Full Text Available Background/Aims: To explore the effects of sulforaphane (SFN on neuronal apoptosis in hippocampus and memory impairment in diabetic rats. Methods: Thirty male rats were randomly divided into normal control, diabetic model and SFN treatment groups (N = 10 in each group. Streptozotocin (STZ was applied to establish diabetic model. Water Morris maze task was applied to test learning and memory. Tunel assaying was used to detect apoptosis in hippocampus. The expressions of Caspase-3 and myeloid cell leukemia 1(MCL-1 were detected by western blotting. Neurotrophic factor levels and AKT/GSK3β pathway were also detected. Results: Compared with normal control, learning and memory were apparently impaired, with up-regulation of Caspase-3 and down-regulation of MCL-1 in diabetic rats. Apoptotic neurons were also found in CA1 region after diabetic modeling. By contrast, SFN treatment prevented the memory impairment, decreased the apoptosis of hippocampal neurons. SFN also attenuated the abnormal expression of Caspase-3 and MCL-1 in diabetic model. Mechanically, SFN treatment reversed diabetic modeling-induced decrease of p-Akt, p-GSK3β, NGF and BDNF expressions. Conclusion: SFN could prevent the memory impairment and apoptosis of hippocampal neurons in diabetic rat. The possible mechanism was related to the regulation of neurotropic factors and Akt/GSK3β pathway.
Full Text Available Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2% for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE, choline acetylase (ChAT and α7 nicotinic receptor (α7-nAChR were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane.
Alzoubi, Karem H; Rababa'h, Abeer M; Owaisi, Amani; Khabour, Omar F
Sleep deprivation (SD) negatively impacts memory, which was related to oxidative stress induced damage. L-carnitine is a naturally occurring compound, synthesized endogenously in mammalian species and known to possess antioxidant properties. In this study, the effect of L-carnitine on learning and memory impairment induced by rapid eye movement sleep (REM-sleep) deprivation was investigated. REM-sleep deprivation was induced using modified multiple platform model (8h/day, for 6 weeks). Simultaneously, L-carnitine was administered (300mg/kg/day) intraperitoneally for 6 weeks. Thereafter, the radial arm water maze (RAWM) was used to assess spatial learning and memory. Additionally, the hippocampus levels of antioxidant biomarkers/enzymes: reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS) were assessed. The results showed that chronic REM-sleep deprivation impaired both short- and long-term memory (Psleep deprivation induced reduction in the hippocampus ratio of GSH/GSSG, activity of catalase, GPx, and SOD. No change was observed in TBARS among tested groups (P>0.05). In conclusion, chronic REM-sleep deprivation induced memory impairment, and treatment with L-carnitine prevented this impairment through normalizing antioxidant mechanisms in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.
Ota, Simone M; Moreira, Karin Di Monteiro; Suchecki, Deborah; Oliveira, Maria Gabriela M; Tiba, Paula A
Pre-training rapid eye movement sleep (REMS) deprivation affects memory acquisition and/or consolidation. It also produces major REMS rebound at the cost of waking and slow wave sleep (SWS). Given that both SWS and REMS appear to be important for memory processes, REMS rebound after training may disrupt the organization of sleep cycles, i.e., excessive amount of REMS and/or little SWS after training could be harmful for memory formation. To examine whether lithium, a drug known to increase SWS and reduce REMS, could prevent the memory impairment induced by pre-training sleep deprivation. Animals were divided in 2 groups: cage control (CC) and REMS-deprived (REMSDep), and then subdivided into 4 subgroups, treated either with vehicle or 1 of 3 doses of lithium (50, 100, and 150 mg/kg) 2 h before training on the multiple trial inhibitory avoidance task. Animals were tested 48 h later to make sure that the drug had been already metabolized and eliminated. Another set of animals was implanted with electrodes and submitted to the same experimental protocol for assessment of drug-induced sleep-wake changes. Wistar male rats weighing 300-400 g. Sleep deprived rats required more trials to learn the task and still showed a performance deficit during test, except from those treated with 150 mg/kg of lithium, which also reduced the time spent in REM sleep during sleep recovery. Lithium reduced rapid eye movement sleep and prevented memory impairment induced by sleep deprivation. These results indicate that these phenomena may be related, but cause-effect relationship cannot be ascertained.
Sui, Zifang; Qi, Ce; Huang, Yunxiang; Ma, Shufeng; Wang, Xinguo; Le, Guowei; Sun, Jin
Aqueous extracts from Asparagus officinalis L. stems (AEAS) are rich in polysaccharides, gamma-amino butyric acid (GABA), and steroidal saponin. This study was designed to investigate the effects of AEAS on learning, memory, and acetylcholinesterase-related activity in a scopolamine-induced model of amnesia. Sixty ICR mice were randomly divided into 6 groups (n = 10) including the control group (CT), scopolamine group (SC), donepezil group (DON), low, medium, and high dose groups of AEAS (LS, MS, HS; 1.6 mL kg -1 , 8 mL kg -1 , 16 mL kg -1 ). The results showed that 8 mL kg -1 of AEAS used in this study significantly reversed scopolamine-induced cognitive impairments in mice in the novel object recognition test (P < 0.05) and the Y-maze test (P < 0.05), and also improved the latency to escape in the Morris water maze test (P < 0.05). Moreover, it significantly increased acetylcholine and inhibited acetylcholinesterase activity in the hippocampus, which was directly related to the reduction in learning and memory impairments. It also reversed scopolamine-induced reduction in the hippocampal brain-derived neurotrophic factor (BDNF) and the cAMP response element-binding protein (CREB) mRNA expression. AEAS protected against scopolamine-induced memory deficits. In conclusion, AEAS protected learning and memory function in mice by enhancing the activity of the cholinergic nervous system, and increasing BDNF and CREB expression. This suggests that AEAS has the potential to prevent cognitive impairments in age-related diseases, such as Alzheimer's disease.
Lee, Jin-Seok; Kim, Hyeong-Geug; Lee, Hye-Won; Kim, Won-Yong; Ahn, Yo-Chan; Son, Chang-Gue
The Pinus densiflora leaf has been traditionally used to treat mental health disorders as a traditional Chinese medicine. Here we examined the ethnopharmacological relevance of pine needle on memory impairment caused by stress. To elucidate the possible modulatory actions of 30% ethanolic pine needle extract (PNE) on stress-induced hippocampal excitotoxicity, we adopted an acute restraint stress mouse model. Mice were orally administered with PNE (25, 50, or 100mg/kg) or ascorbic acid (100mg/kg) for 9 days, and were then subjected to restraint stress (6h/day) for 3 days (from experimental day 7-9). To evaluate spatial cognitive and memory function, the Morris water maze was performed during experimental days 5-9. Restraint stress induced the memory impairment (the prolonged escape latency and cumulative path-length, and reduced time spent in the target quadrant), and these effects were significantly prevented by PNE treatment. The levels of corticosterone and its receptor in the sera/hippocampus were increased by restraint stress, which was normalized by PNE treatment. Restraint stress elicited the hippocampal excitotoxicity, the inflammatory response and oxidative injury as demonstrated by the increased glutamate levels, altered levels of tumor necrosis factor (TNF)-α and imbalanced oxidant-antioxidant balance biomarkers. Two immunohistochemistry activities against glial fibrillary acidic protein (GFAP)-positive astrocytes and neuronal nuclei (NeuN)-positive neurons supported the finding of excitotoxicity especially in the cornu ammonis (CA)3 region of the hippocampus. Those alterations were notably attenuated by administration of PNE. The above findings showed that PNE has pharmacological properties that modulate the hippocampal excitotoxicity-derived memory impairment under severe stress conditions. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
Spinetta, Michael J; Woodlee, Martin T; Feinberg, Leila M; Stroud, Chris; Schallert, Kellan; Cormack, Lawrence K; Schallert, Timothy
Ethanol and caffeine are two of the most widely consumed drugs in the world, often used in the same setting. Animal models may help to understand the conditions under which incidental memories formed just before ethanol intoxication might be lost or become difficult to retrieve. Ethanol-induced retrograde amnesia was investigated using a new odor-recognition test. Rats thoroughly explored a wood bead taken from the cage of another rat, and habituated to this novel odor (N1) over three trials. Immediately following habituation, rats received saline, 25 mg/kg pentylenetetrazol (a seizure-producing agent known to cause retrograde amnesia) to validate the test, 1.0 g/kg ethanol, or 3.0 g/kg ethanol. The next day, they were presented again with N1 and also a bead from a new rat's cage (N2). Rats receiving saline or the lower dose of ethanol showed overnight memory for N1, indicated by preferential exploration of N2 over N1. Rats receiving pentylenetetrazol or the higher dose of ethanol appeared not to remember N1, in that they showed equal exploration of N1 and N2. Caffeine (5 mg/kg), delivered either 1 h after the higher dose of ethanol or 20 min prior to habituation to N1, negated ethanol-induced impairment of memory for N1. A combination of a phosphodiesterase-5 inhibitor and an adenosine A(2A) antagonist, mimicking two major mechanisms of action of caffeine, likewise prevented the memory impairment, though either drug alone had no such effect. Binge alcohol can induce retrograde, caffeine-reversible disruption of social odor memory storage or recall.
Bagci, Eyup; Aydin, Emel; Ungureanu, Eugen; Hritcu, Lucian
Anthriscus nemorosa (Bieb.) Sprengel is used for medicinal purposes in traditional medicine around the world, including Turkey. Ethnobotanical studies suggest that Anthriscus essential oil could improve memory in Alzheimer's disease. The current study was hypothesized to investigate the beneficial effects of inhaled Anthriscus nemorosa essential oil on memory, anxiety and depression in scopolamine-treated rats. Anthriscus nemorosa essential oil was administered by inhalation in the doses of 1% and 3% for 21 continuous days and scopolamine (0.7mg/kg) was injected intraperitoneally 30min before the behavioral testing. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by elevated plus-maze and forced swimming tests. As expected, the scopolamine alone-treated rats exhibited the following: decrease the percentage of the spontaneous alternation in Y-maze test, increase the number of working and reference memory errors in radial arm-maze test, decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. However, dual scopolamine and Anthriscus nemorosa essential oil-treated rats showed significant improvement of memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. These results suggest that Anthriscus nemorosa essential oil inhalation can prevent scopolamine-induced memory impairment, anxiety and depression. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Full Text Available High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g. was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF and phosphorylated cAMP-response element binding protein (pCREB in the CA1 and dentate gyrus areas (DG of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus.
Full Text Available Systemic lipopolysaccharide (LPS induces an acute inflammatory response in the central nervous system (CNS (“neuroinflammation” characterized by altered functions of microglial cells, the major resident immune cells of the CNS, and an increased inflammatory profile that can result in long-term neuronal cell damage and severe behavioral and cognitive consequences. Curcumin, a natural compound, exerts CNS anti-inflammatory and neuroprotective functions mainly after chronic treatment. However, its effect after acute treatment has not been well investigated. In the present study, we provide evidence that 50 mg/kg of curcumin, orally administered for 2 consecutive days before a single intraperitoneal injection of a high dose of LPS (5 mg/kg in young adult mice prevents the CNS immune response. Curcumin, able to enter brain tissue in biologically relevant concentrations, reduced acute and transient microglia activation, pro-inflammatory mediator production, and the behavioral symptoms of sickness. In addition, short-term treatment with curcumin, administered at the time of LPS challenge, anticipated the recovery from memory impairments observed 1 month after the inflammatory stimulus, when mice had completely recovered from the acute neuroinflammation. Together, these results suggest that the preventive effect of curcumin in inhibiting the acute effects of neuroinflammation could be of value in reducing the long-term consequences of brain inflammation, including cognitive deficits such as memory dysfunction.
Full Text Available Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT, forced swimming test (FST, and Morris water maze (MWM. Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.
Tripathi, Sunil Jamuna; Chakraborty, Suwarna; Srikumar, B N; Raju, T R; Shankaranarayana Rao, B S
Chronic stress causes detrimental effects on various forms of learning and memory. The basolateral amygdala (BLA) not only plays a crucial role in mediating certain forms of memory, but also in the modulation of the effects of stress. Chronic immobilization stress (CIS) results in hypertrophy of the BLA, which is believed to be one of the underlying causes for stress' effects on learning. Thus, it is plausible that preventing the effects of CIS on amygdala would preclude its deleterious cognitive effects. Accordingly, in the first part, we evaluated the effect of excitotoxic lesion of the BLA on chronic stress-induced hippocampal-dependent spatial learning using a partially baited radial arm maze task. The BLA was ablated bilaterally using ibotenic acid prior to CIS. Chronically stressed rats showed impairment in spatial learning with decreased percentage correct choice and increased reference memory errors. Excitotoxic lesion of the BLA prevented the impairment in spatial learning and reference memory. In the retention test, lesion of the BLA was able to rescue the chronic stress-induced impairment. Interestingly, stress-induced enhanced plasma corticosterone levels were partially prevented by the lesion of BLA. These results motivated us to evaluate if the same effects can be observed with temporary inactivation of BLA, only during stress. We found that chronic stress-induced spatial learning deficits were also prevented by temporary inactivation of the BLA. Additionally, temporary inactivation of BLA partially precluded the stress-induced increase in plasma corticosterone levels. Thus, inactivation of BLA precludes stress-induced spatial learning deficits, and enhanced plasma corticosterone levels. It is speculated that BLA inactivation-induced reduction in corticosterone levels during stress, might be crucial in restoring spatial learning impairments. Our study provides evidence that amygdalar modulation during stress might be beneficial for strategic
Wong, Aimée A; Brown, Richard E
The DBA/2J mouse is a model of pigmentary glaucoma in humans as it shows age-related increases in intraocular pressure (IOP), retinal ganglion cell death and visual impairment. Previously, we showed that visual ability declines from 9 to 12 months of age and visual impairment is correlated with poor learning and memory performance in visuo-spatial tasks but not in tasks that do not depend on visual cues. To test the "sensory impairment" hypothesis of aging, which postulates that sensory impaired individuals are disadvantaged in their performance on psychometric tests as a direct result of difficulties in sensory perception, we treated DBA/2J mice with a conventional glaucoma medication used in humans (Timoptic-XE, 0.00, 0.25, or 0.50%) daily from 9 weeks to 12 months of age to determine whether prevention of vision loss prevented the decline in visuo-spatial learning and memory performance. At all ages tested (3, 6, 9, and 12 months of age), mice treated with Timoptic-XE (0.25 and 0.50%) maintained a high level of performance, while 12 month old control mice (0.00%) exhibited impaired performance in visually-dependent, but not non-visual tasks. These results demonstrate that when sensory function is preserved, cognitive performance is normalized. Thus, as in many aging humans, DBA/2J mice show age-related decrements in performance on visually presented cognitive tests, not because of cognitive impairment but as a direct consequence of poor visual ability. Our results demonstrate that age-related impairment in performance in visuo-spatial tasks in DBA/2J mice can be prevented by the preservation of visual ability.
Full Text Available The DBA/2J mouse is a model of pigmentary glaucoma in humans as it shows age‐related increases in intraocular pressure, retinal ganglion cell death and visual impairment. Previously, we showed that visual ability declines from 9 ‐12 months of age and visual impairment is correlated with poor learning and memory performance in visuo‐spatial tasks but not in tasks that do not depend on visual cues. To test the sensory impairment hypothesis of aging, which postulates that sensory impaired individuals are disadvantaged in their performance on psychometric tests as a direct result of difficulties in sensory perception, we treated DBA/2J mice with a conventional glaucoma medication used in humans (Timoptic‐XE, 0.00, 0.25 or 0.50% daily from 9 weeks to 12 months of age to determine whether prevention of vision loss prevented the decline in visuo-spatial learning and memory performance. At all ages tested (3, 6, 9 and 12 months of age, mice treated with Timoptic-XE (0.25 and 0.50% maintained a high level of performance, while 12 month old control mice (0.00% exhibited impaired performance in visually‐dependent, but not non‐visual tasks. These results demonstrate that when sensory function is preserved, cognitive performance is normalized. Thus, as in many aging humans, DBA/2J mice show age-related decrements in performance on visually presented cognitive tests, not because of cognitive impairment but as a direct consequence of poor visual ability. Our results demonstrate that age-related impairment in performance in visuo-spatial tasks in DBA/2J mice can be prevented by the preservation of visual ability.
Marisco, Patricia C; Carvalho, Fabiano B; Rosa, Michelle M; Girardi, Bruna A; Gutierres, Jessié M; Jaques, Jeandre A S; Salla, Ana P S; Pimentel, Víctor C; Schetinger, Maria Rosa C; Leal, Daniela B R; Mello, Carlos F; Rubin, Maribel A
Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5'-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5'-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5'-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.
Full Text Available Jie Luo, Su Min, Ke Wei, Jun Cao, Bin Wang, Ping Li, Jun Dong, Yuanyuan Liu Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Although a rapid and efficient psychiatric treatment, electroconvulsive therapy (ECT induces memory impairment. Modified ECT requires anesthesia for safety purposes. Although traditionally found to exert amnesic effects in general anesthesia, which is an inherent part of modified ECT, some anesthetics have been found to protect against ECT-induced cognitive impairment. However, the mechanisms remain unclear. We investigated the effects of propofol (2,6-diisopropylphenol on memory in depressed rats undergoing electroconvulsive shock (ECS, the analog of ECT in animals, under anesthesia as well as its mechanisms.Methods: Chronic unpredictable mild stresses were adopted to reproduce depression in a rodent model. Rats underwent ECS (or sham ECS with anesthesia with propofol or normal saline. Behavior was assessed in sucrose preference, open field and Morris water maze tests. Hippocampal long-term potentiation (LTP was measured using electrophysiological techniques. PSD-95, CREB, and p-CREB protein expression was assayed with western blotting.Results: Depression induced memory damage, and downregulated LTP, PSD-95, CREB, and p-CREB; these effects were exacerbated in depressed rats by ECS; propofol did not reverse the depression-induced changes, but when administered in modified ECS, propofol improved memory and reversed the downregulation of LTP and the proteins. Conclusion: These findings suggest that propofol prevents ECS-induced memory impairment, and modified ECS under anesthesia with propofol improves memory in depressed rats, possibly by reversing the excessive changes in hippocampal synaptic plasticity. These observations provide a novel insight into potential targets for optimizing the clinical use of ECT for psychiatric
Tamano, Haruna; Fukura, Kotaro; Suzuki, Miki; Sakamoto, Kazuhiro; Yokogoshi, Hidehiko; Takeda, Atsushi
Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. On the basis of the preventive effect of theanine intake after birth on mild stress-induced attenuation of hippocamapal CA1 long-term potentiation (LTP), the present study evaluated the effect of theanine intake after weaning on stress-induced impairments of LTP and recognition memory. Young rats were fed water containing 0.3% theanine for 3 weeks after weaning and subjected to water immersion stress for 30min, which was more severe than tail suspension stress for 30s used previously. Serum corticosterone levels were lower in theanine-administered rats than in the control rats even after exposure to stress. CA1 LTP induced by a 100-Hz tetanus for 1s was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an N-methyl-d-aspartate (NMDA) receptor antagonist, in hippocampal slices from the control rats and was attenuated by water immersion stress. In contrast, CA1 LTP was not significantly inhibited in the presence of APV in hippocampal slices from theanine-administered rats and was not attenuated by the stress. Furthermore, object recognition memory was impaired in the control rats, but not in theanine-administered rats. The present study indicates the preventive effect of theanine intake after weaning on stress-induced impairments of hippocampal LTP and recognition memory. It is likely that the modification of corticosterone secretion after theanine intake is involved in the preventive effect. Copyright © 2013 Elsevier Inc. All rights reserved.
João M N Duarte
Full Text Available Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1 and A(2A receptors emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli. Thus, we took advantage of a novel animal model of type 2 diabetes to investigate the behavioural, neurochemical and morphological modifications present in the hippocampus and tested if caffeine consumption might prevent these changes. We used a model closely mimicking the human type 2 diabetes condition, NONcNZO10/LtJ mice, which become diabetic at 7-11 months when kept under an 11% fat diet. Caffeine (1 g/l was applied in the drinking water from 7 months onwards. Diabetic mice displayed a decreased spontaneous alternation in the Y-maze accompanied by a decreased density of nerve terminal markers (synaptophysin, SNAP25, mainly glutamatergic (vesicular glutamate transporters, and increased astrogliosis (GFAP immunoreactivity compared to their wild type littermates kept under the same diet. Furthermore, diabetic mice displayed up-regulated A(2A receptors and down-regulated A(1 receptors in the hippocampus. Caffeine consumption restored memory performance and abrogated the diabetes-induced loss of nerve terminals and astrogliosis. These results provide the first evidence that type 2 diabetic mice display a loss of nerve terminal markers and astrogliosis, which is associated with memory impairment; furthermore, caffeine consumption prevents synaptic dysfunction and astrogliosis as well as memory impairment in type 2 diabetes.
Duarte, João M N; Agostinho, Paula M; Carvalho, Rui A; Cunha, Rodrigo A
Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1) and A(2A) receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli. Thus, we took advantage of a novel animal model of type 2 diabetes to investigate the behavioural, neurochemical and morphological modifications present in the hippocampus and tested if caffeine consumption might prevent these changes. We used a model closely mimicking the human type 2 diabetes condition, NONcNZO10/LtJ mice, which become diabetic at 7-11 months when kept under an 11% fat diet. Caffeine (1 g/l) was applied in the drinking water from 7 months onwards. Diabetic mice displayed a decreased spontaneous alternation in the Y-maze accompanied by a decreased density of nerve terminal markers (synaptophysin, SNAP25), mainly glutamatergic (vesicular glutamate transporters), and increased astrogliosis (GFAP immunoreactivity) compared to their wild type littermates kept under the same diet. Furthermore, diabetic mice displayed up-regulated A(2A) receptors and down-regulated A(1) receptors in the hippocampus. Caffeine consumption restored memory performance and abrogated the diabetes-induced loss of nerve terminals and astrogliosis. These results provide the first evidence that type 2 diabetic mice display a loss of nerve terminal markers and astrogliosis, which is associated with memory impairment; furthermore, caffeine consumption prevents synaptic dysfunction and astrogliosis as well as memory impairment in type 2 diabetes.
Varun K Gupta
Full Text Available Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ, increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse.
Lutiana R. Simões
Full Text Available The aim of this study was to investigate the effects of lithium on brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, and glial cell line-derived neurotrophic factor (GDNF expression in the hippocampus and on memory in experimental pneumococcal meningitis. The mood-stabilizer lithium is known as a neuroprotective agent with many effects on the brain. In this study, animals received either artificial cerebrospinal fluid or Streptococcus pneumoniae suspension at a concentration of 5 × 109 CFU/mL. Eighteen hours after induction, all animals received ceftriaxone. The animals received saline or lithium (47.5 mg/kg or tamoxifen (1 mg/kg as adjuvant treatment, and they were separated into six groups: control/saline, control/lithium, control/tamoxifen, meningitis/saline, meningitis/lithium, and meningitis/tamoxifen. Ten days after meningitis induction, animals were subjected to open-field habituation and the step-down inhibitory avoidance tasks. Immediately after these tasks, the animals were killed and their hippocampus was removed to evaluate the expression of BDNF, NGF, and GDNF. In the meningitis group, treatment with lithium and tamoxifen resulted in improvement in memory. Meningitis group showed decreased expression of BDNF and GDNF in the hippocampus while lithium reestablished the neurotrophin expression. Lithium was able to prevent memory impairment and reestablishes hippocampal neurotrophin expression in experimental pneumococcal meningitis.
Baird, Gillian; Dworzynski, Katharina; Slonims, Vicky; Simonoff, Emily
Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific. Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9y 9m, SD 2y 6mo) with current,…
Dinamarca, M C; Cerpa, W; Garrido, J; Hancke, J L; Inestrosa, N C
The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid beta-peptide (Abeta). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on Abeta-induced spatial memory impairments and on Abeta neurotoxicity. We report here that hyperforin: (1) decreases amyloid deposit formation in rats injected with amyloid fibrils in the hippocampus; (2) decreases the neuropathological changes and behavioral impairments in a rat model of amyloidosis; (3) prevents Abeta-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and Abeta oligomers, avoiding the increase in reactive oxidative species associated with amyloid toxicity. Both effects could be explained by the capacity of hyperforin to disaggregate amyloid deposits in a dose and time-dependent manner and to decrease Abeta aggregation and amyloid formation. Altogether these evidences suggest that hyperforin may be useful to decrease amyloid burden and toxicity in AD patients, and may be a putative therapeutic agent to fight the disease.
Sun, Bao-Fei; Wang, Qing-Qing; Yu, Zi-Jiang; Yu, Yan; Xiao, Chao-Lun; Kang, Chao-Sheng; Ge, Guo; Linghu, Yan; Zhu, Jun-De; Li, Yu-Mei; Li, Qiang-Ming; Luo, Shi-Peng; Yang, Dang; Li, Lin; Zhang, Wen-Yan
High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM) of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g.) was administered daily for 12 weeks. We found that arsenic at dos...
Dinel, A L; Rey, C; Baudry, C; Fressange-Mazda, C; Le Ruyet, P; Nadjar, A; Pallet, P; Joffre, C; Layé, S
Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical for brain development and later life cognitive functions. The main brain PUFAs are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for the n-6 family, which are provided to the post-natal brain by breast milk or infant formula. Recently, the use of dairy lipids (DL) in replacement of vegetable lipids (VL) was revealed to potently promote the accretion of DHA in the developing brain. Brain DHA, in addition to be a key component of brain development, display potent anti-inflammatory activities, which protect the brain from adverse inflammatory events. In this work, we evaluated the protective effect of partial replacement of VL by DL, supplemented or not with DHA and ARA, on post-natal inflammation and its consequence on memory. Mice were fed with diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp DL) from the first day of gestation until adulthood. At post-natal day 14 (PND14), pups received a single administration of the endotoxin lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and neurogenesis were measured. In a second set of experiments, memory and neurogenesis were measured at adulthood. Overall, our data showed that lipid quality of the diet modulates early life LPS effect on microglia phenotype, brain cytokine expression and neurogenesis at PND14 and memory at adulthood. In particular, Bal DL diet protects from the adverse effect of early life LPS exposure on PND14 neurogenesis and adult spatial memory. Copyright © 2016 Elsevier Ltd. All rights reserved.
Arafa, Nadia M S; Ali, Elham H A; Hassan, Mohamed Kamel
Canagliflozin (CAN) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated to improve glycemic control in adults with type 2 diabetes mellitus. There is a little information about its effect on the cholinergic system that proposed mechanism for memory improvement occurring by SGLT2 drugs. This study aimed to estimate the effect of CAN as compared to galantamine (GAL) treatments for two weeks on scopolamine hydrobromide (SCO)-induced memory dysfunction in experimental rats. Animals divided into six groups; control (CON), CAN, GAL, SCO, SCO + CAN and SCO + GAL. Results indicated significant decrease in body weights of the CAN groups as compared to control values. Moreover, in the SCO + CAN and SCO + GAL the number of arm entry and number of correct alternation in Y maze task increased and showed improvement in the water maze task, acetylcholinesterase (AChE) activities decreased significantly, while monoamines levels significantly increased compared with the SCO group values. Results also recorded acetylcholine M1 receptor (M1 mAChR) in SCO + CAN or SCO + GAL groups in comparison with the SCO group. The study suggested that canagliflozin might improve memory dysfunction induced by scopolamine hydrobromide via cholinergic and monoamines system. Copyright © 2017 Elsevier B.V. All rights reserved.
Noorbakhshnia, Maryam; Karimi-Zandi, Leila
There is a growing body of evidence that neuroinflammation can impair memory. It has been indicated that Portulaca oleracea Linn. (POL), possess anti-inflammatory activity and might improve memory disruption caused by inflammation. In this study the effect of pre-treatment with the hydro-alcoholic extract of POL on memory retrieval investigated in lipopolysaccharide (LPS) treated rats. Male Wistar rats (200-220g) received either a control diet or a diet containing of POL (400mg/kg, p.o.) for 14days. Then, they received injections of either saline or LPS (1mg/kg, i.p.). In all the experimental groups, 4h following the last injection, passive avoidance learning (PAL) and memory test was performed. The retention test was done 24h after the training and then the animals were sacrificed. Hippocampal TNF-α levels measured using ELISA as one criteria of LPS-induced neuroinflammation. The results indicated that LPS significantly impaired PAL and memory and increased TNF-α levels in hippocampus tissue. Pre-treatment with POL improved memory in control rats and prevented memory and TNF-α deterioration in LPS treated rats. Taken together, the results of this study suggest that the hydro-alcoholic extract of POL may improve memory deficits in LPS treated rats, possibly via inhibition of TNF-α and anti-inflammatory activity. Copyright © 2016 Elsevier Inc. All rights reserved.
Zhao, H; Ji, Z-H; Liu, C; Yu, X-Y
Studies demonstrated that chronic high-dose homocysteine administration induced learning and memory impairment in animals. Atractylenolide III (Aen-III), a neuroprotective constituent of Atractylodis macrocephalae Koidz, was isolated in our previous study. In this study, we investigated potential benefits of Aen-III in preventing learning and memory impairment following chronic high-dose homocysteine administration in rats. Results showed that administration of Aen-III significantly ameliorated learning and memory impairment induced by chronic high-dose homocysteine administration in rats, decreased homocysteine-induced reactive oxygen species (ROS) formation and restored homocysteine-induced decrease of phosphorylated protein kinase C expression level. Moreover, Aen-III protected primary cultured neurons from apoptotic death induced by homocysteine treatment. This study provides the first evidence for the neuroprotective effect of Aen-III in preventing learning and impairment induced by chronic administration of homocysteine. Aen-III may have therapeutic potential in treating homocysteine-mediated cognitive impairment and neuronal injury. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Espinosa, Janaína; Rocha, Andreia; Nunes, Fernanda; Costa, Marcelo S; Schein, Vanessa; Kazlauckas, Vanessa; Kalinine, Eduardo; Souza, Diogo O; Cunha, Rodrigo A; Porciúncula, Lisiane O
Intracerebroventricular (icv) streptozotocin (STZ) administration induces pathological and behavioral alterations similar to those observed in Alzheimer's disease (AD) and is thus considered an experimental model of sporadic AD. Since caffeine (an adenosine receptor antagonist) and selective antagonists of adenosine A2A receptors modify the course of memory impairment in different amyloid-β-based experimental models of AD, we now tested the impact of caffeine on STZ-induced dementia and associated neurodegeneration in the hippocampus as well as on the expression and density of adenosine receptors. Adult male rats received a bilateral infusion of saline or STZ (3 mg/kg, icv), which triggered memory deficits after four weeks, as gauged by impaired object recognition memory. This was accompanied by a reduced NeuN immunoreactivity in the hippocampal CA1 region and an increased expression and density of adenosine A2A receptors (A2AR), but not A1R, in the hippocampus. Caffeine consumption (1 g/L in the drinking water starting 2 weeks before the STZ challenge) prevented the STZ-induced memory impairment and neurodegeneration as well as the upregulation of A2AR. These findings provide the first demonstration that caffeine prevents sporadic dementia and implicate the control of central A2AR as its likely mechanism of action.
Álvarez-Ruíz, Yarummy; Carrillo-Mora, Paul
Previous studies in transgenic mice models of Alzheimer's disease (AD) have demonstrated an age dependent memory reconsolidation failure, suggesting that this may be an additional mechanism that contributes to the memory impairment observed in AD. However, so far it is unknown whether this effect can be caused by exogenous administration of amyloid beta (Aβ). The purpose was to determine the effects of soluble Aβ 25-35 on reconsolidation of object recognition memory (ORM) in rats, and assess whether these effects can be prevented by lithium carbonate (LiCa). In this study, male Wistar rats were used and the following groups were formed (N=6-13): (a) control, given saline solution; (b) [NMDA antagonist] MK-801 (0.1 mg/kg); (c) LiCa (350 mg/kg); (d) Aβ 25-35 (100 μM) injected into both hippocampi; and (e) Aβ 25-35+LiCa. In all cases, treatments were administered with or without reactivation of memory. The results showed that soluble Aβ 25-35 produces ORM impairment similar to MK-801 when given shortly after memory reactivation, and this effect is prevented by prior administration of LiCa. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Mancini, Simona; Balducci, Claudia; Micotti, Edoardo; Tolomeo, Daniele; Forloni, Gianluigi; Masserini, Massimo; Re, Francesca
The failure of clinical trials largely focused on mild to moderate stages of Alzheimer disease has suggested to the scientific community that the effectiveness of Amyloid-β (Aβ)-centered treatments should be evaluated starting as early as possible, well before irreversible brain damage has occurred. Accordingly, also the preclinical development of new therapies should be carried out taking into account this suggestion. In the present investigation we evaluated the efficacy of a treatment with liposomes multifunctionalized for crossing the blood-brain barrier and targeting Aβ, carried out on young APP/PS1 Tg mice, taken as a model of pre-symptomatic disease stage. Liposomes were administered once a week to Tg mice for 7months, starting at the age of 5months and up to the age of 12 when they display AD-like cognitive and brain biochemical/anatomical features. The treatment prevented the onset of the long-term memory impairment and slowed down the deposition of brain Aβ; at anatomical level, prevented both ventricle enlargement and entorhinal cortex thickness reduction, otherwise occurring in untreated mice. Strikingly, these effects were maintained 3months after treatment discontinuation. An increase of Aβ levels in the liver was detected at the end of the treatment, then followed also by reduction of brain Amyloid Precursor Protein and increase of Aβ-degrading enzymes. These results suggest that the treatment promotes brain Aβ clearance by a peripheral 'sink' effect and ultimately affects Aβ turnover in the brain. Worth of note, the treatment was apparently not toxic for all the organs analyzed, in particular for brain, as suggested by the lower brain TNF-α and MDA levels, and by higher level of SOD activity in treated mice. Together, these findings promote a very early treatment with multi-functional liposomes as a well-tolerated nanomedicine-based approach, potentially suitable for a disease-modifying therapy of AD, able to delay or prevent relevant
Saab, Bechara J; Maclean, Ashley J B; Kanisek, Marijana; Zurek, Agnieszka A; Martin, Loren J; Roder, John C; Orser, Beverley A
Memory blockade is an essential component of the anesthetic state. However, postanesthesia memory deficits represent an undesirable and poorly understood adverse effect. Inhibitory α5 subunit-containing γ-aminobutyric acid subtype A receptors (α5GABAA) are known to play a critical role in memory processes and are highly sensitive to positive modulation by anesthetics. We postulated that inhibiting the activity of α5GABAA receptors during isoflurane anesthesia would prevent memory deficits in the early postanesthesia period. Mice were pretreated with L-655,708, an α5GABAA receptor-selective inverse agonist, or vehicle. They were then exposed to isoflurane for 1 h (1.3%, or 1 minimum alveolar concentration, or air-oxygen control). Then, either 1 or 24 h later, mice were conditioned in fear-associated contextual and cued learning paradigms. In addition, the effect of L-655,708 on the immobilizing dose of isoflurane was studied. Motor coordination, sedation, anxiety, and the concentration of isoflurane in the brain at 5 min, 1 h, and 24 h after isoflurane were also examined. Motor and sensory function recovered within minutes after termination of isoflurane administration. In contrast, a robust deficit in contextual fear memory persisted for at least 24 h. The α5GABAA receptor inverse agonist, L-655,708, completely prevented memory deficits without changing the immobilizing dose of isoflurane. Trace concentrations of isoflurane were measured in the brain 24 h after treatment. Memory deficits occurred long after the sedative, analgesic, and anxiolytic effects of isoflurane subsided. L-655,708 prevented memory deficit, suggesting that an isoflurane interaction at α5GABAA receptors contributes to memory impairment during the early postanesthesia period.
Otis, James M; Fitzgerald, Michael K; Mueller, Devin
Retrieval of drug-associated memories is critical for maintaining addictive behaviors, as presentation of drug-associated cues can elicit drug seeking and relapse. Recently, we and others have demonstrated that β-adrenergic receptor (β-AR) activation is necessary for retrieval using both rat and human memory models. Importantly, blocking retrieval with β-AR antagonists persistently impairs retrieval and provides protection against subsequent reinstatement. However, the neural locus at which β-ARs are required for maintaining retrieval and subsequent reinstatement is unclear. Here, we investigated the necessity of dorsal hippocampus (dHipp) β-ARs for drug-associated memory retrieval. Using a cocaine conditioned place preference (CPP) model, we demonstrate that local dHipp β-AR blockade before a CPP test prevents CPP expression shortly and long after treatment, indicating that dHipp β-AR blockade induces a memory retrieval disruption. Furthermore, this retrieval disruption provides long-lasting protection against cocaine-induced reinstatement. The effects of β-AR blockade were dependent on memory reactivation and were not attributable to reconsolidation disruption as blockade of β-ARs immediately after a CPP test had little effect on subsequent CPP expression. Thus, cocaine-associated memory retrieval is mediated by β-AR activity within the dHipp, and disruption of this activity could prevent cue-induced drug seeking and relapse long after treatment.
Duarte, João M. N.; Agostinho, Paula M.; Carvalho, Rui A.; Cunha, Rodrigo A.
Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1) and A(2A) receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different...
Full Text Available Abstract Aging is a progressive process related to the accumulation of oxidative damage and neuroinflammation. We tried to find the anti-amnesic effect of the Scutellaria baicalens Georgia (SBG ethanol extract and its major ingredients. The antioxidative effect of SBG on the mice model with memory impairment induced by chronic injection of D-galactose and sodium nitrate was studied. The Y-maze test was used to evaluate the learning and memory function of mice. The activities of superoxide dismutase, catalase and the content of malondialdehyde in brain tissue were used for the antioxidation activities. Neuropathological alteration and expression of bcl-2 protein were investigated in the hippocampus by immunohistochemical staining. ROS, neuroinflammation and apoptosis related molecules expression such as Cox-2, iNOS, procaspase-3, cleaved caspase-3, 8 and 9, bcl-2 and bax protein and the products of iNOS and Cox-2, NO, PGE2, were studied using LPS-activated Raw 264.7 cells and microglia BV2 cells. The cognition of mice was significantly improved by the treatment of baicalein and 50 and 100 mg/kg of SBG in Y-maze test. Both SBG groups showed strong antioxidation, antiinflammation effects with significantly decreased iNOS and Cox-2 expression, NO and PGE2 production, increased bcl-2 and decreased bax and cleaved caspase-3 protein expression in LPS induced Raw 264.7 and BV2 cells. We also found that apoptotic pathway was caused by the intrinsic mitochondrial pathway with the decreased cleaved caspase-9 and unchanged cleaved caspase-8 expression. These findings suggest that SBG, especially high dose, 100 mg/kg, improved the memory impairments significantly and showed antioxidation, antiinflammation and intrinsic caspase-mediated apoptosis effects.
Han, Huili; Dai, Chunfang; Dong, Zhifang
A growing body of evidence has shown that chronic treatment with fluoxetine, a widely prescribed medication for treatment of depression, can affect synaptic plasticity in the adult central nervous system. However, it is not well understood whether acute fluoxetine influences synaptic plasticity, especially on hippocampal CA1 long-term depression (LTD), and if so, whether it subsequently impacts hippocampal-dependent spatial memory. Here, we reported that LTD facilitated by elevated-platform stress in hippocampal slices was completely prevented by fluoxetine administration (10 mg/kg, i.p.) 30 min before stress. The LTD was not, however, significantly inhibited by fluoxetine administration immediately after stress. Similarly, fluoxetine incubation (10 μM) during electrophysiological recordings also displayed no influence on the stress-facilitated LTD. In addition, behavioral results showed that a single fluoxetine treatment 30 min before but not after acute stress fully reversed the impairment of spatial memory retrieval in the Morris water maze paradigm. Taken together, these results suggest that acute fluoxetine treatment only before, but not after stress, can prevent hippocampal CA1 LTD and spatial memory retrieval impairment caused by behavioral stress in adult animals. PMID:26218751
Fernanda S Rodrigues
Full Text Available BACKGROUND AND AIMS: Glutaric aciduria type I (GA-I is characterized by accumulation of glutaric acid (GA and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC on theses markers. METHODS: Rat pups were injected with GA (5 umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life, and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period. LPS (2 mg/kg; E.coli 055 B5 or vehicle (saline 0.9% was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed. RESULTS: GA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers. CONCLUSIONS: These results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could
Nuseir, Khawla Q; Alzoubi, Karem H; Alhusban, Ahmed; Bawaane, Areej; Al-Azzani, Mohammed; Khabour, Omar F
Pain in neonates is associated with short and long-term adverse outcomes. Data demonstrated that long-term consequences of untreated pain are linked to the plasticity of the neonate's brain. Sucrose is effective and safe for reducing painful procedures from single events. However, the mechanism of sucrose-induced analgesia is not fully understood. The role of the opioid system in this analgesia using the opioid receptor antagonist Naltrexone was investigated, plus the long-term effects on learning and memory formation during adulthood. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution and/or naltrexone were administered before the pricks. All treatments started on day one of birth and continued for two weeks. At the end of 8weeks, behavioral studies were conducted to test spatial learning and memory using radial arm water maze (RAWM), and pain threshold via foot-withdrawal response to a hot plate. The hippocampus was dissected; levels of brain derived neurotrophic factor (BDNF) and endorphins were assessed using ELISA. Acute repetitive neonatal pain increased pain sensitivity later in life, while naltrexone with sucrose decreased pain sensitivity. Naltrexone and/or sucrose prevented neonatal pain induced impairment of long-term memory, while neonatal pain decreased levels of BDNF in the hippocampus; this decrease was averted by sucrose and naltrexone. Sucrose with naltrexone significantly increased β-endorphin levels in noxiously stimulated rats. In conclusion, naltrexone and sucrose can reverse increased pain sensitivity and impaired long-term memory induced by acute repetitive neonatal pain probably by normalizing BDNF expression and increasing β-endorphin levels. Copyright © 2017 Elsevier Inc. All rights reserved.
Palchykova, S.; Tobler, I.
It is now well known that daily torpor induces a sleep deficit. Djungarian hamsters emerging from this hypometabolic state spend most of the time in sleep. This sleep is characterized by high initial values of EEG slow-wave activity (SWA) that monotonically decline during recovery sleep. These features resemble the changes seen in numerous species during recovery after prolonged wakefulness or sleep deprivation (SD). When hamsters are totally or partially sleep deprived immediately after emerging from torpor, an additional increase in SWA can be induced. It has been therefore postulated, that these slow- waves are homeostatically regulated, as predicted by the two-process model of sleep regulation, and that during daily torpor a sleep deficit is accumulated as it is during prolonged waking. The predominance of SWA in the frontal EEG observed both after SD and daily torpor provides further evidence for the similarity of these conditions. It has been shown in several animal and human studies that sleep can enhance memory consolidation, and that SD leads to memory impairment. Preliminary data obtained in the Djungarian hamster showed that both SD and daily torpor result in object recognition deficits. Thus, animals subjected to SD immediately after learning, or if they underwent an episode of daily torpor between learning and retention, displayed impaired recognition memory for complex object scenes. The investigation of daily torpor can reveal mechanisms that could have important implications for hypometabolic state induction in other mammalian species, including humans.
Fukushima-Nakayama, Y; Ono, Takehito; Hayashi, M; Inoue, M; Wake, H; Ono, Takashi; Nakashima, T
Mastication is an indispensable oral function related to physical, mental, and social health throughout life. The elderly tend to have a masticatory dysfunction due to tooth loss and fragility in the masticatory muscles with aging, potentially resulting in impaired cognitive function. Masticatory stimulation has influence on the development of the central nervous system (CNS) as well as the growth of maxillofacial tissue in children. Although the relationship between mastication and cognitive function is potentially important in the growth period, the cellular and molecular mechanisms have not been sufficiently elucidated. Here, we show that the reduced mastication resulted in impaired spatial memory and learning function owing to the morphological change and decreased activity in the hippocampus. We used an in vivo model for reduced masticatory stimuli, in which juvenile mice were fed with powder diet and found that masticatory stimulation during the growth period positively regulated long-term spatial memory to promote cognitive function. The functional linkage between mastication and brain was validated by the decrease in neurons, neurogenesis, neuronal activity, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. These findings taken together provide in vivo evidence for a functional linkage between mastication and cognitive function in the growth period, suggesting a need for novel therapeutic strategies in masticatory function-related cognitive dysfunction.
Chen, Nannan; Guo, Aike; Li, Yan
Age-related memory impairment (AMI) is a phenomenon observed from invertebrates to human. Memory extinction is proposed to be an active inhibitory modification of memory, however, whether extinction is affected in aging animals remains to be elucidated. Employing a modified paradigm for studying memory extinction in fruit flies, we found that only the stable, but not the labile memory component was suppressed by extinction, thus effectively resulting in higher memory loss in aging flies. Strikingly, young flies were able to fully restore the stable memory component 3 h post extinction, while aging flies failed to do so. In conclusion, our findings reveal that both accelerated extinction and impaired restoration contribute to memory impairment in aging animals. Copyright © 2015 Elsevier Inc. All rights reserved.
Vargas-López, Viviana; Lamprea, Marisol R; Múnera, Alejandro
Acute stress induced before spatial training impairs memory consolidation. Although non-epigenetic underpinning of such effect has been described, the epigenetic mechanisms involved have not yet been studied. Since spatial training and intense stress have opposite effects on histone acetylation balance, it is conceivable that disruption of such balance may underlie acute stress-induced spatial memory consolidation impairment and that inhibiting histone deacetylases prevents such effect. Trichostatin-A (TSA, a histone deacetylase inhibitor) was used to test its effectiveness in preventing stress' deleterious effect on memory. Male Wistar rats were trained in a spatial task in the Barnes maze; 1-h movement restraint was applied to half of them before training. Immediately after training, stressed and non-stressed animals were randomly assigned to receive either TSA (1mg/kg) or vehicle intraperitoneal injection. Twenty-four hours after training, long-term spatial memory was tested; plasma and brain tissue were collected immediately after the memory test to evaluate corticosterone levels and histone H3 acetylation in several brain areas. Stressed animals receiving vehicle displayed memory impairment, increased plasma corticosterone levels and markedly reduced histone H3 acetylation in prelimbic cortex and hippocampus. Such effects did not occur in stressed animals treated with TSA. The aforementioned results support the hypothesis that acute stress induced-memory impairment is related to histone deacetylation. Copyright © 2016 Elsevier Inc. All rights reserved.
Henry, Lucy A.; Botting, Nicola
Children with developmental language impairments (DLI) are often reported to show difficulties with working memory. This review describes the four components of the well-established working memory model, and considers whether there is convincing evidence for difficulties within each component in children with DLI. The emphasis is on the most…
Cognato, Giana P; Agostinho, Paula M; Hockemeyer, Jörg; Müller, Christa E; Souza, Diogo O; Cunha, Rodrigo A
Seizures early in life cause long-term behavioral modifications, namely long-term memory deficits in experimental animals. Since caffeine and adenosine A(2A) receptor (A(2A)R) antagonists prevent memory deficits in adult animals, we now investigated if they also prevented the long-term memory deficits caused by a convulsive period early in life. Administration of kainate (KA, 2 mg/kg) to 7-days-old (P7) rats caused a single period of self-extinguishable convulsions which lead to a poorer memory performance in the Y-maze only when rats were older than 90 days, without modification of locomotion or anxiety-like behavior in the elevated-plus maze. In accordance with the relationship between synaptotoxicity and memory dysfunction, the hippocampus of these adult rats treated with kainate at P7 displayed a lower density of synaptic proteins such as SNAP-25 and syntaxin (but not synaptophysin), as well as vesicular glutamate transporters type 1 (but not vesicular GABA transporters), with no changes in PSD-95, NMDA receptor subunits (NR1, NR2A, NR2B) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunits (GluR1, GluR2) compared with controls. Caffeine (1 g/L) or the A(2A)R antagonist, KW6002 (3 mg/kg) applied in the drinking water from P21 onwards, prevented these memory deficits in P90 rats treated with KA at P7, as well as the accompanying synaptotoxicity. These results show that a single convulsive episode in early life causes a delayed memory deficit in adulthood accompanied by a glutamatergic synaptotoxicity that was prevented by caffeine or adenosine A(2A)R antagonists.
Full Text Available Although the semantic memory impairment has been largely documented in Alzheimer's disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment. The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests.
Lum, Jarrad A.G.; Ullman, Michael T.; Conti-Ramsden, Gina
This study examined verbal declarative memory functioning in SLI and its relationship to working memory. Encoding, recall, and recognition of verbal information was examined in children with SLI who had below average working memory (SLILow WM), children with SLI who had average working memory (SLIAvg. WM) and, a group of non-language impaired children with average working memory (TDAvg. WM). The SLILow WM group was significantly worse than both the SLIAvg. WM and TDAvg. WM groups at encoding ...
Brewin, Chris R; Mersaditabari, Niloufar
Dissociation is a phenomenon common in a number of psychological disorders and has been frequently suggested to impair memory for traumatic events. In this study we explored the effects of dissociation on visual memory. A dissociative state was induced experimentally using a mirror-gazing task and its short-term effects on memory performance were investigated. Sixty healthy individuals took part in the experiment. Induced dissociation impaired visual memory performance relative to a control condition; however, the degree of dissociation was not associated with lower memory scores in the experimental group. The results have theoretical and practical implications for individuals who experience frequent dissociative states such as patients with posttraumatic stress disorder (PTSD). Copyright © 2013 Elsevier Inc. All rights reserved.
