Subjective deficits of attention, cognition and depression in patients with narcolepsy.

PubMed

Zamarian, Laura; Högl, Birgit; Delazer, Margarete; Hingerl, Katharina; Gabelia, David; Mitterling, Thomas; Brandauer, Elisabeth; Frauscher, Birgit

2015-01-01

Patients with narcolepsy often complain about attention deficits in everyday situations. In comparison with these subjective complaints, deficits in objective testing are subtler. The present study assessed the relationships between subjective complaints, objectively measured cognitive performance, disease-related variables, and mood. A total of 51 patients with narcolepsy and 35 healthy controls responded to questionnaires regarding subjectively perceived attention deficits, sleepiness, anxiety and depression. Moreover, they performed an extensive neuropsychological assessment tapping into attention, executive functions, and memory. Patients rated their level of attention in everyday situations to be relatively poor. In an objective assessment of cognitive functioning, they showed only slight attention and executive function deficits. The subjective ratings of attention deficits significantly correlated with ratings of momentary sleepiness, anxiety, and depression, but not with objectively measured cognitive performance. Momentary sleepiness and depression predicted almost 39% of the variance in the ratings of subjectively perceived attention deficits. The present study showed that sleepiness and depression, more than objective cognitive deficits, might play a role in the subjectively perceived attention deficits of patients with narcolepsy. The results suggested that when counselling and treating patients with narcolepsy, clinicians should pay attention to potential depression because subjective cognitive complaints may not relate to objective cognitive impairments. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Caffeine alleviates progressive motor deficits in a transgenic mouse model of spinocerebellar ataxia.

PubMed

Gonçalves, Nélio; Simões, Ana T; Prediger, Rui D; Hirai, Hirokazu; Cunha, Rodrigo A; Pereira de Almeida, Luís

2017-03-01

Machado-Joseph disease (MJD) is a neurodegenerative spinocerebellar ataxia (SCA) associated with an expanded polyglutamine tract within ataxin-3 for which there is currently no available therapy. We previously showed that caffeine, a nonselective adenosine receptor antagonist, delays the appearance of striatal damage resulting from expression of full-length mutant ataxin-3. Here we investigated the ability of caffeine to alleviate behavioral deficits and cerebellar neuropathology in transgenic mice with a severe ataxia resulting from expression of a truncated fragment of polyglutamine-expanded ataxin-3 in Purkinje cells. Control and transgenic c57Bl6 mice expressing in the mouse cerebella a truncated form of human ataxin-3 with 69 glutamine repeats were allowed to freely drink water or caffeinated water (1g/L). Treatments began at 7 weeks of age, when motor and ataxic phenotype emerges in MJD mice, and lasted up to 20 weeks. Mice were tested in a panel of locomotor behavioral paradigms, namely rotarod, beam balance and walking, pole, and water maze cued-platform version tests, and then sacrificed for cerebellar histology. Caffeine consumption attenuated the progressive loss of general and fine-tuned motor function, balance, and grip strength, in parallel with preservation of cerebellar morphology through decreasing the loss of Purkinje neurons and the thinning of the molecular layer in different folia. Caffeine also rescued the putative striatal-dependent executive and cognitive deficiencies in MJD mice. Our findings provide the first in vivo demonstration that caffeine intake alleviates behavioral disabilities in a severely impaired animal model of SCA. Ann Neurol 2017;81:407-418. © 2016 American Neurological Association.

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.

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.

Cognitive Behavioral Therapies in older adults with depression and cognitive deficits: a systematic review.

PubMed

Simon, Sharon Sanz; Cordás, Táki Athanássios; Bottino, Cássio M C

2015-03-01

The objective of this study is to investigate the effectiveness of cognitive behavioral therapies (CBTs) in improving depressive symptoms, disability, and cognition in older adults with depression and cognitive deficits. It was performed a systematic search for articles published between 1994 and February 2014 in the MEDLINE/Pubmed, PsycINFO, and SCIELO. The studies should have provided information about benefits after CBTs to older adults with depression and cognitive deficits. Cognitive behavioral therapy focused on problem solving is the main approach studied, having better effectiveness than supportive therapy in randomized clinical trials. Significant improvements in mood and disability were consistent, although evidence of changes in cognitive measures is controversial, less studied, and limited. Nevertheless, improvements in executive functions, processing speed, and changes in patients' perspectives of problem solving skills, such as generating alternatives and decision-making, were described. Also, it would be necessary that future studies more often evaluate cognitive status of depressed elders, as well as cognitive changes after psychotherapy. It should be emphasized that there is a lack of studies in this field, and more approaches in CBTs need to be investigated to this population. Older adults with depression and cognitive deficits can benefit from CBTs. Improvements in mood and disability are more consistent than changes in cognition, which are little studied after CBTs. It is necessary more studies in the field, as well as, to investigate more approaches in CBTs to older adults with depression and cognitive deficits. Copyright © 2014 John Wiley & Sons, Ltd.

Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy.

PubMed

Frank, Jennifer Sandson; Vance, David E; Triebel, Kristen L; Meneses, Karen M

2015-12-01

Adjuvant treatments, specifically chemotherapy and hormonal therapy, have dramatically increased breast cancer survival, resulting in increased attention to the residual effects of treatment. Breast cancer survivors (BCS) frequently report that cognitive deficits are a particular source of distress, interfering with many aspects of quality of life. The literature on neuropsychological performance measures in BCS supports the reality of subtle cognitive deficits after both chemotherapy and hormonal therapy. This premise is supported by recent imaging studies, which reveal anatomical changes after chemotherapy as well as changes in patterns of neural activation while performing cognitive tasks. This review suggests that, even when performance on neuropsychological performance measures is within normal limits, BCS may be using increased cognitive resources in the face of reduced cognitive reserve. Potential interventions for cognitive deficits after adjuvant therapy include prescriptions for healthy living, pharmacotherapy, complementary therapy, and cognitive remediation therapy directed toward specific cognitive deficits or a combination of several strategies.

Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats.

PubMed

Liu, Xianchu; Liu, Ming; Mo, Yanzhi; Peng, Huan; Gong, Jingbo; Li, Zhuang; Chen, Jiaxue; Xie, Jingtao

2016-04-01

Previous research demonstrated that diabetes is one of the leading causes of learning and memory deficits. Naringin, a bioflavonoid isolated from grapefruits and oranges, has potent protective effects on streptozotocin (STZ)-induced diabetic rats. Recently, the effects of naringin on learning and memory performances were monitored in many animal models of cognitive impairment. However, to date, no studies have investigated the ameliorative effects of naringin on diabetes-associated cognitive decline (DACD). In this study, we investigated the effects of naringin, using a STZ-injected rat model and explored its potential mechanism. Diabetic rats were treated with naringin (100 mg/kg/d) for 7 days. The learning and memory function were assessed by Morris water maze test. The oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)] and inflammatory cytokines (TNF-a, IL-1β, and IL-6) were measured in hippocampus using corresponding commercial kits. The mRNA and protein levels of PPARγ were evaluated by real time (RT)-PCR and Western blot analysis. The results showed that supplementation of naringin improved learning and memory performances compared with the STZ group. Moreover, naringin supplement dramatically increased SOD levels, reduced MDA levels, and alleviated TNF-α, IL-1β, and IL-6 compared with the STZ group in the hippocampus. The pretreatment with naringin also significantly increased PPARγ expression. Our results showed that naringin may be a promising therapeutic agent for improving cognitive decline in DACD.

Cognitive Deficits in Schizophrenia: Understanding the Biological Correlates and Remediation Strategies

PubMed Central

Tripathi, Adarsh; Shukla, Rashmi

2018-01-01

Cognitive deficits are one of the core symptoms of schizophrenia that evolve during the course of schizophrenia, after being originated even before the onset of illness. Existing pharmacological and biological treatment modalities fall short to meet the needs to improve the cognitive symptoms; hence, various cognitive remediation strategies have been adopted to address these deficits. Research evidences suggest that cognitive remediation measures improve the functioning, limit disability bettering the quality of life. The functional outcomes of cognitive remediation in schizophrenia are resultant of neurobiological changes in specific brain areas. Recent years witnessed significant innovations in cognitive remediation strategies in schizophrenia. This comprehensive review highlights the biological correlates of cognitive deficits in schizophrenia and the remedial measures with evidence base. PMID:29397662

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.

Cognitive Deficits and Positively Biased Self-Perceptions in Children with ADHD

ERIC Educational Resources Information Center

McQuade, Julia D.; Tomb, Meghan; Hoza, Betsy; Waschbusch, Daniel A.; Hurt, Elizabeth A.; Vaughn, Aaron J.

2011-01-01

This study examined the relation between cognitive deficits and positive bias in a sample of 272 children with and without Attention Deficit Hyperactivity Disorder (ADHD; 7-12 years old). Results indicated that children with ADHD with and without biased self-perceptions exhibit differences in specific cognitive deficits (executive processes,…

Cognitive deficits in heart failure: Re-cognition of vulnerability as a strange new world.

PubMed

Sloan, Rebecca S; Pressler, Susan J

2009-01-01

Patients with chronic heart failure (HF) have impairment in memory, psychomotor speed, and executive function. The aim of this study was to describe how individuals with HF and cognitive deficits manage self-care in their daily lives. Using an interpretive phenomenology method, HF patients completed unstructured face-to-face interviews about their ability to manage complex health regimens and maintain their health-related quality of life. Analysis of data was aided by use of Atlas.ti computer software. The sample consisted of 12 patients (10 men; aged 43-81 years) who had previously undergone neuropsychological testing and were found to have deficits in 3 or more cognitive domains. Patients confirmed that they followed the advice of healthcare providers by adherence to medication regimens, dietary sodium restrictions, and HF self-care. One overarching theme was identified: "Re-cognition of Vulnerability: A Strange New World." This theme was further differentiated into 3 components: (1) not recognizing cognitive deficits; (2) recognizing cognitive deficits, described as (a) never could remember anything, (b) just old age, (c) HF-related change, and (d) making normal accommodations; and (3) recognizing vulnerability, explained by perception of (a) cognitive, (b) physical, and (c) social vulnerabilities, as well as perception of (d) the nearness of death. Although the study was designed to focus on the cognitive changes in HF patients, it was difficult to separate cognitive, physical, and social challenges. These changes are most useful when taken as a constellation. Healthcare professionals can use the knowledge to identify problems and interventions for HF patients.

Cognitive Control Deficits Associated with Antisocial Personality Disorder and Psychopathy

PubMed Central

Zeier, Joshua D.; Baskin-Sommers, Arielle R.; Newman, Joseph P.; Racer, Kristina Hiatt

2011-01-01

Antisociality has been linked to a variety of executive functioning deficits, including poor cognitive control. Surprisingly, cognitive control deficits are rarely found in psychopathic individuals, despite their notoriously severe and persistent antisocial behavior. In fact, primary (low-anxious) psychopathic individuals display superior performance on cognitive control-type tasks under certain circumstances. To clarify these seemingly contradictory findings, we administered a response competition (i.e. flanker) task to incarcerated offenders, who were assessed for Antisocial Personality Disorder (APD) symptoms and psychopathy. As hypothesized, APD related to poorer accuracy, especially on incongruent trials. Contrary to expectation, however, the same pattern of results was found in psychopathy. Additional analyses indicated that these effects of APD and psychopathy were associated with overlapping variance. The findings suggest that psychopathy and APD symptoms are both associated with deficits in cognitive control, and that this deficit relates to general antisociality as opposed to a specific antisocial syndrome. PMID:22452754

Cognitive control deficits associated with antisocial personality disorder and psychopathy.

PubMed

Zeier, Joshua D; Baskin-Sommers, Arielle R; Hiatt Racer, Kristina D; Newman, Joseph P

2012-07-01

Antisociality has been linked to a variety of executive functioning deficits, including poor cognitive control. Surprisingly, cognitive control deficits are rarely found in psychopathic individuals, despite their notoriously severe and persistent antisocial behavior. In fact, primary (low-anxious) psychopathic individuals display superior performance on cognitive control-type tasks under certain circumstances. To clarify these seemingly contradictory findings, we administered a response competition (i.e., flanker) task to incarcerated offenders, who were assessed for Antisocial Personality Disorder (APD) symptoms and psychopathy. As hypothesized, APD related to poorer accuracy, especially on incongruent trials. Contrary to expectation, however, the same pattern of results was found in psychopathy. Additional analyses indicated that these effects of APD and psychopathy were associated with overlapping variance. The findings suggest that psychopathy and APD symptoms are both associated with deficits in cognitive control, and that this deficit relates to general antisociality as opposed to a specific antisocial syndrome. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Speech Deficits in Serious mental Illness: A Cognitive Resource Issue?

PubMed Central

Cohen, Alex S.; McGovern, Jessica E.; Dinzeo, Thomas J.; Covington, Michael A.

2014-01-01

Speech deficits, notably those involved in psychomotor retardation, blunted affect, alogia and poverty of content of speech, are pronounced in a wide range of serious mental illnesses (e.g., schizophrenia, unipolar depression, bipolar disorders). The present project evaluated the degree to which these deficits manifest as a function of cognitive resource limitations. We examined natural speech from 52 patients meeting criteria for serious mental illnesses (i.e., severe functional deficits with a concomitant diagnosis of schizophrenia, unipolar and/or bipolar affective disorders) and 30 non-psychiatric controls using a range of objective, computer-based measures tapping speech production (“alogia”), variability (“blunted vocal affect”) and content (“poverty of content of speech”). Subjects produced natural speech during a baseline condition and while engaging in an experimentally-manipulated cognitively-effortful task. For correlational analysis, cognitive ability was measured using a standardized battery. Generally speaking, speech deficits did not differ as a function of SMI diagnosis. However, every speech production and content measure was significantly abnormal in SMI versus control groups. Speech variability measures generally did not differ between groups. For both patients and controls as a group, speech during the cognitively-effortful task was sparser and less rich in content. Relative to controls, patients were abnormal under cognitive load with respect only to average pause length. Correlations between the speech variables and cognitive ability were only significant for this same variable: average pause length. Results suggest that certain speech deficits, notably involving pause length, may manifest as a function of cognitive resource limitations. Implications for treatment, research and assessment are discussed. PMID:25464920

Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients

PubMed Central

Woo, Young Sup; Rosenblat, Joshua D.; Kakar, Ron; Bahk, Won-Myong; McIntyre, Roger S.

2016-01-01

Cognitive deficits in major depressive disorder (MDD) patients have been described in numerous studies. However, few reports have aimed to describe cognitive deficits in the remitted state of MDD and the mediational effect of cognitive deficits on occupational outcome. The aim of the current review is to synthesize the literature on the mediating and moderating effects of specific domains of cognition on occupational impairment among people with remitted MDD. In addition, predictors of cognitive deficits found to be vocationally important will be examined. Upon examination of the extant literature, attention, executive function and verbal memory are areas of consistent impairment in remitted MDD patients. Cognitive domains shown to have considerable impact on vocational functioning include deficits in memory, attention, learning and executive function. Factors that adversely affect cognitive function related to occupational accommodation include higher age, late age at onset, residual depressive symptoms, history of melancholic/psychotic depression, and physical/psychiatric comorbidity, whereas higher levels of education showed a protective effect against cognitive deficit. Cognitive deficits are a principal mediator of occupational impairment in remitted MDD patients. Therapeutic interventions specifically targeting cognitive deficits in MDD are needed, even in the remitted state, to improve functional recovery, especially in patients who have a higher risk of cognitive deficit. PMID:26792035

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder: Current Status and Working Hypotheses

ERIC Educational Resources Information Center

Vaidya, Chandan J.; Stollstorff, Melanie

2008-01-01

Cognitive neuroscience studies of Attention Deficit Hyperactivity Disorder (ADHD) suggest multiple loci of pathology with respect to both cognitive domains and neural circuitry. Cognitive deficits extend beyond executive functioning to include spatial, temporal, and lower-level "nonexecutive" functions. Atypical functional anatomy extends beyond…

Speech deficits in serious mental illness: a cognitive resource issue?

PubMed

Cohen, Alex S; McGovern, Jessica E; Dinzeo, Thomas J; Covington, Michael A

2014-12-01

Speech deficits, notably those involved in psychomotor retardation, blunted affect, alogia and poverty of content of speech, are pronounced in a wide range of serious mental illnesses (e.g., schizophrenia, unipolar depression, bipolar disorders). The present project evaluated the degree to which these deficits manifest as a function of cognitive resource limitations. We examined natural speech from 52 patients meeting criteria for serious mental illnesses (i.e., severe functional deficits with a concomitant diagnosis of schizophrenia, unipolar and/or bipolar affective disorders) and 30 non-psychiatric controls using a range of objective, computer-based measures tapping speech production ("alogia"), variability ("blunted vocal affect") and content ("poverty of content of speech"). Subjects produced natural speech during a baseline condition and while engaging in an experimentally-manipulated cognitively-effortful task. For correlational analysis, cognitive ability was measured using a standardized battery. Generally speaking, speech deficits did not differ as a function of SMI diagnosis. However, every speech production and content measure was significantly abnormal in SMI versus control groups. Speech variability measures generally did not differ between groups. For both patients and controls as a group, speech during the cognitively-effortful task was sparser and less rich in content. Relative to controls, patients were abnormal under cognitive load with respect only to average pause length. Correlations between the speech variables and cognitive ability were only significant for this same variable: average pause length. Results suggest that certain speech deficits, notably involving pause length, may manifest as a function of cognitive resource limitations. Implications for treatment, research and assessment are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

Perceived Cognitive Deficits in a Sample of Persons Living With Multiple Sclerosis.

PubMed

Henneghan, Ashley; Stuifbergen, Alexa; Becker, Heather; Kullberg, Vicki; Gloris, Nicole

2017-10-01

The aims of this study were to describe the nature and diversity of perceived cognitive deficits using the Perceived Deficits Questionnaire (PDQ), to assess the reliability of the PDQ, and to explore self-reported predictors of PDQ scores in a large community-based sample of persons with multiple sclerosis (MS). Persons with MS enrolled in a randomized controlled trial provided demographic data and completed the PDQ along with measures of cognitive and memory strategies, cognitive abilities, self-efficacy, and depressive symptoms and neuropsychological tests. Most of the 183 participants were non-Hispanic white women, approximately 49 years old, and diagnosed with MS 12.5 years prior. The most frequent cognitive complaints regarded trouble remembering telephone numbers, mind drifting, and forgetting why one came into a room. The PDQ scores were significantly related to self-rated cognitive abilities, depressive symptoms, self-efficacy, and use of cognitive strategies, but not to scores on neuropsychological performance tests. When controlling for other variables, self-rated cognitive abilities was the strongest, significant predictor of perceived cognitive deficits. Persons with MS most frequently experience deficits related to short-term memory and attention. The PDQ total is a reliable measure of perceived cognitive deficits in persons with MS, is feasible for use by nurses in clinical settings-can be administered in approximately 5 minutes, and is easily scored.

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.

Ursolic acid improves domoic acid-induced cognitive deficits in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Dong-mei; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province; Lu, Jun, E-mail: lu-jun75@163.com

Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitivemore » deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders.« less

Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease.

PubMed

Santana, Maxwell B; Halje, Pär; Simplício, Hougelle; Richter, Ulrike; Freire, Marco Aurelio M; Petersson, Per; Fuentes, Romulo; Nicolelis, Miguel A L

2014-11-19

Although deep brain electrical stimulation can alleviate the motor symptoms of Parkinson disease (PD), just a small fraction of patients with PD can take advantage of this procedure due to its invasive nature. A significantly less invasive method--epidural spinal cord stimulation (SCS)--has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through SCS are unknown. Here, we show that SCS reproducibly alleviates motor deficits in a primate model of PD. Simultaneous neuronal recordings from multiple structures of the cortico-basal ganglia-thalamic loop in parkinsonian monkeys revealed abnormal highly synchronized neuronal activity within each of these structures and excessive functional coupling among them. SCS disrupted this pathological circuit behavior in a manner that mimics the effects caused by pharmacological dopamine replacement therapy or deep brain stimulation. These results suggest that SCS should be considered as an additional treatment option for patients with PD. Copyright © 2014 Elsevier Inc. All rights reserved.

[Epigenetic research of cognitive deficit in schizophrenia: some methodological considerations].

PubMed

Lezheiko, T V; Alfimova, M V

To highlights the problems of assessing cognitive deficits in schizophrenia, relevant to the epigenetic, as well as a wide range of other approaches to the search for biological bases of cognition. The literature on the weaknesses in the evaluation of cognitive functions in patients with schizophrenia are summarized and discussed. The analysis is illustrated by our experience in developing a cognitive battery and a sample to examine relationships between DNA methylation in blood cells and cognitive deficits in schizophrenia. It has been shown that to assess cognitive deficits in patients and to reduce the influence of confounders in epigenetic analysis it is necessary (1) to use a battery with the existing co-normative data in the target population, which allows to evaluate representativeness of control and patients included in the study sample, (2) to verify the theoretically driven battery structure using normative population and a cohort of patients, (3) to balance groups of cases and controls on the number, age and sex, for which an individual matching of cases and controls is best suited, (4) to conduct an additional statistical analysis controlling for education and smoking.

Deficits in Social Cognition: An Unveiled Signature of Multiple Sclerosis.

PubMed

Chalah, Moussa A; Ayache, Samar S

2017-03-01

Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system, representing the primary cause of non-traumatic disability in young adults. Cognitive dysfunction can affect patients at any time during the disease process and might alter the six core functional domains. Social cognition is a multi-component construct that includes the theory of mind, empathy and social perception of emotions from facial, bodily and vocal cues. Deficits in this cognitive faculty might have a drastic impact on interpersonal relationships and quality of life (QoL). Although exhaustive data exist for non-social cognitive functions in MS, only a little attention has been paid for social cognition. The objectives of the present work are to reappraise the definition and anatomy of social cognition and evaluate the integrity of this domain across MS studies. We will put special emphasis on neuropsychological and neuroimaging studies concerning social cognitive performance in MS. Studies were selected in conformity with PRISMA guidelines. We looked for computerized databases (PubMed, Medline, and Scopus) that index peer-reviewed journals to identify published reports in English and French languages that mention social cognition and multiple sclerosis, regardless of publication year. We combined keywords as follows: (facial emotion or facial expression or emotional facial expressions or theory of mind or social cognition or empathy or affective prosody) AND multiple sclerosis AND (MRI or functional MRI or positron emission tomography or functional imaging or structural imaging). We also scanned references from articles aiming to get additional relevant studies. In total, 26 studies matched the abovementioned criteria (26 neuropsychological studies including five neuroimaging studies). Available data support the presence of social cognitive deficits even at early stages of MS. The increase in disease burden along with the "multiple disconnection syndrome

Neuroprotective role of Ginkgo biloba against cognitive deficits associated with Bisphenol A exposure: An animal model study.

PubMed

El Tabaa, Manar Mohammed; Sokkar, Samia Salem; Ramadan, Ehab Sayed; Abd El Salam, Inas Zakria; Zaid, Anis

2017-09-01

Our study aimed to elucidate to what extent Ginkgo biloba (Gb) can protect rats from cognitive deficits induced by exposure to Bisphenol A (BPA) at high dose. Therefore, sixty male Wistar rats were randomly divided into four groups of 15 animals in each group: Vehicle group, Gb-control group, BPA-exposed group and Gb pre-treated group. All administrations were given daily by an oral gavage once a day for eight weeks. Cognitive function was assessed using Morris water maze; Y-maze and Novel object recognition tasks. Additionally, hippocampal levels of DA, NE and 5-HT were measured. BPA-induced oxidative stress was evaluated by determining SOD activity, NO and MDA levels in rat hippocampus as well as level of circulating adiponectin. Moreover, histopathological changes in CA3 region of rat hippocampus and immunohistochemical expression of NF-κB and Caspase-3 were investigated. We found that Gb pretreatment significantly improved cognitive performance; may be via increasing hippocampal levels of estrogen-dependent biogenic amines. At the same time, Gb could strictly control BPA-induced oxidative stress by improving SOD activity and adiponectin level with decrease in NO and MDA levels. Lastly, Gb alleviated the histopathological injuries induced by BPA and inhibited NF-κB and caspase-3 activation. In conclusion, our results suggested that Gb has potential to ameliorate BPA-induced hippocampal neuronal damage and subsequent cognitive deficits through mechanisms involving its ability to enhance the release of biogenic amines as well as its antioxidant and adiponectin pro-secretory effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion

PubMed Central

Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

2015-01-01

Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0–3), but not the late stage after rUCCAO (day 4–32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD. PMID:26174710

Psychosocial support and cognitive deficits in adults with schizophrenia.

PubMed

Dalagdi, Aikaterini; Arvaniti, Aikaterini; Papatriantafyllou, John; Xenitidis, Kiriakos; Samakouri, Maria; Livaditis, Miltos

2014-08-01

In recent decades there has been an increasing interest in cognitive deficits in schizophrenia. However, only a few studies have examined the impact of psychosocial support on the prevention of cognitive deterioration in patients who suffer from schizophrenia. The aims of the present study are: (1) to confirm the presence of cognitive deficits among patients with schizophrenia; (2) to explore any correlations between such deficits and a range of clinical and/or demographic characteristics of the patients; and (3) to investigate any association between cognitive deficits and psychosocial support. A total of 118 patients with schizophrenia (the patient group) and 102 healthy volunteers (the control group) had a cognitive assessment using a battery of neuropsychological tests. The patients were allocated to one of the following groups: (1) patients under routine outpatient follow-up; or (2) patients receiving or having recently received intensive psychosocial support, in addition to follow-up. This included daily participation in vocational and recreational activities provided by dedicated mental health day centers. The findings of the neuropsychological testing of individuals in all groups were compared, after controlling for clinical or demographic factors. The scores in the neuropsychological tests were lower overall in the patients group compared to healthy volunteers. Within the patients group, those receiving/having received psychosocial support had higher scores compared to those on routine follow-up alone. There were no significant differences between patients currently receiving psychosocial support and those having received it in the past. Lower education, age and illness duration (but not severity of positive or negative symptoms) were factors associated with lower test scores. The study provides some evidence that psychosocial support may be beneficial for the cognitive functioning of patients with schizophrenia and this benefit may be a lasting one. �

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits

PubMed Central

Gaudier-Diaz, Monica M.; Weinhold, Kellie R.; DeVries, A. Courtney

2017-01-01

Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits.

PubMed

Orchard, Tonya S; Gaudier-Diaz, Monica M; Weinhold, Kellie R; Courtney DeVries, A

2017-02-01

Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the

Evidence for distinct cognitive deficits after focal cerebellar lesions.

PubMed

Gottwald, B; Wilde, B; Mihajlovic, Z; Mehdorn, H M

2004-11-01

Anatomical evidence and lesion studies, as well as functional magnetic resonance imaging (fMRI) studies, indicate that the cerebellum contributes to higher cognitive functions. Cerebellar posterior lateral regions seem to be relevant for cognition, while vermal lesions seem to be associated with changes in affect. However, the results remain controversial. Deficits of patients are sometimes still attributed to motor impairment. We present data from a detailed neuropsychological examination of 21 patients with cerebellar lesions due to tumour or haematoma, and 21 controls matched for age, sex, and years of education. Patients showed deficits in executive function, and in attentional processes such as working memory and divided attention. Further analysis revealed that patients with right-sided lesions were in general more impaired than those with left-sided lesions. Those hypotheses that suggest that lesions of the right cerebellar hemisphere lead to verbal deficits, while those of the left lead to non-verbal deficits, have in part been confirmed. The generally greater impairment of those patients with a right-sided lesion has been interpreted as resulting from the connection of the right cerebellum to the left cerebral hemisphere, which is dominant for language functions and crucial for right hand movements. Motor impairment was correlated with less than half of the cognitive measures, with no stronger tendency for correlation with cognitive tests that require motor responses discernible. The results are discussed on the basis of an assumption that the cerebellum has a predicting and preparing function, indicating that cerebellar lesions lead to a "dysmetria of thought."

Profile of cognitive deficits and associations with depressive symptoms and intelligence in chronic early-onset schizophrenia patients.

PubMed

Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte; Pagsberg, Anne Katrine; Christensen, Anne Marie Raaberg; Nordentoft, Merete; Mortensen, Erik Lykke

2013-10-01

Cognitive deficits in several domains have been demonstrated in early-onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early-onset schizophrenia patients, assess the potential associations with depressive symptom severity, and examine whether cognitive deficits within several domains reflect intelligence impairments. This study compared attention, visual-construction, aspects of visual and verbal memory, and executive functions in chronic, early-onset schizophrenia patients (mean age = 20.7 years) (N = 18) and healthy controls (N = 38). Schizophrenia diagnoses were established at the time of the patients' first clinical presentation during childhood or adolescence and were confirmed five years later. In the chronic phase of early-onset schizophrenia, significant deficits were observed in all specific cognitive functions. The profile of cognitive deficits was jagged, and visual-construction, attention, and one aspect of verbal memory (verbal stories recall) were differentially impaired. Deficits of visual recall, visual recognition, and executive functions were accounted for by deficits in intelligence, while this was not the case for deficits of verbal recall of stories or attention. No significant associations were observed between the severity of cognitive deficits and that of depressive symptoms. Chronic, early-onset schizophrenia is characterized by a broad and jagged profile of cognitive deficits. Deficits of attention and verbal recall of stories appear not to be accounted for by deficits in intelligence, and the severity of cognitive deficits seems independent from that of depressive symptoms. © 2013 The Scandinavian Psychological Associations.

Gray matter morphological anomalies in the cerebellar vermis in first-episode schizophrenia patients with cognitive deficits.

PubMed

Wang, Jingjuan; Zhou, Li; Cui, Chunlei; Liu, Zhening; Lu, Jie

2017-11-22

Cognitive deficits are a core feature of early schizophrenia. However, the pathological foundations underlying cognitive deficits are still unknown. The present study examined the association between gray matter density and cognitive deficits in first-episode schizophrenia. Structural magnetic resonance imaging of the brain was performed in 34 first-episode schizophrenia patients and 21 healthy controls. Patients were divided into two subgroups according to working memory task performance. The three groups were well matched for age, gender, and education, and the two patient groups were also further matched for diagnosis, duration of illness, and antipsychotic treatment. Voxel-based morphometric analysis was performed to estimate changes in gray matter density in first-episode schizophrenia patients with cognitive deficits. The relationships between gray matter density and clinical outcomes were explored. Patients with cognitive deficits were found to have reduced gray matter density in the vermis and tonsil of cerebellum compared with patients without cognitive deficits and healthy controls, decreased gray matter density in left supplementary motor area, bilateral precentral gyrus compared with patients without cognitive deficits. Classifier results showed GMD in cerebellar vermis tonsil cluster could differentiate SZ-CD from controls, left supplementary motor area cluster could differentiate SZ-CD from SZ-NCD. Gray matter density values of the cerebellar vermis cluster in patients groups were positively correlated with cognitive severity. Decreased gray matter density in the vermis and tonsil of cerebellum may underlie early psychosis and serve as a candidate biomarker for schizophrenia with cognitive deficits.

GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia.

PubMed

Gonzalez-Burgos, Guillermo; Fish, Kenneth N; Lewis, David A

2011-01-01

Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

PubMed Central

Gonzalez-Burgos, Guillermo; Fish, Kenneth N.; Lewis, David A.

2011-01-01

Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions. PMID:21904685

Effect of Treating Anxiety Disorders on Cognitive Deficits and Behaviors Associated with Attention Deficit Hyperactivity Disorder: A Preliminary Study.

PubMed

Denis, Isabelle; Guay, Marie-Claude; Foldes-Busque, Guillaume; BenAmor, Leila

2016-06-01

Twenty-five percent of children with ADHD also have an anxiety disorder (AD). As per Quay and in light of Barkley's model, anxiety may have a protective effect on cognitive deficits and behaviors associated with ADHD. This study aimed to evaluate the effect of treating AD on cognitive deficits and behaviors associated with ADHD in children with both disorders. Twenty-four children with ADHD and AD were divided into two groups: treatment for AD, and wait list. Participants were assessed at pre-treatment, post-treatment, and 6-month follow-up with the ADIS-C, the CBCL, and neuropsychological measures. The results revealed a significant improvement in automatic response inhibition and flexibility, and a decrease in inattention/hyperactivity behaviors following the treatment for AD. No significant differences were observed in motor response inhibition, working memory, or attention deficits. The results do not seem to support Quay's hypothesis: treating AD did not exacerbate cognitive deficits and behaviors associated with ADHD in our sample.

A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits.

PubMed

Leiser, Steven C; Bowlby, Mark R; Comery, Thomas A; Dunlop, John

2009-06-01

Cognition, memory, and attention and arousal have been linked to nicotinic acetylcholine receptors (nAChRs). Thus it is not surprising that nAChRs have been strongly implicated as therapeutic targets for treating cognitive deficits in disorders such as schizophrenia and Alzheimer's disease (AD). In particular the alpha7 (alpha7) nAChR has been closely linked with normalization of P50 auditory evoked potential (AEP) gating deficits, and to a lesser extent improvements in pre-pulse inhibition (PPI) of the acoustic startle response. These two brain phenomena can be considered as pre-attentive, occurring while sensory information is being processed, and are important endophenotypes in schizophrenia with deficits likely contributing to the cognitive fragmentation associated with the disease. In addition alpha7 nAChRs have been implicated in attention, in particular under high attentional demand, and in more demanding working memory tasks such as long delays in delayed matching tasks. Efficacy of alpha7 nAChR agonists across a range of cognitive processes ranging from pre-attentive to attentive states and working and recognition memory provides a solid basis for their pro-cognitive effects. This review will focus on the recent work highlighting the role of alpha7 in cognition and cognitive processes.

A specific cognitive deficit within semantic cognition across a multi-generational family

PubMed Central

Briscoe, Josie; Chilvers, Rebecca; Baldeweg, Torsten; Skuse, David

2012-01-01

We report a study of eight members of a single family (aged 8–72 years), who all show a specific deficit in linking semantic knowledge to language. All affected members of the family had high levels of overall intelligence; however, they had profound difficulties in prose and sentence recall, listening comprehension and naming. The behavioural deficit was remarkably consistent across affected family members. Structural neuroimaging data revealed grey matter abnormalities in the left infero-temporal cortex and fusiform gyri: brain areas that have been associated with integrative semantics. This family demonstrates, to our knowledge, the first example of a heritable, highly specific abnormality affecting the interface between language and cognition in humans and has important implications for our understanding of the genetic basis of cognition. PMID:22719041

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

PubMed

Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

2017-10-01

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition

BDNF (brain-derived neurotrophic factor) serum levels in schizophrenic patients with cognitive deficits

NASA Astrophysics Data System (ADS)

Utami, N.; Effendy, E.; Amin, M. M.

2018-03-01

Schizophrenia is a complex neurodevelopmental disorder with cognitive impairment as the main part. BDNF regulates aspects of developmental plasticity in the brain and is involved in cognitive function. Cognitive functions include capabilities such as attention, executive functioning, assessing, monitoring and evaluating. The aim of the study was to know the BDNF levels in schizophrenic patients with cognitive deficits. The study was held in October 2016 - March 2017, and was the first in Indonesia, especially in North Sumatra. The study was approved by the medical ethics committee of the University of North Sumatera. The study is descriptive based on a retrospective method with cross-sectional approach. The subject is 40 male schizophrenia. Cognitive deficits were assessed by MoCA-Ina. BDNF serum levels were analyzed using the quantitative sandwich enzyme immunoassay. The average MoCA-Ina score is 21.03±5.21. This suggests that there is a cognitive function deficit in schizophrenic patients. The mean serum BDNF level was 26629±6762. MoCA-Ina scores in schizophrenic patients <26 who experienced a deficit of 77.5% and serum BDNF levels with normal values ranging from 6.186 to 42.580pg/ml.

Mangiferin regulates cognitive deficits and heme oxygenase-1 induced by lipopolysaccharide in mice.

PubMed

Fu, Yanyan; Liu, Hongzhi; Song, Chengjie; Zhang, Fang; Liu, Yi; Wu, Jian; Wen, Xiangru; Liang, Chen; Ma, Kai; Li, Lei; Zhang, Xunbao; Shao, Xiaoping; Sun, Yafeng; Du, Yang; Song, Yuanjian

2015-12-01

Accumulating evidence reveals that lipopolysaccharide (LPS) can induce neuroinflammation, ultimately leading to cognitive deficits. Mangiferin, a natural glucoxilxanthone, is known to possess various biological activities. The present study aimed to investigate the effects of mangiferin on LPS-induced cognitive deficits and explore the underlying mechanisms. Brain injury was induced in mice via intraperitoneal LPS injection (1mg/kg) for five consecutive days. Mangiferin was orally pretreatmented (50mg/kg) for seven days and then treatmented (50mg/kg) for five days after LPS injection. The Morris water maze was used to detect changes in cognitive function. Immunohistochemical and immunoblotting were respectively performed to measure the expression of interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) in the hippocampus. The results showed that mangiferin can ameliorate cognitive deficits. Moreover, mangiferin decreased LPS-induced IL-6 production and increase HO-1 in the hippocampus. Taken together, these results suggest that mangiferin attenuates LPS-induced cognitive deficits, which may be potentially linked to modulating HO-1 in the hippocampus. Copyright © 2015. Published by Elsevier B.V.

Social Cognition Deficits: Current Position and Future Directions for Neuropsychological Interventions in Cerebrovascular Disease.

PubMed

Njomboro, Progress

2017-01-01

Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits). In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients' performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments.

Social Cognition Deficits: Current Position and Future Directions for Neuropsychological Interventions in Cerebrovascular Disease

PubMed Central

2017-01-01

Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits). In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients' performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments. PMID:28729755

Structural correlates of cognitive deficit and elevated gamma noise power in schizophrenia.

PubMed

Suazo, Vanessa; Díez, Álvaro; Montes, Carlos; Molina, Vicente

2014-03-01

The aim of this study was to assess the relation between cognition, gray matter (GM) volumes and gamma noise power (amount of background oscillatory activity in the gamma band) in schizophrenia. We explored the relation between cognitive performance and regional GM volumes using voxel-based morphometry (VBM), in order to discover if the association between gamma noise power (an electroencephalography measurement of background activity in the gamma band) and cognition is observed through structural deficits related to the disease. Noise power, magnetic resonance imaging and cognitive assessments were obtained in 17 drug-free paranoid patients with schizophrenia and 13 healthy controls. In comparison with controls, patients showed GM deficits at posterior cingulate (bilateral),left inferior parietal (supramarginal gyrus) and left inferior dorsolateral prefrontal regions. Patients exhibited a direct association between performance in working memory and right temporal (superior and inferior gyri) GM densities. They also displayed a negative association between right anterior cerebellum volume and gamma noise power at the frontal midline (Fz) site. A structural deficit in the cerebellum may be involved in gamma activity disorganization in schizophrenia. Temporal structural deficits may relate to cognitive dysfunction in this illness. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Deficits in social cognition and response flexibility in pediatric bipolar disorder.

PubMed

McClure, Erin B; Treland, Julia E; Snow, Joseph; Schmajuk, Mariana; Dickstein, Daniel P; Towbin, Kenneth E; Charney, Dennis S; Pine, Daniel S; Leibenluft, Ellen

2005-09-01

Little is known about neuropsychological and social-cognitive function in patients with pediatric bipolar disorder. Identification of specific deficits and strengths that characterize pediatric bipolar disorder would facilitate advances in diagnosis, treatment, and research on pathophysiology. The purpose of this study was to test the hypothesis that youths with bipolar disorder would perform more poorly than matched healthy comparison subjects on measures of social cognition, motor inhibition, and response flexibility. Forty outpatients with pediatric bipolar disorder and 22 comparison subjects (no differences in age, gender, and IQ) completed measures of social cognition (the pragmatic judgment subtest of the Comprehensive Assessment of Spoken Language, facial expression recognition subtests of the Diagnostic Analysis of Nonverbal Accuracy Scale, the oral expression subtest of the Test of Language Competence), inhibition and response flexibility (stop and stop-change tasks), and motor inhibition (continuous performance tasks). Pediatric bipolar disorder patients performed more poorly than comparison subjects on social-cognitive measures (pragmatic judgment of language, facial expression recognition) and on a task requiring response flexibility. These deficits were present in euthymic patients. Differences between patients and comparison subjects could not be attributed to comorbid attention deficit hyperactivity disorder. Findings of impaired social cognition and response flexibility in youths with pediatric bipolar disorder suggest continuity between pediatric bipolar disorder and adult bipolar disorder. These findings provide a foundation for neurocognitive research designed to identify the neural mechanisms underlying these deficits.

