and cholinergic neurons in the medial septum, and enlarged the size of lateral ventricle. BM administration reversed these OBX-induced neurochemical and histological alterations, except the decrease of GluR1 phosphorylation, and enhanced CREB phosphorylation. Moreover, BM treatment inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BM treatment ameliorates OBX-induced cognition dysfunction via a mechanism involving enhancement of synaptic plasticity-related signaling and BDNF transcription and protection of cholinergic systems from OBX-induced neuronal damage.

  2. Reduced ERPs and theta oscillations underlie working memory deficits in Toxoplasma gondii infected seniors.

    PubMed

    Gajewski, Patrick D; Falkenstein, Michael; Hengstler, Jan G; Golka, Klaus

    2016-10-01

    Toxoplasma gondii is one of the most widespread infections in humans. Recent studies give evidence for memory deficits in infected older adults. To investigate working memory dysfunction in infected elderly, a double-blinded electrophysiological study was conducted. 84 persons derived from a sample of 131 healthy participants with the mean age of 70 years were assigned to two groups of 42 non-infected and 42 infected individuals. The outcome measures were behavioral performance, target and response-related ERPs, and time-frequency wavelets during performance in a n-back working-memory task. The infected individuals showed a reduced rate of detected targets and diminished P3b amplitude both in target-locked as well as response-locked data compared to the non-infected group. Time-frequency decomposition of the EEG-signals revealed lower evoked power in the theta frequency range in the target-locked as well as in the response-locked data in infected individuals. The reported effects were comparable with differences between healthy young and old adults described previously. Taking together, the reduced working-memory performance accompanied by an attenuated P3b and frontal theta activity may suggest neurotransmitter imbalance like dopamine and norepinephrine in T. gondii infected individuals. In face of a high prevalence of T. gondii infection and the increasing ratio of older population their accelerated memory decline may have substantial socioeconomic consequences.

  3. Aerobic exercise attenuates inhibitory avoidance memory deficit induced by paradoxical sleep deprivation in rats.

    PubMed

    Fernandes, Jansen; Baliego, Luiz Guilherme Zaccaro; Peixinho-Pena, Luiz Fernando; de Almeida, Alexandre Aparecido; Venancio, Daniel Paulino; Scorza, Fulvio Alexandre; de Mello, Marco Tulio; Arida, Ricardo Mario

    2013-09-05

    The deleterious effects of paradoxical sleep deprivation (SD) on memory processes are well documented. Physical exercise improves many aspects of brain functions and induces neuroprotection. In the present study, we investigated the influence of 4 weeks of treadmill aerobic exercise on both long-term memory and the expression of synaptic proteins (GAP-43, synapsin I, synaptophysin, and PSD-95) in normal and sleep-deprived rats. Adult Wistar rats were subjected to 4 weeks of treadmill exercise training for 35 min, five times per week. Twenty-four hours after the last exercise session, the rats were sleep-deprived for 96 h using the modified multiple platform method. To assess memory after SD, all animals underwent training for the inhibitory avoidance task and were tested 24h later. The aerobic exercise attenuated the long-term memory deficit induced by 96 h of paradoxical SD. Western blot analysis of the hippocampus revealed increased levels of GAP-43 in exercised rats. However, the expression of synapsin I, synaptophysin, and PSD-95 was not modified by either exercise or SD. Our results suggest that an aerobic exercise program can attenuate the deleterious effects of SD on long-term memory and that this effect is not directly related to changes in the expression of the pre- and post-synaptic proteins analyzed in the study.

  4. Characteristics of prospective memory deficits in HIV-seropositive substance-dependent individuals: preliminary observations.

    PubMed

    Martin, Eileen M; Nixon, Heather; Pitrak, David L; Weddington, William; Rains, Niles A; Nunnally, Gerald; Grbesic, Silvana; Gonzalez, Raul; Jacobus, Joanna; Bechara, Antoine

    2007-07-01

    The construct of "prospective memory" (PM) refers to a type of episodic memory for a future intention or "remembering what one must do." This function has been proposed as a candidate mechanism underlying behaviors of critical importance in HIV disease, including adherence with medication regimens and continued engagement in risk behavior. We administered tasks of time-based and event-based prospective memory and control tasks of retrospective and working memory to 31 HIV-seropositive and 35 HIV-seronegative substance-dependent individuals (SDIs). We found that compared with HIV- controls HIV+ participants showed deficits in time-based but not event-based PM. Retrospective, but not working, memory performance correlated significantly with time-based PM performance. In addition, performance on the time-based PM task was a significant predictor of scores on a self-report measure of risky sexual and injection practices. These preliminary data provide new and unique findings regarding the components of executive function mediated by prefrontal cortical systems that are impaired among HIV+ SDIs and their relevance to "real-world" behaviors.

  5. Experimental sleep deprivation as a tool to test memory deficits in rodents

    PubMed Central

    Colavito, Valeria; Fabene, Paolo F.; Grassi-Zucconi, Gigliola; Pifferi, Fabien; Lamberty, Yves; Bentivoglio, Marina; Bertini, Giuseppe

    2013-01-01

    Paradigms of sleep deprivation (SD) and memory testing in rodents (laboratory rats and mice) are here reviewed. The vast majority of these studies have been aimed at understanding the contribution of sleep to cognition, and in particular to memory. Relatively little attention, instead, has been devoted to SD as a challenge to induce a transient memory impairment, and therefore as a tool to test cognitive enhancers in drug discovery. Studies that have accurately described methodological aspects of the SD protocol are first reviewed, followed by procedures to investigate SD-induced impairment of learning and memory consolidation in order to propose SD protocols that could be employed as cognitive challenge. Thus, a platform of knowledge is provided for laboratory protocols that could be used to assess the efficacy of drugs designed to improve memory performance in rodents, including rodent models of neurodegenerative diseases that cause cognitive deficits, and Alzheimer's disease in particular. Issues in the interpretation of such preclinical data and their predictive value for clinical translation are also discussed. PMID:24379759

  6. Selective deficit of spatial short-term memory: Role of storage and rehearsal mechanisms.

    PubMed

    Bonnì, Sonia; Perri, Roberta; Fadda, Lucia; Tomaiuolo, Francesco; Koch, Giacomo; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

    2014-10-01

    We report the neuropsychological and MRI investigation of a patient (GP) who developed a selective impairment of spatial short-term memory (STM) following damage to the dorso-mesial areas of the right frontal lobe. We assessed in this patient spatial STM with an experimental procedure that evaluated immediate and 5-20 s delayed recall of verbal, visual and spatial stimuli. The patient scored significantly worse than normal controls on tests that required delayed recall of spatial data. This could not be ascribed to a deficit of spatial episodic long-term memory because amnesic patients performed normally on these tests. Conversely, the patient scored in the normal range on tests of immediate recall of verbal, visual and spatial data and tests of delayed recall of verbal and visual data. Comparison with a previously described patient who had a selective deficit in immediate spatial recall and an ischemic lesion that affected frontal and parietal dorso-mesial areas in the right hemisphere (Carlesimo GA, Perri R, Turriziani P, Tomaiuolo F, Caltagirone C. Remembering what but not where: independence of spatial and visual working memory in the human brain. Cortex. 2001 Sep; 37(4):519-34) suggests that the right parietal areas are involved in the short-term storage of spatial information and that the dorso-mesial regions of the right frontal underlie mechanisms for the delayed maintenance of the same data.

  7. Intracranial electrode implantation produces regional neuroinflammation and memory deficits in rats

    SciTech Connect

    Kuttner-Hirshler, Y.; Biegon, A.; Kuttner-Hirshler, Y.; Polat, U.; Biegon, A.

    2009-12-21

    Deep brain stimulation (DBS) is an established treatment for advanced Parkinson's disease (PD). The procedure entails intracranial implantation of an electrode in a specific brain structure followed by chronic stimulation. Although the beneficial effects of DBS on motor symptoms in PD are well known, it is often accompanied by cognitive impairments, the origin of which is not fully understood. To explore the possible contribution of the surgical procedure itself, we studied the effect of electrode implantation in the subthalamic nucleus (STN) on regional neuroinflammation and memory function in rats implanted bilaterally with stainless steel electrodes. Age-matched sham and intact rats were used as controls. Brains were removed 1 or 8 weeks post-implantation and processed for in vitro autoradiography with [(3)H]PK11195, an established marker of microglial activation. Memory function was assessed by the novel object recognition test (ORT) before surgery and 2 and 8 weeks after surgery. Electrode implantation produced region-dependent changes in ligand binding density in the implanted brains at 1 as well as 8 weeks post-implantation. Cortical regions showed more intense and widespread neuroinflammation than striatal or thalamic structures. Furthermore, implanted animals showed deficits in ORT performance 2 and 8 weeks post-implantation. Thus, electrode implantation resulted in a widespread and persistent neuroinflammation and sustained memory impairment. These results suggest that the insertion and continued presence of electrodes in the brain, even without stimulation, may lead to inflammation-mediated cognitive deficits in susceptible individuals, as observed in patients treated with DBS.

  8. Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny.

    PubMed

    Wimmer, M E; Briand, L A; Fant, B; Guercio, L A; Arreola, A C; Schmidt, H D; Sidoli, S; Han, Y; Garcia, B A; Pierce, R C

    2017-02-21

    Paternal environmental perturbations including exposure to drugs of abuse can produce profound effects on the physiology and behavior of offspring via epigenetic modifications. Here we show that adult drug-naive male offspring of cocaine-exposed sires have memory formation deficits and associated reductions in NMDA receptor-mediated hippocampal synaptic plasticity. Reduced levels of the endogenous NMDA receptor co-agonist d-serine were accompanied by increased expression of the d-serine degrading enzyme d-amino acid oxidase (Dao1) in the hippocampus of cocaine-sired male progeny. Increased Dao1 transcription was associated with enrichment of permissive epigenetic marks on histone proteins in the hippocampus of male cocaine-sired progeny, some of which were enhanced near the Dao1 locus. Finally, hippocampal administration of d-serine reversed both the memory formation and synaptic plasticity deficits. Collectively, these results demonstrate that paternal cocaine exposure produces epigenetic remodeling in the hippocampus leading to NMDA receptor-dependent memory formation and synaptic plasticity impairments only in male progeny, which has significant implications for the male descendants of chronic cocaine users.Molecular Psychiatry advance online publication, 21 February 2017; doi:10.1038/mp.2017.8.

  9. 1'-Acetoxychavicol acetate ameliorates age-related spatial memory deterioration by increasing serum ketone body production as a complementary energy source for neuronal cells.

    PubMed

    Kojima-Yuasa, Akiko; Yamamoto, Tomiya; Yaku, Keisuke; Hirota, Shiori; Takenaka, Shigeo; Kawabe, Kouichi; Matsui-Yuasa, Isao

    2016-09-25

    1'-Acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Alpinia galangal. Here, we examined the effect of ACA on learning and memory in senescence-accelerated mice prone 8 (SAMP8). In mice that were fed a control diet containing 0.02% ACA for 25 weeks, the learning ability in the Morris water maze test was significantly enhanced in comparison with mice that were fed the control diet alone. In the Y-maze test, SAMP8 mice showed decreased spontaneous alterations in comparison with senescence-accelerated resistant/1 (SAMR1) mice, a homologous control, which was improved by ACA pretreatment. Serum metabolite profiles were obtained by GC-MS analysis, and each metabolic profile was plotted on a 3D score plot. Based upon the diagram, it can be seen that the distribution areas for the three groups were completely separate. Furthermore, the contents of β-hydroxybutyric acid and palmitic acid in the serum of SAMP8-ACA mice were higher than those of SAMP8-control mice and SAMR1-control mice. We also found that SAMR1 mice did not show histological abnormalities, whereas histological damage in the CA1 region of the hippocampus in SAMP8-control mice was observed. However, SAMP8-ACA mice were observed in a similar manner as SAMR1 mice. These findings confirm that ACA increases the serum concentrations of β-hydroxybutyric acid and palmitic acid levels and thus these fuels might contribute to the maintenance of the cognitive performance of SAMP8 mice.

  10. Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model.

    PubMed

    Ponce-Lopez, Teresa; Liy-Salmeron, Gustavo; Hong, Enrique; Meneses, Alfredo

    2011-12-02

    Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3β (p-GSK3β) and total GSK3β levels were determined, and importantly GSK3β regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3β levels, while total GSK3β did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3β levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of

  11. Characterising subtypes of hippocampal sclerosis and reorganisation: Correlation with pre and post-operative memory deficit.

    PubMed

    Prada Jardim, Anaclara; Liu, Joan; Baber, Jack; Michalak, Zuzanna; Reeves, Cheryl; Ellis, Matthew; Novy, Jan; de Tisi, Jane; McEvoy, Andrew; Miserocchi, Anna; Targas Yacubian, Elza Marcia; Sisodiya, Sanjay; Thompson, Pamela; Thom, Maria

    2017-04-05

    Neuropathological subtypes of hippocampal sclerosis (HS) in temporal lobe epilepsy (2013 ILAE classification) are based on the qualitative assessment of patterns of neuronal loss with NeuN. In practice, some cases appear indeterminate between type 1 (CA1 and CA4 loss) and type 2 HS (CA1 loss) and we predicted that MAP2 would enable a more stringent classification. HS subtypes, as well as the accompanying alteration of axonal networks, regenerative capacity and neurodegeneration have been previously correlated with outcome and memory deficits and may provide prognostic clinical information. We selected 92 cases: 52 type 1 HS, 15 type 2 HS, 18 Indeterminate-HS and 7 no-HS. Quantitative analysis was carried out on NeuN and MAP2 stained sections and a labelling index (LI) calculated for six hippocampal subfields. We also evaluated hippocampal regenerative activity (MCM2, nestin, olig2, calbindin), degeneration (AT8/phosphorylated tau) and mossy-fibre pathway re-organisation (ZnT3). Pathology measures were correlated with clinical epilepsy history, memory and naming test scores and post-operative outcomes, at one year following surgery. MAP2 LI in Indeterminate-HS was statistically similar to type 2 HS but this clustering was not shown with NeuN. Moderate verbal and visual memory deficits were noted in all HS types, including 54% and 69% of type 2 HS. Memory deficits correlated with several pathology factors including lower NeuN or MAP2 LI in CA4, CA1, dentate gyrus and subiculum and poor preservation of the mossy fibre pathway. Decline in memory at one year associated with AT8 labelling in the subiculum and dentate gyrus but not HS type. We conclude that MAP2 is a helpful addition in the classification of HS in some cases. Classification of HS subtype, however, did not significantly correlate with outcome or pre or post-operative memory dysfunction, which was associated with multiple pathology factors including hippocampal axonal pathways, regenerative capacity and

  12. Working Memory Deficits in Children with Reading Difficulties: Memory Span and Dual Task Coordination

    ERIC Educational Resources Information Center

    Wang, Shinmin; Gathercole, Susan E.

    2013-01-01

    The current study investigated the cause of the reported problems in working memory in children with reading difficulties. Verbal and visuospatial simple and complex span tasks, and digit span and reaction times tasks performed singly and in combination, were administered to 46 children with single word reading difficulties and 45 typically…

  13. Impaired encoding of rapid pitch information underlies perception and memory deficits in congenital amusia

    PubMed Central

    Albouy, Philippe; Cousineau, Marion; Caclin, Anne; Tillmann, Barbara; Peretz, Isabelle

    2016-01-01

    Recent theories suggest that the basis of neurodevelopmental auditory disorders such as dyslexia or specific language impairment might be a low-level sensory dysfunction. In the present study we test this hypothesis in congenital amusia, a neurodevelopmental disorder characterized by severe deficits in the processing of pitch-based material. We manipulated the temporal characteristics of auditory stimuli and investigated the influence of the time given to encode pitch information on participants’ performance in discrimination and short-term memory. Our results show that amusics’ performance in such tasks scales with the duration available to encode acoustic information. This suggests that in auditory neuro-developmental disorders, abnormalities in early steps of the auditory processing can underlie the high-level deficits (here musical disabilities). Observing that the slowing down of temporal dynamics improves amusics’ pitch abilities allows considering this approach as a potential tool for remediation in developmental auditory disorders. PMID:26732511

  14. Tau Reduction Diminishes Spatial Learning and Memory Deficits after Mild Repetitive Traumatic Brain Injury in Mice

    PubMed Central

    Cheng, Jason S.; Craft, Ryan; Yu, Gui-Qiu; Ho, Kaitlyn; Wang, Xin; Mohan, Geetha; Mangnitsky, Sergey; Ponnusamy, Ravikumar; Mucke, Lennart

    2014-01-01

    Objective Because reduction of the microtubule-associated protein Tau has beneficial effects in mouse models of Alzheimer's disease and epilepsy, we wanted to determine whether this strategy can also improve the outcome of mild traumatic brain injury (TBI). Methods We adapted a mild frontal impact model of TBI for wildtype C57Bl/6J mice and characterized the behavioral deficits it causes in these animals. The Barnes maze, Y maze, contextual and cued fear conditioning, elevated plus maze, open field, balance beam, and forced swim test were used to assess different behavioral functions. Magnetic resonance imaging (MRI, 7 Tesla) and histological analysis of brain sections were used to look for neuropathological alterations. We also compared the functional effects of this TBI model and of controlled cortical impact in mice with two, one or no Tau alleles. Results Repeated (2-hit), but not single (1-hit), mild frontal impact impaired spatial learning and memory in wildtype mice as determined by testing of mice in the Barnes maze one month after the injury. Locomotor activity, anxiety, depression and fear related behaviors did not differ between injured and sham-injured mice. MRI imaging did not reveal focal injury or mass lesions shortly after the injury. Complete ablation or partial reduction of tau prevented deficits in spatial learning and memory after repeated mild frontal impact. Complete tau ablation also showed a trend towards protection after a single controlled cortical impact. Complete or partial reduction of tau also reduced the level of axonopathy in the corpus callosum after repeated mild frontal impact. Interpretation Tau promotes or enables the development of learning and memory deficits and of axonopathy after mild TBI, and tau reduction counteracts these adverse effects. PMID:25551452

  15. Pesticides induce spatial memory deficits with synaptic impairments and an imbalanced tau phosphorylation in rats.

    PubMed

    Chen, Ning-Ning; Luo, Dan-Ju; Yao, Xiu-Qing; Yu, Cong; Wang, Yi; Wang, Qun; Wang, Jian-Zhi; Liu, Gong-Ping

    2012-01-01

    Pesticides are widely used in agriculture, and epidemiological studies suggest that pesticide exposure is a risk factor for Alzheimer's disease (AD), but the mechanisms are elusive. Here, we studied the effects of pesticide exposure on the cognitive ability and the underlying mechanisms in rats. Deltamethrin and carbofuran were administered respectively into the rats once a day for 28 days by gavage. We found that pesticide exposure induced spatial learning and memory deficits with a simultaneous decrease of N-methyl-D-aspartate receptor 1, synaptophysin, and synapsin I, all of which are memory-related synaptic proteins. Pesticide exposure also induced tau hyperphosphorylation at multiple AD-related phosphorylation sites with activation of glycogen synthase kinase-3β and inhibition of protein phosphatase-2A. Additionally, neuron loss in the hippocampus and cortex was observed upon administration of the pesticides. These results indicate that the pesticides exposure could induce AD-like pathology and cognitive abnormality in rats.

  16. Early hippocampal volume loss as a marker of eventual memory deficits caused by repeated stress

    PubMed Central

    Rahman, Mohammed Mostafizur; Callaghan, Charlotte K.; Kerskens, Christian M.; Chattarji, Sumantra; O’Mara, Shane M.

    2016-01-01

    Exposure to severe and prolonged stress has detrimental effects on the hippocampus. However, relatively little is known about the gradual changes in hippocampal structure, and its behavioral consequences, over the course of repeated stress. Behavioral analyses during 10 days of chronic stress pointed to a delayed decline in spatial memory, the full impact of which is evident only after the end of stress. In contrast, concurrent volumetric measurements in the same animals revealed significant reduction in hippocampal volumes in stressed animals relative to their unstressed counterparts, as early as the third day of stress. Notably, animals that were behaviorally the worst affected at the end of chronic stress suffered the most pronounced early loss in hippocampal volume. Together, these findings support the view that not only is smaller hippocampal volume linked to stress-induced memory deficits, but it may also act as an early risk factor for the eventual development of cognitive impairments seen in stress-related psychiatric disorders. PMID:27374165

  17. Spontaneous Strategy Use Protects Against Visual Working Memory Deficits in Older Adults Infected with HIV

    PubMed Central

    Woods, Steven Paul; Weber, Erica; Cameron, Marizela V.; Dawson, Matthew S.; Delano-Wood, Lisa; Bondi, Mark W.; Grant, Igor

    2010-01-01

    Recent studies suggest that older human immunodeficiency virus (HIV)-infected adults are at particular risk for HIV-associated neurocognitive disorders (HAND), including dementia. Deficits in attention/working memory are posited to play a central role in the development of HAND among older adults. The aim of the present study was to examine the possible protective benefits of spontaneous strategy use during a visual working memory task in 46 older and 42 younger adults infected with HIV. Results revealed a significant interaction between age and strategy use, with older adults who used a meta-cognitive strategy demonstrating superior working memory performance versus non-strategy users. This effect was not observed in the younger HIV-infected sample and was not better explained by possible confounding factors, such as education, comorbid medical conditions, or HIV disease severity. Within the older group, strategy use was associated with better executive functions and higher estimated verbal intelligence. Findings from this study suggest that working memory declines in older HIV-infected adults are moderated by the use of higher-level mnemonic strategies and may inform cognitive neurorehabilitation efforts to improve cognitive and everyday functioning outcomes in older persons living with HIV infection. PMID:20876195

  18. Working memory deficits in developmental dyscalculia: The importance of serial order.

    PubMed

    Attout, Lucie; Majerus, Steve

    2015-01-01

    Although a number of studies suggests a link between working memory (WM) storage capacity of short-term memory and calculation abilities, the nature of verbal WM deficits in children with developmental dyscalculia (DD) remains poorly understood. We explored verbal WM capacity in DD by focusing on the distinction between memory for item information (the items to be retained) and memory for order information (the order of the items within a list). We hypothesized that WM for order could be specifically related to impaired numerical abilities given that recent studies suggest close interactions between the representation of order information in WM and ordinal numerical processing. We investigated item and order WM abilities as well as basic numerical processing abilities in 16 children with DD (age: 8-11 years) and 16 typically developing children matched on age, IQ, and reading abilities. The DD group performed significantly poorer than controls in the order WM condition but not in the item WM condition. In addition, the DD group performed significantly slower than the control group on a numerical order judgment task. The present results show significantly reduced serial order WM abilities in DD coupled with less efficient numerical ordinal processing abilities, reflecting more general difficulties in explicit processing of ordinal information.

  19. Spontaneous strategy use protects against visual working memory deficits in older adults infected with HIV.

    PubMed

    Woods, Steven Paul; Weber, Erica; Cameron, Marizela V; Dawson, Matthew S; Delano-Wood, Lisa; Bondi, Mark W; Grant, Igor

    2010-12-01

    Recent studies suggest that older human immunodeficiency virus (HIV)-infected adults are at particular risk for HIV-associated neurocognitive disorders (HAND), including dementia. Deficits in attention/working memory are posited to play a central role in the development of HAND among older adults. The aim of the present study was to examine the possible protective benefits of spontaneous strategy use during a visual working memory task in 46 older and 42 younger adults infected with HIV. Results revealed a significant interaction between age and strategy use, with older adults who used a meta-cognitive strategy demonstrating superior working memory performance versus non-strategy users. This effect was not observed in the younger HIV-infected sample and was not better explained by possible confounding factors, such as education, comorbid medical conditions, or HIV disease severity. Within the older group, strategy use was associated with better executive functions and higher estimated verbal intelligence. Findings from this study suggest that working memory declines in older HIV-infected adults are moderated by the use of higher-level mnemonic strategies and may inform cognitive neurorehabilitation efforts to improve cognitive and everyday functioning outcomes in older persons living with HIV infection.

  20. Memory Deficit is Associated with Worse Functional Trajectories Among Older Adults in Low Vision Rehabilitation for Macular Disease

    PubMed Central

    Whitson, Heather E.; Whitaker, Diane; Sanders, Linda L.; Potter, Guy G.; Cousins, Scott W.; Ansah, Deidra; McConnell, Eleanor; Pieper, Carl F.; Landerman, Lawrence; Steffens, David C.; Cohen, Harvey J.

    2012-01-01

    Objectives Older adults with macular disease are at increased risk of memory decline and incident dementia. Low vision rehabilitation (LVR) aims to preserve independence in people with irreversible vision loss, but comorbid memory problems could limit the success of rehabilitation. This study examined whether performance on a brief memory test is related to functional outcomes among older patients undergoing LVR for macular disease. Design Observational cohort study of patients receiving outpatient LVR Setting Academic center Participants 91 seniors (average age 80.1 years) with macular disease Measurements Memory was assessed at baseline with a 10-word list; memory deficit was defined as immediate recall of ≤ two words. Vision-related function was measured with the 25-item Visual Function Questionnaire (VFQ-25)administered at baseline and during subsequent interviews (mean length of follow up = 115 days). Linear mixed models (LMMs) were constructed to compare average trajectories of four VFQ-25 subscales: near activities, distance activities, dependency, and role difficulty. Results The 29.7% of patients with memory deficit tended to decline in ability to accomplish activities that involve near vision. Controlling for age, sex, and education, the functional trajectory of participants with memory deficit differed significantly from that of participants with better memory (p=0.002), who tended to report improvements in ability to accomplish near activities. Conclusion Among older adults receiving LVR for macular disease, those with memory deficit experienced worse functional trajectories in their ability to perform specific visually mediated tasks. A brief memory screen may help explain variability in rehabilitation outcomes and identify patients who might require special accommodations. PMID:23126548

  1. Visual short-term memory deficits in REM sleep behaviour disorder mirror those in Parkinson’s disease

    PubMed Central

    Rolinski, Michal; Baig, Fahd; Giehl, Kathrin; Quinnell, Timothy; Zaiwalla, Zenobia; Mackay, Clare E.; Husain, Masud; Hu, Michele T. M.

    2016-01-01

    Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson’s disease. Here we examined visual short-term memory deficits—long associated with Parkinson’s disease—in patients with REM sleep behaviour disorder without Parkinson’s disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson’s disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson’s disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson’s disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson’s disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of ‘prodromal’ Parkinson’s disease that might be useful in tracking disease progression and for disease-modifying intervention trials. PMID:26582557

  2. Effects of (-)-sesamin on chronic stress-induced memory deficits in mice.

    PubMed

    Zhao, Ting Ting; Shin, Keon Sung; Park, Hyun Jin; Kim, Kyung Sook; Lee, Kung Eun; Cho, Yoon Jeong; Lee, Myung Koo

    2016-11-10

    This study investigated the effects of (-)-sesamin on memory deficits induced by chronic electric footshock (EF)-induced stress in mice. Mice were treated with (-)-sesamin (25 and 50mg/kg, p.o., daily for 21day) prior to chronic EF stress (0.6mA, 1s every 5s for 3min, daily for 21day). Transfer retention latencies in the elevated plus maze test and N-methyl-d-aspartate (NMDA) receptor (type 1) phosphorylation in the hippocampus increased with chronic EF stress, and they were reduced by treatment with (-)-sesamin at both doses. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-responsive element binding protein (CREB), which were reduced by chronic EF stress, were increased by treatment with (-)-sesamin. Retention latencies in the passive avoidance test and dopamine levels in the substantia nigra-striatum were also reduced by chronic EF stress, and similarly recovered with (-)-sesamin treatment. These results suggest that (-)-sesamin ameliorates the effects of chronic EF stress-induced spatial and habit learning memory deficits by modulating both NMDA receptor and dopaminergic neuronal systems.

