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

PubMed

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

2014-10-01

Evaluation of the efficacy of novel therapeutics for potential treatment of Alzheimer's disease (AD) requires an animal model that develops age-related cognitive deficits reproducibly between independent groups of investigators. Herein we assessed comparative temporal changes in spatial memory function in two commercially available transgenic mouse models of AD using the Morris water maze (MWM), incorporating both visible and hidden platform training. Individual cohorts of cDNA-based 'line 85'-derived double-transgenic mice coexpressing the 'Swedish' mutation of amyloid precursor protein (APPSwe) and the presenillin 1 (PS1) 'dE9' mutation were assessed in the MWM at mean ages of 3.6, 9.3 and 14.8 months. We found significant deficits in spatial memory retention in APPSwe/PS1dE9 mice aged 3.6 months and robust deficits in spatial memory acquisition and retention in APPSwe/PS1dE9 mice aged 9.3 months, with a further significant decline by age 14.8 months. β-Amyloid deposits were present in brain sections by 7.25 months of age. In contrast, MWM studies with individual cohorts (aged 4-21 months) of single-transgenic genomic-based APPSwe mice expressing APPSwe on a yeast artificial chromosomal (YAC) construct showed no significant deficits in spatial memory acquisition until 21 months of age. There were no significant deficits in spatial memory retention up to 21 months of age and β-amyloid deposits were not present in brain sections up to 24 months of age. These data, generated using comprehensive study designs, show that APPSwe/PS1dE9 but not APPSwe YAC mice appear to provide a suitably robust model of AD for efficacy assessment of novel AD treatments in development. © 2014 Wiley Publishing Asia Pty Ltd.

A Comparison of Normal Forgetting, Psychopathology, and Information-Processing Models of Reported Amnesia for Recent Sexual Trauma

PubMed Central

Mechanic, Mindy B.; Resick, Patricia A.; Griffin, Michael G.

2010-01-01

This study assessed memories for sexual trauma in a nontreatment-seeking sample of recent rape victims and considered competing explanations for failed recall. Participants were 92 female rape victims assessed within 2 weeks of the rape; 62 were also assessed 3 months postassault. Memory deficits for parts of the rape were common 2 weeks postassault (37%) but improved over the 3-month window studied (16% still partially amnesic). Hypotheses evaluated competing models of explanation that may account for reported recall deficits. Results are most consistent with information-processing models of traumatic memory. PMID:9874908

Examining procedural working memory processing in obsessive-compulsive disorder.

PubMed

Shahar, Nitzan; Teodorescu, Andrei R; Anholt, Gideon E; Karmon-Presser, Anat; Meiran, Nachshon

2017-07-01

Previous research has suggested that a deficit in working memory might underlie the difficulty of obsessive-compulsive disorder (OCD) patients to control their thoughts and actions. However, a recent meta-analyses found only small effect sizes for working memory deficits in OCD. Recently, a distinction has been made between declarative and procedural working memory. Working memory in OCD was tested mostly using declarative measurements. However, OCD symptoms typically concerns actions, making procedural working-memory more relevant. Here, we tested the operation of procedural working memory in OCD. Participants with OCD and healthy controls performed a battery of choice reaction tasks under high and low procedural working memory demands. Reaction-times (RT) were estimated using ex-Gaussian distribution fitting, revealing no group differences in the size of the RT distribution tail (i.e., τ parameter), known to be sensitive to procedural working memory manipulations. Group differences, unrelated to working memory manipulations, were found in the leading-edge of the RT distribution and analyzed using a two-stage evidence accumulation model. Modeling results suggested that perceptual difficulties might underlie the current group differences. In conclusion, our results suggest that procedural working-memory processing is most likely intact in OCD, and raise a novel, yet untested assumption regarding perceptual deficits in OCD. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

PubMed

Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

2015-01-01

We have recently shown that the M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance in rodents and non-human primates administered the muscarinic receptor antagonist scopolamine. The purpose of the present experiments was to characterize the effects of PQCA in a model more relevant to the disease pathology of Alzheimer's disease. Tg2576 transgenic mice that have elevated Aβ were tested in the novel object recognition task to characterize recognition memory as a function of age and treatment with the PQCA. The effects of PQCA were compared to the acetylcholinesterase inhibitor donepezil, the standard of care for Alzheimer's disease. In addition, the effect of co-administering PQCA and donepezil was evaluated. Aged Tg2576 mice demonstrated a deficit in recognition memory that was significantly attenuated by PQCA. The positive control donepezil also reversed the deficit. Furthermore, doses of PQCA and donepezil that were inactive on their own were found to improve recognition memory when given together. These studies suggest that M1 muscarinic receptor positive allosteric modulation can ameliorate memory deficits in disease relevant models of Alzheimer's disease. These data, combined with our previous findings demonstrating PQCA improves scopolamine-induced cognitive deficits in both rodents and non-human primates, suggest that M1 positive allosteric modulators have therapeutic potential for the treatment of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Gypenosides ameliorate memory deficits in MPTP-lesioned mouse model of Parkinson's disease treated with L-DOPA.

PubMed

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

2017-09-06

Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA). MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days. After the final treatments, behavioral changes were assessed in all mice using passive avoidance and elevated plus-maze tests. We then evaluated the biochemical influences of GPS treatment on levels of tyrosine hydroxylase (TH), dopamine, N-methyl-D-aspartate (NMDA) receptors, extracellular signal-regulated kinase (ERK1/2), and cyclic AMP-response element binding protein (CREB) phosphorylation. MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits. Treatment with GPS (50 mg/kg) also improved L-DOPA (25 mg/kg)-treated MPTP lesion-induced decreases in retention latency on the passive avoidance test, as well as levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum. GPS treatment also attenuated increases in retention transfer latency on the elevated plus-maze test and in NMDA receptor expression, as well as decreases in the phosphorylation of ERK1/2 and CREB in the hippocampus. Treatment with L-DOPA (10 mg/kg) also ameliorated deficits in habit learning and spatial memory in MPTP-lesioned mice, and this effect was further enhanced by treatment with GPS (50 mg/kg). GPS ameliorate deficits in habit learning and spatial memory by modulating the dopaminergic neuronal and N-methyl-D-aspartate receptor-mediated signaling systems in MPTP-lesioned mice treated with L-DOPA. GPS may serve as an adjuvant therapeutic agent for memory deficits in patients with PD receiving L-DOPA.

Object location and object recognition memory impairments, motivation deficits and depression in a model of Gulf War illness.

PubMed

Hattiangady, Bharathi; Mishra, Vikas; Kodali, Maheedhar; Shuai, Bing; Rao, Xiolan; Shetty, Ashok K

2014-01-01

Memory and mood deficits are the enduring brain-related symptoms in Gulf War illness (GWI). Both animal model and epidemiological investigations have indicated that these impairments in a majority of GW veterans are linked to exposures to chemicals such as pyridostigmine bromide (PB, an antinerve gas drug), permethrin (PM, an insecticide) and DEET (a mosquito repellant) encountered during the Persian Gulf War-1. Our previous study in a rat model has shown that combined exposures to low doses of GWI-related (GWIR) chemicals PB, PM, and DEET with or without 5-min of restraint stress (a mild stress paradigm) causes hippocampus-dependent spatial memory dysfunction in a water maze test (WMT) and increased depressive-like behavior in a forced swim test (FST). In this study, using a larger cohort of rats exposed to GWIR-chemicals and stress, we investigated whether the memory deficiency identified earlier in a WMT is reproducible with an alternative and stress free hippocampus-dependent memory test such as the object location test (OLT). We also ascertained the possible co-existence of hippocampus-independent memory dysfunction using a novel object recognition test (NORT), and alterations in mood function with additional tests for motivation and depression. Our results provide new evidence that exposure to low doses of GWIR-chemicals and mild stress for 4 weeks causes deficits in hippocampus-dependent object location memory and perirhinal cortex-dependent novel object recognition memory. An open field test performed prior to other behavioral analyses revealed that memory impairments were not associated with increased anxiety or deficits in general motor ability. However, behavioral tests for mood function such as a voluntary physical exercise paradigm and a novelty suppressed feeding test (NSFT) demonstrated decreased motivation levels and depression. Thus, exposure to GWIR-chemicals and stress causes both hippocampus-dependent and hippocampus-independent memory impairments as well as mood dysfunction in a rat model.

Faster Forgetting Contributes to Impaired Spatial Memory in the PDAPP Mouse: Deficit in Memory Retrieval Associated with Increased Sensitivity to Interference?

ERIC Educational Resources Information Center

Daumas, Stephanie; Sandin, Johan; Chen, Karen S.; Kobayashi, Dione; Tulloch, Jane; Martin, Stephen J.; Games, Dora; Morris, Richard G. M.

2008-01-01

Two experiments were conducted to investigate the possibility of faster forgetting by PDAPP mice (a well-established model of Alzheimer's disease as reported by Games and colleagues in an earlier paper). Experiment 1, using mice aged 13-16 mo, confirmed the presence of a deficit in a spatial reference memory task in the water maze by hemizygous…

Schizophrenia-Related Microdeletion Impairs Emotional Memory through MicroRNA-Dependent Disruption of Thalamic Inputs to the Amygdala.

PubMed

Eom, Tae-Yeon; Bayazitov, Ildar T; Anderson, Kara; Yu, Jing; Zakharenko, Stanislav S

2017-05-23

Individuals with 22q11.2 deletion syndrome (22q11DS) are at high risk of developing psychiatric diseases such as schizophrenia. Individuals with 22q11DS and schizophrenia are impaired in emotional memory, anticipating, recalling, and assigning a correct context to emotions. The neuronal circuits responsible for these emotional memory deficits are unknown. Here, we show that 22q11DS mouse models have disrupted synaptic transmission at thalamic inputs to the lateral amygdala (thalamo-LA projections). This synaptic deficit is caused by haploinsufficiency of the 22q11DS gene Dgcr8, which is involved in microRNA processing, and is mediated by the increased dopamine receptor Drd2 levels in the thalamus and by reduced probability of glutamate release from thalamic inputs. This deficit in thalamo-LA synaptic transmission is sufficient to cause fear memory deficits. Our results suggest that dysregulation of the Dgcr8-Drd2 mechanism at thalamic inputs to the amygdala underlies emotional memory deficits in 22q11DS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Declarative memory deficits and schizophrenia: problems and prospects.

PubMed

Stone, William S; Hsi, Xiaolu

2011-11-01

Cognitive deficits are among the most important factors leading to poor functional outcomes in schizophrenia, with deficits in declarative memory among the largest and most robust of these. Thus far, attempts to enhance cognition in schizophrenia have shown only modest success, which underlies increasing efforts to develop effective treatment strategies. This review is divided into three main parts. The first section delineates the nature and extent of the deficits in both patients with schizophrenia and in their adult, non-psychotic relatives. The second part focuses on structural and functional abnormalities in the hippocampus, both in people with schizophrenia and in animal studies that model relevant features of the illness. The third section views problems in declarative memory and hippocampal function from the perspective of elevated rates of common medical disorders in schizophrenia, with a focus on insulin insensitivity/diabetes. The likelihood that poor glucose regulation/availability contribute to declarative memory deficits and hippocampal abnormalities is considered, along with the possibility that schizophrenia and poor glucose regulation share common etiologic elements, and with clinical implications of this perspective for enhancing declarative memory. Copyright © 2011 Elsevier Inc. All rights reserved.

Memory deficits with intact cognitive control in the methylazoxymethanol acetate (MAM) exposure model of neurodevelopmental insult.

PubMed

O'Reilly, Kally C; Perica, Maria I; Fenton, André A

2016-10-01

Cognitive impairments are amongst the most debilitating deficits of schizophrenia and the best predictor of functional outcome. Schizophrenia is hypothesized to have a neurodevelopmental origin, making animal models of neurodevelopmental insult important for testing predictions that early insults will impair cognitive function. Rats exposed to methylazoxymethanol acetate (MAM) at gestational day 17 display morphological, physiological and behavioral abnormalities relevant to schizophrenia. Here we investigate the cognitive abilities of adult MAM rats. We examined brain activity in MAM rats by histochemically assessing cytochrome oxidase enzyme activity, a metabolic marker of neuronal activity. To assess cognition, we used a hippocampus-dependent two-frame active place avoidance paradigm to examine learning and spatial memory, as well as cognitive control and flexibility using the same environment and evaluating the same set of behaviors. We confirmed that adult MAM rats have altered hippocampal morphology and brain function, and that they are hyperactive in an open field. The latter likely indicates MAM rats have a sensorimotor gating deficit that is common to many animal models used for schizophrenia research. On first inspection, cognitive control seems impaired in MAM rats, indicated by more errors during the two-frame active place avoidance task. Because MAM rats are hyperactive throughout place avoidance training, we considered the possibility that the hyperlocomotion may account for the apparent cognitive deficits. These deficits were reduced on the basis of measures of cognitive performance that account for motor activity differences. However, though other aspects of memory are intact, the ability of MAM rats to express trial-to-trial memory is delayed compared to control rats. These findings suggest that spatial learning and cognitive abilities are largely intact, that the most prominent cognitive deficit is specific to acquiring memory in the MAM neurodevelopmental model, and that hyperactivity can confound assessments of cognition in animal models of mental dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice.

PubMed

Boerner, Thomas; Bygrave, Alexei M; Chen, Jingkai; Fernando, Anushka; Jackson, Stephanie; Barkus, Chris; Sprengel, Rolf; Seeburg, Peter H; Harrison, Paul J; Gilmour, Gary; Bannerman, David M; Sanderson, David J

2017-04-01

Group II metabotropic glutamate receptor agonists have been suggested as potential anti-psychotics, at least in part, based on the observation that the agonist LY354740 appeared to rescue the cognitive deficits caused by non-competitive N-methyl-d-aspartate receptor (NMDAR) antagonists, including spatial working memory deficits in rodents. Here, we tested the ability of LY354740 to rescue spatial working memory performance in mice that lack the GluA1 subunit of the AMPA glutamate receptor, encoded by Gria1, a gene recently implicated in schizophrenia by genome-wide association studies. We found that LY354740 failed to rescue the spatial working memory deficit in Gria1 -/- mice during rewarded alternation performance in the T-maze. In contrast, LY354740 did reduce the locomotor hyperactivity in these animals to a level that was similar to controls. A similar pattern was found with the dopamine receptor antagonist haloperidol, with no amelioration of the spatial working memory deficit in Gria1 -/- mice, even though the same dose of haloperidol reduced their locomotor hyperactivity. These results with LY354740 contrast with the rescue of spatial working memory in models of glutamatergic hypofunction using non-competitive NMDAR antagonists. Future studies should determine whether group II mGluR agonists can rescue spatial working memory deficits with other NMDAR manipulations, including genetic models and other pharmacological manipulations of NMDAR function. © 2017 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Aging selectively impairs recollection in recognition memory for pictures: Evidence from modeling and ROC curves

PubMed Central

Howard, Marc W.; Bessette-Symons, Brandy; Zhang, Yaofei; Hoyer, William J.

2006-01-01

Younger and older adults were tested on recognition memory for pictures. The Yonelinas high threshold (YHT) model, a formal implementation of two-process theory, fit the response distribution data of both younger and older adults significantly better than a normal unequal variance signal detection model. Consistent with this finding, non-linear zROC curves were obtained for both groups. Estimates of recollection from the YHT model were significantly higher for younger than older adults. This deficit was not a consequence of a general decline in memory; older adults showed comparable overall accuracy and in fact a non-significant increase in their familiarity scores. Implications of these results for theories of recognition memory and the mnemonic deficit associated with aging are discussed. PMID:16594795

Memantine Protects Rats Treated with Intrathecal Methotrexate from Developing Spatial Memory Deficits

PubMed Central

Cole, Peter D.; Vijayanathan, Veena; Ali, Nafeeza F.; Wagshul, Mark E.; Tanenbaum, Eric J.; Price, Jeremy; Dalal, Vidhi; Gulinello, Maria E.

2014-01-01

Purpose To test whether memantine can prevent methotrexate-induced cognitive deficits in a preclinical model. Experimental Design After noting that methotrexate exposure induces prolonged elevations of the glutamate analog homocysteic acid (HCA) within cerebrospinal fluid, we tested whether intrathecal injection of HCA would produce memory deficits similar to those observed after intrathecal methotrexate. We then tested whether memantine, an antagonist of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors, could protect animals treated with clinically relevant doses of intrathecal methotrexate against developing memory deficits. Finally, we asked whether memantine affected this pathway beyond inhibiting the NMDA receptor by altering expression of the NMDA receptor or affecting concentrations of HCA or glutamate within the central nervous system. Results Four intrathecal doses of methotrexate induced deficits in spatial memory, persisting at least one month following the final injection. Intrathecal HCA was sufficient to reproduce this deficit. Concurrent administration of memantine during the period of methotrexate exposure was protective, decreasing the incidence of methotrexate-induced spatial memory deficits from 56% to 20% (P < 0.05). Memantine neither altered expression of NMDA receptors within the hippocampus nor blunted the methotrexate-induced increases in glutamate or HCA. Conclusions Excitotoxic glutamate analogs including HCA contribute to cognitive deficits observed after intrathecal methotrexate. Memantine, an NMDA receptor antagonist, reduces the incidence of cognitive deficits in rats treated with intrathecal methotrexate, and may therefore benefit patients with cancer receiving similar treatment. PMID:23833301

Impaired verbal short-term memory in Down syndrome reflects a capacity limitation rather than atypically rapid forgetting.

PubMed

M Purser, Harry R; Jarrold, Christopher

2005-05-01

Individuals with Down syndrome suffer from relatively poor verbal short-term memory. Recent work has indicated that this deficit is not caused by problems of audition, speech, or articulatory rehearsal within the phonological loop component of Baddeley and Hitch's working memory model. Given this, two experiments were conducted to investigate whether abnormally rapid decay underlies the deficit. In a first experiment, we attempted to vary the time available for decay using a modified serial recall procedure that had both verbal and visuospatial conditions. No evidence was found to suggest that forgetting is abnormally rapid in phonological memory in Down syndrome, but a selective phonological memory deficit was indicated. A second experiment further investigated possible problems of decay in phonological memory, restricted to item information. The results indicated that individuals with Down syndrome do not show atypically rapid item forgetting from phonological memory but may have a limited-capacity verbal short-term memory system.

Dominance of objects over context in a mediotemporal lobe model of schizophrenia.

PubMed

Talamini, Lucia M; Meeter, Martijn

2009-08-04

A large body of evidence suggests impaired context processing in schizophrenia. Here we propose that this impairment arises from defective integration of mediotemporal 'what' and 'where' routes, carrying object and spatial information to the hippocampus. We have previously shown, in a mediotemporal lobe (MTL) model, that the abnormal connectivity between MTL regions observed in schizophrenia can explain the episodic memory deficits associated with the disorder. Here we show that the same neuropathology leads to several context processing deficits observed in patients with schizophrenia: 1) failure to choose subordinate stimuli over dominant ones when the former fit the context, 2) decreased contextual constraints in memory retrieval, as reflected in increased false alarm rates and 3) impaired retrieval of contextual information in source monitoring. Model analyses show that these deficits occur because the 'schizophrenic MTL' forms fragmented episodic representations, in which objects are overrepresented at the expense of spatial contextual information. These findings highlight the importance of MTL neuropathology in schizophrenia, demonstrating that it may underlie a broad spectrum of deficits, including context processing and memory impairments. It is argued that these processing deficits may contribute to central schizophrenia symptoms such as contextually inappropriate behavior, associative abnormalities, conversational drift, concreteness and delusions.

Working Memory in Children With Neurocognitive Effects From Sickle Cell Disease: Contributions of the Central Executive and Processing Speed

PubMed Central

Smith, Kelsey E.; Schatz, Jeffrey

2017-01-01

Children with sickle cell disease (SCD) are at risk for working memory deficits due to multiple disease processes. We assessed working memory abilities and related functions in 32 school-age children with SCD and 85 matched comparison children using Baddeley’s working memory model as a framework. Children with SCD performed worse than controls for working memory, central executive function, and processing/rehearsal speed. Central executive function was found to mediate the relationship between SCD status and working memory, but processing speed did not. Cognitive remediation strategies that focus on central executive processes may be important for remediating working memory deficits in SCD. PMID:27759435

Increased stress reactivity is associated with cognitive deficits and decreased hippocampal brain-derived neurotrophic factor in a mouse model of affective disorders.

PubMed

Knapman, A; Heinzmann, J-M; Hellweg, R; Holsboer, F; Landgraf, R; Touma, C

2010-07-01

Cognitive deficits are a common feature of major depression (MD), with largely unknown biological underpinnings. In addition to the affective and cognitive symptoms of MD, a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly observed in these patients. Increased plasma glucocorticoid levels are known to render the hippocampus susceptible to neuronal damage. This structure is important for learning and memory, creating a potential link between HPA axis dysregulation and cognitive deficits in depression. In order to further elucidate how altered stress responsiveness may contribute to the etiology of MD, three mouse lines with high (HR), intermediate (IR), or low (LR) stress reactivity were generated by selective breeding. The aim of the present study was to investigate whether increased stress reactivity is associated with deficits in hippocampus-dependent memory tests. To this end, we subjected mice from the HR, IR, and LR breeding lines to tests of recognition memory, spatial memory, and depression-like behavior. In addition, measurements of brain-derived neurotrophic factor (BDNF) in the hippocampus and plasma of these animals were conducted. Our results demonstrate that HR mice exhibit hippocampus-dependent memory deficits along with decreased hippocampal, but not plasma, BDNF levels. Thus, the stress reactivity mouse lines are a promising animal model of the cognitive deficits in MD with the unique feature of a genetic predisposition for an altered HPA axis reactivity, which provides the opportunity to explore the progression of the symptoms of MD, predisposing genetic factors as well as new treatment strategies. Copyright 2009 Elsevier Ltd. All rights reserved.

ADHD and Working Memory: The Impact of Central Executive Deficits and Exceeding Storage/Rehearsal Capacity on Observed Inattentive Behavior

ERIC Educational Resources Information Center

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

2010-01-01

Inattentive behavior is considered a core and pervasive feature of ADHD; however, an alternative model challenges this premise and hypothesizes a functional relationship between working memory deficits and inattentive behavior. The current study investigated whether inattentive behavior in children with ADHD is functionally related to the…

Lateral and Anterior Thalamic Lesions Impair Independent Memory Systems

ERIC Educational Resources Information Center

Mitchell, Anna S.; Dalrymple-Alford, John C.

2006-01-01

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,…

Danish dementia mice suggest that loss of function and not the amyloid cascade causes synaptic plasticity and memory deficits

PubMed Central

Tamayev, Robert; Matsuda, Shuji; Fà, Mauro; Arancio, Ottavio; D’Adamio, Luciano

2010-01-01

According to the prevailing “amyloid cascade hypothesis,” genetic dementias such as Alzheimer’s disease and familial Danish dementia (FDD) are caused by amyloid deposits that trigger tauopathy, neurodegeneration, and behavioral/cognitive alterations. To efficiently reproduce amyloid lesions, murine models of human dementias invariably use transgenic expression systems. However, recent FDD transgenic models showed that Danish amyloidosis does not cause memory defects, suggesting that other mechanisms cause Danish dementia. We studied an animal knock-in model of FDD (FDDKI/+) genetically congruous with human cases. FDDKI/+ mice present reduced Bri2 levels, impaired synaptic plasticity and severe hippocampal memory deficits. These animals show no cerebral lesions that are reputed characteristics of human dementia, such as tangles or amyloid plaques. Bri2+/− mice exhibit synaptic and memory deficits similar to FDDKI/+ mice, and memory loss of FDDKI/+ mice is prevented by expression of WT BRI2, indicating that Danish dementia is caused by loss of BRI2 function. Together, the data suggest that clinical dementia in Danish patients occurs via a loss of function mechanism and not as a result of amyloidosis and tauopathy. PMID:21098268

Danish dementia mice suggest that loss of function and not the amyloid cascade causes synaptic plasticity and memory deficits.

PubMed

Tamayev, Robert; Matsuda, Shuji; Fà, Mauro; Arancio, Ottavio; D'Adamio, Luciano

2010-11-30

According to the prevailing "amyloid cascade hypothesis," genetic dementias such as Alzheimer's disease and familial Danish dementia (FDD) are caused by amyloid deposits that trigger tauopathy, neurodegeneration, and behavioral/cognitive alterations. To efficiently reproduce amyloid lesions, murine models of human dementias invariably use transgenic expression systems. However, recent FDD transgenic models showed that Danish amyloidosis does not cause memory defects, suggesting that other mechanisms cause Danish dementia. We studied an animal knock-in model of FDD (FDD(KI/+)) genetically congruous with human cases. FDD(KI/+) mice present reduced Bri2 levels, impaired synaptic plasticity and severe hippocampal memory deficits. These animals show no cerebral lesions that are reputed characteristics of human dementia, such as tangles or amyloid plaques. Bri2(+/-) mice exhibit synaptic and memory deficits similar to FDD(KI/+) mice, and memory loss of FDD(KI/+) mice is prevented by expression of WT BRI2, indicating that Danish dementia is caused by loss of BRI2 function. Together, the data suggest that clinical dementia in Danish patients occurs via a loss of function mechanism and not as a result of amyloidosis and tauopathy.

Theories of Memory and Aging: A Look at the Past and a Glimpse of the Future

PubMed Central

Festini, Sara B.

2017-01-01

The present article reviews theories of memory and aging over the past 50 years. Particularly notable is a progression from early single-mechanism perspectives to complex multifactorial models proposed to account for commonly observed age deficits in memory function. The seminal mechanistic theories of processing speed, limited resources, and inhibitory deficits are discussed and viewed as especially important theories for understanding age-related memory decline. Additionally, advances in multivariate techniques including structural equation modeling provided new tools that led to the development of more complex multifactorial theories than existed earlier. The important role of neuroimaging is considered, along with the current prevalence of intervention studies. We close with predictions about new directions that future research on memory and aging will take. PMID:27257229

Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors.

PubMed

Provencio, Jose Javier; Swank, Valerie; Lu, Haiyan; Brunet, Sylvain; Baltan, Selva; Khapre, Rohini V; Seerapu, Himabindu; Kokiko-Cochran, Olga N; Lamb, Bruce T; Ransohoff, Richard M

2016-05-01

Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats

PubMed Central

Carter, Angela N.; Born, Heather A.; Levine, Amber T.; Dao, An T.; Zhao, Amanda J.; Lee, Wai L.

2017-01-01

Numerous studies have shown epilepsy-associated cognitive deficits, but less is known about the effects of one single generalized seizure. Recent studies demonstrate that a single, self-limited seizure can result in memory deficits and induces hyperactive phosphoinositide 3-kinase/Akt (protein kinase B)/mechanistic target of rapamycin (PI3K/Akt/mTOR) signaling. However, the effect of a single seizure on subcellular structures such as dendritic spines and the role of aberrant PI3K/Akt/mTOR signaling in these seizure-induced changes are unclear. Using the pentylenetetrazole (PTZ) model, we induced a single generalized seizure in rats and: (1) further characterized short- and long-term hippocampal and amygdala-dependent memory deficits, (2) evaluated whether there are changes in dendritic spines, and (3) determined whether inhibiting hyperactive PI3K/Akt/mTOR signaling rescued these alterations. Using the PI3K inhibitor wortmannin (Wort), we partially rescued short- and long-term memory deficits and altered spine morphology. These studies provide evidence that pathological PI3K/Akt/mTOR signaling plays a role in seizure-induced memory deficits as well as aberrant spine morphology. PMID:28612047

Restoring synaptic plasticity and memory in mouse models of Alzheimer's disease by PKR inhibition.

PubMed

Hwang, Kyoung-Doo; Bak, Myeong Seong; Kim, Sang Jeong; Rhee, Sangmyung; Lee, Yong-Seok

2017-12-13

Alzheimer's disease (AD) is a neurodegenerative disorder associated with deficits in cognition and synaptic plasticity. While accumulation of amyloid β (Aβ) and hyper-phosphorylation of tau are parts of the etiology, AD can be caused by a large number of different genetic mutations and other unknown factors. Considering such a heterogeneous nature of AD, it would be desirable to develop treatment strategies that can improve memory irrespective of the individual causes. Reducing the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) was shown to enhance long-term memory and synaptic plasticity in naïve mice. Moreover, hyper-phosphorylation of eIF2α is observed in the brains of postmortem AD patients. Therefore, regulating eIF2α phosphorylation can be a plausible candidate for restoring memory in AD by targeting memory-enhancing mechanism. In this study, we examined whether PKR inhibition can rescue synaptic and learning deficits in two different AD mouse models; 5XFAD transgenic and Aβ 1-42 -injected mice. We found that the acute treatment of PKR inhibitor (PKRi) can restore the deficits in long-term memory and long-term potentiation (LTP) in both mouse models without affecting the Aβ load in the hippocampus. Our results prove the principle that targeting memory enhancing mechanisms can be a valid candidate for developing AD treatment.

Autobiographical Memory and Suicide Attempts in Schizophrenia

ERIC Educational Resources Information Center

Pettersen, Kenneth; Rydningen, Nora Nord; Christensen, Tore Buer; Walby, Fredrik A.

2010-01-01

According to the cry of pain model of suicidal behavior, an over-general autobiographical memory function is often found in suicide attempters. The model has received empirical support in several studies, mainly of depressed patients. The present study investigated whether deficits in autobiographical memory may be associated with an increased…

Attention and working memory deficits in a perinatal nicotine exposure mouse model.

PubMed

Zhang, Lin; Spencer, Thomas J; Biederman, Joseph; Bhide, Pradeep G

2018-01-01

Cigarette smoking by pregnant women is associated with a significant increase in the risk for cognitive disorders in their children. Preclinical models confirm this risk by showing that exposure of the developing brain to nicotine produces adverse behavioral outcomes. Here we describe behavioral phenotypes resulting from perinatal nicotine exposure in a mouse model, and discuss our findings in the context of findings from previously published studies using preclinical models of developmental nicotine exposure. Female C57Bl/6 mice received drinking water containing nicotine (100μg/ml) + saccharin (2%) starting 3 weeks prior to breeding and continuing throughout pregnancy, and until 3 weeks postpartum. Over the same period, female mice in two control groups received drinking water containing saccharin (2%) or plain drinking water. Offspring from each group were weaned at 3-weeks of age and subjected to behavioral analyses at 3 months of age. We examined spontaneous locomotor activity, anxiety-like behavior, spatial working memory, object based attention, recognition memory and impulsive-like behavior. We found significant deficits in attention and working memory only in male mice, and no significant changes in the other behavioral phenotypes in male or female mice. Exposure to saccharin alone did not produce significant changes in either sex. The perinatal nicotine exposure produced significant deficits in attention and working memory in a sex-dependent manner in that the male but not female offspring displayed these behaviors. These behavioral phenotypes are associated with attention deficit hyperactivity disorder (ADHD) and have been reported in other studies that used pre- or perinatal nicotine exposure. Therefore, we suggest that preclinical models of developmental nicotine exposure could be useful tools for modeling ADHD and related disorders.

Histamine H1 receptor antagonist cetirizine impairs working memory processing speed, but not episodic memory.

PubMed

van Ruitenbeek, P; Vermeeren, A; Riedel, W J

2010-09-01

The histaminergic neurotransmitter system is currently under investigation as a target for drug treatment of cognitive deficits in clinical disorders. The therapeutic potential of new drugs may initially be screened using a model of histaminergic dysfunction, for example, as associated with the use of centrally active antihistamines. Of the selective second generation antihistamines, cetirizine has been found to have central nervous system effects. The aim of the present study was to determine whether cetirizine can be used as a tool to model cognitive deficits associated with histaminergic hypofunction. The study was conducted according to a three-way, double-blind, cross-over design. Treatments were single oral doses of cetirizine 10 and 20 mg and placebo. Effects on cognition were assessed using tests of word learning, memory scanning, vigilance, divided attention, tracking and visual information processing speed. Cetirizine 10 mg impaired tracking performance and both doses impaired memory scanning speed. None of the other measures indicated impaired performance. Cetirizine affects information processing speed, but these effects were not sufficient to serve as a model for cognitive deficits in clinical disorders.

Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

PubMed

Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

2018-04-05

Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

Some Surprising Findings on the Involvement of the Parietal Lobe in Human Memory

PubMed Central

Olson, Ingrid R.; Berryhill, Marian

2009-01-01

The posterior parietal lobe is known to play some role in a far-flung list of mental processes: linking vision to action (saccadic eye movements, reaching, grasping), attending to visual space, numerical calculation, and mental rotation. Here we review findings from humans and monkeys that illuminate an untraditional function of this region: memory. Our review draws on neuroimaging findings that have repeatedly identified parietal lobe activations associated with short-term or working memory and episodic memory. We also discuss recent neuropsychological findings showing that individuals with parietal lobe damage exhibit both working memory and long-term memory deficits. These deficits are not ubiquitous; they are only evident under certain retrieval demands. Our review elaborates on these findings and evaluates various theories about the mechanistic role of the posterior parietal lobe in memory. The available data point towards the conclusion that the posterior parietal lobe plays an important role in memory retrieval irrespective of elapsed time. The two models that are best supported by existing data are the Attention to Memory Model and the Subjective Memory Model. We conclude by formalizing several open questions that are intended to encourage future research. PMID:18848635

Cdk5 Contributes to Huntington's Disease Learning and Memory Deficits via Modulation of Brain Region-Specific Substrates.

PubMed

Alvarez-Periel, Elena; Puigdellívol, Mar; Brito, Verónica; Plattner, Florian; Bibb, James A; Alberch, Jordi; Ginés, Silvia

2017-12-29

Cognitive deficits are a major hallmark of Huntington's disease (HD) with a great impact on the quality of patient's life. Gaining a better understanding of the molecular mechanisms underlying learning and memory impairments in HD is, therefore, of critical importance. Cdk5 is a proline-directed Ser/Thr kinase involved in the regulation of synaptic plasticity and memory processes that has been associated with several neurodegenerative disorders. In this study, we aim to investigate the role of Cdk5 in learning and memory impairments in HD using a novel animal model that expresses mutant huntingtin (mHtt) and has genetically reduced Cdk5 levels. Genetic reduction of Cdk5 in mHtt knock-in mice attenuated both corticostriatal learning deficits as well as hippocampal-dependent memory decline. Moreover, the molecular mechanisms by which Cdk5 counteracts the mHtt-induced learning and memory impairments appeared to be differentially regulated in a brain region-specific manner. While the corticostriatal learning deficits are attenuated through compensatory regulation of NR2B surface levels, the rescue of hippocampal-dependent memory was likely due to restoration of hippocampal dendritic spine density along with an increase in Rac1 activity. This work identifies Cdk5 as a critical contributor to mHtt-induced learning and memory deficits. Furthermore, we show that the Cdk5 downstream targets involved in memory and learning decline differ depending on the brain region analyzed suggesting that distinct Cdk5 effectors could be involved in cognitive impairments in HD.

Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model

PubMed Central

Osborne, Ashleigh L; Solowij, Nadia; Babic, Ilijana; Huang, Xu-Feng; Weston-Green, Katrina

2017-01-01

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with 10 mg/kg CBD (CONT+CBD, POLY+CBD; n=12 per group) or vehicle (VEH; CONT+VEH, POLY+VEH; n=12 per group) for 3 weeks. Body weight, food and water intake was measured weekly. The Novel Object Recognition and rewarded T-maze alternation tests assessed recognition and working memory, respectively, and the social interaction test assessed sociability. POLY+VEH offspring exhibited impaired recognition and working memory, and reduced social interaction compared to CONT+VEH offspring (p<0.01). CBD treatment significantly improved recognition, working memory and social interaction deficits in the poly I:C model (p<0.01 vs POLY+VEH), did not affect total body weight gain, food or water intake, and had no effect in control animals (all p>0.05). In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection. These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia. PMID:28230072

Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model.

PubMed

Osborne, Ashleigh L; Solowij, Nadia; Babic, Ilijana; Huang, Xu-Feng; Weston-Green, Katrina

2017-06-01

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with 10 mg/kg CBD (CONT+CBD, POLY+CBD; n=12 per group) or vehicle (VEH; CONT+VEH, POLY+VEH; n=12 per group) for 3 weeks. Body weight, food and water intake was measured weekly. The Novel Object Recognition and rewarded T-maze alternation tests assessed recognition and working memory, respectively, and the social interaction test assessed sociability. POLY+VEH offspring exhibited impaired recognition and working memory, and reduced social interaction compared to CONT+VEH offspring (p<0.01). CBD treatment significantly improved recognition, working memory and social interaction deficits in the poly I:C model (p<0.01 vs POLY+VEH), did not affect total body weight gain, food or water intake, and had no effect in control animals (all p>0.05). In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection. These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia.

Dominance of Objects over Context in a Mediotemporal Lobe Model of Schizophrenia

PubMed Central

Talamini, Lucia M.; Meeter, Martijn

2009-01-01

Background A large body of evidence suggests impaired context processing in schizophrenia. Here we propose that this impairment arises from defective integration of mediotemporal ‘what’ and ‘where’ routes, carrying object and spatial information to the hippocampus. Methodology and Findings We have previously shown, in a mediotemporal lobe (MTL) model, that the abnormal connectivity between MTL regions observed in schizophrenia can explain the episodic memory deficits associated with the disorder. Here we show that the same neuropathology leads to several context processing deficits observed in patients with schizophrenia: 1) failure to choose subordinate stimuli over dominant ones when the former fit the context, 2) decreased contextual constraints in memory retrieval, as reflected in increased false alarm rates and 3) impaired retrieval of contextual information in source monitoring. Model analyses show that these deficits occur because the ‘schizophrenic MTL’ forms fragmented episodic representations, in which objects are overrepresented at the expense of spatial contextual information. Conclusions and Significance These findings highlight the importance of MTL neuropathology in schizophrenia, demonstrating that it may underlie a broad spectrum of deficits, including context processing and memory impairments. It is argued that these processing deficits may contribute to central schizophrenia symptoms such as contextually inappropriate behavior, associative abnormalities, conversational drift, concreteness and delusions. PMID:19652706

The reduction of adult neurogenesis in depression impairs the retrieval of new as well as remote episodic memory

PubMed Central

Fang, Jing; Demic, Selver; Cheng, Sen

2018-01-01

Major depressive disorder (MDD) is associated with an impairment of episodic memory, but the mechanisms underlying this deficit remain unclear. Animal models of MDD find impaired adult neurogenesis (AN) in the dentate gyrus (DG), and AN in DG has been suggested to play a critical role in reducing the interference between overlapping memories through pattern separation. Here, we study the effect of reduced AN in MDD on the accuracy of episodic memory using computational modeling. We focus on how memory is affected when periods with a normal rate of AN (asymptomatic states) alternate with periods with a low rate (depressive episodes), which has never been studied before. Also, unlike previous models of adult neurogenesis, which consider memories as static patterns, we model episodic memory as sequences of neural activity patterns. In our model, AN adds additional random components to the memory patterns, which results in the decorrelation of similar patterns. Consistent with previous studies, higher rates of AN lead to higher memory accuracy in our model, which implies that memories stored in the depressive state are impaired. Intriguingly, our model makes the novel prediction that memories stored in an earlier asymptomatic state are also impaired by a later depressive episode. This retrograde effect exacerbates with increased duration of the depressive episode. Finally, pattern separation at the sensory processing stage does not improve, but rather worsens, the accuracy of episodic memory retrieval, suggesting an explanation for why AN is found in brain areas serving memory rather than sensory function. In conclusion, while cognitive retrieval biases might contribute to episodic memory deficits in MDD, our model suggests a mechanistic explanation that affects all episodic memories, regardless of emotional relevance. PMID:29879169

The reduction of adult neurogenesis in depression impairs the retrieval of new as well as remote episodic memory.

PubMed

Fang, Jing; Demic, Selver; Cheng, Sen

2018-01-01

Major depressive disorder (MDD) is associated with an impairment of episodic memory, but the mechanisms underlying this deficit remain unclear. Animal models of MDD find impaired adult neurogenesis (AN) in the dentate gyrus (DG), and AN in DG has been suggested to play a critical role in reducing the interference between overlapping memories through pattern separation. Here, we study the effect of reduced AN in MDD on the accuracy of episodic memory using computational modeling. We focus on how memory is affected when periods with a normal rate of AN (asymptomatic states) alternate with periods with a low rate (depressive episodes), which has never been studied before. Also, unlike previous models of adult neurogenesis, which consider memories as static patterns, we model episodic memory as sequences of neural activity patterns. In our model, AN adds additional random components to the memory patterns, which results in the decorrelation of similar patterns. Consistent with previous studies, higher rates of AN lead to higher memory accuracy in our model, which implies that memories stored in the depressive state are impaired. Intriguingly, our model makes the novel prediction that memories stored in an earlier asymptomatic state are also impaired by a later depressive episode. This retrograde effect exacerbates with increased duration of the depressive episode. Finally, pattern separation at the sensory processing stage does not improve, but rather worsens, the accuracy of episodic memory retrieval, suggesting an explanation for why AN is found in brain areas serving memory rather than sensory function. In conclusion, while cognitive retrieval biases might contribute to episodic memory deficits in MDD, our model suggests a mechanistic explanation that affects all episodic memories, regardless of emotional relevance.

A Single-System Model Predicts Recognition Memory and Repetition Priming in Amnesia

PubMed Central

Kessels, Roy P.C.; Wester, Arie J.; Shanks, David R.

2014-01-01

We challenge the claim that there are distinct neural systems for explicit and implicit memory by demonstrating that a formal single-system model predicts the pattern of recognition memory (explicit) and repetition priming (implicit) in amnesia. In the current investigation, human participants with amnesia categorized pictures of objects at study and then, at test, identified fragmented versions of studied (old) and nonstudied (new) objects (providing a measure of priming), and made a recognition memory judgment (old vs new) for each object. Numerous results in the amnesic patients were predicted in advance by the single-system model, as follows: (1) deficits in recognition memory and priming were evident relative to a control group; (2) items judged as old were identified at greater levels of fragmentation than items judged new, regardless of whether the items were actually old or new; and (3) the magnitude of the priming effect (the identification advantage for old vs new items) overall was greater than that of items judged new. Model evidence measures also favored the single-system model over two formal multiple-systems models. The findings support the single-system model, which explains the pattern of recognition and priming in amnesia primarily as a reduction in the strength of a single dimension of memory strength, rather than a selective explicit memory system deficit. PMID:25122896

Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease

PubMed Central

Kuboyama, Tomoharu; Hirotsu, Keisuke; Arai, Tetsuya; Yamasaki, Hiroo; Tohda, Chihiro

2017-01-01

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. PMID:29184495

Persistent Short-Term Memory Defects Following Sleep Deprivation in a Drosophila Model of Parkinson Disease

PubMed Central

Seugnet, Laurent; Galvin, James E.; Suzuki, Yasuko; Gottschalk, Laura; Shaw, Paul J.

2009-01-01

Study Objectives: Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. It is associated with motor deficits, sleep disturbances, and cognitive impairment. The pathology associated with PD and the effects of sleep deprivation impinge, in part, upon common molecular pathways suggesting that sleep loss may be particularly deleterious to the degenerating brain. Thus we investigated the long-term consequences of sleep deprivation on short-term memory using a Drosophila model of Parkinson disease. Participants: Transgenic strains of Drosophila melanogaster. Design: Using the GAL4-UAS system, human α-synuclein was expressed throughout the nervous system of adult flies. α-Synuclein expressing flies (αS flies) and the corresponding genetic background controls were sleep deprived for 12 h at age 16 days and allowed to recover undisturbed for at least 3 days. Short-term memory was evaluated using aversive phototaxis suppression. Dopaminergic systems were assessed using mRNA profiling and immunohistochemistry. Measurments and Results: When sleep deprived at an intermediate stage of the pathology, αS flies showed persistent short-term memory deficits that lasted ≥ 3 days. Cognitive deficits were not observed in younger αS flies nor in genetic background controls. Long-term impairments were not associated with accelerated loss of dopaminergic neurons. However mRNA expression of the dopamine receptors dDA1 and DAMB were significantly increased in sleep deprived αS flies. Blocking D1-like receptors during sleep deprivation prevented persistent short-term memory deficits. Importantly, feeding flies the polyphenolic compound curcumin blocked long-term learning deficits. Conclusions: These data emphasize the importance of sleep in a degenerating/reorganizing brain and shows that pathological processes induced by sleep deprivation can be dissected at the molecular and cellular level using Drosophila genetics. Citation: Seugnet L; Galvin JE; Suzuki Y; Gottschalk L; Shaw PJ. Persistent short-term memory defects following sleep deprivation in a drosophila model of parkinson disease. SLEEP 2009;32(8):984-992. PMID:19725249

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2015-01-01

Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI). Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity. PMID:26900567

Association between early attention-deficit/hyperactivity symptoms and current verbal and visuo-spatial short-term memory.

PubMed

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

2013-01-01

Deficits in short-term memory are common in adolescents with attention-deficit/hyperactivity disorder (ADHD), but their current ADHD symptoms cannot well predict their short-term performance. Taking a developmental perspective, we wanted to clarify the association between ADHD symptoms at early childhood and short-term memory in late childhood and adolescence. The participants included 401 patients with a clinical diagnosis of DSM-IV ADHD, 213 siblings, and 176 unaffected controls aged 8-17 years (mean age, 12.02 ± 2.24). All participants and their mothers were interviewed using the Chinese Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia to obtain information about ADHD symptoms and other psychiatric disorders retrospectively, at an earlier age first, then currently. The participants were assessed with the Wechsler Intelligence Scale for Children--3rd edition, including Digit Span, and the Spatial working memory task of the Cambridge Neuropsychological Test Automated Battery. Multi-level regression models were used for data analysis. Although crude analyses revealed that inattention, hyperactivity, and impulsivity symptoms significantly predicted deficits in short-term memory, only inattention symptoms had significant effects (all p<0.001) in a model that included all three ADHD symptoms. After further controlling for comorbidity, age of assessment, treatment with methylphenidate, and Full-scale IQ, the severity of childhood inattention symptoms was still significantly associated with worse verbal (p = 0.008) and spatial (p ranging from 0.017 to 0.002) short-term memory at the current assessment. Therefore, our findings suggest that earlier inattention symptoms are associated with impaired verbal and visuo-spatial short-term memory at a later development stage. Impaired short-term memory in adolescence can be detected earlier by screening for the severity of inattention in childhood. Copyright © 2012 Elsevier Ltd. All rights reserved.

Olfactory discrimination and memory deficits in the Flinders Sensitive Line rodent model of depression.

PubMed

Cook, A; Pfeiffer, L-M; Thiele, S; Coenen, V A; Döbrössy, M D

2017-10-01

Major Depressive Disorder (MDD) is a heterogeneous psychiatric disorder with broad symptomatic manifestations. The current study examined, for the first time, olfactory memory and discrimination in the Flinders Sensitive Line (FSL) rodent model of depression. Male FSL rats and controls were trained on an Olfactory Discrimination (OD) and a Social Interaction (SI) test. On the OD test, the FSL and controls performed similarly at the shortest inter-trial interval (5min), however, with extended delay of 30min, the FSLs had a recall and odour discrimination deficit. At the longest delay (60min) both groups performed poorly. The FSL rats i.) had a deficit in olfactory discrimination suggesting impairment in olfactory memory and recall; ii.) were less likely to socialize with unfamiliar rats. The data suggests that FSL animals have an impaired olfactory information processing capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of a subpsychotic dose of ketamine on recognition and source memory for agency: implications for pharmacological modelling of core symptoms of schizophrenia.

PubMed

Honey, Garry D; O'loughlin, Chris; Turner, Danielle C; Pomarol-Clotet, Edith; Corlett, Philip R; Fletcher, Paul C

2006-02-01

Ketamine is increasingly used to model the cognitive deficits and symptoms of schizophrenia. We investigated the extent to which ketamine administration in healthy volunteers reproduces the deficits in episodic recognition memory and agency source monitoring reported in schizophrenia. Intravenous infusions of placebo or 100 ng/ml ketamine were administered to 12 healthy volunteers in a double-blind, placebo-controlled, randomized, within-subjects study. In response to presented words, the subject or experimenter performed a deep or shallow encoding task, providing a 2(drug) x 2(depth of processing) x 2(agency) factorial design. At test, subjects discriminated old/new words, and recalled the sources (task and agent). Data were analyzed using multinomial modelling to identify item recognition, source memory for agency and task, and guessing biases. Under ketamine, item recognition and cued recall of deeply encoded items were impaired, replicating previous findings. In contrast to schizophrenia, there was a reduced tendency to externalize agency source guessing biases under ketamine. While the recognition memory deficit observed with ketamine is consistent with previous work and with schizophrenia, the changes in source memory differ from those reported in schizophrenic patients. This difference may account for the pattern of psychopathology induced by ketamine.

Verbal Working Memory in Children with Mild Intellectual Disabilities

ERIC Educational Resources Information Center

Van der Molen, M. J.; Van Luit, J. E. H.; Jongmans, M. J.; Van der Molen, M. W.

2007-01-01

Background: Previous research into working memory of individuals with intellectual disabilities (ID) has established clear deficits. The current study examined working memory in children with mild ID (IQ 55-85) within the framework of the Baddeley model, fractionating working memory into a central executive and two slave systems, the phonological…

Interaction between emotion and memory: importance of mammillary bodies damage in a mouse model of the alcoholic Korsakoff syndrome.

PubMed

Béracochéa, Daniel

2005-01-01

Chronic alcohol consumption (CAC) can lead to the Korsakoff syndrome (KS), a memory deficiency attributed to diencephalic damage and/or to medial temporal or cortical related dysfunction. The etiology of KS remains unclear. Most animal models of KS involve thiamine-deficient diets associated with pyrithiamine treatment. Here we present a mouse model of CAC-induced KS. We demonstrate that CAC-generated retrieval memory deficits in working/ episodic memory tasks, together with a reduction of fear reactivity, result from damage to the mammillary bodies (MB). Experimental lesions of MB in non-alcoholic mice produced the same memory and emotional impairments. Drugs having anxiogenic-like properties counteract such impairments produced by CAC or by MB lesions. We suggest (a) that MB are the essential components of a brain network underlying emotional processes, which would be critically important in the retrieval processes involved in working/ episodic memory tasks, and (b) that failure to maintain emotional arousal due to MB damage can be a main factor of CAC-induced memory deficits. Overall, our animal model fits well with general neuropsychological and anatomic impairments observed in KS.

Interaction Between Emotion and Memory: Importance of Mammillary Bodies Damage in a Mouse Model of the Alcoholic Korsakoff Syndrome

PubMed Central

Béracochéa, Daniel

2005-01-01

Chronic alcohol consumption (CAC) can lead to the Korsakoff syndrome (KS), a memory deficiency attributed to diencephalie damage and/or to medial temporal or cortical related dysfunction. The etiology of KS remains unclear. Most animal models of KS involve thiaminedeficient diets associated with pyrithiamine treatment. Here we present a mouse model of CAC-induced KS. We demonstrate that CAC-generated retrieval memory deficits in working/ episodic memory tasks, together with a reduction of fear reactivity, result from damage to the mammillary bodies (MB). Experimental lesions of MB in non-alcoholic mice produced the same memory and emotional impairments. Drugs having anxiogenic-like properties counteract such impairments produced by CAC or by MB lesions. We suggest (a) that MB are the essential components of a brain network underlying emotional processes, which would be critically important in the retrieval processes involved in working/ episodic memory tasks, and (b) that failure to maintain emotional arousal due to MB damage can be a main factor of CAC-induced memory deficits. Overall, our animal model fits well with general neuropsychological and anatomic impairments observed in KS. PMID:16444899

Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

PubMed Central

Hanlon, Lauren A.; Huh, Jimmy W.

2016-01-01

Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

Working Memory Differences Between Children Living in Rural and Urban Poverty

PubMed Central

Tine, Michele

2014-01-01

This study was designed to investigate if the working memory profiles of children living in rural poverty are distinct from the working memory profiles of children living in urban poverty. Verbal and visuospatial working memory tasks were administered to sixth-grade students living in low-income rural, low-income urban, high-income rural, and high-income urban developmental contexts. Both low-income rural and low-income urban children showed working memory deficits compared with their high-income counterparts, but their deficits were distinct. Low-income urban children exhibited symmetrical verbal and visuospatial working memory deficits compared with their high-income urban counterparts. Meanwhile, low-income rural children exhibited asymmetrical deficits when compared with their high-income rural counterparts, with more extreme visuospatial working memory deficits than verbal working memory deficits. These results suggest that different types of poverty are associated with different working memory abilities. PMID:25554726

Working Memory Differences Between Children Living in Rural and Urban Poverty.

PubMed

Tine, Michele

2014-10-02

This study was designed to investigate if the working memory profiles of children living in rural poverty are distinct from the working memory profiles of children living in urban poverty. Verbal and visuospatial working memory tasks were administered to sixth-grade students living in low-income rural, low-income urban, high-income rural, and high-income urban developmental contexts. Both low-income rural and low-income urban children showed working memory deficits compared with their high-income counterparts, but their deficits were distinct. Low-income urban children exhibited symmetrical verbal and visuospatial working memory deficits compared with their high-income urban counterparts. Meanwhile, low-income rural children exhibited asymmetrical deficits when compared with their high-income rural counterparts, with more extreme visuospatial working memory deficits than verbal working memory deficits. These results suggest that different types of poverty are associated with different working memory abilities.

Episodic and working memory function in Primary Progressive Aphasia: A meta-analysis.

PubMed

Eikelboom, Willem S; Janssen, Nikki; Jiskoot, Lize C; van den Berg, Esther; Roelofs, Ardi; Kessels, Roy P C

2018-06-18

The distinction between Primary Progressive Aphasia (PPA) variants remains challenging for clinicians, especially for the non-fluent (nfv-PPA) and the logopenic variants (lv-PPA). Previous research suggests that memory tests might aid this differentiation. This meta-analysis compares memory function among PPA variants. Effects sizes were extracted from 41 studies (N = 849). Random-effects models were used to compare performance on episodic and working memory tests among PPA patients and healthy controls, and between the PPA variants. Memory deficits were frequently observed in PPA compared to controls, with large effect sizes for lv-PPA (Hedges' g = -2.04 [-2.58 to -1.49]), nfv-PPA (Hedges' g = -1.34 [-1.69 to -1.00]), and the semantic variant (sv-PPA; Hedges' g = -1.23 [-1.50 to -0.97]). Sv-PPA showed primarily verbal memory deficits, whereas lv-PPA showed worse performance than nfv-PPA on both verbal and non-verbal memory tests. Memory deficits were more pronounced in lv-PPA compared to nfv-PPA. This suggests that memory tests may be helpful to distinguish between these PPA variants. Copyright © 2018. Published by Elsevier Ltd.

Peripheral Nerve Injury Leads to Working Memory Deficits and Dysfunction of the Hippocampus by Upregulation of TNF-α in Rodents

PubMed Central

Ren, Wen-Jie; Liu, Yong; Zhou, Li-Jun; Li, Wei; Zhong, Yi; Pang, Rui-Ping; Xin, Wen-Jun; Wei, Xu-Hong; Wang, Jun; Zhu, He-Quan; Wu, Chang-You; Qin, Zhi-Hai; Liu, Guosong; Liu, Xian-Guo

2011-01-01

Patients with chronic pain usually suffer from working memory deficits, which may decrease their intellectual ability significantly. Despite intensive clinical studies, the mechanism underlying this form of memory impairment remains elusive. In this study, we investigated this issue in the spared nerve injury (SNI) model of neuropathic pain, a most common form of chronic pain. We found that SNI impaired working memory and short-term memory in rats and mice. To explore the potential mechanisms, we studied synaptic transmission/plasticity in hippocampus, a brain region critically involved in memory function. We found that frequency facilitation, a presynaptic form of short-term plasticity, and long-term potentiation at CA3–CA1 synapses were impaired after SNI. Structurally, density of presynaptic boutons in hippocampal CA1 synapses was reduced significantly. At the molecular level, we found that tumor necrosis factor-α (TNF-α) increased in cerebrospinal fluid, in hippocampal tissue and in plasma after SNI. Intracerebroventricular or intrahippocampal injection of recombinant rat TNF mimicked the effects of SNI in naive rats, whereas inhibition of TNF-α or genetic deletion of TNF receptor 1 prevented both memory deficits and synaptic dysfunction induced by SNI. As TNF-α is critical for development of neuropathic pain, we suggested that the over-production of TNF-α following peripheral nerve injury might lead to neuropathic pain and memory deficits, simultaneously. PMID:21289602

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

ERIC Educational Resources Information Center

Larsen, Jessica Maria

2011-01-01

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

The relation between receptive grammar and procedural, declarative, and working memory in specific language impairment.

PubMed

Conti-Ramsden, Gina; Ullman, Michael T; Lum, Jarrad A G

2015-01-01

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.

MRI morphometry of mamillary bodies, caudate nuclei, and prefrontal cortices after chemotherapy for childhood leukemia: multivariate models of early and late developing memory subsystems.

PubMed

Ciesielski, K T; Lesnik, P G; Benzel, E C; Hart, B L; Sanders, J A

1999-06-01

Neurotoxic intrathecal chemotherapy for childhood acute lymphoblastic leukemia (ALL) affects developing structures and functions of memory and learning subsystems selectively. Results show significant reductions in magnetic resonance imaging morphometry of mamillary bodies, components of the corticolimbic-diencephalic subsystem subserving functionally later developing, single-trial memory, nonsignificant changes in bilateral heads of the caudate nuclei, components of the corticostriatal subsystem subserving functionally earlier developing, multitrial learning, significant reductions in prefrontal cortical volume, visual and verbal single-trial memory deficits, and visuospatial, but not verbal, multitrial learning deficits. Multiple regression models provide evidence for partial dissociation and connectivity between the subsystems, and suggest that greater involvement of caudate may compensate for inefficient corticolimbic-diencephalic components.

A novel computational model to probe visual search deficits during motor performance

PubMed Central

Singh, Tarkeshwar; Fridriksson, Julius; Perry, Christopher M.; Tryon, Sarah C.; Ross, Angela; Fritz, Stacy

2016-01-01

Successful execution of many motor skills relies on well-organized visual search (voluntary eye movements that actively scan the environment for task-relevant information). Although impairments of visual search that result from brain injuries are linked to diminished motor performance, the neural processes that guide visual search within this context remain largely unknown. The first objective of this study was to examine how visual search in healthy adults and stroke survivors is used to guide hand movements during the Trail Making Test (TMT), a neuropsychological task that is a strong predictor of visuomotor and cognitive deficits. Our second objective was to develop a novel computational model to investigate combinatorial interactions between three underlying processes of visual search (spatial planning, working memory, and peripheral visual processing). We predicted that stroke survivors would exhibit deficits in integrating the three underlying processes, resulting in deteriorated overall task performance. We found that normal TMT performance is associated with patterns of visual search that primarily rely on spatial planning and/or working memory (but not peripheral visual processing). Our computational model suggested that abnormal TMT performance following stroke is associated with impairments of visual search that are characterized by deficits integrating spatial planning and working memory. This innovative methodology provides a novel framework for studying how the neural processes underlying visual search interact combinatorially to guide motor performance. NEW & NOTEWORTHY Visual search has traditionally been studied in cognitive and perceptual paradigms, but little is known about how it contributes to visuomotor performance. We have developed a novel computational model to examine how three underlying processes of visual search (spatial planning, working memory, and peripheral visual processing) contribute to visual search during a visuomotor task. We show that deficits integrating spatial planning and working memory underlie abnormal performance in stroke survivors with frontoparietal damage. PMID:27733596

Prolonged running, not fluoxetine treatment, increases neurogenesis, but does not alter neuropathology, in the 3xTg mouse model of Alzheimer's disease.

PubMed

Marlatt, Michael W; Potter, Michelle C; Bayer, Thomas A; van Praag, Henriette; Lucassen, Paul J

2013-01-01

Reductions in adult neurogenesis have been documented in the original 3xTg mouse model of Alzheimer's disease (AD), notably occurring at the same age when spatial memory deficits and amyloid plaque pathology appeared. As this suggested reduced neurogenesis was associated with behavioral deficits, we tested whether activity and pharmacological stimulation could prevent memory deficits and modify neurogenesis and/or neuropathology in the 3xTg model backcrossed to the C57Bl/6 strain. We chronically administered the antidepressant fluoxetine to one group of mice, allowed access to a running wheel in another, and combined both treatments in a third cohort. All treatments lasted for 11 months. The female 3xTg mice failed to exhibit any deficits in spatial learning and memory as measured in the Morris water maze, indicating that when backcrossed to the C57Bl/6 strain, the 3xTg mice lost the behavioral phenotype that was present in the original 3xTg mouse maintained on a hybrid background. Despite this, the backcrossed 3xTg mice expressed prominent intraneuronal amyloid beta (Aβ) levels in the cortex and amygdala, with lower levels in the CA1 area of the hippocampus. In the combined cohort, fluoxetine treatment interfered with exercise and reduced the total distance run. The extent of Aβ neuropathology, the tau accumulations, or BDNF levels, were not altered by prolonged exercise. Thus, neuropathology was present but not paralleled by spatial memory deficits in the backcrossed 3xTg mouse model of AD. Prolonged exercise for 11 months did improve the long-term survival of newborn neurons generated during middle-age, whereas fluoxetine had no effect. We further review and discuss the relevant literature in this respect.

Adolescent social defeat decreases spatial working memory performance in adulthood.