D-Aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice.

PubMed

Palazzo, Enza; Luongo, Livio; Guida, Francesca; Marabese, Ida; Romano, Rosaria; Iannotta, Monica; Rossi, Francesca; D'Aniello, Antimo; Stella, Luigi; Marmo, Federica; Usiello, Alessandro; de Bartolomeis, Andrea; Maione, Sabatino; de Novellis, Vito

2016-07-01

D-Aspartate (D-Asp) is a free D-amino acid detected in multiple brain regions and putative precursor of endogenous N-methyl-D-aspartate (NMDA) acting as agonist at NMDA receptors. In this study, we investigated whether D-Asp (20 mM) in drinking solution for 1 month affects pain responses and pain-related emotional, and cognitive behaviour in a model of neuropathic pain induced by the spared nerve injury (SNI) of the sciatic nerve in mice. SNI mice developed mechanical allodynia and motor coordination impairment 30 days after SNI surgery. SNI mice showed cognitive impairment, anxiety and depression-like behaviour, reduced sociability in the three chamber sociability paradigm, increased expression of NR2B subunit of NMDA receptor and Homer 1a in the medial prefrontal cortex (mPFC). The expression of (post synaptic density) PSD-95 and Shank 1was instead unaffected in the mPFC of the SNI mice. Treatment with D-Asp drinking solution, started right after the SNI (day 0), alleviated mechanical allodynia, improved cognition and motor coordination and increased social interaction. D-Asp also restored the levels of extracellular D-Asp, Homer 1a and NR2B subunit of the NMDA receptor to physiological levels and reduced Shank1 and PSD-95 protein levels in the mPFC. Amitriptyline, a tricyclic antidepressant used also to alleviate neuropathic pain in humans, reverted mechanical allodynia and cognitive impairment, and unlike D-Asp, was effective in reducing depression and anxiety-like behaviour in the SNI mice and increased PSD protein level. Altogether these findings demonstrate that D-Asp improves sensorial, motor and cognitive-like symptoms related to chronic pain possibly through glutamate neurotransmission normalization in neuropathic mice.

Meta-analysis of social cognition in attention-deficit/hyperactivity disorder (ADHD): comparison with healthy controls and autistic spectrum disorder.

PubMed

Bora, E; Pantelis, C

2016-03-01

Impairment in social cognition is an established finding in autism spectrum disorders (ASD). Emerging evidence suggests that attention-deficit/hyperactivity disorder (ADHD) might be also associated with deficits in theory of mind (ToM) and emotion recognition. However, there are inconsistent findings, and it has been debatable whether such deficits persist beyond childhood and how similar social cognitive deficits are in ADHD v. ASD. We conducted a meta-analysis of social cognition, including emotion recognition and ToM, studies in ADHD compared with healthy controls and ASD. The current meta-analysis involved 44 studies comparing ADHD (n = 1999) with healthy controls (n = 1725) and 17 studies comparing ADHD (n = 772) with ASD (n = 710). Facial and vocal emotion recognition (d = 0.40-0.44) and ToM (d = 0.43) abilities were significantly impaired in ADHD. The most robust facial emotion recognition deficits were evident in anger and fear. Social cognitive deficits were either very subtle (emotion recognition) or non-significant (ToM) in adults with ADHD. Deficits in social cognition, especially ToM, were significantly more pronounced in ASD compared with ADHD. General cognitive impairment has contributed to social cognitive deficits in ADHD. Performance of individuals with ADHD on social cognition lies intermediate between ASD and healthy controls. However, developmental trajectories of social cognition probably differ between ADHD and ASD as social cognitive deficits in ADHD might be improving with age in most individuals. There is a need for studies investigating a potential subtype of ADHD with persistent social cognitive deficits and exploring longitudinal changes in social cognition during development.

Diet-induced obesity attenuates endotoxin-induced cognitive deficits.

PubMed

Setti, Sharay E; Littlefield, Alyssa M; Johnson, Samantha W; Kohman, Rachel A

2015-03-15

Activation of the immune system can impair cognitive function, particularly on hippocampus dependent tasks. Several factors such as normal aging and prenatal experiences can modify the severity of these cognitive deficits. One additional factor that may modulate the behavioral response to immune activation is obesity. Prior work has shown that obesity alters the activity of the immune system. Whether diet-induced obesity (DIO) influences the cognitive deficits associated with inflammation is currently unknown. The present study explored whether DIO alters the behavioral response to the bacterial endotoxin, lipopolysaccharide (LPS). Female C57BL/6J mice were fed a high-fat (60% fat) or control diet (10% fat) for a total of five months. After consuming their respective diets for four months, mice received an LPS or saline injection and were assessed for alterations in spatial learning. One month later, mice received a second injection of LPS or saline and tissue samples were collected to assess the inflammatory response within the periphery and central nervous system. Results showed that LPS administration impaired spatial learning in the control diet mice, but had no effect in DIO mice. This lack of a cognitive deficit in the DIO female mice is likely due to a blunted inflammatory response within the brain. While cytokine production within the periphery (i.e., plasma, adipose, and spleen) was similar between the DIO and control mice, the DIO mice failed to show an increase in IL-6 and CD74 in the brain following LPS administration. Collectively, these data indicate that DIO can reduce aspects of the neuroinflammatory response as well as blunt the behavioral reaction to an immune challenge. Copyright © 2014 Elsevier Inc. All rights reserved.

Self-Instructional Cognitive Training to Reduce Impulsive Cognitive Style in Children with Attention Deficit with Hyperactivity Disorder

ERIC Educational Resources Information Center

Rivera-Flores, Gladys Wilma

2015-01-01

Introduction: Children with attention deficit with hyperactivity disorder (ADHD) have an impulsive, rigid and field-dependent cognitive style. This study examines whether self-instructional cognitive training reduces impulsive cognitive style in children diagnosed with this disorder. Method: The subjects were 10 children between the ages of 6 and…

Lithium treatment alleviates impaired cognition in a mouse model of Fragile X Syndrome

PubMed Central

King, Margaret K.; Jope, Richard S.

2013-01-01

Fragile X Syndrome (FXS) is caused by suppressed expression of fragile X mental retardation protein (FMRP), which results in intellectual disability accompanied by many variably manifested characteristics, such as hyperactivity, seizures, and autistic-like behaviors. Treatment of mice that lack FMRP, Fmr1 knockout (KO) mice, with lithium has been reported to ameliorate locomotor hyperactivity, prevent hypersensitivity to audiogenic seizures, improve passive avoidance behavior, and attenuate sociability deficits. To focus on the defining characteristic of FXS, which is cognitive impairment, we tested if lithium treatment ameliorated impairments in four cognitive tasks in Fmr1 KO mice, tested if the response to lithium differed in adolescent and adult mice, and tested if therapeutic effects persisted after discontinuation of lithium administration. Fmr1 KO mice displayed impaired cognition in the novel object detection task, temporal ordering for objects task, and coordinate and categorical spatial processing tasks. Chronic lithium treatment of adolescent (from 4–8 weeks of age) and adult (from 8–12 weeks of age) mice abolished cognitive impairments in all four cognitive tasks. Cognitive deficits returned after lithium treatment was discontinued for 4 weeks. These results demonstrate that Fmr1 KO mice exhibit severe impairments in these cognitive tasks, that lithium is equally effective in normalizing cognition in these tasks whether it is administered to young or adult mice, and that lithium administration must be continued for the cognitive improvements to be sustained. These findings provide further evidence that lithium administration may be beneficial for individuals with FXS. PMID:23941202

A neurocomputational account of cognitive deficits in Parkinson’s disease

PubMed Central

Hélie, Sébastien; Paul, Erick J.; Ashby, F. Gregory

2014-01-01

Parkinson’s disease (PD) is caused by the accelerated death of dopamine (DA) producing neurons. Numerous studies documenting cognitive deficits of PD patients have revealed impairments in a variety of tasks related to memory, learning, visuospatial skills, and attention. While there have been several studies documenting cognitive deficits of PD patients, very few computational models have been proposed. In this article, we use the COVIS model of category learning to simulate DA depletion and show that the model suffers from cognitive symptoms similar to those of human participants affected by PD. Specifically, DA depletion in COVIS produced deficits in rule-based categorization, non-linear information-integration categorization, probabilistic classification, rule maintenance, and rule switching. These were observed by simulating results from younger controls, older controls, PD patients, and severe PD patients in five well-known tasks. Differential performance among the different age groups and clinical populations was modeled simply by changing the amount of DA available in the model. This suggests that COVIS may not only be an adequate model of the simulated tasks and phenomena but also more generally of the role of DA in these tasks and phenomena. PMID:22683450

Neurocognitive impairment in deficit and non-deficit schizophrenia: a meta-analysis.

PubMed

Bora, E; Binnur Akdede, B; Alptekin, K

2017-10-01

Most studies suggested that patients with deficit schizophrenia have more severe impairment compared with patients with non-deficit schizophrenia. However, it is not clear whether deficit and non-deficit schizophrenia are associated with differential neurocognitive profiles. The aim of this meta-analytic review was to compare cognitive performances of deficit and non-deficit patients with each other and with healthy controls. In the current meta-analysis, differences in cognitive abilities between 897 deficit and 1636 non-deficit patients with schizophrenia were examined. Cognitive performances of 899 healthy controls were also compared with 350 patients with deficit and 592 non-deficit schizophrenia. Both deficit (d = 1.04-1.53) and non-deficit (d = 0.68-1.19) schizophrenia were associated with significant deficits in all cognitive domains. Deficit patients underperformed non-deficit patients in all cognitive domains (d = 0.24-0.84) and individual tasks (d = 0.39-0.93). The relationship between deficit syndrome and impairment in olfaction, social cognition, verbal fluency, and speed-based cognitive tasks were relatively stronger. Our findings suggest that there is consistent evidence for a significant relationship between deficit syndrome and more severe cognitive impairment in schizophrenia.

Prevention, Rehabilitation, and Mitigation Strategies of Cognitive Deficits in Aging with HIV: Implications for Practice and Research

PubMed Central

Vance, David E.

2013-01-01

Highly active antiretroviral therapy has given the chance to those living with HIV to keep on living, allowing them the opportunity to age and perhaps age successfully. Yet, there are severe challenges to successful aging with HIV, one of which is cognitive deficits. Nearly half of those with HIV experience cognitive deficits that can interfere with everyday functioning, medical decision making, and quality of life. Given that cognitive deficits develop with more frequency and intensity with increasing age, concerns mount that as people age with HIV, they may experience more severe cognitive deficits. These concerns become especially germane given that by 2015, 50% of those with HIV will be 50 and older, and this older cohort of adults is expected to grow. As such, this paper focuses on the etiologies of such cognitive deficits within the context of cognitive reserve and neuroplasticity. From this, evidence-based and hypothetical prevention (i.e., cognitive prescriptions), rehabilitation (i.e., speed of processing training), and mitigation (i.e., spaced retrieval method) strategies are reviewed. Implications for nursing practice and research are posited. PMID:23431469

Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder.

PubMed

Gong, Liang; Yin, Yingying; He, Cancan; Ye, Qing; Bai, Feng; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun

2017-01-01

Neuroimaging studies have demonstrated that major depressive disorder (MDD) patients show blunted activity responses to reward-related tasks. However, whether abnormal reward circuits affect cognition and depression in MDD patients remains unclear. Seventy-five drug-naive MDD patients and 42 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. The bilateral nucleus accumbens (NAc) were selected as seeds to construct reward circuits across all subjects. A multivariate linear regression analysis was employed to investigate the neural substrates of cognitive function and depression severity on the reward circuits in MDD patients. The common pathway underlying cognitive deficits and depression was identified with conjunction analysis. Compared with CN subjects, MDD patients showed decreased reward network connectivity that was primarily located in the prefrontal-striatal regions. Importantly, distinct and common neural pathways underlying cognition and depression were identified, implying the independent and synergistic effects of cognitive deficits and depression severity on reward circuits. This study demonstrated that disrupted topological organization within reward circuits was significantly associated with cognitive deficits and depression severity in MDD patients. These findings suggest that in addition to antidepressant treatment, normalized reward circuits should be a focus and a target for improving depression and cognitive deficits in MDD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Converging on a core cognitive deficit: the impact of various neurodevelopmental insults on cognitive control

PubMed Central

O'Reilly, Kally C.; Kao, Hsin-Yi; Lee, Heekyung; Fenton, André A.

2014-01-01

Despite substantial effort and immense need, the treatment options for major neuropsychiatric illnesses like schizophrenia are limited and largely ineffective at improving the most debilitating cognitive symptoms that are central to mental illness. These symptoms include cognitive control deficits, the inability to selectively use information that is currently relevant and ignore what is currently irrelevant. Contemporary attempts to accelerate progress are in part founded on an effort to reconceptualize neuropsychiatric illness as a disorder of neural development. This neuro-developmental framework emphasizes abnormal neural circuits on the one hand, and on the other, it suggests there are therapeutic opportunities to exploit the developmental processes of excitatory neuron pruning, inhibitory neuron proliferation, elaboration of myelination, and other circuit refinements that extend through adolescence and into early adulthood. We have crafted a preclinical research program aimed at cognition failures that may be relevant to mental illness. By working with a variety of neurodevelopmental rodent models, we strive to identify a common pathophysiology that underlies cognitive control failure as well as a common strategy for improving cognition in the face of neural circuit abnormalities. Here we review our work to characterize cognitive control deficits in rats with a neonatal ventral hippocampus lesion and rats that were exposed to Methylazoxymethanol acetate (MAM) in utero. We review our findings as they pertain to early developmental processes, including neurogenesis, as well as the power of cognitive experience to refine neural circuit function within the mature and maturing brain's cognitive circuitry. PMID:24966811

Cognitive-Linguistic Deficit and Speech Intelligibility in Chronic Progressive Multiple Sclerosis

ERIC Educational Resources Information Center

Mackenzie, Catherine; Green, Jan

2009-01-01

Background: Multiple sclerosis is a disabling neurological disease with varied symptoms, including dysarthria and cognitive and linguistic impairments. Association between dysarthria and cognitive-linguistic deficit has not been explored in clinical multiple sclerosis studies. Aims: In patients with chronic progressive multiple sclerosis, the…

Neurally dissociable cognitive components of reading deficits in subacute stroke.

PubMed

Boukrina, Olga; Barrett, A M; Alexander, Edward J; Yao, Bing; Graves, William W

2015-01-01

According to cognitive models of reading, words are processed by interacting orthographic (spelling), phonological (sound), and semantic (meaning) information. Despite extensive study of the neural basis of reading in healthy participants, little group data exist on patients with reading deficits from focal brain damage pointing to critical neural systems for reading. Here, we report on one such study. We have performed neuropsychological testing and magnetic resonance imaging on 11 patients with left-hemisphere stroke (<=5 weeks post-stroke). Patients completed tasks assessing cognitive components of reading such as semantics (matching picture or word choices to a target based on meaning), phonology (matching word choices to a target based on rhyming), and orthography (a two-alternative forced choice of the most plausible non-word). They also read aloud pseudowords and words with high or low levels of usage frequency, imageability, and spelling-sound consistency. As predicted by the cognitive model, when averaged across patients, the influence of semantics was most salient for low-frequency, low-consistency words, when phonological decoding is especially difficult. Qualitative subtraction analyses revealed lesion sites specific to phonological processing. These areas were consistent with those shown previously to activate for phonology in healthy participants, including supramarginal, posterior superior temporal, middle temporal, inferior frontal gyri, and underlying white matter. Notable divergence between this analysis and previous functional imaging is the association of lesions in the mid-fusiform gyrus and anterior temporal lobe with phonological reading deficits. This study represents progress toward identifying brain lesion-deficit relationships in the cognitive components of reading. Such correspondences are expected to help not only better understand the neural mechanisms of reading, but may also help tailor reading therapy to individual neurocognitive

Review of recent studies on interventions for cognitive deficits in patients with cancer.

PubMed

Gehring, Karin; Roukema, Jan Anne; Sitskoorn, Margriet M

2012-02-01

Research has demonstrated that patients with cancer experience cognitive deficits, often due to aggressive anticancer treatments. In this article, we critically review the interventional studies that have been conducted to investigate beneficial effects on cognitive function in cancer patients. Pharmacological agents that have been studied include psychostimulants, such as methylphenidate and modafinil, erythropoietin, and hormonal (supplement) treatments for patients who receive hormonal suppression therapy. In addition, several cognitive rehabilitation programs have been evaluated in cancer patients. Recently, the approach of physical exercise to treat cognitive deficits has received great interest, and findings from novel studies are keenly anticipated. Although, in general, the studies reviewed were well designed, future studies may wish to include larger sample sizes and pay more attention to the accurate assessment of cognitive function.

A Cross-Sectional Study of the Relationship of Physical Activity with Depression and Cognitive Deficit in Older Adults.

PubMed

Paulo T, R S; Tribess, Sheilla; Sasaki, Jeffer Eidi; Meneguci, Joilson; Martins, Cristiane A; Freitas, Ismael F; Romo-Perez, Vicente; Virtuoso, Jair S

2016-04-01

The aim of this study was to examine the association of physical activity with depression and cognition deficit, separately and combined, in Brazilian older adults. We analyzed data from 622 older adults. Physical activity was assessed using the International Physical Activity Questionnaire. Depressive symptoms were assessed using the Geriatric Depression Scale, while cognitive deficit was assessed using the Mini-Mental State Examination. Multinomial logistic regressions were used to assess associations of depression and cognitive deficit with sociodemographic, health, and behavioral variables. Prevalence of physical inactivity (< 150 min of moderate-to-vigorous physical activity/ week), depression, and cognitive deficit were 35.7%, 37.4%, and 16.7%. Physical inactivity was associated with depression (OR: 1.83, 95% CI: 1.14-2.94) and with depression and cognitive deficit combined (OR: 4.23, 95% CI: 2.01-8.91). Physically inactive participants were also more likely to present limitations in orientation and language functions. Physical inactivity was associated with depression and also with depression and cognitive deficit combined in older adults.

Reading Comprehension in Children with ADHD: Cognitive Underpinnings of the Centrality Deficit

PubMed Central

Miller, Amanda C.; Keenan, Janice M.; Betjemann, Rebecca S.; Willcutt, Erik; Pennington, Bruce F.; Olson, Richard K.

2012-01-01

We examined reading comprehension in children with ADHD by assessing their ability to build a coherent mental representation that allows them to recall central and peripheral information. We compared children with ADHD (mean age 9.78) to word reading-matched controls (mean age 9.89) on their ability to retell a passage. We found that even though children with ADHD recalled more central than peripheral information, they showed their greatest deficit, relative to controls, on central information – a centrality deficit (Miller & Keenan, 2009). We explored the cognitive underpinnings of this deficit using regressions to compare how well cognitive factors (working memory, inhibition, processing speed, and IQ) predicted the ability to recall central information, after controlling for word reading ability, and whether these cognitive factors interacted with ADHD symptoms. Working memory accounted for the most unique variance. Although previous evidence for reading comprehension difficulties in children with ADHD have been mixed, this study suggests that even when word reading ability is controlled, children with ADHD have difficulty building a coherent mental representation, and this difficulty is likely related to deficits in working memory. PMID:23054132

High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion

PubMed Central

Zuloaga, Kristen L; Johnson, Lance A; Roese, Natalie E; Marzulla, Tessa; Zhang, Wenri; Nie, Xiao; Alkayed, Farah N; Hong, Christine; Grafe, Marjorie R; Pike, Martin M; Raber, Jacob

2015-01-01

Diabetes causes endothelial dysfunction and increases the risk of vascular cognitive impairment. However, it is unknown whether diabetes causes cognitive impairment due to reductions in cerebral blood flow or through independent effects on neuronal function and cognition. We addressed this using right unilateral common carotid artery occlusion to model vascular cognitive impairment and long-term high-fat diet to model type 2 diabetes in mice. Cognition was assessed using novel object recognition task, Morris water maze, and contextual and cued fear conditioning. Cerebral blood flow was assessed using arterial spin labeling magnetic resonance imaging. Vascular cognitive impairment mice showed cognitive deficit in the novel object recognition task, decreased cerebral blood flow in the right hemisphere, and increased glial activation in white matter and hippocampus. Mice fed a high-fat diet displayed deficits in the novel object recognition task, Morris water maze and fear conditioning tasks and neuronal loss, but no impairments in cerebral blood flow. Compared to vascular cognitive impairment mice fed a low fat diet, vascular cognitive impairment mice fed a high-fat diet exhibited reduced cued fear memory, increased deficit in the Morris water maze, neuronal loss, glial activation, and global decrease in cerebral blood flow. We conclude that high-fat diet and chronic hypoperfusion impair cognitive function by different mechanisms, although they share commons features, and that high-fat diet exacerbates vascular cognitive impairment pathology. PMID:26661233

Variability in Depressive Symptoms of Cognitive Deficit and Cognitive Bias During the First 2 Years After Diagnosis in Australian Men With Prostate Cancer.

PubMed

Sharpley, Christopher F; Bitsika, Vicki; Christie, David R H

2016-01-01

The incidence and contribution to total depression of the depressive symptoms of cognitive deficit and cognitive bias in prostate cancer (PCa) patients were compared from cohorts sampled during the first 2 years after diagnosis. Survey data were collected from 394 patients with PCa, including background information, treatments, and disease status, plus total scores of depression and scores for subscales of the depressive symptoms of cognitive bias and cognitive deficit via the Zung Self-Rating Depression Scale. The sample was divided into eight 3-monthly time-since-diagnosis cohorts and according to depression severity. Mean scores for the depressive symptoms of cognitive deficit were significantly higher than those for cognitive bias for the whole sample, but the contribution of cognitive bias to total depression was stronger than that for cognitive deficit. When divided according to overall depression severity, patients with clinically significant depression showed reversed patterns of association between the two subsets of cognitive symptoms of depression and total depression compared with those patients who reported less severe depression. Differences in the incidence and contribution of these two different aspects of the cognitive symptoms of depression for patients with more severe depression argue for consideration of them when assessing and diagnosing depression in patients with PCa. Treatment requirements are also different between the two types of cognitive symptoms of depression, and several suggestions for matching treatment to illness via a personalized medicine approach are discussed. © The Author(s) 2014.

The effects of cognitive rehabilitation on social knowledge in patients with schizophrenia.

PubMed

Matsui, Mié; Arai, Hirofumi; Yonezawa, Mineo; Sumiyoshi, Tomiki; Suzuki, Michio; Kurachi, Masayoshi

2009-07-01

This study examined the extent to which cognitive rehabilitation alleviates cognitive deficits in schizophrenia compared to treatment as usual, and explored the mediating and moderating effects on cognitive improvement. Two groups who received cognitive rehabilitation and treatment as usual were assessed at baseline, three months (immediately post-intervention) and at follow-up (three months post-intervention). Cognitive rehabilitation focused on deficits in social knowledge and was conducted once a week for three months. The principles of errorless leaning and scaffolding informed the intervention. Outcomes were assessed using Script Test measures of social cognition. Other cognitive functions (executive functions and memory) and clinical symptoms were also assessed. Script Test for social knowledge and Rule Shift Test for cognitive flexibility scores were significantly better post-intervention in the cognitive rehabilitation group, while in the control group only free recall Script Test scores improved. Cognitive rehabilitation focused on social knowledge deficits can contribute to improvements in the social cognitive abilities of schizophrenic patients. Improvements in social cognitive functioning were durable at three-month follow-up. Cognitive rehabilitation can clearly benefit schizophrenic patients, at least when combined with atypical antipsychotic medication.

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.

Color discrimination deficits in Parkinson's disease are related to cognitive impairment and white-matter alterations.

PubMed

Bertrand, Josie-Anne; Bedetti, Christophe; Postuma, Ronald B; Monchi, Oury; Génier Marchand, Daphné; Jubault, Thomas; Gagnon, Jean-François

2012-12-01

Color discrimination deficit is a common nonmotor manifestation of Parkinson's disease (PD). However, the pathophysiology of this dysfunction remains poorly understood. Although retinal structure changes found in PD have been suggested to cause color discrimination deficits, the impact of cognitive impairment and cortical alterations remains to be determined. We investigated the contribution of cognitive impairment to color discrimination deficits in PD and correlated them with cortical anomalies. Sixty-six PD patients without dementia and 20 healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a comprehensive neuropsychological assessment for mild cognitive impairment diagnosis. In a subgroup of 26 PD patients, we also used high-definition neuroanatomical magnetic resonance imaging for cortical thickness and diffusion tensor analysis. PD patients with mild cognitive impairment performed poorly on the Farnsworth-Munsell 100 hue test compared with PD patients without mild cognitive impairment and controls. In PD patients, performance on the Farnsworth-Munsell 100 hue test was correlated with measures of visuospatial abilities and executive functions. Neuroimaging analysis revealed higher mean and radial diffusivity values in right posterior white-matter structures that correlated with poor performance on the Farnsworth-Munsell 100 hue test. No cortical thickness correlation reached significance. This study showed that cognitive impairment makes a major contribution to the color discrimination deficits reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may reflect cognitive impairment more than color discrimination deficits in PD. Poor performance on the Farnsworth-Munsell 100 hue test was also associated with white-matter alterations in right posterior brain regions. Copyright © 2012 Movement Disorder Society.

Cognitive rehabilitation training in patients with brain tumor-related epilepsy and cognitive deficits: a pilot study.

PubMed

Maschio, Marta; Dinapoli, Loredana; Fabi, Alessandra; Giannarelli, Diana; Cantelmi, Tonino

2015-11-01

The aim of this pilot observational study was to evaluate effect of cognitive rehabilitation training (RehabTr) on cognitive performances in patients with brain tumor-related epilepsy (BTRE) and cognitive disturbances. Medical inclusion criteria: patients (M/F) ≥ 18 years ≤ 75 with symptomatic seizures due to primary brain tumors or brain metastases in stable treatment with antiepileptic drugs; previous surgical resection or biopsy; >70 Karnofsky Performance Status; stable oncological disease. Eligible patients recruited from 100 consecutive patients with BTRE at first visit to our Center from 2011 to 2012. All recruited patients were administered battery of neuropsychological tests exploring various cognitive domains. Patients considered to have a neuropsychological deficit were those with at least one test score for a given domain indicative of impairment. Thirty patients out of 100 showed cognitive deficits, and were offered participation in RehabTr, of which 16 accepted (5 low grade glioma, 4 high grade glioma, 2 glioblastoma, 2 meningioma and 3 metastases) and 14 declined for various reasons. The RehabTr consisted of one weekly individual session of 1 h, for a total of 10 weeks, carried out by a trained psychologist. The functions trained were: memory, attention, visuo-spatial functions, language and reasoning by means of Training NeuroPsicologico (TNP(®)) software. To evaluate the effect of the RehabTr, the same battery of tests was administered directly after cognitive rehabilitation (T1), and at six-month follow-up (T2). Statistical analysis with Student T test for paired data showed that short-term verbal memory, episodic memory, fluency and long term visuo-spatial memory improved immediately after the T1 and remained stable at T2. At final follow-up all patients showed an improvement in at least one domain that had been lower than normal at baseline. Our results demonstrated a positive effect of rehabilitative training at different times, and, for

Attention and Other Cognitive Deficits in Aphasia: Presence and Relation to Language and Communication Measures

ERIC Educational Resources Information Center

Murray, Laura L.

2012-01-01

Purpose: This study was designed to further elucidate the relationship between cognition and aphasia, with a focus on attention. It was hypothesized that individuals with aphasia would display variable deficit patterns on tests of attention and other cognitive functions and that their attention deficits, particularly those of complex attention…

A cognitive psychometric model for the psychodiagnostic assessment of memory-related deficits.

PubMed

Alexander, Gregory E; Satalich, Timothy A; Shankle, W Rodman; Batchelder, William H

2016-03-01

Clinical tests used for psychodiagnostic purposes, such as the well-known Alzheimer's Disease Assessment Scale: Cognitive subscale (ADAS-Cog), include a free-recall task. The free-recall task taps into latent cognitive processes associated with learning and memory components of human cognition, any of which might be impaired with the progression of Alzheimer's disease (AD). A Hidden Markov model of free recall is developed to measure latent cognitive processes used during the free-recall task. In return, these cognitive measurements give us insight into the degree to which normal cognitive functions are differentially impaired by medical conditions, such as AD and related disorders. The model is used to analyze the free-recall data obtained from healthy elderly participants, participants diagnosed as having mild cognitive impairment, and participants diagnosed with early AD. The model is specified hierarchically to handle item differences because of the serial position curve in free recall, as well as within-group individual differences in participants' recall abilities. Bayesian hierarchical inference is used to estimate the model. The model analysis suggests that the impaired patients have the following: (1) long-term memory encoding deficits, (2) short-term memory (STM) retrieval deficits for all but very short time intervals, (3) poorer transfer into long-term memory for items successfully retrieved from STM, and (4) poorer retention of items encoded into long-term memory after longer delays. Yet, impaired patients appear to have no deficit in immediate recall of encoded words in long-term memory or for very short time intervals in STM. (c) 2016 APA, all rights reserved).

THE ORIGINS OF COGNITIVE DEFICITS IN VICTIMIZED CHILDREN: IMPLICATIONS FOR NEUROSCIENTISTS AND CLINICIANS

PubMed Central

Danese, Andrea; Moffitt, Terrie E; Arseneault, Louise; Bleiberg, Ben A; Dinardo, Perry B; Gandelman, Stephanie B; Houts, Renate; Ambler, Antony; Fisher, Helen; Poulton, Richie; Caspi, Avshalom

2016-01-01

OBJECTIVE Individuals reporting a history of childhood violence victimization have impaired brain function. However, the clinical significance, reproducibility, and causality of these findings are disputed. We directly tested these research gaps. METHOD We tested the association between prospectively-collected measures of childhood violence victimization and cognitive functions in childhood, adolescence, and adulthood among 2,232 members of the UK E-Risk Study and 1,037 members of the New Zealand Dunedin Study, who were followed-up from birth until ages 18 and 38 years, respectively. We used multiple measures of victimization and cognition, and included comparisons of cognitive scores for twins discordant for victimization. RESULTS We found that individuals exposed to childhood victimization had pervasive impairments in clinically-relevant cognitive functions including general intelligence, executive function, processing speed, memory, perceptual reasoning, and verbal comprehension in adolescence and adulthood. However, the observed cognitive deficits in victimized individuals were largely explained by cognitive deficits that predated childhood victimization and by confounding genetic and environmental risks. CONCLUSIONS Findings from two population-representative birth cohorts totaling more than 3,000 individuals and born 20 years and 20,000 kilometers apart suggest that the association between childhood violence victimization and later cognition is largely non-causal, in contrast to conventional interpretations. These findings urge adopting a more circumspect approach to causal inference in the neuroscience of stress. Clinically, cognitive deficits should be conceptualized as individual risk factors for victimization as well as potential complicating features during treatment. PMID:27794691

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

Spinocerebellar ataxia: a critical review of cognitive and socio-cognitive deficits.

PubMed

Giocondo, Flora; Curcio, Giuseppe

2018-02-01

The primary aim of this contribution is to provide a critical discussion on cognitive and sociocognitive implications of spinocerebellar ataxias (SCAs) subtypes. The term SCA refers to a group of neurodegenerative disorders that have been increasingly investigated in the last years, sharing the characteristic of progressive ataxia resulting from degeneration of cerebellum and its connections. In past decades only involvement of cerebellum in behaviour and timing has been investigated, bringing to the belief about its central role in timing of movement and sensation, particularly for short intervals of time. Only very recently the cerebellum has been considered as a potentially important centre for cognitive processing and related spheres of social cognition, so that several studies with SCA patients have been carried out on these topics: as a consequence a section of this review will be dedicated to this important aspect. After a brief discussion on most commonly used methods to assess cognitive and socio-cognitive abilities in SCAs, cognitive and socio-cognitive profiles of principal SCA subtypes have been thoroughly reviewed and critically discussed. Due to the very poor literature in this field the most common SCA variants have been fully included (i.e. SCA1, SCA2, SCA3, SCA6 and SCA7). A comparative summary of the main characteristics of cognitive and social cognition deficit in SCA subtypes has been proposed together with a research agenda for future investigation in this field principally aimed at using measures of cognition and/or social cognition as potential predictors of the extent and progression of disease.

No lower cognitive functioning in older adults with attention-deficit/hyperactivity disorder.

PubMed

Semeijn, E J; Korten, N C M; Comijs, H C; Michielsen, M; Deeg, D J H; Beekman, A T F; Kooij, J J S

2015-09-01

Research illustrates cognitive deficits in children and younger adults with attention-deficit/hyperactivity disorder (ADHD). Few studies have focused on the cognitive functioning in older adults. This study investigates the association between ADHD and cognitive functioning in older adults. Data were collected in a cross-sectional side study of the Longitudinal Aging Study Amsterdam (LASA). A diagnostic interview to diagnose ADHD was administered among a subsample (N = 231, age 60-94). ADHD symptoms and diagnosis were assessed with the Diagnostic Interview for ADHD in Adults (DIVA) 2.0. Cognitive functioning was assessed with tests in the domains of executive functioning, information processing speed, memory, and attention/working memory. Regression analyses indicate that ADHD diagnosis and ADHD severity were only negatively associated with cognitive functioning in the attention/working memory domain. When adjusting for depression, these associations were no longer significant. The study shows that ADHD in older adults is associated with lower cognitive functioning in the attention/working memory domain. However, this was partly explained by depressive symptoms.

Multimodal Intervention Trial for Cognitive Deficits in Neurofibromatosis Type 1: Efficacy of Computerized Cognitive Training and Stimulant Medication

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-1-0508 TITLE: Multimodal Intervention Trial for Cognitive Deficits in Neurofibromatosis Type 1: Efficacy of...Computerized Cognitive Training and Stimulant Medication PRINCIPAL INVESTIGATOR: Maria T. Acosta, M.D. CONTRACTING ORGANIZATION: Children’s National Health...database. 15. SUBJECT TERMS Neurofibromatosis, cognition , pediatric, computerized training programs, working memory 16. SECURITY CLASSIFICATION OF: 17

Cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability.

PubMed

van Duijvenbode, Neomi; Didden, Robert; VanDerNagel, Joanne El; Korzilius, Hubert Plm; Engels, Rutger Cme

2018-03-01

We examined cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability (MBID). Problematic drinkers were expected to show a significantly lower estimated performance IQ (PIQ), but not a lower estimated verbal IQ (VIQ), compared to light drinkers. Participants ( N = 474) were divided into four groups based on IQ and severity of alcohol use-related problems. IQ was estimated using (a short form of) the Wechsler Adult Intelligence Scale third edition. Severity of alcohol use-related problems was assessed using the Alcohol Use Disorder Identification Test. Overall, there were no significant differences between light and problematic drinkers on estimated VIQ. Within the group without MBID, estimated PIQ was significantly lower. Estimated PIQ was not lower in problematic drinkers with MBID compared to light drinkers with MBID. The results are indicative of cognitive deficits in problematic drinkers without MBID. Screening for cognitive deficits with additional instruments is advised.

Memory deficits for facial identity in patients with amnestic mild cognitive impairment (MCI).

PubMed

Savaskan, Egemen; Summermatter, Daniel; Schroeder, Clemens; Schächinger, Hartmut

2018-01-01

Faces are among the most relevant social stimuli revealing an encounter's identity and actual emotional state. Deficits in facial recognition may be an early sign of cognitive decline leading to social deficits. The main objective of the present study is to investigate if individuals with amnestic mild cognitive impairment show recognition deficits in facial identity. Thirty-seven individuals with amnestic mild cognitive impairment, multiple-domain (15 female; age: 75±8 yrs.) and forty-one healthy volunteers (24 female; age 71±6 yrs.) participated. All participants completed a human portrait memory test presenting unfamiliar faces with happy and angry emotional expressions. Five and thirty minutes later, old and new neutral faces were presented, and discrimination sensitivity (d') and response bias (C) were assessed as signal detection parameters of cued facial identity recognition. Memory performance was lower in amnestic mild cognitive impairment as compared to control subjects, mainly because of an altered response bias towards an increased false alarm rate (favoring false OLD ascription of NEW items). In both groups, memory performance declined between the early and later testing session, and was always better for acquired happy than angry faces. Facial identity memory is impaired in patients with amnestic mild cognitive impairment. Liberalization of the response bias may reflect a socially motivated compensatory mechanism maintaining an almost identical recognition hit rate of OLD faces in individuals with amnestic mild cognitive impairment.

Effects of decompressive surgery on prognosis and cognitive deficits in herpes simplex encephalitis.

PubMed

Midi, Ipek; Tuncer, Nese; Midi, Ahmet; Mollahasanoglu, Aynur; Konya, Deniz; Sav, Aydin

2007-01-01

Herpes simplex encephalitis (HSE) is a serious viral infection with a high rate of mortality. The most commonly seen complications are behavioral changes, seizures and memory deficits. We report the case of a 37-year-old man with HSE in the right temporal lobe and a severe midline shift who was treated with acyclovir. The patient underwent anterior temporal lobe resection. Although HSE can cause permanent cognitive deficits, in this case, early surgical intervention minimized any deficit, as determined by detailed neuropsychological examination. Surgical decompression is indicated as early as possible in severe cases. This case report emphasizes the effect of surgical decompression for HSE on cognitive function, which has rarely been mentioned before.

Effects of Decompressive Surgery on Prognosis and Cognitive Deficits in Herpes Simplex Encephalitis

PubMed Central

Midi, Ipek; Tuncer, Nese; Midi, Ahmet; Mollahasanoglu, Aynur; Konya, Deniz; Sav, Aydın

2007-01-01

Herpes simplex encephalitis (HSE) is a serious viral infection with a high rate of mortality. The most commonly seen complications are behavioral changes, seizures and memory deficits. We report the case of a 37-year-old man with HSE in the right temporal lobe and a severe midline shift who was treated with acyclovir. The patient underwent anterior temporal lobe resection. Although HSE can cause permanent cognitive deficits, in this case, early surgical intervention minimized any deficit, as determined by detailed neuropsychological examination. Surgical decompression is indicated as early as possible in severe cases. This case report emphasizes the effect of surgical decompression for HSE on cognitive function, which has rarely been mentioned before. PMID:18430984

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.

The Origins of Cognitive Deficits in Victimized Children: Implications for Neuroscientists and Clinicians.

PubMed

Danese, Andrea; Moffitt, Terrie E; Arseneault, Louise; Bleiberg, Ben A; Dinardo, Perry B; Gandelman, Stephanie B; Houts, Renate; Ambler, Antony; Fisher, Helen L; Poulton, Richie; Caspi, Avshalom

2017-04-01

Individuals reporting a history of childhood violence victimization have impaired brain function. However, the clinical significance, reproducibility, and causality of these findings are disputed. The authors used data from two large cohort studies to address these research questions directly. The authors tested the association between prospectively collected measures of childhood violence victimization and cognitive functions in childhood, adolescence, and adulthood among 2,232 members of the U.K. E-Risk Study and 1,037 members of the New Zealand Dunedin Study who were followed up from birth until ages 18 and 38 years, respectively. Multiple measures of victimization and cognition were used, and comparisons were made of cognitive scores for twins discordant for victimization. Individuals exposed to childhood victimization had pervasive impairments in clinically relevant cognitive functions, including general intelligence, executive function, processing speed, memory, perceptual reasoning, and verbal comprehension in adolescence and adulthood. However, the observed cognitive deficits in victimized individuals were largely explained by cognitive deficits that predated childhood victimization and by confounding genetic and environmental risks. Findings from two population-representative birth cohorts totaling more than 3,000 individuals and born 20 years and 20,000 km apart suggest that the association between childhood violence victimization and later cognition is largely noncausal, in contrast to conventional interpretations. These findings support the adoption of a more circumspect approach to causal inference in the neuroscience of stress. Clinically, cognitive deficits should be conceptualized as individual risk factors for victimization as well as potential complicating features during treatment.