  3. Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model

    PubMed Central

    Hüttenrauch, M; Brauß, A; Kurdakova, A; Borgers, H; Klinker, F; Liebetanz, D; Salinas-Riester, G; Wiltfang, J; Klafki, H W; Wirths, O

    2016-01-01

    The evidence for a protective role of physical activity on the risk and progression of Alzheimer's disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron loss and associated behavioral impairment in the Tg4-42 mouse model of AD. Tg4-42 mice overexpress Aβ4-42 without any mutations, and develop an age-dependent hippocampal neuron loss associated with a severe memory decline. We demonstrate that long-term voluntary exercise diminishes CA1 neuron loss and completely rescues spatial memory deficits in different experimental settings. This was accompanied by changes in the gene expression profile of Tg4-42 mice. Deep sequencing analysis revealed an upregulation of chaperones involved in endoplasmatic reticulum protein processing, which might be intimately linked to the beneficial effects seen upon long-term exercise. We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia. PMID:27138799

  4. Ear2 Deletion Causes Early Memory and Learning Deficits in APP/PS1 Mice

    PubMed Central

    Kummer, Markus P.; Hammerschmidt, Thea; Martinez, Ana; Terwel, Dick; Eichele, Gregor; Witten, Anika; Figura, Stefanie; Stoll, Monika; Schwartz, Stephanie; Pape, Hans-Christian; Schultze, Joachim L.; Weinshenker, David

    2014-01-01

    To assess the consequences of locus ceruleus (LC) degeneration and subsequent noradrenaline (NA) deficiency in early Alzheimer's disease (AD), mice overexpressing mutant amyloid precursor protein and presenilin-1 (APP/PS1) were crossed with Ear2(−/−) mice that have a severe loss of LC neurons projecting to the hippocampus and neocortex. Testing spatial memory and hippocampal long-term potentiation revealed an impairment in APP/PS1 Ear2(−/−) mice, whereas APP/PS1 or Ear2(−/−) mice showed only minor changes. These deficits were associated with distinct synaptic changes including reduced expression of the NMDA 2A subunit and increased levels of NMDA receptor 2B in APP/PS1 Ear2(−/−) mice. Acute pharmacological replacement of NA by l-threo-DOPS partially restored phosphorylation of β-CaMKII and spatial memory performance in APP/PS1 Ear2(−/−) mice. These changes were not accompanied by altered APP processing or amyloid β peptide (Aβ) deposition. Thus, early LC degeneration and subsequent NA reduction may contribute to cognitive deficits via CaMKII and NMDA receptor dysfunction independent of Aβ and suggests that NA supplementation could be beneficial in treating AD. PMID:24966384

  5. Dehydroepiandrosterone administration improves memory deficits following transient brain ischemia through sigma-1 receptor stimulation.

    PubMed

    Yabuki, Yasushi; Shinoda, Yasuharu; Izumi, Hisanao; Ikuno, Tatuya; Shioda, Norifumi; Fukunaga, Kohji

    2015-10-05

    Dehydroepiandrosterone (DHEA) is the most abundant neurosteroid synthesized de novo in the central nervous system. Oral DHEA administration elicits neuroprotection and cognitive improvement, but mechanisms underlying these functions in cerebral ischemia have remained unclear. Since DHEA is the endogenous ligand for the sigma-1 receptor (σ1R), we determined whether oral DHEA administration prevents neuronal cell death and improves cognition via σ1R stimulation in brain ischemia using a 20-min bilateral common carotid artery occlusion (BCCAO) mouse model. Twenty-four hours after BCCAO ischemia, mice were administered DHEA (15 or 30mg/kg p.o.) daily for 11 consecutive days. Memory deficits following brain ischemia were improved by DHEA administration dose-dependently. Accordingly, DHEA administration significantly prevented neuronal cell death in the hippocampal CA1 region in BCCAO mice. Interestingly, DHEA administration rescued decreases in Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) in the CA1 region. Moreover, DHEA administration significantly ameliorated decreases in adenosine 5'-triphosphate (ATP) levels and decreased σ1R expression levels in CA1 following BCCAO ischemia. Finally, co-treatment of mice with the σ1R antagonist NE-100 (1mg/kg, p.o.) blocked DHEA effects on memory improvement and neuroprotection in ischemic mice. Taken together, DHEA prevents neuronal cell death and activates CaMKII via σ1R stimulation, thereby improving cognitive deficits following brain ischemia.

  6. Schizophrenia is associated with a pattern of spatial working memory deficits consistent with cortical disinhibition.

    PubMed

    Starc, Martina; Murray, John D; Santamauro, Nicole; Savic, Aleksandar; Diehl, Caroline; Cho, Youngsun T; Srihari, Vinod; Morgan, Peter T; Krystal, John H; Wang, Xiao-Jing; Repovs, Grega; Anticevic, Alan

    2017-03-01

    Schizophrenia is associated with severe cognitive deficits, including impaired working memory (WM). A neural mechanism that may contribute to WM impairment is the disruption in excitation-inhibition (E/I) balance in cortical microcircuits. It remains unknown, however, how these alterations map onto quantifiable behavioral deficits in patients. Based on predictions from a validated microcircuit model of spatial WM, we hypothesized two key behavioral consequences: i) increased variability of WM traces over time, reducing performance precision; and ii) decreased ability to filter out distractors that overlap with WM representations. To test model predictions, we studied N=27 schizophrenia patients and N=28 matched healthy comparison subjects (HCS) who performed a spatial WM task designed to test the computational model. Specifically, we manipulated delay duration and distractor distance presented during the delay. Subjects used a high-sensitivity joystick to indicate the remembered location, yielding a continuous response measure. Results largely followed model predictions, whereby patients exhibited increased variance and less WM precision as the delay period increased relative to HCS. Schizophrenia patients also exhibited increased WM distractibility, with reports biased toward distractors at specific spatial locations, as predicted by the model. Finally, the magnitude of the WM drift and distractibility were significantly correlated, indicating a possibly shared underlying mechanism. Effects are consistent with elevated E/I ratio in schizophrenia, establishing a framework for translating neural circuit computational model of cognition to human experiments, explicitly testing mechanistic behavioral hypotheses of cellular-level neural deficits in patients.

  7. Prospective Memory Deficits in Ecstasy Users: Effects of Longer Ongoing Task Delay Interval

    PubMed Central

    WEINBORN, MICHAEL; WOODS, STEVEN PAUL; NULSEN, CLAIRE; PARK, KATHERINE

    2011-01-01

    Ecstasy use has been associated with neurotoxicity and neurocognitive impairment in a variety of domains, including prospective memory (ProM), which involves the delayed execution of a previously encoded intention in response to a specific cue. The present study adopted the multiprocess theory of ProM to evaluate the hypothesis that ecstasy users would evidence differentially impaired ProM on longer versus shorter ongoing task delays. Ecstasy (n = 31) users, high-risk alcohol users (n = 21) and healthy nonusers (n = 31) completed the short (2-min) and long (15-min) delay ProM scales of the Memory for Intentions Screening Test. Results showed a significant group by ProM delay interaction, such that ecstasy users performed comparably to the comparison groups on short-delay trials, but were impaired on long-delay ProM, particularly for time-based cues. Among the ecstasy users, long-delay ProM was positively associated with risky decision-making, but not with retrospective memory or other aspects of executive functions. These findings suggest that ecstasy users may be particularly susceptible to deficits in strategic target monitoring and maintenance of cue-intention pairings over longer ProM delays. Findings are discussed in the context of their potential everyday functioning (e.g., academic, vocational) and treatment implications for ecstasy users. PMID:22047194

  8. Heterozygous deletion of the LRFN2 gene is associated with working memory deficits.

    PubMed

    Thevenon, Julien; Souchay, Céline; Seabold, Gail K; Dygai-Cochet, Inna; Callier, Patrick; Gay, Sébastien; Corbin, Lucie; Duplomb, Laurence; Thauvin-Robinet, Christel; Masurel-Paulet, Alice; El Chehadeh, Salima; Avila, Magali; Minot, Delphine; Guedj, Eric; Chancenotte, Sophie; Bonnet, Marlène; Lehalle, Daphne; Wang, Ya-Xian; Kuentz, Paul; Huet, Frédéric; Mosca-Boidron, Anne-Laure; Marle, Nathalie; Petralia, Ronald S; Faivre, Laurence

    2016-06-01

    Learning disabilities (LDs) are a clinically and genetically heterogeneous group of diseases. Array-CGH and high-throughput sequencing have dramatically expanded the number of genes implicated in isolated intellectual disabilities and LDs, highlighting the implication of neuron-specific post-mitotic transcription factors and synaptic proteins as candidate genes. We report a unique family diagnosed with autosomal dominant learning disability and a 6p21 microdeletion segregating in three patients. The 870 kb microdeletion encompassed the brain-expressed gene LRFN2, which encodes for a synaptic cell adhesion molecule. Neuropsychological assessment identified selective working memory deficits, with borderline intellectual functioning. Further investigations identified a defect in executive function, and auditory-verbal processes. These data were consistent with brain MRI and FDG-PET functional brain imaging, which, when compared with controls, revealed abnormal brain volume and hypometabolism of gray matter structures implicated in working memory. We performed electron microscopy immunogold labeling demonstrating the localization of LRFN2 at synapses of cerebellar and hippocampal rat neurons, often associated with the NR1 subunit of N-methyl-D-aspartate receptors (NMDARs). Altogether, the combined approaches imply a role for LRFN2 in LD, specifically for working memory processes and executive function. In conclusion, the identification of familial cases of clinically homogeneous endophenotypes of LD might help in both the management of patients and genetic counseling for families.

  9. Urtica dioica modulates hippocampal insulin signaling and recognition memory deficit in streptozotocin induced diabetic mice.

    PubMed

    Patel, Sita Sharan; Gupta, Sahil; Udayabanu, Malairaman

    2016-06-01

    Diabetes mellitus has been associated with functional abnormalities in the hippocampus and performance of cognitive function. Urtica dioica (UD) has been used in the treatment of diabetes. In our previous report we observed that UD extract attenuate diabetes mediated associative and spatial memory dysfunction. The present study aimed to evaluate the effect of UD extract on mouse model of diabetes-induced recognition memory deficit and explore the possible mechanism behind it. Streptozotocin (STZ) (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes followed by UD extract (50 mg/kg, oral) or rosiglitazone (ROSI) (5 mg/kg, oral) administration for 8 weeks. STZ induced diabetic mice showed significant decrease in hippocampal insulin signaling and translocation of glucose transporter type 4 (GLUT4) to neuronal membrane resulting in cognitive dysfunction and hypolocomotion. UD treatment effectively improved hippocampal insulin signaling, glucose tolerance and recognition memory performance in diabetic mice, which was comparable to ROSI. Further, diabetes mediated oxidative stress and inflammation was reversed by chronic UD or ROSI administration. UD leaves extract acts via insulin signaling pathway and might prove to be effective for the diabetes mediated central nervous system complications.

  10. Risk for Mild Cognitive Impairment Is Associated With Semantic Integration Deficits in Sentence Processing and Memory

    PubMed Central

    Stine-Morrow, Elizabeth A. L.

    2016-01-01

    Objectives. We examined the degree to which online sentence processing and offline sentence memory differed among older adults who showed risk for amnestic and nonamnestic varieties of mild cognitive impairment (MCI), based on psychometric classification. Method. Participants (N = 439) read a series of sentences in a self-paced word-by-word reading paradigm for subsequent recall and completed a standardized cognitive test battery. Participants were classified into 3 groups: unimpaired controls (N = 281), amnestic MCI (N = 94), or nonamnestic MCI (N = 64). Results. Relative to controls, both MCI groups had poorer sentence memory and showed reduced sentence wrap-up effects, indicating reduced allocation to semantic integration processes. Wrap-up effects predicted subsequent recall in the control and nonamnestic groups. The amnestic MCI group showed poorer recall than the nonamnestic MCI group, and only the amnestic MCI group showed no relationship between sentence wrap-up and recall. Discussion. Our findings suggest that psychometrically defined sub-types of MCI are associated with unique deficits in sentence processing and can differentiate between the engagement of attentional resources during reading and the effectiveness of engaging attentional resources in producing improved memory. PMID:25190209

  11. Arithmetic facts storage deficit: the hypersensitivity-to-interference in memory hypothesis.

    PubMed

    De Visscher, Alice; Noël, Marie-Pascale

    2014-05-01

    Dyscalculia, or mathematics learning disorders, is currently known to be heterogeneous (Wilson & Dehaene, ). While various profiles of dyscalculia coexist, a general and persistent hallmark of this math learning disability is the difficulty in memorizing arithmetic facts (Geary, Hoard & Hamson, ; Jordan & Montani, ; Slade & Russel, ). Arithmetic facts are simple arithmetic problems that are solved by direct retrieval from memory. Recently, De Visscher and Noël () showed hypersensitivity-to-interference in memory in an adult suffering from a specific deficit of arithmetic facts storage. According to the authors, arithmetic facts share many features. The overlapping of these features between arithmetic facts may provoke interference. Consequently, learners who are hypersensitive-to-interference could have considerable difficulties in storing arithmetic facts. The present study aims at testing this new hypothesis on fourth-grade children who are learning multiplication tables. Among 101 children that were assessed, 23 low arithmetic facts learners were selected because of their low score in arithmetic facts fluency (controlling for processing speed). Twenty-three control children were selected, matched for classroom, gender, and age. In addition to a subtest of global reasoning, these participants were given a multiplication production task and a memorization task of low- and high-interference associations. The results show that children with low arithmetic fluencies experience hypersensitivity-to-interference in memory compared with children with typical arithmetic fluencies.

  12. Dot Enumeration Perceptual Organization Task (DEPOT): evidence for a short-term visual memory deficit in schizophrenia.

    PubMed

    Rabinowicz, E F; Opler, L A; Owen, D R; Knight, R A

    1996-08-01

    The Dot Enumeration Perceptual Organization Task (DEPOT) evaluates the validity of 2 specific competing cognitive models of early input dysfunction in schizophrenic individuals: a primary Stage 1, sensory store, perceptual organization deficit vs. a Stage 2, short-term visual memory (STVM) deficit. DEPOT was also designed to assess the hypothesis that schizophrenic individuals tend to perform poorly on all cognitive tasks. In DEPOT both number and form judgments are made about the same dot patterns. A response delay manipulation assesses the persistence and operation of STVM. The study included 41 psychotic inpatients (8 with acute and 16 with chronic schizophrenia and 7 with bipolar and 10 with nonbipolar affective disorder) and 38 controls (22 college students and 16 hospital personnel). Although the pattern of results was consistent with neither the Stage 1 deficit nor the general deficit hypotheses, a Stage 2, STVM deficit hypothesis could account parsimoniously for the data.

  13. Little exercise, big effects: Reversing aging and infection-induced memory deficits, and underlying processes

    PubMed Central

    Barrientos, Ruth M.; Frank, Matthew G.; Crysdale, Nicole Y.; Chapman, Timothy R.; Ahrendsen, Jared T.; Day, Heidi E.W.; Campeau, Serge; Watkins, Linda R.; Patterson, Susan L.; Maier, Steven F.

    2011-01-01

    We have previously found that healthy aged rats are more likely to suffer profound memory impairments following a severe bacterial infection than are younger adult rats. Such a peripheral challenge is capable of producing a neuroinflammatory response, and in the aged brain this response is exaggerated and prolonged. Normal aging primes, or sensitizes microglia and this appears to be the source of this amplified inflammatory response. Among the outcomes of this exaggerated neuroinflammatory response are impairments in synaptic plasticity, and reductions of brain derived neurotrophic factor (BDNF), both of which have been associated with cognitive impairments. Since it has been shown that physical exercise increases BDNF mRNA in the hippocampus, the present study examined voluntary exercise in 24 mos old F344xBN rats as a neuroprotective therapeutic in our bacterial infection model. Although aged rats ran only an average of 0.7 km per week, this small amount of exercise was sufficient to completely reverse infection-induced impairments in hippocampus-dependent long-term memory compared to sedentary animals. Strikingly, exercise prevented the infection-induced exaggerated neuroinflammatory response and the blunted BDNF mRNA induction seen in the hippocampus of sedentary rats. Moreover, voluntary exercise abrogated age-related microglial sensitization, suggesting a possible mechanism for exercise-induced neuroprotection in aging. PMID:21832188

  14. Faster Forgetting Contributes to Impaired Spatial Memory in the PDAPP Mouse: Deficit in Memory Retrieval Associated with Increased Sensitivity to Interference?

    ERIC Educational Resources Information Center

    Daumas, Stephanie; Sandin, Johan; Chen, Karen S.; Kobayashi, Dione; Tulloch, Jane; Martin, Stephen J.; Games, Dora; Morris, Richard G. M.

    2008-01-01

    Two experiments were conducted to investigate the possibility of faster forgetting by PDAPP mice (a well-established model of Alzheimer's disease as reported by Games and colleagues in an earlier paper). Experiment 1, using mice aged 13-16 mo, confirmed the presence of a deficit in a spatial reference memory task in the water maze by hemizygous…

  15. Working memory and visuospatial deficits correlate with oculomotor control in children with fetal alcohol spectrum disorder.

    PubMed

    Paolozza, Angelina; Rasmussen, Carmen; Pei, Jacqueline; Hanlon-Dearman, Ana; Nikkel, Sarah M; Andrew, Gail; McFarlane, Audrey; Samdup, Dawa; Reynolds, James N

    2014-04-15

    Previous studies have demonstrated that children with Fetal Alcohol Spectrum Disorder (FASD) exhibit deficits in measures of eye movement control that probe aspects of visuospatial processing and working memory. The goal of the present study was to examine, in a large cohort of children with FASD, prenatal alcohol exposure (PAE) but not FASD, and typically developing control children, the relationship between performance in eye movement tasks and standardized psychometric tests that assess visuospatial processing and working memory. Participants for this dataset were drawn from a large, multi-site investigation, and included children and adolescents aged 5-17 years diagnosed with an FASD (n=71), those with PAE but no clinical FASD diagnosis (n=20), and typically developing controls (n=111). Participants completed a neurobehavioral test battery and a series of saccadic eye movement tasks. The FASD group performed worse than controls on the psychometric and eye movement measures of working memory and visuospatial skills. Within the FASD group, digit recall, block recall, and animal sorting were negatively correlated with sequence errors on the memory-guided task, and arrows was negatively correlated with prosaccade endpoint error. There were no significant correlations in the control group. These data suggest that psychometric tests and eye movement control tasks may assess similar domains of cognitive function, and these assessment tools may be measuring overlapping brain regions damaged due to prenatal alcohol exposure. The results of this study demonstrate that eye movement control tasks directly relate to outcome measures obtained with psychometric tests and are able to assess multiple domains of cognition simultaneously, thereby allowing for an efficient and accurate assessment.

  16. Early postnatal nociceptive stimulation results in deficits of spatial memory in male rats.

    PubMed

    Amaral, Cristiane; Antonio, Bruno; Oliveira, Maria Gabriela Menezes; Hamani, Clement; Guinsburg, Ruth; Covolan, Luciene

    2015-11-01

    Prematurely-born infants are exposed to multiple invasive procedures while in the intensive care unit. Newborn rats and humans have similar behavioral responses to noxious stimulation. Previous studies have shown that early noxious stimuli may alter dentate gyrus neurogenesis and the behavioral repertoire of adult rats. We evaluated the late effects of noxious stimulation administered during different phases of development on two spatial memory tests; object recognition (OR) and Morris water maze (WM) tests. Noxious stimulation was induced by an intra-plantar injection of complete Freund's adjuvant (CFA) on postnatal (P) day 1 (group P1) or 8 (P8). Control animals were not stimulated. Behavioral tests were conducted on P60 in both male and female animals. In the WM, three domains were evaluated: acquisition, probe trial performance and reversal re-acquisition. The number of Nissl stained cells in the dentate granule cell layer was assessed by stereological counting. The OR test revealed that P1 male rats had poor long-term memory compared to the control and P8 groups. In the WM, no short- or long-term memory differences were detected between early postnatal-stimulated male and female rats and their respective controls. However, the ability to find the hidden platform in a new position was reduced in P1 male rats. The number of dentate granule cells in P8 males was higher than in all other groups. This study demonstrates that noxious stimulation on P1 results in spatial learning deficits in male animals, but does not disrupt the development of the hippocampus-dependent strategies of learning and memory.

  17. Can Motivation Normalize Working Memory and Task Persistence in Children with Attention-Deficit/Hyperactivity Disorder? The Effects of Money and Computer-Gaming

    ERIC Educational Resources Information Center

    Dovis, Sebastiaan; van der Oord, Saskia; Wiers, Reinout W.; Prins, Pier J. M.

    2012-01-01

    Visual-spatial "Working Memory" (WM) is the most impaired executive function in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Some suggest that deficits in executive functioning are caused by motivational deficits. However, there are no studies that investigate the effects of motivation on the visual-spatial WM of children with-…

  18. Physical exercise prevents short and long-term deficits on aversive and recognition memory and attenuates brain oxidative damage induced by maternal deprivation.

    PubMed

    Neves, Ben-Hur; Menezes, Jefferson; Souza, Mauren Assis; Mello-Carpes, Pâmela B

    2015-12-01

    It is known from previous research that physical exercise prevents long-term memory deficits induced by maternal deprivation in rats. But we could not assume similar effects of physical exercise on short-term memory, as short- and long-term memories are known to result from some different memory consolidation processes. Here we demonstrated that, in addition to long-term memory deficit, the short-term memory deficit resultant from maternal deprivation in object recognition and aversive memory tasks is also prevented by physical exercise. Additionally, one of the mechanisms by which the physical exercise influences the memory processes involves its effects attenuating the oxidative damage in the maternal deprived rats' hippocampus and prefrontal cortex.

  19. Object location and object recognition memory impairments, motivation deficits and depression in a model of Gulf War illness

    PubMed Central

    Hattiangady, Bharathi; Mishra, Vikas; Kodali, Maheedhar; Shuai, Bing; Rao, Xiolan; Shetty, Ashok K.

    2014-01-01

    Memory and mood deficits are the enduring brain-related symptoms in Gulf War illness (GWI). Both animal model and epidemiological investigations have indicated that these impairments in a majority of GW veterans are linked to exposures to chemicals such as pyridostigmine bromide (PB, an antinerve gas drug), permethrin (PM, an insecticide) and DEET (a mosquito repellant) encountered during the Persian Gulf War-1. Our previous study in a rat model has shown that combined exposures to low doses of GWI-related (GWIR) chemicals PB, PM, and DEET with or without 5-min of restraint stress (a mild stress paradigm) causes hippocampus-dependent spatial memory dysfunction in a water maze test (WMT) and increased depressive-like behavior in a forced swim test (FST). In this study, using a larger cohort of rats exposed to GWIR-chemicals and stress, we investigated whether the memory deficiency identified earlier in a WMT is reproducible with an alternative and stress free hippocampus-dependent memory test such as the object location test (OLT). We also ascertained the possible co-existence of hippocampus-independent memory dysfunction using a novel object recognition test (NORT), and alterations in mood function with additional tests for motivation and depression. Our results provide new evidence that exposure to low doses of GWIR-chemicals and mild stress for 4 weeks causes deficits in hippocampus-dependent object location memory and perirhinal cortex-dependent novel object recognition memory. An open field test performed prior to other behavioral analyses revealed that memory impairments were not associated with increased anxiety or deficits in general motor ability. However, behavioral tests for mood function such as a voluntary physical exercise paradigm and a novelty suppressed feeding test (NSFT) demonstrated decreased motivation levels and depression. Thus, exposure to GWIR-chemicals and stress causes both hippocampus-dependent and hippocampus-independent memory

  20. Object location and object recognition memory impairments, motivation deficits and depression in a model of Gulf War illness.

    PubMed

    Hattiangady, Bharathi; Mishra, Vikas; Kodali, Maheedhar; Shuai, Bing; Rao, Xiolan; Shetty, Ashok K

    2014-01-01

    Memory and mood deficits are the enduring brain-related symptoms in Gulf War illness (GWI). Both animal model and epidemiological investigations have indicated that these impairments in a majority of GW veterans are linked to exposures to chemicals such as pyridostigmine bromide (PB, an antinerve gas drug), permethrin (PM, an insecticide) and DEET (a mosquito repellant) encountered during the Persian Gulf War-1. Our previous study in a rat model has shown that combined exposures to low doses of GWI-related (GWIR) chemicals PB, PM, and DEET with or without 5-min of restraint stress (a mild stress paradigm) causes hippocampus-dependent spatial memory dysfunction in a water maze test (WMT) and increased depressive-like behavior in a forced swim test (FST). In this study, using a larger cohort of rats exposed to GWIR-chemicals and stress, we investigated whether the memory deficiency identified earlier in a WMT is reproducible with an alternative and stress free hippocampus-dependent memory test such as the object location test (OLT). We also ascertained the possible co-existence of hippocampus-independent memory dysfunction using a novel object recognition test (NORT), and alterations in mood function with additional tests for motivation and depression. Our results provide new evidence that exposure to low doses of GWIR-chemicals and mild stress for 4 weeks causes deficits in hippocampus-dependent object location memory and perirhinal cortex-dependent novel object recognition memory. An open field test performed prior to other behavioral analyses revealed that memory impairments were not associated with increased anxiety or deficits in general motor ability. However, behavioral tests for mood function such as a voluntary physical exercise paradigm and a novelty suppressed feeding test (NSFT) demonstrated decreased motivation levels and depression. Thus, exposure to GWIR-chemicals and stress causes both hippocampus-dependent and hippocampus-independent memory

  1. Intranasal Insulin Prevents Anesthesia-Induced Spatial Learning and Memory Deficit in Mice

    PubMed Central

    Zhang, Yongli; Dai, Chun-ling; Chen, Yanxing; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2016-01-01

    Elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer’s disease (AD). At present, there is no treatment that can prevent anesthesia-induced postoperative cognitive dysfunction. Here, we treated mice with daily intranasal administration of insulin (1.75 U/day) for one week before anesthesia induced by intraperitoneal injection of propofol and maintained by inhalation of sevoflurane for 1 hr. We found that the insulin treatment prevented anesthesia-induced deficit in spatial learning and memory, as measured by Morris water maze task during 1–5 days after exposure to anesthesia. The insulin treatment also attenuated anesthesia-induced hyperphosphorylation of tau and promoted the expression of synaptic proteins and insulin signaling in the brain. These findings show a therapeutic potential of intranasal administration of insulin before surgery to reduce the risk of anesthesia-induced cognitive decline and AD. PMID:26879001

  2. Scopolamine and MK801-induced working memory deficits in rats are not reversed by CBD-rich cannabis extracts.

    PubMed

    Fadda, Paola; Robinson, Lianne; Fratta, Walter; Pertwee, Roger G; Riedel, Gernot

    2006-04-03

    Smoking marijuana causes working and short-term memory deficits, an effect that is mediated by cannabinoid receptor (CB1) activation in the brain. While this may be due to the main psychoactive constituent Delta9-tetrahydrocannabinol (Delta9-THC), plant extracts also contain other cannabinoid and terpenoid compounds with unknown properties. Towards this end, we have recently shown that high concentrations of plant extracts rich in cannabidiol (CBD) can reverse working memory deficits induced by Delta9-THC which is a remaining contaminant of this extract [Fadda P, Robinson L, Fratta W, Pertwee RG, Riedel G. Differential effects of THC- and CBD-rich cannabis-extracts on working memory in rats. Neuropahrmacology 2004;47:1170-9]. Since this effect was dose-dependent and indicative of memory enhancing qualities of the CBD-rich extract, this prompted a wider investigation into the effects of CBD on other forms of amnesia in order to determine the mechanism of action and to reveal its potency against anticholinergic and antiglutamatergic agents. We employed a spatial delayed matching to position task in the open-field water maze. Both scopolamine (0.2 mg/kg i.p.) and dizocilpine (MK801: 0.1mg/kg i.p.) impaired working memory at delays of 30 s and 4 h. Two doses of CBD-rich extracts (5 and 10 mg/kg), which did not affect working memory when given alone, were unable to reverse these deficits when co-administered with scopolamine or MK801. These data suggest that reversal of working memory deficits by CBD-rich extracts are specific to the cannabinoid system and do not compensate for acutely induced cholinergic or glutamatergic receptor hypoactivity.