PubMed

Novick, Andrew M; Miiller, Leah C; Forster, Gina L; Watt, Michael J

2013-10-17

Adolescent social stress is associated with increased incidence of mental illnesses in adulthood that are characterized by deficits in cognitive focus and flexibility. Such enhanced vulnerability may be due to psychosocial stress-induced disruption of the developing mesocortical dopamine system, which plays a fundamental role in facilitating complex cognitive processes such as spatial working memory. Adolescent rats exposed to repeated social defeat as a model of social stress develop dopaminergic hypofunction in the medial prefrontal cortex as adults. To evaluate a direct link between adolescent social stress and later deficits in cognitive function, the present study tested the effects of adolescent social defeat on two separate tests of spatial working memory performance. Adult rats exposed to adolescent social defeat and their controls were trained on either the delayed win-shift task or the delayed alternating T-Maze task and then challenged with various delay periods. To evaluate potential differences in motivation for the food reward used in memory tasks, consumption and conditioned place preference for sweetened condensed milk were tested in a separate cohort of previously defeated rats and controls. Compared to controls, adult rats defeated in adolescence showed a delay-dependent deficit in spatial working memory performance, committing more errors at a 90 s and 5 min delay period on the T-maze and win-shift tasks, respectively. Observed memory deficits were likely independent of differences in reward motivation, as conditioned place preference for the palatable food used on both tasks was similar between the adolescent social defeat group and control. The results demonstrate that severe social stressors during adolescence can produce long term deficits in aspects of cognitive function. Given the dependence of spatial working memory on prefrontal dopamine, pharmacologically reversing dopaminergic deficiencies caused by adolescent social stress has the potential to treat such cognitive deficits.

Memory impairment is associated with the loss of regular oestrous cycle and plasma oestradiol levels in an activity-based anorexia animal model.

PubMed

Paulukat, Lisa; Frintrop, Linda; Liesbrock, Johanna; Heussen, Nicole; Johann, Sonja; Exner, Cornelia; Kas, Martien J; Tolba, Rene; Neulen, Joseph; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

2016-06-01

Patients with anorexia nervosa (AN) suffer from neuropsychological deficits including memory impairments. Memory partially depends on 17β-oestradiol (E2), which is reduced in patients with AN. We assessed whether memory functions correlate with E2 plasma levels in the activity-based anorexia (ABA) rat model. Nine 4-week-old female Wistar rats were sacrificed directly after weight loss of 20-25% (acute starvation), whereas 17 animals had additional 2-week weight-holding (chronic starvation). E2 serum levels and novel object recognition tasks were tested before and after starvation and compared with 21 normally fed controls. Starvation disrupted menstrual cycle and impaired memory function, which became statistically significant in the chronic state (oestrous cycle (P < 0.001), E2 levels (P = 0.011) and object recognition memory (P = 0.042) compared to controls). E2 reduction also correlated with the loss of memory in the chronic condition (r = 0.633, P = 0.020). Our results demonstrate that starvation reduces the E2 levels which are associated with memory deficits in ABA rats. These effects might explain reduced memory capacity in patients with AN as a consequence of E2 deficiency and the potentially limited effectiveness of psychotherapeutic interventions in the starved state. Future studies should examine whether E2 substitution could prevent cognitive deficits and aid in earlier readiness for therapy.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2009-04-29

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

Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.

PubMed

Hara, Yuta; Ago, Yukio; Higuchi, Momoko; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

2017-11-01

Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2weeks improved prenatal VPA-induced social interaction deficits for at least 24h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of γ-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia

PubMed Central

2012-01-01

Background A mutation in the BRI2/ITM2b gene causes familial Danish dementia (FDD). BRI2 is an inhibitor of amyloid-β precursor protein (APP) processing, which is genetically linked to Alzheimer’s disease (AD) pathogenesis. The FDD mutation leads to a loss of BRI2 protein and to increased APP processing. APP haplodeficiency and inhibition of APP cleavage by β-secretase rescue synaptic/memory deficits of a genetically congruous mouse model of FDD (FDDKI). β-cleavage of APP yields the β-carboxyl-terminal (β-CTF) and the amino-terminal-soluble APPβ (sAPPβ) fragments. γ-secretase processing of β-CTF generates Aβ, which is considered the main cause of AD. However, inhibiting Aβ production did not rescue the deficits of FDDKI mice, suggesting that sAPPβ/β-CTF, and not Aβ, are the toxic species causing memory loss. Results Here, we have further analyzed the effect of γ-secretase inhibition. We show that treatment with a γ-secretase inhibitor (GSI) results in a worsening of the memory deficits of FDDKI mice. This deleterious effect on memory correlates with increased levels of the β/α-CTFs APP fragments in synaptic fractions isolated from hippocampi of FDDKI mice, which is consistent with inhibition of γ-secretase activity. Conclusion This harmful effect of the GSI is in sharp contrast with a pathogenic role for Aβ, and suggests that the worsening of memory deficits may be due to accumulation of synaptic-toxic β/α-CTFs caused by GSI treatment. However, γ-secretase cleaves more than 40 proteins; thus, the noxious effect of GSI on memory may be dependent on inhibition of cleavage of one or more of these other γ-secretase substrates. These two possibilities do not need to be mutually exclusive. Our results are consistent with the outcome of a clinical trial with the GSI Semagacestat, which caused a worsening of cognition, and advise against targeting γ-secretase in the therapy of AD. Overall, the data also indicate that FDDKI is a valuable mouse model to study AD pathogenesis and predict the clinical outcome of therapeutic agents for AD. PMID:22537414

Inhibition of γ-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia.

PubMed

Tamayev, Robert; D'Adamio, Luciano

2012-04-26

A mutation in the BRI2/ITM2b gene causes familial Danish dementia (FDD). BRI2 is an inhibitor of amyloid-β precursor protein (APP) processing, which is genetically linked to Alzheimer's disease (AD) pathogenesis. The FDD mutation leads to a loss of BRI2 protein and to increased APP processing. APP haplodeficiency and inhibition of APP cleavage by β-secretase rescue synaptic/memory deficits of a genetically congruous mouse model of FDD (FDDKI). β-cleavage of APP yields the β-carboxyl-terminal (β-CTF) and the amino-terminal-soluble APPβ (sAPPβ) fragments. γ-secretase processing of β-CTF generates Aβ, which is considered the main cause of AD. However, inhibiting Aβ production did not rescue the deficits of FDDKI mice, suggesting that sAPPβ/β-CTF, and not Aβ, are the toxic species causing memory loss. Here, we have further analyzed the effect of γ-secretase inhibition. We show that treatment with a γ-secretase inhibitor (GSI) results in a worsening of the memory deficits of FDDKI mice. This deleterious effect on memory correlates with increased levels of the β/α-CTFs APP fragments in synaptic fractions isolated from hippocampi of FDDKI mice, which is consistent with inhibition of γ-secretase activity. This harmful effect of the GSI is in sharp contrast with a pathogenic role for Aβ, and suggests that the worsening of memory deficits may be due to accumulation of synaptic-toxic β/α-CTFs caused by GSI treatment. However, γ-secretase cleaves more than 40 proteins; thus, the noxious effect of GSI on memory may be dependent on inhibition of cleavage of one or more of these other γ-secretase substrates. These two possibilities do not need to be mutually exclusive. Our results are consistent with the outcome of a clinical trial with the GSI Semagacestat, which caused a worsening of cognition, and advise against targeting γ-secretase in the therapy of AD. Overall, the data also indicate that FDDKI is a valuable mouse model to study AD pathogenesis and predict the clinical outcome of therapeutic agents for AD.

β- but not γ-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia.

PubMed

Tamayev, Robert; Matsuda, Shuji; Arancio, Ottavio; D'Adamio, Luciano

2012-03-01

A mutation in the BRI2/ITM2b gene causes loss of BRI2 protein leading to familial Danish dementia (FDD). BRI2 deficiency of FDD provokes an increase in amyloid-β precursor protein (APP) processing since BRI2 is an inhibitor of APP proteolysis, and APP mediates the synaptic/memory deficits in FDD. APP processing is linked to Alzheimer disease (AD) pathogenesis, which is consistent with a common mechanism involving toxic APP metabolites in both dementias. We show that inhibition of APP cleavage by β-secretase rescues synaptic/memory deficits in a mouse model of FDD. β-cleavage of APP yields amino-terminal-soluble APPβ (sAPPβ) and β-carboxyl-terminal fragments (β-CTF). Processing of β-CTF by γ-secretase releases amyloid-β (Aβ), which is assumed to cause AD. However, inhibition of γ-secretase did not ameliorate synaptic/memory deficits of FDD mice. These results suggest that sAPPβ and/or β-CTF, rather than Aβ, are the toxic species causing dementia, and indicate that reducing β-cleavage of APP is an appropriate therapeutic approach to treating human dementias. Our data and the failures of anti-Aβ therapies in humans advise against targeting γ-secretase cleavage of APP and/or Aβ. Copyright © 2012 EMBO Molecular Medicine.

β- but not γ-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia

PubMed Central

Tamayev, Robert; Matsuda, Shuji; Arancio, Ottavio; D'Adamio, Luciano

2012-01-01

A mutation in the BRI2/ITM2b gene causes loss of BRI2 protein leading to familial Danish dementia (FDD). BRI2 deficiency of FDD provokes an increase in amyloid-β precursor protein (APP) processing since BRI2 is an inhibitor of APP proteolysis, and APP mediates the synaptic/memory deficits in FDD. APP processing is linked to Alzheimer disease (AD) pathogenesis, which is consistent with a common mechanism involving toxic APP metabolites in both dementias. We show that inhibition of APP cleavage by β-secretase rescues synaptic/memory deficits in a mouse model of FDD. β-cleavage of APP yields amino-terminal-soluble APPβ (sAPPβ) and β-carboxyl-terminal fragments (β-CTF). Processing of β-CTF by γ-secretase releases amyloid-β (Aβ), which is assumed to cause AD. However, inhibition of γ-secretase did not ameliorate synaptic/memory deficits of FDD mice. These results suggest that sAPPβ and/or β-CTF, rather than Aβ, are the toxic species causing dementia, and indicate that reducing β-cleavage of APP is an appropriate therapeutic approach to treating human dementias. Our data and the failures of anti-Aβ therapies in humans advise against targeting γ-secretase cleavage of APP and/or Aβ. PMID:22170863

Working Memory Functioning in Children with Learning Disorders and Specific Language Impairment

ERIC Educational Resources Information Center

Schuchardt, Kirsten; Bockmann, Ann-Katrin; Bornemann, Galina; Maehler, Claudia

2013-01-01

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…

Detecting spatial memory deficits beyond blindness in tg2576 Alzheimer mice.

PubMed

Yassine, Nour; Lazaris, Anelise; Dorner-Ciossek, Cornelia; Després, Olivier; Meyer, Laurence; Maitre, Michel; Mensah-Nyagan, Ayikoe Guy; Cassel, Jean-Christophe; Mathis, Chantal

2013-03-01

The retinal degeneration Pde6b(rd1) (rd) mutation can be a major pitfall in behavioral studies using tg2576 mice bred on a B6:SJL genetic background, 1 of the most widely used models of Alzheimer's disease. After a pilot study in wild type mice, performance of 8- and 16-month-old tg2576 mice were assessed in several behavioral tasks with the challenge of selecting 1 or more task(s) showing robust memory deficits on this genetic background. Water maze acquisition was impossible in rd homozygotes, whereas Y-maze alternation, object recognition, and olfactory discrimination were unaffected by both the transgene and the rd mutation. Spatial memory retention of 8- and 16-month-old tg2576 mice, however, was dramatically affected independently of the rd mutation when mice had to recognize a spatial configuration of objects or to perform the Barnes maze. Thus, the latter tasks appear extremely useful to evaluate spatial memory deficits and to test cognitive therapies in tg2576 mice and other mouse models bred on a background susceptible to visual impairment. Copyright © 2013 Elsevier Inc. All rights reserved.

Use of an eight-arm radial water maze to assess working and reference memory following neonatal brain injury.

PubMed

Penley, Stephanie C; Gaudet, Cynthia M; Threlkeld, Steven W

2013-12-04

Working and reference memory are commonly assessed using the land based radial arm maze. However, this paradigm requires pretraining, food deprivation, and may introduce scent cue confounds. The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs. Specifically, subjects are required to avoid the arms previously used for escape during each testing day (working memory) as well as avoid the fixed arms, which never contain escape platforms (reference memory). Re-entries into arms that have already been used for escape during a testing session (and thus the escape platform has been removed) and re-entries into reference memory arms are indicative of working memory deficits. Alternatively, first entries into reference memory arms are indicative of reference memory deficits. We used this maze to compare performance of rats with neonatal brain injury and sham controls following induction of hypoxia-ischemia and show significant deficits in both working and reference memory after eleven days of testing. This protocol could be easily modified to examine many other models of learning impairment.

Spontaneously hypertensive rat (SHR) as an animal model for ADHD: a short overview.

PubMed

Meneses, Alfredo; Perez-Garcia, Georgina; Ponce-Lopez, Teresa; Tellez, Ruth; Gallegos-Cari, Andrea; Castillo, Carlos

2011-01-01

Diverse studies indicate that attention-deficit hyperactivity disorder (ADHD) is associated with alterations in encoding processes, including working or short-term memory. Some ADHD dysfunctional domains are reflected in the spontaneously hypertensive rat (SHR). Because ADHD, drugs and animal models are eliciting a growing interest, hence the aim of this work is to present a brief overview with a focus on the SHR as an animal model for ADHD and memory deficits. Thus, this paper reviews the concept of SHR as a model system for ADHD, comparing SHR, Wistar-Kyoto and Sprague-Dawley rats with a focus on the hypertension level and working, short-term memory and attention in different behavioral tasks, such as open field, five choice serial reaction time, water maze, passive avoidance, and autoshaping. In addition, drug treatments (d-amphetamine and methylphenidate) are evaluated.

Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

PubMed Central

Heisler, Jillian M.; O’Connor, Jason C.

2015-01-01

Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

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

PubMed

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

2014-10-01

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

Deficits in learning and memory in mice with a mutation of the candidate dyslexia susceptibility gene Dyx1c1.

PubMed

Rendall, Amanda R; Tarkar, Aarti; Contreras-Mora, Hector M; LoTurco, Joseph J; Fitch, R Holly

2017-09-01

Dyslexia is a learning disability characterized by difficulty learning to read and write. The underlying biological and genetic etiology remains poorly understood. One candidate gene, dyslexia susceptibility 1 candidate 1 (DYX1C1), has been shown to be associated with deficits in short-term memory in dyslexic populations. The purpose of the current study was to examine the behavioral phenotype of a mouse model with a homozygous conditional (forebrain) knockout of the rodent homolog Dyx1c1. Twelve Dyx1c1 conditional homozygous knockouts, 7 Dyx1c1 conditional heterozygous knockouts and 6 wild-type controls were behaviorally assessed. Mice with the homozygous Dyx1c1 knockout showed deficits on memory and learning, but not on auditory or motor tasks. These findings affirm existing evidence that DYX1C1 may play an underlying role in the development of neural systems important to learning and memory, and disruption of this function could contribute to the learning deficits seen in individuals with dyslexia. Copyright © 2015 Elsevier Inc. All rights reserved.

Persistent short-term memory defects following sleep deprivation in a drosophila model of Parkinson disease.

PubMed

Seugnet, Laurent; Galvin, James E; Suzuki, Yasuko; Gottschalk, Laura; Shaw, Paul J

2009-08-01

Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. It is associated with motor deficits, sleep disturbances, and cognitive impairment. The pathology associated with PD and the effects of sleep deprivation impinge, in part, upon common molecular pathways suggesting that sleep loss may be particularly deleterious to the degenerating brain. Thus we investigated the long-term consequences of sleep deprivation on shortterm memory using a Drosophila model of Parkinson disease. Transgenic strains of Drosophila melanogaster. Using the GAL4-UAS system, human alpha-synuclein was expressed throughout the nervous system of adult flies. Alpha-synuclein expressing flies (alpha S flies) and the corresponding genetic background controls were sleep deprived for 12 h at age 16 days and allowed to recover undisturbed for at least 3 days. Short-term memory was evaluated using aversive phototaxis suppression. Dopaminergic systems were assessed using mRNA profiling and immunohistochemistry. MEASURMENTS AND RESULTS: When sleep deprived at an intermediate stage of the pathology, alpha S flies showed persistent short-term memory deficits that lasted > or = 3 days. Cognitive deficits were not observed in younger alpha S flies nor in genetic background controls. Long-term impairments were not associated with accelerated loss of dopaminergic neurons. However mRNA expression of the dopamine receptors dDA1 and DAMB were significantly increased in sleep deprived alpha S flies. Blocking D1-like receptors during sleep deprivation prevented persistent shortterm memory deficits. Importantly, feeding flies the polyphenolic compound curcumin blocked long-term learning deficits. These data emphasize the importance of sleep in a degenerating/reorganizing brain and shows that pathological processes induced by sleep deprivation can be dissected at the molecular and cellular level using Drosophila genetics.

Animal Model of Methylphenidate's Longterm Memory-Enhancing Effects

ERIC Educational Resources Information Center

Carmack, Stephanie A.; Howell, Kristin K.; Rasaei, Kleou; Reas, Emilie T.; Anagnostaras, Stephan G.

2014-01-01

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a…

Beneficial effect of etazolate on depression-like behavior and, learning, and memory impairment in a model of Parkinson's disease.

PubMed

Alzoubi, Karem H; Mokhemer, Enas; Abuirmeileh, Amjad N

2018-09-17

The aim of this study was to evaluate etazolate against depression-like behavior and, learning and memory impairment induced by 6- hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD). This aim was achieved through comparing 6-OHDA lesioned rats in the presence and absence of etazolate. The 6-OHDA was used to induce lesion as a model of PD. Etazolate was administered at a dose of 1 mg/kg/day for 14 days, starting 7 days after lesion induction. Apomorphine-induced rotation test was used to evaluate 6-OHDA-induced motor deficits, tail suspension test was used to assess depression-like symptoms, and the radial arms water maze (RAWM) was used to evaluate special learning and memory functions. Antioxidant biomarkers and BDNF protein levels were assessed in the hippocampus. Results revealed that etazolate administration significantly improved 6-OHDA-induced PD related symptoms including motor deficits, depression-like behavior and impairment of both short- and long- term memory. Moreover, etazolate significantly prevented 6-OHDA-induced reduction in oxidative stress biomarkers (GSH/GSSG ratio, GPx) and BDNF levels. In conclusion, motor dysfunction, depressive- like behavior, and learning and memory deficits in the 6-OHDA rat model of PD can be significantly prevented by etazolate. This prevention could be attributed to etazolate's ability to prevent reduction in antioxidative stress biomarkers and BDNF levels. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2011-07-01

We assessed the ability of two groups of patients with mild Alzheimer's disease (AD) and two groups of older adults to monitor the likely accuracy of recognition judgments and source identification judgments about who spoke something earlier. Alzheimer's patients showed worse performance on both memory judgments and were less able to monitor with confidence ratings the likely accuracy of both kinds of memory judgments, as compared to a group of older adults who experienced the identical study and test conditions. Critically, however, when memory performance was made comparable between the AD patients and the older adults (e.g., by giving AD patients extra exposures to the study materials), AD patients were still greatly impaired at monitoring the likely accuracy of their recognition and source judgments. This result indicates that the monitoring impairment in AD patients is actually worse than their memory impairment, as otherwise there would have been no differences between the two groups in monitoring performance when there were no differences in accuracy. We discuss the brain correlates of this memory-monitoring deficit and also propose a Remembrance-Evaluation model of memory-monitoring. Copyright © 2011 Elsevier Ltd. All rights reserved.

Preterm Infant Hippocampal Volumes Correlate with Later Working Memory Deficits

ERIC Educational Resources Information Center

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

2008-01-01

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

A prenatal nicotine exposure mouse model of methylphenidate responsive ADHD-associated cognitive phenotypes.

PubMed

Zhu, Jinmin; Fan, Fangfang; McCarthy, Deirdre M; Zhang, Lin; Cannon, Elisa N; Spencer, Thomas J; Biederman, Joseph; Bhide, Pradeep G

2017-05-01

Prenatal exposure to nicotine via cigarette smoke or other forms of tobacco use is a significant environmental risk factor for attention deficit hyperactivity disorder (ADHD). The neurobiological mechanisms underlying the link between prenatal nicotine exposure (PNE) and ADHD are not well understood. Animal models, especially rodent models, are beginning to bridge this gap in knowledge. Although ADHD is characterized by hyperactivity, inattention, impulsivity and working memory deficits, the majority of the animal models are based on only one or two ADHD associated phenotypes, in particular, hyperactivity or inattention. We report a PNE mouse model that displays the full range of ADHD associated behavioral phenotypes including working memory deficit, attention deficit and impulsive-like behavior. All of the ADHD-associated phenotypes respond to a single administration of a therapeutic equivalent dose of methylphenidate. In an earlier study, we showed that PNE produces hyperactivity, frontal cortical hypodopaminergic state and thinning of the cingulate cortex. Collectively, these data suggest that the PNE mouse model recapitulates key features of ADHD and may be a suitable preclinical model for ADHD research. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Episodic memory impairment in systemic lupus erythematosus: involvement of thalamic structures.

PubMed

Zimmermann, Nicolle; Corrêa, Diogo Goulart; Netto, Tania Maria; Kubo, Tadeu; Pereira, Denis Batista; Fonseca, Rochele Paz; Gasparetto, Emerson Leandro

2015-02-01

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.

Physical exercise prevents short and long-term deficits on aversive and recognition memory and attenuates brain oxidative damage induced by maternal deprivation.

PubMed

Neves, Ben-Hur; Menezes, Jefferson; Souza, Mauren Assis; Mello-Carpes, Pâmela B

2015-12-01

It is known from previous research that physical exercise prevents long-term memory deficits induced by maternal deprivation in rats. But we could not assume similar effects of physical exercise on short-term memory, as short- and long-term memories are known to result from some different memory consolidation processes. Here we demonstrated that, in addition to long-term memory deficit, the short-term memory deficit resultant from maternal deprivation in object recognition and aversive memory tasks is also prevented by physical exercise. Additionally, one of the mechanisms by which the physical exercise influences the memory processes involves its effects attenuating the oxidative damage in the maternal deprived rats' hippocampus and prefrontal cortex.

Auditory and Visual Working Memory Functioning in College Students with Attention-Deficit/Hyperactivity Disorder and/or Learning Disabilities.

PubMed

Liebel, Spencer W; Nelson, Jason M

2017-12-01

We investigated the auditory and visual working memory functioning in college students with attention-deficit/hyperactivity disorder, learning disabilities, and clinical controls. We examined the role attention-deficit/hyperactivity disorder subtype status played in working memory functioning. The unique influence that both domains of working memory have on reading and math abilities was investigated. A sample of 268 individuals seeking postsecondary education comprise four groups of the present study: 110 had an attention-deficit/hyperactivity disorder diagnosis only, 72 had a learning disability diagnosis only, 35 had comorbid attention-deficit/hyperactivity disorder and learning disability diagnoses, and 60 individuals without either of these disorders comprise a clinical control group. Participants underwent a comprehensive neuropsychological evaluation, and licensed psychologists employed a multi-informant, multi-method approach in obtaining diagnoses. In the attention-deficit/hyperactivity disorder only group, there was no difference between auditory and visual working memory functioning, t(100) = -1.57, p = .12. In the learning disability group, however, auditory working memory functioning was significantly weaker compared with visual working memory, t(71) = -6.19, p < .001, d = -0.85. Within the attention-deficit/hyperactivity disorder only group, there were no auditory or visual working memory functioning differences between participants with either a predominantly inattentive type or a combined type diagnosis. Visual working memory did not incrementally contribute to the prediction of academic achievement skills. Individuals with attention-deficit/hyperactivity disorder did not demonstrate significant working memory differences compared with clinical controls. Individuals with a learning disability demonstrated weaker auditory working memory than individuals in either the attention-deficit/hyperactivity or clinical control groups. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice.

PubMed

Rey, Nolwen L; Jardanhazi-Kurutz, Daniel; Terwel, Dick; Kummer, Markus P; Jourdan, Francois; Didier, Anne; Heneka, Michael T

2012-02-01

Neuronal loss in the locus coeruleus (LC) is 1 of the early pathological events in Alzheimer's disease (AD). Projections of noradrenergic neurons of the LC innervate the olfactory bulb (OB). Because olfactory deficits have been reported in early AD, we investigated the effect of induced LC degeneration on olfactory memory and discrimination in an AD mouse model. LC degeneration was induced by treating APP/PS1 mice with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP4) repeatedly between 3 and 12 months of age. Short term odor retention, ability for spontaneous habituation to an odor, and spontaneous odor discrimination were assessed by behavioral tests. DSP4 treatment in APP/PS1 mice resulted in an exacerbation of short term olfactory memory deficits and more discrete weakening of olfactory discrimination abilities, suggesting that LC degeneration contributes to olfactory deficits observed in AD. Importantly, DSP4 treatment also increased amyloid β (Aβ) deposition in the olfactory bulb of APP/PS1 mice, which correlated with olfactory memory, not with discrimination deficits. Copyright © 2012 Elsevier Inc. All rights reserved.

Applications of the Morris water maze in translational traumatic brain injury research.

PubMed

Tucker, Laura B; Velosky, Alexander G; McCabe, Joseph T

2018-05-01

Acquired traumatic brain injury (TBI) is frequently accompanied by persistent cognitive symptoms, including executive function disruptions and memory deficits. The Morris Water Maze (MWM) is the most widely-employed laboratory behavioral test for assessing cognitive deficits in rodents after experimental TBI. Numerous protocols exist for performing the test, which has shown great robustness in detecting learning and memory deficits in rodents after infliction of TBI. We review applications of the MWM for the study of cognitive deficits following TBI in pre-clinical studies, describing multiple ways in which the test can be employed to examine specific aspects of learning and memory. Emphasis is placed on dependent measures that are available and important controls that must be considered in the context of TBI. Finally, caution is given regarding interpretation of deficits as being indicative of dysfunction of a single brain region (hippocampus), as experimental models of TBI most often result in more diffuse damage that disrupts multiple neural pathways and larger functional networks that participate in complex behaviors required in MWM performance. Published by Elsevier Ltd.

Serotonin Control of Thermotaxis Memory Behavior in Nematode Caenorhabditis elegans

PubMed Central

Guo, Yuling; Wang, Daoyong; Li, Chaojun; Wang, Dayong

2013-01-01

Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans. PMID:24223727

CRTC1 Function During Memory Encoding Is Disrupted in Neurodegeneration.

PubMed

Parra-Damas, Arnaldo; Chen, Meng; Enriquez-Barreto, Lilian; Ortega, Laura; Acosta, Sara; Perna, Judith Camats; Fullana, M Neus; Aguilera, José; Rodríguez-Alvarez, José; Saura, Carlos A

2017-01-15

Associative memory impairment is an early clinical feature of dementia patients, but the molecular and cellular mechanisms underlying these deficits are largely unknown. In this study, we investigated the functional regulation of the cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) by associative learning in physiological and neurodegenerative conditions. We evaluated the activation of CRTC1 in the hippocampus of control mice and mice lacking the Alzheimer's disease-linked presenilin genes (presenilin conditional double knockout [PS cDKO]) after one-trial contextual fear conditioning by using biochemical, immunohistochemical, and gene expression analyses. PS cDKO mice display classical features of neurodegeneration occurring in Alzheimer's disease including age-dependent cortical atrophy, neuron loss, dendritic degeneration, and memory deficits. Context-associative learning, but not single context or unconditioned stimuli, induces rapid dephosphorylation (Ser151) and translocation of CRTC1 from the cytosol/dendrites to the nucleus of hippocampal neurons in the mouse brain. Accordingly, context-associative learning induces differential CRTC1-dependent transcription of c-fos and the nuclear receptor subfamily 4 (Nr4a) genes Nr4a1-3 in the hippocampus through a mechanism that involves CRTC1 recruitment to CRE promoters. Deregulation of CRTC1 dephosphorylation, nuclear translocation, and transcriptional function are associated with long-term contextual memory deficits in PS cDKO mice. Importantly, CRTC1 gene therapy in the hippocampus ameliorates context memory and transcriptional deficits and dendritic degeneration despite ongoing cortical degeneration in this neurodegeneration mouse model. These findings reveal a critical role of CRTC1 in the hippocampus during associative memory, and provide evidence that CRTC1 deregulation underlies memory deficits during neurodegeneration. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

PubMed

Guez, Jonathan; Naveh-Benjamin, Moshe

2016-09-01

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

Examining the Pathways between Self-Awareness and Well-Being in Mild-Moderate Alzheimer’s Disease

PubMed Central

Cines, Sarah; Farrell, Meagan; Steffener, Jason; Sullo, Liz; Huey, Ted; Karlawish, Jason; Cosentino, Stephanie

2015-01-01

Objective To investigate the relationship between awareness of memory loss and psychological well-being in a non-clinically depressed sample of participants with mild-moderate Alzheimer’s disease. Method Study participants (n=104) enrolled through Columbia University Medical Center and the University of Pennsylvania completed clinical and cognitive assessments. Participants were rated with regard to their degree of awareness of memory deficits and completed questionnaires relating to their psychological well-being, including mood and quality of life (QOL). Mediating models were used to establish the relationship between awareness, depression, and QOL, as well as to examine potential mediators of awareness and depression including psychological distress, objective memory deficits, and negative self-ratings. Results There was a direct association between awareness of memory deficits and depressed mood, but not awareness and QOL. However, there was an indirect association between awareness and QOL through depression. Neither psychological distress, memory deficits, nor negative self-ratings mediated the relationship between awareness and depression. Conclusions Awareness is associated with depressed mood in non-clinically depressed participants with mild to moderate AD. However, depressed mood does not appear to reflect the direct psychological reaction to awareness of memory loss. Moreover, awareness has only an indirect association with QOL via depressed mood. These results suggest that preserved awareness does not have a direct negative impact on overall psychological well-being in AD. PMID:26560509

Chronic 5-HT4 receptor agonist treatment restores learning and memory deficits in a neuroendocrine mouse model of anxiety/depression.

PubMed

Darcet, Flavie; Gardier, Alain M; David, Denis J; Guilloux, Jean-Philippe

2016-03-11

Cognitive disturbances are often reported as serious invalidating symptoms in patients suffering from major depression disorders (MDD) and are not fully corrected by classical monoaminergic antidepressant drugs. If the role of 5-HT4 receptor agonists as cognitive enhancers is well established in naïve animals or in animal models of cognitive impairment, their cognitive effects in the context of stress need to be examined. Using a mouse model of anxiety/depression (CORT model), we reported that a chronic 5-HT4 agonist treatment (RS67333, 1.5mg/kg/day) restored chronic corticosterone-induced cognitive deficits, including episodic-like, associative and spatial learning and memory impairments. On the contrary, a chronic monoaminergic antidepressant drug treatment with fluoxetine (18mg/kg/day) only partially restored spatial learning and memory deficits and had no effect in the associative/contextual task. These results suggest differential mechanisms underlying cognitive effects of these drugs. Finally, the present study highlights 5-HT4 receptor stimulation as a promising therapeutic mechanism to alleviate cognitive symptoms related to MDD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Long-Term Memory Performance in Adult ADHD.

PubMed

Skodzik, Timo; Holling, Heinz; Pedersen, Anya

2017-02-01

Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

Neuropathology and functional deficits in a model of birth asphyxia in the precocial spiny mouse (Acomys cahirinus).

PubMed

Hutton, Lisa C; Ratnayake, Udani; Shields, Amy; Walker, David W

2009-01-01

Birth asphyxia can result in sensory impairment, learning and memory deficits without gross brain injury and severe motor deficits. We developed a model of birth asphyxia resulting in mild neurological injury and cognitive impairment using a long-gestation species with precocial fetal development. Spiny mice (Acomys cahirinus) underwent caesarean-section delivery or 7.5 min of asphyxia at 37 days gestational age (term is 39 days). Brain histology was examined at 1 and 7 days of age, and behaviour was evaluated to 28 days of age. Asphyxiated offspring showed significant impairment in non-spatial memory and learning tasks, accompanied by central nervous system inflammation and increased apoptotic cell death but without the presence of large necrotic or cystic lesions. Copyright 2009 S. Karger AG, Basel.

Ameliorative effect of rosmarinic acid on scopolamine-induced memory impairment in rats.

PubMed

Hasanein, Parisa; Mahtaj, Azam Kazemian

2015-01-12

Rosmarinic acid (RA) is a natural phenol that exerts different biological activities, such as antioxidant activity and neuroprotective effects. In this study, we hypothesized that administration of RA (8, 16, and 32 mg/kg, p.o.) for 7 days would effect on scopolamine-induced cognitive dysfunction as an extensively used model of cognitive impairment. The rats were divided into 10 groups. The acquisition trial was done 1h after the last administration of RA. Animals were divided into control, RA (8, 16, and 32 mg/kg) and donepezil (2 mg/kg) treated controls, scopolamine, RA (8, 16, and 32 mg/kg), and donepezil (2 mg/kg) treated scopolamine groups. Memory impairment was induced by scopolamine treatment (1 mg/kg, i.p.) 30 min after the administration of RA, donepezil, or saline. Scopolamine administration caused cognition deficits in the PAL and memory paradigm. While orally RA administration (16 and 32 mg/kg) improved learning and memory in control rats, it reversed learning and memory deficits of scopolamine received groups. Administration of RA at the dose of 8 mg/kg did not alter cognitive function in control and scopolamine treated groups. The combination of anticholinesterase, neuroprotective, and antioxidant properties of RA may all be responsible for the observed effects. These results indicate the beneficial effects of subchronic RA administration in passive avoidance learning and memory in control rats as well as in a pharmacological model of cholinergic deficit which continue to expand the knowledge base in creating new treatment strategies for cognition deficits and dementia. Of course, further studies are warranted for clinical use of RA in the management of demented subjects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The protective effect of hydrogen sulfide (H2S) on traumatic brain injury (TBI) induced memory deficits in rats.

PubMed

Karimi, Seyed Asaad; Hosseinmardi, Narges; Janahmadi, Mahyar; Sayyah, Mohammad; Hajisoltani, Razieh

2017-09-01

Traumatic brain injury (TBI), as an expanding public health epidemic, is a common cause of death among youth. TBI is associated with cognitive deficits and memory impairment. Hydrogen sulfide (H 2 S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the central nervous system. In the present study the potential neuroprotective role of sodium hydrosulfide (NaHS), an H 2 S donor on TBI induced memory deficit in a rat model of controlled cortical impact (CCI) injury was investigated. CCI model was used to induce TBI. Male rats were randomly assigned into the following groups: control, sham, sham treated with NaHS, TBI, and TBI treated with NaHS (3 and 5mg/kg). NaHS was injected intraperitoneally 5min before TBI induction. Learning and memory were assessed using Morris water maze (MWM) on days 8-12 following injury. CCI resulted in MWM deficits. Injured animals showed a slower rate of acquisition with respect to the sham-operated animals [F (1, 24)=13.97, P<0.01, two-way ANOVA]. NaHS improved spatial memory impairment of injured rats. Treatment with NaHS (5 mg/kg) decreased the escape latency [F (1, 24)=7.559, P<0.05, two-way ANOVA] and traveled distance [F (1, 12)=6.398, P<0.05, Two way ANOVA)]. In probe test, injured animals spent less time in target zone (P<0.05, unpaired t-test) and NaHS did not have any effect on this parameter (p>0.05, one way ANOVA). These findings suggest that NaHS has a neuroprotective effect on TBI-induced memory impairment in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Adolescent social defeat decreases spatial working memory performance in adulthood

PubMed Central

2013-01-01

Background Adolescent social stress is associated with increased incidence of mental illnesses in adulthood that are characterized by deficits in cognitive focus and flexibility. Such enhanced vulnerability may be due to psychosocial stress-induced disruption of the developing mesocortical dopamine system, which plays a fundamental role in facilitating complex cognitive processes such as spatial working memory. Adolescent rats exposed to repeated social defeat as a model of social stress develop dopaminergic hypofunction in the medial prefrontal cortex as adults. To evaluate a direct link between adolescent social stress and later deficits in cognitive function, the present study tested the effects of adolescent social defeat on two separate tests of spatial working memory performance. Methods Adult rats exposed to adolescent social defeat and their controls were trained on either the delayed win-shift task or the delayed alternating T-Maze task and then challenged with various delay periods. To evaluate potential differences in motivation for the food reward used in memory tasks, consumption and conditioned place preference for sweetened condensed milk were tested in a separate cohort of previously defeated rats and controls. Results Compared to controls, adult rats defeated in adolescence showed a delay-dependent deficit in spatial working memory performance, committing more errors at a 90 s and 5 min delay period on the T-maze and win-shift tasks, respectively. Observed memory deficits were likely independent of differences in reward motivation, as conditioned place preference for the palatable food used on both tasks was similar between the adolescent social defeat group and control. Conclusions The results demonstrate that severe social stressors during adolescence can produce long term deficits in aspects of cognitive function. Given the dependence of spatial working memory on prefrontal dopamine, pharmacologically reversing dopaminergic deficiencies caused by adolescent social stress has the potential to treat such cognitive deficits. PMID:24134918

The role of reduced working memory storage and processing resources in the associative memory deficit of older adults: simulation studies with younger adults.

PubMed

Hara, Yoko; Naveh-Benjamin, Moshe

2015-01-01

Previous research indicates that relative to younger adults, older adults show a larger decline in long-term memory (LTM) for associations than for the components that make up these associations. The purpose of the present study was to investigate whether we can impair associative memory performance in young adults by reducing their working memory (WM) resources, hence providing potential clues regarding the underlying causes of the associative memory deficit in older adults. With two experiments, we investigated whether we can reduce younger adults' long-term associative memory using secondary tasks in which either storage or processing WM loads were manipulated, while participants learned name-face pairs and then remembered the names, the faces, and the name-face associations. Results show that reducing either the storage or the processing resources of WM produced performance patterns of an associative long-term memory deficit in young adults. Furthermore, younger adults' associative memory deficit was a function of their performance on a working memory span task. These results indicate that one potential reason older adults have an associative deficit is a reduction in their WM resources but further research is needed to assess the mechanisms involved in age-related associative memory deficits.

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

ERIC Educational Resources Information Center

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

2011-01-01

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

Increasing CREB Function in the CA1 Region of Dorsal Hippocampus Rescues the Spatial Memory Deficits in a Mouse Model of Alzheimer's Disease

PubMed Central

Yiu, Adelaide P; Rashid, Asim J; Josselyn, Sheena A

2011-01-01

The principal defining feature of Alzheimer's disease (AD) is memory impairment. As the transcription factor CREB (cAMP/Ca2+ responsive element-binding protein) is critical for memory formation across species, we investigated the role of CREB in a mouse model of AD. We found that TgCRND8 mice exhibit a profound impairment in the ability to form a spatial memory, a process that critically relies on the dorsal hippocampus. Perhaps contributing to this memory deficit, we observed additional deficits in the dorsal hippocampus of TgCRND8 mice in terms of (1) biochemistry (decreased CREB activation in the CA1 region), (2) neuronal structure (decreased spine density and dendritic complexity of CA1 pyramidal neurons), and (3) neuronal network activity (decreased arc mRNA levels following behavioral training). Locally and acutely increasing CREB function in the CA1 region of dorsal hippocampus of TgCRND8 mice was sufficient to restore function in each of these key domains (biochemistry, neuronal structure, network activity, and most importantly, memory formation). The rescue produced by increasing CREB was specific both anatomically and behaviorally and independent of plaque load or Aβ levels. Interestingly, humans with AD show poor spatial memory/navigation and AD brains have disrupted (1) CREB activation, and (2) spine density and dendritic complexity in hippocampal CA1 pyramidal neurons. These parallel findings not only confirm that TgCRND8 mice accurately model key aspects of human AD, but furthermore, suggest the intriguing possibility that targeting CREB may be a useful therapeutic strategy in treating humans with AD. PMID:21734652

Neuronal histamine and the interplay of memory, reinforcement and emotions.

PubMed

Dere, E; Zlomuzica, A; De Souza Silva, M A; Ruocco, L A; Sadile, A G; Huston, J P

2010-12-31

The biogenic amine histamine is an important neurotransmitter-neuromodulator in the central nervous system that has been implicated in a variety of biological functions including thermo- and immunoregulation, food intake, seizures, arousal, anxiety, reward and memory. The review of the pertinent literature indicates that the majority of findings are compatible with the appraisal that the inhibition of histaminergic neurotransmission impairs learning and memory formation, decreases cortical activation and arousal, has a suppressive effect on behavioral measures of fear and anxiety, exponentiates the rewarding effects of drugs of abuse and intracranial brain stimulation. In contrast, the stimulation of histaminergic neurotransmission can ameliorate learning and memory impairments that are associated with various experimental deficit models and pathological conditions. Clinical investigations with patients suffering from neurodegenerative diseases such as Alzheimer's and Parkinson's disease demonstrate pathological alterations in the brain's histaminergic system, which, in some cases are correlated with the severity of cognitive deficits. The role of the brain's histamine system in episodic memory formation and the potential of histamine-related drugs to ameliorate cognitive deficits in early stages of neurodegenerative diseases are discussed. Copyright © 2010 Elsevier B.V. All rights reserved.

Disruption of Attention by Irrelevant Stimuli in Serial Recall

ERIC Educational Resources Information Center

Lange, Elke B.

2005-01-01

In four experiments the behavioral consequences of an involuntary attentional distraction concerning memory performance was investigated. The working memory model of Cowan (1995) predicts a performance deficit for memory representations that are held in an active state when the focus of attention is distracted by a change in physical properties.…

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

PubMed Central

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

2013-01-01

Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI. PMID:23653600

Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke

PubMed Central

Ramsey, Lenny E.; Metcalf, Nicholas V.; Chacko, Ravi V.; Weinberger, Kilian; Baldassarre, Antonello; Hacker, Carl D.; Shulman, Gordon L.; Corbetta, Maurizio

2016-01-01

Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain–behavior relationships in stroke. PMID:27402738

Disinhibition, an emerging pharmacology of learning and memory.

PubMed

Möhler, Hanns; Rudolph, Uwe

2017-01-01

Learning and memory are dependent on interactive excitatory and inhibitory mechanisms. In this review, we discuss a mechanism called disinhibition, which is the release of an inhibitory constraint that effectively results in an increased activity in the target neurons (for example, principal or projection neurons). We focus on discussing the role of disinhibition in learning and memory at a basic level and in disease models with cognitive deficits and highlight a strategy to reverse cognitive deficits caused by excess inhibition, through disinhibition of α5-containing GABA A receptors mediating tonic inhibition in the hippocampus, based on subtype-selective negative allosteric modulators as a novel class of drugs.

Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies.

PubMed

Schröder, Nadja; Figueiredo, Luciana Silva; de Lima, Maria Noêmia Martins

2013-01-01

Over the last decades, studies from our laboratory and other groups using animal models have shown that iron overload, resulting in iron accumulation in the brain, produces significant cognitive deficits. Iron accumulation in the hippocampus and the basal ganglia has been related to impairments in spatial memory, aversive memory, and recognition memory in rodents. These results are corroborated by studies showing that the administration of iron chelators attenuates cognitive deficits in a variety of animal models of cognitive dysfunction, including aging and Alzheimer's disease models. Remarkably, recent human studies using magnetic resonance image techniques have also shown a consistent correlation between cognitive dysfunction and iron deposition, mostly in the hippocampus, cortical areas, and basal ganglia. These findings may have relevant implications in the light of the knowledge that iron accumulates in brain regions of patients suffering from neurodegenerative diseases. A better understanding of the functional consequences of iron dysregulation in aging and neurological diseases may help to identify novel targets for treating memory problems that afflict a growing aging population.

Episodic and Semantic Autobiographical Memory in Adults with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Crane, Laura; Goddard, Lorna

2008-01-01

Episodic and semantic autobiographical memories were examined in a group of adults with autism spectrum disorders (ASD) and a control group matched for age, gender and IQ. Results demonstrated a personal episodic memory deficit in the ASD group in the absence of a personal semantic memory deficit, suggesting a deficit dissociation between these…

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

PubMed

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

2016-03-01

The ability to remember is influenced by environmental and lifestyle factors, such as stress and diet. A flavanol contained in chocolate, epicatechin (Epi), has been shown to enhance long-term memory (LTM) formation in Lymnaea. Combining two stressors (low-calcium pond water and crowding) blocks learning and all forms of memory; that is, this combination of environmentally relevant stressors creates a memory-unfriendly state. We tested the hypothesis that Epi will immediately reverse the memory-unfriendly state, i.e. that snails in the memory-deficit state when trained in Epi will immediately become competent to learn and form memory. We found that Epi not only reverses the memory-deficit state but also further enhances LTM formation. Thus, a naturally occurring bioactive plant compound can overcome a memory-unfriendly state. This supports the idea that bioactive substances may mitigate memory-making deficits that, for example, occur with ageing. © 2016. Published by The Company of Biologists Ltd.

Thrombin-induced microglial activation impairs hippocampal neurogenesis and spatial memory ability in mice.

PubMed

Yang, Yuan; Zhang, Meikui; Kang, Xiaoni; Jiang, Chen; Zhang, Huan; Wang, Pei; Li, Jingjing

2015-09-26

To investigate the effects of microglia/macrophages activation induced by intrastriatal thrombin injection on dentate gyrus neurogenesis and spatial memory ability in mice. The male C57BL/6 mice were divided into 4 groups of 10: sham, intracerebral hemorrhage (ICH), ICH + hirudin (thrombin inhibitor), and ICH + indometacin (Indo, an anti-inflammation drug). ICH model was created by intrastriatal thrombin (1U) injection. BrdU (50 mg/kg) was administrated on the same day after surgery for 6 consecutive days. Motor functions were evaluated with rotarod and beam walking tests. The spatial memory deficit was measured with Morris water maze (MWM). Cell quantification was performed for doublecortin (DCX, immature neuron), BrdU (S-phase proliferating cell population) and CD68 (activated microglia/macrophage) immune-reactive cells. Microglia/macrophages activation induced by intrastriatal thrombin injection reduced hippocampal neurogenesis and impaired spatial memory ability, but did not affect the motor function at 3 and 5 days post-injury. Both hirudin and indometacin reduced microglia/macrophages activation, enhanced hippocampal neurogenesis, and improved spatial memory ability in mice. Microglia/macrophages activation induced by intrastriatal thrombin injection might be responsible for the spatial memory deficit. Targeting both thrombin and inflammation systems in acute phase of ICH might be important in alleviating the significant spatial memory deficits.

A biased competition account of attention and memory in Alzheimer's disease

PubMed Central

Finke, Kathrin; Myers, Nicholas; Bublak, Peter; Sorg, Christian

2013-01-01

The common view of Alzheimer's disease (AD) is that of an age-related memory disorder, i.e. declarative memory deficits are the first signs of the disease and associated with progressive brain changes in the medial temporal lobes and the default mode network. However, two findings challenge this view. First, new model-based tools of attention research have revealed that impaired selective attention accompanies memory deficits from early pre-dementia AD stages on. Second, very early distributed lesions of lateral parietal networks may cause these attention deficits by disrupting brain mechanisms underlying attentional biased competition. We suggest that memory and attention impairments might indicate disturbances of a common underlying neurocognitive mechanism. We propose a unifying account of impaired neural interactions within and across brain networks involved in attention and memory inspired by the biased competition principle. We specify this account at two levels of analysis: at the computational level, the selective competition of representations during both perception and memory is biased by AD-induced lesions; at the large-scale brain level, integration within and across intrinsic brain networks, which overlap in parietal and temporal lobes, is disrupted. This account integrates a large amount of previously unrelated findings of changed behaviour and brain networks and favours a brain mechanism-centred view on AD. PMID:24018724

A biased competition account of attention and memory in Alzheimer's disease.

PubMed

Finke, Kathrin; Myers, Nicholas; Bublak, Peter; Sorg, Christian

2013-10-19

The common view of Alzheimer's disease (AD) is that of an age-related memory disorder, i.e. declarative memory deficits are the first signs of the disease and associated with progressive brain changes in the medial temporal lobes and the default mode network. However, two findings challenge this view. First, new model-based tools of attention research have revealed that impaired selective attention accompanies memory deficits from early pre-dementia AD stages on. Second, very early distributed lesions of lateral parietal networks may cause these attention deficits by disrupting brain mechanisms underlying attentional biased competition. We suggest that memory and attention impairments might indicate disturbances of a common underlying neurocognitive mechanism. We propose a unifying account of impaired neural interactions within and across brain networks involved in attention and memory inspired by the biased competition principle. We specify this account at two levels of analysis: at the computational level, the selective competition of representations during both perception and memory is biased by AD-induced lesions; at the large-scale brain level, integration within and across intrinsic brain networks, which overlap in parietal and temporal lobes, is disrupted. This account integrates a large amount of previously unrelated findings of changed behaviour and brain networks and favours a brain mechanism-centred view on AD.

[Source-monitoring deficits in schizophrenia: review and pharmacotherapeutic implications].

PubMed

Juhász, Levente Zsolt; Bartkó, György

2007-03-01

The disturbance of source-monitoring is one of the various impairments in cognitive functioning observed in schizophrenic patients. The process of source-monitoring allows individuals to distinguish self generated thoughts and behaviours from those generated by others. The aim of the present study is to review the general psychological definition of source memory and source-monitoring and its neurological basis as well as the models for explanation of source-monitoring deficits. The relationship between source-monitoring-deficits and psychopathological symptoms as well as the effect of antipsychotic treatment on source-monitoring disturbances are introduced. There is evidence suggesting, that a selective source-monitoring deficit is in the occurrence of auditory hallucinations. The disturbance of prospective memory may influence unfavorably the compliance. Administration of antipsychotics in general can improve source-monitoring deficits. The neuropsychiatric perspective provides a more accurate and comprehensive understanding of schizophrenia.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2015-01-01

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

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

PubMed

Chen, Tina; Naveh-Benjamin, Moshe

2012-09-01

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

Reduction in open field activity in the absence of memory deficits in the AppNL-G-F knock-in mouse model of Alzheimer's disease.

PubMed

Whyte, Lauren S; Hemsley, Kim M; Lau, Adeline A; Hassiotis, Sofia; Saito, Takashi; Saido, Takaomi C; Hopwood, John J; Sargeant, Timothy J

2018-01-15

The recent development of knock-in mouse models of Alzheimer's disease provides distinct advantages over traditional transgenic mouse models that rely on over-expression of amyloid precursor protein. Two such knock-in models that have recently been widely adopted by Alzheimer's researchers are the App NL-F and App NL-G-F mice. This study aimed to further characterise the behavioural phenotype and amyloid plaque distribution of App NL-G-F/NL-G-F (C57BL/6J background) mice at six-months of age. An attempt to replicate a previous study that observed deficits in working memory in the Y-maze, showed no difference between App NL-G-F/NL-G-F and wild-type mice. Further assessment of these mice using the novel object recognition test and Morris water maze also revealed no differences between App NL-G-F/NL-G-F and wild-type mice. Despite a lack of demonstrated cognitive deficits, we report a reduction in locomotor/exploratory activity in an open field. Histological examination of App NL-G-F/NL-G-F mice showed widespread distribution of amyloid plaques at this age. We conclude that whilst at six-months of age, memory deficits are not sufficiently robust to be replicated in varying environments, amyloid plaque burden is significant in App NL-G-F/NL-G-F knock-in brain. Copyright © 2017 Elsevier B.V. All rights reserved.

NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication.

PubMed

Olszewski, Rafal T; Janczura, Karolina J; Bzdega, Tomasz; Der, Elise K; Venzor, Faustino; O'Rourke, Brennen; Hark, Timothy J; Craddock, Kirsten E; Balasubramanian, Shankar; Moussa, Charbel; Neale, Joseph H

2017-09-01

Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1.5 h) and long- (24 h) term novel object recognition tests were used to assess memory. Treatment with ZJ43 or 2-PMPA prior to acquisition trials increased long-term memory in mGluR2, but not mGluR3, ko mice. Nine month-old triple transgenic Alzheimer's disease model mice exhibited impaired short-term novel object recognition memory that was rescued by treatment with a NAAG peptidase inhibitor. NAAG peptidase inhibitors and the group II mGluR agonist, LY354740, reversed the short-term memory deficit induced by acute ethanol administration in wild type mice. 2-PMPA also moderated the effect of ethanol on short-term memory in mGluR2 ko mice but failed to do so in mGluR3 ko mice. LY354740 and ZJ43 blocked ethanol-induced motor activation. Both GCPII inhibitors and LY354740 also significantly moderated the loss of motor coordination induced by 2.1 g/kg ethanol treatment. These data support the conclusion that inhibitors of glutamate carboxypeptidase II are efficacious in object recognition models of normal memory and memory deficits via an mGluR3 mediated process, actions that could have widespread clinical applications.

Combined effects of THC and caffeine on working memory in rats

PubMed Central

Panlilio, Leigh V; Ferré, Sergi; Yasar, Sevil; Thorndike, Eric B; Schindler, Charles W; Goldberg, Steven R

2012-01-01

BACKGROUND AND PURPOSE Cannabis and caffeine are two of the most widely used psychoactive substances. Δ9-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. EXPERIMENTAL APPROACH Rats were given THC (0, 1 and 3 mg·kg−1, i.p.) along with caffeine (0, 1, 3 and 10 mg·kg−1, i.p.), the selective adenosine A1-receptor antagonist CPT (0, 3 and 10 mg·kg−1) or the selective adenosine A2A-receptor antagonist SCH58261 (0 and 5 mg·kg−1) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. KEY RESULTS THC alone produced memory deficits at 3 mg·kg−1. The initial exposure to caffeine (10 mg·kg−1) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg·kg−1) was combined with caffeine (10 mg·kg−1) or CPT (10 mg·kg−1), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. CONCLUSION AND IMPLICATIONS Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A1 receptors modulate cannabinoid signalling in the hippocampus. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21699509

Verbal Short-term Memory in Down's Syndrome: An Articulatory Loop Deficit?

ERIC Educational Resources Information Center

Vicari, S.; Marotta, L.; Carlesimo, G. A.

2004-01-01

Verbal short-term memory, as measured by digit or word span, is generally impaired in individuals with Down's syndrome (DS) compared to mental age-matched controls. Moving from the working memory model, the present authors investigated the hypothesis that impairment in some of the articulatory loop sub-components is at the base of the deficient…

Impaired Verbal Short-Term Memory in down Syndrome Reflects a Capacity Limitation Rather than Atypically Rapid Forgetting

ERIC Educational Resources Information Center

M. Purser, H.R.; Jarrold, C.

2005-01-01

Individuals with Down syndrome suffer from relatively poor verbal short-term memory. Recent work has indicated that this deficit is not caused by problems of audition, speech, or articulatory rehearsal within the phonological loop component of Baddeley and Hitch's working memory model. Given this, two experiments were conducted to investigate…

Does Working Memory Impact Functional Outcomes in Individuals With ADHD: A Qualitative and Comprehensive Literature Review.

PubMed

Fried, Ronna; Abrams, Jessica; Hall, Anna; Feinberg, Leah; Pope, Amanda; Biederman, Joseph

2017-09-01

Working Memory (WM) is a domain of executive functioning often impaired in individuals with ADHD. Although assumed to cause difficulties across functioning, the scope of impairments from WM deficits in ADHD has not been investigated. The aim of this study was to examine outcomes associated with WM deficits in ADHD. We conducted a search of the scientific literature on WM deficits, and Freedom From Distractibility (FFD), in ADHD using PubMed and PsycInfo databases. The final sample included 11 controlled studies of WM/FFD deficits in ADHD with operationalized assessment of outcomes in academic, social, and emotional areas. WM assessment was divided into auditory-verbal memory (AVM) and spatial-visual memory (SWM). Seven studies examined WM deficits in academic functioning, eight studies assessed WM deficits in social functioning, and three assessed WM deficits in psychopathology. The majority of the literature suggests that WM deficits affect primarily academic functioning.

A heuristic model for working memory deficit in schizophrenia.

PubMed

Qi, Zhen; Yu, Gina P; Tretter, Felix; Pogarell, Oliver; Grace, Anthony A; Voit, Eberhard O

2016-11-01

The life of schizophrenia patients is severely affected by deficits in working memory. In various brain regions, the reciprocal interactions between excitatory glutamatergic neurons and inhibitory GABAergic neurons are crucial. Other neurotransmitters, in particular dopamine, serotonin, acetylcholine, and norepinephrine, modulate the local balance between glutamate and GABA and therefore regulate the function of brain regions. Persistent alterations in the balances between the neurotransmitters can result in working memory deficits. Here we present a heuristic computational model that accounts for interactions among neurotransmitters across various brain regions. The model is based on the concept of a neurochemical interaction matrix at the biochemical level and combines this matrix with a mobile model representing physiological dynamic balances among neurotransmitter systems associated with working memory. The comparison of clinical and simulation results demonstrates that the model output is qualitatively very consistent with the available data. In addition, the model captured how perturbations migrated through different neurotransmitters and brain regions. Results showed that chronic administration of ketamine can cause a variety of imbalances, and application of an antagonist of the D2 receptor in PFC can also induce imbalances but in a very different manner. The heuristic computational model permits a variety of assessments of genetic, biochemical, and pharmacological perturbations and serves as an intuitive tool for explaining clinical and biological observations. The heuristic model is more intuitive than biophysically detailed models. It can serve as an important tool for interdisciplinary communication and even for psychiatric education of patients and relatives. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. Copyright © 2016 Elsevier B.V. All rights reserved.

Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase-mTORC1 Translational Pathway.

PubMed

Bavley, Charlotte C; Rice, Richard C; Fischer, Delaney K; Fakira, Amanda K; Byrne, Maureen; Kosovsky, Maria; Rizzo, Bryant K; Del Prete, Dolores; Alaedini, Armin; Morón, Jose A; Higgins, Joseph J; D'Adamio, Luciano; Rajadhyaksha, Anjali M

2018-03-14

A homozygous nonsense mutation in the cereblon ( CRBN ) gene results in autosomal recessive, nonsyndromic intellectual disability that is devoid of other phenotypic features, suggesting a critical role of CRBN in mediating learning and memory. In this study, we demonstrate that adult male Crbn knock-out ( Crbn KO ) mice exhibit deficits in hippocampal-dependent learning and memory tasks that are recapitulated by focal knock-out of Crbn in the adult dorsal hippocampus, with no changes in social or repetitive behavior. Cellular studies identify deficits in long-term potentiation at Schaffer collateral CA1 synapses. We further show that Crbn is robustly expressed in the mouse hippocampus and Crbn KO mice exhibit hyperphosphorylated levels of AMPKα (Thr172). Examination of processes downstream of AMP-activated protein kinase (AMPK) finds that Crbn KO mice have a selective impairment in mediators of the mTORC1 translation initiation pathway in parallel with lower protein levels of postsynaptic density glutamatergic proteins and higher levels of excitatory presynaptic markers in the hippocampus with no change in markers of the unfolded protein response or autophagy pathways. Acute pharmacological inhibition of AMPK activity in adult Crbn KO mice rescues learning and memory deficits and normalizes hippocampal mTORC1 activity and postsynaptic glutamatergic proteins without altering excitatory presynaptic markers. Thus, this study identifies that loss of Crbn results in learning, memory, and synaptic defects as a consequence of exaggerated AMPK activity, inhibition of mTORC1 signaling, and decreased glutamatergic synaptic proteins. Thus, Crbn KO mice serve as an ideal model of intellectual disability to further explore molecular mechanisms of learning and memory. SIGNIFICANCE STATEMENT Intellectual disability (ID) is one of the most common neurodevelopmental disorders. The cereblon ( CRBN ) gene has been linked to autosomal recessive, nonsyndromic ID, characterized by an intelligence quotient between 50 and 70 but devoid of other phenotypic features, making cereblon an ideal protein for the study of the fundamental aspects of learning and memory. Here, using the cereblon knock-out mouse model, we show that cereblon deficiency disrupts learning, memory, and synaptic function via AMP-activated protein kinase hyperactivity, downregulation of mTORC1, and dysregulation of excitatory synapses, with no changes in social or repetitive behaviors, consistent with findings in the human population. This establishes the cereblon knock-out mouse as a model of pure ID without the confounding behavioral phenotypes associated with other current models of ID. Copyright © 2018 the authors 0270-6474/18/382781-16$15.00/0.

3,4-Methylenedioxymethamphetamine in Adult Rats Produces Deficits in Path Integration and Spatial Reference Memory

PubMed Central

Able, Jessica A.; Gudelsky, Gary A.; Vorhees, Charles V.; Williams, Michael T.

2010-01-01

Background ±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that causes cognitive deficits in humans. A rat model for learning and memory deficits has not been established, although some cognitive deficits have been reported. Methods Male Sprague-Dawley rats were treated with MDMA (15 mg/kg × 4 doses) or saline (SAL) (n = 20/treatment group) and tested in different learning paradigms: 1) path integration in the Cincinnati water maze (CWM), 2) spatial learning in the Morris water maze (MWM), and 3) novel object recognition (NOR). One week after drug administration, testing began in the CWM, then four phases of MWM, and finally NOR. Following behavioral testing, monoamine levels were assessed. Results ±3,4-Methylenedioxymethamphetamine-treated rats committed more CWM errors than did SAL-treated rats. ±3,4-Methylenedioxymethamphetamine-treated animals were further from the former platform position during each 30-second MWM probe trial but showed no differences during learning trials with the platform present. There were no group differences in NOR. ± 3,4-Methylenedioxymethamphetamine depleted serotonin in all brain regions and dopamine in the striatum. Conclusions ±3,4-Methylenedioxymethamphetamine produced MWM reference memory deficits even after complex learning in the CWM, where deficits in path integration learning occurred. Assessment of path integration may provide a sensitive index of MDMA-induced learning deficits. PMID:16324685

Mitochondrial Superoxide Contributes to Hippocampal Synaptic Dysfunction and Memory Deficits in Angelman Syndrome Model Mice.