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

PubMed Central

Liu, Xiao; Li, Jitao; Guo, Chunmei; Wang, Hongli; Sun, Yaxin; Wang, Han; Su, Yun-Ai; Li, Keqing; Si, Tianmei

2018-01-01

Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine. PMID:29375333

Temporary microglia-depletion after cosmic radiation modifies phagocytic activity and prevents cognitive deficits.

PubMed

Krukowski, Karen; Feng, Xi; Paladini, Maria Serena; Chou, Austin; Sacramento, Kristen; Grue, Katherine; Riparip, Lara-Kirstie; Jones, Tamako; Campbell-Beachler, Mary; Nelson, Gregory; Rosi, Susanna

2018-05-18

Microglia are the main immune component in the brain that can regulate neuronal health and synapse function. Exposure to cosmic radiation can cause long-term cognitive impairments in rodent models thereby presenting potential obstacles for astronauts engaged in deep space travel. The mechanism/s for how cosmic radiation induces cognitive deficits are currently unknown. We find that temporary microglia depletion, one week after cosmic radiation, prevents the development of long-term memory deficits. Gene array profiling reveals that acute microglia depletion alters the late neuroinflammatory response to cosmic radiation. The repopulated microglia present a modified functional phenotype with reduced expression of scavenger receptors, lysosome membrane protein and complement receptor, all shown to be involved in microglia-synapses interaction. The lower phagocytic activity observed in the repopulated microglia is paralleled by improved synaptic protein expression. Our data provide mechanistic evidence for the role of microglia in the development of cognitive deficits after cosmic radiation exposure.

Self-perceived cognitive deficits and occupational outcome in persons with schizophrenia.

PubMed

Verdoux, Hélène; Monello, Florence; Goumilloux, Régis; Cougnard, Audrey; Prouteau, Antoinette

2010-07-30

A two-year prospective follow-up study was used to explore whether self-perceived cognitive deficits (SPCD) predict occupational outcome in persons with schizophrenia. Cognitive complaints were assessed using the Scale to Investigate Cognition in Schizophrenia (SSTICS) in persons with schizophrenia requesting disability status. A higher level of SPCD was associated with better occupational outcome, independently from other characteristics. Persons with better social functioning may have a higher level of metacognition allowing a greater awareness of their cognitive difficulties. Measures of cognitive complaints should be complemented by objective testing to assess potential for vocational rehabilitation. Copyright 2010 Elsevier Ltd. All rights reserved.

Cognitive Patterns and Learning Disabilities in Cleft Palate Children with Verbal Deficits.

ERIC Educational Resources Information Center

Richman, Lynn C.

1980-01-01

The study examined patterns of cognitive ability in 57 cleft lip and palate children (ages 7 to 9) with verbal deficit, but without general intellectual retardation to evaluate whether the verbal disability displayed by these children was related primarily to a specific verbal expression deficit or a more general symbolic mediation problem.…

Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy.

PubMed

Kaur, Harpreet; Patro, Ishan; Tikoo, Kulbhushan; Sandhir, Rajat

2015-10-01

Evidence suggests that glial cells play a critical role in inflammation in chronic epilepsy, contributing to perpetuation of seizures and cognitive dysfunctions. The present study was designed to evaluate the beneficial effect of curcumin, a polyphenol with pleiotropic properties, on cognitive deficits and inflammation in chronic epilepsy. Kindled model of epilepsy was induced by administering sub-convulsive dose of pentylenetetrazole (PTZ) at 40 mg/kg, i.p. every alternative day for 30 days to Wistar rats. The animals were assessed for cognitive deficits by Morris water maze and inflammatory response in terms of microglial and astrocyte activation. PTZ treated animals had increased escape latency suggesting impaired cognitive functions. Further, an increased expression of astrocyte (GFAP) and microglial (Iba-1) activation markers were observed in terms of mRNA and protein levels in the PTZ treated animals. Concomitantly, mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokine (MCP-1) were increased in hippocampus and cortex. Immunoreactivity to anti-GFAP and anti-Iba-1 antibodies was also enhanced in hippocampus and cortex suggesting gliosis in PTZ treated animals. However, curcumin administration at a dose of 100 mg/kg to PTZ animals prevented cognitive deficits. A significant decrease in pro-inflammatory cytokines and chemokine expression was observed in hippocampus and cortex of PTZ treated rats supplemented with curcumin. In addition, curcumin also attenuated increased expression of GFAP and Iba-1 in animals with PTZ induced chronic epilepsy. Moreover, immunohistochemical analysis also showed significant reduction in number of activated glial cells on curcumin administration to PTZ treated animals. Taken together, these findings suggest that curcumin is effective in attenuating glial activation and ameliorates cognitive deficits in chronic epilepsy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of voluntary and treadmill exercise on spontaneous withdrawal signs, cognitive deficits and alterations in apoptosis-associated proteins in morphine-dependent rats.

PubMed

Mokhtari-Zaer, Amin; Ghodrati-Jaldbakhan, Shahrbanoo; Vafaei, Abbas Ali; Miladi-Gorji, Hossein; Akhavan, Maziar M; Bandegi, Ahmad Reza; Rashidy-Pour, Ali

2014-09-01

Chronic exposure to morphine results in cognitive deficits and alterations of apoptotic proteins in favor of cell death in the hippocampus, a brain region critically involved in learning and memory. Physical activity has been shown to have beneficial effects on brain health. In the current work, we examined the effects of voluntary and treadmill exercise on spontaneous withdrawal signs, the associated cognitive defects, and changes of apoptotic proteins in morphine-dependent rats. Morphine dependence was induced through bi-daily administrations of morphine (10mg/kg) for 10 days. Then, the rats were trained under two different exercise protocols: mild treadmill exercise or voluntary wheel exercise for 10 days. After exercise training, their spatial learning and memory and aversive memory were examined by a water maze and by an inhibitory avoidance task, respectively. The expression of the pro-apoptotic protein Bax and the anti-apoptotic protein Bcl-2 in the hippocampus were determined by immunoblotting. We found that chronic exposure to morphine impaired spatial and aversive memory and remarkably suppressed the expression of Bcl-2, but Bax expression remained constant. Both voluntary and treadmill exercise alleviated memory impairment, increased the expression of Bcl-2 protein, and only the later suppressed the expression of Bax protein in morphine-dependent animals. Moreover, both exercise protocols diminished the occurrence of spontaneous morphine withdrawal signs. Our findings showed that exercise reduces the spontaneous morphine-withdrawal signs, blocks the associated impairment of cognitive performance, and overcomes morphine-induced alterations in apoptotic proteins in favor of cell death. Thus, exercise may be a useful therapeutic strategy for cognitive and behavioral deficits in addict individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

Successful evaluation of cognitive function and the nature of cognitive deficits among people with schizophrenia in clinical rehabilitation settings.

PubMed

John, Alexander Panickacheril; Yeak, Kim; Ayres, Helen; Sevastos, Marie; Moore, Elizabeth

2016-08-01

Despite possessing considerable relevance for planning and delivery of effective rehabilitation interventions, systematic evaluation of cognitive function is often ignored in clinical practice. This paper describes a successful method for measuring cognitive function and the nature of cognitive deficits (CD) in people with schizophrenia admitted to psychiatric rehabilitation services. Data on the cognitive functioning of consecutive patients with schizophrenia / schizoaffective disorder admitted during a 5-year period to a public in-patient rehabilitation facility was collated retrospectively and analysed. The Brief Assessment of Cognition in Schizophrenia (BACS) was used to evaluate cognitive function. It was possible to administer the BACS to 122 of 135 consecutive admissions. The mean composite score on the BACS was 1.8 standard deviations below the norm, and 43% had moderate or severe CD. The BACS sub-tests of list learning and symbol coding revealed more severe deficits. The study indicates that evaluation of cognitive function using brief instruments is feasible in psychiatric rehabilitation settings. Global and domain-specific CD were prevalent among people with schizophrenia. In view of the strong association of cognitive functioning with community functioning and rehabilitation outcomes, further studies exploring the feasibility and utility of routinely evaluating cognitive function are warranted. © The Royal Australian and New Zealand College of Psychiatrists 2016.

Cognitive Deficits and Related Brain Lesions in Patients With Chronic Heart Failure.

PubMed

Frey, Anna; Sell, Roxane; Homola, György A; Malsch, Carolin; Kraft, Peter; Gunreben, Ignaz; Morbach, Caroline; Alkonyi, Bálint; Schmid, Eric; Colonna, Isabella; Hofer, Edith; Müllges, Wolfgang; Ertl, Georg; Heuschmann, Peter; Solymosi, László; Schmidt, Reinhold; Störk, Stefan; Stoll, Guido

2018-05-31

This study sought to determine the spectrum of brain lesions seen in heart failure (HF) patients and the extent to which lesion type contributes to cognitive impairment. Cognitive deficits have been reported in patients with HF. A total of 148 systolic and diastolic HF patients (mean age 64 ± 11 years; 16% female; mean left ventricular ejection fraction 43 ± 8%) were extensively evaluated within 2 days by cardiological, neurological, and neuropsychological testing and brain magnetic resonance imaging (MRI). A total of 288 healthy, sex- and age-matched subjects sampled from the Austrian Stroke Prevention Study served as MRI controls. Deficits in reaction times were apparent in 41% of patients and deficits in verbal memory in 46%. On brain MRI, patients showed more advanced medial temporal lobe atrophy (MTA) (Scheltens score) compared to controls (2.1 ± 0.9 vs. 1.0 ± 0.6; p < 0.001). The degree of MTA was strongly associated with the severity of cognitive impairment, whereas the extent of white matter hyperintensities was similar in patients and controls. Moreover, patients had a 2.7-fold increased risk for presence of clinically silent lacunes. HF patients exhibit cognitive deficits in the domains of attention and memory. MTA but not white matter lesion load seems to be related to cognitive impairment. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Social-cognitive deficits in normal aging

PubMed Central

Moran, Joseph M.; Jolly, Eshin; Mitchell, Jason P.

2012-01-01

A sizeable number of studies have implicated the default network (e.g., medial prefrontal and parietal cortices) in tasks that require participants to infer the mental states of others—that is, to mentalize. Parallel research has demonstrated that default network function declines over the lifespan, suggesting that older adults may show impairments in social-cognitive tasks that require mentalizing. Older and younger human adults were scanned using functional magnetic resonance imaging (fMRI) while performing three different social-cognitive tasks. Across three mentalizing paradigms, younger and older adults viewed animated shapes in brief social vignettes, stories about a person's moral actions and false belief stories. Consistent with predictions, older adults responded less accurately to stories about others' false beliefs and made less use of actors' intentions to judge the moral permissibility of behavior. These impairments in performance during social-cognitive tasks were accompanied by age-related decreases across all three paradigms in the BOLD response of a single brain region—dorsomedial prefrontal cortex. These findings suggest specific, task-independent age-related deficits in mentalizing that are localizeable to changes in circumscribed subregions of the default network. PMID:22514317

Pattern of social cognition deficits in individuals with borderline personality disorder.

PubMed

Anupama V; Bhola, Poornima; Thirthalli, Jagadisha; Mehta, Urvakhsh Meherwan

2018-03-01

Social cognition deficits have been implicated in the affect regulation and interpersonal difficulties seen in borderline personality disorder (BPD). The study examined patterns of social cognition abilities, using self-report and task-based measures, among individuals diagnosed with BPD. The sample included a clinical group of 20 patients diagnosed with BPD and 20 age and gender-matched control group participants from the community with no psychiatric diagnosis. The measures included the Mentalization Questionnaire, the Reading the Mind in the Eyes Test and the Social Cognition Rating Tool in Indian Setting. Results indicated that the clinical group had lower self-reported mentalizing ability. Facial emotion recognition ability was significantly lower for the clinical group, particularly for photographs of the eye region with positive and neutral valences. The clinical group had significantly higher personalizing bias, and greater difficulties in social perception. The two groups did not differ on first and second order theory of mind, recognition of faux pas and externalizing bias. The results point to the links between social cognition deficits and interpersonal difficulties among persons with BPD. Implications include the need for pre-therapy assessment of the magnitude and patterns of social cognition difficulties in BPD, the development of culturally and ecologically valid assessments and the evaluation of interventions for social cognition vulnerabilities among individuals with BPD. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions

PubMed Central

Beilharz, Jessica E.; Maniam, Jayanthi; Morris, Margaret J.

2015-01-01

It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments. PMID:26274972

Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions.

PubMed

Beilharz, Jessica E; Maniam, Jayanthi; Morris, Margaret J

2015-08-12

It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments.

Juvenile treatment with a novel mGluR2 agonist/mGluR3 antagonist compound, LY395756, reverses learning deficits and cognitive flexibility impairments in adults in a neurodevelopmental model of schizophrenia.

PubMed

Li, Meng-Lin; Gulchina, Yelena; Monaco, Sarah A; Xing, Bo; Ferguson, Brielle R; Li, Yan-Chun; Li, Feng; Hu, Xi-Quan; Gao, Wen-Jun

2017-04-01

Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms. Therefore, treating cognitive deficits at an early stage is a realistic approach. In this study, we tested whether an early treatment targeting mGluR2 would be effective in ameliorating cognitive impairments in the methylazoxymethanol acetate (MAM) model of SCZ. We investigated the effects of an mGluR2 agonist/mGluR3 antagonist, LY395756 (LY39), on the NMDAR expression and function in juveniles, as well as cognitive deficits in adult rats after juvenile treatment. We found that gestational MAM exposure induced a significant decrease in total protein levels of the NMDAR subunit, NR2B, and a significant increase of pNR2BTyr1472 in the juvenile rat PFC. Treatment with LY39 in juvenile MAM-exposed rats effectively recovered the disrupted NMDAR expression. Furthermore, a subchronic LY39 treatment in juvenile MAM-exposed rats also alleviated the learning deficits and cognitive flexibility impairments when tested with a cross-maze based set-shifting task in adults. Therefore, our study demonstrates that targeting dysfunctional NMDARs with an mGluR2 agonist during the early stage of SCZ could be an effective strategy in preventing the development and progression in addition to ameliorating cognitive impairments of SCZ. Copyright © 2017 Elsevier Inc. All rights reserved.

[Cognitive deficits in first episode psychosis patients and people at risk for psychosis: from diagnosis to treatment].

PubMed

Lecardeur, L; Meunier-Cussac, S; Dollfus, S

2013-05-01

Up to now, studies have not demonstrated significant efficacy of antipsychotics on cognitive impairments in patients with psychotic disorders. These cognitive deficits are of particular interest since they traditionally start early before the diagnosis of psychosis. They are observed during premorbid and prodromal stages, and during the first episode of psychosis. Moreover, cognitive impairments may be detected without any psychotic symptoms (such as positive symptoms) suggesting their development independently of the psychotic symptoms. Cognitive disturbances consist of impairments of episodic and working memories, intellectual functioning, executive functions (planning, inhibition, and cognitive flexibility), selective and sustained attentions and social cognition (emotion, recognition, theory of mind). The altered cognitive functions observed in schizophrenia are the same as in earlier stages but at a lower level of severity. Data suggest that cognitive deficits can be considered as vulnerability markers of psychosis since they have been described in healthy relatives of psychotic patients with high genetic risk. Cognitive deficits might also be considered as predictive of the occurrence of the disease after the first episode of psychosis. Indeed, retrospective studies suggest cognitive impairments in patients with schizophrenia during premorbid and prodromal phases but not in bipolar patients. Cognitive assessment might be of particular interest in people at risk for psychosis, in order to differentiate diagnostic outcomes. Cognitive functioning impairs until the diagnosis of first episode psychosis, even though cognitive profiles are quite heterogeneous in these patients. Once the diagnosis of schizophrenia is considered, cognitive deficits may be stable, although the literature is still controversial. Several factors such as symptoms and gender can contribute in diversifying the cognitive profiles. Moreover, age of onset might worsen the prognosis because of

Cognitive deficits of executive functions and decision-making in obsessive-compulsive disorder.

PubMed

Dittrich, Winand H; Johansen, Thomas

2013-10-01

The nature of cognitive deficits in obsessive-compulsive disorder (OCD) is characterized by contradictory findings in terms of specific neuropsychological deficits. Selective impairments have been suggested to involve visuospatial memory, set shifting, decision-making and response inhibition. The aim of this study was to investigate cognitive deficits in decision-making and executive functioning in OCD. It was hypothesized that the OCD patients would be less accurate in their responses compared to the healthy controls in rational decision-making on a version of the Cambridge gambling task (CGT) and on the color-word interference test and on a version of the Tower of Hanoi test (tower test) of executive functioning. Thirteen participants with OCD were compared to a group of healthy controls (n = 13) matched for age, gender, education and verbal IQ. Results revealed significant differences between the OCD group and the healthy control group on quality of decision-making on the CGT and for achievement score on the tower test. On these two tasks the OCD group performed worse than the healthy control group. The symptom-dimension analysis revealed performance differences where safety checking patients were impaired on the tower test compared to contamination patients. Results are discussed in the framework of cognition and emotion processing and findings implicate that OCD models should address, specifically, the interaction between cognition and emotion. Here the emotional disruption hypothesis is forwarded to account for the dysfunctional behaviors in OCD. Further implications regarding methodological and inhibitory factors affecting cognitive information processing are highlighted. © 2013 The Scandinavian Psychological Associations.

D-Serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats.

PubMed

Karasawa, Jun-Ichi; Hashimoto, Kenji; Chaki, Shigeyuki

2008-01-10

Compounds enhancing N-methyl-d-aspartate (NMDA) glutamate receptor function have been reported to improve cognitive deficits. Since cognitive deficits are considered to be the core symptom of schizophrenia, enhancing NMDA receptor function represents a promising approach to treating schizophrenia. In the present study, we investigated whether d-serine or a glycine transporter inhibitor N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS), both of which enhance NMDA receptor function, could improve MK-801-induced cognitive deficits in rats, and compared their effects with those of the atypical antipsychotic clozapine and of the typical antipsychotic haloperidol. To assess cognitive function, we used a novel object recognition test in rats that measured spontaneous exploratory activity of a novel object when paired with a familiar object. We then evaluated the effects of the compounds on cognitive deficits induced by treatment with MK-801, the NMDA receptor antagonist. Pretreatment with clozapine (1, 5 mg/kg, i.p.) but not haloperidol (0.03, 0.1 mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits. Pretreatment with D-serine at 800 mg/kg (i.p.) or NFPS (0.3, 1 mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits under this test paradigm. These findings suggest that impaired preference for novel objects induced by MK-801 in the novel object recognition test could be a useful animal model for evaluating the efficacy of compounds targeting the cognitive deficits observed in schizophrenic patients. The results also suggest that enhancing NMDA receptor function is an effective way for treating the cognitive deficits associated with schizophrenia.

A Low Vision Rehabilitation Program for Patients with Mild Cognitive Deficits

PubMed Central

Whitson, Heather E.; Whitaker, Diane; Potter, Guy; McConnell, Eleanor; Tripp, Fay; Sanders, Linda L.; Muir, Kelly W.; Cohen, Harvey J.; Cousins, Scott W.

2012-01-01

Objective To design and pilot test a low vision rehabilitation program for patients with macular disease and cognitive deficits. Methods The Memory or Reasoning Enhanced Low Vision Rehabilitation (MORE-LVR) program was created by a team representing optometry, occupational therapy, ophthalmology, neuropsychology, and geriatrics. Key components of MORE-LVR are: 1) repetitive training with a therapist twice weekly over a 6-week period, 2) simplified training experience addressing no more than three individualized goals in a minimally distracting environment, 3) involvement of an informal companion (friend or family member). Eligible patients were recruited from an LVR clinic; measures were compared before and after the 6 week program. Results Twelve non-demented patients (mean age 84.5 years, 75% female) who screened positive for cognitive deficits completed the MORE-LVR intervention. Participants demonstrated improved scores on the National Eye Institute’s Visual Function Questionnaire (VFQ-25) composite score (47.2±16.3 to 54.8±13.8, p=0.01) and near activities score (21.5±14.0 to 41.0±23.1, p=0.02), timed performance measures (writing a grocery list [p=0.03], filling in a crossword puzzle answer [p=0.003]), a score indicating satisfaction with independence (p=0.05), and logical memory (p=0.02). All patients and companions reported progress toward at least one individualized goal; >70% reported progress toward all three goals. Conclusions This pilot study demonstrates feasibility of an LVR program for macular disease patients with mild cognitive deficits. Participants demonstrated improvements in vision-related function and cognitive measures and expressed high satisfaction. Future work is needed to determine if MORE-LVR is superior to usual outpatient LVR for persons with co-existing visual and cognitive impairments. PMID:23619914

The Comprehension of Syntactic and Affective Prosody by Adults with Autism Spectrum Disorder without Accompanying Cognitive Deficits

ERIC Educational Resources Information Center

Martzoukou, Maria; Papadopoulou, Despina; Kosmidis, Mary-Helen

2017-01-01

The present study investigates the comprehension of syntactic and affective prosody in adults with autism spectrum disorder without accompanying cognitive deficits (ASD w/o cognitive deficits) as well as age-, education- and gender-matched unimpaired adults, while processing orally presented sentences. Two experiments were conducted: (a) an…

Cognitive deficits and predictors 3 years after diagnosis of a pilocytic astrocytoma in childhood.

PubMed

Aarsen, Femke K; Paquier, Philippe F; Arts, Willem-Frans; Van Veelen, Marie-Lise; Michiels, Erna; Lequin, Maarten; Catsman-Berrevoets, Coriene E

2009-07-20

PURPOSE To prospectively study cognitive deficits and predictors 3 years after diagnosis in a large series of pediatric patients treated for pilocytic astrocytoma (PA). PATIENTS AND METHODS Sixty-one of 67 children were grouped according to infratentorial, supratentorial midline, and supratentorial hemispheric site. Intelligence, memory, attention, language, visual-spatial, and executive functions were assessed. Included predictors were sex, age, relapse, diagnosis-assessment interval, hydrocephalus, kind of treatment, and tumor variables. Results All children with PA had problems with sustained attention and speed. In the infratentorial group, there also were deficits in verbal intelligence, visual-spatial memory, executive functioning, and naming. Verbal intelligence and verbal memory problems occurred in the brainstem tumor group. The supratentorial hemispheric tumor group had additional problems with selective attention and executive functioning, and the supratentorial midline tumor group displayed no extra impairments. More specifically, the dorsal supratentorial midline tumor group displayed problems with language and verbal memory. Predictors for lower cognitive functioning were hydrocephalus, radiotherapy, residual tumor size, and age; predictors for better functioning were chemotherapy or treatment of hydrocephalus. Almost 60% of children had problems with academic achievement, for which risk factors were relapse and younger age at diagnosis. CONCLUSION Despite normal intelligence at long-term follow-up, children treated for PA display invalidating cognitive impairments. Adequate treatment of hydrocephalus is important for a more favorable long-term cognitive outcome. Even children without initial severe deficits may develop cognitive impairments years after diagnosis, partly because of the phenomenon of growing into deficit, which has devastating implications for academic achievement and quality of life (QOL).

Mentalization deficit in bipolar patients during an acute depressive and manic episode: association with cognitive functions.

PubMed

Bodnar, Anna; Rybakowski, Janusz K

2017-12-06

A number of studies in bipolar patients have shown a deficit in mentalization (theory of mind), one of the main aspects of social cognition. The aim of current study was to assess both cognitive and affective mentalization in well-defined groups of depressed and manic bipolar patients, compared to healthy control subjects, using a battery of tests measuring mentalization processes. The second aim was to investigate a possible relationship between cognitive and affective mentalization and cognitive functions in bipolar patients during a depressive and manic episode. The study involved 25 bipolar disorder type I patients (10 male, 15 female) during a depressive episode (mean 24 ± 2 points in the 17-item Hamilton Depression Rating Scale) and 25 patients (10 male, 15 female) during a manic episode (mean 27 ± 4 points in the Young Mania Rating Scale). The control group consisted of 25 healthy subjects (10 male, 15 female) without psychiatric disorders. To measure mentalization, a revised version of the Reading the Mind in the Eyes (R-MET), the Strange Stories (SS), the Faux Pas Recognition (FPR), and the Moving Shapes Paradigm (MSP) tests were used. Assessment of cognitive functioning was made using the Digit Span, Trail Making, and Wisconsin Card Sorting Tests. In bipolar patients significant deficits in both cognitive and affective mentalization were demonstrated during both acute depressive and manic episodes. The impairment in FPR in manic patients was more severe than that in the depressive ones. On the other hand, in MSP, manic patients showed significantly increased intentionality for non-mentalization animations, compared with depressive patients and for "cause and effect" animations compared with control subjects. A significant relationship was found between the decrease in cognitive and affective mentalization and deficits of cognitive functions during both the depressive and manic episodes. The results obtained confirm the deficits of mentalization in

Subacute ibuprofen treatment rescues the synaptic and cognitive deficits in advanced-aged mice

PubMed Central

Rogers, Justin T.; Liu, Chia-Chen; Zhao, Na; Wang, Jian; Putzke, Travis; Yang, Longyu; Shinohara, Mitsuru; Fryer, John D.; Kanekiyo, Takahisa; Bu, Guojun

2017-01-01

Aging is accompanied by increased neuroinflammation, synaptic dysfunction and cognitive deficits both in rodents and humans, yet the onset and progression of these deficits throughout the life span remain unknown. These aging-related deficits affect the quality of life and present challenges to our aging society. Here, we defined age-dependent and progressive impairments of synaptic and cognitive functions and showed that reducing astrocyte-related neuroinflammation through anti-inflammatory drug treatment in aged mice reverses these events. By comparing young (3 months), middle-aged (18 months), aged (24 months) and advanced-aged wild-type mice (30 months), we found that the levels of an astrocytic marker, GFAP, progressively increased after 18 months of age, which preceded the decreases of the synaptic marker PSD-95. Hippocampal long-term potentiation (LTP) was also suppressed in an age-dependent manner, where significant deficits were observed after 24 months of age. Fear conditioning tests demonstrated that associative memory in the context and cued conditions was decreased starting at the ages of 18 and 30 months, respectively. When the mice were tested on hidden platform water maze, spatial learning memory was significantly impaired after 24 months of age. Importantly, subacute treatment with the anti-inflammatory drug ibuprofen suppressed astrocyte activation, and restored synaptic plasticity and memory function in advanced-aged mice. These results support the critical contribution of aging-related inflammatory responses to hippocampal-dependent cognitive function and synaptic plasticity, in particular during advanced aging. Our findings provide strong evidence that suppression of neuroinflammation could be a promising treatment strategy to preserve cognition during aging. PMID:28254590

16p11.2 Deletion mice display cognitive deficits in touchscreen learning and novelty recognition tasks.

PubMed

Yang, Mu; Lewis, Freeman C; Sarvi, Michael S; Foley, Gillian M; Crawley, Jacqueline N

2015-12-01

Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/-) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2+/- mice, confirming previous findings. A similarly robust deficit in object location memory was discovered in +/-, indicating impaired spatial novelty recognition. Generalizability of novelty recognition deficits in +/- mice extended to preference for social novelty. Robust learning deficits and cognitive inflexibility were detected using Bussey-Saksida touchscreen operant chambers. During acquisition of pairwise visual discrimination, +/- mice required significantly more training trials to reach criterion than wild-type littermates (+/+), and made more errors and correction errors than +/+. In the reversal phase, all +/+ reached criterion, whereas most +/- failed to reach criterion by the 30-d cutoff. Contextual and cued fear conditioning were normal in +/-. These cognitive phenotypes may be relevant to some aspects of cognitive impairments in humans with 16p11.2 deletion, and support the use of 16p11.2+/- mice as a model system for discovering treatments for cognitive impairments in 16p11.2 deletion syndrome. © 2015 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

PubMed Central

Kesby, James P.; Markou, Athina; Semenova, Svetlana

2014-01-01

Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

Brain catechol-o-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice

PubMed Central

Detrait, E.R.; Carr, G.V.; Ferraille, S.; Weinberger, D.R.; Lamberty, Y.

2015-01-01

The critical involvement of dopamine in cognitive processes has been well established, suggesting therapies targeting dopamine metabolism may alleviate cognitive dysfunction. COMT is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition for alleviating cognitive impairment. A brain penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine (PCP)-treated rats and COMT–Val transgenic mice. In a Novel Object Recognition (NOR) procedure, tolcapone counteracted a 24h-dependent forgetting of a familiar object and counteracted PCP-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor which does not readily cross the blood-brain barrier failed to show efficacy at doses up to 30mg/kg. Tolcapone at a dose of 30 mg/kg also improved NOR performance in the transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders. PMID:26919286

Thunbergia laurifolia extract ameliorates cognitive and emotional deficits in olfactorectomized mice.

PubMed

Rojsanga, Piyanuch; Sithisarn, Pongtip; Tanaka, Ken; Mizuki, Daishu; Matsumoto, Kinzo

2015-08-01

Thunbergia laurifolia Lindl. (Acanthaceae) is a Thai medicinal plant used for the detoxification of poison which is likely to be beneficial for the treatment of cognitive deficits including Alzheimer's disease. To elucidate the effects of Thunbergia laurifolia leaf extract (TLL) on cognitive dysfunction and depression-like behavior in olfactory bulbectomized mice (OBX). OBX mice were treated daily with TLL at the dose of 250 and 500 mg/kg, tacrine, and imipramine, on the day after 10 d of OBX operation. The effects of TLL on cognitive and depression-like behavior of the animals were analyzed. After completing behavioral experiments, the expression levels of cholinergic marker genes encoding ChAT and muscarinic M1 receptor were quantitatively analyzed. TLL and tacrine reduced OBX-induced cognitive deficits in the object recognition test (ORT) with the time spent for the novel object two times longer than that of the familiar object. Moreover, TLL at the dose of 500 mg/kg and imipramine ameliorated depression-like behavior in the tail suspension test (TST) by reducing the duration of immobility from 25.18% to 3.16% and from 25.18% to 6.48%, respectively. TLL at the dose of 250 and 500 mg/kg reversed the OBX-induced down-regulation of ChAT mRNA expression in the hippocampus from 0.12 to 0.17 and 0.24, respectively, while the down-regulation of mRNA expression of muscarinic M1 receptor was also reversed by TLL from 0.23 to 0.38 and 0.48, respectively. TLL ameliorates non-spatial short-term memory deficits in OBX mice, and has the potential to exhibit an antidepressant-like action.

Deficits in Domains of Social Cognition in Schizophrenia: A Meta-Analysis of the Empirical Evidence

PubMed Central

Savla, Gauri N.

2013-01-01

Objective: Social cognition is strongly associated with functional outcome in schizophrenia, making it an important target for treatment. Our goal was to examine the average magnitude of differences between schizophrenia patients (SCs) and normal comparison (NCs) patients across multiple domains of social cognition recognized by the recent NIMH consensus statement: theory of mind (ToM), social perception, social knowledge, attributional bias, emotion perception, and emotion processing. Method: We conducted a meta-analysis of peer-reviewed studies of social cognition in schizophrenia, published between 1980 and November, 2011. Results: 112 studies reporting results from 3908 SCs and 3570 NCs met our inclusion criteria. SCs performed worse than NCs across all domains, with large effects for social perception (g = 1.04), ToM (g = 0.96), emotion perception (g = 0.89), and emotion processing (g = 0.88). Regression analyses showed that statistically significant heterogeneity in effects within domains was not explained by age, education, or gender. Greater deficits in social and emotion perception were associated with inpatient status, and greater deficits in emotion processing were associated with longer illness duration. Conclusions: Despite the limitations of existing studies, including lack of standardization or psychometric validation of measures, the evidence for deficits across multiple social cognitive domains in schizophrenia is clear. Future research should examine the role of neurobiological and psychosocial factors in models linking various aspects of deficit in schizophrenia, including social cognition, in order to identify targets for intervention. PMID:22949733

University Students With Poor Reading Comprehension: The Hidden Cognitive Processing Deficit.

PubMed

Georgiou, George K; Das, J P

2015-01-01

The present study aimed to examine the nature of the working memory and general cognitive ability deficits experienced by university students with a specific reading comprehension deficit. A total of 32 university students with poor reading comprehension but average word-reading skills and 60 age-matched controls with no comprehension difficulties participated in the study. The participants were assessed on three verbal working memory tasks that varied in terms of their processing demands and on the Das-Naglieri Cognitive Assessment System, which was used to operationalize intelligence. The results indicated first that the differences between poor and skilled comprehenders on working memory were amplified as the processing demands of the tasks increased. In addition, although poor comprehenders as a group had average intelligence, they experienced significant difficulties in simultaneous and successive processing. Considering that working memory and general cognitive ability are highly correlated processes, these findings suggest that the observed differences between poor and skilled comprehenders are likely a result of a deficient information processing system. © Hammill Institute on Disabilities 2013.

In search of multimodal neuroimaging biomarkers of cognitive deficits in schizophrenia.

PubMed

Sui, Jing; Pearlson, Godfrey D; Du, Yuhui; Yu, Qingbao; Jones, Thomas R; Chen, Jiayu; Jiang, Tianzi; Bustillo, Juan; Calhoun, Vince D

2015-12-01

The cognitive deficits of schizophrenia are largely resistant to current treatments and thus are a lifelong illness burden. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) provides a reliable and valid assessment of cognition across major cognitive domains; however, the multimodal brain alterations specifically associated with MCCB in schizophrenia have not been examined. The interrelationships between MCCB and the abnormalities seen in three types of neuroimaging-derived maps-fractional amplitude of low-frequency fluctuations (fALFF) from resting-state functional magnetic resonance imaging (MRI), gray matter (GM) density from structural MRI, and fractional anisotropy from diffusion MRI-were investigated by using multiset canonical correlation analysis in data from 47 schizophrenia patients treated with antipsychotic medications and 50 age-matched healthy control subjects. One multimodal component (canonical variant 8) was identified as both group differentiating and significantly correlated with the MCCB composite. It demonstrated 1) increased cognitive performance associated with higher fALFF (intensity of regional spontaneous brain activity) and higher GM volumes in thalamus, striatum, hippocampus, and the mid-occipital region, with co-occurring fractional anisotropy changes in superior longitudinal fascicules, anterior thalamic radiation, and forceps major; 2) higher fALFF but lower GM volume in dorsolateral prefrontal cortex related to worse cognition in schizophrenia; and 3) distinct domains of MCCB might exhibit dissociable multimodal signatures, e.g., increased fALFF in inferior parietal lobule particularly correlated with decreased social cognition. Medication dose did not relate to these findings in schizophrenia. Our results suggest linked functional and structural deficits in distributed cortico-striato-thalamic circuits may be closely related to MCCB-measured cognitive

Hypoglycemia induced by insulin as a triggering factor of cognitive deficit in diabetic children.

PubMed

Rodrigues Vilela, Vanessa; de Castro Ruiz Marques, Any; Schamber, Christiano Rodrigues; Bazotte, Roberto Barbosa

2014-01-01

This paper provides an overview of insulin-induced hypoglycemia as a triggering factor of cognitive deficit in children with type 1 diabetes mellitus. For this purpose, databases from 1961 to 2013 were used with the objective of detecting the primary publications that address the impact of hypoglycemia on cognitive performance of diabetic children. The results obtained from experimental animals were excluded. The majority of studies demonstrated that the cognitive deficit in diabetic children involves multiple factors including duration, intensity, severity, and frequency of hypoglycemia episodes. Additionally, age at the onset of type 1 diabetes also influences the cognitive performance, considering that early inception of the disease is a predisposing factor for severe hypoglycemia. Furthermore, the results suggest that there is a strong correlation between brain damage caused by hypoglycemia and cognitive deterioration. Therefore, a more cautious follow-up and education are needed to impede and treat hypoglycemia in children with diabetes mellitus.

Hypoglycemia Induced by Insulin as a Triggering Factor of Cognitive Deficit in Diabetic Children

PubMed Central

Rodrigues Vilela, Vanessa; de Castro Ruiz Marques, Any; Schamber, Christiano Rodrigues

2014-01-01

This paper provides an overview of insulin-induced hypoglycemia as a triggering factor of cognitive deficit in children with type 1 diabetes mellitus. For this purpose, databases from 1961 to 2013 were used with the objective of detecting the primary publications that address the impact of hypoglycemia on cognitive performance of diabetic children. The results obtained from experimental animals were excluded. The majority of studies demonstrated that the cognitive deficit in diabetic children involves multiple factors including duration, intensity, severity, and frequency of hypoglycemia episodes. Additionally, age at the onset of type 1 diabetes also influences the cognitive performance, considering that early inception of the disease is a predisposing factor for severe hypoglycemia. Furthermore, the results suggest that there is a strong correlation between brain damage caused by hypoglycemia and cognitive deterioration. Therefore, a more cautious follow-up and education are needed to impede and treat hypoglycemia in children with diabetes mellitus. PMID:24790575

Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice.

PubMed

Kesby, James P; Markou, Athina; Semenova, Svetlana

2015-01-01

Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e. similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Stable cognitive deficits in schizophrenia patients with comorbid obsessive-compulsive symptoms: a 12-month longitudinal study.

PubMed

Schirmbeck, Frederike; Rausch, Franziska; Englisch, Susanne; Eifler, Sarah; Esslinger, Christine; Meyer-Lindenberg, Andreas; Zink, Mathias

2013-11-01

Amongst schizophrenia patients, a large subgroup of up to 25% also suffers from comorbid obsessive-compulsive symptoms (OCSs). The association between comorbid OCSs in these patients and neuropsychological impairment remains unclear and somewhat contradictory. Longitudinal approaches investigating the stability of OCS-associated cognitive deficits are missing. Thirty-seven patients with schizophrenia and comorbid OCSs and 43 schizophrenia patients without OCS were assessed with a comprehensive cognitive test battery and compared at baseline and, again, 12 months later. Schizophrenia patients with comorbid OCSs showed significant pronounced deficits, with increasing effect sizes over the 12-month assessment period in specific cognitive areas such as visuospatial perception and visual memory (WAIS-R block design, Rey-Osterrieth Complex Figure Test), executive functioning (perseveration in the Wisconsin Card Sorting test), and cognitive flexibility (Trail Making test B). These cognitive domains are correlated with OCS severity and are known to be candidate cognitive domains in obsessive-compulsive disorder (OCD). OCSs in schizophrenia is associated with specific and longitudinally stable cognitive deficits, strongly arguing for at least partially overlapping neurobiological mechanisms with OCD. Prospective studies involving patients with at-risk mental states for psychosis are necessary to decipher the interaction of cognitive impairment and the clinical manifestations of schizophrenia and OCSs. This might facilitate the definition of patients at high risk for OCSs, an early detection of subclinical levels, therapeutic interventions, and clinical monitoring.

Cognitive Deficits in Schizophrenia: Focus on Neuronal Nicotinic Acetylcholine Receptors and Smoking

PubMed Central

Lasalde-Dominicci, Jose

2015-01-01

Patients with schizophrenia present with deficits in specific areas of cognition. These are quantifiable by neuropsychological testing and can be clinically observable as negative signs. Concomitantly, they self-administer nicotine in the form of cigarette smoking. Nicotine dependence is more prevalent in this patient population when compared to other psychiatric conditions or to non-mentally ill people. The target for nicotine is the neuronal nicotinic acetylcholine receptor (nAChR). There is ample evidence that these receptors are involved in normal cognitive operations within the brain. This review describes neuronal nAChR structure and function, focusing on both cholinergic agonist-induced nAChR desensitization and nAChR up-regulation. The several mechanisms proposed for the nAChR up-regulation are examined in detail. Desensitization and up-regulation of nAChRs may be relevant to the physiopathology of schizophrenia. The participation of several subtypes of neuronal nAChRs in the cognitive processing of non-mentally ill persons and schizophrenic patients is reviewed. The role of smoking is then examined as a possible cognitive remediator in this psychiatric condition. Finally, pharmacological strategies focused on neuronal nAChRs are discussed as possible therapeutic avenues that may ameliorate the cognitive deficits of schizophrenia. PMID:17554626

Diagnosing Contributions of Sensory and Cognitive Deficits to Hearing Dysfunction in Blast Exposed/TBI Service Members

DTIC Science & Technology

2016-10-01

1 AWARD NUMBER: W81XWH-15-1-0490 TITLE: Diagnosing Contributions of Sensory and Cognitive Deficits to Hearing Dysfunction in Blast-Exposed/ TBI...3. DATES COVERED 15 Sep 2015 - 14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Diagnosing Contributions of Sensory and Cognitive Deficits to...installed at WRNMMC, and is running finalized versions of both the auditory and visual selective attention tasks. Subject recruitment has started, and

Cognitive Deficits in Adults with ADHD Go beyond Comorbidity Effects

ERIC Educational Resources Information Center

Silva, Katiane L.; Guimaraes-da-Silva, Paula O.; Grevet, Eugenio H.; Victor, Marcelo M.; Salgado, Carlos A. I.; Vitola, Eduardo S.; Mota, Nina R.; Fischer, Aline G.; Contini, Veronica; Picon, Felipe A.; Karam, Rafael G.; Belmonte-de-Abreu, Paulo; Rohde, Luis A.; Bau, Claiton H. D.