Full Text Available Diminished estrogen influence at menopause is reported to be associated with cognitive decline, heightened anxiety and hypertension. While estrogen therapy is often prescribed to overcome these behavioral and physiological deficits, antioxidants which have been shown beneficial are gaining nutritional intervention and popularity. Therefore, in the present study, utilizing the antioxidant properties of grapes, we have examined effect of 3 weeks of grape powder (GP; 15 g/L dissolved in tap water treatment on anxiety-like behavior, learning-memory impairment and high blood pressure in ovariectomized (OVX rats. Four groups of female Wistar rats were used; sham control, sham-GP treated, OVX and OVX+GP treated. We observed a significant increase in systolic and diastolic blood pressure in OVX rats as compared to sham-controls. Furthermore, ovariectomy increased anxiety-like behavior and caused learning and memory impairment in rats as compared to sham-controls. Interestingly, providing grape powder treated water to OVX rats restored both systolic and diastolic blood pressure, decreased anxiety-like behavior and improved memory function. Moreover, OVX rats exhibited an impaired long term potentiation which was restored with grape powder treatment. Furthermore, ovariectomy increased oxidative stress in the brain, serum and urine, selectively decreasing antioxidant enzyme, glyoxalase-1 protein expression in the hippocampus but not in the cortex and amygdala of OVX rats, while grape powder treatment reversed these effects. Other antioxidant enzyme levels, including manganese superoxide dismutase (SOD and Cu/Zn SOD remained unchanged. We suggest that grape powder by regulating oxidative stress mechanisms exerts its protective effect on blood pressure, learning-memory and anxiety-like behavior. Our study is the first to examine behavioral, biochemical, physiological and electrophysiological outcome of estrogen depletion in rats and to test protective role
Bisby, James A; Burgess, Neil
The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine the effects of emotion on memory for items and their associations. By presenting neutral and negative items with background contexts, Experiment 1 demonstrated that item memory was facilitated by emotional affect, whereas memory for an associated context was reduced. In Experiment 2, arousal was manipulated independently of the memoranda, by a threat of shock, whereby encoding trials occurred under conditions of threat or safety. Memory for context was equally impaired by the presence of negative affect, whether induced by threat of shock or a negative item, relative to retrieval of the context of a neutral item in safety. In Experiment 3, participants were presented with neutral and negative items as paired associates, including all combinations of neutral and negative items. The results showed both above effects: compared to a neutral item, memory for the associate of a negative item (a second item here, context in Experiments 1 and 2) is impaired, whereas retrieval of the item itself is enhanced. Our findings suggest that negative affect impairs associative memory while recognition of a negative item is enhanced. They support dual-processing models in which negative affect or stress impairs hippocampal-dependent associative memory while the storage of negative sensory/perceptual representations is spared or even strengthened.
Gopie, Nigel; Craik, Fergus I M; Hasher, Lynn
Older adults are assumed to have poor destination memory-knowing to whom they tell particular information-and anecdotes about them repeating stories to the same people are cited as informal evidence for this claim. Experiment 1 assessed young and older adults' destination memory by having participants tell facts (e.g., "A dime has 118 ridges around its edge") to pictures of famous people (e.g., Oprah Winfrey). Surprise recognition memory tests, which also assessed confidence, revealed that older adults, compared to young adults, were disproportionately impaired on destination memory relative to spared memory for the individual components (i.e., facts, faces) of the episode. Older adults also were more confident that they had not told a fact to a particular person when they actually had (i.e., a miss); this presumably causes them to repeat information more often than young adults. When the direction of information transfer was reversed in Experiment 2, such that the famous people shared information with the participants (i.e., a source memory experiment), age-related memory differences disappeared. In contrast to the destination memory experiment, older adults in the source memory experiment were more confident than young adults that someone had shared a fact with them when a different person actually had shared the fact (i.e., a false alarm). Overall, accuracy and confidence jointly influence age-related changes to destination memory, a fundamental component of successful communication. (c) 2010 APA, all rights reserved).
Barber, Sarah J; Mather, Mara
Negative stereotypes about aging can impair older adults' memory via stereotype threat; however, the mechanisms underlying this phenomenon are unclear. In two experiments, we tested competing predictions derived from two theoretical accounts of stereotype threat: executive-control interference and regulatory fit. Older adults completed a working memory test either under stereotype threat about age-related memory declines or not under such threat. Monetary incentives were manipulated such that recall led to gains or forgetting led to losses. The executive-control-interference account predicts that stereotype threat decreases the availability of executive-control resources and hence should impair working memory performance. The regulatory-fit account predicts that threat induces a prevention focus, which should impair performance when gains are emphasized but improve performance when losses are emphasized. Results were consistent only with the regulatory-fit account. Although stereotype threat significantly impaired older adults' working memory performance when remembering led to gains, it significantly improved performance when forgetting led to losses.
Ferreira, L B T; Oliveira, S L B; Raya, J; Esumi, L A; Hipolide, D C
Sleep deprivation impairs performance in emotional memory tasks, however this effect on memory is not completely understood. Possible mechanisms may involve an alteration in neurotransmission systems, as shown by the fact that many drugs that modulate neural pathways can prevent memory impairment by sleep loss. Gastrin releasing peptide (GRP) is a neuropeptide that emerged as a regulatory molecule of emotional memory through the modulation of other neurotransmission systems. Thus, the present study addressed the effect of intraperitoneal (IP) administration of bombesin (BB) (2.5, 5.0 and 10.0μg/kg), a GRP agonist, on the performance of Wistar rats in a multiple trail inhibitory avoidance (MTIA) task, after sleep deprivation, using the modified multiple platforms method (MMPM). Sleep deprived animals exhibited acquisition and retention impairment that was not prevented by BB injection. In addition, non-sleep deprived animals treated with BB before and after the training session, but not before the test, have shown a retention deficit. In summary, BB did not improve the memory impairment by sleep loss and, under normal conditions, produced a memory consolidation deficit. Copyright © 2017 Elsevier B.V. All rights reserved.
Lucas S. Broster
Full Text Available We review recent work on emotional memory enhancement in older adults and patients with mild cognitive impairment or Alzheimer dementia and evaluate the viability of incorporating emotional components into cognitive rehabilitation for these groups. First, we identify converging evidence regarding the effects of emotional valence on working memory in healthy aging. Second, we introduce work that suggests a more complex role for emotional memory enhancement in aging and identify a model capable of unifying disparate research findings. Third, we identify neuroimaging evidence that the amygdala may play a key role in mediating emotional memory enhancement in mild cognitive impairment and early Alzheimer dementia. Finally, we assess the theoretical feasibility of incorporating emotional content into cognitive rehabilitation given all available evidence.
Kluen, Lisa Marieke; Agorastos, Agorastos; Wiedemann, Klaus; Schwabe, Lars
Memory generalization is essential for adaptive decision-making and action. Our ability to generalize across past experiences relies on medial-temporal lobe structures, known to be highly sensitive to stress. Recent evidence suggests that stressful events may indeed interfere with memory generalization. Yet, the mechanisms involved in this generalization impairment are unknown. We tested here whether a pharmacological elevation of major stress mediators-noradrenaline and glucocorticoids-is sufficient to disrupt memory generalization. In a double-blind, placebo-controlled design, healthy men and women received orally a placebo, hydrocortisone, the α2-adrenoceptor antagonist yohimbine that leads to increased noradrenergic stimulation, or both drugs, before they completed an associative learning task probing memory generalization. Drugs left learning performance intact. Yohimbine, however, led to a striking generalization impairment in women, but not in men. Hydrocortisone, in turn, had no effect on memory generalization, neither in men nor in women. The present findings indicate that increased noradrenergic activity, but not cortisol, is sufficient to disrupt memory generalization in a sex-specific manner, with relevant implications for stress-related mental disorders characterized by generalization deficits.
Zhao, Xiaohui; Kotilinek, Linda A; Smith, Benjamin; Hlynialuk, Chris; Zahs, Kathleen; Ramsden, Martin; Cleary, James; Ashe, Karen H
In Alzheimer's disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, Δtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with AD. The expression of tau mutants that resisted caspase-2 cleavage prevented tau from infiltrating spines, dislocating glutamate receptors and impairing synaptic function in cultured neurons, and it prevented memory deficits and neurodegeneration in mice. Decreasing the levels of caspase-2 restored long-term memory in mice that had existing deficits. Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines.
Gajewski, Patrick D; Falkenstein, Michael; Hengstler, Jan G; Golka, Klaus
Almost 30% of humans present a Toxoplasma gondii positive antibody status and its prevalence increases with age. The central nervous system is the main target. However, little is known about the influence of asymptomatic i.e. latent Toxoplasmosis on cognitive functions in humans. To investigate neurocognitive dysfunctions in asymptomatic older adults with T. gondii positive antibody status a double-blinded neuropsychological study was conducted. The participants were classified from a population-based sample (N=131) of healthy participants with an age of 65 years and older into two groups with 42 individuals each: Toxoplasmosis positive (T-pos; IgG>50 IU/ml) and Toxoplasmosis negative (T-neg; IgG=0 IU/ml). The outcome measures were a computer-based working-memory test (2-back) and several standardized psychometric tests of memory and executive cognitive functions. T-pos seniors showed an impairment of different aspects of memory. The rate of correctly detected target symbols in a 2-back task was decreased by nearly 9% (P=0.020), corresponding to a performance reduction of about 35% in working memory relative to the T-neg group. Moreover, T-pos seniors had a lower performance in a verbal memory test, both regarding immediate recall (10% reduction; P=0.022), delayed recognition (6%; P=0.037) and recall from long-term memory assessed by the word fluency tests (12%; P=0.029). In contrast, executive functions were not affected. The effects remained mostly unchanged after controlling for medication. The impairment of memory functions in T-pos seniors was accompanied by a decreased self-reported quality of life. Because of the high prevalence of asymptomatic Toxoplasmosis and an increasing population of older adults this finding is of high relevance for public health. Copyright © 2013 Elsevier Inc. All rights reserved.
Palmer, Matthew A; Sauer, James D; Ling, Angus; Riza, Joshua
Cravings for food and other substances can impair cognition. We extended previous research by testing the effects of caffeine cravings on cued-recall and recognition memory tasks, and on the accuracy of judgements of learning (JOLs; predicted future recall) and feeling-of-knowing (FOK; predicted future recognition for items that cannot be recalled). Participants (N = 55) studied word pairs (POND-BOOK) and completed a cued-recall test and a recognition test. Participants made JOLs prior to the cued-recall test and FOK judgements prior to the recognition test. Participants were randomly allocated to a craving or control condition; we manipulated caffeine cravings via a combination of abstinence, cue exposure, and imagery. Cravings impaired memory performance on the cued-recall and recognition tasks. Cravings also impaired resolution (the ability to distinguish items that would be remembered from those that would not) for FOK judgements but not JOLs, and reduced calibration (correspondence between predicted and actual accuracy) for JOLs but not FOK judgements. Additional analysis of the cued-recall data suggested that cravings also reduced participants' ability to monitor the likely accuracy of answers during the cued-recall test. These findings add to prior research demonstrating that memory strength manipulations have systematically different effects on different types of metacognitive judgements.
Newton, Jeremy W; Hobbs, Sue D
The current study investigated effects of simulated memory impairment on recall of child sexual abuse (CSA) information. A total of 144 adults were tested for memory of a written CSA scenario in which they role-played as the victim. There were four experimental groups and two testing sessions. During Session 1, participants read a CSA story and recalled it truthfully (Genuine group), omitted CSA information (Omission group), exaggerated CSA information (Commission group), or did not recall the story at all (No Rehearsal group). One week later, at Session 2, all participants were told to recount the scenario truthfully, and their memory was then tested using free recall and cued recall questions. The Session 1 manipulation affected memory accuracy during Session 2. Specifically, compared with the Genuine group's performance, the Omission, Commission, or No Rehearsal groups' performance was characterized by increased omission and commission errors and decreased reporting of correct details. Victim blame ratings (i.e., victim responsibility and provocativeness) and participant gender predicted increased error and decreased accuracy, whereas perpetrator blame ratings predicted decreased error and increased accuracy. Findings are discussed in relation to factors that may affect memory for CSA information. Copyright © 2015 John Wiley & Sons, Ltd.
Levy, Daniel A.; Squire, Larry R.; Hopkins, Ramona O.
In humans, impaired recognition memory following lesions thought to be limited to the hippocampal region has been demonstrated for a wide variety of tasks. However, the importance of the human hippocampus for olfactory recognition memory has scarcely been explored. We evaluated the ability of memory-impaired patients with damage thought to be…
Atsak, Piray; Hauer, Daniela; Campolongo, Patrizia; Schelling, Gustav; McGaugh, James L.; Roozendaal, Benno
There is extensive evidence that glucocorticoid hormones impair the retrieval of memory of emotionally arousing experiences. Although it is known that glucocorticoid effects on memory retrieval impairment depend on rapid interactions with arousal-induced noradrenergic activity, the exact mechanism underlying this presumably nongenomically mediated glucocorticoid action remains to be elucidated. Here, we show that the hippocampal endocannabinoid system, a rapidly activated retrograde messenger system, is involved in mediating glucocorticoid effects on retrieval of contextual fear memory. Systemic administration of corticosterone (0.3–3 mg/kg) to male Sprague–Dawley rats 1 h before retention testing impaired the retrieval of contextual fear memory without impairing the retrieval of auditory fear memory or directly affecting the expression of freezing behavior. Importantly, a blockade of hippocampal CB1 receptors with AM251 prevented the impairing effect of corticosterone on retrieval of contextual fear memory, whereas the same impairing dose of corticosterone increased hippocampal levels of the endocannabinoid 2-arachidonoylglycerol. We also found that antagonism of hippocampal β-adrenoceptor activity with local infusions of propranolol blocked the memory retrieval impairment induced by the CB receptor agonist WIN55,212–2. Thus, these findings strongly suggest that the endocannabinoid system plays an intermediary role in regulating rapid glucocorticoid effects on noradrenergic activity in impairing memory retrieval of emotionally arousing experiences. PMID:22331883
Bahuleyan, Biju; Singh, Satendra
Olfactory disorders are noted in a majority of neurodegenerative diseases, but they are often misjudged and are rarely rated in the clinical setting. Severe changes in the olfactory tests are observed in Parkinson's disease. Olfactory deficits are an early feature in Alzheimer's disease and they worsen with the disease progression. Alterations in the olfactory function are also noted after severe head injuries, temporal lobe epilepsy, multiple sclerosis, and migraine. The purpose of the present review was to discuss the available scientific knowledge on the olfactory memory and to relate its impairment with neurodegenerative diseases.
Planche, Vincent; Panatier, Aude; Hiba, Bassem; Ducourneau, Eva-Gunnel; Raffard, Gerard; Dubourdieu, Nadège; Maitre, Marlène; Lesté-Lasserre, Thierry; Brochet, Bruno; Dousset, Vincent; Desmedt, Aline; Oliet, Stéphane H; Tourdias, Thomas
Memory impairment is an early and disabling manifestation of multiple sclerosis whose anatomical and biological substrates are still poorly understood. We thus investigated whether memory impairment encountered at the early stage of the disease could be explained by a differential vulnerability of particular hippocampal subfields. By using experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, we identified that early memory impairment was associated with selective alteration of the dentate gyrus as pinpointed in vivo with diffusion-tensor-imaging (DTI). Neuromorphometric analyses and electrophysiological recordings confirmed dendritic degeneration, alteration in glutamatergic synaptic transmission and impaired long-term synaptic potentiation selectively in the dentate gyrus, but not in CA1, together with a more severe pattern of microglial activation in this subfield. Systemic injections of the microglial inhibitor minocycline prevented DTI, morphological, electrophysiological and behavioral impairments in EAE-mice. Furthermore, daily infusions of minocycline specifically within the dentate gyrus were sufficient to prevent memory impairment in EAE-mice while infusions of minocycline within CA1 were inefficient. We conclude that early memory impairment in EAE is due to a selective disruption of the dentate gyrus associated with microglia activation. These results open new pathophysiological, imaging, and therapeutic perspectives for memory impairment in multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.
Potagas, Constantin; Kasselimis, Dimitrios; Evdokimidis, Ioannis
The aim of the present study is to investigate short-term memory and working memory deficits in aphasics in relation to the severity of their language impairment. Fifty-eight aphasic patients participated in this study. Based on language assessment, an aphasia score was calculated for each patient. Memory was assessed in two modalities, verbal and spatial. Mean scores for all memory tasks were lower than normal. Aphasia score was significantly correlated with performance on all memory tasks. Correlation coefficients for short-term memory and working memory were approximately of the same magnitude. According to our findings, severity of aphasia is related with both verbal and spatial memory deficits. Moreover, while aphasia score correlated with lower scores in both short-term memory and working memory tasks, the lack of substantial difference between corresponding correlation coefficients suggests a possible primary deficit in information retention rather than impairment in working memory. Copyright © 2011 Elsevier Ltd. All rights reserved.
Sahlholm, Kristoffer; Valle-León, Marta; Fernández-Dueñas, Víctor; Ciruela, Francisco
Pridopidine is in clinical trials for Huntington's disease treatment. Originally developed as a dopamine D 2 receptor (D 2 R) ligand, pridopidine displays about 100-fold higher affinity for the sigma-1 receptor (sigma-1R). Interestingly, pridopidine slows disease progression and improves motor function in Huntington's disease model mice and, in preliminarily reports, Huntington's disease patients. The present study examined the anti-amnesic potential of pridopidine. Thus, memory impairment was produced in mice by administration of phencyclidine (PCP, 10 mg/kg/day) for 10 days, followed by 14 days' treatment with pridopidine (6 mg/kg/day), or saline. Finally, novel object recognition performance was assessed in the animals. Mice receiving PCP and saline exhibited deficits in novel object recognition, as expected, while pridopidine treatment counteracted PCP-induced memory impairment. The effect of pridopidine was attenuated by co-administration of the sigma receptor antagonist, NE-100 (10 mg/kg). Our results suggest that pridopidine exerts anti-amnesic and potentially neuroprotective actions. These data provide new insights into the therapeutic potential of pridopidine as a pro-cognitive drug.
Keane, M M; Gabrieli, J D; Monti, L A; Fleischman, D A; Cantor, J M; Noland, J S
To examine the status of conceptual memory processes in amnesia, a conceptual memory task with implicit or explicit task instructions was given to amnesic and control groups. After studying a list of category exemplars, participants saw category labels and were asked to generate as many exemplars as possible (an implicit memory task) or to generate exemplars that had been in the prior study list (an explicit memory task). After incidental deep or shallow encoding of exemplars, amnesic patients showed normal implicit memory performance (priming), a normal levels-of-processing effect on priming, and impaired explicit memory performance. After intentional encoding of exemplars, amnesic patients showed impaired implicit and explicit memory performance. Results suggest that although amnesic patients can show impairments on implicit and explicit conceptual memory tasks, their deficit does not generalize to all conceptual memory tasks.
Lum, Jarrad A.G.; Conti-Ramsden, Gina; Page, Debra; Ullman, Michael T.
According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the affected brain structures. In contrast, declarative memory is expected to remain largely intact, and should play an important compensatory role for grammar. These claims were tested by examining measures of working, declarative and procedural memory in 51 children with SLI and 51 matched typically-developing (TD) children (mean age 10). Working memory was assessed with the Working Memory Test Battery for Children, declarative memory with the Children’s Memory Scale, and procedural memory with a visuo-spatial Serial Reaction Time task. As compared to the TD children, the children with SLI were impaired at procedural memory, even when holding working memory constant. In contrast, they were spared at declarative memory for visual information, and at declarative memory in the verbal domain after controlling for working memory and language. Visuo-spatial short-term memory was intact, whereas verbal working memory was impaired, even when language deficits were held constant. Correlation analyses showed neither visuo-spatial nor verbal working memory was associated with either lexical or grammatical abilities in either the SLI or TD children. Declarative memory correlated with lexical abilities in both groups of children. Finally, grammatical abilities were associated with procedural memory in the TD children, but with declarative memory in the children with SLI. These findings replicate and extend previous studies of working, declarative and procedural memory in SLI. Overall, we
Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle
Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal…
Lum, J. A. G.; Conti-Ramsden, G.; Page, D.
at declarative memory for visual information, and at declarative memory in the verbal domain after controlling for working memory and language. Visuo-spatial short-term memory was intact, whereas verbal working memory was impaired, even when language deficits were held constant. Correlation analyses showed......According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which...... in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the affected brain structures. In contrast, declarative memory is expected to remain largely intact...
Zhang, Shixing; Yin, Yan; Lu, Huimin; Guo, Aike
Dopamine is necessary for the aversive olfactory associative memory formation in Drosophila, but its effect on other stages of memory is not known. Herein, we studied the effect of enhanced dopaminergic signaling on aversive olfactory memory retention in flies. We used l-3,4-dihydroxyphenylalanine (l-DOPA) to elevate dopamine levels: l-DOPA-treated flies exhibited a normal learning performance, but a decrease in 1-h memory. Dopamine transporter (DAT) mutant flies or flies treated with the DAT inhibitor desipramine exhibited poor memory retention. Flies subjected to heat stress after training exhibited a decrease in memory. Memory was restored by blocking dopaminergic neuronal output during heat stress, suggesting that dopamine is involved in heat stress-induced memory impairment in flies. Taken together, our findings suggest that increased dopaminergic signaling impairs aversive olfactory memory retention in flies.
Braun, Kees P J
PURPOSE OF REVIEW: Cognitive impairments are common in children with epilepsy. They may already be present before the onset of epilepsy or occur – and even progress – during its course. Many variables contribute to cognitive dysfunction. Those that can be targeted to prevent (further) cognitive
Archibald, Lisa M. D.; Harder Griebeling, Katherine
Background: Working memory deficits have been found for children with specific language impairment (SLI) on tasks imposing increasing short-term memory load with or without additional, consistent (and simple) processing load. Aims: To examine the processing function of working memory in children with low language (LL) by employing tasks imposing…
Liu, Jianlin; Abdin, Edimansyah; Vaingankar, Janhavi A; Shafie, Saleha B; Jeyagurunathan, Anitha; Shahwan, Shazana; Magadi, Harish; Ng, Li Ling; Chong, Siow Ann; Subramaniam, Mythily
Previous research has studied the relationships among unawareness of memory impairment, depression, and dementia in older adults with severe dementia, but it has not considered the associations and clinical implications at earlier stages of memory impairment. This study therefore sought to examine the relationship among unawareness of memory impairment, depression, and dementia in older adults with memory impairment in Singapore. The participants were 751 older adults with memory impairment in Singapore. They were assessed for objective and subjective memory loss, depression, and dementia severity. Participants' subjective memory loss was determined based on a self-appraisal question on memory, and their objective memory loss was calculated based on their performance on three cognitive tasks. Unawareness was assessed based on the contrast between subjective and objective memory loss. Descriptive statistics revealed a high prevalence of unawareness (80.4%). Logistic regression analysis revealed that gender and marital status were significantly associated with unawareness. Men (odds ratio (OR) = 2.5) and those who were divorced or separated (OR = 23.0) were more likely to be unaware than women and those who were married, respectively. After chronic conditions and demographic characteristics were controlled for, multivariate logistic regression analyses revealed that older adults with depression were less likely (OR = 0.2) to be unaware than those without depression. Unawareness was also related with dementia severity; older adults with questionable (OR = 0.3) and mild dementia (OR = 0.4) were less likely to be unaware than someone without dementia. Unawareness of memory impairment was common among older adults with memory impairment. However, unawareness may be the result of denial as a strategy for coping with memory loss of which the older adult is aware. Psychological care should be integrated into the overall treatment management of dementia to
van Daal, John; Verhoeven, Ludo; van Leeuwe, Jan; van Balkom, Hans
In the present study, the relations of various aspects of working memory to various aspects of language problems in a clinical sample of 97 Dutch speaking 5-year-old children with severe language problems were studied. The working memory and language abilities of the children were examined using an extensive battery of tests. Working memory was operationalized according to the model of Baddeley. Confirmative factor analyses revealed three memory factors: phonological, visual and central executive. Language was construed as a multifactorial construct, and confirmative factor analyses revealed four factors: lexical-semantic abilities, phonological abilities, syntactic abilities and speech production abilities. Moderate to high correlations were found between the memory and language factors. Structural equation modelling was used to further explore the relations between the different factors. Phonological memory was found to predict phonological abilities; central-executive memory predicted lexical-semantic abilities; and visual memory predicted speech production abilities. Phonological abilities also predicted syntactic abilities. Both the theoretical and clinical implications of the findings are discussed. The reader will be introduced to the concepts of multifactorial components of working memory as well as language impairment. Secondly the reader will recognize that working memory and language impairment factors can be related. Particular emphasis will be placed on phonological memory, central-executive memory and visual memory and their possible prediction of specific components of language impairment.
Campêlo, Clarissa L C; Santos, José R; Silva, Anatildes F; Dierschnabel, Aline L; Pontes, André; Cavalcante, Jeferson S; Ribeiro, Alessandra M; Silva, Regina H
Previous studies showed that the repeated administration with a low dose of reserpine (RES) induces a gradual appearance of motor signs and cognitive deficits compatible with parkinsonism in rodents. Environmental stimulation has neuroprotective effects in animal models of neurodegenerative damage, including acutely induced parkinsonism. We investigated the effects of exposure to an enriched environment (EE) on motor, cognitive and neuronal (levels of tyrosine hydroxylase, TH and brain derived neurotrophic factor, BDNF) deficits induced by a progressive model of Parkinson's disease (PD) in mice. Male mice were repeatedly treated with vehicle or 0.1mg/kg of RES (s.c) and kept under two housing conditions: standard environment (SE) and EE. In animals kept in SE, the treatment with RES induced deficits in motor function (catalepsy test, open field and oral movements), in novel object recognition (NOR) and plus-maze discriminative avoidance tasks. The environmental stimulation facilitated the recovery of motor deficits assessed by the catalepsy test after the end of treatment. Additionally, exposure to EE prevented the memory deficit in the NOR task. Treatment with RES induced a reduction in the number of TH positive cells in SNpc and VTA, which recovered 30days after the end of treatment. Finally, RES reduced the levels of BDNF in the striatum and the exposure to the EE prevented this effect. These results suggest that plastic brain changes induced by EE promote beneficial effects on the progression of neuronal impairment related to PD. Copyright © 2017 Elsevier B.V. All rights reserved.
Mao, Xinrui; You, Yuqi; Li, Wen; Guo, Chunyan
Substantial advancements in understanding emotional modulation of item memory notwithstanding, controversies remain as to how emotion influences source memory. Using an emotional extrinsic source memory paradigm combined with remember/know judgments and two key event-related potentials (ERPs)-the FN400 (a frontal potential at 300-500 ms related to familiarity) and the LPC (a later parietal potential at 500-700 ms related to recollection), our research investigated the impact of emotion on extrinsic source memory and the underlying processes. We varied a semantic prompt (either "people" or "scene") preceding a study item to manipulate the extrinsic source. Behavioral data indicated a significant effect of emotion on "remember" responses to extrinsic source details, suggesting impaired recollection-based source memory in emotional (both positive and negative) relative to neutral conditions. In parallel, differential FN400 and LPC amplitudes (correctly remembered - incorrectly remembered sources) revealed emotion-related interference, suggesting impaired familiarity and recollection memory of extrinsic sources associated with positive or negative items. These findings thus lend support to the notion of emotion-induced memory trade off: while enhancing memory of central items and intrinsic/integral source details, emotion nevertheless disrupts memory of peripheral contextual details, potentially impairing both familiarity and recollection. Importantly, that positive and negative items result in comparable memory impairment suggests that arousal (vs. affective valence) plays a critical role in modulating dynamic interactions among automatic and elaborate processes involved in memory. Copyright © 2015 Elsevier B.V. All rights reserved.
Neuroimaging studies have provided considerable evidence for frontal lobe involvement in memory processing. Memory impairments arc also frequently reported in patients with frontal lobe lesions. However detailed anatomical localisation is rare, making integration of lesion and imaging findings difficult. An investigation of the functional and anatomical contributions of the frontal lobes to memory was conducted in 42 patients with frontal lobe lesions, examining memory processes identified in...
MacKenzie, Graham; Powell, Tim F; Donaldson, David I
Despite widespread belief that memory is enhanced by emotion, evidence also suggests that emotion can impair memory. Here we test predictions inspired by object-based binding theory, which states that memory enhancement or impairment depends on the nature of the information to be retrieved. We investigated emotional memory in the context of source retrieval, using images of scenes that were negative, neutral or positive in valence. At study each scene was paired with a colour and during retrieval participants reported the source colour for recognised scenes. Critically, we isolated effects of valence by equating stimulus arousal across conditions. In Experiment 1 colour borders surrounded scenes at study: memory impairment was found for both negative and positive scenes. Experiment 2 used colours superimposed over scenes at study: valence affected source retrieval, with memory impairment for negative scenes only. These findings challenge current theories of emotional memory by showing that emotion can impair memory for both intrinsic and extrinsic source information, even when arousal is equated between emotional and neutral stimuli, and by dissociating the effects of positive and negative emotion on episodic memory retrieval.
Gold, Jeffrey J.; Smith, Christine N.; Bayley, Peter J.; Shrager, Yael; Brewer, James B.; Stark, Craig E. L.; Hopkins, Ramona O.; Squire, Larry R.
We studied item and source memory with fMRI in healthy volunteers and carried out a parallel study in memory-impaired patients. In experiment 1, volunteers studied a list of words in the scanner and later took an item memory test and a source memory test. Brain activity in the hippocampal region, perirhinal cortex, and parahippocampal cortex was associated with words that would later be remembered (item memory). The activity in these regions that predicted subsequent success at item memory pr...
Full Text Available In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.
Full Text Available Background: Despite some studies indicating improving role of stress on memory consolidation, very few animal and human studies show that stress impairs reconsolidation of memories. This study aimed to determine the effect of stress on autobiographical memory reconsolidation.Materials and Methods: The present study was done with an experimental method (Solomon Four-Group design. The statistical society of this study was all undergraduate female students in 2009-2010 academic year at Tabriz University. Forty students were selected using random cluster sampling, and we ensure about their physical and mental health by GHQ-28 and interview. Tools for this study were cueing autobiographical memory test, SECPT (for raising blood pressure and stress induction, autobiographical memory test, PANAS and general health questionnaire (GHQ-28. MANOVA was used for data analysis by SPSS-17.Results: The results show that stress after activation of memory impairs memory for neutral events (p0.05. None of stress and memory activation alone had effect on memory performance (p>0.05.Conclusion: These findings indicate that stress impairs autobiographical memory reconsolidation, which is opposite to its effects on memory consolidation, so it supports the view that consolidation and reconsolidation are separate process.
Pagnussat, N; Almeida, A S; Marques, D M; Nunes, F; Chenet, G C; Botton, P H S; Mioranzza, S; Loss, C M; Cunha, R A; Porciúncula, L O
Caffeine (a non-selective adenosine receptor antagonist) prevents memory deficits in aging and Alzheimer's disease, an effect mimicked by adenosine A2 A receptor, but not A1 receptor, antagonists. Hence, we investigated the effects of adenosine receptor agonists and antagonists on memory performance and scopolamine-induced memory impairment in mice. We determined whether A2 A receptors are necessary for the emergence of memory impairments induced by scopolamine and whether A2 A receptor activation triggers memory deficits in naïve mice, using three tests to assess short-term memory, namely the object recognition task, inhibitory avoidance and modified Y-maze. Scopolamine (1.0 mg·kg(-1) , i.p.) impaired short-term memory performance in all three tests and this scopolamine-induced amnesia was prevented by the A2 A receptor antagonist (SCH 58261, 0.1-1.0 mg·kg(-1) , i.p.) and by the A1 receptor antagonist (DPCPX, 0.2-5.0 mg·kg(-1) , i.p.), except in the modified Y-maze where only SCH58261 was effective. Both antagonists were devoid of effects on memory or locomotion in naïve rats. Notably, the activation of A2 A receptors with CGS 21680 (0.1-0.5 mg·kg(-1) , i.p.) before the training session was sufficient to trigger memory impairment in the three tests in naïve mice, and this effect was prevented by SCH 58261 (1.0 mg·kg(-1) , i.p.). Furthermore, i.c.v. administration of CGS 21680 (50 nmol) also impaired recognition memory in the object recognition task. These results show that A2 A receptors are necessary and sufficient to trigger memory impairment and further suggest that A1 receptors might also be selectively engaged to control the cholinergic-driven memory impairment. © 2015 The British Pharmacological Society.
Muñoz-López, Mónica; Hoskote, Aparna; Chadwick, Martin J; Dzieciol, Anna M; Gadian, David G; Chong, Kling; Banks, Tina; de Haan, Michelle; Baldeweg, Torsten; Mishkin, Mortimer; Vargha-Khadem, Faraneh
Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8-16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory. © 2017 Wiley Periodicals, Inc. © 2017 The Authors. Hippocampus Published by Wiley Periodicals, Inc.
Stamm, Andrew W.; Nguyen, Nam D.; Seicol, Benjamin J.; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert; Wamsley, Erin J.
Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into…
Bogdanov, Mario; Schwabe, Lars
Stress is known to impair working memory performance. This disruptive effect of stress on working memory has been linked to a decrease in the activity of the dorsolateral prefrontal cortex (dlPFC). In the present experiment, we tested whether transcranial direct current stimulation (tDCS) of the dlPFC can prevent stress-induced working memory impairments. We tested 120 healthy participants in a 2 d, sham-controlled, double-blind between-subjects design. Participants completed a test of their individual baseline working memory capacity on day 1. On day 2, participants were exposed to either a stressor or a control manipulation before they performed a visuospatial and a verbal working memory task. While participants completed the tasks, anodal, cathodal, or sham tDCS was applied over the right dlPFC. Stress impaired working memory performance in both tasks, albeit to a lesser extent in the verbal compared with the visuospatial working memory task. This stress-induced working memory impairment was prevented by anodal, but not sham or cathodal, stimulation of the dlPFC. Compared with sham or cathodal stimulation, anodal tDCS led to significantly better working memory performance in both tasks after stress. Our findings indicate a causal role of the dlPFC in working memory impairments after acute stress and point to anodal tDCS as a promising tool to reduce cognitive deficits related to working memory in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Working memory deficits are prominent in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Similar working memory impairments have been observed in healthy individuals exposed to acute stress. So far, attempts to prevent such stress-induced working memory deficits focused mainly on pharmacological interventions. Here, we tested the idea that transcranial direct current stimulation of the dorsolateral prefrontal
Dara S Manoach
Full Text Available Although disturbed sleep is a prominent feature of schizophrenia, its relation to the pathophysiology, signs, and symptoms of schizophrenia remains poorly understood. Sleep disturbances are well known to impair cognition in healthy individuals. Yet, in spite of its ubiquity in schizophrenia, abnormal sleep has generally been overlooked as a potential contributor to cognitive deficits. Amelioration of cognitive deficits is a current priority of the schizophrenia research community, but most efforts to define, characterize, and quantify cognitive deficits focus on cross-sectional measures. While this approach provides a valid snapshot of function, there is now overwhelming evidence that critical aspects of learning and memory consolidation happen offline, both over time and with sleep. Initial memory encoding is followed by a prolonged period of consolidation, integration, and reorganization, that continues over days or even years. Much of this evolution of memories is mediated by sleep. This article briefly reviews (i abnormal sleep in schizophrenia, (ii sleep-dependent memory consolidation in healthy individuals, (iii recent findings of impaired sleep-dependent memory consolidation in schizophrenia, and (iv implications of impaired sleep-dependent memory consolidation in schizophrenia. This literature suggests that abnormal sleep in schizophrenia disrupts attention and impairs sleep-dependent memory consolidation and task automation. We conclude that these sleep-dependent impairments may contribute substantially to generalized cognitive deficits in schizophrenia. Understanding this contribution may open new avenues to ameliorating cognitive dysfunction and thereby improve outcome in schizophrenia.
Full Text Available Although nicotine can enhance some cognitive functions, cigarette smoking may impair memory and sleep quality. Our aim was to investigate the impact of cigarette smoking on memory and sleep quality in healthy smokers. Sixty-eight healthy participants (34 smokers and 34 controls completed the Wechsler Memory Scale-Revised and a Chinese version of the Pittsburgh Sleep Quality Index. The Wilcoxon signed ranks test was performed, and Hochberg’s Sharpened Bonferroni correction was applied for multiple comparisons. The results show that current smokers had a worse visual memory compared to nonsmokers. There was no significant correlation between the index of Wechsler Memory Scale-Revised and Fagerström test for nicotine dependence. Moreover, smokers had poorer sleep quality. Cigarette smoking might impair memory and adversely influence sleep quality.
Boesveldt, S.; Muinck Keizer, de R.J.O.; Wolters, E.C.H.; Berendse, H.W.
The results of previous studies in small groups of Parkinson's disease (PD) patients are inconclusive with regard to the presence of an odor recognition memory impairment in PD. The aim of the present study was to investigate odor recognition memory in PD in a larger group of patients. Odor
Kessels, RPC; de Haan, EHF; Kappelle, LJ; Postma, A
There is evidence that object-location memory consists of three separate processes, that is, positional memory, binding of objects to locations, and a possible integration mechanism. A group of 26 patients with lesions following ischaemic stroke was studied to find evidence for selective impairments
Bisby, J. A.; Burgess, N.
The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine the effects of emotion on memory for items and their associations. By presenting neutral and negative items with background contexts, Experiment 1 ...
Lum, Jarrad A.G.; Conti-Ramsden, Gina; Page, Debra; Ullman, Michael T.
According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the...
Bisby, James A.; Burgess, Neil
The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine…
Vogel, Asmus; Gade, Anders; Stokholm, Jette
The presence and the nature of semantic memory dysfunction in Alzheimer's disease (AD) have been widely debated. This study aimed to determine the frequency of impaired semantic test performances in mild AD and to study whether incipient semantic impairments could be identified in predementia AD...
Tillmann, Barbara; Lévêque, Yohana; Fornoni, Lesly; Albouy, Philippe; Caclin, Anne
Congenital amusia is a neuro-developmental disorder of music perception and production. The hypothesis is that the musical deficits arise from altered pitch processing, with impairments in pitch discrimination (i.e., pitch change detection, pitch direction discrimination and identification) and short-term memory. The present review article focuses on the deficit of short-term memory for pitch. Overall, the data discussed here suggest impairments at each level of processing in short-term memory tasks; starting with the encoding of the pitch information and the creation of the adequate memory trace, the retention of the pitch traces over time as well as the recollection and comparison of the stored information with newly incoming information. These impairments have been related to altered brain responses in a distributed fronto-temporal network, associated with decreased connectivity between these structures, as well as in abnormalities in the connectivity between the two auditory cortices. In contrast, amusic participants׳ short-term memory abilities for verbal material are preserved. These findings show that short-term memory deficits in congenital amusia are specific to pitch, suggesting a pitch-memory system that is, at least partly, separated from verbal memory. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2015 Elsevier B.V. All rights reserved.
Bizzo, Bernardo Canedo; Sanchez, Tiago Arruda; Tukamoto, Gustavo; Zimmermann, Nicolle; Netto, Tania Maria; Gasparetto, Emerson Leandro
The purpose of this study was to investigate differences in brain cortical thickness of systemic lupus erythematosus (SLE) patients with and without episodic memory impairment and healthy controls. We studied 51 patients divided in 2 groups (SLE with episodic memory deficit, n = 17; SLE without episodic memory deficit, n = 34) by the Rey Auditory Verbal Learning Test and 34 healthy controls. Groups were paired based on sex, age, education, Mini-Mental State Examination score, and accumulation of disease burden. Cortical thickness from magnetic resonance imaging scans was determined using the FreeSurfer software package. SLE patients with episodic memory deficits presented reduced cortical thickness in the left supramarginal cortex and superior temporal gyrus when compared to the control group and in the right superior frontal, caudal, and rostral middle frontal and precentral gyri when compared to the SLE group without episodic memory impairment considering time since diagnosis of SLE as covaried. There were no significant differences in the cortical thickness between the SLE without episodic memory and control groups. Different memory-related cortical regions thinning were found in the episodic memory deficit group when individually compared to the groups of patients without memory impairment and healthy controls. Copyright © 2016 by the American Society of Neuroimaging.
Ennis, Naomi; Roy, Sylvain; Topolovec-Vranic, Jane
Cognitive impairment may interfere with an individual's ability to function independently in the community and may increase the risk of becoming and remaining homeless. The purpose of this study was to systematically review the literature on memory deficits among people who are homeless in order to gain a better understanding of its nature, causes and prevalence. Studies that measured memory functioning as an outcome among a sample of homeless persons were included. Data on sampling, outcome measures, facet of memory explored and prevalence of memory impairment were extracted from all selected research studies. Included studies were evaluated using a critical appraisal process targetted for reviewing prevalence studies. Eleven studies were included in the review. Verbal memory was the most commonly studied facet of memory. Potential contributing factors to memory deficits among persons who are homeless were explored in seven studies. Memory deficits were common among the samples of homeless persons studied. However, there was a great deal of variation in the methodology and quality of the included studies. Conceptualisations of "homelessness" also differed across studies. There is a need for more controlled research using validated neuropsychological tools to evaluate memory impairment among people who are homeless.
More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug
Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.
Zhu, Biao; Dong, Yuanlin; Xu, Zhipeng; Gompf, Heinrich S; Ward, Sarah A P; Xue, Zhanggang; Miao, Changhong; Zhang, Yiying; Chamberlin, Nancy L; Xie, Zhongcong
Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24 h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7 days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7 days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus-independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients. Copyright © 2012 Elsevier Inc. All rights reserved.
Vogel, Asmus; Gade, Anders; Stokholm, Jette
The presence and the nature of semantic memory dysfunction in Alzheimer's disease (AD) have been widely debated. This study aimed to determine the frequency of impaired semantic test performances in mild AD and to study whether incipient semantic impairments could be identified in predementia AD....... Five short neuropsychological tests sensitive to semantic memory and easily applicable in routine practice were administered to 102 patients with mild AD (Mini-Mental State Examination score above 19), 22 predementia AD patients and 58 healthy subjects. 'Category fluency' and 'naming of famous faces......' were the most frequently impaired tests in both patient groups. The study demonstrated that impairments on semantically related tests are common in mild AD and may exist prior to the clinical diagnosis. The results imply that assessment of semantic memory is relevant in the evaluation of patients...
Waring, J D; Dimsdale-Zucker, H R; Flannery, S; Budson, A E; Kensinger, E A
Young and older adults experience benefits in attention and memory for emotional compared to neutral information, but this memory benefit is greatly diminished in Alzheimer's disease (AD). Little is known about whether this impairment arises early or late in the time course between healthy aging and AD. This study compared memory for positive, negative, and neutral items with neutral backgrounds between patients with mild cognitive impairment (MCI) and healthy older adults. We also used a divided attention condition in older adults as a possible model for the deficits observed in MCI patients. Results showed a similar pattern of selective memory for emotional items while forgetting their backgrounds in older adults and MCI patients, but MCI patients had poorer memory overall. Dividing attention during encoding disproportionately reduced memory for backgrounds (versus items) relative to a full attention condition. Participants performing in the lower half on the divided attention task qualitatively and quantitatively mirrored the results in MCI patients. Exploratory analyses comparing lower- and higher-performing MCI patients showed that only higher-performing MCI patients had the characteristic scene memory pattern observed in healthy older adults. Together, these results suggest that the effects of emotion on memory are relatively well preserved for patients with MCI, although emotional memory patterns may start to be altered once memory deficits become more pronounced. Copyright © 2017 Elsevier Ltd. All rights reserved.
Bareggi, [No Value; Ferini-Strambi, L; Pirola, R; Smirne, S
Flunitrazepam was administered to volunteers in three different oral doses. The effects on psychomotor sedation, attention, working memory and explicit memory were then assessed at various intervals after dosing and compared with levels of the drug in the plasma. Three groups of 12 healthy males
Bareggi, [No Value; Ferini-Strambi, L; Pirola, R; Smirne, S
Flunitrazepam was administered to volunteers in three different oral doses. The effects on psychomotor sedation, attention, working memory and explicit memory were then assessed at various intervals after dosing and compared with levels of the drug in the plasma. Three groups of 12 healthy males
Smith, Alexandra E; Slivicki, Richard A; Hohmann, Andrea G; Crystal, Jonathon D
Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that have a negative impact on the quality of life of cancer survivors. Cognitive side effects occur across a variety of domains, including memory, executive function, and processing speed. Such impairments are exacerbated under cognitive challenges and a subgroup of patients experience long-term impairments. Episodic memory in rats can be examined using a source memory task. In the current study, rats received paclitaxel, a taxane-derived chemotherapeutic agent, and learning and memory functioning was examined using the source memory task. Treatment with paclitaxel did not impair spatial and episodic memory, and paclitaxel treated rats were not more susceptible to cognitive challenges. Under conditions in which memory was not impaired, paclitaxel treatment impaired learning of new rules, documenting a decreased sensitivity to changes in experimental contingencies. These findings provide new information on the nature of cancer chemotherapy-induced cognitive impairments, particularly regarding the incongruent vulnerability of episodic memory and new learning following treatment with paclitaxel. Copyright © 2016 Elsevier B.V. All rights reserved.
Full Text Available Objective(s: Crocin influences many biological functions including memory and learning. The present study was aimed to investigate the effects of crocin on learning and memory impairments in streptozotocine-induced diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (IP injection of streptozotocin (STZ, 45 mg/kg. Transfer latency (TL paradigm in elevated plus-maze (EPM was used as an index of learning and memory. Plasma levels of total antioxidant capacity (TAC and malondialdehyde (MDA, blood levels of glucose, and serum concentrations of insulin were measured. The number of hippocampal neurons was also counted. Results: STZ increased acquisition transfer latency (TL1 and retention transfer latency (TL2, and MDA, decreased transfer latency shortening (TLs and TCA, produced hyperglycemia and hypoinsulinemia, and reduced the number of neurons in the hippocampus. Learning and memory impairments and blood TCA, MDA, glucose, and insulin changes induced by streptozotocin were improved with long-term IP injection of crocin at doses of 15 and 30 mg/kg. Crocin prevented hippocampal neurons number loss in diabetic rats. Conclusion: The results indicate that oxidative stress, hyperglycemia, hypoinsulinemia, and reduction of hippocampal neurons may be involved in learning and memory impairments in STZ-induced diabetic rats. Antioxidant, antihyperglycemic, antihypoinsulinemic, and neuroprotective activities of crocin might be involved in improving learning and memory impairments.
Brébion, Gildas; Bressan, Rodrigo A; Ohlsen, Ruth I; David, Anthony S
Memory impairments in patients with schizophrenia have been associated with various cognitive and clinical factors. Hallucinations have been more specifically associated with errors stemming from source monitoring failure. We conducted a broad investigation of verbal memory and visual memory as well as source memory functioning in a sample of patients with schizophrenia. Various memory measures were tallied, and we studied their associations with processing speed, working memory span, and positive, negative, and depressive symptoms. Superficial and deep memory processes were differentially associated with processing speed, working memory span, avolition, depression, and attention disorders. Auditory/verbal and visual hallucinations were differentially associated with specific types of source memory error. We integrated all the results into a revised version of a previously published model of memory functioning in schizophrenia. The model describes the factors that affect memory efficiency, as well as the cognitive underpinnings of hallucinations within the source monitoring framework. © 2013.
Gopie, Nigel; Craik, Fergus I. M.; Hasher, Lynn
Older adults are assumed to have poor destination memory— knowing to whom they tell particular information—and anecdotes about them repeating stories to the same people are cited as informal evidence for this claim. Experiment 1 assessed young and older adults’ destination memory by having participants tell facts (e.g., “A dime has 118 ridges around its edge”) to pictures of famous people (e.g., Oprah Winfrey). Surprise recognition memory tests, which also assessed confidence, revealed that o...
Barbeau, Emmanuel J; Didic, Mira; Joubert, Sven; Guedj, Eric; Koric, Lejla; Felician, Olivier; Ranjeva, Jean-Philippe; Cozzone, Patrick; Ceccaldi, Mathieu
An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted.
Alekseichuk, Ivan; Pabel, Stefanie Corinna; Antal, Andrea; Paulus, Walter
There is a growing interest in large-scale connectivity as one of the crucial factors in working memory. Correlative evidence has revealed the anatomical and electrophysiological players in the working memory network, but understanding of the effective role of their connectivity remains elusive. In this double-blind, placebo-controlled study we aimed to identify the causal role of theta phase connectivity in visual-spatial working memory. The frontoparietal network was over- or de-synchronized in the anterior-posterior direction by multi-electrode, 6 Hz transcranial alternating current stimulation (tACS). A decrease in memory performance and increase in reaction time was caused by frontoparietal intrahemispheric desynchronization. According to the diffusion drift model, this originated in a lower signal-to-noise ratio, known as the drift rate index, in the memory system. The EEG analysis revealed a corresponding decrease in phase connectivity between prefrontal and parietal areas after tACS-driven desynchronization. The over-synchronization did not result in any changes in either the behavioral or electrophysiological levels in healthy participants. Taken together, we demonstrate the feasibility of manipulating multi-site large-scale networks in humans, and the disruptive effect of frontoparietal desynchronization on theta phase connectivity and visual-spatial working memory.
Coppin, Géraldine; Nolan-Poupart, Sarah; Jones-Gotman, Marilyn; Small, Dana M
Obesity has been associated with impaired executive functions including working memory. Less explored is the influence of obesity on learning and memory. In the current study we assessed stimulus reward association learning, explicit learning and memory and working memory in healthy weight, overweight and obese individuals. Explicit learning and memory did not differ as a function of group. In contrast, working memory was significantly and similarly impaired in both overweight and obese individuals compared to the healthy weight group. In the first reward association learning task the obese, but not healthy weight or overweight participants consistently formed paradoxical preferences for a pattern associated with a negative outcome (fewer food rewards). To determine if the deficit was specific to food reward a second experiment was conducted using money. Consistent with Experiment 1, obese individuals selected the pattern associated with a negative outcome (fewer monetary rewards) more frequently than healthy weight individuals and thus failed to develop a significant preference for the most rewarded patterns as was observed in the healthy weight group. Finally, on a probabilistic learning task, obese compared to healthy weight individuals showed deficits in negative, but not positive outcome learning. Taken together, our results demonstrate deficits in working memory and stimulus reward learning in obesity and suggest that obese individuals are impaired in learning to avoid negative outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.
Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule
Borcel, Erika; Pérez-Alvarez, Laura; Herrero, Ana Isabel
In this study, we examined whether chronic stress in adulthood can exert long-term effects on spatial-cognitive abilities and on the survival of newborn hippocampal cells in aging animals. Male Wistar rats were subjected to chronic unpredictable stress at midlife (12 months old) and then reexposed...... in the hippocampus. Interestingly, spatial-memory performance in the Morris water maze was positively correlated with the number of newborn cells that survived in the dentate gyrus: better spatial memory in the water maze was associated with more 5-bromo-2-deoxyuridine (BrdU)-labeled cells. Administration of FGL......, a peptide mimetic of neural cell adhesion molecule, during the 4 weeks of continuous stress not only prevented the deleterious effects of chronic stress on spatial memory, but also reduced the survival of the newly generated hippocampal cells in aging animals. FGL treatment did not, however, prevent...