  3. Event-based prospective memory deficits in individuals with high depressive symptomatology: problems controlling attentional resources?

    PubMed

    Li, Yanqi Ryan; Loft, Shayne; Weinborn, Michael; Maybery, Murray T

    2014-01-01

    Depression has been found to be related to neurocognitive deficits in areas important to successful prospective memory (PM) performance, including executive function, attention, and retrospective memory. However, research specific to depression and PM has produced a mixed pattern of results. The current study further examined the task conditions in which event-based PM deficits may emerge in individuals with high depressive symptomatology (HDS) relative to individuals with low depressive symptomatology (LDS) and the capacity of HDS individuals to allocate attentional resources to event-based PM tasks. Sixty-four participants (32 HDS, 32 LDS) were required to make a PM response when target words were presented during an ongoing lexical decision task. When the importance of the ongoing task was emphasized, response time costs to the ongoing task, and PM accuracy, did not differ between the HDS and LDS groups. This finding is consistent with previous research demonstrating that event-based PM task accuracy is not always impaired by depression, even when the PM task is resource demanding. When the importance of the PM task was emphasized, costs to the ongoing task further increased for both groups, indicating an increased allocation of attentional resources to the PM task. Crucially, while a corresponding improvement in PM accuracy was observed in the LDS group when the importance of the PM task was emphasized, this was not true for the HDS group. The lack of improved PM accuracy in the HDS group compared with the LDS group despite evidence of increased cognitive resources allocated to PM tasks may have been due to inefficiency in the application of the allocated attention, a dimension likely related to executive function difficulties in depression. Qualitatively different resource allocation patterns may underlie PM monitoring in HDS versus LDS individuals.

  4. Scopolamine-induced deficits in social memory in mice: reversal by donepezil.

    PubMed

    Riedel, G; Kang, S H; Choi, D Y; Platt, B

    2009-12-01

    Deficits in social behaviour is a characteristic of numerous mental disorders including autism, schizophrenia, depression and Alzheimer's disease. For the assessment of pharmacological and genetic experimental disease models, conventional social interaction tasks bear the uncertainty that any drug-induced abnormality of the investigator may feed back to the drug-free companion modifying its reactions. A considerable technical improvement was recently reported by Moy et al. [Moy SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson T, et al. Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behaviours in mice. Genes Brain Behav 2004;3:287-302] in which the drug free partner is confined to a small cage and social contacts of the investigator are recorded uncontaminated of any social reactions of the stranger. Using this novel behavioural paradigm, we here show in C57Bl/6 female mice that sociability (social interaction with a stranger mouse) is not impaired after administration of the anxiolytic diazepam (0.1-1 mg/kg) or the muscarinic antagonist scopolamine hydrobromide (0.1-1 mg/kg). However, social memory tested after a short time interval was impaired by both drugs in a dose-dependent manner (diazepam: > or = 0.5mg/kg; scopolamine: > or = 0.3mg/kg). The scopolamine-induced short-term memory deficit was reversed to normal by the choline esterase inhibitor donepezil (1 mg/kg). Given this dependence of social recognition on the cholinergic system, combined with the clinical observation of reduced social contacts in dementia patients, sociability may offer a novel endpoint biomarker with translational value in experimental models of cognitive dysfunction.

  5. Creativity and Working Memory in Gifted Students with and without Characteristics of Attention Deficit Hyperactive Disorder: Lifting the Mask

    ERIC Educational Resources Information Center

    Fugate, C. Matthew; Zentall, Sydney S.; Gentry, Marcia

    2013-01-01

    There have been some behavioral indicators and some types of task performance that suggest greater creativity in students with attention deficit hyperactive disorder (ADHD). This evidence would appear counterintuitive given that lower working memory (i.e., holding information in mind for novel recombinations) has often been documented in students…

  6. Perceptually or conceptually driven recognition: on the specificities of the memory deficit in schizophrenia.

    PubMed

    Guillaume, Fabrice; Thomas, Emilie; Faget, Catherine; Richieri, Raphaelle; Lançon, Christophe

    2015-02-28

    This study explored the effects of exemplar changes on visual object recognition in patients with schizophrenia and paired control subjects. The experimental design was derived from the process-dissociation procedure (PDP: Jacoby, 1991). The objects presented at test could be the same exemplar as at study (physically identical picture), a different exemplar of the same object category, or a new, non-studied object. In the inclusion task, participants had to generalize their recognition to the conceptual level by accepting both different and identical exemplars as old. In the exclusion task, on the other hand, they had to accept only the same exemplars of the studied objects as old. Overall, performance was better on the inclusion task than on the exclusion task; schizophrenia patients performed worse than controls on the inclusion task but not the exclusion task, misrecognizing different exemplars more often than healthy controls. The present findings reveal that both recollection and familiarity are impaired in patients with schizophrenia, who present a relational, conceptually driven memory deficit. This deficit does not allow them to recognize an object as a member of a specific category independently of perceptual variations. This retrieval mode influences their subjective awareness of items׳ familiarity, and should be considered as a target for remediation.

  7. Combination of attentional and spatial working memory deficits in Bálint–Holmes syndrome

    PubMed Central

    Pisella, Laure; Biotti, Damien; Vighetto, Alain

    2015-01-01

    This study aims to investigate whether attention and spatiotemporal integration deficits are dissociated in patients with bilateral posterior cortical atrophy (PCA), and whether it is their combination that leads to a severe clinical handicap. We recorded performance and ocular behavior of four PCA patients and four age-matched controls in visual search and counting tasks. We measured the percentage of targets detected and the mean detection time in a “pop-out” search. We also compared counting ability when a set of dots is presented briefly (in healthy individuals, the automatic deployment of attention over space allows a fast estimation of quantity) or for unlimited duration (favoring sequential counting, hence spatiotemporal integration). All patients showed reduced deployment of attention over space (simultanagnosia), resulting in increased visual search times and underestimations of the number of briefly presented dots. Only two patients showed ocular revisiting behavior that caused frequent omissions in visual search and overestimations of the number of dots presented for unlimited duration. The impairment to deploy attention is considered here as a bilateral covert attention deficit. Disorganized ocular exploration appears to be independent and is hypothesized to result from processes maintaining a salience map over time (spatial working memory) and especially across saccades. PMID:25708555

  8. Spermine improves recognition memory deficit in a rodent model of Huntington's disease.

    PubMed

    Velloso, Nádia A; Dalmolin, Gerusa D; Gomes, Guilherme M; Rubin, Maribel A; Canas, Paula M; Cunha, Rodrigo A; Mello, Carlos F

    2009-11-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder associated with motor and cognitive impairment. Intrastriatal administration of quinolinic acid (QA) causes neurodegeneration, glial proliferation and cognitive impairment in animals, which are similar to these seen in human HD. Since polyamines improve memory in cognitive tasks, we now tested if the post-training intrastriatal administration of spermine, an agonist of the polyamine site at the NMDA receptor, reverses the deficits in the object recognition task induced by QA. Bilateral striatal injections of QA (180 or 360 nmol/site) caused object recognition impairment, neuronal death and reactive astrogliosis. A single injection of spermine (0.1 and 1 nmol/site), 5 days after QA injection, reversed QA-induced impairment of object recognition task. Spermine (0.1 nmol/site) also inhibited QA-induced reactive astrogliosis measured by a semi-quantitative determination of GFAP immunolabelling, but did not alter neuronal death, measured by a semi-quantitative determination of fluoro-Jade C staining. These results suggest that polyamine binding sites may be considered a novel therapeutic target to prevent reactive astrogliosis and mnemonic deficits in HD.

  9. Attention-Deficit/Hyperactivity Disorder and working memory: a task switching paradigm.

    PubMed

    Wu, K K; Anderson, V; Castiello, U

    2006-11-01

    This study investigated working memory (WM) in children with Attention-Deficit/Hyperactivity Disorder (ADHD) using a task switching paradigm with Stroop color-word stimuli which required participants to switch from color-naming to word-reading. High and low WM load conditions were compared by manipulation of task reminders as a tempo cue. The sample comprised 83 children with ADHD and 29 normal children comparable in age (aged 7 to 13). Within the ADHD group, participants were divided according to the presence or absence of Learning Disability (LD). Results indicated that children with ADHD had slower response times and less accurate responses in general, however, the ADHD groups were not consistently slower in the high WM load condition. Instead, an impairment in adjusting response speed to cope with higher task demands (i.e., high WM load condition) was found. These results do not support the previously documented association between ADHD and a primary deficit in WM for task switching. However, children with ADHD do demonstrate a specific difficulty in slowing down for a demanding task. Present findings suggest that earlier proposals of under-arousal and poor state regulation in ADHD deserve renewed attention.

  10. Age-Related Synapse Loss In Hippocampal CA3 Is Not Reversed By Caloric Restriction

    PubMed Central

    Adams, Michelle M.; Donohue, Howard S.; Linville, M. Constance; Iversen, Elizabeth A.; Newton, Isabel G.; Brunso-Bechtold, Judy K.

    2010-01-01

    Caloric restriction (CR) is a reduction of total caloric intake without a decrease in micronutrients or a disproportionate reduction of any one dietary component. While CR attenuates age-related cognitive deficits in tasks of hippocampal-dependent memory, the cellular mechanisms by which CR improves this cognitive decline are poorly understood. Previously, we have reported age-related decreases in key synaptic proteins in the CA3 region of the hippocampus that are stabilized by lifelong CR. In the present study, we examined possible age-related changes in the functional microcircuitry of the synapses in the stratum lacunosum-moleculare (SL-M) of the CA3 region of the hippocampus, and whether lifelong CR might prevent these age-related alterations. We used serial electron microscopy to reconstruct and classify SL-M synapses and their postsynaptic spines. We analyzed synapse number and size as well as spine surface area and volume in young (10 mos.) and old (29 mos) ad libitum fed rats and in old rats that were calorically restricted from 4 months of age. We limited our analysis to SL-M because previous work demonstrated age-related decreases in synaptophysin confined to this specific layer and region of the hippocampus. The results revealed an age-related decrease in macular axo-spinous synapses that was not reversed by CR that occurred in the absence of changes in the size of synapses or spines. Thus, the benefits of CR for CA3 function and synaptic plasticity may involve other biological effects including the stabilization of synaptic proteins levels in the face of age-related synapse loss. PMID:20854882

  11. Lithium attenuates scopolamine-induced memory deficits with inhibition of GSK-3β and preservation of postsynaptic components.

    PubMed

    Wu, Yuan-Yuan; Wang, Xiong; Tan, Lu; Liu, Dan; Liu, Xing-Hua; Wang, Qun; Wang, Jian-Zhi; Zhu, Ling-Qiang

    2013-01-01

    Cholinergic dysfunction plays a crucial role in the memory deterioration of Alzheimer's disease, but the molecular mechanism is not fully understood. By employing a widely recognized cholinergic dysfunction rat model that was produced by intraperitoneal injection of scopolamine, we investigated the mechanisms underlying scopolamine-induced memory deficits. We found that scopolamine caused spatial learning and memory deficits that involved activation of glycogen synthase kinase-3β (GSK-3β) and impairments of dendrite arborization and spine formation/maturation associated with alterations of AMPAR, Homer1, and CREB. Pretreatment by intraperitoneal injection of lithium, an inhibitor of GSK-3, for one week prevented the synaptic changes and the learning and memory deficits induced by scopolamine. Lithium treatment also activated cholineacetyltransferase and inhibited acetylcholinesterase, which might have also contributed to the improved memory. Our findings suggest that GSK-3β may be a key molecular mediator of cholinergic synaptic dysfunction, and that inhibition of GSK-3β by lithium may be promising in protecting cholinergic synaptic functions.

  12. CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease

    PubMed Central

    Caccamo, Antonella; Maldonado, Monica A.; Bokov, Alex F.; Majumder, Smita; Oddo, Salvatore

    2010-01-01

    Cognitive dysfunction and memory loss are common features of Alzheimer's disease (AD). Abnormalities in the expression profile of immediate early genes that play a critical role in memory formation, such as the cAMP-response element binding protein (CREB), have been reported in the brains of AD patients. Here we show that amyloid-β (Aβ) accumulation, which plays a primary role in the cognitive deficits of AD, interferes with CREB activity. We further show that restoring CREB function via brain viral delivery of the CREB-binding protein (CBP) improves learning and memory deficits in an animal model of AD. Notably, such improvements occur without changes in Aβ and tau pathology, and instead are linked to an increased level of brain-derived neurotrophic factor. The resulting data suggest that Aβ-induced learning and memory deficits are mediated by alterations in CREB function, based on the finding that restoring CREB activity by directly modulating CBP levels in the brains of adult mice is sufficient to ameliorate learning and memory. Therefore, increasing CBP expression in adult brains may be a valid therapeutic approach not only for AD, but also for various brain disorders characterized by alterations in immediate early genes, further supporting the concept that viral vector delivery may be a viable therapeutic approach in neurodegenerative diseases. PMID:21149712

  13. Learning and memory deficits in mice lacking protease activated receptor-1.

    PubMed

    Almonte, Antoine G; Hamill, Cecily E; Chhatwal, Jasmeer P; Wingo, Thomas S; Barber, Jeremy A; Lyuboslavsky, Polina N; David Sweatt, J; Ressler, Kerry J; White, David A; Traynelis, Stephen F

    2007-10-01

    The roles of serine proteases and protease activated receptors have been extensively studied in coagulation, wound healing, inflammation, and neurodegeneration. More recently, serine proteases have been suggested to influence synaptic plasticity. In this context, we examined the role of protease activated receptor 1 (PAR1), which is activated following proteolytic cleavage by thrombin and plasmin, in emotionally motivated learning. We were particularly interested in PAR1 because its activation enhances the function of NMDA receptors, which are required for some forms of synaptic plasticity. We examined several baseline behavioral measures, including locomotor activity, expression of anxiety-like behavior, motor task acquisition, nociceptive responses, and startle responses in C57Bl/6 mice in which the PAR1 receptor has been genetically deleted. In addition, we evaluated learning and memory in these mice using two memory tasks, passive avoidance and cued fear-conditioning. Whereas locomotion, pain response, startle, and measures of baseline anxiety were largely unaffected by PAR1 removal, PAR1-/- animals showed significant deficits in a passive avoidance task and in cued fear conditioning. These data suggest that PAR1 may play an important role in emotionally motivated learning.

  14. Contribution of organizational strategy to verbal learning and memory in adults with attention-deficit/hyperactivity disorder.

    PubMed

    Roth, Robert M; Wishart, Heather A; Flashman, Laura A; Riordan, Henry J; Huey, Leighton; Saykin, Andrew J

    2004-01-01

    Statistical mediation modeling was used to test the hypothesis that poor use of a semantic organizational strategy contributes to verbal learning and memory deficits in adults with attention-deficit/hyperactivity disorder (ADHD). Comparison of 28 adults with ADHD and 34 healthy controls revealed lower performance by the ADHD group on tests of verbal learning and memory, sustained attention, and use of semantic organization during encoding. Mediation modeling indicated that state anxiety, but not semantic organization, significantly contributed to the prediction of both learning and delayed recall in the ADHD group. The pattern of findings suggests that decreased verbal learning and memory in adult ADHD is due in part to situational anxiety and not to poor use of organizational strategies during encoding.

  15. Age-Related Macular Degeneration

    MedlinePlus

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  16. Escitalopram improves memory deficits induced by maternal separation in the rat.

    PubMed

    Couto, Frederico Simões do; Batalha, Vânia L; Valadas, Jorge S; Data-Franca, João; Ribeiro, Joaquim A; Lopes, Luísa V

    2012-11-15

    Maternal separation (MS) induces depressive-like behavior and long-term changes in cognition in rats. Escitalopram is an antidepressant drug shown to reverse the depressive-like features caused by this stress model. However, it is not known if it can ameliorate the affected cognition. We now characterized the effect of escitalopram on hippocampal-dependent memory in rats submitted to the MS protocol. Male Wistar rats were assigned either to control (CTR) or maternal separated (MS) group. MS were separated from their dams between 2-14 postnatal days (PND) for 180min daily. Escitalopram was given in food pellets (0.34g/kg/day first 2 weeks and 0.41g/kg/day the subsequent period, average dose 25mg/kg) from PND 43 onwards, during 1 month. Depressive behavior was assessed in the forced swimming test (FST), and memory performance in the Morris water maze (MWM). Escitalopram significantly improved the FST's latency to despair in the MS group (n=6), but did not change the immobility time. All groups showed a significant learning effect in the MWM over time, but no differences have been found upon treatment (n=6). However, escitalopram treatment significantly increased the time spent on the platform quadrant in the probe trial in the MS group. We report here that chronic treatment with escitalopram is able to improve hippocampal dependent memory in a chronic stress model, while not changing the learning ability. Moreover, this is accompanied by an amelioration of the depressive like behavior. These results support the use of escitalopram to tackle underlying cognitive deficits caused by stress in early-life.

  17. D-cycloserine in Prelimbic Cortex Reverses Scopolamine-Induced Deficits in Olfactory Memory in Rats

    PubMed Central

    Portero-Tresserra, Marta; Cristóbal-Narváez, Paula; Martí-Nicolovius, Margarita; Guillazo-Blanch, Gemma; Vale-Martínez, Anna

    2013-01-01

    A significant interaction between N-methyl-D-aspartate (NMDA) and muscarinic receptors has been suggested in the modulation of learning and memory processes. The present study further investigates this issue and explores whether d-cycloserine (DCS), a partial agonist at the glycine binding site of the NMDA receptors that has been regarded as a cognitive enhancer, would reverse scopolamine (SCOP)-induced amnesia in two olfactory learning tasks when administered into the prelimbic cortex (PLC). Thus, in experiment 1, DCS (10 µg/site) was infused prior to acquisition of odor discrimination (ODT) and social transmission of food preference (STFP), which have been previously characterized as paradigms sensitive to PLC muscarinic blockade. Immediately after learning such tasks, SCOP was injected (20 µg/site) and the effects of both drugs (alone and combined) were tested in 24-h retention tests. To assess whether DCS effects may depend on the difficulty of the task, in the STFP the rats expressed their food preference either in a standard two-choice test (experiment 1) or a more challenging three-choice test (experiment 2). The results showed that bilateral intra-PLC infusions of SCOP markedly disrupted the ODT and STFP memory tests. Additionally, infusions of DCS alone into the PLC enhanced ODT but not STFP retention. However, the DCS treatment reversed SCOP-induced memory deficits in both tasks, and this effect seemed more apparent in ODT and 3-choice STFP. Such results support the interaction between the glutamatergic and the cholinergic systems in the PLC in such a way that positive modulation of the NMDA receptor/channel, through activation of the glycine binding site, may compensate dysfunction of muscarinic neurotransmission involved in stimulus-reward and relational learning tasks. PMID:23936452

  18. Hippocampal brain-derived neurotrophic factor mediates recovery from chronic stress-induced spatial reference memory deficits.

    PubMed

    Ortiz, J Bryce; Mathewson, Coy M; Hoffman, Ann N; Hanavan, Paul D; Terwilliger, Ernest F; Conrad, Cheryl D

    2014-11-01

    Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain-derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the dorsal hippocampal cornu ammonis (CA)3 region with an adeno-associated viral vector containing the sequence for a short hairpin RNA (shRNA) directed against BDNF or a scrambled sequence (Scr). Rats were then chronically restrained (wire mesh, 6 h/day for 21 days) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trials. Rats in the Str-Imm group, regardless of adeno-associated viral contents, committed more errors in the spatial reference memory domain on the single retention trial during day 3 than did the non-stressed controls. Importantly, the typical improvement in spatial memory following the recovery from chronic stress was blocked with the shRNA against BDNF, as Str-Rec-shRNA performed worse on the RAWM compared with the non-stressed controls or Str-Rec-Scr. The stress effects were specific for the reference memory domain, but knockdown of hippocampal BDNF in unstressed controls briefly disrupted spatial working memory as measured by repeated entry errors on day 2 of training. These results demonstrated that hippocampal BDNF was necessary for the recovery from stress-induced hippocampal-dependent spatial memory deficits in the reference memory domain.

  19. Competing Core Processes in Attention-Deficit/Hyperactivity Disorder (ADHD): Do Working Memory Deficiencies Underlie Behavioral Inhibition Deficits?

    ERIC Educational Resources Information Center

    Alderson, R. Matt; Rapport, Mark D.; Hudec, Kristen L.; Sarver, Dustin E.; Kofler, Michael J.

    2010-01-01

    The current study examined competing predictions of the working memory and behavioral inhibition models of ADHD. Behavioral inhibition was measured using a conventional stop-signal task, and central executive, phonological, and visuospatial working memory components (Baddeley 2007) were assessed in 14 children with ADHD and 13 typically developing…

  20. [Memory functions in children with attention deficit/hyperactivity disorder--the effects of methylphenidate on them].

    PubMed

    Kitazawa, Sanae; Hirabayashi, Shinichi; Kobayashi, Mio

    2004-01-01

    The memory functions or capacities in attention-deficit/hyperactivity disorder (AD/HD) are still not clear, though it has been pointed that the working memory in AD/HD could be impaired due to difficulties of motor inhibition or self-regulation. We examined the Auditory Verbal Learning Test (AVLT) and the Rey-Osterrieth Complex Figure Test (RCFT) in addition to the memory tasks of ordinary intelligence tests (WISC-III and K-ABC) in children with AD/HD. Whether these results could be improved by methylphenidate administration or not was also evaluated. Over the half cases had normal results without medication. Some cases in whom methylphenidate were clinically effective showed improved memory functions, especially in the auditory long-term memory, after methylphenidate administration. In conclusion, memory capacities seem normal in AD/HD. Methylphenidate does not have an effect on the memory capacities, but may improve the strategies in which the short-term memory can be effectively transferred to the long-term memory.

  1. Glabridin as a major active isoflavan from Glycyrrhiza glabra (licorice) reverses learning and memory deficits in diabetic rats.

    PubMed

    Hasanein, Parisa

    2011-06-01

    Cognitive impairment occurs in diabetes mellitus. Glabridin as a major active flavonoids in Glycyrrhiza glabra (licorice) improves learning and memory in mice. In the present study, we investigated the effect of chronic treatment with glabridin (5, 25 and 50 mg/kg, p.o.) on cognitive function in control and streptozotocin (STZ)-induced diabetic rats.Animals were divided into untreated control, glabridin-treated control (5, 25 and 50 mg/kg), untreated diabetic and glabridin treated diabetic (5, 25 and 50 mg/kg) groups. Treatments were begun at the onset of hyperglycemia. Passive avoidance learning (PAL) and memory was assessed 30 days later. Diabetes caused cognition deficits in the PAL and memory paradigm. While oral glabridin administration (25 and 50 mg/kg) improved learning and memory in non-diabetic rats, it reversed learning and memory deficits of diabetic rats. Low dose glabridin (5 mg/kg) did not alter cognitive function in non-diabetic and diabetic groups. Glabridin treatment partially improved the reduced body weight and hyperglycemia of diabetic rats although the differences were not significant. The combination of antioxidant, neuroprotective and anticholinesterase properties of glabridin may all be responsible for the observed effects. These results show that glabridin prevented the deleterious effects of diabetes on learning and memory in rats. Further studies are warranted for clinical use of glabridin in the management of demented diabetic patients.

  2. Association between early attention-deficit/hyperactivity symptoms and current verbal and visuo-spatial short-term memory.

    PubMed

    Gau, Susan Shur-Fen; Chiang, Huey-Ling

    2013-01-01

    Deficits in short-term memory are common in adolescents with attention-deficit/hyperactivity disorder (ADHD), but their current ADHD symptoms cannot well predict their short-term performance. Taking a developmental perspective, we wanted to clarify the association between ADHD symptoms at early childhood and short-term memory in late childhood and adolescence. The participants included 401 patients with a clinical diagnosis of DSM-IV ADHD, 213 siblings, and 176 unaffected controls aged 8-17 years (mean age, 12.02 ± 2.24). All participants and their mothers were interviewed using the Chinese Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia to obtain information about ADHD symptoms and other psychiatric disorders retrospectively, at an earlier age first, then currently. The participants were assessed with the Wechsler Intelligence Scale for Children--3rd edition, including Digit Span, and the Spatial working memory task of the Cambridge Neuropsychological Test Automated Battery. Multi-level regression models were used for data analysis. Although crude analyses revealed that inattention, hyperactivity, and impulsivity symptoms significantly predicted deficits in short-term memory, only inattention symptoms had significant effects (all p<0.001) in a model that included all three ADHD symptoms. After further controlling for comorbidity, age of assessment, treatment with methylphenidate, and Full-scale IQ, the severity of childhood inattention symptoms was still significantly associated with worse verbal (p = 0.008) and spatial (p ranging from 0.017 to 0.002) short-term memory at the current assessment. Therefore, our findings suggest that earlier inattention symptoms are associated with impaired verbal and visuo-spatial short-term memory at a later development stage. Impaired short-term memory in adolescence can be detected earlier by screening for the severity of inattention in childhood.

  3. Time perception impairment in early-to-moderate stages of Huntington's disease is related to memory deficits.

    PubMed

    Righi, Stefania; Galli, Luca; Paganini, Marco; Bertini, Elisabetta; Viggiano, Maria Pia; Piacentini, Silvia

    2016-01-01

    Huntington's disease (HD) primarily affects striatum and prefrontal dopaminergic circuits which are fundamental neural correlates of the timekeeping mechanism. The few studies on HD mainly investigated motor timing performance in second durations. The present work explored time perception in early-to-moderate symptomatic HD patients for seconds and milliseconds with the aim to clarify which component of the scalar expectancy theory (SET) is mainly responsible for HD timing defect. Eleven HD patients were compared to 11 controls employing two separate temporal bisection tasks in second and millisecond ranges. Our results revealed the same time perception deficits for seconds and milliseconds in HD patients. Time perception impairment in early-to-moderate stages of Huntington's disease is related to memory deficits. Furthermore, both the non-systematical defect of temporal sensitivity and the main impairment of timing performance in the extreme value of the psychophysical curves suggested an HD deficit in the memory component of the SET. This result was further confirmed by the significant correlations between time perception performance and long-term memory test scores. Our findings added important preliminary data for both a deeper comprehension of HD time-keeping deficits and possible implications on neuro-rehabilitation practices.