2013-01-01

Objective: This study addresses if deficits in cognitive, attention, and inhibitory control performance in adults with ADHD are better explained by the disorder itself or by comorbid conditions. Method Adult patients with ADHD ("n" = 352) and controls ("n" = 94) were evaluated in the ADHD program of a tertiary hospital. The…

Executive Functions, Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research.

PubMed

Le Berre, Anne-Pascale; Fama, Rosemary; Sullivan, Edith V

2017-08-01

Alcoholism is a complex and dynamic disease, punctuated by periods of abstinence and relapse, and influenced by a multitude of vulnerability factors. Chronic excessive alcohol consumption is associated with cognitive deficits, ranging from mild to severe, in executive functions, memory, and metacognitive abilities, with associated impairment in emotional processes and social cognition. These deficits can compromise efforts in initiating and sustaining abstinence by hampering efficacy of clinical treatment and can obstruct efforts in enabling good decision making success in interpersonal/social interactions, and awareness of cognitive and behavioral dysfunctions. Despite evidence for differences in recovery levels of selective cognitive processes, certain deficits can persist even with prolonged sobriety. Herein is presented a review of alcohol-related cognitive impairments affecting component processes of executive functioning, memory, and the recently investigated cognitive domains of metamemory, social cognition, and emotional processing; also considered are trajectories of cognitive recovery with abstinence. Finally, in the spirit of critical review, limitations of current knowledge are noted and avenues for new research efforts are proposed that focus on (i) the interaction among emotion-cognition processes and identification of vulnerability factors contributing to the development of emotional and social processing deficits and (ii) the time line of cognitive recovery by tracking alcoholism's dynamic course of sobriety and relapse. Knowledge about the heterochronicity of cognitive recovery in alcoholism has the potential of indicating at which points during recovery intervention may be most beneficial. Copyright © 2017 by the Research Society on Alcoholism.

Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats.

PubMed

De Bruin, N M W J; Kiliaan, A J; De Wilde, M C; Broersen, L M

2003-07-01

Rationale. Hypertension is considered a risk factor for the development of cognitive disorders, because of its negative effects on cerebral vasculature and blood flow. Genetically induced hypertension in rats has been associated with a range of cognitive impairments. Therefore, spontaneously hypertensive rats (SHR) can potentially be used as a model for cognitive deficits in human subjects. Consecutively, it can be determined whether certain food components can improve cognition in these rats. Objective. The present study aimed to determine whether SHR display specific deficits in attention, learning, and memory function. Additionally, effects of chronic uridine and choline administration were studied. Methods. 5-7 months old SHR were compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. (a) The operant delayed non-matching-to-position (DNMTP) test was used to study short-term memory function. (b) The five-choice serial reaction time (5-CSRT) task was used to assess selective visual attention processes. (c) Finally, the Morris water maze (MWM) acquisition was used as a measure for spatial learning and mnemonic capabilities. Results. (1) SHR exhibited significantly impaired performance in the 5-CSRT test in comparison with the two other rat strains. Both the SHR and WKY showed deficits in spatial learning when compared with the SD rats. (2) Uridine and choline supplementation normalized performance of SHR in the 5-CSRT test. (3) In addition, uridine and choline treatment improved MWM acquisition in both WKY and SHR rats. Conclusion. The present results show that the SHR have a deficiency in visual selective attention and spatial learning. Therefore, the SHR may provide an interesting model in the screening of substances with therapeutic potential for treatment of cognitive disorders. A combination of uridine and choline administration improved selective attention and spatial learning in SHR.

Number Processing and Heterogeneity of Developmental Dyscalculia: Subtypes with Different Cognitive Profiles and Deficits

ERIC Educational Resources Information Center

Skagerlund, Kenny; Träff, Ulf

2016-01-01

This study investigated if developmental dyscalculia (DD) in children with different profiles of mathematical deficits has the same or different cognitive origins. The defective approximate number system hypothesis and the access deficit hypothesis were tested using two different groups of children with DD (11-13 years old): a group with…

Deficit of entropy modulation of the EEG in schizophrenia associated to cognitive performance and symptoms. A replication study.

PubMed

Molina, Vicente; Bachiller, Alejandro; Gomez-Pilar, Javier; Lubeiro, Alba; Hornero, Roberto; Cea-Cañas, Benjamín; Valcárcel, César; Haidar, Mahmoun-Karim; Poza, Jesús

2018-05-01

Spectral entropy (SE) is a measurement from information theory field that provides an estimation of EEG regularity and may be useful as a summary of its spectral properties. Previous studies using small samples reported a deficit of EEG entropy modulation in schizophrenia during cognitive activity. The present study is aimed at replicating this finding in a larger sample, to explore its cognitive and clinical correlates and to discard antipsychotic treatment as the main source of that deficit. We included 64 schizophrenia patients (21 first episodes, FE) and 65 healthy controls. We computed SE during performance of an odd-ball paradigm, at the windows prior (-300 to 0ms) and following (150 to 450ms) stimulus presentation. Modulation of SE was defined as the difference between post- and pre-stimulus windows. In comparison to controls, patients showed a deficit of SE modulation over frontal and central regions, also shown by FE patients. Baseline SE did not differ between patients and controls. Modulation deficit was directly associated with cognitive deficits and negative symptoms, and inversely with positive symptoms. SE modulation was not related to antipsychotic doses. Patients also showed a smaller change of median frequency (i.e., smaller slowing of oscillatory activity) of the EEG from pre- to post-stimulus windows. These results support that a deficit of fast modulation contributes to cognitive deficits and symptoms in schizophrenia patients. Copyright © 2017 Elsevier B.V. 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.

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

PubMed

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

2015-08-01

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

The association between cognitive deficits and prefrontal hemodynamic responses during performance of working memory task in patients with schizophrenia.

PubMed

Pu, Shenghong; Nakagome, Kazuyuki; Itakura, Masashi; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

2016-04-01

Schizophrenia-associated cognitive deficits are resistant to treatment and thus pose a lifelong burden. The Brief Assessment of Cognition in Schizophrenia (BACS) provides reliable and valid assessments across cognitive domains. However, because the prefrontal functional abnormalities specifically associated with the level of cognitive deficits in schizophrenia have not been examined, we explored this relationship. Patients with schizophrenia (N=87) and matched healthy controls (N=50) participated in the study. Using near-infrared spectroscopy (NIRS), we measured the hemodynamic responses in the prefrontal and superior temporal cortical surface areas during a working memory task. Correlation analyses revealed a relationship between the hemodynamics and the BACS composite and domain scores. Hemodynamic responses of the left dorsolateral prefrontal cortex (DLPFC) and left frontopolar cortex (FPC) in the higher-level-of-cognitive-function schizophrenia group were weaker than the responses of the controls but similar to those of the lower-level-of-cognitive-function schizophrenia group. However, hemodynamic responses in the right DLPFC, bilateral ventrolateral PFC (VLPFC), and right temporal regions decreased with increasing cognitive deficits. In addition, the hemodynamic response correlated positively with the level of cognitive function (BACS composite scores) in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions in schizophrenia. The correlation was driven by all BACS domains. Our results suggest that the linked functional deficits in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions may be related to BACS-measured cognitive impairments in schizophrenia and show that linking the neurocognitive deficits and brain abnormalities can increase our understanding of schizophrenia pathophysiology. Copyright © 2015 Elsevier B.V. All rights reserved.

Using upper limb kinematics to assess cognitive deficits in people living with both HIV and stroke.

PubMed

Bui, Kevin D; Rai, Roshan; Johnson, Michelle J

2017-07-01

In this study, we aim to explore ways to objectively assess cognitive deficits in the stroke and HIV/stroke populations, where cognitive and motor impairments can be hard to separate. Using an upper limb rehabilitation robot called the Haptic TheraDrive, we collect performance error scores and motor learning data on the impaired and unimpaired limb during a trajectory tracking task. We compare these data to clinical cognitive scores. The preliminary results suggest a possible relationship between unimpaired upper limb performance error and visuospatial/executive function cognitive domains, but more work needs to be done to further investigate this. The potential of using robot-assisted technologies to measure unimpaired limb kinematics as a tool to assess cognitive deficits would be useful to inform more effective rehabilitation strategies for HIV, stroke, and HIV/stroke populations.

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.

Effect of Neuroscience-Based Cognitive Skill Training on Growth of Cognitive Deficits Associated with Learning Disabilities in Children Grades 2-4

ERIC Educational Resources Information Center

Avtzon, Sarah Abitbol

2012-01-01

Working memory, executive functions, and cognitive processes associated with specific academic areas, are empirically identified as being the core underlying cognitive deficits in students with specific learning disabilities. Using Hebb's theory of neuroplasticity and the principle of automaticity as theoretical bases, this experimental study…

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."

Uncaria rhynchophylla ameliorates cognitive deficits induced by D-galactose in mice.

PubMed

Xian, Yan-Fang; Lin, Zhi-Xiu; Zhao, Ming; Mao, Qing-Qiu; Ip, Siu-Po; Che, Chun-Tao

2011-12-01

The stem with hooks of Uncaria rhynchophylla is a component herb of many traditional formulae for the treatment of neurodegenerative diseases. However, scientific evidence of the efficacy of Uncaria rhynchophylla in the treatment of Alzheimer's disease (AD) in animal models is lacking. Thus, in the present study, we investigated whether the 70 % aqueous ethanol extract of Uncaria rhynchophylla (EUR) could protect against D-galactose (D-gal)-induced cognitive deficits in mice. Mice were given a subcutaneous injection of D-gal (50 mg/kg) and orally administered EUR (100, 200, or 400 mg/kg) daily for 8 weeks. The effect of EUR on D-gal-induced cognitive deficits was evaluated by measuring behavioral and neurochemical parameters of AD and the antioxidant status of brain tissue. The results showed that EUR (200 or 400 mg/kg) significantly increased exploratory behavior (assessed by an open-field test) and improved spatial learning and memory function (assessed by the Morris water maze test) in D-gal-treated mice. In addition, EUR (200 or 400 mg/kg) significantly increased the levels of acetylcholine and glutathione and decreased the activity of acetylcholinesterase and the level of malondialdehyde in the brains of D-gal-treated mice. These results indicate that EUR ameliorates cognitive deficits induced by D-gal in mice, and that this action may be mediated, at least in part, by the inhibition of acetylcholinesterase activity and the enhancement of the antioxidant status of brain tissue. © Georg Thieme Verlag KG Stuttgart · New York.

Association of Social Frailty With Both Cognitive and Physical Deficits Among Older People.

PubMed

Tsutsumimoto, Kota; Doi, Takehiko; Makizako, Hyuma; Hotta, Ryo; Nakakubo, Sho; Makino, Keitaro; Suzuki, Takao; Shimada, Hiroyuki

2017-07-01

Our objective was to investigate the association between social frailty and cognitive and physical function among older adults. This was a cross-sectional study. We examined community-dwelling adults in Japan. Participants comprised 4425 older Japanese people from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Social frailty was defined by using responses to 5 questions (going out less frequently, rarely visiting friends, feeling unhelpful to friends or family, living alone, and not talking with someone every day). Participants showing none of these components were considered nonfrail; those showing 1 component were considered prefrail; and those showing 2 or more components were considered frail. To screen for cognitive deficits, we assessed memory, attention, executive function, and processing speed. Having 2 or more tests with age-adjusted scores of at least 1.5 standard deviations below the reference threshold was sufficient to be characterized as cognitively deficient. To screen for physical function deficits, we assessed walking speed (<1.0 m/s cut-off) and grip strength (<26 kg for men; <18 kg for women cut-off). Scoring below the cut-off point on 1 or more tests was sufficient to be characterized as physically deficient. The prevalence of social frailty was the following: nonfrailty, 64.1% (N = 2835); social prefrailty, 24.8% (N = 1097); social frailty, 11.1% (N = 493; P for trend < .001). All cognitive function tests (word list memory, Trail Making Test parts A and B, and the symbol digit-substitution task) significantly varied between social frailty groups; physical function (gait speed and grip strength) also varied between social frailty groups (all Ps for trend <.001). Referred to social nonfrailty, social frailty was independently associated with each cognitive deficit (odds ratio = 1.61, 95% confidence interval 1.13-2.30) and deficits in physical function (odds ratio = 1.99, 95% confidence interval 1

Correlation between insight dimensions and cognitive functions in patients with deficit and nondeficit schizophrenia.

PubMed

Pegoraro, Luiz F L; Dantas, Clarissa R; Banzato, Claudio E M; Fuentes, Daniel

2013-06-01

Previous studies have shown correlations between poor insight and neurocognitive impairment in schizophrenia. Deficit schizophrenia has been associated with worse cognitive functioning and poorer insight. This study aimed at investigating the relationship between insight dimensions (measured by Schedule for the Assessment of Insight-Expanded Version and its factors) and specific neurocognitive functions (assessed through a battery of neuropsychological tests) considering separately patients with deficit (n=29) and nondeficit schizophrenia (n=44), categorized according to the Schedule for the Deficit Syndrome. We found that working memory correlated positively and significantly with awareness of mental illness in both groups. In nondeficit group, awareness of mental illness correlated additionally with verbal fluency and attention. If confirmed by further studies, these results may have important consequences, such as the need of tailoring differently cognitive rehabilitation for each group. Copyright © 2013 Elsevier B.V. All rights reserved.

Social cognition deficits and the 'ultra high risk' for psychosis population: a review of literature.

PubMed

Thompson, Andrew D; Bartholomeusz, Cali; Yung, Alison R

2011-08-01

A number of risk factors for developing a psychotic disorder have been investigated in the 'ultra high risk' (UHR) population, including neurocognitive abilities, social functioning and, more recently, social cognition. We aimed to review the literature on social cognition in the UHR population. Literature was restricted to English articles and identified using Pubmed, Medline, PsychINFO and CINAHLplus, as well as the reference lists of published studies and reviews. Search terms included social cognition, theory of mind, emotion recognition, attributional style, social knowledge, social perception, 'at risk mental state', psychosis prodrome 'clinical high risk' and 'ultra high risk'. Inclusion criteria were an outcome measure of a social cognition task and an UHR population defined by a structured validated instrument. Seven original research articles met the inclusion criteria, one of which was a conference abstract. One of the two studies that assessed theory of mind, two of the four studies that assessed emotion recognition and both the two studies that assessed social perception/knowledge found significant deficits in UHR patients. The single study that assessed attributional bias also reported differences in UHR patients compared with healthy controls. There is limited published literature on social cognitive performance in the UHR population. Despite this, deficits in certain social cognitive abilities do appear to be present, but further research with more reliable cross-cultural measures is needed. The characterization of social cognitive deficits in the UHR populations may aid in the identification of potential markers for development of a subsequent psychotic disorder, as well as targets for early intervention. © 2011 Blackwell Publishing Asia Pty Ltd.

Methylthioninium chloride reverses cognitive deficits induced by scopolamine: comparison with rivastigmine.

PubMed

Deiana, Serena; Harrington, Charles R; Wischik, Claude M; Riedel, Gernot

2009-01-01

The cholinergic system is involved in cognition as well as in age-related cognitive decline and Alzheimer disease (AD). Cholinergic enhancers ameliorate AD symptoms and represent the main current therapy for AD. MTC (Methylthioninium chloride), an antioxidant with metabolism-enhancing properties may be a novel candidate with pro-cognitive capacities. This study was performed: (1) to assess the pro-cognitive efficacy of MTC and establish its dose-response; (2) to compare the efficacy of MTC with rivastigmine and (3) to determine the potential for combination therapy by co-administration of MTC and rivastigmine. Spatial cognition of female NMRI mice was tested in a reference memory water maze task. Subjects received intra-peritoneal injections of scopolamine (0.5 mg/kg) followed by vehicle, and/or MTC and/or rivastigmine (0.15-4 mg/kg MTC; 0.1-0.5 mg/kg rivastigmine) in mono or combination treatment. Scopolamine treatment prevented spatial learning in NMRI female mice and the deficit was reversed by both rivastigmine and MTC in a dose-dependent manner. Mono-therapy with high doses of rivastigmine (>0.5 mg/kg) caused severe side effects but MTC was safe up to 4 mg/kg. Co-administration of sub-effective doses of both drugs acted synergistically in reversing learning deficits and scopolamine-induced memory impairments. In our model, MTC reversed the spatial learning impairment. When combined with the ChEI rivastigmine, the effect of MTC appeared to be amplified indicating that combination therapy could potentially improve not only symptoms but also contribute beneficially to neuronal metabolism by minimising side effects at lower doses.

Resting fMRI measures are associated with cognitive deficits in schizophrenia assessed by the MATRICS consensus cognitive battery

NASA Astrophysics Data System (ADS)

He, Hao; Bustillo, Juan; Du, Yuhui; Yu, Qingbao; Jones, Thomas R.; Jiang, Tianzi; Calhoun, Vince D.; Sui, Jing

2015-03-01

The cognitive deficits of schizophrenia are largely resistant to current treatment, and are thus a life-long burden to patients. The MATRICS consensus cognitive battery (MCCB) provides a reliable and valid assessment of cognition across a comprehensive set of cognitive domains for schizophrenia. In resting-state fMRI, functional connectivity associated with MCCB has not yet been examined. In this paper, the interrelationships between MCCB and the abnormalities seen in two types of functional measures from resting-state fMRI—fractional amplitude of low frequency fluctuations (fALFF) and functional network connectivity (FNC) maps were investigated in data from 47 schizophrenia patients and 50 age-matched healthy controls. First, the fALFF maps were generated and decomposed by independent component analysis (ICA), and then the component showing the highest correlation with MCCB composite scores was selected. Second, the whole brain was separated into functional networks by group ICA, and the FNC maps were calculated. The FNC strengths with most significant correlations with MCCB were displayed and spatially overlapped with the fALFF component of interest. It demonstrated increased cognitive performance associated with higher fALFF values (intensity of regional spontaneous brain activity) in prefrontal regions, inferior parietal lobe (IPL) but lower ALFF values in thalamus, striatum, and superior temporal gyrus (STG). Interestingly, the FNC showing significant correlations with MCCB were in well agreement with the activated regions with highest z-values in fALFF component. Our results support the view that functional deficits in distributed cortico-striato-thalamic circuits and inferior parietal lobe may account for several aspects of cognitive impairment in schizophrenia.

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.

How culture shapes social cognition deficits in mental disorders: A review.

PubMed

Koelkebeck, Katja; Uwatoko, Teruhisa; Tanaka, Jiro; Kret, Mariska Esther

2017-04-01

Social cognitive skills are indispensable for successful communication with others. Substantial research has determined deficits in these abilities in patients with mental disorders. In neurobiological development and continuing into adulthood, cross-cultural differences in social cognition have been demonstrated. Moreover, symptomatic patterns in mental disorders may vary according to the cultural background of an individual. Cross-cultural studies can thus help in understanding underlying (biological) mechanisms and factors that influence behavior in health and disease. In addition, studies that apply novel paradigms assessing the impact of culture on cognition may benefit and advance neuroscience research. In this review, the authors give an overview of cross-cultural research in the field of social cognition in health and in mental disorders and provide an outlook on future research directions, taking a neuroscience perspective.

Is a picture worth a thousand (forgotten) words?: neuroimaging evidence for the cognitive deficits in 'chemo-fog'/'chemo-brain'.

PubMed

Raffa, R B

2010-02-01

The diminution in cognitive function reported to occur in patients treated with adjuvant cancer chemotherapy (a phenomenon known as 'chemo-fog, 'chemo-brain' or similar designation) is supported with varying degrees of evidence by prospective and retrospective clinical studies. However, the cognitive deficits are often subtle and the methodologies used to measure them not consistent. Additionally, patients might be able to compensate for the deficits, thereby leading to underestimates of the problem by this type of assessment. For these reasons, direct neuroimaging techniques might provide additional insight. The relatively few such studies, and fewer electrophysiological studies, offer an alternative way to evaluate changes that might be related to cognitive deficits in patients treated with cancer chemotherapeutic regimens.

Abnormal frontal theta oscillations underlie the cognitive flexibility deficits in children with high-functioning autism spectrum disorders.

PubMed

Yeung, Michael K; Han, Yvonne M Y; Sze, Sophia L; Chan, Agnes S

2016-03-01

Deficits in cognitive flexibility have been suggested to underlie the repetitive and stereotyped behavior in individuals with autism spectrum disorders (ASD). Because cognitive flexibility is primarily mediated by the frontal lobe, where structural and functional abnormalities have been extensively found in these individuals, it is conceivable that their deficits in cognitive flexibility are related to abnormal activations of the frontal lobe. The present study investigates cognitive flexibility and its underlying neurophysiological activities as indicated by theta oscillations in children with ASD. Twenty-five children with high-functioning ASD and 25 IQ- and age-matched typically developing (TD) children were subjected to neuropsychological assessments on cognitive flexibility and electroencephalography recordings. The children with ASD performed significantly worse than the TD children across the tasks of cognitive flexibility, including the modified Wisconsin Card Sorting Test (WCST). These children also demonstrated a reduced increase of the theta power localized in multiple brain regions, including various sectors of the frontal lobe at the late stage (i.e., 600 ms-900 ms poststimulus interval) but not the early stage (i.e., 250 ms-550 ms poststimulus interval) of the performance of the modified WCST. The suppressed late frontal theta activities were further shown to be significantly correlated with a poorer performance on the cognitive flexibility measures. Our findings suggest that abnormal activations of multiple cortical regions, especially the frontal lobe, form the neural basis of the cognitive flexibility deficits in children with ASD. In addition, we found an EEG marker of cognitive flexibility which could be used to monitor treatment outcomes objectively. (c) 2016 APA, all rights reserved).

Motivational deficits and cognitive test performance in schizophrenia.

PubMed

Fervaha, Gagan; Zakzanis, Konstantine K; Foussias, George; Graff-Guerrero, Ariel; Agid, Ofer; Remington, Gary

2014-09-01

Motivational and cognitive deficits are core features of schizophrenia, both closely linked with functional outcomes. Although poor effort and decreased motivation are known to affect performance on cognitive tests, the extent of this relationship is unclear in patients with schizophrenia. To evaluate the association between intrinsic motivation and cognitive test performance in patients with schizophrenia. Cross-sectional and 6-month prospective follow-up study performed at 57 sites in the United States, including academic and community medical treatment centers, participating in the Clinical Antipsychotic Trials of Intervention Effectiveness study. The primary sample included 431 stable patients with a DSM-IV diagnosis of schizophrenia currently receiving a stable medication regimen. Cognitive performance and intrinsic motivation were evaluated using a comprehensive neuropsychological test battery and a derived measure from the Heinrichs-Carpenter Quality of Life Scale, respectively. Symptom severity and functional status were also assessed. The primary outcome variable was global neurocognition. Individual domains of cognition were also evaluated for their association with motivation. Level of intrinsic motivation was significantly and positively correlated with global cognitive test performance, a relationship that held for each domain of cognition evaluated (correlation range, 0.20-0.34; P < .001). This association was found to be reliable after statistically accounting for positive, negative, depressive, and overall symptom severity (P < .05) and after accounting for community functioning (P < .001). The relationship between motivation and cognitive performance also remained significant after controlling for antipsychotic dose (P < .05). Prospective increase in motivation during the 6-month follow-up was also found to be significantly related to improvement in global cognitive performance (P < .05). The present findings provide strong

Tauopathy contributes to synaptic and cognitive deficits in a murine model for Alzheimer's disease.

PubMed

Stancu, Ilie-Cosmin; Ris, Laurence; Vasconcelos, Bruno; Marinangeli, Claudia; Goeminne, Léonie; Laporte, Vincent; Haylani, Laetitia E; Couturier, Julien; Schakman, Olivier; Gailly, Philippe; Pierrot, Nathalie; Kienlen-Campard, Pascal; Octave, Jean-Noël; Dewachter, Ilse

2014-06-01

Tau alterations are now considered an executor of neuronal demise and cognitive dysfunction in Alzheimer's disease (AD). Mouse models combining amyloidosis and tauopathy and their parental counterparts are important tools to further investigate the interplay of abnormal amyloid-β (Aβ) and Tau species in pathogenesis, synaptic and neuronal dysfunction, and cognitive decline. Here, we crossed APP/PS1 mice with 5 early-onset familial AD mutations (5xFAD) and TauP301S (PS19) transgenic mice, denoted F(+)/T(+) mice, and phenotypically compared them to their respective parental strains, denoted F(+)/T(-) and F(-)/T(+) respectively, as controls. We found dramatically aggravated tauopathy (~10-fold) in F(+)/T(+) mice compared to the parental F(-)/T(+) mice. In contrast, amyloidosis was unaltered compared to the parental F(+)/T(-) mice. Tauopathy was invariably and very robustly aggravated in hippocampal and cortical brain regions. Most important, F(+)/T(+) displayed aggravated cognitive deficits in a hippocampus-dependent spatial navigation task, compared to the parental F(+)/T(-) strain, while parental F(-)/T(+) mice did not display cognitive impairment. Basal synaptic transmission was impaired in F(+)/T(+) mice compared to nontransgenic mice and the parental strains (≥40%). Finally, F(+)/T(+) mice displayed a significant hippocampal atrophy (~20%) compared to nontransgenic mice, in contrast to the parental strains. Our data indicate for the first time that pathological Aβ species (or APP/PS1) induced changes in Tau contribute to cognitive deficits correlating with synaptic deficits and hippocampal atrophy in an AD model. Our data lend support to the amyloid cascade hypothesis with a role of pathological Aβ species as initiator and pathological Tau species as executor. © FASEB.

Pharmacological and genetic reversal of age-dependent cognitive deficits attributable to decreased presenilin function.

PubMed

McBride, Sean M J; Choi, Catherine H; Schoenfeld, Brian P; Bell, Aaron J; Liebelt, David A; Ferreiro, David; Choi, Richard J; Hinchey, Paul; Kollaros, Maria; Terlizzi, Allison M; Ferrick, Neal J; Koenigsberg, Eric; Rudominer, Rebecca L; Sumida, Ai; Chiorean, Stephanie; Siwicki, Kathleen K; Nguyen, Hanh T; Fortini, Mark E; McDonald, Thomas V; Jongens, Thomas A

2010-07-14

Alzheimer's disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced.

Optimizing Cognitive Function in Persons With Chronic Pain.

PubMed

Baker, Katharine S; Georgiou-Karistianis, Nellie; Gibson, Stephen J; Giummarra, Melita J

2017-05-01

Cognitive functioning is commonly disrupted in people living with chronic pain, yet it is an aspect of pain that is often not routinely assessed in pain management settings, and there is a paucity of research on treatments or strategies to alleviate the problem. The purpose of this review is to outline recent research on cognitive deficits seen in chronic pain, to give an overview of the mechanisms involved, advocate cognitive functioning as an important target for treatment in pain populations, and discuss ways in which it may be assessed and potentially remediated. A narrative review. There are several options for remediation, including compensatory, restorative, and neuromodulatory approaches to directly modify cognitive functioning, as well as physical, psychological, and medication optimization methods to target secondary factors (mood, sleep, and medications) that may interfere with cognition. We highlight the potential to enhance cognitive functions and identify the major gaps in the research literature.

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.

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

Cognitive deficits and educational loss in children with schistosome infection—A systematic review and meta-analysis

PubMed Central

Bustinduy, Amaya L.; Nkwata, Allan K.; Martinez, Leonardo; Pabalan, Noel; Boivin, Michael J.; King, Charles H.

2018-01-01

Background By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. Methodology/Principal findings This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains—learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5–19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The

Cognitive deficits and educational loss in children with schistosome infection-A systematic review and meta-analysis.

PubMed

Ezeamama, Amara E; Bustinduy, Amaya L; Nkwata, Allan K; Martinez, Leonardo; Pabalan, Noel; Boivin, Michael J; King, Charles H

2018-01-01

By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in

Cognitive deficit in methamphetamine users relative to childhood academic performance: link to cortical thickness.

PubMed

Dean, Andy C; Morales, Angelica M; Hellemann, Gerhard; London, Edythe D

2018-04-20

Individuals with cognitive problems may be predisposed to develop substance use disorders; therefore, differences in cognitive function between methamphetamine users and control participants may be attributable to premorbid factors rather than methamphetamine use. The goal of this study was to clarify the extent to which this is the case. Childhood academic transcripts were obtained for 37 methamphetamine-dependent adults and 41 control participants of similar educational level and premorbid IQ. Each participant completed a comprehensive cognitive battery and received a structural magnetic resonance imaging scan. Data from control participants and linear regression were used to develop a normative model to describe the relationship between childhood academic performance and scores on the cognitive battery. Using this model, cognitive performance of methamphetamine users was predicted from their premorbid academic scores. Results indicated that methamphetamine users' childhood grade point average was significantly lower than that of the control group (p < 0.05). Further, methamphetamine users' overall cognitive performance was lower than was predicted from their grade point average prior to methamphetamine use (p = 0.001), with specific deficits in attention/concentration and memory (ps < 0.01). Memory deficits were associated with lower whole-brain cortical thickness (p < 0.05). Thus, in addition to having an apparent premorbid weakness in cognition, methamphetamine users exhibit subsequent cognitive function that is significantly lower than premorbid estimates would predict. The results support the view that chronic methamphetamine use causes a decline in cognition and/or a failure to develop normative cognitive abilities, although aside from methamphetamine use per se, other drug use and unidentified factors likely contribute to the observed effects.

The allusive cognitive deficit in paranoia: the case for mental time travel or cognitive self-projection.

PubMed

Corcoran, R

2010-08-01

Delusional beliefs are characteristic of psychosis and, of the delusions, the paranoid delusion is the single most common type associated with psychosis. The many years of research focused on neurocognition in schizophrenia, using standardized neurocognitive tests, have failed to find conclusive cognitive deficits in relation to positive symptoms. However, UK-based psychological research has identified sociocognitive anomalies in relation to paranoid thinking in the form of theory of mind (ToM), causal reasoning and threat-related processing anomalies. Drawing from recent neuroscientific research on the default mode network, this paper asserts that the common theme running through the psychological tests that are sensitive to the cognitive impairment of paranoia is the need to cognitively project the self through time, referred to as mental time travel. Such an understanding of the cognitive roots of paranoid ideation provides a synthesis between psychological and biological accounts of psychosis while also retaining the powerful argument that understanding abnormal thinking must start with models of normal cognition. This is the core theme running through the cognitive psychological literature of psychiatric disorders that enables research from this area to inform psychological therapy.

The effects of sigma (σ1) receptor-selective ligands on muscarinic receptor antagonist-induced cognitive deficits in mice

PubMed Central

Malik, Maninder; Rangel-Barajas, Claudia; Sumien, Nathalie; Su, Chang; Singh, Meharvan; Chen, Zhenglan; Huang, Ren-Qi; Meunier, Johann; Maurice, Tangui; Mach, Robert H; Luedtke, Robert R

2015-01-01

Background and Purpose Cognitive deficits in patients with Alzheimer's disease, Parkinson's disease, traumatic brain injury and stroke often involve alterations in cholinergic signalling. Currently available therapeutic drugs provide only symptomatic relief. Therefore, novel therapeutic strategies are needed to retard and/or arrest the progressive loss of memory. Experimental Approach Scopolamine-induced memory impairment provides a rapid and reversible phenotypic screening paradigm for cognition enhancement drug discovery. Male C57BL/6J mice given scopolamine (1 mg·kg−1) were used to evaluate the ability of LS-1–137, a novel sigma (σ1) receptor-selective agonist, to improve the cognitive deficits associated with muscarinic antagonist administration. Key Results LS-1–137 is a high-affinity (Ki = 3.2 nM) σ1 receptor agonist that is 80-fold selective for σ1, compared with σ2 receptors. LS-1–137 binds with low affinity at D2-like (D2, D3 and D4) dopamine and muscarinic receptors. LS-1–137 was found to partially reverse the learning deficits associated with scopolamine administration using a water maze test and an active avoidance task. LS-1–137 treatment was also found to trigger the release of brain-derived neurotrophic factor from rat astrocytes. Conclusions and Implications The σ1 receptor-selective compound LS-1–137 may represent a novel candidate cognitive enhancer for the treatment of muscarinic receptor-dependent cognitive deficits. PMID:25573298

Emotional bias of cognitive control in adults with childhood attention-deficit/hyperactivity disorder

PubMed Central

Schulz, Kurt P.; Bédard, Anne-Claude V.; Fan, Jin; Clerkin, Suzanne M.; Dima, Danai; Newcorn, Jeffrey H.; Halperin, Jeffrey M.

2014-01-01

Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD) across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functional magnetic resonance imaging while performing a face emotion go/no-go task. Event-related analyses contrasted activation and functional connectivity for cognitive control collapsed over face valence and tested for variations in activation for response execution and inhibition as a function of face valence. Probands with childhood ADHD made fewer correct responses and inhibitions overall than comparison subjects, but demonstrated comparable effects of face emotion on response execution and inhibition. The two groups showed similar frontotemporal activation for cognitive control collapsed across face valence, but differed in the functional connectivity of the right dorsolateral prefrontal cortex, with fewer interactions with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in probands than in comparison subjects. Further, valence-dependent activation for response execution was seen in the amygdala, ventral striatum, subgenual cingulate cortex, and orbitofrontal cortex in comparison subjects but not in probands. The findings point to functional anomalies in limbic networks for both the valence-dependent biasing of cognitive control and the valence-independent cognitive control of face emotion processing in probands with childhood ADHD. This limbic dysfunction could impact cognitive control in emotional contexts and may contribute to the social and emotional problems associated with ADHD. PMID:24918067

Emotional bias of cognitive control in adults with childhood attention-deficit/hyperactivity disorder.

PubMed

Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Clerkin, Suzanne M; Dima, Danai; Newcorn, Jeffrey H; Halperin, Jeffrey M

2014-01-01

Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD) across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functional magnetic resonance imaging while performing a face emotion go/no-go task. Event-related analyses contrasted activation and functional connectivity for cognitive control collapsed over face valence and tested for variations in activation for response execution and inhibition as a function of face valence. Probands with childhood ADHD made fewer correct responses and inhibitions overall than comparison subjects, but demonstrated comparable effects of face emotion on response execution and inhibition. The two groups showed similar frontotemporal activation for cognitive control collapsed across face valence, but differed in the functional connectivity of the right dorsolateral prefrontal cortex, with fewer interactions with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in probands than in comparison subjects. Further, valence-dependent activation for response execution was seen in the amygdala, ventral striatum, subgenual cingulate cortex, and orbitofrontal cortex in comparison subjects but not in probands. The findings point to functional anomalies in limbic networks for both the valence-dependent biasing of cognitive control and the valence-independent cognitive control of face emotion processing in probands with childhood ADHD. This limbic dysfunction could impact cognitive control in emotional contexts and may contribute to the social and emotional problems associated with ADHD.

Edaravone alleviates cisplatin-induced neurobehavioral deficits via modulation of oxidative stress and inflammatory mediators in the rat hippocampus.

PubMed

Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Ahmed, Sahabuddin; Dwivedi, Durgesh; Saroha, Babita; Lahkar, Mangala

2016-11-15

Cisplatin is a chemotherapeutic agent used in the treatment of malignant tumors. A major clinical limitation of cisplatin is its potential toxic effects, including neurotoxicity. Edaravone, a potent free radical scavenger, has been reported to have the neuroprotective effect against neurological deficits. The aim of the present study was to determine the neuroprotective effect of edaravone against cisplatin-induced behavioral and biochemical anomalies in male Wistar rats. Our results showed that cisplatin (5mg/kg/week, i.p.) administration for seven weeks caused marked cognitive deficits and motor incoordination in rats. This was accompanied by oxido-nitrosative stress, neuroinflammation, NF-κB activation and down-regulation of Nrf2/HO-1 gene expression level in the hippocampus. Edaravone (10mg/kg/week, i.p.) treatment for seven weeks inhibited the aforementioned neurobehavioral and neurochemical deficits. Furthermore, edaravone was found to up-regulate the gene expression level of Nrf2/HO-1 and prevented the cisplatin-induced NF-κB activation. These findings demonstrated that oxido-nitrosative stress and inflammatory signaling mediators play a key role in the development of cisplatin-induced neurobehavioral deficits which were prevented by edaravone treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Teacher Beliefs and Responses toward Student Misbehavior: Influence of Cognitive Skill Deficits

ERIC Educational Resources Information Center

Hart, Susan Crandall; DiPerna, James Clyde

2017-01-01

This study aimed to examine whether having knowledge of student cognitive skill deficits changes teacher beliefs and responses in regard to classroom misbehavior. Teachers (N = 272) were randomly assigned to an experimental or control condition. Although teachers in both conditions read the same vignette describing a student's misbehavior, the…

Cognitive and behavior deficits in sickle cell mice are associated with profound neuropathologic changes in hippocampus and cerebellum

PubMed Central

Wang, Li; Almeida, Luis E.F.; de Souza Batista, Celia M.; Khaibullina, Alfia; Xu, Nuo; Albani, Sarah; Guth, Kira A.; Seo, Ji Sung; Quezado, Martha; Quezado, Zenaide M.N.

2015-01-01

Strokes are perhaps the most serious complications of sickle cell disease (SCD) and by the fifth decade occur in approximately 25% of patients. While most patients do not develop strokes, mounting evidence indicates that even without brain abnormalities on imaging studies, SCD patients can present profound neurocognitive dysfunction. We sought to evaluate the neurocognitive behavior profile of humanized SCD mice (Townes, BERK) and to identify hematologic and neuropathologic abnormalities associated with the behavioral alterations observed in these mice. Heterozygous and homozygous Townes mice displayed severe cognitive deficits shown by significant delays in spatial learning compared to controls. Homozygous Townes also had increased depression- and anxiety-like behaviors as well as reduced performance on voluntary wheel running compared to controls. Behavior deficits observed in Townes were also seen in BERKs. Interestingly, most deficits in homozygotes were observed in older mice and were associated with worsening anemia. Further, neuropathologic abnormalities including the presence of large bands of dark/pyknotic (shrunken) neurons in CA1 and CA3 fields of hippocampus and evidence of neuronal dropout in cerebellum were present in homozygotes but not control Townes. These observations suggest that cognitive and behavioral deficits in SCD mice mirror those described in SCD patients and that aging, anemia, and profound neuropathologic changes in hippocampus and cerebellum are possible biologic correlates of those deficits. These findings support using SCD mice for studies of cognitive deficits in SCD and point to vulnerable brain areas with susceptibility to neuronal injury in SCD and to mechanisms that potentially underlie those deficits. PMID:26462816

Cognitive processes in spatial mapping: Evidence from a developmental spatial deficit.

PubMed

Hatfield, Miles; Reilhac, Caroline; Cowley, Hannah; Chang, Elizabeth; McCloskey, Michael

2017-07-01

We report a case study of an adolescent girl (N.K.Y.) with a developmental deficit affecting spatial processing. In a simple spatial mapping task, N.K.Y. shows a striking dissociation: She succeeds in one variant of the experiment in which the stimuli are objects, but struggles in a structurally identical task with people as stimuli. We present evidence that this dissociation stems from a tendency to automatically adopt the spatial perspective of other people, but not objects-a phenomenon also observed in neurotypical individuals. When adopting another person's perspective, N.K.Y. imagines herself in the other's position, representing the other's left and right as if it were her own. N.K.Y.'s deficit in relating left-right information to her own body then disrupts her performance. Our results shed light on the nature of N.K.Y.'s deficit as well as the cognitive operations involved in spatial perspective taking.

Modeling cognitive deficits following neurodegenerative diseases and traumatic brain injuries with deep convolutional neural networks.