PubMed

Santini, Emanuela; Turner, Kathryn L; Ramaraj, Akila B; Murphy, Michael P; Klann, Eric; Kaphzan, Hanoch

2015-12-09

Angelman syndrome (AS) is a neurodevelopmental disorder associated with developmental delay, lack of speech, motor dysfunction, and epilepsy. In the majority of the patients, AS is caused by the deletion of small portions of maternal chromosome 15 harboring the UBE3A gene. This results in a lack of expression of the UBE3A gene because the paternal allele is genetically imprinted. The UBE3A gene encodes an enzyme termed ubiquitin ligase E3A (E6-AP) that targets proteins for degradation by the 26S proteasome. Because neurodegenerative disease and other neurodevelopmental disorders have been linked to oxidative stress, we asked whether mitochondrial reactive oxygen species (ROS) played a role in impaired synaptic plasticity and memory deficits exhibited by AS model mice. We discovered that AS mice have increased levels of superoxide in area CA1 of the hippocampus that is reduced by MitoQ 10-methanesuflonate (MitoQ), a mitochondria-specific antioxidant. In addition, we found that MitoQ rescued impairments in hippocampal synaptic plasticity and deficits in contextual fear memory exhibited by AS model mice. Our findings suggest that mitochondria-derived oxidative stress contributes to hippocampal pathophysiology in AS model mice and that targeting mitochondrial ROS pharmacologically could benefit individuals with AS. Oxidative stress has been hypothesized to contribute to the pathophysiology of neurodevelopmental disorders, including autism spectrum disorders and Angelman syndrome (AS). Herein, we report that AS model mice exhibit elevated levels of mitochondria-derived reactive oxygen species in pyramidal neurons in hippocampal area CA1. Moreover, we demonstrate that the administration of MitoQ (MitoQ 10-methanesuflonate), a mitochondria-specific antioxidant, to AS model mice normalizes synaptic plasticity and restores memory. Finally, our findings suggest that antioxidants that target the mitochondria could be used therapeutically to ameliorate synaptic and cognitive deficits in individuals with AS. Copyright © 2015 the authors 0270-6474/15/3516213-08$15.00/0.

Copper chelator induced efficient episodic memory recovery in a non-transgenic Alzheimer's mouse model.

PubMed

Ceccom, Johnatan; Coslédan, Frédéric; Halley, Hélène; Francès, Bernard; Lassalle, Jean Michel; Meunier, Bernard

2012-01-01

Alzheimer's disease (AD) is a neurodegenerative syndrom involving many different biological parameters, including the accumulation of copper metal ions in Aβ amyloid peptides due to a perturbation of copper circulation and homeostasis within the brain. Copper-containing amyloids activated by endogenous reductants are able to generate an oxidative stress that is involved in the toxicity of abnormal amyloids and contribute to the progressive loss of neurons in AD. Since only few drugs are currently available for the treatment of AD, we decided to design small molecules able to interact with copper and we evaluated these drug-candidates with non-transgenic mice, since AD is mainly an aging disease, not related to genetic disorders. We created a memory deficit mouse model by a single icv injection of Aβ(1-42) peptide, in order to mimic the early stage of the disease and the key role of amyloid oligomers in AD. No memory deficit was observed in the control mice with the antisense Aβ(42-1) peptide. Here we report the capacity of a new copper-specific chelating agent, a bis-8-aminoquinoline PA1637, to fully reverse the deficit of episodic memory after three weeks of treatment by oral route on non-transgenic amyloid-impaired mice. Clioquinol and memantine have been used as comparators to validate this fast and efficient mouse model.

Nicotine versus 6-hydroxy-l-nicotine against chlorisondamine induced memory impairment and oxidative stress in the rat hippocampus.

PubMed

Hritcu, Lucian; Ionita, Radu; Motei, Diana Elena; Babii, Cornelia; Stefan, Marius; Mihasan, Marius

2017-02-01

6-Hydroxy-l-nicotine (6HLN), a nicotine derivative from nicotine degradation by Arthrobacter nicotinovorans pAO1 strain was found to improve behavioral deficits and to reverse oxidative stress in the rat hippocampus. Rats were given CHL (10mg/kg, i.p.) were used as an Alzheimer's disease-like model. The nicotine (0.3mg/kg) and 6HLN (0.3mg/kg) were administered alone or in combination in the CHL-treated rats. Memory-related behaviors were evaluated using Y-maze and radial arm-maze tests. The antioxidant enzymes activity and the levels of the biomarkers of oxidative stress were measured in the hippocampus. Statistical analyses were performed using two-way ANOVA and Tukey's post hoc test. F values for which p<0.05 were regarded as statistically significant. CHL-caused memory deficits and oxidative stress enhancing were observed. Both nicotine and 6HLN administration attenuated the cognitive deficits and recovered the antioxidant capacity in the rat hippocampus of the CHL rat model. Our results suggest that 6HLN versus nicotine confers anti-amnesic properties in the CHL-induced a rat model of memory impairment via reversing cholinergic function and decreasing brain oxidative stress, suggesting the use of this compound as an alternative agent in AD treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome

PubMed Central

Kazim, Syed Faraz; Blanchard, Julie; Bianchi, Riccardo; Iqbal, Khalid

2017-01-01

Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3β) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model. PMID:28368015

Memory functioning in children with reading disabilities and/or attention deficit/hyperactivity disorder: a clinical investigation of their working memory and long-term memory functioning.

PubMed

Kibby, Michelle Y; Cohen, Morris J

2008-11-01

We examined memory functioning in children with reading disabilities (RD), Attention deficit/hyperactivity disorder (ADHD), and RD/ADHD using a clinic sample with a clinical instrument: the Children's Memory Scale, enhancing its generalizability. Participants included 23 children with RD, 30 with ADHD, 30 with RD/ADHD, and 30 controls. Children with RD presented with reduced verbal short-term memory (STM) but intact visual STM, central executive (CE), and long-term memory (LTM) functioning. Their deficit in STM appeared specific to tasks requiring phonetic coding of material. Children with ADHD displayed intact CE and LTM functioning but reduced visual-spatial STM, especially when off stimulant medication. Children with RD/ADHD had deficits consistent with both disorders.

Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function.

PubMed

Sharif, Rojin; Aghsami, Mehdi; Gharghabi, Mehdi; Sanati, Mehdi; Khorshidahmad, Tina; Vakilzadeh, Gelareh; Mehdizadeh, Hajar; Gholizadeh, Shervin; Taghizadeh, Ghorban; Sharifzadeh, Mohammad

2017-01-01

Oxidative stress and mitochondrial dysfunction play indispensable role in memory and learning impairment. Growing evidences have shed light on anti-oxidative role for melatonin in memory deficit. We have previously reported that inhibition of protein kinase A by H-89 can induce memory impairment. Here, we investigated the effect of melatonin on H-89 induced spatial memory deficit and pursued their interactive consequences on oxidative stress and mitochondrial function in Morris Water Maze model. Rats received melatonin (50 and 100μg/kg/side) and H-89(10μM) intra-hippocampally 30min before each day of training. Animals were trained for 4 consecutive days, each containing one block from four trials. Oxidative stress indices, including thiobarbituric acid (TBARS), reactive oxygen species (ROS), thiol groups, and ferric reducing antioxidant power (FRAP) were assessed using spectrophotometer. Mitochondrial function was evaluated through measuring ROS production, mitochondrial membrane potential (MMP), swelling, outer membrane damage, and cytochrome c release. As expected from our previous report, H-89 remarkably impaired memory by increasing the escape latency and traveled distance. Intriguingly, H-89 significantly augmented TBARS and ROS levels, caused mitochondrial ROS production, swelling, outer membrane damage, and cytochrome c release. Moreover, H-89 lowered thiol, FRAP, and MMP values. Intriguingly, melatonin pre-treatment not only effectively hampered H-89-mediated spatial memory deficit at both doses, but also reversed the H-89 effects on mitochondrial and biochemical indices upon higher dose. Collectively, these findings highlight a protective role for melatonin against H-89-induced memory impairment and indicate that melatonin may play a therapeutic role in the treatment of oxidative- related neurodegenerative disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Working and strategic memory deficits in schizophrenia

NASA Technical Reports Server (NTRS)

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

1998-01-01

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

Prostaglandin E2 EP2 activation reduces memory decline in R6/1 mouse model of Huntington's disease by the induction of BDNF-dependent synaptic plasticity.

PubMed

Anglada-Huguet, Marta; Vidal-Sancho, Laura; Giralt, Albert; García-Díaz Barriga, Gerardo; Xifró, Xavier; Alberch, Jordi

2016-11-01

Huntington's disease (HD) patients and mouse models show learning and memory impairment even before the onset of motor symptoms. Deficits in hippocampal synaptic plasticity have been involved in the HD memory impairment. Several studies show that prostaglandin E2 (PGE2) EP2 receptor stimulates synaptic plasticity and memory formation. However, this role was not explored in neurodegenerative diseases. Here, we investigated the capacity of PGE2 EP2 receptor to promote synaptic plasticity and memory improvements in a model of HD, the R6/1 mice, by administration of the agonist misoprostol. We found that misoprostol increases dendritic branching in cultured hippocampal neurons in a brain-derived neurotrophic factor (BDNF)-dependent manner. Then, we implanted an osmotic mini-pump system to chronically administrate misoprostol to R6/1 mice from 14 to 18weeks of age. We observed that misoprostol treatment ameliorates the R6/1 long-term memory deficits as analyzed by the T-maze spontaneous alternation task and the novel object recognition test. Importantly, administration of misoprostol promoted the expression of hippocampal BDNF. Moreover, the treatment with misoprostol in R6/1 mice blocked the reduction in the number of PSD-95 and VGluT-1 positive particles observed in hippocampus of vehicle-R6/1 mice. In addition, we observed an increase of cAMP levels in the dentate ` of WT and R6/1 mice treated with misoprostol. Accordingly, we showed a reduction in the number of mutant huntingtin nuclear inclusions in the dentate gyrus of R6/1 mice. Altogether, these results suggest a putative therapeutic effect of PGE2 EP2 receptor in reducing cognitive deficits in HD. Copyright © 2016. Published by Elsevier Inc.

Everyday and prospective memory deficits in ecstasy/polydrug users.

PubMed

Hadjiefthyvoulou, Florentia; Fisk, John E; Montgomery, Catharine; Bridges, Nikola

2011-04-01

The impact of ecstasy/polydrug use on real-world memory (i.e. everyday memory, cognitive failures and prospective memory [PM]) was investigated in a sample of 42 ecstasy/polydrug users and 31 non-ecstasy users. Laboratory-based PM tasks were administered along with self-reported measures of PM to test whether any ecstasy/polydrug-related impairment on the different aspects of PM was present. Self-reported measures of everyday memory and cognitive failures were also administered. Ecstasy/polydrug associated deficits were observed on both laboratory and self-reported measures of PM and everyday memory. The present study extends previous research by demonstrating that deficits in PM are real and cannot be simply attributed to self-misperceptions. The deficits observed reflect some general capacity underpinning both time- and event-based PM contexts and are not task specific. Among this group of ecstasy/polydrug users recreational use of cocaine was also prominently associated with PM deficits. Further research might explore the differential effects of individual illicit drugs on real-world memory.

Suppressing Irrelevant Information from Working Memory: Evidence for Domain-Specific Deficits in Poor Comprehenders

ERIC Educational Resources Information Center

Pimperton, Hannah; Nation, Kate

2010-01-01

Previous research has suggested that children with specific reading comprehension deficits (poor comprehenders) show an impaired ability to suppress irrelevant information from working memory, with this deficit detrimentally impacting on their working memory ability, and consequently limiting their reading comprehension performance. However, the…

Neuropsychological and hypothalamic-pituitary-axis function in female patients with melancholic and non-melancholic depression.

PubMed

Michopoulos, Ioannis; Zervas, Iannis M; Pantelis, Chris; Tsaltas, Eleftheria; Papakosta, Vassiliki-Maria; Boufidou, Fotini; Nikolaou, Chrissoula; Papageorgiou, Charalambos; Soldatos, Costas R; Lykouras, Lefteris

2008-06-01

Executive function deficits in depression implicate involvement of frontal-striatal circuits. However, studies of hypothalamic-pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal-hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits. Forty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex-age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured. The MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group. MDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.

Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

PubMed

Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

2016-03-15

Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity. Copyright © 2015 Elsevier B.V. All rights reserved.

The misnomer of attention-deficit hyperactivity disorder.

PubMed

Wasserman, Theodore; Wasserman, Lori Drucker

2015-01-01

We propose that attention-deficit disorder represents an inefficiency of an integrated system designed to allocate working memory to designated tasks rather than the absence or dysfunction of a particular form of attention. A significant portion of this inefficiency in the allocation of working memory represents poor engagement of the reward circuit with distinct circuits of learning and performance that control instrumental conditioning (learning). Efficient attention requires the interaction of these circuits. For a significant percentage of individuals who present with attention-deficit disorder, their problems represent the engagement, or lack thereof, of the motivational and reward circuit as opposed to problems, or disorders of attention traditionally defined as problems with orienting, focusing, and sustaining. We demonstrate that there is an integrated system of working-memory allocation that responds by recruiting relevant aspects of both cortex and subcortex to the demands of the task being encountered. In this model, attention is viewed as a gating function determined by novelty, flight-or-fight response, and reward history/valence affecting motivation. We view the traditional models of attention, rather than describe specific types of attention per se, as representing the description of the behavioral output of this integrated orienting and engagement system designed to allocate working memory to task-specific stimuli.

Childhood Obesity and Academic Performance: The Role of Working Memory

PubMed Central

Wu, Nan; Chen, Yulu; Yang, Jinhua; Li, Fei

2017-01-01

The present study examined the role of working memory in the association between childhood obesity and academic performance, and further determined whether memory deficits in obese children are domain-specific to certain tasks or domain-general. A total of 227 primary school students aged 10–13 years were analyzed for weight and height, of which 159 children (44 “obese,” 23 “overweight,” and 92 “normal weight”) filled out questionnaires on school performance and socioeconomic status. And then, all subjects finished three kinds of working memory tasks based on the digit memory task in 30 trials, which were image-generated with a series of numbers recall trial sets. After each trial set, subjects were given 5 s to recall and write down the numbers which hand appeared in the trial, in the inverse order in which they had appeared. The results showed there were significant academic performance differences among the three groups, with normal-weight children scoring higher than overweight and obese children after Bonferroni correction. A mediation model revealed a partial indirect effect of working memory in the relationship between obesity and academic performance. Although the performance of obese children in basic working memory tests was poorer than that of normal-weight children, they recalled more items than normal-weight children in working memory tasks involving with food/drink. Working memory deficits partially explain the poor academic performance of obese children. Those results indicated the obese children show domain-specific working memory deficits, whereas they recall more items than normal-weight children in working memory tasks associated with food/drink. PMID:28469593

Childhood Obesity and Academic Performance: The Role of Working Memory.

PubMed

Wu, Nan; Chen, Yulu; Yang, Jinhua; Li, Fei

2017-01-01

The present study examined the role of working memory in the association between childhood obesity and academic performance, and further determined whether memory deficits in obese children are domain-specific to certain tasks or domain-general. A total of 227 primary school students aged 10-13 years were analyzed for weight and height, of which 159 children (44 "obese," 23 "overweight," and 92 "normal weight") filled out questionnaires on school performance and socioeconomic status. And then, all subjects finished three kinds of working memory tasks based on the digit memory task in 30 trials, which were image-generated with a series of numbers recall trial sets. After each trial set, subjects were given 5 s to recall and write down the numbers which hand appeared in the trial, in the inverse order in which they had appeared. The results showed there were significant academic performance differences among the three groups, with normal-weight children scoring higher than overweight and obese children after Bonferroni correction. A mediation model revealed a partial indirect effect of working memory in the relationship between obesity and academic performance. Although the performance of obese children in basic working memory tests was poorer than that of normal-weight children, they recalled more items than normal-weight children in working memory tasks involving with food/drink. Working memory deficits partially explain the poor academic performance of obese children. Those results indicated the obese children show domain-specific working memory deficits, whereas they recall more items than normal-weight children in working memory tasks associated with food/drink.

Working Memory Compensates for Hearing Related Phonological Processing Deficit

ERIC Educational Resources Information Center

Classon, Elisabet; Rudner, Mary; Ronnberg, Jerker

2013-01-01

Acquired hearing impairment is associated with gradually declining phonological representations. According to the Ease of Language Understanding (ELU) model, poorly defined representations lead to mismatch in phonologically challenging tasks. To resolve the mismatch, reliance on working memory capacity (WMC) increases. This study investigated…

Biflorin Ameliorates Memory Impairments Induced by Cholinergic Blockade in Mice

PubMed Central

Jeon, Se Jin; Kim, Boseong; Ryu, Byeol; Kim, Eunji; Lee, Sunhee; Jang, Dae Sik; Ryu, Jong Hoon

2017-01-01

To examine the effect of biflorin, a component of Syzygium aromaticum, on memory deficit, we introduced a scopolamine-induced cognitive deficit mouse model. A single administration of biflorin increased latency time in the passive avoidance task, ameliorated alternation behavior in the Y-maze, and increased exploration time in the Morris water maze task, indicating the improvement of cognitive behaviors against cholinergic dysfunction. The biflorin-induced reverse of latency in the scopolamine-treated group was attenuated by MK-801, an NMDA receptor antagonist. Biflorin also enhanced cognitive function in a naïve mouse model. To understand the mechanism of biflorin for memory amelioration, we performed Western blot. Biflorin increased the activation of protein kinase C-ζ and its downstream signaling molecules in the hippocampus. These results suggest that biflorin ameliorates drug-induced memory impairment by modulation of protein kinase C-ζ signaling in mice, implying that biflorin could function as a possible therapeutic agent for the treatment of cognitive problems. PMID:27829270

Mathematical outcomes and working memory in children with TBI and orthopedic injury.

PubMed

Raghubar, Kimberly P; Barnes, Marcia A; Prasad, Mary; Johnson, Chad P; Ewing-Cobbs, Linda

2013-03-01

This study compared mathematical outcomes in children with predominantly moderate to severe traumatic brain injury (TBI; n550) or orthopedic injury (OI; n547) at 2 and 24 months post-injury. Working memory and its contribution to math outcomes at 24 months post-injury was also examined. Participants were administered an experimental cognitive addition task and standardized measures of calculation, math fluency, and applied problems; as well as experimental measures of verbal and visual-spatial working memory. Although children with TBI did not have deficits in foundational math fact retrieval, they performed more poorly than OIs on standardized measures of math. In the TBI group, performance on standardized measures was predicted by age at injury, socioeconomic status, and the duration of impaired consciousness. Children with TBI showed impairments on verbal, but not visual working memory relative to children with OI. Verbal working memory mediated group differences on math calculations and applied problems at 24 months post-injury. Children with TBI have difficulties in mathematics, but do not have deficits in math fact retrieval, a signature deficit of math disabilities. Results are discussed with reference to models of mathematical cognition and disability and the role of working memory in math learning and performance for children with TBI.

Mathematical Outcomes and Working Memory in Children With TBI and Orthopedic Injury

PubMed Central

Raghubar, Kimberly P.; Barnes, Marcia A.; Prasad, Mary; Johnson, Chad P.; Ewing-Cobbs, Linda

2013-01-01

This study compared mathematical outcomes in children with predominantly moderate to severe traumatic brain injury (TBI; n =50) or orthopedic injury (OI; n=47) at 2 and 24 months post-injury. Working memory and its contribution to math outcomes at 24 months post-injury was also examined. Participants were administered an experimental cognitive addition task and standardized measures of calculation, math fluency, and applied problems; as well as experimental measures of verbal and visual-spatial working memory. Although children with TBI did not have deficits in foundational math fact retrieval, they performed more poorly than OIs on standardized measures of math. In the TBI group, performance on standardized measures was predicted by age at injury, socioeconomic status, and the duration of impaired consciousness. Children with TBI showed impairments on verbal, but not visual working memory relative to children with OI. Verbal working memory mediated group differences on math calculations and applied problems at 24 months post-injury. Children with TBI have difficulties in mathematics, but do not have deficits in math fact retrieval, a signature deficit of math disabilities. Results are discussed with reference to models of mathematical cognition and disability and the role of working memory in math learning and performance for children with TBI. PMID:23164058

Hippocampal place cell and inhibitory neuron activity in disrupted-in-schizophrenia-1 mutant mice: implications for working memory deficits

PubMed Central

Mesbah-Oskui, Lia; Georgiou, John; Roder, John C

2015-01-01

Background: Despite the prevalence of working memory deficits in schizophrenia, the neuronal mechanisms mediating these deficits are not fully understood. Importantly, deficits in spatial working memory are identified in numerous mouse models that exhibit schizophrenia-like endophenotypes. The hippocampus is one of the major brain regions that actively encodes spatial location, possessing pyramidal neurons, commonly referred to as ‘place cells’, that fire in a location-specific manner. This study tests the hypothesis that mice with a schizophrenia-like endophenotype exhibit impaired encoding of spatial location in the hippocampus. Aims: To characterize hippocampal place cell activity in mice that exhibit a schizophrenia-like endophenotype. Methods: We recorded CA1 place cell activity in six control mice and six mice that carry a point mutation in the disrupted-in-schizophrenia-1 gene (Disc1-L100P) and have previously been shown to exhibit deficits in spatial working memory. Results: The spatial specificity and stability of Disc1-L100P place cells were similar to wild-type place cells. Importantly, however, Disc1-L100P place cells exhibited a higher propensity to increase their firing rate in a single, large location of the environment, rather than multiple smaller locations, indicating a generalization in their spatial selectivity. Alterations in the signaling and numbers of CA1 putative inhibitory interneurons and decreased hippocampal theta (5–12 Hz) power were also identified in the Disc1-L100P mice. Conclusions: The generalized spatial selectivity of Disc1-L100P place cells suggests a simplification of the ensemble place codes that encode individual locations and subserve spatial working memory. Moreover, these results suggest that deficient working memory in schizophrenia results from an impaired ability to uniquely code the individual components of a memory sequence. PMID:27280123

Impact of statins on cognitive deficits in adult male rodents after traumatic brain injury: a systematic review.

PubMed

Peng, Weijun; Yang, Jingjing; Yang, Bo; Wang, Lexing; Xiong, Xin-gui; Liang, Qinghua

2014-01-01

The efficacy of statin treatment on cognitive decline is controversial, and the effect of statins on cognitive deficits in individuals with traumatic brain injury (TBI) has yet to be investigated. Therefore, we systematically reviewed the effect of statins on cognitive deficits in adult male rodents after TBI. After identifying eligible studies by searching four electronic databases on February 28, 2014, we assessed study quality, evaluated the efficacy of statin treatment, and performed stratified metaregression and metaregression to assess the influence of study design on statin efficacy. Eleven studies fulfilled our inclusion criteria from a total of 183 publications. The overall methodological quality of these studies was poor. Meta-analysis showed that statins exert statistically significant positive effects on cognitive performance after TBI. Stratified analysis showed that atorvastatin has the greatest effect on acquisition memory, simvastatin has the greatest effect on retention memory, and statin effects on acquisition memory are higher in closed head injury models. Metaregression analysis further showed that that animal species, study quality, and anesthetic agent impact statin effects on retention memory. We conclude that statins might reduce cognitive deficits after TBI. However, additional well-designed and well-reported animal studies are needed to inform further clinical study.

Role of state-dependent learning in the cognitive effects of caffeine in mice.

PubMed

Sanday, Leandro; Zanin, Karina A; Patti, Camilla L; Fernandes-Santos, Luciano; Oliveira, Larissa C; Longo, Beatriz M; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

2013-08-01

Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine before training and/or before testing both in the plus-maze discriminative avoidance task (an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity) and in the inhibitory avoidance task, a classic paradigm for evaluating memory in rodents. Pre-training caffeine administration did not modify learning, but produced an anxiogenic effect and impaired memory retention. While pre-test administration of caffeine did not modify retrieval on its own, the pre-test administration counteracted the memory deficit induced by the pre-training caffeine injection in both the plus-maze discriminative and inhibitory avoidance tasks. Our data demonstrate that caffeine-induced memory deficits are critically related to state-dependent learning, reinforcing the importance of considering the participation of state-dependency on the interpretation of the cognitive effects of caffeine. The possible participation of caffeine-induced anxiety alterations in state-dependent memory deficits is discussed.

Exploring the Effects of Working Memory on Time Perception in Attention Deficit Hyperactivity Disorder.

PubMed

Lee, Hom-Yi; Yang, En-Lin

2018-01-01

Children with attention deficit hyperactivity disorder (ADHD) are often reported to have deficits of time perception. However, there is a strong relation between performance on tasks of working memory and time perception. Thus, it is possible that the poor performance of children with ADHD on time perception results from their deficit of working memory. In this study, the working memory of participants was separately assessed; therefore, we could explore the relationship between working memory and time perception of children with ADHD. Fifty-six children with ADHD and those of healthy controls completed tasks measuring working memory and time perception. The results showed that the time discrimination ability of children with ADHD was poorer than that of controls. However, there was a strong association between time perception and working memory. After controlling working memory and intelligence, the time discrimination ability of children with ADHD was not significantly poorer than that of controls. We suggest that there is an interdependent relationship between time perception and working memory for children with ADHD.

A Neural Network Model of the Effects of Entrenchment and Memory Development on Grammatical Gender Learning

ERIC Educational Resources Information Center

Monner, Derek; Vatz, Karen; Morini, Giovanna; Hwang, So-One; DeKeyser, Robert

2013-01-01

To investigate potential causes of L2 performance deficits that correlate with age of onset, we use a computational model to explore the individual contributions of L1 entrenchment and aspects of memory development. Since development and L1 entrenchment almost invariably coincide, studying them independently is seldom possible in humans. To avoid…

Word frequency influences on the list length effect and associative memory in young and older adults.

PubMed

Badham, Stephen P; Whitney, Cora; Sanghera, Sumeet; Maylor, Elizabeth A

2017-07-01

Many studies show that age deficits in memory are smaller for information supported by pre-experimental experience. Many studies also find dissociations in memory tasks between words that occur with high and low frequencies in language, but the literature is mixed regarding the extent of word frequency effects in normal ageing. We examined whether age deficits in episodic memory could be influenced by manipulations of word frequency. In Experiment 1, young and older adults studied short and long lists of high- and low-frequency words for free recall. The list length effect (the drop in proportion recalled for longer lists) was larger in young compared to older adults and for high- compared to low-frequency words. In Experiment 2, young and older adults completed item and associative recognition memory tests with high- and low-frequency words. Age deficits were greater for associative memory than for item memory, demonstrating an age-related associative deficit. High-frequency words led to better associative memory performance whilst low-frequency words resulted in better item memory performance. In neither experiment was there any evidence for age deficits to be smaller for high- relative to low-frequency words, suggesting that word frequency effects on memory operate independently from effects due to cognitive ageing.

Subchronic Glucocorticoid Receptor Inhibition Rescues Early Episodic Memory and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer's Disease

PubMed Central

Lanté, Fabien; Chafai, Magda; Raymond, Elisabeth Fabienne; Salgueiro Pereira, Ana Rita; Mouska, Xavier; Kootar, Scherazad; Barik, Jacques; Bethus, Ingrid; Marie, Hélène

2015-01-01

The early phase of Alzheimer's disease (AD) is characterized by hippocampus-dependent memory deficits and impaired synaptic plasticity. Increasing evidence suggests that stress and dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis, marked by the elevated circulating glucocorticoids, are risk factors for AD onset. How these changes contribute to early hippocampal dysfunction remains unclear. Using an elaborated version of the object recognition task, we carefully monitored alterations in key components of episodic memory, the first type of memory altered in AD patients, in early symptomatic Tg2576 AD mice. We also combined biochemical and ex vivo electrophysiological analyses to reveal novel cellular and molecular dysregulations underpinning the onset of the pathology. We show that HPA axis, circadian rhythm, and feedback mechanisms, as well as episodic memory, are compromised in this early symptomatic phase, reminiscent of human AD pathology. The cognitive decline could be rescued by subchronic in vivo treatment with RU486, a glucocorticoid receptor antagonist. These observed phenotypes were paralleled by a specific enhancement of N-Methyl-D-aspartic acid receptor (NMDAR)-dependent LTD in CA1 pyramidal neurons, whereas LTP and metabotropic glutamate receptor-dependent LTD remain unchanged. NMDAR transmission was also enhanced. Finally, we show that, as for the behavioral deficit, RU486 treatment rescues this abnormal synaptic phenotype. These preclinical results define glucocorticoid signaling as a contributing factor to both episodic memory loss and early synaptic failure in this AD mouse model, and suggest that glucocorticoid receptor targeting strategies could be beneficial to delay AD onset. PMID:25622751

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

ERIC Educational Resources Information Center

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

2014-01-01

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

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

ERIC Educational Resources Information Center

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

2008-01-01

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

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

ERIC Educational Resources Information Center

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

2013-01-01

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

The neuropsychology of emerging psychosis and the role of working memory in episodic memory encoding.

PubMed

Pflueger, Marlon O; Calabrese, Pasquale; Studerus, Erich; Zimmermann, Ronan; Gschwandtner, Ute; Borgwardt, Stefan; Aston, Jacqueline; Stieglitz, Rolf-Dieter; Riecher-Rössler, Anita

2018-01-01

Episodic memory encoding and working memory (WM) deficits are among the first cognitive signs and symptoms in the course of schizophrenia spectrum disorders. However, it is not clear whether the deficit pattern is generalized or specific in nature. We hypothesized that encoding deficits at an early stage of the disease might be due to the more fundamental WM deficits. We examined episodic memory encoding and WM by administering the California Verbal Learning Test, a 2-back task, and the Wisconsin Card Sorting Test in 90 first-episode psychosis (FE) patients and 116 individuals with an at-risk mental state for psychosis (ARMS) compared to 57 healthy subjects. Learning progress, but not span of apprehension, was diminished to a similar extent in both the ARMS and the FE. We showed that this was due to WM impairment by applying a structural equation approach. Thus, we conclude that verbal memory encoding deficits are secondary to primary WM impairment in emerging psychosis.

Low Dose Prenatal Alcohol Exposure Does Not Impair Spatial Learning and Memory in Two Tests in Adult and Aged Rats

PubMed Central

Cullen, Carlie L.; Burne, Thomas H. J.; Lavidis, Nickolas A.; Moritz, Karen M.

2014-01-01

Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol) ethanol (EtOH) or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult) or 15 months (Aged) of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance. PMID:24978807

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

PubMed

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

2016-12-01

Compared with same-age typically developing peers, school-age children with specific language impairment (SLI) exhibit significant deficits in spoken sentence comprehension. They also demonstrate a range of memory limitations. Whether these 2 deficit areas are related is unclear. The present review article aims to (a) review 2 main theoretical accounts of SLI sentence comprehension and various studies supporting each and (b) offer a new, broader, more integrated memory-based framework to guide future SLI research, as we believe the available evidence favors a memory-based perspective of SLI comprehension limitations. We reviewed the literature on the sentence comprehension abilities of English-speaking children with SLI from 2 theoretical perspectives. The sentence comprehension limitations of children with SLI appear to be more fully captured by a memory-based perspective than by a syntax-specific deficit perspective. Although a memory-based view appears to be the better account of SLI sentence comprehension deficits, this view requires refinement and expansion. Current memory-based perspectives of adult sentence comprehension, with proper modification, offer SLI investigators new, more integrated memory frameworks within which to study and better understand the sentence comprehension abilities of children with SLI.

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

PubMed Central

Gillam, Ronald B.; Evans, Julia L.

2016-01-01

Purpose Compared with same-age typically developing peers, school-age children with specific language impairment (SLI) exhibit significant deficits in spoken sentence comprehension. They also demonstrate a range of memory limitations. Whether these 2 deficit areas are related is unclear. The present review article aims to (a) review 2 main theoretical accounts of SLI sentence comprehension and various studies supporting each and (b) offer a new, broader, more integrated memory-based framework to guide future SLI research, as we believe the available evidence favors a memory-based perspective of SLI comprehension limitations. Method We reviewed the literature on the sentence comprehension abilities of English-speaking children with SLI from 2 theoretical perspectives. Results The sentence comprehension limitations of children with SLI appear to be more fully captured by a memory-based perspective than by a syntax-specific deficit perspective. Conclusions Although a memory-based view appears to be the better account of SLI sentence comprehension deficits, this view requires refinement and expansion. Current memory-based perspectives of adult sentence comprehension, with proper modification, offer SLI investigators new, more integrated memory frameworks within which to study and better understand the sentence comprehension abilities of children with SLI. PMID:27973643

Memory Impairment in Multiple Sclerosis is Due to a Core Deficit in Initial Learning

PubMed Central

DeLuca, John; Leavitt, Victoria M.; Chiaravalloti, Nancy; Wylie, Glenn

2013-01-01

Persons with multiple sclerosis (MS) suffer memory impairment, but research on the nature of MS-related memory problems is mixed. Some have argued for a core deficit in retrieval, while others have identified deficient initial learning as the core deficit. We used a selective reminding paradigm to determine whether deficient initial learning or delayed retrieval represents the primary memory deficit in 44 persons with MS. Brain atrophy was measured from high-resolution MRIs. Regression analyses examined the impact of brain atrophy on (a) initial learning and delayed retrieval separately, and then (b) delayed retrieval controlling for initial learning. Brain atrophy was negatively associated with both initial learning and delayed retrieval (ps < .01), but brain atrophy was unrelated to retrieval when controlling for initial learning (p > .05). In addition, brain atrophy was associated with inefficient learning across initial acquisition trials, and brain atrophy was unrelated to delayed recall among MS subjects who successfully acquired the word list (although such learning frequently required many exposures). Taken together, memory deficits in MS are a result of deficits in initial learning; moreover, initial learning mediates the relationship between brain atrophy and subsequent retrieval, thereby supporting the core learning-deficit hypothesis of memory impairment in MS. PMID:23832311

Apolipoprotein E4 causes age- and Tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice.

PubMed

Andrews-Zwilling, Yaisa; Bien-Ly, Nga; Xu, Qin; Li, Gang; Bernardo, Aubrey; Yoon, Seo Yeon; Zwilling, Daniel; Yan, Tonya Xue; Chen, Ligong; Huang, Yadong

2010-10-13

Apolipoprotein E4 (apoE4) is the major genetic risk factor for Alzheimer's disease. However, the underlying mechanisms are unclear. We found that female apoE4 knock-in (KI) mice had an age-dependent decrease in hilar GABAergic interneurons that correlated with the extent of learning and memory deficits, as determined in the Morris water maze, in aged mice. Treating apoE4-KI mice with daily peritoneal injections of the GABA(A) receptor potentiator pentobarbital at 20 mg/kg for 4 weeks rescued the learning and memory deficits. In neurotoxic apoE4 fragment transgenic mice, hilar GABAergic interneuron loss was even more pronounced and also correlated with the extent of learning and memory deficits. Neurodegeneration and tauopathy occurred earliest in hilar interneurons in apoE4 fragment transgenic mice; eliminating endogenous Tau prevented hilar GABAergic interneuron loss and the learning and memory deficits. The GABA(A) receptor antagonist picrotoxin abolished this rescue, while pentobarbital rescued learning deficits in the presence of endogenous Tau. Thus, apoE4 causes age- and Tau-dependent impairment of hilar GABAergic interneurons, leading to learning and memory deficits in mice. Consequently, reducing Tau and enhancing GABA signaling are potential strategies to treat or prevent apoE4-related Alzheimer's disease.

Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction and Spatial Memory Deficits Reminiscent of Early Alzheimer's Disease

PubMed Central

Fu, Hongjun; Rodriguez, Gustavo A.; Herman, Mathieu; Emrani, Sheina; Nahmani, Eden; Barrett, Geoffrey; Figueroa, Helen Y.; Goldberg, Eliana

2017-01-01

Summary The earliest stages of Alzheimer's disease (AD) are characterized by the formation of mature tangles in the entorhinal cortex and disorientation and confusion navigating familiar places. The medial entorhinal cortex (MEC) contains specialized neurons called grid cells that form part of the spatial navigation system. Here we show in a transgenic mouse model expressing mutant human tau predominantly in the EC that the formation of mature tangles in old mice was associated with excitatory cell loss and deficits in grid cell function, including destabilized grid fields and reduced firing rates, as well as altered network activity. Overt tau pathology in the aged mice was accompanied by spatial memory deficits. Therefore, tau pathology initiated in the entorhinal cortex could lead to deficits in grid cell firing and underlie the deterioration of spatial cognition seen in human AD. PMID:28111080

Working memory and organizational skills problems in ADHD.

PubMed

Kofler, Michael J; Sarver, Dustin E; Harmon, Sherelle L; Moltisanti, Allison; Aduen, Paula A; Soto, Elia F; Ferretti, Nicole

2018-01-01

This study tested model-driven predictions regarding working memory's role in the organizational problems associated with ADHD. Children aged 8-13 (M = 10.33, SD = 1.42) with and without ADHD (N = 103; 39 girls; 73% Caucasian/Non-Hispanic) were assessed on multiple, counterbalanced working memory tasks. Parents and teachers completed norm-referenced measures of organizational problems (Children's Organizational Skills Scale; COSS). Results confirmed large magnitude working memory deficits (d = 1.24) and organizational problems in ADHD (d = 0.85). Bias-corrected, bootstrapped conditional effects models linked impaired working memory with greater parent- and teacher-reported inattention, hyperactivity/impulsivity, and organizational problems. Working memory predicted organization problems across all parent and teacher COSS subscales (R 2  = .19-.23). Approximately 38%-57% of working memory's effect on organization problems was conveyed by working memory's association with inattentive behavior. Unique effects of working memory remained significant for both parent- and teacher-reported task planning, as well as for teacher-reported memory/materials management and overall organization problems. Attention problems uniquely predicted worse organizational skills. Hyperactivity was unrelated to parent-reported organizational skills, but predicted better teacher-reported task planning. Children with ADHD exhibit multisetting, broad-based organizational impairment. These impaired organizational skills are attributable in part to performance deficits secondary to working memory dysfunction, both directly and indirectly via working memory's role in regulating attention. Impaired working memory in ADHD renders it extraordinarily difficult for these children to consistently anticipate, plan, enact, and maintain goal-directed actions. © 2017 Association for Child and Adolescent Mental Health.

Salience of working-memory maintenance and manipulation deficits in schizophrenia

PubMed Central

Hill, S. K.; Griffin, G. B.; Miura, T. Kazuto; Herbener, E. S.; Sweeney, J. A.

2011-01-01

Background Encoding and maintenance of information in working memory, followed by internal manipulation of that information for planning adaptive behavior, are two key components of working-memory systems. Both processes have been reported to be impaired in schizophrenia, but few studies have directly compared the relative severity of these abnormalities, or the degree to which manipulation deficits might be secondary to alterations in maintenance processes. Method Clinically stable schizophrenia patients (n=25) and a demographically similar healthy comparison group (n=24) were administered a verbal span task with three levels of working-memory load. Maintenance was assessed using sequential position questions. Manipulation processes were assessed by requiring comparison of the relative sequential position of test items, which entailed simultaneous serial search strategies regarding item order. Results Both groups showed reduced accuracy and increased reaction time for manipulation compared with maintenance processing. There were significant patient impairments across working-memory loads. There was no differential deficit in manipulation processing, and effect sizes of relative deficit in the patient group were higher for maintenance than manipulation processing. Conclusions The strong correlation for maintenance and manipulation deficits suggest that impairments in the ability to internally manipulate information stored in working-memory systems are not greater than alterations in the encoding and maintaining of information in working memory and that disturbances in maintenance processing may contribute to deficits in higher-order working-memory operations. PMID:20214839

Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A2A Receptor in Hippocampal Glutamate Synapses.

PubMed

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

2017-03-01

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.

Persistent impairment in working memory following severe hyperglycemia in newly diagnosed type 2 diabetes.

PubMed

Cerasuolo, Joseph; Izzo, Anthony

2017-01-01

Acute hyperglycemia has been shown to cause cognitive impairments in animal models. There is growing appreciation of the numerous effects of hyperglycemia on neuronal function as well as blood-brain barrier function. In humans, hypoglycemia is well known to cause cognitive deficits acutely, but hyperglycemia has been less well studied. We present a case of selective neurocognitive deficits in the setting of acute hyperglycemia. A 60-year-old man was admitted to the hospital for an episode of acute hyperglycemia in the setting of newly diagnosed diabetes mellitus precipitated by steroid use. He was managed with insulin therapy and discharged home, and later, presented with complaints of memory impairment. Deficits included impairment in his declarative and working memory, to the point of significant impairment in his overall functioning. The patient had no structural lesions on MRI imaging of the brain or other systemic illnesses to explain his specific deficits. We suggest that his acute hyperglycemia may have caused neurological injury, and may be responsible for our patient's memory complaints. Acute hyperglycemia has been associated with poor outcomes in several different central nervous system injuries including cerebrovascular accident and hypoxic injury.Hyperglycemia is responsible for accumulation of reactive oxygen species in the brain, resulting in advanced glycosylated end products and a proinflammatory response that may lead to cellular injury.Further research is needed to define the impact of both acute and chronic hyperglycemia on cognitive impairment and memory.

Rapamycin Reverses Status Epilepticus-Induced Memory Deficits and Dendritic Damage

PubMed Central

Brewster, Amy L.; Lugo, Joaquin N.; Patil, Vinit V.; Lee, Wai L.; Qian, Yan; Vanegas, Fabiola; Anderson, Anne E.

2013-01-01

Cognitive impairments are prominent sequelae of prolonged continuous seizures (status epilepticus; SE) in humans and animal models. While often associated with dendritic injury, the underlying mechanisms remain elusive. The mammalian target of rapamycin complex 1 (mTORC1) pathway is hyperactivated following SE. This pathway modulates learning and memory and is associated with regulation of neuronal, dendritic, and glial properties. Thus, in the present study we tested the hypothesis that SE-induced mTORC1 hyperactivation is a candidate mechanism underlying cognitive deficits and dendritic pathology seen following SE. We examined the effects of rapamycin, an mTORC1 inhibitor, on the early hippocampal-dependent spatial learning and memory deficits associated with an episode of pilocarpine-induced SE. Rapamycin-treated SE rats performed significantly better than the vehicle-treated rats in two spatial memory tasks, the Morris water maze and the novel object recognition test. At the molecular level, we found that the SE-induced increase in mTORC1 signaling was localized in neurons and microglia. Rapamycin decreased the SE-induced mTOR activation and attenuated microgliosis which was mostly localized within the CA1 area. These findings paralleled a reversal of the SE-induced decreases in dendritic Map2 and ion channels levels as well as improved dendritic branching and spine density in area CA1 following rapamycin treatment. Taken together, these findings suggest that mTORC1 hyperactivity contributes to early hippocampal-dependent spatial learning and memory deficits and dendritic dysregulation associated with SE. PMID:23536771

Transcranial direct current stimulation improves short-term memory in an animal model of attention-deficit/hyperactivity disorder.

PubMed

Leffa, Douglas Teixeira; de Souza, Andressa; Scarabelot, Vanessa Leal; Medeiros, Liciane Fernandes; de Oliveira, Carla; Grevet, Eugenio Horacio; Caumo, Wolnei; de Souza, Diogo Onofre; Rohde, Luis Augusto Paim; Torres, Iraci L S

2016-02-01

Attention deficit hyperactivity disorder (ADHD) is characterized by impairing levels of hyperactivity, impulsivity and inattention. However, different meta-analyses have reported disruptions in short and long-term memory in ADHD patients. Previous studies indicate that mnemonic dysfunctions might be the result of deficits in attentional circuits, probably due to ineffective dopaminergic modulation of hippocampal synaptic plasticity. In this study we aimed to evaluate the potential therapeutic effects of a neuromodulatory technique, transcranial direct current stimulation (tDCS), in short-term memory (STM) deficits presented by the spontaneous hypertensive rats (SHR), the most widely used animal model of ADHD. Adult male SHR and Wistar Kyoto rats (WKY) were subjected to a constant electrical current of 0.5 mA intensity applied on the frontal cortex for 20 min/day during 8 days. STM was evaluated with an object recognition test conducted in an open field. Exploration time and locomotion were recorded, and brain regions were dissected to determine dopamine and BDNF levels. SHR spent less time exploring the new object when compared to WKY, and tDCS improved object recognition deficits in SHR without affecting WKY performance. Locomotor activity was higher in SHR and it was not affected by tDCS. After stimulation, dopamine levels were increased in the hippocampus and striatum of both strains, while BDNF levels were increased only in the striatum of WKY. These findings suggest that tDCS on the frontal cortex might be able to improve STM deficits present in SHR, which is potentially related to dopaminergic neurotransmission in the hippocampus and striatum of those animals. Copyright © 2016. Published by Elsevier B.V.

Short-term and working memory impairments in aphasia.

PubMed

Potagas, Constantin; Kasselimis, Dimitrios; Evdokimidis, Ioannis

2011-08-01

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.

Autobiographical memory and suicide attempts in schizophrenia.

PubMed

Pettersen, Kenneth; Rydningen, Nora Nord; Christensen, Tore Buer; Walby, Fredrik A

2010-08-01

According to the cry of pain model of suicidal behavior, an over-general autobiographical memory function is often found in suicide attempters. The model has received empirical support in several studies, mainly of depressed patients. The present study investigated whether deficits in autobiographical memory may be associated with an increased frequency of suicide attempts in patients with schizophrenia. We found support for our hypothesis that patients with schizophrenia and previous suicide attempts have an over-generalized autobiographical memory compared to patients with schizophrenia without previous suicide attempts. Adjustment for sociodemographic and clinical variables did not change the results.

Do cognitive deficits predict negative emotionality and aggression in schizophrenia?

PubMed

Ahmed, Anthony O; Richardson, Jenae; Buckner, Alex; Romanoff, Sabrina; Feder, Michelle; Oragunye, Njideka; Ilnicki, Andriana; Bhat, Ishrat; Hoptman, Matthew J; Lindenmayer, Jean-Pierre

2018-01-01

Schizophrenia is associated with an elevated risk of aggression. Cognitive deficits have been associated with inpatient aggression and future violence. The relationship between cognitive deficits and violent behavior has however been inconsistent across studies. In addition, studies have failed to inform how cognitive deficits may contribute to aggression in schizophrenia. The current study examined the association of cognitive deficits with schizophrenia-related aggression and violent offending. It also explored the putative mediating role of negative emotionality on the impact of cognitive deficits on aggression. People with schizophrenia and schizoaffective disorder (N = 78) were recruited from a state hospital. Participants were classified based on their history of violent offending. Participants completed measures of cognition, symptoms, and aggression. Deficits in working memory, reasoning/problem-solving, and verbal learning were the most prioritized for the prediction of violent offender status. Violent offenders demonstrated greater impairments in most cognitive domains especially working memory and verbal learning. Offenders also demonstrated greater negative emotionality, excitement/agitation, and incidents of verbal and physical aggression. Negative emotionality and excitement/agitation fully transmitted the effect of cognitive deficits on impulsive aggression in meditational models. Cognitive deficits increase the risk of impulsive aggression in schizophrenia via inefficient regulation of negative affective states. Copyright © 2017 Elsevier B.V. All rights reserved.

Opposite monosynaptic scaling of BLP–vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory

PubMed Central

Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

2016-01-01

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP–vCA1 connection. Optogenetic disruption of BLP–vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP–vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP–vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP–vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory. PMID:27411738

Opposite monosynaptic scaling of BLP-vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory.

PubMed

Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-Lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

2016-07-14

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP-vCA1 connection. Optogenetic disruption of BLP-vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP-vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP-vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP-vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory.

Metamemory in children with autism: exploring "feeling-of-knowing" in episodic and semantic memory.

PubMed

Wojcik, Dominika Z; Moulin, Chris J A; Souchay, Celine

2013-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder primarily affecting social function and communication. Recently, there has been an interest in whether people with ASD also show memory deficits. Studies in ASD have revealed subtle impairments on tasks requiring participants to learn new information (episodic memory), but intact performance on general knowledge tasks (semantic memory). The novelty of this study was to explore metamemory (i.e., awareness of memory performance) and to examine whether children with ASD suffer from a generalized metamemory deficit common to all forms of memory, or would only present deficits on episodic metamemory tasks. To assess metamemory functioning we administered 2 feeling-of-knowing (FOK) tasks, 1 for episodic and 1 for semantic materials. In these tasks, participants are asked to predict the likelihood of subsequently recognizing currently unrecalled information. It was found that children with autism made inaccurate FOK predictions, but only for episodic materials. A specific deficit in meta-cognition emerges for only one set of materials. We argue that this deficit can be conceived of as reflecting a deficit in recollection, stemming from an inability to cast the self in the past and retrieve information about the study episode.

Repeated recall as an intervention to improve memory performance in heart failure patients.

PubMed

Viveiros, Jennifer; Sethares, Kristen; Shapiro, Amy

2017-12-01

Up to 50% of heart failure patients demonstrate aspects of cognitive impairment, including memory deficit. Novel interventions are needed to address memory deficit among heart failure patients. The goal of this study was to evaluate the testing effect as an intervention to improve memory performance in heart failure patients. This was a randomized controlled clinical trial ( N=84) comparing the memory performance of heart failure patients with and without mild cognitive impairment after a repeated testing intervention. Memory performance was measured by verbal word pair associates recall scores, between attention control and experimental subjects. Patients had a mean age of 71.7 ± 13.3 years and similar baseline memory (immediate p=.79 and delayed p=.47). Overall, there were no significant differences in memory between experimental and control subjects, respectively (67.2±18.87 vs. 61.9±22.3, verbal word pair associates, t = -1.179, p=.24). In the final hierarchical regression model, age ( p=.018) and education ( p=.006) were significant predictors of memory performance, with the intervention approaching significance ( p=.079). Although not statistically significant, the intervention group reported better memory. Age and education continue to be significant contributors to memory performance in the heart failure population. Continued development of interventions to improve memory performance in heart failure patients is indicated.

Kamikihi-to (KKT) rescues axonal and synaptic degeneration associated with memory impairment in a mouse model of Alzheimer's disease, 5XFAD.

PubMed

Tohda, Chihiro; Nakada, Rie; Urano, Takuya; Okonogi, Akira; Kuboyama, Tomoharu

2011-12-01

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. Current agents for AD are employed for symptomatic therapy and insufficient to cure. We consider that this is quite necessary for AD treatment and have investigated axon/synapse formation-promoting activity. The aim of this study is to investigate the effects of Kamikihi-to [KKT; traditional Japanese (Kampo) medicine] on memory deficits in an AD model, 5XFAD. KKT (200 mg/kg, p.o.) was administered for 15 days to 5XFAD mice. Object recognition memory was tested in vehicle-treated wild-type and 5XFAD mice and KKT-treated 5XFAD mice. KKT-treated 5XFAD mice showed significant improvement of object recognition memory. KKT treatment significantly reduced the number of amyloid plaques in the frontal cortex and hippocampus. Only inside of amyloid plaques were abnormal structures such as bulb-like axons and swollen presynaptic boutons observed. These degenerated axons and presynaptic terminals were significantly reduced by KKT treatment in the frontal cortex. In primary cortical neurons, KKT treatment significantly increased axon length when applied after Aβ(25-35)-induced axonal atrophy had progressed. In conclusion, KKT improved object recognition memory deficit in an AD model 5XFAD mice. Restoration of degenerated axons and synapses may be associated with the memory recovery by KKT.

Restoration of Dopamine Release Deficits during Object Recognition Memory Acquisition Attenuates Cognitive Impairment in a Triple Transgenic Mice Model of Alzheimer's Disease

ERIC Educational Resources Information Center

Guzman-Ramos, Kioko; Moreno-Castilla, Perla; Castro-Cruz, Monica; McGaugh, James L.; Martinez-Coria, Hilda; LaFerla, Frank M.; Bermudez-Rattoni, Federico

2012-01-01

Previous findings indicate that the acquisition and consolidation of recognition memory involves dopaminergic activity. Although dopamine deregulation has been observed in Alzheimer's disease (AD) patients, the dysfunction of this neurotransmitter has not been investigated in animal models of AD. The aim of this study was to assess, by in vivo…

Combined effects of THC and caffeine on working memory in rats.

PubMed

Panlilio, Leigh V; Ferré, Sergi; Yasar, Sevil; Thorndike, Eric B; Schindler, Charles W; Goldberg, Steven R

2012-04-01

Cannabis and caffeine are two of the most widely used psychoactive substances. Δ(9) -Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. Rats were given THC (0, 1 and 3 mg·kg(-1) , i.p.) along with caffeine (0, 1, 3 and 10 mg·kg(-1) , i.p.), the selective adenosine A(1) -receptor antagonist CPT (0, 3 and 10 mg·kg(-1) ) or the selective adenosine A(2A) -receptor antagonist SCH58261 (0 and 5 mg·kg(-1) ) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. THC alone produced memory deficits at 3 mg·kg(-1) . The initial exposure to caffeine (10 mg·kg(-1) ) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg·kg(-1) ) was combined with caffeine (10 mg·kg(-1) ) or CPT (10 mg·kg(-1) ), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A(1) receptors modulate cannabinoid signalling in the hippocampus. This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

Rivastigmine reverses cognitive deficit and acetylcholinesterase activity induced by ketamine in an animal model of schizophrenia.

PubMed

Zugno, Alexandra I; Julião, Ricardo Filipe; Budni, Josiane; Volpato, Ana Maria; Fraga, Daiane B; Pacheco, Felipe D; Deroza, Pedro F; Luca, Renata D; de Oliveira, Mariana B; Heylmann, Alexandra S; Quevedo, João

2013-09-01

Schizophrenia is one of the most disabling mental disorders that affects up to 1 % of the population worldwide. Although the causes of this disorder remain unknown, it has been extensively characterized by a broad range of emotional, ideational and cognitive impairments. Studies indicate that schizophrenia affects neurotransmitters such as dopamine, glutamate and acetylcholine. Recent studies suggest that rivastigmine (an acetylcholinesterase inhibitor) is important to improve the cognitive symptoms of schizophrenia. Therefore, the present study evaluated the protective effect of rivastigmine against the ketamine-induced behavioral (hyperlocomotion and cognitive deficit) and biochemical (increase of acetylcholinesterase activity) changes which characterize an animal model of schizophrenia in rats. Our results indicated that rivastigmine was effective to improve the cognitive deficit in different task (immediate memory, long term memory and short term memory) induced by ketamine in rats. Moreover, we observed that rivastigmina reversed the increase of acetylcholinesterase activity induced by ketamine in the cerebral cortex, hippocampus and striatum. However, rivastigmine was not able to prevent the ketamine-induced hyperlocomotion. In conslusion, ours results indicate that cholinergic system might be an important therapeutic target in the physiopathology of schizophrenia, mainly in the cognition, but additional studies should be carried.

The Effect of Synchronized Forced Running with Chronic Stress on Short, Mid and Long- term Memory in Rats.

PubMed

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

2013-03-01

Impairment of learning and memory processes has been demonstrated by many studies using different stressors. Other reports suggested that exercise has a powerful behavioral intervention to improve cognitive function and brain health. In this research, we investigated protective effects of treadmill running on chronic stress-induced memory deficit in rats. Fifty male Wistar rats were randomly divided into five groups (n=10) as follows: Control (Co), Sham (Sh), Stress (St), Exercise (Ex) and Stress and Exercise (St & Ex) groups. Chronic restraint stress was applied by 6h/day/21days and also treadmill running at a speed 20-21m/min for 1h/day/21days. Memory function was evaluated by the passive avoidance test in different intervals (1, 7 and 21 days) after foot shock. OUR RESULTS SHOWED THAT: 1) Although exercise alone showed beneficial effects especially on short and mid-term memory (P<0.05) in comparison with control group, but synchronized exercise with stress had not significantly improved short, mid and long-term memory deficit in stressed rats. 2) Short and mid-term memory deficit was significantly (P<0.05) observed in synchronized exercise with stress and stress groups with respect to normal rats. 3) Memory deficit in synchronized exercise with stress group was nearly similar to stressed rats. 4) Helpful effects of exercise were less than harmful effects of stress when they were associated together. The data correspond to the possibility that although treadmill running alone has helpful effects on learning and memory consolidation, but when it is synchronized with stress there is no significant benefit and protective effects in improvement of memory deficit induced by chronic stress. However, it is has a better effect than no training on memory deficit in stressed rats.

Neuroprotective evidence of alpha-lipoic acid and desvenlafaxine on memory deficit in a neuroendocrine model of depression.

PubMed

de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; Vasconcelos, Germana Silva; da Silva Medeiros, Ingridy; Silva, Márcia Calheiros Chaves; Mouaffak, Fayçal; Kebir, Oussama; da Silva Leite, Cláudio Manuel Gonçalves; Patrocinio, Manoel Cláudio Azevedo; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

2018-05-07

Cognitive impairment is present in patients with depression. We hypothesized that alpha-lipoic acid (ALA) can reduce cognitive impairment, especially when combined to antidepressants. Female mice received vehicle or corticosterone (CORT) 20 mg/kg, s.c. for 14 days. From the 15th to 21st day, the animals were divided in groups: vehicle, CORT, CORT+desvenlafaxine (DVS) 10 or 20 mg/kg, ALA 100 or 200 mg/kg, DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Tail suspension (TST), social interaction (SIT), novel object recognition (NOR), and Y-maze tests were conducted. Acetylcholinesterase activity (AChE) was measured in the prefrontal cortex (PFC), hippocampus (HC), and striatum (ST). CORT caused depressive-like behavior, impairment in SIT, and cognitive deficits. Alpha-lipoic acid and DVS, alone or combined, reversed CORT effect on TST. In the NOR, ALA200 alone, DVS10+ALA100, or DVS10+ALA200 reversed the deficits in short-term memory, while DVS20 alone or DVS20+ALA200 reversed the deficits in long-term memory. In the Y-maze test, ALA200 alone, DVS20+ALA100, or DVS20+ALA200 reversed the deficits caused by CORT in the working memory. CORT increased AChE in the PFC, HC, and ST. ALA200 alone or DVS20+ALA200 reversed this effect in the PFC, while DVS20 or DVS20+ALA100 reversed this effect in the HC. In the ST, DVS10 or 20, alone or combined, and ALA100 reversed the effects of CORT. These results suggest that DVS+ALA, by reversing CORT-induced memory and social deficits, seems to be a promising therapy for the treatment of depression and reversal of cognitive impairment observed in this disorder.

Methionine increases BDNF DNA methylation and improves memory in epilepsy.

PubMed

Parrish, R Ryley; Buckingham, Susan C; Mascia, Katherine L; Johnson, Jarvis J; Matyjasik, Michal M; Lockhart, Roxanne M; Lubin, Farah D

2015-04-01

Temporal lobe epilepsy (TLE) patients exhibit signs of memory impairments even when seizures are pharmacologically controlled. Surprisingly, the underlying molecular mechanisms involved in TLE-associated memory impairments remain elusive. Memory consolidation requires epigenetic transcriptional regulation of genes in the hippocampus; therefore, we aimed to determine how epigenetic DNA methylation mechanisms affect learning-induced transcription of memory-permissive genes in the epileptic hippocampus. Using the kainate rodent model of TLE and focusing on the brain-derived neurotrophic factor (Bdnf) gene as a candidate of DNA methylation-mediated transcription, we analyzed DNA methylation levels in epileptic rats following learning. After detection of aberrant DNA methylation at the Bdnf gene, we investigated functional effects of altered DNA methylation on hippocampus-dependent memory formation in our TLE rodent model. We found that behaviorally driven BdnfDNA methylation was associated with hippocampus-dependent memory deficits. Bisulfite sequencing revealed that decreased BdnfDNA methylation levels strongly correlated with abnormally high levels of BdnfmRNA in the epileptic hippocampus during memory consolidation. Methyl supplementation via methionine (Met) increased BdnfDNA methylation and reduced BdnfmRNA levels in the epileptic hippocampus during memory consolidation. Met administration reduced interictal spike activity, increased theta rhythm power, and reversed memory deficits in epileptic animals. The rescue effect of Met treatment on learning-induced BdnfDNA methylation, Bdnf gene expression, and hippocampus-dependent memory, were attenuated by DNA methyltransferase blockade. Our findings suggest that manipulation of DNA methylation in the epileptic hippocampus should be considered as a viable treatment option to ameliorate memory impairments associated with TLE.

Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice.

PubMed

Jin, Ge; Bai, Dafeng; Yin, Shiliang; Yang, Zhihang; Zou, Dan; Zhang, Zhong; Li, Xiaoxiu; Sun, Yan; Zhu, Qiwen

2016-08-26

Silibinin was reported to be effective in reversing the learning and memory deficits of several AD animal models. These improvements are thought to be regulated by various factors, including antioxidative stress, inhibition of acetylcholinesterase activity and Aβ aggregation. However, there are still no reports that demonstrate the effect of silibinin on microglia activation in vivo. Thus, in this study, we used the senescence-accelerated mouse (SAMP8) strain to test the effects of silibinin on behavioral impairments and microglia activation-induced neuroinflammation. Silibinin treatment significantly rescued memory deficits in novel object recognition test and Morris water maze test. Silibinin treatment significantly attenuated microglial activation; down-regulated the level of the proinflammatory cytokine IL-6, anti-inflammatory cytokine IL-4, and inflammation-associated proteins, iNOS and COX-2; and further modulated MAPK to protect neural cells. These results suggest that silibinin could be a potential candidate for the therapy of neurodegenerative disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Confabulation behavior and false memories in Korsakoff's syndrome: role of source memory and executive functioning.

PubMed

Kessels, Roy P C; Kortrijk, Hans E; Wester, Arie J; Nys, Gudrun M S

2008-04-01

Confabulation behavior is common in patients with Korsakoff's syndrome. A distinction can be made between spontaneous and provoked confabulations, which may have different underlying cognitive mechanisms. Provoked confabulations may be related to intrusions on memory tests, whereas spontaneous confabulations may be due to executive dysfunction or a source memory deficit. In 19 chronic Korsakoff patients, spontaneous confabulations were quantified by third-party rating (Likert scale). Provoked confabulations were assessed using the Dalla Barba Confabulation Battery. Furthermore, assessment of executive function was performed using an extensive neuropsychological battery. False memories (i.e. intrusions) and source memory were measured using twoparallelversions of a word-list learning paradigm (a modification of the Rey Auditory Verbal Learning Test). There were deficits in source memory, in which patients incorrectly assigned previously learned words to an incorrect word list. Also, Korsakoff patients had extensive executive deficits, but no relationship between the severity of these deficits and the severity of confabulation or intrusions on a memory task was found. The present findings provide evidence for a dissociation between spontaneous confabulation, provoked confabulation and false memories.

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

PubMed Central

Parsley, Margaret A.; Guptarak, Jutatip; Spratt, Heidi; Sell, Stacy L.