  4. Memory for Sequences of Events Impaired in Typical Aging

    ERIC Educational Resources Information Center

    Allen, Timothy A.; Morris, Andrea M.; Stark, Shauna M.; Fortin, Norbert J.; Stark, Craig E. L.

    2015-01-01

    Typical aging is associated with diminished episodic memory performance. To improve our understanding of the fundamental mechanisms underlying this age-related memory deficit, we previously developed an integrated, cross-species approach to link converging evidence from human and animal research. This novel approach focuses on the ability to…

  5. Target-specific vulnerability of excitatory synapses leads to deficits in associative memory in a model of intellectual disorder.

    PubMed

    Houbaert, Xander; Zhang, Chun-Lei; Gambino, Frédéric; Lepleux, Marilyn; Deshors, Melissa; Normand, Elisabeth; Levet, Florian; Ramos, Mariana; Billuart, Pierre; Chelly, Jamel; Herzog, Etienne; Humeau, Yann

    2013-08-21

    Intellectual disorders (IDs) have been regularly associated with morphological and functional deficits at glutamatergic synapses in both humans and rodents. How these synaptic deficits may lead to the variety of learning and memory deficits defining ID is still unknown. Here we studied the functional and behavioral consequences of the ID gene il1rapl1 deficiency in mice and reported that il1rapl1 constitutive deletion alters cued fear memory formation. Combined in vivo and in vitro approaches allowed us to unveil a causal relationship between a marked inhibitory/excitatory (I/E) imbalance in dedicated amygdala neuronal subcircuits and behavioral deficits. Cell-targeted recordings further demonstrated a morpho-functional impact of the mutation at thalamic projections contacting principal cells, whereas the same afferents on interneurons are unaffected by the lack of Il1rapl1. We thus propose that excitatory synapses have a heterogeneous vulnerability to il1rapl1 gene constitutive mutation and that alteration of a subset of excitatory synapses in neuronal circuits is sufficient to generate permanent cognitive deficits.

  6. Sex-dependent modulation of age-related cognitive decline by the L-type calcium channel gene Cacna1c (Cav 1.2).

    PubMed

    Zanos, Panos; Bhat, Shambhu; Terrillion, Chantelle E; Smith, Robert J; Tonelli, Leonardo H; Gould, Todd D

    2015-10-01

    Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively. Hippocampal expression of Cacna1c mRNA was measured by quantitative polymerase chain reaction. Ageing was associated with object recognition and contextual/emotional memory deficits, and a significant increase in hippocampal Cacna1c mRNA expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA expression in both young and old animals. However, haploinsufficient mice did not manifest an age-related increase in expression of this gene. Behaviourally, Cacna1c haploinsufficiency prevented object recognition deficits during ageing in both male and female mice. A significant correlation between higher Cacna1c levels and decreased object recognition performance was observed in both sexes. Also, a sex-dependent protective role of decreased Cacna1c levels in contextual/emotional memory loss has been observed, specifically in male mice. These data provide evidence for an association between increased hippocampal Cacna1c expression and age-related cognitive decline. Additionally, they indicate an interaction between the Cacna1c gene and sex in the modulation of age-related contextual memory declines.

  7. Maternal administration of melatonin prevents spatial learning and memory deficits induced by developmental ethanol and lead co-exposure.

    PubMed

    Soleimani, Elham; Goudarzi, Iran; Abrari, Kataneh; Lashkarbolouki, Taghi

    2017-05-01

    Melatonin is a radical scavenger with the ability to remove reactive oxidant species. There is report that co-exposure to lead and ethanol during developmental stages induces learning and memory deficits and oxidative stress. Here, we studied the effect of melatonin, with strong antioxidant properties, on memory deficits induced by lead and ethanol co-exposure and oxidative stress in hippocampus. Pregnant rats in lead and ethanol co-exposure group received lead acetate of 0.2% in distilled drinking water and ethanol (4g/kg) by oral gavages once daily from the 5th day of gestation until weaning. Rats received 10mg/kg melatonin by oral gavages. On postnatal days (PD) 30, rats trained with six trials per day for 6 consecutive days in the water maze. On day 37, a probe test was done and oxidative stress markers in the hippocampus were evaluated. Results demonstrated lead and ethanol co-exposed rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency in probe trial test and had significantly higher malondialdehyde (MDA) levels, significantly lower superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities in the hippocampus. Melatonin treatment could improve memory deficits, antioxidants activity and reduced MDA levels in the hippocampus. We conclude, co-exposure to lead and ethanol impair memory and melatonin can prevent from it by oxidative stress modulation.

  8. The effect of BLA GABA(A) receptors in anxiolytic-like effect and aversive memory deficit induced by ACPA

    PubMed Central

    Kangarlu-Haghighi, Katayoon; Oryan, Shahrbanoo; Nasehi, Mohammad; Zarrindast, Mohammad-Reza

    2015-01-01

    The roles of GABAergic receptors of the Basolateral amygdala (BLA) in the cannabinoid CB1 receptor agonist (arachydonilcyclopropylamide; ACPA)-induced anxiolytic-like effect and aversive memory deficit in adult male mice were examined in elevated plus-maze task. Results showed that pre-test intra-peritoneal injection of ACPA induced anxiolytic-like effect (at dose of 0.05 mg/kg) and aversive memory deficit (at doses of 0.025 and 0.05 mg/kg). The results revealed that Pre-test intra-BLA infusion of muscimol (GABAA receptor agonist; at doses of 0.1 and 0.2 µg/mouse) or bicuculline (GABAA receptor antagonist; at all doses) impaired and did not alter aversive memory, respectively. All previous GABA agents did not have any effects on anxiety-like behaviors. Interestingly, pretreatment with a sub-threshold dose of muscimol (0.025 µg/mouse) and bicuculline (0.025 µg/mouse) did not alter anxiolytic-like behaviors induced by ACPA, while both drugs restored ACPA-induced amnesia. Moreover, muscimol or bicuculline increased and decreased ACPA-induced locomotor activity, respectively. Finally the data may indicate that BLA GABAA receptors have critical and different roles in anxiolytic-like effect, aversive memory deficit and locomotor activity induced by ACPA. PMID:26648818

  9. Age-related macular degeneration.

    PubMed

    Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y

    2012-05-05

    Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies.

  10. Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users

    PubMed Central

    Havranek, Michael M; Vonmoos, Matthias; Müller, Christian P; Büetiger, Jessica R; Tasiudi, Eve; Hulka, Lea M; Preller, Katrin H; Mössner, Rainald; Grünblatt, Edna; Seifritz, Erich; Quednow, Boris B

    2015-01-01

    Cocaine users consistently develop working memory (WM) impairments but the mediating molecular mechanisms are unknown so far. Recent evidence suggests that the serotonin (5-HT) system is altered by chronic cocaine use, while also being involved in WM processing. Thus, we investigated the effects of genetic variations impacting 5-HT activity and of peripheral 5-HT transporter (5-HTT) mRNA expression on WM performance in cocaine users and stimulant naive controls. Two hundred twenty participants (126 cocaine users, 94 controls) were assessed with visuospatial, spatial, and verbal WM tasks, genotyped for the length polymorphism in the promoter region of the 5-HTT (5-HTTLPR), the variable number of tandem repeats in the second intron of the 5-HTT (VNTR In2), two single-nucleotide polymorphisms (rs4570625 and rs1386497) in the tryptophan hydroxylase-2 (TPH2) gene and quantified for peripheral 5-HTT mRNA expression in whole-blood samples. Several significant gene × environment interactions between 5-HT genotypes and cocaine use on WM emerged: in cocaine users, the long/long (5-HTTLPR), 9+10/9+10 (VNTR In2) and C/C (TPH2 rs1386497) genotypes were risk alleles for WM impairments, whereas in healthy controls these polymorphisms were associated with improved WM performance. Analogously, high 5-HTT mRNA levels were associated with worse executive WM performance in cocaine users but with increased performance in controls. These gene × environment interactions suggest that the 5-HT system has an important role in the development of cognitive deficits in chronic cocaine users. Hence, pharmacological compounds targeting 5-HT neurotransmission might be promising for the treatment of cognitive deficits in cocaine dependence. PMID:26013962

  11. Prefrontal dysconnectivity links to working memory deficit in first-episode schizophrenia.

    PubMed

    Fang, Xiaojing; Wang, Yulin; Cheng, Luqi; Zhang, Yuanchao; Zhou, Yuan; Wu, Shihao; Huang, Huan; Zou, Jilin; Chen, Cheng; Chen, Jun; Wang, Huiling; Jiang, Tianzi

    2017-03-13

    Working memory (WM) deficit is a core feature of schizophrenia and is characterized by abnormal functional integration in the prefrontal cortex, including the dorsolateral prefrontal cortex (dLPFC), dorsal anterior cingulate cortex (dACC), and ventrolateral prefrontal cortex (vLPFC). However, the specific mechanism by which the abnormal neuronal circuits that involve these brain regions contribute to this deficit is still unclear. Therefore, this study focused on these regions and sought to answer which abnormal causal relationships in these regions can be linked to impaired WM in schizophrenia. We used spectral dynamic causal modeling to estimate directed (effective) connectivity between these regions based on resting-state functional magnetic resonance imaging data from healthy control (HC) subjects and patients with first-episode schizophrenia (FES). By comparing these effective connections in the controls and patients, we found that the effective connectivity from the dACC to the dLPFC and from the right dLPFC to the left vLPFC was weaker in the FES group than in the HC group. Furthermore, these effective connections displayed a positive correlation with WM performance in the HCs. However, in the FES patients, the effective connectivity from the dACC to the dLPFC was not correlated with WM performance, and the effective connectivity from the right dLPFC to the left vLPFC was negatively correlated with WM performance. These results could be explained by an aberrant top-down mechanism of WM processing and provide new evidence for the dysconnectivity hypothesis of schizophrenia.

  12. Pro-Cognitive Properties of the Immunomodulatory Polypeptide Complex, Yolkin, from Chicken Egg Yolk and Colostrum-Derived Substances: Analyses Based on Animal Model of Age-Related Cognitive Deficits.

    PubMed

    Lemieszewska, Marta; Jakubik-Witkowska, Marta; Stańczykiewicz, Bartłomiej; Zambrowicz, Aleksandra; Zabłocka, Agnieszka; Polanowski, Antoni; Trziszka, Tadeusz; Rymaszewska, Joanna

    2016-10-01

    The study aimed to assess the effect of the polypeptide Y complex (Yolkin), isolated from chicken egg yolk, on behavioural and cognitive functions. It also aimed to compare this activity with colostrum-derived substances (Colostrinin, Coloco), which have a confirmed impact on learning and memory. In the study, the effect of Yolkin, administered to rats of different ages, who performed various tasks involving spatial and episodic memory, motor functions and exploratory behavior, was assessed. The experiment was carried out in rats which were 6 and 12 months old. Two different doses of the studied specimens based on previous comparative studies and two different routes of administration (oral and retroperitoneal) were used. A series of behavioural tests were carried out, including an open field test, a novel object recognition test and a Morris water maze. They were used to evaluate the impact of the studied specimen on improving locomotor function and exploratory behaviour, preventing their decline and assess the functioning of episodic and spatial memory in aging rats. The administration of Yolkin gave distinct effects compared to colostrum-derived substances, although confirmed its suggested pro-cognitive action. Therefore, it may be used to enhance cognitive functions and inhibit the progression of dementia in the course of neurodegenerative disorders.

  13. Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS.

    PubMed

    Longoni, Giulia; Rocca, Maria A; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2015-01-01

    The hippocampus has a critical role in episodic memory and visuospatial learning and consolidation. We assessed the patterns of whole and regional hippocampal atrophy in a large group of multiple sclerosis (MS) patients, and their correlations with neuropsychological impairment. From 103 MS patients and 28 healthy controls (HC), brain dual-echo and high-resolution 3D T1-weighted images were acquired using a 3.0-Tesla scanner. All patients underwent a neuropsychological assessment of hippocampal-related cognitive functions, including Paired Associate Word Learning, Short Story, delayed recall of Rey-Osterrieth Complex Figure and Paced Auditory Serial Attention tests. The hippocampi were manually segmented and volumes derived. Regional atrophy distribution was assessed using a radial mapping analysis. Correlations between hippocampal atrophy and clinical, neuropsychological and MRI metrics were also evaluated. Hippocampal volume was reduced in MS patients vs HC (p < 0.001 for both right and hippocampus). In MS patients, radial atrophy affected CA1 subfield and subiculum of posterior hippocampus, bilaterally. The dentate hilus (DG:H) of the right hippocampal head was also affected. Regional hippocampal atrophy correlated with brain T2 and T1 lesion volumes, while no correlation was found with disability. Damage to the CA1 and subiculum was significantly correlated to the performances at hippocampal-targeted neuropsychological tests. These results show that hippocampal subregions have a different vulnerability to MS-related damage, with a relative sparing of the head of the left hippocampus. The assessment of regional hippocampal atrophy may help explain deficits of specific cognitive functions in MS patients, including memory and visuospatial abilities.

  14. Working Memory Training in the Form of Structured Games in Children with Attention Deficit Hyperactivity Disorder.

    PubMed

    Khalili Kermani, Fatemeh; Mohammadi, Mohammad Reza; Yadegari, Fariba; Haresabadi, Fatemeh; Sadeghi, Seyed Mehdi

    2016-10-01

    Objective: In this study, a new training method of working memory (WM) was used in the form of structured games, and the effect of training was evaluated with a controlled design. The training method of WM in the form of structured games includes 20 sets of structured games that can improve WM and performance of executive functions. Method: Sixty children with attention deficit hyperactivity disorder (ADHD) aged 8.5 to 11.2 years (35 boys), using no stimulant medication were selected. We randomly assigned 30 participants to the experimental group and provided them with WM training. The training was in the form of structured games and was offered to the participants in two 60-minute sessions weekly for 12 weeks. Other participants were assigned to the control group, receiving no treatment. All the participants were also evaluated at follow-up 6 months later. The main measures were the Child Behavior Checklist (CBCL), the Digit Span and Symbol Search B subscale of the Wechsler Intelligence Scale for Children (WISC-IV); and scores of dictation and mathematics were used in terms of pre and post-test. Results: The results of the t-test revealed a significant improvement in the post-test measures as well as a significant reduction of parents' reports of inattentiveness, and improvement in academic performance in the experimental group. However, no significant changes were found in the control group. Conclusion: The academic and working memory improvements were primarily due to the training method of WM. Our findings suggest that the training method of WM in the form of structured games may be a practical method for treating children with ADHD, but it needs to be further investigated.

  15. Working Memory Training in the Form of Structured Games in Children with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Khalili Kermani, Fatemeh; Mohammadi, Mohammad Reza; Yadegari, Fariba; Haresabadi, Fatemeh; Sadeghi, Seyed Mehdi

    2016-01-01

    Objective: In this study, a new training method of working memory (WM) was used in the form of structured games, and the effect of training was evaluated with a controlled design. The training method of WM in the form of structured games includes 20 sets of structured games that can improve WM and performance of executive functions. Method: Sixty children with attention deficit hyperactivity disorder (ADHD) aged 8.5 to 11.2 years (35 boys), using no stimulant medication were selected. We randomly assigned 30 participants to the experimental group and provided them with WM training. The training was in the form of structured games and was offered to the participants in two 60-minute sessions weekly for 12 weeks. Other participants were assigned to the control group, receiving no treatment. All the participants were also evaluated at follow-up 6 months later. The main measures were the Child Behavior Checklist (CBCL), the Digit Span and Symbol Search B subscale of the Wechsler Intelligence Scale for Children (WISC-IV); and scores of dictation and mathematics were used in terms of pre and post-test. Results: The results of the t-test revealed a significant improvement in the post-test measures as well as a significant reduction of parents’ reports of inattentiveness, and improvement in academic performance in the experimental group. However, no significant changes were found in the control group. Conclusion: The academic and working memory improvements were primarily due to the training method of WM. Our findings suggest that the training method of WM in the form of structured games may be a practical method for treating children with ADHD, but it needs to be further investigated. PMID:28050182

  16. Cannabis-related episodic memory deficits and hippocampal morphological differences in healthy individuals and schizophrenia subjects.

    PubMed

    Smith, Matthew J; Cobia, Derin J; Reilly, James L; Gilman, Jodi M; Roberts, Andrea G; Alpert, Kathryn I; Wang, Lei; Breiter, Hans C; Csernansky, John G

    2015-09-01

    Cannabis use has been associated with episodic memory (EM) impairments and abnormal hippocampus morphology among both healthy individuals and schizophrenia subjects. Considering the hippocampus' role in EM, research is needed to evaluate the relationship between cannabis-related hippocampal morphology and EM among healthy and clinical groups. We examined differences in hippocampus morphology between control and schizophrenia subjects with and without a past (not current) cannabis use disorder (CUD). Subjects group-matched on demographics included 44 healthy controls (CON), 10 subjects with a CUD history (CON-CUD), 28 schizophrenia subjects with no history of substance use disorders (SCZ), and 15 schizophrenia subjects with a CUD history (SCZ-CUD). Large-deformation, high-dimensional brain mapping with MRI produced surface-based representations of the hippocampus that were compared across all four groups and correlated with EM and CUD history. Surface maps of the hippocampus were generated to visualize morphological differences. CON-CUD and SCZ-CUD were characterized by distinct cannabis-related hippocampal shape differences and parametric deficits in EM performance. Shape differences observed in CON-CUD were associated with poorer EM performance, while shape differences observed in SCZ-CUD were associated with a longer duration of CUD and shorter duration of CUD remission. A past history of CUD may be associated with notable differences in hippocampal morphology and EM impairments among adults with and without schizophrenia. Although the results may be compatible with a causal hypothesis, we must consider that the observed cannabis-related shape differences in the hippocampus could also be explained as biomarkers of a neurobiological susceptibility to poor memory or the effects of cannabis.

  17. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy.

  18. 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…

  19. Subchronic glucocorticoid receptor inhibition rescues early episodic memory and synaptic plasticity deficits in a mouse model of Alzheimer's disease.

    PubMed

    Lanté, Fabien; Chafai, Magda; Raymond, Elisabeth Fabienne; Pereira, Ana Rita Salgueiro; Mouska, Xavier; Kootar, Scherazad; Barik, Jacques; Bethus, Ingrid; Marie, Hélène

    2015-06-01

    The early phase of Alzheimer's disease (AD) is characterized by hippocampus-dependent memory deficits and impaired synaptic plasticity. Increasing evidence suggests that stress and dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis, marked by the elevated circulating glucocorticoids, are risk factors for AD onset. How these changes contribute to early hippocampal dysfunction remains unclear. Using an elaborated version of the object recognition task, we carefully monitored alterations in key components of episodic memory, the first type of memory altered in AD patients, in early symptomatic Tg2576 AD mice. We also combined biochemical and ex vivo electrophysiological analyses to reveal novel cellular and molecular dysregulations underpinning the onset of the pathology. We show that HPA axis, circadian rhythm, and feedback mechanisms, as well as episodic memory, are compromised in this early symptomatic phase, reminiscent of human AD pathology. The cognitive decline could be rescued by subchronic in vivo treatment with RU486, a glucocorticoid receptor antagonist. These observed phenotypes were paralleled by a specific enhancement of N-Methyl-D-aspartic acid receptor (NMDAR)-dependent LTD in CA1 pyramidal neurons, whereas LTP and metabotropic glutamate receptor-dependent LTD remain unchanged. NMDAR transmission was also enhanced. Finally, we show that, as for the behavioral deficit, RU486 treatment rescues this abnormal synaptic phenotype. These preclinical results define glucocorticoid signaling as a contributing factor to both episodic memory loss and early synaptic failure in this AD mouse model, and suggest that glucocorticoid receptor targeting strategies could be beneficial to delay AD onset.

  20. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    PubMed Central

    Crosson, Bruce; McGregor, Keith M.; Nocera, Joe R.; Drucker, Jonathan H.; Tran, Stella M.; Butler, Andrew J.

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  1. Functional neuroimaging of visuospatial working memory tasks enables accurate detection of attention deficit and hyperactivity disorder

    PubMed Central

    Hammer, Rubi; Cooke, Gillian E.; Stein, Mark A.; Booth, James R.

    2015-01-01

    Finding neurobiological markers for neurodevelopmental disorders, such as attention deficit and hyperactivity disorder (ADHD), is a major objective of clinicians and neuroscientists. We examined if functional Magnetic Resonance Imaging (fMRI) data from a few distinct visuospatial working memory (VSWM) tasks enables accurately detecting cases with ADHD. We tested 20 boys with ADHD combined type and 20 typically developed (TD) boys in four VSWM tasks that differed in feedback availability (feedback, no-feedback) and reward size (large, small). We used a multimodal analysis based on brain activity in 16 regions of interest, significantly activated or deactivated in the four VSWM tasks (based on the entire participants' sample). Dimensionality of the data was reduced into 10 principal components that were used as the input variables to a logistic regression classifier. fMRI data from the four VSWM tasks enabled a classification accuracy of 92.5%, with high predicted ADHD probability values for most clinical cases, and low predicted ADHD probabilities for most TDs. This accuracy level was higher than those achieved by using the fMRI data of any single task, or the respective behavioral data. This indicates that task-based fMRI data acquired while participants perform a few distinct VSWM tasks enables improved detection of clinical cases. PMID:26509111

  2. Treatment effects of Cardiotrophin-1 (CT-1) on streptozotocin-induced memory deficits in mice.

    PubMed

    Wang, Dongmei; Liu, Xiaozhuan; Liu, Yumei; Shen, Guomin; Zhu, Xiaoying; Li, Sanqiang

    2017-03-08

    Increasing evidence has shown that diabetes-associated cognitive impairment is correlated with mitochondrial dysfunction and resultant synaptic injury as well as brain insulin resistance. Cardiotrophin-1 (CT-1), a regulator of energy metabolism, has been shown to exhibit impressive neuroprotective effects. In this study, we evaluated the effects of CT-1 on brain pathological features in intracerebroventrical-streptozotocin (ICV-STZ)-treated mouse model, and explored its potential mechanisms. STZ was injected twice (3mg/kg, ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with CT-1 (1μg/day, ICV) starting from the first dose of STZ for 14days showed that CT-1 significantly improved learning and memory deficits, alleviated mitochondrial dysfunction, and increased synaptic density in the CA1 region of the hippocampus in ICV-STZ-treated mice. Moreover, CT-1 significantly enhanced insulin signaling pathway in the hippocampus of ICV-STZ-treated mice when compared with the control. However, all the protective effects including biochemistry, pathological changes and cognitive function could be blocked by an ICV injection of Compound C, a specific AMPK inhibitor. Taken together, these results suggested that CT-1 improves pathological changes and cognitive impairments via AMPK activation in ICV-STZ mice.

  3. Enduring deficits in memory and neuronal pathology after blast-induced traumatic brain injury

    PubMed Central

    Sajja, Venkata Siva Sai Sujith; Hubbard, W. Brad; Hall, Christina S.; Ghoddoussi, Farhad; Galloway, Matthew P.; VandeVord, Pamela J.

    2015-01-01

    Few preclinical studies have assessed the long-term neuropathology and behavioral deficits after sustaining blast-induced neurotrauma (BINT). Previous studies have shown extensive astrogliosis and cell death at acute stages (<7 days) but the temporal response at a chronic stage has yet to be ascertained. Here, we used behavioral assays, immmunohistochemistry and neurochemistry in limbic areas such as the amygdala (Amy), Hippocampus (Hipp), nucleus accumbens (Nac), and prefrontal cortex (PFC), to determine the long-term effects of a single blast exposure. Behavioral results identified elevated avoidance behavior and decreased short-term memory at either one or three months after a single blast event. At three months after BINT, markers for neurodegeneration (FJB) and microglia activation (Iba-1) increased while index of mature neurons (NeuN) significantly decreased in all brain regions examined. Gliosis (GFAP) increased in all regions except the Nac but only PFC was positive for apoptosis (caspase-3). At three months, tau was selectively elevated in the PFC and Hipp whereas α-synuclein transiently increased in the Hipp at one month after blast exposure. The composite neurochemical measure, myo-inositol+glycine/creatine, was consistently increased in each brain region three months following blast. Overall, a single blast event resulted in enduring long-term effects on behavior and neuropathological sequelae. PMID:26537106

  4. Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid

    PubMed Central

    Kang, Jin Yong; Park, Seon Kyeong; Guo, Tian Jiao; Ha, Jeong Su; Lee, Du Sang; Kim, Jong Min; Lee, Uk; Kim, Dae Ok

    2016-01-01

    The antiamnesic effect of 3,5-dicaffeoylquinic acid (3,5-diCQA) as the main phenolic compound in Artemisia argyi H. extract on cognitive dysfunction induced by trimethyltin (TMT) (7.1 μg/kg of body weight; intraperitoneal injection) was investigated in order to assess its ameliorating function in mice. In several behavioral tests, namely, the Y-maze, passive avoidance, and Morris water maze (MWM) test, 3,5-diCQA significantly ameliorated learning and memory deficits. After the behavioral tests, brain tissues from the mice were analyzed to characterize the basis of the neuroprotective effect. Acetylcholine (ACh) levels increased, whereas the activity of acetylcholinesterase (AChE) decreased upon administration of 3,5-diCQA. In addition, 3,5-diCQA effectively protected against an increase in malondialdehyde (MDA) content, an increase in the oxidized glutathione (GSH) ratio, and a decline of total superoxide dismutase (SOD) level. 3,5-diCQA may prevent neuronal apoptosis through the protection of mitochondrial activities and the repression of apoptotic signaling molecules such as p-Akt, BAX, and p-tau (Ser 404). PMID:28105250

  5. Age-Related Macular Degeneration.

    PubMed

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision.

  6. Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction, and Spatial Memory Deficits Reminiscent of Early Alzheimer's Disease.

    PubMed

    Fu, Hongjun; Rodriguez, Gustavo A; Herman, Mathieu; Emrani, Sheina; Nahmani, Eden; Barrett, Geoffrey; Figueroa, Helen Y; Goldberg, Eliana; Hussaini, S Abid; Duff, Karen E

    2017-02-08

    The earliest stages of Alzheimer's disease (AD) are characterized by the formation of mature tangles in the entorhinal cortex and disorientation and confusion when navigating familiar places. The medial entorhinal cortex (MEC) contains specialized neurons called grid cells that form part of the spatial navigation system. Here we show in a transgenic mouse model expressing mutant human tau predominantly in the EC that the formation of mature tangles in old mice was associated with excitatory cell loss and deficits in grid cell function, including destabilized grid fields and reduced firing rates, as well as altered network activity. Overt tau pathology in the aged mice was accompanied by spatial memory deficits. Therefore, tau pathology initiated in the entorhinal cortex could lead to deficits in grid cell firing and underlie the deterioration of spatial cognition seen in human AD.