PubMed

Lusch, Bethany; Weholt, Jake; Maia, Pedro D; Kutz, J Nathan

2018-06-01

The accurate diagnosis and assessment of neurodegenerative disease and traumatic brain injuries (TBI) remain open challenges. Both cause cognitive and functional deficits due to focal axonal swellings (FAS), but it is difficult to deliver a prognosis due to our limited ability to assess damaged neurons at a cellular level in vivo. We simulate the effects of neurodegenerative disease and TBI using convolutional neural networks (CNNs) as our model of cognition. We utilize biophysically relevant statistical data on FAS to damage the connections in CNNs in a functionally relevant way. We incorporate energy constraints on the brain by pruning the CNNs to be less over-engineered. Qualitatively, we demonstrate that damage leads to human-like mistakes. Our experiments also provide quantitative assessments of how accuracy is affected by various types and levels of damage. The deficit resulting from a fixed amount of damage greatly depends on which connections are randomly injured, providing intuition for why it is difficult to predict impairments. There is a large degree of subjectivity when it comes to interpreting cognitive deficits from complex systems such as the human brain. However, we provide important insight and a quantitative framework for disorders in which FAS are implicated. Copyright © 2018 Elsevier Inc. All rights reserved.

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder

PubMed Central

Bilder, Robert M.; Loo, Sandra; McGough, James J.; Whelan, Fiona; Hellemann, Gerhard; Sugar, Catherine; Del’Homme, Melissa; Sturm, Alexandra; Cowen, Jennifer; Hanada, Grant; McCracken, James T.

2016-01-01

Objective Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. Method Children with ADHD (n = 182; age 7–14 years) completed an eight-week double blind randomized controlled trial with three arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A non-clinical comparison group (n = 93) had baseline testing, and a subset was re-tested 8 weeks later (n = 38). Analyses examined treatment effects in four cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables. Results The ADHD group showed impaired working memory relative to the non-clinical comparison group (effect size = −0.53 SD units). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN, but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group. Conclusion Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone, and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear necessary to achieve normalization of cognitive function in ADHD. Clinical trial registration information Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http

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.

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation

PubMed Central

Rubia, Katya

2018-01-01

This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly “switched off” hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation.

PubMed

Rubia, Katya

2018-01-01

This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly "switched off" hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near

Novel technology for treating individuals with aphasia and concomitant cognitive deficits.

PubMed

Cherney, Leora R; Halper, Anita S

2008-01-01

This article describes three individuals with aphasia and concomitant cognitive deficits who used state-of-theart computer software for training conversational scripts. Participants were assessed before and after 9 weeks of a computer script training program. For each participant, three individualized scripts were developed, recorded on the software, and practiced sequentially at home. Weekly meetings with the speech-language pathologist occurred to monitor practice and assess progress. Baseline and posttreatment scripts were audiotaped, transcribed, and compared to the target scripts for content, grammatical productivity, and rate of production of script-related words. Interviews were conducted at the conclusion of treatment. There was great variability in improvements across scripts, with two participants improving on two of their three scripts in measures of content, grammatical productivity, and rate of production of scriptrelated words. One participant gained more than 5 points on the Aphasia Quotient of the Western Aphasia Battery. Five positive themes were consistently identified from exit interviews: increased verbal communication, improvements in other modalities and situations, communication changes noticed by others, increased confidence, and satisfaction with the software. Computer-based script training potentially may be an effective intervention for persons with chronic aphasia and concomitant cognitive deficits.

Evaluating the Specificity of Cognitive Control Deficits in Schizophrenia Using Antisaccades, Functional Magnetic Resonance Imaging, and Healthy Individuals With Poor Cognitive Control.

PubMed

Rodrigue, Amanda L; Schaeffer, David J; Pierce, Jordan E; Clementz, Brett A; McDowell, Jennifer E

2018-01-01

Cognitive control impairments in schizophrenia (SZ) can be evaluated using antisaccade tasks and functional magnetic resonance imaging (fMRI). Studies, however, often compare people with SZ to high performing healthy people, making it unclear if antisaccade-related disruptions are specific to the disease or due to generalized deficits in cognitive control. We included two healthy comparison groups in addition to people with SZ: healthy people with high cognitive control (HCC), who represent a more typical comparison group, and healthy people with low cognitive control (LCC), who perform similarly on antisaccade measures as people with SZ. Using two healthy comparison groups may help determine which antisaccade-related deficits are specific to SZ (distinguish SZ from LCC and HCC groups) and which are due to poor cognitive control (distinguish the LCC and SZ groups from the HCC group). People with SZ and healthy people with HCC or LCC performed an antisaccade task during fMRI acquisition. LCC and SZ groups showed under-activation of saccade circuitry. SZ-specific disruptions were observed in the left superior temporal gyrus and insula during error trials (suppression of activation in the SZ group compared to the LCC and HCC group). Differences related to antisaccade errors may distinguish people with SZ from healthy people with LCC.

The Outcome of a Social Cognitive Training for Mainstream Adolescents with Social Communication Deficits in a Chinese Community

ERIC Educational Resources Information Center

Lee, Kathy Y. S.; Crooke, Pamela J.; Lui, Aster L. Y.; Kan, Peggy P. K.; Mark, Yuen-mai; van Hasselt, Charles Andrew; Tong, Michael C. F.

2016-01-01

The use of cognitive-based strategies for improving social communication behaviours for individuals who have solid language and cognition is an important question. This study investigated the outcome of teaching Social Thinking®, a framework based in social-cognition, to Chinese adolescents with social communication deficits. Thirty-nine students…

Understanding Cognitive Deficits in Parkinson's Disease: Lessons from Preclinical Animal Models

ERIC Educational Resources Information Center

Solari, Nicola; Bonito-Oliva, Alessandra; Fisone, Gilberto; Brambilla, Riccardo

2013-01-01

Parkinson's disease (PD) has been, until recently, mainly defined by the presence of characteristic motor symptoms, such as rigidity, tremor, bradykinesia/akinesia, and postural instability. Accordingly, pharmacological and surgical treatments have so far addressed these motor disturbances, leaving nonmotor, cognitive deficits an unmet…

Inducing Autophagy by Rapamycin Before, but Not After, the Formation of Plaques and Tangles Ameliorates Cognitive Deficits

PubMed Central

Majumder, Smita; Richardson, Arlan; Strong, Randy; Oddo, Salvatore

2011-01-01

Previous studies have shown that inducing autophagy ameliorates early cognitive deficits associated with the build-up of soluble amyloid-β (Aβ). However, the effects of inducing autophagy on plaques and tangles are yet to be determined. While soluble Aβ and tau represent toxic species in Alzheimer's disease (AD) pathogenesis, there is well documented evidence that plaques and tangles also are detrimental to normal brain function. Thus, it is critical to assess the effects of inducing autophagy in an animal model with established plaques and tangles. Here we show that rapamycin, when given prophylactically to 2-month-old 3xTg-AD mice throughout their life, induces autophagy and significantly reduces plaques, tangles and cognitive deficits. In contrast, inducing autophagy in 15-month-old 3xTg-AD mice, which have established plaques and tangles, has no effects on AD-like pathology and cognitive deficits. In conclusion, we show that autophagy induction via rapamycin may represent a valid therapeutic strategy in AD when administered early in the disease progression. PMID:21980451

Emotion recognition and cognitive empathy deficits in adolescent offenders revealed by context-sensitive tasks

PubMed Central

Gonzalez-Gadea, Maria Luz; Herrera, Eduar; Parra, Mario; Gomez Mendez, Pedro; Baez, Sandra; Manes, Facundo; Ibanez, Agustin

2014-01-01

Emotion recognition and empathy abilities require the integration of contextual information in real-life scenarios. Previous reports have explored these domains in adolescent offenders (AOs) but have not used tasks that replicate everyday situations. In this study we included ecological measures with different levels of contextual dependence to evaluate emotion recognition and empathy in AOs relative to non-offenders, controlling for the effect of demographic variables. We also explored the influence of fluid intelligence (FI) and executive functions (EFs) in the prediction of relevant deficits in these domains. Our results showed that AOs exhibit deficits in context-sensitive measures of emotion recognition and cognitive empathy. Difficulties in these tasks were neither explained by demographic variables nor predicted by FI or EFs. However, performance on measures that included simpler stimuli or could be solved by explicit knowledge was either only partially affected by demographic variables or preserved in AOs. These findings indicate that AOs show contextual social-cognition impairments which are relatively independent of basic cognitive functioning and demographic variables. PMID:25374529

Lack of association between mutation size and cognitive/behavior deficits in fragile X males: A brief report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisch, G.S.; Carpenter, N.; Simensen, R.

1996-08-09

Previously, researchers reported molecular-neurobehavioral or molecular-cognitive associations in individuals with fra(X) (fragile X) mutation. However, not all investigators have noted molecular-behavioral relationships. Consequently, we examined prospectively 30 fra(X) males age 3-15 years from four testing sites to determine whether there was a relationship between mutation size and degree of either cognitive or adaptive behavior deficit. To measure cognitive abilities, all individuals were administered the Stanford-Binet (4th edition) IQ test. To evaluate adaptive behavior (DQ) skills, all individuals were assessed using the Vineland Adaptive Behavior Scale. To determine fra(X) status, genomic DNA from all individuals was extracted and digested with EcoRImore » and EagI restriction enzymes. Southern blots were prepared and hybridized with the pE5.1 probe. The Pearson correlation coefficient between full mutation size and composite IQ score revealed a non-significant, near-zero association (r = 0.06; P > .76). The Pearson coefficient between mutation size and DQ also showed a non-significant, near-zero association (r = 0.06; P >.73). We conclude that while fra(X) mutation produces cognitive and behavior deficits in males who inherit the defective gene, there is no relationship between mutation size and degree of deficit. 14 refs., 2 figs.« less

Understanding the effects of stimulant medications on cognition in individuals with attention-deficit hyperactivity disorder: a decade of progress.

PubMed

Swanson, James; Baler, Ruben D; Volkow, Nora D

2011-01-01

The use of stimulant drugs for the treatment of children with attention-deficit hyperactivity disorder (ADHD) is one of the most widespread pharmacological interventions in child psychiatry and behavioral pediatrics. This treatment is well grounded on controlled studies showing efficacy of low oral doses of methylphenidate and amphetamine in reducing the behavioral symptoms of the disorder as reported by parents and teachers, both for the cognitive (inattention and impulsivity) and non-cognitive (hyperactivity) domains. Our main aim is to review the objectively measured cognitive effects that accompany the subjectively assessed clinical responses to stimulant medications. Recently, methods from the cognitive neurosciences have been used to provide information about brain processes that underlie the cognitive deficits of ADHD and the cognitive effects of stimulant medications. We will review some key findings from the recent literature, and then offer interpretations of the progress that has been made over the past decade in understanding the cognitive effects of stimulant medication on individuals with ADHD.

Late-Life Depressive Symptoms and Lifetime History of Major Depression: Cognitive Deficits are Largely Due to Incipient Dementia rather than Depression.

PubMed

Heser, Kathrin; Bleckwenn, Markus; Wiese, Birgitt; Mamone, Silke; Riedel-Heller, Steffi G; Stein, Janine; Lühmann, Dagmar; Posselt, Tina; Fuchs, Angela; Pentzek, Michael; Weyerer, Siegfried; Werle, Jochen; Weeg, Dagmar; Bickel, Horst; Brettschneider, Christian; König, Hans-Helmut; Maier, Wolfgang; Scherer, Martin; Wagner, Michael

2016-08-01

Late-life depression is frequently accompanied by cognitive impairments. Whether these impairments indicate a prodromal state of dementia, or are a symptomatic expression of depression per se is not well-studied. In a cohort of very old initially non-demented primary care patients (n = 2,709, mean age = 81.1 y), cognitive performance was compared between groups of participants with or without elevated depressive symptoms and with or without subsequent dementia using ANCOVA (adjusted for age, sex, and education). Logistic regression analyses were computed to predict subsequent dementia over up to six years of follow-up. The same analytical approach was performed for lifetime major depression. Participants with elevated depressive symptoms without subsequent dementia showed only small to medium cognitive deficits. In contrast, participants with depressive symptoms with subsequent dementia showed medium to very large cognitive deficits. In adjusted logistic regression models, learning and memory deficits predicted the risk for subsequent dementia in participants with depressive symptoms. Participants with a lifetime history of major depression without subsequent dementia showed no cognitive deficits. However, in adjusted logistic regression models, learning and orientation deficits predicted the risk for subsequent dementia also in participants with lifetime major depression. Marked cognitive impairments in old age depression should not be dismissed as "depressive pseudodementia", but require clinical attention as a possible sign of incipient dementia. Non-depressed elderly with a lifetime history of major depression, who remained free of dementia during follow-up, had largely normal cognitive performance.

Cognitive remediation of attention deficits following acquired brain injury: A systematic review and meta-analysis.

PubMed

Virk, Sohaib; Williams, Tracey; Brunsdon, Ruth; Suh, Flora; Morrow, Angie

2015-01-01

Attention deficits are common after acquired brain injury (ABI) and adversely impact academic, vocational and social outcomes. The role of cognitive interventions in post-ABI attention rehabilitation remains unclear. To evaluate effectiveness of cognitive interventions in treating attention deficits following ABI and to explore differences in treatment effect between ABI etiologies. MEDLINE, EMBASE, PsycINFO and CENTRAL databases were searched for randomized controlled trials (RCTs). Studies were selected by three reviewers. Study quality was assessed using Cochrane Collaboration tool for RCTs. Effect sizes (Hedge's g) for each attentional domain were meta-analyzed with subgroup analysis by ABI etiology. Twelve RCTs with 584 participants were included, representing individuals with stroke, traumatic brain injury (TBI) and CNS-impacting malignancy. Cognitive rehabilitation improved divided attention in stroke survivors (g 0.67; 95% confidence interval, 0.35-0.98; p <  0.0001) but not other ABI populations. Sustained, selective and alternating attention, and inhibition were not significantly improved in any ABI population. Follow-up data showed no evidence of long-term benefit. Cognitive rehabilitation resulted in short-term improvements in divided attention following stroke, but not after TBI or CNS-impacting malignancy. Cognitive interventions did not significantly improve other attentional domains in participants with stroke, TBI or CNS-impacting malignancy.

Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: A preliminary investigation.

PubMed

McLean, Samantha L; Harte, Michael K; Neill, Joanna C; Young, Andrew Mj

2017-06-01

Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR). Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for 7 days, followed by 7 days washout. In vivo microdialysis was carried out prior to, during and following the NOR task. Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial ( p < 0.01). scPCP produced a significant deficit in NOR ( p < 0.05 vs. control) and no PFC dopamine increase was observed. These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology.

Cognitive remission: a novel objective for the treatment of major depression?

PubMed

Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A; Maes, Michael; Fernandes, Brisa S; Berk, Michael; Carvalho, André F

2016-01-22

Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.

The alteration of autophagy and apoptosis in the hippocampus of rats with natural aging-dependent cognitive deficits.

PubMed

Yu, Yang; Feng, Linjing; Li, Junnan; Lan, Xiaoxin; A, Lixiang; Lv, Xiaoyan; Zhang, Ming; Chen, Li

2017-09-15

The present study was aim to explore aging-dependent changes in hippocampal autophagy and apoptosis in a natural aging rat model from adult to old stages and to discover a suitable age for treating neurodegenerative diseases. Wistar rats at 5, 18 and 24months of age were used to mimic the adulthood, initial old, and old phases, respectively. The learning and cognitive ability of the rats was detected by the Morris water maze test. Morphological changes in the hippocampus were observed. Expressions of apoptosis and autophagy-related proteins were examined by Western blot. The adult group (5months) exhibited high levels of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II and cell survival, maintaining normal learning and cognitive function and integrated hippocampal morphology. The initial old group (18 months) presented a reduced number of neurons and cognitive deficits, and exhibited high levels of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to the adult group. The old group (24 months) exhibited a high level of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and a low level of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to its younger group, as well as significant neuronal death and cognitive deficits. The degree of autophagy was generally consistent with its negative regulator, the PI3K/Akt/mTOR axis, in all groups. Our data suggest that cognitive deficits are first observed in the initial old stage. The levels of autophagy and apoptosis tend to be opposite in the adult and old phases. High levels of autophagy and apoptosis coexist in the initial old stage. Our study indicates that up-regulation of autophagy in the initial old phase to anti-cognitive deficits must be further evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Mice heterozygous for an inactivated allele of the schizophrenia associated Brd1 gene display selective cognitive deficits with translational relevance to schizophrenia.

PubMed

Qvist, Per; Rajkumar, Anto P; Redrobe, John P; Nyegaard, Mette; Christensen, Jane H; Mors, Ole; Wegener, Gregers; Didriksen, Michael; Børglum, Anders D

2017-05-01

Schizophrenia is a debilitating brain disorder characterized by disturbances of emotion, perception and cognition. Cognitive impairments predict functional outcome in schizophrenia and are detectable even in the prodromal stage of the disorder. However, our understanding of the underlying neurobiology is limited and procognitive treatments remain elusive. We recently demonstrated that mice heterozygous for an inactivated allele of the schizophrenia-associated Brd1 gene (Brd1 +/ - mice) display behaviors reminiscent of schizophrenia, including impaired social cognition and long-term memory. Here, we further characterize performance of these mice by following the preclinical guidelines recommended by the 'Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)' and 'Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS)' initiatives to maximize translational value. Brd1 +/- mice exhibit relational encoding deficits, compromised working and long term memory, as well as impaired executive cognitive functioning with cognitive behaviors relying on medial prefrontal cortex being particularly affected. Akin to patients with schizophrenia, the cognitive deficits displayed by Brd1 +/ - mice are not global, but selective. Our results underline the value of Brd1 +/ - mice as a promising tool for studying the neurobiology of cognitive deficits in schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive Training and Work Therapy for the Treatment of Verbal Learning and Memory Deficits in Veterans With Alcohol Use Disorders.

PubMed

Bell, Morris D; Vissicchio, Nicholas A; Weinstein, Andrea J

2016-01-01

This study focused on the efficacy of cognitive training for verbal learning and memory deficits in a population of older veterans with alcohol use disorders. Veterans with alcohol use disorders, who were in outpatient treatment at VA facilities and in early-phase recovery (N = 31), were randomized to receive a three-month trial of daily cognitive training plus work therapy (n = 15) or work therapy alone (n = 16), along with treatment as usual. Participants completed assessments at baseline and at three- and six-month follow-ups; the Hopkins Verbal Learning Task (HVLT) was the primary outcome measure. Participants were primarily male (97%) and in their mid-50s (M = 55.16, SD = 5.16) and had been sober for 1.64 (SD = 2.81) months. Study retention was excellent (91% at three-month follow-up) and adherence to treatment in both conditions was very good. On average, participants in the cognitive training condition had more than 41 hours of cognitive training, and both conditions had more than 230 hours of productive activity. HVLT results at three-month follow-up revealed significant condition effects favoring cognitive training for verbal learning (HVLT Trial-3 T-score, p < .005, Cohen's d = 1.3) and verbal memory (HVLT Total T-score, p < .01, Cohen's d = 1.1). Condition effects were sustained at six-month follow-up. At baseline, 55.9% of participants showed a significant deficit in verbal memory and 58.8% showed a deficit in verbal learning compared with a premorbid estimate of verbal IQ. At three-month follow-up there was a significant reduction in the number of participants in the cognitive training condition with clinically significant verbal memory deficits (p < .01, number needed to treat = 3.0) compared with the work therapy alone condition and a trend toward significance for verbal learning deficits, which was not sustained at six-month follow-up. This National Institute on Drug Abuse-funded pilot study demonstrates that cognitive training within the context

Face-Name Associative Recognition Deficits in Subjective Cognitive Decline and Mild Cognitive Impairment.

PubMed

Polcher, Alexandra; Frommann, Ingo; Koppara, Alexander; Wolfsgruber, Steffen; Jessen, Frank; Wagner, Michael

2017-01-01

There is a need for more sensitive neuropsychological tests to detect subtle cognitive deficits emerging in the preclinical stage of Alzheimer's disease (AD). Associative memory is a cognitive function supported by the hippocampus and affected early in the process of AD. We developed a short computerized face-name associative recognition test (FNART) and tested whether it would detect memory impairment in memory clinic patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). We recruited 61 elderly patients with either SCD (n = 32) or MCI (n = 29) and 28 healthy controls (HC) and compared performance on FNART, self-reported cognitive deterioration in different domains (ECog-39), and, in a reduced sample (n = 46), performance on the visual Paired Associates Learning of the CANTAB battery. A significant effect of group on FNART test performance in the total sample was found (p < 0.001). Planned contrasts indicated a significantly lower associative memory performance in the SCD (p = 0.001, d = 0.82) and MCI group (p < 0.001, d = 1.54), as compared to HCs, respectively. The CANTAB-PAL discriminated only between HC and MCI, possibly because of reduced statistical power. Adjusted for depression, performance on FNART was significantly related to ECog-39 Memory in SCD patients (p = 0.024) but not in MCI patients. Associative memory is substantially impaired in memory clinic patients with SCD and correlates specifically with memory complaints at this putative preclinical stage of AD. Further studies will need to examine the predictive validity of the FNART in SCD patients with regard to longitudinal (i.e., conversion to MCI/AD) and biomarker outcomes.

Parsing cognitive and emotional empathy deficits for negative and positive stimuli in frontotemporal dementia.

PubMed

Oliver, Lindsay D; Mitchell, Derek G V; Dziobek, Isabel; MacKinley, Julia; Coleman, Kristy; Rankin, Katherine P; Finger, Elizabeth C

2015-01-01

Behavioural variant frontotemporal dementia (bvFTD) is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe atrophy primarily affecting social cognition and emotion, including loss of empathy. Many consider empathy to be a multidimensional construct, including cognitive empathy (the ability to adopt and understand another's perspective) and emotional empathy (the capacity to share another's emotional experience). Cognitive and emotional empathy deficits have been associated with bvFTD; however, little is known regarding the performance of patients with bvFTD on behavioural measures of emotional empathy, and whether empathic responses differ for negative versus positive stimuli. 24 patients with bvFTD and 24 healthy controls completed the Multifaceted Empathy Test (MET; Dziobek et al., 2008), a performance-based task that taps both cognitive and emotional facets of empathy, and allows for the discrimination of responses to negative versus positive realistic images. MET scores were also compared with caregiver ratings of patient behaviour on the Interpersonal Reactivity Index, which assesses patients' everyday demonstrations of perspective taking and empathic concern. Patients with bvFTD were less accurate than controls at inferring mental states for negative and positive stimuli. They also demonstrated lower levels of shared emotional experience, more positive emotional reactions, and diminished arousal to negative social stimuli relative to controls. Patients showed reduced emotional reactions to negative non-social stimuli as well. Lastly, the MET and IRI measures of emotional empathy were found to be significantly correlated within the bvFTD group. The results suggest that patients with bvFTD show a global deficit in cognitive empathy, and deficient emotional empathy for negative, but not positive, experiences. Further, a generalized emotional processing impairment for negative stimuli was observed, which could contribute to the

Berberine alleviates postoperative cognitive dysfunction by suppressing neuroinflammation in aged mice.

PubMed

Zhang, Zhijie; Li, Xiuhua; Li, Fayin; An, Lijun

2016-09-01

Postoperative cognitive dysfunction (POCD) is a significant cause of morbidity after surgery, especially for the elderly. Accumulating evidence has demonstrated that neuroinflammation plays a key role in the pathogenesis of POCD. Thus, we hypothesized that berberine, an isoquinoline alkaloid with anti-inflammatory effects, could improve surgery-induced cognitive impairment. Twenty-month-old male C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to mimic the clinical human abdominal surgery. For the interventional studies, mice received berberine (10mg/kg) or vehicle intraperitoneally. For the in vitro study, we examined the effects of berberine on lipopolysaccharide (LPS)-induced inflammatory mediators by cultured BV2 cells. Behavioral tests, expressions of IBA1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were performed at the indicated time points. In the present study, we showed that surgery impaired the contextual fear memory, as evidenced by the significantly decreased freezing time to the context. This behavioral change coincided with marked increases in IBA1, TNF-α, IL-1β, and IL-6 in the prefrontal cortex and hippocampus only at 24h but not 7 d after surgery. In BV2 cells, LPS induced significantly increased TNF-α and IL-1β expressions. Notably, berberine treatment rescued surgery-induced cognitive impairment and inhibited the release of IBA1, IL-1β, and IL-6 in the hippocampus. In line with the in vivo study, berberine treatment suppressed LPS-stimulated production of TNF-α and IL-1β in BV2 cells. In conclusion, our study suggests that berberine could alleviate POCD by suppressing neuroinflammation in aged mice. Copyright © 2016 Elsevier B.V. All rights reserved.

Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity.

PubMed

Mahati, K; Bhagya, V; Christofer, T; Sneha, A; Shankaranarayana Rao, B S

2016-10-01

Severe depression compromises structural and functional integrity of the brain and results in impaired learning and memory, maladaptive synaptic plasticity as well as degenerative changes in the hippocampus and amygdala. The precise mechanisms underlying cognitive dysfunctions in depression remain largely unknown. On the other hand, enriched environment (EE) offers beneficial effects on cognitive functions, synaptic plasticity in the hippocampus. However, the effect of EE on endogenous depression associated cognitive dysfunction has not been explored. Accordingly, we have attempted to address this issue by investigating behavioural, structural and synaptic plasticity mechanisms in an animal model of endogenous depression after exposure to enriched environment. Our results demonstrate that depression is associated with impaired spatial learning and enhanced anxiety-like behaviour which is correlated with hypotrophy of the dentate gyrus and amygdalar hypertrophy. We also observed a gross reduction in the hippocampal long-term potentiation (LTP). We report a complete behavioural recovery with reduced indices of anhedonia and behavioural despair, reduced anxiety-like behaviour and improved spatial learning along with a complete restoration of dentate gyrus and amygdalar volumes in depressive rats subjected to EE. Enrichment also facilitated CA3-Schaffer collateral LTP. Our study convincingly proves that depression-induces learning deficits and impairs hippocampal synaptic plasticity. It also highlights the role of environmental stimuli in restoring depression-induced cognitive deficits which might prove vital in outlining more effective strategies to treat major depressive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder.

PubMed

Bilder, Robert M; Loo, Sandra K; McGough, James J; Whelan, Fiona; Hellemann, Gerhard; Sugar, Catherine; Del'Homme, Melissa; Sturm, Alexandra; Cowen, Jennifer; Hanada, Grant; McCracken, James T

2016-08-01

Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. Children with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A nonclinical comparison group (n = 93) had baseline testing, and a subset was retested 8 weeks later (n = 38). Analyses examined treatment effects in 4 cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables. The ADHD group showed impaired working memory relative to the nonclinical comparison group (effect size = -0.53 SD unit). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group. Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear to be necessary to achieve normalization of cognitive function in ADHD. Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273. Copyright © 2016 American Academy of Child and Adolescent

Disrupted white matter structure underlies cognitive deficit in hypertensive patients.

PubMed

Li, Xin; Ma, Chao; Sun, Xuan; Zhang, Junying; Chen, Yaojing; Chen, Kewei; Zhang, Zhanjun

2016-09-01

Hypertension is considered a risk factor of cognitive impairments and could result in white matter changes. Current studies on hypertension-related white matter (WM) changes focus only on regional changes, and the information about global changes in WM structure network is limited. We assessed the cognitive function in 39 hypertensive patients and 37 healthy controls with a battery of neuropsychological tests. The WM structural networks were constructed by utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. The direct and indirect correlations among cognitive impairments, brain WM network disruptions and hypertension were analyzed with structural equation modelling (SEM). Hypertensive patients showed deficits in executive function, memory and attention compared with controls. An aberrant connectivity of WM networks was found in the hypertensive patients (P Eglob = 0.005, P Lp = 0.005), especially in the frontal and parietal regions. Importantly, SEM analysis showed that the decline of executive function resulted from aberrant WM networks in hypertensive patients (p = 0.3788, CFI = 0.99). These results suggest that the cognitive decline in hypertensive patients was due to frontal and parietal WM disconnections. Our findings highlight the importance of brain protection in hypertension patients. • Hypertension has a negative effect on the performance of the cognitive domains • Reduced efficiencies of white matter networks were shown in hypertension • Disrupted white matter networks are responsible for poor cognitive function in hypertension.

Polygenic risk score, genome-wide association, and gene set analyses of cognitive domain deficits in schizophrenia.

PubMed

Nakahara, Soichiro; Medland, Sarah; Turner, Jessica A; Calhoun, Vince D; Lim, Kelvin O; Mueller, Bryon A; Bustillo, Juan R; O'Leary, Daniel S; Vaidya, Jatin G; McEwen, Sarah; Voyvodic, James; Belger, Aysenil; Mathalon, Daniel H; Ford, Judith M; Guffanti, Guia; Macciardi, Fabio; Potkin, Steven G; van Erp, Theo G M

2018-06-12

This study assessed genetic contributions to six cognitive domains, identified by the MATRICS Cognitive Consensus Battery as relevant for schizophrenia, cognition-enhancing, clinical trials. Psychiatric Genomics Consortium Schizophrenia polygenic risk scores showed significant negative correlations with each cognitive domain. Genome-wide association analyses identified loci associated with attention/vigilance (rs830786 within HNF4G), verbal memory (rs67017972 near NDUFS4), and reasoning/problem solving (rs76872642 within HDAC9). Gene set analysis identified unique and shared genes across cognitive domains. These findings suggest involvement of common and unique mechanisms across cognitive domains and may contribute to the discovery of new therapeutic targets to treat cognitive deficits in schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Cognitive Deficits in Problematic Drinkers with and without Mild to Borderline Intellectual Disability

ERIC Educational Resources Information Center

van Duijvenbode, Neomi; Didden, Robert; VanDerNagel, Joanne E. L.; Korzilius, Hubert P. L. M.; Engels, Rutger C. M. E.

2018-01-01

We examined cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability (MBID). Problematic drinkers were expected to show a significantly lower estimated performance IQ (PIQ), but not a lower estimated verbal IQ (VIQ), compared to light drinkers. Participants (N = 474) were divided into four groups based…

Novel Technology for Treating Individuals with Aphasia and Concomitant Cognitive Deficits

PubMed Central

Cherney, Leora R.; Halper, Anita S.

2009-01-01

Purpose This article describes three individuals with aphasia and concomitant cognitive deficits who used state-of-the-art computer software for training conversational scripts. Method Participants were assessed before and after 9 weeks of a computer script training program. For each participant, three individualized scripts were developed, recorded on the software, and practiced sequentially at home. Weekly meetings with the speech-language pathologist occurred to monitor practice and assess progress. Baseline and posttreatment scripts were audiotaped, transcribed, and compared to the target scripts for content, grammatical productivity, and rate of production of script-related words. Interviews were conducted at the conclusion of treatment. Results There was great variability in improvements across scripts, with two participants improving on two of their three scripts in measures of content, grammatical productivity, and rate of production of script-related words. One participant gained more than 5 points on the Aphasia Quotient of the Western Aphasia Battery. Five positive themes were consistently identified from exit interviews: increased verbal communication, improvements in other modalities and situations, communication changes noticed by others, increased confidence, and satisfaction with the software. Conclusion Computer-based script training potentially may be an effective intervention for persons with chronic aphasia and concomitant cognitive deficits. PMID:19158062

[Postoperative cognitive deficits].

PubMed

Kalezić, Nevena; Dimitrijević, Ivan; Leposavić, Ljubica; Kocica, Mladen; Bumbasirević, Vesna; Vucetić, Cedomir; Paunović, Ivan; Slavković, Nemanja; Filimonović, Jelena

2006-01-01

Cognitive dysfunctions are relatively common in postoperative and critically ill patients. This complication not only compromises recovery after surgery, but, if persistent, it minimizes and compromises surgery itself. Risk factors of postoperative cognitive disorders can be divided into age and comorbidity dependent, and those related to anesthesia and surgery. Cardiovascular, orthopedic and urologic surgery carries high risk of postoperative cognitive dysfunction. It can also occur in other types of surgical treatment, especially in elderly. Among risk factors of cognitive disorders, associated with comorbidity, underlying psychiatric and neurological disorders, substance abuse and conditions with elevation of intracranial pressure are in the first place in postoperative patients. Preoperative and perioperative predisposing conditions for cognitive dysfunction and their incidence were described in our paper. These are: geriatric patients, patients with substance abuse, preexisting psychiatric or cognitive disorders, neurologic disease with high intracranial pressure, cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent porphyria, operation type, brain hypoxia, changes in blood glucose level, electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative awareness. For each of these factors, evaluation, prevention and treatment strategies were suggested, with special regard on anesthetic technique.

Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Ontiveros, Esperanza; Gómez-Garza, Gilberto; Barragán-Mejía, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R; Henríquez-Roldán, Carlos; Pérez-Guillé, Beatriz; Torres-Jardón, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C; Engle, Randall W

2008-11-01

Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.

Comparison of the recovery patterns of language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke.

PubMed

Vukovic, Mile; Vuksanovic, Jasmina; Vukovic, Irena

2008-01-01

In this study we investigated the recovery patterns of language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke. The correlation of specific language functions and cognitive functions was analyzed in the acute phase and 6 months later. Significant recovery of the tested functions was observed in both groups. However, in patients with post-traumatic language processing deficits the degree of recovery of most language functions and some cognitive functions was higher. A significantly greater correlation was revealed within language and cognitive functions, as well as between language functions and other aspects of cognition in patients with post-traumatic language processing deficits than in patients with aphasia following a stroke. Our results show that patients with post-traumatic language processing deficits have a different recovery pattern and a different pattern of correlation between language and cognitive functions compared to patients with aphasia following a stroke. (1) Better understanding of the differences in recovery of language and cognitive functions in patients who have suffered strokes and those who have experienced traumatic brain injury. (2) Better understanding of the relationship between language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke. (3) Better understanding of the factors influencing recovery.

Naringin ameliorates cognitive deficits via oxidative stress, proinflammatory factors and the PPARγ signaling pathway in a type 2 diabetic rat model.

PubMed

Qi, Zhonghua; Xu, Yinghui; Liang, Zhanhua; Li, Sheng; Wang, Jie; Wei, Yi; Dong, Bin

2015-11-01

Naringenin is a flavonoid polyphenolic compound, which facilitates the removal of free radicals, oxidative stress and inflammation. The present study aimed to obtain a better understanding of the effects of curcumin on the regulation of diabetes‑associated cognitive decline, and its underlying mechanisms. An experimental diabetes mellitus (DM) rat model was induced by streptozoticin (50 mg/kg). Following treatment with naringin (100 and 200 mg/kg) for 16 weeks, the body weight and blood glucose levels of the DM rats were measured. A morris water maze test was used to analyze the effects of naringin on the cognitive deficit of the DM rats. The levels of oxidative stress, proinflammatory factors, caspase‑3 and caspase‑9, and the protein expression of peroxisome proliferator‑activated receptor γ (PPARγ) were quantified in the DM rats using a commercially‑available kit and western blot assay, respectively. In addition, a GW9662 PPARγ inhibitor (0.3 mg/kg) was administered to the DM rats to determine whether PPARγ affected the effects of naringin on the cognitive deficit of the DM rats. The results demonstrated that naringin increased the body weight, blood glucose levels, and cognitive deficits of the DM rats. The levels of oxidative stress and proinflammatory factors in the naringin‑treated rats were significantly lower, compared with those of the DM rats. In addition, naringin activated the protein expression of PPARγ, and administration of the PPARγ inhibitor decreased the protein expression of PPARγ, and attenuated the effects of naringin on cognitive deficit. The results also demonstrated that naringin decreased the expression levels of caspase‑3 and caspase‑9 in the DM rats. These results suggested that naringin ameliorated cognitive deficits via oxidative stress, proinflammatory factors and the PPARγ signaling pathway in the type 2 diabetic rat model. Furthermore, oxidative stress, proinflammatory factors and PPARγ signaling may be

Cognitive deficits in obese persons with and without binge eating disorder. Investigation using a mental flexibility task.

PubMed

Mobbs, Olivia; Iglesias, Katia; Golay, Alain; Van der Linden, Martial

2011-08-01

Studies suggest that cognitive deficits and attentional biases play a role in the development and maintenance of obesity and eating disorders. In this study, we simultaneously examine attentional biases, as well as inhibitory control and mental flexibility, which are keys to controlling unwanted behaviors and thoughts in obese patients with and without binge eating disorder. 16 obese patients with binge eating disorder and 16 patients without binge eating disorder were compared with 16 normal-weight controls on a "food/body-mental flexibility task", which allows the investigation of inhibitory control, mental flexibility and attention for stimuli related to the body and food. All obese patients made significantly more errors (i.e., pressing a key when a distracter displayed) and more omissions (i.e., not pressing a key when a target displayed) than controls in both food and body sections of the task. Obese participants with binge eating disorder made significantly more errors and omissions than those without binge eating disorder. No difference between groups was found concerning mental flexibility and cognitive biases for food- and body-related targets. These results suggest that obese patients have a general inhibition problem and difficulty focusing attention, which do not depend on the types of stimuli processed. The results also suggest that these cognitive deficits are more severe in obese patients with binge eating disorder, which indicates that there is a continuum of increasing inhibition and cognitive problems with increasingly disordered eating. These cognitive deficits may contribute to problematic eating behaviors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Social Cognition Deficits: The Key to Discriminate Behavioral Variant Frontotemporal Dementia from Alzheimer's Disease Regardless of Amnesia?

PubMed

Bertoux, Maxime; de Souza, Leonardo Cruz; O'Callaghan, Claire; Greve, Andrea; Sarazin, Marie; Dubois, Bruno; Hornberger, Michael

2016-01-01

Relative sparing of episodic memory is a diagnostic criterion of behavioral variant frontotemporal dementia (bvFTD). However, increasing evidence suggests that bvFTD patients can show episodic memory deficits at a similar level as Alzheimer's disease (AD). Social cognition tasks have been proposed to distinguish bvFTD, but no study to date has explored the utility of such tasks for the diagnosis of amnestic bvFTD. Here, we contrasted social cognition performance of amnestic and non-amnestic bvFTD from AD, with a subgroup having confirmed in vivo pathology markers. Ninety-six participants (38 bvFTD and 28 AD patients as well as 30 controls) performed the short Social-cognition and Emotional Assessment (mini-SEA). BvFTD patients were divided into amnestic versus non-amnestic presentation using the validated Free and Cued Selective Reminding Test (FCSRT) assessing episodic memory. As expected, the accuracy of the FCSRT to distinguish the overall bvFTD group from AD was low (69.7% ) with ∼50% of bvFTD patients being amnestic. By contrast, the diagnostic accuracy of the mini-SEA was high (87.9% ). When bvFTD patients were split on the level of amnesia, mini-SEA diagnostic accuracy remained high (85.1% ) for amnestic bvFTD versus AD and increased to very high (93.9% ) for non-amnestic bvFTD versus AD. Social cognition deficits can distinguish bvFTD and AD regardless of amnesia to a high degree and provide a simple way to distinguish both diseases at presentation. These findings have clear implications for the diagnostic criteria of bvFTD. They suggest that the emphasis should be on social cognition deficits with episodic memory deficits not being a helpful diagnostic criterion in bvFTD.

Concussive Brain Trauma in the Mouse Results in Acute Cognitive Deficits and Sustained Impairment of Axonal Function

PubMed Central

Creed, Jennifer A.; DiLeonardi, Ann Mae; Fox, Douglas P.; Tessler, Alan R.

2011-01-01

Abstract Concussive brain injury (CBI) accounts for approximately 75% of all brain-injured people in the United States each year and is particularly prevalent in contact sports. Concussion is the mildest form of diffuse traumatic brain injury (TBI) and results in transient cognitive dysfunction, the neuropathologic basis for which is traumatic axonal injury (TAI). To evaluate the structural and functional changes associated with concussion-induced cognitive deficits, adult mice were subjected to an impact on the intact skull over the midline suture that resulted in a brief apneic period and loss of the righting reflex. Closed head injury also resulted in an increase in the wet weight:dry weight ratio in the cortex suggestive of edema in the first 24 h, and the appearance of Fluoro-Jade-B-labeled degenerating neurons in the cortex and dentate gyrus of the hippocampus within the first 3 days post-injury. Compared to sham-injured mice, brain-injured mice exhibited significant deficits in spatial acquisition and working memory as measured using the Morris water maze over the first 3 days (p<0.001), but not after the fourth day post-injury. At 1 and 3 days post-injury, intra-axonal accumulation of amyloid precursor protein in the corpus callosum and cingulum was accompanied by neurofilament dephosphorylation, impaired transport of Fluoro-Gold and synaptophysin, and deficits in axonal conductance. Importantly, deficits in retrograde transport and in action potential of myelinated axons continued to be observed until 14 days post-injury, at which time axonal degeneration was apparent. These data suggest that despite recovery from acute cognitive deficits, concussive brain trauma leads to axonal degeneration and a sustained perturbation of axonal function. PMID:21299360

Mori Folium and Mori Fructus Mixture Attenuates High-Fat Diet-Induced Cognitive Deficits in Mice

PubMed Central

Jeong, Hyun Uk; Park, Gunhyuk; Kim, Hocheol; Lim, Yunsook; Oh, Myung Sook

2015-01-01

Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE) for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities. PMID:25945108

Mori folium and mori fructus mixture attenuates high-fat diet-induced cognitive deficits in mice.