2018-01-01

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, few studies have investigated the long-term effects of injury in rodent models of TBI. Shown here are behavioral measures that are well-established in TBI research for times early after injury, such as two weeks, until two months. Some of these methods have previously been used at later times after injury, up to one year, but by very few laboratories. The methods demonstrated here are a short neurological assessment to test reflexes, a Beam-Balance to test balance, a Beam-Walk to test balance and motor coordination, and a working memory version of the Morris water maze that can be sensitive to deficits in reference memory. Male rats were handled and pre-trained to neurological, balance, and motor coordination tests prior to receiving parasagittal fluid percussion injury (FPI) or sham injury. Rats can be tested on the short neurological assessment (neuroscore), the beam-balance, and the Beam-Walk multiple times, while testing on the water maze can only be done once. This difference is because rats can remember the task, thus confounding the results if repeated testing is attempted in the same animal. When testing from one to three days after injury, significant differences are detected in all three non-cognitive tasks. However, differences in the Beam-Walk task were not detectable at later time points (after 3 months). Deficits were detected at 3 months in the Beam-Balance and at 6 months in the neuroscore. Deficits in working memory were detected out to 12 months after injury, and a deficit in a reference memory first appeared at 12 months. Thus, standard behavioral tests can be useful measures of persistent behavioral deficits after FPI. PMID:29443022

Face Recognition Deficits in Autism Spectrum Disorders Are Both Domain Specific and Process Specific

PubMed Central

Weigelt, Sarah; Koldewyn, Kami; Kanwisher, Nancy

2013-01-01

Although many studies have reported face identity recognition deficits in autism spectrum disorders (ASD), two fundamental question remains: 1) Is this deficit “process specific” for face memory in particular, or does it extend to perceptual discrimination of faces as well? And 2) Is the deficit “domain specific” for faces, or is it found more generally for other social or even nonsocial stimuli? The answers to these questions are important both for understanding the nature of autism and its developmental etiology, and for understanding the functional architecture of face processing in the typical brain. Here we show that children with ASD are impaired (compared to age and IQ-matched typical children) in face memory, but not face perception, demonstrating process specificity. Further, we find no deficit for either memory or perception of places or cars, indicating domain specificity. Importantly, we further showed deficits in both the perception and memory of bodies, suggesting that the relevant domain of deficit may be social rather than specifically facial. These results provide a more precise characterization of the cognitive phenotype of autism and further indicate a functional dissociation between face memory and face perception. PMID:24040276

Effects of selective phosphodiesterases-4 inhibitors on learning and memory: a review of recent research.

PubMed

Peng, Sheng; Sun, Haiyan; Zhang, Xiaoqing; Liu, Gongjian; Wang, Guanglei

2014-09-01

Phosphodiesterase-4 (PDE-4) regulates the intracellular level of cyclic adenosine monophosphate. Recent studies demonstrated that PDE-4 inhibitors can counteract deficits in long-term memory caused by aging or increased expression of mutant forms of human amyloid precursor proteins, and can influence the process of memory function and cognitive enhancement. Therapeutics, such as ketamine, a drug used in clinical anesthesia, can also cause memory deficits as adverse effects. Targeting PDE-4 with selective inhibitors may offer a novel therapeutic strategy to prevent, slow the progress, and, eventually, treat memory deficits.

Component processes of memory in alcoholism: pattern of compromise and neural substrates.

PubMed

Pitel, Anne-Lise; Eustache, Francis; Beaunieux, Helene

2014-01-01

Initially, alcohol-related memory deficits were considered only through the prism of Korsakoff's syndrome (KS). It is now clear, however, that chronic alcohol consumption results in memory disorders in alcoholics without ostensible neurologic complications, such as Wernicke's encephalopathy and KS. Most of the principal memory components are affected, including working memory, episodic memory, semantic memory, perceptual memory, and procedural memory. The extent of those cognitive impairments depends on several factors, such as age, gender, nutritional status, and psychiatric comorbidity. While memory disorders, especially episodic memory deficits, are largely definitive in patients with KS, recovery of memory abilities has been described with abstinence in uncomplicated alcoholics. Neuropsychologic impairments, and especially memory disorders, must be evaluated at alcohol treatment entry because they could impede patients from benefiting fully from cognitive and behavioral treatment approaches for alcohol dependence. Screening of memory deficits could also enable clinicians to detect, among alcoholics without ostensible neurologic complications, those at risk of developing permanent and debilitating amnesia that features KS. © 2014 Elsevier B.V. All rights reserved.

The narcoleptic cognitive pupillary response.

PubMed

O'Neill, W D; Trick, K P

2001-09-01

It has been reported that narcoleptics exhibit deficits in short-term memory, list recall, and stimulus frequency estimation compared with control subjects. It is also well-known that pupil dilation during cognitive tasks is a measure of subject attention state. Here we present results from six narcoleptics and six controls, a total of 360 experimental records in which pupillograms were made during cognitive tests, which indicate that narcoleptics begin pupillary dilations at a smaller diameter, begin dilating earlier poststimulus, attain higher pupillary diameter velocities, yet achieve the same equilibrium dilation diameter as controls. These findings are derived from statistical tests performed on the parameters of a nonlinear regression model of pupillary cognitive dilation as a function of time. In our experiments, the standard 1-s interdigit time between cognitive stimuli was increased to 2.3 s, which yielded pupillographic time records showing that the process of short-term memory overload sets in gradually at about four memory digits for controls and three memory digits for narcoleptics. We suggest our results can be partially explained by a narcoleptic stimulus-encoding deficit, which limits the time available for subjects to rehearse cognitive tasks. However, we also report the unexpected finding that the inferred encoding deficit is a transient one in that repeated tasks at the same memory load elicit a near normal naroleptic pupillary dilation.

Structural correlates of subjective and objective memory performance in multiple sclerosis.

PubMed

Pardini, Matteo; Bergamino, Maurizio; Bommarito, Giulia; Bonzano, Laura; Luigi Mancardi, Gian; Roccatagliata, Luca

2014-04-01

Subjective and objective memory deficits represent a frequent and ill-understood aspect of multiple sclerosis (MS), and a significant cause of disability and quality of life reduction. The aim of the study is to verify the role of hippocampal and temporal associative fibers' damage in MS-related memory complaints. To reach this aim, 25 patients with low disability relapsing-remitting MS and 19 healthy controls were included in the study. All subjects underwent 3D T1 structural imaging and Diffusion Tensor Imaging. Additionally, MS patients underwent neuropsychological evaluation of objective (Selective Reminding Test and Spatial Recall Test) and of subjective (Perceived Deficit Questionnaire, Retrospective and Prospective Memory Subscales) memory deficits. Normalized hippocampal volume (NHV) and mean Fractional Anisotropy (FA) for the uncinate fasciculus (UF) and for the ventral division of the cingulum bundle (VCB) were calculated for all subjects. We showed that, compared to controls, MS subjects presented with reduced right NHV and with reduced mean FA bilaterally in the UF and the VCB. In the MS group, verbal memory scores correlated with left NHV, spatial memory scores correlated with right NHV, while perceived retrospective and prospective memory deficits correlated with left VCB and left UF mean FA respectively. Our data confirm an early involvement of memory-related brain structures in MS patients. Our data suggest that verbal and nonverbal memory as well as perceived retrospective and prospective memory deficits are related to alterations of discrete anatomical structures in the low-disability phase of MS. Copyright © 2013 Wiley Periodicals, Inc.

Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

PubMed Central

Amodeo, Dionisio A.; Grospe, Gena; Zang, Hui; Dwivedi, Yogesh; Ragozzino, Michael E.

2016-01-01

Central infusion of the Na+/K+-ATPase inhibitor, ouabain in rats serves as an animal model of mania because it leads to hyperactivity, as well as reproduces ion dysregulation and reduced BDNF levels similar to that observed in bipolar disorder. Bipolar disorder is also associated with cognitive inflexibility and working memory deficits. It is unknown whether ouabain treatment in rats leads to similar cognitive flexibility and working memory deficits. The present study examined the effects of an intracerebral ventricular infusion of ouabain in rats on spontaneous alternation, probabilistic reversal learning and BDNF expression levels in the frontal cortex. Ouabain treatment significantly increased locomotor activity, but did not affect alternation performance in a Y-maze. Ouabain treatment selectively impaired reversal learning in a spatial discrimination task using an 80/20 probabilistic reinforcement procedure. The reversal learning deficit in ouabain-treated rats resulted from an impaired ability to maintain a new choice pattern (increased regressive errors). Ouabain treatment also decreased sensitivity to negative feedback during the initial phase of reversal learning. Expression of BDNF mRNA and protein levels was downregulated in the frontal cortex which also negatively correlated with regressive errors. These findings suggest that the ouabain model of mania may be useful in understanding the neuropathophysiology that contributes to cognitive flexibility deficits and test potential treatments to alleviate cognitive deficits in bipolar disorder. PMID:27267245

Effects of mild cognitive impairment on emotional scene memory

PubMed Central

Waring, J.D.; Dimsdale-Zucker, H.R.; Flannery, S.; Budson, A.E.; Kensinger, E.A.

2017-01-01

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. PMID:28089697

Memory functions of children born with asymmetric intrauterine growth restriction.

PubMed

Geva, Ronny; Eshel, Rina; Leitner, Yael; Fattal-Valevski, Aviva; Harel, Shaul

2006-10-30

Learning difficulties are frequently diagnosed in children born with intrauterine growth restriction (IUGR). Models of various animal species with IUGR were studied and demonstrated specific susceptibility and alterations of the hippocampal formation and its related neural structures. The main purpose was to study memory functions of children born with asymmetric IUGR in a large-scale cohort using a long-term prospective paradigm. One hundred and ten infants diagnosed with IUGR were followed-up from birth to 9 years of age. Their performance was compared with a group of 63 children with comparable gestational age and multiple socioeconomic factors. Memory functions (short-term, super- and long-term spans) for different stimuli types (verbal and visual) were evaluated using Visual Auditory Digit Span tasks (VADS), Rey Auditory Verbal Learning Test (Rey-AVLT), and Rey Osterrieth Complex Figure Test (ROCF). Children with IUGR had short-term memory difficulties that hindered both serial verbal processing system and simultaneous processing of high-load visuo-spatial stimuli. The difficulties were not related to prematurity, neonatal complications or growth catch-up, but were augmented by lower maternal education. Recognition skills and benefits from reiteration, typically affected by hippocampal dysfunction, were preserved in both groups. Memory profile of children born with IUGR is characterized primarily by a short-term memory deficit that does not necessarily comply with a typical hippocampal deficit, but rather may reflect an executive short-term memory deficit characteristic of anterior hippocampal-prefrontal network. Implications for cognitive intervention are discussed.

Dissociation of Short- and Long-Term Face Memory: Evidence from Long-Term Recency Effects in Temporal Lobe Epilepsy

ERIC Educational Resources Information Center

Bengner, T.; Malina, T.

2007-01-01

We tested whether memory deficits in temporal lobe epilepsy (TLE) are better described by a single- or dual-store memory model. To this aim, we analyzed the influence of TLE and proactive interference (PI) on immediate and 24-h long-term recency effects during face recognition in 16 healthy participants and 18 right and 21 left non-surgical TLE…

Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway.

PubMed

Zhang, Lu; Fang, Yu; Xu, Yuming; Lian, Yajun; Xie, Nanchang; Wu, Tianwen; Zhang, Haifeng; Sun, Limin; Zhang, Ruifang; Wang, Zhenhua

2015-01-01

Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer's disease (AD). However, the molecular mechanisms underlying curcumin's effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer's disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

Working memory - not processing speed - mediates fluid intelligence deficits associated with attention deficit/hyperactivity disorder symptoms.

PubMed

Brydges, Christopher R; Ozolnieks, Krista L; Roberts, Gareth

2017-09-01

Attention deficit/hyperactivity disorder (ADHD) is a psychological condition characterized by inattention and hyperactivity. Cognitive deficits are commonly observed in ADHD patients, including impaired working memory, processing speed, and fluid intelligence, the three of which are theorized to be closely associated with one another. In this study, we aimed to determine if decreased fluid intelligence was associated with ADHD, and was mediated by deficits in working memory and processing speed. This study tested 142 young adults from the general population on a range of working memory, processing speed, and fluid intelligence tasks, and an ADHD self-report symptoms questionnaire. Results showed that total and hyperactive ADHD symptoms correlated significantly and negatively with fluid intelligence, but this association was fully mediated by working memory. However, inattentive symptoms were not associated with fluid intelligence. Additionally, processing speed was not associated with ADHD symptoms at all, and was not uniquely predictive of fluid intelligence. The results provide implications for working memory training programs for ADHD patients, and highlight potential differences between the neuropsychological profiles of ADHD subtypes. © 2015 The British Psychological Society.

The diagnostic utility of behavioral checklists in identifying children with ADHD and children with working memory deficits.

PubMed

Alloway, Tracy Packiam; Gathercole, Susan E; Holmes, Joni; Place, Maurice; Elliott, Julian G; Hilton, Kerry

2009-09-01

The present study investigated whether children with ADHD and those with working memory impairments have a common behavioral profile in the classroom. Three teacher checklists were used: the Conners' teacher rating scale (CTRS), the behavior rating inventory of executive function (BRIEF), and the working memory rating scale. The Conners' continuous performance test (CPT) was also included to determine whether there is a correspondence between performance on this widely used cognitive measure of attention deficits and teacher ratings of classroom behavior. All three behavior scales, but not the CPT, were able to successfully discriminate children with ADHD and those with working memory deficits from typically-developing children. Both the CTRS and the BRIEF discriminated a significant proportion of the children with ADHD from those with working memory deficits, indicating that while both groups exhibit behavioral problems in the classroom, they are characterized by differential attention profiles. The children with ADHD were identified on the basis of oppositional and hyperactive behavior, while those with working memory deficits were more inattentive.

Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer's disease: an exploration of underlying mechanisms.

PubMed

Kiasalari, Zahra; Heydarifard, Rana; Khalili, Mohsen; Afshin-Majd, Siamak; Baluchnejadmojarad, Tourandokht; Zahedi, Elham; Sanaierad, Ashkan; Roghani, Mehrdad

2017-06-01

Alzheimer's disease (AD) is a neurodegenerative disorder with irreversible loss of intellectual abilities. Current therapies for AD are still insufficient. In this study, the effect of ellagic acid on learning and memory deficits was evaluated in intrahippocampal amyloid beta (Aβ 25-35 )-microinjected rats and its modes of action were also explored. AD rat model was induced by bilateral intrahippocampal microinjection of Aβ 25-35 and ellagic acid was daily administered (10, 50, and 100 mg/kg), and learning, recognition memory, and spatial memory were evaluated in addition to histochemical assessment, oxidative stress, cholinesterases activity, and level of nuclear factor-kappaB (NF-κB), Toll-like receptor 4 (TLR4), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The amyloid beta-microinjected rats showed a lower discrimination ratio in novel object and alternation score in Y maze tasks and exhibited an impairment of retention and recall capability in passive avoidance paradigm and higher working and reference memory errors in radial arm maze (RAM). In addition, amyloid beta group showed a lower number of Nissl-stained neurons in CA1 area in addition to enhanced oxidative stress, higher activity of cholinesterases, greater level of NF-κB and TLR4, and lower level of nuclear/cytoplasmic ratio for Nrf2 and ellagic acid at a dose of 100 mg/kg significantly prevented most of these abnormal alterations. Ellagic acid pretreatment of intrahippocampal amyloid beta-microinjected rats could dose-dependently improve learning and memory deficits via neuronal protection and at molecular level through mitigation of oxidative stress and acetylcholinesterase (AChE) activity and modulation of NF-κB/Nrf2/TLR4 signaling pathway.

Beneficial effects of semantic memory support on older adults' episodic memory: Differential patterns of support of item and associative information.

PubMed

Mohanty, Praggyan Pam; Naveh-Benjamin, Moshe; Ratneshwar, Srinivasan

2016-02-01

The effects of two types of semantic memory support-meaningfulness of an item and relatedness between items-in mitigating age-related deficits in item and associative, memory are examined in a marketing context. In Experiment 1, participants studied less (vs. more) meaningful brand logo graphics (pictures) paired with meaningful brand names (words) and later were assessed by item (old/new) and associative (intact/recombined) memory recognition tests. Results showed that meaningfulness of items eliminated age deficits in item memory, while equivalently boosting associative memory for older and younger adults. Experiment 2, in which related and unrelated brand logo graphics and brand name pairs served as stimuli, revealed that relatedness between items eliminated age deficits in associative memory, while improving to the same degree item memory in older and younger adults. Experiment 2 also provided evidence for a probable boundary condition that could reconcile seemingly contradictory extant results. Overall, these experiments provided evidence that although the two types of semantic memory support can improve both item and associative memory in older and younger adults, older adults' memory deficits can be eliminated when the type of support provided is compatible with the type of information required to perform well on the test. (c) 2016 APA, all rights reserved).

Short-term memory impairment after isoflurane in mice is prevented by the α5 γ-aminobutyric acid type A receptor inverse agonist L-655,708.

PubMed

Saab, Bechara J; Maclean, Ashley J B; Kanisek, Marijana; Zurek, Agnieszka A; Martin, Loren J; Roder, John C; Orser, Beverley A

2010-11-01

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.

The role of aging in intra-item and item-context binding processes in visual working memory.

PubMed

Peterson, Dwight J; Naveh-Benjamin, Moshe

2016-11-01

Aging is accompanied by declines in both working memory and long-term episodic memory processes. Specifically, important age-related memory deficits are characterized by performance impairments exhibited by older relative to younger adults when binding distinct components into a single integrated representation, despite relatively intact memory for the individual components. While robust patterns of age-related binding deficits are prevalent in studies of long-term episodic memory, observations of such deficits in visual working memory (VWM) may depend on the specific type of binding process being examined. For instance, a number of studies indicate that processes involved in item-context binding of items to occupied spatial locations within visual working memory are impaired in older relative to younger adults. Other findings suggest that intra-item binding of visual surface features (e.g., color, shape), compared to memory for single features, within visual working memory, remains relatively intact. Here, we examined each of these binding processes in younger and older adults under both optimal conditions (i.e., no concurrent load) and concurrent load (e.g., articulatory suppression, backward counting). Experiment 1 revealed an age-related intra-item binding deficit for surface features under no concurrent load but not when articulatory suppression was required. In contrast, in Experiments 2 and 3, we observed an age-related item-context binding deficit regardless of the level of concurrent load. These findings reveal that the influence of concurrent load on distinct binding processes within VWM, potentially those supported by rehearsal, is an important factor mediating the presence or absence of age-related binding deficits within VWM. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Visuo-spatial memory deficits following medial temporal lobe damage: A comparison of three patient groups.

PubMed

Esfahani-Bayerl, Nazli; Finke, Carsten; Braun, Mischa; Düzel, Emrah; Heekeren, Hauke R; Holtkamp, Martin; Hasper, Dietrich; Storm, Christian; Ploner, Christoph J

2016-01-29

The contributions of the hippocampal formation and adjacent regions of the medial temporal lobe (MTL) to memory are still a matter of debate. It is currently unclear, to what extent discrepancies between previous human lesion studies may have been caused by the choice of distinct patient models of MTL dysfunction, as disorders affecting this region differ in selectivity, laterality and mechanisms of post-lesional compensation. Here, we investigated the performance of three distinct patient groups with lesions to the MTL with a battery of visuo-spatial short-term memory tasks. Thirty-one subjects with either unilateral damage to the MTL (postsurgical lesions following resection of a benign brain tumor, 6 right-sided lesions, 5 left) or bilateral damage (10 post-encephalitic lesions, 10 post-anoxic lesions) performed a series of tasks requiring short-term memory of colors, locations or color-location associations. We have shown previously that performance in the association task critically depends on hippocampal integrity. Patients with postsurgical damage of the MTL showed deficient performance in the association task, but performed normally in color and location tasks. Patients with left-sided lesions were almost as impaired as patients with right-sided lesions. Patients with bilateral post-encephalitic lesions showed comparable damage to MTL sub-regions and performed similarly to patients with postsurgical lesions in the association task. However, post-encephalitic patients showed additional impairments in the non-associative color and location tasks. A strikingly similar pattern of deficits was observed in post-anoxic patients. These results suggest a distinct cerebral organization of associative and non-associative short-term memory that was differentially affected in the three patient groups. Thus, while all patient groups may provide appropriate models of medial temporal lobe dysfunction in associative visuo-spatial short-term memory, additional deficits in non-associative memory tasks likely reflect damage of regions outside the MTL. Importantly, the choice of a patient model in human lesion studies of the MTL significantly influences overall performance patterns in visuo-spatial memory tasks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Auditory verbal memory and psychosocial symptoms are related in children with idiopathic epilepsy.

PubMed

Schaffer, Yael; Ben Zeev, Bruria; Cohen, Roni; Shuper, Avinoam; Geva, Ronny

2015-07-01

Idiopathic epilepsies are considered to have relatively good prognoses and normal or near normal developmental outcomes. Nevertheless, accumulating studies demonstrate memory and psychosocial deficits in this population, and the prevalence, severity and relationships between these domains are still not well defined. We aimed to assess memory, psychosocial function, and the relationships between these two domains among children with idiopathic epilepsy syndromes using an extended neuropsychological battery and psychosocial questionnaires. Cognitive abilities, neuropsychological performance, and socioemotional behavior of 33 early adolescent children, diagnosed with idiopathic epilepsy, ages 9-14years, were assessed and compared with 27 age- and education-matched healthy controls. Compared to controls, patients with stabilized idiopathic epilepsy exhibited higher risks for short-term memory deficits (auditory verbal and visual) (p<0.0001), working memory deficits (p<0.003), auditory verbal long-term memory deficits (p<0.0021), and more frequent psychosocial symptoms (p<0.0001). The severity of auditory verbal memory deficits was related to severity of psychosocial symptoms among the children with epilepsy but not in the healthy controls. Results suggest that deficient auditory verbal memory may be compromising psychosocial functioning in children with idiopathic epilepsy, possibly underscoring that cognitive variables, such as auditory verbal memory, should be assessed and treated in this population to prevent secondary symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Obesity and insulin resistance are associated with reduced activity in core memory regions of the brain.

PubMed

Cheke, Lucy G; Bonnici, Heidi M; Clayton, Nicola S; Simons, Jon S

2017-02-01

Increasing research in animals and humans suggests that obesity may be associated with learning and memory deficits, and in particular with reductions in episodic memory. Rodent models have implicated the hippocampus in obesity-related memory impairments, but the neural mechanisms underlying episodic memory deficits in obese humans remain undetermined. In the present study, lean and obese human participants were scanned using fMRI while completing a What-Where-When episodic memory test (the "Treasure-Hunt Task") that assessed the ability to remember integrated item, spatial, and temporal details of previously encoded complex events. In lean participants, the Treasure-Hunt task elicited significant activity in regions of the brain known to be important for recollecting episodic memories, such as the hippocampus, angular gyrus, and dorsolateral prefrontal cortex. Both obesity and insulin resistance were associated with significantly reduced functional activity throughout the core recollection network. These findings indicate that obesity is associated with reduced functional activity in core brain areas supporting episodic memory and that insulin resistance may be a key player in this association. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

PubMed Central

Darcet, Flavie; Gardier, Alain M.; Gaillard, Raphael; David, Denis J.; Guilloux, Jean-Philippe

2016-01-01

Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age) could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed. PMID:26901205

Working Memory, Reading, and Mathematical Skills in Children with Developmental Coordination Disorder

ERIC Educational Resources Information Center

Alloway, Tracy Packiam

2007-01-01

The aim of the present study was investigate the relationship between working memory and reading and mathematical skills in 55 children diagnosed with developmental coordination disorder (DCD). The findings indicate a pervasive memory deficit in all memory measures. In particular, deficits observed in visuospatial short-term and working memory…

Working Memory Involved in Predicting Future Outcomes Based on Past Experiences

ERIC Educational Resources Information Center

Dretsch, Michael N.; Tipples, Jason

2008-01-01

Deficits in working memory have been shown to contribute to poor performance on the Iowa Gambling Task [IGT: Bechara, A., & Martin, E.M. (2004). "Impaired decision making related to working memory deficits in individuals with substance addictions." "Neuropsychology," 18, 152-162]. Similarly, a secondary memory load task has been shown to impair…

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

ERIC Educational Resources Information Center

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

2004-01-01

Objective: To investigate the effect of methylphenidate (MPH) on visual-spatial memory, as measured by subtests of the Cambridge Neuropsychological Testing Automated Battery (CANTAB), in children with attention-deficit/hyperactivity disorder (ADHD). Visual-spatial memory is a core component of working memory that has been shown to be impaired in…

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

PubMed

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

2015-04-01

Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed Central

Jung, Wookyoung; Lee, Seung-Hwan

2016-01-01

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

Objectively-Measured Impulsivity and Attention-Deficit/Hyperactivity Disorder (ADHD): Testing Competing Predictions from the Working Memory and Behavioral Inhibition Models of ADHD

ERIC Educational Resources Information Center

Raiker, Joseph S.; Rapport, Mark D.; Kofler, Michael J.; Sarver, Dustin E.

2012-01-01

Impulsivity is a hallmark of two of the three DSM-IV ADHD subtypes and is associated with myriad adverse outcomes. Limited research, however, is available concerning the mechanisms and processes that contribute to impulsive responding by children with ADHD. The current study tested predictions from two competing models of ADHD--working memory (WM)…

Relationship between hippocampal subfield volumes and memory deficits in patients with thalamus infarction.

PubMed

Chen, Li; Luo, Tianyou; Lv, Fajin; Shi, Dandan; Qiu, Jiang; Li, Qi; Fang, Weidong; Peng, Juan; Li, Yongmei; Zhang, Zhiwei; Li, Yang

2016-09-01

Clinical studies have shown that thalamus infarction (TI) affects memory function. The thalamic nucleus is directly or indirectly connected to the hippocampal system in animal models. However, this connection has not been investigated using structural magnetic resonance imaging (MRI) in humans. From the pathological perspective, TI patients may serve as valid models for revealing the interaction between the thalamus and hippocampus in memory function. In this study, we aim to assess different hippocampal subfield volumes in TI patients and control subjects using MRI and test their associations with memory function. A total of 37 TI patients (TI group), 38 matched healthy control subjects (HC group), and 22 control patients with other stroke location (SC group) underwent 3.0-T MRI scans and clinical memory examinations. Hippocampal subfield volumes were measured and compared by using FreeSurfer software. We examined the correlation between hippocampal subfield volumes and memory scores. Smaller ipsilesional presubiculum and subiculum volumes were observed, and former was related to graphics recall in both left and right TI patients. The left subiculum volume was correlated with short-delayed recall in left TI patients. The right presubiculum volume was correlated with short- and long-delayed recall in right TI patients. TI was found to result in hippocampal abnormality and memory deficits, and its neural mechanisms might be related with and interaction between the thalamus and hippocampus.

Octadecylpropyl Sulfamide Reduces Neurodegeneration and Restores the Memory Deficits Induced by Hypoxia-Ischemia in Mice

PubMed Central

Kossatz, Elk; Silva-Peña, Daniel; Suárez, Juan; de Fonseca, Fernando R.; Maldonado, Rafael; Robledo, Patricia

2018-01-01

The PPAR-α agonist, oleoylethanolamide (OEA) has neuroprotective properties in stroke models. However, its rapid degradation represents a limitation for an effective therapeutic approach. In this study, we evaluated the effects of a stable OEA-modeled compound, octadecylpropyl sulfamide (SUL) on the cognitive, behavioral, cellular and molecular alterations associated with hypoxia-ischemia (HI) in mice. Mice subjected to HI were treated with the PPAR-α antagonist GW6471 (GW) (1 mg/kg) followed 15 min later by SUL (3 and 10 mg/kg). Behavioral, motor, and cognitive tests were carried out 24 h and 7 days after the HI. The levels of microglia, reactive astrocytes and neuronal nuclei were studied using immunofluorescence, and the expression of genes related to the N-acyl-ethanolamides/endocannabinoid signaling systems was determined by qRT-PCR at the end of the experimental sequence. HI induced brain damage in the ipsilateral hippocampus and cortex, which lead to severe memory impairments, and motor coordination deficits. Significant neuronal loss, increased microglia and reactive astrocytes, and compensatory changes in genes associated with the inflammation/immune and endocannabinoid systems were observed in these brain structures of lesioned mice. SUL reversed the memory and motor deficits, decreased the overexpression of microglia and astrocytes, and reduced neurodegeneration induced by HI. Cnr1 and Cnr2 gene expression was modulated by SUL in both sham and HI mice, while Pparα and Faah expression was regulated in HI mice. GW completely blocked the beneficial actions of SUL. These findings suggest that treatment with SUL reduces brain damage and the associated motor and memory deficits induced by HI probably by normalizing the changes in neuroinflammation/immune system mediators. PMID:29725299

Octadecylpropyl Sulfamide Reduces Neurodegeneration and Restores the Memory Deficits Induced by Hypoxia-Ischemia in Mice.

PubMed

Kossatz, Elk; Silva-Peña, Daniel; Suárez, Juan; de Fonseca, Fernando R; Maldonado, Rafael; Robledo, Patricia

2018-01-01

The PPAR-α agonist, oleoylethanolamide (OEA) has neuroprotective properties in stroke models. However, its rapid degradation represents a limitation for an effective therapeutic approach. In this study, we evaluated the effects of a stable OEA-modeled compound, octadecylpropyl sulfamide (SUL) on the cognitive, behavioral, cellular and molecular alterations associated with hypoxia-ischemia (HI) in mice. Mice subjected to HI were treated with the PPAR-α antagonist GW6471 (GW) (1 mg/kg) followed 15 min later by SUL (3 and 10 mg/kg). Behavioral, motor, and cognitive tests were carried out 24 h and 7 days after the HI. The levels of microglia, reactive astrocytes and neuronal nuclei were studied using immunofluorescence, and the expression of genes related to the N -acyl-ethanolamides/endocannabinoid signaling systems was determined by qRT-PCR at the end of the experimental sequence. HI induced brain damage in the ipsilateral hippocampus and cortex, which lead to severe memory impairments, and motor coordination deficits. Significant neuronal loss, increased microglia and reactive astrocytes, and compensatory changes in genes associated with the inflammation/immune and endocannabinoid systems were observed in these brain structures of lesioned mice. SUL reversed the memory and motor deficits, decreased the overexpression of microglia and astrocytes, and reduced neurodegeneration induced by HI. Cnr1 and Cnr2 gene expression was modulated by SUL in both sham and HI mice, while Ppar α and Faah expression was regulated in HI mice. GW completely blocked the beneficial actions of SUL. These findings suggest that treatment with SUL reduces brain damage and the associated motor and memory deficits induced by HI probably by normalizing the changes in neuroinflammation/immune system mediators.

Fus1 KO Mouse As a Model of Oxidative Stress-Mediated Sporadic Alzheimer's Disease: Circadian Disruption and Long-Term Spatial and Olfactory Memory Impairments

PubMed Central

Coronas-Samano, Guillermo; Baker, Keeley L.; Tan, Winston J. T.; Ivanova, Alla V.; Verhagen, Justus V.

2016-01-01

Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4–5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1), disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK), autophagy (decreased levels of LC3-II), PKC (decreased levels of RACK1) and calcium signaling (decreased levels of Calb2) in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus), in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term), olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie), spatial memory (learning impairments on finding the platform in the Morris water maze) and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation), association memory (passive avoidance) or in species-typical behavior (nest building) and no increased anxiety (open field, light-dark box) or depression/anhedonia (sucrose preference) at this relatively young age. These neurobehavioral deficits of the Fus1 KO mice at this relatively young age are highly relevant to sAD, making them suitable for effective research on pharmacological targets in the context of early intervention of sAD. PMID:27895577

Ecstasy Exposure & Gender: Examining Components of Verbal Memory Functioning

PubMed Central

Price, Jenessa S.; Shear, Paula; Lisdahl, Krista M.

2014-01-01

Objective Studies have demonstrated verbal memory deficits associated with past year ecstasy use, although specific underlying components of these deficits are less understood. Further, prior research suggests potential gender differences in ecstasy-induced serotonergic changes. Therefore, the current study investigated whether gender moderated the relationship between ecstasy exposure and components of verbal memory after controlling for polydrug use and confounding variables. Method Data were collected from 65 polydrug users with a wide range of ecstasy exposure (ages 18–35; 48 ecstasy and 17 marijuana users; 0–2310 ecstasy tablets). Participants completed a verbal learning and memory task, psychological questionnaires, and a drug use interview. Results Increased past year ecstasy exposure predicted poorer short and long delayed free and cued recalls, retention, and recall discrimination. Male ecstasy users were more susceptible to dose-dependent deficits in retention than female users. Conclusion Past year ecstasy consumption was associated with verbal memory retrieval, retention, and discrimination deficits in a dose-dependent manner in a sample of healthy young adult polydrug users. Male ecstasy users were at particular risk for deficits in retention following a long delay. Gender difference may be reflective of different patterns of polydrug use as well as increased hippocampal sensitivity. Future research examining neuronal correlates of verbal memory deficits in ecstasy users are needed. PMID:25545890

Ecstasy exposure & gender: examining components of verbal memory functioning.

PubMed

Price, Jenessa S; Shear, Paula; Lisdahl, Krista M

2014-01-01

Studies have demonstrated verbal memory deficits associated with past year ecstasy use, although specific underlying components of these deficits are less understood. Further, prior research suggests potential gender differences in ecstasy-induced serotonergic changes. Therefore, the current study investigated whether gender moderated the relationship between ecstasy exposure and components of verbal memory after controlling for polydrug use and confounding variables. Data were collected from 65 polydrug users with a wide range of ecstasy exposure (ages 18-35; 48 ecstasy and 17 marijuana users; 0-2310 ecstasy tablets). Participants completed a verbal learning and memory task, psychological questionnaires, and a drug use interview. Increased past year ecstasy exposure predicted poorer short and long delayed free and cued recalls, retention, and recall discrimination. Male ecstasy users were more susceptible to dose-dependent deficits in retention than female users. Past year ecstasy consumption was associated with verbal memory retrieval, retention, and discrimination deficits in a dose-dependent manner in a sample of healthy young adult polydrug users. Male ecstasy users were at particular risk for deficits in retention following a long delay. Gender difference may be reflective of different patterns of polydrug use as well as increased hippocampal sensitivity. Future research examining neuronal correlates of verbal memory deficits in ecstasy users are needed.

Effects of dimethylaminoethanol pyroglutamate (DMAE p-Glu) against memory deficits induced by scopolamine: evidence from preclinical and clinical studies.

PubMed

Blin, Olivier; Audebert, Christine; Pitel, Séverine; Kaladjian, Arthur; Casse-Perrot, Catherine; Zaim, Mohammed; Micallef, Joelle; Tisne-Versailles, Jacky; Sokoloff, Pierre; Chopin, Philippe; Marien, Marc

2009-12-01

Dimethylaminoethanol pyroglutamate (DMAE p-Glu) is a compound resulting from the reaction between dimethylaminoethanol (an indirect precursor of acetylcholine) and pyroglutamic acid (a cyclic derivative of glutamic acid having procholinergic properties and promnesic effects in both animals and man). The present study undertook preclinical and clinical evaluations to test a potential therapeutic utility for DMAE p-Glu in cognitive impairments related to central cholinergic deficit. In preclinical study, DMAE p-Glu was studied in rats by intracerebral microdialysis in conscious freely moving animals, on performance of rats in the Morris water maze test of spatial memory, and on the deficit in passive avoidance behavior induced by scopolamine. The clinical study examined the effect of DMAE p-Glu on cognitive deficits induced by an intravenous injection of scopolamine in healthy young male subjects. In rat experiments, DMAE p-Glu increased the extracellular levels of choline and acetylcholine in the medial prefrontal cortex, as assessed by intracerebral microdialysis, improved performance in a test of spatial memory, and reduced scopolamine-induced memory deficit in passive avoidance behavior. Clinical study results show that scopolamine induced a memory deficit and that DMAE p-Glu produced a significant positive effect on scores in the Buschke test, as well as a slight but significant difference on choice reaction time. These results indicate that DMAE p-Glu reduces the deleterious effect of scopolamine on long-term memory in healthy volunteers and suggest that DMAE p-Glu might be effective in reducing memory deficits in patients with cognitive impairment.

Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment.

PubMed

Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M

2014-06-30

Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients. Patient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences. The presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe dysfunction between ALS and aMCI patients, and support temporal lobe dysfunction as a mechanism underlying the distinct cognitive impairments observed in ALS.

Category-Specific Naming and Recognition Deficits in Temporal Lobe Epilepsy Surgical Patients

PubMed Central

Drane, Daniel L.; Ojemann, George A.; Aylward, Elizabeth; Ojemann, Jeffrey G.; Johnson, L. Clark; Silbergeld, Daniel L.; Miller, John W.; Tranel, Daniel

2008-01-01

Objective Based upon Damasio's “Convergence Zone” model of semantic memory, we predicted that epilepsy surgical patients with anterior temporal lobe (TL) seizure onset would exhibit a pattern of category-specific naming and recognition deficits not observed in patients with seizures arising elsewhere. Methods We assessed epilepsy patients with unilateral seizure onset of anterior TL or other origin (n = 22), pre- or postoperatively, using a set of category-specific items and a conventional measure of visual naming (Boston Naming Test: BNT). Results Category-specific naming deficits were exhibited by patients with dominant anterior TL seizure onset/resection for famous faces and animals, while category-specific recognition deficits for these same categories were exhibited by patients with nondominant anterior TL onset/resection. Patients with other seizure onset did not exhibit category-specific deficits. Naming and recognition deficits were frequently not detected by the BNT, which samples only a limited range of stimuli. Interpretation Consistent with the “convergence zone” framework, results suggest that the nondominant anterior TL plays a major role in binding sensory information into conceptual percepts for certain stimuli, while dominant TL regions function to provide a link to verbal labels for these percepts. Although observed category-specific deficits were striking, they were often missed by the BNT, suggesting that they are more prevalent than recognized in both pre- and postsurgical epilepsy patients. Systematic investigation of these deficits could lead to more refined models of semantic memory, aid in the localization of seizures, and contribute to modifications in surgical technique and patient selection in epilepsy surgery to improve neurocognitive outcome. PMID:18206185

Spatial Working Memory Deficits in Male Rats Following Neonatal Hypoxic Ischemic Brain Injury Can Be Attenuated by Task Modifications

PubMed Central

Smith, Amanda L.; Hill, Courtney A.; Alexander, Michelle; Szalkowski, Caitlin E.; Chrobak, James J.; Rosenkrantz, Ted S.; Fitch, R. Holly

2014-01-01

Hypoxia-ischemia (HI; reduction in blood/oxygen supply) is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA). Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P)7, an age comparable to a term (GA 36–38) human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD—a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are crucial to accommodating memory deficits in children suffering from cognitive impairments following neonatal HI. PMID:24961760

The full-length form of the Drosophila amyloid precursor protein is involved in memory formation.

PubMed

Bourdet, Isabelle; Preat, Thomas; Goguel, Valérie

2015-01-21

The APP plays a central role in AD, a pathology that first manifests as a memory decline. Understanding the role of APP in normal cognition is fundamental in understanding the progression of AD, and mammalian studies have pointed to a role of secreted APPα in memory. In Drosophila, we recently showed that APPL, the fly APP ortholog, is required for associative memory. In the present study, we aimed to characterize which form of APPL is involved in this process. We show that expression of a secreted-APPL form in the mushroom bodies, the center for olfactory memory, is able to rescue the memory deficit caused by APPL partial loss of function. We next assessed the impact on memory of the Drosophila α-secretase kuzbanian (KUZ), the enzyme initiating the nonamyloidogenic pathway that produces secreted APPLα. Strikingly, KUZ overexpression not only failed to rescue the memory deficit caused by APPL loss of function, it exacerbated this deficit. We further show that in addition to an increase in secreted-APPL forms, KUZ overexpression caused a decrease of membrane-bound full-length species that could explain the memory deficit. Indeed, we observed that transient expression of a constitutive membrane-bound mutant APPL form is sufficient to rescue the memory deficit caused by APPL reduction, revealing for the first time a role of full-length APPL in memory formation. Our data demonstrate that, in addition to secreted APPL, the noncleaved form is involved in memory, raising the possibility that secreted and full-length APPL act together in memory processes. Copyright © 2015 the authors 0270-6474/15/351043-09$15.00/0.

Effects of β-hydroxy-β-methyl butyrate on working memory and cognitive flexibility in an animal model of aging.

PubMed

Hankosky, Emily R; Sherrill, Luke K; Ruvola, Lauren A; Haake, Rachel M; Kim, Taehyeon; Hammerslag, Lindsey R; Kougias, Daniel G; Juraska, Janice M; Gulley, Joshua M

2017-09-01

Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) on working memory and cognitive flexibility. Beginning ∼12 months of age, male and female Long-Evans rats were given twice daily access to sipper tubes containing calcium HMB (450 mg/kg) or vehicle (285 mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process.

Long-Term Episodic Memory in Children with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Skowronek, Jeffrey S.; Leichtman, Michelle D.; Pillemer, David B.

2008-01-01

Twenty-nine grade-matched 4th-8th-grade males, 12 with attention-deficit/hyperactivity disorder (ADHD) (age M = 12.2 years, SD = 1.48), and 17 without (age M = 11.5, SD = 1.59), completed two working memory tasks (digit span and the Simon game) and three long-term episodic memory tasks (a personal event memory task, story memory task, and picture…

SU30. Long-Term Memory Deficits in Schizophrenia: Are All Things Equal?

PubMed Central

Rossell, Susan

2017-01-01

Abstract Background: Kraepelin and Bleulernoted that patients with schizophrenia had significant cognitive deficits over a century ago; however, their observations with regard to long-term memory have not born out within empirical studies. They reported that episodic memory was intact but indicated that organization of memories, or semantic memory, was disordered. This study aimed to synthesize a century of research in the 2 long-term memory processes of episodic and semantic memory across the psychosis continuum: chronic patients, first-episode patients, high risk for psychosis cohorts, and persons with high schizotypy. Methods: A systematic review and meta-analysis was completed within the 2 domains of long-term memory across the psychosis continuum. Search terms included long-term memory, episodic, semantic, and derivations of these terms. The data were synthesized independently for episodic and semantic memory. Four independent populations were investigated: chronic patients, first-episode patients, high risk for psychosis cohorts, and persons with high schizotypy. Our approach followed the PRISMA guidelines. Thus, the pooled mean effect sizes are reported for 8 analyses. These effect sizes represent case cohort in comparison to a healthy control cohort. Results: The results were as follows, for episodic memory: chronic patients d = 1.12, first-episode patients d = 1.12, high risk d = 1.14, and high schizotypy d = 0.13. Thus, establishing that there is poor evidence of episodic memory deficits in persons with high schizotypy. For semantic memory, the literature showed a different pattern: chronic patients d = 1.2, first-episode patients d = 1.08, high risk d = 1.16, and high schizotypy d = 0.95. Thus, a consistent degree of semantic memory deficits across the continuum. Conclusion: The literature suggests a dissociated pattern of long-term memory deficits; whereby semantic memory abnormalities are more likely to be considered endophenotypes or cognitive markers for schizophrenia than episodic memory deficits. Differential patterns of semantic memory organization are argued to be present prior to the onset of the disorder. There is additional evidence to suggest that idiosyncratic storage of semantic material underlies the development of the usual beliefs and speech patterns present in the forms of delusions and formal thought disorder. Consequently, semantic memory might be a useful target for cognitive remediation.

Source Memory in Korsakoff Syndrome: Disentangling the Mechanisms of Temporal Confusion.

PubMed

Brion, Mélanie; de Timary, Philippe; Pitel, Anne-Lise; Maurage, Pierre

2017-03-01

Korsakoff syndrome (KS), most frequently resulting from alcohol dependence (ALC), is characterized by severe anterograde amnesia. It has been suggested that these deficits may extend to other memory components, and notably source memory deficits involved in the disorientation and temporal confusion frequently observed in KS. However, the extent of this source memory impairment in KS and its usefulness for the differential diagnosis between ALC and KS remain unexplored. Nineteen patients with KS were compared with 19 alcohol-dependent individuals and 19 controls in a source memory test exploring temporal context confusions ("continuous recognition task"). Episodic memory and psychopathological comorbidities were controlled for. While no source memory deficit was observed in ALC, KS was associated with a significant presence of temporal context confusion, even when the influence of comorbidities was taken into account. This source memory impairment did not appear to be related to performances on episodic memory or executive functions. Patients with KS displayed source memory deficits, as indexed by temporal context confusions. The absence of a relationship with episodic memory performances seems to indicate that source memory impairment is not a mere by-product of amnesia. As ALC was associated with preserved source memory, the presence of temporal context confusion may serve as a complementary tool for the differential diagnosis between ALC and KS. Copyright © 2017 by the Research Society on Alcoholism.

Using visual lateralization to model learning and memory in zebrafish larvae

PubMed Central

Andersson, Madelene Åberg; Ek, Fredrik; Olsson, Roger

2015-01-01

Impaired learning and memory are common symptoms of neurodegenerative and neuropsychiatric diseases. Present, there are several behavioural test employed to assess cognitive functions in animal models, including the frequently used novel object recognition (NOR) test. However, although atypical functional brain lateralization has been associated with neuropsychiatric conditions, spanning from schizophrenia to autism, few animal models are available to study this phenomenon in learning and memory deficits. Here we present a visual lateralization NOR model (VLNOR) in zebrafish larvae as an assay that combines brain lateralization and NOR. In zebrafish larvae, learning and memory are generally assessed by habituation, sensitization, or conditioning paradigms, which are all representatives of nondeclarative memory. The VLNOR is the first model for zebrafish larvae that studies a memory similar to the declarative memory described for mammals. We demonstrate that VLNOR can be used to study memory formation, storage, and recall of novel objects, both short and long term, in 10-day-old zebrafish. Furthermore we show that the VLNOR model can be used to study chemical modulation of memory formation and maintenance using dizocilpine (MK-801), a frequently used non-competitive antagonist of the NMDA receptor, used to test putative antipsychotics in animal models. PMID:25727677

Inefficient Executive Cognitive Control in Schizophrenia Is Preceded by Altered Functional Activation during Information Encoding: An fMRI Study

ERIC Educational Resources Information Center

Schlosser, Ralf G. M.; Koch, Kathrin; Wagner, Gerd; Nenadic, Igor; Roebel, Martin; Schachtzabel, Claudia; Axer, Martina; Schultz, Christoph; Reichenbach, Jurgen R.; Sauer, Heinrich

2008-01-01

Working memory deficits are a core feature of schizophrenia. Previous working memory studies suggest a load dependent storage deficit. However, explicit studies of higher executive working memory processes are limited. Moreover, few studies have examined whether subcomponents of working memory such as encoding and maintenance of information are…

Duration of Auditory Sensory Memory in Parents of Children with SLI: A Mismatch Negativity Study

ERIC Educational Resources Information Center

Barry, Johanna G.; Hardiman, Mervyn J.; Line, Elizabeth; White, Katherine B.; Yasin, Ifat; Bishop, Dorothy V. M.

2008-01-01

In a previous behavioral study, we showed that parents of children with SLI had a subclinical deficit in phonological short-term memory. Here, we tested the hypothesis that they also have a deficit in nonverbal auditory sensory memory. We measured auditory sensory memory using a paradigm involving an electrophysiological component called the…

Verbal memory in drug-naive, newly diagnosed Parkinson's disease. The retrieval deficit hypothesis revisited.

PubMed

Brønnick, Kolbjørn; Alves, Guido; Aarsland, Dag; Tysnes, Ole-Bjørn; Larsen, Jan Petter

2011-01-01

The retrieval deficit hypothesis on memory impairment in patients with Parkinson's disease (PD) implies a selective impairment in recall of learned material with normal encoding, retention, and recognition. This hypothesis has been challenged by new data. We have therefore investigated verbal memory and learning in a large sample of newly diagnosed, drug naïve, non-demented patients with PD. From a sample of patients with PD from the Norwegian ParkWest study, 133 PD patients and 133 controls matched on sex, age, and education were included. The California Verbal Learning Test-2 (CVLT-2) was used to assess verbal memory. Patients performed significantly worse than controls on free and cued recall as well as on recognition memory. Patients used the semantic clustering learning strategy significantly less extensively than the controls and the learning slope of the PD patients was significantly less steep. There was no difference in retention when controlling for encoding. Patients did not perform better on the recognition measure or on cued recall (d-prime), as compared to free recall. Executive functions explained a substantial part of the memory deficits. This study suggests that memory impairment in drug naïve early PD to a large degree is a deficit of learning/ encoding and not of retention or retrieval. An implication is that the retrieval deficit hypothesis should be moderated in its general form. Executive deficits and less extensive use of the efficient semantic clustering learning strategy had a strong impact on learning and memory. (c) 2010 APA, all rights reserved.

Memory-guided reaching in a patient with visual hemiagnosia.

PubMed

Cornelsen, Sonja; Rennig, Johannes; Himmelbach, Marc

2016-06-01

The two-visual-systems hypothesis (TVSH) postulates that memory-guided movements rely on intact functions of the ventral stream. Its particular importance for memory-guided actions was initially inferred from behavioral dissociations in the well-known patient DF. Despite of rather accurate reaching and grasping movements to visible targets, she demonstrated grossly impaired memory-guided grasping as much as impaired memory-guided reaching. These dissociations were later complemented by apparently reversed dissociations in patients with dorsal damage and optic ataxia. However, grasping studies in DF and optic ataxia patients differed with respect to the retinotopic position of target objects, questioning the interpretation of the respective findings as a double dissociation. In contrast, the findings for reaching errors in both types of patients came from similar peripheral target presentations. However, new data on brain structural changes and visuomotor deficits in DF also questioned the validity of a double dissociation in reaching. A severe visuospatial short-term memory deficit in DF further questioned the specificity of her memory-guided reaching deficit. Therefore, we compared movement accuracy in visually-guided and memory-guided reaching in a new patient who suffered a confined unilateral damage to the ventral visual system due to stroke. Our results indeed support previous descriptions of memory-guided movements' inaccuracies in DF. Furthermore, our data suggest that recently discovered optic-ataxia like misreaching in DF is most likely caused by her parieto-occipital and not by her ventral stream damage. Finally, multiple visuospatial memory measurements in HWS suggest that inaccuracies in memory-guided reaching tasks in patients with ventral damage cannot be explained by visuospatial short-term memory or perceptual deficits, but by a specific deficit in visuomotor processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-04-01

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

Conduction Aphasia, Sensory-Motor Integration, and Phonological Short-Term Memory--An Aggregate Analysis of Lesion and fMRI Data

ERIC Educational Resources Information Center

Buchsbaum, Bradley R.; Baldo, Juliana; Okada, Kayoko; Berman, Karen F.; Dronkers, Nina; D'Esposito, Mark; Hickok, Gregory

2011-01-01

Conduction aphasia is a language disorder characterized by frequent speech errors, impaired verbatim repetition, a deficit in phonological short-term memory, and naming difficulties in the presence of otherwise fluent and grammatical speech output. While traditional models of conduction aphasia have typically implicated white matter pathways,…

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

PubMed

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

2016-01-01

Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson's disease. Here we examined visual short-term memory deficits--long associated with Parkinson's disease--in patients with REM sleep behaviour disorder without Parkinson's disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson's disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson's disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson's disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson's disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of 'prodromal' Parkinson's disease that might be useful in tracking disease progression and for disease-modifying intervention trials. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Episodic Memory in Alzheimer Disease, Frontotemporal Dementia, and Dementia With Lewy Bodies/Parkinson Disease Dementia: Disentangling Retrieval From Consolidation.

PubMed

Economou, Alexandra; Routsis, Christopher; Papageorgiou, Sokratis G

2016-01-01

Differences in episodic memory performance in patients with Alzheimer disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB)/Parkinson disease with dementia (PDD) are inconsistent and task dependent. The inconsistencies may be attributed to the different tasks drawing on different memory processes. Few studies have examined episodic memory impairment in the above groups using memory tests that facilitate encoding, to distinguish memory deficits due to impairment of specific processes. We examined the memory performance of 106 AD patients, 51 FTD patients, 26 DLB/PDD patients, and 37 controls using the Five-Words Test, a 5-item memory test that facilitates encoding. The patient groups did not differ in modified Mini Mental State Examination scores. AD patients scored lowest on the Five-Words Test overall, and showed the greatest reduction from immediate total recall to delayed free recall relative to the other 2 groups, consistent with a predominantly consolidation deficit. DLB/PDD patients showed the largest improvement from delayed free to delayed total recall relative to the other 2 groups, consistent with a predominantly retrieval deficit. Deficits in both consolidation and retrieval underlie the memory impairment of the patients, to different extents, and contribute to the theoretical understanding of the nature of the memory impairment of the patient groups.

Cortical Thickness and Episodic Memory Impairment in Systemic Lupus Erythematosus.

PubMed

Bizzo, Bernardo Canedo; Sanchez, Tiago Arruda; Tukamoto, Gustavo; Zimmermann, Nicolle; Netto, Tania Maria; Gasparetto, Emerson Leandro

2017-01-01

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.

Effects of Mangifera indica fruit extract on cognitive deficits in mice.

PubMed

Kumar, Sokindra; Maheshwari, Kamal Kishore; Singh, Vijender

2009-07-01

Mangos are a source of bioactive compounds with potential health-promoting activity. The present work was undertaken to evaluate the ethanolic extract of Mangifera indica L. fruit on cognitive performances. The models used to study the effect on cognitive performances are step down passive avoidance task and elevated plus maze task in mice. Chronic treatment (7 days) of extract and vitamin C significantly (p < 0.05) reversed the aging and scopolamine induced memory deficits in both paradigms. Preliminary phytochemical screening revealed the presence of free sugars, saponins, tannins, and flavonoids. The results suggestthe extract contained pharmacologically active principles that are memory-enhancing in nature.

Betaine reverses the memory impairments in a chronic cerebral hypoperfusion rat model.

PubMed

Nie, Chunjie; Nie, Huijuan; Zhao, Yin; Wu, Jianzhao; Zhang, Xiaojian

2016-02-26

Vascular dementia (VaD) is the second reason for the cognitive decline in aged people, but the effective therapy is still missing. The chronic cerebral hypoperfusion (CCH) had been widely found in VaD patients and is thought to be the key reason for cognitive impairment. Betaine is a natural product that had been implicated in many biological processes and had been used for the therapy of some neurodegenerative disease, such as Alzheimer's disease. In this study, we reported that betaine treatment could rescue the memory deficits induced by two-vessel occlusion (2-VO), a widely used CCH rat model. Betaine also restored the expression of PSD93, PSD95 and MAP2 to preserve the synaptic functions. Furthermore, betaine could reduce the oxidative stress by suppressing the MDA and ROS and enhancing the SOD and GSH. Overall, betaine treatment is able to rescue the memory deficits in CCH rats, which provide an experimental basis for the therapy of VaD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Progression of multiple behavioral deficits with various ages of onset in a murine model of Hurler syndrome.

PubMed

Pan, Dao; Sciascia, Anthony; Vorhees, Charles V; Williams, Michael T

2008-01-10

Mucopolysaccharidosis type I (MPS I) is one of the most common lysosomal storage diseases with progressive neurological dysfunction. To characterize the chronological behavioral profiles and identify the onset of functional deficits in a MPS I mouse model (IDUA(-/-)), we evaluated anxiety, locomotor behavior, startle, spatial learning and memory with mice at 2, 4, 6 and 8 months of age. In automated open-field test, IDUA(-/-) mice showed hypoactivity as early as 2 months of age and altered anxiety starting from 6 months of age during the initial exploratory phase, even though normal habituation was observed at all ages. In the marble-burying task, the anxiety-like compulsive behavior was normal in IDUA(-/-) mice at almost all tested ages, but significantly reduced in 8-month old male IDUA(-/-) mice which coincided with the rapid death of IDUA(-/-) males starting from 7 months of age. In the Morris water maze, IDUA(-/-) mice exhibited impaired proficient learning only at 4 months of age during the acquisition phase. Spatial memory deficits were observed in IDUA(-/-) mice during both 1 and 7 days probe trials at 4 and 8 months of age. The IDUA(-/-) mice performed normally in a novel object recognition task at younger ages until 8 months old when reduced visual cognitive memory retention was noted in the IDUA(-/-) mice. In addition, 8-month-old IDUA(-/-) mice failed to habituate to repeated open-field exposure, suggesting deficits in non-aversive and non-associative memory. In acoustic startle assessment, significantly more non-responders were found in IDUA(-/-) mice, but normal performance was seen in those that did show a response. These results presented a temporal evaluation of phenotypic behavioral dysfunctions in IDUA(-/-) mice from adolescence to maturity, indicating the impairments, with different ages of onset, in locomotor and anxiety-like compulsive behaviors, spatial learning and memory, visual recognition and short-term non-associative memory retention. This study would also provide guidelines for the experimental designs of behavioral evaluation on innovative therapies for the treatment of MPS type I.

Visuospatial deficits in schizophrenia: central executive and memory subsystems impairments.

PubMed

Leiderman, Eduardo A; Strejilevich, Sergio A

2004-06-01

Object and spatial visual working memory are impaired in schizophrenic patients. It is not clear if the impairments reside in each memory subsystem alone or also in the central executive component that coordinates these processes. In order to elucidate which memory component is impaired, we developed a paradigm with single spatial and object working memory tasks and dual ones with two different delays (5 and 30 s). Fifteen schizophrenic patients and 14 control subjects performed these tests. Schizophrenic patients had a poorer performance compared to normal controls in all tasks and in all time delays. Both schizophrenics and controls performed significantly worse in the object task than in the spatial task. The performance was even worse in the dual task compared to the singles ones in schizophrenic patients but not in controls. These data suggest that visuospatial performance deficits in schizophrenia are due to both visuospatial memory subsystems impairments and central executive ones. The pattern of deficits observed points to a codification or evocation deficit and not to a maintenance one.

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

PubMed

Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

2017-01-01

The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

Short-term exposure to a diet high in fat and sugar, or liquid sugar, selectively impairs hippocampal-dependent memory, with differential impacts on inflammation.

PubMed

Beilharz, J E; Maniam, J; Morris, M J

2016-06-01

Chronic high-energy diets are known to induce obesity and impair memory; these changes have been associated with inflammation in brain areas crucial for memory. In this study, we investigated whether inflammation could also be related to diet-induced memory deficits, prior to obesity. We exposed rats to chow, chow supplemented with a 10% sucrose solution (Sugar) or a diet high in fat and sugar (Caf+Sugar) and assessed hippocampal-dependent and perirhinal-dependent memory at 1 week. Both high-energy diet groups displayed similar, selective hippocampal-dependent memory deficits despite the Caf+Sugar rats consuming 4-5 times more energy, and weighing significantly more than the other groups. Extreme weight gain and excessive energy intake are therefore not necessary for deficits in memory. Weight gain across the diet period however, was correlated with the memory deficits, even in the Chow rats. The Sugar rats had elevated expression of a number of inflammatory genes in the hippocampus and WAT compared to Chow and Caf+Sugar rats but not in the perirhinal cortex or hypothalamus. Blood glucose concentrations were also elevated in the Sugar rats, and were correlated with the hippocampal inflammatory markers. Together, these results indicate that liquid sugar can rapidly elevate markers of central and peripheral inflammation, in association with hyperglycemia, and this may be related to the memory deficits in the Sugar rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Long-term memory for verbal and visual information in Down syndrome and Williams syndrome: performance on the Doors and People test.

PubMed

Jarrold, Christopher; Baddeley, Alan D; Phillips, Caroline

2007-02-01

Previous studies have suggested that Williams syndrome and Down syndrome may be associated with specific short-term memory deficits. Individuals with Williams syndrome perform relatively poorly on tests of visuo-spatial short-term memory and individuals with Down syndrome show a relative deficit on verbal short-term memory tasks. However, these patterns of impairments may reflect the impact of generally impaired visuo-spatial processing skills in Williams syndrome, and verbal abilities in Down syndrome. The current study explored this possibility by assessing long-term memory among 15 individuals with Williams syndrome and 20 individuals with Down syndrome using the Doors and People test, a battery which assesses recall and recognition of verbal and visual information. Individuals' performance was standardised for age and level of intellectual ability with reference to that shown by a sample of 110 typically developing children. The results showed that individuals with Down syndrome have no differential deficits in long-term memory for verbal information, implying that verbal short-term memory deficits in this population are relatively selective. Instead both individuals with Down syndrome and with Williams syndrome showed some evidence of relatively poor performance on tests of long-term memory for visual information. It is therefore possible that visuo-spatial short-term memory deficits that have previously been demonstrated in Williams syndrome may be secondary to more general problems in visuo-spatial processing in this population.

Verbal Working Memory in Children With Cochlear Implants

PubMed Central

Caldwell-Tarr, Amanda; Low, Keri E.; Lowenstein, Joanna H.

2017-01-01

Purpose Verbal working memory in children with cochlear implants and children with normal hearing was examined. Participants Ninety-three fourth graders (47 with normal hearing, 46 with cochlear implants) participated, all of whom were in a longitudinal study and had working memory assessed 2 years earlier. Method A dual-component model of working memory was adopted, and a serial recall task measured storage and processing. Potential predictor variables were phonological awareness, vocabulary knowledge, nonverbal IQ, and several treatment variables. Potential dependent functions were literacy, expressive language, and speech-in-noise recognition. Results Children with cochlear implants showed deficits in storage and processing, similar in size to those at second grade. Predictors of verbal working memory differed across groups: Phonological awareness explained the most variance in children with normal hearing; vocabulary explained the most variance in children with cochlear implants. Treatment variables explained little of the variance. Where potentially dependent functions were concerned, verbal working memory accounted for little variance once the variance explained by other predictors was removed. Conclusions The verbal working memory deficits of children with cochlear implants arise due to signal degradation, which limits their abilities to acquire phonological awareness. That hinders their abilities to store items using a phonological code. PMID:29075747

Visual cognition in amnesic H.M.: selective deficits on the What's-Wrong-Here and Hidden-Figure tasks.