  7. Memory deficits and oxidative stress in cerebral ischemia-reperfusion: neuroprotective role of physical exercise and green tea supplementation.

    PubMed

    Schimidt, Helen L; Vieira, Aline; Altermann, Caroline; Martins, Alexandre; Sosa, Priscila; Santos, Francielli W; Mello-Carpes, Pâmela B; Izquierdo, Ivan; Carpes, Felipe P

    2014-10-01

    Ischemic stroke is a major cause of morbidity and mortality all over the world. Among impairments observed in survivors there is a significant cognitive learning and memory deficit. Neuroprotective strategies are being investigated to minimize such deficits after an ischemia event. Here we investigated the neuroprotective potential of physical exercise and green tea in an animal model of ischemia-reperfusion. Eighty male rats were divided in 8 groups and submitted to either transient brain ischemia-reperfusion or a sham surgery after 8 weeks of physical exercise and/or green tea supplementation. Ischemia-reperfusion was performed by bilateral occlusion of the common carotid arteries during 30 min. Later, their memory was evaluated in an aversive and in a non-aversive task, and hippocampus and prefrontal cortex were removed for biochemical analyses of possible oxidative stress effects. Ischemia-reperfusion impaired learning and memory. Reactive oxygen species were increased in the hippocampus and prefrontal cortex. Eight weeks of physical exercise and/or green tea supplementation before the ischemia-reperfusion event showed a neuroprotective effect; both treatments in separate or together reduced the cognitive deficits and were able to maintain the functional levels of antioxidant enzymes and glutathione.

  8. Memory-related deficits following selective hippocampal expression of Swedish mutation amyloid precursor protein in the rat.

    PubMed

    Gong, Yan; Meyer, Edwin M; Meyers, Craig A; Klein, Ronald L; King, Michael A; Hughes, Jeffrey A

    2006-08-01

    The gene encoding for the Swedish double mutation (K595N/M596L) of amyloid precursor protein (APP695Swe) was expressed bilaterally in adult rat hippocampus to determine its long-term effects on memory-related behavior as well as amyloid deposition. Recombinant adeno-associated viral serotype 2 (rAAV2) vectors were injected that contained either non-expressing DNA or cDNA encoding for APP695Swe under control of a chicken beta actin/cytomegalovirus promoter/enhancer. Immunolabeling human APP with the antibody 6E10 was observed throughout the cytoplasm of aspiny and, to a lesser extent, spine-bearing hippocampal neurons 6 and 12 months post-injection of the APP695Swe but not control vector. Abeta1-42 immunolabeling was identified in unusual immunoreactive objects within the hilus of the dentate gyrus and in the granule cell layer, proximal to the injection site. At 12 months post-transduction, rats that received the APP695Swe gene also demonstrated significant deficits in the acquisition and probe components of the spatial-memory-related Morris water task compared to control animals. These behavioral deficits occurred in the absence of any amyloid plaques, gliosis, or FluoroJade labeling of dying neurons. In conclusion, prolonged and localized APP695Swe expression in hippocampal neurons is sufficient to produce memory deficits without plaque formation or neuronal loss.

  9. Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway.

    PubMed

    Zhang, Lu; Fang, Yu; Xu, Yuming; Lian, Yajun; Xie, Nanchang; Wu, Tianwen; Zhang, Haifeng; Sun, Limin; Zhang, Ruifang; Wang, Zhenhua

    2015-01-01

    Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer's disease (AD). However, the molecular mechanisms underlying curcumin's effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer's disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

  10. Aspects of grammar sensitive to procedural memory deficits in children with specific language impairment.

    PubMed

    Sengottuvel, Kuppuraj; Rao, Prema K S

    2013-10-01

    Procedural deficit hypothesis claims that language deficit in children with specific language impairment is affiliated to sequence learning problems. However, studies did not explore on aspects of grammar vulnerable to sequence learning deficits. The present study makes predictions for aspects of grammar that could be sensitive to procedural deficits based on core ideas of procedural deficit hypothesis. The hypothesis for the present study was that the grammatical operations that require greater sequencing abilities (such as inflectional operations) would be more affected in children with language impairment. Further, the influence of sequencing difficulties would be even greater in agglutinating inflectional languages. An adapted serial reaction time task for sequence learning measurements along with grammatical tasks on derivation, inflection, and sentence complexity were examined on typically developing and language impaired children. Results were in favor of procedural deficit hypothesis and its close relation to non-adjacent grammatical operations. The findings were discussed using procedural deficits, declarative compensatory mechanism, and statistical learning deficits.

  11. Mitochondrial Abnormalities and Synaptic Loss Underlie Memory Deficits Seen in Mouse Models of Obesity and Alzheimer’s Disease

    PubMed Central

    Martins, Isaura V.A.; Rivers-Auty, Jack; Allan, Stuart M.; Lawrence, Catherine B.

    2016-01-01

    Obesity is associated with impaired memory in humans, and obesity induced by high-fat diets leads to cognitive deficits in rodents and in mouse models of Alzheimer’s disease (AD). However, it remains unclear how high-fat diets contribute to memory impairment. Therefore, we tested the effect of a high-fat diet on memory in male and female control non-transgenic (Non-Tg) and triple-transgenic AD (3xTgAD) mice and determined if a high-fat diet caused similar ultrastructural abnormalities to those observed in AD. Behavior was assessed in mice on control or high-fat diet at 4, 8, or 14 months of age and ultrastructural analysis at 8 months of age. A high-fat diet increased body weight, fat weight, and insulin levels with some differences in these metabolic responses observed between Non-Tg and 3xTgAD mice. In both sexes, high-fat feeding caused memory impairments in Non-Tg mice and accelerated memory deficits in 3xTgAD mice. In 3xTgAD mice, changes in hippocampal mitochondrial morphology were observed in capillaries and brain neuropil that were accompanied by a reduction in synapse number. A high-fat diet also caused mitochondria abnormalities and a reduction in synapse number in Non-Tg mice, but did not exacerbate the changes seen in 3xTgAD mice. Our data demonstrate that a high-fat diet affected memory in Non-Tg mice and produced similar impairments in mitochondrial morphology and synapse number comparable to those seen in AD mice, suggesting that the detrimental effects of a high-fat diet on memory might be due to changes in mitochondrial morphology leading to a reduction in synaptic number. PMID:27802235

  12. Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction.

    PubMed

    Kim, D-M; Leem, Y-H

    2016-06-02

    Chronic stress has a detrimental effect on neurological insults, psychiatric deficits, and cognitive impairment. In the current study, chronic stress was shown to impair learning and memory functions, in addition to reducing in hippocampal Adenosine monophosphate-activated protein kinase (AMPK) activity. Similar reductions were also observed for brain-derived neurotrophic factor (BDNF), synaptophysin, and post-synaptic density-95 (PSD-95) levels, all of which was counter-regulated by a regime of regular and prolonged exercise. A 21-day restraint stress regimen (6 h/day) produced learning and memory deficits, including reduced alternation in the Y-maze and decreased memory retention in the water maze test. These effects were reversed post-administration by a 3-week regime of treadmill running (19 m/min, 1 h/day, 6 days/week). In hippocampal primary culture, phosphorylated-AMPK (phospho-AMPK) and BDNF levels were enhanced in a dose-dependent manner by 5-amimoimidazole-4-carboxamide riboside (AICAR) treatment, and AICAR-treated increase was blocked by Compound C. A 7-day period of AICAR intraperitoneal injections enhanced alternation in the Y-maze test and reduced escape latency in water maze test, along with enhanced phospho-AMPK and BDNF levels in the hippocampus. The intraperitoneal injection of Compound C every 4 days during exercise intervention diminished exercise-induced enhancement of memory improvement during the water maze test in chronically stressed mice. Also, chronic stress reduced hippocampal neurogenesis (lower Ki-67- and doublecortin-positive cells) and mRNA levels of BDNF, synaptophysin, and PSD-95. Our results suggest that regular and prolonged exercise can alleviate chronic stress-induced hippocampal-dependent memory deficits. Hippocampal AMPK-engaged BDNF induction is at least in part required for exercise-induced protection against chronic stress.

  13. Effects of (-)-sesamin on motor and memory deficits in an MPTP-lesioned mouse model of Parkinson's disease treated with l-DOPA.

    PubMed

    Zhao, T T; Shin, K S; Kim, K S; Park, H J; Kim, H J; Lee, K E; Lee, M K

    2016-12-17

    The present study investigated the effects of (-)-sesamin on motor and memory deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA). MPTP-lesioned (30mg/kg/day, 5days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25mg/kg l-DOPA for 21days. However, daily treatment with (-)-sesamin (25 and 50mg/kg) for 21days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with l-DOPA (25mg/kg). Both (-)-sesamin doses reduced decreases in the retention latency time in the passive avoidance test, latency to fall of rotarod test and distance traveled in the open field test, and attenuated decreases in tyrosine hydroxylase (TH)-immunopositive cells, dopamine, and its metabolites in the substantia nigra-striatum. (-)-Sesamin reduced increases in the retention transfer latency time in the elevated plus-maze test and N-methyl-d-aspartate receptor (NMDAR) expression and reduced decreases in the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus. In contrast, daily treatment with 10mg/kg l-DOPA for 21days ameliorated memory deficits in MPTP-lesioned mice, and this effect was further improved by treatment with (-)-sesamin (25 and 50mg/kg). These results suggest that (-)-sesamin protects against habit learning memory deficits by activating the dopamine neuronal system, while spatial memory deficits are decreased by its modulatory effects on the NMDAR-ERK1/2-CREB system. Accordingly, (-)-sesamin may act as an adjuvant phytonutrient for motor and memory deficits in patients with PD receiving l-DOPA.

  14. Age-related eye disease.

    PubMed

    Voleti, Vinod B; Hubschman, Jean-Pierre

    2013-05-01

    As with many organs, compromised function of the eye is accompanied with age and has become increasingly prevalent with the aging population. When decreased visual loss becomes significant, patients' ability to perform activities of daily living becomes compromised. This decrease in function is met with morbidity and mortality, as well as a large socioeconomic burden throughout the world. This review summarizes the most common age-related eye diseases, including cataract, glaucoma, diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration. Although our understanding of the genetic and biochemical pathways of these diseases is sill at its primitive stages, we have become able to help our patients improve the quality of life as they age.

  15. Improving Working Memory in Children with Attention-Deficit/Hyperactivity Disorder: The Separate and Combined Effects of Incentives and Stimulant Medication

    ERIC Educational Resources Information Center

    Strand, Michael T.; Hawk, Larry W., Jr.; Bubnik, Michelle; Shiels, Keri; Pelham, William E., Jr.; Waxmonsky, James G.

    2012-01-01

    Working memory (WM) is considered a core deficit in Attention-Deficit/Hyperactivity Disorder (ADHD), with numerous studies demonstrating impaired WM among children with ADHD. We tested the degree to which WM in children with ADHD was improved by performance-based incentives, an analog of behavioral intervention. In two studies, WM performance was…

  16. Working Memory Arrest in Children with High-Functioning Autism Compared to Children with Attention-Deficit/Hyperactivity Disorder: Results from a 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Andersen, Per N.; Skogli, Erik W.; Hovik, Kjell T.; Geurts, Hilde; Egeland, Jens; Øie, Merete

    2015-01-01

    The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically…

  17. A Characterization of Visual, Semantic and Auditory Memory in Children with Combination-Type Attention Deficit, Primarily Inattentive, and a Control Group

    ERIC Educational Resources Information Center

    Ramirez, Luz Angela; Arenas, Angela Maria; Henao, Gloria Cecilia

    2005-01-01

    Introduction: This investigation describes and compares characteristics of visual, semantic and auditory memory in a group of children diagnosed with combined-type attention deficit with hyperactivity, attention deficit predominating, and a control group. Method: 107 boys and girls were selected, from 7 to 11 years of age, all residents in the…

  18. A Meta-Analysis of Working Memory Deficits in Children with Learning Difficulties: Is There a Difference between Verbal Domain and Numerical Domain?

    ERIC Educational Resources Information Center

    Peng, Peng; Fuchs, Douglas

    2016-01-01

    Children with learning difficulties suffer from working memory (WM) deficits. Yet the specificity of deficits associated with different types of learning difficulties remains unclear. Further research can contribute to our understanding of the nature of WM and the relationship between it and learning difficulties. The current meta-analysis…

  19. Fornix as an imaging marker for episodic memory deficits in healthy aging and in various neurological disorders

    PubMed Central

    Douet, Vanessa; Chang, Linda

    2015-01-01

    The fornix is a part of the limbic system and constitutes the major efferent and afferent white matter tracts from the hippocampi. The underdevelopment of or injuries to the fornix are strongly associated with memory deficits. Its role in memory impairments was suggested long ago with cases of surgical forniceal transections. However, recent advances in brain imaging techniques, such as diffusion tensor imaging, have revealed that macrostructural and microstructural abnormalities of the fornix correlated highly with declarative and episodic memory performance. This structure appears to provide a robust and early imaging predictor for memory deficits not only in neurodegenerative and neuroinflammatory diseases, such as Alzheimer's disease and multiple sclerosis, but also in schizophrenia and psychiatric disorders, and during neurodevelopment and “typical” aging. The objective of the manuscript is to present a systematic review regarding published brain imaging research on the fornix, including the development of its tracts, its role in various neurological diseases, and its relationship to neurocognitive performance in human studies. PMID:25642186

  20. A neurodevelopmental approach to understanding memory processes among intellectually gifted youth with attention-deficit hyperactivity disorder.

    PubMed

    Whitaker, Ashley M; Bell, Terece S; Houskamp, Beth M; O'Callaghan, Erin T

    2015-01-01

    Intellectual giftedness is associated with strong strategic verbal memory while attention-deficit hyperactivity disorder (ADHD) is associated with strategic verbal memory deficits; however, no previous research has explored how this contradiction manifests in gifted populations with diagnoses of ADHD. The purpose of this study was to explore strategic verbal memory processes among intellectually gifted youth with and without ADHD to provide clarification regarding this specific aspect of neuropsychological functioning within this population. One hundred twenty-five youth completed neuropsychological evaluations including the Wechsler Intelligence Scale for Children-Fourth Edition and California Verbal Learning Test-Children's Version (CVLT-C). Results revealed significant differences between groups, with intellectually gifted youth with ADHD achieving lower T scores on CVLT-C Trials 1 through 5 compared with intellectually gifted youth without ADHD, and intellectually gifted youth with ADHD achieving higher T scores than youth of average intellectual abilities with ADHD. Additionally, repeated-measures analysis of variance revealed a main effect improvement among gifted youth with ADHD in short-delay recall when provided with organizational cues. Findings revealed new evidence about the role of twice exceptionality (specifically intellectual giftedness and ADHD) in strategic verbal memory and have important implications for parents, educators, psychologists and neuropsychologists, and other mental health professionals working with this population.

  1. Minocycline ameliorates D-galactose-induced memory deficits and loss of Arc/Arg3.1 expression.

    PubMed

    Li, Xu; Lu, Fen; Li, Wei; Xu, Jun; Sun, Xiao-Jing; Qin, Ling-Zhi; Zhang, Qian-Lin; Yao, Yong; Yu, Qing-Kai; Liang, Xin-Liang

    2016-10-01

    Dysfunction of learning and memory is widely found in many neurological diseases. Understanding how to preserve the normal function of learning and memory will be extremely beneficial for the treatment of these diseases. However, the possible protective effect of minocycline in memory impairment is unknown. We used the well-established D-galactose rat amnesia model and two behavioral tasks, the Morris water maze and the step-down task, for memory evaluation. Western blot and PCR were used to examine the protein and mRNA levels of Arc/Arg3.1. We report that minocycline supplementation ameliorates both the spatial and fear memory deficits caused by D-galactose. We also found that Arc/Arg3.1, c-fos, and brain-derived neurotrophic factor levels are decreased in the D-galactose animal model, and that minocycline reverses the protein and mRNA levels of Arc in the hippocampus, suggesting the potential role of Arc/Arg3.1 in minocycline's neuroprotective mechanism. Our study strongly suggests that minocycline can be used as a novel treatment for memory impairment in neurological diseases.

  2. Effects of Aging on the Neural Correlates of Successful Item and Source Memory Encoding

    ERIC Educational Resources Information Center

    Dennis, Nancy A.; Hayes, Scott M.; Prince, Steven E.; Madden, David J.; Huettel, Scott A.; Cabeza, Roberto

    2008-01-01

    To investigate the neural basis of age-related source memory (SM) deficits, young and older adults were scanned with fMRI while encoding faces, scenes, and face-scene pairs. Successful encoding activity was identified by comparing encoding activity for subsequently remembered versus forgotten items or pairs. Age deficits in successful encoding…

  3. Kv4.2 knockout mice display learning and memory deficits in the Lashley maze

    PubMed Central

    Smith, Gregory D.; Gao, Nan; Lugo, Joaquin N.

    2017-01-01

    Background: Potassium channels have been shown to be involved in neural plasticity and learning. Kv4.2 is a subunit of the A-type potassium channel. Kv4.2 channels modulate excitability in the dendrites of pyramidal neurons in the cortex and hippocampus. Deletion of Kv4.2 results in spatial learning and conditioned fear deficits; however, previous studies have only examined deletion of Kv4.2 in aversive learning tests. Methods: For the current study, we used the Lashley maze as an appetitive learning test. We examined Kv4.2 wildtype (WT) and knockout (KO) mice in the Lashley maze over 4 days during adulthood. The first day consisted of habituating the mice to the maze. The mice then received five trials per day for the next 3 days. The number of errors and the time to the goal box was recorded for each trial. The goal box contained a weigh boat with an appetitive reward (gelatin with sugar). There was an intertrial interval of 15 minutes. Results: We found that Kv4.2 KO mice committed more errors across the trials compared to the WT mice p<0.001. There was no difference in the latency to find the goal box over the period. Discussion: Our finding that deletion of Kv4.2 resulted in more errors in the Lashley maze across 15 trials contribute to a growing body of evidence that Kv4.2 channels are significantly involved in learning and memory. PMID:28163893

  4. Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

    PubMed

    Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

    2016-03-15

    Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity.

  5. Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.

    PubMed

    Yadav, Roopali; Hillman, Brandon G; Gupta, Subhash C; Suryavanshi, Pratyush; Bhatt, Jay M; Pavuluri, Ratnamala; Stairs, Dustin J; Dravid, Shashank M

    2013-01-01

    Glutamate delta-1 (GluD1) receptors are expressed throughout the forebrain during development with high levels in the hippocampus during adulthood. We have recently shown that deletion of GluD1 receptor results in aberrant emotional and social behaviors such as hyperaggression and depression-like behaviors and social interaction deficits. Additionally, abnormal expression of synaptic proteins was observed in amygdala and prefrontal cortex of GluD1 knockout mice (GluD1 KO). However the role of GluD1 in learning and memory paradigms remains unknown. In the present study we evaluated GluD1 KO in learning and memory tests. In the eight-arm radial maze GluD1 KO mice committed fewer working memory errors compared to wildtype mice but had normal reference memory. Enhanced working memory in GluD1 KO was also evident by greater percent alternation in the spontaneous Y-maze test. No difference was observed in object recognition memory in the GluD1 KO mice. In the Morris water maze test GluD1 KO mice showed no difference in acquisition but had longer latency to find the platform in the reversal learning task. GluD1 KO mice showed a deficit in contextual and cue fear conditioning but had normal latent inhibition. The deficit in contextual fear conditioning was reversed by D-Cycloserine (DCS) treatment. GluD1 KO mice were also found to be more sensitive to foot-shock compared to wildtype. We further studied molecular changes in the hippocampus, where we found lower levels of GluA1, GluA2 and GluK2 subunits while a contrasting higher level of GluN2B in GluD1 KO. Additionally, we found higher postsynaptic density protein 95 (PSD95) and lower glutamate decarboxylase 67 (GAD67) expression in GluD1 KO. We propose that GluD1 is crucial for normal functioning of synapses and absence of GluD1 leads to specific abnormalities in learning and memory. These findings provide novel insights into the role of GluD1 receptors in the central nervous system.

  6. Age-related macular degeneration

    PubMed Central

    Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

    2011-01-01

    Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

  7. Thalamo-Cortical Disruption Contributes to Short-Term Memory Deficits in Patients with Medial Temporal Lobe Damage.

    PubMed

    Voets, Natalie L; Menke, Ricarda A L; Jbabdi, Saad; Husain, Masud; Stacey, Richard; Carpenter, Katherine; Adcock, Jane E

    2015-11-01

    Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction. We used diffusion-weighted magnetic resonance imaging-based tractography to identify anatomical subdivisions in patients with MTL epilepsy. From these, we measured resting-state functional connectivity with detailed cortical divisions of the frontal, temporal, and parietal lobes. Whereas thalamo-temporal functional connectivity reflected LTM performance, thalamo-prefrontal functional connectivity specifically predicted STM performance. Notably, patients with hippocampal volume loss showed thalamic volume loss, most prominent in the pulvinar region, not detected in patients with normal hippocampal volumes. Aberrant thalamo-cortical connectivity in the epileptic hemisphere was mirrored in a loss of behavioral association with STM performance specifically in patients with hippocampal atrophy. These findings identify thalamo-cortical disruption as a potential mechanism contributing to STM deficits in the context of MTL damage.

  8. Thalamo-Cortical Disruption Contributes to Short-Term Memory Deficits in Patients with Medial Temporal Lobe Damage

    PubMed Central

    Voets, Natalie L.; Menke, Ricarda A. L.; Jbabdi, Saad; Husain, Masud; Stacey, Richard; Carpenter, Katherine; Adcock, Jane E.

    2015-01-01

    Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction. We used diffusion-weighted magnetic resonance imaging-based tractography to identify anatomical subdivisions in patients with MTL epilepsy. From these, we measured resting-state functional connectivity with detailed cortical divisions of the frontal, temporal, and parietal lobes. Whereas thalamo-temporal functional connectivity reflected LTM performance, thalamo-prefrontal functional connectivity specifically predicted STM performance. Notably, patients with hippocampal volume loss showed thalamic volume loss, most prominent in the pulvinar region, not detected in patients with normal hippocampal volumes. Aberrant thalamo-cortical connectivity in the epileptic hemisphere was mirrored in a loss of behavioral association with STM performance specifically in patients with hippocampal atrophy. These findings identify thalamo-cortical disruption as a potential mechanism contributing to STM deficits in the context of MTL damage. PMID:26009613

  9. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

    PubMed

    Yazir, Yusufhan; Utkan, Tijen; Gacar, Nejat; Aricioglu, Feyza

    2015-01-01

    A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation.

  10. Memory deficits in patients with schizophrenia: preliminary data from the Wechsler Memory Scale-Third Edition support earlier findings.

    PubMed Central

    Hawkins, K A

    1999-01-01

    OBJECTIVE: To determine whether memory data presented for a schizophrenia sample in the Technical Manual of the Wechsler Memory Scale-Third Edition support trends identified in a previously published review of studies employing an earlier version of the instrument, the Wechsler Memory Scale-Revised. DESIGN: Archival: reformulation of published data. PATIENTS: Patients with schizophrenia, Alzheimer's disease, Korsakoff's syndrome or traumatic brain injury (TBI) for whom intelligence and memory data were reported in the Technical Manual of the Wechsler Adult Intelligence Scale-Third Edition Wechsler Memory Scale-Third Edition (WAIS-III WMS-III). OUTCOME MEASURES: Mean Full Scale, Verbal, and Performance Intelligence Quotients of the WAIS-III and mean WMS-III Immediate and General Memory Indexes. Single-trial learning and learning slope data were also culled from the WAIS-III WMS-III Technical Manual. RESULTS: Memory indexes for patients with Alzheimer's disease or Korsakoff's syndrome were substantially lower than those for patients with schizophrenia or TBI. In tests of learning processes, patients with schizophrenia had an inferior ability to repeat material presented just once, in comparison with the standardization sample. However, they did relatively better with repeated presentations than patients with Alzheimer's disease or Korsakoff's syndrome. The learning slope for patients with schizophrenia demonstrated an ability to absorb and consolidate increasing amounts of material with repeated exposure that is inconsistent with pronounced memory impairment. CONCLUSIONS: Although patients with schizophrenia exhibit new learning deficiencies, their memory capabilities are not substantially weaker than their general intellectual abilities, and do not approach the memory impairment exhibited by patients with Alzheimer's disease or Korsakoff's syndrome. PMID:10516802

  11. Subchronic Glucocorticoid Receptor Inhibition Rescues Early Episodic Memory and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer's Disease

    PubMed Central

    Lanté, Fabien; Chafai, Magda; Raymond, Elisabeth Fabienne; Salgueiro Pereira, Ana Rita; Mouska, Xavier; Kootar, Scherazad; Barik, Jacques; Bethus, Ingrid; Marie, Hélène

    2015-01-01

    The early phase of Alzheimer's disease (AD) is characterized by hippocampus-dependent memory deficits and impaired synaptic plasticity. Increasing evidence suggests that stress and dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis, marked by the elevated circulating glucocorticoids, are risk factors for AD onset. How these changes contribute to early hippocampal dysfunction remains unclear. Using an elaborated version of the object recognition task, we carefully monitored alterations in key components of episodic memory, the first type of memory altered in AD patients, in early symptomatic Tg2576 AD mice. We also combined biochemical and ex vivo electrophysiological analyses to reveal novel cellular and molecular dysregulations underpinning the onset of the pathology. We show that HPA axis, circadian rhythm, and feedback mechanisms, as well as episodic memory, are compromised in this early symptomatic phase, reminiscent of human AD pathology. The cognitive decline could be rescued by subchronic in vivo treatment with RU486, a glucocorticoid receptor antagonist. These observed phenotypes were paralleled by a specific enhancement of N-Methyl-D-aspartic acid receptor (NMDAR)-dependent LTD in CA1 pyramidal neurons, whereas LTP and metabotropic glutamate receptor-dependent LTD remain unchanged. NMDAR transmission was also enhanced. Finally, we show that, as for the behavioral deficit, RU486 treatment rescues this abnormal synaptic phenotype. These preclinical results define glucocorticoid signaling as a contributing factor to both episodic memory loss and early synaptic failure in this AD mouse model, and suggest that glucocorticoid receptor targeting strategies could be beneficial to delay AD onset. PMID:25622751

  12. Escitalopram Ameliorates Tau Hyperphosphorylation and Spatial Memory Deficits Induced by Protein Kinase A Activation in Sprague Dawley Rats.