Zhu, Zijian; Wang, Yingying; Cao, Zhijun; Chen, Biqing; Cai, Huaqian; Wu, Yanhong; Rao, Yi
Memory is a dynamic process. While memory becomes increasingly resistant to interference after consolidation, a brief reactivation renders it unstable again. Previous studies have shown that interference, when applied upon reactivation, impairs the consolidated memory, presumably by disrupting the reconsolidation of the memory. However, attempts have failed in disrupting human declarative memory, raising a question about whether declarative memory becomes unstable upon reactivation. Here, we used a double-cue/one-target paradigm, which associated the same target with two different cues in initial memory formation. Only one cue/target association was later reactivated and treated with behavioral interference. Our results showed, for the first time, that reactivation-coupled interference caused cue-independent memory impairment that generalized to other cues associated with the memory. Critically, such memory impairment appeared immediately after interference, before the reconsolidation process was completed, suggesting that common manipulations of reactivation-coupled interference procedures might disrupt other processes in addition to the reconsolidation process in human declarative memory. Copyright © 2016. Published by Elsevier B.V.
Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Ingkaninan, Kornkanok; Wittaya-Areekul, Sakchai
To date, the effective preventive paradigm against mild cognitive impairment (MCI) is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv). At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism. PMID:24672632
Full Text Available To date, the effective preventive paradigm against mild cognitive impairment (MCI is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv. At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.
Full Text Available Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool's development, which is not complete 8 weeks after secondary immunization.
Gutiérrez, Ranier; De la Cruz, Vanesa; Rodriguez-Ortiz, Carlos J.; Bermudez-Rattoni, Federico
The relevance of perirhinal cortical cholinergic and glutamatergic neurotransmission for taste recognition memory and learned taste aversion was assessed by microinfusions of muscarinic (scopolamine), NMDA (AP-5), and AMPA (NBQX) receptor antagonists. Infusions of scopolamine, but not AP5 or NBQX, prevented the consolidation of taste recognition memory using attenuation of neophobia as an index. In addition, learned taste aversion in both short- and long-term memory tests was exclusively impa...
Alhaider, Ibrahim A; Aleisa, Abdulaziz M; Tran, Trinh T; Alzoubi, Karem H; Alkadhi, Karim A
This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats. We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/L in drinking water) on memory impairment in acutely (24 h) sleep-deprived adult male Wistar rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory- and synaptic plasticity-related signaling molecules after E-LTP induction. The results showed that chronic caffeine treatment prevented impairment of hippocampus-dependent learning, shortterm memory and E-LTP of area CA1 in the sleep-deprived rats. In correlation, chronic caffeine treatment prevented sleep deprivation-associated decrease in the levels of phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) during expression of E-LTP. The results suggest that long-term use of a low dose of caffeine prevents impairment of short-term memory and E-LTP in acutely sleep-deprived rats.
Full Text Available Several experiments have demonstrated an intimate relationship between hippocampal theta rhythm (4-12 Hz and memory. Lesioning the medial septum or fimbria-fornix, a fiber track connecting the hippocampus and the medial septum, abolishes the theta rhythm and results in a severe impairment in declarative memory. To assess whether there is a causal relationship between hippocampal theta and memory formation we investigated whether restoration of hippocampal theta by electrical stimulation during the encoding phase also restores fimbria-fornix lesion induced memory deficit in rats in the fear conditioning paradigm. Male Wistar rats underwent sham or fimbria-fornix lesion operation. Stimulation electrodes were implanted in the ventral hippocampal commissure and recording electrodes in the septal hippocampus. Artificial theta stimulation of 8 Hz was delivered during 3-min free exploration of the test cage in half of the rats before aversive conditioning with three foot shocks during 2 min. Memory was assessed by total freezing time in the same environment 24 h and 28 h after fear conditioning, and in an intervening test session in a different context. As expected, fimbria-fornix lesion impaired fear memory and dramatically attenuated hippocampal theta power. Artificial theta stimulation produced continuous theta oscillations that were almost similar to endogenous theta rhythm in amplitude and frequency. However, contrary to our predictions, artificial theta stimulation impaired conditioned fear response in both sham and fimbria-fornix lesioned animals. These data suggest that restoration of theta oscillation per se is not sufficient to support memory encoding after fimbria-fornix lesion and that universal theta oscillation in the hippocampus with a fixed frequency may actually impair memory.
Barber, Sarah J.; Franklin, Nancy; Naka, Makiko; Yoshimura, Hiroki
Source monitoring is made difficult when the similarity between candidate sources increases. The current work examines how individual differences in social intelligence and perspective-taking abilities serve to increase source similarity and thus negatively impact source memory. Strangers first engaged in a cooperative storytelling task. On each…
Kim P C Kuypers
Full Text Available Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT. The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment was defined as decrement in memory performance that exceeded the cut-off value of 1.5 times the standard deviation of the average score in the healthy control sample. The primary question was whether being an Ecstasy user (E-user was predictive of having clinically deficient memory performance compared to a healthy control group.WLT data were pooled from four experimental MDMA studies that compared memory performance during placebo and MDMA intoxication. Control data were taken from healthy volunteers with no drug use history who completed the WLT as part of a placebo-controlled clinical trial. This resulted in a sample size of 65 E-users and 65 age- and gender-matched healthy drug-naïve controls. All participants were recruited by similar means and were tested at the same testing facilities using identical standard operating procedures. Data were analyzed using linear mixed-effects models, Bayes factor, and logistic regressions.Findings were that verbal memory performance of placebo-treated E-users did not differ from that of controls, and there was substantial evidence in favor of the null hypothesis. History of use was not predictive of memory impairment. During MDMA intoxication of E-users, verbal memory was impaired.The combination of the acute and long-term findings demonstrates that, while clinically relevant memory impairment is present during intoxication, it is absent during abstinence. This suggests that use of Ecstasy/MDMA does not lead to clinically deficient memory performance in the long term. Additionally, it has to be investigated whether the current findings apply to more complex cognitive
Kuypers, Kim P C; Theunissen, Eef L; van Wel, Janelle H P; de Sousa Fernandes Perna, Elizabeth B; Linssen, Anke; Sambeth, Anke; Schultz, Benjamin G; Ramaekers, Johannes G
Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT). The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment was defined as decrement in memory performance that exceeded the cut-off value of 1.5 times the standard deviation of the average score in the healthy control sample. The primary question was whether being an Ecstasy user (E-user) was predictive of having clinically deficient memory performance compared to a healthy control group. WLT data were pooled from four experimental MDMA studies that compared memory performance during placebo and MDMA intoxication. Control data were taken from healthy volunteers with no drug use history who completed the WLT as part of a placebo-controlled clinical trial. This resulted in a sample size of 65 E-users and 65 age- and gender-matched healthy drug-naïve controls. All participants were recruited by similar means and were tested at the same testing facilities using identical standard operating procedures. Data were analyzed using linear mixed-effects models, Bayes factor, and logistic regressions. Findings were that verbal memory performance of placebo-treated E-users did not differ from that of controls, and there was substantial evidence in favor of the null hypothesis. History of use was not predictive of memory impairment. During MDMA intoxication of E-users, verbal memory was impaired. The combination of the acute and long-term findings demonstrates that, while clinically relevant memory impairment is present during intoxication, it is absent during abstinence. This suggests that use of Ecstasy/MDMA does not lead to clinically deficient memory performance in the long term. Additionally, it has to be investigated whether the current findings apply to more complex cognitive measures in diverse
Winston, Gavin P; Stretton, Jason; Sidhu, Meneka K; Symms, Mark R; Thompson, Pamela J; Duncan, John S
Purpose: Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. Methods: We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. Key Findings: Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of
Majerus, Steve; Attout, Lucie; Artielle, Marie-Amélie; Van der Kaa, Marie-Anne
Verbal short-term memory (STM) impairment represents a frequent and long-lasting deficit in aphasia, and it will prevent patients from recovering fully functional language abilities. The aim of this study was to obtain a more precise understanding of the nature of verbal STM impairment in aphasia, by determining whether verbal STM impairment is merely a consequence of underlying language impairment, as suggested by linguistic accounts of verbal STM, or whether verbal STM impairment reflects an additional, specific deficit. We investigated this question by contrasting item-based STM measures, supposed to depend strongly upon language activation, and order-based STM measures, supposed to reflect the operation of specific, serial order maintenance mechanisms, in a sample of patients with single-word processing deficits at the phonological and/or lexical level. A group-level analysis showed robust impairment for both item and serial order STM aspects in the aphasic group relative to an age-matched control group. An analysis of individual profiles revealed an important heterogeneity of verbal STM profiles, with patients presenting either selective item STM deficits, selective order STM deficits, generalized item and serial order STM deficits or no significant STM impairment. Item but not serial order STM impairment correlated with the severity of phonological impairment. These results disconfirm a strong version of the linguistic account of verbal STM impairment in aphasia, by showing variable impairment to both item and serial order processing aspects of verbal STM. Copyright © 2015 Elsevier Ltd. All rights reserved.
Ryu, Seon Young; Lee, Sang Bong; Kim, Tae Woo; Lee, Taek Jun
Memory complaints are a frequent phenomenon in elderly individuals and can lead to opportunistic help-seeking behavior. The aim of this study was to compare different aspects of memory complaints (i.e., prospective versus retrospective complaints) in individuals with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (aMCI), and mild Alzheimer's disease (AD). The study included a total of 115 participants (mean age: 68.82 ± 8.83 years) with SCI (n = 34), aMCI (n = 46), and mild AD (n = 35). Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which consists of 16 items that describe everyday memory failure of both prospective memory (PM) and retrospective memory (RM). For aMCI and AD subjects, informants also completed an informant-rating of the PRMQ. All participants completed detailed neuropsychological tests. Results show that PM complaints were equivalent among the three groups. However, RM complaints differed. Specifically, RM complaints in aMCI were higher than SCI, but similar to AD. Informant-reported memory complaints were higher for AD than aMCI. Our study suggests that RM complaints of memory complaints may be helpful in discriminating between SCI and aMCI, but both PM and RM complaints are of limited value in differentiating aMCI from AD.
Oei, N.Y.L.; Everaerd, W.T.A.M.; Elzinga, B.M.; van Well, S.; Bermond, B.
Stress and cortisol are known to impair memory retrieval of well-consolidated declarative material. The effects of cortisol on memory retrieval may in particular be due to glucocorticoid (GC) receptors in the hippocampus and prefrontal cortex (PFC). Therefore, effects of stress and cortisol should
Rajasekar, N; Dwivedi, Subhash; Tota, Santosh Kumar; Kamat, Pradeep Kumar; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh
Okadaic acid (OKA) has been observed to cause memory impairment in human subjects having seafood contaminated with dinoflagellate (Helicondria okadai). OKA induces tau hyperphosphorylation and oxidative stress leading to memory impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced memory impairment. Therefore, present study evaluated the effect of curcumin on OKA (100ng, intracerebrally) induced memory impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in memory impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca(2+))i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50mg/kg) for 13 days significantly improved memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca(2+))i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive impairment. © 2013 Elsevier B.V. All rights reserved.
Tesler, Noemi; Latshang, Tsogyal D; Lo Cascio, Christian M; Stadelmann, Katrin; Stoewhas, Anne-Christin; Kohler, Malcolm; Bloch, Konrad E; Achermann, Peter; Huber, Reto
Several studies showed beneficial effects of sleep on memory performance. Slow waves, the electroencephalographic characteristic of deep sleep, reflected on the neuronal level by synchronous slow oscillations, seem crucial for these benefits. Traveling to moderate altitudes decreases deep sleep. In a randomized cross-over design healthy male subjects performed a visuo-motor learning task in Zurich (490 m) and at Davos Jakobshorn (2590 m) in random order. Memory performance was assessed immediately after learning, before sleep, and in the morning after a night of sleep. Sleep EEG recordings were performed during the nights. Our findings show an altitude induced reduction of sleep dependent memory performance. Moreover, this impaired sleep dependent memory performance was associated with reduced slow wave derived measures of neuronal synchronization. Our results are consistent with a critical role of slow waves for the beneficial effects of sleep on memory that is susceptible to natural environmental influences. Copyright © 2014 Elsevier Inc. All rights reserved.
Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A
Caffeine alleviates cognitive impairment associated with a variety of health conditions. In this study, we examined the effect of caffeine treatment on chronic stress- and/or high fat-high carbohydrate Western diet (WD)-induced impairment of learning and memory in rats. Chronic psychosocial stress, WD and caffeine (0.3 g/L in drinking water) were simultaneously administered for 3 months to adult male Wistar rats. At the conclusion of the 3 months, and while the previous treatments continued, rats were tested in the radial arm water maze (RAWM) for learning, short-term and long-term memory. This procedure was applied on a daily basis to all animals for 5 consecutive days or until the animal reaches days to criterion (DTC) in the 12th learning trial and memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Chronic stress and/or WD groups caused impaired learning, which was prevented by chronic caffeine administration. In the memory tests, chronic caffeine administration also prevented memory impairment during chronic stress conditions and/or WD. Furthermore, DTC value for caffeine treated stress, WD, and stress/WD groups indicated that caffeine normalizes memory impairment in these groups. These results showed that chronic caffeine administration prevented stress and/or WD-induced impairment of spatial learning and memory. Copyright © 2012 Elsevier B.V. All rights reserved.
Grilli, Matthew D; Glisky, Elizabeth L
The ability to imagine an elaborative event from a personal perspective relies on several cognitive processes that may potentially enhance subsequent memory for the event, including visual imagery, semantic elaboration, emotional processing, and self-referential processing. In an effort to find a novel strategy for enhancing memory in memory-impaired individuals with neurological damage, we investigated the mnemonic benefit of a method we refer to as self-imagining-the imagining of an event from a realistic, personal perspective. Fourteen individuals with neurologically based memory deficits and 14 healthy control participants intentionally encoded neutral and emotional sentences under three instructions: structural-baseline processing, semantic processing, and self-imagining. Findings revealed a robust "self-imagination effect (SIE)," as self-imagination enhanced recognition memory relative to deep semantic elaboration in both memory-impaired individuals, F(1, 13) = 32.11, p memory disorder nor were they related to self-reported vividness of visual imagery, semantic processing, or emotional content of the materials. The findings suggest that the SIE may depend on unique mnemonic mechanisms possibly related to self-referential processing and that imagining an event from a personal perspective makes that event particularly memorable even for those individuals with severe memory deficits. Self-imagining may thus provide an effective rehabilitation strategy for individuals with memory impairment.
Bäuml, Karl-Heinz T; Samenieh, Anuscheh
Research from the past decades has shown that retrieval of a specific memory (e.g., retrieving part of a previous vacation) typically attenuates retrieval of other memories (e.g., memories for other details of the event), causing retrieval-induced forgetting. More recently, however, it has been shown that retrieval can both attenuate and aid recall of other memories (K.-H. T. Bäuml & A. Samenieh, 2010). To identify the circumstances under which retrieval aids recall, the authors examined retrieval dynamics in listwise directed forgetting, context-dependent forgetting, proactive interference, and in the absence of any induced memory impairment. They found beneficial effects of selective retrieval in listwise directed forgetting and context-dependent forgetting but detrimental effects in all the other conditions. Because context-dependent forgetting and listwise directed forgetting arguably reflect impaired context access, the results suggest that memory retrieval aids recall of memories that are subject to impaired context access but attenuates recall in the absence of such circumstances. The findings are consistent with a 2-factor account of memory retrieval and suggest the existence of 2 faces of memory retrieval. 2012 APA, all rights reserved
Kim, Dong Hyun; Choi, Seong-Min; Jho, Jihoon; Park, Man-Seok; Kang, Jisu; Park, Se Jin; Ryu, Jong Hoon; Jo, Jihoon; Kim, Hyun Hee; Kim, Byeong C
Dysfunctions in the perirhinal cortex (PRh) are associated with visual recognition memory deficit, which is frequently detected in the early stage of Alzheimer's disease. Muscarinic acetylcholine receptor-dependent long-term depression (mAChR-LTD) of synaptic transmission is known as a key pathway in eliciting this type of memory, and Tg2576 mice expressing enhanced levels of Aβ oligomers are found to have impaired mAChR-LTD in this brain area at as early as 3 months of age. We found that the administration of Aβ oligomers in young normal mice also induced visual recognition memory impairment and perturbed mAChR-LTD in mouse PRh slices. In addition, when mice were treated with infliximab, a monoclonal antibody against TNF-α, visual recognition memory impaired by pre-administered Aβ oligomers dramatically improved and the detrimental Aβ effect on mAChR-LTD was annulled. Taken together, these findings suggest that Aβ-induced inflammation is mediated through TNF-α signaling cascades, disturbing synaptic transmission in the PRh, and leading to visual recognition memory deficits. Copyright © 2016 Elsevier B.V. All rights reserved.
Shinagawa, Shunichiro; Toyota, Yasutaka; Matsumoto, Teruhisa; Sonobe, Naomi; Adachi, Hiroyoshi; Mori, Takaaki; Ishikawa, Tomohisa; Fukuhara, Ryuji; Ikeda, Manabu
The aim of this study was to use the Rivermead Behavioural Memory Test (RBMT) to evaluate everyday memory impairment among community-dwelling elderly who had normal cognitive function and performed daily activities normally but displayed memory impairments, and to diagnose the condition as either mild cognitive impairment or dementia. Among the 1,290 community-dwelling elderly persons who participated in the study, 72 subjects scored higher than 24 on the Mini-Mental State Examination (MMSE): these subjects performed daily activities normally, but their family members reported that they showed memory impairments. Fifty-two subjects completed RBMT, Clinical Dementia Rating, and brain computed tomography, and a final diagnosis was established. The mean standard profile score was 15.1±5.0 and mean screening score was 6.4±3.0. RBMT score was correlated with the MMSE score. Nine of the subjects were diagnosed with dementia and 26 of them were found to be normal. RBMT achieved 100% sensitivity and specificity with regard to the differentiation of subjects with Alzheimer's disease. However, some subjects were diagnosed with dementia even though their RBMT score was higher than the cut-off score. RBMT was useful in detecting memory impairments of Alzheimer's disease (AD) subjects in community-based surveys. However, some subjects were diagnosed with dementia because of the existence of other cognitive impairments among community-dwelling elderly. (author)
Cunha, Rodrigo A; Agostinho, Paula M
Caffeine, the most widely consumed psychoactive drug, enhances attention/vigilance, stabilizes mood, and might also independently enhance cognitive performance. Notably, caffeine displays clearer and more robust beneficial effects on memory performance when memory is perturbed by stressful or noxious stimuli either in human or animal studies. Thus, caffeine restores memory performance in sleep-deprived or aged human individuals, a finding replicated in rodent animal models. Likewise, in animal models of Alzheimer's disease (AD), caffeine alleviates memory dysfunction, which is in accordance with the tentative inverse correlation between caffeine intake and the incidence of AD in different (but not all) cohorts. Caffeine also affords beneficial effects in animal models of conditions expected to impair memory performance such as Parkinson's disease, chronic stress, type 2 diabetes, attention deficit and hyperactivity disorder, early life convulsions, or alcohol-induced amnesia. Thus, caffeine should not be viewed as a cognitive enhancer but instead as a cognitive normalizer. Interestingly, these beneficial effects of caffeine on stress-induced memory disturbance are mimicked by antagonists of adenosine A2A receptors. This prominent role of A2A receptors in preventing memory deterioration is probably related to the synaptic localization of this receptor in limbic areas and its ability to control glutamatergic transmission, especially NMDA receptor-dependent plasticity, and to control apoptosis, brain metabolism, and the burden of neuroinflammation. This opens the real and exciting possibility that caffeine consumption might be a prophylactic strategy and A2A receptor antagonists may be a novel therapeutic option to manage memory dysfunction both in AD and in other chronic neurodegenerative disorders where memory deficits occur.
Guimond, Synthia; Hawco, Colin; Lepage, Martin
Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome. Copyright © 2017. Published by Elsevier Ltd.
Kojima, T; Karino, S; Yumoto, M; Funayama, M
A 42-year-old man suffered damage to the left supra-sylvian areas due to a stroke and presented with verbal short-term memory (STM) deficits. He occasionally could not recall even a single syllable that he had heard one second before. A study of mismatch negativity using magnetoencephalography suggested that the duration of auditory sensory (echoic) memory traces was reduced on the affected side of the brain. His maximum digit span was four with auditory presentation (equivalent to the 1st percentile for normal subjects), whereas it was up to six with visual presentation (almost within the normal range). He simply showed partial recall in the digit span task, and there was no self correction or incorrect reproduction. From these findings, reduced echoic memory was thought to have affected his verbal short-term retention. Thus, the impairment of verbal short-term memory observed in this patient was "pure auditory" unlike previously reported patients with deficits of the phonological short-term store (STS), which is the next higher-order memory system. We report this case to present physiological and behavioral data suggesting impaired short-term storage of verbal information, and to demonstrate the influence of deterioration of echoic memory on verbal STM.
Full Text Available Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase kinase-3β (GSK-3β activity affects memory. Constitutively active GSK-3β is required for memory retrieval, and propofol has been shown to inhibit GSK-3β. Thus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3β activity. Adult Sprague-Dawley rats were trained on a Morris water maze task (eight acquisition trials in one session and subjected under the influence of a subhypnotic dose of propofol to a 24-hour probe trial memory retrieval test. The results showed that rats receiving pretest propofol (25 mg/kg spent significantly less time in the target quadrant but showed no change in locomotor activity compared with those in the control group. Memory retrieval was accompanied by reduced phosphorylation of the serine-9 residue of GSK-3β in the hippocampus, whereas phosphorylation of the tyrosine-216 residue was unaffected. However, propofol blocked this retrieval-associated serine-9 phosphorylation. These findings suggest that subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3β signaling in the hippocampus.
Silver, Henry; Bilker, Warren B
Memory is impaired in schizophrenia patients but it is not clear whether this is specific to the illness and whether different types of memory (verbal and nonverbal) or memories in different cognitive domains (executive, object recognition) are similarly affected. To study relationships between memory impairments and schizophrenia we compared memory functions in 77 schizophrenia patients, 58 elderly healthy individuals and 41 young healthy individuals. Tests included verbal associative and logical memory and memory in executive and object recognition domains. We compared relationships of memory functions to each other and to other cognitive functions including psychomotor speed and verbal and spatial working memory. Compared to the young healthy group, schizophrenia patients and elderly healthy individuals showed similar severe impairment in logical memory and in the ability to learn new associations (NAL), and similar but less severe impairment in spatial working memory and executive and object memory. Verbal working memory was significantly more impaired in schizophrenia patients than in the healthy elderly. Verbal episodic memory impairment in schizophrenia may share common mechanisms with similar impairment in healthy aging. Impairment in verbal working memory in contrast may reflect mechanisms specific to schizophrenia. Study of verbal explicit memory impairment tapped by the NAL index may advance understanding of abnormal hippocampus dependent mechanisms common to schizophrenia and aging. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Hansson, K; Forsberg, J; Löfqvist, A; Mäki-Torkko, E; Sahlén, B
Working memory is considered to influence a range of linguistic skills, i.e. vocabulary acquisition, sentence comprehension and reading. Several studies have pointed to limitations of working memory in children with specific language impairment. Few studies, however, have explored the role of working memory for language deficits in children with hearing impairment. The first aim was to compare children with mild-to-moderate bilateral sensorineural hearing impairment, children with a preschool diagnosis of specific language impairment and children with normal language development, aged 9-12 years, for language and working memory. The special focus was on the role of working memory in learning new words for primary school age children. The assessment of working memory included tests of phonological short-term memory and complex working memory. Novel word learning was assessed according to the methods of. In addition, a range of language tests was used to assess language comprehension, output phonology and reading. Children with hearing impairment performed significantly better than children with a preschool diagnosis of specific language impairment on tasks assessing novel word learning, complex working memory, sentence comprehension and reading accuracy. No significant correlation was found between phonological short-term memory and novel word learning in any group. The best predictor of novel word learning in children with specific language impairment and in children with hearing impairment was complex working memory. Furthermore, there was a close relationship between complex working memory and language in children with a preschool diagnosis of specific language impairment but not in children with hearing impairment. Complex working memory seems to play a significant role in vocabulary acquisition in primary school age children. The interpretation is that the results support theories suggesting a weakened influence of phonological short-term memory on novel word
Lum, Jarrad A. G.; Bleses, Dorthe
It has been proposed that the language problems in specific language impairment (SLI) arise from basal ganglia abnormalities that lead to impairments with procedural and working memory but not declarative memory. In SLI, this profile of memory functioning has been hypothesized to underlie grammatical impairment but leave lexical knowledge…
Wunderli, Michael D; Vonmoos, Matthias; Fürst, Marina; Schädelin, Katrin; Kraemer, Thomas; Baumgartner, Markus R; Seifritz, Erich; Quednow, Boris B
Chronic use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has repeatedly been associated with deficits in working memory, declarative memory, and executive functions. However, previous findings regarding working memory and executive function are inconclusive yet, as in most studies concomitant stimulant use, which is known to affect these functions, was not adequately controlled for. Therefore, we compared the cognitive performance of 26 stimulant-free and largely pure (primary) MDMA users, 25 stimulant-using polydrug MDMA users, and 56 MDMA/stimulant-naïve controls by applying a comprehensive neuropsychological test battery. Neuropsychological tests were grouped into four cognitive domains. Recent drug use was objectively quantified by 6-month hair analyses on 17 substances and metabolites. Considerably lower mean hair concentrations of stimulants (amphetamine, methamphetamine, methylphenidate, cocaine), opioids (morphine, methadone, codeine), and hallucinogens (ketamine, 2C-B) were detected in primary compared to polydrug users, while both user groups did not differ in their MDMA hair concentration. Cohen's d effect sizes for both comparisons, i.e., primary MDMA users vs. controls and polydrug MDMA users vs. controls, were highest for declarative memory (d primary =.90, d polydrug =1.21), followed by working memory (d primary =.52, d polydrug =.96), executive functions (d primary =.46, d polydrug =.86), and attention (d primary =.23, d polydrug =.70). Thus, primary MDMA users showed strong and relatively discrete declarative memory impairments, whereas MDMA polydrug users displayed broad and unspecific cognitive impairments. Consequently, even largely pure chronic MDMA use is associated with decreased performance in declarative memory, while additional deficits in working memory and executive functions displayed by polydrug MDMA users are likely driven by stimulant co-use. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.
Efimova, O I; Anokhin, K V
We studied the involvement of DNA synthesis into molecular mechanisms of long-term memory. Nucleoside analogue 5-bromo-2'-deoxyuridine (BrdU) is known to incorporate into synthesizing DNA and prevent subsequent DNA replication from this region. To investigate the effect of BrdU administration on long-term memory, terrestrial gastropods edible snails Helix lucorum were trained in the food aversion paradigm. Single-session training (carrot presentation combined with application of 10% quinine solution, three carrot presentations with 10-min intervals) resulted in the formation of long-term memory that persisted for at least 45° days. BrdU administration (250 mg/kg) 30 min before training impaired long-term memory tested 24 h later. Immunohistochemical study revealed BrdU incorporation in the nuclei of identified neurons of defensive behavior.
Svensson, Maria; Hallin, Thord; Broms, Jonas; Ekstrand, Joakim; Tingström, Anders
Electroconvulsive therapy (ECT) is one of the most efficient treatments for severe major depression, but some patients suffer from retrograde memory loss after treatment. Electroconvulsive seizures (ECS), an animal model of ECT, have repeatedly been shown to increase hippocampal neurogenesis, and multiple ECS treatments cause retrograde amnesia in hippocampus-dependent memory tasks. Since recent studies propose that addition of newborn hippocampal neurons might degrade existing memories, we investigated whether the memory impairment after multiple ECS treatments is a cumulative effect of repeated treatments, or if it is the result of a delayed effect after a single ECS. We used the hippocampus-dependent memory task Morris water maze (MWM) to evaluate spatial memory. Rats were exposed to an 8-day training paradigm before receiving either a single ECS or sham treatment and tested in the MWM 24 h, 72 h, or 7 days after this treatment, or multiple (four) ECS or sham treatments and tested 7 days after the first treatment. A single ECS treatment was not sufficient to cause retrograde amnesia whereas multiple ECS treatments strongly disrupted spatial memory in the MWM. The retrograde amnesia after multiple ECS is a cumulative effect of repeated treatments rather than a delayed effect after a single ECS.
Cai, Wen-Hui; Blundell, Jacqueline; Han, Jie; Greene, Robert W; Powell, Craig M
Pavlovian fear conditioning provides one of the best rodent models of acquired anxiety disorders, including posttraumatic stress disorder. Injection of a variety of drugs after training in fear-conditioning paradigms can impair consolidation of fear memories. Indeed, early clinical trials suggest that immediate administration of such drugs after a traumatic event may decrease the risk of developing posttraumatic stress disorder in humans (Pitman et al., 2002; Vaiva et al., 2003). The use of such a treatment is limited by the difficulty of treating every patient at risk and by the difficulty in predicting which patients will experience chronic adverse consequences. Recent clinical trials suggest that administration of glucocorticoids may have a beneficial effect on established posttraumatic stress disorder (Aerni et al., 2004) and specific phobia (Soravia et al., 2006). Conversely, glucocorticoid administration after training is known to enhance memory consolidation (McGaugh and Roozendaal, 2002; Roozendaal, 2002). From a clinical perspective, enhancement of a fear memory or a reactivated fear memory would not be desirable. We report here that when glucocorticoids are administered immediately after reactivation of a contextual fear memory, subsequent recall is significantly diminished. Additional experiments support the interpretation that glucocorticoids not only decrease fear memory retrieval but, in addition, augment consolidation of fear memory extinction rather than decreasing reconsolidation. These findings provide a rodent model for a potential treatment of established acquired anxiety disorders in humans, as suggested by others (Aerni et al., 2004; Schelling et al., 2004), based on a mechanism of enhanced extinction.
Lum, Jarrad A. G.; Gelgic, Celin; Conti-Ramsden, Gina
Background: Much evidence has accumulated to indicate memory deficits in children with specific language impairment. However, most research has focused on working memory impairments in these children. Less is known about the functioning of other memory systems in this population. Aims: This study examined procedural and declarative memory in young…
Armstrong, Kristan; Williams, Lisa E; Heckers, Stephan
Patients with schizophrenia have widespread cognitive impairments, with selective deficits in relational memory. We previously reported a differential relational memory deficit in schizophrenia using the Associative Inference Paradigm (AIP), a task suggested by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative to examine relational memory. However, the AIP had limited feasibility for testing in schizophrenia because of high attrition of schizophrenia patients during training. Here we developed and tested a revised version of the AIP to improve feasibility. 30 healthy control and 37 schizophrenia subjects received 3 study-test sessions on 3 sets of paired associates: H-F1 (house paired with face), H-F2 (same house paired with new face), and F3-F4 (two novel faces). After training, subjects were tested on the trained, noninferential Face-Face pairs (F3-F4) and novel, inferential Face-Face pairs (F1-F2), constructed from the faces of the trained House-Face pairs. Schizophrenia patients were significantly more impaired on the inferential F1-F2 pairs than the noninferential F3-F4 pairs, providing evidence for a differential relational memory deficit. Only 8% of schizophrenia patients were excluded from testing because of poor training performance. The revised AIP confirmed the previous finding of a relational memory deficit in a larger and more representative sample of schizophrenia patients.
Kavé, Gitit; Heinik, Jeremia
This study examines which cognitive measure best accounts for perseverations in individuals with memory impairment. The sample included 85 individuals, of whom 21 had subjective memory concerns, 27 had mild cognitive impairment, and 37 had Alzheimer's disease. Participants produced responses on a semantic category fluency task and on the ideational fluency (IF) task from the Cambridge Cognitive Examination-Revised. Measures of word finding, working memory, and abstract thinking were also assessed. Significant group differences in percentage of perseverations emerged on both tasks. No cognitive measure accounted for the percentage of perseverations on the semantic fluency task. A measure of abstract thinking was the best predictor of the percentage of perseverations on the IF task, followed by a measure of working memory. The underlying cognitive mechanisms that lead to perseverations differ across tasks, with perseverations on the IF task reflecting both conceptual deficits and working memory limitations. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Sardari, Maryam; Rezayof, Ameneh; Khodagholi, Fariba; Zarrindast, Mohammad-Reza
The present study was designed to investigate the involvement of GABA-A receptors of the basolateral amygdala (BLA) in the impairing effect of acute stress on memory retrieval. The BLAs of adult male Wistar rats were bilaterally cannulated and memory retrieval was measured in a step-through type passive avoidance apparatus. Acute stress was evoked by placing the animals on an elevated platform for 10, 20 and 30 min. The results indicated that exposure to 20 and 30 min stress, but not 10 min, before memory retrieval testing (pre-test exposure to stress) decreased the step-through latency, indicating stress-induced memory retrieval impairment. Intra-BLA microinjection of a GABA-A receptor agonist, muscimol (0.005-0.02 μg/rat), 5 min before exposure to an ineffective stress (10 min exposure to stress) induced memory retrieval impairment. It is important to note that pre-test intra-BLA microinjection of the same doses of muscimol had no effect on memory retrieval in the rats unexposed to 10 min stress. The blockade of GABA-A receptors of the BLA by injecting an antagonist, bicuculline (0.4-0.5 μg/rat), 5 min before 20 min exposure to stress, prevented stress-induced memory retrieval. Pre-test intra-BLA microinjection of the same doses of bicuculline (0.4-0.5 μg/rat) in rats unexposed to 20 min stress had no effect on memory retrieval. In addition, pre-treatment with bicuculline (0.1-0.4 μg/rat, intra-BLA) reversed muscimol (0.02 μg/rat, intra-BLA)-induced potentiation on the effect of stress in passive avoidance learning. It can be concluded that pre-test exposure to stress can induce memory retrieval impairment and the BLA GABA-A receptors may be involved in stress-induced memory retrieval impairment.
Chen, Yuncai; Molet, Jenny; Lauterborn, Julie C; Trieu, Brian H; Bolton, Jessica L; Patterson, Katelin P; Gall, Christine M; Lynch, Gary; Baram, Tallie Z
. Mechanistically, corticosterone and CRH synergized at the spine-actin regulator RhoA, promoting its deactivation and degradation, respectively, and destabilizing spines. Notably, blocking both hormones, but not each alone, prevented the enduring memory problems after acute concurrent stresses. Therefore, synergistic actions of corticosterone and CRH underlie enduring memory impairments after concurrent acute stresses, which might be relevant to spatial memory deficits described in posttraumatic stress disorder. Copyright © 2016 the authors 0270-6474/16/3611295-13$15.00/0.
Abush, Hila; Akirav, Irit
Repeated stress is one of the environmental factors that precipitates and exacerbates mental illnesses like depression and anxiety as well as cognitive impairments. We have previously shown that cannabinoids can prevent the effects of acute stress on learning and memory. Here we aimed to find whether chronic cannabinoid treatment would alleviate the long-term effects of exposure to chronic restraint stress on memory and plasticity as well as on behavioral and neuroendocrine measures of anxiety and depression. Late adolescent rats were exposed to chronic restraint stress for 2 weeks followed each day by systemic treatment with vehicle or with the CB1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). Thirty days after the last exposure to stress, rats demonstrated impaired long-term potentiation (LTP) in the ventral subiculum-nucleus accumbens (NAc) pathway, impaired performance in the prefrontal cortex (PFC)-dependent object-recognition task and the hippocampal-dependent spatial version of this task, increased anxiety levels, and significantly reduced expression of glucocorticoid receptors (GRs) in the amygdala, hippocampus, PFC, and NAc. Chronic WIN55,212-2 administration prevented the stress-induced impairment in LTP levels and in the spatial task, with no effect on stress-induced alterations in unconditioned anxiety levels or GR levels. The CB1 antagonist AM251 (0.3 mg/kg) prevented the ameliorating effects of WIN55,212-2 on LTP and short-term memory. Hence, the beneficial effects of WIN55,212-2 on memory and plasticity are mediated by CB1 receptors and are not mediated by alterations in GR levels in the brain areas tested. Our findings suggest that cannabinoid receptor activation could represent a novel approach to the treatment of cognitive deficits that accompany a variety of stress-related neuropsychiatric disorders.
Wang, Yuan-Lin; Li, Feng; Chen, Xin
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. Copyright © 2016 Elsevier B.V. All rights reserved.
Blank, Martina; Petry, Fernanda S; Lichtenfels, Martina; Valiati, Fernanda E; Dornelles, Arethuza S; Roesler, Rafael
Relatively little is known about the requirement of signaling initiated by brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), in the early phases of memory consolidation, as well as about its possible functional interactions with epigenetic mechanisms. Here we show that blocking TrkB in the dorsal hippocampus after learning or retrieval impairs retention of memory for inhibitory avoidance (IA). More importantly, the impairing effect of TrkB antagonism on consolidation was completely prevented by the histone deacetylase (HDAC) inhibitor sodium butyrate (NaB). Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or NaB before training, followed by an infusion of either vehicle (VEH) or the selective TrkB antagonist ANA-12 immediately after training. In a second experiment, the infusions were administered before and after retrieval. ANA-12 after either training or retrieval produced a significant impairment in a subsequent memory retention test. Pretraining administration of NaB prevented the effect of ANA-12, although NaB given before retrieval did not alter the impairment resulting from TrkB blockade. The results indicate that inhibition of BDNF/TrkB in the hippocampus can hinder consolidation and reconsolidation of IA memory. However, TrkB activity is not required for consolidation in the presence of NaB, suggesting that a dysfunction in BDNF/TrkB signaling can be fully compensated by HDAC inhibition to allow hippocampal memory formation.
Kuboyama, Tomoharu; Hirotsu, Keisuke; Arai, Tetsuya; Yamasaki, Hiroo; Tohda, Chihiro
Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia ; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.
Yamada, Marina; Chiba, Tomohiro; Sasabe, Jumpei; Terashita, Kenzo; Aiso, Sadakazu; Matsuoka, Masaaki
Humanin (HN) and its derivatives, such as Colivelin (CLN), suppress neuronal death induced by insults related to Alzheimer's disease (AD) by activating STAT3 in vitro. They also ameliorate functional memory impairment of mice induced by anticholinergic drugs or soluble toxic amyloid-beta (Abeta) in vivo when either is directly administered into the cerebral ventricle or intraperitoneally injected. However, the mechanism underlying the in vivo effect remains uncharacterized. In addition, from the standpoint of clinical application, drug delivery methods that are less invasive and specific to the central nervous system (CNS) should be developed. In this study, we show that intranasally (i.n.) administered CLN can be successfully transferred to CNS via the olfactory bulb. Using several behavioral tests, we have demonstrated that i.n. administered CLN ameliorates memory impairment of AD models in a dose-responsive manner. Attenuation of AD-related memory impairment by HN derivatives such as CLN appears to be correlated with an increase in STAT3 phosphorylation levels in the septohippocampal region, suggesting that anti-AD activities of HN derivatives may be mediated by activation of STAT3 in vivo as they are in vitro. We further demonstrate that CLN treatment inhibits an Abeta induced decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the medial septum. Combined with the finding that HN derivatives upregulate mRNA expression of neuronal ChAT and vesicular acetylcholine transporter (VAChT) in vitro, it is assumed that CLN may ameliorate memory impairment of AD models by supporting cholinergic neurotransmission, which is at least partly mediated by STAT3-mediated transcriptional upregulation of ChAT and VAChT.
Sagana, Anna; Sauerland, Melanie; Merckelbach, Harald
Choice blindness refers to the phenomenon that people can be easily misled about the choices they made in the recent past. The aim of this study was to explore the cognitive mechanisms underlying choice blindness. Specifically, we tested whether memory impairment may account for choice blindness. A total of N = 88 participants provided sympathy ratings on 10-point scales for 20 female faces. Subsequently, participants motivated some of their ratings. However, on three trials, they were presen...
... all of us can work to prevent it, visit www.WhiteHouse.gov/ONDCP and www.NHTSA.gov/Impaired . NOW... Driving Prevention Month reminds us of the importance of celebrating safely. Every year, accidents... or drunk driving, and we rededicate ourselves to preventing it this December and throughout the year...
Colin James Smith
Full Text Available More than 2.5 million Americans suffer a traumatic brain injury (TBI each year. Even mild to moderate traumatic brain injury causes long-lasting neurological effects. Despite its prevalence, no therapy currently exists to treat the underlying cause of cognitive impairment suffered by TBI patients. Following lateral fluid percussion injury (LFPI, the most widely used experimental model of TBI, we investigated alterations in working memory and excitatory/inhibitory synaptic balance in the prefrontal cortex. LFPI impaired working memory as assessed with a T-maze behavioral task. Field excitatory postsynaptic potentials recorded in the prefrontal cortex were reduced in slices derived from brain-injured mice. Spontaneous and miniature excitatory postsynaptic currents onto layer 2/3 neurons were more frequent in slices derived from LFPI mice while inhibitory currents onto layer 2/3 neurons were smaller after LFPI. Additionally, an increase in action potential threshold and concomitant decrease in firing rate was observed in layer 2/3 neurons in slices from injured animals. Conversely, no differences in excitatory or inhibitory synaptic transmission onto layer 5 neurons were observed; however, layer 5 neurons demonstrated a decrease in input resistance and action potential duration after LFPI. These results demonstrate synaptic and intrinsic alterations in prefrontal circuitry that may underlie working memory impairment caused by TBI.
Butterworth, B; Cipolotti, L; Warrington, E K
We document the dissociation of preserved calculation skills in a patient with impaired auditory short-term memory. The patient (MRF) had a memory span of three digits. Furthermore, he showed rapid decrement in performance of single digits and letters with both auditory and visual presentation in the Brown-Peterson forgetting task. Analysis of his calculation skills revealed a normal ability to solve auditorily presented multidigit addition and subtraction problems such as 173 + 68 and to execute the Paced Auditory Serial Addition Task (Sampson, 1956, 1958; Gronwall, 1977). In addition, his performance on other tests, including arithmetic manipulation of natural numbers, decimals and fractions, approximation, magnitude, ratio, and percentage, appeared to be normal (Hitch, 1978b). It is argued that these findings require a revision of Baddeley and Hitch's (1974) concept of the function of working memory.
Yuan, Yuxiang; Chen, Zhiqi; Li, Lu; Li, Xing; Xia, Qian; Zhang, Hong; Duan, Qiming; Zhao, Yin
Primary open angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide. Previous MRI studies have revealed that POAG can be associated with alterations in hippocampal function. Thus, the aim of this study was to investigate a relationship between chronic high intraocular pressure (IOP) and hippocampal changes in a rat model. We used behavioural tests to assess learning and memory ability, and additionally investigated the hippocampal expression of pathological amyloid beta (Aβ), phospho-tau, and related pathway proteins. Chronic high IOP impaired learning and memory in rats and concurrently increased Aβ and phospho-tau expression in the hippocampus by altering the activation of different kinase (GSK-3β, BACE1) and phosphatase (PP2A) proteins in the hippocampus. This study provides novel evidence for the relationship between high IOP and hippocampal alterations, especially in the context of learning and memory. Copyright © 2017 Elsevier B.V. All rights reserved.
Full Text Available Previous studies showed that feigning amnesia for a crime impairs actual memory for the target event. Lack of rehearsal has been proposed as an explanation for this memory-undermining effect of feigning. The aim of the present study was to replicate and extend previous research adopting a mock crime video instead of a narrative story. We showed participants a video of a violent crime. Next, they were requested to imagine that they had committed this offense and to either feign amnesia or confess the crime. A third condition was included: Participants in the delayed test-only control condition did not receive any instruction. On subsequent recall tests, participants in all three conditions were instructed to report as much information as possible about the offense. On the free recall test, feigning amnesia impaired memory for the video clip, but participants who were asked to feign crime-related amnesia outperformed controls. However, no differences between simulators and confessors were found on both correct cued recollection or on distortion and commission rates. We also explored whether inner speech might modulate memory for the crime. Inner speech traits were not found to be related to the simulating amnesia effect. Theoretical and practical implications of our results are discussed.
Mangiulli, Ivan; van Oorsouw, Kim; Curci, Antonietta; Merckelbach, Harald; Jelicic, Marko
Previous studies showed that feigning amnesia for a crime impairs actual memory for the target event. Lack of rehearsal has been proposed as an explanation for this memory-undermining effect of feigning. The aim of the present study was to replicate and extend previous research adopting a mock crime video instead of a narrative story. We showed participants a video of a violent crime. Next, they were requested to imagine that they had committed this offense and to either feign amnesia or confess the crime. A third condition was included: Participants in the delayed test-only control condition did not receive any instruction. On subsequent recall tests, participants in all three conditions were instructed to report as much information as possible about the offense. On the free recall test, feigning amnesia impaired memory for the video clip, but participants who were asked to feign crime-related amnesia outperformed controls. However, no differences between simulators and confessors were found on both correct cued recollection or on distortion and commission rates. We also explored whether inner speech might modulate memory for the crime. Inner speech traits were not found to be related to the simulating amnesia effect. Theoretical and practical implications of our results are discussed.
Allen, Timothy A.; Morris, Andrea M.; Stark, Shauna M.; Fortin, Norbert J.
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 remember sequences of events, an important feature of episodic memory. Unlike existing paradigms, this task is nonspatial, nonverbal, and can be used to isolate different cognitive processes that may be differentially affected in aging. Here, we used this task to make a comprehensive comparison of sequence memory performance between younger (18–22 yr) and older adults (62–86 yr). Specifically, participants viewed repeated sequences of six colored, fractal images and indicated whether each item was presented “in sequence” or “out of sequence.” Several out of sequence probe trials were used to provide a detailed assessment of sequence memory, including: (i) repeating an item from earlier in the sequence (“Repeats”; e.g., ABADEF), (ii) skipping ahead in the sequence (“Skips”; e.g., ABDDEF), and (iii) inserting an item from a different sequence into the same ordinal position (“Ordinal Transfers”; e.g., AB3DEF). We found that older adults performed as well as younger controls when tested on well-known and predictable sequences, but were severely impaired when tested using novel sequences. Importantly, overall sequence memory performance in older adults steadily declined with age, a decline not detected with other measures (RAVLT or BPS-O). We further characterized this deficit by showing that performance of older adults was severely impaired on specific probe trials that required detailed knowledge of the sequence (Skips and Ordinal Transfers), and was associated with a shift in their underlying mnemonic representation of the sequences. Collectively, these findings provide unambiguous evidence that the
Pearson-Leary, Jiah; McNay, Ewan C.
Increasing evidence suggests that abnormal brain accumulation of amyloid-β1–42 (Aβ1–42) oligomers plays a causal role in Alzheimer’s disease (AD), and in particular may cause the cognitive deficits that are the hallmark of AD. In vitro, Aβ1–42 oligomers impair insulin signaling and suppress neural functioning. We previously showed that endogenous insulin signaling is an obligatory component of normal hippocampal function, and that disrupting this signaling led to a rapid impairment of spatial working memory, while delivery of exogenous insulin to the hippocampus enhanced both memory and metabolism; diet-induced insulin resistance both impaired spatial memory and prevented insulin from increasing metabolism or cognitive function. Hence, we tested the hypothesis that Aβ1–42 oligomers could acutely impair hippocampal metabolic and cognitive processes in vivo in the rat. Our findings support this hypothesis: Aβ1–42 oligomers impaired spontaneous alternation behavior while preventing the task-associated dip in hippocampal ECF glucose observed in control animals. In addition, Aβ1–42 oligomers decreased plasma membrane translocation of the insulin-sensitive glucose transporter 4 (GluT4), and impaired insulin signaling as measured by phosphorylation of Akt. These data show in vivo that Aβ1–42 oligomers can rapidly impair hippocampal cognitive and metabolic processes, and provide support for the hypothesis that elevated Aβ1–42 leads to cognitive impairment via interference with hippocampal insulin signaling. PMID:22430529
Gutierrez, Ranier; De la Cruz, Vanesa; Rodriguez-Ortiz, Carlos J.; Bermudez-Rattoni, Federico
The relevance of perirhinal cortical cholinergic and glutamatergic neurotransmission for taste recognition memory and learned taste aversion was assessed by microinfusions of muscarinic (scopolamine), NMDA (AP-5), and AMPA (NBQX) receptor antagonists. Infusions of scopolamine, but not AP5 or NBQX, prevented the consolidation of taste recognition…
Cowell, Rosemary A; Bussey, Timothy J; Saksida, Lisa M
Object recognition is the canonical test of declarative memory, the type of memory putatively impaired after damage to the temporal lobes. Studies of object recognition memory have helped elucidate the anatomical structures involved in declarative memory, indicating a critical role for perirhinal cortex. We offer a mechanistic account of the effects of perirhinal cortex damage on object recognition memory, based on the assumption that perirhinal cortex stores representations of the conjunctions of visual features possessed by complex objects. Such representations are proposed to play an important role in memory when it is difficult to solve a task using representations of only individual visual features of stimuli, thought to be stored in regions of the ventral visual stream caudal to perirhinal cortex. The account is instantiated in a connectionist model, in which development of object representations with visual experience provides a mechanism for judgment of previous occurrence. We present simulations addressing the following empirical findings: (1) that impairments after damage to perirhinal cortex (modeled by removing the "perirhinal cortex" layer of the network) are exacerbated by lengthening the delay between presentation of to-be-remembered items and test, (2) that such impairments are also exacerbated by lengthening the list of to-be-remembered items, and (3) that impairments are revealed only when stimuli are trial unique rather than repeatedly presented. This study shows that it may be possible to account for object recognition impairments after damage to perirhinal cortex within a hierarchical, representational framework, in which complex conjunctive representations in perirhinal cortex play a critical role.
Ye, Qi; Kim, Jonghan
Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout (Hfe (-/-)) and wild-type (Hfe (+/+)) mice mice were intranasally-instilled with manganese chloride (MnCl2 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in Hfe (+/+) mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, Hfe (-/-) mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in Hfe (+/+) mice, but not in Hfe (-/-) mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of
.03, P = 0.04]. NREM slow oscillation power did not correlate with memory consolidation. All results retained significance after controlling for age and BMI. In sum, participants with mild OSA had impaired memory consolidation and results were mediated by N2 sigma power. These results suggest that N2 sigma power could serve as biomarker of risk for cognitive dysfunction in children with sleep disordered breathing.