PubMed

Kim, Hyo Geun; Jeong, Hyun Uk; Park, Gunhyuk; Kim, Hocheol; Lim, Yunsook; Oh, Myung Sook

2015-01-01

Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE) for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities.

Stimulation of 5-HT2C Receptors Improves Cognitive Deficits Induced by Human Tryptophan Hydroxylase 2 Loss of Function Mutation

PubMed Central

Del'Guidice, Thomas; Lemay, Francis; Lemasson, Morgane; Levasseur-Moreau, Jean; Manta, Stella; Etievant, Adeline; Escoffier, Guy; Doré, François Y; Roman, François S; Beaulieu, Jean-Martin

2014-01-01

Polymorphisms in the gene encoding the serotonin synthesis enzyme Tph2 have been identified in mental illnesses, including bipolar disorder, major depression, autism, schizophrenia, and ADHD. Deficits in cognitive flexibility and perseverative behaviors are shared common symptoms in these disorders. However, little is known about the impact of Tph2 gene variants on cognition. Mice expressing a human TPH2 variant (Tph2-KI) were used to investigate cognitive consequences of TPH2 loss of function and pharmacological treatments. We applied a recently developed behavioral assay, the automated H-maze, to study cognitive functions in Tph2-KI mice. This assay involves the consecutive discovery of three different rules: a delayed alternation task, a non-alternation task, and a delayed reversal task. Possible contribution of locomotion, reward, and sensory perception were also investigated. The expression of loss-of-function mutant Tph2 in mice was associated with impairments in reversal learning and cognitive flexibility, accompanied by perseverative behaviors similar to those observed in human clinical studies. Pharmacological restoration of 5-HT synthesis with 5-hydroxytryptophan or treatment with the 5-HT2C receptor agonist CP809.101 reduced cognitive deficits in Tph2-KI mice and abolished perseveration. In contrast, treatment with the psychostimulant methylphenidate exacerbated cognitive deficits in mutant mice. Results from this study suggest a contribution of TPH2 in the regulation of cognition. Furthermore, identification of a role for a 5-HT2 receptor agonist as a cognition-enhancing agent in mutant mice suggests a potential avenue to explore for the personalized treatment of cognitive symptoms in humans with reduced 5-HT synthesis and TPH2 polymorphisms. PMID:24196946

White matter lesions and the cholinergic deficit in aging and mild cognitive impairment.

PubMed

Richter, Nils; Michel, Anne; Onur, Oezguer A; Kracht, Lutz; Dietlein, Markus; Tittgemeyer, Marc; Neumaier, Bernd; Fink, Gereon R; Kukolja, Juraj

2017-05-01

In Alzheimer's disease (AD), white matter lesions (WMLs) are associated with an increased risk of progression from mild cognitive impairment (MCI) to dementia, while memory deficits have, at least in part, been linked to a cholinergic deficit. We investigated the relationship between WML load assessed with the Scheltens scale, cerebral acetylcholinesterase (AChE) activity measured with [ 11 C]N-methyl-4-piperidyl acetate PET, and neuropsychological performance in 17 patients with MCI due to AD and 18 cognitively normal older participants. Only periventricular, not nonperiventricular, WML load negatively correlated with AChE activity in both groups. Memory performance depended on periventricular and total WML load across groups. Crucially, AChE activity predicted memory function better than WML load, gray matter atrophy, or age. The effects of WML load on memory were fully mediated by AChE activity. Data suggest that the contribution of WML to the dysfunction of the cholinergic system in MCI due to AD depends on WML distribution. Pharmacologic studies are warranted to explore whether this influences the response to cholinergic treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive deficit and poverty in the first 5 years of childhood in Bangladesh.

PubMed

Hamadani, Jena D; Tofail, Fahmida; Huda, Syed N; Alam, Dewan S; Ridout, Deborah A; Attanasio, Orazio; Grantham-McGregor, Sally M

2014-10-01

We aimed to determine the timing and size of the cognitive deficit associated with poverty in the first 5 years of life and to examine the role of parental characteristics, pre- and postnatal growth, and stimulation in the home in Bangladeshi children. We hypothesized that the effect of poverty on cognition begins in infancy and is mainly mediated by these factors. We enrolled 2853 singletons, a subsample from a pregnancy supplementation trial in a poor rural area. We assessed mental development at 7, 18, and 64 months; anthropometry at birth, 12, 24, and 64 months; home stimulation at 18 and 64 months; and family's socioeconomic background. In multiple regression analyses, we examined the effect of poverty at birth on IQ at 64 months and the extent that other factors mediated the effect. A mean cognitive deficit of 0.2 (95% confidence interval -0.4 to -0.02) z scores between the first and fifth wealth quintiles was apparent at 7 months and increased to 1.2 (95% confidence interval -1.3 to -1.0) z scores of IQ by 64 months. Parental education, pre- and postnatal growth in length, and home stimulation mediated 86% of the effects of poverty on IQ and had independent effects. Growth in the first 2 years had larger effects than later growth. Home stimulation had effects throughout the period. Effects of poverty on children's cognition are mostly mediated through parental education, birth size, growth in the first 24 months, and home stimulation in the first 5 years. Copyright © 2014 by the American Academy of Pediatrics.

ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice

PubMed Central

Yildirim, Emre; Connor, David A.; Gould, Thomas J.

2015-01-01

Nicotine withdrawal produces cognitive deficits that can predict relapse. Amelioration of these cognitive deficits emerges as a target in current smoking cessation therapies. In rodents, withdrawal from chronic nicotine disrupts contextual fear conditioning (CFC), whereas acute nicotine enhances this hippocampus-specific learning and memory. These modifications are mediated by β2-subunit-containing (β2*) nicotinic acetylcholine receptors in the hippocampus. We aimed to test ABT-089, a partial agonist of α4β2*, and ABT-107, an α7 nicotinic acetylcholine receptor agonist, for amelioration of cognitive deficits induced by withdrawal from chronic nicotine in mice. Mice underwent chronic nicotine administration (12.6 mg/kg/day or saline for 12 days), followed by 24 h of withdrawal. At the end of withdrawal, mice received 0.3 or 0.6 mg/kg ABT-089 or 0.3 mg/kg ABT-107 (doses were determined through initial dose–response experiments and prior studies) and were trained and tested for CFC. Nicotine withdrawal produced deficits in CFC that were reversed by acute ABT-089, but not ABT-107. Cued conditioning was not affected. Taken together, our results suggest that modulation of hippocampal learning and memory using ABT-089 may be an effective component of novel therapeutic strategies for nicotine addiction. PMID:25426579

Neurocognitive impairment in the deficit subtype of schizophrenia.

PubMed

Fervaha, Gagan; Agid, Ofer; Foussias, George; Siddiqui, Ishraq; Takeuchi, Hiroyoshi; Remington, Gary

2016-08-01

Schizophrenia is a heterogeneous disorder characterized by numerous diverse signs and symptoms. Individuals with prominent, persistent, and idiopathic negative symptoms are thought to encompass a distinct subtype of schizophrenia. Previous work, including studies involving neuropsychological evaluations, has supported this position. The present study sought to further examine whether deficit patients are cognitively distinct from non-deficit patients with schizophrenia. A comprehensive neurocognitive battery including tests of verbal memory, vigilance, processing speed, reasoning, and working memory was administered to 657 patients with schizophrenia. Of these, 144 (22 %) patients were classified as deficit patients using a proxy identification method based on severity, persistence over time, and possible secondary sources (e.g., depression) of negative symptoms. Deficit patients with schizophrenia performed worse on all tests of cognition relative to non-deficit patients. These patients were characterized by a generalized cognitive impairment on the order of about 0.4 standard deviations below that of non-deficit patients. However, when comparing deficit patients to non-deficit patients who also present with negative symptoms, albeit not enduring or primary, no group differences in cognitive performance were found. Furthermore, a discriminant function analysis classifying patients into deficit/non-deficit groups based on cognitive scores demonstrated only 62.3 % accuracy, meaning over one-third of individuals were misclassified. The deficit subtype of schizophrenia is not markedly distinct from non-deficit schizophrenia in terms of neurocognitive performance. While deficit patients tend to have poorer performance on cognitive tests, the magnitude of this effect is relatively modest, translating to over 70 % overlap in scores between groups.

Glycogen synthase kinase-3 inhibitors reverse deficits in long-term potentiation and cognition in Fragile X mice

PubMed Central

Franklin, Aimee V.; King, Margaret K.; Palomo, Valle; Martinez, Ana; McMahon, Lori L.; Jope, Richard S.

2013-01-01

Background Identifying feasible therapeutic interventions is crucial for ameliorating the intellectual disability and other afflictions of Fragile X Syndrome (FXS), the most common inherited cause of intellectual disability and autism. Hippocampal glycogen synthase kinase-3 (GSK3) is hyperactive in the mouse model of FXS (FX mice), and hyperactive GSK3 promotes locomotor hyperactivity and audiogenic seizure susceptibility in FX mice, raising the possibility that specific GSK3 inhibitors may improve cognitive processes. Methods We tested if specific GSK3 inhibitors improve deficits in N-methyl-D-aspartate receptor (NMDAR)-dependent long term potentiation (LTP) at medial perforant path synapses onto dentate granule cells (MPP-DGC) and dentate gyrus-dependent cognitive behavioral tasks. Results GSK3 inhibitors completely rescued deficits in LTP at MPP-DGC synapses in FX mice. Furthermore, synaptosomes from the dentate gyrus of FX mice displayed decreased inhibitory serine-phosphorylation of GSK3β compared with wild-type littermates. The potential therapeutic utility of GSK3 inhibitors was further tested on dentate gyrus-dependent congnitive behaviors. In vivo administration of GSK3 inhibitors completely reversed impairments in several cognitive tasks in FX mice, including novel object detection, coordinate and categorical spatial processing, and temporal ordering for visual objects. Conclusions These findings establish that synaptic plasticity and cognitive deficits in FX mice can be improved by intervention with inhibitors of GSK3, which may prove therapeutically beneficial in FXS. PMID:24041505

The effects of oxytocin on social cognition in borderline personality disorder.

PubMed

Servan, A; Brunelin, J; Poulet, E

2018-02-01

Deficits in social cognition and interpersonal difficulties are key features in borderline personality disorder. Social cognition refers to the function of perceiving and adequately dealing with social signals, leading to the establishment and maintenance of healthy and positive social relationships. Evidence suggests that oxytocin (OT) may improve social cognition and human social behavior. Recently, several studies have highlighted the beneficial effects of oxytocin in several psychiatric conditions involving social cognition deficits such as schizophrenia, autism or social phobia. However, despite growing interest, the effects of oxytocin in patients with borderline personality disorder are far from being clearly demonstrated. The objective of this work was to review and discuss studies investigating the interest of oxytocin in alleviating social cognition deficits in patients with borderline personality disorder (recognition of emotion, trust and cooperation, affective and cognitive empathy, emotional expression and social problem-solving). A systematic review of the literature was conducted up to September 31, 2016 on the Pubmed, Science direct, Medline and Scopus databases using "borderline personality disorder" and "oxytocin" as keywords. To be included, studies were to include patients with borderline personality disorder; to investigate social cognition and to investigate the effect of oxytocin on social cognition in patients with TPB. The initial search yielded 52 articles. Among them, 11 studies were selected according to the PRISMA criteria. The effect of oxytocin on social cognition in patients with borderline personality disorder was mainly investigated in relation to recognition of emotions and trust and cooperation. We did not find any studies investigating the effect of oxytocin on affective and cognitive empathy, emotional expression or social problem-solving abilities. In patients with borderline personality disorder, oxytocin had a beneficial

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles

PubMed Central

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2017-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8–9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits. PMID:28101068

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles.

PubMed

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2016-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8-9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits.

Cognitive Deficits Underlying Error Behavior on a Naturalistic Task after Severe Traumatic Brain Injury

PubMed Central

Hendry, Kathryn; Ownsworth, Tamara; Beadle, Elizabeth; Chevignard, Mathilde P.; Fleming, Jennifer; Griffin, Janelle; Shum, David H. K.

2016-01-01

People with severe traumatic brain injury (TBI) often make errors on everyday tasks that compromise their safety and independence. Such errors potentially arise from the breakdown or failure of multiple cognitive processes. This study aimed to investigate cognitive deficits underlying error behavior on a home-based version of the Cooking Task (HBCT) following TBI. Participants included 45 adults (9 females, 36 males) with severe TBI aged 18–64 years (M = 37.91, SD = 13.43). Participants were administered the HBCT in their home kitchens, with audiovisual recordings taken to enable scoring of total errors and error subtypes (Omissions, Additions, Estimations, Substitutions, Commentary/Questions, Dangerous Behavior, Goal Achievement). Participants also completed a battery of neuropsychological tests, including the Trail Making Test, Hopkins Verbal Learning Test-Revised, Digit Span, Zoo Map test, Modified Stroop Test, and Hayling Sentence Completion Test. After controlling for cooking experience, greater Omissions and Estimation errors, lack of goal achievement, and longer completion time were significantly associated with poorer attention, memory, and executive functioning. These findings indicate that errors on naturalistic tasks arise from deficits in multiple cognitive domains. Assessment of error behavior in a real life setting provides insight into individuals' functional abilities which can guide rehabilitation planning and lifestyle support. PMID:27790099

Relationships among cognitive deficits and component skills of reading in younger and older students with developmental dyslexia.

PubMed

Park, Heeyoung; Lombardino, Linda J

2013-09-01

Processing speed deficits along with phonological awareness deficits have been identified as risk factors for dyslexia. This study was designed to examine the behavioral profiles of two groups, a younger (6-8 years) and an older (10-15 years) group of dyslexic children for the purposes of (1) evaluating the degree to which phonological awareness and processing speed deficits occur in the two developmental cohorts; (2) determining the strength of relationships between the groups' respective mean scores on cognitive tasks of phonological awareness and processing speed and their scores on component skills of reading; and (3) evaluating the degree to which phonological awareness and processing speed serve as concurrent predictors of component reading skills for each group. The mean scaled scores for both groups were similar on all but one processing speed task. The older group was significantly more depressed on a visual matching test of attention, scanning, and speed. Correlations between reading skills and the cognitive constructs were very similar for both age-groups. Neither of the two phonological awareness tasks correlated with either of the two processing speed tasks or with any of the three measures of reading. One of the two processing speed measures served as a concurrent predictor of word- and text-level reading in the younger, however, only the rapid naming measure functioned as a concurrent predictor of word reading in the older group. Conversely, phonological processing measures did not serve as concurrent predictors for word-level or text-level reading in either of the groups. Descriptive analyses of individual subjects' deficits in the domains of phonological awareness and processing speed revealed that (1) both linguistic and nonlinguistic processing speed deficits in the younger dyslexic children occurred at higher rates than deficits in phonological awareness and (2) cognitive deficits within and across these two domains were greater in the older

Effects of APOE ε4, age, and HIV on glial metabolites and cognitive deficits.

PubMed

Chang, Linda; Jiang, Caroline; Cunningham, Eric; Buchthal, Steven; Douet, Vanessa; Andres, Marilou; Ernst, Thomas

2014-06-17

We aimed to evaluate the combined effects of HIV and APOE ε4 allele(s) on glial metabolite levels, and on known cognitive deficits associated with either condition, across the ages. One hundred seventy-seven participants, primarily of white and mixed race (97 seronegative subjects: aged 44.7 ± 1.3 years, 85 [87.6%] men, 28 [28.9%] APOE ε4+; 80 HIV+ subjects: aged 47.3 ± 1.1 years, 73 [91.3%] men, 23 [28.8%] APOE ε4+), were assessed cross-sectionally for metabolite concentrations using proton magnetic resonance spectroscopy in 4 brain regions and for neuropsychological performance. Frontal white matter myo-inositol was elevated in subjects with HIV across the age span but showed age-dependent increase in seronegative subjects, especially in APOE ε4+ carriers. In contrast, only seronegative APOE ε4+ subjects showed elevated myo-inositol in parietal cortex. All APOE ε4+ subjects had lower total creatine in basal ganglia. While all HIV subjects showed greater cognitive deficits, HIV+ APOE ε4+ subjects had the poorest executive function, fluency memory, and attention/working memory. Higher myo-inositol levels were associated with poorer fine motor function across all subjects, slower speed of information processing in APOE ε4+ subjects, and worse fluency in HIV+ APOE ε4+ subjects. In frontal white matter of subjects with HIV, the persistent elevation and lack of normal age-dependent increase in myo-inositol suggest that persistent glial activation attenuated the typical antagonistic pleiotropic effects of APOE ε4 on neuroinflammation. APOE ε4 negatively affects energy metabolism in brain regions rich in dopaminergic synapses. The combined effects of HIV infection and APOE ε4 may lead to greater cognitive deficits, especially in those with greater neuroinflammation. APOE ε4 allele(s) may be a useful genetic marker to identify white and mixed-race HIV subjects at risk for cognitive decline. © 2014 American Academy of Neurology.

Overstimulation of newborn mice leads to behavioral differences and deficits in cognitive performance

PubMed Central

Christakis, D. A.; Ramirez, J. S. B.; Ramirez, J. M.

2012-01-01

Observational studies in humans have found associations between overstimulation in infancy via excessive television viewing and subsequent deficits in cognition and attention. We developed and tested a mouse model of overstimulation whereby p10 mice were subjected to audio (70 db) and visual stimulation (flashing lights) for six hours per day for a total of 42 days. 10 days later cognition and behavior were tested using the following tests: Light Dark Latency, Elevated Plus Maze, Novel Object Recognition, and Barnes Maze. In all tests, overstimulated mice performed significantly worse compared to controls suggesting increased activity and risk taking, diminished short term memory, and decreased cognitive function. These findings suggest that excessive non-normative stimulation during critical periods of brain development can have demonstrable untoward effects on subsequent neurocognitive function. PMID:22855702

Emotional Intelligence deficits in schizophrenia: The impact of non-social cognition.

PubMed

Frajo-Apor, Beatrice; Pardeller, Silvia; Kemmler, Georg; Welte, Anna-Sophia; Hofer, Alex

2016-04-01

Previous studies using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) revealed significant performance deficits across all areas of Emotional Intelligence (EI) in schizophrenia patients compared to healthy controls. However, none of these studies has investigated a potential influence of non-social cognition on these findings. 56 schizophrenia outpatients and 84 control subjects were investigated using the MSCEIT and the Brief Assessment of Cognition in Schizophrenia (BACS). Analyses of covariance were performed with adjustment for the BACS composite score and education. To investigate this issue in more detail, a mediation analysis was conducted. Patients showed significantly lower EI and non-social cognition levels compared to healthy controls. After adjustment for BACS composite score and education, only the group difference in the "managing emotions" branch and thus in the "strategic" EI part of the MSCEIT remained statistically significant, whereas for all other MSCEIT branches (perceiving, using, understanding emotions) statistical significance was lost. The mediation analysis revealed that the difference between schizophrenia patients and controls regarding the MSCEIT total score was almost fully attributable to the mediating effect of non-social cognition. Our findings suggest that in schizophrenia patients EI is largely influenced by non-social cognitive functioning. Only the "managing emotions" branch was found to be independent of non-social cognition. Consequently, non-social cognitive performance was mainly responsible for the observed differences in EI between schizophrenia patients and controls. This has to be taken into account when interpreting MSCEIT data in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognitive-Behavioral Therapy for Depression Using Mind Over Mood: CBT Skill Use and Differential Symptom Alleviation.

PubMed

Hawley, Lance L; Padesky, Christine A; Hollon, Steven D; Mancuso, Enza; Laposa, Judith M; Brozina, Karen; Segal, Zindel V

2017-01-01

Cognitive-behavioral therapy (CBT) for depression is highly effective. An essential element of this therapy involves acquiring and utilizing CBT skills; however, it is unclear whether the type of CBT skill used is associated with differential symptom alleviation. Outpatients (N = 356) diagnosed with a primary mood disorder received 14 two-hour group sessions of CBT for depression, using the Mind Over Mood protocol. In each session, patients completed the Beck Depression Inventory and throughout the week they reported on their use of CBT skills: behavioral activation (BA), cognitive restructuring (CR), and core belief (CB) strategies. Bivariate latent difference score (LDS) longitudinal analyses were used to examine patterns of differential skill use and subsequent symptom change, and multigroup LDS analyses were used to determine whether longitudinal associations differed as a function of initial depression severity. Higher levels of BA use were associated with a greater subsequent decrease in depressive symptoms for patients with mild to moderate initial depression symptoms relative to those with severe symptoms. Higher levels of CR use were associated with a greater subsequent decrease in depressive symptoms, whereas higher levels of CB use were followed by a subsequent increase in depressive symptoms, regardless of initial severity. Results indicated that the type of CBT skill used is associated with differential patterns of subsequent symptom change. BA use was associated with differential subsequent change as a function of initial severity (patients with less severe depression symptoms demonstrated greater symptom improvement), whereas CR use was associated with symptom alleviation and CB use with an increase in subsequent symptoms as related to initial severity. Copyright © 2016. Published by Elsevier Ltd.

Cognitive deficits in amyotrophic lateral sclerosis evaluated by event-related potentials.

PubMed

Ogawa, Tomohiro; Tanaka, Hideaki; Hirata, Koichi

2009-04-01

To determine the cognitive profiles in non-demented, relatively less handicapped patients with early-stage sporadic amyotrophic lateral sclerosis (ALS) by using neuropsychological tests, event-related potentials (ERPs) and clinical scale. We recruited 19 patients with sporadic ALS (eight with limb-onset, 11 with bulbar-onset) and 19 controls. In addition to the mini-mental state examination and the Wechsler adult intelligence scale-revised, we assessed the frontal lobe function with Wisconsin card sorting test, Stroop test and trail making test. We used auditory 'oddball' counting paradigm for the ERPs under 20-channel electroencephalogram (EEG) recording. Global field power (GFP) was computed, and its peak amplitudes and latencies of N1/N2/P3 were determined. The results of ERP and neuropsychological tests were correlated with respiratory function and clinical scale. No global cognitive impairment except for subtle frontal dysfunction was detected, although N1/N2/P3 GFP latencies were significantly prolonged in ALS patients than in the controls. Vital capacity correlated with P3 GFP amplitude, and the relative bulbar functional rating scale correlated with P3 GFP latency. Our findings indicated the presence of sub-clinical cognitive deficits in non-demented, sporadic ALS patients. In addition, clinical sub-types and respiratory function dependently influenced cognitive function in patients with sporadic ALS. ERP confirmed cognitive impairment in patients with sporadic ALS.

A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis.

PubMed

Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

2017-01-01

Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models. Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.

Fronto-temporal connectivity predicts cognitive empathy deficits and experiential negative symptoms in schizophrenia.

PubMed

Abram, Samantha V; Wisner, Krista M; Fox, Jaclyn M; Barch, Deanna M; Wang, Lei; Csernansky, John G; MacDonald, Angus W; Smith, Matthew J

2017-03-01

Impaired cognitive empathy is a core social cognitive deficit in schizophrenia associated with negative symptoms and social functioning. Cognitive empathy and negative symptoms have also been linked to medial prefrontal and temporal brain networks. While shared behavioral and neural underpinnings are suspected for cognitive empathy and negative symptoms, research is needed to test these hypotheses. In two studies, we evaluated whether resting-state functional connectivity between data-driven networks, or components (referred to as, inter-component connectivity), predicted cognitive empathy and experiential and expressive negative symptoms in schizophrenia subjects. Study 1: We examined associations between cognitive empathy and medial prefrontal and temporal inter-component connectivity at rest using a group-matched schizophrenia and control sample. We then assessed whether inter-component connectivity metrics associated with cognitive empathy were also related to negative symptoms. Study 2: We sought to replicate the connectivity-symptom associations observed in Study 1 using an independent schizophrenia sample. Study 1 results revealed that while the groups did not differ in average inter-component connectivity, a medial-fronto-temporal metric and an orbito-fronto-temporal metric were related to cognitive empathy. Moreover, the medial-fronto-temporal metric was associated with experiential negative symptoms in both schizophrenia samples. These findings support recent models that link social cognition and negative symptoms in schizophrenia. Hum Brain Mapp 38:1111-1124, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Protective Effects of Foods Containing Flavonoids on Age-Related Cognitive Decline.

PubMed

Gildawie, Kelsea R; Galli, Rachel L; Shukitt-Hale, Barbara; Carey, Amanda N

2018-06-01

Evidence suggests that flavonoids, polyphenolic compounds found in many plant-derived foods, such as berries, may allay cognitive impairment. We review recent research exploring the protective effects of flavonoids on age-related cognitive decline and neurodegenerative disorders in humans and animals. We also address the mechanisms by which flavonoids may exert their effects and promising avenues of future research. Flavonoids have been found to decrease neuroinflammation, reduce oxidative stress, and mediate neuroplasticity in animal models of neurodegeneration and aging. Injecting flavonoids encased in metal nanoparticles may further enhance the efficacy of flavonoids. Animal studies also demonstrate that flavonoid supplementation may alleviate neurodegenerative cognitive and memory impairments. Limited human studies, however, demonstrate the need for further clinical research investigating flavonoids. Flavonoid supplementation, as well as dietary modification to include whole foods high in flavonoids, may provide therapeutic potential for aging individuals experiencing cognitive deficits resulting from neurodegeneration.

Blocking leukotriene synthesis attenuates the pathophysiology of traumatic brain injury and associated cognitive deficits

PubMed Central

Corser-Jensen, Chelsea E.; Goodell, Dayton J.; Freund, Ronald K.; Serbedzija, Predrag; Murphy, Robert C.; Farias, Santiago E.; Dell'Acqua, Mark L.; Frey, Lauren C.; Serkova, Natalie; Heidenreich, Kim A.

2014-01-01

Neuroinflammation is a component of secondary injury following traumatic brain injury (TBI) that can persist beyond the acute phase. Leukotrienes are potent, pro-inflammatory lipid mediators generated from membrane phospholipids. In the absence of injury, leukotrienes are undetectable in brain, but after trauma they are rapidly synthesized by a transcellular event involving infiltrating neutrophils and endogenous brain cells. Here, we investigate the efficacy of MK-886, an inhibitor of 5-lipoxygenase activating protein (FLAP), in blocking leukotriene synthesis, secondary brain damage, synaptic dysfunction, and cognitive impairments after TBI. Male Sprague Dawley rats (9-11 weeks) received either MK-886 or vehicle after they were subjected to unilateral moderate fluid percussion injury (FPI) to assess the potential clinical use of FLAP inhibitors for TBI. MK-886 was also administered before FPI to determine the preventative potential of FLAP inhibitors. MK-886 given before or after injury significantly blocked the production of leukotrienes, measured by reverse-phase liquid chromatography coupled to tandem mass spectrometry (RP LC-MS/MS), and brain edema, measured by T2-weighted magnetic resonance imaging (MRI). MK-886 significantly attenuated blood-brain barrier disruption in the CA1 hippocampal region and deficits in long-term potentiation (LTP) at CA1 hippocampal synapses. The prevention of FPI-induced synaptic dysfunction by MK-886 was accompanied by fewer deficits in post-injury spatial learning and memory performance in the radial arms water maze (RAWM). These results indicate that leukotrienes contribute significantly to secondary brain injury and subsequent cognitive deficits. FLAP inhibitors represent a novel anti-inflammatory approach for treating human TBI that is feasible for both intervention and prevention of brain injury and neurologic deficits. PMID:24681156

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

[PASS neurocognitive dysfunction in attention deficit].

PubMed

Pérez-Alvarez, F; Timoneda-Gallart, C

Attention deficit disorder shows both cognitive and behavioral patterns. To determine a particular PASS (planning, attention, successive and simultaneous) pattern in order to early diagnosis and remediation according to PASS theory. 80 patients were selected from the neuropediatric attendance, aged 6 to 12 years old, 55 boys and 25 girls. Inclusion criteria were inattention (80 cases) and inattention with hyperactive symptoms (40 cases) according to the Diagnostic and Statistical Manual (DSM-IV). Exclusion criteria were the criteria of phonologic awareness previously reported, considered useful to diagnose dyslexia. A control group of 300 individuals, aged 5 to 12 years old, was used, criteria above mentioned being controlled. DN:CAS (Das-Naglieri Cognitive Assessment System) battery, translated to native language, was given to assess PASS cognitive processes. Results were analyzed with cluster analysis and t-Student test. Statistical factor analysis of the control group had previously identified the four PASS processes: planning, attention, successive and simultaneous. The dendrogram of the cluster analysis discriminated three categories of attention deficit disorder: 1. The most frequent, with planning deficit; 2. Without planning deficit but with deficit in other processes, and 3. Just only a few cases, without cognitive processing deficit. Cognitive deficiency in terms of means of scores was statistically significant when compared to control group (p = 0.001). According to PASS pattern, planning deficiency is a relevant factor. Neurological planning is not exactly the same than neurological executive function. The behavioral pattern is mainly linked to planning deficiency, but also to other PASS processing deficits and even to no processing deficit.

Diabetes and Cognitive Deficits in Chronic Schizophrenia: A Case-Control Study

PubMed Central

Han, Mei; Huang, Xu-Feng; Chen, Da Chun; Xiu, Meihong; Kosten, Thomas R.; Zhang, Xiang Yang

2013-01-01

Cognitive impairment occurs in both schizophrenia and diabetes. There is currently limited understanding whether schizophrenia with diabetes has more serious cognitive deficits than schizophrenia without diabetes or diabetes only. This study assessed cognitive performance in 190 healthy controls, 106 diabetes only, 127 schizophrenia without diabetes and 55 schizophrenia with diabetes. This study was conducted from January 2008 to December 2010. Compared to healthy controls, all patient groups had significantly decreased total and five index RBANS scores (all p<0.01–p<0.001), except for the visuospatial/constructional index. Schizophrenia with diabetes performed worse than schizophrenia without diabetes in immediate memory (p<0.01) and total RBANS scores (<0.05), and showed a trend for decreased attention (p = 0.052) and visuospatial/constructional capacity (p = 0.063). Schizophrenia with diabetes performed worse than diabetes only in immediate memory (p<0.001) and attention (p<0.05), and showed a trend for decreased total RBANS scores (p = 0.069). Regression analysis showed that the RBANS had modest correlations with schizophrenia’ PANSS scores, their duration of current antipsychotic treatment, and diagnosis of diabetes. Schizophrenia with co-morbid diabetes showed more cognitive impairment than schizophrenia without diabetes and diabetes only, especially in immediate memory and attention. PMID:23840437

Blue-yellow colour vision impairment and cognitive deficits in occasional and dependent stimulant users.

PubMed

Hulka, Lea M; Wagner, Michael; Preller, Katrin H; Jenni, Daniela; Quednow, Boris B

2013-04-01

Specific blue-yellow colour vision impairment has been reported in dependent cocaine users and it was postulated that drug-induced changes in retinal dopamine neurotransmission are responsible. However, it is unclear whether these changes are confined to chronic cocaine users, whether they are specific for dopaminergic stimulants such as cocaine and amphetamine and whether they are related to cognitive functions such as working memory, encoding and consolidation. In 47 occasional and 29 dependent cocaine users, 23 MDMA (commonly known as 'ecstasy') users and 47 stimulant-naive controls, colour vision discrimination was measured with the Lanthony Desaturated Panel D-15 Test and memory performance with the Auditory Verbal Learning Test. Both occasional and dependent cocaine users showed higher colour confusion indices than controls. Users of the serotonergic stimulant MDMA (26%), occasional (30%) and dependent cocaine users (34%) exhibited more frequent blue-yellow colour vision disorders compared to controls (9%). Inferior performance of MDMA users was caused by a subgroup with high amphetamine co-use (55%), while MDMA use alone was not associated with decreased blue-yellow discrimination (0%). Cognitive performance was worse in cocaine users with colour vision disorder compared to users and controls with intact colour vision and both colour vision impairment and cognitive deficits were related to cocaine use. Occasional cocaine and amphetamine use might induce blue-yellow colour vision impairment, whereas the serotonergic stimulant MDMA does not impair colour vision. The association between colour vision impairment and cognitive deficits in cocaine users may reflect that retinal and cerebral dopamine alterations are linked to a certain degree.

Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma.

PubMed

Fjalldal, S; Follin, C; Svärd, D; Rylander, L; Gabery, S; Petersén, Å; van Westen, D; Sundgren, P C; Björkman-Burtscher, I M; Lätt, J; Ekman, B; Johanson, A; Erfurth, E M

2018-06-01

Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. The South Medical Region of Sweden (2.5 million inhabitants). Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients. Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. Right uncinate fasciculus was significantly altered ( P  ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge ( P  = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP. © 2018 The authors.

Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition-Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats.

PubMed

Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Hong; Li, Xiao-Li; Bai, Feng; Ren, Qing-Guo; Zhang, Zhi-Jun

2017-04-01

Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473-phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3β (inactive form) with no significant changes in the levels of total GSK-3β and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3β pathway plays an important role in regulating synaptic plasticity in SI rats.

Novel spiroimidazopyridine derivative SAK3 improves methimazole-induced cognitive deficits in mice.

PubMed

Noreen, Husain; Yabuki, Yasushi; Fukunaga, Kohji

2017-09-01

Methimazole (MMI) is a first-line therapy used to manage hyperthyroidism and Graves' disease. Despite its therapeutic benefit, chronic MMI administration can lead to hypothyroidism and perturb brain homeostasis in patients, resulting in neuropsychiatric disorders such as depression and cognitive dysfunction. We recently developed the spiroimidazopyridine derivative SAK3 as cognitive enhancer; however, mechanisms underlying its activity remained unclear. Here, we show that SAK3 potentially improves cognitive impairment seen following MMI-induced hypothyroidism. Twenty-four hours after MMI (75 mg/kg, i.p.) treatment, we administered SAK3 (0.1, 0.5 and 1 mg/kg, p.o.) to mice daily for 7 days. MMI treatment alone disrupted olfactory bulb (OB) glomerular structure, as assessed by staining with the olfactory marker protein (OMP), reduced the number of choline acetyl transferase (ChAT)-immunoreactive neurons in medial septum (MS), and significantly impaired cognition. SAK3 (0.5 and 1 mg/kg, p.o.) administration significantly restored the number of cholinergic MS neurons in MMI-treated mice, and SAK3 treatment at a higher dose significantly improved cognitive deficits seen in MMI-treated control mice. Overall, our study suggests that SAK3 treatment could antagonize such impairment in patients with hypothyroidism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood.

PubMed

Shirai, Yumi; Fujita, Yuko; Hashimoto, Ryota; Ohi, Kazutaka; Yamamori, Hidenaga; Yasuda, Yuka; Ishima, Tamaki; Suganuma, Hiroyuki; Ushida, Yusuke; Takeda, Masatoshi; Hashimoto, Kenji

2015-01-01

Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA) neurons expressing parvalbumin (PV), which is also involved in cognitive impairment. Sulforaphane (SFN), an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP). Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN) during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed) in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.

Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood

PubMed Central

Shirai, Yumi; Fujita, Yuko; Hashimoto, Ryota; Ohi, Kazutaka; Yamamori, Hidenaga; Yasuda, Yuka; Ishima, Tamaki; Suganuma, Hiroyuki; Ushida, Yusuke; Takeda, Masatoshi; Hashimoto, Kenji

2015-01-01

Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA) neurons expressing parvalbumin (PV), which is also involved in cognitive impairment. Sulforaphane (SFN), an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP). Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN) during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed) in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood. PMID:26107664

On-road driving impairments and associated cognitive deficits after stroke.

PubMed

Devos, Hannes; Tant, Mark; Akinwuntan, Abiodun E

2014-01-01

Little is known about the critical on-road driving skills that get affected after a stroke. The purpose of this study was to investigate the key on-road driving impairments and their associated cognitive deficits after a stroke. A second aim was to investigate if lateralization of stroke impacts results of the cognitive and on-road driving tests. In this cross-sectional study, 99 participants with a first-ever stroke who were actively driving prior to stroke underwent a cognitive battery and a standardized road test that evaluated 13 specific on-road driving skills. These on-road driving skills were mapped onto an existing, theoretical framework that categorized the on-road items into hierarchic clusters of operational, tactical, visuo-integrative, and mixed driving skills. The total score on the road test and the on-road decision, made by a certified fitness-to-drive expert, decided the main outcome. The critical on-road driving skills predicting the on-road decision were identified using logistic regression analysis. Linear regression analysis was employed to determine the cognitive impairments leading to poor total on-road scores. Analyses were repeated for right- and left-sided strokes. In all, 37 persons scored poorly on the road test. These participants performed worse in all hierarchic clusters of on-road driving. Performances on the operational cluster and the visuo-integrative cluster best predicted on-road decisions (R(2) = 0.60). 'Lane changing' and 'understanding, insight, and quality of traffic participation' were the critical skill deficits leading to poor performance on the road test (R(2) = 0.65). Divided attention was the main determinant of on-road scores in the total group (R(2) = 0.06). Participants with right-sided stroke performed worse on visual field, visual neglect, visual scanning, visuo-constructive skills, and divided attention compared with those with left-sided stroke. Divided attention was the main determinant of total on-road scores

The nature of social cognitive deficits in children and adults with Klinefelter syndrome (47,XXY).

PubMed

van Rijn, S; de Sonneville, L; Swaab, H

2018-02-06

About 1 in 650 boys are born with an extra X chromosome (47,XXY or Klinefelter syndrome). 47,XXY is associated with vulnerabilities in socio-emotional development. This study was designed to assess types of cognitive deficits in individuals with 47,XXY that may contribute to social-emotional dysfunction, and to evaluate the nature of such deficits at various levels: ranging from basic visuospatial processing deficits, impairments in face recognition (FR), to emotion expression impairments. A total of 70 boys and men with 47,XXY, aged 8 to 60 years old, participated in the study. The subtests feature identification, FR and identification of facial emotions of the Amsterdam Neuropsychological Tasks were used. Level of intellectual functioning was assessed with the child and adult versions of the Wechsler Intelligence Scales. Reaction time data showed that in the 47,XXY group, 17% had difficulties in visuospatial processing (no social load), 26% had difficulties with FR (medium social load) and an even higher number of 33% had difficulties with facial expressions of emotions (high-social load). Information processing impairments increased as a function of "social load" of the stimuli, independent of intellectual functioning. Taken together, our data suggest that on average individuals with XXY may have more difficulties in information processing when "social load" increases, suggesting a specific difficulty in the higher-order labeling and interpretation of social cues, which cannot be explained by more basic visuospatial perceptual skills. Considering the increased risk for social cognitive impairments, routine assessment of social cognitive functioning as part of neuropsychological screening is warranted. © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

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.

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

Dexmedetomidine alleviates anxiety-like behaviors and cognitive impairments in a rat model of post-traumatic stress disorder.

PubMed

Ji, Mu-Huo; Jia, Min; Zhang, Ming-Qiang; Liu, Wen-Xue; Xie, Zhong-Cong; Wang, Zhong-Yun; Yang, Jian-Jun

2014-10-03

Post-traumatic stress disorder (PTSD) is a psychiatric disease that has substantial health implications, including high rates of health morbidity and mortality, as well as increased health-related costs. Although many pharmacological agents have proven the effects on the development of PTSD, current pharmacotherapies typically only produce partial improvement of PTSD symptoms. Dexmedetomidine is a selective, short-acting α2-adrenoceptor agonist, which has anxiolytic, sedative, and analgesic effects. We therefore hypothesized that dexmedetomidine possesses the ability to prevent the development of PTSD and alleviate its symptoms. By using the rat model of PTSD induced by five electric foot shocks followed by three weekly exposures to situational reminders, we showed that the stressed rats displayed pronounced anxiety-like behaviors and cognitive impairments compared to the controls. Notably, repeated administration of 20μg/kg dexmedetomidine showed impaired fear conditioning memory, decreased anxiety-like behaviors, and improved spatial cognitive impairments compared to the vehicle-treated stressed rats. These data suggest that dexmedetomidine may exert preventive and protective effects against anxiety-like behaviors and cognitive impairments in the rats with PTSD after repeated administration. Copyright © 2014 Elsevier Inc. All rights reserved.