    PubMed

    Ren, Qing-Guo; Wang, Yan-Juan; Gong, Wei-Gang; Xu, Lin; Zhang, Zhi-Jun

    2015-01-01

    Here, we investigated the effect of escitalopram pretreatment on protein kinase A (PKA)-induced tau hyperphosphorylation and spatial memory deficits in rats using western blot and behavioral tests, respectively. We demonstrated that escitalopram effectively ameliorated tau hyperphosphorylation and the spatial memory deficits induced by PKA activation. We measured the total and activity-dependent Ser9-phosphorylated levels of glycogen synthase kinase (GSK)-3β in hippocampal extracts. No significant change in the total level of GSK-3β was observed between the different groups. However, compared with forskolin injection alone, pretreatment with escitalopram increased the level of Ser9-phosphorylated GSK-3β. We also demonstrated that escitalopram increased Akt phosphorylation at Ser473 (the active form of Akt). Furthermore, we identified other important kinases and phosphatases, such as protein phosphatase 2A, extracellular signal-regulated kinases 1 and 2, and MAP kinase kinase-1/2, that have previously been reported to play a crucial role in tau phosphorylation; however, we did not detect any significant change in the activation of these kinases or phosphatases in our study. We unexpectedly demonstrated that forskolin caused anxiety-like behavior in rats, and pretreatment with escitalopram did not significantly ameliorate the anxiety-like behavior induced by forskolin. These data provide the first evidence that escitalopram ameliorates forskolin-induced tau hyperphosphorylation and spatial memory impairment in rats; these effects do not occur via the anti-anxiety activity of escitalopram but may involve the Akt/GSK-3β signaling pathway.

  13. Citalopram attenuates tau hyperphosphorylation and spatial memory deficit induced by social isolation rearing in middle-aged rats.

    PubMed

    Ren, Qing-Guo; Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Qi-Da; Zhang, Zhi-Jun

    2015-05-01

    Social isolation (SI) is considered as a chronic stress. Here, middle-aged rats (8 months) were group or isolation reared for 6 weeks. Following the initial two-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Changes in recognition memory, depression and anxiety-like behavior, and phosphorylated tau were investigated. We found that SI did not lead to obvious depression/anxiety-like behavior in middle-aged rats. Memory deficits and increased tau hyperphosphorylation at Tau-1, Ser396 episodes could be almost reversed by citalopram. The level of Ser9-phosphorylated GSK-3β (inactive form) was significantly decreased in the SI group which also could be almost reversed by citalopram, suggesting that the citalopram could prevent GSK-3β from SI-induced overactivation. The melatonin level was decreased in SI group compared with group housed (GH) group, and citalopram could partly restore the level of melatonin. We also found that citalopram could increase MT1 and MT2 in mRNA level. Our results demonstrate that citalopram increases the level of melatonin which negatively regulates GSK-3β and attenuates tau hyperphosphorylation and spatial memory deficit induced by SI in middle-aged rats. Suggesting that SI might constitute a risk factor for Alzheimer's disease (AD), and citalopram may represent a therapeutic strategy for the treatment of AD.

  14. MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice.

    PubMed

    Murai, S; Saito, H; Abe, E; Masuda, Y; Odashima, J; Itoh, T

    1994-01-01

    The effects of acute and chronic administration of MKC-231, a new choline uptake enhancer, and two other nootropic agents, linopiridine (Dup 996) and tetrahydroaminoacridine (THA) on working memory deficits and decreased hippocampal acetylcholine (ACh) content were studied in a delayed non-matching to sample task, using a T-maze, in ethylcholine aziridinium ion (AF64A)-treated mice. Treatment with AF64A (3.5 nmol, i.c.v.) produced memory deficits and decreased hippocampal ACh content. In acute behavioral experiments, MKC-231 and THA had no significant effect on AF64A-induced memory deficits at any doses tested (0.3, 1.0 and 3.0 mg/kg), whereas Dup 996, at a dose of 1.0 mg/kg, significantly improved memory deficits. In chronic experiments, MKC-231 improved memory deficit at all doses tested (0.3, 1.0, or 3.0 mg/kg p.o., once daily for 11 days) and Dup 996 did so only at a dose of 3.0 mg/kg, whereas THA did not improve memory deficit at any doses tested. In acute neurochemical experiments, MKC-231 and THA did not reverse the AF64A-induced hippocampal ACh depletion. Dup 996, however, further decreased hippocampal ACh content compared to that in the AF64A-treated group. In chronic experiments, MKC-231 significantly reversed hippocampal ACh depletion at doses of 0.3 and 1.0 mg/kg, whereas neither Dup 996 nor THA reversed hippocampal ACh depletion at any doses tested. These results indicate that MKC-231 improved the AF64A-induced working memory deficit and hippocampal ACh depletion, probably by recovering reduced high-affinity choline uptake and ACh release.

  15. Pharmacological Blockade of Serotonin 5-HT7 Receptor Reverses Working Memory Deficits in Rats by Normalizing Cortical Glutamate Neurotransmission

    PubMed Central

    Bonaventure, Pascal; Aluisio, Leah; Shoblock, James; Boggs, Jamin D.; Fraser, Ian C.; Lord, Brian; Lovenberg, Timothy W.; Galici, Ruggero

    2011-01-01

    The role of 5-HT7 receptor has been demonstrated in various animal models of mood disorders; however its function in cognition remains largely speculative. This study evaluates the effects of SB-269970, a selective 5-HT7 antagonist, in a translational model of working memory deficit and investigates whether it modulates cortical glutamate and/or dopamine neurotransmission in rats. The effect of SB-269970 was evaluated in the delayed non-matching to position task alone or in combination with MK-801, a non-competitive NMDA receptor antagonist, and, in separate experiments, with scopolamine, a non-selective muscarinic antagonist. SB-269970 (10 mg/kg) significantly reversed the deficits induced by MK-801 (0.1 mg/kg) but augmented the deficit induced by scopolamine (0.06 mg/kg). The ability of SB-269970 to modulate MK-801-induced glutamate and dopamine extracellular levels was separately evaluated using biosensor technology and microdialysis in the prefrontal cortex of freely moving rats. SB-269970 normalized MK-801 -induced glutamate but not dopamine extracellular levels in the prefrontal cortex. Rat plasma and brain concentrations of MK-801 were not affected by co-administration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. These results indicate that 5-HT7 receptor antagonists might reverse cognitive deficits associated with NMDA receptor hypofunction by selectively normalizing glutamatergic neurotransmission. PMID:21701689

  16. Combination of chronic stress and ovariectomy causes conditioned fear memory deficits and hippocampal cholinergic neuronal loss in mice.

    PubMed

    Takuma, K; Mizoguchi, H; Funatsu, Y; Hoshina, Y; Himeno, Y; Fukuzaki, E; Kitahara, Y; Arai, S; Ibi, D; Kamei, H; Matsuda, T; Koike, K; Inoue, M; Nagai, T; Yamada, K

    2012-04-05

    We have recently found that the combination of ovariectomy (OVX) and chronic restraint stress (CS) causes hippocampal pyramidal cell loss and cognitive dysfunction in female rats and that estrogen replacement prevents the OVX/CS-induced morphological and behavioral changes. In this study, to clarify the mechanisms underlying the OVX/CS-mediated memory impairment further, we examined the roles of cholinergic systems in the OVX/CS-induced memory impairment in mice. Female Slc:ICR strain mice were randomly divided into two groups: OVX and sham-operated groups. Two weeks after the operation, the mice of each group were further assigned to CS (6 h/day) or non-stress group. Following the 3-week-stress period, all mice were subjected to contextual fear conditioning, and context- and tone-dependent memory tests were conducted 1 or 24 h after the conditioning. Overburden with 3 weeks of CS from 2 weeks after OVX impaired context- and tone-dependent freezing and the OVX/CS caused significant Nissl-stained neuron-like cell loss in the hippocampal CA3 region, although OVX and CS alone did not cause such behavioral and histological changes. Replacement of 17β-estradiol for 5 weeks after OVX suppressed OVX/CS-induced memory impairment and hippocampal Nissl-positive cell loss. Furthermore, the OVX/CS mice exhibited a significant decrease in choline acetyltransferase in the hippocampus compared with other groups. The cholinesterase inhibitors donepezil and galantamine ameliorated OVX/CS-induced memory impairment. These data suggest that cholinergic dysfunction may be involved in the OVX/CS-induced conditioned fear memory impairment. Overall, our findings suggest that the OVX/CS mouse model is useful to study the mechanisms underlying estrogen loss-induced memory deficits.

  17. Learning and Memory Deficits in Male Adult Mice Treated with a Benzodiazepine Sleep-Inducing Drug during the Juvenile Period

    PubMed Central

    Furukawa, Yusuke; Tanemura, Kentaro; Igarashi, Katsuhide; Ideta-Otsuka, Maky; Aisaki, Ken-Ichi; Kitajima, Satoshi; Kitagawa, Masanobu; Kanno, Jun

    2016-01-01

    Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian central nervous system, is also known to be important for brain development. Therefore, disturbances of GABA receptor (GABA-R) mediated signaling (GABA-R signal) during brain development may influence normal brain maturation and cause late-onset brain malfunctions. In this study, we examined whether the stimulation of the GABA-R signal during brain development induces late-onset adverse effects on the brain in adult male mice. To stimulate the GABA-R signal, we used either the benzodiazepine sleep-inducing drug triazolam (TZ) or the non-benzodiazepine drug zolpidem (ZP). We detected learning and memory deficits in mice treated with TZ during the juvenile period, as seen in the fear conditioning test. On the other hand, ZP administration during the juvenile period had little effect. In addition, decreased protein expression of GluR1 and GluR4, which are excitatory neurotransmitter receptors, was detected in the hippocampi of mice treated with TZ during the juvenile period. We measured mRNA expression of the immediate early genes (IEGs), which are neuronal activity markers, in the hippocampus shortly after the administration of TZ or ZP to juvenile mice. Decreased IEG expression was detected in mice with juvenile TZ administration, but not in mice with juvenile ZP administration. Our findings demonstrate that TZ administration during the juvenile period can induce irreversible learning and memory deficits in adult mice. It may need to take an extra care for the prescription of benzodiazepine sleep-inducing drugs to juveniles because it might cause learning and memory deficits. PMID:27489535

  18. Voluntary exercise rescues deficits in spatial memory and long-term potentiation in prenatal ethanol-exposed male rats.

    PubMed

    Christie, Brian R; Swann, Sarah E; Fox, Christopher J; Froc, David; Lieblich, Stephanie E; Redila, Van; Webber, Alina

    2005-03-01

    Prenatal ethanol exposure can lead to long-lasting impairments in the ability to process spatial information in rats, as well as produce long-lasting deficits in the ability of animals to exhibit long-term potentiation, a biological model of learning and memory processing. Conversely, we have recently shown that both spatial memory and long-term potentiation can be enhanced in animals that are given access to a running wheel in their home cage. In the present study, Sprague-Dawley rat dams were given one of three diets throughout gestation: (i) a liquid diet containing ethanol (35.5% ethanol-derived calories); (ii) a liquid diet, isocaloric to the ethanol diet, but with maltose-dextrin substituting for the ethanol derived calories and (iii) an ad libitum diet of standard rat chow. At weaning (28 days) animals were housed individually in either a standard rat cage, or a cage that contained a running wheel. Adult offspring were tested on a two trial version of the Morris water maze beginning at postnatal day 60, for five consecutive days. Following this, the capacity of the perforant path to dentate gyrus pathway to sustain long-term potentiation was examined in these animals using theta-patterned conditioning stimuli. Our results demonstrate that prenatal ethanol exposure can produce pronounced deficits in both spatial memory and long-term potentiation, but that allowing animal's access to voluntary exercise can attenuate these deficits to the point that those exposed to ethanol prenatally can no longer be differentiated from control animals. These findings indicate that voluntary exercise may have therapeutic benefits for individuals that have undergone prenatal ethanol exposure.

  19. Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats.

    PubMed

    Dossat, Amanda M; Jourdi, Hussam; Wright, Katherine N; Strong, Caroline E; Sarkar, Ambalika; Kabbaj, Mohamed

    2017-01-06

    In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones.

  20. Age-related macular degeneration.

    PubMed

    Cheung, Lily K; Eaton, Angie

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease.

  1. Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats

    NASA Technical Reports Server (NTRS)

    Clarke, M. S.; Prendergast, M. A.; Terry, A. V. Jr

    1999-01-01

    performance, or in tests of general locomotor activity. Furthermore, latencies to select a lever in the DSDT were not affected. These results suggest that PF-68 induced deficits in learning and memory without confounding peripheral motor, sensory, or motivational effects at the tested doses. Furthermore, none of the doses induced a conditioned taste aversion to a novel 0.1% saccharin solution indicating a lack of nausea or gastrointestinal malaise induced by the compound. The data indicate that increases in neuronal plasma membrane order may have significant effects on neurotransmitter function as well as learning and memory processes. Furthermore, compounds such as PF-68 may also offer novel tools for studying the role of neuronal PMO in mnemonic processes and changes in PMO resulting from age-related disorders such as AD.

  2. 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.

  3. Resistance Exercise Reduces Seizure Occurrence, Attenuates Memory Deficits and Restores BDNF Signaling in Rats with Chronic Epilepsy.

    PubMed

    de Almeida, Alexandre Aparecido; Gomes da Silva, Sérgio; Lopim, Glauber Menezes; Vannucci Campos, Diego; Fernandes, Jansen; Cabral, Francisco Romero; Arida, Ricardo Mario

    2017-04-01

    Epilepsy is a disease characterized by recurrent, unprovoked seizures. Cognitive impairment is an important comorbidity of chronic epilepsy. Human and animal model studies of epilepsy have shown that aerobic exercise induces beneficial structural and functional changes and reduces the number of seizures. However, little is yet understood about the effects of resistance exercise on epilepsy. We evaluated the effects of a resistance exercise program on the number of seizures, long-term memory and expression/activation of signaling proteins in rats with epilepsy. The number of seizures was quantified by video-monitoring and long-term memory was assessed by an inhibitory avoidance test. Using western blotting, multiplex and enzyme-linked immunosorbent assays, we determined the effects of a 4-week resistance exercise program on IGF-1 and BDNF levels and ERK, CREB, mTOR activation in the hippocampus of rats with epilepsy. Rats with epilepsy submitted to resistance exercise showed a decrease in the number of seizures compared to non-exercised epileptic rats. Memory deficits were attenuated by resistance exercise. Rats with epilepsy showed an increase in IGF-1 levels which were restored to control levels by resistance exercise. BDNF levels and ERK and mTOR activation were decreased in rats with epilepsy and resistance exercise restored these to control levels. In conclusion, resistance exercise reduced seizure occurrence and mitigated memory deficits in rats with epilepsy. These resistance exercise-induced beneficial effects can be related to changes in IGF-1 and BDNF levels and its signaling protein activation. Our findings indicate that the resistance exercise might be included as complementary therapeutic strategy for epilepsy treatment.

  4. The association between cognitive deficits and prefrontal hemodynamic responses during performance of working memory task in patients with schizophrenia.

    PubMed

    Pu, Shenghong; Nakagome, Kazuyuki; Itakura, Masashi; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

    2016-04-01

    Schizophrenia-associated cognitive deficits are resistant to treatment and thus pose a lifelong burden. The Brief Assessment of Cognition in Schizophrenia (BACS) provides reliable and valid assessments across cognitive domains. However, because the prefrontal functional abnormalities specifically associated with the level of cognitive deficits in schizophrenia have not been examined, we explored this relationship. Patients with schizophrenia (N=87) and matched healthy controls (N=50) participated in the study. Using near-infrared spectroscopy (NIRS), we measured the hemodynamic responses in the prefrontal and superior temporal cortical surface areas during a working memory task. Correlation analyses revealed a relationship between the hemodynamics and the BACS composite and domain scores. Hemodynamic responses of the left dorsolateral prefrontal cortex (DLPFC) and left frontopolar cortex (FPC) in the higher-level-of-cognitive-function schizophrenia group were weaker than the responses of the controls but similar to those of the lower-level-of-cognitive-function schizophrenia group. However, hemodynamic responses in the right DLPFC, bilateral ventrolateral PFC (VLPFC), and right temporal regions decreased with increasing cognitive deficits. In addition, the hemodynamic response correlated positively with the level of cognitive function (BACS composite scores) in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions in schizophrenia. The correlation was driven by all BACS domains. Our results suggest that the linked functional deficits in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions may be related to BACS-measured cognitive impairments in schizophrenia and show that linking the neurocognitive deficits and brain abnormalities can increase our understanding of schizophrenia pathophysiology.

  5. Variation in Parasympathetic Dysregulation Moderates Short-term Memory Problems in Childhood Attention-Deficit/Hyperactivity Disorder.

    PubMed

    Ward, Anthony R; Alarcón, Gabriela; Nigg, Joel T; Musser, Erica D

    2015-11-01

    Although attention deficit/hyperactivity disorder (ADHD) is associated with impairment in working memory and short-term memory, up to half of individual children with ADHD perform within a normative range. Heterogeneity in other ADHD-related mechanisms, which may compensate for or combine with cognitive weaknesses, is a likely explanation. One candidate is the robustness of parasympathetic regulation (as indexed by respiratory sinus arrhythmia; RSA). Theory and data suggest that a common neural network is likely tied to both heart-rate regulation and certain cognitive functions (including aspects of working and short-term memory). Cardiac-derived indices of parasympathetic reactivity were collected during short-term memory (STM) storage and rehearsal tasks from 243 children (116 ADHD, 127 controls). ADHD was associated with lower STM performance, replicating previous work. In addition, RSA reactivity moderated the association between STM and ADHD - both as a category and a dimension - independent of comorbidity. Specifically, conditional effects revealed that high levels of withdrawal interacted with weakened STM but high levels of augmentation moderated a positive association predicting ADHD. Thus, variations in parasympathetic reactivity may help explain neuropsychological heterogeneity in ADHD.

  6. The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze.

    PubMed

    Hosseini, Mahmoud; Hadjzadeh, Mosa Al-Reza; Derakhshan, Mohammad; Havakhah, Shahrzad; Rassouli, Fatemeh Behnam; Rakhshandeh, Hassan; Saffarzadeh, Fatema

    2010-03-01

    Functional consequences of hypothyroidism include impaired learning and memory and inability to produce long-term potentiation (LTP) in hippocampus. Olibanum has been used for variety of therapeutic purposes. In traditional medicine, oilbanum is used to enhance learning and memory. In the present study the effect of olibanum on memory deficit in hypothyroid rats was investigated. Male wistar rats were divided into four groups and treated for 180 days. Group 1 received tap drinking water while in group 2, 0.03% methimazol was added to drinking water. Group 3 and 4 were treated with 0.03% methimazole as well as 100 and 500 mg/kg olibanum respectively. The animals were tested in Morris water maze. The swimming speed was significantly lower and the distance and time latency were higher in group 2 compared with group 1. In groups 3 and 4 the swimming speed was significantly higher while, the length of the swim path and time latency were significantly lower in comparison with group 2. It is concluded that methimazole-induced hypothyroidism impairs learning and memory in adult rats which could be prevented by using olibanum.

  7. Decrease of ERK/MAPK overactivation in prefrontal cortex reverses early memory deficit in a mouse model of Alzheimer's disease.

    PubMed

    Feld, Mariana; Krawczyk, María C; Sol Fustiñana, M; Blake, Mariano G; Baratti, Carlos M; Romano, Arturo; Boccia, Mariano M

    2014-01-01

    Alzheimer's disease (AD) can be considered as a disease of memory in its initial clinical stages. Amyloid-β (Aβ) peptide accumulation is central to the disease initiation leading later to intracellular neurofibrillary tangles (NFTs) of cytoskeletal tau protein formation. It is under discussion whether different Aβ levels of aggregation, concentration, brain area, and/or time of exposure might be critical to the disease progression, as well as which intracellular pathways it activates. The aim of the present work was to study memory-related early molecular and behavioral alterations in a mouse model of AD, in which a subtle deregulation of the physiologic function of Aβ can be inferred. For this purpose we used triple-transgenic (3xTg) mice, which develop Aβ and tau pathology resembling the disease progression in humans. Memory impairment in novel object recognition task was evident by 5 months of age in 3xTg mice. Hippocampus and prefrontal cortex extra-nuclear protein extracts developed differential patterns of Aβ aggregation. ERK1/MAPK showed higher levels of cytosolic activity at 3 months and higher levels of nuclear activity at 6 months in the prefrontal cortex. No significant differences were found in JNK and NF-κB activity and in calcineurin protein levels. Finally, intra-PFC administration of a MEK inhibitor in 6-month-old 3xTg mice was able to reverse memory impairment, suggesting that ERK pathway alterations might at least partially explain memory deficits observed in this model, likely as a consequence of memory trace disruption.

  8. Age-related deficits in guided search using cues.

    PubMed

    Gottlob, Lawrence R

    2006-09-01

    The ability of young and older adults to engage in guided conjunction search was tested in 2 experiments. In the cued condition, a picture of the target was presented before the search. In the noncued condition, there was no picture of the target. In Experiment 1, the cue was presented for 200 ms; the magnitude of the cuing effect (noncued response time--cued response time) was greater for the young than for the older observers. In Experiment 2 (older observers only), the cue duration was doubled, and older observers had a larger magnitude of cuing effect than found in Experiment 1 but not as large as what would be expected under generalized slowing. The results indicated that older observers had difficulty with interpreting the cue and setting search parameters when the target varied across trials.

  9. Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome.

    PubMed

    Lee, Yong-Seok; Ehninger, Dan; Zhou, Miou; Oh, Jun-Young; Kang, Minkyung; Kwak, Chuljung; Ryu, Hyun-Hee; Butz, Delana; Araki, Toshiyuki; Cai, Ying; Balaji, J; Sano, Yoshitake; Nam, Christine I; Kim, Hyong Kyu; Kaang, Bong-Kiun; Burger, Corinna; Neel, Benjamin G; Silva, Alcino J

    2014-12-01

    In Noonan syndrome (NS) 30-50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated mutations in Ptpn11, which encodes the nonreceptor protein tyrosine phosphatase Shp2, show hippocampal-dependent impairments in spatial learning and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of an NS-associated allele PTPN11(D61G) in adult mouse hippocampus results in increased baseline excitatory synaptic function and deficits in LTP and spatial learning, which can be reversed by a mitogen-activated protein kinase kinase (MEK) inhibitor. Furthermore, brief treatment with lovastatin reduces activation of the GTPase Ras-extracellular signal-related kinase (Erk) pathway in the brain and normalizes deficits in LTP and learning in adult Ptpn11(D61G/+) mice. Our results demonstrate that increased basal Erk activity and corresponding baseline increases in excitatory synaptic function are responsible for the LTP impairments and, consequently, the learning deficits in mouse models of NS. These data also suggest that lovastatin or MEK inhibitors may be useful for treating the cognitive deficits in NS.

  10. Comparative behavioral and neurochemical analysis of phenytoin and valproate treatment on epilepsy induced learning and memory deficit: Search for add on therapy.

    PubMed

    Mishra, Awanish; Goel, Rajesh Kumar

    2015-08-01

    Our previous work demonstrated, chronic epilepsy affects learning and memory of rodents along with peculiar neurochemical changes in discrete brain parts. Most commonly used antiepileptic drugs (phenytoin and sodium valproate) also worsen learning and memory in the patients with epilepsy. Therefore this study was designed to carry out comparison of behavioral and neurochemical changes with phenytoin and sodium valproate treatment in pentylenetetrazole-kindling induced learning and memory deficit to devise add on therapy for this menace. For the experimental epilepsy, animals were kindled using PTZ (35 mg/kg; i.p., at 48 ± 2 h intervals) and successful kindled animals were involved in the study. These kindled animals were treated with saline, phenytoin (30 mg/kg/day, i.p.) and sodium valproate (300 mg/kg/day, i.p.) for 20 days. These animals were challenged with PTZ challenging dose (35 mg/kg) on day 5, 10, 15 and 20 to evaluate the effect on seizure severity score on different days. Effect on learning and memory was evaluated using elevated plus maze and passive shock avoidance paradigm. On day 20, after behavioral evaluations, animals were sacrificed to analyze glutamate, GABA, norepinephrine, dopamine, serotonin, total nitrite level and acetylcholinesterase level in cortex and hippocampus. Behavioral evaluations suggested that phenytoin and sodium valproate treatment significantly reduced seizure severity in the kindled animals, while sodium valproate treatment controls seizures with least memory deficit in comparison to phenytoin. Neurochemical findings revealed that elevated cortical acetylcholinesterase level could be one of the responsible factors leading to memory deficit in phenytoin treated animals. However sodium valproate treatment reduced cortical acetylcholinesterase level and had least debilitating consequences on memory deficit. Therefore, attenuation of elevated AChE activity can be one of add-on approach for management of memory deficit

  11. Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazol-induced kindling and associated depression and memory deficit.

    PubMed

    Pahwa, Priyanka; Goel, Rajesh Kumar

    2016-04-01

    Asparagus racemosus (A. racemosus) roots are extensively used in traditional medicine for the management of epilepsy. The aim of the present study was to investigate the ameliorative effect of A. racemosus root extract (ARE) against pentylenetetrazol-induced kindling and associated depression and memory deficit. Kindling was successfully induced by repeated administration of a subconvulsant dose of PTZ (35 mg/kg; i.p.) at an interval of 48 ± 2 h in 43 days (21 injections). Pretreatment with valproate (300 mg/kg; i.p.), a major antiepileptic drug as well as ARE significantly suppressed the progression of kindling. Moreover, ARE also ameliorated the kindling-associated depression and memory deficit as indicated by decreased immobility time and increased step-down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complemented with analogous neurochemical changes. In conclusion, the results of the present study showed that ARE treatment has an ameliorative effect against PTZ-induced kindling and associated behavioral comorbidities.

  12. Right-sided representational neglect after left brain damage in a case without visuospatial working memory deficits.

    PubMed

    van Dijck, Jean-Philippe; Gevers, Wim; Lafosse, Christophe; Fias, Wim

    2013-10-01

    Brain damaged patients suffering from representational neglect (RN) fail to report, orient to, or verbally describe contra-lesional elements of imagined environments or objects. So far this disorder has only been reported after right brain damage, leading to the idea that only the right hemisphere is involved in this deficit. A widely accepted account attributes RN to a lateralized impairment in the visuospatial component of working memory. So far, however, this hypothesis has not been tested in detail. In the present paper, we describe, for the first time, the case of a left brain damaged patient suffering from right-sided RN while imagining both known and new environments and objects. An in-depth evaluation of her visuospatial working memory abilities, with special focus on the presence of a lateralized deficit, did not reveal any abnormality. In sharp contrast, her ability to memorize visual information was severely compromised. The implications of these results are discussed in the light of recent insights in the neglect syndrome.

  13. Do Children with Phonological Delay Have Phonological Short-Term and Phonological Working Memory Deficits?

    ERIC Educational Resources Information Center

    Waring, Rebecca; Eadie, Patricia; Liow, Susan Rickard; Dodd, Barbara

    2017-01-01

    While little is known about why children make speech errors, it has been hypothesized that cognitive-linguistic factors may underlie phonological speech sound disorders. This study compared the phonological short-term and phonological working memory abilities (using immediate memory tasks) and receptive vocabulary size of 14 monolingual preschool…

  14. Peripheral bacterial endotoxin administration triggers both memory consolidation and reconsolidation deficits in mice.