PubMed

MacKay, Donald G; James, Lori E

2009-10-01

Two experiments compared the visual cognition performance of amnesic H.M. and memory-normal controls matched for age, background, intelligence, and education. In Experiment 1 H.M. exhibited deficits relative to the controls in detecting "erroneous objects" in complex visual scenes--for example, a bird flying inside a fishbowl. In Experiment 2 H.M. exhibited deficits relative to the controls in standard Hidden-Figure tasks when detecting unfamiliar targets but not when detecting familiar targets--for example, circles, squares, and right-angle triangles. H.M.'s visual cognition deficits were not due to his well-known problems in explicit learning and recall, inability to comprehend or remember the instructions, general slowness, motoric difficulties, low motivation, low IQ relative to the controls, or working-memory limitations. Parallels between H.M.'s selective deficits in visual cognition, language, and memory are discussed. These parallels contradict the standard "systems theory" account of H.M.'s condition but comport with the hypothesis that H.M. has difficulty representing unfamiliar but not familiar information in visual cognition, language, and memory. Implications of our results are discussed for binding theory and the ongoing debate over what counts as "memory" versus "not-memory."

[Physiopathology of autobiographical memory in aging: episodic and semantic distinction, clinical findings and neuroimaging studies].

PubMed

Piolino, Pascale; Martinelli, Pénélope; Viard, Armelle; Noulhiane, Marion; Eustache, Francis; Desgranges, Béatrice

2010-01-01

From an early age, autobiographical memory models our feeling of identity and continuity. It grows throughout lifetime with our experiences and is built up from general self-knowledge and specific memories. The study of autobiographical memory depicts the dynamic and reconstructive features of this type of long-term memory, combining both semantic and episodic aspects, its strength and fragility. In this article, we propose to illustrate the properties of autobiographical memory from the field of cognitive psychology, neuropsychology and neuroimaging research through the analysis of the mechanisms of disturbance in normal and Alzheimer's disease. We show that the cognitive and neural bases of autobiographical memory are distinct in both cases. In normal aging, autobiographical memory retrieval is mainly dependent on frontal/executive function and on sense of reexperiencing specific context connected to hippocampal regions regardless of memory remoteness. In Alzheimer's disease, autobiographical memory deficit, characterized by a Ribot's temporal gradient, is connected to different regions according to memory remoteness. Our functional neuroimaging results suggest that patients at the early stage can compensate for their massive deficit of episodic recent memories correlated to hippocampal alteration with over general remote memories related to prefrontal regions. On the whole, the research findings allowed initiating new autobiographical memory studies by comparing normal and pathological aging and developing cognitive methods of memory rehabilitation in patients based on preserved personal semantic capacity. © Société de Biologie, 2010.

Apoptosis of mouse hippocampal cells induced by Taenia crassiceps metacestode factor.

PubMed

Zepeda, N; Solano, S; Copitin, N; Chávez, J L; Fernández, A M; García, F; Tato, P; Molinari, J L

2017-03-01

Seizures, headache, depression and neurological deficits are the signs and symptoms most frequently reported in human neurocysticercosis. However, the cause of the associated learning and memory deficits is unknown. Here, we used Taenia crassiceps infection in mice as a model of human cysticercosis. The effects of T. crassiceps metacestode infection or T. crassiceps metacestode factor (MF) treatment on mouse hippocampal cells were studied; control mice were included. At 45 days after infection or treatment of the mice with MF, all mice were anaesthetized and perfused transcardially with saline followed by phosphate-buffered 10% formalin. Then the brains were carefully removed. Coronal sections stained using several techniques were analysed. Extensive and significant apoptosis was found in the experimental animals, mainly in the dentate gyrus, CA1, CA2, CA3 and neighbouring regions, in comparison with the apparently intact cells from control mice (P < 0.01). These results suggest that neurological deficits, especially the learning and memory deficits, may be generated by extensive apoptosis of hippocampal cells.

Effects of medicinal plants on Alzheimer's disease and memory deficits

PubMed Central

Akram, Muhammad; Nawaz, Allah

2017-01-01

Alzheimer's disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer's disease. However, the proper treatment option is still not available. There is no cure for Alzheimer's disease, but symptomatic treatment may improve the memory and other dementia related problems. Traditional medicine is practiced worldwide as memory enhancer since ancient times. Natural therapy including herbs and medicinal plants has been used in the treatment of memory deficits such as dementia, amnesia, as well as Alzheimer's disease since a long time. Medicinal plants have been used in different systems of medicine, particularly Unani system of medicines and exhibited their powerful roles in the management and cure of memory disorders. Most of herbs and plants have been chemically evaluated and their efficacy has also been proven in clinical trials. However, the underlying mechanisms of actions are still on the way. In this paper, we have reviewed the role of different medicinal plants that play an important role in the treatment of Alzheimer's disease and memory deficits using conventional herbal therapy. PMID:28553349

CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory

PubMed Central

Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J

2016-01-01

Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV. DOI: http://dx.doi.org/10.7554/eLife.20985.001 PMID:27996938

Congenital amusia: a short-term memory deficit for non-verbal, but not verbal sounds.

PubMed

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

2009-12-01

Congenital amusia refers to a lifelong disorder of music processing and is linked to pitch-processing deficits. The present study investigated congenital amusics' short-term memory for tones, musical timbres and words. Sequences of five events (tones, timbres or words) were presented in pairs and participants had to indicate whether the sequences were the same or different. The performance of congenital amusics confirmed a memory deficit for tone sequences, but showed normal performance for word sequences. For timbre sequences, amusics' memory performance was impaired in comparison to matched controls. Overall timbre performance was found to be correlated with melodic contour processing (as assessed by the Montreal Battery of Evaluation of Amusia). The present findings show that amusics' deficits extend to non-verbal sound material other than pitch, in this case timbre, while not affecting memory for verbal material. This is in line with previous suggestions about the domain-specificity of congenital amusia.

Poor comprehenders in the classroom: teacher ratings of behavior in children with poor reading comprehension and its relationship with individual differences in working memory.

PubMed

Pimperton, Hannah; Nation, Kate

2014-01-01

Differing etiological explanations have been proposed to account for poor comprehenders' difficulties with reading comprehension, with some researchers emphasizing working memory deficits and others arguing for oral language weaknesses playing a key causal role. The authors contrasted these two theoretical accounts using data obtained from direct measures of working memory and from teacher ratings of poor comprehenders' behavior in the classroom. At the group level, poor comprehenders showed weaknesses on verbal but not nonverbal working memory tasks, in keeping with the "language account." However, they also showed evidence of elevated levels of problem behaviors specifically associated with working memory deficits. Further analysis revealed that these group differences in working-memory-related problem behaviors were carried by a small subgroup of poor comprehenders who also displayed domain-general (verbal and nonverbal) working memory problems, argued to be reflective of "genuine" underlying working memory deficits.

Gulf War agent exposure causes impairment of long-term memory formation and neuropathological changes in a mouse model of Gulf War Illness.

PubMed

Zakirova, Zuchra; Tweed, Miles; Crynen, Gogce; Reed, Jon; Abdullah, Laila; Nissanka, Nadee; Mullan, Myles; Mullan, Michael J; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

2015-01-01

Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component such as memory deficits, neurological, and musculoskeletal problems. There are ample data that demonstrate that exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and pesticides such as permethrin (PER), were key contributors to the etiology of GWI post deployment to the Persian GW. In the current study, we examined the consequences of acute (10 days) exposure to PB and PER in C57BL6 mice. Learning and memory tests were performed at 18 days and at 5 months post-exposure. We investigated the relationship between the cognitive phenotype and neuropathological changes at short and long-term time points post-exposure. No cognitive deficits were observed at the short-term time point, and only minor neuropathological changes were detected. However, cognitive deficits emerged at the later time point and were associated with increased astrogliosis and reduction of synaptophysin staining in the hippocampi and cerebral cortices of exposed mice, 5 months post exposure. In summary, our findings in this mouse model of GW agent exposure are consistent with some GWI symptom manifestations, including delayed onset of symptoms and CNS disturbances observed in GWI veterans.

Gulf War Agent Exposure Causes Impairment of Long-Term Memory Formation and Neuropathological Changes in a Mouse Model of Gulf War Illness

PubMed Central

Zakirova, Zuchra; Tweed, Miles; Crynen, Gogce; Reed, Jon; Abdullah, Laila; Nissanka, Nadee; Mullan, Myles; Mullan, Michael J.; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

2015-01-01

Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component such as memory deficits, neurological, and musculoskeletal problems. There are ample data that demonstrate that exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and pesticides such as permethrin (PER), were key contributors to the etiology of GWI post deployment to the Persian GW. In the current study, we examined the consequences of acute (10 days) exposure to PB and PER in C57BL6 mice. Learning and memory tests were performed at 18 days and at 5 months post-exposure. We investigated the relationship between the cognitive phenotype and neuropathological changes at short and long-term time points post-exposure. No cognitive deficits were observed at the short-term time point, and only minor neuropathological changes were detected. However, cognitive deficits emerged at the later time point and were associated with increased astrogliosis and reduction of synaptophysin staining in the hippocampi and cerebral cortices of exposed mice, 5 months post exposure. In summary, our findings in this mouse model of GW agent exposure are consistent with some GWI symptom manifestations, including delayed onset of symptoms and CNS disturbances observed in GWI veterans. PMID:25785457

The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects.

PubMed

Sadeghi, Akram; Hami, Javad; Razavi, Shahnaz; Esfandiary, Ebrahim; Hejazi, Zahra

2016-01-01

Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus. The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms. Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes. Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals.

Can Motivation Normalize Working Memory and Task Persistence in Children with Attention-Deficit/Hyperactivity Disorder? The Effects of Money and Computer-Gaming

ERIC Educational Resources Information Center

Dovis, Sebastiaan; van der Oord, Saskia; Wiers, Reinout W.; Prins, Pier J. M.

2012-01-01

Visual-spatial "Working Memory" (WM) is the most impaired executive function in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Some suggest that deficits in executive functioning are caused by motivational deficits. However, there are no studies that investigate the effects of motivation on the visual-spatial WM of children with-…

A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice.

PubMed

Ronca, Richard D; Myers, Alyssa M; Ganea, Doina; Tuma, Ronald F; Walker, Ellen A; Ward, Sara Jane

2015-10-01

We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size. Mice received three injections of the CB2 selective agonist O-1966 or vehicle 1h prior to and 2 and 5days following induction of stroke. Infarct size was assessed at 1, 3, or 7days post-injury and learning and memory effects of injury and O-1966 treatment were assessed on days 6 and 7 using a novel object recognition task and an operant acquisition and retention procedure. O-1966 treated mice had significantly smaller infarct volumes compared with vehicle treated mice. Photoinjury was also associated with a significant memory impairment on day 7 post-injury, and this deficit was reversed with O-1966 treatment. Surprisingly, sham-operated mice receiving O-1966 treatment showed a significant learning deficit in both the recognition and operant tasks compared with vehicle treated sham mice. We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia, but may dysregulate glial or neuronal function of learning and memory circuits in the absence of injury and/or inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

A Contextual View of Adult Learning and Memory.

ERIC Educational Resources Information Center

Glynn, Shawn M.

Explanations of age-related differences in adult memory usually assume two forms: processing deficits and structural deficits. Processing deficit explanations attribute recall differences to a failure of older adults to effectively use the processes of attention, organization, mediation (the use of such devices as visual images and verbal images…

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

ERIC Educational Resources Information Center

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

2012-01-01

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

Measuring Working Memory Deficits in Aphasia

ERIC Educational Resources Information Center

Mayer, Jamie F.; Murray, Laura L.

2012-01-01

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

Computerized Training of Working Memory in Children with ADHD-A Randomized, Controlled Trial

ERIC Educational Resources Information Center

Klingberg, Torkel; Fernell, Elisabeth; Olesen, Pernille J.; Johnson, Mats; Gustafsson, Per; Dahlstrom, Kerstin; Gillberg, Christopher G.; Forssberg, Hans; Westerberg, Helena

2005-01-01

Objective: Deficits in executive functioning, including working memory (WM) deficits, have been suggested to be important in attention-deficit/hyperactivity disorder (ADHD). During 2002 to 2003, the authors conducted a multicenter, randomized, controlled, double-blind trial to investigate the effect of improving WM by computerized, systematic…

Phonological Storage and Executive Function Deficits in Children with Mathematics Difficulties

ERIC Educational Resources Information Center

Peng, Peng; Congying, Sun; Beilei, Li; Sha, Tao

2012-01-01

Children with mathematics difficulties suffer from working memory deficits. This study investigated the deficit profile of phonological storage and executive functions in working memory among children with mathematics difficulties. Based on multiple instruments and two assessment points, 68 children were screened out of 805 fifth graders. Of these…

Organizational and visual memory deficits in schizophrenia and bipolar psychoses using the Rey-Osterrieth complex figure: effects of duration of illness.

PubMed

Seidman, Larry J; Lanca, Margaret; Kremen, William S; Faraone, Stephen V; Tsuang, Ming T

2003-10-01

Verbal declarative memory deficits in schizophrenia are well documented whereas visual declarative memory is less studied. Moreover, there are limited data on whether organizational and visual memory deficits are specific to schizophrenic psychoses. We compared visual memory and organizational function in patients with chronic schizophrenia (n=79) and chronic bipolar psychotic disorder (n=14), and in healthy controls (n=84) using the Rey-Osterrieth Complex Figure (ROCF), testing whether organizational impairments (i.e., executive dysfunctions) account for the visual memory deficit. Groups were comparable on age, handedness and expected intellectual ability (based on single word reading). Using analyses of covariance with sex, parental SES and ethnicity as co-variates, patients with schizophrenia were significantly more impaired than controls on copy accuracy, on recall accuracy, and on percent accuracy of recall. Patients with schizophrenia used a more detail-oriented style on copy and recall and had significantly worse recognition memory. After co-varying IQ, copy organization was also significantly different between the groups. Results for accuracy of copy and recall were not significantly attenuated when controlling for copy organization. Duration of illness was associated with visual memory. Bipolar patients performed at an intermediate level between controls and patients with schizophrenia. The data suggest that in schizophrenia, patients have a visual memory disorder characterized by both organizational processing impairments and retention difficulties, and that there is a decline in visual memory functions with duration of illness. Further research is required to determine whether similar mechanisms underlie the neurocognitive deficits in these psychotic disorders.

Effects of mild cognitive impairment on emotional scene memory.

PubMed

Waring, J D; Dimsdale-Zucker, H R; Flannery, S; Budson, A E; Kensinger, E A

2017-02-01

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.

Deficits in temporal order memory induced by interferon-alpha (IFN-α) treatment are rescued by aerobic exercise.

PubMed

Barlow, Sally; Fahey, Briana; Smith, Kimberley J; Passecker, Johannes; Della-Chiesa, Andrea; Hok, Vincent; Day, Jennifer S; Callaghan, Charlotte K; O'Mara, Shane M

2018-05-18

Patients receiving cytokine immunotherapy with IFN-α frequently present with neuropsychiatric consequences and cognitive impairments, including a profound depressive-like symptomatology. While the neurobiological substrates of the dysfunction that leads to adverse events in IFN-α-treated patients remains ill-defined, dysfunctions of the hippocampus and prefrontal cortex (PFC) are strong possibilities. To date, hippocampal deficits have been well-characterised; there does however remain a lack of insight into the nature of prefrontal participation. Here, we used a PFC-supported temporal order memory paradigm to examine if IFN-α treatment induced deficits in performance; additionally, we used an object recognition task to assess the integrity of the perirhinal cortex (PRH). Finally, the utility of exercise as an ameliorative strategy to recover temporal order deficits in rats was also explored. We found that IFN-α-treatment impaired temporal order memory discriminations, whereas recognition memory remained intact, reflecting a possible dissociation between recognition and temporal order memory processing. Further characterisation of temporal order memory impairments using a longitudinal design revealed that deficits persisted for 10 weeks following cessation of IFN-α-treatment. Finally, a 6 week forced exercise regime reversed IFN-α-induced deficits in temporal order memory. These data provide further insight into the circuitry involved in cognitive impairments arising from IFN-α-treatment. Here we suggest that PFC (or the hippocampo-prefrontal pathway) may be compromised whilst the function of the PRH is preserved. Deficits may persist after cessation of IFN-α-treatment which suggests that extended patient monitoring is required. Aerobic exercise may be restorative and could prove beneficial for patients treated with IFN-α. Copyright © 2018 Elsevier Inc. All rights reserved.

The relation between working memory components and ADHD symptoms from a developmental perspective.

PubMed

Tillman, Carin; Eninger, Lilianne; Forssman, Linda; Bohlin, Gunilla

2011-01-01

The objective was to examine the relations between attention deficit hyperactivity disorder (ADHD) symptoms and four working memory (WM) components (short-term memory and central executive in verbal and visuospatial domains) in 284 6-16-year-old children from the general population. The results showed that verbal and visuospatial short-term memory and verbal central executive uniquely contributed to inattention symptoms. Age interacted with verbal short-term memory in predicting inattention, with the relation being stronger in older children. These findings support the notion of ADHD as a developmental disorder, with changes in associated neuropsychological deficits across time. The results further indicate ADHD-related deficits in several specific WM components.

A multiple deficit model of reading disability and attention-deficit/hyperactivity disorder: searching for shared cognitive deficits.

PubMed

McGrath, Lauren M; Pennington, Bruce F; Shanahan, Michelle A; Santerre-Lemmon, Laura E; Barnard, Holly D; Willcutt, Erik G; Defries, John C; Olson, Richard K

2011-05-01

This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity. A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique predictor of RD and response inhibition as a unique predictor of ADHD. Processing speed, naming speed, and verbal working memory were modeled as potential shared cognitive deficits. Model fit indices from the SEM indicated satisfactory fit. Closer inspection of the path weights revealed that processing speed was the only cognitive variable with significant unique relationships to RD and ADHD dimensions, particularly inattention. Moreover, the significant correlation between reading and inattention was reduced to non-significance when processing speed was included in the model, suggesting that processing speed primarily accounted for the phenotypic correlation (or comorbidity) between reading and inattention. This study illustrates the power of a multiple deficit approach to complex developmental disorders and psychopathologies, particularly for exploring comorbidities. The theoretical role of processing speed in the developmental pathways of RD and ADHD and directions for future research are discussed. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.

Neuritin reverses deficits in murine novel object associative recognition memory caused by exposure to extremely low-frequency (50 Hz) electromagnetic fields

PubMed Central

Zhao, Qian-Ru; Lu, Jun-Mei; Yao, Jin-Jing; Zhang, Zheng-Yu; Ling, Chen; Mei, Yan-Ai

2015-01-01

Animal studies have shown that electromagnetic field exposure may interfere with the activity of brain cells, thereby generating behavioral and cognitive disturbances. However, the underlying mechanisms and possible preventions are still unknown. In this study, we used a mouse model to examine the effects of exposure to extremely low-frequency (50 Hz) electromagnetic fields (ELF MFs) on a recognition memory task and morphological changes of hippocampal neurons. The data showed that ELF MFs exposure (1 mT, 12 h/day) induced a time-dependent deficit in novel object associative recognition memory and also decreased hippocampal dendritic spine density. This effect was observed without corresponding changes in spontaneous locomotor activity and was transient, which has only been seen after exposing mice to ELF MFs for 7-10 days. The over-expression of hippocampal neuritin, an activity-dependent neurotrophic factor, using an adeno-associated virus (AAV) vector significantly increased the neuritin level and dendritic spine density. This increase was paralleled with ELF MFs exposure-induced deficits in recognition memory and reductions of dendritic spine density. Collectively, our study provides evidence for the association between ELF MFs exposure, impairment of recognition memory, and resulting changes in hippocampal dendritic spine density. Neuritin prevented this ELF MFs-exposure-induced effect by increasing the hippocampal spine density. PMID:26138388

Neuritin reverses deficits in murine novel object associative recognition memory caused by exposure to extremely low-frequency (50 Hz) electromagnetic fields.

PubMed

Zhao, Qian-Ru; Lu, Jun-Mei; Yao, Jin-Jing; Zhang, Zheng-Yu; Ling, Chen; Mei, Yan-Ai

2015-07-03

Animal studies have shown that electromagnetic field exposure may interfere with the activity of brain cells, thereby generating behavioral and cognitive disturbances. However, the underlying mechanisms and possible preventions are still unknown. In this study, we used a mouse model to examine the effects of exposure to extremely low-frequency (50 Hz) electromagnetic fields (ELF MFs) on a recognition memory task and morphological changes of hippocampal neurons. The data showed that ELF MFs exposure (1 mT, 12 h/day) induced a time-dependent deficit in novel object associative recognition memory and also decreased hippocampal dendritic spine density. This effect was observed without corresponding changes in spontaneous locomotor activity and was transient, which has only been seen after exposing mice to ELF MFs for 7-10 days. The over-expression of hippocampal neuritin, an activity-dependent neurotrophic factor, using an adeno-associated virus (AAV) vector significantly increased the neuritin level and dendritic spine density. This increase was paralleled with ELF MFs exposure-induced deficits in recognition memory and reductions of dendritic spine density. Collectively, our study provides evidence for the association between ELF MFs exposure, impairment of recognition memory, and resulting changes in hippocampal dendritic spine density. Neuritin prevented this ELF MFs-exposure-induced effect by increasing the hippocampal spine density.

The hippocampo-amygdala control of contextual fear expression is affected in a model of intellectual disability.

PubMed

Zhang, Chun-Lei; Houbaert, Xander; Lepleux, Marilyn; Deshors, Melissa; Normand, Elisabeth; Gambino, Frédéric; Herzog, Etienne; Humeau, Yann

2015-11-01

The process of learning mainly depends on the ability to store new information, while the ability to retrieve this information and express appropriate behaviors are also crucial for the adaptation of individuals to environmental cues. Thereby, all three components contribute to the cognitive fitness of an individual. While a lack of behavioral adaptation is a recurrent trait of intellectually disabled patients, discriminating between memory formation, memory retrieval or behavioral expression deficits is not easy to establish. Here, we report some deficits in contextual fear behavior in knockout mice for the intellectual disability gene Il1rapl1. Functional in vivo experiments revealed that the lack of conditioned response resulted from a local inhibitory to excitatory (I/E) imbalance in basolateral amygdala (BLA) consecutive to a loss of excitatory drive onto BLA principal cells by caudal hippocampus axonal projections. A normalization of the fear behavior was obtained in adult mutant mice following opsin-based in vivo synaptic priming of hippocampo-BLA synapses in adult il1rapl1 knockout mice, indicating that synaptic efficacy at hippocampo-BLA projections is crucial for contextual fear memory expression. Importantly, because this restoration was obtained after the learning phase, our results suggest that some of the genetically encoded cognitive deficits in humans may originate from a lack of restitution of genuinely formed memories rather than an exclusive inability to store new memories.

Dopaminergic basis for deficits in working memory but not attentional set-shifting in Parkinson's disease.

PubMed

Lewis, Simon J G; Slabosz, Aleksandra; Robbins, Trevor W; Barker, Roger A; Owen, Adrian M

2005-01-01

Although Parkinson's disease is a common neurodegenerative disorder characterised by its motoric symptoms, there is an increasing recognition of accompanying impairments in cognition that have a profound impact on the quality of life of these patients. These deficits predominantly affect executive function and impairments of working memory have been frequently reported. However, the underlying neurochemical and pathological basis for these deficits are not well understood. In this study, 20 patients were tested 'on' and 'off' levodopa (L-dopa) medication on a task that allowed different aspects of working memory function such as maintenance, retrieval and manipulation to be tested within the same general paradigm as well as on an unrelated test of attentional set-shifting, which is known to be sensitive to deficits in early Parkinson's disease. Compared to healthy volunteers, PD patients were impaired at manipulation more than maintenance or retrieval of information within working memory. The patients were also impaired at the attentional set-shifting task. However, whereas L-dopa ameliorated the working memory deficit in manipulation (improving both accuracy and cognitive response time), it had no effect on the attentional set-shifting impairment. These results confirm that working memory deficits in PD are both psychologically specific and related to dopamine depletion. It is anticipated that greater understanding of these mechanisms will lead to future therapeutic improvements.

Transcranial oscillatory direct current stimulation during sleep improves declarative memory consolidation in children with attention-deficit/hyperactivity disorder to a level comparable to healthy controls.

PubMed

Prehn-Kristensen, Alexander; Munz, Manuel; Göder, Robert; Wilhelm, Ines; Korr, Katharina; Vahl, Wiebke; Wiesner, Christian D; Baving, Lioba

2014-01-01

Slow oscillations (<1 Hz) during slow wave sleep (SWS) promote the consolidation of declarative memory. Children with attention-deficit/hyperactivity disorder (ADHD) have been shown to display deficits in sleep-dependent consolidation of declarative memory supposedly due to dysfunctional slow brain rhythms during SWS. Using transcranial oscillating direct current stimulation (toDCS) at 0.75 Hz, we investigated whether an externally triggered increase in slow oscillations during early SWS elevates memory performance in children with ADHD. 12 children with ADHD underwent a toDCS and a sham condition in a double-blind crossover study design conducted in a sleep laboratory. Memory was tested using a 2D object-location task. In addition, 12 healthy children performed the same memory task in their home environment. Stimulation enhanced slow oscillation power in children with ADHD and boosted memory performance to the same level as in healthy children. These data indicate that increasing slow oscillation power during sleep by toDCS can alleviate declarative memory deficits in children with ADHD. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

A longitudinal study of neuropsychological functioning and academic achievement in children with and without signs of attention-deficit/hyperactivity disorder.

PubMed

Rennie, Brandon; Beebe-Frankenberger, Margaret; Swanson, H Lee

2014-01-01

Attention-deficit/hyperactivity disorder (ADHD) in childhood is associated with poor academic functioning. Deficits in academic functioning have proven to be less responsive to intervention than behavioral deficits in this population, yet the causes of this academic underperformance are not well understood. The purpose of this study is to examine the relationship between ADHD and academic performance in elementary-aged children in a developmental context. To do this, we study important cognitive variables and academic achievement over a three-year timeframe. Based on teacher ratings of ADHD, children were divided into a high symptom group (n = 17) and a low symptom group (n = 34). A thorough battery of cognitive and academic tests was administered at Time 1 and again 2 years later. Cognitive measures focused specifically on working memory and response inhibition. RESULTS indicate that children who have high levels of ADHD signs differ from their low-sign peers in academic achievement and in several cognitive domains. Differences in cognitive functioning show a developmental trend consistent with earlier developmental delays in response inhibition and later delays in working memory. Working memory appears to be particularly important in several academic domains. Importantly, in a longitudinal model, working memory was more predictive of math achievement for students demonstrating signs of ADHD than for those who did not. The relationship between these cognitive variables and academic functioning are explicated in the domains of reading, math, and problem solving.

Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine.

PubMed

Ando, Susumu; Kobayashi, Satoru; Waki, Hatsue; Kon, Kazuo; Fukui, Fumiko; Tadenuma, Tomoko; Iwamoto, Machiko; Takeda, Yasuo; Izumiyama, Naotaka; Watanabe, Kazutada; Nakamura, Hiroaki

2002-11-01

A rat dementia model with cognitive deficits was generated by synapse-specific lesions using botulinum neurotoxin (BoNTx) type B in the entorhinal cortex. To detect cognitive deficits, different tasks were needed depending upon the age of the model animals. Impaired learning and memory with lesions were observed in adult rats using the Hebb-Williams maze, AKON-1 maze and a continuous alternation task in T-maze. Cognitive deficits in lesioned aged rats were detected by a continuous alternation and delayed non-matching-to-sample tasks in T-maze. Adenovirus-mediated BDNF gene expression enhanced neuronal plasticity, as revealed by behavioral tests and LTP formation. Chronic administration of carnitine over time pre- and post-lesions seemed to partially ameliorate the cognitive deficits caused by the synaptic lesion. The carnitine-accelerated recovery from synaptic damage was observed by electron microscopy. These results demonstrate that the BoNTx-lesioned rat can be used as a model for dementia and that cognitive deficits can be alleviated in part by BDNF gene transfer or carnitine administration. Copyright 2002 Wiley-Liss, Inc.

Working memory arrest in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder: results from a 2-year longitudinal study.

PubMed

Andersen, Per N; Skogli, Erik W; Hovik, Kjell T; Geurts, Hilde; Egeland, Jens; Øie, Merete

2015-05-01

The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically developing children (age 9-16 years) were included at baseline and followed up approximately 25 months later. The children were given a letter/number sequencing task to assess verbal working memory. The performance of children with high-functioning autism on verbal working memory did not improve after 2 years, while improvement was observed in children with attention-deficit/hyperactivity disorder and typically developing children. The results indicate a different developmental trajectory for verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. More research is needed to construct a developmental framework more suitable for children with autism spectrum disorder. © The Author(s) 2014.

Effects of Ketamine on Context-Processing Performance in Monkeys: A New Animal Model of Cognitive Deficits in Schizophrenia

PubMed Central

Blackman, Rachael K; MacDonald, Angus W; Chafee, Matthew V

2013-01-01

Cognitive deficits are at the crux of why many schizophrenia patients have poor functional outcomes. One of the cognitive symptoms experienced by schizophrenia patients is a deficit in context processing, the ability to use contextual information stored in working memory to adaptively respond to subsequent stimuli. As such, context processing can be thought of as the intersection between working memory and executive control. Although deficits in context processing have been extensively characterized by neuropsychological testing in schizophrenia patients, they have never been effectively translated to an animal model of the disease. To bridge that gap, we trained monkeys to perform the same dot pattern expectancy (DPX) task, which has been used to measure context-processing deficits in human patients with schizophrenia. In the DPX task, the first stimulus in each trial provides the contextual information that subjects must remember in order to appropriately respond to the second stimulus in the trial. We found that administration of ketamine, an N-methyl-D-aspartate receptor antagonist, in monkeys caused a dose-dependent failure in context processing, replicating in monkeys the same specific pattern of errors committed by patients with schizophrenia when performing the same task. Therefore, our results provide the first evidence that context-processing dysfunction can be modeled in animals. Replicating a schizophrenia-like behavioral performance pattern in monkeys performing the same task used in humans provides a strong bridge to better understand the biological basis for this psychiatric disease and its cognitive manifestations using animal models. PMID:23660706

Interference control in working memory: comparing groups of children with atypical development.

PubMed

Palladino, Paola; Ferrari, Marcella

2013-01-01

The study aimed to test whether working memory deficits in children at risk of Learning Disabilities (LD) and/or attention deficit/hyperactivity disorder (ADHD) can be attributed to deficits in interference control, thereby implicating prefrontal systems. Two groups of children known for showing poor working memory (i.e., children with poor comprehension and children with ADHD) were compared to a group of children with specific reading decoding problems (i.e., having severe problems in phonological rather than working memory) and to a control group. All children were tested with a verbal working memory task. Interference control of irrelevant items was examined by a lexical decision task presented immediately after the final recall in about half the trials, selected at random. The interference control measure was therefore directly related to working memory performance. Results confirmed deficient working memory performance in poor comprehenders and children at risk of ADHD + LD. More interestingly, this working memory deficit was associated with greater activation of irrelevant information than in the control group. Poor decoders showed more efficient interference control, in contrast to poor comprehenders and ADHD + LD children. These results indicated that interfering items were still highly accessible to working memory in children who fail the working memory task. In turn, these findings strengthen and clarify the role of interference control, one of the most critical prefrontal functions, in working memory.

Changes in Tryptophan Catabolite (TRYCAT) Pathway Patterning Are Associated with Mild Impairments in Declarative Memory in Schizophrenia and Deficits in Semantic and Episodic Memory Coupled with Increased False-Memory Creation in Deficit Schizophrenia.

PubMed

Kanchanatawan, Buranee; Hemrungrojn, Solaphat; Thika, Supaksorn; Sirivichayakul, Sunee; Ruxrungtham, Kiat; Carvalho, André F; Geffard, Michel; Anderson, George; Maes, Michael

2018-06-01

Evidence indicates that schizophrenia and in particular negative symptoms and deficit schizophrenia are accompanied by neurocognitive impairments and changes in the patterning of the tryptophan catabolite (TRYCAT) pathway. This cross-sectional study was carried out to examine the associations between cognitive functions (as measured with Consortium to Establish a Registry for Alzheimer's disease (CERAD)) and TRYCAT pathway patterning in patients with (n = 40) and without (n = 40) deficit schizophrenia and normal controls (n = 40). Cognitive measures were assessed with the Verbal Fluency Test (VFT), Boston Naming Test (BNT), Mini-Mental State Examination (MMSE), Word List Memory (WLM), Constructional Praxis, Word List Recall (WLRecall), and Word List Recognition (WLRecognition), while TRYCAT measurements assessed the IgA/IgM responses to noxious TRYCATs, namely quinolinic acid (QA), 3-OH-kynurenine (3HK), picolinic acid (PA), and xanthurenic (XA) acid, and more protective (PRO) TRYCATs, including kynurenic acid (KA) and anthranilic acid (AA). IgA NOX/PRO, IgM KA/3HK, and IgA/IgM NOX/PRO ratios were computed. Schizophrenia was accompanied by lower VFT and WLM, while BNT (dysnomia) and MMSE are significantly lower in multiple- than first-episode schizophrenia. Deficit schizophrenia is strongly associated with worse outcomes on VFT, MMSE, WLM, WLRecall, WLRecognition, and delayed recall savings and increased false memories. Around 40-50% of the variance in negative symptoms' scores was explained by VFT, WLM, WLRecall, and MMSE. Increases in IgA NOX/PRO, IgM KA/3HK, and/or IgA/IgM NOX/PRO ratios were associated with impairments in VFT, BNT, MMSE, WLM, WLRecall, WLRecognition, and false-memory creation. In conclusion, nondeficit schizophrenia is accompanied by mild memory impairments, while disease progression is accompanied by broader cognitive impairments. Deficit schizophrenia and negative symptoms are strongly associated with deficits in working memory, delayed recall and recognition, and increased false-memory creation. These cognitive impairments and memory deficits are in part explained by increased production and/or attenuated regulation of TRYCATs with neurotoxic, excitotoxic, immune-inflammatory, oxidative, and nitrosative potential, which may contribute to neuroprogression.

ADHD and working memory: the impact of central executive deficits and exceeding storage/rehearsal capacity on observed inattentive behavior.

PubMed

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

2010-02-01

Inattentive behavior is considered a core and pervasive feature of ADHD; however, an alternative model challenges this premise and hypothesizes a functional relationship between working memory deficits and inattentive behavior. The current study investigated whether inattentive behavior in children with ADHD is functionally related to the domain-general central executive and/or subsidiary storage/rehearsal components of working memory. Objective observations of children's attentive behavior by independent observers were conducted while children with ADHD (n = 15) and typically developing children (n = 14) completed counterbalanced tasks that differentially manipulated central executive, phonological storage/rehearsal, and visuospatial storage/rehearsal demands. Results of latent variable and effect size confidence interval analyses revealed two conditions that completely accounted for the attentive behavior deficits in children with ADHD: (a) placing demands on central executive processing, the effect of which is evident under even low cognitive loads, and (b) exceeding storage/rehearsal capacity, which has similar effects on children with ADHD and typically developing children but occurs at lower cognitive loads for children with ADHD.

An Intracellular Threonine of Amyloid-β Precursor Protein Mediates Synaptic Plasticity Deficits and Memory Loss

PubMed Central

Lombino, Franco; Biundo, Fabrizio; Tamayev, Robert; Arancio, Ottavio; D’Adamio, Luciano

2013-01-01

Mutations in Amyloid-ß Precursor Protein (APP) and BRI2/ITM2b genes cause Familial Alzheimer and Danish Dementias (FAD/FDD), respectively. APP processing by BACE1, which is inhibited by BRI2, yields sAPPß and ß-CTF. ß-CTF is cleaved by gamma-secretase to produce Aß. A knock-in mouse model of FDD, called FDDKI, shows deficits in memory and synaptic plasticity, which can be attributed to sAPPß/ß-CTF but not Aß. We have investigated further the pathogenic function of ß-CTF focusing on Thr668 of ß-CTF because phosphorylation of Thr668 is increased in AD cases. We created a knock-in mouse bearing a Thr668Ala mutation (APPTA mice) that prevents phosphorylation at this site. This mutation prevents the development of memory and synaptic plasticity deficits in FDDKI mice. These data are consistent with a role for the carboxyl-terminal APP domain in the pathogenesis of dementia and suggest that averting the noxious role of Thr668 is a viable therapeutic strategy for human dementias. PMID:23451158

Emerging Depression Is Associated with Face Memory Deficits in Adolescent Girls

ERIC Educational Resources Information Center

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

2011-01-01

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

Clinical correlates of working memory deficits in youth with and without ADHD: A controlled study.

PubMed

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

2016-01-01

Both working memory (WM; a brain system that provides temporary storage and manipulation of the information) and attention-deficit/hyperactivity disorder (ADHD) have been associated with educational deficits. Since WM deficits are prevalent in children with ADHD, the main aim of the present study was to examine whether educational deficits are driven by working memory deficits or driven by the effect of ADHD itself. Participants were referred youth with (N = 276) and without (N = 241) ADHD ascertained from pediatric and psychiatric sources. Assessment included measures of psychiatric, psychosocial, educational, and cognitive functioning. Education deficits were defined as grade retention or placement in special classes and were assessed using interviews and written rating scales. Working memory was assessed using the Wechsler Intelligence Scale for Children-Revised (WISC-R) Freedom from Distractibility (FFD) factor based on Digit Span, Arithmetic, and Coding. Significantly more youth with ADHD had WM deficits than controls (31.9% vs. 13.7%, p < .05). In ADHD children, WM deficits were significantly (p < .01) associated with an increased risk for grade retention and placement in special classes as well as lower scores on reading and math achievement tests than for ADHD children without WM deficits. In contrast, no other differences were noted in other areas of functioning. Although WM deficits also had some adverse impact on educational and cognitive correlates in non-ADHD controls, these differences failed to attain statistical significance. WM deficits significantly and selectively increase the risk for academic deficits and cognitive dysfunction in children with ADHD beyond those conferred by ADHD. Screening for WM deficits may help identify children with ADHD at high risk for academic and cognitive dysfunction.

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

PubMed Central

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

2016-01-01

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

Mechanism and treatment for the learning and memory deficits associated with mouse models of Noonan syndrome

PubMed Central

Lee, Yong-Seok; Ehninger, Dan; Zhou, Miou; Oh, Jun-Young; Kang, Minkyung; Kwak, Chuljung; Ryu, Hyun-Hee; Butz, Delana; Araki, Toshiyuki; Cai, Ying; Balaji, J.; Sano, Yoshitake; Nam, Christine I.; Kim, Hyong Kyu; Kaang, Bong-Kiun; Burger, Corinna; Neel, Benjamin G.; Silva, Alcino J.

2015-01-01

In Noonan Syndrome (NS) 30% to 50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated Ptpn11 mutations show hippocampal-dependent spatial learning impairments and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of the PTPN11D61G in adult hippocampus results in increased baseline excitatory synaptic function, deficits in LTP and spatial learning, which can all be reversed by a MEK inhibitor. Furthermore, brief treatment with lovastatin reduces Ras-Erk activation in the brain, and normalizes the LTP and learning deficits in adult Ptpn11D61G/+ mice. Our results demonstrate that increased basal Erk activity and corresponding baseline increases in excitatory synaptic function are responsible for the LTP impairments and, consequently, the learning deficits in mouse models of NS. These data also suggest that lovastatin or MEK inhibitors may be useful for treating the cognitive deficits in NS. PMID:25383899

Strategic retrieval, confabulations, and delusions: theory and data.

PubMed

Gilboa, Asaf

2010-01-01

Based on Moscovitch and Winocur's "working with memory" framework, confabulation is described as a deficit in strategic retrieval processes. The present paper suggests that only a confluence of deficits on multiple memory-related processes leads to confabulation. These are divided into three categories. Core processes that are unique to confabulation and required for its evolution include: (1) an intuitive, rapid, preconscious "feeling of rightness" monitoring, (2) an elaborate conscious "editor" monitoring, and (3) control processes that mediate the decision whether to act upon a retrieved memory. The second category is deficits on constitutional processes which are required for confabulation to occur but are not unique to it. These include the formation of erroneous memory representation, (temporal) context confusion, and deficits in retrieval cue generation. Finally, associated Features of confabulations determine the content "flavour" and frequency of confabulation but are not required for their evolution. Some associated features are magnification of normal reconstructive memory processes such as reliance on generic/schematic representations, and positivity biases in memory, whereas others are abnormal such as perseveration or source memory deficits. Data on deficits in core processes in confabulation are presented. Next, the apparent correspondences between confabulation and delusion are discussed. Considering confabulation within a strategic memory framework may help elucidate both the commonalities and differences between the two symptoms. Delusions are affected by a convergence of abnormal perception and encoding of information, associated with aberrant cognitive schema structure and disordered belief monitoring. Whereas confabulation is primarily a disorder of retrieval, mnemonic aspects of delusions can be described as primarily a disorder of input and integration of information. It is suggested that delusions might share some of the associated features of confabulation but not its core and constitutional processes. Preliminary data in support of this view are presented.

Working Memory in the Classroom: An Inside Look at the Central Executive.

PubMed

Barker, Lauren A

2016-01-01

This article provides a review of working memory and its application to educational settings. A discussion of the varying definitions of working memory is presented. Special attention is given to the various multidisciplinary professionals who work with students with working memory deficits, and their unique understanding of the construct. Definitions and theories of working memory are briefly summarized and provide the foundation for understanding practical applications of working memory to assessment and intervention. Although definitions and models of working memory abound, there is limited consensus regarding universally accepted definitions and models. Current research indicates that developing new models of working memory may be an appropriate paradigm shift at this time. The integration of individual practitioner's knowledge regarding academic achievement, working memory and processing speed could provide a foundation for the future development of new working memory models. Future directions for research should aim to explain how tasks and behaviors are supported by the substrates of the cortico-striatal and the cerebro-cerebellar systems. Translation of neurobiological information into educational contexts will be helpful to inform all practitioners' knowledge of working memory constructs. It will also allow for universally accepted definitions and models of working memory to arise and facilitate more effective collaboration between disciplines working in educational setting.

Exploration of a 'double-jeopardy' hypothesis within working memory profiles for children with specific language impairment.

PubMed

Briscoe, J; Rankin, P M

2009-01-01

Children with specific language impairment (SLI) often experience difficulties in the recall and repetition of verbal information. Archibald and Gathercole (2006) suggested that children with SLI are vulnerable across two separate components of a tripartite model of working memory (Baddeley and Hitch 1974). However, the hierarchical relationship between the 'slave' systems (temporary storage) and the central executive components places a particular challenge for interpreting working memory profiles within a tripartite model. This study aimed to examine whether a 'double-jeopardy' assumption is compatible with a hierarchical relationship between the phonological loop and central executive components of the working memory model in children with SLI. If a strong double-jeopardy assumption is valid for children with SLI, it was predicted that raw scores of working memory tests thought to tap phonological loop and central executive components of tripartite working memory would be lower than the scores of children matched for chronological age and those of children matched for language level, according to independent sources of constraint. In contrast, a hierarchical relationship would imply that a weakness in a slave component of working memory (the phonological loop) would also constrain performance on tests tapping a super-ordinate component (central executive). This locus of constraint would predict that scores of children with SLI on working memory tests that tap the central executive would be weaker relative to the scores of chronological age-matched controls only. Seven subtests of the Working Memory Test Battery for Children (Digit recall, Word recall, Non-word recall, Word matching, Listening recall, Backwards digit recall and Block recall; Pickering and Gathercole 2001) were administered to 14 children with SLI recruited via language resource bases and specialist schools, as well as two control groups matched on chronological age and vocabulary level, respectively. Mean group differences were ascertained by directly comparing raw scores on memory tests linked to different components of the tripartite model using a series of multivariate analyses. The majority of working memory scores of the SLI group were depressed relative to chronological age-matched controls, with the exception of spatial recall (block tapping) and word (order) matching tasks. Marked deficits in serial recall of words and digits were evident, with the SLI group scoring more poorly than the language-ability matched control group on these measures. Impairments of the SLI group on phonological loop tasks were robust, even when covariance with executive working memory scores was accounted for. There was no robust effect of group on complex working memory (central executive) tasks, despite a slight association between listening recall and phonological loop measures. A predominant feature of the working memory profile of SLI was a marked deficit on phonological loop tasks. Although scores on complex working memory tasks were also depressed, there was little evidence for a strong interpretation of double-jeopardy within working memory profiles for these children, rather these findings were consistent with an interpretation of a constraint on phonological loop for children with SLI that operated at all levels of a hierarchical tripartite model of working memory (Baddeley and Hitch 1974). These findings imply that low scores on complex working memory tasks alone do not unequivocally imply an independent deficit in central executive (domain-general) resources of working memory and should therefore be treated cautiously in a clinical context.

The effects of attention on age-related relational memory deficits: Evidence from a novel attentional manipulation

PubMed Central

Kim, So-Yeon; Giovanello, Kelly S.

2011-01-01

Healthy aging is often accompanied by episodic memory decline. Prior studies have consistently demonstrated that older adults show disproportionate deficits in relational memory (RM) relative to item memory (IM). Despite rich evidence of an age-related RM deficit, the source of this deficit remains unspecified. One of the most widely investigated factors of age-related RM impairment is a reduction in attentional resources. However, no prior studies have demonstrated that reduced attentional resources are the critical source of age-related RM deficits. Here, we utilized qualitatively different attention tasks, and tested whether reduced attention for relational processing underlies the RM deficit observed in aging. In Experiment 1, we imposed either item-detection or relation-detection attention tasks on young adults during episodic memory encoding, and found that only the concurrent attention task involving relational processing disproportionately impaired RM performance in young adults. Moreover, by ruling out the possible confound of task-difficulty on the disproportionate RM impairment, we further demonstrated that reduced relational attention is a key factor for the age-related RM deficit. In Experiment 2, we replicated the results from Experiment 1 using different materials of stimuli and found that the effect of relational attention on RM is material-general. The results of Experiment 2 also showed that reducing attentional resources for relational processing in young adults strikingly equated their RM performance to that of older adults. Thus, the current study documents the first evidence that reduced attentional resources for relational processing are a critical factor for the relational memory impairment observed in aging. PMID:21707178

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

ERIC Educational Resources Information Center

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

2005-01-01

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

Addressing Working Memory in Children with Autism through Behavioral Intervention

ERIC Educational Resources Information Center

Baltruschat, Lisa; Hasselhorn, Marcus; Tarbox, Jonathan; Dixon, Dennis R.; Najdowski, Adel C.; Mullins, Ryan D.; Gould, Evelyn R.

2011-01-01

Children with autism often struggle with executive function (EF) deficits, particularly with regard to working memory (WM). Despite the documented deficits in these areas, very little controlled research has evaluated treatments for remediation of EF or WM deficits in children with autism. This study examined the use of positive reinforcement for…

The Item-Specific Deficit Approach to evaluating verbal memory dysfunction: rationale, psychometrics, and application.

PubMed

Wright, Matthew J; Woo, Ellen; Schmitter-Edgecombe, Maureen; Hinkin, Charles H; Miller, Eric N; Gooding, Amanda L

2009-10-01

In the current study, we introduce the Item-Specific Deficit Approach (ISDA), a novel method for characterizing memory process deficits in list-learning data. To meet this objective, we applied the ISDA to California Verbal Learning Test (CVLT) data collected from a sample of 132 participants (53 healthy participants and 79 neurologically compromised participants). Overall, the ISDA indices measuring encoding, consolidation, and retrieval deficits demonstrated advantages over some traditional indices and indicated acceptable reliability and validity. Currently, the ISDA is intended for experimental use, although further research may support its utility for characterizing memory impairments in clinical assessments.

Effect of pregabalin on fear-based conditioned avoidance learning and spatial learning in a mouse model of scopolamine-induced amnesia.

PubMed

Sałat, Kinga; Podkowa, Adrian; Malikowska, Natalia; Trajer, Jędrzej

2017-03-01

Cognitive deficits are one of the frequent symptoms accompanying epilepsy or its treatment. In this study, the effect on cognition of intraperitoneally administered antiepileptic drug, pregabalin (10 mg/kg), was investigated in scopolamine-induced memory-impaired mice in the passive avoidance task and Morris water maze task. The effect of scopolamine and pregabalin on animals' locomotor activity was also studied. In the retention phase of the passive avoidance task, pregabalin reversed memory deficits induced by scopolamine (p < 0.05). During the acquisition phase of the Morris water maze pregabalin-treated memory-impaired mice performed the test with longer escape latencies than the vehicle-treated mice (significant at p < 0.05 on Day 5, and at p < 0.001 on Day 6). There were no differences in this parameter between the scopolamine-treated control group and pregabalin-treated memory-impaired mice, which indicated that pregabalin had no influence on spatial learning in this task. During the probe trial a significant difference (p < 0.05) was observed in terms of the mean number of target crossings between vehicle-treated mice and pregabalin-treated memory-impaired mice but there was no difference between the scopolamine-treated control group and mice treated with pregabalin + scopolamine. Pregabalin did not influence locomotor activity increased by scopolamine. In passive avoidance task, pregabalin reversed learning deficits induced by scopolamine. In the Morris water maze, pregabalin did not influence spatial learning deficits induced by scopolamine. These results are relevant for epileptic patients treated with pregabalin and those who use it for other therapeutic indications (anxiety, pain).

Juvenile Traumatic Brain Injury Results in Cognitive Deficits Associated with Impaired Endoplasmic Reticulum Stress and Early Tauopathy.

PubMed

Hylin, Michael J; Holden, Ryan C; Smith, Aidan C; Logsdon, Aric F; Qaiser, Rabia; Lucke-Wold, Brandon P

2018-05-22

The leading cause of death in the juvenile population is trauma, and in particular neurotrauma. The juvenile brain response to neurotrauma is not completely understood. Endoplasmic reticulum (ER) stress has been shown to contribute to injury expansion and behavioral deficits in adult rodents and furthermore has been seen in adult postmortem human brains diagnosed with chronic traumatic encephalopathy. Whether endoplasmic reticulum stress is increased in juveniles with traumatic brain injury (TBI) is poorly delineated. We investigated this important topic using a juvenile rat controlled cortical impact (CCI) model. We proposed that ER stress would be significantly increased in juvenile rats following TBI and that this would correlate with behavioral deficits using a juvenile rat model. A juvenile rat (postnatal day 28) CCI model was used. Binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP) were measured at 4 h in the ipsilateral pericontusion cortex. Hypoxia-inducible factor (HIF)-1α was measured at 48 h and tau kinase measured at 1 week and 30 days. At 4 h following injury, BiP and CHOP (markers of ER stress) were significantly elevated in rats exposed to TBI. We also found that HIF-1α was significantly upregulated 48 h following TBI showing delayed hypoxia. The early ER stress activation was additionally asso-ciated with the activation of a known tau kinase, glycogen synthase kinase-3β (GSK-3β), by 1 week. Tau oligomers measured by R23 were significantly increased by 30 days following TBI. The biochemical changes following TBI were associated with increased impulsive-like or anti-anxiety behavior measured with the elevated plus maze, deficits in short-term memory measured with novel object recognition, and deficits in spatial memory measured with the Morris water maze in juvenile rats exposed to TBI. These results show that ER stress was increased early in juvenile rats exposed to TBI, that these rats developed tau oligomers over the course of 30 days, and that they had significant short-term and spatial memory deficits following injury. © 2018 S. Karger AG, Basel.

Verbal Short-Term Memory in Individuals with Congenital Articulatory Disorders: New Empirical Data and Review of the Literature

ERIC Educational Resources Information Center

Carlesimo, G. A.; Galloni, F.; Bonanni, R.; Sabbadini, M.

2006-01-01

Background: To investigate the nature of the articulatory rehearsal mechanism of the Articulatory Loop in Baddeley's Working Memory model, it seems particularly important to study individuals who developed a deficit (dysarthria) or total abolition (anarthria) of the ability to articulate language following a cerebral lesion. Method: In this study,…

Memory deficits in abstinent MDMA (ecstasy) users: neuropsychological evidence of frontal dysfunction.

PubMed

Quednow, Boris B; Jessen, Frank; Kuhn, Kai-Uwe; Maier, Wolfgang; Daum, Irene; Wagner, Michael

2006-05-01

Chronic administration of the common club drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is associated with long-term depletion of serotonin (5-HT) and loss of 5-HT axons in the brains of rodents and non-human primates, and evidence suggests that recreational MDMA consumption may also affect the human serotonergic system. Moreover, it was consistently shown that abstinent MDMA users have memory deficits. Recently, it was supposed that these deficits are an expression of a temporal or rather hippocampal dysfunction caused by the serotonergic neurotoxicity of MDMA. The aim of this study is to examine the memory deficits of MDMA users neuropsychologically in order to evaluate the role of different brain regions. Nineteen male abstinent MDMA users, 19 male abstinent cannabis users and 19 male drug-naive control subjects were examined with a German version of the Rey Auditory Verbal Learning Test (RAVLT). MDMA users showed widespread and marked verbal memory deficits, compared to drug-naive controls as well as compared to cannabis users, whereas cannabis users did not differ from control subjects in their memory performance. MDMA users revealed impairments in learning, consolidation, recall and recognition. In addition, they also showed a worse recall consistency and strong retroactive interference whereby both measures were previously associated with frontal lobe function. There was a significant correlation between memory performance and the amount of MDMA taken. These results suggest that the memory deficits of MDMA users are not only the result of a temporal or hippocampal dysfunction, but also of a dysfunction of regions within the frontal cortex.

Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits.

PubMed

Downey, Luke A; Sands, Helen; Jones, Lewis; Clow, Angela; Evans, Phil; Stalder, Tobias; Parrott, Andrew C

2015-05-01

The goals of this study were to measure the neurocognitive performance of recent users of recreational Ecstasy and investigate whether it was associated with the stress hormone cortisol. The 101 participants included 27 recent light users of Ecstasy (one to four times in the last 3 months), 23 recent heavier Ecstasy users (five or more times) and 51 non-users. Rivermead paragraph recall provided an objective measure for immediate and delayed recall. The prospective and retrospective memory questionnaire provided a subjective index of memory deficits. Cortisol levels were taken from near-scalp 3-month hair samples. Cortisol was significantly raised in recent heavy Ecstasy users compared with controls, whereas hair cortisol in light Ecstasy users was not raised. Both Ecstasy groups were significantly impaired on the Rivermead delayed word recall, and both groups reported significantly more retrospective and prospective memory problems. Stepwise regression confirmed that lifetime Ecstasy predicted the extent of these memory deficits. Recreational Ecstasy is associated with increased levels of the bio-energetic stress hormone cortisol and significant memory impairments. No significant relationship between cortisol and the cognitive deficits was observed. Ecstasy users did display evidence of a metacognitive deficit, with the strength of the correlations between objective and subjective memory performances being significantly lower in the Ecstasy users. Copyright © 2015 John Wiley & Sons, Ltd.

Acute memory deficits in chemotherapy-treated adults.

PubMed

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

2017-11-01

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

Differential Behavioral and Biochemical Responses to Caffeine in Male and Female Rats from a Validated Model of Attention Deficit and Hyperactivity Disorder.

PubMed

Nunes, Fernanda; Pochmann, Daniela; Almeida, Amanda Staldoni; Marques, Daniela Melo; Porciúncula, Lisiane de Oliveira

2018-03-20

Epidemiological studies suggest sex differences in attention deficit and hyperactivity disorder (ADHD) symptomatology. The potential benefits of caffeine have been reported in the management of ADHD, but its effects were not properly addressed with respect to sex differences. The present study examined the effects of caffeine (0.3 g/L) administered since childhood in the behavior and brain-derived neurotrophic factor (BDNF) and its related proteins in both sexes of a rat model of ADHD (spontaneously hypertensive rats-SHR). Hyperlocomotion, recognition, and spatial memory disturbances were observed in adolescent SHR rats from both sexes. However, females showed lack of habituation and worsened spatial memory. Although caffeine was effective against recognition memory impairment in both sexes, spatial memory was recovered only in female SHR rats. Besides, female SHR rats showed exacerbated hyperlocomotion after caffeine treatment. SHR rats from both sexes presented increases in the BDNF, truncated and phospho-TrkB receptors and also phospho-CREB levels in the hippocampus. Caffeine normalized BDNF in males and truncated TrkB receptor at both sexes. These findings provide insight into the potential of caffeine against fully cognitive impairment displayed by females in the ADHD model. Besides, our data revealed that caffeine intake since childhood attenuated behavioral alterations in the ADHD model associated with changes in BDNF and TrkB receptors in the hippocampus.

Pharmacological Blockade of Serotonin 5-HT7 Receptor Reverses Working Memory Deficits in Rats by Normalizing Cortical Glutamate Neurotransmission

PubMed Central

Bonaventure, Pascal; Aluisio, Leah; Shoblock, James; Boggs, Jamin D.; Fraser, Ian C.; Lord, Brian; Lovenberg, Timothy W.; Galici, Ruggero

2011-01-01

The role of 5-HT7 receptor has been demonstrated in various animal models of mood disorders; however its function in cognition remains largely speculative. This study evaluates the effects of SB-269970, a selective 5-HT7 antagonist, in a translational model of working memory deficit and investigates whether it modulates cortical glutamate and/or dopamine neurotransmission in rats. The effect of SB-269970 was evaluated in the delayed non-matching to position task alone or in combination with MK-801, a non-competitive NMDA receptor antagonist, and, in separate experiments, with scopolamine, a non-selective muscarinic antagonist. SB-269970 (10 mg/kg) significantly reversed the deficits induced by MK-801 (0.1 mg/kg) but augmented the deficit induced by scopolamine (0.06 mg/kg). The ability of SB-269970 to modulate MK-801-induced glutamate and dopamine extracellular levels was separately evaluated using biosensor technology and microdialysis in the prefrontal cortex of freely moving rats. SB-269970 normalized MK-801 -induced glutamate but not dopamine extracellular levels in the prefrontal cortex. Rat plasma and brain concentrations of MK-801 were not affected by co-administration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. These results indicate that 5-HT7 receptor antagonists might reverse cognitive deficits associated with NMDA receptor hypofunction by selectively normalizing glutamatergic neurotransmission. PMID:21701689

Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice.

PubMed

Cabral-Costa, J V; Andreotti, D Z; Mello, N P; Scavone, C; Camandola, S; Kawamoto, E M

2018-06-05

Phosphatase and tensin homolog (PTEN) is an important protein with key modulatory functions in cell growth and survival. PTEN is crucial during embryogenesis and plays a key role in the central nervous system (CNS), where it directly modulates neuronal development and synaptic plasticity. Loss of PTEN signaling function is associated with cognitive deficits and synaptic plasticity impairment. Accordingly, Pten mutations have a strong link with autism spectrum disorder. In this study, neuronal Pten haploinsufficient male mice were subjected to a long-term environmental intervention - intermittent fasting (IF) - and then evaluated for alterations in exploratory, anxiety and learning and memory behaviors. Although no significant effects on spatial memory were observed, mutant mice showed impaired contextual fear memory in the passive avoidance test - an outcome that was effectively rescued by IF. In this study, we demonstrated that IF modulation, in addition to its rescue of the memory deficit, was also required to uncover behavioral phenotypes otherwise hidden in this neuronal Pten haploinsufficiency model.

Elevating Integrin-linked Kinase Expression has Rescued Hippocampal Neurogenesis and Memory Deficits in an AD animal Model.

PubMed

Xu, Xu-Feng; Wang, You-Cui; Zong, Liang; Chen, Zhe-Yu; Li, Yan

2018-05-19

Alterations in adult neurogenesis have been regarded as a major cause of cognitive impairment in Alzheimer's disease (AD). The underlying mechanism of neurogenesis deficiency in AD remains unclear. In this study, we reported that Integrin-linked Kinase (ILK) protein levels and phosphorylation were significantly decreased in the hippocampus of APP/PS1 mice. Increased ILK expression of dentate gyrus (DG) rescued the hippocampus-dependent neurogenesis and memory deficits in APP/PS1 mice. Moreover, we demonstrated that the effect of ILK overexpression in the hippocampus was exerted via AKT-GSK3β pathway. Finally, we found that Fluoxetine, a selective serotonin reuptake inhibitor, could improve the impaired hippocampal neurogenesis and memory by enhancing ILK-AKT-GSK3β pathway activity in APP/PS1 mice. Thus, these findings demonstrated the effects of ILK on neurogenesis and memory recovery, suggesting that ILK is an important therapeutic target for AD prevention and treatment. Copyright © 2018. Published by Elsevier B.V.

Caspase-2 cleavage of tau reversibly impairs memory.

PubMed

Zhao, Xiaohui; Kotilinek, Linda A; Smith, Benjamin; Hlynialuk, Chris; Zahs, Kathleen; Ramsden, Martin; Cleary, James; Ashe, Karen H

2016-11-01

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.

Long-term phenylbutyrate administration prevents memory deficits in Tg2576 mice by decreasing Abeta.

PubMed

Ricobaraza, Ana; Cuadrado-Tejedor, Mar; Garcia-Osta, Ana

2011-06-01

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.

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

PubMed Central

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

2006-01-01

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

Working memory deficits in boys with attention deficit/hyperactivity disorder (ADHD): An examination of orthographic coding and episodic buffer processes.

PubMed

Alderson, R Matt; Kasper, Lisa J; Patros, Connor H G; Hudec, Kristen L; Tarle, Stephanie J; Lea, Sarah E

2015-01-01

The episodic buffer component of working memory was examined in children with attention deficit/hyperactivity disorder (ADHD) and typically developing peers (TD). Thirty-two children (ADHD = 16, TD = 16) completed three versions of a phonological working memory task that varied with regard to stimulus presentation modality (auditory, visual, or dual auditory and visual), as well as a visuospatial task. Children with ADHD experienced the largest magnitude working memory deficits when phonological stimuli were presented via a unimodal, auditory format. Their performance improved during visual and dual modality conditions but remained significantly below the performance of children in the TD group. In contrast, the TD group did not exhibit performance differences between the auditory- and visual-phonological conditions but recalled significantly more stimuli during the dual-phonological condition. Furthermore, relative to TD children, children with ADHD recalled disproportionately fewer phonological stimuli as set sizes increased, regardless of presentation modality. Finally, an examination of working memory components indicated that the largest magnitude between-group difference was associated with the central executive. Collectively, these findings suggest that ADHD-related working memory deficits reflect a combination of impaired central executive and phonological storage/rehearsal processes, as well as an impaired ability to benefit from bound multimodal information processed by the episodic buffer.