Uncovering the Neural Bases of Cognitive and Affective Empathy Deficits in Alzheimer's Disease and the Behavioral-Variant of Frontotemporal Dementia.

PubMed

Dermody, Nadene; Wong, Stephanie; Ahmed, Rebekah; Piguet, Olivier; Hodges, John R; Irish, Muireann

2016-05-30

Loss of empathy is a core presenting feature of the behavioral-variant of frontotemporal dementia (bvFTD), resulting in socioemotional difficulties and behavioral transgressions. In contrast, interpersonal functioning remains relatively intact in Alzheimer's disease (AD), despite marked cognitive decline. The neural substrates mediating these patterns of loss and sparing in social functioning remain unclear, yet are relevant for our understanding of the social brain. We investigated cognitive versus affective aspects of empathy using the Interpersonal Reactivity Index (IRI) in 25 AD and 24 bvFTD patients and contrasted their performance with 22 age- and education-matched controls. Cognitive empathy was comparably compromised in AD and bvFTD, whereas affective empathy was impaired exclusively in bvFTD. While controlling for overall cognitive dysfunction ameliorated perspective-taking deficits in AD, empathy loss persisted across cognitive and affective domains in bvFTD. Voxel-based morphometry analyses revealed divergent neural substrates of empathy loss in each patient group. Perspective-taking deficits correlated with predominantly left-sided temporoparietal atrophy in AD, whereas widespread bilateral frontoinsular, temporal, parietal, and occipital atrophy was implicated in bvFTD. Reduced empathic concern in bvFTD was associated with atrophy in the left orbitofrontal, inferior frontal, and insular cortices, and the bilateral mid-cingulate gyrus. Our findings suggest that social cognitive deficits in AD arise largely as a consequence of global cognitive dysfunction, rather than a loss of empathy per se. In contrast, loss of empathy in bvFTD reflects the deterioration of a distributed network of frontoinsular and temporal structures that appear crucial for monitoring and processing social information.

An Integrative, Cognitive-Behavioral, Systemic Approach to Working with Students Diagnosed with Attention Deficit Hyperactive Disorder

ERIC Educational Resources Information Center

Shillingford, Margaret Ann; Lambie, Glenn W.; Walter, Sara Meghan

2007-01-01

Attention deficit hyperactive disorder (ADHD) is a prevalent diagnostic disorder for many students, which correlates with negative academic, social, and personal consequences. This article presents an integrative, cognitive-behavioral, systemic approach that offers behaviorally based interventions for professional school counselors to support…

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

USDA-ARS?s Scientific Manuscript database

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

Differential profiles in auditory social cognition deficits between adults with autism and schizophrenia spectrum disorders: A preliminary analysis.

PubMed

Tobe, Russell H; Corcoran, Cheryl M; Breland, Melissa; MacKay-Brandt, Anna; Klim, Casimir; Colcombe, Stanley J; Leventhal, Bennett L; Javitt, Daniel C

2016-08-01

Impairment in social cognition, including emotion recognition, has been extensively studied in both Autism Spectrum Disorders (ASD) and Schizophrenia (SZ). However, the relative patterns of deficit between disorders have been studied to a lesser degree. Here, we applied a social cognition battery incorporating both auditory (AER) and visual (VER) emotion recognition measures to a group of 19 high-functioning individuals with ASD relative to 92 individuals with SZ, and 73 healthy control adult participants. We examined group differences and correlates of basic auditory processing and processing speed. Individuals with SZ were impaired in both AER and VER while ASD individuals were impaired in VER only. In contrast to SZ participants, those with ASD showed intact basic auditory function. Our finding of a dissociation between AER and VER deficits in ASD relative to Sz support modality-specific theories of emotion recognition dysfunction. Future studies should focus on visual system-specific contributions to social cognitive impairment in ASD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mapping the neuroanatomic substrates of cognition in familial attention deficit hyperactivity disorder.

PubMed

Muster, Rachel; Choudhury, Saadia; Sharp, Wendy; Kasparek, Steven; Sudre, Gustavo; Shaw, Philip

2018-05-24

While the neuroanatomic substrates of symptoms of attention deficit hyperactivity disorder (ADHD) have been investigated, less is known about the neuroanatomic correlates of cognitive abilities pertinent to the disorder, particularly in adults. Here we define the neuroanatomic correlates of key cognitive abilities and determine if there are associations with histories of psychostimulant medication. We acquired neuroanatomic magnetic resonance imaging data from 264 members of 60 families (mean age 29.5; s.d. 18.4, 116 with ADHD). Using linear mixed model regression, we tested for associations between cognitive abilities (working memory, information processing, intelligence, and attention), symptoms and both cortical and subcortical volumes. Symptom severity was associated with spatial working memory (t = -3.77, p = 0.0002), processing speed (t = -2.95, p = 0.004) and a measure of impulsive responding (t = 2.19, p = 0.03); these associations did not vary with age (all p > 0.1). Neuroanatomic associations of cognition varied by task but centered on prefrontal, lateral parietal and temporal cortical regions, the thalamus and putamen. The neuroanatomic correlates of ADHD symptoms overlapped significantly with those of working memory (Dice's overlap coefficient: spatial, p = 0.003; verbal, p = 0.001) and information processing (p = 0.02). Psychostimulant medication history was associated with neither cognitive skills nor with a brain-cognition relationships. Diagnostic differences in the cognitive profile of ADHD does not vary significantly with age; nor were cognitive differences associated with psychostimulant medication history. The neuroanatomic substrates of working memory and information overlapped with those for symptoms within these extended families, consistent with a pathophysiological role for these cognitive skills in familial ADHD.

A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis

PubMed Central

Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

2017-01-01

ABSTRACT. Background. Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. Objective: This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Methods: Medline, Web of Knowledge and PsycINFO were searched, using the terms: “vascular mild cognitive impairment” OR “vascular cognitive impairment no dementia” OR “vascular mild neurocognitive disorder” AND “dysexecutive” OR “executive function”. Meta-analyses were conducted for each of the selected tests, using random-effect models. Results: Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. Conclusion: A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control. PMID:29354217

Mindfulness-based cognitive therapy for depressed individuals improves suppression of irrelevant mental-sets.

PubMed

Greenberg, Jonathan; Shapero, Benjamin G; Mischoulon, David; Lazar, Sara W

2017-04-01

An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in depression. Mindfulness-based cognitive therapy (MBCT) was specifically designed to help depressed individuals avoid getting caught in such irrelevant mental-sets. In the current study, a group assigned to MBCT plus treatment-as-usual (n = 22) exhibited significantly lower depression scores and greater improvements in irrelevant mental-set suppression compared to a wait-list plus treatment-as-usual (n = 18) group. Improvements in mental-set-suppression were associated with improvements in depression scores. Results provide the first evidence that MBCT can improve suppression of irrelevant mental-sets and that such improvements are associated with depressive alleviation.

Cognitive and behavioral deficits in premature graduates of intensive care.

PubMed

Perlman, Jeffrey M

2002-12-01

A substantial number of VLBW graduates of intensive care develop cognitive and behavioral problems, even in the absence of neuroimaging abnormalities. Although this article has highlighted the potential, important, contributing role of medical and stressful, neonatal, environmental conditions to the development of these deficits, it is not all-encompassing, and there are additional prenatal (ie, in utero stress, drug exposure) and neonatal (ie, infectious) contributing factors. The long-term, outcome data presented in this article are pertinent to the more mature, VLBW infant, and it remains unclear and critically important to delineate the long-term, neurobehavioral outcome of those extremely low birth-weight survivors born at the cutting limit of viability.

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

PubMed

Nakagawa, Yutaka; Chiba, Kenji

2016-09-01

Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Early Developmental Disturbances of Cortical Inhibitory Neurons: Contribution to Cognitive Deficits in Schizophrenia

PubMed Central

Volk, David W.; Lewis, David A.

2014-01-01

Cognitive dysfunction is a disabling and core feature of schizophrenia. Cognitive impairments have been linked to disturbances in inhibitory (gamma-aminobutyric acid [GABA]) neurons in the prefrontal cortex. Cognitive deficits are present well before the onset of psychotic symptoms and have been detected in early childhood with developmental delays reported during the first year of life. These data suggest that the pathogenetic process that produces dysfunction of prefrontal GABA neurons in schizophrenia may be related to altered prenatal development. Interestingly, adult postmortem schizophrenia brain tissue studies have provided evidence consistent with a disease process that affects different stages of prenatal development of specific subpopulations of prefrontal GABA neurons. Prenatal ontogeny (ie, birth, proliferation, migration, and phenotypic specification) of distinct subpopulations of cortical GABA neurons is differentially regulated by a host of transcription factors, chemokine receptors, and other molecular markers. In this review article, we propose a strategy to investigate how alterations in the expression of these developmental regulators of subpopulations of cortical GABA neurons may contribute to the pathogenesis of cortical GABA neuron dysfunction and consequently cognitive impairments in schizophrenia. PMID:25053651

Canonical correlation analysis of synchronous neural interactions and cognitive deficits in Alzheimer's dementia

NASA Astrophysics Data System (ADS)

Karageorgiou, Elissaios; Lewis, Scott M.; Riley McCarten, J.; Leuthold, Arthur C.; Hemmy, Laura S.; McPherson, Susan E.; Rottunda, Susan J.; Rubins, David M.; Georgopoulos, Apostolos P.

2012-10-01

In previous work (Georgopoulos et al 2007 J. Neural Eng. 4 349-55) we reported on the use of magnetoencephalographic (MEG) synchronous neural interactions (SNI) as a functional biomarker in Alzheimer's dementia (AD) diagnosis. Here we report on the application of canonical correlation analysis to investigate the relations between SNI and cognitive neuropsychological (NP) domains in AD patients. First, we performed individual correlations between each SNI and each NP, which provided an initial link between SNI and specific cognitive tests. Next, we performed factor analysis on each set, followed by a canonical correlation analysis between the derived SNI and NP factors. This last analysis optimally associated the entire MEG signal with cognitive function. The results revealed that SNI as a whole were mostly associated with memory and language, and, slightly less, executive function, processing speed and visuospatial abilities, thus differentiating functions subserved by the frontoparietal and the temporal cortices. These findings provide a direct interpretation of the information carried by the SNI and set the basis for identifying specific neural disease phenotypes according to cognitive deficits.

[The cognitive paradigm in the rehabilitation of schizophrenia - focusing on cognitive remediation].

PubMed

Muth, Veronika; Gyüre, Támas; Váradi, Enikö

2015-09-01

Neurocognitive deficits are core features of schizophrenia and well known to the specialists, concerning researches in Hungary as well. Significance of the topic derives from the fact that according to our present knowledge this is the prime symptom principally affecting everyday functioning and limits benefit of rehabilitation opportunities. The classic psychiatric rehabilitation toolset, either pharmacological or psychosocial, does not provide effective and specific assistance to alleviate the symptoms of the neurocognitive deficits. Despite the increasing presence of the neurocognitive-oriented rehabilitation in international publications and professional forums, cognitive development is rather neglected topic in the Hungarian literature; while the therapeutic practice - with the exception of one institution - is absent from the repertoire of the Hungarian rehabilitation. The purpose of this study is the multi-faceted presentation of recent results in the field of the cognitive remediation, describing the position of cognitive training and its place in the rehabilitation of schizophrenia, with the aim to gain reputation and promote clinical practice among the Hungarian experts. Cognitive remediation is a behavioral training, based on learning theory, with the aim of extensive and long-lasting improvement of cognitive functions of patients suffering from schizophrenia or other mental disorders. Despite the deceptively similar acronym it is important to distinguish this method from the cognitive behavioral therapy which shows similarity in its learning theory basis, but remediation involves much more educational features. Cognitive remediation is not a unified technique, different settings are known, but regardless of form factors it clearly has a specific and positive effect on the neurocognitive functions. It fits well into the rehabilitation methodology, in fact this embeddedness significantly increases its effectiveness and supports emergence of skills in

The Cognitive Abilities and Skills of Children Who Suffer from Attention Deficit and Hyperactivity Disorder (ADHD) in Kuwait State

ERIC Educational Resources Information Center

Mohammed, Ali Mohammed Haidar

2016-01-01

The present study aims to identify the level of cognitive skills and abilities of children who suffer from the Attention Deficit and Hyperactivity Disorder (ADHD) and the differences in the level of cognitive skills and abilities according to the age group and the level of academic achievement. To achieve the objective of the study, a…

The effect of cognitive remediation in individuals at ultra-high risk for psychosis: a systematic review.

PubMed

Glenthøj, Louise Birkedal; Hjorthøj, Carsten; Kristensen, Tina Dam; Davidson, Charlie Andrew; Nordentoft, Merete

2017-01-01

Cognitive deficits are prominent features of the ultra-high risk state for psychosis that are known to impact functioning and course of illness. Cognitive remediation appears to be the most promising treatment approach to alleviate the cognitive deficits, which may translate into functional improvements. This study systematically reviewed the evidence on the effectiveness of cognitive remediation in the ultra-high risk population. The electronic databases MEDLINE, PsycINFO, and Embase were searched using keywords related to cognitive remediation and the UHR state. Studies were included if they were peer-reviewed, written in English, and included a population meeting standardized ultra-high risk criteria. Six original research articles were identified. All the studies provided computerized, bottom-up-based cognitive remediation, predominantly targeting neurocognitive function. Four out of five studies that reported a cognitive outcome found cognitive remediation to improve cognition in the domains of verbal memory, attention, and processing speed. Two out of four studies that reported on functional outcome found cognitive remediation to improve the functional outcome in the domains of social functioning and social adjustment. Zero out of the five studies that reported such an outcome found cognitive remediation to affect the magnitude of clinical symptoms. Research on the effect of cognitive remediation in the ultra-high risk state is still scarce. The current state of evidence indicates an effect of cognitive remediation on cognition and functioning in ultra-high risk individuals. More research on cognitive remediation in ultra-high risk is needed, notably in large-scale trials assessing the effect of neurocognitive and/or social cognitive remediation on multiple outcomes.

Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis

PubMed Central

Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A.; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M.; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio

2017-01-01

Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ1–42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ1–42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS. PMID:29209169

Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis.

PubMed

Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio

2017-01-01

Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ 1-42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ 1-42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS.

Selective cognitive empathy deficit in adolescents with restrictive anorexia nervosa

PubMed Central

Calderoni, Sara; Fantozzi, Pamela; Maestro, Sandra; Brunori, Elena; Narzisi, Antonio; Balboni, Giulia; Muratori, Filippo

2013-01-01

Background A growing, but conflicting body of literature suggests altered empathic abilities in subjects with anorexia nervosa-restricting type (AN-R). This study aims to characterize the cognitive and affective empathic profiles of adolescents with purely AN-R. Methods As part of a standardized clinical and research protocol, the Interpersonal Reactivity Index (IRI), a valid and reliable self-reported instrument to measure empathy, was administered to 32 female adolescents with AN-R and in 41 healthy controls (HC) comparisons, matched for age and gender. Correlational analyses were performed to evaluate the links between empathy scores and psychopathological measures. Results Patients scored significantly lower than HC on cognitive empathy (CE), while they did not differ from controls on affective empathy (AE). The deficit in CE was not related to either disease severity nor was it related to associated psychopathology. Conclusion These results, albeit preliminary, suggest that a dysfunctional pattern of CE capacity may be a stable trait of AN-R that should be taken into account not only for the clinical management, but also in preventive and therapeutic intervention. PMID:24204149

Effects of environmental enrichment on behavioral and spatial cognitive deficits in morphine-dependent and -withdrawn rats.

PubMed

Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein

2017-02-01

This study was designed to examine the effect of environmental enrichment during morphine dependence and withdrawal on morphine-induced behavioral and spatial cognitive disorders in morphine-withdrawn rats. Adult male Wistar rats (190 ± 20 g) were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days. Rats were reared in SE or EE during the development of dependence on morphine and withdrawal. Then, rats were tested for spatial learning and memory (the water maze), spontaneous withdrawal signs, and grooming behavior. We found that the EE blocked chronic morphine-induced partial impairments of spatial memory retention. Moreover, the EE diminished the occurrence of spontaneous morphine withdrawal signs as mild and the self-grooming behavior. Our findings showed that EE ameliorates chronic morphine-induced partial deficits of spatial cognition, obsessive-like behavior, and the overall severity of the morphine withdrawal. Thus, environmental enrichment may be a potential therapeutic strategy for spatial memory and behavioral deficits in morphine-dependent individuals.

Manganese exposure and cognitive deficits: a growing concern for manganese neurotoxicity.

PubMed

Roels, H A; Bowler, R M; Kim, Y; Claus Henn, B; Mergler, D; Hoet, P; Gocheva, V V; Bellinger, D C; Wright, R O; Harris, M G; Chang, Y; Bouchard, M F; Riojas-Rodriguez, H; Menezes-Filho, J A; Téllez-Rojo, Martha Maria

2012-08-01

This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age. Copyright © 2012 Elsevier Inc. All rights reserved.

Innovative Management of Budget Deficits: A Proportional Salary and Time Reduction Scheme.

ERIC Educational Resources Information Center

Sloper, David

1989-01-01

An approach to institutional budgeting designed to alleviate accumulated deficits is described. The proposal introduces flexibility into the salary component, alleviating cash flow difficulties in the short to medium term and encouraging more proactive budgeting, by allowing employees to contract for reduced annual salary in exchange for reduced…

A Case Study of the Cognitive and Behavioral Deficits of Temporal Lobe Damage in Herpes Simplex Encephalitis.

ERIC Educational Resources Information Center

Greer, Margaret K.; And Others

1989-01-01

This case study illustrates the highly significant language difficulties, marked memory deficits, and propensity for physical aggression following temporal lobe damage brought about by herpes encephalitis, and presents the usefulness of a new diagnostic measure in delineating such a variable cognitive pattern. (Author)

Sleep quality affects cognitive functioning in returning combat veterans beyond combat exposure, PTSD, and mild TBI history.

PubMed

Martindale, Sarah L; Morissette, Sandra B; Rowland, Jared A; Dolan, Sara L

2017-01-01

The purpose of this study was to determine how sleep quality affects cognitive functioning in returning combat veterans after accounting for effects of combat exposure, posttraumatic stress disorder (PTSD), and mild traumatic brain injury (mTBI) history. This was a cross-sectional assessment study evaluating combat exposure, PTSD, mTBI history, sleep quality, and neuropsychological functioning. One hundred and nine eligible male Iraq/Afghanistan combat veterans completed an assessment consisting of a structured clinical interview, neuropsychological battery, and self-report measures. Using partial least squares structural equation modeling, combat experiences and mTBI history were not directly associated with sleep quality. PTSD was directly associated with sleep quality, which contributed to deficits in neuropsychological functioning independently of and in addition to combat experiences, PTSD, and mTBI history. Combat experiences and PTSD were differentially associated with motor speed. Sleep affected cognitive function independently of combat experiences, PTSD, and mTBI history. Sleep quality also contributed to cognitive deficits beyond effects of PTSD. An evaluation of sleep quality may be a useful point of clinical intervention in combat veterans with cognitive complaints. Improving sleep quality could alleviate cognitive complaints, improving veterans' ability to engage in treatment. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Effects of URB597 as an inhibitor of fatty acid amide hydrolase on WIN55, 212-2-induced learning and memory deficits in rats.

PubMed

Hasanein, Parisa; Teimuri Far, Massoud

2015-04-01

Cannabinoid and endocannabinoid systems have been implicated in several physiological functions including modulation of cognition. In this study we evaluated the effects and interaction between fatty-acid amide hydrolase (FAAH) inhibitor URB597 and CB1 receptor agonist WIN55, 212-2 on memory using object recognition and passive avoidance learning (PAL) tests. Learning and memory impairment was induced by WIN 55, 212-2 administration (1mg/kg, i.p.) 30min before the acquisition trial. URB597 (0.1, 0.3 and 1mg/kg, i.p.) or SR141716A (1mg/kg, i.p.) was injected to rats 10min before WIN 55, 212-2 or URB597 respectively. URB597 (0.3 and 1mg/kg) but not 0.1mg/kg induced higher discrimination index (DI) in object recognition test and enhanced memory acquisition in PAL test. The cognitive enhancing effect of URB597 was blocked by a CB1 receptor antagonist, SR141716A which at this dose alone had no effect on cognition. WIN55, 212-2 caused cognition deficits in both tests. URB597 (0.3 and 1mg/kg) treatment could alleviate the negative influence of WIN 55, 212-2 on cognition and memory. These results indicate URB597 potential to protect against memory deficits induced by cannabinoid. Therefore, in combination with URB597 beneficial effects, this study suggests that URB597 has recognition and acquisition memory enhancing effects. It may also constitute a novel approach for the treatment of cannabinoid induced memory deficits and lead to a better understanding of the brain mechanisms underlying cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive impairment in COPD: should cognitive evaluation be part of respiratory assessment?

PubMed Central

Gloeckl, Rainer; Vogiatzis, Ioannis; Kenn, Klaus

2017-01-01

Cognitive impairment is highly prevalent in patients with COPD and demonstrates multiple detrimental effects on many aspects of patient state and therapeutic outcomes. It is attributed to several overlapping pathophysiological factors, with the most common being the low level of oxygen saturation due to respiratory insufficiency. Despite the impact of cognitive impairment on clinical outcomes, the screening for coexisting cognitive deficits which may interfere with the successful progress of respiratory treatment is yet neglected. There is a special consideration that cognitive deficits should be taken into account when developing respiratory therapy plans. Cognitively impaired patients are likely to require more support and have need of an individualised respiratory care plan which can also be beneficial for their cognitive deficits. Pulmonary rehabilitation as a multidisciplinary approach could be prioritised for COPD patients with cognitive impairment. Educational aims To illustrate the common signs of cognitive impairment and define potential associations between lung and cognitive dysfunction. To illustrate the potential influence of cognitive deficits on the optimal progress of respiratory therapy. To illustrate the importance of cognitive evaluation as part of a comprehensive clinical assessment for patients suspected of suffering cognitive impairment. PMID:29184593

Awake craniotomy in a developmentally delayed blind man with cognitive deficits.

PubMed

Burbridge, Mark; Raazi, Mateen

2013-04-01

To describe the complex perioperative considerations and anesthetic management of a cognitively delayed blind adult male who underwent awake craniotomy to remove a left anterior temporal lobe epileptic focus. A 28-yr-old left-handed blind cognitively delayed man was scheduled for awake craniotomy to resect a left anterior temporal lobe epileptic focus due to intractable epilepsy despite multiple medications. His medical history was also significant for retinopathy of prematurity that rendered him legally blind in both eyes and an intracerebral hemorrhage shortly after birth that resulted in a chronic brain injury and developmental delay. His cognitive capacity was comparable with that of an eight year old. Since patient cooperation was the primary concern during the awake electrocorticography phase of surgery, careful assessment of the patient's ability to tolerate the procedure was undertaken. There was extensive planning between surgeons and anesthesiologists, and a patient-specific pharmacological strategy was devised to facilitate surgery. The operation proceeded without complication, the patient has remained seizure-free since the procedure, and his quality of life has improved dramatically. This case shows that careful patient assessment, effective interdisciplinary communication, and a carefully tailored anesthetic strategy can facilitate an awake craniotomy in a potentially uncooperative adult patient with diminished mental capacity and sensory deficits.

Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging.

PubMed

Fliss, Rafika; Lemerre, Marion; Mollard, Audrey

2016-06-01

Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed.

Failures of cognitive control or attention? The case of stop-signal deficits in schizophrenia.

PubMed

Matzke, Dora; Hughes, Matthew; Badcock, Johanna C; Michie, Patricia; Heathcote, Andrew

2017-05-01

We used Bayesian cognitive modelling to identify the underlying causes of apparent inhibitory deficits in the stop-signal paradigm. The analysis was applied to stop-signal data reported by Badcock et al. (Psychological Medicine 32: 87-297, 2002) and Hughes et al. (Biological Psychology 89: 220-231, 2012), where schizophrenia patients and control participants made rapid choice responses, but on some trials were signalled to stop their ongoing response. Previous research has assumed an inhibitory deficit in schizophrenia, because estimates of the mean time taken to react to the stop signal are longer in patients than controls. We showed that these longer estimates are partly due to failing to react to the stop signal ("trigger failures") and partly due to a slower initiation of inhibition, implicating a failure of attention rather than a deficit in the inhibitory process itself. Correlations between the probability of trigger failures and event-related potentials reported by Hughes et al. are interpreted as supporting the attentional account of inhibitory deficits. Our results, and those of Matzke et al. (2016), who report that controls also display a substantial although lower trigger-failure rate, indicate that attentional factors need to be taken into account when interpreting results from the stop-signal paradigm.

The Neural Substrates of Cognitive Control Deficits in Autism Spectrum Disorders

PubMed Central

Solomon, Marjorie; Ozonoff, Sally; Ursu, Stefan; Ravizza, Susan; Cummings, Neil; Ly, Stanford; Carter, Cameron

2009-01-01

Executive functions deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive functions deficits in ASDs, and only one in adolescents. The current study examined cognitive control –the ability to maintain task context online to support adaptive functioning in the face of response competition—in 22 adolescents aged 12–18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7, 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms. PMID:19410583

Amantadine Ameliorates Dopamine-Releasing Deficits and Behavioral Deficits in Rats after Fluid Percussion Injury

PubMed Central

Huang, Eagle Yi-Kung; Tsui, Pi-Fen; Kuo, Tung-Tai; Tsai, Jing-Jr.; Chou, Yu-Ching; Ma, Hsin-I; Chiang, Yung-Hsiao; Chen, Yuan-Hao

2014-01-01

Aims To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery. Materials and Methods In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. Rats subjected to 6-Pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group) or amantadine hydrochloride, with a releasing rate of 3.6mg/kg/hour for 8 weeks. The dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (FSCV) and high-pressure liquid chromatography (HPLC). Novel object recognition (NOR) and fixed-speed rotarod (FSRR) behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury. Results Sequential dopamine-release deficits were revealed in 6-Pa-fluid-percussion cerebral cortical injured animals. The reuptake rate (tau value) of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. Cognitive and motor learning impairments were shown evidenced by the NOR and FSRR behavioral tests after injury. Chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion. Conclusion Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury. PMID:24497943

Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect visuo‐perceptual deficits

PubMed Central

Schwarzkopf, Dietrich S.; Bahrami, Bahador; Fleming, Stephen M.; Jackson, Ben M.; Goch, Tristam J. C.; Saygin, Ayse P.; Miller, Luke E.; Pappa, Katerina; Pavisic, Ivanna; Schade, Rachel N.; Noyce, Alastair J.; Crutch, Sebastian J.; O'Keeffe, Aidan G.; Schrag, Anette E.; Morris, Huw R.

2018-01-01

ABSTRACT Background: People with Parkinson's disease (PD) who develop visuo‐perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuo‐perceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo‐perceptual deficits in PD. Objective: We developed an online platform to test visuo‐perceptual function. We hypothesised that (1) visuo‐perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias. Methods: We assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks. Results: People with PD were worse than controls at object recognition, showing no deficits in other visuo‐perceptual tests. Specifically, they were worse at identifying skewed images (P < .0001); at detecting hidden objects (P = .0039); at identifying objects in peripheral vision (P < .0001); and at detecting biological motion (P = .0065). In contrast, people with PD were not worse at mental rotation or subjective size perception. Using signal detection modelling, we found this effect was driven by change in perceptual sensitivity rather than response bias. Conclusions: Online tests can detect visuo‐perceptual deficits in people with PD, with object recognition particularly affected. Ultimately, visuo‐perceptual tests may be developed to identify at‐risk patients for clinical trials to slow PD dementia. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:29473691

Number Processing and Heterogeneity of Developmental Dyscalculia: Subtypes With Different Cognitive Profiles and Deficits.

PubMed

Skagerlund, Kenny; Träff, Ulf

2016-01-01

This study investigated if developmental dyscalculia (DD) in children with different profiles of mathematical deficits has the same or different cognitive origins. The defective approximate number system hypothesis and the access deficit hypothesis were tested using two different groups of children with DD (11-13 years old): a group with arithmetic fact dyscalculia (AFD) and a group with general dyscalculia (GD). Several different aspects of number magnitude processing were assessed in these two groups and compared with age-matched typically achieving children. The GD group displayed weaknesses with both symbolic and nonsymbolic number processing, whereas the AFD group displayed problems only with symbolic number processing. These findings provide evidence that the origins of DD in children with different profiles of mathematical problems diverge. Children with GD have impairment in the innate approximate number system, whereas children with AFD suffer from an access deficit. These findings have implications for researchers' selection procedures when studying dyscalculia, and also for practitioners in the educational setting. © Hammill Institute on Disabilities 2014.

Activation of the canonical nuclear factor-κB pathway is involved in isoflurane-induced hippocampal interleukin-1β elevation and the resultant cognitive deficits in aged rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zheng-Qian; Rong, Xiao-Ying; Liu, Ya-Jie

Highlights: •Isoflurane induces hippocampal IL-1β elevation and cognitive deficits in aged rats. •Isoflurane transiently activates the canonical NF-κB pathway in aged rat hippocampus. •NF-κB inhibitor mitigates isoflurane-induced IL-1β elevation and cognitive deficits. •We report a linkage between NF-κB signaling, IL-1β expression, and cognitive changes. -- Abstract: Although much recent evidence has demonstrated that neuroinflammation contributes to volatile anesthetic-induced cognitive deficits, there are few existing mechanistic explanations for this inflammatory process. This study was conducted to investigate the effects of the volatile anesthetic isoflurane on canonical nuclear factor (NF)-κB signaling, and to explore its association with hippocampal interleukin (IL)-1β levels andmore » anesthetic-related cognitive changes in aged rats. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in IκB kinase and IκB phosphorylation, as well as a reduction in the NF-κB inhibitory protein (IκBα), were observed in the hippocampi of isoflurane-exposed rats compared with control rats. These events were accompanied by an increase in NF-κB p65 nuclear translocation at 6 h after isoflurane exposure and hippocampal IL-1β elevation from 1 to 6 h after isoflurane exposure. Nevertheless, no significant neuroglia activation was observed. Pharmacological inhibition of NF-κB activation by pyrrolidine dithiocarbamate markedly suppressed the IL-1β increase and NF-κB signaling, and also mitigated the severity of cognitive deficits in the Morris water maze task. Overall, our results demonstrate that isoflurane-induced cognitive deficits may stem from upregulation of hippocampal IL-1β, partially via activation of the canonical NF-κB pathway, in aged rats.« less

Intra-regional and inter-regional abnormalities and cognitive control deficits in young adult smokers.

PubMed

Feng, Dan; Yuan, Kai; Li, Yangding; Cai, Chenxi; Yin, Junsen; Bi, Yanzhi; Cheng, Jiadong; Guan, Yanyan; Shi, Sha; Yu, Dahua; Jin, Chenwang; Lu, Xiaoqi; Qin, Wei; Tian, Jie

2016-06-01

Tobacco use during later adolescence and young adulthood may cause serious neurophysiological changes; rationally, it is extremely important to study the relationship between brain dysfunction and behavioral performances in young adult smokers. Previous resting state studies investigated the neural mechanisms in smokers. Unfortunately, few studies focused on spontaneous activity differences between young adult smokers and nonsmokers from both intra-regional and inter-regional levels, less is known about the association between resting state abnormalities and behavioral deficits. Therefore, we used fractional amplitude of low frequency fluctuation (fALFF) and resting state functional connectivity (RSFC) to investigate the resting state spontaneous activity differences between young adult smokers and nonsmokers. A correlation analysis was carried out to assess the relationship between neuroimaging findings and clinical information (pack-years, cigarette dependence, age of onset and craving score) as well as cognitive control deficits measured by the Stroop task. Consistent with previous addiction findings, our results revealed the resting state abnormalities within frontostriatal circuits, i.e., enhanced spontaneous activity of the caudate and reduced functional strength between the caudate and anterior cingulate cortex (ACC) in young adult smokers. Moreover, the fALFF values of the caudate were correlated with craving and RSFC strength between the caudate and ACC was associated with the cognitive control impairments in young adult smokers. Our findings could lead to a better understanding of intrinsic functional architecture of baseline brain activity in young smokers by providing regional and brain circuit spontaneous neuronal activity properties as well as their association with cognitive control impairments.

Do complaints of everyday cognitive failures in high schizotypy relate to emotional working memory deficits in the lab?

PubMed

Carrigan, Nicole; Barkus, Emma; Ong, Adriel; Wei, Maryann

2017-10-01

Individuals high on schizotypy complain of increased cognitive failures in everyday life. However, the neuropsychological performance of this group does not consistently indicate underlying ability deficits. It is possible that current neuropsychological tests lack ecological validity. Given the increased affective reactivity of high schizotypes, they may be more sensitive to emotional content interfering with cognitive ability. This study sought to explore whether an affective n-back working memory task would elicit impaired performance in schizotypy, echoing complaints concerning real world cognition. 127 healthy participants completed self-report measures of schizotypy and cognitive failures and an affective n-back working memory task. This task was varied across three levels of load (1- to 3-back) and four types of stimulus emotion (neutral, fearful, happy, sad). Differences between high (n=39) and low (n=48) schizotypy groups on performance outcomes of hits and false alarms were examined, with emotion and load as within-groups variables. As expected, high schizotypes reported heightened vulnerability to cognitive failures. They also demonstrated a relative working memory impairment for emotional versus neutral stimuli, whereas low schizotypes did not. High schizotypes performed most poorly in response to fearful stimuli. For false alarms, there was an interaction between schizotypy, load, and emotion, such that high schizotypy was associated with deficits in response to fearful stimuli only at higher levels of task difficulty. Inclusion of self-reported cognitive failures did not account for this. These findings suggest that the "gap" between subjective and objective cognition in schizotypy may reflect the heightened emotional demands associated with cognitive functioning in the real world, although other factors also seem to play a role. There is a need to improve the ecological validity of objective assessments, whilst also recognizing that self

A metacognitive perspective on the cognitive deficits experienced in intellectually threatening environments.

PubMed

Schmader, Toni; Forbes, Chad E; Zhang, Shen; Mendes, Wendy Berry

2009-05-01

Three studies tested the hypothesis that negative metacognitive interpretations of anxious arousal under stereotype threat create cognitive deficits in intellectually threatening environments. Study 1 showed that among minority and White undergraduates, anxiety about an intelligence test predicted lower working memory when participants were primed with doubt as compared to confidence. Study 2 replicated this pattern with women and showed it to be unique to intellectually threatening environments. Study 3 used emotional reappraisal as an individual difference measure of the tendency to metacognitively reinterpret negative emotions and found that when sympathetic activation was high (indexed by salivary alpha-amylase), women who tended to reappraise negative feelings performed better in math and felt less self-doubt than those low in reappraisal. Overall, findings highlight how metacognitive interpretations of affect can undermine cognitive efficiency under stereotype threat and offer implications for the situational and individual difference variables that buffer people from these effects.

Cognition, social cognition and functional disability in early-stage schizophrenia: A study from southern India.

PubMed

Kurtz, Matthew M; Gopal, Subhashini; John, Sujit; Thara, R

2018-04-24

In high-income countries a wealth of studies has revealed cognitive and social cognitive deficits in schizophrenia and a close relationship of these deficits to psychosocial functioning. Studies examining these illness features in middle and low-income countries are rare, particularly in early-stage samples. Sixty adult participants within 5 years of diagnosis with schizophrenia and 53 matched, healthy control were assessed with the MATRICS Consensus Cognitive Battery and the PEAT emotion identification task at study entry, and the WHODAS functioning scale one year later. Deficits on cognitive instruments ranged from d = 0.64-1.04 and were consistent with those reported in Western samples. Negative symptoms were linked to function longitudinally. Deficits in social cognitive skills and longitudinal links between cognition and functioning were not evident. These findings suggest a highly consistent magnitude of neurocognitive deficits in people with schizophrenia across widely varying cultures, but with limited evidence of social cognitive skill deficits using Western-based instruments. There was little evidence of a relationship between cognition and psychosocial disability in people with early-stage schizophrenia in this sample. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of elderly drivers whose crash involvement risks are alleviated by passenger presence.

PubMed

Nakagawa, Yoshinori; Park, Kaechang

2014-01-01

It is essential to find measures to compensate for the decline in elderly drivers' driving ability in order to meet their mobility needs and ensure their safety when driving. Although it has been well documented that elderly drivers' risks of crash involvement are alleviated by the presence of passengers, few studies have investigated whether the protective effect of passengers is influenced by driver characteristics including the degree of cognitive impairment. This study aimed to identify subgroups of elderly drivers whose crash involvement risks are more effectively alleviated by passenger presence. After dividing elderly drivers into three levels of cognitive impairment, as measured by the Short-Memory Questionnaire, and two gender groups, the present study found that only male drivers in the middle cognitive level benefited from passenger presence. The effectiveness of passenger presence may be more successfully achieved by proper selection of the appropriate range of cognitive decline and gender.

16p11.2 Deletion Mice Display Cognitive Deficits in Touchscreen Learning and Novelty Recognition Tasks

ERIC Educational Resources Information Center

Yang, Mu; Lewis, Freeman C.; Sarvi, Michael S.; Foley, Gillian M.; Crawley, Jacqueline N.

2015-01-01

Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/-) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2…

Ameliorating mitochondrial dysfunction restores carbon ion-induced cognitive deficits via co-activation of NRF2 and PINK1 signaling pathway.

PubMed

Liu, Yang; Yan, Jiawei; Sun, Cao; Li, Guo; Li, Sirui; Zhang, Luwei; Di, Cuixia; Gan, Lu; Wang, Yupei; Zhou, Rong; Si, Jing; Zhang, Hong

2018-07-01

Carbon ion therapy is a promising modality in radiotherapy to treat tumors, however, a potential risk of induction of late normal tissue damage should still be investigated and protected. The aim of the present study was to explore the long-term cognitive deficits provoked by a high-linear energy transfer (high-LET) carbon ions in mice by targeting to hippocampus which plays a crucial role in memory and learning. Our data showed that, one month after 4 Gy carbon ion exposure, carbon ion irradiation conspicuously resulted in the impaired cognitive performance, neurodegeneration and neuronal cell death, as well as the reduced mitochondrial integrity, the disrupted activities of tricarboxylic acid cycle flux and electron transport chain, and the depressed antioxidant defense system, consequently leading to a decline of ATP production and persistent oxidative damage in the hippocampus region. Mechanistically, we demonstrated the disruptions of mitochondrial homeostasis and redox balance typically characterized by the disordered mitochondrial dynamics, mitophagy and glutathione redox couple, which is closely associated with the inhibitions of PINK1 and NRF2 signaling pathway as the key regulators of molecular responses in the context of neurotoxicity and neurodegenerative disorders. Most importantly, we found that administration with melatonin as a mitochondria-targeted antioxidant promoted the PINK1 accumulation on the mitochondrial membrane, and augmented the NRF2 accumulation and translocation. Moreover, melatonin pronouncedly enhanced the molecular interplay between NRF2 and PINK1. Furthermore, in the mouse hippocampal neuronal cells, overexpression of NRF2/PINK1 strikingly protected the hippocampal neurons from carbon ion-elicited toxic insults. Thus, these data suggest that alleviation of the sustained mitochondrial dysfunction and oxidative stress through co-modulation of NRF2 and PINK1 may be in charge of restoration of the cognitive impairments in a mouse

Neurocognitive deficits in older patients with cancer.