    PubMed

    Kranjac, Dinko; McLinden, Kristina A; Deodati, Lauren E; Papini, Mauricio R; Chumley, Michael J; Boehm, Gary W

    2012-01-01

    Peripherally administered inflammatory stimuli, such as lipopolysaccharide (LPS), induce the synthesis and release of proinflammatory cytokines and chemokines in the periphery and the central nervous system, and trigger a variety of neurobiological responses. Indeed, prior reports indicate that peripheral LPS administration in rats disrupts contextual fear memory consolidation processes, potentially due to elevated cytokine expression. We used a similar, but partially olfaction-based, contextual fear conditioning paradigm to examine the effects of LPS on memory consolidation and reconsolidation in mice. Additionally, interleukin-1β (IL-1β), brain-derived neurotrophic factor (BDNF), and zinc finger (Zif)-268 mRNA expression in the hippocampus and the cortex, along with peripheral cytokines and chemokines, were assessed. As hypothesized, LPS administered immediately or 2 h, but not 12 h, post-training impaired memory consolidation processes that support the storage of the conditioned contextual fear memory. Additionally, as hypothesized, LPS administered immediately following the fear memory trace reactivation session impaired memory reconsolidation processes. Four hours post-injection, both central cytokine and peripheral cytokine and chemokine levels were heightened in LPS-treated animals, with a simultaneous decrease in BDNF, but not Zif-268, mRNA. Collectively, these data reinforce prior work showing LPS- and cytokine-related effects on memory consolidation, and extend this work to memory reconsolidation.

  15. Modeling Phonological Core Deficits Within a Working Memory Architecture in Children and Adults With Developmental Dyslexia

    ERIC Educational Resources Information Center

    Berninger, Virginia W.; Abbott, Robert D.; Thomson, Jennifer; Wagner, Richard; Swanson, H. Lee; Wijsman, Ellen M.; Raskind, Wendy

    2006-01-01

    Recent theoretical advances in working memory guided analyses of cognitive measures in 122 children with dyslexia and their 200 affected biological parents in families with a multigenerational history of dyslexia. Both children and adults were most severely impaired, on average, in three working memory components- phonological word-form storage,…

  16. A Meta-Analysis of Working Memory Deficits in Children With Learning Difficulties: Is There a Difference Between Verbal Domain and Numerical Domain?

    PubMed

    Peng, Peng; Fuchs, Douglas

    2016-01-01

    Children with learning difficulties suffer from working memory (WM) deficits. Yet the specificity of deficits associated with different types of learning difficulties remains unclear. Further research can contribute to our understanding of the nature of WM and the relationship between it and learning difficulties. The current meta-analysis synthesized research on verbal WM and numerical WM among children with reading difficulties (RD), children with mathematics difficulties (MD), and children with reading and mathematics difficulties (RDMD). A total of 29 studies subsuming 110 comparisons were included. Results showed that compared to typically developing children, all learning difficulty groups demonstrated deficits in verbal WM and numerical WM, with RDMD children showing the most severe WM deficits. MD children and RD children showed comparable verbal WM deficits, but MD children showed more severe numerical WM deficits than RD children. Neither severity of learning difficulties nor type of academic screening emerged as a moderator of WM deficit profiles. Although the findings indicate the domain-general nature of WM deficits in RD, MD, and RDMD children, the numerical WM deficits of children with MD and RDMD may reflect the domain-specific nature of WM deficits.

  17. The Role of Text Memory in Inferencing and in Comprehension Deficits

    PubMed Central

    Hua, Anh N.; Keenan, Janice M.

    2014-01-01

    Comprehension tests often compare accuracy on inferential versus literal questions and find inferential harder than literal, and poor comprehenders performing worse than controls. Difficulties in integration are assumed to be the reason. This research explores another reason – differences in memory for the passage information underlying the questions. Thirty-nine poor comprehenders and 39 controls were given multiple-paragraph passages, which they retold before answering questions. Retellings permitted assessing question accuracy as a function of memory for the text underlying each question. Inferential accuracy was poorer than literal, and the expected group effect obtained. However, when text memory was perfect, group differences disappeared, indicating that poor comprehenders can generate inferences as well as controls, if they have the relevant information in memory. These findings show that text memory is crucial in distinguishing poor comprehension. PMID:25328376

  18. Amnesic H.M.'s performance on the language competence test: parallel deficits in memory and sentence production.

    PubMed

    MacKay, Donald G; James, Lori E; Hadley, Christopher B

    2008-04-01

    To test conflicting hypotheses regarding amnesic H.M.'s language abilities, this study examined H.M.'s sentence production on the Language Competence Test (Wiig & Secord, 1988). The task for H.M. and 8 education-, age-, and IQ-matched controls was to describe pictures using a single grammatical sentence containing prespecified target words. The results indicated selective deficits in H.M.'s picture descriptions: H.M. produced fewer single grammatical sentences, included fewer target words, and described the pictures less completely and accurately than did the controls. However, H.M.'s deficits diminished with repeated processing of unfamiliar stimuli and disappeared for familiar stimuli-effects that help explain why other researchers have concluded that H.M.'s language production is intact. Besides resolving the conflicting hypotheses, present results replicated other well-controlled sentence production results and indicated that H.M.'s language and memory exhibit parallel deficits and sparing. Present results comport in detail with binding theory but pose problems for current systems theories of H.M.'s condition.

  19. Self-predictions of prospective memory in HIV-associated neurocognitive disorders: evidence of a metamemory deficit.

    PubMed

    Casaletto, Kaitlin Blackstone; Doyle, Katie L; Weber, Erica; Woods, Steven Paul

    2014-12-01

    HIV-associated neurocognitive disorders (HAND) are associated with deficits in prospective memory (PM; "remembering to remember"), conferring risk of daily functioning declines. However, self-perceptions of PM functioning are not reliably associated with PM performance in HIV, suggesting a possible deficit in awareness of PM abilities (meta-PM). Our study examined meta-PM in HAND and its correlates using self-predictions of laboratory-based PM performance. Performance-based PM abilities, self-reported prediction of PM performance, and PM complaints in everyday life were assessed in 49 individuals with HAND, 93 HIV+ without HAND (HIV+ noHAND), and 121 seronegative adults (HIV-). After controlling for group-level differences, HAND was associated with a greater number of PM symptoms in everyday life and worse PM performance when compared with both HIV+ noHAND and HIV- samples. Although HAND individuals reported somewhat lower predictions regarding their laboratory PM performance relative to the other study groups, they nevertheless exhibited significantly greater inaccurate overconfidence in time-based PM abilities. Within the HAND group, overconfidence in time-based meta-PM was associated with executive dysfunction and antiretroviral (ARV) nonadherence. HAND individuals evidenced a moderate deficit in awareness of PM functioning characterized by overconfidence in time-based PM abilities. Overconfidence in PM may result in absence of compensatory strategy use, and lead to increased errors in daily functioning (e.g., ARV nonadherence).

  20. Self-Predictions of Prospective Memory in HIV-Associated Neurocognitive Disorders: Evidence of a Metamemory Deficit

    PubMed Central

    Casaletto, Kaitlin Blackstone; Doyle, Katie L.; Weber, Erica; Woods, Steven Paul; Heaton, Robert K.; Grant, Igor; Atkinson, J. Hampton; Ellis, Ronald J.; Letendre, Scott; Marcotte, Thomas D.; Marquie-Beck, Jennifer; Sherman, Melanie; Ellis, Ronald J.; Letendre, Scott; McCutchan, J. Allen; Best, Brookie; Schrier, Rachel; Rosario, Debra; Heaton, Robert K.; Atkinson, J. Hampton; Woods, Steven Paul; D, Psy; Marcotte, Thomas D.; Cherner, Mariana; Moore, David J.; Dawson, Matthew; Fennema-Notestine, Christine; Buchsbaum, Monte S.; Hesselink, John; Archibald, Sarah L.; Brown, Gregory; Buxton, Richard; Dale, Anders; Liu, Thomas; Masliah, Eliezer; Achim, Cristian; Smith, David M.; Richman, Douglas; McCutchan, J. Allen; Cherner, Mariana; Achim, Cristian; Lipton, Stuart; Atkinson, J. Hampton; Marquie-Beck, Jennifer; Gamst, Anthony C.; Cushman, Clint; Abramson, Ian; Vaida, Florin; Deutsch, Reena; Umlauf, Anya

    2014-01-01

    HIV-associated neurocognitive disorders (HAND) are associated with deficits in prospective memory (PM; “remembering to remember”), conferring risk of daily functioning declines. However, self-perceptions of PM functioning are not reliably associated with PM performance in HIV, suggesting a possible deficit in awareness of PM abilities (meta-PM). Our study examined meta-PM in HAND and its correlates using self-predictions of laboratory-based PM performance. Performance-based PM abilities, self-reported prediction of PM performance, and PM complaints in everyday life were assessed in 49 individuals with HAND, 93 HIV+ without HAND (HIV+ noHAND), and 121 seronegative adults (HIV−). After controlling for group-level differences, HAND was associated with a greater number of PM symptoms in everyday life and worse PM performance when compared with both HIV+ noHAND and HIV− samples. Although HAND individuals reported somewhat lower predictions regarding their laboratory PM performance relative to the other study groups, they nevertheless exhibited significantly greater inaccurate overconfidence in time-based PM abilities. Within the HAND group, overconfidence in time-based meta-PM was associated with executive dysfunction and antiretroviral (ARV) nonadherence. HAND individuals evidenced a moderate deficit in awareness of PM functioning characterized by overconfidence in time-based PM abilities. Overconfidence in PM may result in absence of compensatory strategy use, and lead to increased errors in daily functioning (e.g., ARV nonadherence). PMID:25404005

  1. Working memory dysfunction associated with brain functional deficits and cellular metabolic changes in patients with generalized anxiety disorder.

    PubMed

    Moon, Chung-Man; Sundaram, Thirunavukkarasu; Choi, Nam-Gil; Jeong, Gwang-Woo

    2016-08-30

    Generalized anxiety disorder (GAD) is associated with brain functional and morphological changes in connected with emotional dysregulation and cognitive deficit. This study dealt with the neural functional deficits and metabolic abnormalities in working memory (WM) task with emotion-inducing distractors in patients with GAD. Fourteen patients with GAD and 14 healthy controls underwent functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy ((1)H-MRS) at 3T. In response to the emotional distractors in WM tasks, the patients concurrently showed higher activity in the hippocampus and lower activities in the superior occipital gyrus, superior parietal gyrus, dorsolateral prefrontal cortex (DLPFC) and precentral gyrus compared to the controls. MRS revealed significantly lower choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) ratios in the DLPFC. In particular, the Cho ratios were positively correlated with the brain activities based on blood oxygenation level-dependent signal change in the DLPFC. This study provides the first evidence for the association between the metabolic alterations and functional deficit in WM processing with emotion-inducing distractors in GAD. These findings will be helpful to understand the neural dysfunction in connection with WM impairment in GAD.

  2. Chronic exposure of rats to noise: relationship between long-term memory deficits and slow wave sleep disturbances.

    PubMed

    Rabat, A; Bouyer, J J; George, O; Le Moal, M; Mayo, W

    2006-08-10

    Noise is now recognized as a serious health problem in our modern societies. Although its deleterious and direct effects on cognitive tasks (long-term memory, mental arithmetic activity, visual tasks, etc.) are clearly admitted, no studies have determined a delayed indirect effect of noise on cognitive processes. Furthermore, the link between sleep disturbances related to environmental noise (EN) exposure and these indirect deteriorations of human performances has never been demonstrated. This could be due to inappropriate evaluation of sleep as well as to uncontrolled and confounding factors such as sex, age, and also inter-individual vulnerability. Based on a recently validated animal model [Rabat A, Bouyer JJ, Aran JM, Le Moal M, Mayo W. Chronic exposure to an environmental noise permanently disturbs sleep in rats: inter-individual vulnerability. Brain Res 2005;1059:72-82], aims of the present study were (i) to determine long-term memory (LTM) deficits following a chronic exposure to EN and (ii) to link these behavioral problems to sleep disturbances related to EN. For this purpose in a first experiment, LTM performances were evaluated before and following 9 days of EN. Results show LTM deficits following a chronic exposure to EN with inter-individual vulnerability. Vulnerability profile was related to the psychobiological profile of rats. Results of the second experiment show LTM deficits correlated to both debt of slow wave sleep (SWS) and to daily decrease of SWS bout duration. Our results demonstrate that chronic exposure to noise indirectly disturbs LTM possibly through SWS disturbances and suggest a possible role of the stress hormonal axis in these biological effects of noise.

  3. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

    PubMed

    Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

    2016-04-01

    Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD.

  4. Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence.

    PubMed

    Roman-Urrestarazu, Andres; Lindholm, Päivi; Moilanen, Irma; Kiviniemi, Vesa; Miettunen, Jouko; Jääskeläinen, Erika; Mäki, Pirjo; Hurtig, Tuula; Ebeling, Hanna; Barnett, Jennifer H; Nikkinen, Juha; Suckling, John; Jones, Peter B; Veijola, Juha; Murray, Graham K

    2016-05-01

    When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnorma lities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20-24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20-24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time.

  5. Rutin protects against neuronal damage in vitro and ameliorates doxorubicin-induced memory deficits in vivo in Wistar rats

    PubMed Central

    Ramalingayya, Grandhi Venkata; Cheruku, Sri Pragnya; Nayak, Pawan G; Kishore, Anoop; Shenoy, Rekha; Rao, Chamallamudi Mallikarjuna; Krishnadas, Nandakumar

    2017-01-01

    Doxorubicin (DOX) is the most widely used broad-spectrum anticancer agent, either alone or in combination, for most cancers including breast cancer. Long-term use of chemotherapeutic agents to treat breast cancer patients results in cognitive complications with a negative impact on survivors’ quality of life. The study objective was to evaluate rutin (RUT) for its neuroprotective effect against DOX in human neuroblastoma (IMR32) cells in vitro and study its potential to ameliorate DOX-induced cognitive dysfunction in Wistar rats. Cell viability assay (3-[4,5 dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide), neurite growth assay, detection of apoptosis by (acridine orange/ethidium bromide) staining, intracellular reactive oxygen species (ROS) assay, and flowcytometric analysis were carried out to assess neuroprotective potential against DOX. An in vivo study was conducted for assessing protective effect of RUT against memory deficit associated with DOX-induced chemobrain using object recognition task (ORT). Locomotion was assessed using open field test. Serum biochemistry, acetylcholinesterase, oxidative stress markers in hippocampus, and frontal cortex were assessed. Histopathological analysis of major organ systems was also carried out. Prior exposure to RUT at 100 µM protected IMR32 cells from DOX (1 µM) neurotoxicity. DOX exposure resulted in increased cellular death, apoptosis, and intracellular ROS generation with inhibition of neurite growth in differentiated IMR32 cells, which was significantly ameliorated by RUT. Cognitive dysfunction was induced in Wistar rats by administering ten cycles of DOX (2.5 mg/kg, intra-peritoneal, once in 5 days), as we observed significant impairment of episodic memory in ORT. Coadministration with RUT (50 mg/kg, per os) significantly prevented memory deficits in vivo without any confounding influence on locomotor activity. RUT also offered protection against DOX-induced myelosuppression, cardiotoxicity, and

  6. Rutin protects against neuronal damage in vitro and ameliorates doxorubicin-induced memory deficits in vivo in Wistar rats.

    PubMed

    Ramalingayya, Grandhi Venkata; Cheruku, Sri Pragnya; Nayak, Pawan G; Kishore, Anoop; Shenoy, Rekha; Rao, Chamallamudi Mallikarjuna; Krishnadas, Nandakumar

    2017-01-01

    Doxorubicin (DOX) is the most widely used broad-spectrum anticancer agent, either alone or in combination, for most cancers including breast cancer. Long-term use of chemotherapeutic agents to treat breast cancer patients results in cognitive complications with a negative impact on survivors' quality of life. The study objective was to evaluate rutin (RUT) for its neuroprotective effect against DOX in human neuroblastoma (IMR32) cells in vitro and study its potential to ameliorate DOX-induced cognitive dysfunction in Wistar rats. Cell viability assay (3-[4,5 dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide), neurite growth assay, detection of apoptosis by (acridine orange/ethidium bromide) staining, intracellular reactive oxygen species (ROS) assay, and flowcytometric analysis were carried out to assess neuroprotective potential against DOX. An in vivo study was conducted for assessing protective effect of RUT against memory deficit associated with DOX-induced chemobrain using object recognition task (ORT). Locomotion was assessed using open field test. Serum biochemistry, acetylcholinesterase, oxidative stress markers in hippocampus, and frontal cortex were assessed. Histopathological analysis of major organ systems was also carried out. Prior exposure to RUT at 100 µM protected IMR32 cells from DOX (1 µM) neurotoxicity. DOX exposure resulted in increased cellular death, apoptosis, and intracellular ROS generation with inhibition of neurite growth in differentiated IMR32 cells, which was significantly ameliorated by RUT. Cognitive dysfunction was induced in Wistar rats by administering ten cycles of DOX (2.5 mg/kg, intra-peritoneal, once in 5 days), as we observed significant impairment of episodic memory in ORT. Coadministration with RUT (50 mg/kg, per os) significantly prevented memory deficits in vivo without any confounding influence on locomotor activity. RUT also offered protection against DOX-induced myelosuppression, cardiotoxicity, and

  7. Dipeptide preparation Noopept prevents scopolamine-induced deficit of spatial memory in BALB/c mice.

    PubMed

    Belnik, A P; Ostrovskaya, R U; Poletaeva, I I

    2007-04-01

    The effect of original nootropic preparation Noopept on learning and long-term memory was studied with BALB/c mice. Scopolamine (1 mg/kg) impaired long-term memory trace, while Noopept (0.5 mg/kg) had no significant effect. Noopept completely prevented the development of cognitive disorders induced by scopolamine (blockade of muscarinic cholinergic receptors). Our results confirmed the presence of choline-positive effect in dipeptide piracetam analogue Noopept on retrieval of learned skill of finding a submerged platform (spatial memory). We conclude that the effectiveness of this drug should be evaluated in patients with Alzheimer's disease.

  8. Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss.

    PubMed

    Havekes, Robbert; Bruinenberg, Vibeke M; Tudor, Jennifer C; Ferri, Sarah L; Baumann, Arnd; Meerlo, Peter; Abel, Ted

    2014-11-19

    The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation.

  9. Ameliorative effect of a hippocampal metabotropic glutamate- receptor agonist on histamine H1 receptor antagonist-induced memory deficit in rats.

    PubMed

    Masuoka, Takayoshi; Mikami, Azusa; Kamei, Chiaki

    2010-01-01

    This study was performed to investigate the ameliorative effects of metabotropic glutamate (mGlu)-receptor agonists on histamine H(1) receptor antagonist-induced spatial memory deficit and the decrease in hippocampal theta activity in rats. Intraperitoneal injection of pyrilamine (35 mg/kg) resulted in impaired reference and working memory in the radial maze task and decreased hippocampal theta amplitude and power. The working memory deficit and decreased hippocampal theta power induced by pyrilamine were ameliorated by intrahippocampal injection of (RS)-3,5-dihydroxyphenylglycine (DHPG) (1 and 10 microg/side), a group I mGlu-receptor agonist; however, intrahippocampal injection of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC), a group II mGlu-receptor agonist, and L-(+)-2-amino-4-phosphonobutyric acid (L-AP4), a group III mGlu-receptor agonist, showed no significant effect on the pyrilamine-induced memory deficit and decreased hippocampal theta activity. These results indicate that the activation of hippocampal group I mGlu receptors, but not group II and III mGlu receptors, improve the histamine H(1) receptor antagonist-induced working memory deficit and decreased hippocampal theta activity.

  10. Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

    PubMed Central

    Bruinenberg, Vibeke M.; Tudor, Jennifer C.; Ferri, Sarah L.; Baumann, Arnd; Meerlo, Peter

    2014-01-01

    The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object–location task. Five hours of total sleep deprivation directly following training impaired the formation of object–location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation. PMID:25411499

  11. [Effect and mechanism of Coeloglossum viride var. bracteatum extract on scopolamine-induced deficits of learning and memory behavior of rodents].

    PubMed

    Li, Min; Wang, Ya-fang; Ma, Bo; Liu, Geng-tao; Zhang, Jian-jun

    2009-05-01

    The aim of the present study is to investigate the effect and mechanism of Coeloglossum viride var. bracteatum extract (CE) on scopolamine-induced learning and memory deficits. Learning and memory deficits of mice were evaluated by step-down passive avoidance test. Long-term potentiation of rats was detected in the dentate gyrus of hippocampus. Brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities were also determined. The results showed that scopolamine impaired learning and memory performance and LTP induction in hippocampus. Oral administration of CE (5, 10, and 20 mg x kg(-1)) significantly alleviated scopolamine-induced memory deficits measured by step-down test (P < 0.05). CE (5 mg x kg(-1), ip) significantly reversed the inhibitory effect of scopolamine on LTP in rats. In addition, CE was found to increase the activity of ChAT in rat brain. These results suggested that CE could alleviate scopolamine-induced learning and memory deficits, which might be due to the LTP-improvement and ChAT activity enhancement.

  12. Piracetam prevents memory deficit induced by postnatal propofol exposure in mice.

    PubMed

    Wang, Yuan-Lin; Li, Feng; Chen, Xin

    2016-05-15

    Postnatal propofol exposure impairs hippocampal synaptic development and memory. However, the effective agent to alleviate the impairments was not verified. In this study, piracetam, a positive allosteric modulator of AMPA receptor was administered following a seven-day propofol regime. Two months after propofol administration, hippocampal long-term potentiation (LTP) and long-term memory decreased, while intraperitoneal injection of piracetam at doses of 100mg/kg and 50mg/kg following last propofol exposure reversed the impairments of memory and LTP. Mechanically, piracetam reversed propofol exposure-induced decrease of BDNF and phosphorylation of mTor. Similar as piracetam, BDNF supplementary also ameliorated propofol-induced abnormalities of synaptic plasticity-related protein expressions, hippocampal LTP and long-term memory. These results suggest that piracetam prevents detrimental effects of propofol, likely via activating BDNF synthesis.

  13. Social interaction rescues memory deficit in an animal model of Alzheimer's disease by increasing BDNF-dependent hippocampal neurogenesis.

    PubMed

    Hsiao, Ya-Hsin; Hung, Hui-Chi; Chen, Shun-Hua; Gean, Po-Wu

    2014-12-03

    It has been recognized that the risk of cognitive decline during aging can be reduced if one maintains strong social connections, yet the neural events underlying this beneficial effect have not been rigorously studied. Here, we show that amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice demonstrate improvement in memory after they are cohoused with wild-type mice. The improvement was associated with increased protein and mRNA levels of BDNF in the hippocampus. Concomitantly, the number of BrdU(+)/NeuN(+) cells in the hippocampal dentate gyrus was significantly elevated after cohousing. Methylazoxymethanol acetate, a cell proliferation blocker, markedly reduced BrdU(+) and BrdU/NeuN(+) cells and abolished the effect of social interaction. Selective ablation of mitotic neurons using diphtheria toxin (DT) and a retrovirus vector encoding DT receptor abolished the beneficial effect of cohousing. Knockdown of BDNF by shRNA transfection blocked, whereas overexpression of BDNF mimicked the memory-improving effect. A tropomyosin-related kinase B agonist, 7,8-dihydroxyflavone, occluded the effect of social interaction. These results demonstrate that increased BDNF expression and neurogenesis in the hippocampus after cohousing underlie the reversal of memory deficit in APP/PS1 mice.

  14. Behavioral phenotype of maLPA1-null mice: increased anxiety-like behavior and spatial memory deficits

    PubMed Central

    Santin, L.J.; Bilbao, A.; Pedraza, C.; Matas-Rico, E.; López-Barroso, D.; Castilla-Ortega, E.; Sánchez-López, J.; Riquelme, R.; Varela-Nieto, I.; de la Villa, P.; Suardíaz, M.; Chun, J.; De Fonseca, F. Rodriguez; Estivill-Torrús, G.

    2016-01-01

    Lysophosphatidic acid (LPA) has emerged as a new regulatory molecule in the brain. Recently, some studies have demonstrated a role for this molecule and its LPA1 receptor in the regulation of plasticity and neurogenesis in the adult brain. However, no systematic studies have been conducted to investigate whether the LPA1 receptor is involved in behavior. Here we studied the phenotype of maLPA1–null mice, which bear a targeted deletion at the lpa1 locus, in a battery of tests examining neurologic performance, habituation in exploratory behavior in response to low and mild anxiety environments and spatial memory. MaLPA1-null mutants showed deficits in both olfaction and somesthesis, but not in retinal or auditory functions. Sensorimotor coordination was impaired only in the equilibrium and grasping reflexes. The mice also showed impairments in neuromuscular strength and analgesic response. No additional differences were observed in the rest of the tests used to study sensoriomotor orientation, limb reflexes, and coordinated limb use. At behavioral level, maLPA1-null mice showed an impaired exploration in the open field and increased anxiety-like response when exposed to the elevated plus maze. Furthermore, the mice exhibit impaired spatial memory retention and reduced use of spatial strategies in the Morris water maze. We propose that the LPA1 receptor may play a major role in both spatial memory and response to anxiety-like conditions. PMID:19689455

  15. Experience-Based Mitigation of Age-Related Performance Declines: Evidence from Air Traffic Control

    ERIC Educational Resources Information Center

    Nunes, Ashley; Kramer, Arthur F.

    2009-01-01

    Previous research has found age-related deficits in a variety of cognitive processes. However, some studies have demonstrated age-related sparing on tasks where individuals have substantial experience, often attained over many decades. Here, the authors examined whether decades of experience in a fast-paced demanding profession, air traffic…

  16. Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats

    PubMed Central

    Azman, Khairunnuur Fairuz; Abdul Aziz, Che Badariah; Othman, Zahiruddin

    2016-01-01

    Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A), 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF) concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC) and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system. PMID:27119005

  17. Spatial working memory and arithmetic deficits in children with nonverbal learning difficulties.

    PubMed

    Mammarella, Irene Cristina; Lucangeli, Daniela; Cornoldi, Cesare

    2010-01-01

    Visuospatial working memory and its involvement in arithmetic were examined in two groups of 7- to 11-year-olds: one comprising children described by teachers as displaying symptoms of nonverbal learning difficulties (N = 21), the other a control group without learning disabilities (N = 21). The two groups were matched for verbal abilities, age, gender, and sociocultural level. The children were presented with a visuospatial working memory battery of recognition tests involving visual, spatial-sequential and spatial-simultaneous processes, and two arithmetic tasks (number ordering and written calculations). The two groups were found to differ on some spatial tasks but not in the visual working memory tasks. On the arithmetic tasks, the children with nonverbal learning difficulties made more errors than controls in calculation and were slower in number ordering. A discriminant function analysis confirmed the crucial role of spatial-sequential working memory in distinguishing between the two groups. Results are discussed with reference to spatial working memory and arithmetic difficulties in nonverbal learning disabilities. Implications for the relationship between visuospatial working memory and arithmetic are also considered.

  18. Associations between trait anhedonia and emotional memory deficits in females with schizophrenia versus major depression.