Episodic and working memory deficits in alcoholic Korsakoff patients: the continuity theory revisited.

PubMed

Pitel, Anne Lise; Beaunieux, Hélène; Witkowski, Thomas; Vabret, François; de la Sayette, Vincent; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis

2008-07-01

The exact nature of episodic and working memory impairments in alcoholic Korsakoff patients (KS) remains unclear, as does the specificity of these neuropsychological deficits compared with those of non-Korsakoff alcoholics (AL). The goals of the present study were therefore to (1) specify the nature of episodic and working memory impairments in KS, (2) determine the specificity of the KS neuropsychological profile compared with the AL profile, and (3) observe the distribution of individual performances within the 2 patient groups. We investigated episodic memory (encoding and retrieval abilities, contextual memory and state of consciousness associated with memories), the slave systems of working memory (phonological loop, visuospatial sketchpad and episodic buffer) and executive functions (inhibition, flexibility, updating and integration abilities) in 14 strictly selected KS, 40 AL and 55 control subjects (CS). Compared with CS, KS displayed impairments of episodic memory encoding and retrieval, contextual memory, recollection, the slave systems of working memory and executive functions. Although episodic memory was more severely impaired in KS than in AL, the single specificity of the KS profile was a disproportionately large encoding deficit. Apart from organizational and updating abilities, the slave systems of working memory and inhibition, flexibility and integration abilities were impaired to the same extent in both alcoholic groups. However, some KS were unable to complete the most difficult executive tasks. There was only a partial overlap of individual performances by KS and AL for episodic memory and a total mixture of the 2 groups for working memory. Korsakoff's syndrome encompasses impairments of the different episodic and working memory components. AL and KS displayed similar profiles of episodic and working memory deficits, in accordance with neuroimaging investigations showing similar patterns of brain damage in both alcoholic groups.

Working, declarative and procedural memory in specific language impairment

PubMed Central

Lum, Jarrad A.G.; Conti-Ramsden, Gina; Page, Debra; Ullman, Michael T.

2012-01-01

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 suggest that the evidence largely supports the predictions of the PDH. PMID:21774923

Assessing neurocognitive function in psychiatric disorders: A roadmap for enhancing consensus

PubMed Central

Ahmari, Susanne E.; Eich, Teal; Cebenoyan, Deniz; Smith, Edward E.; Simpson, H. Blair

2014-01-01

It has been challenging to identify core neurocognitive deficits that are consistent across multiple studies in patients with Obsessive Compulsive Disorder (OCD). In turn, this leads to difficulty in translating findings from human studies into animal models to dissect pathophysiology. In this article, we use primary data from a working memory task in OCD patients to illustrate this issue. Working memory deficiencies have been proposed as an explanatory model for the evolution of checking compulsions in a subset of OCD patients. However, findings have been mixed due to variability in task design, examination of spatial vs. verbal working memory, and heterogeneity in patient populations. Two major questions therefore remain: first, do OCD patients have disturbances in working memory? Second, if there are working memory deficits in OCD, do they cause checking compulsions?. In order to investigate these questions, we tested 19 unmedicated OCD patients and 23 matched healthy controls using a verbal working memory task that has increased difficulty/task-load compared to classic digit-span tasks. OCD patients did not significantly differ in their performance on this task compared to healthy controls, regardless of the outcome measure used (i.e. reaction time or accuracy). Exploratory analyses suggest that a subset of patients with predominant doubt/checking symptoms may have decreased memory confidence despite normal performance on trials with the highest working memory load. These results suggest that other etiologic factors for checking compulsions should be considered. In addition, they serve as a touchstone for discussion, and therefore help us to generate a roadmap for increasing consensus in the assessment of neurocognitive function in psychiatric disorders. PMID:24994503

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

PubMed Central

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

2013-01-01

Purpose A central question in Childhood Apraxia of Speech (CAS) is whether the core phenotype is limited to transcoding (planning/programming) deficits or if speakers with CAS also have deficits in auditory-perceptual encoding (representational) and/or memory (storage and retrieval of representations) processes. We addressed this and other questions using responses to the Syllable Repetition Task (SRT: Shriberg et al., 2009). Method The SRT was administered to 369 individuals in four groups: (a) Typical Speech-Language (119), (b) Speech Delay-Typical Language (140), (c) Speech Delay-Language Impairment (70), and (d) idiopathic or neurogenetic CAS (40). Results CAS participants had significantly lower SRT competence, encoding, memory, and transcoding scores than controls. They were 8.3 times more likely than controls to have SRT transcoding scores below 80%. Conclusions Speakers with CAS have speech processing deficits in encoding, memory, and transcoding. The SRT currently has moderate diagnostic accuracy to identify transcoding deficits, the signature feature of CAS. PMID:22489736

Working memory deficits affect risky decision-making in methamphetamine users with attention-deficit/hyperactivity disorder.

PubMed

Duarte, Nichole A; Woods, Steven Paul; Rooney, Alexandra; Atkinson, J Hampton; Grant, Igor

2012-04-01

Methamphetamine (MA) use and Attention-Deficit/Hyperactivity Disorder (ADHD) commonly co-occur and are independently associated with dysregulation of frontostriatal loops and risky decision-making; however, whether their comorbidity exacerbates risky decision-making is not known. This study evaluated 23 participants with histories of MA dependence and ADHD (MA+ADHD+), 25 subjects with MA dependence alone (MA+ADHD-), and 22 healthy adults (MA-ADHD-), who completed the Iowa Gambling Task (IGT) as part of a larger neuropsychiatric research evaluation. Results showed a significant interaction between ADHD, MA, and working memory, such that individuals with working memory deficits in the MA+ADHD+ cohort demonstrated the strongest propensity to select cards from "disadvantageous" versus "advantageous" decks on the IGT. This effect was not better explained by other psychiatric, substance use, neuromedical, or cognitive factors. Findings suggest that working memory deficits may moderate the expression of risky decision-making in MA users with ADHD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Working memory deficits in adults with attention-deficit/hyperactivity disorder (ADHD): an examination of central executive and storage/rehearsal processes.

PubMed

Alderson, R Matt; Hudec, Kristen L; Patros, Connor H G; Kasper, Lisa J

2013-05-01

The current study was the first to use a regression approach to examine the unique contributions of central executive (CE) and storage/rehearsal processes to working memory (WM) deficits in adults with ADHD. Thirty-seven adults (ADHD = 21, HC = 16) completed phonological (PH) and visuospatial (VS) working memory tasks. While both groups performed significantly better during the PH task relative to the VS task, adults with ADHD exhibited significant deficits across both working memory modalities. Further, the ADHD group recalled disproportionately fewer PH and VS stimuli as set-size demands increased. Overall, the CE and PH storage/rehearsal processes of adults with ADHD were both significantly impaired relative to those of the healthy control adults; however, the magnitude of the CE effect size was much smaller compared to previous studies of children with the disorder. Collectively, results provide support for a lifelong trajectory of WM deficits in ADHD. © 2013 American Psychological Association

Short-Term Memory Limitations in Children: Capacity or Processing Deficits?

ERIC Educational Resources Information Center

Chi, Michelene T. H.

1976-01-01

Evaluates the assertion that short-term memory (STM) capacity increases with age and concludes that the STM capacity limitation in children is due to the deficits in the processing strategies and speeds, which presumably improve with age through cumulative learning. (JM) Available from: Memory and Cognition, Psychonomic Society, 1018 West 34…

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

ERIC Educational Resources Information Center

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

2012-01-01

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

Developmental Dyslexia and Explicit Long-Term Memory

ERIC Educational Resources Information Center

Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

2010-01-01

The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

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

ERIC Educational Resources Information Center

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

2013-01-01

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

A Specific Deficit in Visuospatial Simultaneous Working Memory in Down Syndrome

ERIC Educational Resources Information Center

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

2009-01-01

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

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

ERIC Educational Resources Information Center

Webster, Raymond E.; And Others

1996-01-01

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

Visuospatial working memory underlies choice-impulsivity in boys with attention-deficit/hyperactivity disorder.

PubMed

Patros, Connor H G; Alderson, R Matt; Lea, Sarah E; Tarle, Stephanie J; Kasper, Lisa J; Hudec, Kristen L

2015-03-01

The present study examined the directional relationship between choice-impulsivity and separate indices of phonological and visuospatial working memory performance in boys (aged 8-12 years) with (n=16) and without ADHD (n=19). Results indicated that high ratings of overall ADHD, inattention, and hyperactivity were significantly associated with increased impulsivity and poorer phonological and visuospatial working memory performance. Further, results from bias-corrected bootstrapped mediation analyses revealed a significant indirect effect of visuospatial working memory performance, through choice-impulsivity, on overall ADHD, inattention, and hyperactivity/impulsivity. Collectively, the findings suggest that deficits of visuospatial working memory underlie choice-impulsivity, which in turn contributes to the ADHD phenotype. Moreover, these findings are consistent with a growing body of literature that identifies working memory as a central neurocognitive deficit of ADHD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cognitive benefits of memantine in Alzheimer's 5XFAD model mice decline during advanced disease stages.

PubMed

Devi, Latha; Ohno, Masuo

2016-05-01

Memantine, a noncompetitive NMDA receptor antagonist with neuroprotective properties, has been used for the treatment of Alzheimer's disease (AD). Administration of memantine to various transgenic AD mice has been reported to improve cognitive deficits, very often completely back to normal wild-type control levels. However, such great benefits of memantine in preclinical studies do not translate into clinical results of this drug, showing only marginal and transient efficacy in moderate to severe AD. To further address in vivo efficacy, we compared the effects of memantine at different disease stages in 5XFAD mice, one of the rapid-onset and most aggressive amyloid models. Specifically, we administered memantine once daily for 30 days to 5XFAD mice, which showed moderate (6-7 months of age) and robust (12-15 months) β-amyloid (Aβ) accumulation. Treatments with memantine (10mg/kg, i.p.) reversed memory impairments in the younger 5XFAD mice, as tested by the contextual fear conditioning and spontaneous alternation Y-maze paradigms. Memantine had no effects on soluble Aβ oligomer or total Aβ42 levels in 5XFAD mouse brains. In contrast, subchronic treatments with memantine showed no behavioral benefits in the older 5XFAD group, which exhibited more profound memory deficits concomitant with highly increased concentrations of Aβ as compared with those of the younger 5XFAD group. Since subchronic memantine at the higher dose (30 mg/kg) impaired memory performances in wild-type controls, we further tested acute administration of 50mg/kg memantine, which was reported to enhance hippocampal adult neurogenesis and memory function. However, this treatment also failed to rescue memory deficits in 12-15-month-old 5XFAD mice. Collectively, our results demonstrate that cognitive benefits of memantine independent of Aβ reductions were no longer observed in the 5XFAD Alzheimer mouse model during advanced stages, which may be reflective of the limited efficacy of memantine in clinical settings. Copyright © 2016 Elsevier Inc. All rights reserved.

Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users.

PubMed

McCann, Una D; Kuwabara, Hiroto; Kumar, Anil; Palermo, Michael; Abbey, Rubyna; Brasic, James; Ye, Weiguo; Alexander, Mohab; Dannals, Robert F; Wong, Dean F; Ricaurte, George A

2008-02-01

Studies in abstinent methamphetamine (METH) users have demonstrated reductions in brain dopamine transporter (DAT) binding potential (BP), as well as cognitive and motor deficits, but it is not yet clear whether cognitive deficits and brain DAT reductions fully reverse with sustained abstinence, or whether behavioral deficits in METH users are related to dopamine (DA) deficits. This study was conducted to further investigate potential persistent psychomotor deficits secondary to METH abuse, and their relationship to brain DAT availability, as measured using quantitative PET methods with [(11)C]WIN 35428. Twenty-two abstinent METH users and 17 healthy non-METH using controls underwent psychometric testing to test the hypothesis that METH users would demonstrate selective deficits in neuropsychiatric domains known to involve DA neurons (e.g., working memory, executive function, motor function). A subset of subjects also underwent PET scanning with [(11)C]WIN 35428. METH users were found to have modest deficits in short-term memory, executive function, and manual dexterity. Exploratory correlational analyses revealed that deficits in memory, but not those in executive or motor function, were associated with decreases in striatal DAT BP. These results suggest a possible relationship between DAT BP and memory deficits in abstinent METH users, and lend support to the notion that METH produces lasting effects on central DA neurons in humans. As METH can also produce toxic effects on serotonin (5-HT) neurons, further study is needed to address the potential role of brain 5-HT depletion in cognitive deficits in abstinent METH users. (c) 2007 Wiley-Liss, Inc.

Memory outcomes following cognitive interventions in children with neurological deficits: A review with a focus on under-studied populations.

PubMed

Schaffer, Yael; Geva, Ronny

2016-01-01

Given the primary role of memory in children's learning and well-being, the aim of this review was to examine the outcomes of memory remediation interventions in children with neurological deficits as a function of the affected memory system and intervention method. Fifty-seven studies that evaluated the outcome of memory interventions in children were identified. Thirty-four studies met the inclusion criteria, and were included in a systematic review. Diverse rehabilitation methods for improving explicit and implicit memory in children were reviewed. The analysis indicates that teaching restoration strategies may improve, and result in the generalisation of, semantic memory and working memory performance in children older than 7 years with mild to moderate memory deficits. Factors such as longer protocols, emotional support, and personal feedback contribute to intervention efficacy. In addition, the use of compensation aids seems to be highly effective in prospective memory tasks. Finally, the review unveiled a lack of studies with young children and the absence of group interventions. These findings point to the importance of future evidence-based intervention protocols in these areas.

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

PubMed

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

2018-02-25

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

Neural bases of orthographic long-term memory and working memory in dysgraphia

PubMed Central

Purcell, Jeremy; Hillis, Argye E.; Capasso, Rita; Miceli, Gabriele

2016-01-01

Spelling a word involves the retrieval of information about the word’s letters and their order from long-term memory as well as the maintenance and processing of this information by working memory in preparation for serial production by the motor system. While it is known that brain lesions may selectively affect orthographic long-term memory and working memory processes, relatively little is known about the neurotopographic distribution of the substrates that support these cognitive processes, or the lesions that give rise to the distinct forms of dysgraphia that affect these cognitive processes. To examine these issues, this study uses a voxel-based mapping approach to analyse the lesion distribution of 27 individuals with dysgraphia subsequent to stroke, who were identified on the basis of their behavioural profiles alone, as suffering from deficits only affecting either orthographic long-term or working memory, as well as six other individuals with deficits affecting both sets of processes. The findings provide, for the first time, clear evidence of substrates that selectively support orthographic long-term and working memory processes, with orthographic long-term memory deficits centred in either the left posterior inferior frontal region or left ventral temporal cortex, and orthographic working memory deficits primarily arising from lesions of the left parietal cortex centred on the intraparietal sulcus. These findings also contribute to our understanding of the relationship between the neural instantiation of written language processes and spoken language, working memory and other cognitive skills. PMID:26685156

Remembering preservation in hippocampal amnesia

PubMed Central

Clark, Ian A.; Maguire, Eleanor A.

2017-01-01

The lesion-deficit model dominates neuropsychology. This is unsurprising given powerful demonstrations that focal brain lesions can affect specific aspects of cognition. Nowhere is this more evident than in patients with bilateral hippocampal damage. In the last sixty years the amnesia and other impairments exhibited by these patients have helped to delineate the functions of the hippocampus and shape the field of memory. We do not question the value of this approach. However, less prominent are the cognitive processes that remain intact following hippocampal lesions. Here, we collate the piecemeal reports of preservation of function following focal bilateral hippocampal damage, highlighting a wealth of information often veiled by the field’s focus on deficits. We consider how a systematic understanding of what is preserved as well as what is lost could add an important layer of precision to models of memory and the hippocampus. PMID:26361051

Out-of-body–induced hippocampal amnesia

PubMed Central

Bergouignan, Loretxu; Nyberg, Lars; Ehrsson, H. Henrik

2014-01-01

Theoretical models have suggested an association between the ongoing experience of the world from the perspective of one’s own body and hippocampus-based episodic memory. This link has been supported by clinical reports of long-term episodic memory impairments in psychiatric conditions with dissociative symptoms, in which individuals feel detached from themselves as if having an out-of-body experience. Here, we introduce an experimental approach to examine the necessary role of perceiving the world from the perspective of one’s own body for the successful episodic encoding of real-life events. While participants were involved in a social interaction, an out-of-body illusion was elicited, in which the sense of bodily self was displaced from the real body to the other end of the testing room. This condition was compared with a well-matched in-body illusion condition, in which the sense of bodily self was colocalized with the real body. In separate recall sessions, performed ∼1 wk later, we assessed the participants’ episodic memory of these events. The results revealed an episodic recollection deficit for events encoded out-of-body compared with in-body. Functional magnetic resonance imaging indicated that this impairment was specifically associated with activity changes in the posterior hippocampus. Collectively, these findings show that efficient hippocampus-based episodic-memory encoding requires a first-person perspective of the natural spatial relationship between the body and the world. Our observations have important implications for theoretical models of episodic memory, neurocognitive models of self, embodied cognition, and clinical research into memory deficits in psychiatric disorders. PMID:24616529

Out-of-body-induced hippocampal amnesia.

PubMed

Bergouignan, Loretxu; Nyberg, Lars; Ehrsson, H Henrik

2014-03-25

Theoretical models have suggested an association between the ongoing experience of the world from the perspective of one's own body and hippocampus-based episodic memory. This link has been supported by clinical reports of long-term episodic memory impairments in psychiatric conditions with dissociative symptoms, in which individuals feel detached from themselves as if having an out-of-body experience. Here, we introduce an experimental approach to examine the necessary role of perceiving the world from the perspective of one's own body for the successful episodic encoding of real-life events. While participants were involved in a social interaction, an out-of-body illusion was elicited, in which the sense of bodily self was displaced from the real body to the other end of the testing room. This condition was compared with a well-matched in-body illusion condition, in which the sense of bodily self was colocalized with the real body. In separate recall sessions, performed ∼1 wk later, we assessed the participants' episodic memory of these events. The results revealed an episodic recollection deficit for events encoded out-of-body compared with in-body. Functional magnetic resonance imaging indicated that this impairment was specifically associated with activity changes in the posterior hippocampus. Collectively, these findings show that efficient hippocampus-based episodic-memory encoding requires a first-person perspective of the natural spatial relationship between the body and the world. Our observations have important implications for theoretical models of episodic memory, neurocognitive models of self, embodied cognition, and clinical research into memory deficits in psychiatric disorders.

Appetite Loss and Neurocognitive Deficits in Late-Life Depression

PubMed Central

Potter, Guy G.; McQuoid, Douglas R.; Steffens, David C.

2015-01-01

Objectives Examine association of appetite loss symptoms to neurocognitive performance in late-life depression (LLD). Methods Cross-sectional data from individuals aged 60+ with Major Depressive Disorder (N =322). Participants received clinical assessment of depression and neuropsychological testing. Factor analysis was used to characterize depression symptom factors, and composite scales were developed for episodic memory, psychomotor executive functions, verbal fluency, and working memory span. Results Factor analysis produced a five-factor solution: (1) Anhedonia/Sadness, (2) Suicidality/Guilt, (3) Appetite/Weight Loss, (4) Sleep Disturbance, and (5) Anxiety/Tension. In separate multivariate models for each neurocognitive domain and including all 5 depression factors, higher appetite-loss-related symptoms were associated with lower performance in episodic memory, psychomotor executive functions, and verbal fluency; results were significant with covariates of age, education, race, sex, age of depression onset, and illness burden. No other depression factors were associated with neurocognitive performance in these models. In an additional set of models, the Appetite factor mediated the association between global depression severity and neurocognitive performance. Discussion A factor of appetite and weight loss symptoms in LLD was uniquely associated with neurocognitive performance, in contrast to lack of association among other depression symptom factors. Conclusion Cognitive deficits are a major adverse outcome of LLD, and prominent appetite loss during acute depression may be a marker for these deficits, independent of overall depression severity. Research is needed to understand the mechanisms that may explain this association, and how it is related to the cognitive and symptomatic course of LLD. PMID:25315155

Working memory and attention deficits in adolescent offspring of schizophrenia or bipolar patients: comparing vulnerability markers.

PubMed

Diwadkar, Vaibhav A; Goradia, Dhruman; Hosanagar, Avinash; Mermon, Diana; Montrose, Debra M; Birmaher, Boris; Axelson, David; Rajarathinem, R; Haddad, Luay; Amirsadri, Ali; Zajac-Benitez, Caroline; Rajan, Usha; Keshavan, Matcheri S

2011-07-01

Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in brain circuits that subserve these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree. Three groups (n=100 subjects; range: 10-20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2s & 12s); sustained attention processing was assessed using the Continuous Performance Task-Identical Pairs version. SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls. These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP. Copyright © 2011 Elsevier Inc. All rights reserved.

Retrograde amnesia: a study of its relation to anterograde amnesia and semantic memory deficits.

PubMed

Schmidtke, K; Vollmer, H

1997-04-01

This group study of 24 amnesic patients and 40 control subjects examined the hypothesis that retrograde memory deficits result from a combination of two impairment mechanisms: (1) a deficit in the retrieval of contents that is related to dysfunctioning of the hippocampal anterograde memory system, and (2) a deficit in the storage and/or retrieval of contents that is related to concomitant neocortical lesions. Retrograde amnesia was evaluated with the use of new Famous Persons and Autobiographical Memory Tests. The postulated components of retrograde memory impairment were assessed using the Wechsler Memory Scale and a new Semantic Memory Test, respectively. Regression analyses showed that recent episodic autobiography was exclusively related to the hippocampal component, while memory for famous persons and childhood autobiography was related to the neocortical component. In the case of details concerning people of recent fame, both components were identified as independent determinants. The temporal gradient of patients' impairment at the Famous Persons Test was marked for detailed knowledge, but small for overlearned knowledge. The present results thus support the combination hypothesis. They conform to the view that the transition from a hippocampus-dependent to a neocortex-dependent mnemonic representation of new contents is mediated by reiteration, and occurs within 5-10 years.

Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory.

PubMed

Guo, Lengqiu; Guo, Zhuangli; Luo, Xiaoqing; Liang, Rui; Yang, Shui; Ren, Haigang; Wang, Guanghui; Zhen, Xuechu

2016-12-02

Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

ERIC Educational Resources Information Center

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

2013-01-01

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

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

ERIC Educational Resources Information Center

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

2016-01-01

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

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

ERIC Educational Resources Information Center

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

2011-01-01

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

First-Grade Predictors of Mathematical Learning Disability: A Latent Class Trajectory Analysis

PubMed Central

Geary, David C.; Bailey, Drew H.; Littlefield, Andrew; Wood, Phillip; Hoard, Mary K.; Nugent, Lara

2009-01-01

Kindergarten to 3rd grade mathematics achievement scores from a prospective study of mathematical development were subjected to latent growth trajectory analyses (n = 306). The four corresponding classes included children with mathematical learning disability (MLD, 6% of sample), and low (LA, 50%), typically (TA, 39%) and high (HA, 5%) achieving children. The groups were administered a battery of intelligence (IQ), working memory, and mathematical-cognition measures in 1st grade. The children with MLD had general deficits in working memory and IQ, and potentially more specific deficits on measures of number sense. The LA children did not have working memory or IQ deficits, but showed moderate deficits on these number sense measures and for addition fact retrieval. The distinguishing features of the HA children were a strong visuospatial working memory, a strong number sense, and frequent use of memory-based processes to solve addition problems. Implications for the early identification of children at risk for poor mathematics achievement are discussed. PMID:20046817

Comparative behavioral and neurochemical analysis of phenytoin and valproate treatment on epilepsy induced learning and memory deficit: Search for add on therapy.

PubMed

Mishra, Awanish; Goel, Rajesh Kumar

2015-08-01

Our previous work demonstrated, chronic epilepsy affects learning and memory of rodents along with peculiar neurochemical changes in discrete brain parts. Most commonly used antiepileptic drugs (phenytoin and sodium valproate) also worsen learning and memory in the patients with epilepsy. Therefore this study was designed to carry out comparison of behavioral and neurochemical changes with phenytoin and sodium valproate treatment in pentylenetetrazole-kindling induced learning and memory deficit to devise add on therapy for this menace. For the experimental epilepsy, animals were kindled using PTZ (35 mg/kg; i.p., at 48 ± 2 h intervals) and successful kindled animals were involved in the study. These kindled animals were treated with saline, phenytoin (30 mg/kg/day, i.p.) and sodium valproate (300 mg/kg/day, i.p.) for 20 days. These animals were challenged with PTZ challenging dose (35 mg/kg) on day 5, 10, 15 and 20 to evaluate the effect on seizure severity score on different days. Effect on learning and memory was evaluated using elevated plus maze and passive shock avoidance paradigm. On day 20, after behavioral evaluations, animals were sacrificed to analyze glutamate, GABA, norepinephrine, dopamine, serotonin, total nitrite level and acetylcholinesterase level in cortex and hippocampus. Behavioral evaluations suggested that phenytoin and sodium valproate treatment significantly reduced seizure severity in the kindled animals, while sodium valproate treatment controls seizures with least memory deficit in comparison to phenytoin. Neurochemical findings revealed that elevated cortical acetylcholinesterase level could be one of the responsible factors leading to memory deficit in phenytoin treated animals. However sodium valproate treatment reduced cortical acetylcholinesterase level and had least debilitating consequences on memory deficit. Therefore, attenuation of elevated AChE activity can be one of add-on approach for management of memory deficit associated with conventional AEDs.

Considering the role of semantic memory in episodic future thinking: evidence from semantic dementia.

PubMed

Irish, Muireann; Addis, Donna Rose; Hodges, John R; Piguet, Olivier

2012-07-01

Semantic dementia is a progressive neurodegenerative condition characterized by the profound and amodal loss of semantic memory in the context of relatively preserved episodic memory. In contrast, patients with Alzheimer's disease typically display impairments in episodic memory, but with semantic deficits of a much lesser magnitude than in semantic dementia. Our understanding of episodic memory retrieval in these cohorts has greatly increased over the last decade, however, we know relatively little regarding the ability of these patients to imagine and describe possible future events, and whether episodic future thinking is mediated by divergent neural substrates contingent on dementia subtype. Here, we explored episodic future thinking in patients with semantic dementia (n=11) and Alzheimer's disease (n=11), in comparison with healthy control participants (n=10). Participants completed a battery of tests designed to probe episodic and semantic thinking across past and future conditions, as well as standardized tests of episodic and semantic memory. Further, all participants underwent magnetic resonance imaging. Despite their relatively intact episodic retrieval for recent past events, the semantic dementia cohort showed significant impairments for episodic future thinking. In contrast, the group with Alzheimer's disease showed parallel deficits across past and future episodic conditions. Voxel-based morphometry analyses confirmed that atrophy in the left inferior temporal gyrus and bilateral temporal poles, regions strongly implicated in semantic memory, correlated significantly with deficits in episodic future thinking in semantic dementia. Conversely, episodic future thinking performance in Alzheimer's disease correlated with atrophy in regions associated with episodic memory, namely the posterior cingulate, parahippocampal gyrus and frontal pole. These distinct neuroanatomical substrates contingent on dementia group were further qualified by correlational analyses that confirmed the relation between semantic memory deficits and episodic future thinking in semantic dementia, in contrast with the role of episodic memory deficits and episodic future thinking in Alzheimer's disease. Our findings demonstrate that semantic knowledge is critical for the construction of novel future events, providing the necessary scaffolding into which episodic details can be integrated. Further research is necessary to elucidate the precise contribution of semantic memory to future thinking, and to explore how deficits in self-projection manifest on behavioural and social levels in different dementia subtypes.

Fluoxetine prevents the memory deficits and reduction in hippocampal cell proliferation caused by valproic acid.

PubMed

Welbat, Jariya Umka; Sangrich, Preeyanuch; Sirichoat, Apiwat; Chaisawang, Pornthip; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanun; Wigmore, Peter

2016-12-01

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 © 2016. Published by Elsevier B.V. All rights reserved.

Basic Information Processing Abilities at 11 years Account for Deficits in IQ Associated with Preterm Birth.

PubMed

Rose, Susan A; Feldman, Judith F; Jankowski, Jeffery J; Van Rossem, Ronan

2011-07-01

Although it is well established that preterms as a group do poorly relative to their full-term peers on tests of global cognitive functioning, the basis for this relative deficiency is less understood. The present paper examines preterm deficits in core cognitive abilities and determines their role in mediating preterm/full-term differences in IQ. The performance of 11-year-old children born preterm (birth weight <1750g) and their full-term controls were compared on a large battery of 15 tasks, covering four basic cognitive domains -- memory, attention, speed of processing and representational competence. The validity of these four domains was established using latent variables and confirmatory factor analysis (CFA). Preterms showed pervasive deficits within and across domains. Additionally, preterm deficits in IQ were completely mediated by these four cognitive domains in a structural equation model involving a cascade from elementary abilities (attention and speed), to more complex abilities (memory and representational competence), to IQ. The similarity of findings to those obtained with this cohort in infancy and toddlerhood suggest that preterm deficits persist - across time, across task, and from the non-verbal to the verbal period.

Autistic-like behaviour in Scn1a+/- mice and rescue by enhanced GABA-mediated neurotransmission.

PubMed

Han, Sung; Tai, Chao; Westenbroek, Ruth E; Yu, Frank H; Cheah, Christine S; Potter, Gregory B; Rubenstein, John L; Scheuer, Todd; de la Iglesia, Horacio O; Catterall, William A

2012-09-20

Haploinsufficiency of the SCN1A gene encoding voltage-gated sodium channel Na(V)1.1 causes Dravet's syndrome, a childhood neuropsychiatric disorder including recurrent intractable seizures, cognitive deficit and autism-spectrum behaviours. The neural mechanisms responsible for cognitive deficit and autism-spectrum behaviours in Dravet's syndrome are poorly understood. Here we report that mice with Scn1a haploinsufficiency exhibit hyperactivity, stereotyped behaviours, social interaction deficits and impaired context-dependent spatial memory. Olfactory sensitivity is retained, but novel food odours and social odours are aversive to Scn1a(+/-) mice. GABAergic neurotransmission is specifically impaired by this mutation, and selective deletion of Na(V)1.1 channels in forebrain interneurons is sufficient to cause these behavioural and cognitive impairments. Remarkably, treatment with low-dose clonazepam, a positive allosteric modulator of GABA(A) receptors, completely rescued the abnormal social behaviours and deficits in fear memory in the mouse model of Dravet's syndrome, demonstrating that they are caused by impaired GABAergic neurotransmission and not by neuronal damage from recurrent seizures. These results demonstrate a critical role for Na(V)1.1 channels in neuropsychiatric functions and provide a potential therapeutic strategy for cognitive deficit and autism-spectrum behaviours in Dravet's syndrome.

Basic Information Processing Abilities at 11 years Account for Deficits in IQ Associated with Preterm Birth

PubMed Central

Rose, Susan A.; Feldman, Judith F.; Jankowski, Jeffery J.; Van Rossem, Ronan

2011-01-01

Although it is well established that preterms as a group do poorly relative to their full-term peers on tests of global cognitive functioning, the basis for this relative deficiency is less understood. The present paper examines preterm deficits in core cognitive abilities and determines their role in mediating preterm/full-term differences in IQ. The performance of 11-year-old children born preterm (birth weight <1750g) and their full-term controls were compared on a large battery of 15 tasks, covering four basic cognitive domains -- memory, attention, speed of processing and representational competence. The validity of these four domains was established using latent variables and confirmatory factor analysis (CFA). Preterms showed pervasive deficits within and across domains. Additionally, preterm deficits in IQ were completely mediated by these four cognitive domains in a structural equation model involving a cascade from elementary abilities (attention and speed), to more complex abilities (memory and representational competence), to IQ. The similarity of findings to those obtained with this cohort in infancy and toddlerhood suggest that preterm deficits persist – across time, across task, and from the non-verbal to the verbal period. PMID:21643482

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

PubMed

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

2008-11-21

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

Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

PubMed

Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

2016-06-01

Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits.

Antidepressant Effect and Recognition Memory Improvement of Two Novel Plant Extract Combinations - Antistress I and Anti-stress II on Rats Subjected to a Model of Mild Chronic Stress.

PubMed

Kandilarov, Ilin K; Zlatanova, Hristina I; Georgieva-Kotetarova, Maria T; Kostadinova, Ivanka I; Katsarova, Mariana N; Dimitrova, Stela Z; Lukanov, Ludmil K; Sadakov, Ferit

2018-03-01

Chronic stress is one of the main factors which lead to depression - a psychiatric disorder affecting millions of people and predicted to be the second ranked cause of premature death in 2020. Depression is often associated with cognitive disturbances and memory deficit. Plant based therapy could be effective in the treatment of mild to moderate depression due to its low level of adverse reaction, its good tolerability and compliance. 72 male Wistar rats, divided in 9 groups were given orally for 8 weeks two combinations of dry plant extracts - Antistress I and Antistress II and five individual dry extracts obtained from Serratula coronata, Hypericum perforatum, Valeriana officinalis, Crataegus monogyna and Melissa officinalis. The animals were exposed to a chronic unpredictable mild stress for 8 weeks. The depression-like symptoms were evaluated with Forced swim test while the assessment of the memory deficit was performed with Novel object recognition test. Antistress II demonstrates antidepressant effect while Antistress I doesn't improve the depressive-like symptoms. The individual extracts of Hypericum perforatum and Valeriana officinalis also possess antidepressant properties. Antistress II improves the cognition as well as the individual extracts of Hypericum perforatum, Valeriana officinalis and especially Serratula coronata. Dry extract from Serratula tend to have the best effect regarding the recognition memory. The effect of Antistress I on memory deficit is negligible. Antistress II possesses antidepressant effect and improves the recognition memory while Antistress I doesn't demonstrate any of the above-described effects.

Effects of gender and executive function on visuospatial working memory in adult obsessive-compulsive disorder.

PubMed

Martoni, Riccardo Maria; Salgari, Giulia; Galimberti, Elisa; Cavallini, Maria Cristina; O'Neill, Joseph

2015-12-01

Visuospatial working memory (VSWM) is the ability of the brain to transiently store and manipulate visual information. VSWM deficiencies have been reported in obsessive-compulsive disorder (OCD), but not consistently, perhaps due to variability in task design and clinical patient factors. To explore this variability, this study assessed effects of the design factors task difficulty and executive organizational strategy and of the clinical factors gender, OCD symptom dimension, and duration of illness on VSWM in OCD. The CANTAB spatial working memory, spatial recognition memory, delayed matching to sample, and stop signal tasks were administered to 42 adult OCD patients and 42 age- and sex-matched healthy controls. Aims were to detect a possible VSWM deficit in the OCD sample, to evaluate influences of the above task and patient factors, to determine the specificity of the deficit to the visuospatial subdomain, and to examine effects of sustained attention as potential neurocognitive confound. We confirmed previous findings of a VSWM deficit in OCD that was more severe for greater memory load (task difficulty) and that was affected by task strategy (executive function). We failed to demonstrate significant deficits in neighboring or confounding neurocognitive subdomains (visual object recognition or visual object short-term memory, sustained attention). Notably, the VSWM deficit was only significant for female patients, adding to evidence for sexual dimorphism in OCD. Again as in prior work, more severe OCD symptoms in the symmetry dimension (but no other dimension) significantly negatively impacted VSWM. Duration of illness had no significant effect on VSWM. VSWM deficits in OCD appear more severe with higher task load and may be mediated through poor task strategy. Such deficits may present mainly in female patients and in (male and female) patients with symmetry symptoms.

Pathophysiology and Treatment of Memory Dysfunction after Traumatic Brain Injury

PubMed Central

Paterno, Rosalia; Folweiler, Kaitlin A.; Cohen, Akiva S.

2018-01-01

Memory is fundamental to everyday life, and cognitive impairments resulting from traumatic brain injury (TBI) have devastating effects on TBI survivors. A contributing component to memory impairments caused by TBI are alterations in the neural circuits associated with memory function. In this review, we aim to bring together experimental findings that characterize behavioral memory deficits and the underlying pathophysiology of memory-involved circuits after TBI. While there is little doubt that TBI causes memory and cognitive dysfunction, it is difficult to conclude which memory phase i.e., encoding, maintenance or retrieval is specifically altered by TBI. This is most likely due to variation in behavioral protocols and experimental models. Additionally we review a selection of experimental treatments that hold translational potential to mitigate memory dysfunction following injury. PMID:28500417

Investigation of left and right lateral fluid percussion injury in C57BL6/J mice: In vivo functional consequences

PubMed Central

Schurman, Lesley D.; Smith, Terry L.; Morales, Anthony J.; Lee, Nancy N.; Reeves, Thomas M.; Phillips, Linda L.; Lichtman, Aron H.

2017-01-01

Although rodent models of traumatic brain injury (TBI) reliably produce cognitive and motor disturbances, behavioral characterization resulting from left and right hemisphere injuries remains unexplored. Here we examined the functional consequences of targeting the left versus right parietal cortex in lateral fluid percussion injury, on Morris water maze (MWM) spatial memory tasks (fixed platform and reversal) and neurological motor deficits (neurological severity score and rotarod). In the MWM fixed platform task, right lateral injury produced a small delay in acquisition rate compared to left. However, injury to either hemisphere resulted in probe trial deficits. In the MWM reversal task, left-right performance deficits were not evident, though left lateral injury produced mild acquisition and probe trial deficits compared to sham controls. Additionally, left and right injury produced similar neurological motor task deficits, impaired righting times, and lesion volumes. Injury to either hemisphere also produced robust ipsilateral, and modest contralateral, morphological changes in reactive microglia and astrocytes. In conclusion, left and right lateral TBI impaired MWM performance, with mild fixed platform acquisition rate differences, despite similar motor deficits, histological damage, and glial cell reactivity. Thus, while both left and right lateral TBI produce cognitive deficits, laterality in mouse MWM learning and memory merits consideration in the investigation of TBI-induced cognitive consequences. PMID:28527714

Investigation of left and right lateral fluid percussion injury in C57BL6/J mice: In vivo functional consequences.

PubMed

Schurman, Lesley D; Smith, Terry L; Morales, Anthony J; Lee, Nancy N; Reeves, Thomas M; Phillips, Linda L; Lichtman, Aron H

2017-07-13

Although rodent models of traumatic brain injury (TBI) reliably produce cognitive and motor disturbances, behavioral characterization resulting from left and right hemisphere injuries remains unexplored. Here we examined the functional consequences of targeting the left versus right parietal cortex in lateral fluid percussion injury, on Morris water maze (MWM) spatial memory tasks (fixed platform and reversal) and neurological motor deficits (neurological severity score and rotarod). In the MWM fixed platform task, right lateral injury produced a small delay in acquisition rate compared to left. However, injury to either hemisphere resulted in probe trial deficits. In the MWM reversal task, left-right performance deficits were not evident, though left lateral injury produced mild acquisition and probe trial deficits compared to sham controls. Additionally, left and right injury produced similar neurological motor task deficits, impaired righting times, and lesion volumes. Injury to either hemisphere also produced robust ipsilateral, and modest contralateral, morphological changes in reactive microglia and astrocytes. In conclusion, left and right lateral TBI impaired MWM performance, with mild fixed platform acquisition rate differences, despite similar motor deficits, histological damage, and glial cell reactivity. Thus, while both left and right lateral TBI produce cognitive deficits, laterality in mouse MWM learning and memory merits consideration in the investigation of TBI-induced cognitive consequences. Copyright © 2017. Published by Elsevier B.V.

Working memory impairment in probands with schizoaffective disorder and first degree relatives of schizophrenia probands extend beyond deficits predicted by generalized neuropsychological impairment.

PubMed

Kristian Hill, S; Buchholz, Alison; Amsbaugh, Hayley; Reilly, James L; Rubin, Leah H; Gold, James M; Keefe, Richard S E; Pearlson, Godfrey D; Keshavan, Matcheri S; Tamminga, Carol A; Sweeney, John A

2015-08-01

Working memory impairment is well established in psychotic disorders. However, the relative magnitude, diagnostic specificity, familiality pattern, and degree of independence from generalized cognitive deficits across psychotic disorders remain unclear. Participants from the Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study included probands with schizophrenia (N=289), psychotic bipolar disorder (N=227), schizoaffective disorder (N=165), their first-degree relatives (N=315, N=259, N=193, respectively), and healthy controls (N=289). All were administered the WMS-III Spatial Span working memory test and the Brief Assessment of Cognition in Schizophrenia (BACS) battery. All proband groups displayed significant deficits for both forward and backward span compared to controls. However, after covarying for generalized cognitive impairments (BACS composite), all proband groups showed a 74% or greater effect size reduction with only schizoaffective probands showing residual backward span deficits compared to controls. Significant familiality was seen in schizophrenia and bipolar pedigrees. In relatives, both forward and backward span deficits were again attenuated after covarying BACS scores and residual backward span deficits were seen in relatives of schizophrenia patients. Overall, both probands and relatives showed a similar pattern of robust working memory deficits that were largely attenuated when controlling for generalized cognitive deficits. Copyright © 2015 Elsevier B.V. All rights reserved.

Memory-guided saccades in youth-onset psychosis and attention deficit hyperactivity disorder (ADHD).

PubMed

White, Tonya; Mous, Sabine; Karatekin, Canan

2014-08-01

Working memory deficits have been shown to be present in children and adolescents with schizophrenia and attention deficit hyperactivity disorder. Considering the differences in clinical characteristics between these disorders, it was the goal of this study to assess differences in the specific components of working memory in children and adolescents with psychosis and attention deficit hyperactivity disorder. Children and adolescents (age range 8-20 years) with either a non-affective psychotic disorder (n = 25), attention deficit hyperactivity disorder (n = 33) and controls (n = 58) were administered an oculomotor delayed-response task using both a recall and a control condition. Memory-guided saccades were measured during delay periods of 2, 8 and 20 s. Although both clinical groups were less accurate than controls, there was no evidence of a disproportionate impairment in recall. In addition, there was no evidence of a delay-dependent impairment in psychosis; however, there was a delay-dependent impairment in attention deficit hyperactivity disorder when corrective saccades were included. Speed of information processing was correlated with distance errors in psychosis, suggesting that speed of encoding the stimulus location may have constrained the accuracy of the saccades. Our findings support impairments during encoding in the psychosis group and a delay-dependent deficit in the attention deficit hyperactivity disorder group. © 2013 Wiley Publishing Asia Pty Ltd.

Gestational methylazoxymethanol exposure leads to NMDAR dysfunction in hippocampus during early development and lasting deficits in learning.

PubMed

Snyder, Melissa A; Adelman, Alicia E; Gao, Wen-Jun

2013-01-01

The N-methyl-D-aspartate (NMDA) receptor has long been associated with learning and memory processes as well as diseased states, particularly in schizophrenia (SZ). Additionally, SZ is increasingly recognized as a neurodevelopmental disorder with cognitive impairments often preceding the onset of psychosis. However, the cause of these cognitive deficits and what initiates the pathological process is unknown. Growing evidence has implicated the glutamate system and, in particular, N-methyl-D-aspartate receptor (NMDAR) dysfunction in the pathophysiology of SZ. Yet, the vast majority of SZ-related research has focused on NMDAR function in adults leaving the role of NMDARs during development uncharacterized. We used the prenatal methylazoxymethanol acetate (MAM, E17) exposure model to determine the alterations of NMDAR protein levels and function, as well as associated cognitive deficits during development. We found that MAM-exposed animals have significantly altered NMDAR protein levels and function in the juvenile and adolescent hippocampus. Furthermore, these changes are associated with learning and memory deficits in the Morris Water Maze. Thus, in the prenatal MAM-exposure SZ model, NMDAR expression and function is altered during the critical period of hippocampal development. These changes may be involved in disease initiation and cognitive impairment in the early stage of SZ.

Acute treatment with bis selenide, an organic compound containing the trace element selenium, prevents memory deficits induced by reserpine in rats.

PubMed

Bortolatto, Cristiani Folharini; Guerra Souza, Ana Cristina; Wilhelm, Ethel Antunes; Nogueira, Cristina Wayne

2013-01-01

Taking into account the promising pharmacological actions of (Z)-2,3-bis(4-chlorophenylselanyl) prop-2-en-1-ol) (bis selenide), an organic compound containing the trace element selenium, and the constant search for drugs that improve the cognitive performance, the objective of the present study was to investigate whether bis selenide treatment ameliorates memory deficits induced by reserpine in rats. For this aim, male adult rats received a single subcutaneous injection of reserpine (1 mg/kg), a biogenic amine-depleting agent used to induce memory deficit. After 24 h, bis selenide at doses of 25 and 50 mg/kg was administered to rats by intragastric route, and 1 h later, the animals were submitted to behavior tasks. The effects of acute administration of bis selenide on memory were evaluated by social recognition, step-down passive avoidance, and object recognition paradigms. Exploratory and locomotor activities of rats were determined using the open-field test. Analysis of data revealed that the social memory disruption caused by reserpine was reversed by bis selenide at both doses. In addition, bis selenide, at the highest dose, prevented the memory deficit resulting from reserpine administration to rats in step-down passive avoidance and object recognition tasks. No significant alterations in locomotor and exploratory behaviors were found in animals treated with reserpine and/or bis selenide. Results obtained from distinct memory behavioral paradigms revealed that an acute treatment with bis selenide attenuated memory deficits induced by reserpine in rats.

Original nootropic drug noopept prevents memory deficit in rats with muscarinic and nicotinic receptor blockade.

PubMed

Radionova, K S; Belnik, A P; Ostrovskaya, R U

2008-07-01

Antiamnesic activity of Noopept was studied on the original three-way model of conditioned passive avoidance response, which allows studying spatial component of memory. Cholinoceptor antagonists of both types (scopolamine and mecamylamine) decreased entry latency and reduced the probability for selection of the safe compartment. Noopept abolished the antiamnesic effect of cholinoceptor antagonists and improved spatial preference.

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

ERIC Educational Resources Information Center

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

2011-01-01

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

Short-Term Memory of Children with Mental Retardation: Structural Defects or Control Deficits.

ERIC Educational Resources Information Center

Katims, David S.

The short-term memory of 24 retarded and 24 nonretarded individuals, aged 10 to 14, under conditions of restricted cognitive strategy use was investigated. An attempt was made to determine whether short-term memory difficulties of persons with mental retardation are caused by deficits in voluntary cognitive strategies, such as the organization and…

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

ERIC Educational Resources Information Center

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

2008-01-01

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

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

ERIC Educational Resources Information Center

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

2004-01-01

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

The association of perceived stress and verbal memory is greater in HIV-infected versus HIV-uninfected women.

PubMed

Rubin, Leah H; Cook, Judith A; Weber, Kathleen M; Cohen, Mardge H; Martin, Eileen; Valcour, Victor; Milam, Joel; Anastos, Kathryn; Young, Mary A; Alden, Christine; Gustafson, Deborah R; Maki, Pauline M

2015-08-01

In contrast to findings from cohorts comprised primarily of HIV-infected men, verbal memory deficits are the largest cognitive deficit found in HIV-infected women from the Women's Interagency HIV Study (WIHS), and this deficit is not explained by depressive symptoms or substance abuse. HIV-infected women may be at greater risk for verbal memory deficits due to a higher prevalence of cognitive risk factors such as high psychosocial stress and lower socioeconomic status. Here, we investigate the association between perceived stress using the Perceived Stress Scale (PSS-10) and verbal memory performance using the Hopkins Verbal Learning Test (HVLT) in 1009 HIV-infected and 496 at-risk HIV-uninfected WIHS participants. Participants completed a comprehensive neuropsychological test battery which yielded seven cognitive domain scores, including a primary outcome of verbal memory. HIV infection was not associated with a higher prevalence of high perceived stress (i.e., PSS-10 score in the top tertile) but was associated with worse performance on verbal learning (p < 0.01) and memory (p < 0.001), as well as attention (p = 0.02). Regardless of HIV status, high stress was associated with poorer performance in those cognitive domains (p's < 0.05) as well as processing speed (p = 0.01) and executive function (p < 0.01). A significant HIV by stress interaction was found only for the verbal memory domain (p = 0.02); among HIV-infected women only, high stress was associated with lower performance (p's < 0.001). That association was driven by the delayed verbal memory measure in particular. These findings suggest that high levels of perceived stress contribute to the deficits in verbal memory observed in WIHS women.

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

PubMed

Saunders, Nichole L J; Summers, Mathew J

2011-03-01

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

Deficits in visual working-memory capacity and general cognition in African Americans with psychosis.

PubMed

Mathias, Samuel R; Knowles, Emma E M; Barrett, Jennifer; Beetham, Tamara; Leach, Olivia; Buccheri, Sebastiano; Aberizk, Katrina; Blangero, John; Poldrack, Russell A; Glahn, David C

2018-03-01

On average, patients with psychosis perform worse than controls on visual change-detection tasks, implying that psychosis is associated with reduced capacity of visual working memory (WM). In the present study, 79 patients diagnosed with various psychotic disorders and 166 controls, all African Americans, completed a change-detection task and several other neurocognitive measures. The aims of the study were to (1) determine whether we could observe a between-group difference in performance on the change-detection task in this sample; (2) establish whether such a difference could be specifically attributed to reduced WM capacity (k); and (3) estimate k in the context of the general cognitive deficit in psychosis. Consistent with previous studies, patients performed worse than controls on the change-detection task, on average. Bayesian hierarchical cognitive modeling of the data suggested that this between-group difference was driven by reduced k in patients, rather than differences in other psychologically meaningful model parameters (guessing behavior and lapse rate). Using the same modeling framework, we estimated the effect of psychosis on k while controlling for general intellectual ability (g, obtained from the other neurocognitive measures). The results suggested that reduced k in patients was stronger than predicted by the between-group difference in g. Moreover, a mediation analysis suggested that the relationship between psychosis and g (i.e., the general cognitive deficit) was mediated by k. The results were consistent with the idea that reduced k is a specific deficit in psychosis, which contributes to the general cognitive deficit. Copyright © 2017 Elsevier B.V. All rights reserved.

Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice.

PubMed

Campêlo, Clarissa L C; Santos, José R; Silva, Anatildes F; Dierschnabel, Aline L; Pontes, André; Cavalcante, Jeferson S; Ribeiro, Alessandra M; Silva, Regina H

2017-06-15

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.

Intact short-term memory and impaired executive functions in obsessive compulsive disorder.

PubMed

Demeter, Gyula; Racsmány, Mihály; Csigó, Katalin; Harsányi, András; Németh, Attila; Döme, László

2013-01-30

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 < 0.05) and perseverative errors (r(28) = 0.385, p < 0.05) in the WCST. Our results gave evidence that executive functions are impaired while 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.

Self, memory, and imagining the future in a case of psychogenic amnesia.

PubMed

Rathbone, Clare J; Ellis, Judi A; Baker, Ian; Butler, Chris R

2015-01-01

We report a case of psychogenic amnesia and examine the relationships between autobiographical memory impairment, the self, and ability to imagine the future. Case study JH, a 60-year-old male, experienced a 6-year period of pervasive psychogenic amnesia covering all life events from childhood to the age of 53. JH was tested during his amnesic period and again following hypnotherapy and the recovery of his memories. JH's amnesia corresponded with deficits in self-knowledge and imagining the future. Results are discussed with reference to models of self and memory and processes involving remembering and imagining.

Emotional memory in schizophrenia.

PubMed

Herbener, Ellen S

2008-09-01

Emotional memories play an important role in our day-to-day experience, informing many of our minute-to-minute decisions (eg, where to go for dinner, what are the likely consequences of not attending a meeting), as well as our long-term goal setting. Individuals with schizophrenia appear to be impaired in memory for emotional experiences, particularly over longer delay periods, which may contribute to deficits in goal-related behavior and symptoms of amotivation and anhedonia. This article reviews factors that are known to influence emotional memory in healthy subjects, applies these factors to results from emotional memory studies with individuals with schizophrenia, and then uses extant neurobiological models of emotional memory formation to develop hypotheses about biological processes that might particularly contribute to emotional memory impairment in schizophrenia.

State orientation and memory load impair prospective memory performance in older compared to younger persons.

PubMed

Kaschel, Reiner; Kazén, Miguel; Kuhl, Julius

2017-07-01

A modified event-based paradigm of prospective memory was applied to investigate intention initiation in older and younger participants under high versus low memory load (subsequent episodic word recall vs. recognition). State versus action orientation, a personality dimension related to intention enactment, was also measured. State-oriented persons show a superiority effect for the storage of intentions in an explicit format but have a paradoxical deficit in their actual enactment. We predicted an interaction between aging, personality, and memory load, with longer intention-initiation latencies and higher omission rates for older state-oriented participants under high memory load. Results were consistent with predictions and are interpreted according to current personality and prospective memory models of aging.

Neuropsychological deficits in temporal lobe epilepsy: A comprehensive review

PubMed Central

Zhao, Fengqing; Kang, Hai; You, LIbo; Rastogi, Priyanka; Venkatesh, D.; Chandra, Mina

2014-01-01

Temporal lobe epilepsy (TLE) is the most prevalent form of complex partial seizures with temporal lobe origin of electrical abnormality. Studies have shown that recurrent seizures affect all aspects of cognitive functioning, including memory, language, praxis, executive functions, and social judgment, among several others. In this article, we will review these cognitive impairments along with their neuropathological correlates in a comprehensive manner. We will see that neuropsychological deficits are prevalent in TLE. Much of the effort has been laid on memory due to the notion that temporal lobe brain structures involved in TLE play a central role in consolidating information into memory. It seems that damage to the mesial structure of the temporal lobe, particularly the amygdale and hippocampus, has the main role in these memory difficulties and the neurobiological plausibility of the role of the temporal lobe in different aspects of memory. Here, we will cover the sub-domains of working memory and episodic memory deficits. This is we will further proceed to evaluate the evidences of executive function deficits in TLE and will see that set-shifting among other EFs is specifically affected in TLE as is social cognition. Finally, critical components of language related deficits are also found in the form of word-finding difficulties. To conclude, TLE affects several of cognitive function domains, but the etiopathogenesis of all these dysfunctions remain elusive. Further well-designed studies are needed for a better understanding of these disorders. PMID:25506156

Auditory sensory memory and language abilities in former late talkers: a mismatch negativity study.

PubMed

Grossheinrich, Nicola; Kademann, Stefanie; Bruder, Jennifer; Bartling, Juergen; Von Suchodoletz, Waldemar

2010-09-01

The present study investigated whether (a) a reduced duration of auditory sensory memory is found in late talking children and (b) whether deficits of sensory memory are linked to persistent difficulties in language acquisition. Former late talkers and children without delayed language development were examined at the age of 4 years and 7 months using mismatch negativity (MMN) with interstimulus intervals (ISIs) of 500 ms and 2000 ms. Additionally, short-term memory, language skills, and nonverbal intelligence were assessed. MMN mean amplitude was reduced for the ISI of 2000 ms in former late talking children both with and without persistent language deficits. In summary, our findings suggest that late talkers are characterized by a reduced duration of auditory sensory memory. However, deficits in auditory sensory memory are not sufficient for persistent language difficulties and may be compensated for by some children.

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

PubMed

Naveh-Benjamin, Moshe; Kilb, Angela

2014-09-01

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

Iconic Decay in Schizophrenia

PubMed Central

Hahn, Britta; Kappenman, Emily S.; Robinson, Benjamin M.; Fuller, Rebecca L.; Luck, Steven J.; Gold, James M.

2011-01-01

Working memory impairment is considered a core deficit in schizophrenia, but the precise nature of this deficit has not been determined. Multiple lines of evidence implicate deficits at the encoding stage. During encoding, information is held in a precategorical sensory store termed iconic memory, a literal image of the stimulus with high capacity but rapid decay. Pathologically increased iconic decay could reduce the number of items that can be transferred into working memory before the information is lost and could thus contribute to the working memory deficit seen in the illness. The current study used a partial report procedure to test the hypothesis that patients with schizophrenia (n = 37) display faster iconic memory decay than matched healthy control participants (n = 28). Six letters, arranged in a circle, were presented for 50 ms. Following a variable delay of 0–1000 ms, a central arrow cue indicated the item to be reported. In both patients and control subjects, recall accuracy decreased with increasing cue delay, reflecting decay of the iconic representation of the stimulus array. Patients displayed impaired memory performance across all cue delays, consistent with an impairment in working memory, but the rate of iconic memory decay did not differ between patients and controls. This provides clear evidence against faster loss of iconic memory representations in schizophrenia, ruling out iconic decay as an underlying source of the working memory impairment in this population. Thus, iconic decay rate can be added to a growing list of unimpaired cognitive building blocks in schizophrenia. PMID:20053864

Iconic decay in schizophrenia.

PubMed

Hahn, Britta; Kappenman, Emily S; Robinson, Benjamin M; Fuller, Rebecca L; Luck, Steven J; Gold, James M

2011-09-01

Working memory impairment is considered a core deficit in schizophrenia, but the precise nature of this deficit has not been determined. Multiple lines of evidence implicate deficits at the encoding stage. During encoding, information is held in a precategorical sensory store termed iconic memory, a literal image of the stimulus with high capacity but rapid decay. Pathologically increased iconic decay could reduce the number of items that can be transferred into working memory before the information is lost and could thus contribute to the working memory deficit seen in the illness. The current study used a partial report procedure to test the hypothesis that patients with schizophrenia (n = 37) display faster iconic memory decay than matched healthy control participants (n = 28). Six letters, arranged in a circle, were presented for 50 ms. Following a variable delay of 0-1000 ms, a central arrow cue indicated the item to be reported. In both patients and control subjects, recall accuracy decreased with increasing cue delay, reflecting decay of the iconic representation of the stimulus array. Patients displayed impaired memory performance across all cue delays, consistent with an impairment in working memory, but the rate of iconic memory decay did not differ between patients and controls. This provides clear evidence against faster loss of iconic memory representations in schizophrenia, ruling out iconic decay as an underlying source of the working memory impairment in this population. Thus, iconic decay rate can be added to a growing list of unimpaired cognitive building blocks in schizophrenia.

What part of working memory is not working in ADHD? Short-term memory, the central executive and effects of reinforcement.

PubMed

Dovis, Sebastiaan; Van der Oord, Saskia; Wiers, Reinout W; Prins, Pier J M

2013-08-01

Deficits in Working Memory (WM) are related to symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). In children with ADHD visuospatial WM is most impaired. WM is composed of Short-Term Memory (STM) and a Central Executive (CE). Therefore, deficits in either or both STM and the CE may account for WM impairments in children with ADHD. WM-component studies investigating this find deficits in both STM and the CE. However, recent studies show that not only cognitive deficits, but also motivational deficits give rise to the aberrant WM performance of children with ADHD. To date, the influence of these motivational deficits on the components of WM has not been investigated. This study examined the effects of a standard (feedback-only) and a high level of reinforcement (feedback + 10 euros) on the visuospatial WM-, visuospatial STM-, and the CE performance of 86 children with ADHD and 62 typically-developing controls. With standard reinforcement the STM, CE, and WM performance of children with ADHD was worse than that of controls. High reinforcement improved STM and WM performance more in children with ADHD than in controls, but was unable to normalize their performance. High reinforcement did not appear to improve the CE-related performance of children with ADHD and controls. Motivational deficits have a detrimental effect on both the visuospatial WM performance and the STM performance of children with ADHD. Aside from motivational deficits, both the visuospatial STM and the CE of children with ADHD are impaired, and give rise to their deficits in visuospatial WM.

Working memory deficits in children with reading difficulties: memory span and dual task coordination.

PubMed

Wang, Shinmin; Gathercole, Susan E

2013-05-01

The current study investigated the cause of the reported problems in working memory in children with reading difficulties. Verbal and visuospatial simple and complex span tasks, and digit span and reaction times tasks performed singly and in combination, were administered to 46 children with single word reading difficulties and 45 typically developing children matched for age and nonverbal ability. Children with reading difficulties had pervasive deficits in the simple and complex span tasks and had poorer abilities to coordinate two cognitive demanding tasks. These findings indicate that working memory problems in children with reading difficulties may reflect a core deficit in the central executive. Copyright © 2012 Elsevier Inc. All rights reserved.

Tests of the DRYAD theory of the age-related deficit in memory for context: Not about context, and not about aging

PubMed Central

Benjamin, Aaron S.; Diaz, Michael; Matzen, Laura E.; Johnson, Benjamin

2011-01-01

Older adults exhibit a disproportionate deficit in their ability to recover contextual elements or source information about prior encounters with stimuli. A recent theoretical account, DRYAD (Benjamin, 2010), attributes this selective deficit to a global decrease in memory fidelity with age, moderated by weak representation of contextual information. The predictions of DRYAD are tested here in three experiments. We show that an age-related deficit obtains for whichever aspect of the stimulus subjects’ attention is directed away from during encoding (Experiment 1), suggesting a central role for attention in producing the age-related deficit in context. We also show that an analogous deficit can be elicited within young subjects with a manipulation of study time (Experiment 2), suggesting that any means of reducing memory fidelity yields an interaction of the same form as the age-related effect. Experiment 3 evaluates the critical prediction of DRYAD that endorsement probability in an exclusion task should vary nonmonotonically with memory strength. This prediction was confirmed by assessing the shape of the forgetting function in a continuous exclusion task. The results are consistent with the DRYAD account of aging and memory judgments and do not support the widely held view that aging entails the selective disruption of processes involved in encoding, storing, or retrieving contextual information. PMID:21875219

Tests of the DRYAD theory of the age-related deficit in memory for context: not about context, and not about aging.