Full Text Available Verbal memory (VM represents one of the most affected cognitive domains in schizophrenia. Multiple studies have shown that schizophrenia is associated with cortical abnormalities, but it remains unclear whether these are related to VM impairments. Considering the vast literature demonstrating the role of the frontal cortex, the parahippocampal cortex, and the hippocampus in VM, we examined the cortical thickness/volume of these regions. We used a categorical approach whereby 27 schizophrenia patients with ‘moderate to severe’ VM impairments were compared to 23 patients with ‘low to mild’ VM impairments and 23 healthy controls. A series of between-group vertex-wise GLM on cortical thickness were performed for specific regions of interest defining the parahippocampal gyrus and the frontal cortex. When compared to healthy controls, patients with ‘moderate to severe’ VM impairments revealed significantly thinner cortex in the left frontal lobe, and the parahippocampal gyri. When compared to patients with ‘low to mild’ VM impairments, patients with ‘moderate to severe’ VM impairments showed a trend of thinner cortex in similar regions. Virtually no differences were observed in the frontal area of patients with ‘low to mild’ VM impairments relative to controls. No significant group differences were observed in the hippocampus. Our results indicate that patients with greater VM impairments demonstrate significant cortical thinning in regions known to be important in VM performance. Treating VM deficits in schizophrenia could have a positive effect on the brain; thus, subgroups of patients with more severe VM deficits should be a prioritized target in the development of new cognitive treatments.
Coradazzi, Marino; Gulino, Rosario; Fieramosca, Francesco; Falzacappa, Lucia Verga; Riggi, Margherita; Leanza, Giampiero
Noradrenergic neurons in the locus coeruleus play a role in learning and memory, and their loss is an early event in Alzheimer's disease pathogenesis. Moreover, noradrenaline may sustain hippocampal neurogenesis; however, whether are these events related is still unknown. Four to five weeks following the selective immunotoxic ablation of locus coeruleus neurons, young adult rats underwent reference and working memory tests, followed by postmortem quantitative morphological analyses to assess the extent of the lesion, as well as the effects on proliferation and/or survival of neural progenitors in the hippocampus. When tested in the Water Maze task, lesioned animals exhibited no reference memory deficit, whereas working memory abilities were seen significantly impaired, as compared with intact or sham-lesioned controls. Stereological analyses confirmed a dramatic noradrenergic neuron loss associated to reduced proliferation, but not survival or differentiation, of 5-bromo-2'deoxyuridine-positive progenitors in the dentate gyrus. Thus, ascending noradrenergic afferents may be involved in more complex aspects of cognitive performance (i.e., working memory) possibly via newly generated progenitors in the hippocampus. Copyright © 2016 Elsevier Inc. All rights reserved.
Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.
Niyuhire, Floride; Varvel, Stephen A; Martin, Billy R; Lichtman, Aron H
Marijuana (Cannabis sativa) and its primary psychoactive component, delta-9-tetrahydrocannabinol (Delta(9)-THC), have long been known to disrupt cognition in humans. Although Delta(9)-THC and other cannabinoids disrupt performance in a wide range of animal models of learning and memory, few studies have investigated the effects of smoked marijuana in these paradigms. Moreover, in preclinical studies, cannabinoids are generally administered before acquisition, and because retention is generally evaluated soon afterward, it is difficult to distinguish between processes related to acquisition and retrieval. In the present study, we investigated the specific effects of marijuana smoke and injected Delta(9)-THC on acquisition versus memory retrieval in a mouse repeated acquisition Morris water-maze task. To distinguish between these processes, subjects were administered Delta(9)-THC or they were exposed to marijuana smoke either 30 min before acquisition or 30 min before the retention test. Inhalation of marijuana smoke or injected Delta(9)-THC impaired the ability of the mice to learn the location of the hidden platform and to recall the platform location once learning had already taken place. In contrast, neither drug impaired performance in a cued task in which the platform was made visible. Finally, the cannabinoid-1 (CB(1)) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (rimonabant) blocked the memory disruptive effects of both Delta(9)-THC and marijuana. These data represent the first evidence demonstrating that marijuana impairs memory retrieval through a CB(1) receptor mechanism of action and independently of its effects on sensorimotor performance, motivation, and initial acquisition.
Spiegel, Amy M.; Koh, Ming Teng; Vogt, Nicholas M.; Rapp, Peter R.; Gallagher, Michela
Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age-related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well-characterized model in which outbred, aged, male Long-Evans rats exhibit a spectrum of individual differences in hippocampal-dependent memory. Selected interneuron populations in the hippocampus were visualized for stereological quantification with a panel of immunocytochemical markers, including glutamic acid decarboxylase-67 (GAD67), somatostatin, and neuropeptide Y. The overall pattern of results was that, although the numbers of GAD67- and somatostatin-positive interneurons declined with age across multiple fields of the hippocampus, alterations specifically related to the cognitive outcome of aging were observed exclusively in the hilus of the dentate gyrus. Because the total number of NeuN-immunoreactive hilar neurons was unaffected, the decline observed with other markers likely reflects a loss of target protein rather than neuron death. In support of that interpretation, treatment with the atypical antiepileptic levetiracetam at a low dose shown previously to improve behavioral performance fully restored hilar SOM expression in aged, memory-impaired rats. Age-related decreases in GAD67- and somatostatin-immunoreactive neuron number beyond the hilus were regionally selective and spared the CA1 field of the hippocampus entirely. Together these findings confirm the vulnerability of hippocampal interneurons to normal aging and highlight that the integrity of a specific subpopulation in the hilus is coupled with age-related memory impairment. PMID:23749483
Riedel, W; Hogervorst, E; Leboux, R; Verhey, F; van Praag, H; Jolles, J
Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.
Oba, Hikaru; Matsuoka, Teruyuki; Imai, Ayu; Fujimoto, Hiroshi; Kato, Yuka; Shibata, Keisuke; Nakamura, Kaeko; Narumoto, Jin
To investigate the effects of interactions between memory impairment, depressive symptoms, and anosognosia. Anosognosia for memory impairment was assessed in 118 patients with Alzheimer's disease (AD), 47 patients with mild cognitive impairment (MCI), and 17 non-diagnosed controls (NC) using a questionnaire and evaluation of the anosognosia score as the discrepancy between ratings of the patient and a relative. Demographic characteristics, such as the relationship of the patient with the relative and the activities of daily living (ADL) were evaluated. Memory impairment was evaluated with the Rivermead Behavioral Memory Test (RBMT), depressive symptoms were evaluated using the Geriatric Depression Scale (GDS) 15 items version. In the MCI group, a stepwise multiple regression analysis showed an interaction between RBMT and GDS scores, and simple slope analysis indicated that scores for RBMT at low GDS (-1 standard deviation) were positively correlated with self-rated memory impairment. In the AD group, the relationship of the patient with the relative, ADL, and GDS and RBMT scores were associated with the anosognosia score. Patients with MCI who have no depressive symptoms may be able to more accurately evaluate their memory impairment than those who have depressive symptoms and patients with AD. The evaluation by relatives, depressive symptoms or ADL of patients may distort evaluation of anosognosia for memory impairment in patients with AD or MCI. It seems necessary to include not only depression scale scores but also results of objective memory tests in the patients' medical information for the correct assessment of anosognosia.
Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan
Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. Copyright © 2015 Elsevier Inc. All rights reserved.
Full Text Available Mild cognitive impairment (MCI is considered a transitional stage between healthy aging and dementia, specifically Alzheimer’s disease (AD. The most common cognitive impairment of MCI includes episodic memory loss and difficulties in working memory (WM. Interference can deplete WM, and an optimal WM performance requires an effective control of attentional resources between the memoranda and the incoming stimuli. Difficulties in handling interference lead to forgetting. However, the interplay between interference and WM in MCI is not well understood and needs further investigation. The current study investigated the effect of interference during a WM task in 20 MCIs and 20 healthy elder volunteers. Participants performed a delayed match-to-sample paradigm which consisted in two interference conditions, distraction and interruption, and one control condition without any interference. Results evidenced a disproportionate impact of interference on the WM performance of MCIs, mainly in the presence of interruption. These findings demonstrate that interference, and more precisely interruption, is an important proxy for memory-related deficits in MCI. Thus the current findings reveal novel evidence regarding the causes of WM forgetting in MCI patients, associated with difficulties in the mechanisms of attentional control.
Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin
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. Copyright © 2014 Elsevier Ltd. All rights reserved.
Kelley, Matthew R; Parihar, Sushmeena A
The present study explored the influence of part-set cues in semantic memory using tests of "free" recall, reconstruction of order, and serial recall. Nine distinct categories of information were used (e.g., Zodiac signs, Harry Potter books, Star Wars films, planets). The results showed part-set cueing impairment for all three "free" recall sets, whereas part-set cueing facilitation was evident for five of the six ordered sets. Generally, the present results parallel those often observed across episodic tasks, which could indicate that similar mechanisms contribute to part-set cueing effects in both episodic and semantic memory. A novel anchoring explanation of part-set cueing facilitation in order and spatial tasks is provided.
Wantz, Andrea L; Martarelli, Corinna S; Cazzoli, Dario; Kalla, Roger; Müri, René; Mast, Fred W
A large body of research demonstrated that participants preferably look back to the encoding location when retrieving visual information from memory. However, the role of this 'looking back to nothing' is still debated. The goal of the present study was to extend this line of research by examining whether an important area in the cortical representation of the oculomotor system, the frontal eye field (FEF), is involved in memory retrieval. To interfere with the activity of the FEF, we used inhibitory continuous theta burst stimulation (cTBS). Before stimulation was applied, participants encoded a complex scene and performed a short-term (immediately after encoding) or long-term (after 24 h) recall task, just after cTBS over the right FEF or sham stimulation. cTBS did not affect overall performance, but stimulation and statement type (object vs. location) interacted. cTBS over the right FEF tended to impair object recall sensitivity, whereas there was no effect on location recall sensitivity. These findings suggest that the FEF is involved in retrieving object information from scene memory, supporting the hypothesis that the oculomotor system contributes to memory recall.
Soga, Keishi; Kamijo, Keita; Masaki, Hiroaki
We investigated how aerobic exercise during encoding affects hippocampus-dependent memory through a source memory task that assessed hippocampus-independent familiarity and hippocampus-dependent recollection processes. Using a within-participants design, young adult participants performed a memory-encoding task while performing a cycling exercise or being seated. The subsequent retrieval phase was conducted while sitting on a chair. We assessed behavioral and event-related brain potential measures of familiarity and recollection processes during the retrieval phase. Results indicated that source accuracy was lower for encoding with exercise than for encoding in the resting condition. Event-related brain potential measures indicated that the parietal old/new effect, which has been linked to recollection processing, was observed in the exercise condition, whereas it was absent in the rest condition, which is indicative of exercise-induced hippocampal activation. These findings suggest that aerobic exercise during encoding impairs hippocampus-dependent memory, which may be attributed to inefficient source encoding during aerobic exercise.
Scheef, Lukas; Spottke, Annika; Daerr, Moritz; Joe, Alexius; Striepens, Nadine; Kölsch, Heike; Popp, Julius; Daamen, Marcel; Gorris, Dominik; Heneka, Michael T; Boecker, Henning; Biersack, Hans J; Maier, Wolfgang; Schild, Hans H; Wagner, Michael; Jessen, Frank
To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects. [¹⁸F]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested. The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline. The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.
Tudor, Jennifer C; Davis, Emily J; Peixoto, Lucia; Wimmer, Mathieu E; van Tilborg, Erik; Park, Alan J; Poplawski, Shane G; Chung, Caroline W; Havekes, Robbert; Huang, Jiayan; Gatti, Evelina; Pierre, Philippe; Abel, Ted
Sleep deprivation is a public health epidemic that causes wide-ranging deleterious consequences, including impaired memory and cognition. Protein synthesis in hippocampal neurons promotes memory and cognition. The kinase complex mammalian target of rapamycin complex 1 (mTORC1) stimulates protein synthesis by phosphorylating and inhibiting the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2). We investigated the involvement of the mTORC1-4EBP2 axis in the molecular mechanisms mediating the cognitive deficits caused by sleep deprivation in mice. Using an in vivo protein translation assay, we found that loss of sleep impaired protein synthesis in the hippocampus. Five hours of sleep loss attenuated both mTORC1-mediated phosphorylation of 4EBP2 and the interaction between eukaryotic initiation factor 4E (eIF4E) and eIF4G in the hippocampi of sleep-deprived mice. Increasing the abundance of 4EBP2 in hippocampal excitatory neurons before sleep deprivation increased the abundance of phosphorylated 4EBP2, restored the amount of eIF4E-eIF4G interaction and hippocampal protein synthesis to that seen in mice that were not sleep-deprived, and prevented the hippocampus-dependent memory deficits associated with sleep loss. These findings collectively demonstrate that 4EBP2-regulated protein synthesis is a critical mediator of the memory deficits caused by sleep deprivation. Copyright © 2016, American Association for the Advancement of Science.
Hulst, H.E.; Schoonheim, M.M.; van Geest, Q.; Uitdehaag, B.M.J.; Barkhof, F.; Geurts, J.J.G.
Background: Memory impairment is frequent in multiple sclerosis (MS), but it is unclear what functional brain changes underlie this cognitive deterioration. Objective: To investigate functional hippocampal activation and connectivity, in relation to memory performance in MS. Methods: Structural and
Wheelan, Nicola; Webster, Scott P.; Kenyon, Christopher J.; Caughey, Sarah; Walker, Brian R.; Holmes, Megan C.; Seckl, Jonathan R.; Yau, Joyce L.W.
High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals. PMID:25497454
Wheelan, Nicola; Webster, Scott P; Kenyon, Christopher J; Caughey, Sarah; Walker, Brian R; Holmes, Megan C; Seckl, Jonathan R; Yau, Joyce L W
High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.
Gupta, V.K.; Scheunemann, L.; Eisenberg, T.; Mertel, S.; Bhukel, A.; Koemans, T.S.; Kramer, J.M.; Liu, K.S.; Schroeder, S.; Stunnenberg, H.G.; Sinner, F.; Magnes, C.; Pieber, T.R.; Dipt, S.; Fiala, A.; Schenck, A.; Schwaerzel, M.; Madeo, F.; Sigrist, S.J.
Age-dependent memory impairment is known to occur in several organisms, including Drosophila, mouse and human. However, the fundamental cellular mechanisms that underlie these impairments are still poorly understood, effectively hampering the development of pharmacological strategies to treat the
Full Text Available Choice blindness refers to the phenomenon that people can be easily misled about the choices they made in the recent past. The aim of this study was to explore the cognitive mechanisms underlying choice blindness. Specifically, we tested whether memory impairment may account for choice blindness. A total of N = 88 participants provided sympathy ratings on 10-point scales for 20 female faces. Subsequently, participants motivated some of their ratings. However, on three trials, they were presented with sympathy ratings that deviated from their original ratings by three full scale points. On nearly 41% of the trials, participants failed to detect (i.e., were blind the manipulation. After a short interval, participants were informed that some trials had been manipulated and were asked to recall their original ratings. Participants adopted the manipulated outcome in only 3% of the trials. Furthermore, the extent to which the original ratings were accurately remembered was not higher for detected as compared with non-detected trials. From a theoretical point of view our findings indicate that memory impairment does not fully account for blindness phenomena.
Sagana, Anna; Sauerland, Melanie; Merckelbach, Harald
Choice blindness refers to the phenomenon that people can be easily misled about the choices they made in the recent past. The aim of this study was to explore the cognitive mechanisms underlying choice blindness. Specifically, we tested whether memory impairment may account for choice blindness. A total of N = 88 participants provided sympathy ratings on 10-point scales for 20 female faces. Subsequently, participants motivated some of their ratings. However, on three trials, they were presented with sympathy ratings that deviated from their original ratings by three full scale points. On nearly 41% of the trials, participants failed to detect (i.e., were blind) the manipulation. After a short interval, participants were informed that some trials had been manipulated and were asked to recall their original ratings. Participants adopted the manipulated outcome in only 3% of the trials. Furthermore, the extent to which the original ratings were accurately remembered was not higher for detected as compared with non-detected trials. From a theoretical point of view our findings indicate that memory impairment does not fully account for blindness phenomena.
Hannula, Deborah E.; Tranel, Daniel; Allen, John S.; Kirchhoff, Brenda A.; Nickel, Allison E.; Cohen, Neal J.
Objective The objective of this study was to examine the dependence of item memory and relational memory on medial temporal lobe (MTL) structures. Patients with amnesia, who either had extensive MTL damage or damage that was relatively restricted to the hippocampus, were tested, as was a matched comparison group. Disproportionate relational memory impairments were predicted for both patient groups, and those with extensive MTL damage were also expected to have impaired item memory. Method Participants studied scenes, and were tested with interleaved two-alternative forced-choice probe trials. Probe trials were either presented immediately after the corresponding study trial (lag 1), five trials later (lag 5), or nine trials later (lag 9) and consisted of the studied scene along with a manipulated version of that scene in which one item was replaced with a different exemplar (item memory test) or was moved to a new location (relational memory test). Participants were to identify the exact match of the studied scene. Results As predicted, patients were disproportionately impaired on the test of relational memory. Item memory performance was marginally poorer among patients with extensive MTL damage, but both groups were impaired relative to matched comparison participants. Impaired performance was evident at all lags, including the shortest possible lag (lag 1). Conclusions The results are consistent with the proposed role of the hippocampus in relational memory binding and representation, even at short delays, and suggest that the hippocampus may also contribute to successful item memory when items are embedded in complex scenes. PMID:25068665
Tuscher, Jennifer J; Szinte, Julia S; Starrett, Joseph R; Krentzel, Amanda A; Fortress, Ashley M; Remage-Healey, Luke; Frick, Karyn M
The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in the dorsal hippocampus observed 30min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents. Copyright © 2016 Elsevier Inc. All rights reserved.
Klimkowicz-Mrowiec, Aleksandra; Slowik, Agnieszka; Krzywoszanski, Lukasz; Herzog-Krzywoszanska, Radosława; Szczudlik, Andrzej
Consistent evidence from human and experimental animals studies indicates that memory is organized into two relatively independent systems with different functions and brain mechanisms. The explicit memory system, dependent on the hippocampus and adjacent medial temporal lobe structures, refers to conscious knowledge acquisition and intentional recollection of previous experiences. The implicit memory system, dependent on the striatum, refers to learning of complex information without awareness or intention. The functioning of implicit memory can be observed in progressive, gradual improvement across many trials in performance on implicit learning tasks. The influence of explicit memory on implicit memory has not been precisely identified yet. According to data from some studies, explicit memory seems to exhibit no influence on implicit memory,whereas the other studies indicate that explicit memory may inhibit or facilitate implicit memory. The analysis of performance on implicit learning tasks in patients with different severity of explicit memory impairment due to Alzheimer's disease allows one to identify the potential influence of the explicit memory system on the implicit memory system. 51 patients with explicit memory impairment due to Alzheimer's disease (AD) and 36 healthy controls were tested. Explicit memory was examined by means of a battery of neuropsychological tests. Implicit habit learning was examined on probabilistic classification task (weather prediction task). Patients with moderate explicit memory impairment performed the implicit task significantly better than those with mild AD and controls. Results of our study support the hypothesis of competition between the implicit and explicit memory systems in humans.
Kamboj, Sunjeev K; Curran, H Valerie
Benzodiazepines and anticholinergic drugs have repeatedly been shown to impair episodic memory for emotionally neutral material in humans. However, their effect on memory for emotionally laden stimuli has been relatively neglected. We sought to investigate the effects of the benzodiazepine, lorazepam, and the anticholinergic, scopolamine, on incidental episodic memory for neutral and emotional components of a narrative memory task in humans. A double-blind, placebo-controlled independent group design was used with 48 healthy volunteers to examine the effects of these drugs on emotional and neutral episodic memory. As expected, the emotional memory advantage was retained for recall and recognition memory under placebo conditions. However, lorazepam and scopolamine produced anterograde recognition memory impairments on both the neutral and emotional components of the narrative, although floor effects were obtained for recall memory. Furthermore, compared with placebo, recognition memory for both central (gist) and peripheral (detail) aspects of neutral and emotional elements of the narrative was poorer after either drug. Benzodiazepine-induced GABAergic enhancement or scopolamine-induced cholinergic hypofunction results in a loss of the enhancing effect of emotional arousal on memory. Furthermore, lorazepam- and scopolamine-induced memory impairment for both gist (which is amygdala dependent) and detail raises the possibility that their effects on emotional memory do not depend only on the amygdala. We discuss the results with reference to potential clinical/forensic implications of processing emotional memories under conditions of globally impaired episodic memory.
Kim, Soyeon; Liu, Zhongxu; Glizer, Daniel; Tannock, Rosemary; Woltering, Steven
To investigate neural and behavioural correlates of visual encoding during a working memory (WM) task in young adults with and without Attention-Deficit/Hyperactivity Disorder (ADHD). A sample of 30 college students currently meeting a diagnosis of ADHD and 25 typically developing students, matched on age and gender, performed a delayed match-to-sample task with low and high memory load conditions. Dense-array electroencephalography was recorded. Specifically, the P3, an event related potential (ERP) associated with WM, was examined because of its relation with attentional allocation during WM. Task performance (accuracy, reaction time) as well as performance on other neuropsychological tasks of WM was analyzed. Neural differences were found between the groups. Specifically, the P3 amplitude was smaller in the ADHD group compared to the comparison group for both load conditions at parietal-occipital sites. Lower scores on behavioural working memory tasks were suggestive of impaired behavioural WM performance in the ADHD group. Findings from this study provide the first evidence of neural differences in the encoding stage of WM in young adults with ADHD, suggesting ineffective allocation of attentional resources involved in encoding of information in WM. These findings, reflecting alternate neural functioning of WM, may explain some of the difficulties related to WM functioning that college students with ADHD report in their every day cognitive functioning. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Optale, Gabriele; Urgesi, Cosimo; Busato, Valentina; Marin, Silvia; Piron, Lamberto; Priftis, Konstantinos; Gamberini, Luciano; Capodieci, Salvatore; Bordin, Adalberto
Memory decline is a prevalent aspect of aging but may also be the first sign of cognitive pathology. Virtual reality (VR) using immersion and interaction may provide new approaches to the treatment of memory deficits in elderly individuals. The authors implemented a VR training intervention to try to lessen cognitive decline and improve memory functions. The authors randomly assigned 36 elderly residents of a rest care facility (median age 80 years) who were impaired on the Verbal Story Recall Test either to the experimental group (EG) or the control group (CG). The EG underwent 6 months of VR memory training (VRMT) that involved auditory stimulation and VR experiences in path finding. The initial training phase lasted 3 months (3 auditory and 3 VR sessions every 2 weeks), and there was a booster training phase during the following 3 months (1 auditory and 1 VR session per week). The CG underwent equivalent face-to-face training sessions using music therapy. Both groups participated in social and creative and assisted-mobility activities. Neuropsychological and functional evaluations were performed at baseline, after the initial training phase, and after the booster training phase. The EG showed significant improvements in memory tests, especially in long-term recall with an effect size of 0.7 and in several other aspects of cognition. In contrast, the CG showed progressive decline. The authors suggest that VRMT may improve memory function in elderly adults by enhancing focused attention.
Barsegyan, Areg; Mackenzie, Scott M.; Kurose, Brian D.; McGaugh, James L.; Roozendaal, Benno
It is well established that acute administration of adrenocortical hormones enhances the consolidation of memories of emotional experiences and, concurrently, impairs working memory. These different glucocorticoid effects on these two memory functions have generally been considered to be independently regulated processes. Here we report that a glucocorticoid receptor agonist administered into the medial prefrontal cortex (mPFC) of male Sprague-Dawley rats both enhances memory consolidation and impairs working memory. Both memory effects are mediated by activation of a membrane-bound steroid receptor and depend on noradrenergic activity within the mPFC to increase levels of cAMP-dependent protein kinase. These findings provide direct evidence that glucocorticoid effects on both memory consolidation and working memory share a common neural influence within the mPFC. PMID:20810923
Tyurenkov, I N; Volotova, E V; Kurkin, D V
This work was aimed at evaluating the influence of gliatilin administration on the spatial memory in aged rats. Cognitive function and spatial memory in animals was evaluated using radial (8-beam) maze test. Errors of working spatial memory and reference memory were used as indicators of impaired cognitive function. It was found that aged (24-month) rats compared with younger (6-months) age group exhibited cognitive impairment, as manifested by deterioration of short- and long-term memory processes. Course administration of gliatilin in rats of the older age group at a dose of 100 mg/kg resulted in significant improvement of the working and reference spatial memory in aged rats.
van Geldorp, Bonnie; Heringa, Sophie M; van den Berg, Esther; Olde Rikkert, Marcel G M; Biessels, Geert Jan; Kessels, Roy P C
Recent studies indicate that in both normal and pathological aging working memory (WM) performance deteriorates, especially when associations have to be maintained. However, most studies typically do not assess the relationship between WM and episodic memory formation. In the present study, we examined WM and episodic memory formation in normal aging and in patients with early Alzheimer's disease (mild cognitive impairment, MCI; and Alzheimer's dementia, AD). In the first study, 26 young adults (mean age 29.6 years) were compared to 18 middle-aged adults (mean age 52.2 years) and 25 older adults (mean age 72.8 years). We used an associative delayed-match-to-sample WM task, which requires participants to maintain two pairs of faces and houses presented on a computer screen for short (3 s) or long (6 s) maintenance intervals. After the WM task, an unexpected subsequent associative memory task was administered (two-alternative forced choice). In the second study, 27 patients with AD and 19 patients with MCI were compared to 25 older controls, using the same paradigm as that in Experiment 1. Older adults performed worse than both middle-aged and young adults. No effect of delay was observed in the healthy adults, and pairs that were processed during long maintenance intervals were not better remembered in the subsequent memory task. In the MCI and AD patients, longer maintenance intervals hampered the task performance. Also, both patient groups performed significantly worse than controls on the episodic memory task as well as the associative WM task. Aging and AD present with a decline in WM binding, a finding that extends similar results in episodic memory. Longer delays in the WM task did not affect episodic memory formation. We conclude that WM deficits are found when WM capacity is exceeded, which may occur during associative processing.
Full Text Available BackgroundsSeveral domains of cognitive function, including learning memory and executive function, are impaired in mood disorders. Also, the relationship between disturbances of these two cognitive domains has been suggested. In line with the recent initiative to establish a standard measure of cognitive decline in bipolar disorder, the present study was conducted to (1 test the criterion-related validity and test–retest reliability of the California Verbal Learning Test (CVLT-II Japanese version, and (2 determine if type of word learning tasks (i.e., with or without a category structure affects severity of verbal memory deficits in patients with subsyndromal bipolar disorder.MethodsThirty-six patients with bipolar disorder with mild symptoms and 42 healthy volunteers participated in the study. We first compared effect sizes for memory deficits in patients among the CVLT-II, Brief Assessment of Cognition in Schizophrenia (BACS, and Hopkins Verbal Memory Tests-Revised (HVLT-R. We next evaluated the correlations between scores of the CVLT-II vs. those of the BACS and HVLT-R. Bipolar patients were re-assessed with the same (standard or alternate forms of the CVLT-II and HVLT-R 1 month later.ResultsScores on the CVLT-II 1–5 Free Recall and Long-delay Free Recall, as well as the HVLT-R Immediate Recall, but not the BACS List Learning were significantly lower for patients compared to control subjects. The effect sizes for cognitive decline due to the illness were comparable when measured by the CVLT-II and HVLT-R, ranging from 0.5 to 0.6. CVLT-II scores were significantly correlated with those of the HVLT-R and BACS. Test–retest reliability of the CVLT-II was acceptable, and no significant practice effect was observed when the alternate form was used. There was no consistent relationship between mood symptoms and performance on the CVLT-II.ConclusionThese results suggest the CVLT-II Japanese version is able to discriminate between bipolar
Sumiyoshi, Tomiki; Toyomaki, Atsuhito; Kawano, Naoko; Kitajima, Tomoko; Kusumi, Ichiro; Ozaki, Norio; Iwata, Nakao; Sueyoshi, Kazuki; Nakagome, Kazuyuki
Several domains of cognitive function, including learning memory and executive function, are impaired in mood disorders. Also, the relationship between disturbances of these two cognitive domains has been suggested. In line with the recent initiative to establish a standard measure of cognitive decline in bipolar disorder, the present study was conducted to (1) test the criterion-related validity and test-retest reliability of the California Verbal Learning Test (CVLT)-II Japanese version, and (2) determine if type of word learning tasks (i.e., with or without a category structure) affects severity of verbal memory deficits in patients with subsyndromal bipolar disorder. Thirty-six patients with bipolar disorder with mild symptoms and 42 healthy volunteers participated in the study. We first compared effect sizes for memory deficits in patients among the CVLT-II, Brief Assessment of Cognition in Schizophrenia (BACS), and Hopkins Verbal Memory Tests-Revised (HVLT-R). We next evaluated the correlations between scores of the CVLT-II vs. those of the BACS and HVLT-R. Bipolar patients were re-assessed with the same (standard) or alternate forms of the CVLT-II and HVLT-R 1 month later. Scores on the CVLT-II 1-5 Free Recall and Long-delay Free Recall, as well as the HVLT-R Immediate Recall, but not the BACS List Learning were significantly lower for patients compared to control subjects. The effect sizes for cognitive decline due to the illness were comparable when measured by the CVLT-II and HVLT-R, ranging from 0.5 to 0.6. CVLT-II scores were significantly correlated with those of the HVLT-R and BACS. Test-retest reliability of the CVLT-II was acceptable, and no significant practice effect was observed when the alternate form was used. There was no consistent relationship between mood symptoms and performance on the CVLT-II. These results suggest the CVLT-II Japanese version is able to discriminate between bipolar disorder patients and healthy controls with good
Joubert, Sven; Brambati, Simona M.; Ansado, Jennyfer; Barbeau, Emmanuel J.; Felician, Olivier; Didic, Mira; Lacombe, Jacinthe; Goldstein, Rachel; Chayer, Celine; Kergoat, Marie-Jeanne
Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to…
Conti-Ramsden, Gina; Ullman, Michael T.; Lum, Jarrad A. G.
What memory systems underlie grammar in children, and do these differ between typically developing children and children with specific language impairment (SLI)? Whilst there is substantial evidence linking certain memory deficits to the language problems in children with SLI, few studies have investigated multiple memory systems simultaneously, examining not only possible memory deficits but also memory abilities that may play a compensatory role. This study examined the extent to which proc...
Henry, Michelle; Thomas, Kevin G F; Ross, Ian L
Patients with Addison's disease frequently self-report memory and attention difficulties, even when on standard replacement therapy. However, few published studies examine, using objective measures and assessing across multiple domains, the cognitive functioning of Addison's disease patients relative to healthy controls. The primary aim of this study was to investigate whether the previously reported subjective cognitive deficits in Addison's disease are confirmed by objective measures. Conducting comprehensive neuropsychological assessments of patients with relatively rare clinical disorders, such as Addison's disease, is challenging because access to those patients is often limited, and because their medical condition might prevent extended testing sessions. Brief telephonic cognitive assessments are a useful tool in such circumstances. Hence, we administered the Brief Test of Adult Cognition by Telephone to 27 Addison's disease patients and 27 matched healthy controls. The instrument provides objective assessment of episodic memory, working memory, executive functioning, reasoning, and speed of processing. Statistical analyses confirmed that, as expected, patients performed significantly more poorly than controls on the episodic memory subtest. There were, however, no significant between-group differences on the attention, executive functioning, reasoning, and speed of processing subtests. Furthermore, patients with a longer duration of illness performed more poorly across all domains of cognition. We conclude that, for Addison's disease patients, previously reported subjective cognitive deficits are matched by objective impairment, but only in the domain of episodic memory. Future research might investigate (a) whether these memory deficits are material-specific (i.e., whether non-verbal memory is also affected), and (b) the neurobiological mechanisms underlying these deficits.
Almaguer-Melian, William; Bergado-Rosado, Jorge; Pavón-Fuentes, Nancy; Alberti-Amador, Esteban; Mercerón-Martínez, Daymara; Frey, Julietta U
Novelty processing can transform short-term into long-term memory. We propose that this memory-reinforcing effect of novelty could be explained by mechanisms outlined in the "synaptic tagging hypothesis." Initial short-term memory is sustained by a transient plasticity change at activated synapses and sets synaptic tags. These tags are later able to capture and process the plasticity-related proteins (PRPs), which are required to transform a short-term synaptic change into a long-term one. Novelty is involved in inducing the synthesis of PRPs [Moncada D, et al. (2011) Proc Natl Acad Sci USA 108:12937-12936], which are then captured by the tagged synapses, consolidating memory. In contrast to novelty, stress can impair learning, memory, and synaptic plasticity. Here, we address questions as to whether novelty-induced PRPs are able to prevent the loss of memory caused by stress and if the latter would not interact with the tag-setting process. We used water-maze (WM) training as a spatial learning paradigm to test our hypothesis. Stress was induced by a strong foot shock (FS; 5 × 1 mA, 2 s) applied 5 min after WM training. Our data show that FS reduced long-term but not short-term memory in the WM paradigm. This negative effect on memory consolidation was time- and training-dependent. Interestingly, novelty exposure prevented the stress-induced memory loss of the spatial task and increased BDNF and Arc expression. This rescuing effect was blocked by anisomycin, suggesting that WM-tagged synapses were not reset by FS and were thus able to capture the novelty-induced PRPs, re-establishing FS-impaired long-term memory.
Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina Del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F; Vieta, Eduard
Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients' psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.
Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F
Abstract Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients’ psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. PMID:28498954
Gifford, Katherine A; Liu, Dandan; Damon, Stephen M; Chapman, William G; Romano Iii, Raymond R; Samuels, Lauren R; Lu, Zengqi; Jefferson, Angela L
A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood. We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI. MCI participants were drawn from the Alzheimer's Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n = 191, 77 ± 7 years; complaint n = 206, 73 ± 8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness). Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E4 status, found that cognitive complaint related to immediate (β = -1.07, p memory performances assessed on a serial list learning task (β = -1.06, p = 0.001) but no other cognitive measures or neuroimaging markers. Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer's disease, across the cognitive aging spectrum.
Full Text Available Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs. We here investigated whether interfering with connexin43 (Cx43 HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19 into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.
Allé, Mélissa C; Manning, Liliann; Potheegadoo, Jevita; Coutelle, Romain; Danion, Jean-Marie; Berna, Fabrice
Autobiographical memory, central in human cognition and every day functioning, enables past experienced events to be remembered. A variety of disorders affecting autobiographical memory are characterized by the difficulty of retrieving specific detailed memories of past personal events. Owing to the impact of autobiographical memory impairment on patients' daily life, it is necessary to better understand these deficits and develop relevant methods to improve autobiographical memory. The primary objective of the present systematic PRISMA review was to give an overview of the first empirical evidence of the potential of wearable cameras in autobiographical memory investigation in remediating autobiographical memory impairments. The peer-reviewed literature published since 2004 on the usefulness of wearable cameras in research protocols was explored in 3 databases (PUBMED, PsycINFO, and Google Scholar). Twenty-eight published studies that used a protocol involving wearable camera, either to explore wearable camera functioning and impact on daily life, or to investigate autobiographical memory processing or remediate autobiographical memory impairment, were included. This review analyzed the potential of wearable cameras for 1) investigating autobiographical memory processes in healthy volunteers without memory impairment and in clinical populations, and 2) remediating autobiographical memory in patients with various kinds of memory disorder. Mechanisms to account for the efficacy of wearable cameras are also discussed. The review concludes by discussing certain limitations inherent to using cameras, and new research perspectives. Finally, ethical issues raised by this new technology are considered.
Herszage, Jasmine; Censor, Nitzan
The ability of the human brain to successively learn or perform two competing tasks constitutes a major challenge in daily function. Indeed, exposing the brain to two different competing memories within a short temporal offset can induce interference, resulting in deteriorated performance in at least one of the learned memories [1-4]. Although previous studies have investigated online interference and its effects on performance [5-13], whether the human brain can enable long-term prevention of future interference is unknown. To address this question, we utilized the memory reactivation-reconsolidation framework [2, 12] stemming from studies at the synaptic level [14-17], according to which reactivation of a memory enables its update. In a set of experiments, using the motor sequence learning task  we report that a unique pairing of reactivating the original memory (right hand) in synchrony with novel memory trials (left hand) prevented future interference between the two memories. Strikingly, these effects were long-term and observed a month following reactivation. Further experiments showed that preventing future interference was not due to practice per se, but rather specifically depended on a limited time window induced by reactivation of the original memory. These results suggest a mechanism according to which memory reactivation enables long-term prevention of interference, possibly by creating an updated memory trace integrating original and novel memories during the reconsolidation time window. The opportunity to induce a long-term preventive effect on memories may enable the utilization of strategies optimizing normal human learning, as well as recovery following neurological insults. Copyright © 2017 Elsevier Ltd. All rights reserved.
Alloway, Tracy Packiam; Archibald, Lisa
The authors compared 6- to 11-year-olds with developmental coordination disorder (DCD) and those with specific language impairment (SLI) on measures of memory (verbal and visuospatial short-term and working memory) and learning (reading and mathematics). Children with DCD with typical language skills were impaired in all four areas of memory…
Desmottes, Lise; Meulemans, Thierry; Maillart, Christelle
According to the Procedural Deficit Hypothesis (PDH), difficulties in the procedural memory system may contribute to the language difficulties encountered by children with Specific Language Impairment (SLI). Most studies investigating the PDH have used the sequence learning paradigm; however these studies have principally focused on initial sequence learning in a single practice session. The present study sought to extend these investigations by assessing the consolidation stage and longer-term retention of implicit sequence-specific knowledge in 42 children with or without SLI. Both groups of children completed a serial reaction time task and were tested 24h and one week after practice. Results showed that children with SLI succeeded as well as children with typical development (TD) in the early acquisition stage of the sequence learning task. However, as training blocks progressed, only TD children improved their sequence knowledge while children with SLI did not appear to evolve any more. Moreover, children with SLI showed a lack of the consolidation gains in sequence knowledge displayed by the TD children. Overall, these results were in line with the predictions of the PDH and suggest that later learning stages in procedural memory are impaired in SLI. Copyright © 2015 Elsevier Ltd. All rights reserved.
Rouleau, Isabelle; Dagenais, Emmanuelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre
Multiple sclerosis (MS) is a progressive disease of the central nervous system affecting information processing speed, episodic memory, attention, and executive functions. MS patients also often report prospective memory (PM) failures that directly impact their functional autonomy, including professional and social life. The purpose of this paper was to review the literature concerning the assessment and remediation of PM deficits in MS. The literature pertaining to PM impairment in MS was carefully reviewed using PubMed, PsyINFO, and Google Scholar, as well as cross-references from the articles published on this topic. Since PM rehabilitation in MS patients is still in its infancy, this review mainly focuses on studies that have directly assessed PM through various measures including questionnaires, standardized clinical tests, and experimental procedures. This literature review confirms the presence of PM deficits in MS patients, even in the early stages of the disease. A further need for controlled studies on PM assessment and PM interventions in patients with MS is stressed.
Kim, Ah Hyun; Chun, Hye Jeong; Lee, Seulah; Kim, Hyung Sik; Lee, Jaewon
Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is commonly used in commercial and household products, such as, computers, televisions, mobile phones, and electronic boards. TBBPA can accumulate in human body fluids, and it has been reported that TBBPA possesses endocrine disruptive activity. However, the neurotoxic effect of TBBPA on hippocampal neurogenesis has not yet been investigated. Accordingly, the present study was undertaken to evaluate the effect of TBBPA on adult hippocampal neurogenesis and cognitive function. Male C57BL/6 mice were orally administrated vehicle or TBBPA (20 mg/kg, 100 mg/kg, or 500 mg/kg daily) for two weeks. TBBPA was observed to significantly and dose-dependently reduce the survival of newly generated cells in the hippocampus but not to affect the proliferation of newly generated cells. Numbers of hippocampal BrdU and NeuN positive cells were dose-dependently reduced by TBBPA, indicating impaired neurogenesis in the hippocampus. Interestingly, glial activation without neuronal death was observed in hippocampi exposed to TBBPA. Furthermore, memory retention was found to be adversely affected by TBBPA exposure by a mechanism involving suppression of the BDNF-CREB signaling pathway. The study suggests high dose TBBPA disrupts hippocampal neurogenesis and induces associated memory deficits. Copyright © 2017 Elsevier Ltd. All rights reserved.
Zhou, Heng; Zhou, Qixin; Xu, Lin
Contextual fear memory depends on the hippocampus, but the role of unilateral hippocampus in this type of memory remains unclear. Herein, pharmacological inactivation or excitotoxic lesions were used to study the role of unilateral hippocampus in the stages of contextual fear memory. The pharmacological experiments revealed that compared with the control groups, unilateral hippocampal blockade did not impair 1-day recent memory following learning, whereas bilateral hippocampal blockade significantly impaired this memory. The lesion experiments showed that compared with the control groups, the formed contextual fear memory was retained for 7 days and that 30-day remote memory was markedly reduced in unilateral hippocampal lesion groups. These results indicate that an intact bilateral hippocampus is required for the formation of remote memory and that unilateral hippocampus is sufficient for recent contextual fear memory.
Mowrey, Wenzhu B; Lipton, Richard B; Katz, Mindy J; Ramratan, Wendy S; Loewenstein, David A; Zimmerman, Molly E; Buschke, Herman
The Memory Binding Test (MBT), previously known as Memory Capacity Test, has demonstrated discriminative validity for distinguishing persons with amnestic mild cognitive impairment (aMCI) and dementia from cognitively normal elderly. We aimed to assess the predictive validity of the MBT for incident aMCI. In a longitudinal, community-based study of adults aged 70+, we administered the MBT to 246 cognitively normal elderly adults at baseline and followed them annually. Based on previous work, a subtle reduction in memory binding at baseline was defined by a Total Items in the Paired (TIP) condition score of ≤22 on the MBT. Cox proportional hazards models were used to assess the predictive validity of the MBT for incident aMCI accounting for the effects of covariates. The hazard ratio of incident aMCI was also assessed for different prediction time windows ranging from 4 to 7 years of follow-up, separately. Among 246 controls who were cognitively normal at baseline, 48 developed incident aMCI during follow-up. A baseline MBT reduction was associated with an increased risk for developing incident aMCI (hazard ratio (HR) = 2.44, 95% confidence interval: 1.30-4.56, p = 0.005). When varying the prediction window from 4-7 years, the MBT reduction remained significant for predicting incident aMCI (HR range: 2.33-3.12, p: 0.0007-0.04). Persons with poor performance on the MBT are at significantly greater risk for developing incident aMCI. High hazard ratios up to seven years of follow-up suggest that the MBT is sensitive to early disease.
A. I. Tröster
Full Text Available Memory dysfunction is a frequent concomitant of Parkinson's disease (PD. Historically, two classes of hypotheses, focusing on different cognitive mechanisms, have been advanced to explain this memory impairment: one postulating retrieval deficits (common to several neurodegenerative disorders involving the basal ganglia, and the other postulating frontally mediated executive deficits as fundamental to memory impairment. After outlining empirical support for the retrieval deficit hypothesis, research on the more recent “frontal executive deficit hypothesis” is reviewed, and major challenges to this hypothesis are identified. It is concluded that the frontal executive deficit hypothesis cannot adequately account for all memory impairments in PD, and that a more parsimonious theoretical account might invoke a distinction between prospective and declarative memory impairments. It is suggested that there may be three subgroups of PD patients: one demonstrating prospective memory dysfunction only, one with declarative memory dysfunction only, and one with both prospective and declarative memory dysfunction. Consequently, PD might provide a useful model within which to investigate the relationship between prospective and declarative memory.
Jackson, David A; Michael, Trevin; Vieira de Abreu, Adriana; Agrawal, Rahul; Bortolato, Marco; Fisher, Simon J
People with insulin-treated diabetes are uniquely at risk for severe hypoglycemia-induced brain damage. Since calcium influx may mediate brain damage, we tested the hypothesis that the calcium channel blocker, verapamil, would significantly reduce brain damage and cognitive impairment caused by severe hypoglycemia. Ten-week-old Sprague-Dawley rats were randomly assigned to one of three treatments; 1) control hyperinsulinemic (200 mU.kg -1 min -1 ) euglycemic (80-100mg/dl) clamps (n=14), 2) hyperinsulinemic hypoglycemic (10-15mg/dl) clamps (n=16), or 3) hyperinsulinemic hypoglycemic clamps followed by a single treatment with verapamil (20mg/kg) (n=11). As compared to euglycemic controls, hypoglycemia markedly increased dead/dying neurons in the hippocampus and cortex, by 16-fold and 14-fold, respectively. Verapamil treatment strikingly decreased hypoglycemia-induced hippocampal and cortical damage, by 87% and 94%, respectively. Morris Water Maze probe trial results demonstrated that hypoglycemia induced a retention, but not encoding, memory deficit (noted by both abolished target quadrant preference and reduced target quadrant time). Verapamil treatment significantly rescued spatial memory as noted by restoration of target quadrant preference and target quadrant time. In summary, a one-time treatment with verapamil following severe hypoglycemia prevented neural damage and memory impairment caused by severe hypoglycemia. For people with insulin treated diabetes, verapamil may be a useful drug to prevent hypoglycemia-induced brain damage. © 2018 by the American Diabetes Association.
Full Text Available The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments.
Schuchardt, Kirsten; Bockmann, Ann-Katrin; Bornemann, Galina; Maehler, Claudia
Purpose: On the basis of Baddeley's working memory model (1986), we examined working memory functioning in children with learning disorders with and without specific language impairment (SLI). We pursued the question whether children with learning disorders exhibit similar working memory deficits as children with additional SLI. Method: In…
Wardlaw, Sarah M.; Phan, Trongha X.; Saraf, Amit; Chen, Xuanmao; Storm, Daniel R.
Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1[superscript -/-] mice, which are arrhythmic…
Full Text Available Memory impairments in Alzheimer’s disease (AD occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia; PR is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.
Full Text Available Abstract Background Betaine (glycine betaine or trimethylglycine plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well known. In this study, we investigated the effects of betaine on lipopolysaccharide (LPS-induced memory impairment and on mRNA expression levels of proinflammatory molecules, glial markers, and GABA transporter 2 (GAT2, a betaine/GABA transporter. Methods Mice were continuously treated with betaine for 13 days starting 1 day before they were injected with LPS, or received subacute or acute administration of betaine shortly before or after LPS injection. Then, their memory function was evaluated using Y-maze and novel object recognition tests 7 and 10-12 days after LPS injection (30 μg/mouse, i.c.v., respectively. In addition, mRNA expression levels in hippocampus were measured by real-time RT-PCR at different time points. Results Repeated administration of betaine (0.163 mmol/kg, s.c. prevented LPS-induced memory impairment. GAT2 mRNA levels were significantly increased in hippocampus 24 hr after LPS injection, and administration of betaine blocked this increase. However, betaine did not affect LPS-induced increases in levels of mRNA related to inflammatory responses. Both subacute administration (1 hr before, and 1 and 24 hr after LPS injection and acute administration (1 hr after LPS injection of betaine also prevented LPS-induced memory impairment in the Y-maze test. Conclusions These data suggest that betaine has protective effects against LPS-induced memory impairment and that prevention of LPS-induced changes in GAT2 mRNA expression is crucial to this ameliorating effect.
Gifford, Katherine A.; Liu, Dandan; Damon, Stephen M.; Chapman, William G.; Romano, Raymond R.; Samuels, Lauren R.; Lu, Zengqi; Jefferson, Angela L.
Background A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood. Objective We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI. Method MCI participants were drawn from the Alzheimer’s Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n=191, 77±7 years; complaint n=206, 73±8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness). Results Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E-4 status, found that cognitive complaint related to immediate (β=−1.07, pmemory performances assessed on a serial list learning task (β=−1.06, p=0.001) but no other cognitive measures or neuroimaging markers. Conclusions Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer’s disease, across the cognitive aging spectrum. PMID:25281602
Stark, Craig E L; Squire, Larry R
In a prior study of continuous recognition performance, data were reported in support of the hypothesis that the hippocampus is not needed to remember the individual components of a stimulus but is important for remembering associations between its components (Kroll et al. 1996. J Mem Lang 35:176-196). Patients with left hippocampal damage were able to endorse recently encountered words and to reject novel words, as well as disyllabic words in which one of the syllables had been previously encountered. However, they failed to reject words in which both syllables had been encountered independently in different words. We present data from five experiments designed to examine this finding in more detail. In each experiment, five patients with bilateral hippocampal damage and eight controls were tested using the same protocol as Kroll et al. (1996). On each trial, a two-component stimulus was presented. Stimuli could be entirely novel, novel with one previously encountered (repeated) component, novel but with both components repeated, or a true repetition. The first experiment was a direct replication using the same disyllabic words as Kroll et al. (1996). The second experiment used pseudo-words, constructed of two monosyllabic words (e.g., jambark). The third experiment used the same pairs of monosyllabic words, but presented separately on the screen to encourage participants to treat each component independently. The fourth experiment used pairs of objects, and the fifth experiment used face-house pairs. In all five experiments, patients with hippocampal damage exhibited impaired recognition memory. The impairment extended across all trial types with no evidence that hippocampal damage selectively (or disproportionately) impaired the associative or conjunctive component of memory. We discuss our findings in the light of the work by Kroll et al. (1996) and other recent neuropsychological, electrophysiological, and neuroimaging studies of hippocampal function and
Yan-Jiong Chen; Teng Chen; Yan-Ling Liu; Qing Zhong; Yan-Fang Yu; Hong-Liang Su; Haroldo A.Toque; Yong-Hui Dang; Feng Chen; Ming Xu
[Objective] The purpose of this study was to investigate the effect of methamphetamine (MA) on spatial learning and memory and the role of tetrahydropalmatine (THP) in MA-induced changes in these phenomena in mice.[Methods]Male C57BL/6 mice were randomly divided into eight groups,according to different doses of MA,different doses of THP,treatment with both MA and THP,and saline controls.Spatial learning and memory were assessed using the Morris water maze.Western blot was used to detect the expression of extracellular signal-regulated protein kinase (ERK) in the mouse prefrontal cortex (PFC) and hippocampus.[Results] Repeated MA treatment significantly increased the escape latency in the learning phase and decreased the number of platform site crossings in the memory-test phase.ERK1/2 expression was decreased in the PFC but not in the hippocampus of the MA-treated mice.Repeated THP treatment alone did not affect the escape latency,the number of platform site crossings or the total ERK1/2 expression in the brain.Statistically significantly shorter escape latencies and more platform site crossings occurred in MA+THP-trcatcd mice than in MA-treated mice.[Conclusion]Repeated MA administration impairs spatial learning and memory in mice,and its co-administration with THP prevents this impairment,which is probably attributable to changed ERK1/2 expression in the PFC.This study contributes to uncovering the mechanism underlying MA abuse,and to exploring potential therapies.
Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1−/− mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippoca...
Raio, Candace M.; Brignoni-Perez, Edith; Goldman, Rachel; Phelps, Elizabeth A.
Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays an important role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent research in rodents found that exposure to stress led to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress responses, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, one day later participants in the stress group (n = 27) demonstrated significantly less
Sekeres, Melanie J.; Bonasia, Kyra; St-Laurent, Marie; Pishdadian, Sara; Winocur, Gordon; Grady, Cheryl; Moscovitch, Morris
Episodic memories undergo qualitative changes with time, but little is known about how different aspects of memory are affected. Different types of information in a memory, such as perceptual detail, and central themes, may be lost at different rates. In patients with medial temporal lobe damage, memory for perceptual details is severely impaired,…
Chen, Zi-Xiang; Xue, Li; Liang, Chun-Yu; Wang, Li-Li; Mei, Wei; Zhang, Qiang; Zhao, Hu
Faking memory impairment means normal people complain lots of memory problems without organic damage in forensic assessments. Using alternative forced-choice paradigm, containing digital or autobiographical information, previous neuroimaging studies have indicated that faking memory impairment could cause the activation in the prefrontal and parietal regions, and might involve a fronto-parietal-subcortical circuit. However, it is still unclear whether different memory types have influence on faking or not. Since different memory types, such as long-term memory (LTM) and short-term memory (STM), were found supported by different brain areas, we hypothesized that feigned STM or LTM impairment had distinct neural activation mapping. Besides that, some common neural correlates may act as the general characteristic of feigned memory impairment. To verify this hypothesis, the functional magnetic resonance imaging (fMRI) combined with an alternative word forced-choice paradigm were used in this study. A total of 10 right-handed participants, in this study, had to perform both STW and LTM tasks respectively under answering correctly, answering randomly and feigned memory impairment conditions. Our results indicated that the activation of the left superior frontal gyrus and the left medial frontal gyrus was associated with feigned LTM impairment, whereas the left superior frontal gyrus, the left precuneus and the right anterior cingulate cortex (ACC) were highly activated while feigning STM impairment. Furthermore, an overlapping was found in the left superior frontal gyrus, and it suggested that the activity of the left superior frontal gyrus might be acting as a specific marker of feigned memory impairment. Copyright © 2015. Published by Elsevier Ltd.
De Belder, Maya; Santens, Patrick; Sieben, Anne; Fias, Wim
Working memory (WM) problems are commonly observed in Alzheimer's disease (AD), but the affected mechanisms leading to impaired WM are still insufficiently understood. The ability to efficiently process serial order in WM has been demonstrated to be fundamental to fluent daily life functioning. The decreased capability to mentally process serial position in WM has been put forward as the underlying explanation for generally compromised WM performance. Determine which mechanisms, such as order processing, are responsible for deficient WM functioning in AD. A group of AD patients (n = 32) and their partners (n = 25), assigned to the control group, were submitted to an extensive battery of neuropsychological and experimental tasks, assessing general cognitive state and functioning of several aspects related to serial order WM. The results revealed an impaired ability to bind item information to serial position within WM in AD patients compared to controls. It was additionally observed that AD patients experienced specific difficulties with directing spatial attention when searching for item information stored in WM. The processing of serial order and the allocation of attentional resources are both disrupted, explaining the generally reduced WM functioning in AD patients. Further studies should now clarify whether this observation could explain disease-related problems for other cognitive functions such as verbal expression, auditory comprehension, or planning.
Parra-Díaz, P; García-Casares, N
Given that surgical treatment of refractory mesial temporal lobe epilepsy may cause memory impairment, determining which patients are eligible for surgery is essential. However, there is little agreement on which presurgical memory assessment methods are best able to predict memory outcome after surgery and identify those patients with a greater risk of surgery-induced memory decline. We conducted a systematic literature review to determine which presurgical memory assessment methods best predict memory outcome. The literature search of PubMed gathered articles published between January 2005 and December 2015 addressing pre- and postsurgical memory assessment in mesial temporal lobe epilepsy patients by means of neuropsychological testing, functional MRI, and other neuroimaging techniques. We obtained 178 articles, 31 of which were included in our review. Most of the studies used neuropsychological tests and fMRI; these methods are considered to have the greatest predictive ability for memory impairment. Other less frequently used techniques included the Wada test and FDG-PET. Current evidence supports performing a presurgical assessment of memory function using both neuropsychological tests and functional MRI to predict memory outcome after surgery. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Chen, Xing-jie; Wang, Ya; Wang, Yi; Yang, Tian-xiao; Zou, Lai-quan; Huang, Jia; Li, Feng-hua; Chen, An-tao; Wang, Wei-hong; Zheng, Han-feng; Cheung, Eric F C; Shum, David H K; Chan, Raymond C K
Prospective memory (PM) refers to the ability to remember to carry out intended actions after a delay. PM impairments are common in schizophrenia patients and are thought to be related to their prefrontal cortex dysfunction; however, this has not yet been examined directly in the research literature. The current study aimed to examine abnormalities in brain activation during PM task performance in schizophrenia patients. Twenty-two schizophrenia patients and 25 matched healthy controls were scanned in a 3-T MRI machine while performing a PM task. The results showed that compared to the healthy controls, schizophrenia patients performed significantly worse on the PM task. Furthermore, they exhibited decreased brain activation in frontal cortex including the right superior frontal gyri (Brodmann area 10), and other related brain areas like the anterior cingulate gyrus, parietal and temporal cortex, including precuneus, and some subcortext, including parahippocampal gyrus and putamen. These findings confirm the involvement and importance of the prefrontal cortex in PM and show evidence of hypofrontality in schizophrenia patients while performing a PM task. PsycINFO Database Record (c) 2016 APA, all rights reserved.
Vasconcelos, Andrea R; Yshii, Lidia M; Viel, Tania A; Buck, Hudson S; Mattson, Mark P; Scavone, Cristoforo; Kawamoto, Elisa M
Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels. Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.
Goldston, David B.; Walrath, Christine M.; McKeon, Richard; Puddy, Richard W.; Lubell, Keri M.; Potter, Lloyd B.; Rodi, Michael S.
In response to calls for greater efforts to reduce youth suicide, the Garrett Lee Smith (GLS) Memorial Act has provided funding for 68 state, territory, and tribal community grants, and 74 college campus grants for suicide prevention efforts. Suicide prevention activities supported by GLS grantees have included education, training programs…
Liao, Tien You; Tzeng, Wen-Yu; Wu, Hsin-Hua; Cherng, Chianfang G; Wang, Ching-Yi; Hu, Sherry S-J; Yu, Lung
Since brain proteins such as protein kinase C (PKC), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) are involved in the establishment and maintenance of psychostimulant memory, we sought to determine if systemic treatment with rottlerin, a natural compound affecting all these proteins, may modulate stimulant-supported memory. Stimulant-induced conditioned place preference (CPP) was used in modeling stimulant-supported memory. Three cocaine (10 mg/kg; COC) or three methamphetamine (1 mg/kg; MA) conditioning trials reliably established the drug-induced CPP in male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 h prior to the first COC or first MA conditioning trial prevented the establishment of CPP. Following the establishment of the COC- or MA-induced CPP, saline conditioning trial was used to extinguish the CPP. Rottlerin (5 mg/kg, intra-peritoneal (i.p.)) administered 20 h prior to the first saline conditioning trial diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Rottlerin (5 mg/kg, i.p.) produced a fast-onset and long-lasting increase in hippocampal BDNF levels. However, treatment with a BDNF tropomyosin receptor kinase B (TrkB) receptor antagonist, K252a (5 μg/kg), did not affect rottlerin's suppressing effect on COC-induced CPP and treatment with 7,8-dihydroxyflavone (10 mg/kg x 6, 7,8-DHF), a selective TrkB agonist, prior to each conditioning trial did not affect COC-induced CPP. These results suggest that systemic rottlerin treatment may impair the formation of COC- and MA-supported memory. Importantly, such a treatment may advance our understanding of the underlying mechanism through which extinction training resulted in the "forgetting" of the COC- and MA-supported memory.
Colombo, Michael; D'Amato, Michael R.; Rodman, Hillary R.; Gross, Charles G.
Monkeys that were trained to perform auditory and visual short-term memory tasks (delayed matching-to-sample) received lesions of the auditory association cortex in the superior temporal gyrus. Although visual memory was completely unaffected by the lesions, auditory memory was severely impaired. Despite this impairment, all monkeys could discriminate sounds closer in frequency than those used in the auditory memory task. This result suggests that the superior temporal cortex plays a role in auditory processing and retention similar to the role the inferior temporal cortex plays in visual processing and retention.
Abdullahi, Payman Rasise; Eskandarian, Sharaf; Ghanbari, Ali; Rashidy-Pour, Ali
There is increasing evidence that oxytocin is involved in learning and memory process. This study investigated the effects of blockade of oxytocin receptors using the selective oxytocin receptor antagonist atosiban (ATO) on contextual fear memory consolidation and reconsolidation in male rats. Post-training injections of different doses of ATO (1, 10, 100 or 1000 µg/kg) impaired the 48 h retention performance in a dose-dependent manner. The same doses of ATO following memory reactivation did not impair subsequent expression of contextual fear memories which formed under low or high shock intensities and tested 24 h or one week following memory reactivation. Also, no effect was found when ATO was administrated in the absence of memory reactivation. Our finding is the first report that indicates endogenous oxytocin released during training play an important role in the consolidation, but not reconsolidation of contextual fear memory in rats. Copyright © 2018. Published by Elsevier B.V.
Mattfeld, Aaron T.; Whitfield-Gabrieli, Susan; Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Fried, Ronna; Gabrieli, John D.E.
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. PMID:26900567
Aaron T. Mattfeld
Full Text Available 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.
Mattfeld, Aaron T; Whitfield-Gabrieli, Susan; Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Fried, Ronna; Gabrieli, John D E
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.
Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence
Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9-10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
Wang, Fang; Song, Yan-Feng; Yin, Jie; Liu, Zi-Hua; Mo, Xiao-Dan; Wang, De-Gui; Gao, Li-Ping; Jing, Yu-Hong
Estrogen influences memory formation and insulin sensitivity. Meanwhile, glucose utilization directly affects learning and memory, which are modulated by insulin signals. Therefore, this study investigated whether or not the effect of estrogen on memory is associated with the regulatory effect of this hormone on glucose metabolism. The relative expression of estrogen receptor β (ERβ) and glucose transporter type 4 (GLUT4) in the hippocampus of rats were evaluated by western blot. Insulin level was assessed by ELISA and quantitative RT-PCR, and spatial memory was tested by the Morris water maze. Glucose utilization in the hippocampus was measured by 2-NBDG uptake analysis. Results showed that ovariectomy impaired the spatial memory of rats. These impairments are similar as the female rats treated with the ERβ antagonist tamoxifen (TAM). Estrogen blockade by ovariectomy or TAM treatment obviously decreased glucose utilization. This phenomenon was accompanied by decreased insulin level and GLUT4 expression in the hippocampus. The female rats were neutralized with hippocampal insulin with insulin antibody, which also impaired memory and local glucose consumption. These results indicated that estrogen blockade impaired the spatial memory of the female rats. The mechanisms by which estrogen blockade impaired memory partially contributed to the decline in hippocampal insulin signals, which diminished glucose consumption.
Full Text Available Background and Aim: Reading is the most important human need for learning. In normal-hearing people working memory is a predictor of reading comprehension. In this study the relationship between working memory and reading comprehension skills was studied in hearing-impaired children, and then compared with the normal-hearing group.Methods: This was a descriptive-analytic study. The working memory and reading comprehension skills of 18 (8 male, 10 female sever hearing-impaired children in year five of exceptional schools were compared by means of a reading test with 18 hearing children as control group. The subjects in the control group were of the same gender and educational level of the sample group.Results: The children with hearing loss performed similarly to the normal-hearing children in tasks related to auditory-verbal memory of sounds (reverse, visual-verbal memory of letters, and visual-verbal memory of pictures. However, they showed lower levels of performance in reading comprehension (p<0.001. Moreover, no significant relationship was observed between working memory and reading comprehension skills.Conclusion: Findings indicated that children with hearing loss have a significant impairment in the reading comprehension skill. Impairment in language knowledge and vocabulary may be the main cause of poor reading comprehension in these children. In hearing-impaired children working memory is not a strong predictor of reading comprehension.
Objective Previously, four months of a blueberry-enriched (BB) antioxidant diet prevented impaired object recognition memory in aged rats. Experiment 1 determined whether one and two-month BB diets would have a similar effect and whether the benefits would disappear promptly after terminating the d...
Weon, Jin Bae; Jung, Youn Sik; Ma, Choong Je
Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer's disease.
Jo, Seonmi; Yarishkin, Oleg; Hwang, Yu Jin; Chun, Ye Eun; Park, Mijeong; Woo, Dong Ho; Bae, Jin Young; Kim, Taekeun; Lee, Jaekwang; Chun, Heejung; Park, Hyun Jung; Lee, Da Yong; Hong, Jinpyo; Kim, Hye Yun; Oh, Soo-Jin; Park, Seung Ju; Lee, Hyo; Yoon, Bo-Eun; Kim, YoungSoo; Jeong, Yong; Shim, Insop; Bae, Yong Chul; Cho, Jeiwon; Kowall, Neil W; Ryu, Hoon; Hwang, Eunmi; Kim, Daesoo; Lee, C Justin
In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.
McEntee, William J.; Mair, Robert G.
The concentration of the primary brain metabolite of norepinephrine is diminished in the lumbar spinal fluid of patients with Korsakoff's syndrome. The extent of its reduction is correlated with measures of memory impairment. (BB)
Clausen, Bettina; Schachtman, Todd R.; Mark, Louise T.
to examine the effects on memory: cross-maze and object recognition task. Systemic administration reduced spatial exploration in cross-maze as well as in an open field test, and also reduced object exploration. Spatial (hippocampus-dependent) short-term memory was inhibited in the cross-maze and non......-spatial short-term object retention was also impaired. In contrast to these systemic effects, bilateral injections of SCH23390 into the prelimbic cortices altered neither spatial nor object exploration, but did inhibit short-term memory in both cross-maze and object recognition task. Therefore, the inhibiting......D1-receptor antagonism is known to impair rodent memory but also inhibits spontaneous exploration of stimuli to be remembered. Hypo-exploration could contribute to impaired memory by influencing event processing. In order to explore this effect, the D1 receptor antagonist, SCH23390...
Kozlov, Michail D; Hughes, Robert W; Jones, Dylan M
Several studies have suggested that short-term memory is generally improved by chewing gum. However, we report the first studies to show that chewing gum impairs short-term memory for both item order and item identity. Experiment 1 showed that chewing gum reduces serial recall of letter lists. Experiment 2 indicated that chewing does not simply disrupt vocal-articulatory planning required for order retention: Chewing equally impairs a matched task that required retention of list item identity. Experiment 3 demonstrated that manual tapping produces a similar pattern of impairment to that of chewing gum. These results clearly qualify the assertion that chewing gum improves short-term memory. They also pose a problem for short-term memory theories asserting that forgetting is based on domain-specific interference given that chewing does not interfere with verbal memory any more than tapping. It is suggested that tapping and chewing reduce the general capacity to process sequences.
LAWLOR, BRIAN; COEN, ROBERT; O'MARA, SHANE MICHAEL
PUBLISHED Background: Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impa...
Irish, Muireann; Lawlor, Brian A; Coen, Robert F; O'Mara, Shane M
Abstract Background Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of di...
Kozlov, Michail D; Hughes, Robert W; Jones, Dylan M
Several studies have suggested that short-term memory is generally improved by chewing gum. However, we report the first studies to show that chewing gum impairs short-term memory for both item order and item identity. Experiment 1 showed that chewing gum reduces serial recall of letter lists. Experiment 2 indicated that chewing does not simply disrupt vocal-articulatory planning required for order retention: Chewing equally impairs a matched task that required retention of list item identity...
Chen, Gui-Hai; Xia, Lan; Wang, Fang; Li, Xue-Wei; Jiao, Chuan-An
Memory impairment is a frequent complaint in insomniacs; however, it is not consistently demonstrated. It is unknown whether memory impairment in insomniacs involves neuroendocrine dysfunction. The participants in this study were selected from the clinical setting and included 21 patients with chronic insomnia disorder (CID), 25 patients with insomnia and comorbid depressive disorder (CDD), and 20 control participants without insomnia. We evaluated spatial working and reference memory, object working and reference memory, and object recognition memory using the Nine Box Maze Test. We also evaluated serum neuroendocrine hormone levels. Compared to the controls, the CID patients made significantly more errors in spatial working and object recognition memory (p memory types (p memory (r = .534, p = .033) and negatively correlated with the errors in object recognition memory (r = -.659, p = .006) in the CID patients. The results suggest that the CID patients had selective memory impairment, which may be mediated by increased cortisol levels. © 2016 Society for Psychophysiological Research.
Yu, Dafu; Zhou, Heng; Zou, Lin; Jiang, Yong; Wu, Xiaoqun; Jiang, Lizhu; Zhou, Qixin; Yang, Yuexiong; Xu, Lin; Mao, Rongrong
Thyroid hormone (TH) receptors are highly distributed in the hippocampus, which plays a vital role in memory processes. However, how THs are involved in the different stages of memory process is little known. Herein, we used hippocampus dependent contextual fear conditioning to address the effects of hippocampal THs on the different stages of fear memory. First, we found that a single systemic levothyroxine (LT 4 ) administration increased the level of free triiodothyronine (FT 3 ) and free tetraiodothyroxine (FT 4 ) not only in serum but also in hippocampus. In addition, a single systemic LT 4 administration immediately after fear conditioning significantly impaired fear memory. These results indicated the important role of hippocampal THs in fear memory process. To further confirm the effects of hippocampal THs on the different stages of fear memory, LT 4 (0.4 μg/μl, 1 μl/side) was injected bilaterally into hippocampus. Rats given LT 4 into hippocampus before training or tests had no effect on the acquisition or retrieval of fear memory, however rats given LT 4 into hippocampus either immediately or 2 h after training showed being significantly impaired fear memory, which demonstrated LT 4 administration into hippocampus impairs the consolidation but has no effect on the acquisition and retrieval of fear memory. Furthermore, hippocampal injection of LT 4 did not affect rats' locomotor activity, thigmotaxis and THs level in prefrontal cortex (PFC) and serum. These findings may have important implications for understanding mechanisms underlying contribution of THs to memory disorders.
Busquets-Garcia, Arnau; Gomis-González, Maria; Srivastava, Raj Kamal; Cutando, Laura; Ortega-Alvaro, Antonio; Ruehle, Sabine; Remmers, Floortje; Bindila, Laura; Bellocchio, Luigi; Marsicano, Giovanni; Lutz, Beat; Maldonado, Rafael; Ozaita, Andrés
Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine β-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH(+) cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders.
Walsh-Messinger, Julie; Ramirez, Paul Michael; Wong, Philip; Antonius, Daniel; Aujero, Nicole; McMahon, Kevin; Opler, Lewis A; Malaspina, Dolores
Emotion plays a critical role in cognition and goal-directed behavior via complex interconnections between the emotional and motivational systems. It has been hypothesized that the impairment in goal-directed behavior widely noted in schizophrenia may result from defects in the interaction between the neural (ventral) emotional system and (rostral) cortical processes. The present study examined the impact of emotion on attention and memory in schizophrenia. Twenty-five individuals with schizophrenia related psychosis and 25 healthy control subjects were administered a computerized task in which they were asked to search for target images during a Rapid Serial Visual Presentation of pictures. Target stimuli were either positive or negative, or neutral images presented at either 200ms or 700ms lag. Additionally, a visual hedonic task was used to assess differences between the schizophrenia group and controls on ratings of valence and arousal from the picture stimuli. Compared to controls, individuals with schizophrenia detected fewer emotional images under both the 200ms and 700ms lag conditions. Multivariate analyses showed that the schizophrenia group also detected fewer positive images under the 700ms lag condition and fewer negative images under the 200ms lag condition. Individuals with schizophrenia reported higher pleasantness and unpleasantness ratings than controls in response to neutral stimuli, while controls reported higher arousal ratings for neutral and positive stimuli compared to the schizophrenia group. These results highlight dysfunction in the neural modulation of emotion, attention, and cortical processing in schizophrenia, adding to the growing but mixed body of literature on emotion processing in the disorder. Published by Elsevier B.V.
Aydin, Emel; Hritcu, Lucian; Dogan, Gulden; Hayta, Sukru; Bagci, Eyup
In the present study, we identified the effects of inhaled Pimpinella peregrina essential oil (1 and 3 %, for 21 continuous days) on scopolamine-induced memory impairment, anxiety, and depression in laboratory rats. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by means of the elevated plus-maze and forced swimming tests. The scopolamine alone-treated rats exhibited the following: decrease of the spontaneous alternation percentage in Y-maze test, increase of the number of working and reference memory errors in radial arm-maze test, along with decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. Inhalation of the P. peregrina essential oil significantly improved memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. Our results suggest that the P. peregrina essential oil inhalation ameliorates scopolamine-induced memory impairment, anxiety, and depression. Moreover, studies on the P. peregrina essential oil may open a new therapeutic window for the prevention of neurological abnormalities closely related to Alzheimer's disease.
Full Text Available Background and Aim: Specific language impairment (SLI, one variety of developmental language disorder, has attracted much interest in recent decades. Much research has been conducted to discover why some children have a specific language impairment. So far, research has failed to identify a reason for this linguistic deficiency. Some researchers believe language disorder causes defects in phonological working memory and affects auditory processing speed. Therefore, this study reviews the results of research investigating these two factors in children with specific language impairment.Recent Findings: Studies have shown that children with specific language impairment face constraints in phonological working memory capacity. Memory deficit is one possible cause of linguistic disorder in children with specific language impairment. However, in these children, disorder in information processing speed is observed, especially regarding the auditory aspect.Conclusion: Much more research is required to adequately explain the relationship between phonological working memory and auditory processing speed with language. However, given the role of phonological working memory and auditory processing speed in language acquisition, a focus should be placed on phonological working memory capacity and auditory processing speed in the assessment and treatment of children with a specific language impairment.
Ha, Tae Hyon; Kim, Ji Sun; Chang, Jae Seung; Oh, Sung Hee; Her, Ju Young; Cho, Hyun Sang; Park, Tae Sung; Shin, Soon Young; Ha, Kyooseob
To compare verbal and visual memory performances between patients with bipolar I disorder (BD I) and patients with bipolar II disorder (BD II) and to determine whether memory deficits were mediated by impaired organizational strategies. Performances on the Korean-California Verbal Learning Test (K-CVLT) and the Rey-Osterrieth Complex Figure Test (ROCF) in 37 patients with BD I, 46 patients with BD II and 42 healthy subjects were compared. Mediating effects of impaired organization strategies on poor delayed recall was tested by comparing direct and mediated models using multiple regression analysis. Both patients groups recalled fewer words and figure components and showed lower Semantic Clustering compared to controls. Verbal memory impairment was partly mediated by difficulties in Semantic Clustering in both subtypes, whereas the mediating effect of Organization deficit on the visual memory impairment was present only in BD I. In all mediated models, group differences in delayed recall remained significant. Our findings suggest that memory impairment may be one of the fundamental cognitive deficits in bipolar disorders and that executive dysfunctions can exert an additional influence on memory impairments.
K. M. Volkers
Full Text Available Background. Physical performances and cognition are positively related in cognitively healthy people. The aim of this study was to examine whether physical performances are related to specific cognitive functioning in older people with mild to severe cognitive impairment. Methods. This cross-sectional study included 134 people with a mild to severe cognitive impairment (mean age 82 years. Multiple linear regression was performed, after controlling for covariates and the level of global cognition, with the performances on mobility, strength, aerobic fitness, and balance as predictors and working memory and episodic memory as dependent variables. Results. The full models explain 49–57% of the variance in working memory and 40–43% of episodic memory. Strength, aerobic fitness, and balance are significantly associated with working memory, explaining 3–7% of its variance, irrespective of the severity of the cognitive impairment. Physical performance is not related to episodic memory in older people with mild to severe cognitive impairment. Conclusions. Physical performance is associated with working memory in older people with cognitive impairment. Future studies should investigate whether physical exercise for increased physical performance can improve cognitive functioning. This trial is registered with ClinicalTrials.gov NTR1482.
Moreau, Noémie; Viallet, François; Champagne-Lavau, Maud
Theory of mind (TOM) refers to the ability to infer one's own and other's mental states. Growing evidence highlighted the presence of impairment on the most complex TOM tasks in Alzheimer disease (AD). However, how TOM deficit is related to other cognitive dysfunctions and more specifically to episodic memory impairment - the prominent feature of this disease - is still under debate. Recent neuroanatomical findings have shown that remembering past events and inferring others' states of mind share the same cerebral network suggesting the two abilities share a common process .This paper proposes to review emergent evidence of TOM impairment in AD patients and to discuss the evidence of a relationship between TOM and episodic memory. We will discuss about AD patients' deficit in TOM being possibly related to their difficulties in recollecting memories of past social interactions. Copyright © 2013 Elsevier B.V. All rights reserved.
Lull, R.B.; Cetin, Y.; Bushman, B.J.
Research suggests that exposure to media containing violence and sex impairs attention and memory. Learning a foreign language is one domain in which attention and memory are critical. Two experiments addressed whether exposure to media containing violence and sex interferes with foreign-language
Spanoudis, George C.; Natsopoulos, Demetrios
Memory and language operate in synergy. Recent literature stresses the importance of memory functioning in interpreting language deficits. Two groups of 50 children each, ages 8-12 were studied. The first group included children with specific language impairment, while the participants in the second group were typically developing children. The…
Marton, Klara; Schwartz, Richard G.
This study examined the interaction between working memory and language comprehension in children with specific language impairment (SLI), focusing on the function of the central executive component and its interaction with the phonological loop (A. D. Baddeley, 1986) in complex working memory tasks. Thirteen children with SLI and 13 age-matched…
Kessels, R.P.C.; Meulenbroek, O.V.; Fernandez, G.S.E.; Olde Rikkert, M.G.M.
Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically
Kessels, R.P.C.; Meulenbroek, O.V.; Fernandez, G.S.E.; Olde Rikkert, M.G.M.
Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically
Tranel, Daniel; Adolphs, Ralph; Buchanan, Tony W.
Stress can enhance or impair memory performance. Both cortisol release and sympathetic nervous system responses have been implicated in these differential effects. Here we investigated how memory retrieval might be affected by stress-induced cortisol release, independently of sympathetic nervous system stress responses. Thirty-two healthy…
Montgomery, James W.; Evans, Julia L.
Purpose: This study investigated the association of 2 mechanisms of working memory (phonological short-term memory [PSTM], attentional resource capacity/allocation) with the sentence comprehension of school-age children with specific language impairment (SLI) and 2 groups of control children. Method: Twenty-four children with SLI, 18 age-matched…
Rindal, Eric J.; DeFranco, Rachel M.; Rich, Patrick R.; Zaragoza, Maria S.
In a recent PNAS article, Chan and LaPaglia (2013) provided arguments and evidence to support the claim that reactivating a witnessed memory (by taking a test) renders the memory labile and susceptible to impairment by subsequent misinformation. In the current article, we argue that Chan and LaPaglia's (2013) findings are open to alternative…
Chan, Ming-Huan [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Institute of Neuroscience, National Changchi University, Taipei, Taiwan (China); Chung, Shiang-Sheng [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Department of Pharmacy, Yuli Veterans Hospital, Hualien, Taiwan (China); Stoker, Astrid K.; Markou, Athina [Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (United States); Chen, Hwei-Hsien, E-mail: email@example.com [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China)
Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene
Chan, Ming-Huan; Chung, Shiang-Sheng; Stoker, Astrid K.; Markou, Athina; Chen, Hwei-Hsien
Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene
Herrlinger, Kelli A; Nieman, Kristin M; Sanoshy, Kristen D; Fonseca, Brenda A; Lasrado, Joanne A; Schild, Arianne L; Maki, Kevin C; Wesnes, Keith A; Ceddia, Michael A
The purpose of this study was to investigate the effects of supplementation with a spearmint (Mentha spicata L.) extract, high in polyphenols including rosmarinic acid, on cognitive performance, sleep, and mood in individuals with age-associated memory impairment (AAMI). Subjects with AAMI (N = 90; 67% female; age = 59.4 ± 0.6 years) were randomly assigned (n = 30/group) to consume 900, 600, or 0 mg/day (two capsules, once daily) spearmint extract for 90 days, in this double-blind, placebo-controlled trial. Assessments were completed for cognition (days 0, 45, and 90), sleep (days 0 and 90), and mood (days 0 and 90) by using the Cognitive Drug Research (CDR) System ™ , Leeds Sleep Evaluation Questionnaire (LSEQ), and Profile of Mood States (POMS ™ ), respectively. Quality of working memory and spatial working memory accuracy improved after supplementation with 900 mg/day spearmint extract by 15% (p = 0.0469) and 9% (p = 0.0456), respectively, versus placebo. Subjects consuming 900 mg/day spearmint extract reported improvement in their ability to fall asleep, relative to subjects consuming placebo (p = 0.0046). Overall treatment effects were evident for vigor-activity (p = 0.0399), total mood disturbance (p = 0.0374), and alertness and behavior following wakefulness (p = 0.0415), with trends observed for improvements after spearmint supplementation relative to placebo. These results suggest that the distinct spearmint extract may be a beneficial nutritional intervention for cognitive health in older subjects with AAMI.
Chaby, Lauren E.; Cavigelli, Sonia A.; Hirrlinger, Amy M.; Lim, James; Warg, Kendall M.; Braithwaite, Victoria A.
HIGHLIGHTS This study tested the effects of adolescent-stress on adult learning and memory. Adolescent-stressed rats had enhanced reversal learning compared to unstressed rats. Adolescent-stress exposure made working memory more vulnerable to disturbance. Adolescent-stress did not affect adult associative learning or reference memory. Exposure to acute stress can cause a myriad of cognitive impairments, but whether negative experiences continue to hinder individual as they ag...
Yamazaki, Daisuke; Horiuchi, Junjiro; Saitoe, Minoru
Age-related memory impairment （AMI） is an important phenotype of brain aging. Understandingthe molecular mechanisms underlying AMI is important not only from a scientific viewpoint but also for thedevelopment of therapeutics that may eventually lead to developing drugs to combat memory loss. AMI has beengenerally considered to be an overall or nonspecifi c decay of memory processes that results from dysfunction ofneural networks. However, extensive behavioral genetic characterization of AMI w...
Bennett, IJ; Golob, EJ; Parker, ES; Starr, A
Amnestic mild cognitive impairment (MCI) is a selective episodic memory deficit that often indicates early Alzheimer's disease. Episodic memory function in MCI is typically defined by deficits in free recall, but can also be tested using recognition procedures. To assess both recall and recognition in MCI, MCI (n = 21) and older comparison (n = 30) groups completed the USC-Repeatable Episodic Memory Test. Subjects memorized two verbally presented 15-item lists. One list was used for three fre...
Lu, Zhong-Lin; Neuse, James; Madigan, Stephen; Dosher, Barbara Anne
In a previous clinical report, unusually fast decay of iconic memory was obtained from a subject who later developed Alzheimer's disease. By using the partial-report paradigm, iconic memory (a form of visual sensory memory) in a group of observers with mild cognitive impairments (MCI) was characterized and compared with that of young college-age adults and older controls. Relatively long stimulus exposures were used for all three groups to ensure that older observers could perceive the stimul...
Full Text Available Collapsin response mediator protein 1 (CRMP1 is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1-/- mice exhibited behavioral abnormalities related to schizophrenia. The crmp1-/- mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1-/- mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1-/- mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1-/- mouse may model endophenotypes present in this neuropsychiatric disorder.
Rothwell, Cailin M; Lukowiak, Ken D
Stressor-induced memory enhancement has previously been shown to involve DNA methylation in the mollusc Lymnaea stagnalis . Specifically, injection of the DNA methylation inhibitor 5-AZA one hour before exposure to a memory-enhancing stressor obstructs memory augmentation. However, the duration of the influence of 5-AZA on this memory enhancement has not yet been examined. In this study, 2 memory-enhancing stressors (a thermal stress and exposure to the scent of a predator) were used to examine whether injection of the DNA methylation inhibitor 5-AZA 24 hours before stress exposure would still impair memory enhancement. Indeed, it was observed that memory is still obstructed when 5-AZA is injected 24 hours before exposure to either of these stressors in Lymnaea . Understanding that 5-AZA still effectively impairs memory enhancement after a period of 24 hours is valuable because it indicates that experimental manipulations do not need to be made within one hour after the injection of this DNA methylation inhibitor and can instead be made within one day (i.e. 24 hours). These results will allow for a future examination of the possible involvement of DNA methylation in memory enhancement related to longer-term stressors or environmental changes. This study further elucidates the involvement of epigenetic changes in memory enhancement in Lymnaea , providing insight into the process of memory formation in this mollusc.
Wong, Ling M.; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.
Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with…
Malstadt, Nadine; Hasselhorn, Marcus; Lehmann, Martin
This study examined supraspan free recall in children with and without spelling impairment. A repeated free recall task involving overt rehearsal and three computer-based adaptive working memory tasks were administered to 54 eight-year-old children. Children without spelling impairments tended to recall more items than did those children with…
A. V. Ivanov
Full Text Available Epilepsy is the disease resulting in impaired cognitive function. The paper deals with the use of nootropics against the background of an anticonvulsant effect. Results of experiments on rats showed that investigated nootropics piracetam (500 mg/kg, citicoline (500 mg/kg, memantine (10 mg/kg in combination with sodium valproate (80 mg/kg improve memory and do not change its anticonvulsant effect.
Atsak, Piray; Guenzel, Friederike M; Kantar-Gok, Deniz; Zalachoras, Ioannis; Yargicoglu, Piraye; Meijer, Onno C; Quirarte, Gina L; Wolf, Oliver T; Schwabe, Lars; Roozendaal, Benno
Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1mg/kg), the corticosterone-synthesis inhibitor metyrapone (35mg/kg) or were left untreated 1h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress
Rzezak, Patrícia; Lima, Ellen Marise; Gargaro, Ana Carolina; Coimbra, Erica; de Vincentiis, Silvia; Velasco, Tonicarlo Rodrigues; Leite, João Pereira; Busatto, Geraldo F; Valente, Kette D
Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints. Copyright © 2017 Elsevier Inc. All rights reserved.
Santa, Tomofumi; Kirino, Yutaka; Watanabe, Satoshi; Shirahata, Takaaki; Tsunoda, Makoto
The terrestrial slug "Limax" is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC…
Erfanparast, Amir; Tamaddonfard, Esmaeal; Nemati, Shaghayegh
In the present study, we investigated the effects of microinjection of vitamin B 12 into the hippocampus on the orofacial pain and memory impairments induced by scopolamine and orofacial pain. In ketamine-xylazine anesthetized rats, the right and left sides of the dorsal hippocampus (CA1) were implanted with two guide cannulas. Orofacial pain was induced by subcutaneous injection of formalin (1.5%, 50μl) into the right vibrissa pad, and the durations of face rubbing were recorded at 3-min blocks for 45min. Morris water maze (MWM) was used for evaluation of learning and memory. Finally, locomotor activity was assessed using an open-field test. Vitamin B 12 attenuated both phases of formalin-induced orofacial pain. Prior administration of naloxone and naloxonazine, but not naltrindole and nor-binaltorphimine, prevented this effect. Vitamin B 12 and physostigmine decreased latency time as well as traveled distance in Morris water maze. In addition, these chemicals improved scopolamine-induced memory impairment. The memory impairment induced by orofacial pain was improved by vitamin B 12 and physostigmine used alone. Naloxone prevented, whereas physostigmine enhanced the memory improving effect of vitamin B 12 in the pain-induced memory impairment. All the above-mentioned chemicals did not alter locomotor activity. The results of the present study showed that at the level of the dorsal hippocampus, vitamin B 12 modulated orofacial pain through a mu-opioid receptor mechanism. In addition, vitamin B 12 contributed to hippocampal cholinergic system in processing of memory. Moreover, cholinergic and opioid systems may be involved in improving effect of vitamin B 12 on pain-induced memory impairment. Copyright © 2016 Elsevier Inc. All rights reserved.
Irish, Muireann; Lawlor, Brian A; Coen, Robert F; O'Mara, Shane M
Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.
Lawlor Brian A
Full Text Available Abstract Background Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD and is also a defining feature of amnestic Mild Cognitive Impairment (MCI, which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory, associative memory (face-name pairings, spatial memory (route learning and recall, and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. Results The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months, 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. Conclusions As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.
Abstract Background Decline in episodic memory is one of the hallmark features of Alzheimer\\'s disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient\\'s daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants\\' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. Results The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. Conclusions As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.
Full Text Available The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-α and IL-1β in the hippocampus tissue. In addition, the TNF-α synthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-α is critically involved in the paclitaxel-induced impairment of learning and memory function.
Costa, Alberto; Monaco, Marco; Zabberoni, Silvia; Peppe, Antonella; Perri, Roberta; Fadda, Lucia; Iannarelli, Francesca; Caltagirone, Carlo; Carlesimo, Giovanni A.
The hypothesis has been advanced that memory disorders in individuals with Parkinson’s disease (PD) are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI) are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD), and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (pcued recall (p>0.10) task, and they performed better than aMCINPD subjects on both recall measures (p0.10) but it was significantly higher than that of the aMCINPD sample (precall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042). Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning. PMID:24465977
Full Text Available The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn—a brain region critical for olfactory memory formation—causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism.
Drago, Ilaria; Davis, Ronald L
The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn)-a brain region critical for olfactory memory formation-causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Kaddah, F A; Shoeib, R M; Mahmoud, H E
Children with Specific Language Impairment (SLI) may have some kind of memory disorder that could increase their linguistic impairment. This study assessed the short-term memory skills in Arabic speaking children with either Expressive Language Impairment (ELI) or Receptive/Expressive Language Impairment (R/ELI) in comparison to controls in order to estimate the nature and extent of any specific deficits in these children that could explain the different prognostic results of language intervention. Eighteen children were included in each group. Receptive, expressive and total language quotients were calculated using the Arabic language test. Assessment of auditory and visual short-term memory was done using the Arabic version of the Illinois Test of Psycholinguistic Abilities. Both groups of SLI performed significantly lower linguistic abilities and poorer auditory and visual short-term memory in comparison to normal children. The R/ELI group presented an inferior performance than the ELI group in all measured parameters. Strong association was found between most tasks of auditory and visual short-term memory and linguistic abilities. The results of this study highlighted a specific degree of deficit of auditory and visual short-term memories in both groups of SLI. These deficits were more prominent in R/ELI group. Moreover, the strong association between the different auditory and visual short-term memories and language abilities in children with SLI must be taken into account when planning an intervention program for these children.
Zhou, Baozhu; Li, Maoxing; Cao, Xinyuan; Zhang, Quanlong; Liu, Yantong; Ma, Qiang; Qiu, Yan; Luan, Fei; Wang, Xianmin
Exposure to hypobaric hypoxia causes oxidative stress, neuronal degeneration and apoptosis that leads to memory impairment. Though oxidative stress contributes to neuronal degeneration and apoptosis in hypobaric hypoxia, the ability for phenylethanoid glycosides of Pedicularis muscicola Maxim (PhGs) to reverse high altitude memory impairment has not been studied. Rats were supplemented with PhGs orally for a week. After the fourth day of drug administration, rats were exposed to a 7500 m altitude simulation in a specially designed animal decompression chamber for 3 days. Spatial memory was assessed by the 8-arm radial maze test before and after exposure to hypobaric hypoxia. Histological assessment of neuronal degeneration was performed by hematoxylin-eosin (HE) staining. Changes in oxidative stress markers and changes in the expression of the apoptotic marker, caspase-3, were assessed in the hippocampus. Our results demonstrated that after exposure to hypobaric hypoxia, PhGs ameliorated high altitude memory impairment, as shown by the decreased values obtained for reference memory error (RME), working memory error (WME), and total error (TE). Meanwhile, administration of PhGs decreased hippocampal reactive oxygen species levels and consequent lipid peroxidation by elevating reduced glutathione levels and enhancing the free radical scavenging enzyme system. There was also a decrease in the number of pyknotic neurons and a reduction in caspase-3 expression in the hippocampus. These findings suggest that PhGs may be used therapeutically to ameliorate high altitude memory impairment. Copyright © 2016 Elsevier Inc. All rights reserved.
Li, Xinjian; Yu, Feng; Guo, Aike
Sleep is crucial to memory consolidation in humans and other animals; however, the effect of insufficient sleep on subsequent learning and memory remains largely elusive. Learning and memory after 1-day sleep deprivation (slpD) was evaluated using Pavlovian olfactory conditioning in Drosophila, and locomotor activity was measured using the Drosophila Activity Monitoring System in a 12:12 light-dark cycle. We found that slpD specifically impaired 1-h memory in wild type Canton-S flies, and this effect could persist for at least 2 h. However, alternative stresses (heat stress, oxidative stress, starvation, and rotation stress) did not result in a similar effect and left the flies' memory intact. Mechanistic studies demonstrated that flies with either silenced transmission of the mushroom body (MB) during slpD or down-regulated cAMP levels in the MB demonstrated no slpD-induced 1-h memory impairment. We found that slpD specifically impaired 1-h memory in Drosophila, and either silencing of MB transmission during slpD or down-regulation of the cAMP level in the MB protected the flies from slpD-induced impairment.
Stephanie E Tanninen
Full Text Available Memory in trace eyeblink conditioning is mediated by an inter-connected network that involves the hippocampus (HPC, several neocortical regions, and the cerebellum. This network reorganizes after learning as the center of the network shifts from the HPC to the medial prefrontal cortex (mPFC. Despite the network reorganization, the lateral entorhinal cortex (LEC plays a stable role in expressing recently acquired HPC-dependent memory as well as remotely acquired mPFC-dependent memory. Entorhinal involvement in recent memory expression may be attributed to its previously proposed interactions with the HPC. In contrast, it remains unknown how the LEC participates in memory expression after the network disengages from the HPC. The present study tested the possibility that the LEC and mPFC functionally interact during remote memory expression by examining the impact of pharmacological inactivation of the LEC in one hemisphere and the mPFC in the contralateral hemisphere on memory expression in rats. Memory expression one day and one month after learning was significantly impaired after LEC-mPFC inactivation; however, the degree of impairment was comparable to that after unilateral LEC inactivation. Unilateral mPFC inactivation had no effect on recent or remote memory expression. These results suggest that the integrity of the LEC in both hemispheres is necessary for memory expression. Functional interactions between the LEC and mPFC should therefore be tested with an alternative design.
Daal, J.G.H.L. van; Verhoeven, L.T.W.; Leeuwe, J.F.J. van; Balkom, L.J.M. van
In the present study, the relations of various aspects of working memory to various aspects of language problems in a clinical sample of 97 Dutch speaking 5-year-old children with severe language problems were studied. The working memory and language abilities of the children were examined using an
Barense, M.D.; Groen, I.I.A.; Lee, A.C.H.; Yeung, L.K.; Brady, S.M.; Gregory, M.; Kapur, N.; Bussey, T.J.; Saksida, L.M.; Henson, R.N.A.
Memory and perception have long been considered separate cognitive processes, and amnesia resulting from medial temporal lobe (MTL) damage is thought to reflect damage to a dedicated memory system. Recent work has questioned these views, suggesting that amnesia can result from impoverished
Zuniga, Krystle E; Mackenzie, Michael J; Kramer, Arthur; McAuley, Edward
The relationship between subjective memory impairment (SMI), future cognitive decline, and negative health status provides an opportunity for interventions to reduce memory complaints in high-risk groups. This study aimed to examine the relationship between SMI and indicators of well-being in older adults enrolled in an exercise trial. Additionally, the study examined whether two different modes of exercise training, aerobic walking and non-aerobic flexibility, toning, and balance, differentially influenced subjective memory across the trial. Community-dwelling older adults (n = 179, mean age = 66.4 years) were randomly assigned to a walking or flexibility, toning, and balance group for 12 months. Subjective memory, happiness, perceived stress, and symptom reporting were measured at baseline, 6 months, and 12 months. A main effect of subjective memory indicated that individuals with the fewest memory complaints had lower perceived stress (P happiness levels (P memory complaints in high-risk groups. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.
Kessels, Roy P C; Meulenbroek, Olga; Fernández, Guillén; Olde Rikkert, Marcel G M
Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically aging older adults and 15 amnestic MCI patients as to their working-memory capacities for object-location information and potential differential effects of memory load and additional context cues. An age-related deficit in visuospatial working-memory maintenance was found that became more pronounced with increasing task demands. The MCI group additionally showed reduced maintenance of bound information, i.e., object-location associations, again especially at elevated memory load. No effects of contextual cueing were found. The current findings indicate that working memory should be considered when screening patients for suspected MCI and monitoring its progression.
Jacobs, Joshua; Miller, Jonathan; Lee, Sang Ah; Coffey, Tom; Watrous, Andrew J; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn; Gross, Robert E; Sheth, Sameer A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Kahana, Michael J; Rizzuto, Daniel S
Deep brain stimulation (DBS) has shown promise for treating a range of brain disorders and neurological conditions. One recent study showed that DBS in the entorhinal region improved the accuracy of human spatial memory. Based on this line of work, we performed a series of experiments to more fully characterize the effects of DBS in the medial temporal lobe on human memory. Neurosurgical patients with implanted electrodes performed spatial and verbal-episodic memory tasks. During the encoding periods of both tasks, subjects received electrical stimulation at 50 Hz. In contrast to earlier work, electrical stimulation impaired memory performance significantly in both spatial and verbal tasks. Stimulation in both the entorhinal region and hippocampus caused decreased memory performance. These findings indicate that the entorhinal region and hippocampus are causally involved in human memory and suggest that refined methods are needed to use DBS in these regions to improve memory. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Seo, Eun Hyun; Choo, I L Han
Although amnestic mild cognitive impairment (aMCI) could have various biological characteristics, little attention has been given to the nature of episodic memory decline in aMCI with pathophysiologies other than Alzheimer's disease (AD), i.e., aMCI with low beta-amyloid (Aβ) burden. This study aimed to identify the functional neural basis of episodic memory impairment in aMCI with Aβ burden negative (aMCI-Aβ-) and to compare these results with aMCI with Aβ burden positive (aMCI-Aβ+). Individuals with aMCI (n = 498) were selected from the Alzheimer's Disease Neuroimaging Initiative database. Based on the mean florbetapir standard uptake value ratio, participants were classified as aMCI-Aβ- or aMCI-Aβ+. Correlations between memory scores and regional cerebral glucose metabolism (rCMglc) were analyzed separately for the two subgroups using a multiple regression model. For aMCI-Aβ-, significant positive correlations between memory and rCMglc were found in the bilateral claustrum, right thalamus, left anterior cingulate cortex, left insula, and right posterior cingulate. For aMCI-Aβ+, significant positive correlations between memory and rCMglc were found in the temporoparietal areas. These correlation patterns remained unchanged when clinical severity was added as a covariate Our findings indicate that memory impairment in aMCI-Aβ- is related to multimodal integrative processing and the attentional control system, whereas memory impairment in aMCI-Aβ+ is related to the typical brain memory systems and AD signature. These results suggest that although the two subgroups are clinically in the same category as aMCI, the memory impairment process depends on completely different functional brain regions according to their Aβ burden level.
Kliegel, Matthias; Altgassen, Mareike; Hering, Alexandra; Rose, Nathan S
The present review discusses the current state of research on the clinical neuropsychology of prospective memory in Parkinson's disease. To do so the paper is divided in two sections. In the first section, we briefly outline key features of the (partly implicit) rationale underlying the available literature on the clinical neuropsychology of prospective memory. Here, we present a conceptual model that guides our approach to the clinical neuropsychology of prospective memory in general and to the effects of Parkinson's disease on prospective memory in particular. In the second section, we use this model to guide our review of the available literature and suggest some open issues and future directions motivated by previous findings and the proposed conceptual model. The review suggests that certain phases of the prospective memory process (intention formation und initiation) are particularly impaired by Parkinson's disease. In addition, it is argued that prospective memory may be preserved when tasks involve specific features (e.g., focal cues) that reduce the need for strategic monitoring processes. In terms of suggestions for future directions, it is noted that intervention studies are needed which target the specific phases of the prospective memory process that are impaired in Parkinson's disease, such as planning interventions. Moreover, it is proposed that prospective memory deficits in Parkinson's disease should be explored in the context of a general impairment in the ability to form an intention and plan or coordinate an appropriate series of actions. Copyright © 2011 Elsevier Ltd. All rights reserved.
Ji, Zhi-Hong; Xu, Zhong-Qi; Zhao, Hong; Yu, Xin-Yu
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory decline and cognitive impairment. Amyloid beta (Aβ) has been proposed as the causative role for the pathogenesis of AD. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. Daucosterol palmitate (DSP), a plant steroid with anti-glutamate excitotoxicity effect, was isolated from the anti-aging traditional Chinese medicinal herb Alpinia oxyphylla Miq. in our previous study. Based on the anti-glutamate excitotoxicity effect of DSP, in this study we investigated potential benefit and mechanism of DSP in ameliorating learning and memory impairment in AD model rats. Results from this study showed that DSP administration effectively ameliorated Aβ-induced learning and memory impairment in rats, markedly inhibited Aβ-induced hippocampal ROS production, effectively prevented Aβ-induced hippocampal neuronal damage and significantly restored hippocampal synaptophysin expression level. This study suggests that DSP may be a potential candidate for development as a therapeutic agent for AD cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.