    PubMed

    Olsen, Emily K; Bjorkquist, Olivia A; Bodapati, Anjuli S; Shankman, Stewart A; Herbener, Ellen S

    2015-12-15

    Individuals with schizophrenia (SZ) and individuals with major depressive disorder (MDD) demonstrate impaired emotional memory and decreased enjoyment of pleasant experiences (e.g., anhedonia). However, it is unclear whether these impairments reflect similar or different processes in the two diagnostic groups. This study compared emotional memory performance in three groups of females - controls, MDD, and SZ. Given that physical and social trait anhedonia has been shown to differentiate course of illness and emotional functioning within each disorder, the present study also examined whether trait anhedonia related to emotional memory differently in the groups. Participants viewed emotional and neutral images and twenty-four hours later completed an incidental recognition test. SZ participants demonstrated a trend for the worst memory performance. Across all groups, high intensity and negative images were remembered most accurately, while groups were not differentially influenced by the valence of the stimuli. Physical anhedonia was predictive of reduced memory for negative stimuli across all diagnostic groups. Group specific findings indicated that higher levels of social anhedonia were predictive of poorer memory, but only in the SZ group. Effects remained significant when controlling for depressive symptoms. Results are considered in light of the differing role of anhedonia in SZ and MDD.

  19. Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats.

    PubMed

    Azman, Khairunnuur Fairuz; Zakaria, Rahimah; Abdul Aziz, Che Badariah; Othman, Zahiruddin

    2016-01-01

    Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A), 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF) concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC) and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system.

  20. Auditory Temporal Processing and Working Memory: Two Independent Deficits for Dyslexia

    ERIC Educational Resources Information Center

    Fostick, Leah; Bar-El, Sharona; Ram-Tsur, Ronit

    2012-01-01

    Dyslexia is a neuro-cognitive disorder with a strong genetic basis, characterized by a difficulty in acquiring reading skills. Several hypotheses have been suggested in an attempt to explain the origin of dyslexia, among which some have suggested that dyslexic readers might have a deficit in auditory temporal processing, while others hypothesized…

  1. "Gadd45b" Knockout Mice Exhibit Selective Deficits in Hippocampus-Dependent Long-Term Memory

    ERIC Educational Resources Information Center

    Leach, Prescott T.; Poplawski, Shane G.; Kenney, Justin W.; Hoffman, Barbara; Liebermann, Dan A.; Abel, Ted; Gould, Thomas J.

    2012-01-01

    Growth arrest and DNA damage-inducible [beta] ("Gadd45b") has been shown to be involved in DNA demethylation and may be important for cognitive processes. "Gadd45b" is abnormally expressed in subjects with autism and psychosis, two disorders associated with cognitive deficits. Furthermore, several high-throughput screens have identified "Gadd45b"…

  2. Effects of Verbal Working Memory Deficits on Metaphor Comprehension in Patients with Parkinson's Disease

    ERIC Educational Resources Information Center

    Monetta, Laura; Pell, Marc D.

    2007-01-01

    This research studied one aspect of pragmatic language processing, the ability to understand metaphorical language, to determine whether patients with Parkinson disease (PD) are impaired for these abilities, and whether cognitive resource limitations/fronto-striatal dysfunction contributes to these deficits. Seventeen PD participants and healthy…

  3. Tart cherries improve working memory in aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on cognitive tasks that require the use of spatial learning and memory. In previous studies, we have shown the beneficial effects of various dark-colored berry fruits (blueberries, strawberries, and blackberries) in reversing age-related deficits in behavioral and...

  4. HIV-infected persons with bipolar disorder are less aware of memory deficits as compared to HIV-infected persons without bipolar disorder

    PubMed Central

    Blackstone, Kaitlin; Tobin, Alexis; Posada, Carolina; Gouaux, Ben; Grant, Igor; Moore, David J.

    2012-01-01

    Episodic memory deficits are common in HIV infection and bipolar disorder, but patient insight into such deficits remains unclear. Thirty-four HIV-infected individuals without bipolar disorder l(HIV+/BD−) and 47 HIV+ individuals with comorbid bipolar disorder (HIV+/BD+) were administered the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised to examine objective learning/memory functioning. Subjective memory complaints were assessed via the memory subscale of the Patient’s Assessment of Own Functioning Inventory. HIV+/BD+ individuals performed poorer on tests of visual learning and visual/verbal recall compared to HIV+/BD− participants (ps<0.05). Memory complaints only predicted verbal learning (at a trend level, p=0.10) and recall (p=0.03) among the HIV+/BD− individuals. Memory complaints were not associated with memory performance within the HIV+/BD+ group (ps>0.10). Memory complaints were associated with affective symptoms in both groups. These complaints were also predictive of immunosuppression, higher unemployment, and greater dependence on Activities of Daily Living among the HIV+/BD+ individuals (ps<0.05). Awareness of memory abilities was particularly poor among HIV+/BD+ individuals (i.e., objective learning/memory did not correspond to reported complaints), which has important implications for the capacity of these individuals to engage in error-monitoring and compensatory strategies in daily life. Memory complaints are associated with depressed mood regardless of group membership. Among HIV+/BD+ individuals, these complaints may also signify worse HIV disease status and problems with everyday functioning. Clinicians and researchers should be cognizant of what these complaints indicate in order to lead treatment most effectively; use of objective neurocognitive assessments may still be warranted when working with these populations. PMID:22571839

  5. Aging affects the interaction between attentional control and source memory: an fMRI study.

    PubMed

    Dulas, Michael R; Duarte, Audrey

    2014-12-01

    Age-related source memory impairments may be due, at least in part, to deficits in executive processes mediated by the PFC at both study and test. Behavioral work suggests that providing environmental support at encoding, such as directing attention toward item-source associations, may improve source memory and reduce age-related deficits in the recruitment of these executive processes. The present fMRI study investigated the effects of directed attention and aging on source memory encoding and retrieval. At study, participants were shown pictures of objects. They were either asked to attend to the objects and their color (source) or to their size. At test, participants determined if objects were seen before, and if so, whether they were the same color as previously. Behavioral results showed that direction of attention improved source memory for both groups; however, age-related deficits persisted. fMRI results revealed that, across groups, direction of attention facilitated medial temporal lobe-mediated contextual binding processes during study and attenuated right PFC postretrieval monitoring effects at test. However, persistent age-related source memory deficits may be related to increased recruitment of medial anterior PFC during encoding, indicative of self-referential processing, as well as underrecruitment of lateral anterior PFC-mediated relational processes. Taken together, this study suggests that, even when supported, older adults may fail to selectively encode goal-relevant contextual details supporting source memory performance.

  6. Interleukin-1beta induces anorexia but not spatial learning and memory deficits in the rat.

    PubMed

    Thomson, Lisa M; Sutherland, Robert J

    2006-06-30

    Sickness behaviors are a set of adaptive responses to infection that include lethargy, anorexia, and, of direct relevance to this work, learning and memory impairments. The proinflammatory cytokine, interleukin-1 beta (IL-1beta) has been proposed as the primary peripheral mediator of these sickness behaviors, though few studies have investigated the effects of peripheral IL-1beta on learning and memory. We used three different versions of the Morris water task (Morris water task), a spatial learning and memory task, to separately assess the effects of peripheral IL-1beta on acquisition, consolidation, and retention of spatial location information. Using a dose that induced anorexia, assessed as a significant reduction in body weight, we observed no performance impairments in the IL-1beta-treated rats across the different versions of the task, suggesting that peripheral IL-1beta alone is insufficient to induce spatial learning and memory impairments in the rat. The observed dissociation of anorexia and cognitive dysfunction suggests that, either spatial learning and memory are not principal components of the sickness response, or cognitive dysfunction requires different or additional peripheral mediator(s).

  7. Inhibitory avoidance memory deficit induced by scopolamine: interaction with glutamatergic system in the nucleus accumbens.

    PubMed

    Pakpour, Bahareh; Ahmadi, Shamseddin; Nayer-Nouri, Touraj; Oryan, Shahrbanoo; Zarrindast, Mohammad Reza

    2010-12-01

    The possible involvement of N-methyl-D-aspartate (NMDA) receptors of the nucleus accumbens (NAc) in amnesia induced by scopolamine was investigated. An inhibitory (passive) avoidance task was used for memory assessment in male Wistar rats. The results revealed that intra-NAc administration of a nonselective muscarinic acetylcholine antagonist, scopolamine (1 and 2 g/rat) impaired memory consolidation in the animals when tested 24 h later. Post-training intra-NAc administration of NMDA (0.005 and 0.01 g/rat) also impaired memory consolidation, whereas post-training intra-NAc administration of the NMDA receptor antagonist, MK-801 (0.5, 1 and 1.5 g/rat) did not. Intra-NAc co-administration of an ineffective dose of NMDA with ineffective doses of scopolamine (0.25 and 0.5 g/rat) after training had no significant effect on memory consolidation, but intra-NAc injections of effective doses of NMDA (0.005 and 0.01 g/rat) prevented the amnesic effect of an effective dose of scopolamine (2 g/rat). In contrast, intra-NAc co-administration of MK-801 (0.5, 1 and 1.5 g/rat) along with an effective dose of scopolamine (2 g/rat) did not prevent the effect of the latter drug. It can be concluded that NMDA receptors in the NAc are involved in the modulation of memory consolidation that was affected by scopolamine.

  8. Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents

    PubMed Central

    Gui, Wen-Shan; Wei, Xiao; Mai, Chun-Lin; Murugan, Madhuvika; Wu, Long-Jun; Xin, Wen-Jun; Zhou, Li-Jun

    2016-01-01

    Background Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Results Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Conclusions Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression. PMID:27175012

  9. Voluntary exercise does not ameliorate spatial learning and memory deficits induced by chronic administration of nandrolone decanoate in rats.

    PubMed

    Tanehkar, Fatemeh; Rashidy-Pour, Ali; Vafaei, Abbas Ali; Sameni, Hamid Reza; Haghighi, Saeed; Miladi-Gorji, Hossien; Motamedi, Fereshteh; Akhavan, Maziar Mohammad; Bavarsad, Kowsar

    2013-01-01

    Chronic exposure to the anabolic androgenic steroids (AAS) nandrolone decanoate (ND) in supra-physiological doses is associated with learning and memory impairments. Given the well-known beneficial effects of voluntary exercise on cognitive functions, we examined whether voluntary exercise would improve the cognitive deficits induced by chronic administration of ND. We also investigated the effects of ND and voluntary exercise on hippocampal BDNF levels. The rats were randomly distributed into 4 experimental groups: the vehicle-sedentary group, the ND-sedentary group, the vehicle-exercise group, and the ND-exercise group. The vehicle-exercise and the ND-exercise groups were allowed to freely exercise in a running wheel for 15 days. The vehicle-sedentary and the ND-sedentary groups were kept sedentary for the same period. Vehicle or ND injections were started 14 days prior to the voluntary exercise and continued throughout the 15 days of voluntary exercise. After the 15-day period, the rats were trained and tested on a water maze spatial task using four trials per day for 5 consecutive days followed by a probe trial two days later. Exercise significantly improved performance during both the training and retention of the water maze task, and enhanced hippocampal BDNF. ND impaired spatial learning and memory, and this effect was not rescued by exercise. ND also potentiated the exercise-induced increase in hippocampal BDNF levels. These results seem to indicate that voluntary exercise is unable to improve the disruption of cognitive functions by chronic ND. Moreover, increased levels of BDNF may play a role in ND-induced impairments in learning and memory. The harmful effects of ND and other AAS on learning and memory should be taken into account when athletes decide to use AAS for performance or body image improvement.

  10. Dietary supplementation of walnuts improves memory deficits and learning skills in transgenic mouse model of Alzheimer's disease.

    PubMed

    Muthaiyah, Balu; Essa, Musthafa M; Lee, Moon; Chauhan, Ved; Kaur, Kulbir; Chauhan, Abha

    2014-01-01

    Previous in vitro studies have shown that walnut extract can inhibit amyloid-β (Aβ) fibrillization, can solubilize its fibrils, and has a protective effect against Aβ-induced oxidative stress and cellular death. In this study, we analyzed the effect of dietary supplementation with walnuts on learning skills, memory, anxiety, locomotor activity, and motor coordination in the Tg2576 transgenic (tg) mouse model of Alzheimer's disease (AD-tg). From the age of 4 months, the experimental groups of AD-tg mice were fed custom-mixed diets containing 6% walnuts (T6) or 9% walnuts (T9), i.e., equivalent to 1 or 1.5 oz, respectively, of walnuts per day in humans. The control groups, i.e., AD-tg and wild-type mice, were fed a diet without walnuts (T0, Wt). These experimental and control mice were examined at the ages of 13-14 months by Morris water maze (for spatial memory and learning ability), T maze (for position discrimination learning ability), rotarod (for psychomotor coordination), and elevated plus maze (for anxiety-related behavior). AD-tg mice on the control diet (T0) showed memory deficit, anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability, and motor coordination compared to the Wt mice on the same diet. The AD-tg mice receiving the diets with 6% or 9% walnuts (T6 and T9) showed a significant improvement in memory, learning ability, anxiety, and motor development compared to the AD-tg mice on the control diet (T0). There was no statistically significant difference in behavioral performance between the T6/T9 mice on walnuts-enriched diets and the Wt group on the control diet. These findings suggest that dietary supplementation with walnuts may have a beneficial effect in reducing the risk, delaying the onset, or slowing the progression of, or preventing AD.

  11. Early postnatal maternal deprivation in rats induces memory deficits in adult life that can be reversed by donepezil and galantamine.

    PubMed

    Benetti, Fernando; Mello, Pâmela Billig; Bonini, Juliana Sartori; Monteiro, Siomara; Cammarota, Martín; Izquierdo, Iván

    2009-02-01

    Early postnatal maternal deprivation is known to cause long-lasting neurobiological effects. Here, we investigated whether some of the cognitive aspects of these deficits might be related to a disruption of the cholinergic system. Pregnant Wistar rats were individually housed and maintained on a 12:12h light/dark cycle with food and water freely available. The mothers were separated from their pups for 3h per day from postnatal day 1 (PND-1) to PND-10. To do that, the dams were moved to a different cage and the pups maintained in the original home cage, which was transferred to a different room kept at 32 degrees C. After they reached 120-150 days of age, maternal-deprived and non-deprived animals were either sacrificed for brain acetylcholinesterase measurement, or trained and tested in an object recognition task and in a social recognition task as described by Rossato et al. (2007) [Rossato, J.I., Bevilaqua, L. R.M., Myskiw, J.C., Medina, J.H., Izquierdo, I., Cammarota, M. 2007. On the role hippocampal synthesis in the consolidation and reconsolidation of object recognition memory. Learn. Mem. 14, 36-46] and Lévy et al. (2003) [Lévy, F., Melo. A.I., Galef. B.G. Jr., Madden, M., Fleming. A.S. 2003. Complete maternal deprivation affects social, but not spatial, learning in adult rats. Dev. Psychobiol. 43, 177-191], respectively. There was increased acetylcholinesterase activity in hippocampus and perirhinal cortex of the deprived animals. In addition, they showed a clear impairment in memory of the two recognition tasks measured 24h after training. Oral administration of the acetylcholinesterase inhibitors, donepezil or galantamine (1mg/kg) 30min before training reversed the memory impairments caused by maternal deprivation. The findings suggest that maternal deprivation affects memory processing at adulthood through a change in brain cholinergic systems.

  12. Age-related changes in the use of regular patterns for auditory scene analysis.

    PubMed

    Rimmele, Johanna; Schröger, Erich; Bendixen, Alexandra

    2012-07-01

    A recent approach to auditory processing suggests a close relationship of regularity processing in auditory sensory memory (ASM) and stream segregation, such that within-stream regularities can be used to stabilize stream segregation. The present study investigates age-related changes in how regular patterns are used for auditory scene analysis (ASA), when the stream containing the regularity is attended or unattended. In order to accomplish an intensity level deviant detection task, participants had to segregate the task-relevant pure tone sequence from an irrelevant distractor pure tone sequence, which randomly varied in level. In three conditions a simple spectro-temporal regularity ("Isochronous"), a more complex spectro-temporal regularity ("Rhythmic"), or no regularity ("Random") was embedded in either the attended target sequence (Experiment 1), or the unattended distractor sequence (Experiment 2). When the sequence containing the regularity was attended, older participants showed a similar increase of performance to younger adults in the conditions with regular patterns ("Isochronous" and "Rhythmic") compared to the "Random" condition. In contrast, when the sequence containing the regularity was unattended, older adults showed a specific performance decline compared to younger adults in the "Isochronous" condition. Results suggest a link between impaired automatic processing of regularities in ASM, and age-related deficits in the use of regular patterns for ASA.

  13. Involvement of dopaminergic and cholinergic systems in social isolation-induced deficits in social affiliation and conditional fear memory in mice.

    PubMed

    Okada, R; Fujiwara, H; Mizuki, D; Araki, R; Yabe, T; Matsumoto, K

    2015-07-23

    Post-weaning social isolation rearing (SI) in rodents elicits various behavioral abnormalities including attention deficit hyperactivity disorder-like behaviors. In order to obtain a better understanding of SI-induced behavioral abnormalities, we herein investigated the effects of SI on social affiliation and conditioned fear memory as well as the neuronal mechanism(s) underlying these effects. Four-week-old male mice were group-housed (GH) or socially isolated for 2-4 weeks before the experiments. The social affiliation test and fear memory conditioning were conducted at the age of 6 and 7 weeks, respectively. SI mice were systemically administered saline or test drugs 30 min before the social affiliation test and fear memory conditioning. Contextual and auditory fear memories were elucidated 1 and 4 days after fear conditioning. Social affiliation and contextual and auditory fear memories were weaker in SI mice than in GH mice. Methylphenidate (MPH), an inhibitor for dopamine transporters, ameliorated the SI-induced social affiliation deficit and the effect was attenuated by SCH23390, a D1 receptor antagonist, but not by sulpiride, a D2 receptor antagonist. On the other hand, tacrine, an acetylcholinesterase inhibitor, had no effect on this deficit. In contrast, tacrine improved SI-induced deficits in fear memories in a manner that was reversed by the muscarinic receptor antagonist scopolamine, while MPH had no effect on memory deficits. Neurochemical studies revealed that SI down-regulated the expression levels of the phosphorylated forms of neuro-signaling proteins, calmodulin-dependent kinase II (p-CaMKII), and cyclic AMP-responsive element binding protein (p-CREB), as well as early growth response protein-1 (Egr-1) in the hippocampus. The administration of MPH or tacrine before fear conditioning had no effect on the levels of the phosphorylated forms of the neuro-signaling proteins elucidated following completion of the auditory fear memory test; however

  14. Spatial memory deficit across aging: current insights of the role of 5-HT7 receptors

    PubMed Central

    Beaudet, Gregory; Bouet, Valentine; Jozet-Alves, Christelle; Schumann-Bard, Pascale; Dauphin, François; Paizanis, Eleni; Boulouard, Michel; Freret, Thomas

    2015-01-01

    Elderly persons often face biological, psychological or social changes over time that may cause discomfort or morbidity. While some cognitive domains remain stable over time, others undergo a decline. Spatial navigation is a complex cognitive function essential for independence, safety and quality of life. While egocentric (body-centered) navigation is quite preserved during aging, allocentric (externally-centered) navigation—based on a cognitive map using distant landmarks—declines with age. Recent preclinical studies showed that serotonergic 5-HT7 receptors are localized in brain regions associated with allocentric spatial navigation processing. Behavioral assessments with pharmacological or genetic tools have confirmed the role of 5-HT7 receptors in allocentric navigation. Moreover, few data suggested a selective age-related decrease in the expression of 5-HT7 receptors in pivotal brain structures implicated in allocentric navigation such as the hippocampal CA3 region. We aim to provide a short overview of the potential role of 5-HT7 receptors in spatial navigation, and to argue for their interests as therapeutic targets against age-related cognitive decline. PMID:25642173

  15. Spatial memory deficit across aging: current insights of the role of 5-HT7 receptors.

    PubMed

    Beaudet, Gregory; Bouet, Valentine; Jozet-Alves, Christelle; Schumann-Bard, Pascale; Dauphin, François; Paizanis, Eleni; Boulouard, Michel; Freret, Thomas

    2014-01-01

    Elderly persons often face biological, psychological or social changes over time that may cause discomfort or morbidity. While some cognitive domains remain stable over time, others undergo a decline. Spatial navigation is a complex cognitive function essential for independence, safety and quality of life. While egocentric (body-centered) navigation is quite preserved during aging, allocentric (externally-centered) navigation-based on a cognitive map using distant landmarks-declines with age. Recent preclinical studies showed that serotonergic 5-HT7 receptors are localized in brain regions associated with allocentric spatial navigation processing. Behavioral assessments with pharmacological or genetic tools have confirmed the role of 5-HT7 receptors in allocentric navigation. Moreover, few data suggested a selective age-related decrease in the expression of 5-HT7 receptors in pivotal brain structures implicated in allocentric navigation such as the hippocampal CA3 region. We aim to provide a short overview of the potential role of 5-HT7 receptors in spatial navigation, and to argue for their interests as therapeutic targets against age-related cognitive decline.

  16. Acute treatment with bis selenide, an organic compound containing the trace element selenium, prevents memory deficits induced by reserpine in rats.

    PubMed

    Bortolatto, Cristiani Folharini; Guerra Souza, Ana Cristina; Wilhelm, Ethel Antunes; Nogueira, Cristina Wayne

    2013-01-01

    Taking into account the promising pharmacological actions of (Z)-2,3-bis(4-chlorophenylselanyl) prop-2-en-1-ol) (bis selenide), an organic compound containing the trace element selenium, and the constant search for drugs that improve the cognitive performance, the objective of the present study was to investigate whether bis selenide treatment ameliorates memory deficits induced by reserpine in rats. For this aim, male adult rats received a single subcutaneous injection of reserpine (1 mg/kg), a biogenic amine-depleting agent used to induce memory deficit. After 24 h, bis selenide at doses of 25 and 50 mg/kg was administered to rats by intragastric route, and 1 h later, the animals were submitted to behavior tasks. The effects of acute administration of bis selenide on memory were evaluated by social recognition, step-down passive avoidance, and object recognition paradigms. Exploratory and locomotor activities of rats were determined using the open-field test. Analysis of data revealed that the social memory disruption caused by reserpine was reversed by bis selenide at both doses. In addition, bis selenide, at the highest dose, prevented the memory deficit resulting from reserpine administration to rats in step-down passive avoidance and object recognition tasks. No significant alterations in locomotor and exploratory behaviors were found in animals treated with reserpine and/or bis selenide. Results obtained from distinct memory behavioral paradigms revealed that an acute treatment with bis selenide attenuated memory deficits induced by reserpine in rats.

  17. There are multiple contributors to the verbal short-term memory deficit in children with developmental reading disabilities.

    PubMed

    Kibby, Michelle Y

    2009-09-01

    Prior research has put forth at least four possible contributors to the verbal short-term memory (VSTM) deficit in children with developmental reading disabilities (RD): poor phonological awareness that affects phonological coding into VSTM, a less effective phonological store, slow articulation rate, and fewer/poorer quality long-term memory (LTM) representations. This project is among the first to test the four suppositions in one study. Participants included 18 children with RD and 18 controls. VSTM was assessed using Baddeley's model of the phonological loop. Findings suggest all four suppositions are correct, depending upon the type of material utilized. Children with RD performed comparably to controls in VSTM for common words but worse for less frequent words and nonwords. Furthermore, only articulation rate predicted VSTM for common words, whereas Verbal IQ and articulation rate predicted VSTM for less frequent words, and phonological awareness and articulation rate predicted VSTM for nonwords. Overall, findings suggest that the mechanism(s) used to code and store items by their meaning is intact in RD, and the deficit in VSTM for less frequent words may be a result of fewer/poorer quality LTM representations for these words. In contrast, phonological awareness and the phonological store are impaired, affecting VSTM for items that are coded phonetically. Slow articulation rate likely affects VSTM for most material when present. When assessing reading performance, VSTM predicted decoding skill but not word identification after controlling Verbal IQ and phonological awareness. Thus, VSTM likely contributes to reading ability when words are novel and must be decoded.

  18. Of goals and habits: age-related and individual differences in goal-directed decision-making.

    PubMed

    Eppinger, Ben; Walter, Maik; Heekeren, Hauke R; Li, Shu-Chen

    2013-01-01

    In this study we investigated age-related and individual differences in habitual (model-free) and goal-directed (model-based) decision-making. Specifically, we were interested in three questions. First, does age affect the balance between model-based and model-free decision mechanisms? Second, are these age-related changes due to age differences in working memory (WM) capacity? Third, can model-based behavior be affected by manipulating the distinctiveness of the reward value of choice options? To answer these questions we used a two-stage Markov decision task in in combination with computational modeling to dissociate model-based and model-free decision mechanisms. To affect model-based behavior in this task we manipulated the distinctiveness of reward probabilities of choice options. The results show age-related deficits in model-based decision-making, which are particularly pronounced if unexpected reward indicates the need for a shift in decision strategy. In this situation younger adults explore the task structure, whereas older adults show perseverative behavior. Consistent with previous findings, these results indicate that older adults have deficits in the representation and updating of expected reward value. We also observed substantial individual differences in model-based behavior. In younger adults high WM capacity is associated with greater model-based behavior and this effect is further elevated when reward probabilities are more distinct. However, in older adults we found no effect of WM capacity. Moreover, age differences in model-based behavior remained statistically significant, even after controlling for WM capacity. Thus, factors other than decline in WM, such as deficits in the in the integration of expected reward value into strategic decisions may contribute to the observed impairments in model-based behavior in older adults.

  19. Prospective study of Dietary Approaches to Stop Hypertension– and Mediterranean-style dietary patterns and age-related cognitive change: the Cache County Study on Memory, Health and Aging123

    PubMed Central

    Munger, Ronald G; Cutler, Adele; Quach, Anna; Bowles, Austin; Corcoran, Christopher; Tschanz, JoAnn T; Norton, Maria C; Welsh-Bohmer, Kathleen A

    2013-01-01

    Background: Healthy dietary patterns may protect against age-related cognitive decline, but results of studies have been inconsistent. Objective: We examined associations between Dietary Approaches to Stop Hypertension (DASH)– and Mediterranean-style dietary patterns and age-related cognitive change in a prospective, population-based study. Design: Participants included 3831 men and women ≥65 y of age who were residents of Cache County, UT, in 1995. Cognitive function was assessed by using the Modified Mini-Mental State Examination (3MS) ≤4 times over 11 y. Diet-adherence scores were computed by summing across the energy-adjusted rank-order of individual food and nutrient components and categorizing participants into quintiles of the distribution of the diet accordance score. Mixed-effects repeated-measures models were used to examine 3MS scores over time across increasing quintiles of dietary accordance scores and individual food components that comprised each score. Results: The range of rank-order DASH and Mediterranean diet scores was 1661–25,596 and 2407–26,947, respectively. Higher DASH and Mediterranean diet scores were associated with higher average 3MS scores. People in quintile 5 of DASH averaged 0.97 points higher than those in quintile 1 (P = 0.001). The corresponding difference for Mediterranean quintiles was 0.94 (P = 0.001). These differences were consistent over 11 y. Higher intakes of whole grains and nuts and legumes were also associated with higher average 3MS scores [mean quintile 5 compared with 1 differences: 1.19 (P < 0.001), 1.22 (P < 0.001), respectively]. Conclusions: Higher levels of accordance with both the DASH and Mediterranean dietary patterns were associated with consistently higher levels of cognitive function in elderly men and women over an 11-y period. Whole grains and nuts and legumes were positively associated with higher cognitive functions and may be core neuroprotective foods common to various healthy plant

  20. The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

    PubMed

    Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

    2015-01-01