PubMed

Benjamin, Aaron S; Diaz, Michael; Matzen, Laura E; Johnson, Benjamin

2012-06-01

Older adults exhibit a disproportionate deficit in their ability to recover contextual elements or source information about prior encounters with stimuli. A recent theoretical account, DRYAD, attributes this selective deficit to a global decrease in memory fidelity with age, moderated by weak representation of contextual information. The predictions of DRYAD are tested here in three experiments. We show that an age-related deficit obtains for whichever aspect of the stimulus subjects' attention is directed away from during encoding (Experiment 1), suggesting a central role for attention in producing the age-related deficit in context. We also show that an analogous deficit can be elicited within young subjects with a manipulation of study time (Experiment 2), suggesting that any means of reducing memory fidelity yields an interaction of the same form as the age-related effect. Experiment 3 evaluates the critical prediction of DRYAD that endorsement probability in an exclusion task should vary nonmonotonically with memory strength. This prediction was confirmed by assessing the shape of the forgetting function in a continuous exclusion task. The results are consistent with the DRYAD account of aging and memory judgments and do not support the widely held view that aging entails the selective disruption of processes involved in encoding, storing, or retrieving contextual information. PsycINFO Database Record (c) 2012 APA, all rights reserved

A Meta-Analysis of Working Memory Deficits in Children with Learning Difficulties: Is There a Difference between Verbal Domain and Numerical Domain?

ERIC Educational Resources Information Center

Peng, Peng; Fuchs, Douglas

2016-01-01

Children with learning difficulties suffer from working memory (WM) deficits. Yet the specificity of deficits associated with different types of learning difficulties remains unclear. Further research can contribute to our understanding of the nature of WM and the relationship between it and learning difficulties. The current meta-analysis…

Functional retrograde amnesia: a multiple case study.

PubMed

Fujiwara, Esther; Brand, Matthias; Kracht, Lutz; Kessler, Josef; Diebel, Andrea; Netz, Johannes; Markowitsch, Hans J

2008-01-01

Functional retrograde amnesia (RA) is a rare pathology and has been rarely studied in detail across different patients. We extensively examined five functional RA patients and compared their neuropsychological profile including anterograde and retrograde memory performance, executive functions, emotional processing, and formally assessed psychiatric symptoms. Across patients, neuropsychological deficits beyond RA were most consistently seen in executive functions and attention suggesting that these dysfunctions contribute to the remote memory deficit. In a majority of the patients, problems in social cognition and emotional behaviour were reflected in Theory of Mind deficits and accompanying psychiatric symptoms. Aberrances in a measure of social desirability were detected, pointing to repressive tendencies in three out of the five patients. Future studies of functional RA patients may investigate more specifically which frontal-lobe associated (dys-) functions contribute to the memory retrieval deficit. Moreover, studying more closely the interaction between social cognition, repressive personality style and memory inhibition in this disease seems worthwhile pursuing.

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

PubMed

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

2011-09-01

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

Loss of hfe function reverses impaired recognition memory caused by olfactory manganese exposure in mice.

PubMed

Ye, Qi; Kim, Jonghan

2015-03-01

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 anti-oxidant enzymes in the PFC.

Routes to short-term memory indexing: lessons from deaf native users of American Sign Language.

PubMed

Hirshorn, Elizabeth A; Fernandez, Nina M; Bavelier, Daphne

2012-01-01

Models of working memory (WM) have been instrumental in understanding foundational cognitive processes and sources of individual differences. However, current models cannot conclusively explain the consistent group differences between deaf signers and hearing speakers on a number of short-term memory (STM) tasks. Here we take the perspective that these results are not due to a temporal order-processing deficit in deaf individuals, but rather reflect different biases in how different types of memory cues are used to do a given task. We further argue that the main driving force behind the shifts in relative biasing is a consequence of language modality (sign vs. speech) and the processing they afford, and not deafness, per se.

Routes to short term memory indexing: Lessons from deaf native users of American Sign Language

PubMed Central

Hirshorn, Elizabeth A.; Fernandez, Nina M.; Bavelier, Daphne

2012-01-01

Models of working memory (WM) have been instrumental in understanding foundational cognitive processes and sources of individual differences. However, current models cannot conclusively explain the consistent group differences between deaf signers and hearing speakers on a number of short-term memory (STM) tasks. Here we take the perspective that these results are not due to a temporal order-processing deficit in deaf individuals, but rather reflect different biases in how different types of memory cues are used to do a given task. We further argue that the main driving force behind the shifts in relative biasing is a consequence of language modality (sign vs. speech) and the processing they afford, and not deafness, per se. PMID:22871205

A computational language approach to modeling prose recall in schizophrenia

PubMed Central

Rosenstein, Mark; Diaz-Asper, Catherine; Foltz, Peter W.; Elvevåg, Brita

2014-01-01

Many cortical disorders are associated with memory problems. In schizophrenia, verbal memory deficits are a hallmark feature. However, the exact nature of this deficit remains elusive. Modeling aspects of language features used in memory recall have the potential to provide means for measuring these verbal processes. We employ computational language approaches to assess time-varying semantic and sequential properties of prose recall at various retrieval intervals (immediate, 30 min and 24 h later) in patients with schizophrenia, unaffected siblings and healthy unrelated control participants. First, we model the recall data to quantify the degradation of performance with increasing retrieval interval and the effect of diagnosis (i.e., group membership) on performance. Next we model the human scoring of recall performance using an n-gram language sequence technique, and then with a semantic feature based on Latent Semantic Analysis. These models show that automated analyses of the recalls can produce scores that accurately mimic human scoring. The final analysis addresses the validity of this approach by ascertaining the ability to predict group membership from models built on the two classes of language features. Taken individually, the semantic feature is most predictive, while a model combining the features improves accuracy of group membership prediction slightly above the semantic feature alone as well as over the human rating approach. We discuss the implications for cognitive neuroscience of such a computational approach in exploring the mechanisms of prose recall. PMID:24709122

[Comparison of the Wechsler Memory Scale-III and the Spain-Complutense Verbal Learning Test in acquired brain injury: construct validity and ecological validity].

PubMed

Luna-Lario, P; Pena, J; Ojeda, N

2017-04-16

To perform an in-depth examination of the construct validity and the ecological validity of the Wechsler Memory Scale-III (WMS-III) and the Spain-Complutense Verbal Learning Test (TAVEC). The sample consists of 106 adults with acquired brain injury who were treated in the Area of Neuropsychology and Neuropsychiatry of the Complejo Hospitalario de Navarra and displayed memory deficit as the main sequela, measured by means of specific memory tests. The construct validity is determined by examining the tasks required in each test over the basic theoretical models, comparing the performance according to the parameters offered by the tests, contrasting the severity indices of each test and analysing their convergence. The external validity is explored through the correlation between the tests and by using regression models. According to the results obtained, both the WMS-III and the TAVEC have construct validity. The TAVEC is more sensitive and captures not only the deficits in mnemonic consolidation, but also in the executive functions involved in memory. The working memory index of the WMS-III is useful for predicting the return to work at two years after the acquired brain injury, but none of the instruments anticipates the disability and dependence at least six months after the injury. We reflect upon the construct validity of the tests and their insufficient capacity to predict functionality when the sequelae become chronic.

Postnatal choline levels mediate cognitive deficits in a rat model of schizophrenia.

PubMed

Corriveau, Jennifer A; Glenn, Melissa J

2012-11-01

In the present study, we investigated whether the essential nutrient choline may protect against schizophrenic-like cognitive deficits in a rat model. Theories regarding the etiology of schizophrenia suggest that early life events render an individual more vulnerable to adult challenges, and the combination may precipitate disease onset. To model this, the adult male offspring of dams who either experienced stress during late gestation or did not were given a 5 mg/kg dose of the NMDA antagonist,MK-801. The presence of both the prenatal challenge of stress and the adult challenge of MK-801 was expected to impair memory in these offspring. Memory was not expected to be impaired in rats that did not experience prenatal stress, but did receive MK-801 as adults. To study whether choline levels altered outcomes in these groups, rats were fed a choline-supplemented, -deficient, or standard diet during the period between the two challenges: beginning at weaning and continuing for 25 days. All rats consumed regular rat chow thereafter. The efficacy of the model was confirmed in the standard fed rats in that only those that were prenatally stressed and received MK-801 as adults displayed impaired memory on a novelty preference test of object recognition. Contrary to this finding and consistent with our hypothesis, choline-supplemented rats that were also both prenatally stressed and given MK-801 as adults showed intact memory. Choline deficiency impaired memory in rats that were just prenatally stressed, just given MK-801 as adults, and subjected to both. Thus, a choline deficient diet may render rats vulnerable to either challenge. Taken together, we offer evidence that developmental choline levels modulate the effects of prenatal stress and/or MK-801 and thereby alter the cognitive outcome in a rat model of schizophrenia.

Postnatal choline levels mediate cognitive deficits in a rat model of schizophrenia

PubMed Central

Corriveau, Jennifer A.; Glenn, Melissa J.

2012-01-01

In the present study, we investigated whether the essential nutrient choline may protect against schizophrenic-like cognitive deficits in a rat model. Theories regarding the etiology of schizophrenia suggest that early life events render an individual more vulnerable to adult challenges, and the combination may precipitate disease onset. To model this, the adult male offspring of dams who either experienced stress during late gestation or did not were given a 5 mg/kg dose of the NMDA antagonist, MK-801. The presence of both the prenatal challenge of stress and the adult challenge of MK-801 was expected to impair memory in these offspring. Memory was not expected to be impaired in rats that did not experience prenatal stress, but did receive MK-801 as adults. To study whether choline levels altered outcomes in these groups, rats were fed a choline-supplemented, -deficient, or standard diet during the period between the two challenges: beginning at weaning and continuing for 25 days. All rats consumed regular rat chow thereafter. The efficacy of the model was confirmed in the standard fed rats in that only those that were prenatally stressed and received MK-801 as adults displayed impaired memory on a novelty preference test of object recognition. Contrary to this finding and consistent with our hypothesis, choline-supplemented rats that were also both prenatally stressed and given MK-801 as adults showed intact memory. Choline deficiency impaired memory in rats that were just prenatally stressed, just given MK-801 as adults, and subjected to both. Thus, a choline deficient diet may render rats vulnerable to either challenge. Taken together, we offer evidence that developmental choline levels modulate the effects of prenatal stress and/or MK-801 and thereby alter the cognitive outcome in a rat model of schizophrenia. PMID:22917834

Muscarinic Receptor-Dependent Long Term Depression in the Perirhinal Cortex and Recognition Memory are Impaired in the rTg4510 Mouse Model of Tauopathy.

PubMed

Scullion, Sarah E; Barker, Gareth R I; Warburton, E Clea; Randall, Andrew D; Brown, Jonathan T

2018-02-26

Neurodegenerative diseases affecting cognitive dysfunction, such as Alzheimer's disease and fronto-temporal dementia, are often associated impairments in the visual recognition memory system. Recent evidence suggests that synaptic plasticity, in particular long term depression (LTD), in the perirhinal cortex (PRh) is a critical cellular mechanism underlying recognition memory. In this study, we have examined novel object recognition and PRh LTD in rTg4510 mice, which transgenically overexpress tau P301L . We found that 8-9 month old rTg4510 mice had significant deficits in long- but not short-term novel object recognition memory. Furthermore, we also established that PRh slices prepared from rTg4510 mice, unlike those prepared from wildtype littermates, could not support a muscarinic acetylcholine receptor-dependent form of LTD, induced by a 5 Hz stimulation protocol. In contrast, bath application of the muscarinic agonist carbachol induced a form of chemical LTD in both WT and rTg4510 slices. Finally, when rTg4510 slices were preincubated with the acetylcholinesterase inhibitor donepezil, the 5 Hz stimulation protocol was capable of inducing significant levels of LTD. These data suggest that dysfunctional cholinergic innervation of the PRh of rTg4510 mice, results in deficits in synaptic LTD which may contribute to aberrant recognition memory in this rodent model of tauopathy.

Citalopram restores short-term memory deficit and non-cognitive behaviors in APP/PS1 mice while halting the advance of Alzheimer's disease-like pathology.

PubMed

Zhang, Qin; Yang, Chen; Liu, Tianyao; Liu, Liang; Li, Fen; Cai, Yulong; Lv, Keyi; Li, Xin; Gao, Junwei; Sun, Dayu; Xu, Haiwei; Yang, Qingwu; Fan, Xiaotang

2018-03-15

Alzheimer's disease (AD) is the most common cause of dementia. In addition to cognitive impairments, deficits in non-cognitive behaviors are also common neurological sequelae in AD. Here, we show that complex behavioral deficits in 7-month-old APPswe/PSEN1dE9 (APP/PS1) mice include impairments in object recognition, deficient social interaction, increased depression and buried marbles. Citalopram, one of the selective serotonin reuptake inhibitors (SSRIs), ameliorated the amyloid deposition in AD patients and transgenic animal models. After treatment for 4 weeks, citalopram rescued the deficits in short-term memory, sociability and depression in these mice. Further immunohistochemical analysis showed chronic citalopram treatment significantly attenuated β-amyloid deposition and microglial activation in the brains of APP/PS1 mice as demonstrated previously. Parvalbumin (PV) interneurons, which are the primary cellular subtype of GABAergic neurons and considered indispensable for short-term memory and social interaction, also contributed to the progress of depression. Additionally, we found the citalopram could significantly increase the PV-positive neurons in the cortex of APP/PS1 mice without alteration in the hippocampus, which might contribute to the improvement of behavioral performance. Our findings suggest that citalopram might be a potential candidate for the early treatment of AD. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2011-01-25

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

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

PubMed Central

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

2011-01-01

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

Effects of aging and divided attention on memory for items and their contexts.

PubMed

Craik, Fergus I M; Luo, Lin; Sakuta, Yuiko

2010-12-01

It is commonly found that memory for context declines disproportionately with aging, arguably due to a general age-related deficit in associative memory processes. One possible mechanism for such deficits is an age-related reduction in available processing resources. In two experiments we compared the effects of aging to the effects of division of attention in younger adults on memory for items and context. Using a technique proposed by Craik (1989), linear functions relating memory performance for items and their contexts were derived for a Young Full Attention group, a Young Divided Attention group, and an Older Adult group. Results suggested that the Old group showed an additional deficit in associative memory that was not mimicked by divided attention. It is speculated that both divided attention and aging are associated with a loss of available processing resources that may reflect inefficient frontal lobe functioning, whereas the additional age-related decrement in associative memory may reflect inefficient processing in medial-temporal regions. (c) 2010 APA, all rights reserved).

Cognitive deficits in individuals with methamphetamine use disorder: A meta-analysis.

PubMed

Potvin, Stéphane; Pelletier, Julie; Grot, Stéphanie; Hébert, Catherine; Barr, Alasdair M; Lecomte, Tania

2018-05-01

Methamphetamine has long been considered as a neurotoxic substance causing cognitive deficits. Recently, however, the magnitude and the clinical significance of the cognitive effects associated with methamphetamine use disorder (MUD) have been debated. To help clarify this controversy, we performed a meta-analysis of the cognitive deficits associated with MUD. A literature search yielded 44 studies that assessed cognitive dysfunction in 1592 subjects with MUD and 1820 healthy controls. Effect size estimates were calculated using the Comprehensive Meta-Analysis, for the following 12 cognitive domains: attention, executive functions, impulsivity/reward processing, social cognition, speed of processing, verbal fluency/language, verbal learning and memory, visual learning and memory, visuo-spatial abilities and working memory. Findings revealed moderate impairment across most cognitive domains, including attention, executive functions, language/verbal fluency, verbal learning and memory, visual memory and working memory. Deficits in impulsivity/reward processing and social cognition were more prominent, whereas visual learning and visuo-spatial abilities were relatively spared cognitive domains. A publication bias was observed. These results show that MUD is associated with broad cognitive deficits that are in the same range as those associated with alcohol and cocaine use disorder, as recently shown by way of meta-analysis. The prominent effects of MUD on social cognition and impulsivity/reward processing are based on a small number of studies, and as such, these results will need to be replicated. The functional consequences (social and occupational) of the cognitive deficits of methamphetamine will also need to be determined. Copyright © 2018 Elsevier Ltd. All rights reserved.

Linalool Ameliorates Memory Loss and Behavioral Impairment Induced by REM-Sleep Deprivation through the Serotonergic Pathway.

PubMed

Lee, Bo Kyung; Jung, An Na; Jung, Yi-Sook

2018-07-01

Rapid eye movement (REM) sleep has an essential role in the process of learning and memory in the hippocampus. It has been reported that linalool, a major component of Lavandula angustifolia , has antioxidant, anti-inflammatory, and neuroprotective effects, along with other effects. However, the effect of linalool on the cognitive impairment and behavioral alterations that are induced by REM-sleep deprivation has not yet been elucidated. Several studies have reported that REM-sleep deprivation-induced memory deficits provide a well-known model of behavioral alterations. In the present study, we examined whether linalool elicited an anti-stress effect, reversing the behavioral alterations observed following REM-sleep deprivation in mice. Furthermore, we investigated the underlying mechanism of the effect of linalool. Spatial memory and learning memory were assessed through Y maze and passive avoidance tests, respectively, and the forced swimming test was used to evaluate anti-stress activity. The mechanisms through which linalool improves memory loss and behavioral alterations in sleep-deprived mice appeared to be through an increase in the serotonin levels. Linalool significantly ameliorated the spatial and learning memory deficits, and stress activity observed in sleep-deprived animals. Moreover, linalool led to serotonin release, and cortisol level reduction. Our findings suggest that linalool has beneficial effects on the memory loss and behavioral alterations induced by REM-sleep deprivation through the regulation of serotonin levels.

Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model.

PubMed

Monyak, R E; Emerson, D; Schoenfeld, B P; Zheng, X; Chambers, D B; Rosenfelt, C; Langer, S; Hinchey, P; Choi, C H; McDonald, T V; Bolduc, F V; Sehgal, A; McBride, S M J; Jongens, T A

2017-08-01

Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low intelligence quotent and a wide range of other symptoms including disordered sleep and autism. Although FXS is the most prevalent inherited cause of intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. Examination of the insulin signaling (IS) pathway revealed elevated levels of Drosophila insulin-like peptide 2 (Dilp2) in the IPCs and elevated IS in the dfmr1 mutant brain. Consistent with a causal role for elevated IS in dfmr1 mutant phenotypes, the expression of dfmr1 specifically in the IPCs reduced IS, and genetic reduction of the insulin pathway also led to amelioration of circadian and memory defects. Furthermore, we showed that treatment with the FDA-approved drug metformin also rescued memory. Finally, we showed that reduction of IS is required at different time points to rescue circadian behavior and memory. Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients.

A distinct pattern of memory and attention deficiency in patients with depression.

PubMed

Luo, Lan-Lan; Chen, Xin; Chai, Yan; Li, Jin-Hong; Zhang, Mian; Zhang, Jian-Ning

2013-03-01

Depression related cognitive deficits are frequently considered as simple epiphenomena of the disorder. However, whether or not the depression might directly bring about cognitive deficits is still under investigation. This study was to investigate the distinct pattern of cognitive deficits in patients with depression by comparing the cognitive function before and after anti-depressive drug therapy. Sixty cases of patients, first-time diagnosed with depression, were assessed by 17-item Hamilton Rating Scale for Depression (HAMD17scale). The memory ability was tested by quantitatively clinical memory scale, while the attention ability by modified Ruff 2&7 Selective Attention Test. Forty-two healthy volunteers were recruited as controls. The depressive patients were treated with Venlafaxine (75 - 300 mg/d), Fluoxetine (20 - 40 mg/d), Paroxetine (20 - 40 mg/d), and Sertraline (50 - 150 mg/d). After 12 weeks treatment, patients were tested again by HAMD17scale, quantitatively clinical memory scale, and modified Ruff 2&7 selective attention test to assess the effect of anti-depressive drugs on cognitive deficits. The memory quotient (MQ) was significantly lowered in depressive patients. The selection speed was also significantly decreased and the number of missing and error hits increased in the depression group as compared to control. However, there was no significant difference in clinical memory scale and Ruff 2&7 selective attention test between mild-to-moderate and severe depression group. Importantly, after anti-depressive drug therapy, the HAMD17 scale scores in depressive patients were significantly decreased, but the MQ, directional memory (DM), free recall (FR), associative learning (AL), and face recognition were comparable with those before the treatment. Furthermore, the selection speed and the number of missing and error hits were also not significantly different after anti-depressive drugs treatment. Depressive patients suffer from short-term memory deficits, and attention extent, stability and rearrangement deficiency. Even though anti-depressive drugs sufficiently relieve the cardinal presentation of depression, they could not successfully alleviate the accompanying cognitive deficits. This might indicate a distinct pattern of cognitive deficits in patients with depression.

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

PubMed Central

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

2014-01-01

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

Speech Perception and Short Term Memory Deficits in Persistent Developmental Speech Disorder

PubMed Central

Kenney, Mary Kay; Barac-Cikoja, Dragana; Finnegan, Kimberly; Jeffries, Neal; Ludlow, Christy L.

2008-01-01

Children with developmental speech disorders may have additional deficits in speech perception and/or short-term memory. To determine whether these are only transient developmental delays that can accompany the disorder in childhood or persist as part of the speech disorder, adults with a persistent familial speech disorder were tested on speech perception and short-term memory. Nine adults with a persistent familial developmental speech disorder without language impairment were compared with 20 controls on tasks requiring the discrimination of fine acoustic cues for word identification and on measures of verbal and nonverbal short-term memory. Significant group differences were found in the slopes of the discrimination curves for first formant transitions for word identification with stop gaps of 40 and 20 ms with effect sizes of 1.60 and 1.56. Significant group differences also occurred on tests of nonverbal rhythm and tonal memory, and verbal short-term memory with effect sizes of 2.38, 1.56 and 1.73. No group differences occurred in the use of stop gap durations for word identification. Because frequency-based speech perception and short-term verbal and nonverbal memory deficits both persisted into adulthood in the speech-impaired adults, these deficits may be involved in the persistence of speech disorders without language impairment. PMID:15896836

Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: insights from molecular, cellular and synaptic studies

PubMed Central

Moscato, Emilia H.; Jain, Ankit; Peng, Xiaoyu; Hughes, Ethan G.; Dalmau, Josep; Balice-Gordon, Rita J.

2010-01-01

Recently, several novel, potentially lethal, and treatment-responsive syndromes that affect hippocampal and cortical function have been shown to be associated with auto-antibodies against synaptic antigens, notably glutamate or GABA-B receptors. Patients with these auto-antibodies, sometimes associated with teratomas and other neoplasms, present with psychiatric symptoms, seizures, memory deficits, and decreased level of consciousness. These symptoms often improve dramatically after immunotherapy or tumor resection. Here we discuss studies of the cellular and synaptic effects of these antibodies in hippocampal neurons in vitro and preliminary work in rodent models. Our work suggests that patient antibodies lead to rapid and reversible removal of neurotransmitter receptors from synaptic sites, leading to changes in synaptic and circuit function that in turn are likely to lead to behavioral deficits. We also discuss several of the many questions raised by these and related disorders. Determining the mechanisms underlying these novel anti-neurotransmitter receptor encephalopathies will provide insights into the cellular and synaptic bases of the memory and cognitive deficits that are hallmarks of these disorders, and potentially suggest avenues for therapeutic intervention. PMID:20646055

Insulin potentiates the therapeutic effect of memantine against central STZ-induced spatial learning and memory deficit.

PubMed

Bahramian, Abbas; Rastegar, Karim; Namavar, Mohammad Reza; Moosavi, Maryam

2016-09-15

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Memantine has been approved for moderate to severe AD, but evidence indicates that it does not modify disease progression. Recently insulin has been found to exert some beneficial effects on cognition. This study aimed to compare the protective effects of memantine and insulin in an animal model of memory deficit. It also evaluated the effects of combination therapy of these drugs. Adult male Sprague-Dawely rats approximately 8-10 weeks old were used. The canules were implanted bilaterally into lateral ventricles. STZ was administered on days 1 and 3 (3mg/kg in divided doses) and Memantine (5 or 10mg/kg/ip) or/and Insulin (3 or 6mU/icv) were started from day 4 and continued till day 13. The animal's learning and memory capability was assessed on days 14-16 using Morris water maze. On day 17 a visible platform test was done to assess the animals' visuomotor ability. After completion of behavioral studies the brain sections were stained with hematoxylin and eosin for routine histological evaluation. The results show that memantine in doses 5 and 10mg/kg improved memory at day 3 of training and memantine 5mg/kg was more potent than memantine 10mg/kg. Insulin in dose 3mU, but not 6 mU, reversed STZ-induced memory deficit from day 2 of training. When insulin was added to memantine, it increased the potency of memantine 5mg/kg in preventing a memory deficit, but surprisingly was not successful in impeding STZ-induced amnesia, in combination with memantine 10mg/kg. This research work revealed that insulin act more efficiently than memantine in reversing STZ-induced memory impairment. Additionally combination of insulin and memantine seems to act better than memantine alone, providing that a dose adjustment has been done. This study suggests considering the combination therapy of memantine and insulin in dementia and AD. Copyright © 2016 Elsevier B.V. All rights reserved.

Do Immediate Memory Deficits in Students with Learning Disabilities in Reading Reflect a Developmental Lag or Deficit?: A Selective Meta-Analysis of the Literature.

ERIC Educational Resources Information Center

O'Shaughnessy, Tam E.; Swanson, H. Lee

1998-01-01

A study synthesized findings of 41 studies that compared children with and without learning disabilities in reading on immediate-memory performance. Results indicate children with learning disabilities were distinctly disadvantaged compared to average readers when memory manipulations required the naming of visual information and task conditions…

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

ERIC Educational Resources Information Center

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

2016-01-01

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

Metamemory Ability in Learning Disabled Children with and without a Memory Deficit.

ERIC Educational Resources Information Center

Goldstein, David; Golding, Jonathan

Normal children (N=8) and two groups of 8 learning disabled (LD) elementary grade children, one with and one without a short-term memory deficit, were administered a battery of questions concerning knowledge of how their memories function (metamemory). Metamemory was found to be deficient only in the subgroup of LD children with a short-term…

Computerized Working-Memory Training as a Candidate Adjunctive Treatment for Addiction

PubMed Central

Bickel, Warren K.; Moody, Lara; Quisenberry, Amanda

2014-01-01

Alcohol and other drug dependencies are, in part, characterized by deficits in executive functioning, including working memory. Working-memory training is a candidate computerized adjunctive intervention for the treatment of alcoholism and other drug dependencies. This article reviews emerging evidence for computerized working memory training as an efficacious adjunctive treatment for drug dependence and highlights future challenges and opportunities in the field of working-memory training, including duration of training needed, persistence of improvements and utility of booster sessions, and selection of patients based on degree of deficits. PMID:26259006

A selective memory deficit caused by autoimmune encephalopathy associated with Hashimoto thyroiditis.

PubMed

Koros, Christos; Economou, Alexandra; Mastorakos, George; Bonakis, Anastasios; Kalfakis, Nikolaos; Papageorgiou, Sokratis G

2012-09-01

We report a longstanding selective memory deficit in a euthyroid 45-year-old woman who was being treated with levothyroxine for Hashimoto thyroiditis. The patient had complained of memory problems and deterioration of her concentration skills for about 2 years. Her endocrinologist thought that she was depressed. The patient's physical examination was normal. She scored a full 30 points on the Mini-Mental State Examination, but neuropsychological evaluation showed a significant deficit in her verbal memory. Routine blood tests and cerebrospinal fluid analysis showed only antithyroid peroxidase antibodies. Brain magnetic resonance imaging was normal. Electroencephalogram showed scarce intermittent bilateral multifocal theta waves. We increased the patient's daily dose of levothyroxine and started her on dexamethasone therapy. Five months later, we repeated the entire evaluation and found both her cognitive function and her electroencephalogram to be normal. Autoimmune encephalopathy associated with Hashimoto thyroiditis is already known to present with either stroke-like episodes or diffuse progressive deterioration. Our patient shows that the encephalopathy can present as a chronic selective memory deficit that can spare executive functions and short-term memory. This presentation can be missed or mistaken for depression, but can be diagnosed with a detailed neuropsychological evaluation.

Deficits in discrimination after experimental frontal brain injury are mediated by motivation and can be improved by nicotinamide administration.

PubMed

Vonder Haar, Cole; Maass, William R; Jacobs, Eric A; Hoane, Michael R

2014-10-15

One of the largest challenges in experimental neurotrauma work is the development of models relevant to the human condition. This includes both creating similar pathophysiology as well as the generation of relevant behavioral deficits. Recent studies have shown that there is a large potential for the use of discrimination tasks in rats to detect injury-induced deficits. The literature on discrimination and TBI is still limited, however. The current study investigated motivational and motor factors that could potentially contribute to deficits in discrimination. In addition, the efficacy of a neuroprotective agent, nicotinamide, was assessed. Rats were trained on a discrimination task and motivation task, given a bilateral frontal controlled cortical impact TBI (+3.0 AP, 0.0 ML from bregma), and then reassessed. They were also assessed on motor ability and Morris water maze (MWM) performance. Experiment 1 showed that TBI resulted in large deficits in discrimination and motivation. No deficits were observed on gross motor measures; however, the vehicle group showed impairments in fine motor control. Both injured groups were impaired on the reference memory MWM, but only nicotinamide-treated rats were impaired on the working memory MWM. Nicotinamide administration improved performance on discrimination and motivation measures. Experiment 2 evaluated retraining on the discrimination task and suggested that motivation may be a large factor underlying discrimination deficits. Retrained rats improved considerably on the discrimination task. The tasks evaluated in this study demonstrate robust deficits and may improve the detection of pharmaceutical effects by being very sensitive to pervasive cognitive deficits that occur after frontal TBI.

Episodic Memory Impairments in Primary Brain Tumor Patients.

PubMed

Durand, Thomas; Berzero, Giulia; Bompaire, Flavie; Hoffmann, Sabine; Léger, Isabelle; Jego, Virginie; Baruteau, Marie; Delgadillo, Daniel; Taillia, Hervé; Psimaras, Dimitri; Ricard, Damien

2018-01-04

Cognitive investigations in brain tumor patients have mostly explored episodic memory without differentiating between encoding, storage, and retrieval deficits. The aim of this study is to offer insight into the memory sub-processes affected in primary brain tumor patients and propose an appropriate assessment method. We retrospectively reviewed the clinical and memory assessments of 158 patients with primary brain tumors who had presented to our departments with cognitive complaints and were investigated using the Free and Cued Selective Reminding Test. Retrieval was the process of episodic memory most frequently affected, with deficits in this domain detected in 92% of patients with episodic memory impairments. Storage and encoding deficits were less prevalent, with impairments, respectively, detected in 41% and 23% of memory-impaired patients. The pattern of episodic memory impairment was similar across different tumor histologies and treatment modalities. Although all processes of episodic memory were found to be impaired, retrieval was by far the most widely affected function. A thorough assessment of all three components of episodic memory should be part of the regular neuropsychological evaluation in patients with primary brain tumors. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Deficits in working memory and motor performance in the APP/PS1ki mouse model for Alzheimer's disease.

PubMed

Wirths, Oliver; Breyhan, Henning; Schäfer, Stephanie; Roth, Christian; Bayer, Thomas A

2008-06-01

The APP/PS1ki mouse model for Alzheimer's disease (AD) exhibits robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss starting at 6 months of age. It expresses human mutant APP751 with the Swedish and London mutations together with two FAD-linked knocked-in mutations (PS1 M233T and PS1 L235P) in the murine PS1 gene. The present report covers a phenotypical analysis of this model using either behavioral tests for working memory and motor performance, as well as an analysis of weight development and body shape. At the age of 6 months, a dramatic, age-dependent change in all of these properties and characteristics was observed, accompanied by a significantly reduced ability to perform working memory and motor tasks. The APP/PS1ki mice were smaller and showed development of a thoracolumbar kyphosis, together with an incremental loss of body weight. While 2-month-old APP/PS1ki mice were inconspicuous in all of these tasks and properties, there is a massive age-related impairment in all tested behavioral paradigms. We have previously reported robust axonal degeneration in brain and spinal cord, as well as abundant hippocampal CA1 neuron loss starting at 6 months of age in the APP/PS1ki mouse model, which coincides with the onset of motor and memory deficits described in the present report.

Working Memory Arrest in Children with High-Functioning Autism Compared to Children with Attention-Deficit/Hyperactivity Disorder: Results from a 2-Year Longitudinal Study

ERIC Educational Resources Information Center

Andersen, Per N.; Skogli, Erik W.; Hovik, Kjell T.; Geurts, Hilde; Egeland, Jens; Øie, Merete

2015-01-01

The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically…

A Characterization of Visual, Semantic and Auditory Memory in Children with Combination-Type Attention Deficit, Primarily Inattentive, and a Control Group

ERIC Educational Resources Information Center

Ramirez, Luz Angela; Arenas, Angela Maria; Henao, Gloria Cecilia

2005-01-01

Introduction: This investigation describes and compares characteristics of visual, semantic and auditory memory in a group of children diagnosed with combined-type attention deficit with hyperactivity, attention deficit predominating, and a control group. Method: 107 boys and girls were selected, from 7 to 11 years of age, all residents in the…

Improving Working Memory in Children with Attention-Deficit/Hyperactivity Disorder: The Separate and Combined Effects of Incentives and Stimulant Medication

ERIC Educational Resources Information Center

Strand, Michael T.; Hawk, Larry W., Jr.; Bubnik, Michelle; Shiels, Keri; Pelham, William E., Jr.; Waxmonsky, James G.

2012-01-01

Working memory (WM) is considered a core deficit in Attention-Deficit/Hyperactivity Disorder (ADHD), with numerous studies demonstrating impaired WM among children with ADHD. We tested the degree to which WM in children with ADHD was improved by performance-based incentives, an analog of behavioral intervention. In two studies, WM performance was…

Interference control, working memory, concept shifting, and verbal fluency in adults with attention-deficit/hyperactivity disorder (ADHD).

PubMed

Marchetta, Natalie D J; Hurks, Petra P M; Krabbendam, Lydia; Jolles, Jelle

2008-01-01

In this study, the authors aimed to examine 4 domains of executive functioning in adults with attention-deficit/hyperactivity disorder (ADHD)--namely interference control, concept shifting, verbal fluency, and verbal working memory. Four groups of participants were included: (a) adults diagnosed with ADHD (ADHD-super(-); n = 20), (b) adults diagnosed with both ADHD and 1 or more comorbid disorder(s) (ADHD-super(+); n = 22), (c) adults referred for ADHD because of ADHD symptomatology but not diagnosed as such (non-ADHD; n = 34), and (d) healthy controls (n = 136). ADHD-related deficits (independent of comorbidity) were revealed for concept shifting and verbal working memory. In addition, the ADHD-super(+) and non-ADHD groups displayed deficits in terms of general processing speed. Given that these deficits were not found in the ADHD-super(-) group, the authors contend that these deficits are likely attributable to comorbidity rather than ADHD itself. Contrary to the authors' expectations, these findings do not correspond with the cognitive subtype hypothesis.

Sleep, Torpor and Memory Impairment

NASA Astrophysics Data System (ADS)

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.

Comparable performance of patients with obsessive-compulsive disorder (OCD) and healthy controls for verbal and nonverbal memory accuracy and confidence: time to forget the forgetfulness hypothesis of OCD?

PubMed

Moritz, Steffen; Kloss, Martin; von Eckstaedt, Francesca Vitzthum; Jelinek, Lena

2009-04-30

The memory deficit or forgetfulness hypothesis of obsessive-compulsive disorder (OCD) has received considerable attention and empirical effort over the past decades. The present study aimed to provide a fair test of its various formulations: (1) memory dysfunction in OCD is ubiquitous, that is, manifests irrespective of modality and material; (2) memory dysfunction is found for nonverbal but not verbal material, (3) memory dysfunction is secondary to executive impairment; and (4) memory dysfunction affects meta-memory rather than memory accuracy. Participants comprised 43 OCD patients and 46 healthy controls who were tested on the Picture Word Memory Test (PWMT), which provides several unconfounded parameters for nonverbal and verbal memory accuracy and confidence measures across different time-points. In addition, the Trail-Making Test B was administered to test assumption number 3. Replicating earlier work of our group, samples displayed similar performance on all indices. None of the different formulations of the memory deficit hypothesis were supported. In view of waning evidence for a global memory deficit in OCD, neuropsychological research on OCD should more thoroughly investigate moderators and triggers of occasional instances of impaired performance, particularly cognitive biases such as perfectionism and an inflated sense of responsibility.

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

PubMed

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

2011-12-02

Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3β (p-GSK3β) and total GSK3β levels were determined, and importantly GSK3β regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3β levels, while total GSK3β did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3β levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of signaling cascade of insulin receptor. 2011 Elsevier B.V. All rights reserved.

The neuroscience of positive memory deficits in depression

PubMed Central

Dillon, Daniel G.

2015-01-01

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

Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates.

PubMed

Barendse, Evelien M; Hendriks, Marc Ph; Jansen, Jacobus Fa; Backes, Walter H; Hofman, Paul Am; Thoonen, Geert; Kessels, Roy Pc; Aldenkamp, Albert P

2013-06-04

Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum.

Sleep Promotes Consolidation of Emotional Memory in Healthy Children but Not in Children with Attention-Deficit Hyperactivity Disorder

PubMed Central

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

2013-01-01

Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline–corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD. PMID:23734235

Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe): development and validation.

PubMed

Viswanath, Biju; Harihara, Shashidhara N; Nahar, Abhinav; Phutane, Vivek Haridas; Taksal, Aarati; Thirthalli, Jagadisha; Gangadhar, Bangalore N

2013-06-01

The use of electroconvulsive therapy (ECT) in treatment of psychiatric disorders is associated with adverse cognitive effects. There is a need to develop a short assessment tool of cognitive functions during the course of ECT. This study aimed at developing and validating a short, sensitive battery to assess cognitive deficits associated with ECT in India. Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe), a brief cognitive battery (20-30 min) to assess verbal, visual, working and autobiographic memory, sustained attention, psychomotor speed and subjective memory impairment, was administered to 30 in-patients receiving bilateral ECT, one day after the 1st, 3rd and 6th ECT. Data was analysed using repeated measures analysis of variance and Pearson's correlation. Significant deficits were found in verbal, visual and autobiographic memory, psychomotor speed. Subjective experience of memory loss correlated positively with verbal memory impairment. B4ECT-ReCoDe, a brief, sensitive measure of cognitive impairments associated with ECT can be used in routine clinical practice. Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2016-01-01

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

Theory of mind and verbal working memory deficits in parents of autistic children.

PubMed

Gokcen, Sezen; Bora, Emre; Erermis, Serpil; Kesikci, Hande; Aydin, Cahide

2009-03-31

The objective of this study was to investigate the potential values of executive function and social cognition deficits as endophenotypes of autism. While theory of mind (ToM) is generally accepted as a unitary concept, some have suggested that ToM may be separated into two components (mental state reasoning and decoding). In this study, both aspects of ToM and verbal working memory abilities were investigated with relatively demanding tasks. The authors used a neurocognitive battery to compare the executive function and social cognition skills of 76 parents of autistic probands with 41 parents of healthy children. Both groups were matched for IQ, age and gender. Index parents had verbal working memory deficits. They had also low performance on a mental state reasoning task. Index parents had difficulties in reasoning about others' emotions. In contrast to findings in the control group, low performance of mental state reasoning ability was not associated with working memory deficit in index parents. Social cognition and working memory impairments may represent potential endophenotypes, related to an underlying vulnerability for autistic spectrum disorders.

Experimental 'jet lag' inhibits adult neurogenesis and produces long-term cognitive deficits in female hamsters.

PubMed

Gibson, Erin M; Wang, Connie; Tjho, Stephanie; Khattar, Neera; Kriegsfeld, Lance J

2010-12-01

Circadian disruptions through frequent transmeridian travel, rotating shift work, and poor sleep hygiene are associated with an array of physical and mental health maladies, including marked deficits in human cognitive function. Despite anecdotal and correlational reports suggesting a negative impact of circadian disruptions on brain function, this possibility has not been experimentally examined. In the present study, we investigated whether experimental 'jet lag' (i.e., phase advances of the light:dark cycle) negatively impacts learning and memory and whether any deficits observed are associated with reductions in hippocampal cell proliferation and neurogenesis. Because insults to circadian timing alter circulating glucocorticoid and sex steroid concentrations, both of which influence neurogenesis and learning/memory, we assessed the contribution of these endocrine factors to any observed alterations. Circadian disruption resulted in pronounced deficits in learning and memory paralleled by marked reductions in hippocampal cell proliferation and neurogenesis. Significantly, deficits in hippocampal-dependent learning and memory were not only seen during the period of the circadian disruption, but also persisted well after the cessation of jet lag, suggesting long-lasting negative consequences on brain function. Together, these findings support the view that circadian disruptions suppress hippocampal neurogenesis via a glucocorticoid-independent mechanism, imposing pronounced and persistent impairments on learning and memory.

Basic numerical processing, calculation, and working memory in children with dyscalculia and/or ADHD symptoms.

PubMed

Kuhn, Jörg-Tobias; Ise, Elena; Raddatz, Julia; Schwenk, Christin; Dobel, Christian

2016-09-01

Deficits in basic numerical skills, calculation, and working memory have been found in children with developmental dyscalculia (DD) as well as children with attention-deficit/hyperactivity disorder (ADHD). This paper investigates cognitive profiles of children with DD and/or ADHD symptoms (AS) in a double dissociation design to obtain a better understanding of the comorbidity of DD and ADHD. Children with DD-only (N = 33), AS-only (N = 16), comorbid DD+AS (N = 20), and typically developing controls (TD, N = 40) were assessed on measures of basic numerical processing, calculation, working memory, processing speed, and neurocognitive measures of attention. Children with DD (DD, DD+AS) showed deficits in all basic numerical skills, calculation, working memory, and sustained attention. Children with AS (AS, DD+AS) displayed more selective difficulties in dot enumeration, subtraction, verbal working memory, and processing speed. Also, they generally performed more poorly in neurocognitive measures of attention, especially alertness. Children with DD+AS mostly showed an additive combination of the deficits associated with DD-only and A_Sonly, except for subtraction tasks, in which they were less impaired than expected. DD and AS appear to be related to largely distinct patterns of cognitive deficits, which are present in combination in children with DD+AS.

Spatial memory: a Rosetta stone for rat and human hippocampal discourse: Theoretical comment on Goodrich-Hunsaker and Hopkins (2010).

PubMed

Sutherland, Robert J

2010-06-01

The article by Goodrich-Hunsaker and Hopkins (2010, this issue) takes up an important place among in the recent contributions on the role of the hippocampus in memory. They evaluate the effect of bilateral damage to the hippocampus on performance by human participants in a virtual 8-arm radial maze. The hippocampal damage appears to be highly selective and nearly complete. Exactly as with selective hippocampal damage in rats, the human participants showed a deficit in accurately choosing rewarded versus never-rewarded arms and a deficit in avoiding reentering recently visited arms. The results are triply significant: (1) They provide good support for the idea that the wealth of neurobiological information, from network to synapse to gene, on spatial memory in the rat may apply as a whole to the human hippocampal memory system; (2) They affirm the utility of human virtual task models of rat spatial memory tasks; (3) They support one interpretation of the dampening of the hippocampal functional MRI (fMRI) blood oxygen level-dependent (BOLD) signal during performance of the virtual radial arm maze observed by Astur et al. (2005).

Effects of heavy particle irradiation and diet on object recognition memory in rats

NASA Astrophysics Data System (ADS)

Rabin, Bernard M.; Carrihill-Knoll, Kirsty; Hinchman, Marie; Shukitt-Hale, Barbara; Joseph, James A.; Foster, Brian C.

2009-04-01

On long-duration missions to other planets astronauts will be exposed to types and doses of radiation that are not experienced in low earth orbit. Previous research using a ground-based model for exposure to cosmic rays has shown that exposure to heavy particles, such as 56Fe, disrupts spatial learning and memory measured using the Morris water maze. Maintaining rats on diets containing antioxidant phytochemicals for 2 weeks prior to irradiation ameliorated this deficit. The present experiments were designed to determine: (1) the generality of the particle-induced disruption of memory by examining the effects of exposure to 56Fe particles on object recognition memory; and (2) whether maintaining rats on these antioxidant diets for 2 weeks prior to irradiation would also ameliorate any potential deficit. The results showed that exposure to low doses of 56Fe particles does disrupt recognition memory and that maintaining rats on antioxidant diets containing blueberry and strawberry extract for only 2 weeks was effective in ameliorating the disruptive effects of irradiation. The results are discussed in terms of the mechanisms by which exposure to these particles may produce effects on neurocognitive performance.

Revisiting the continuum hypothesis: toward an in-depth exploration of executive functions in korsakoff syndrome.

PubMed

Brion, Mélanie; Pitel, Anne-Lise; Beaunieux, Hélène; Maurage, Pierre

2014-01-01

Korsakoff syndrome (KS) is a neurological state mostly caused by alcohol-dependence and leading to disproportionate episodic memory deficits. KS patients present more severe anterograde amnesia than Alcohol-Dependent Subjects (ADS), which led to the continuum hypothesis postulating a progressive increase in brain and cognitive damages during the evolution from ADS to KS. This hypothesis has been extensively examined for memory but is still debated for other abilities, notably executive functions (EF). EF have up to now been explored by unspecific tasks in KS, and few studies explored their interactions with memory. Exploring EF in KS by specific tasks based on current EF models could thus renew the exploration of the continuum hypothesis. This paper will propose a research program aiming at: (1) clarifying the extent of executive dysfunctions in KS by tasks focusing on specific EF subcomponents; (2) determining the differential EF deficits in ADS and KS; (3) exploring EF-memory interactions in KS with innovative tasks. At the fundamental level, this exploration will test the continuum hypothesis beyond memory. At the clinical level, it will propose new rehabilitation tools focusing on the EF specifically impaired in KS.

Revisiting the Continuum Hypothesis: Toward an In-Depth Exploration of Executive Functions in Korsakoff Syndrome

PubMed Central

Brion, Mélanie; Pitel, Anne-Lise; Beaunieux, Hélène; Maurage, Pierre

2014-01-01

Korsakoff syndrome (KS) is a neurological state mostly caused by alcohol-dependence and leading to disproportionate episodic memory deficits. KS patients present more severe anterograde amnesia than Alcohol-Dependent Subjects (ADS), which led to the continuum hypothesis postulating a progressive increase in brain and cognitive damages during the evolution from ADS to KS. This hypothesis has been extensively examined for memory but is still debated for other abilities, notably executive functions (EF). EF have up to now been explored by unspecific tasks in KS, and few studies explored their interactions with memory. Exploring EF in KS by specific tasks based on current EF models could thus renew the exploration of the continuum hypothesis. This paper will propose a research program aiming at: (1) clarifying the extent of executive dysfunctions in KS by tasks focusing on specific EF subcomponents; (2) determining the differential EF deficits in ADS and KS; (3) exploring EF-memory interactions in KS with innovative tasks. At the fundamental level, this exploration will test the continuum hypothesis beyond memory. At the clinical level, it will propose new rehabilitation tools focusing on the EF specifically impaired in KS. PMID:25071526

Auditory Deficits in Amusia Extend Beyond Poor Pitch Perception

PubMed Central

Whiteford, Kelly L.; Oxenham, Andrew J.

2017-01-01

Congenital amusia is a music perception disorder believed to reflect a deficit in fine-grained pitch perception and/or short-term or working memory for pitch. Because most measures of pitch perception include memory and segmentation components, it has been difficult to determine the true extent of pitch processing deficits in amusia. It is also unclear whether pitch deficits persist at frequencies beyond the range of musical pitch. To address these questions, experiments were conducted with amusics and matched controls, manipulating both the stimuli and the task demands. First, we assessed pitch discrimination at low (500 Hz and 2000 Hz) and high (8000 Hz) frequencies using a three-interval forced-choice task. Amusics exhibited deficits even at the highest frequency, which lies beyond the existence region of musical pitch. Next, we assessed the extent to which frequency coding deficits persist in one- and two-interval frequency-modulation (FM) and amplitude-modulation (AM) detection tasks at 500 Hz at slow (fm = 4 Hz) and fast (fm = 20 Hz) modulation rates. Amusics still exhibited deficits in one-interval FM detection tasks that should not involve memory or segmentation. Surprisingly, amusics were also impaired on AM detection, which should not involve pitch processing. Finally, direct comparisons between the detection of continuous and discrete FM demonstrated that amusics suffer deficits both in coding and segmenting pitch information. Our results reveal auditory deficits in amusia extending beyond pitch perception that are subtle when controlling for memory and segmentation, and are likely exacerbated in more complex contexts such as musical listening. PMID:28315696

Famous face identification in temporal lobe epilepsy: Support for a multimodal integration model of semantic memory

PubMed Central

Drane, Daniel L.; Ojemann, Jeffrey G.; Phatak, Vaishali; Loring, David W.; Gross, Robert E.; Hebb, Adam O.; Silbergeld, Daniel L.; Miller, John W.; Voets, Natalie L.; Saindane, Amit M.; Barsalou, Lawrence; Meador, Kimford J.; Ojemann, George A.; Tranel, Daniel

2012-01-01

This study aims to demonstrate that the left and right anterior temporal lobes (ATLs) perform critical but unique roles in famous face identification, with damage to either leading to differing deficit patterns reflecting decreased access to lexical or semantic concepts but not their degradation. Famous face identification was studied in 22 presurgical and 14 postsurgical temporal lobe epilepsy (TLE) patients and 20 healthy comparison subjects using free recall and multiple choice (MC) paradigms. Right TLE patients exhibited presurgical deficits in famous face recognition, and postsurgical deficits in both famous face recognition and familiarity judgments. However, they did not exhibit any problems with naming before or after surgery. In contrast, left TLE patients demonstrated both pre-and postsurgical deficits in famous face naming but no significant deficits in recognition or familiarity. Double dissociations in performance between groups were alleviated by altering task demands. Postsurgical right TLE patients provided with MC options correctly identified greater than 70% of famous faces they initially rated as unfamiliar. Left TLE patients accurately chose the name for nearly all famous faces they recognized (based on their verbal description) but initially failed to name, although they tended to rapidly lose access to this name. We believe alterations in task demands activate alternative routes to semantic and lexical networks, demonstrating that unique pathways to such stored information exist, and suggesting a different role for each ATL in identifying visually presented famous faces. The right ATL appears to play a fundamental role in accessing semantic information from a visual route, with the left ATL serving to link semantic information to the language system to produce a specific name. These findings challenge several assumptions underlying amodal models of semantic memory, and provide support for the integrated multimodal theories of semantic memory and a distributed representation of concepts. PMID:23040175

Famous face identification in temporal lobe epilepsy: support for a multimodal integration model of semantic memory.

PubMed

Drane, Daniel L; Ojemann, Jeffrey G; Phatak, Vaishali; Loring, David W; Gross, Robert E; Hebb, Adam O; Silbergeld, Daniel L; Miller, John W; Voets, Natalie L; Saindane, Amit M; Barsalou, Lawrence; Meador, Kimford J; Ojemann, George A; Tranel, Daniel

2013-06-01

This study aims to demonstrate that the left and right anterior temporal lobes (ATLs) perform critical but unique roles in famous face identification, with damage to either leading to differing deficit patterns reflecting decreased access to lexical or semantic concepts but not their degradation. Famous face identification was studied in 22 presurgical and 14 postsurgical temporal lobe epilepsy (TLE) patients and 20 healthy comparison subjects using free recall and multiple choice (MC) paradigms. Right TLE patients exhibited presurgical deficits in famous face recognition, and postsurgical deficits in both famous face recognition and familiarity judgments. However, they did not exhibit any problems with naming before or after surgery. In contrast, left TLE patients demonstrated both pre- and postsurgical deficits in famous face naming but no significant deficits in recognition or familiarity. Double dissociations in performance between groups were alleviated by altering task demands. Postsurgical right TLE patients provided with MC options correctly identified greater than 70% of famous faces they initially rated as unfamiliar. Left TLE patients accurately chose the name for nearly all famous faces they recognized (based on their verbal description) but initially failed to name, although they tended to rapidly lose access to this name. We believe alterations in task demands activate alternative routes to semantic and lexical networks, demonstrating that unique pathways to such stored information exist, and suggesting a different role for each ATL in identifying visually presented famous faces. The right ATL appears to play a fundamental role in accessing semantic information from a visual route, with the left ATL serving to link semantic information to the language system to produce a specific name. These findings challenge several assumptions underlying amodal models of semantic memory, and provide support for the integrated multimodal theories of semantic memory and a distributed representation of concepts. Copyright © 2012 Elsevier Ltd. All rights reserved.

Edaravone injection reverses learning and memory deficits in a rat model of vascular dementia.

PubMed

Li, Xu; Lu, Fen; Li, Wei; Qin, Lingzhi; Yao, Yong; Ge, Xuerong; Yu, Qingkai; Liang, Xinliang; Zhao, Dongmei; Li, Xiaohong; Zhang, Jiewen

2017-01-01

Edaravone is a novel free radical scavenger that exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Recently, it was reported that edaravone could alleviate the pathology and cognitive deficits of Alzheimer's disease patients. However, its relevance to vascular dementia (VaD) is not clear. In this study, we partially occluded the bilateral carotid arteries of rats surgically to induce chronic cerebral hypoperfusion (CCH), a well-known rat model of VaD. Water maze and step-down inhibitory test were used to evaluate the memory deficit. The activities of superoxide dismutase (SOD) and lactate dehydrogenase (LDH), the content of malondialdehyde (MDA) and total reactive oxygen species were measured to evaluate the oxidative stress level. Western blot analysis was used to evaluate the synaptic protein expression. It was found that treatment with edaravone for a 5-week period was able to reverse both spatial and fear-memory deficits in rats with CCH. Edaravone significantly reduced the level of oxidative stress in the brains of rats with CCH by increasing SOD activity and decreasing the content of MDA, LDH, and total reactive oxygen species. Furthermore, edaravone treatment also restored the levels of multiple synaptic proteins in the hippocampi of rats with CCH. Our data provide direct evidence supporting the neuroprotective effects of edaravone in VaD. We propose that the alleviation of oxidative stress and restoration of synaptic proteins play important roles in neuroprotection. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Autobiographical memory: a clinical perspective.

PubMed

Urbanowitsch, Nadja; Gorenc, Lina; Herold, Christina J; Schröder, Johannes

2013-12-10

Autobiographical memory (ABM) comprises memories of one's own past that are characterized by a sense of subjective time and autonoetic awareness. Although ABM deficits are among the primary symptoms of patients with major psychiatric conditions such as mild cognitive impairment (MCI) and Alzheimer Disease (AD) or chronic schizophrenia large clinical studies are scarce. We therefore summarize and discuss the results of our clinical studies on ABM deficits in the respective conditions. In these studies ABM was assessed by using the same instrument - i.e., the Erweitertes Autobiographisches Gedächtnis Inventar (E-AGI) - thus allowing a direct comparison between diagnostic groups. Episodic ABM, especially the richness of details was impaired already in MCI and in beginning AD. Semantic memories were spared until moderate stages, indicating a dissociation between both memory systems. A recency effect was detectable in cognitively unimpaired subjects and vanished in patients with AD. A similar pattern of deficits was found in patients with chronic schizophrenia but not in patients with major depression. These ABM deficits were not accounted for by gender, or education level and did not apply for the physiological ageing process in otherwise healthy elderly. In conclusion, ABM deficits are frequently found in AD and chronic schizophrenia and primarily involve episodic rather than semantic memories. This dissociation corresponds to the multiple trace theory which hypothesized that these memory functions refer to distinct neuronal systems. The semi-structured interview E-AGI used to discern ABM changes provided a sufficient reliability measures, moreover potential effects of a number of important confounders could be falsified so far. These findings underline the relevance of ABM-assessments in clinical practice.

Deficits of long-term memory in ecstasy users are related to cognitive complexity of the task.

PubMed

Brown, John; McKone, Elinor; Ward, Jeff

2010-03-01

Despite animal evidence that methylenedioxymethamphetamine (ecstasy) causes lasting damage in brain regions related to long-term memory, results regarding human memory performance have been variable. This variability may reflect the cognitive complexity of the memory tasks. However, previous studies have tested only a limited range of cognitive complexity. Furthermore, comparisons across different studies are made difficult by regional variations in ecstasy composition and patterns of use. The objective of this study is to evaluate ecstasy-related deficits in human verbal memory over a wide range of cognitive complexity using subjects drawn from a single geographical population. Ecstasy users were compared to non-drug using controls on verbal tasks with low cognitive complexity (stem completion), moderate cognitive complexity (stem-cued recall and word list learning) and high cognitive complexity (California Verbal Learning Test, Verbal Paired Associates and a novel Verbal Triplet Associates test). Where significant differences were found, both groups were also compared to cannabis users. More cognitively complex memory tasks were associated with clearer ecstasy-related deficits than low complexity tasks. In the most cognitively demanding task, ecstasy-related deficits remained even after multiple learning opportunities, whereas the performance of cannabis users approached that of non-drug using controls. Ecstasy users also had weaker deliberate strategy use than both non-drug and cannabis controls. Results were consistent with the proposal that ecstasy-related memory deficits are more reliable on tasks with greater cognitive complexity. This could arise either because such tasks require a greater contribution from the frontal lobe or because they require greater interaction between multiple brain regions.

The contribution of acetylcholine and dopamine to subprocesses of visual working memory--what patients with amnestic mild cognitive impairment and Parkinson׳s disease can tell us.

PubMed

Blatt, Joana; Vellage, Anne; Baier, Bernhard; Müller, Notger G

2014-08-01

Attentional selection, i.e. filtering out of irrelevant sensory input and information storage are two crucial components of working memory (WM). It has been proposed that the two processes are mediated by different neurotransmitters, namely acetylcholine for attentional selection and dopamine for memory storage. However, this hypothesis has been challenged by others, who for example linked a lack in dopamine levels in the brain to filtering deficits. Here we tested the above mentioned hypothesis in two patient cohorts which either served as a proxy for a cholinergic or a dopaminergic deficit. The first group comprised 18 patients with amnestic mild cognitive impairment (aMCI), the second 22 patients with Parkinson׳s disease (PD). The two groups did not differ regarding their overall cognitive abilities. Both patient groups as well as a control group without neurological deficits (n=25) performed a visuo-spatial working memory task in which both the necessity to filter out irrelevant information and memory load, i.e. the number of items to be held in memory, were manipulated. In accordance with the primary hypothesis, aMCI patients displayed problems with filtering, i.e., were especially impaired when the task required ignoring distracting stimuli. PD patients on the other hand showed difficulties when memory load was increased suggesting that they mainly suffered from a storage deficit. In sum, this study underlines how the investigation of neurologic patients with a presumed neurotransmitter deficit can aid to clarify these neurotransmitters׳ contribution to specific cognitive functions. Copyright © 2014 Elsevier Ltd. All rights reserved.

A meta-analysis of working memory impairments in survivors of moderate-to-severe traumatic brain injury.

PubMed

Dunning, Darren L; Westgate, Briony; Adlam, Anna-Lynne R

2016-10-01

To establish the magnitude of deficits in working memory (WM) and short-term memory (STM) in those with moderate-to-severe traumatic brain injury (TBI) relative to age-matched, healthy controls and to explore the moderating effects of time since injury and age at injury on these impairments. Twenty-one studies that compared the WM and/or STM abilities of individuals with at least a moderate TBI relative to healthy controls were included in a random effects meta-analysis. Measures used to examine memory performance were categorized by modality (visuospatial, verbal) and memory system (WM, STM). Individuals with TBI had significant deficits in verbal STM (Cohen's d = .41), visuospatial WM (Cohen's d = .69), and verbal WM (Cohen's d = .37) relative to controls. Greater decrements in verbal STM and verbal WM skills were associated with longer time postinjury. Larger deficits were observed in verbal WM abilities in individuals with older age at injury. Evidence for WM impairments following TBI is consistent with previous research. Larger verbal STM and verbal WM deficits were related to a longer time postinjury, suggesting that these aspects of memory do not "recover" over time and instead, individuals might show increased rates of cognitive decline. Age at injury was associated with the severity of verbal WM impairments, with larger deficits evident for injuries that occurred later in life. Further research needs to chart the long-term effects of TBI on WM and to compare the effects of injury on verbal relative to visuospatial memory. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Component deficits of visual neglect: "Magnetic" attraction of attention vs. impaired spatial working memory.

PubMed

Toba, Monica N; Rabuffetti, Marco; Duret, Christophe; Pradat-Diehl, Pascale; Gainotti, Guido; Bartolomeo, Paolo

2018-01-31

Visual neglect is a disabling consequence of right hemisphere damage, whereby patients fail to detect left-sided objects. Its precise mechanisms are debated, but there is some consensus that distinct component deficits may variously associate and interact in different patients. Here we used a touch-screen based procedure to study two putative component deficits of neglect, rightward "magnetic" attraction of attention and impaired spatial working memory, in a group of 47 right brain-damaged patients, of whom 33 had signs of left neglect. Patients performed a visual search task on three distinct conditions, whereby touched targets could (1) be tagged, (2) disappear or (3) show no change. Magnetic attraction of attention was defined as more left neglect on the tag condition than on the disappear condition, where right-sided disappeared targets could not capture patients' attention. Impaired spatial working memory should instead produce more neglect on the no change condition, where no external cue indicated that a target had already been explored, than on the tag condition. Using a specifically developed analysis algorithm, we identified significant differences of performance between the critical conditions. Neglect patients as a group performed better on the disappear condition than on the no change condition and also better in the tag condition comparing with the no change condition. No difference was found between the tag condition and the disappear condition. Some of our neglect patients had dissociated patterns of performance, with predominant magnetic attraction or impaired spatial working memory. Anatomical results issued from both grey matter analysis and fiber tracking were consistent with the typical patterns of fronto-parietal and occipito-frontal disconnection in neglect, but did not identify lesional patterns specifically associated with one or another deficit, thus suggesting the possible co-localization of attentional and working memory processes in fronto-parietal networks. These findings give support to the hypothesis of the co-occurrence of distinct cognitive deficits in visual neglect and stress the necessity of multi-component models of visuospatial disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

A quantitative meta-analysis of neurocognitive functioning in posttraumatic stress disorder

PubMed Central

Scott, J. Cobb; Matt, Georg E.; Wrocklage, Kristen M.; Crnich, Cassandra; Jordan, Jessica; Southwick, Steven M.; Krystal, John H.; Schweinsburg, Brian C.