Seidman, Larry J; Meyer, Eric C; Giuliano, Anthony J; Breiter, Hans C; Goldstein, Jill M; Kremen, William S; Thermenos, Heidi W; Toomey, Rosemary; Stone, William S; Tsuang, Ming T; Faraone, Stephen V
The search for predictors of schizophrenia has accelerated with a growing focus on early intervention and prevention of psychotic illness. Studying nonpsychotic relatives of individuals with schizophrenia enables identification of markers of vulnerability for the illness independent of confounds associated with psychosis. The goal of these studies was to develop new auditory continuous performance tests (ACPTs) and evaluate their effects in individuals with schizophrenia and their relatives. We carried out two studies of auditory vigilance with tasks involving working memory (WM) and interference control with increasing levels of cognitive load to discern the information-processing vulnerabilities in a sample of schizophrenia patients, and two samples of nonpsychotic relatives of individuals with schizophrenia and controls. Study 1 assessed adults (mean age = 41), and Study 2 assessed teenagers and young adults age 13-25 (M = 19). Patients with schizophrenia were impaired on all five versions of the ACPTs, whereas relatives were impaired only on WM tasks, particularly the two interference tasks that maximize cognitive load. Across all groups, the interference tasks were more difficult to perform than the other tasks. Schizophrenia patients performed worse than relatives, who performed worse than controls. For patients, the effect sizes were large (Cohen's d = 1.5), whereas for relatives they were moderate (d = ~0.40-0.50). There was no age by group interaction in the relatives-control comparison except for participants schizophrenia.
Javitt, D C; Strous, R D; Grochowski, S; Ritter, W; Cowan, N
Working memory is the type of memory that allows one to hold information in mind while working on a task or problem. The present study investigated attention-independent auditory sensory ("echoic") memory in 18 schizophrenic participants and 17 controls. Schizophrenic participants showed impaired delayed tone matching performance in comparison with controls. However, when groups were matched for performance at 1 s by varying the difficulty of the task across groups, schizophrenic participants showed normal retention of information as reflected in normal tone matching performance. These findings demonstrate that schizophrenic may be in the sensitivity of the system rather than the duration for which memory traces were retained.
Full Text Available Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days of either saline or PCP (10 mg/kg: (1 a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2 brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2-3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2-3 of the prelimbic cortex of the PFC.
Welbat, Jariya Umka; Sangrich, Preeyanuch; Sirichoat, Apiwat; Chaisawang, Pornthip; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanun; Wigmore, Peter
Valproic acid (VPA), a commonly used antiepileptic drug, has been reported to cause cognitive impairments in patients. In a previous study, using a rodent model, we showed that VPA treatment impaired cognition which was associated with a reduction in the cell proliferation required for hippocampal neurogenesis. The antidepressant fluoxetine has been shown to increase hippocampal neurogenesis and to reverse the memory deficits found in a number of pathological conditions. In the present study we investigated the protective effects of fluoxetine treatment against the impairments in memory and hippocampal cell proliferation produced by VPA. Male Sprague Dawley rats received daily treatment with fluoxetine (10mg/kg) by oral gavage for 21days. Some rats were co-administered with VPA (300mg/kg, twice daily i.p. injections) for 14days from day 8 to day 21 of the fluoxetine treatment. Spatial memory was tested using the novel object location (NOL) test. The number of proliferating cells present in the sub granular zone of the dentate gyrus was quantified using Ki67 immunohistochemistry at the end of the experiment. Levels of the receptor Notch1, the neurotrophic factor BDNF and the neural differentiation marker DCX were determined by Western blotting. VPA-treated rats showed memory deficits, a decrease in the number of proliferating cells in the sub granular zone and decreases in the levels of Notch1 and BDNF but not DCX compared to control animals. These changes in behavior, cell proliferation and Notch1 and BDNF were prevented in animals which had received both VPA and fluoxetine. Rats receiving fluoxetine alone did not show a significant difference in the number of proliferating cells or behavior compared to controls. These results demonstrated that the spatial memory deficits and reduction of cell proliferation produced by VPA can be ameliorated by the simultaneous administration of the antidepressant fluoxetine. Crown Copyright Â© 2016. Published by Elsevier B
Ruchel, Jader B; Braun, Josiane B S; Adefegha, Stephen A; Guedes Manzoni, Alessandra; Abdalla, Fátima H; de Oliveira, Juliana S; Trelles, Kelly; Signor, Cristiane; Lopes, Sônia T A; da Silva, Cássia B; Castilhos, Lívia G; Rubin, Maribel A; Leal, Daniela B R
Hyperlipidemia is a risk factor for the development of cognitive dysfunction and atherosclerosis. Natural compounds have recently received special attention in relation to the treatment of disease due to their low cost and wide margin of safety. Thus, the aim of this study was to determine the possible preventive effect of guarana powder (Paullinia cupana) on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative standard. Acute hyperlipidemia was induced with intraperitoneal injections of 500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were separated to assess acetylcholinesterase activity. Our results revealed that guarana powder was able to reduce the levels of TC and LDL-C in a manner similar to simvastatin. Guarana powder also partially reduced the liver damage caused by hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. Guarana powder may therefore be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Kinsella, Glynda J; Ames, David; Storey, Elsdon; Ong, Ben; Pike, Kerryn E; Saling, Michael M; Clare, Linda; Mullaly, Elizabeth; Rand, Elizabeth
Governments are promoting the importance of maintaining cognitive health into older age to minimize risk of cognitive decline and dementia. Older people with amnestic mild cognitive impairment (aMCI) are particularly vulnerable to memory challenges in daily activities and are seeking ways to maintain independent living. To evaluate the effectiveness of memory groups for improving memory strategies and memory ability of older people, especially those with aMCI. 113 healthy older adults (HOA) and 106 adults with aMCI were randomized to a six-week memory group or a waitlist control condition. Outcome was evaluated through knowledge and use of memory strategies, memory ability (self-report and neuropsychological tests), and wellbeing. Assessments included a six-month follow-up. Using intention to treat analyses, there were intervention effects for HOA and aMCI groups in strategy knowledge (HOA: η2= 0.20; aMCI: η2= 0.06), strategy use (HOA: η2= 0.18; aMCI: η2= 0.08), and wellbeing (HOA: η2= 0.11; aMCI: η2= 0.05). There were also intervention effects in the HOA group, but not the aMCI group, in self-reported memory ability (η2= 0.06) and prospective memory tests (η2= 0.02). By six-month follow-up, gains were found on most HOA outcomes. In the aMCI group gains were found in strategy use, and by this stage, gains in prospective memory were also found. Memory groups can engage older people in techniques for maintaining cognitive health and improve memory performance, but more modest benefits are seen for older adults with aMCI.
Bernardi, M M; Macrini, D J; Teodorov, E; Bonamin, L V; Dalboni, L C; Coelho, C P; Chaves-Kirsten, G P; Florio, J C; Queiroz-Hazarbassanov, N; Bondan, E F; Kirsten, T B
Prenatal undernutrition impairs copulatory behavior and increases the tendency to become obese/overweight, which also reduces sexual behavior. Re-feeding rats prenatally undernourished with a normocaloric diet can restore their physiological conditions and copulatory behavior. Thus, the present study investigated whether a hypercaloric diet that is administered in rats during the juvenile period prevents sexual impairments that are caused by maternal food restriction and the tendency to become overweight/obese. Female rats were prenatally fed a 40% restricted diet from gestational day 2 to 18. The pups received a hypercaloric diet from postnatal day (PND) 23 to PND65 (food restricted hypercaloric [FRH] group) or laboratory chow (food restricted control [FRC] group). Pups from non-food-restricted dams received laboratory chow during the entire experiment (non-food-restricted [NFR] group). During the juvenile period and adulthood, body weight gain was evaluated weekly. The day of balanopreputial separation, sexual behavior, sexual organ weight, hypodermal adiposity, striatal dopamine and serotonin, serum testosterone, and tumor necrosis factor α (TNF-α) were evaluated. The FRH group exhibited an increase in body weight on PND58 and PND65. The FRC group exhibited an increase in the latency to the first mount and intromission and an increase in serum TNF-α levels but a reduction of dopaminergic activity. The hypercaloric diet reversed all of these effects but increased adiposity. We concluded that the hypercaloric diet administered during the juvenile period attenuated reproductive impairments that were induced by maternal food restriction through increases in the energy expenditure but not the tendency to become overweight/obese. Copyright © 2017 Elsevier Inc. All rights reserved.
Wang, Gang; Chen, Ling; Pan, Xiaoyu; Chen, Jiechun; Wang, Liqun; Wang, Weijie; Cheng, Ruochuan; Wu, Fan; Feng, Xiaoqing; Yu, Yingcong; Zhang, Han-Ting; O'Donnell, James M; Xu, Ying
Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Aβ) are known to involve cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Activation of cAMP and/or cGMP activities can improve memory performance and decrease the neuroinflammation and apoptosis. However, it remains unknown whether the memory enhancing effect of resveratrol on AD associated cognitive disorders is related to the inhibition of phosphodiesterase 4 (PDE4) subtypes and subsequent increases in intracellular cAMP and/or cGMP activities. This study investigated the effect of resveratrol on Aβ1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Aβ1-42 into bilateral CA1 subregions displayed learning and memory impairment, as evidenced by reduced memory acquisition and retrieval in the water maze and retention in the passive avoidance tasks; it was also significant that neuroinflammatory and pro-apoptotic factors were increased in Aβ1-42-treated mice. Aβ1-42-treated mice also increased in PDE4A, 4B and 4D expression, and decreased in PKA level. However, PKA inhibitor H89, but not PKG inhibitor KT5823, prevented resveratrol's effects on these parameters. Resveratrol also reversed Aβ1-42-induced decreases in phosphorylated cAMP response-element binding protein (pCREB), brain derived neurotrophic factor (BDNF) and anti-apoptotic factor BCl-2 expression, which were reversed by H89. These findings suggest that resveratrol reversing Aβ-induced learning and memory disorder may involve the regulation of neuronal inflammation and apoptosis via PDE4 subtypes related cAMP-CREB-BDNF signaling.
Olver, James S; Pinney, Myra; Maruff, Paul; Norman, Trevor R
Few studies have investigated the effect of an acute psychosocial stress paradigm on impaired attention and working memory in humans. Further, the duration of any stress-related cognitive impairment remains unclear. The aim of this study was to examine the effect of an acute psychosocial stress paradigm, the Trier Social Stress, on cognitive function in healthy volunteers. Twenty-three healthy male and female subjects were exposed to an acute psychosocial stress task. Physiological measures (salivary cortisol, heart rate and blood pressure) and subjective stress ratings were measured at baseline, in anticipation of stress, immediately post-stress and after a period of rest. A neuropsychological test battery including spatial working memory and verbal memory was administered at each time point. Acute psychosocial stress produced significant increases in cardiovascular and subjective measures in the anticipatory and post-stress period, which recovered to baseline after rest. Salivary cortisol steadily declined over the testing period. Acute psychosocial stress impaired delayed verbal recall, attention and spatial working memory. Attention remained impaired, and delayed verbal recall continued to decline after rest. Acute psychosocial stress is associated with an impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in attention and memory. Copyright © 2014 John Wiley & Sons, Ltd.
Full Text Available We previously reported that Fructus mume (F. mume extract shows protective effects on memory impairments and anti-inflammatory effects induced by chronic cerebral hypoperfusion. Neurodegeneration of basal cholinergic neurons is also observed in the brain with chronic cerebral hypoperfusion. Therefore, the present study was conducted to examine whether F. mume extracts enhance cognitive function via the action of cholinergic neuron using a scopolamine-induced animal model of memory impairments. F. mume (50, 100, or 200 mg/kg was administered to C57BL/6 mice for 14 days (days 1–14 and memory impairment was induced by scopolamine (1 mg/kg, a muscarinic receptor antagonist for 7 days (days 8–14. Spatial memory was assessed using Morris water maze and hippocampal level of acetylcholinesterase (AChE and choline acetyltransferase (ChAT was examined by ELISA and immunoblotting. Mice that received scopolamine alone showed impairments in acquisition and retention in Morris water maze task and increased activity of AChE in the hippocampus. Mice that received F. mume and scopolamine showed no scopolamine-induced memory impairment and increased activity of AChE. In addition, treatments of F. mume increased ChAT expression in the hippocampus. These results indicated that F. mume might enhance cognitive function via action of cholinergic neurons.
Johnsen, Grethe E; Asbjørnsen, Arve E
The present study examined mechanisms underlying verbal memory impairments in patients with posttraumatic stress disorder (PTSD). Earlier studies have reported that the verbal learning and memory alterations in PTSD are related to impaired encoding, but the use of encoding and organizational strategies in patients with PTSD has not been fully explored. This study examined organizational strategies in 21 refugees/immigrants exposed to war and political violence who fulfilled DSM-IV criteria for chronic PTSD compared with a control sample of 21 refugees/immigrants with similar exposure, but without PTSD. The California Verbal Learning Test was administered to examine differences in organizational strategies and memory. The semantic clustering score was slightly reduced in both groups, but the serial cluster score was significantly impaired in the PTSD group and they also reported more items from the recency region of the list. In addition, intrusive errors were significantly increased in the PTSD group. The data support an assumption of changed memory strategies in patients with PTSD associated with a specific impairment in executive control. However, memory impairment and the use of ineffective learning strategies may not be related to PTSD symptomatology only, but also to self-reported symptoms of depression and general distress.
Stephen T Chen
Full Text Available INTRODUCTION: Previous research has identified modifiable risk factors for Alzheimer's disease (AD in older adults. Research is limited on the potential link between these risk factors and subjective memory impairment (SMI, which may precede AD and other dementias. Examination of these potential relationships may help identify those at risk for AD at a stage when interventions may delay or prevent further memory problems. The objective of this study was to determine whether risk factors for AD are associated with SMI among different age groups. METHOD: Trained interviewers conducted daily telephone surveys (Gallup-Healthways of a representative community sample of 18,614 U.S. respondents, including 4,425 younger (age 18 to 39 years, 6,365 middle-aged (40 to 59 years, and 7,824 older (60 to 99 years adults. The surveyors collected data on demographics, lifestyles, and medical information. Less education, smoking, hypertension, diabetes, less exercise, obesity and depression, and interactions among them, were examined for associations with SMI. Weighted logistic regressions and chi-square tests were used to calculate odds ratios and confidence intervals for SMI with each risk factor and pairwise interactions across age groups. RESULTS: Depression, less education, less exercise, and hypertension were significantly associated with SMI in all three age groups. Several interactions between risk factors were significant in younger and middle-aged adults and influenced their associations with SMI. Frequency of SMI increased with age and number of risk factors. Odds of having SMI increased significantly with just having one risk factor. CONCLUSIONS: These results indicate that modifiable risk factors for AD are also associated with SMI, suggesting that these relationships occur in a broad range of ages and may be targeted to mitigate further memory problems. Whether modifying these risk factors reduces SMI and the eventual incidence of AD and other
Chen, Stephen T; Siddarth, Prabha; Ercoli, Linda M; Merrill, David A; Torres-Gil, Fernando; Small, Gary W
Previous research has identified modifiable risk factors for Alzheimer's disease (AD) in older adults. Research is limited on the potential link between these risk factors and subjective memory impairment (SMI), which may precede AD and other dementias. Examination of these potential relationships may help identify those at risk for AD at a stage when interventions may delay or prevent further memory problems. The objective of this study was to determine whether risk factors for AD are associated with SMI among different age groups. Trained interviewers conducted daily telephone surveys (Gallup-Healthways) of a representative community sample of 18,614 U.S. respondents, including 4,425 younger (age 18 to 39 years), 6,365 middle-aged (40 to 59 years), and 7,824 older (60 to 99 years) adults. The surveyors collected data on demographics, lifestyles, and medical information. Less education, smoking, hypertension, diabetes, less exercise, obesity and depression, and interactions among them, were examined for associations with SMI. Weighted logistic regressions and chi-square tests were used to calculate odds ratios and confidence intervals for SMI with each risk factor and pairwise interactions across age groups. Depression, less education, less exercise, and hypertension were significantly associated with SMI in all three age groups. Several interactions between risk factors were significant in younger and middle-aged adults and influenced their associations with SMI. Frequency of SMI increased with age and number of risk factors. Odds of having SMI increased significantly with just having one risk factor. These results indicate that modifiable risk factors for AD are also associated with SMI, suggesting that these relationships occur in a broad range of ages and may be targeted to mitigate further memory problems. Whether modifying these risk factors reduces SMI and the eventual incidence of AD and other dementias later in life remains to be determined.
Madan, Christopher R; Fujiwara, Esther; Caplan, Jeremy B; Sommer, Tobias
Emotional arousal is well-known to enhance memory for individual items or events, whereas it can impair association memory. The neural mechanism of this association memory impairment by emotion is not known: In response to emotionally arousing information, amygdala activity may interfere with hippocampal associative encoding (e.g., via prefrontal cortex). Alternatively, emotional information may be harder to unitize, resulting in reduced availability of extra-hippocampal medial temporal lobe support for emotional than neutral associations. To test these opposing hypotheses, we compared neural processes underlying successful and unsuccessful encoding of emotional and neutral associations. Participants intentionally studied pairs of neutral and negative pictures (Experiments 1-3). We found reduced association-memory for negative pictures in all experiments, accompanied by item-memory increases in Experiment 2. High-resolution fMRI (Experiment 3) indicated that reductions in associative encoding of emotional information are localizable to an area in ventral-lateral amygdala, driven by attentional/salience effects in the central amygdala. Hippocampal activity was similar during both pair types, but a left hippocampal cluster related to successful encoding was observed only for negative pairs. Extra-hippocampal associative memory processes (e.g., unitization) were more effective for neutral than emotional materials. Our findings suggest that reduced emotional association memory is accompanied by increases in activity and functional coupling within the amygdala. This did not disrupt hippocampal association-memory processes, which indeed were critical for successful emotional association memory formation. Copyright © 2017 Elsevier Inc. All rights reserved.
Broster, Lucas S; Jenkins, Shonna L; Holmes, Sarah D; Edwards, Matthew G; Jicha, Gregory A; Jiang, Yang
Forms of implicit memory, including repetition effects, are preserved relative to explicit memory in clinical Alzheimer's disease. Consequently, cognitive interventions for persons with Alzheimer's disease have been developed that leverage this fact. However, despite the clinical robustness of behavioral repetition effects, altered neural mechanisms of repetition effects are studied as biomarkers of both clinical Alzheimer's disease and pre-morbid Alzheimer's changes in the brain. We hypothesized that the clinical preservation of behavioral repetition effects results in part from concurrent operation of discrete memory systems. We developed two experiments that included probes of emotional repetition effects differing in that one included an embedded working memory task. We found that neural repetition effects manifested in patients with amnestic mild cognitive impairment, the earliest form of clinical Alzheimer's disease, during emotional working memory tasks, but they did not manifest during the task that lacked the embedded working memory manipulation. Specifically, the working memory task evoked neural repetition effects in the P600 time-window, but the same neural mechanism was only minimally implicated in the task without a working memory component. We also found that group differences in behavioral repetition effects were smaller in the experiment with a working memory task. We suggest that cross-domain cognitive challenge can expose "defunct" neural capabilities of individuals with amnestic mild cognitive impairment. Copyright © 2018. Published by Elsevier Ltd.
Truong, D T; Che, A; Rendall, A R; Szalkowski, C E; LoTurco, J J; Galaburda, A M; Holly Fitch, R
Dyslexia is a complex neurodevelopmental disorder characterized by impaired reading ability despite normal intellect, and is associated with specific difficulties in phonological and rapid auditory processing (RAP), visual attention and working memory. Genetic variants in Doublecortin domain-containing protein 2 (DCDC2) have been associated with dyslexia, impairments in phonological processing and in short-term/working memory. The purpose of this study was to determine whether sensory and behavioral impairments can result directly from mutation of the Dcdc2 gene in mice. Several behavioral tasks, including a modified pre-pulse inhibition paradigm (to examine auditory processing), a 4/8 radial arm maze (to assess/dissociate working vs. reference memory) and rotarod (to examine sensorimotor ability and motor learning), were used to assess the effects of Dcdc2 mutation. Behavioral results revealed deficits in RAP, working memory and reference memory in Dcdc2(del2/del2) mice when compared with matched wild types. Current findings parallel clinical research linking genetic variants of DCDC2 with specific impairments of phonological processing and memory ability. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
Jutta S Mayer
Full Text Available Although impairments in working memory (WM are well documented in schizophrenia, the specific factors that cause these deficits are poorly understood. In this study, we hypothesized that a heightened susceptibility to attentional capture at an early stage of visual processing would result in working memory encoding problems. 30 patients with schizophrenia and 28 demographically matched healthy participants were presented with a search array and asked to report the orientation of the target stimulus. In some of the trials, a flanker stimulus preceded the search array that either matched the color of the target (relevant-flanker capture or appeared in a different color (irrelevant-flanker capture. Working memory capacity was determined in each individual using the visual change detection paradigm. Patients needed considerably more time to find the target in the no-flanker condition. After adjusting the individual exposure time, both groups showed equivalent capture costs in the irrelevant-flanker condition. However, in the relevant-flanker condition, capture costs were increased in patients compared to controls when the stimulus onset asynchrony between the flanker and the search array was high. Moreover, the increase in relevant capture costs correlated negatively with working memory capacity. This study demonstrates preserved stimulus-driven attentional capture but impaired contingent attentional capture associated with low working memory capacity in schizophrenia. These findings suggest a selective impairment of top-down attentional control in schizophrenia, which may impair working memory encoding.
Mayer, Jutta S; Fukuda, Keisuke; Vogel, Edward K; Park, Sohee
Although impairments in working memory (WM) are well documented in schizophrenia, the specific factors that cause these deficits are poorly understood. In this study, we hypothesized that a heightened susceptibility to attentional capture at an early stage of visual processing would result in working memory encoding problems. 30 patients with schizophrenia and 28 demographically matched healthy participants were presented with a search array and asked to report the orientation of the target stimulus. In some of the trials, a flanker stimulus preceded the search array that either matched the color of the target (relevant-flanker capture) or appeared in a different color (irrelevant-flanker capture). Working memory capacity was determined in each individual using the visual change detection paradigm. Patients needed considerably more time to find the target in the no-flanker condition. After adjusting the individual exposure time, both groups showed equivalent capture costs in the irrelevant-flanker condition. However, in the relevant-flanker condition, capture costs were increased in patients compared to controls when the stimulus onset asynchrony between the flanker and the search array was high. Moreover, the increase in relevant capture costs correlated negatively with working memory capacity. This study demonstrates preserved stimulus-driven attentional capture but impaired contingent attentional capture associated with low working memory capacity in schizophrenia. These findings suggest a selective impairment of top-down attentional control in schizophrenia, which may impair working memory encoding.
Sweeney-Reed, Catherine M; Riddell, Patricia M; Ellis, Judi A; Freeman, Jayne E; Nasuto, Slawomir J
The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer's disease, which has been described as a 'disconnection syndrome'.
Sweeney-Reed, Catherine M.; Riddell, Patricia M.; Ellis, Judi A.; Freeman, Jayne E.; Nasuto, Slawomir J.
The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’. PMID:23118992
Adolphs, Ralph; Tranel, Daniel; Denburg, Natalie
Case studies of patients with bilateral amygdala damage and functional imaging studies of normal individuals have demonstrated that the amygdala plays a critical role in encoding emotionally arousing stimuli into long-term declarative memory. However, several issues remain poorly understood: the separate roles of left and right amygdala, the time course over which the amygdala participates in memory consolidation, and the type of knowledge structures it helps consolidate. We investigated thes...
Nategh, Mohsen; Nikseresht, Sara; Khodagholi, Fariba; Motamedi, Fereshteh
Nucleus incertus (NI) is a pontine nucleus which releases mainly GABA and relaxin-3 in rats. Its suggested functions include response to stress, arousal, and modulation of hippocampal theta rhythm. Since the role of NI in learning and memory has not been well characterized, therefore the involvement of this nucleus in spatial learning and memory and the aftermath hippocampal levels of c-fos and pCREB were evaluated. NI was targeted by implanting cannula in male rats. For reference memory, NI was inactivated by lidocaine (0.4 μl, 4%) at three stages of acquisition, consolidation and retrieval in Morris water maze paradigm. For working memory, NI was inactivated in acquisition and retrieval phases. Injection of lidocaine prior to the first training session of reference memory significantly increased the distance moved, suggesting that inactivation of NI delays acquisition in this spatial task. Inactivation also interfered with the retrieval phase of spatial reference memory, as the time in target quadrant for lidocaine group was less, and the escape latency was higher compared to the control group. However, no difference was observed in the consolidation phase. In the working memory task, with inter-trial intervals of 75 min, the escape latency was higher when NI was inactivated in the retrieval phase. In addition, c-fos and pCREB/CREB levels decreased in NI-inhibited rats. This study suggests that nucleus incertus might participate in acquisition of spatial reference, and retrieval of both spatial reference and working memory. Further studies should investigate possible roles of NI in the hippocampal plasticity. Copyright © 2014 Elsevier Inc. All rights reserved.
Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto
Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.
Klooster, Nathaniel B; Cook, Susan W; Uc, Ergun Y; Duff, Melissa C
Hand gesture, a ubiquitous feature of human interaction, facilitates communication. Gesture also facilitates new learning, benefiting speakers and listeners alike. Thus, gestures must impact cognition beyond simply supporting the expression of already-formed ideas. However, the cognitive and neural mechanisms supporting the effects of gesture on learning and memory are largely unknown. We hypothesized that gesture's ability to drive new learning is supported by procedural memory and that procedural memory deficits will disrupt gesture production and comprehension. We tested this proposal in patients with intact declarative memory, but impaired procedural memory as a consequence of Parkinson's disease (PD), and healthy comparison participants with intact declarative and procedural memory. In separate experiments, we manipulated the gestures participants saw and produced in a Tower of Hanoi (TOH) paradigm. In the first experiment, participants solved the task either on a physical board, requiring high arching movements to manipulate the discs from peg to peg, or on a computer, requiring only flat, sideways movements of the mouse. When explaining the task, healthy participants with intact procedural memory displayed evidence of their previous experience in their gestures, producing higher, more arching hand gestures after solving on a physical board, and smaller, flatter gestures after solving on a computer. In the second experiment, healthy participants who saw high arching hand gestures in an explanation prior to solving the task subsequently moved the mouse with significantly higher curvature than those who saw smaller, flatter gestures prior to solving the task. These patterns were absent in both gesture production and comprehension experiments in patients with procedural memory impairment. These findings suggest that the procedural memory system supports the ability of gesture to drive new learning.
Nathaniel Bloem Klooster
Full Text Available Hand gesture, a ubiquitous feature of human interaction, facilitates communication. Gesture also facilitates new learning, benefiting speakers and listeners alike. Thus, gestures must impact cognition beyond simply supporting the expression of already-formed ideas. However, the cognitive and neural mechanisms supporting the effects of gesture on learning and memory are largely unknown. We hypothesized that gesture’s ability to drive new learning is supported by procedural memory and that procedural memory deficits will disrupt gesture production and comprehension. We tested this proposal in patients with intact declarative memory, but impaired procedural memory as a consequence of Parkinson’s disease, and healthy comparison participants with intact declarative and procedural memory. In separate experiments, we manipulated the gestures participants saw and produced in a Tower of Hanoi paradigm. In the first experiment, participants solved the task either on a physical board, requiring high arching movements to manipulate the discs from peg to peg, or on a computer, requiring only flat, sideways movements of the mouse. When explaining the task, healthy participants with intact procedural memory displayed evidence of their previous experience in their gestures, producing higher, more arching hand gestures after solving on a physical board, and smaller, flatter gestures after solving on a computer. In the second experiment, healthy participants who saw high arching hand gestures in an explanation prior to solving the task subsequently moved the mouse with significantly higher curvature than those who saw smaller, flatter gestures prior to solving the task. These patterns were absent in both gesture production and comprehension experiments in patients with procedural memory impairment. These findings suggest that the procedural memory system supports the ability of gesture to drive new learning.
Savaskan, Egemen; Summermatter, Daniel; Schroeder, Clemens; Schächinger, Hartmut
Faces are among the most relevant social stimuli revealing an encounter's identity and actual emotional state. Deficits in facial recognition may be an early sign of cognitive decline leading to social deficits. The main objective of the present study is to investigate if individuals with amnestic mild cognitive impairment show recognition deficits in facial identity. Thirty-seven individuals with amnestic mild cognitive impairment, multiple-domain (15 female; age: 75±8 yrs.) and forty-one healthy volunteers (24 female; age 71±6 yrs.) participated. All participants completed a human portrait memory test presenting unfamiliar faces with happy and angry emotional expressions. Five and thirty minutes later, old and new neutral faces were presented, and discrimination sensitivity (d') and response bias (C) were assessed as signal detection parameters of cued facial identity recognition. Memory performance was lower in amnestic mild cognitive impairment as compared to control subjects, mainly because of an altered response bias towards an increased false alarm rate (favoring false OLD ascription of NEW items). In both groups, memory performance declined between the early and later testing session, and was always better for acquired happy than angry faces. Facial identity memory is impaired in patients with amnestic mild cognitive impairment. Liberalization of the response bias may reflect a socially motivated compensatory mechanism maintaining an almost identical recognition hit rate of OLD faces in individuals with amnestic mild cognitive impairment.
Curtis, Evan T; Jamieson, Randall K
Current theory has divided memory into multiple systems, resulting in a fractionated account of human behaviour. By an alternative perspective, memory is a single system. However, debate over the details of different single-system theories has overshadowed the converging agreement among them, slowing the reunification of memory. Evidence in favour of dividing memory often takes the form of dissociations observed in amnesia, where amnesic patients are impaired on some memory tasks but not others. The dissociations are taken as evidence for separate explicit and implicit memory systems. We argue against this perspective. We simulate two key dissociations between classification and recognition in a computational model of memory, A Theory of Nonanalytic Association. We assume that amnesia reflects a quantitative difference in the quality of encoding. We also present empirical evidence that replicates the dissociations in healthy participants, simulating amnesic behaviour by reducing study time. In both analyses, we successfully reproduce the dissociations. We integrate our computational and empirical successes with the success of alternative models and manipulations and argue that our demonstrations, taken in concert with similar demonstrations with similar models, provide converging evidence for a more general set of single-system analyses that support the conclusion that a wide variety of memory phenomena can be explained by a unified and coherent set of principles.
Reis, Patricia A; Alexandre, Pedro C B; D'Avila, Joana C; Siqueira, Luciana D; Antunes, Barbara; Estato, Vanessa; Tibiriça, Eduardo V; Verdonk, Franck; Sharshar, Tarek; Chrétien, Fabrice; Castro-Faria-Neto, Hugo C; Bozza, Fernando A
Acute brain dysfunction is a frequent condition in sepsis patients and is associated with increased mortality and long-term neurocognitive consequences. Impaired memory and executive function are common findings in sepsis survivors. Although neuroinflammation and blood-brain barrier dysfunction have been associated with acute brain dysfunction and its consequences, no specific treatments are available that prevent cognitive impairment after sepsis. Experimental sepsis was induced in Swiss Webster mice by intraperitoneal injection of cecal material (5mg/kg, 500μL). Control groups (n=5/group each experiment) received 500μL of saline. Support therapy recover (saline 0.9%, 1mL and imipenem 30mg/kg) were applied (6, 24 and 48h post injection, n=5-10/group, each experiment), together or not with additive orally treatment with statins (atorvastatin/simvastatin 20mg/kg b.w.). Survival rate was monitored at 6, 24 and 48h. In a setting of experiments, animals were euthanized at 6 and 24h after induction for biochemical, immunohistochemistry and intravital analysis. Statins did not prevented mortality in septic mice, however survivors presented lower clinical score. At another setting of experiments, after 15days, mice survivors from fecal supernatant peritoneal sepsis presented cognitive dysfunction for contextual hippocampal and aversive amygdala-dependent memories, which was prevented by atorvastatin/simvastatin treatment. Systemic and brain tissue levels of proinflammatory cytokines/chemokines and activation of microglial were lower in septic mice treated with statins. Brain lipid peroxidation and myeloperoxidase levels were also reduced by statins treatment. Intravital examination of the brain vessels of septic animals revealed decreased functional capillary density and increased rolling and adhesion of leukocytes, and blood flow impairment, which were reversed by treatment with statins. In addition, treatment with statins restored the cholinergic vasodilator response
Sardari, M; Rezayof, A; Zarrindast, M-R
The aim of the present study was to investigate the possible role of basolateral amygdala (BLA) 5-HT1A receptors in memory formation under stress. We also examined whether the blockade of these receptors is involved in stress-induced state-dependent memory. Adult male Wistar rats received cannula implants that bilaterally targeted the BLA. Long-term memory was examined using the step-through type of passive avoidance task. Behavioral stress was evoked by exposure to an elevated platform (EP) for 10, 20 and 30min. Post-training exposure to acute stress (30min) impaired the memory consolidation. In addition, pre-test exposure to acute stress-(20 and 30min) induced the impairment of memory retrieval. Interestingly, the memory impairment induced by post-training exposure to stress was restored in the animals that received 20- or 30-min pre-test stress exposure, suggesting stress-induced state-dependent memory retrieval. Post-training BLA-targeted injection of a selective 5-HT1A receptor antagonist, (S)-WAY-100135 (2μg/rat), prevented the impairing effect of stress on memory consolidation. Pre-test injection of the same doses of (S)-WAY-100135 that was targeted to the BLA also reversed stress-induced memory retrieval impairment. It should be considered that post-training or pre-test BLA-targeted injection of (S)-WAY-100135 (0.5-2μg/rat) by itself had no effect on the memory formation. Moreover, pre-test injection of (S)-WAY-100135 (2μg/rat) that targeted the BLA inhibited the stress-induced state-dependent memory retrieval. Taken together, our findings suggest that post-training or pre-test exposure to acute stress induced the impairment of memory consolidation, retrieval and state-dependent learning. The BLA 5-HT1A receptors have a critical role in learning and memory under stress. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Smith, Christine N; Urgolites, Zhisen J; Hopkins, Ramona O; Squire, Larry R
Declarative memory for rapidly learned, novel associations is thought to depend on structures in the medial temporal lobe (MTL), whereas associations learned more gradually can sometimes be supported by nondeclarative memory and by structures outside the MTL. A recent study suggested that even rapidly learned associations can be supported by structures outside the MTL when an incidental encoding procedure termed "fast mapping" (FM) is used. We tested six memory-impaired patients with bilateral damage to hippocampus and one patient with large bilateral lesions of the MTL. Participants saw photographs and names of animals, plants, and foods that were previously unfamiliar (e.g., mangosteen). Instead of asking participants to study name-object pairings for a later memory test (as with traditional memory instructions), participants answered questions that allowed them to infer which object corresponded to a particular name. In a second condition, participants learned name-object associations of unfamiliar items by using standard, explicit encoding instructions (e.g., remember the mangosteen). In FM and explicit encoding conditions, patients were impaired (and performed no better than a group that was given the same tests but had not previously studied the material). The same results were obtained in a second experiment that used the same procedures with modifications to allow for more robust learning and more reliable measures of performance. Thus, our results with the FM procedure and memory-impaired patients yielded the same deficits in learning and memory that have been obtained by using other more traditional paradigms.
Full Text Available Background: Discrepancies persist regarding retainment of emotional enhancement of memory (EEM in mild cognitive impairment (MCI and early Alzheimer’s disease (AD patients. In addition, the neural mechanisms are still poorly understood, little is known about emotional memory related changes in white matter (WM.Objective: To observe whether EEM is absent in amnestic MCI (aMCI and AD patients, and to investigate if emotional memory is associated with WM connections and gray matters (GM of the limbic system networks. Methods: Twenty-one AD patients, 20 aMCI patients and 25 normal controls participated in emotional picture recognition tests and MRI scanning. Tract-based spatial statistics (TBSS and voxel-based morphometry (VBM methods were used to determine white and gray matter changes of patients. Fourteen regions of interest (ROI of WM and 20 ROIs of GM were then selected for the correlation analyses with behavioral scores. Results: The EEM effect was lost in AD patients. Both white and gray matter of the limbic system networks were impaired in AD patients. Significant correlations or tendencies between the bilateral uncinate fasciculus, corpus callosum (genu and body, left cingulum bundle, left parahippocampal WM and the recognition sensitivity of emotional valence pictures, and significant correlations or tendencies between the splenium of corpus callosum, left cingulum bundle, left crus of fornix and stria terminalis and the recognition sensitivity of EEM were found. The volume of left amygdala, bilateral insula, medial frontal lobe, anterior and middle cingulum gyrus were positively correlated with the recognition sensitivity of emotional photos, and the right precuneus was positively correlated with the negative EEM effect. However, the affected brain areas of aMCI patients were more localized, and aMCI patients benefited only from positive stimuli. Conclusion: There are impairments of the limbic system networks of AD patients. Damaged WM
Full Text Available It has been well documented that β-amyloid peptide accumulation and aggregation in the brain plays a crucial role in the pathophysiology of Alzheimer’s disease (AD. However, a new orientation of the amyloid cascade hypothesis has evidenced that soluble forms of the peptide (sAβ are involved in Aβ-induced cognitive impairment and cause rapid disruption of the synaptic mechanisms underlying memory. The primary aim of this study was to elucidate the effects of sAβ, acutely injected intracerebrally (i.c.v., 4 µM, on the short term and long term memory of young adult male rats, by using the novel object recognition task. Glutamatergic receptors have been proposed as mediating the effect of Aβ on synaptic plasticity and memory. Thus, we also investigated the effects of sAβ on prefrontal cortex (PFC glutamate release and the specific contribution of N-methyl-D-aspartate (NMDA receptor modulation to the effects of sAβ administration on the cognitive parameters evaluated. We found that a single i.c.v. injection of sAβ 2h before testing did not alter the ability of rats to differentiate between a familiar and a novel object, in a short term memory test, while it was able to negatively affect consolidation/retrieval of long term memory. Moreover, a significant increase of glutamate levels was found in PFC of rats treated with the peptide 2 h earlier. Interestingly, memory deficit induced by sAβ was reversed by a NMDA-receptor antagonist, memantine (5 mg/kg i.p, administered immediately after the familiarization trial (T1. On the contrary, memantine administered 30 min before T1 trial, was not able to rescue long term memory impairment. Taken together, our results suggest that an acute i.c.v. injection of sAβ peptide interferes with the consolidation/retrieval of long term memory. Moreover, such sAβ-induced effect indicates the involvement of glutamatergic system, proposing that NMDA receptor inhibition might prevent or lead to the recovery of
Argyropoulos, Vassilios; Masoura, Elvira; Tsiakali, Thomai K; Nikolaraizi, Magda; Lappa, Christina
This study investigated the relationship between working memory (WM) and reading abilities among students with visual impairment (VI). Seventy-five students with VI (visually impairment and blindness), aged 10-15 years old participated in the study, of whom 44 were visually impaired and 31 were blind. The participants' reading ability was assessed with the standardized reading ability battery Test-A (Padeliadu & Antoniou, 2008) and their verbal working memory ability was assessed with the listening recall task from the Working Memory Test Battery for Children (Pickering et al., 2001). Data analysis indicated a strong correlation between verbal WM and decoding, reading comprehension and overall reading ability among the participants with VI, while no correlation was found between reading fluency and verbal WM. The present study points out the important role of verbal WM in reading among students who are VI and carries implications for the education of those individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.
Havekes, Robbert; Park, Alan J; Tolentino, Rosa E; Bruinenberg, Vibeke M; Tudor, Jennifer C; Lee, Yool; Hansen, Rolf T; Guercio, Leonardo A; Linton, Edward; Neves-Zaph, Susana R; Meerlo, Peter; Baillie, George S; Houslay, Miles D; Abel, Ted
Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular compartments. The
Busquets-Garcia, Arnau; Gomis-González, Maria; Salgado-Mendialdúa, Victòria; Galera-López, Lorena; Puighermanal, Emma; Martín-García, Elena; Maldonado, Rafael; Ozaita, Andrés
Cannabis affects cognitive performance through the activation of the endocannabinoid system, and the molecular mechanisms involved in this process are poorly understood. Using the novel object-recognition memory test in mice, we found that the main psychoactive component of cannabis, delta9-tetrahydrocannabinol (THC), alters short-term object-recognition memory specifically involving protein kinase C (PKC)-dependent signaling. Indeed, the systemic or intra-hippocampal pre-treatment with the PKC inhibitors prevented the short-term, but not the long-term, memory impairment induced by THC. In contrast, systemic pre-treatment with mammalian target of rapamycin complex 1 inhibitors, known to block the amnesic-like effects of THC on long-term memory, did not modify such a short-term cognitive deficit. Immunoblot analysis revealed a transient increase in PKC signaling activity in the hippocampus after THC treatment. Thus, THC administration induced the phosphorylation of a specific Ser residue in the hydrophobic-motif at the C-terminal tail of several PKC isoforms. This significant immunoreactive band that paralleled cognitive performance did not match in size with the major PKC isoforms expressed in the hippocampus except for PKCθ. Moreover, THC transiently enhanced the phosphorylation of the postsynaptic calmodulin-binding protein neurogranin in a PKC dependent manner. These data demonstrate that THC alters short-term object-recognition memory through hippocampal PKC/neurogranin signaling.
Rosa, Nicole M; Deason, Rebecca G; Budson, Andrew E; Gutchess, Angela H
The present study examined the role of enactment in source memory in a cognitively impaired population. As seen in healthy older adults, it was predicted that source memory in people with mild cognitive impairment due to Alzheimer's disease (MCI-AD) would benefit from the self-reference aspect of enactment. Seventeen participants with MCI-AD and 18 controls worked in small groups to pack a picnic basket and suitcase and were later tested for their source memory for each item. For item memory, self-referencing improved corrected recognition scores for both MCI-AD and control participants. The MCI-AD group did not demonstrate the same benefit as controls in correct source memory for self-related items. However, those with MCI-AD were relatively less likely to misattribute new items to the self and more likely to misattribute new items to others when committing errors, compared with controls. The enactment effect and self-referencing did not enhance accurate source memory more than other referencing for patients with MCI-AD. However, people with MCI-AD benefited in item memory and source memory, being less likely to falsely claim new items as their own, indicating some self-reference benefit occurs for people with MCI-AD. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.
Zimmermann, Nicolle; Corrêa, Diogo Goulart; Netto, Tania Maria; Kubo, Tadeu; Pereira, Denis Batista; Fonseca, Rochele Paz; Gasparetto, Emerson Leandro
Episodic memory deficits in systemic lupus erythematosus (SLE) have been frequently reported in the literature; however, little is known about the neural correlates of these deficits. We investigated differences in the volumes of different brain structures of SLE patients with and without episodic memory impairments diagnosed by the Rey Auditory Verbal Learning Test (RAVLT). Groups were paired based on age, education, sex, Mini Mental State Examination score, accumulation of disease burden (SLICC), and focused attention dimension score. Patients underwent magnetic resonance imaging (MRI). Cortical volumetric reconstruction and segmentation of the MR images were performed with the FreeSurfer software program. SLE patients with episodic memory deficits presented shorter time of diagnosis than SLE patients without episodic memory deficits. ANOVA revealed that SLE patients with episodic memory deficits had a larger third ventricle volume than SLE patients without episodic memory deficits and controls. Additionally, covariance analysis indicated group effects on the bilateral thalamus and on the third ventricle. Our findings indicate that episodic memory may be impaired in SLE patients with normal hippocampal volume. In addition, the thalamus may undergo volumetric changes associated with episodic memory loss in SLE.
Jena B. Hales
Full Text Available Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP. However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3–7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF. In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion.
Iyer, Smita S.; Chatraw, Janel Hart; Tan, Wendy G.; Wherry, E. John; Becker, Todd C.; Ahmed, Rafi; Kapasi, Zoher F.
Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. Here we show that protein energy malnutrition (PEM) induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate-protein (AP) fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV) immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that PEM caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. While antigen-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less-responsive to poly(I:C)-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13 resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals. PMID:22116826
Iyer, Smita S; Chatraw, Janel Hart; Tan, Wendy G; Wherry, E John; Becker, Todd C; Ahmed, Rafi; Kapasi, Zoher F
Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. In this study, we show that protein-energy malnutrition induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate protein (AP)-fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV)-immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that protein-energy malnutrition caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. Whereas Ag-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less responsive to polyinosinic-polycytidylic acid-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13, resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals.
Ye, Byoung Seok; Chin, Juhee; Kim, Seong Yoon; Lee, Jung-Sun; Kim, Eun-Joo; Lee, Yunhwan; Hong, Chang Hyung; Choi, Seong Hye; Park, Kyung Won; Ku, Bon D; Moon, So Young; Kim, SangYun; Han, Seol-Hee; Lee, Jae-Hong; Cheong, Hae-Kwan; Park, Sun Ah; Jeong, Jee Hyang; Na, Duk L; Seo, Sang Won
We evaluate the longitudinal outcomes of amnestic mild cognitive impairment (aMCI) according to the modality of memory impairment involved. We recruited 788 aMCI patients and followed them up. aMCI patients were categorized into three groups according to the modality of memory impairment: Visual-aMCI, only visual memory impaired; Verbal-aMCI, only verbal memory impaired; and Both-aMCI, both visual and verbal memory impaired. Each aMCI group was further categorized according to the presence or absence of recognition failure. Risk of progression to dementia was compared with pooled logistic regression analyses while controlling for age, gender, education, and interval from baseline. Of the sample, 219 (27.8%) aMCI patients progressed to dementia. Compared to the Visual-aMCI group, Verbal-aMCI (OR = 1.98, 95% CI = 1.19-3.28, p = 0.009) and Both-aMCI (OR = 3.05, 95% CI = 1.97-4.71, p Memory recognition failure was associated with increased risk of progression to dementia only in the Visual-aMCI group, but not in the Verbal-aMCI and Both-aMCI groups. The Visual-aMCI without recognition failure group were subcategorized into aMCI with depression, small vessel disease, or accelerated aging, and these subgroups showed a variety of progression rates. Our findings underlined the importance of heterogeneous longitudinal outcomes of aMCI, especially Visual-aMCI, for designing and interpreting future treatment trials in aMCI.
Sulzgruber, Patrick; Kliegel, Andreas; Wandaller, Cosima; Uray, Thomas; Losert, Heidrun; Laggner, Anton N; Sterz, Fritz; Kliegel, Matthias
Deficits in cognitive function are a well-known dysfunction in survivors of cardiac arrest. However, data concerning memory function in this neurological vulnerable patient collective remain scarce and inconclusive. Therefore, we aimed to assess multiple aspects of retrospective and prospective memory performance in patients after cardiac arrest. We prospectively enrolled 33 survivors of cardiac arrest, with cerebral performance categories (CPC) 1 and 2 and a control-group (n=33) matched in sex, age and educational-level. To assess retrospective and prospective memory performance we administrated 4 weeks after cardiac arrest the "Rey Adult Learning Test" (RAVLT), the "Digit-Span-Backwards Test", the "Logic-Memory Test" and the "Red-Pencil Test". Results indicate an impairment in immediate and delayed free recall, but not in recognition. However, the overall impairment in immediate recall was qualified by analyzing RAVLT performance, showing that patients were only impaired in trials 4 and 5 of the learning sequence. Moreover, working and prospective memory as well as prose recall were worse in cardiac arrest survivors. Cranial computed tomography was available in 61% of all patients (n=20) but there was no specific neurological damage detectable that could be linked to this cognitive impairment. Episodic long-term memory functioning appears to be particularly impaired after cardiac arrest. In contrast, short-term memory storage, even tested via free-call, seems not to be affected. Based on cranial computed tomography we suggest that global brain ischemia rather than focal brain lesions appear to underlie these effects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Burke, Hanna M; Robinson, Cristina M; Wentz, Bethany; McKay, Jerel; Dexter, Kyle W; Pisansky, Julia M; Talbot, Jeffery N; Zoladz, Phillip R
It has been suggested that cognitive impairments exhibited by people with post-traumatic stress disorder (PTSD) result from intrusive, flashback memories transiently interfering with ongoing cognitive processing. Researchers have further speculated that females are more susceptible to developing PTSD because they form stronger traumatic memories than males, hence females may be more sensitive to the negative effects of intrusive memories on cognition. We have examined how the reminder of a naturalistic stress experience would affect rat spatial memory and if sex was a contributing factor to such effects. Male and female Sprague-Dawley rats were exposed, without contact, to an adult female cat for 30 min. Five weeks later, the rats were trained to locate a hidden platform in the radial-arm water maze and given a single long-term memory test trial 24 h later. Before long-term memory testing, the rats were given a 30-min reminder of the cat exposure experienced 5 weeks earlier. The results indicated that the stress reminder impaired spatial memory in the female rats only. Control manipulations revealed that this effect was not attributable to the original cat exposure adversely impacting learning that occurred 5 weeks later, or to merely exposing rats to a novel environment or predator-related cues immediately before testing. These findings provide evidence that the reminder of a naturalistic stressful experience can impair cognitive processing in rats; moreover, since female rats were more susceptible to the memory-impairing effects of the stress reminder, the findings could lend insight into the existing sex differences in susceptibility to PTSD.
Behnken, Andreas; Schöning, Sonja; Gerss, Joachim; Konrad, Carsten; de Jong-Meyer, Renate; Zwanzger, Peter; Arolt, Volker
While neuropsychological impairments are well described in acute phases of major depressive disorders (MDD), little is known about the neuropsychological profile in remission. There is evidence for episodic memory impairments in both acute depressed and remitted patients with MDD. Learning and memory depend on individuals' ability to organize information during learning. This study investigates non-verbal memory functions in remitted MDD and whether nonverbal memory performance is mediated by organizational strategies whilst learning. 30 well-characterized fully remitted individuals with unipolar MDD and 30 healthy controls matching in age, sex and education were investigated. Non-verbal learning and memory were measured by the Rey-Osterrieth-Complex-Figure-Test (RCFT). The RCFT provides measures of planning, organizational skills, perceptual and non-verbal memory functions. For assessing the mediating effects of organizational strategies, we used the Savage Organizational Score. Compared to healthy controls, participants with remitted MDD showed more deficits in their non-verbal memory function. Moreover, participants with remitted MDD demonstrated difficulties in organizing non-verbal information appropriately during learning. In contrast, no impairments regarding visual-spatial functions in remitted MDD were observed. Except for one patient, all the others were taking psychopharmacological medication. The neuropsychological function was solely investigated in the remitted phase of MDD. Individuals with MDD in remission showed persistent non-verbal memory impairments, modulated by a deficient use of organizational strategies during encoding. Therefore, our results strongly argue for additional therapeutic interventions in order to improve these remaining deficits in cognitive function. Copyright 2009 Elsevier B.V. All rights reserved.