2014-01-01

Posttraumatic stress disorder (PTSD) is associated with regional alterations in brain structure and function that are hypothesized to contribute to symptoms and cognitive deficits associated with the disorder. We present here the first systematic meta-analysis of neurocognitive outcomes associated with PTSD to examine a broad range of cognitive domains and describe the profile of cognitive deficits, as well as modifying clinical factors and study characteristics. This report is based on data from 60 studies totaling 4,108 participants, including 1,779with PTSD, 1,446 trauma-exposed comparison participants, and 895 healthy comparison participants without trauma exposure. Effect size estimates were calculated using a mixed-effects meta-analysis for nine cognitive domains: attention/working memory, executive functions, verbal learning, verbal memory, visual learning, visual memory, language, speed of information processing, and visuospatial abilities. Analyses revealed significant neurocognitive effects associated with PTSD, although these ranged widely in magnitude, with the largest effect sizes in verbal learning (d =−.62), speed of information processing (d =−.59), attention/working memory (d =−.50), and verbal memory (d =−.46). Effect size estimates were significantly larger in treatment-seeking than community samples and in studies that did not exclude participants with attention-deficit hyperactivity disorder, and effect sizes were affected by between-group IQ discrepancies and the gender composition of the PTSD groups. Our findings indicate that consideration of neuropsychological functioning in attention, verbal memory, and speed of information processing may have important implications for the effective clinical management of persons with PTSD. Results are further discussed in the context of cognitive models of PTSD and the limitations of this literature. PMID:25365762

The effect of white matter hyperintensities on verbal memory: Mediation by temporal lobe atrophy.

PubMed

Swardfager, Walter; Cogo-Moreira, Hugo; Masellis, Mario; Ramirez, Joel; Herrmann, Nathan; Edwards, Jodi D; Saleem, Mahwesh; Chan, Parco; Yu, Di; Nestor, Sean M; Scott, Christopher J M; Holmes, Melissa F; Sahlas, Demetrios J; Kiss, Alexander; Oh, Paul I; Strother, Stephen C; Gao, Fuqiang; Stefanovic, Bojana; Keith, Julia; Symons, Sean; Swartz, Richard H; Lanctôt, Krista L; Stuss, Donald T; Black, Sandra E

2018-02-20

To determine the relationship between white matter hyperintensities (WMH) presumed to indicate disease of the cerebral small vessels, temporal lobe atrophy, and verbal memory deficits in Alzheimer disease (AD) and other dementias. We recruited groups of participants with and without AD, including strata with extensive WMH and minimal WMH, into a cross-sectional proof-of-principle study (n = 118). A consecutive case series from a memory clinic was used as an independent validation sample (n = 702; Sunnybrook Dementia Study; NCT01800214). We assessed WMH volume and left temporal lobe atrophy (measured as the brain parenchymal fraction) using structural MRI and verbal memory using the California Verbal Learning Test. Using path modeling with an inferential bootstrapping procedure, we tested an indirect effect of WMH on verbal recall that depends sequentially on temporal lobe atrophy and verbal learning. In both samples, WMH predicted poorer verbal recall, specifically due to temporal lobe atrophy and poorer verbal learning (proof-of-principle -1.53, 95% bootstrap confidence interval [CI] -2.45 to -0.88; and confirmation -0.66, 95% CI [-0.95 to -0.41] words). This pathway was significant in subgroups with (-0.20, 95% CI [-0.38 to -0.07] words, n = 363) and without (-0.71, 95% CI [-1.12 to -0.37] words, n = 339) AD. Via the identical pathway, WMH contributed to deficits in recognition memory (-1.82%, 95% CI [-2.64% to -1.11%]), a sensitive and specific sign of AD. Across dementia syndromes, WMH contribute indirectly to verbal memory deficits considered pathognomonic of Alzheimer disease, specifically by contributing to temporal lobe atrophy. © 2018 American Academy of Neurology.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

What Is Not Working in Working Memory of Children with Literacy Disorders? Evidence from a Three-Year-Longitudinal Study

ERIC Educational Resources Information Center

Fischbach, Anne; Könen, Tanja; Rietz, Chantal S.; Hasselhorn, Marcus

2014-01-01

The goals of this study were to explore the deficits in working memory associated with literacy disorders (i.e. developmental disorders of reading and/or spelling) and the developmental trajectories of these working memory deficits. The performance of 28 children with literacy disorders was compared to a non-disabled control group with the same…

Impaired event memory and recollection in a case of developmental amnesia.

PubMed

Rosenbaum, R S; Carson, N; Abraham, N; Bowles, B; Kwan, D; Köhler, S; Svoboda, E; Levine, B; Richards, B

2011-10-01

A current debate in the literature is whether all declarative memories and associated memory processes rely on the same neural substrate. Here, we show that H.C., a developmental amnesic person with selective bilateral hippocampal volume loss, has a mild deficit in personal episodic memory, and a more pronounced deficit in public event memory; semantic memory for personal and general knowledge was unimpaired. This was accompanied by a subtle difference in impairment between recollection and familiarity on lab-based tests of recognition memory. Strikingly, H.C.'s recognition did not benefit from a levels-of-processing manipulation. Thus, not all types of declarative memory and related processes can exist independently of the hippocampus even if it is damaged early in life.

Application of the dual-component model of working memory to ADHD:Greater secondary memory deficit despite confounded cognitive differences.

PubMed

Gibson, Bradley S; Gondoli, Dawn M; Ralph, Kathryn J; Sztybel, Pedro

2018-01-01

The dual-component model postulates that working memory capacity consists of two dissociable components: maintenance in primary memory (PM) and retrieval from secondary memory (SM). Recent application of this model to attention-deficit/hyperactivity disorder (ADHD) has revealed that the SM component is more deficient than the PM component across both verbal and spatial modalities. The present study attempts to strengthen this conclusion by addressing two weaknesses in the previous study. First, the present study shows that the SM component continues to be more deficient than the PM component across both modalities under conditions in which (1) all participants were instructed to use the same recall strategy (resulting in the exclusion of fewer participants); and, (2) individual differences in this strategy were controlled. Second, the present study also documents a group difference in word reading efficiency that is confounded with diagnostic status and that might have influenced estimates of PM and SM capacities in the verbal modality. However, although the SM component is more deficient than the PM component in the ADHD group, the magnitude of this interaction does not vary as a function task modality. These findings are interpreted to suggest that the pattern of WM deficiencies observed are part of a causal pathway that can lead to the symptoms of ADHD, as well as to impairments in reading (and intelligence) due to overlapping cue-dependent retrieval mechanisms. These findings provide additional support for the notion that the SM component of WM is an important and neglected target for treatment.

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

PubMed

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

2016-12-01

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

Neurodegeneration in an Animal Model of Chronic Amyloid-beta Oligomer Infusion Is Counteracted by Antibody Treatment Infused with Osmotic Pumps

PubMed Central

Sajadi, Ahmadali; Provost, Chloé; Pham, Brendon; Brouillette, Jonathan

2016-01-01

Decline in hippocampal-dependent explicit memory (memory for facts and events) is one of the earliest clinical symptom of Alzheimer's disease (AD). It is well established that synapse loss and ensuing neurodegeneration are the best predictors for memory impairments in AD. Latest studies have emphasized the neurotoxic role of soluble amyloid-beta oligomers (Aβo) that begin to accumulate in the human brain approximately 10 to 15 yr before the clinical symptoms become apparent. Many reports indicate that soluble Aβo correlate with memory deficits in AD models and humans. The Aβo-induced neurodegeneration observed in neuronal and brain slice cultures has been more challenging to reproduce in many animal models. The model of repeated Aβo infusions shown here overcome this issue and allow addressing two key domains for developing new disease modifying therapies: identify biological markers to diagnose early AD, and determine the molecular mechanisms underpinning Aβo-induced memory deficits at the onset of AD. Since soluble Aβo aggregate relatively fast into insoluble Aβ fibrils that correlate poorly with the clinical state of patients, soluble Aβo are prepared freshly and injected once per day during six days to produce marked cell death in the hippocampus. We used cannula specially design for simultaneous infusions of Aβo and continuous infusion of Aβo antibody (6E10) in the hippocampus using osmotic pumps. This innovative in vivo method can now be used in preclinical studies to validate the efficiency of new AD therapies that might prevent the deposition and neurotoxicity of Aβo in pre-dementia patients. PMID:27585306

MPTP-induced changes in hippocampal synaptic plasticity and memory are prevented by memantine through the BDNF-TrkB pathway

PubMed Central

Zhu, Guoqi; Li, Junyao; He, Ling; Wang, Xuncui; Hong, Xiaoqi

2015-01-01

Background and Purpose Mild cognitive deficit in early Parkinson's disease (PD) has been widely studied. Here we have examined the effects of memantine in preventing memory deficit in experimental PD models and elucidated some of the underlying mechanisms. Experimental Approaches I.p. injection of 1-methyl-4- phenyl-1,2,3,6-tetrahydro pyridine (MPTP) in C57BL/6 mice was used to produce models of PD. We used behavioural tasks to test memory. In vitro, we used slices of hippocampus, with electrophysiological, Western blotting, real time PCR, elisa and immunochemical techniques. Key Results Following MPTP injection, long-term memory was impaired and these changes were prevented by pre-treatment with memantine. In hippocampal slices from MPTP treated mice, long-term potentiation (LTP) –induced by θ burst stimulation (10 bursts, 4 pulses) was decreased, while long-term depression (LTD) induced by low-frequency stimulation (1 Hz, 900 pulses) was enhanced, compared with control values. A single dose of memantine (i.p., 10 mg·kg−1) reversed the decreased LTP and the increased LTD in this PD model. Activity-dependent changes in tyrosine kinase receptor B (TrkB), ERK and brain-derived neurotrophic factor (BDNF) expression were decreased in slices from mice after MPTP treatment. These effects were reversed by pretreatment with memantine. Incubation of slices in vitro with 1-methyl-4-phenylpyridinium (MPP+) decreased depolarization-induced expression of BDNF. This effect was prevented by pretreatment of slices with memantine or with calpain inhibitor III, suggesting the involvement of an overactivated calcium signalling pathway. Conclusions and Implications Memantine should be useful in preventing loss of memory and hippocampal synaptic plasticity in PD models. PMID:25560396

The effect of visual arrangement on visuospatial short-term memory: Insights from children with 22q11.2 deletion syndrome.

PubMed

Attout, Lucie; Noël, Marie-Pascale; Rousselle, Laurence

2018-04-11

Recent models of visuospatial (VSSP) short-term memory postulate the existence of two dissociable mechanisms depending on whether VSSP information is presented simultaneously or sequentially. However, they do not specify to what extent VSSP short-term memory is under the influence of general VSSP processing. This issue was examined in people with 22q11.2 deletion syndrome, a genetic condition involving a VSSP deficit. The configuration of VSSP information was manipulated (structured vs. unstructured) to explore the impact of arrangement on VSSP short-term memory. Two presentation modes were used to see whether the VSSP arrangement has the same impact on simultaneous and sequential short-term memory. Compared to children matched on chronological age, children with 22q11.2 deletion syndrome showed impaired performance only for structured arrangement, regardless of the presentation mode, suggesting an influence of VSSP processing on VSSP short-term memory abilities. A revised cognitive architecture for a model of VSSP short-term memory is proposed.

Using attribute amnesia to test the limits of hyper-binding and associative deficits in working memory.

PubMed

McCormick-Huhn, John M; Chen, Hui; Wyble, Bradley P; Dennis, Nancy A

2018-02-01

Previous work has shown mixed evidence regarding age-related deficits for binding in working memory. The current study used the newly developed attribute amnesia effect (H. Chen & Wyble, 2015a) to test the associative-deficit hypothesis during working memory and to probe whether hyper-binding extends to include binding of de-selected information. In studies of attribute amnesia, participants use target attributes (e.g., identity, color) to demonstrate near ceiling levels of reporting of a second target attribute (e.g., location) across a series of trials (H. Chen & Wyble, 2015a, 2016). Yet, despite having just processed the target-defining attribute, they have difficulty reporting it on a surprise trial. This effect provides several predictions for associative binding in aging. The associative-deficit hypothesis predicts age-related decline on the surprise trial, whereas an extension of hyper-binding predicts age-related increase in performance in older adults. In Experiment 1, when working memory load was low, older adults demonstrated attribute amnesia equal to that found in younger adults. When load increased in Experiment 2, older adults again demonstrated attribute amnesia as well as an age deficit for reporting target attributes. In lieu of spontaneous binding, results suggest that expectancy plays a critical role in older adults' propensity to encode and bind target attributes in working memory. Results further suggest that expectancy alone is not enough for older adults to form bound representations when task demands are high. Taken together results revealed a boundary condition of hyper-binding and further provided conditional support for the associative-deficit hypothesis in working memory. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

CB1 Cannabinoid Receptors Mediate Cognitive Deficits and Structural Plasticity Changes During Nicotine Withdrawal.

PubMed

Saravia, Rocio; Flores, África; Plaza-Zabala, Ainhoa; Busquets-Garcia, Arnau; Pastor, Antoni; de la Torre, Rafael; Di Marzo, Vincenzo; Marsicano, Giovanni; Ozaita, Andrés; Maldonado, Rafael; Berrendero, Fernando

2017-04-01

Tobacco withdrawal is associated with deficits in cognitive function, including attention, working memory, and episodic memory. Understanding the neurobiological mechanisms involved in these effects is crucial because cognitive deficits during nicotine withdrawal may predict relapse in humans. We investigated in mice the role of CB 1 cannabinoid receptors (CB 1 Rs) in memory impairment and spine density changes induced by nicotine withdrawal precipitated by the nicotinic antagonist mecamylamine. Drugs acting on the endocannabinoid system and genetically modified mice were used. Memory impairment during nicotine withdrawal was blocked by the CB 1 R antagonist rimonabant or the genetic deletion of CB 1 R in forebrain gamma-aminobutyric acidergic (GABAergic) neurons (GABA-CB 1 R). An increase of 2-arachidonoylglycerol (2-AG), but not anandamide, was observed during nicotine withdrawal. The selective inhibitor of 2-AG biosynthesis O7460 abolished cognitive deficits of nicotine abstinence, whereas the inhibitor of 2-AG enzymatic degradation JZL184 did not produce any effect in cognitive impairment. Moreover, memory impairment was prevented by the selective mammalian target of rapamycin inhibitor temsirolimus and the protein synthesis inhibitor anisomycin. Mature dendritic spines on CA1 pyramidal hippocampal neurons decreased 4 days after the precipitation of nicotine withdrawal, when the cognitive deficits were still present. Indeed, a correlation between memory performance and mature spine density was found. Interestingly, these structural plasticity alterations were normalized in GABA-CB 1 R conditional knockout mice and after subchronic treatment with rimonabant. These findings underline the interest of CB 1 R as a target to improve cognitive performance during early nicotine withdrawal. Cognitive deficits in early abstinence are associated with increased relapse risk. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Neural bases of orthographic long-term memory and working memory in dysgraphia.

PubMed

Rapp, Brenda; Purcell, Jeremy; Hillis, Argye E; Capasso, Rita; Miceli, Gabriele

2016-02-01

Spelling a word involves the retrieval of information about the word's letters and their order from long-term memory as well as the maintenance and processing of this information by working memory in preparation for serial production by the motor system. While it is known that brain lesions may selectively affect orthographic long-term memory and working memory processes, relatively little is known about the neurotopographic distribution of the substrates that support these cognitive processes, or the lesions that give rise to the distinct forms of dysgraphia that affect these cognitive processes. To examine these issues, this study uses a voxel-based mapping approach to analyse the lesion distribution of 27 individuals with dysgraphia subsequent to stroke, who were identified on the basis of their behavioural profiles alone, as suffering from deficits only affecting either orthographic long-term or working memory, as well as six other individuals with deficits affecting both sets of processes. The findings provide, for the first time, clear evidence of substrates that selectively support orthographic long-term and working memory processes, with orthographic long-term memory deficits centred in either the left posterior inferior frontal region or left ventral temporal cortex, and orthographic working memory deficits primarily arising from lesions of the left parietal cortex centred on the intraparietal sulcus. These findings also contribute to our understanding of the relationship between the neural instantiation of written language processes and spoken language, working memory and other cognitive skills. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

PubMed Central

Bruinenberg, Vibeke M.; Tudor, Jennifer C.; Ferri, Sarah L.; Baumann, Arnd; Meerlo, Peter

2014-01-01

The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object–location task. Five hours of total sleep deprivation directly following training impaired the formation of object–location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation. PMID:25411499

Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss.

PubMed

Havekes, Robbert; Bruinenberg, Vibeke M; Tudor, Jennifer C; Ferri, Sarah L; Baumann, Arnd; Meerlo, Peter; Abel, Ted

2014-11-19

The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation. Copyright © 2014 the authors 0270-6474/14/3415715-07$15.00/0.

Olfactory memory in the old and very old: relations to episodic and semantic memory and APOE genotype.

PubMed

Larsson, Maria; Hedner, Margareta; Papenberg, Goran; Seubert, Janina; Bäckman, Lars; Laukka, Erika J

2016-02-01

The neuroanatomical organization that underlies olfactory memory is different from that of other memory types. The present work examines olfactory memory in an elderly population-based sample (Swedish National Study on Aging and Care in Kungsholmen) aged 60-100 years (n = 2280). We used structural equation modeling to investigate whether olfactory memory in old age is best conceptualized as a distinct category, differentiated from episodic and semantic memory. Further, potential olfactory dedifferentiation and genetic associations (APOE) to olfactory function in late senescence were investigated. Results are in support of a 3-factor solution where olfactory memory, as indexed by episodic odor recognition and odor identification, is modeled separately from episodic and semantic memory for visual and verbal information. Increasing age was associated with poorer olfactory memory performance, and observed age-related deficits were further exacerbated for carriers of the APOE ε4 allele; these effects tended to be larger for olfactory memory compared to episodic and semantic memory pertaining to other sensory systems (vision, auditory). Finally, stronger correlations between olfactory and episodic memory, indicating dedifferentiation, were observed in the older age groups. Copyright © 2016 Elsevier Inc. All rights reserved.

Aerobic exercise and a BDNF-mimetic therapy rescue learning and memory in a mouse model of Down syndrome.

PubMed

Parrini, Martina; Ghezzi, Diego; Deidda, Gabriele; Medrihan, Lucian; Castroflorio, Enrico; Alberti, Micol; Baldelli, Pietro; Cancedda, Laura; Contestabile, Andrea

2017-12-04

Down syndrome (DS) is caused by the triplication of human chromosome 21 and represents the most frequent genetic cause of intellectual disability. The trisomic Ts65Dn mouse model of DS shows synaptic deficits and reproduces the essential cognitive disabilities of the human syndrome. Aerobic exercise improved various neurophysiological dysfunctions in Ts65Dn mice, including hippocampal synaptic deficits, by promoting synaptogenesis and neurotransmission at glutamatergic terminals. Most importantly, the same intervention also prompted the recovery of hippocampal adult neurogenesis and synaptic plasticity and restored cognitive performance in trisomic mice. Additionally, the expression of brain-derived neurotrophic factor (BDNF) was markedly decreased in the hippocampus of patients with DS. Since the positive effect of exercise was paralleled by increased BDNF expression in trisomic mice, we investigated the effectiveness of a BDNF-mimetic treatment with 7,8-dihydroxyflavone at alleviating intellectual disabilities in the DS model. Pharmacological stimulation of BDNF signaling rescued synaptic plasticity and memory deficits in Ts65Dn mice. Based on our findings, Ts65Dn mice benefit from interventions aimed at promoting brain plasticity, and we provide evidence that BDNF signaling represents a potentially new pharmacological target for treatments aimed at rescuing cognitive disabilities in patients with DS.

The antibody rHIgM22 facilitates hippocampal remyelination and ameliorates memory deficits in the cuprizone mouse model of demyelination.

PubMed

Cui, Charlene; Wang, Jing; Mullin, Ariana P; Caggiano, Anthony O; Parry, Tom J; Colburn, Raymond W; Pavlopoulos, Elias

2018-05-15

Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the CNS. In addition to motor, sensory and visual deficits, MS is also characterized by hippocampal demyelination and memory impairment. We recently demonstrated that a recombinant human-derived monoclonal IgM antibody, which is designated rHIgM22 and currently in clinical development for people with MS, accelerates remyelination of the corpus callosum in the brains of cuprizone-treated mice. Here, we investigated the effects of rHIgM22 in the hippocampus and on hippocampal-dependent learning and memory in the same mouse model of cuprizone-induced demyelination and spontaneous remyelination. The degree of hippocampal myelination of cuprizone-fed mice treated with a single dose of rHIgM22 (10 mg/kg of body weight) was examined immediately after the end of the cuprizone diet as well as at different time points during the recovery period with regular food, and compared with that of cuprizone-fed animals treated with either vehicle or human IgM isotype control antibody. Mice fed only regular food were used as controls. Four or five mice per treatment group were examined for each time point. We demonstrate that treatment with rHIgM22 accelerated remyelination of the demyelinated hippocampus. Using two additional cohorts of mice and eight animals per treatment group for each cohort, we also demonstrate that the enhancing effects of rHIgM22 on hippocampal remyelination were accompanied by improved performance in the Morris water maze and amelioration of the memory deficits induced by cuprizone. These results further confirm the remyelination-promoting capabilities of rHIgM22 and support additional investigation of its therapeutic potential in MS. Copyright © 2018. Published by Elsevier B.V.

The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats.

PubMed

Kiasalari, Zahra; Khalili, Mohsen; Shafiee, Samaneh; Roghani, Mehrdad

2016-01-01

Since temporal lobe epilepsy (TLE) is associated with learning and memory impairment, we investigated the beneficial effect of Vitamin E on the impaired learning and memory in the intrahippocampal kainate model of TLE in rats. Rats were divided into sham, Vitamin E-treated sham, kainate, and Vitamin E-treated kainate. Intrahippocampal kainate was used for induction of epilepsy. Vitamin E was injected intraperitoneal (i.p.) at a dose of 200 mg/kg/day started 1 week before surgery until 1 h presurgery. Initial and step-through latencies in the passive avoidance test and alternation behavior percentage in Y-maze were finally determined in addition to measurement of some oxidative stress markers. Kainate injection caused a higher severity and rate of seizures and deteriorated learning and memory performance in passive avoidance paradigm and spontaneous alternation as an index of spatial recognition memory in Y-maze task. Intrahippocampal kainate also led to the elevation of malondialdehyde (MDA) and nitrite and reduced activity of superoxide dismutase (SOD). Vitamin E pretreatment significantly attenuated severity and incidence rate of seizures, significantly improved retrieval and recall in passive avoidance, did not ameliorate spatial memory deficit in Y-maze, and lowered MDA and enhanced SOD activity. Vitamin E improves passive avoidance learning and memory and part of its beneficial effect is due to its potential to mitigate hippocampal oxidative stress.

How Common are WM Deficits in Children with Difficulties in Reading and Mathematics?

PubMed

Gathercole, Susan E; Woolgar, Francesca; Kievit, Rogier A; Astle, Duncan; Manly, Tom; Holmes, Joni

2016-12-01

The extent to which deficits in working memory (WM) are characteristic of children with reading and mathematics difficulties was investigated in a large sample aged 5-15 years reported to have problems in attention, learning and memory. WM performance was highly correlated with reading and mathematics scores. Although deficits in individual tests of short-term memory (STM) and WM occurred in less than half of the children with detected learning difficulties, three-quarters of the children with low reading and mathematics scores obtained one or more WM scores in the deficit range. These findings are consistent with proposals that WM or the broader cognitive dimensions it taps impede school-based learning, and point to the importance of managing WM loads in the classroom.

Shedding light on the association between repetitive negative thinking and deficits in cognitive control - A meta-analysis.

PubMed

Zetsche, Ulrike; Bürkner, Paul-Christian; Schulze, Lars

2018-06-11

Individuals who experience recurrent negative thoughts are at elevated risk for mood and anxiety disorders. It is thus essential to understand why some individuals get stuck in recurrent negative thinking (RNT), whereas others are able to disengage eventually. Theoretical models propose that individuals high in recurrent negative thinking suffer from deficits in controlling the contents of working memory. Empirical findings, however, are inconclusive. In this meta-analysis, we synthesize findings from 94 studies to examine the proposed association between RNT and deficits in cognitive control. We included numerous effect sizes not reported in the primary publications. Moderator analyses tested the influence of variables, such as stimuli valence, cognitive control function (e.g., shifting, discarding), or type of RNT (i.e., rumination or worry). Results demonstrated an association between repetitive negative thinking and deficits in only one specific cognitive control function, namely difficulty discarding no longer relevant material from working memory (r = -0.20). This association remained significant after controlling for level of psychopathology. There was no substantial association between RNT and deficits in any other cognitive control function. All other moderators were not significant. We discuss limitations (e.g., primary sample sizes, reliability of paradigms) and highlight implications for future research and clinical interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adolescents born prematurely with isolated grade 2 haemorrhage in the early 1990s face increased risks of learning challenges.

PubMed

Vohr, Betty R; Allan, Walter; Katz, Karol H; Schneider, Karen; Tucker, Richard; Ment, Laura R

2014-10-01

To compare the impact of low-grade haemorrhage on neurocognitive function in 16-year-old adolescents born preterm, by grade of intraventricular haemorrhage, and term controls. We evaluated 338 preterm adolescents (birth weight 600-1250 g) for intelligence, executive function and memory tasks. Eleven had grade 3-4 haemorrhage, 44 had grade 2, 31 had grade 1, and 251 had no haemorrhage. Group comparisons were made with 102 term age-matched controls, and regression models used to identify the risk that low-grade haemorrhage posed for cognitive, executive function and memory deficits. Preterm adolescents with grade 2 haemorrhage had higher deficit rates of verbal intelligence, receptive vocabulary, phonemic fluency, cognitive flexibility and phonological fluency than preterm adolescents with grade 1 or no haemorrhage, compared with term controls. After excluding preterm adolescents with both grade 2 haemorrhage and cystic periventricular leukomalacia, those with isolated grade 2 haemorrhage remained at greater risk of cognitive and executive function deficits than term controls and of cognitive deficits than preterm adolescents with no haemorrhage. Our findings suggest that preterm adolescents born in the early 1990s with isolated grade 2 haemorrhage are at increased risk of learning challenges, including cognitive and executive function deficits. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

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

PubMed

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

2013-01-01

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

Spatial serial order processing in schizophrenia.

PubMed

Fraser, David; Park, Sohee; Clark, Gina; Yohanna, Daniel; Houk, James C

2004-10-01

The aim of this study was to examine serial order processing deficits in 21 schizophrenia patients and 16 age- and education-matched healthy controls. In a spatial serial order working memory task, one to four spatial targets were presented in a randomized sequence. Subjects were required to remember the locations and the order in which the targets were presented. Patients showed a marked deficit in ability to remember the sequences compared with controls. Increasing the number of targets within a sequence resulted in poorer memory performance for both control and schizophrenia subjects, but the effect was much more pronounced in the patients. Targets presented at the end of a long sequence were more vulnerable to memory error in schizophrenia patients. Performance deficits were not attributable to motor errors, but to errors in target choice. The results support the idea that the memory errors seen in schizophrenia patients may be due to saturating the working memory network at relatively low levels of memory load.

Deficits of learning and memory in Hemojuvelin knockout mice.

PubMed

Li, Jinglong; Zhang, Peng; Liu, Hongju; Ren, Wei; Song, Jinjing; Rao, Elizabeth; Takahashi, Eiki; Zhou, Ying; Li, Weidong; Chen, Xiaoping

2015-10-01

Iron is involved in various physiological processes of the human body to maintain normal functions. Abnormal iron accumulation in brain has been reported as a pathogenesis of several neurodegenerative disorders and cognitive impairments. Hemojuvelin (HVJ) is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis. Although iron accumulation in brain has been related to neurodegenerative diseases, it remains unknown the effect of mutation of HVJ gene on cognitive performance. In our studies, HJV(-/-) mice showed deficits in novel object recognition and Morris water maze tests. Furthermore, the expression ration of apoptotic marker Bax and anti-apoptotic marker Bcl-2 in the hippocampus and prefrontal cortex showed higher levels in HJV(-/-) mice. Our results suggested that deletion of HJV gene could increase apoptosis in brain which might contribute to learning and memory deficits in mutant mice. These results indicated that HJV(-/-) mice would be a useful model to study cognitive impairment induced by iron overload in brain.

Beyond the dual pathway model: evidence for the dissociation of timing, inhibitory, and delay-related impairments in attention-deficit/hyperactivity disorder.

PubMed

Sonuga-Barke, Edmund; Bitsakou, Paraskevi; Thompson, Margaret

2010-04-01

The dual pathway model explains neuro-psychological heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) in terms of dissociable cognitive and motivational deficits each affecting some but not other patients. We explore whether deficits in temporal processing might constitute a third dissociable neuropsychological component of ADHD. Nine tasks designed to tap three domains (inhibitory control, delay aversion and temporal processing) were administered to ADHD probands (n=71; ages 6 to 17 years), their siblings (n=71; 65 unaffected by ADHD) and a group of non-ADHD controls (n=50). IQ and working memory were measured. Temporal processing, inhibitory control and delay-related deficits represented independent neuropsychological components. ADHD children differed from controls on all factors. For ADHD patients, the co-occurrence of inhibitory, temporal processing and delay-related deficits was no greater than expected by chance with substantial groups of patients showing only one problem. Domain-specific patterns of familial co-segregation provided evidence for the validity of neuropsychological subgroupings. The current results illustrate the neuropsychological heterogeneity in ADHD and initial support for a triple pathway model. The findings need to be replicated in larger samples.

Sleep spindles: a physiological marker of age-related changes in gray matter in brain regions supporting motor skill memory consolidation.

PubMed

Fogel, Stuart; Vien, Catherine; Karni, Avi; Benali, Habib; Carrier, Julie; Doyon, Julien

2017-01-01

Sleep is necessary for the optimal consolidation of procedural learning, and in particular, for motor sequential skills. Motor sequence learning remains intact with age, but sleep-dependent consolidation is impaired, suggesting that memory deficits for procedural skills are specifically impacted by age-related changes in sleep. Age-related changes in spindles may be responsible for impaired motor sequence learning consolidation, but the morphological basis for this deficit is unknown. Here, we found that gray matter in the hippocampus and cerebellum was positively correlated with both sleep spindles and offline improvements in performance in young participants but not in older participants. These results suggest that age-related changes in gray matter in the hippocampus relate to spindles and may underlie age-related deficits in sleep-related motor sequence memory consolidation. In this way, spindles can serve as a biological marker for structural brain changes and the related memory deficits in older adults. Copyright © 2016 Elsevier Inc. All rights reserved.

Aging affects the interaction between attentional control and source memory: an fMRI study.

PubMed

Dulas, Michael R; Duarte, Audrey

2014-12-01

Age-related source memory impairments may be due, at least in part, to deficits in executive processes mediated by the PFC at both study and test. Behavioral work suggests that providing environmental support at encoding, such as directing attention toward item-source associations, may improve source memory and reduce age-related deficits in the recruitment of these executive processes. The present fMRI study investigated the effects of directed attention and aging on source memory encoding and retrieval. At study, participants were shown pictures of objects. They were either asked to attend to the objects and their color (source) or to their size. At test, participants determined if objects were seen before, and if so, whether they were the same color as previously. Behavioral results showed that direction of attention improved source memory for both groups; however, age-related deficits persisted. fMRI results revealed that, across groups, direction of attention facilitated medial temporal lobe-mediated contextual binding processes during study and attenuated right PFC postretrieval monitoring effects at test. However, persistent age-related source memory deficits may be related to increased recruitment of medial anterior PFC during encoding, indicative of self-referential processing, as well as underrecruitment of lateral anterior PFC-mediated relational processes. Taken together, this study suggests that, even when supported, older adults may fail to selectively encode goal-relevant contextual details supporting source memory performance.

Treatment of Memory Impairment and Sensorimotor Deficits in an Animal Model for the Gulf War Veterans Illnesses

DTIC Science & Technology

2010-09-01

B.E. and Khan, W.A., (2001b). Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigmine bromide , DEET, and...Induction of urinary excretion of 3-nitrotyrosine, a m arker of oxidative stress foll owing administration of pyridostigmine bromide , N,N-diethyl-m...Abdel-Rahman, A.A., Bull man, S. L., and Khan, W .A., (2004). Co-exposure to pyridostig mine bromide , DEET and/or perm ethrin causes

Vildagliptin, a DPP4 inhibitor, alleviates diabetes-associated cognitive deficits by decreasing the levels of apoptosis-related proteins in the rat hippocampus.

PubMed

Zhang, Dan-Dan; Shi, Nan; Fang, Hui; Ma, Liang; Wu, Wei-Ping; Zhang, Ya-Zhong; Tian, Jin-Li; Tian, Luo-Bing; Kang, Kang; Chen, Si

2018-06-01

Cognitive impairment is a prevalent but underestimated complication of diabetes, which can cause spatial memory and learning deficits. In the present study, a streptozotocin-induced type 2 diabetic rat model was employed to investigate the effects of vildagliptin, a new oral hypoglycemic agent that acts by inhibiting dipeptidyl peptidase-4, on diabetes-associated cognitive impairments, as well as the molecular mechanisms involved. The present findings demonstrated that vildagliptin treatment prevented memory impairment and decreased the apoptosis of hippocampal neurons. It also attenuated the abnormal expression of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein in the diabetic model. Vildagliptin treatment also reversed diabetes-induced decreases in phosphorylated (p)-protein kinase B (Akt) and p-glycogen synthase kinase 3β (GSK3β), brain-derived neurotrophic factor and nerve growth factor expression levels. The results indicated that the administration of vildagliptin exerts a protective effect against cognitive deficits by decreasing the expression of apoptosis-related proteins in the hippocampus and that this protective effect was mediated via the Akt/GSK3β signaling pathway.

Is the word-length effect linked to subvocal rehearsal?

PubMed

Jacquemot, Charlotte; Dupoux, Emmanuel; Bachoud-Lévi, Anne-Catherine

2011-04-01

Models of phonological short-term memory (pSTM) generally distinguish between two components: a phonological buffer and a subvocal rehearsal. Evidence for these two components comes, respectively, from the phonological similarity effect and the word-length effect which disappears under articulatory suppression. But alternative theories posit that subvocal rehearsal is only an optional component of the pSTM. According to them, the depletion of the length effect under articulatory suppression results from the interference of the self-produced speech rather than the disruption of subvocal rehearsal. In order to disentangle these two theories, we tested two patients with a short-term memory deficit. FA, who presents a pseudoword repetition deficit, and FL, who does not. FA's deficit allowed for the observance of an ecological case of subvocal rehearsal disruption without any articulatory suppression task. FA's performance in pSTM tasks reveals as controls a phonological similarity effect, and contrary to controls no word-length effect. In contrast, the second patient, FL, exhibits the same effects as control subjects. This result is in accordance with models of pSTM in which the word-length effect emerges from subvocal rehearsal and disappears when this latter is disrupted. Copyright © 2010 Elsevier Srl. All rights reserved.

Interactions between ifenprodil and dizocilpine on mouse behaviour in models of anxiety and working memory.

PubMed

Fraser, C M; Cooke, M J; Fisher, A; Thompson, I D; Stone, T W

1996-11-01

The N-methyl-D-aspartate (NMDA) receptor polyamine site antagonist, ifenprodil, had no effect on spontaneous alteration or locomotor activity in the Y-maze when given alone. The NMDA receptor/ion channel blocker, dizocilpine, induced a deficit in spontaneous alteration, but when ifenprodil was co-administered with dizocilpine, it showed a strong tendency to attenuate the dizocilpine-induced deficit. In the plus-maze, ifenprodil had an anxiolytic profile which was accompanied by an increase in locomotion. Dizocilpine had an anxiolytic profile in this model and increased locomotor activity. When co-administered with dizocilpine, ifenprodil reduced both the anxiolytic and locomotor effects of dizocilpine. When co-administered with ifenprodil, cyclopentyladenosine (CPA) and 1,3-dipropyl-8-cyclopentylxanthine (CPX) reduced the anxiolytic effect of ifenprodil. CPA and CPX in combination did not reverse the anxiolytic effect of ifenpropil. It is concluded that NMDA antagonists with different sites of action can show distinct behavioural profiles, with dizocilpine but not ifenprodil inducing a deficit in working memory, while both are anxiolytic. Blockade of NMDA receptors by ifenprodil, however, can preclude any response to dizocilpine. The anxiolytic activity of ifenprodil may involve the release of purines acting at adenosine receptors.

Vildagliptin, a DPP4 inhibitor, alleviates diabetes-associated cognitive deficits by decreasing the levels of apoptosis-related proteins in the rat hippocampus

PubMed Central

Zhang, Dan-Dan; Shi, Nan; Fang, Hui; Ma, Liang; Wu, Wei-Ping; Zhang, Ya-Zhong; Tian, Jin-Li; Tian, Luo-Bing; Kang, Kang; Chen, Si

2018-01-01

Cognitive impairment is a prevalent but underestimated complication of diabetes, which can cause spatial memory and learning deficits. In the present study, a streptozotocin-induced type 2 diabetic rat model was employed to investigate the effects of vildagliptin, a new oral hypoglycemic agent that acts by inhibiting dipeptidyl peptidase-4, on diabetes-associated cognitive impairments, as well as the molecular mechanisms involved. The present findings demonstrated that vildagliptin treatment prevented memory impairment and decreased the apoptosis of hippocampal neurons. It also attenuated the abnormal expression of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein in the diabetic model. Vildagliptin treatment also reversed diabetes-induced decreases in phosphorylated (p)-protein kinase B (Akt) and p-glycogen synthase kinase 3β (GSK3β), brain-derived neurotrophic factor and nerve growth factor expression levels. The results indicated that the administration of vildagliptin exerts a protective effect against cognitive deficits by decreasing the expression of apoptosis-related proteins in the hippocampus and that this protective effect was mediated via the Akt/GSK3β signaling pathway.

Individual differences in children's memory and reading comprehension: an investigation of semantic and inhibitory deficits.

PubMed

Cain, Kate

2006-07-01

Three experiments compared the verbal memory skills of children with poor reading comprehension with that of same-age good comprehenders. The aims were to determine if semantic and/or inhibitory deficits explained comprehenders' problems on measures of verbal short-term memory and verbal working memory. In Experiment 1 there were no group differences on word- and number-based measures of short-term storage and no evidence that semantic knowledge mediated word recall. In Experiment 2 poor comprehenders were impaired on word- and number-based assessments of working memory, the greatest deficit found on the word-based task. Error analysis of both word-based tasks revealed that poor comprehenders were more likely to recall items that should have been inhibited than were good comprehenders. Experiment 3 extended this finding: Poor comprehenders were less able to inhibit information that was no longer relevant. Together, these findings suggest that individual differences in inhibitory processing influence the ability to regulate the contents of working memory, which may contribute to the differential memory performance of good and poor comprehenders.

Impaired long-term memory retention: common denominator for acutely or genetically reduced hippocampal neurogenesis in adult mice.

PubMed

Ben Abdallah, Nada M-B; Filipkowski, Robert K; Pruschy, Martin; Jaholkowski, Piotr; Winkler, Juergen; Kaczmarek, Leszek; Lipp, Hans-Peter

2013-09-01

In adult rodents, decreasing hippocampal neurogenesis experimentally using different approaches often impairs performance in hippocampus-dependent processes. Nonetheless, functional relevance of adult neurogenesis is far from being unraveled, and deficits so far described in animal models often lack reproducibility. One hypothesis is that such differences might be the consequence of the extent of the methodological specificity used to alter neurogenesis rather than the extent to which adult neurogenesis is altered. To address this, we focused on cranial irradiation, the most widely used technique to impair hippocampal neurogenesis and consequentially induce hippocampus-dependent behavioral deficits. To investigate the specificity of the technique, we thus exposed 4-5 months old female cyclin D2 knockout mice, a model lacking physiological levels of olfactory and hippocampal neurogenesis, to an X-ray dose of 10 Gy, reported to specifically affect transiently amplifying precursors. After a recovery period of 1.5 months, behavioral tests were performed and probed for locomotor activity, habituation, anxiety, and spatial learning and memory. Spatial learning in the Morris water maze was intact in all experimental groups. Although spatial memory retention assessed 24h following acquisition was also intact in all mice, irradiated wild type and cyclin D2 knockout mice displayed memory deficits one week after acquisition. In addition, we observed significant differences in tests addressing anxiety and locomotor activity dependent on the technique used to alter neurogenesis. Whereas irradiated mice were hyperactive regardless of their genotype, cyclin D2 knockout mice were hypoactive in most of the tests and displayed altered habituation. The present study emphasizes that different approaches aimed at decreasing adult hippocampal neurogenesis may result in distinct behavioral impairments related to locomotion and anxiety. In contrast, spatial long-term memory retention is consistently altered after both approaches suggesting a plausible implication of hippocampal neurogenesis in this cognitive process. Copyright © 2013 Elsevier B.V. All rights reserved.

Decadal-scale ecosystem memory reveals interactive effects of drought and insect defoliation on boreal forest productivity

NASA Astrophysics Data System (ADS)

Itter, M.; D'Orangeville, L.; Dawson, A.; Kneeshaw, D.; Finley, A. O.

2017-12-01

Drought and insect defoliation have lasting impacts on the dynamics of the boreal forest. Impacts are expected to worsen under global climate change as hotter, drier conditions forecast for much of the boreal increase the frequency and severity of drought and defoliation events. Contemporary ecological theory predicts physiological feedbacks in tree responses to drought and defoliation amplify impacts potentially causing large-scale productivity losses and forest mortality. Quantifying the interactive impacts of drought and insect defoliation on regional forest health is difficult given delayed and persistent responses to disturbance events. We developed a Bayesian hierarchical model to estimate forest growth responses to interactions between drought and insect defoliation by species and size class. Delayed and persistent responses to past drought and defoliation were quantified using empirical memory functions allowing for improved detection of interactions. The model was applied to tree-ring data from stands in Western (Alberta) and Eastern (Québec) regions of the Canadian boreal forest with different species compositions, disturbance regimes, and regional climates. Western stands experience chronic water deficit and forest tent caterpillar (FTC) defoliation; Eastern stands experience irregular water deficit and spruce budworm (SBW) defoliation. Ecosystem memory to past water deficit peaked in the year previous to growth and decayed to zero within 5 (West) to 8 (East) years; memory to past defoliation ranged from 8 (West) to 12 (East) years. The drier regional climate and faster FTC defoliation dynamics (compared to SBW) likely contribute to shorter ecosystem memory in the West. Drought and defoliation had the largest negative impact on large-diameter, host tree growth. Surprisingly, a positive interaction was observed between drought and defoliation for large-diameter, non-host trees likely due to reduced stand-level competition for water. Results highlight the temporal persistence of drought and defoliation stress on boreal forest growth dynamics and provide an empirical estimate of their interactive effects with explicit uncertainty.

Semantic and episodic memory in children with temporal lobe epilepsy: do they relate to literacy skills?

PubMed

Lah, Suncica; Smith, Mary Lou

2014-01-01

Children with temporal lobe epilepsy are at risk for deficits in new learning (episodic memory) and literacy skills. Semantic memory deficits and double dissociations between episodic and semantic memory have recently been found in this patient population. In the current study we investigate whether impairments of these 2 distinct memory systems relate to literacy skills. 57 children with unilateral temporal lobe epilepsy completed tests of verbal memory (episodic and semantic) and literacy skills (reading and spelling accuracy, and reading comprehension). For the entire group, semantic memory explained over 30% of variance in each of the literacy domains. Episodic memory explained a significant, but rather small proportion (< 10%) of variance in reading and spelling accuracy, but not in reading comprehension. Moreover, when children with opposite patterns of specific memory impairments (intact semantic/impaired episodic, intact episodic/impaired semantic) were compared, significant reductions in literacy skills were evident only in children with semantic memory impairments, but not in children with episodic memory impairments relative to the norms and to children with temporal lobe epilepsy who had intact memory. Our study provides the first evidence for differential relations between episodic and semantic memory impairments and literacy skills in children with temporal lobe epilepsy. As such, it highlights the urgent need to consider semantic memory deficits in management of children with temporal lobe epilepsy and undertake further research into the nature of reading difficulties of children with semantic memory impairments.

Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.

PubMed

Gui, Wen-Shan; Wei, Xiao; Mai, Chun-Lin; Murugan, Madhuvika; Wu, Long-Jun; Xin, Wen-Jun; Zhou, Li-Jun; Liu, Xian-Guo

2016-01-01

Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression. © The Author(s) 2016.

Independent contribution of temporal beta-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease.

PubMed

Chételat, Gaël; Villemagne, Victor L; Pike, Kerryn E; Ellis, Kathryn A; Bourgeat, Pierrick; Jones, Gareth; O'Keefe, Graeme J; Salvado, Olivier; Szoeke, Cassandra; Martins, Ralph N; Ames, David; Masters, Colin L; Rowe, Christopher C

2011-03-01

The relationship between β-amyloid deposition and memory deficits in early Alzheimer's disease is unresolved, as past studies show conflicting findings. The present study aims to determine the relative contribution of regional β-amyloid deposition, hippocampal atrophy and white matter integrity to episodic memory deficits in non-demented older individuals harbouring one of the characteristic hallmarks of Alzheimer's disease, i.e. with β-amyloid pathology. Understanding these relationships is critical for effective therapeutic development. Brain magnetic resonance imaging and [(11)C]Pittsburgh Compound B-positron emission tomography scans were obtained in 136 non-demented individuals aged over 60 years, including 93 healthy elderly and 43 patients with mild cognitive impairment. Voxel-based correlations were computed between a memory composite score and grey matter volume, white matter volume and β-amyloid deposition imaging datasets. Hierarchical linear regression analyses were then performed using values extracted in regions of most significant correlations to determine the relative contribution of each modality to memory deficits. All analyses were conducted pooling all groups together as well as within separate subgroups of cognitively normal elderly, patients with mild cognitive impairment and individuals with high versus low neocortical β-amyloid. Brain areas of highest correlation with episodic memory deficits were the hippocampi for grey matter volume, the perforant path for white matter volume and the temporal neocortex for β-amyloid deposition. When considering these three variables together, only hippocampal volume and temporal β-amyloid deposition provided independent contributions to memory deficits. In contrast to global β-amyloid deposition, temporal β-amyloid deposition was still related to memory independently from hippocampal atrophy within subgroups of cognitively normal elderly, patients with mild cognitive impairment or cases with high neocortical β-amyloid. In the pre-dementia stage of Alzheimer's disease, subtle episodic memory impairment is related to β-amyloid deposition, especially in the temporal neocortex, and independently from hippocampal atrophy, suggesting that both factors should be independently targeted in therapeutic trials aimed at reducing cognitive decline.

Effects of a Computerized Working Memory Training Program on Working Memory, Attention, and Academics in Adolescents with Severe LD and Comorbid ADHD: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Gray, S. A.; Chaban, P.; Martinussen, R.; Goldberg, R.; Gotlieb, H.; Kronitz, R.; Hockenberry, M.; Tannock, R.

2012-01-01

Background: Youths with coexisting learning disabilities (LD) and attention deficit hyperactivity disorder (ADHD) are at risk for poor academic and social outcomes. The underlying cognitive deficits, such as poor working memory (WM), are not well targeted by current treatments for either LD or ADHD. Emerging evidence suggests that WM might be…

Working memory load affects repetitive behaviour but not cognitive flexibility in adolescent autism spectrum disorder.

PubMed

Wolff, Nicole; Chmielewski, Witold X; Beste, Christian; Roessner, Veit

2017-03-16

Autism spectrum disorder (ASD) is associated with repetitive and stereotyped behaviour, suggesting that cognitive flexibility may be deficient in ASD. A central, yet not examined aspect to understand possible deficits in flexible behaviour in ASD relates (i) to the role of working memory and (ii) to neurophysiological mechanisms underlying behavioural modulations. We analysed behavioural and neurophysiological (EEG) correlates of cognitive flexibility using a task-switching paradigm with and without working memory load in adolescents with ASD and typically developing controls (TD). Adolescents with ASD versus TD show similar performance in task switching with no memory load, indicating that 'pure' cognitive flexibility is not in deficit in adolescent ASD. However performance during task repetition decreases with increasing memory load. Neurophysiological data reflect the pattern of behavioural effects, showing modulations in P2 and P3 event-related potentials. Working memory demands affect repetitive behaviour while processes of cognitive flexibility are unaffected. Effects emerge due to deficits in preparatory attentional processes and deficits in task rule activation, organisation and implementation of task sets when repetitive behaviour is concerned. It may be speculated that the habitual response mode in ASD (i.e. repetitive behaviour) is particularly vulnerable to additional demands on executive control processes.

Where Have I Been? Where Should I Go? Spatial Working Memory on a Radial Arm Maze in a Rat Model of Depression

PubMed Central

Richter, Sophie Helene; Zeuch, Benjamin; Lankisch, Katja; Gass, Peter; Durstewitz, Daniel; Vollmayr, Barbara

2013-01-01

Disturbances in cognitive functioning are among the most debilitating problems experienced by patients with major depression. Investigations of these deficits in animals help to extend and refine our understanding of human emotional disorder, while at the same time providing valid tools to study higher executive functions in animals. We employ the “learned helplessness” genetic rat model of depression in studying working memory using an eight arm radial maze procedure with temporal delay. This so-called delayed spatial win-shift task consists of three phases, training, delay and test, requiring rats to hold information on-line across a retention interval and making choices based on this information in the test phase. According to a 2×2 factorial design, working memory performance of thirty-one congenitally helpless (cLH) and non-helpless (cNLH) rats was tested on eighteen trials, additionally imposing two different delay durations, 30 s and 15 min, respectively. While not observing a general cognitive deficit in cLH rats, the delay length greatly influenced maze performance. Notably, performance was most impaired in cLH rats tested with the shorter 30 s delay, suggesting a stress-related disruption of attentional processes in rats that are more sensitive to stress. Our study provides direct animal homologues of clinically important measures in human research, and contributes to the non-invasive assessment of cognitive deficits associated with depression. PMID:23614050

Progressive Functional Impairments of Hippocampal Neurons in a Tauopathy Mouse Model

PubMed Central

Ciupek, Sarah M.; Cheng, Jingheng; Ali, Yousuf O.; Lu, Hui-Chen

2015-01-01

The age-dependent progression of tau pathology is a major characteristic of tauopathies, including Alzheimer's disease (AD), and plays an important role in the behavioral phenotypes of AD, including memory deficits. Despite extensive molecular and cellular studies on tau pathology, it remains to be determined how it alters the neural circuit functions underlying learning and memory in vivo. In rTg4510 mice, a Tau-P301L tauopathy model, hippocampal place fields that support spatial memories are abnormal at old age (7–9 months) when tau tangles and neurodegeneration are extensive. However, it is unclear how the abnormality in the hippocampal circuit function arises and progresses with the age-dependent progression of tau pathology. Here we show that in young (2–4 months of age) rTg4510 mice, place fields of hippocampal CA1 cells are largely normal, with only subtle differences from those of age-matched wild-type control mice. Second, high-frequency ripple oscillations of local field potentials in the hippocampal CA1 area are significantly reduced in young rTg4510 mice, and even further deteriorated in old rTg4510 mice. The ripple reduction is associated with less bursty firing and altered synchrony of CA1 cells. Together, the data indicate that deficits in ripples and neuronal synchronization occur before overt deficits in place fields in these mice. The results reveal a tau-pathology-induced progression of hippocampal functional changes in vivo. PMID:26019329

Computer-based cognitive retraining for adults with chronic acquired brain injury: a pilot study.

PubMed

Li, Kitsum; Robertson, Julie; Ramos, Joshua; Gella, Stephanie

2013-10-01

This study evaluated the effectiveness of a computer-based cognitive retraining (CBCR) program on improving memory and attention deficits in individuals with a chronic acquired brain injury (ABI). Twelve adults with a chronic ABI demonstrating deficits in memory and attention were recruited from a convenience sample from the community. Using a quasi-experimental one-group pretest-posttest design, a significant improvement was found in both memory and attention scores postintervention using the cognitive screening tool. This study supported the effectiveness of CBCR programs in improving cognitive deficits in memory and attention in individuals with chronic ABI. Further research is recommended to validate these findings with a larger ABI population and to investigate transfer to improvement in occupational performance that supports daily living skills.

Impaired short-term memory for pitch in congenital amusia.

PubMed

Tillmann, Barbara; Lévêque, Yohana; Fornoni, Lesly; Albouy, Philippe; Caclin, Anne

2016-06-01

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.

Thyroid Hormone Supplementation Restores Spatial Memory, Hippocampal Markers of Neuroinflammation, Plasticity-Related Signaling Molecules, and β-Amyloid Peptide Load in Hypothyroid Rats.

PubMed

Chaalal, Amina; Poirier, Roseline; Blum, David; Laroche, Serge; Enderlin, Valérie

2018-05-23

Hypothyroidism is a condition that becomes more prevalent with age. Patients with untreated hypothyroidism have consistently reported symptoms of severe cognitive impairments. In patients suffering hypothyroidism, thyroid hormone supplementation offers the prospect to alleviate the cognitive consequences of hypothyroidism; however, the therapeutic value of TH supplementation remains at present uncertain and the link between cellular modifications associated with hypothyroidism and neurodegeneration remains to be elucidated. In the present study, we therefore evaluated the molecular and behavioral consequences of T3 hormone replacement in an animal model of hypothyroidism. We have previously reported that the antithyroid molecule propylthiouracil (PTU) given in the drinking water favors cerebral atrophy, brain neuroinflammation, Aβ production, Tau hyperphosphorylation, and altered plasticity-related cell-signaling pathways in the hippocampus in association with hippocampal-dependent spatial memory deficits. In the present study, our aim was to explore, in this model, the effect of hippocampal T3 signaling normalization on various molecular mechanisms involved in learning and memory that goes awry under conditions of hypothyroidism and to evaluate its potential for recovery of hippocampal-dependent memory deficits. We report that T3 supplementation can alleviate hippocampal-dependent memory impairments displayed by hypothyroid rats and normalize key markers of thyroid status in the hippocampus, of neuroinflammation, Aβ production, and of cell-signaling pathways known to be involved in synaptic plasticity and memory function. Together, these findings suggest that normalization of hippocampal T3 signaling is sufficient to reverse molecular and cognitive dysfunctions associated with hypothyroidism.

Administration of the TrkB receptor agonist 7,8-dihydroxyflavone prevents traumatic stress-induced spatial memory deficits and changes in synaptic plasticity.

PubMed

Sanz-García, Ancor; Knafo, Shira; Pereda-Pérez, Inmaculada; Esteban, José A; Venero, César; Armario, Antonio

2016-09-01

Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is characterized by cognitive deficits that include impaired explicit memory. The neurobiological bases of such PTSD-associated memory alterations are yet to be elucidated and no satisfactory treatment for them exists. To address this issue, we first studied whether a single exposure of young adult rats (60 days) to immobilization on boards (IMO), a putative model of PTSD, produces long-term behavioral effects (2-8 days) similar to those found in PTSD patients. Subsequently, we investigated whether the administration of the TrkB agonist 7,8-dihydroxyflavone (DHF) 8 h after stress (therapeutic window) ameliorated the PTSD-like effect of IMO and the associated changes in synaptic plasticity. A single IMO exposure induced a spatial memory impairment similar to that found in other animal models of PTSD or in PTSD patients. IMO also increased spine density and long-term potentiation (LTP) in the CA3-CA1 pathway. Significantly, DHF reverted both spatial memory impairment and the increase in LTP, while it produced no effect in the controls. These data provide novel insights into the possible neurobiological substrate for explicit memory impairment in PTSD patients, supporting the idea that the activation of the BDNF/TrkB pathway fulfils a protective role after severe stress. Administration of DHF in the aftermath of a traumatic experience might be relevant to prevent its long-term consequences. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Differences in Memory Functioning between Children with Attention-Deficit/Hyperactivity Disorder and/or Focal Epilepsy

PubMed Central

Lee, Sylvia E.; Kibby, Michelle Y.; Cohen, Morris J.; Stanford, Lisa; Park, Yong; Strickland, Suzanne

2016-01-01

Prior research has shown that attention-deficit/hyperactivity disorder (ADHD) and epilepsy are frequently comorbid and that both disorders are associated with various attention and memory problems. Nonetheless, limited research has been conducted comparing the two disorders in one sample to determine unique versus shared deficits. Hence, we investigated differences in working memory and short-term and delayed recall between children with ADHD, focal epilepsy of mixed foci, comorbid ADHD/epilepsy and controls. Participants were compared on the Core subtests and the Picture Locations subtest of the Children’s Memory Scale (CMS). Results indicated that children with ADHD displayed intact verbal working memory and long-term memory (LTM), as well as intact performance on most aspects of short-term memory (STM). They performed worse than controls on Numbers Forward and Picture Locations, suggesting problems with focused attention and simple span for visual-spatial material. Conversely, children with epilepsy displayed poor focused attention and STM regardless of modality assessed, which affected encoding into LTM. The only loss over time was found for passages (Stories). Working memory was intact. Children with comorbid ADHD/epilepsy displayed focused attention and STM/LTM problems consistent with both disorders, having the lowest scores across the four groups. Hence, focused attention and visual-spatial span appear to be affected in both disorders, whereas additional STM/encoding problems are specific to epilepsy. Children with comorbid ADHD/epilepsy have deficits consistent with both disorders, with slight additive effects. This study suggests that attention and memory testing should be a regular part of the evaluation of children with epilepsy and ADHD. PMID:26156331

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

PubMed

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

2014-03-01

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

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

PubMed Central

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

2014-01-01

Background Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Methods Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 μl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Results Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F 2, 19 = 4.57 p <0.05), higher working memory errors (WME) (F 2, 19 = 5.09, p <0.05) and longer RAM navigation time (F2, 19 = 3.91, p <0.05) for NaOCN relative to NaCN and saline treatments. The long-term working memory was significantly impaired by cyanide with fewer correct arm entries (F 2, 19 = 7.45, p <0.01) and increased working memory errors (F 2, 19 = 9.35 p <0.05) in NaCN relative to NaOCN or vehicle treated animals. Reference memory was not affected by either cyanide or cyanate. Conclusion Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate. PMID:24293006

Memory systems in schizophrenia: Modularity is preserved but deficits are generalized.

PubMed

Haut, Kristen M; Karlsgodt, Katherine H; Bilder, Robert M; Congdon, Eliza; Freimer, Nelson B; London, Edythe D; Sabb, Fred W; Ventura, Joseph; Cannon, Tyrone D

2015-10-01

Schizophrenia patients exhibit impaired working and episodic memory, but this may represent generalized impairment across memory modalities or performance deficits restricted to particular memory systems in subgroups of patients. Furthermore, it is unclear whether deficits are unique from those associated with other disorders. Healthy controls (n=1101) and patients with schizophrenia (n=58), bipolar disorder (n=49) and attention-deficit-hyperactivity-disorder (n=46) performed 18 tasks addressing primarily verbal and spatial episodic and working memory. Effect sizes for group contrasts were compared across tasks and the consistency of subjects' distributional positions across memory domains was measured. Schizophrenia patients performed poorly relative to the other groups on every test. While low to moderate correlation was found between memory domains (r=.320), supporting modularity of these systems, there was limited agreement between measures regarding each individual's task performance (ICC=.292) and in identifying those individuals falling into the lowest quintile (kappa=0.259). A general ability factor accounted for nearly all of the group differences in performance and agreement across measures in classifying low performers. Pathophysiological processes involved in schizophrenia appear to act primarily on general abilities required in all tasks rather than on specific abilities within different memory domains and modalities. These effects represent a general shift in the overall distribution of general ability (i.e., each case functioning at a lower level than they would have if not for the illness), rather than presence of a generally low-performing subgroup of patients. There is little evidence that memory impairments in schizophrenia are shared with bipolar disorder and ADHD. Copyright © 2015 Elsevier B.V. All rights reserved.

Memory systems in schizophrenia: Modularity is preserved but deficits are generalized

PubMed Central

Haut, Kristen M.; Karlsgodt, Katherine H.; Bilder, Robert M.; Congdon, Eliza; Freimer, Nelson; London, Edythe D.; Sabb, Fred W.; Ventura, Joseph; Cannon, Tyrone D.

2015-01-01

Objective Schizophrenia patients exhibit impaired working and episodic memory, but this may represent generalized impairment across memory modalities or performance deficits restricted to particular memory systems in subgroups of patients. Furthermore, it is unclear whether deficits are unique from those associated with other disorders. Method Healthy controls (n=1101) and patients with schizophrenia (n=58), bipolar disorder (n=49) and attention-deficit-hyperactivity-disorder (n=46) performed 18 tasks addressing primarily verbal and spatial episodic and working memory. Effect sizes for group contrasts were compared across tasks and the consistency of subjects’ distributional positions across memory domains was measured. Results Schizophrenia patients performed poorly relative to the other groups on every test. While low to moderate correlation was found between memory domains (r=.320), supporting modularity of these systems, there was limited agreement between measures regarding each individual’s task performance (ICC=.292) and in identifying those individuals falling into the lowest quintile (kappa=0.259). A general ability factor accounted for nearly all of the group differences in performance and agreement across measures in classifying low performers. Conclusions Pathophysiological processes involved in schizophrenia appear to act primarily on general abilities required in all tasks rather than on specific abilities within different memory domains and modalities. These effects represent a general shift in the overall distribution of general ability (i.e., each case functioning at a lower level than they would have if not for the illness), rather than presence of a generally low-performing subgroup of patients. There is little evidence that memory impairments in schizophrenia are shared with bipolar disorder and ADHD. PMID:26299707

Memory deficits due to brain injury: unique PET findings and dream alterations

PubMed Central

Nishida, Masaki; Nariai, Tadashi; Hiura, Mikio; Ishii, Kenji; Nishikawa, Toru

2011-01-01

The authors herein report the case of a young male with memory deficits due to a traumatic head injury, who presented with sleep-related symptoms such as hypersomnia and dream alterations. Although MRI and polysomnography showed no abnormalities, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and 11C flumazenil (FMZ)-PET revealed findings consistent with cerebral damage to the affected temporal region. The memory deficit of the patient gradually improved in parallel with the relief of the sleep-related symptoms. FDG-PET showed considerable improvement in glucose metabolism when he had recovered, however, evidence of neural loss remained in the FMZ-PET findings. PMID:22674950