Bastin, Christine; Van der Linden, Martial; Lekeu, Françoise; Andrés, Pilar; Salmon, Eric
Fourteen patients with frontal lobe lesions and 14 normal subjects were tested on a recognition memory task that required discriminating between target words, new words that are synonyms of the targets and unrelated distractors. A deficit was found in 12 of the patients. Moreover, three different patterns of recognition impairment were identified: (I) poor memory for targets, (II) normal hits but increased false recognitions for both types of distractors, (III) normal hit rates, but increased...
Salgado-Puga, Karla; Prado-Alcalá, Roberto A; Peña-Ortega, Fernando
Alzheimer's disease (AD) is associated with an early hippocampal dysfunction, which is likely induced by an increase in soluble amyloid beta peptide (Aβ). This hippocampal failure contributes to the initial memory deficits observed both in patients and in AD animal models and possibly to the deterioration in activities of daily living (ADL). One typical rodent behavior that has been proposed as a hippocampus-dependent assessment model of ADL in mice and rats is burrowing. Despite the fact that AD transgenic mice show some evidence of reduced burrowing, it has not been yet determined whether or not Aβ can affect this typical rodent behavior and whether this alteration correlates with the well-known Aβ-induced memory impairment. Thus, the purpose of this study was to test whether or not Aβ affects burrowing while inducing hippocampus-dependent memory impairment. Surprisingly, our results show that intrahippocampal application of Aβ increases burrowing while inducing memory impairment. We consider that this Aβ-induced increase in burrowing might be associated with a mild anxiety state, which was revealed by increased freezing behavior in the open field, and conclude that Aβ-induced hippocampal dysfunction is reflected in the impairment of ADL and memory, through mechanisms yet to be determined.
Marciniak, Elodie; Faivre, Emilie; Dutar, Patrick; Alves Pires, Claire; Demeyer, Dominique; Caillierez, Raphaëlle; Laloux, Charlotte; Buée, Luc; Blum, David; Humez, Sandrine
Chemokines are signaling molecules playing an important role in immune regulations. They are also thought to regulate brain development, neurogenesis and neuroendocrine functions. While chemokine upsurge has been associated with conditions characterized with cognitive impairments, their ability to modulate synaptic plasticity remains ill-defined. In the present study, we specifically evaluated the effects of MIP1-α/CCL3 towards hippocampal synaptic transmission, plasticity and spatial memory. We found that CCL3 (50 ng/ml) significantly reduced basal synaptic transmission at the Schaffer collateral-CA1 synapse without affecting NMDAR-mediated field potentials. This effect was ascribed to post-synaptic regulations, as CCL3 did not impact paired-pulse facilitation. While CCL3 did not modulate long-term depression (LTD), it significantly impaired long-term potentiation (LTP), an effect abolished by Maraviroc, a CCR5 specific antagonist. In addition, sub-chronic intracerebroventricular (icv) injections of CCL3 also impair LTP. In accordance with these electrophysiological findings, we demonstrated that the icv injection of CCL3 in mouse significantly impaired spatial memory abilities and long-term memory measured using the two-step Y-maze and passive avoidance tasks. These effects of CCL3 on memory were inhibited by Maraviroc. Altogether, these data suggest that the chemokine CCL3 is an hippocampal neuromodulator able to regulate synaptic plasticity mechanisms involved in learning and memory functions.
Full Text Available Objective To investigate whether gait dysfunction is a predictor of severe spatial learning and memory impairment in aged mice. Methods A total of 100 12-month-old male mice that had no obvious abnormal motor ability and whose Morris water maze performances were not significantly different from those of two-month-old male mice were selected for the study. The selected aged mice were then divided into abnormal or normal gait groups according to the results from the quantitative gait assessment. Gaits of aged mice were defined as abnormal when the values of quantitative gait parameters were two standard deviations (SD lower or higher than those of 2-month-old male mice. Gait parameters included stride length, variability of stride length, base of support, cadence, and average speed. After nine months, mice exhibiting severe spatial learning and memory impairment were separated from mice with mild or no cognitive dysfunction. The rate of severe spatial learning and memory impairment in the abnormal and normal gait groups was tested by a chi-square test and the correlation between gait dysfunction and decline in cognitive function was tested using a diagnostic test. Results The 12-month-old aged mice were divided into a normal gait group (n = 75 and an abnormal gait group (n = 25. Nine months later, three mice in the normal gait group and two mice in the abnormal gait group had died. The remaining mice were subjected to the Morris water maze again, and 17 out of 23 mice in the abnormal gait group had developed severe spatial learning and memory impairment, including six with stride length deficits, 15 with coefficient of variation (CV in stride length, two with base of support (BOS deficits, five with cadence dysfunction, and six with average speed deficits. In contrast, only 15 out of 72 mice in the normal gait group developed severe spatial learning and memory impairment. The rate of severe spatial learning and memory impairment was
Rogers, Timothy T.; Graham, Kim S.; Patterson, Karalyn
To investigate how basic aspects of perception are shaped by acquired knowledge about the world, we assessed colour perception and cognition in patients with semantic dementia (SD), a disorder that progressively erodes conceptual knowledge. We observed a previously undocumented pattern of impairment to colour perception and cognition characterized by: (i) a normal ability to discriminate between only subtly different colours but an impaired ability to group different colours into categories, (ii) normal perception and memory for the colours red, green, and blue but impaired perception and memory for colours lying between these regions of a fully-saturated and luminant spectrum, and (iii) normal naming of polar colours in the opponent-process colour system (red, green, blue, yellow, white, and black) but impaired naming of other basic colours (brown, gray, pink, and orange). The results suggest that fundamental aspects of perception can be shaped by acquired knowledge about the world, but only within limits. PMID:25637227
Malstädt, Nadine; Hasselhorn, Marcus; Lehmann, Martin
This study examined supraspan free recall in children with and without spelling impairment. A repeated free recall task involving overt rehearsal and three computer-based adaptive working memory tasks were administered to 54 eight-year-old children. Children without spelling impairments tended to recall more items than did those children with spelling deficits. Video analyses revealed that recall behaviour was similar in impaired and unimpaired children, indicating that both groups applied similar learning activities. Group differences in number of recalled items were attributed to differences in working memory subcapacities between children with and without spelling impairment, especially with regard to central executive and phonological loop functioning. Copyright © 2012 John Wiley & Sons, Ltd.
Rienstra, Anne; Groot, Paul F C; Spaan, Pauline E J; Majoie, Charles B L M; Nederveen, Aart J; Walstra, Gerard J M; de Jonghe, Jos F M; van Gool, Willem A; Olabarriaga, Silvia D; Korkhov, Vladimir V; Schmand, Ben
Patients with mild cognitive impairment (MCI) do not always convert to dementia. In such cases, abnormal neuropsychological test results may not validly reflect cognitive symptoms due to brain disease, and the usual brain-behavior relationships may be absent. This study examined symptom validity in a memory clinic sample and its effect on the associations between hippocampal volume and memory performance. Eleven of 170 consecutive patients (6.5%; 13% of patients younger than 65 years) referred to memory clinics showed noncredible performance on symptom validity tests (SVTs, viz. Word Memory Test and Test of Memory Malingering). They were compared to a demographically matched group (n = 57) selected from the remaining patients. Hippocampal volume, measured by an automated volumetric method (Freesurfer), was correlated with scores on six verbal memory tests. The median correlation was r = .49 in the matched group. However, the relation was absent (median r = -.11) in patients who failed SVTs. Memory clinic samples may include patients who show noncredible performance, which invalidates their MCI diagnosis. This underscores the importance of applying SVTs in evaluating patients with cognitive complaints that may signify a predementia stage, especially when these patients are relatively young.
Xie, Dan-dan; Cheng, Huai-dong; Yin, Chang-lin; Lü, Xin-yi; Wang, Kai
To explore the profile of false memory in aMCI (amnesia mild cognitive impairment) and to elucidate the neuropsychological mechanism of false memory. False memory provoked by pictures and feeling-of-knowing (FOK) test in episodic memory (EM) were conducted in 25 aMCI patients at our hospital from October 2009 to May 2010. And 25 age and education level-matched healthy patients were recruited into the healthy control (HC) group. As compared with HC group, the rate of false memory was higher in the aMCI group. The rate of false memory in recall stage was 26% ± 7% and that of questionnaire stage 28% ± 12%. And the difference between two group was significant (t = 14.437, 7.597, P false recognition in the aMCI group (41% ± 10%) was higher than the HC group. And the difference was significant (t = 4.207, P false memory in recall and questionnaire stages were positively correlated with FOK-EM in aMCI group (r = 0.563, 0.705, P false memory provoked by pictures. The deficit of memory monitoring in aMCI may be the foundation of false memory.
Guderian, Sebastian; Dzieciol, Anna M; Gadian, David G; Jentschke, Sebastian; Doeller, Christian F; Burgess, Neil; Mishkin, Mortimer; Vargha-Khadem, Faraneh
The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is
Liu, Huiying; Yang, Jinghua; Liu, Qiufang; Jin, Cuihong; Wu, Shengwen; Lu, Xiaobo; Zheng, Linlin; Xi, Qi; Cai, Yuan
Rare earth elements (REEs) are used in many fields for their diverse physical and chemical properties. Surveys have shown that REEs can impair learning and memory in children and cause neurobehavioral defects in animals. However, the mechanism underlying these impairments has not yet been completely elucidated. Lanthanum (La) is often selected to study the effects of REEs. The aim of this study was to investigate the spatial memory impairments induced by lanthanum chloride (LaCl3) and the probable underlying mechanism. Wistar rats were exposed to LaCl3 in drinking water at 0 % (control, 0 mM), 0.25 % (18 mM), 0.50 % (36 mM), and 1.00 % (72 mM) from birth to 2 months after weaning. LaCl3 considerably impaired the spatial learning and memory of rats in the Morris water maze test, damaged the synaptic ultrastructure and downregulated the expression of p-MEK1/2, p-ERK1/2, p-MSK1, p-CREB, c-FOS and BDNF in the hippocampus. These results indicate that LaCl3 exposure impairs the spatial learning and memory of rats, which may be attributed to disruption of the synaptic ultrastructure and inhibition of the ERK/MSK1 signaling pathway in the hippocampus.
Harrison, Neil A; Doeller, Christian F; Voon, Valerie; Burgess, Neil; Critchley, Hugo D
Inflammation impairs cognitive performance and is implicated in the progression of neurodegenerative disorders. Rodent studies demonstrated key roles for inflammatory mediators in many processes critical to memory, including long-term potentiation, synaptic plasticity, and neurogenesis. They also demonstrated functional impairment of medial temporal lobe (MTL) structures by systemic inflammation. However, human data to support this position are limited. Sequential fluorodeoxyglucose positron emission tomography together with experimentally induced inflammation was used to investigate effects of a systemic inflammatory challenge on human MTL function. Fluorodeoxyglucose positron emission tomography scanning was performed in 20 healthy participants before and after typhoid vaccination and saline control injection. After each scanning session, participants performed a virtual reality spatial memory task analogous to the Morris water maze and a mirror-tracing procedural memory control task. Fluorodeoxyglucose positron emission tomography data demonstrated an acute reduction in human MTL glucose metabolism after inflammation. The inflammatory challenge also selectively compromised human spatial, but not procedural, memory; this effect that was independent of actions on motivation or psychomotor response. Effects of inflammation on parahippocampal and rhinal glucose metabolism directly mediated actions of inflammation on spatial memory. These data demonstrate acute sensitivity of human MTL to mild peripheral inflammation, giving rise to associated functional impairment in the form of reduced spatial memory performance. Our findings suggest a mechanism for the observed epidemiologic link between inflammation and risk of age-related cognitive decline and progression of neurodegenerative disorders including Alzheimer's disease. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Oedekoven, Christiane S H; Jansen, Andreas; Keidel, James L; Kircher, Tilo; Leube, Dirk
Associative memory is essential to everyday activities, such as the binding of faces and corresponding names to form single bits of information. However, this ability often becomes impaired with increasing age. The most important neural substrate of associative memory is the hippocampus, a structure crucially implicated in the pathogenesis of Alzheimer's disease (AD). The main aim of this study was to compare neural correlates of associative memory in healthy aging and mild cognitive impairment (MCI), an at-risk state for AD. We used fMRI to investigate differences in brain activation and connectivity between young controls (n = 20), elderly controls (n = 32) and MCI patients (n = 21) during associative memory retrieval. We observed lower hippocampal activation in MCI patients than control groups during a face-name recognition task, and the magnitude of this decrement was correlated with lower associative memory performance. Further, increased activation in precentral regions in all older adults indicated a stronger involvement of the task positive network (TPN) with age. Finally, functional connectivity analysis revealed a stronger link of hippocampal and striatal components in older adults in comparison to young controls, regardless of memory impairment. In elderly controls, this went hand-in-hand with a stronger activation of striatal areas. Increased TPN activation may be linked to greater reliance on cognitive control in both older groups, while increased functional connectivity between the hippocampus and the striatum may suggest dedifferentiation, especially in elderly controls.
Full Text Available Early stages of Alzheimer’s disease (AD are characterized by neuropathological changes within the medial temporal lobe cortex (MTLC, which lead to characteristic impairments in episodic memory, i.e., amnestic mild cognitive impairment (aMCI. Here, we tested the neural correlates of this memory impairment using event-related potentials (ERPs and voxel-based morphometry. Twenty-four participants were instructed to encode lists of words and were tested in a yes/no recognition memory task. The dual-process model of recognition memory dissociates between acontextual familiarity and recollection of contextual details. The early frontal ERP old/new-effect, which is thought to represent a neural correlate of familiarity-based memory, was absent in aMCI, whereas the control group showed a significant early old/new effect at frontal electrodes. This effect was positively correlated with behavioral episodic memory performance. Analyses of brain morphology revealed a focused gray matter loss in the inferior and medial temporal lobes in aMCI versus healthy controls. Moreover, the positive correlation between gray matter volume in the MTLC and the familiarity-related early frontal old/new effect supports the notion that this effect relies upon the integrity of the MTLC. Thus, the present findings might provide a further functional marker for prodromal AD.
Full Text Available The effect of emotional arousal on memory presents a complex pattern with previous studies reporting conflicting results of both improved and reduced memory performance following arousal manipulations. In this study we further tested the effect of negative emotional arousal (NEA on individual-item recognition and associative recognition of neutral stimuli in healthy participants, and hypothesized that NEA will particularly impair associative memory performance. The current study consists of two experiments; in both, participants studied a list of word-pairs and were then tested for items (items recognition test, and for associations (associative recognition test. In the first experiment, the arousal manipulation was induced by flashing emotionally-negative or neutral pictures between study-pairs while in the second experiment arousal was induced by presenting emotionally-negative or neutral pictures between lists. The results of the two experiments converged and supported an associative memory deficit observed under NEA conditions. We suggest that NEA is associated with an altered ability to bind one stimulus to another as a result of impaired recollection, resulting in poorer associative memory performance. The current study findings may contribute to the understanding of the mechanism underlying memory impairments reported in disorders associated with traumatic stress.
Hanslmayr, Simon; Matuschek, Jonas; Fellner, Marie-Christin
Brain oscillations across all frequency bands play a key role for memory formation. Specifically, desynchronization of local neuronal assemblies in the left inferior prefrontal cortex (PFC) in the beta frequency (∼18 Hz) has been shown to be central for encoding of verbal memories. However, it remains elusive whether prefrontal beta desynchronization is causally relevant for memory formation and whether these endogenous beta oscillations can be entrained by external stimulation. By using combined EEG-TMS (transcranial magnetic stimulation), we here address these fundamental questions in human participants performing a word-list learning task. Confirming our predictions, memory encoding was selectively impaired when the left inferior frontal gyrus (IFG) was driven at beta (18.7 Hz) compared to stimulation at other frequencies (6.8 Hz and 10.7 Hz) and to ineffective sham stimulation (18.7 Hz). Furthermore, a sustained oscillatory "echo" in the left IFG, which outlasted the stimulation period by approximately 1.5 s, was observed solely after beta stimulation. The strength of this beta echo was related to memory impairment on a between-subjects level. These results show endogenous oscillatory entrainment effects and behavioral impairment selectively in beta frequency for stimulation of the left IFG, demonstrating an intimate causal relationship between prefrontal beta desynchronization and memory formation. Copyright © 2014 Elsevier Ltd. All rights reserved.
Cha, Hye Jin; Kim, Yun Ji; Jeon, Seo Young; Kim, Young-Hoon; Shin, Jisoon; Yun, Jaesuk; Han, Kyoungmoon; Park, Hye-Kyung; Kim, Hyung Soo
Although alkyl nitrites are used as recreational drugs, there is only little research data regarding their effects on the central nervous system including their neurotoxicity. This study investigated the neurotoxicity of three representative alkyl nitrites (isobutyl nitrite, isoamyl nitrite, and butyl nitrite), and whether it affected learning/memory function and motor coordination in rodents. Morris water maze test was performed in mice after administrating the mice with varying doses of the substances in two different injection schedules of memory acquisition and memory retention. A rota-rod test was then performed in rats. All tested alkyl nitrites lowered the rodents' capacity for learning and memory, as assessed by both the acquisition and retention tests. The results of the rota-rod test showed that isobutyl nitrite in particular impaired motor coordination in chronically treated rats. The mice chronically injected with isoamyl nitrite also showed impaired function, while butyl nitrite had no significant effect. The results of the water maze test suggest that alkyl nitrites may impair learning and memory. Additionally, isoamyl nitrite affected the rodents' motor coordination ability. Collectively, our findings suggest that alkyl nitrites may induce neurotoxicity, especially on the aspect of learning and memory function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Ren, Dayong; Zhao, Fanrui; Liu, Chunlei; Wang, Ji; Guo, Yong; Liu, Jingsheng; Min, Weihong
Walnut protein, which is obtained as a by-product of oil expression, has not been used efficiently. Although walnuts are beneficial for cognitive functioning, the potential of their protein composition in strengthening learning and memory functions remains unknown. In this research, the inhibition of memory impairment by the Manchurian walnut hydrolyzed peptide (MWHP) was evaluated. Small-molecular-weight MWHP (<3 kDa) achieved the optimal antioxidative activity. Therefore, MWHP (<3 kDa) was subjected to the following mice trials to evaluate its attenuation effect on memory impairment. In the Morris water maze test, MWHP shortened the total path for searching the platform, reduced the escape latency, and increased the dwelling distance and time in the coverage zone. MWHP also prolonged the latency and diminished errors in the passive avoidance response tests. These behavioral tests demonstrated that MWHP could inhibit scopolamine-induced memory impairment. MWHP improved memory by reducing oxidative stress, inhibiting apoptosis, regulating neurotransmitter functions, maintaining hippocampal CA3 pyramidal neurons, and increasing p-CaMK II levels in brain tissues. Experimental results proved that MWHP exhibits potential in improving memory and should be used to develop novel functional food. This article is protected by copyright. All rights reserved.
Nasehi, Mohammad; Morteza-Zadeh, Parastoo; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza
In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABA A receptor agents on amnesia induced by a β-carboline alkaloid, harmane in mice. We used a single-trial step-down passive avoidance task to assess memory retention and then, open-field test to assess locomotor activity. The results indicated that post-training intra-CA1 injections of bicuculline - a GABA A receptor antagonist - had no significant effect, while muscimol (0.01 and 0.1μg/mouse) - a GABA A receptor agonist - impaired memory consolidation. Post-training intra-peritoneal (i.p.) infusion of harmane (3 and 5mg/kg) decreased memory consolidation. Furthermore, post-training intra-CA1 administration of sub-threshold dose of bicuculline (0.001μg/mouse) restored, whereas muscimol (0.001μg/mouse) potentiated impairment of memory consolidation induced by harmane. The isobologram analysis revealed that there is an additive effect between harmane and muscimol on impairment of memory consolidation. Moreover, all above doses of drugs did not alter locomotor activity. These findings suggest that GABA A receptors of the CA1 area, at least partly, play a role in modulating the effect of harmane on memory consolidation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Popp, Earl Y.; Serra, Michael J.
Recent research suggests that human memory systems evolved to remember animate things better than inanimate things. In the present experiments, we examined whether these effects occur for both free recall and cued recall. In Experiment 1, we directly compared the effect of animacy on free recall and cued recall. Participants studied lists of…
Kumari, Punita; Kauser, Hina; Wadhwa, Meetu; Roy, Koustav; Alam, Shahnawaz; Sahu, Surajit; Kishore, Krishna; Ray, Koushik; Panjwani, Usha
Fear memory is essential for survival, and its dysregulation leads to disorders. High altitude hypobaric hypoxia (HH) is known to induce cognitive decline. However, its effect on fear memory is still an enigma. We aimed to investigate the temporal effect of HH on fear conditioning and the underlying mechanism. Adult male Sprague-Dawley rats were trained for fear conditioning and exposed to simulated HH equivalent to 25,000 ft for different durations (1, 3, 7, 14 and 21 days). Subsequently, rats were tested for cued and contextual fear conditioning. Neuronal morphology, apoptosis and DNA fragmentation were studied in the medial prefrontal cortex (mPFC), hippocampus and basolateral amygdala (BLA). We observed significant deficit in cued and contextual fear acquisition (at 1, 3 and 7 days) and consolidation (cued at 1 and 3 days and contextual fear at 1, 3 and 7 days) under HH. HH exposure with retraining showed the earlier restoration of contextual fear memory. Further, we found a gradual increase in the number of pyknotic and apoptotic neurons together with the increase in DNA fragmentation in mPFC, hippocampus, and BLA up to 7 days of HH exposure. The present study concludes that HH exposure equivalent to 25000 ft induced cued and contextual fear memory deficit (acquisition and consolidation) which is found to be correlated with the neurodegenerative changes in the limbic brain regions. Copyright © 2018. Published by Elsevier B.V.
Mitchell, Anna S.; Dalrymple-Alford, John C.
Damage to the medial region of the thalamus, both in clinical cases (e.g., patients with infarcts or the Korsakoff's syndrome) and animal lesion models, is associated with variable amnesic deficits. Some studies suggest that many of these memory deficits rely on the presence of lateral thalamic lesions (LT) that include the intralaminar nuclei,…
Verwey, B.; Eling, P.A.T.M.; Wientjes, H.J.F.M.; Zitman, F.G.
Backgroud: a prospective study was done to investigate the presence of anterograde amnesia in suicide attempters who took benzodiazepines (BZ) and to study the correlation with sedation. Method: in 43 patients, who attempted suicide by taking benzodiazepines, memory perfomrance was tested on a
Emanuella Silva Joventino; Lydia Vieira Freitas; Raul Feitoza Rogério; Thaís Marques Lima; Levânia Maria Benevides Dias; Lorena Barbosa Ximenes
The purpose of this study was to describe the experience of nursing students in education interaction with preschoolers’ caregivers as far as prevention of enteroparasitosis in preschoolers is concerned.This is a descriptive study, like a reporting experience. This activity counted with the participation of 09 caregivers, in the months of June and October 2006. The group had active participation in the experiment and the knowledge shared from a Giant Memory Game with pictures dealing with the...
Wardell, Jeffrey D.; Quilty, Lena C.; Hendershot, Christian S.
Impaired control over alcohol is an important risk factor for heavy drinking among young adults and may mediate, in part, the association between personality risk and alcohol problems. Research suggests that trait impulsivity is associated with impaired control over alcohol; however, few studies of this association have included a range of impulsivity facets. The purpose of this study was to examine specific pathways from higher-order impulsivity factors to alcohol problems mediated via impaired control over alcohol. We also examined the moderating role of working memory in these associations. Young heavy drinkers (N=300) completed two multidimensional impulsivity measures (UPPS-P and BIS-11) along with self-report measures of impaired control over alcohol, alcohol use, and alcohol problems. Working memory was assessed using a computerized digit span task. Results showed that the impulsivity facets loaded onto two higher-order factors that were labeled response and reflection impulsivity. Response impulsivity predicted unique variance in self-reported impaired control and alcohol problems, whereas reflection impulsivity predicted unique variance in heavy drinking frequency only. Further, significant indirect associations were observed from response and reflection impulsivity to alcohol problems mediated via impaired control and heavy drinking frequency, respectively. Working memory and sensation seeking were not uniquely associated with the alcohol variables, and no support was found for the moderating role of working memory. The results help to clarify associations among impulsivity, impaired control, and alcohol problems, suggesting that impaired control may play a specific role in the pathway to alcohol problems from response impulsivity but not from reflection impulsivity. PMID:27269291
Lu, Chunming; Qi, Zhenghan; Harris, Adrianne; Weil, Lisa Wisman; Han, Michelle; Halverson, Kelly; Perrachione, Tyler K.; Kjelgaard, Margaret; Wexler, Kenneth; Tager-Flusberg, Helen; Gabrieli, John D. E.
Background Individuals with reading disability and individuals with autism spectrum disorder (ASD) are characterized, respectively, by their difficulties in reading and social communication, but both groups often have impaired phonological working memory (PWM). It is not known whether the impaired PWM reflects distinct or shared neuroanatomical abnormalities in these two diagnostic groups. Methods White-matter structural connectivity via diffusion weighted imaging was examined in 64 children,...
Tveden-Nyborg, Pernille Yde; Johansen, Louise Kruse; Raida, Zindy
C deficiency and neuronal damage in newborn guinea pigs. DESIGN: Thirty 6- to 7-d-old guinea pigs were randomly assigned to 2 groups to receive either a vitamin C-sufficient diet or the same diet containing a low concentration of vitamin C (but adequate to prevent scurvy) for 2 mo. Spatial memory...... was assessed by the Morris Water Maze, and hippocampal neuron numbers were quantified by stereologic techniques. RESULTS: The results showed a reduction in spatial memory (P ... a lower total number of neurons in hippocampal subdivisions (dentate gyrus, cornu ammonis 1, and cornu ammonis 2-3) than did the normal controls (P impaired neuronal development and a functional decrease...
Ito, Koichi; Arko, Matevž; Kawaguchi, Tomohiro; Kikusui, Takefumi; Kuwahara, Masayoshi; Tsubone, Hirokazu
Taurine is a semi-essential amino acid widely distributed in the body and we take in it from a wide range of nutritive-tonic drinks to improve health. To date, we have elucidated that oral supplementation of taurine does not affect learning and memory in the rat. However, there are few studies concerning the direct effects of taurine in the brain at the behavior level. In this study, we intracerebroventricularly administered taurine to rats and aimed to elucidate the acute effects on learning and memory using the Morris water maze method. Escape latency, swim distance, and distance to zone, which is the integral of the distance between the rats and the platform for every 0.16 seconds, were adopted as parameters of the ability of learning and memory. We also tried to evaluate the effect of intraperitoneal taurine administration. Escape latency, swim distance, and distance to zone were significantly longer in the intracerebroventricularly taurine-administered rats than in the saline-administered rats. Mean swimming velocity was comparable between these two groups, although the physical performance was improved by taurine administration. Probe trials showed that the manner of the rats in finding the platform was comparable. In contrast, no significant differences were found between the intraperitoneally taurine-administered rats and the saline-administered rats. These results indicate that taurine administered directly into the brain ventricle suppresses and delays the ability of learning and memory in rats. In contrast, it is implied that taurine administered peripherally was not involved in learning and memory.
Kittelberger, Kara A; Piazza, Fabrizio; Tesco, Giuseppina; Reijmers, Leon G
Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD). It has been proposed that soluble amyloid-beta (Abeta) oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss.
Kittelberger, Kara A.; Piazza, Fabrizio; Tesco, Giuseppina; Reijmers, Leon G.
Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD). It has been proposed that soluble amyloid-beta (Abeta) oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss. PMID:22238679
Kara A Kittelberger
Full Text Available Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD. It has been proposed that soluble amyloid-beta (Abeta oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss.
Das, Sudeshna; Mishra, K P; Ganju, Lilly; Singh, S B
Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region. Active microglial and reactive astrocytic makers were also downregulated after andrographolide treatment. Andrographolide suppressed overexpression of microglial MIP-1α, P2X7 receptor and its downstream signaling mediators including-inflammasome NLRP3, caspase1 and mature IL-1β. Furthermore, in vivo maze studies suggested that andrographolide treatment reversed LPS-induced behavioural and working memory disturbances including regulation of expression of protein markers like PKC, p-CREB, amyloid beta, APP, p-tau, synapsin and PSD-95. Andrographolide, by lowering expression of pro apoptotic genes and enhancing the expression of anti-apoptotic gene showed its anti-apoptotic nature that in turn reduces neurodegeneration. Morphology studies using Nissl and FJB staining also showed the neuroprotective effect of andrographolide in the prefrontal cortex region. The above studies indicated that andrographolide prevented neuroinflammation-associated neurodegeneration and improved synaptic plasticity markers in cortical as well as hippocampal region which suggests that andrographolide could be a novel pharmacological countermeasure for the treatment of neuroinflammation and neurological disorders related to memory impairment. Copyright © 2017 Elsevier B.V. All rights reserved.
Andero, Raül; Daviu, Núria; Escorihuela, Rosa Maria; Nadal, Roser; Armario, Antonio
Post-traumatic stress disorder (PTSD) patients show cognitive deficits, but it is unclear whether these are a consequence of the pathology or a pre-existing factor of vulnerability to PTSD. Animal models may help to demonstrate whether or not exposure to certain stressors can actually induce long-lasting (LL; days) impairment of hippocampus-dependent memory tasks and to characterize neurobiological mechanisms. Adult male rats were exposed to 2-h immobilization on boards (IMO), a severe stressor, and spatial learning in the Morris water maze (MWM) was studied days later. Exposure to IMO did not modify learning or short-term memory in the MWM when learning started 3 or 9 days after IMO, but stressed rats did show impaired long-term memory at both times, in accordance with the severity of the stressor. New treatments to prevent PTSD symptoms are needed. Thus, considering the potential protective role of brain-derived neurotrophic factor (BDNF) on hippocampal function, 7,8-dihydroxyflavone (7,8-DHF), a recently characterized agonist of the BDNF receptor TrkB, was given before or after IMO in additional experiments. Again, exposure to IMO resulted in LL deficit in long-term memory, and such impairment was prevented by the administration of 7,8-DHF either 2 h prior IMO or 8 h after the termination of IMO. The finding that IMO-induced impairment of spatial memory was prevented by pharmacological potentiation of TrkB pathway with 7,8-DHF even when the drug was given 8 h after IMO suggests that IMO-induced impairment is likely to be a LL process that is strongly dependent on the integrity of the BDNF-TrkB system and is susceptible to poststress therapeutic interventions. 7,8-DHF may represent a new therapeutic approach for early treatment of subjects who have suffered traumatic experiences. Copyright © 2010 Wiley Periodicals, Inc.
Lum, Jarrad A. G.; Conti-Ramsden, Gina
This review examined the status of long-term memory systems in specific language impairment (SLI)--declarative memory and aspects of procedural memory in particular. Studies included in the review were identified following a systematic search of the literature and findings combined using meta-analysis. This review showed that individuals with SLI…
Potvin, Stephane; Briand, Catherine; Prouteau, Antoinette; Bouchard, Roch-Hugo; Lipp, Olivier; Lalonde, Pierre; Nicole, Luc; Lesage, Alain; Stip, Emmanuel
It has been suggested that in order to sustain the lifestyle of substance abuse, addicted schizophrenia patients would have less negative symptoms, better social skills, and less cognitive impairments. Mounting evidence supports the first two assumptions, but data lack regarding cognition in dual diagnosis schizophrenia. Seventy-six schizophrenia…
Virginie F Labrousse
Full Text Available Regular consumption of food enriched in omega3 polyunsaturated fatty acids (ω3 PUFAs has been shown to reduce risk of cognitive decline in elderly, and possibly development of Alzheimer's disease. Docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA are the most likely active components of ω3-rich PUFAs diets in the brain. We therefore hypothesized that exposing mice to a DHA and EPA enriched diet may reduce neuroinflammation and protect against memory impairment in aged mice. For this purpose, mice were exposed to a control diet throughout life and were further submitted to a diet enriched in EPA and DHA during 2 additional months. Cytokine expression together with a thorough analysis of astrocytes morphology assessed by a 3D reconstruction was measured in the hippocampus of young (3-month-old and aged (22-month-old mice. In addition, the effects of EPA and DHA on spatial memory and associated Fos activation in the hippocampus were assessed. We showed that a 2-month EPA/DHA treatment increased these long-chain ω3 PUFAs in the brain, prevented cytokines expression and astrocytes morphology changes in the hippocampus and restored spatial memory deficits and Fos-associated activation in the hippocampus of aged mice. Collectively, these data indicated that diet-induced accumulation of EPA and DHA in the brain protects against neuroinflammation and cognitive impairment linked to aging, further reinforcing the idea that increased EPA and DHA intake may provide protection to the brain of aged subjects.
Conti-Ramsden, Gina; Ullman, Michael T; Lum, Jarrad A G
What memory systems underlie grammar in children, and do these differ between typically developing (TD) children and children with specific language impairment (SLI)? Whilst there is substantial evidence linking certain memory deficits to the language problems in children with SLI, few studies have investigated multiple memory systems simultaneously, examining not only possible memory deficits but also memory abilities that may play a compensatory role. This study examined the extent to which procedural, declarative, and working memory abilities predict receptive grammar in 45 primary school aged children with SLI (30 males, 15 females) and 46 TD children (30 males, 16 females), both on average 9;10 years of age. Regression analyses probed measures of all three memory systems simultaneously as potential predictors of receptive grammar. The model was significant, explaining 51.6% of the variance. There was a significant main effect of learning in procedural memory and a significant group × procedural learning interaction. Further investigation of the interaction revealed that procedural learning predicted grammar in TD but not in children with SLI. Indeed, procedural learning was the only predictor of grammar in TD. In contrast, only learning in declarative memory significantly predicted grammar in SLI. Thus, different memory systems are associated with receptive grammar abilities in children with SLI and their TD peers. This study is, to our knowledge, the first to demonstrate a significant group by memory system interaction in predicting grammar in children with SLI and their TD peers. In line with Ullman's Declarative/Procedural model of language and procedural deficit hypothesis of SLI, variability in understanding sentences of varying grammatical complexity appears to be associated with variability in procedural memory abilities in TD children, but with declarative memory, as an apparent compensatory mechanism, in children with SLI.
Park, Sohee; Gooding, Diane C
This chapter focuses on the viability of working memory impairment as an endophenotypic marker of a schizophrenia diathesis. It begins with an introduction of the construct of working memory. It follows with a review of the operational criteria for defining an endophenotype. Research findings regarding the working memory performance of schizophrenia and schizophrenia-spectrum patients, first-degree relatives of schizophrenia patients and healthy controls, are reviewed in terms of the criteria for being considered an endophenotypic marker. Special attention is paid to specific components of the working memory deficit (namely, encoding, maintenance, and manipulation), in terms of which aspects are likely to be the best candidates for endophenotypes. We consider the extant literature regarding working memory performance in bipolar disorder and major depression in order to address the issue of relative specificity to schizophrenia. Despite some unresolved issues, it appears that working memory impairment is a very promising candidate for an endophenotypic marker of a schizophrenia diathesis but not for mood disorders. Throughout this chapter, we identify future directions for research in this exciting and dynamic area of research and evaluate the contribution of working memory research to our understanding of schizophrenia.
Full Text Available This review focuses on the viability of working memory impairment as an endophenotypic marker of a schizophrenia diathesis. It begins with an introduction of the construct of working memory. It follows with a consideration of the operational criteria for defining an endophenotype. Research findings regarding the working memory performance of schizophrenia and schizophrenia-spectrum patients, first-degree relatives of schizophrenia patients and healthy controls, are reviewed in terms of the criteria for being considered an endophenotypic marker. Special attention is paid to specific components of the working memory deficit (namely, encoding, maintenance, and manipulation, in terms of which aspects are likely to be the best candidates for endophenotypes. We examine the extant literature regarding working memory performance in bipolar disorder and major depression in order to address the issue of relative specificity to schizophrenia. Despite some unresolved issues, it appears that working memory impairment is a very promising candidate for an endophenotypic marker of a schizophrenia diathesis but not for mood disorders. Throughout this review, we identify future directions for research in this exciting and dynamic area of research and evaluate the contribution of working memory research to our understanding of schizophrenia.
Celia J A Morgan
Full Text Available Ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, is rising in popularity as a drug of abuse. Preliminary evidence suggests that chronic, heavy ketamine use may have profound effects on spatial memory but the mechanism of these deficits is as yet unclear. This study aimed to examine the neural mechanism by which heavy ketamine use impairs spatial memory processing. In a sample of 11 frequent ketamine users and 15 polydrug controls, matched for IQ, age and years in education. We used fMRI utilising an ROI approach to examine the neural activity of three regions known to support successful navigation; the hippocampus, parahippocampal gyrus and the caudate nucleus during a virtual reality task of spatial memory. Frequent ketamine users displayed spatial memory deficits, accompanied by and related to, reduced activation in both the right hippocampus and left parahippocampal gyrus during navigation from memory, and in the left caudate during memory updating, compared to controls. Ketamine users also exhibited schizotypal and dissociative symptoms that were related to hippocampal activation. Impairments in spatial memory observed in ketamine users are related to changes in medial temporal lobe activation. Disrupted medial temporal lobe function may be a consequence of chronic ketamine abuse and may relate to schizophrenia-like symptomatology observed in ketamine users.
Godinho, Antonio Francisco; de Oliveira Souza, Ana Carolina; Carvalho, Caio Cristóvão; Horta, Daniel França; De Fraia, Daniel; Anselmo, Fabio; Chaguri, João Leandro; Faria, Caique Aparecido
Fipronil (F) a pesticide considered of second generation cause various toxic effects in target and non-target organisms including humans in which provoke neurotoxicity, having the antagonism of gamma-amino butyric acid (GABA) as their main mechanism for toxic action. GABAergic system has been involved in processes related to the memory formation and consolidation. The present work studied the importance of GABA to the mechanisms involved in the very early development of fipronil-induced memory impairment in rats. Memory behavior was assessed using new object recognition task (ORT) and eight radial arm maze task (8-RAM) to study effects on cognitive and spatial memory. Locomotor behavior was assessed using open field task (OF). The dose of fipronil utilized was studied through a pilot experiment. The GABA antagonist picrotoxin (P) was used to enhance fipronil effects on GABAergic system. Fipronil or picrotoxin decrease memory studied in ORT and 8-RAM tasks. Additionally, F and P co-exposure enhanced effects on memory compared to controls, F, and P, suggesting strongly a GABAergic effect. Weight gain modulation and fipronil in blood were utilized as animal's intoxication indicators. In conclusion, here we report that second-generation pesticides, such as fipronil, can have toxic interactions with the CNS of mammals and lead to memory impairment by modulating the GABAergic system. Copyright © 2016 Elsevier Inc. All rights reserved.
Haddad, Anneke D M; Williams, J Mark G; McTavish, Sarah F B; Harmer, Catherine J
Depressed patients perform poorly on tests of autobiographical memory specificity (AMS); this may have negative consequences for other important cognitive abilities, delays recovery from mood episodes, and, in recovered patients, may mediate vulnerability to future episodes. Although the cognitive mechanisms underlying AMS deficits are beginning to be understood, the neurobiological mechanisms remain unclear. Serotonin is implicated in both depression and long-term memory; therefore, temporary lowering of brain serotonin function via acute tryptophan depletion (ATD) offers a means of studying the role of serotonin in autobiographical memory specificity. In this study, 24 previously depressed women underwent low-dose ATD or sham depletion and completed tests of initial and delayed memory, recollection- and familiarity-based recognition, and AMS. ATD did not differentially affect state mood. Compared with sham depletion, ATD impaired immediate recall on the Auditory Verbal Learning Test. Although ATD did not differentially impair recollection- and familiarity-based recognition, it did slow recognition of positive words. ATD also reduced autobiographical memory specificity in response to negative cue words. The results confirm previous findings that low-dose ATD can reinstate depression-congruent biases in cognition without causing depressive mood in vulnerable populations. The ATD-induced reduction in memory specificity suggests that serotonergic dysfunction may mediate depressive deficits in autobiographical memory; the interaction of cognitive and neurobiological vulnerability mechanisms is discussed.
Crawford, Trevor J; Higham, Steve
Dementia (most notably, Alzheimer's Disease) is often associated with impairments of both working memory and inhibitory control. However, it is unclear whether these are functionally distinct impairments. We addressed the issue of whether working memory and inhibitory control can be dissociated, using data from a sample of patients who were recruited in a longitudinal study (Crawford et al., 2013, 2015). The first case revealed a preserved working memory capacity together with poor inhibitory control in the anti-saccade task. A longitudinal follow-up revealed that the defective inhibitory control emerged 12-months before the dementia was evident on the mini-mental state examination assessment. A second case revealed a poor working memory together with a well-preserved level of inhibitory control. The dissociation of working memory and inhibitory control was confirmed statistically in 7 additional cases. These findings yield converging evidence that working memory and inhibitory control are distinct cognitive operations and challenges the Kimberg and Farah (2000) cognitive model of working memory. Copyright © 2015 Elsevier Ltd. All rights reserved.
Bolló-Gasol, S; Piñol-Ripoll, G; Cejudo-Bolivar, J C; Llorente-Vizcaino, A; Peraita-Adrados, H
The Rivermead Behavioural Memory Test (RBMT) is a short, ecologically-valid memory test battery that can provide data about a subject's memory function in daily life. We used RBMT to examine daily memory function in patients with mild cognitive impairment (MCI), Alzheimer disease (AD), and in healthy controls. We also evaluated differences between the memory profiles of subjects whose MCI remained stable after 1 year and those with conversion to AD. Sample of 91 subjects older than 60 years: 30 controls, 27 MCI subjects and 34 AD patients. Subjects were assessed using MMSE and RBMT. The 40 men and 51 women in the sample had a mean age of 74.29±6.71 and 5.87±2.93 years of education. For the total profile and screening RBMT scores (Pde Neurología. Published by Elsevier Espana. All rights reserved.
Siu, Elaine; Man, David W K
Children with Specific Language Impairment present with delayed language development, but do not have a history of hearing impairment, mental deficiency, or associated social or behavioral problems. Non-word repetition was suggested as an index to reflect the capacity of phonological working memory. There is a paucity of such studies among Hong Kong Chinese children. This preliminary study aimed to examine the relationship between phonological working memory and Specific Language Impairment, through the processes of non-word repetition and sentence comprehension, of children with Specific Language Impairment and pre-school children with normal language development. Both groups of children were screened by a standardized language test. A list of Cantonese (the commonest dialect used in Hong Kong) multisyllabic nonsense utterances and a set of 18 sentences were developed for this study. t-tests and Pearson correlation were used to study the relationship between non-word repetition, working memory and specific language impairment. Twenty-three pre-school children with Specific Language Impairment (mean age = 68.30 months; SD = 6.90) and another 23 pre-school children (mean age = 67.30 months; SD = 6.16) participated in the study. Significant difference performance was found between the Specific Language Impairment group and normal language group in the multisyllabic nonsense utterances repetition task and the sentence comprehension task. Length effect was noted in Specific Language Impairment group children, which is consistent with the findings of other literature. In addition, correlations were also observed between the number of nonsense utterances repeated and the number of elements comprehended. Cantonese multisyllabic nonsense utterances might be worth further developing as a screening tool for the early detection of children with Specific Language Impairment.
Full Text Available The hypothesis has been advanced that memory disorders in individuals with Parkinson's disease (PD are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD, and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (p0.10 task, and they performed better than aMCINPD subjects on both recall measures (p0.10 but it was significantly higher than that of the aMCINPD sample (p<0.01. Moreover, PD patients' performance on free recall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042. Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning.
Carrasquillo, Minerva M; Crook, Julia E; Pedraza, Otto; Thomas, Colleen S; Pankratz, V Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G; Ma, Li; Bisceglio, Gina D; Roberts, Rosebud O; Lucas, John A; Smith, Glenn E; Ivnik, Robert J; Machulda, Mary M; Graff-Radford, Neill R; Petersen, Ronald C; Younkin, Steven G; Ertekin-Taner, Nilüfer
We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease. Copyright © 2015 Elsevier Inc. All rights reserved.
Reijmers, L.G.J.E.; Hoekstra, K.; Burbach, J.P.H.; Ree, van J.M.; Spruijt, B.M.
Repeated social defeat followed by individual housing caused a long-term impairment of social memory in male rats. Social memory, as assessed in the social discrimination test using an intertrial interval of 3 min, was impaired for at least 8 weeks after the social defeat experience. Since social
Narimoto, Tadamasa; Matsuura, Naomi; Hiratani, Michio
Previous studies provide clear evidence that visuospatial memory performance in children with attention-deficit/hyperactivity disorder (ADHD) is significantly lower than in typically developing children. In the present study, we investigated a major cause of their low performance using a spatial span test. Possibly, inattention resulting from lack of motivation or interest causes their low performance so that they do not correctly encode targets to be remembered. On the other hand, a deficit in temporary maintenance per se may cause their low performance; that is, their inefficient use of rehearsal during a retention interval may lead to memory traces' fast decay. Results in this study indicated that children with ADHD could sustain attention during the encoding phase. Furthermore, their performance at delayed recall was significantly lower than immediate recall, but delayed recall did not affect typically developing children's performance. These results provide evidence for the likelihood that a factor causing children with ADHD difficulty in temporarily maintaining visuospatial information is fast decay of memory traces as a result of inefficient use of rehearsal, not inattention in the encoding phase.
Salvato, Gerardo; Patai, Eva Z; Nobre, Anna C
It is increasingly recognised that spatial contextual long-term memory (LTM) prepares neural activity for guiding visuo-spatial attention in a proactive manner. In the current study, we investigated whether the decline in explicit memory observed in healthy ageing would compromise this mechanism. We compared the behavioural performance of younger and older participants on learning new contextual memories, on orienting visual attention based on these learnt contextual associations, and on explicit recall of contextual memories. We found a striking dissociation between older versus younger participants in the relationship between the ability to retrieve contextual memories versus the ability to use these to guide attention to enhance performance on a target-detection task. Older participants showed significant deficits in the explicit retrieval task, but their behavioural benefits from memory-based orienting of attention were equivalent to those in young participants. Furthermore, memory-based orienting correlated significantly with explicit contextual LTM in younger adults but not in older adults. These results suggest that explicit memory deficits in ageing might not compromise initial perception and encoding of events. Importantly, the results also shed light on the mechanisms of memory-guided attention, suggesting that explicit contextual memories are not necessary. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Otsuka, Sachio; Saiki, Jun
Prior studies have shown that visual statistical learning (VSL) enhances familiarity (a type of memory) of sequences. How do statistical regularities influence the processing of each triplet element and inserted distractors that disrupt the regularity? Given that increased attention to triplets induced by VSL and inhibition of unattended triplets, we predicted that VSL would promote memory for each triplet constituent, and degrade memory for inserted stimuli. Across the first two experiments, we found that objects from structured sequences were more likely to be remembered than objects from random sequences, and that letters (Experiment 1) or objects (Experiment 2) inserted into structured sequences were less likely to be remembered than those inserted into random sequences. In the subsequent two experiments, we examined an alternative account for our results, whereby the difference in memory for inserted items between structured and random conditions is due to individuation of items within random sequences. Our findings replicated even when control letters (Experiment 3A) or objects (Experiment 3B) were presented before or after, rather than inserted into, random sequences. Our findings suggest that statistical learning enhances memory for each item in a regular set and impairs memory for items that disrupt the regularity. Copyright © 2015 Elsevier B.V. All rights reserved.
Scaini, Giselli; Comim, Clarissa M; Oliveira, Giovanna M T; Pasquali, Matheus A B; Quevedo, João; Gelain, Daniel P; Moreira, José Cláudio F; Schuck, Patrícia F; Ferreira, Gustavo C; Bogo, Maurício R; Streck, Emilio L
Maple syrup urine disease (MSUD) is a neurometabolic disorder that leads to the accumulation of branched-chain amino acids (BCAAs) and their α-keto branched-chain by-products. Because the neurotoxic mechanisms of MSUD are poorly understood, this study aimed to evaluate the effects of chronic administration of a BCAA pool (leucine, isoleucine and valine). This study examined the effects of BCAA administration on spatial memory and the levels of brain-derived neurotrophic factor (BNDF). We examined both pro-BDNF and bdnf mRNA expression levels after administration of BCAAs. Furthermore, this study examined whether antioxidant treatment prevented the alterations induced by BCAA administration. Our results demonstrated an increase in BDNF in the hippocampus and cerebral cortex, accompanied by memory impairment in spatial memory tasks. Additionally, chronic administration of BCAAs did not induce a detectable change in pro-BDNF levels. Treatment with N-acetylcysteine and deferoxamine prevented both the memory deficit and the increase in the BDNF levels induced by BCAA administration. In conclusion, these results suggest that when the brain is chronically exposed to high concentrations of BCAA (at millimolar concentrations) an increase in BDNF levels occurs. This increase in BDNF may be related to the impairment of spatial memory. In addition, we demonstrated that antioxidant treatment prevented the negative consequences related to BCAA administration, suggesting that oxidative stress might be involved in the pathophysiological mechanism(s) underlying the brain damage observed in MSUD.
Michelle S. Goodman
Full Text Available Working memory deficits are common among individuals with Alzheimer’s dementia (AD or mild cognitive impairment (MCI. Yet, little is known about the mechanisms underlying these deficits. Theta-gamma coupling—the modulation of high-frequency gamma oscillations by low-frequency theta oscillations—is a neurophysiologic process underlying working memory. We assessed the relationship between theta-gamma coupling and working memory deficits in AD and MCI. We hypothesized that: (1 individuals with AD would display the most significant working memory impairments followed by MCI and finally healthy control (HC participants; and (2 there would be a significant association between working memory performance and theta-gamma coupling across all participants. Ninety-eight participants completed the N-back working memory task during an electroencephalography (EEG recording: 33 with AD (mean ± SD age: 76.5 ± 6.2, 34 with MCI (mean ± SD age: 74.8 ± 5.9 and 31 HCs (mean ± SD age: 73.5 ± 5.2. AD participants performed significantly worse than control and MCI participants on the 1- and 2-back conditions. Regarding theta-gamma coupling, AD participants demonstrated the lowest level of coupling followed by the MCI and finally control participants on the 2-back condition. Finally, a linear regression analysis demonstrated that theta-gamma coupling (β = 0.69, p < 0.001 was the most significant predictor of 2-back performance. Our results provide evidence for a relationship between altered theta-gamma coupling and working memory deficits in individuals with AD and MCI. They also provide insight into a potential mechanism underlying working memory impairments in these individuals.
Park, Chang-Hyun; Choi, Yun Seo; Jung, A-Reum; Chung, Hwa-Kyoung; Kim, Hyeon Jin; Yoo, Jeong Hyun; Lee, Hyang Woon
Brain functional integration can be disrupted in patients with temporal lobe epilepsy (TLE), but the clinical relevance of this disruption is not completely understood. The authors hypothesized that disrupted functional integration over brain regions remote from, as well as adjacent to, the seizure focus could be related to clinical severity in terms of seizure control and memory impairment. Using resting-state functional MRI data acquired from 48 TLE patients and 45 healthy controls, the authors mapped functional brain networks and assessed changes in a network parameter of brain functional integration, efficiency, to examine the distribution of disrupted functional integration within and between brain regions. The authors assessed whether the extent of altered efficiency was influenced by seizure control status and whether the degree of altered efficiency was associated with the severity of memory impairment. Alterations in the efficiency were observed primarily near the subcortical region ipsilateral to the seizure focus in TLE patients. The extent of regional involvement was greater in patients with poor seizure control: it reached the frontal, temporal, occipital, and insular cortices in TLE patients with poor seizure control, whereas it was limited to the limbic and parietal cortices in TLE patients with good seizure control. Furthermore, TLE patients with poor seizure control experienced more severe memory impairment, and this was associated with lower efficiency in the brain regions with altered efficiency. These findings indicate that the distribution of disrupted brain functional integration is clinically relevant, as it is associated with seizure control status and comorbid memory impairment.
Martinussen, Rhonda; Hayden, Jill; Hogg-Johnson, Sheilah; Tannock, Rosemary
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…
Vuckovich, Joseph A.; Semel, Mara E.; Baxter, Mark G.
A recent study suggests that lesions to all major areas of the cholinergic basal forebrain in the rat (medial septum, horizontal limb of the diagonal band of Broca, and nucleus basalis magnocellularis) impair a spatial working memory task. However, this experiment used a surgical technique that may have damaged cerebellar Purkinje cells. The…
Jonsdottir, S; Bouma, A; Sergeant, JA; Scherder, EJA
The objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 8 1/2- to 12 1/2-year-old
Jondottir, S.; Bouma, A.; Sergeant, J.A.; Scherder, E.J.A.
The objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 81/2- to 121/2-year-old
Jonsdottir, S.; Bouma, A.; Sergeant, J.A.; Scherder, E.J.A.
The objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 81/2- to 121/2-year-old
Li, Zaixin; Zhang, Zhi; Zhang, Jinshan; Jia, Jing; Ding, Jie; Luo, Rongzhen; Liu, Zhangqin
Memory impairment is one of main clinical symptoms of brain senescence. To address the effects of Cordyceps militaris Link extract (CE) on memory impairment, a D-galactose (D-Gal)-induced aging mouse model was employed. Mice injected with D-Gal showed a significant learning and memory impairment that was rescued by CE treatment. The mechanism was further investigated by analyzing the protein level and activity of oxidant and antioxidant molecules, including malondialdehyde (MDA), monoamine oxidase (MAO), total super-oxide dismutase (T-SOD), total antioxidant capacity (T-AOC), glutathione (GSH), and glutathione peroxidase (GSH-px), which played critical roles in the development of brain senescence. The results showed that CE treatment resulted in a significant decrease in the oxidative activity of MAO and the level of MDA, and significantly increased the antioxidant activities of T-SOD and T-AOC in the cerebral cortices. Moreover, the level of GSH and the activity of antioxidant enzymes GSH-px in serum were significantly upregulated after CE treatment. Taken together, our results suggest that Cordyceps militaris extract could ameliorate experimental memory impairment in mice with D-Gal-induced aging through its potent antioxidant activities.
Vugs, Brigitte; Hendriks, Marc; Cuperus, Juliane; Knoors, Harry; Verhoeven, Ludo
Purpose: This longitudinal study examined differences in the development of working memory (WM) between children with specific language impairment (SLI) and typically developing (TD) children. Further, it explored to what extent language at ages 7-8 years could be predicted by measures of language and/or WM at ages 4-5 years. Method: Thirty…
Albouy, Philippe; Mattout, Jeremie; Bouet, Romain; Maby, Emmanuel; Sanchez, Gaetan; Aguera, Pierre-Emmanuel; Daligault, Sebastien; Delpuech, Claude; Bertrand, Olivier; Caclin, Anne; Tillmann, Barbara
Congenital amusia is a lifelong disorder of music perception and production. The present study investigated the cerebral bases of impaired pitch perception and memory in congenital amusia using behavioural measures, magnetoencephalography and voxel-based morphometry. Congenital amusics and matched control subjects performed two melodic tasks (a…
Salvato, G; Patai, EZ; Nobre, AC
It is increasingly recognised that spatial contextual long-term memory (LTM) prepares neural activity for guiding visuo-spatial attention in a proactive manner. In the current study, we investigated whether the decline in explicit memory observed in healthy ageing would compromise this mechanism. We compared the behavioural performance of younger and older participants on learning new contextual memories, on orienting visual attention based on these learnt contextual associations, and on expl...
Langlois, Roxane; Joubert, Sven; Benoit, Sophie; Dostie, Valérie; Rouleau, Isabelle
Ribot's law refers to the better preservation of remote memories compared with recent ones that presumably characterizes retrograde amnesia. Even if Ribot-type temporal gradient has been extensively studied in retrograde amnesia, particularly in Alzheimer's disease (AD), this pattern has not been consistently found. One explanation for these results may be that rehearsal frequency rather than remoteness accounts for the better preservation of these memories. Thus, the aim of present study was to address this question by studying retrograde semantic memory in subjects with amnestic mild cognitive impairment (aMCI) (n = 20), mild AD (n = 20) and in healthy older controls (HC; n = 19). In order to evaluate the impact of repetition as well as the impact of remoteness, we used a test assessing memory for enduring and transient public events that occurred in the recent and remote past. Results show no clear temporal gradient across time periods (1960-1975; 1976-1990; 1991-2005; 2006-2011), but a better performance was observed in all three groups for enduring compared with transient events. Moreover, although deficits were globally found in both patients groups compared with HC, more specific analyses revealed that aMCI patients were only impaired on transient events while AD patients were impaired on both transient and enduring events. Exploratory analyses also revealed a tendency suggesting preservation of remote transient events in aMCI. These findings are discussed with regards to memory consolidation models.
Savage, C R; Baer, L; Keuthen, N J; Brown, H D; Rauch, S L; Jenike, M A
Previous neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure. We examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function. OCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set. Immediate nonverbal memory problems in OCD subjects were mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD.
Bradley H Lee
Full Text Available Anesthetic exposure early in life affects neural development and long-term cognitive function, but our understanding of the types of memory that are altered is incomplete. Specific cognitive tests in rodents that isolate different memory processes provide a useful approach for gaining insight into this issue.Postnatal day 7 (P7 rats were exposed to either desflurane or isoflurane at 1 Minimum Alveolar Concentration for 4 h. Acute neuronal death was assessed 12 h later in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. In separate behavioral experiments, beginning at P48, subjects were evaluated in a series of object recognition tests relying on associative learning, as well as social recognition.Exposure to either anesthetic led to a significant increase in neuroapoptosis in each brain region. The extent of neuronal death did not differ between groups. Subjects were unaffected in simple tasks of novel object and object-location recognition. However, anesthetized animals from both groups were impaired in allocentric object-location memory and a more complex task requiring subjects to associate an object with its location and contextual setting. Isoflurane exposure led to additional impairment in object-context association and social memory.Isoflurane and desflurane exposure during development result in deficits in tasks relying on associative learning and recognition memory. Isoflurane may potentially cause worse impairment than desflurane.
Ozbaki, Jamile; Goudarzi, Iran; Salmani, Mahmoud Elahdadi; Rashidy-Pour, Ali
Objective(s): Due to the prevalence and pervasiveness of stress in modern life and exposure to both chronic and acute stresses, it is not clear whether prior exposure to chronic stress can influence the impairing effects of acute stress on memory retrieval. This issue was tested in this study. Materials and Methods: Adult male Wistar rats were randomly assigned to the following groups: control, acute, chronic, and chronic + acute stress groups. The rats were trained with six trials per day for 6 consecutive days in the water maze. Following training, the rats were either kept in control conditions or exposed to chronic stress in a restrainer 6 hr/day for 21 days. On day 22, a probe test was done to measure memory retention. Time spent in target and opposite areas, platform location latency, and proximity were used as indices of memory retention. To induce acute stress, 30 min before the probe test, animals received a mild footshock. Results: Stressed animals spent significantly less time in the target quadrant and more time in the opposite quadrant than control animals. Moreover, the stressed animals showed significantly increased platform location latency and proximity as compared with control animals. No significant differences were found in these measures among stress exposure groups. Finally, both chronic and acute stress significantly increased corticosterone levels. Conclusion: Our results indicate that both chronic and acute stress impair memory retrieval similarly. Additionally, the impairing effects of chronic stress on memory retrieval were not influenced by acute stress. PMID:27635201
Martins, Alexandre; Schimidt, Helen L; Garcia, Alexandre; Colletta Altermann, Caroline Dalla; Santos, Francielli W; Carpes, Felipe P; da Silva, Weber Cláudio; Mello-Carpes, Pâmela B
Memory and cognition impairments resultant of ischemic stroke could be minimized or avoided by antioxidant supplementation. In this regard, the neuroprotective potential of Green tea from Camellia sinensis has been investigated. However, there is a lack of information regarding the neuroprotective potential of others teas processed from the Camellia sinensis. Here we investigate the neuroprotective role of green, red, white and black tea on memory deficits and brain oxidative stress in a model of ischemic stroke in rats. Our findings show that green and red teas prevent deficits in object and social recognition memories, but only green tea protects against deficits in spatial memory and avoids hippocampal oxidative status and intense necrosis and others alterations in the brain tissue. In summary, green tea shows better neuroprotection in ischemic stroke than the others teas from Camellia sinensis. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ricobaraza, Ana; Cuadrado-Tejedor, Mar; Garcia-Osta, Ana
Aberrations in protein folding, processing, and/or degradation are common features of neurodegenerative diseases, such as Alzheimer's disease (AD). Sodium 4-phenylbutyrate (PBA) is a well-known histone deacetylase inhibitor, which increases gene transcription of a number of genes, and also exerts neuroprotective effects. PBA acts as a chemical chaperone reducing the load of mutant or unfolded proteins during cellular stress. Previously, we reported that 5-week administration of PBA reinstated memory loss and dendritic spine densities in the Tg2576 mouse model of AD. In this study we reported that chronic administration of PBA, starting before the onset of disease symptoms (6 month-old) prevents age-related memory deficits in Tg2576 mice. The amelioration of the memory impairment is associated to a decrease in amyloid beta pathology and the glial fibrillary acidic protein (GFAP), suggesting that inflammation was reduced in PBA-treated animals. Together, the beneficial effects of PBA make it a promising agent for the prevention of AD.
Cooper, Janine M; Lockett, Stephen; McIlroy, Alissandra; Gonzalez, Linda
Children and adolescents with chronic memory impairment may develop coping strategies that enable functioning, yet these often remain undetectable using traditional psychometric measures. Personalized intervention studies that promote the use of such strategies designed specifically for use by this young cohort are scarce. To investigate the effect of a novel virtual reality peer-delivered memory intervention on the everyday functioning and well-being of SE, a 17-year-old female with a history of chronic verbal memory issues, impaired autobiographical event recall and elevated mood symptoms. A single-case ABA experimental design study was used to assess change. Following initial baseline assessment using objective neuropsychological and subjective functional questionnaires and intervention training, case SE used the intervention daily for 3 weeks before repeating key outcome measures. Using non-overlap of all pairs and qualitative feedback analysis, the results revealed a significant increase in event recall and self-reported positive changes to levels of everyday functioning. Supporting autobiographical event recall and prospective memory via a virtual peer-delivered intervention may lead to reduction in cognitive load, and benefit overall well-being and everyday functioning.
Brissart, H; Morele, E; Baumann, C; Debouverie, M
Episodic memory is frequently impaired in multiple sclerosis (MS) patients but the exact nature of the disorder is controversial. It was initially thought to be due to a retrieval deficit but some studies have demonstrated an encoding deficit, which could be linked to a slowing of information processing speed or to a deficit in elaboration of strategies. The main objective of this study is to assess the prevalence and the nature of verbal episodic memory (VEM) impairment in MS patients. We retrieved memory performances of 426 patients [314 F-112 M; mean age: 46.1 years; median Expanded Disability Status Scale (EDSS) score: 3.1] from a neuropsychological data base. VEM was assessed using the 16 words RL-RI 16 test. 66% MS patients present at least one recall impaired in VEM (37.2% from 2 to 5 recall). 14.2% MS patients present an impairment in encoding phase. We observed that 5% of patients presented recognition difficulties. Correlations were observed between VEM performances and EDSS, and disease duration but no group effect (ANOVA) is observed between form of MS and VEM performances. These results confirm the high prevalence of VEM impairment in MS patients. Deficits affect mainly information retrieval in early stage MS patients and are then linked to encoding as disability increases. Storage disorders are infrequent, so cognitive rehabilitation with mental imaging could be effective in MS patients.
Facal, David; Juncos-Rabadán, Onésimo; Pereiro, Arturo X; Lojo-Seoane, Cristina
Mild cognitive impairment (MCI) often includes episodic memory impairment, but can also involve other types of cognitive decline. Although previous studies have shown poorer performance of MCI patients in working memory (WM) span tasks, different MCI subgroups were not studied. In the present exploratory study, 145 participants underwent extensive cognitive evaluation, which included three different WM span tasks, and were classified into the following groups: multiple-domain amnestic MCI (mda-MCI), single-domain amnestic MCI (sda-MCI), and controls. General linear model was conducted by considering the WM span tasks as the within-subject factor; the group (mda-MCI, sda-MCI, and controls) as the inter-subject factor; and processing speed, vocabulary and age as covariates. Multiple linear regression models were also used to test the influence of processing speed, vocabulary, and other cognitive reserve (CR) proxies. Results indicate different levels of impairment of WM, with more severe impairment in mda-MCI patients. The differences were still present when processing resources and CR were controlled. Between-group differences can be understood as a manifestation of the greater severity and widespread memory impairment in mda-MCI patients and may contribute to a better understanding of continuum from normal controls to mda-MCI patients. Processing speed and CR have a limited influence on WM scores, reducing but not removing differences between groups.
Xiaoli, Feng; Junrong, Wu; Xuan, Lai; Yanli, Zhang; Limin, Wei; Jia, Liu; Longquan, Shao
To examine the neurotoxicity of prenatal exposure to ZnO nanoparticles on rat offspring. Pregnant Sprague-Dawley rats were exposed to ZnO nanoparticles (NPs) by gavage. Toxicity was assessed including zinc biodistribution, cerebral histopathology, antioxidant status and learning and memory capability. A significantly elevated concentration of zinc was detected in offspring brains. Transmission electron microscope observations showed abnormal neuron ultrastructures. Histopathologic changes such as decreased proliferation and higher apoptotic death were observed. An obvious imbalanced antioxidant status occurred in brains. Adult experimental offspring exhibited impaired learning and memory behavior in the Morris water maze test compared with control groups. These adverse effects on offspring brain may cause impaired learning and memory capabilities in adulthood, particularly in female rats.
Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M
A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI.
Kessels, R.P.C.; Rijken, S.; Joosten-Weyn Banningh, L.W.A.; Schuylenborgh-van Es, N. van; Olde Rikkert, M.G.M.
Memory for object locations, as part of spatial memory function, has rarely been Studied in patients with Alzheimer dementia (AD), while Studies in patients with Mild Cognitive Impairment (MCI) patients are lacking altogether. The present study examined categorical spatial memory function using the
Kessels, R.P.C.; Rijken, S.; Joosten-Weyn Banningh, L.W.A.; Schuylenborgh-van Es, N. van; Olde Rikkert, M.G.M.
Memory for object locations, as part of spatial memory function, has rarely been studied in patients with Alzheimer dementia (AD), while studies in patients with Mild Cognitive Impairment (MCI) patients are lacking altogether. The present study examined categorical spatial memory function using the
Chauveau, Frédéric; Lange, Maren Denise; Jüngling, Kay; Lesting, Jörg; Seidenbecher, Thomas; Pape, Hans-Christian
Stressful and traumatic events can create aversive memories, which are a predisposing factor for anxiety disorders. The amygdala is critical for transforming such stressful events into anxiety, and the recently discovered neuropeptide S transmitter system represents a promising candidate apt to control these interactions. Here we test the hypothesis that neuropeptide S can regulate stress-induced hyperexcitability in the amygdala, and thereby can interact with stress-induced alterations of fear memory. Mice underwent acute immobilization stress (IS), and neuropeptide S and a receptor antagonist were locally injected into the lateral amygdala (LA) during stress exposure. Ten days later, anxiety-like behavior, fear acquisition, fear memory retrieval, and extinction were tested. Furthermore, patch-clamp recordings were performed in amygdala slices prepared ex vivo to identify synaptic substrates of stress-induced alterations in fear responsiveness. (1) IS increased anxiety-like behavior, and enhanced conditioned fear responses during extinction 10 days after stress, (2) neuropeptide S in the amygdala prevented, while an antagonist aggravated, these stress-induced changes of aversive behaviors, (3) excitatory synaptic activity in LA projection neurons was increased on fear conditioning and returned to pre-conditioning values on fear extinction, and (4) stress resulted in sustained high levels of excitatory synaptic activity during fear extinction, whereas neuropeptide S supported the return of synaptic activity during fear extinction to levels typical of non-stressed animals. Together these results suggest that the neuropeptide S system is capable of interfering with mechanisms in the amygdala that transform stressful events into anxiety and impaired fear extinction.
Full Text Available BACKGROUND: Memory disturbances, in particular episodic verbal memory dysfunction, are the most frequent cognitive impairment observed in multiple sclerosis (MS patients. The use of self-reported outcomes for evaluating treatment and managing care of these subjects has been questioned. The aim of this study was to provide new evidence about the suitability of self-reported outcomes for use in this impaired population by exploring the internal structure, reliability and external validity of a specific quality of life (QoL instrument, the Multiple Sclerosis International Quality of Life questionnaire (MusiQoL. METHODS: DESIGN: cross-sectional study. INCLUSION CRITERIA: MS patients of any disease subtype. DATA COLLECTION: sociodemographic (age, gender, marital status, education level, and occupational activity and clinical data (MS subtype, Expanded Disability Status Scale, disease duration; QoL (MusiQoL and SF36; and memory performance (Grober and Buschke test. In accordance with the French norms of the memory test, non-impaired and impaired populations were defined for short- and long-delay free composites and for short- and long-delay total composites. For the 8 populations, psychometric properties were compared to those reported from the reference population assessed in the validation study. PRINCIPAL FINDINGS: One hundred and twenty-four consecutive patients were enrolled. The analysis performed in the impaired populations showed that the questionnaire structure adequately matched the initial structure of the MusiQoL. The unidimensionality of the dimensions was preserved, and the internal/external validity indices were close to those of the reference population. CONCLUSIONS/SIGNIFICANCE: Our study suggests that memory dysfunction did not compromise the reliability or validity of the self-reported QoL questionnaires.
Brown, Jeremy M; Lansdall, Claire J; Wiggins, Julie; Dawson, Kate E; Hunter, Kristina; Rowe, James B; Parker, Richard A
To validate a short cognitive test: the Test Your Memory for Mild Cognitive Impairment (TYM-MCI) in the diagnosis of patients with amnestic mild cognitive impairment or mild Alzheimer's disease (aMCI/AD). Two hundred and two patients with mild memory problems were recruited. All had 'passed' the Mini-Mental State Examination (MMSE). Patients completed the TYM-MCI, the Test Your Memory test (TYM), MMSE and revised Addenbrooke's Cognitive Examination (ACE-R), had a neurological examination, clinical diagnostics and multidisciplinary team review. As a single test, the TYM-MCI performed as well as the ACE-R in the distinction of patients with aMCI/AD from patients with subjective memory impairment with a sensitivity of 0.79 and specificity of 0.91. Used in combination with the ACE-R, it provided additional value and identified almost all cases of aMCI/AD. The TYM-MCI correctly classified most patients who had equivocal ACE-R scores. Integrated discriminant improvement analysis showed that the TYM-MCI added value to the conventional memory assessment. Patients initially diagnosed as unknown or with subjective memory impairment who were later rediagnosed with aMCI/AD scored poorly on their original TYM-MCI. The TYM-MCI is a powerful short cognitive test that examines verbal and visual recall and is a valuable addition to the assessment of patients with aMCI/AD. It is simple and cheap to administer and requires minimal staff time and training. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Taherian, Fatemeh; Vafaei, Abbas Ali; Vaezi, Gholam Hassan; Eskandarian, Sharaf; Kashef, Adel; Rashidy-Pour, Ali
Introduction Previous studies have demonstrated that the β-adrenergic receptor antagonist propranolol impairs fear memory reconsolidation in experimental animals. There are experimental parameters such as the age and the strength of memory that can interact with pharmacological manipulations of memory reconsolidation. In this study, we investigated the ability of the age and the strength of memory to influence the disrupting effects of propranolol on fear memory reconsolidation in rats. Methods The rats were trained in a contextual fear conditioning using two (weak training) or five (strong training) footshocks (1mA). Propranolol (10mg/kg) injection was immediately followed retrieval of either a one-day recent (weak or strong) or 36-day remote (weak or strong) contextual fear memories. Results We found that propranolol induced a long-lasting impairment of subsequent expression of recent and remote memories with either weak or strong strength. We also found no memory recovery after a weak reminder shock. Furthermore, no significant differences were found on the amount of memory deficit induced by propranolol among memories with different age and strength. Discussion Our data suggest that the efficacy of propranolol in impairing fear memory reconsolidation is not limited to the age or strength of the memory. PMID:25337385
Turk, David J; Brady-van den Bos, Mirjam; Collard, Philip; Gillespie-Smith, Karri; Conway, Martin A; Cunningham, Sheila J
Information that is relevant to oneself tends to be remembered more than information that relates to other people, but the role of attention in eliciting this "self-reference effect" is unclear. In the present study, we assessed the importance of attention in self-referential encoding using an ownership paradigm, which required participants to encode items under conditions of imagined ownership by themselves or by another person. Previous work has established that this paradigm elicits a robust self-reference effect, with more "self-owned" items being remembered than "other-owned" items. Access to attentional resources was manipulated using divided-attention tasks at encoding. A significant self-reference effect emerged under full-attention conditions and was related to an increase in episodic recollection for self-owned items, but dividing attention eliminated this memory advantage. These findings are discussed in relation to the nature of self-referential cognition and the importance of attentional resources at encoding in the manifestation of the self-reference effect in memory.
Crespo, Iris; Santos, Alicia; Valassi, Elena; Pires, Patricia; Webb, Susan M; Resmini, Eugenia
Evaluation of cognitive function in acromegaly has revealed contradictory findings; some studies report normal cognition in patients with long-term cured acromegaly, while others show attention and memory deficits. Moreover, the presence of affective disorders in these patients is common. Our aim was to evaluate memory and decision making in acromegalic patients and explore their relationship with affective disorders like anxiety and depressive symptoms. Thirty-one patients with acromegaly (mean age 49.5 ± 8.5 years, 14 females and 17 males) and thirty-one healthy controls participated in this study. The Iowa Gambling Task (IGT), Rey Auditory Verbal Learning Test, State-Trait Anxiety Inventory, and Beck Depression Inventory-II (BDI-II) were used to evaluate decision making, verbal memory, anxiety, and depressive symptoms, respectively. Acromegalic patients showed impairments in delayed verbal memory (p decision-making strategy compared to controls, choosing a lower number of the safer cards (p memory and decision making were found. Impaired delayed memory and decision making observed in acromegalic patients are related to anxiety and depressive symptoms. Providing emotional support to the patients could improve their cognitive function. A key clinical application of this research is the finding that depressive symptoms and anxiety are essentially modifiable factors.
Erro, Roberto; Santangelo, Gabriella; Barone, Paolo; Picillo, Marina; Amboni, Marianna; Longo, Katia; Giordano, Flavio; Moccia, Marcello; Allocca, Roberto; Pellecchia, Maria Teresa; Vitale, Carmine
Longitudinal studies on healthy participants have shown that subjective memory impairment (defined as subjective cognitive complaints with normal cognitive objective performance) might be a strong predictor of mild cognitive impairment (MCI). Parkinson disease (PD) also manifests cognitive disturbances, but whether subjective memory complaints may predict the development of MCI in PD has not yet been explored. We prospectively screened newly diagnosed, untreated patients with PD in order to evaluate whether subjective memory complaints may predict development of MCI over a 2-year follow-up evaluation. We enrolled 76 de novo untreated patients with PD. Of the 76 patients, 23 (30.3%) complained memory issues. Among the patients cognitively unimpaired at baseline, those with subjective complaints were more likely to develop MCI at follow-up. The regression model confirmed that presence of subjective memory complaints at baseline was an independent predictor of development of MCI at follow-up. This is the first prospective study to explore the relationship between subjective and objective cognitive deficits in newly diagnosed, untreated patients. Our results provide preliminary evidence that subjective memory complaints might predict future development of MCI. © The Author(s) 2014.
Cooper, Janine M; Gadian, David G; Jentschke, Sebastian; Goldman, Allan; Munoz, Monica; Pitts, Georgia; Banks, Tina; Chong, W Kling; Hoskote, Aparna; Deanfield, John; Baldeweg, Torsten; de Haan, Michelle; Mishkin, Mortimer; Vargha-Khadem, Faraneh
Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life. © The Author 2013. Published by Oxford University Press.
Kinsella, Glynda J; Pike, Kerryn E; Cavuoto, Marina G; Lee, Stephen D
There has been a recent rapid development of research characterizing prospective memory performance in mild cognitive impairment (MCI) in older age. However, this body of literature remains largely separated from routine clinical practice in neuropsychology. Furthermore, there is emerging evidence of effective interventions to improve prospective memory performance. Therefore, our objective in this article was to offer a clinical neuropsychological perspective on the existing research in order to facilitate the translation of the evidence-base into clinical practice. By conducting a critical review of the existing research related to prospective memory and MCI, we highlight how this data can be introduced into clinical practice, either within diagnostic assessment or clinical management. Prospective memory is impaired in older adults with MCI, with a pattern of performance that helps with differential diagnosis from healthy aging. Clinical neuropsychologists are encouraged to add prospective memory assessment to their toolbox for diagnostic evaluation of clients with MCI. Preliminary findings of prospective memory interventions in MCI are promising, but more work is required to determine how different approaches translate to increasing independence in everyday life.
Jakobson, L S; Pearson, P M; Robertson, B
Cases of hue-selective dyschomatopsias, together with the results of recent optical imaging studies [Xiao, Y., Casti, A. R. R., Xiao, J., & Kaplan, E. (2006). A spatially organized representation of colour in macaque primary visual cortex. Perception, 35, ECVP Abstract Supplement; Xiao, Y., Wang, Y., & Felleman, D. J. (2003). A spatially organized representation of colour in macaque cortical area V2. Nature, 421, 535-539], have provided support for the idea that different colours are processed in spatially distinct regions of extrastriate cortex. In the present report, we provide evidence suggesting that a similar, but distinct, map may exist for representations of colour in memory. This evidence comes from observations of a young woman (QP) who demonstrates an isolated deficit in colour memory secondary to a concussive episode. Despite having normal colour perception and colour naming skills, and above-average memory skills in other domains, QP's ability to recall visually encoded colour information over short retention intervals is dramatically impaired. Her long-term memory for colour and her colour imagery skills are also abnormal. Surprisingly, however, these impairments are not seen with all hues; specifically, her ability to remember or imagine blue shades is spared. This interesting case contributes to the literature suggesting that colour perception, naming, and memory can be clinically dissociated, and provides insights into the organization of colour information in memory.
Søvik, Eirik; Berthier, Pauline; Klare, William P; Helliwell, Paul; Buckle, Edwina L S; Plath, Jenny A; Barron, Andrew B; Maleszka, Ryszard
Drug addiction is a chronic relapsing behavioral disorder. The high relapse rate has often been attributed to the perseverance of drug-associated memories due to high incentive salience of stimuli learnt under the influence of drugs. Drug addiction has also been interpreted as a memory disorder since drug associated memories are unusually enduring and some drugs, such as cocaine, interfere with neuroepigenetic machinery known to be involved in memory processing. Here we used the honey bee (an established invertebrate model for epigenomics and behavioral studies) to examine whether or not cocaine affects memory processing independently of its effect on incentive salience. Using the proboscis extension reflex training paradigm we found that cocaine strongly impairs consolidation of extinction memory. Based on correlation between the observed effect of cocaine on learning and expression of epigenetic processes, we propose that cocaine interferes with memory processing independently of incentive salience by directly altering DNA methylation dynamics. Our findings emphasize the impact of cocaine on memory systems, with relevance for understanding how cocaine can have such an enduring impact on behavior.
Full Text Available Drug addiction is a chronic relapsing behavioral disorder. The high relapse rate has often been attributed to the perseverance of drug-associated memories due to high incentive salience of stimuli learnt under the influence of drugs. Drug addiction has also been interpreted as a memory disorder since drug associated memories are unusually enduring and some drugs, such as cocaine, interfere with neuroepigenetic machinery known to be involved in memory processing. Here we used the honey bee (an established invertebrate model for epigenomics and behavioral studies to examine whether or not cocaine affects memory processing independently of its effect on incentive salience. Using the proboscis extension reflex training paradigm we found that cocaine strongly impairs consolidation of extinction memory. Based on correlation between the observed effect of cocaine on learning and expression of epigenetic processes, we propose that cocaine interferes with memory processing independently of incentive salience by directly altering DNA methylation dynamics. Our findings emphasize the impact of cocaine on memory systems, with relevance for understanding how cocaine can have such an enduring impact on behavior.
Geldorp, B. van; Heringa, S.M.; Berg, E. van den; Olde Rikkert, M.G.M.; Biessels, G.J.; Kessels, R.P.C.
INTRODUCTION: Recent studies indicate that in both normal and pathological aging working memory (WM) performance deteriorates, especially when associations have to be maintained. However, most studies typically do not assess the relationship between WM and episodic memory formation. In the present
Parikh, Preeyam K; Troyer, Angela K; Maione, Andrea M; Murphy, Kelly J
Older adults with age-normal memory changes and those with amnestic mild cognitive impairment (aMCI) report mild memory difficulties with everyday problems such as learning new names or remembering past events. Although the type and extent of memory changes in these populations have been well documented, little is known about how memory changes impact their everyday lives. Using a qualitative research design, data were collected from three focus groups of older adults with normal memory changes (n = 23) and two focus groups of older adults with aMCI (n = 14). A thematic analysis using the constant comparative method was used to identify the impacts of memory change on key life domains. Four major themes emerged from the two groups, including changes in feelings and views of the self, changes in relationships and social interactions, changes in work and leisure activities, and deliberate increases in compensatory behaviors. Participants described both positive and negative consequences of memory change, and these were more substantial and generally more adverse for individuals with aMCI than for those with age-normal memory changes. There are similarities and important differences in the impact of mild memory change on the everyday lives of older adults with age-normal memory changes and those with aMCI. Findings underscore the need for clinical interventions that aim to minimize the emotional impact of memory changes and that increase leisure and social activity in individuals with aMCI. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Javadi-Paydar, Mehrak; Zakeri, Marjan; Norouzi, Abbas; Rastegar, Hossein; Mirazi, Naser; Dehpour, Ahmad Reza
Granisetron, a serotonin 5-HT(3) receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was administered to scopolamine-induced memory-impaired mice prior to acquisition, consolidation and retrieval phases, either in the presence or in the absence of a non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750 mg/kg). It is demonstrated that granisetron improved memory acquisition in a dose-dependent manner, but it was ineffective on consolidation and retrieval phases of memory. The beneficial effect of granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750 mg/kg) did not potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory acquisition phase. It is concluded that nitric oxide is probably involved in improvement of memory acquisition by granisetron in both spatial recognition memory and fear memory. This article is part of a Special Issue entitled The Cognitive Neuroscience. Copyright © 2011 Elsevier B.V. All rights reserved.
Gao, Jingquan; Wu, Hongmei; Cao, Yonggang; Liang, Shuang; Sun, Caihong; Wang, Peng; Wang, Ji; Sun, Hongli; Wu, Lijie
Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in postnatal brain development. However, there have been no studies investigating the preventive effect of DHA on prenatal valproic acid (VPA)-induced behavioral and molecular alterations in offspring. The present study was to evaluate the neuroprotective effects in offspring using maternal feeding of DHA to rats exposed to VPA in pregnancy. In the present study, rats were exposed to VPA on day 12.5 of pregnancy; DHA was administered at the dosages of 100, 300 and 500 mg/kg/day for 3 weeks from day 1 to 21 of pregnancy. The results showed that maternal feeding of DHA to the prenatal exposed to VPA (1) prevented VPA-induced learning and memory impairment but did not change social-related behavior, (2) increased total DHA content in offspring plasma and hippocampus, (3) rescued VPA-induced neuronal loss and apoptosis of pyramidal cells in hippocampal CA1, (4) influenced the content of malondialdehyde and glutathione and the activities of superoxide dismutase and glutathione in the hippocampus, (5) altered levels of apoptosis-related proteins (Bcl-2, Bax and caspase-3) and inhibited the activity of caspase-3 in offspring hippocampus and (6) enhanced relative levels of p-CaMKII and p-CREB proteins in the hippocampus. These findings suggest that maternal feeding with DHA may prevent prenatal VPA-induced impairment of learning and memory, normalize several different molecules associated with oxidative stress and apoptosis in the hippocampus of offspring, and exert preventive effects on prenatal VPA-induced brain dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.
Hicks, Callum; Ramos, Linnet; Reekie, Tristan A; Narlawar, Rajeshwar; Kassiou, Michael; McGregor, Iain S
Recent in vitro studies suggest that the oxytocin receptor (OTR) agonist WAY 267,464 has vasopressin 1A receptor (V1AR) antagonist effects. This might limit its therapeutic potential due to the positive involvement of the V1AR in social behavior. The objective of this study was to assess functional V1AR antagonist-like effects of WAY 267,464 in vivo using a test of social recognition memory. Adult experimental rats were tested for their recognition of a juvenile conspecific rat that they had briefly met 30 or 120 min previously. The modulatory effects of vasopressin (AVP), the selective V1AR antagonist SR49059, and WAY 267,464 were examined together with those of the selective OTR antagonist Compound 25 (C25). Drugs were administered immediately after the first meeting. Control rats showed recognition of juveniles at a 30 min, but not a 120 min retention interval. AVP (0.005, but not 0.001 mg/kg intraperitoneal (i.p.)) improved memory such that recognition was evident after 120 min. This was prevented by pretreatment with SR49059 (1 mg/kg) and WAY 267,464 (10, 30, and 100 mg/kg). Given alone, SR49059 (1 mg/kg) and WAY 267,464 (30 and 100 mg/kg) impaired memory at a 30 min retention interval. The impairment with WAY 267,464 was not prevented by C25 (5 mg/kg), suggesting V1AR rather than OTR mediation of the effect. Given alone, C25 also impaired memory. These results highlight a tonic role for endogenous AVP (and oxytocin) in social recognition memory and indicate that WAY 267,464 functions in vivo as a V1AR antagonist to prevent the memory-enhancing effects of AVP.
López Hill, Ximena; Richeri, Analía; Scorza, María Cecilia
Cognitive impairment associated with schizophrenia (CIAS) is highly prevalent and affects the overall functioning of patients. Clozapine (Clz), an atypical antipsychotic drug, significantly improves CIAS although the underlying mechanisms remain under study. The role of the 5-HT 1A receptor (5-HT 1A -R) in the ability of Clz to prevent the learning/memory impairment induced by MK-801 was investigated using the modified elevated plus-maze (mEPM) considering the Transfer latency (TL) as an index of spatial memory. We also investigated if changes in hippocampal brain-derived neurotrophic factor (BDNF) levels underlie the behavioral prevention induced by Clz. Clz (0.5 and 1mg/kg)- or vehicle-pretreated Wistar rats were injected with MK-801 (0.05mg/kg) or saline. TL was evaluated 35min later (TL1, acquisition session) while learning/memory performance was measured 24h (TL2, retention session) and 48h later (TL3, long-lasting effect). WAY-100635, a 5-HT 1A -R antagonist, was pre-injected (0.3mg/kg) to examine the presumed 5-HT 1A -R involvement in Clz action. At TL2, another experimental group treated with Clz and MK-801 and its respective control groups were added to measure BDNF protein levels by ELISA. TL1 and TL3 were not significantly modified by the different treatments. MK-801 increased TL2 compared to control group leading a disruption of spatial memory processing which was markedly attenuated by Clz. WAY-100635 suppressed this action supporting a relevant role of 5-HT 1A -R in the Clz mechanism of action to improve spatial memory dysfunction. Although a significant decrease of hippocampal BDNF levels underlies the learning/memory impairment induced by MK-801, this effect was not significantly prevented by Clz. Copyright © 2017 Elsevier Inc. All rights reserved.
Fujiwara, Takeshi; Hoshide, Satoshi; Kanegae, Hiroshi; Eguchi, Kazuo; Kario, Kazuomi
We investigated the association between working memory (WM) impairment and blood pressure variability (BPV) in very elderly patients. Japanese outpatients ≥80 years who engaged in normal activities of daily living were the study cohort. WM function was evaluated by a simple visual WM test consisting of 3 figures. We considered the number of figures recalled by the patient his/her test score. We defined the patients with a score of 0 or 1 as those with WM impairment and those with scores of 2 or 3 as those without. To investigate the relative risk of WM impairment, we evaluated each patient's 24 hour ambulatory systolic blood pressure (SBP) and its weighted standard deviation (SD SBP ), office SBP, and the visit-to-visit SD SBP during the 1 year period from the patient's enrollment. A total of 66 patients (mean 84 ± 3.6 years) showed WM impairment, and 431 patients (mean 83 ± 3.1 years) showed no WM impairment. There were no significant differences in 24 hour ambulatory SBP or office SBP between these two groups. However, the WM impairment patients showed significantly higher weighted SD SBP and visit-to-visit SD SBP values compared to the no-impairment group even after adjusting for age. Among these ≥80-year-old patients, those with the highest quartile of both weighted SD SBP (≥21.4 mm Hg) and visit-to-visit SD SBP (≥14.5 mm Hg) showed the highest relative risk (odds ratio 3.52, 95% confidence interval 1.42-8.72) for WM impairment. Exaggerated blood pressure variability parameters were significantly associated with working memory impairment in very elderly individuals. ©2018 Wiley Periodicals, Inc.
Fortunato-Tavares, Talita; Andrade, Claudia R F; Befi-Lopes, Debora; Limongi, Suelly O; Fernandes, Fernanda D M; Schwartz, Richard G
This study examined syntactic assignment for predicates and reflexives as well as working memory effects in the sentence comprehension of children with Specific Language Impairment (SLI), Down syndrome (DS), high functioning Autism (HFA) and Typical Language Development (TLD). Fifty-seven children (35 boys and 22 girls) performed a computerised picture-selection sentence comprehension task. Predicate attachment and reflexive antecedent assignment (with working memory manipulations) were investigated. The results showed that SLI, HFA and DS children exhibited poorer overall performance than TLD children. Children with SLI exhibited similar performance to the DS and HFA children only when working memory demands were higher. We conclude that children with SLI, HFA and DS differ from children with TLD in their comprehension of predicate and reflexive structures where the knowledge of syntactic assignment is required. Working memory manipulation had different effects on syntactic comprehension depending on language disorder. Intelligence was not an explanatory factor for the differences observed in performance.
Nie, Jia; Zhang, Wei; Chen, Jia; Li, Wendi
Impairments in response inhibition and working memory functions have been found to be closely associated with internet addiction (IA) symptoms and attention-deficit/hyperactivity disorder (ADHD) symptoms. In this study, we examined response inhibition and working memory processes with two different materials (internet-related and internet-unrelated stimuli) among adolescents with IA, ADHD and co-morbid IA/ADHD. Twenty-four individuals with IA, 28 individuals with ADHD, 17 individuals with IA/ADHD, and 26 matched normal controls (NC) individuals were recruited. All participants were measured with a Stop-Signal Task and 2-Back Task under the same experimental conditions. In comparison to the NC group, subjects with IA, ADHD and IA/ADHD demonstrated impaired inhibition and working memory. In addition, in comparison to internet-unrelated conditions, IA and co-morbid subjects performed worse on the internet-related condition in the Stop trials during the stop-signal task, and they showed better working memory on the internet-related condition in the 2-Back Task. The findings of our study suggest individuals with IA and IA/ADHD may be impaired in inhibition and working memory functions that might be linked to poor inhibition specifically related to internet-related stimuli, which will advance our understanding of IA and contribute to prevention and intervention strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Full Text Available Emotionally traumatic experiences can lead to debilitating anxiety disorders, such as phobias and Post-Traumatic Stress Disorder (PTSD. Exposure to such experiences, however, is not sufficient to induce pathology, as only up to one quarter of people exposed to such events develop PTSD. These statistics, combined with findings that smaller hippocampal size prior to the trauma is associated with higher risk of developing PTSD, suggest that there are pre-disposing factors for such pathology. Because prospective studies in humans are limited and costly, investigating such pre-dispositions, and thus advancing understanding of the genesis of such pathologies, requires the use of animal models where predispositions are identified before the emotional trauma. Most existing animal models are retrospective: they classify subjects as those with or without a PTSD-like phenotype long after experiencing a traumatic event. Attempts to create prospective animal models have been largely unsuccessful.Here we report that individual predispositions to a PTSD-like phenotype, consisting of impaired rate and magnitude of extinction of an emotionally traumatic event coupled with long-lasting elevation of acoustic startle responses, can be revealed following exposure to a mild stressor, but before experiencing emotional trauma. We compare, in rats, the utility of several classification criteria and report that a combination of criteria based on acoustic startle responses and behavior in an anxiogenic environment is a reliable predictor of a PTSD-like phenotype.There are individual predispositions to developing impaired extinction and elevated acoustic startle that can be identified after exposure to a mildly stressful event, which by itself does not induce such a behavioral phenotype. The model presented here is a valuable tool for studying the etiology and pathophysiology of anxiety disorders and provides a platform for testing behavioral and pharmacological
Leite, Marlon R; Marcondes Sari, Marcel Henrique; de Freitas, Mayara L; Oliveira, Lia P; Dalmolin, Laíza; Brandão, Ricardo; Zeni, Gilson
The aim of the present study was to evaluate the effects of diphenyl diselenide (PhSe)2 supplemented diet (10ppm) associated to the administration of caffeine (15mg/kg; i.g.) for 30days on the novel object recognition memory in middle-aged rats. The present findings showed that (PhSe)2-supplemented diet enhanced short-term memory, but not long-term memory, of middle-aged rats in the novel object recognition task. The (PhSe)2 supplemented diet associated with caffeine administration improved long-term memory, but did not alter short-term memory, impaired in middle-aged rats. Daily caffeine administration to middle-aged rats had no effect on the memory tasks. Diet supplemented with (PhSe)2 plus caffeine administration increased the number of crossings and rearings reduced in middle-aged rats. Caffeine administration plus (PhSe)2 diets were effective in increasing the number of rearings and crossings, respectively, in middle-aged rats, [(3)H] glutamate uptake was reduced in hippocampal slices of rats from (PhSe)2 and caffeine plus (PhSe)2 groups. In addition, animals supplemented with (PhSe)2 showed an increase in the pCREB/CREB ratio whereas pAkt/Akt ratio was not modified. These results suggest that the effects of (PhSe)2 on the short-term memory may be related to its ability to decrease the uptake of glutamate, influencing the increase of CREB phosphorylation. (PhSe)2-supplemented diet associated to the administration of caffeine improved long-term memory impaired in middle-aged rats, an effect independent of CREB and Akt phosphorylation. Copyright © 2014 Elsevier Inc. All rights reserved.
Loucas, Tom; Riches, Nick Greatorex; Charman, Tony; Pickles, Andrew; Simonoff, Emily; Chandler, Susie; Baird, Gillian
Background: The cognitive bases of language impairment in specific language impairment (SLI) and autism spectrum disorders (ASD) were investigated in a novel non-word comparison task which manipulated phonological short-term memory (PSTM) and speech perception, both implicated in poor non-word repetition. Aims: This study aimed to investigate the…
Demeter, Gyula; Racsmány, Mihály; Csigó, Katalin; Harsányi, András; Németh, Attila; Döme, László
Previous neuropsychological studies produced inconsistent results with tasks tapping short-term verbal and visual-spatial memory and executive functions in obsessive compulsive disorder (OCD). The aim of this study was to investigate the presence of deficits in these cognitive domains. A further goal was to describe the distribution of patients in different impairment ranges for all functions, and clarify the relationship between symptom severity and cognitive impairments. Thirty patients with OCD (DSM-IV) and 30 healthy volunteers were compared using well-known neuropsychological tasks. We assessed short-term verbal memory with the Digit Span Forward and Digit Span Backward Tasks, short-term visual-spatial memory with the Corsi Block Tapping Task, while we measured the level of executive functions with the StroopTask and the Wisconsin Card Sorting Test (WCST). Compared with a matched healthy control group, the performance of OCD patients was in the impaired range only in the two executive tasks. We find a significant positive correlations between the Y-BOCS (Yale-Brown Obsessive Compulsive Scale) total scores and the number of perseverative responses (r(28) = 0.409, p short-term memory is intact in OCD. This is in line with neuropsychological model of OCD that the deficit of cognitive and behavioral inhibition are responsible for the main cognitive findings of this disorder, most prevalently the deficit in set shifting and prepotent response inhibition.
Khodamoradi, Nasrin; Komaki, Alireza; Salehi, Iraj; Shahidi, Siamak; Sarihi, Abdolrahman
Chronic lead (Pb(2+)) exposure has been associated with learning and memory impairments, whereas vitamin E improves cognitive deficits. In this study, using a passive avoidance learning model in rats, we investigated the effects of vitamin E on Pb(2+) exposure-induced learning and memory impairments in rats. In the present study, 56 Wistar male rats (weighting 230-250g) were divided into eight groups (n=7). The Pb(2+) exposure involved gavages of lead acetate solution using three different doses (0.05%, 0.1%, and 0.2%) and the vitamin E consisted of three different doses (10, 25, 50μg/rat) for 30days. After the 30-day period, the rats were tested using a passive avoidance task (acquisition test). In a retrieval test conducted 48h after the training, step through latency (STL) and time in the dark compartment (TDC) were recorded. The statistical analysis of data was performed using ANOVA followed by Tukey's post hoc analysis. In all cases, differences were considered significant if plearning and the TDC, whereas it decreased the STL in the passive avoidance test. Administration of vitamin E ameliorated the effects of Pb(2+) on animal behavior in the passive avoidance learning and memory task. Our results indicate that impairments of learning and memory in Pb(2+)-exposed rats are dose dependent and can be inhibited by antioxidants such as vitamin E. Copyright © 2015 Elsevier Inc. All rights reserved.
Zhao, Shan-shan; Yang, Wei-na; Jin, Hui; Ma, Kai-ge; Feng, Gai-feng
Puerarin (PUE), an isoflavone purified from the root of Pueraria lobata (Chinese herb), has been reported to attenuate learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). In the present study, we tested PUE in a sporadic AD (SAD) mouse model which was induced by the intracerebroventricular injection of streptozotocin (STZ). The mice were administrated PUE (25, 50, or 100mg/kg/d) for 28 days. Learning and memory abilities were assessed by the Morris water maze test. After behavioral test, the biochemical parameters of oxidative stress (glutathione peroxidase (GSH-Px), superoxide dismutases (SOD), and malondialdehyde (MDA)) were measured in the cerebral cortex and hippocampus. The SAD mice exhibited significantly decreased learning and memory ability, while PUE attenuated these impairments. The activities of GSH-Px and SOD were decreased while MDA was increased in the SAD animals. After PUE treatment, the activities of GSH-Px and SOD were elevated, and the level of MDA was decreased. The middle dose PUE was more effective than others. These results indicate that PUE attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice. PUE may be a promising therapeutic agent for SAD. Copyright © 2015 Elsevier Inc. All rights reserved.
Lehrner, J; Coutinho, G; Mattos, P; Moser, D; Pflüger, M; Gleiss, A; Auff, E; Dal-Bianco, P; Pusswald, G; Stögmann, E
Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment. 323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated. Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS. We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.
Machado, Nuno J; Simões, Ana Patrícia; Silva, Henrique B; Ardais, Ana Paula; Kaster, Manuella P; Garção, Pedro; Rodrigues, Diana I; Pochmann, Daniela; Santos, Ana Isabel; Araújo, Inês M; Porciúncula, Lisiane O; Tomé, Ângelo R; Köfalvi, Attila; Vaugeois, Jean-Marie; Agostinho, Paula; El Yacoubi, Malika; Cunha, Rodrigo A; Gomes, Catarina A
Caffeine prophylactically prevents mood and memory impairments through adenosine A 2A receptor (A 2A R) antagonism. A 2A R antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; -22 ± 7 %) and GABAergic (vGAT; -23 ± 8 %) markers in the hippocampus. HM displayed higher A 2A R density (72 ± 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A 2A R agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 ± 8 % vs. 21 ± 5 % in controls) that was restored to control levels (30 ± 10 %) by the A 2A R antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A 2A R controlling synaptic glutamatergic function.
Mantor, Duangkamol; Pratchayasakul, Wasana; Minta, Wanitchaya; Sutham, Wissuta; Palee, Siripong; Sripetchwandee, Jirapas; Kerdphoo, Sasiwan; Jaiwongkum, Thidarat; Sriwichaiin, Sirawit; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C
Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity. Copyright © 2017. Published by Elsevier Inc.