PubMed

Edwards, Beatrice J; Zhang, Xiaotao; Sun, Ming; Holmes, Holly M; Ketonen, Leena; Guha, Nandita; Khalil, Peter; Song, Juhee; Kesler, Shelli; Shah, Jay B; Tripathy, Debasish; Valero, Vicente; Champlin, Richard E

2018-03-09

To assess cognitive function in older adults undergoing cancer care. This is a cross-sectional study, in the University of Texas MD Anderson Cancer Center, in older adults undergoing cancer care. Comprehensive geriatric assessments were conducted prior to surgery, chemotherapy or allogeneic stem cell transplantation, at the Program for Healthy Aging from January 1, 2013 through March 31, 2015. Cognitive assessment was conducted through personal and family interview, and the Montreal cognitive assessment (MoCA). Functional, physical, nutritional, social support, comorbidity assessment and medication review were conducted. Patients with mild cognitive impairment (MCI) or dementia were compared to patients who were cognitively intact. One hundred and ninety-two patients underwent geriatric assessment, mean (±SD) age was 78 ± 7 years, 121 (63%) had some degree of neurocognitive deficit, with 64 patients (33%) presenting with major neurocognitive deficit (dementia), and 57 cases (30%), minor neurocognitive deficit (MCI). Early stage dementia was evident in 50% of cases, moderate stage in 32%, and severe stage in 18%. The prevalence of dementia and MCI were higher than in the general population studies (70-79 years). Associated factors for neurocognitive deficits as compared to older patients with cancer with normal cognition, included a higher comorbidity index (p = 0.04), stroke (p = 0.03), metastatic disease (p = 0.04), and warfarin use (p = 0.03). Neurocognitive deficits (MCI and dementia) are more common in older adults with cancer. Factors associated with neurocognitive deficits include high comorbidity, stroke, warfarin use and metastatic cancer. Identification and management of these conditions is of great relevance in the course of cancer therapy. Copyright © 2018. Published by Elsevier Ltd.

Chronic Desipramine Treatment Rescues Depression-Related, Social and Cognitive Deficits in Engrailed-2 Knockout Mice

PubMed Central

Brielmaier, Jennifer; Senerth, Julia M.; Silverman, Jill L.; Matteson, Paul G.; Millonig, James H.; DiCicco-Bloom, Emanuel; Crawley, Jacqueline N.

2014-01-01

Engrailed-2 (En2) is a homeobox transcription factor that regulates neurodevelopmental processes including neuronal connectivity and elaboration of monoaminergic neurons in the ventral hindbrain. We previously reported abnormalities in brain noradrenergic concentrations in En2 null mutant mice that were accompanied by increased immobility in the forced swim test, relevant to depression. An EN2 genetic polymorphism has been associated with autism spectrum disorders (ASD), and mice with a deletion in En2 display social abnormalities and cognitive deficits that may be relevant to multiple neuropsychiatric conditions. The present study evaluated the ability of chronic treatment with desipramine (DMI), a selective norepinephrine reuptake inhibitor and classical antidepressant, to reverse behavioral abnormalities in En2 −/− mice. DMI treatment significantly reduced immobility in the tail suspension and forced swim tests, restored sociability in the three-chambered social approach task, and reversed impairments in contextual fear conditioning in En2 −/− mice. Our findings indicate that modulation of brain noradrenergic systems rescues the depression-related phenotype in En2 −/− mice and suggest new roles for norepinephrine in the pathophysiology of the social and cognitive deficits seen in neuropsychiatric disorders such as autism or schizophrenia. PMID:24730055

A brain-spine interface alleviating gait deficits after spinal cord injury in primates.

PubMed

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-11-10

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for

A Brain–Spinal Interface Alleviating Gait Deficits after Spinal Cord Injury in Primates

PubMed Central

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D.; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-01-01

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spinal interface in intact monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal interface have all been approved for investigational

Piracetam improves cognitive deficits caused by chronic cerebral hypoperfusion in rats.

PubMed

He, Zhi; Liao, Yun; Zheng, Min; Zeng, Fan-Dian; Guo, Lian-Jun

2008-06-01

Piracetam is the derivate of gamma-aminobutyric acid, which improves the cognition,memory,consciousness, and is widely applied in the clinical treatment of brain dysfunction. In the present experiments, we study the effects of piracetam on chronic cerebral hypoperfused rats and observe its influence on amino acids, synaptic plasticity in the Perforant path-CA3 pathway and apoptosis in vivo. Cerebral hypoperfusion for 30 days by occlusion of bilateral common carotid arteries induced marked amnesic effects along with neuron damage, including: (1) spatial learning and memory deficits shown by longer escape latency and shorter time spent in the target quadrant; (2) significant neuronal loss and nuclei condensation in the cortex and hippocampus especially in CA1 region; (3) lower induction rate of long term potentiation, overexpression of BAX and P53 protein, and lower content of excitatory and inhibitory amino acids in hippocampus. Oral administration of piracetam (600 mg/kg, once per day for 30 days) markedly improved the memory impairment, increased the amino acid content in hippocampus, and attenuated neuronal damage. The ability of piracetam to attenuate memory deficits and neuronal damage after hypoperfusion may be beneficial in cerebrovascular type dementia.

Social Cognition in Children with High-Functioning Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Associations with Executive Functions

PubMed Central

Miranda, Ana; Berenguer, Carmen; Roselló, Belén; Baixauli, Inmaculada; Colomer, Carla

2017-01-01

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders characterized by social impairments. The first objective of this study was to analyze social cognition deficits of children with ADHD, high-functioning ASD (HFASD), and typical development (TD) in their performance on explicit and applied measures of theory of mind (ToM). The second objective was to investigate the relationships between executive functions and social cognition in HFASD and ADHD. One hundred and twenty-six 7- to 11-year old children, 52 with HFASD, 35 with ADHD, and 39 with TD, performed the NEPSY-II social perception subtests. Parents estimated their children's ToM skills using the Theory of Mind Inventory (ToMI). Teacher-reported data from the Behavior Rating Inventory of Executive Function (BRIEF) were also obtained. The HFASD and ADHD groups showed worse performance on the verbal ToM task than the TD group, and only the performance of the HFASD group was significantly lower than the TD group on the contextual ToM task. Parents also estimated that the HFASD group had more difficulties on the applied ToM than the ADHD and TD groups. Furthermore, there is a different executive function-theory of mind link in the HFASD and ADHD groups: behavioral regulation processes such as inhibition and emotional control are more associated with social cognition in children with ADHD, whereas metacognitive processes such as initiation and planning have a strong association with social cognition in children with HFASD. These findings have implications for understanding social perception deficits in neurodevelopmental disorders, highlighting the need for early intervention. PMID:28690570

Social Cognition in Children with High-Functioning Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Associations with Executive Functions.

PubMed

Miranda, Ana; Berenguer, Carmen; Roselló, Belén; Baixauli, Inmaculada; Colomer, Carla

2017-01-01

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders characterized by social impairments. The first objective of this study was to analyze social cognition deficits of children with ADHD, high-functioning ASD (HFASD), and typical development (TD) in their performance on explicit and applied measures of theory of mind (ToM). The second objective was to investigate the relationships between executive functions and social cognition in HFASD and ADHD. One hundred and twenty-six 7- to 11-year old children, 52 with HFASD, 35 with ADHD, and 39 with TD, performed the NEPSY-II social perception subtests. Parents estimated their children's ToM skills using the Theory of Mind Inventory (ToMI). Teacher-reported data from the Behavior Rating Inventory of Executive Function (BRIEF) were also obtained. The HFASD and ADHD groups showed worse performance on the verbal ToM task than the TD group, and only the performance of the HFASD group was significantly lower than the TD group on the contextual ToM task. Parents also estimated that the HFASD group had more difficulties on the applied ToM than the ADHD and TD groups. Furthermore, there is a different executive function-theory of mind link in the HFASD and ADHD groups: behavioral regulation processes such as inhibition and emotional control are more associated with social cognition in children with ADHD, whereas metacognitive processes such as initiation and planning have a strong association with social cognition in children with HFASD. These findings have implications for understanding social perception deficits in neurodevelopmental disorders, highlighting the need for early intervention.

CREB Overexpression Ameliorates Age-related Behavioral and Biophysical Deficits

NASA Astrophysics Data System (ADS)

Yu, Xiao-Wen

Age-related cognitive deficits are observed in both humans and animals. Yet, the molecular mechanisms underlying these deficits are not yet fully elucidated. In aged animals, a decrease in intrinsic excitability of pyramidal neurons from the CA1 sub-region of hippocampus is believed to contribute to age-related cognitive impairments, but the molecular mechanism(s) that modulate both these factors has yet to be identified. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents has been shown to facilitate cognition, and increase intrinsic excitability of their neurons. However, how CREB changes with age, and how that impacts cognition in aged animals, is not clear. Therefore, we first systematically characterized age- and training-related changes in CREB levels in dorsal hippocampus. At a remote time point after undergoing behavioral training, levels of total CREB and activated CREB (phosphorylated at S133, pCREB) were measured in both young and aged rats. We found that pCREB, but not total CREB was significantly reduced in dorsal CA1 of aged rats. Importantly, levels of pCREB were found to be positively correlated with short-term spatial memory in both young and aged rats i.e. higher pCREB in dorsal CA1 was associated with better spatial memory. These findings indicate that an age-related deficit in CREB activity may contribute to the development of age-related cognitive deficits. However, it was still unclear if increasing CREB activity would be sufficient to ameliorate age-related cognitive, and biophysical deficits. To address this question, we virally overexpressed CREB in CA1, where we found the age-related deficit. Young and aged rats received control or CREB virus, and underwent water maze training. While control aged animals exhibited deficits in long-term spatial memory, aged animals with CREB overexpression performed at levels comparable to young animals. Concurrently, aged neurons

Aminoguanidine alleviated MMA-induced impairment of cognitive ability in rats by downregulating oxidative stress and inflammatory reaction.

PubMed

Li, Qiliang; Song, Wenqi; Tian, Ze; Wang, Peichang

2017-03-01

Methylmalonic acidemia (MMA) is the most common organic acidemia in childhood. Many "treated" patients continued to display various degrees of mental retardation and psychomotor delay, which could be caused by brain damage from elevated oxidative stress. Aminoguanidine (AG), a synthetic antioxidant, was tested in a MMA rat model for its potential therapeutic effects on memory impairment. The effects of AG on MMA-induced cognitive impairment in Wistar rats were evaluated with Morris Water Maze. The levels of nerve cell apoptosis and microglial activation were investigated to illustrate the mechanisms of the improvement of cognition with AG treatment in MMA rats. To further explore the mechanism of neuroprotection induced by AG, several biomarkers including free radicals and inflammatory cytokines in the hippocampus were quantified. The results showed that the rats treated with AG exhibited better neurological behavior performances than MMA model rats. The AG-treated rats had a decreased level of apoptosis of the hippocampal neurons, which could be the structural basis of the observed neural behavior protection. In addition, AG treatment significantly inhibited the activation of microglia. The AG-treated rats had decreased levels of IL-1β, IL-6, TNF-α, NO, malonaldehyde and iNOS activities in the hippocampus. The level of glutathione and superoxide dismutase activity in the hippocampus of the AG-treated rats increased significantly. In conclusion, AG could alleviate the MMA-induced cognitive impairment via down-regulating of oxidative stress and inflammatory reaction and provide a basis as a therapeutic potential against MMA-induced cognitive impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

Aβ mediates F-actin disassembly in dendritic spines leading to cognitive deficits in Alzheimer's disease.

PubMed

Kommaddi, Reddy Peera; Das, Debajyoti; Karunakaran, Smitha; Nanguneri, Siddharth; Bapat, Deepti; Ray, Ajit; Shaw, Eisha; Bennett, David A; Nair, Deepak; Ravindranath, Vijayalakshmi

2018-01-31

Dendritic spine loss is recognized as an early feature of Alzheimer's disease (AD), but the underlying mechanisms are poorly understood. Dendritic spine structure is defined by filamentous actin (F-actin) and we observed depolymerization of synaptosomal F-actin accompanied by increased globular-actin (G-actin) at as early as 1 month of age in a mouse model of AD (APPswe/PS1ΔE9, male mice). This led to recall deficit after contextual fear conditioning (cFC) at 2 months of age in APPswe/PS1ΔE9 male mice, which could be reversed by the actin-polymerizing agent jasplakinolide. Further, the F-actin-depolymerizing agent latrunculin induced recall deficit after cFC in WT mice, indicating the importance of maintaining F-/G-actin equilibrium for optimal behavioral response. Using direct stochastic optical reconstruction microscopy (dSTORM), we show that F-actin depolymerization in spines leads to a breakdown of the nano-organization of outwardly radiating F-actin rods in cortical neurons from APPswe/PS1ΔE9 mice. Our results demonstrate that synaptic dysfunction seen as F-actin disassembly occurs very early, before onset of pathological hallmarks in AD mice, and contributes to behavioral dysfunction, indicating that depolymerization of F-actin is causal and not consequent to decreased spine density. Further, we observed decreased synaptosomal F-actin levels in postmortem brain from mild cognitive impairment and AD patients compared with subjects with normal cognition. F-actin decrease correlated inversely with increasing AD pathology (Braak score, Aβ load, and tangle density) and directly with performance in episodic and working memory tasks, suggesting its role in human disease pathogenesis and progression. SIGNIFICANCE STATEMENT Synaptic dysfunction underlies cognitive deficits in Alzheimer's disease (AD). The cytoskeletal protein actin plays a critical role in maintaining structure and function of synapses. Using cultured neurons and an AD mouse model, we show for the

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

PubMed

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

2015-10-01

The purpose of this study was to investigate the role of theta activity in cognitive mapping, and to determine whether age-associated decreased theta power may account for navigational difficulties in elderly individuals. Cerebral activity was recorded using electroencephalograph in young and older individuals performing a spatial memory task that required the creation of cognitive maps. Power spectra were computed in the frontal and parietal regions and correlated with recognition performance. We found that accuracy of cognitive mapping was positively correlated with left frontal theta activity during encoding in young adults but not in older individuals. Compared with young adults, older participants were impaired in the creation of cognitive maps and showed reduced theta and alpha activity at encoding. These results suggest that encoding processes are impaired in older individual, which may explain age-related cognitive mapping deficits. Copyright © 2015 Elsevier Inc. All rights reserved.

Impaired processing speed and attention in first-episode drug naive schizophrenia with deficit syndrome.

PubMed

Chen, Ce; Jiang, Wenhui; Zhong, Na; Wu, Jin; Jiang, Haifeng; Du, Jiang; Li, Ye; Ma, Xiancang; Zhao, Min; Hashimoto, Kenji; Gao, Chengge

2014-11-01

Although first-episode drug naive patients with schizophrenia are known to show cognitive impairment, the cognitive performances of these patients, who suffer deficit syndrome, compared with those who suffer non-deficit syndrome is undetermined. The aim of this study was to compare cognitive performances in first-episode drug-naive schizophrenia with deficit syndrome or non-deficit syndrome. First-episode drug naive patients (n=49) and medicated patients (n=108) with schizophrenia, and age, sex, and education matched healthy controls (n=57 for the first-episode group, and n=128 for the medicated group) were enrolled. Patients were divided into deficit or non-deficit syndrome groups, using the Schedule for Deficit Syndrome. Cognitive performance was assessed using the CogState computerized cognitive battery. All cognitive domains in first-episode drug naive and medicated patients showed significant impairment compared with their respective control groups. Furthermore, cognitive performance in first-episode drug naive patients was significantly worse than in medicated patients. Interestingly, the cognitive performance markers of processing speed and attention, in first-episode drug naive patients with deficit syndrome, were both significantly worse than in equivalent patients without deficit syndrome. In contrast, no differences in cognitive performance were found between the two groups of medicated patients. In conclusion, this study found that first-episode drug naive schizophrenia with deficit syndrome showed significantly impaired processing speed and attention, compared with patients with non-deficit syndrome. These findings highlight processing speed and attention as potential targets for pharmacological and psychosocial interventions in first-episode schizophrenia with deficit syndrome, since these domains are associated with social outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.

Spelling Difficulties in School-Aged Girls with Attention-Deficit/Hyperactivity Disorder: Behavioral, Psycholinguistic, Cognitive, and Graphomotor Correlates

ERIC Educational Resources Information Center

Åsberg Johnels, Jakob; Kopp, Svenny; Gillberg, Christopher

2014-01-01

Writing difficulties are common among children with attention-deficit/hyperactivity disorder (ADHD), but the nature of these difficulties has not been well studied. Here we relate behavioral, psycholinguistic, cognitive (memory/executive), and graphomotor measures to spelling skills in school-age girls with ADHD (n = 30) and an age-matched group…

Primary empathy deficits in frontotemporal dementia.

PubMed

Baez, Sandra; Manes, Facundo; Huepe, David; Torralva, Teresa; Fiorentino, Natalia; Richter, Fabian; Huepe-Artigas, Daniela; Ferrari, Jesica; Montañes, Patricia; Reyes, Pablo; Matallana, Diana; Vigliecca, Nora S; Decety, Jean; Ibanez, Agustin

2014-01-01

Loss of empathy is an early central symptom and diagnostic criterion of the behavioral variant frontotemporal dementia (bvFTD). Although changes in empathy are evident and strongly affect the social functioning of bvFTD patients, few studies have directly investigated this issue by means of experimental paradigms. The current study assessed multiple components of empathy (affective, cognitive and moral) in bvFTD patients. We also explored whether the loss of empathy constitutes a primary deficit of bvFTD or whether it is explained by impairments in executive functions (EF) or other social cognition domains. Thirty-seven bvFTD patients with early/mild stages of the disease and 30 healthy control participants were assessed with a task that involves the perception of intentional and accidental harm. Participants were also evaluated on emotion recognition, theory of mind (ToM), social norms knowledge and several EF domains. BvFTD patients presented deficits in affective, cognitive and moral aspects of empathy. However, empathic concern was the only aspect primarily affected in bvFTD that was neither related nor explained by deficits in EF or other social cognition domains. Deficits in the cognitive and moral aspects of empathy seem to depend on EF, emotion recognition and ToM. Our findings highlight the importance of using tasks depicting real-life social scenarios because of their greater sensitivity in the assessment of bvFTD. Moreover, our results contribute to the understanding of primary and intrinsic empathy deficits of bvFTD and have important theoretical and clinical implications.

Primary empathy deficits in frontotemporal dementia

PubMed Central

Baez, Sandra; Manes, Facundo; Huepe, David; Torralva, Teresa; Fiorentino, Natalia; Richter, Fabian; Huepe-Artigas, Daniela; Ferrari, Jesica; Montañes, Patricia; Reyes, Pablo; Matallana, Diana; Vigliecca, Nora S.; Decety, Jean; Ibanez, Agustin

2014-01-01

Loss of empathy is an early central symptom and diagnostic criterion of the behavioral variant frontotemporal dementia (bvFTD). Although changes in empathy are evident and strongly affect the social functioning of bvFTD patients, few studies have directly investigated this issue by means of experimental paradigms. The current study assessed multiple components of empathy (affective, cognitive and moral) in bvFTD patients. We also explored whether the loss of empathy constitutes a primary deficit of bvFTD or whether it is explained by impairments in executive functions (EF) or other social cognition domains. Thirty-seven bvFTD patients with early/mild stages of the disease and 30 healthy control participants were assessed with a task that involves the perception of intentional and accidental harm. Participants were also evaluated on emotion recognition, theory of mind (ToM), social norms knowledge and several EF domains. BvFTD patients presented deficits in affective, cognitive and moral aspects of empathy. However, empathic concern was the only aspect primarily affected in bvFTD that was neither related nor explained by deficits in EF or other social cognition domains. Deficits in the cognitive and moral aspects of empathy seem to depend on EF, emotion recognition and ToM. Our findings highlight the importance of using tasks depicting real-life social scenarios because of their greater sensitivity in the assessment of bvFTD. Moreover, our results contribute to the understanding of primary and intrinsic empathy deficits of bvFTD and have important theoretical and clinical implications. PMID:25346685

Efficacy of stimulants for cognitive enhancement in non-attention deficit hyperactivity disorder youth: a systematic review

PubMed Central

Bagot, Kara Simone; Kaminer, Yifrah

2015-01-01

Background and Aims Increasing prescription stimulant abuse among youth without diagnoses of attention deficit hyperactivity disorder (ADHD) is of concern. The most frequently cited motive for abuse is improved academic achievement via neurocognitive enhancement. Our aim in reviewing the literature was to identify neurocognitive effects of prescription stimulants in non-ADHD youth. Methods A systematic review was conducted for youth aged 12–25 years using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fourteen papers were included. Results Modafinil appears to improve reaction time (P ≤ 0.04), logical reasoning (P ≤ 0.05) and problem-solving. Methylphenidate appears to improve performance in novel tasks and attention-based tasks (P ≤ 0.05), and reduces planning latency in more complex tasks (P ≤ 0.05). Amphetamine has been shown to improve consolidation of information (0.02 ≥ P ≤ 0.05), leading to improved recall. Across all three types of prescription stimulants, research shows improved attention with lack of consensus on whether these improvements are limited to simple versus complex tasks in varying youth populations. Conclusions The heterogeneity of the non-attention deficit hyperactivity disorder youth population, the variation in cognitive task characteristics and lack of replication of studies makes assessing the potential global neurocognitive benefits of stimulants among non-attention deficit hyper-activity disorder youth difficult; however, some youth may derive benefit in specific cognitive domains. PMID:24749160

Effects of cariprazine, a novel antipsychotic, on cognitive deficit and negative symptoms in a rodent model of schizophrenia symptomatology.

PubMed

Neill, Jo C; Grayson, Ben; Kiss, Béla; Gyertyán, István; Ferguson, Paul; Adham, Nika

2016-01-01

Negative symptoms and cognitive impairment associated with schizophrenia are strongly associated with poor functional outcome and reduced quality of life and remain an unmet clinical need. Cariprazine is a dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors, recently approved by the FDA for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The aim of this study is to evaluate effects of cariprazine in an animal model of cognitive deficit and negative symptoms of schizophrenia. Following sub-chronic PCP administration (2mg/kg, IP for 7 days followed by 7 days drug-free), female Lister Hooded rats were administered cariprazine (0.05, 0.1, or 0.25mg/kg, PO) or risperidone (0.16 or 0.1mg/kg, IP) before testing in novel object recognition (NOR), reversal learning (RL), and social interaction (SI) paradigms. As we have consistently demonstrated, sub-chronic PCP significantly impaired behavior in these tests. Deficits were significantly improved by cariprazine, in a dose dependent manner in the operant RL test with efficacy at lower doses in the NOR and SI tests. Locomotor activity was reduced at the highest doses of 0.1mg/kg and 0.25mg/kg in NOR and SI. Risperidone also reversed the PCP-induced deficit in all tests. In conclusion, cariprazine was effective to overcome PCP-induced deficits in cognition and social behavior in a thoroughly validated rat model in tests representing specific symptom domains in schizophrenia patients. These findings support very recent results showing efficacy of cariprazine in the treatment of negative symptoms in schizophrenia patients. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

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

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.

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.

Cholesteryl Ester Transfer Protein Intimately Involved in Dyslipidemia-Related Susceptibility to Cognitive Deficits in Type 2 Diabetic Patients.

PubMed

Sun, Jie; Cai, Rongrong; Huang, Rong; Wang, Pin; Tian, Sai; Sun, Haixia; Xia, Wenqing; Wang, Shaohua

2016-08-01

Cholesteryl ester transfer protein (CETP) is involved in diabetic dyslipidemia. We aim to test the hypothesis that CETP might be of importance in mediating dyslipidemia-related susceptibility to cognitive deficits in diabetic patients. We recruited 190 type 2 diabetic patients and divided them into two groups according to the Montreal Cognitive Assessment (MoCA) score. The association between CETP and cognitive decline was analyzed with logistic regression and stratification. There were 110 diabetic patients with mild cognition impairment (MCI) and 80 healthy cognition subjects as controls. Dyslipidemia is more common among diabetic patients with MCI; they had a significant increase of serum CETP concentrations, which was negatively correlated with MoCA (r = -0.638; p < 0.001). Negative correlations were also found between the serum CETP concentration with the Auditory Verbal Learning Test (r = -0.266; p = 0.008), indicating memory deficit. Logistic regression analysis revealed that CETP concentration was an independent factor of diabetic MCI (p < 0.001). Further stratification study showed that high serum levels of CETP was an independent risk factor of MCI in diabetic patients with a low density lipoproteins level ≥2.59 mmol/L, or high density lipoproteins level ≤1.0 mmol/L for men and ≤1.3 mmol/L for women, or TG level ≥1.7 mmol/L, after adjusting for age, sex, education, and glucose control (all ps < 0.05). CETP was intimately involved in dyslipidemia-related susceptibility to cognitive decline, especially memory function in type 2 diabetic patients.

Deletion of Selenoprotein M Leads to Obesity without Cognitive Deficits*

PubMed Central

Pitts, Matthew W.; Reeves, Mariclair A.; Hashimoto, Ann C.; Ogawa, Ashley; Kremer, Penny; Seale, Lucia A.; Berry, Marla J.

2013-01-01

Selenium is an essential trace element that is co-translationally incorporated into selenoproteins in the form of the 21st amino acid, selenocysteine. This class of proteins largely functions in oxidation-reduction reactions and is critically involved in maintaining proper redox balance essential to health. Selenoprotein M (SelM) is a thioredoxin-like endoplasmic reticulum-resident protein that is highly expressed in the brain and possesses neuroprotective properties. In this study, we first assessed the regional pattern of SelM expression in the mouse brain to provide insights into the potential functional implications of this protein in physiology and behavior. Next, we generated transgenic mice with a targeted deletion of the SelM gene and subjected them to a battery of neurobehavioral tests to evaluate motor coordination, locomotion, and cognitive function in comparison with wild-type controls. Finally, these mice were tested for several measures of metabolic function and body composition. Our results show that SelM knock-out (KO) mice display no deficits in measures of motor coordination and cognitive function but exhibit increased weight gain, elevated white adipose tissue deposition, and diminished hypothalamic leptin sensitivity. These findings suggest that SelM plays an important role in the regulation of body weight and energy metabolism. PMID:23880772

Cognitive deficits are associated with unemployment in adults with sickle cell anemia.

PubMed

Sanger, Maureen; Jordan, Lori; Pruthi, Sumit; Day, Matthew; Covert, Brittany; Merriweather, Brenda; Rodeghier, Mark; DeBaun, Michael; Kassim, Adetola

2016-08-01

An estimated 25-60% of adults with sickle cell disease (SCD) are unemployed. Factors contributing to the high unemployment rate in this population are not well studied. With the known risk of cognitive deficits associated with SCD, we tested the hypothesis that unemployment is related to decrements in intellectual functioning. We conducted a retrospective chart review of 50 adults with sickle cell anemia who completed cognitive testing, including the Wechsler Adult Intelligence Scale-IV, as part of standard care. Employment status was recorded at the time of testing. Medical variables examined as possible risk factors for unemployment included disease phenotype, cerebral infarction, and pain frequency. The mean age of the sample was 30.7 years (range = 19-59); 56% were women. Almost half of the cohort (44%) were unemployed. In a multivariate logistic regression model, lower IQ scores (odds ratio = 0.88; p = .002, 95% confidence interval, CI [0.82, 0.96]) and lower educational attainment (odds ratio = 0.13; p = .012, 95% CI [0.03, 0.65]) were associated with increasing odds of unemployment. The results suggest that cognitive impairment in adults with sickle cell anemia may contribute to the risk of unemployment. Helping these individuals access vocational rehabilitation services may be an important component of multidisciplinary care.

Cognitive Training for Attention-Deficit/Hyperactivity Disorder: Meta-Analysis of Clinical and Neuropsychological Outcomes From Randomized Controlled Trials

PubMed Central

Cortese, Samuele; Ferrin, Maite; Brandeis, Daniel; Buitelaar, Jan; Daley, David; Dittmann, Ralf W.; Holtmann, Martin; Santosh, Paramala; Stevenson, Jim; Stringaris, Argyris; Zuddas, Alessandro; Sonuga-Barke, Edmund J.S.

2015-01-01

Objective The authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD. Method The authors searched Pubmed, Ovid, Web of Science, ERIC, and CINAHAL databases through May 18, 2014. Data were aggregated using random-effects models. Studies were evaluated with the Cochrane risk of bias tool. Results Sixteen of 695 nonduplicate records were analyzed (759 children with ADHD). When all types of training were considered together, there were significant effects on total ADHD (standardized mean difference [SMD] = 0.37, 95% CI = 0.09–0.66) and inattentive symptoms (SMD = 0.47, 95% CI = 0.14–0.80) for reports by raters most proximal to the treatment setting (i.e., typically unblinded). These figures decreased substantially when the outcomes were provided by probably blinded raters (ADHD total: SMD = 0.20, 95% CI = 0.01–0.40; inattention: SMD = 0.32, 95% CI = −0.01 to 0.66). Effects on hyperactivity/impulsivity symptoms were not significant. There were significant effects on laboratory tests of working memory (verbal: SMD = 0.52, 95% CI = 0.24–0.80; visual: SMD = 0.47, 95% CI = 0.23–0.70) and parent ratings of executive function (SMD = 0.35, 95% CI = 0.08–0.61). Effects on academic performance were not statistically significant. There were no effects of working memory training, specifically on ADHD symptoms. Interventions targeting multiple neuropsychological deficits had large effects on ADHD symptoms rated by most proximal assessors (SMD = 0.79, 95% CI = 0.46–1.12). Conclusion Despite improving working memory performance, cognitive training had limited effects on ADHD symptoms according to assessments based on blinded measures. Approaches targeting multiple neuropsychological processes may optimize the transfer of effects from cognitive deficits to

Cognitive training for attention-deficit/hyperactivity disorder: meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials.

PubMed

Cortese, Samuele; Ferrin, Maite; Brandeis, Daniel; Buitelaar, Jan; Daley, David; Dittmann, Ralf W; Holtmann, Martin; Santosh, Paramala; Stevenson, Jim; Stringaris, Argyris; Zuddas, Alessandro; Sonuga-Barke, Edmund J S

2015-03-01

The authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD. The authors searched Pubmed, Ovid, Web of Science, ERIC, and CINAHAL databases through May 18, 2014. Data were aggregated using random-effects models. Studies were evaluated with the Cochrane risk of bias tool. Sixteen of 695 nonduplicate records were analyzed (759 children with ADHD). When all types of training were considered together, there were significant effects on total ADHD (standardized mean difference [SMD] = 0.37, 95% CI = 0.09-0.66) and inattentive symptoms (SMD = 0.47, 95% CI = 0.14-0.80) for reports by raters most proximal to the treatment setting (i.e., typically unblinded). These figures decreased substantially when the outcomes were provided by probably blinded raters (ADHD total: SMD = 0.20, 95% CI = 0.01-0.40; inattention: SMD = 0.32, 95% CI = -0.01 to 0.66). Effects on hyperactivity/impulsivity symptoms were not significant. There were significant effects on laboratory tests of working memory (verbal: SMD = 0.52, 95% CI = 0.24-0.80; visual: SMD = 0.47, 95% CI = 0.23-0.70) and parent ratings of executive function (SMD = 0.35, 95% CI = 0.08-0.61). Effects on academic performance were not statistically significant. There were no effects of working memory training, specifically on ADHD symptoms. Interventions targeting multiple neuropsychological deficits had large effects on ADHD symptoms rated by most proximal assessors (SMD = 0.79, 95% CI = 0.46-1.12). Despite improving working memory performance, cognitive training had limited effects on ADHD symptoms according to assessments based on blinded measures. Approaches targeting multiple neuropsychological processes may optimize the transfer of effects from cognitive deficits to clinical symptoms. Copyright © 2015 American Academy

Feasibility of the evidence-based cognitive telerehabilitation program Remind for patients with primary brain tumors.

PubMed

van der Linden, Sophie D; Sitskoorn, Margriet M; Rutten, Geert-Jan M; Gehring, Karin

2018-05-01

Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation program developed by our group. We converted the program into the iPad-based cognitive rehabilitation program ReMind, to increase its accessibility. The app incorporates psychoeducation, strategy training and retraining. This pilot study in patients with primary brain tumors evaluates the feasibility of the use of the ReMind-app in a clinical (research) setting in terms of accrual, attrition, adherence and patient satisfaction. The intervention commenced 3 months after resective surgery and patients were advised to spend 3 h per week on the program for 10 weeks. Of 28 eligible patients, 15 patients with presumed low-grade glioma or meningioma provided informed consent. Most important reason for decline was that patients (7) experienced no cognitive complaints. Participants completed on average 71% of the strategy training and 76% of the retraining. Some patients evaluated the retraining as too easy. Overall, 85% of the patients evaluated the intervention as "good" or "excellent". All patients indicated that they would recommend the program to other patients with brain tumors. The ReMind-app is the first evidence-based cognitive telerehabilitation program for adult patients with brain tumors and this pilot study suggests that postoperative cognitive rehabilitation via this app is feasible. Based on patients' feedback, we have expanded the retraining with more difficult exercises. We will evaluate the efficacy of ReMind in an RCT.

Autism-Relevant Social Abnormalities and Cognitive Deficits in Engrailed-2 Knockout Mice

PubMed Central

Brielmaier, Jennifer; Matteson, Paul G.; Silverman, Jill L.; Senerth, Julia M.; Kelly, Samantha; Genestine, Matthieu; Millonig, James H.

2012-01-01

ENGRAILED 2 (En2), a homeobox transcription factor, functions as a patterning gene in the early development and connectivity of rodent hindbrain and cerebellum, and regulates neurogenesis and development of monoaminergic pathways. To further understand the neurobiological functions of En2, we conducted neuroanatomical expression profiling of En2 wildtype mice. RTQPCR assays demonstrated that En2 is expressed in adult brain structures including the somatosensory cortex, hippocampus, striatum, thalamus, hypothalamus and brainstem. Human genetic studies indicate that EN2 is associated with autism. To determine the consequences of En2 mutations on mouse behaviors, including outcomes potentially relevant to autism, we conducted comprehensive phenotyping of social, communication, repetitive, and cognitive behaviors. En2 null mutants exhibited robust deficits in reciprocal social interactions as juveniles and adults, and absence of sociability in adults, replicated in two independent cohorts. Fear conditioning and water maze learning were impaired in En2 null mutants. High immobility in the forced swim test, reduced prepulse inhibition, mild motor coordination impairments and reduced grip strength were detected in En2 null mutants. No genotype differences were found on measures of ultrasonic vocalizations in social contexts, and no stereotyped or repetitive behaviors were observed. Developmental milestones, general health, olfactory abilities, exploratory locomotor activity, anxiety-like behaviors and pain responses did not differ across genotypes, indicating that the behavioral abnormalities detected in En2 null mutants were not attributable to physical or procedural confounds. Our findings provide new insight into the role of En2 in complex behaviors and suggest that disturbances in En2 signaling may contribute to neuropsychiatric disorders marked by social and cognitive deficits, including autism spectrum disorders. PMID:22829897

Cognitive deficits develop 1month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge.

PubMed

Muccigrosso, Megan M; Ford, Joni; Benner, Brooke; Moussa, Daniel; Burnsides, Christopher; Fenn, Ashley M; Popovich, Phillip G; Lifshitz, Jonathan; Walker, Fredrick Rohan; Eiferman, Daniel S; Godbout, Jonathan P

2016-05-01

Traumatic brain injury (TBI) elicits immediate neuroinflammatory events that contribute to acute cognitive, motor, and affective disturbance. Despite resolution of these acute complications, significant neuropsychiatric and cognitive issues can develop and progress after TBI. We and others have provided novel evidence that these complications are potentiated by repeated injuries, immune challenges and stressors. A key component to this may be increased sensitization or priming of glia after TBI. Therefore, our objectives were to determine the degree to which cognitive deterioration occurred after diffuse TBI (moderate midline fluid percussion injury) and ascertain if glial reactivity induced by an acute immune challenge potentiated cognitive decline 30 days post injury (dpi). In post-recovery assessments, hippocampal-dependent learning and memory recall were normal 7 dpi, but anterograde learning was impaired by 30 dpi. Examination of mRNA and morphological profiles of glia 30 dpi indicated a low but persistent level of inflammation with elevated expression of GFAP and IL-1β in astrocytes and MHCII and IL-1β in microglia. Moreover, an acute immune challenge 30 dpi robustly interrupted memory consolidation specifically in TBI mice. These deficits were associated with exaggerated microglia-mediated inflammation with amplified (IL-1β, CCL2, TNFα) and prolonged (TNFα) cytokine/chemokine expression, and a marked reactive morphological profile of microglia in the CA3 of the hippocampus. Collectively, these data indicate that microglia remain sensitized 30 dpi after moderate TBI and a secondary inflammatory challenge elicits robust microglial reactivity that augments cognitive decline. Traumatic brain injury (TBI) is a major risk factor in development of neuropsychiatric problems long after injury, negatively affecting quality of life. Mounting evidence indicates that inflammatory processes worsen with time after a brain injury and are likely mediated by glia. Here

Chotosan ameliorates cognitive and emotional deficits in an animal model of type 2 diabetes: possible involvement of cholinergic and VEGF/PDGF mechanisms in the brain

PubMed Central

2012-01-01

Background Diabetes is one of the risk factors for cognitive deficits such as Alzheimer’s disease. To obtain a better understanding of the anti-dementia effect of chotosan (CTS), a Kampo formula, we investigated its effects on cognitive and emotional deficits of type 2 diabetic db/db mice and putative mechanism(s) underlying the effects. Methods Seven-week-old db/db mice received daily administration of CTS (375 – 750 mg/kg, p.o.) and the reference drug tacrine (THA: 2.5 mg/kg, i.p.) during an experimental period of 7 weeks. From the age of 9-week-old, the animals underwent the novel object recognition test, the modified Y-maze test, and the water maze test to elucidate cognitive performance and the elevated plus maze test to elucidate anxiety-related behavior. After completing behavioral studies, Western blotting and immunohistochemical studies were conducted. Results Compared with age-matched non-diabetic control strain (m/m) mice, db/db mice exhibited impaired cognitive performance and an increased level of anxiety. CTS ameliorated cognitive and emotional deficits of db/db mice, whereas THA improved only cognitive performance. The phosphorylated levels of Akt and PKCα in the hippocampus were significantly lower and higher, respectively, in db/db mice than in m/m mice. Expression levels of the hippocampal cholinergic marker proteins and the number of the septal cholinergic neurons were also reduced in db/db mice compared with those in m/m mice. Moreover, the db/db mice had significantly reduced levels of vasculogenesis/angiogenesis factors, vascular endothelial growth factor (VEGF), VEGF receptor type 2, platelet-derived growth factor-B, and PDGF receptor β, in the hippocampus. CTS and THA treatment reversed these neurochemical and histological alterations caused by diabetes. Conclusion These results suggest that CTS ameliorates diabetes-induced cognitive deficits by protecting central cholinergic and VEGF/PDGF systems via Akt signaling pathway and

Chotosan ameliorates cognitive and emotional deficits in an animal model of type 2 diabetes: possible involvement of cholinergic and VEGF/PDGF mechanisms in the brain.

PubMed

Zhao, Qi; Niu, Yimin; Matsumoto, Kinzo; Tsuneyama, Koichi; Tanaka, Ken; Miyata, Takeshi; Yokozawa, Takako

2012-10-20

Diabetes is one of the risk factors for cognitive deficits such as Alzheimer's disease. To obtain a better understanding of the anti-dementia effect of chotosan (CTS), a Kampo formula, we investigated its effects on cognitive and emotional deficits of type 2 diabetic db/db mice and putative mechanism(s) underlying the effects. Seven-week-old db/db mice received daily administration of CTS (375 - 750 mg/kg, p.o.) and the reference drug tacrine (THA: 2.5 mg/kg, i.p.) during an experimental period of 7 weeks. From the age of 9-week-old, the animals underwent the novel object recognition test, the modified Y-maze test, and the water maze test to elucidate cognitive performance and the elevated plus maze test to elucidate anxiety-related behavior. After completing behavioral studies, Western blotting and immunohistochemical studies were conducted. Compared with age-matched non-diabetic control strain (m/m) mice, db/db mice exhibited impaired cognitive performance and an increased level of anxiety. CTS ameliorated cognitive and emotional deficits of db/db mice, whereas THA improved only cognitive performance. The phosphorylated levels of Akt and PKCα in the hippocampus were significantly lower and higher, respectively, in db/db mice than in m/m mice. Expression levels of the hippocampal cholinergic marker proteins and the number of the septal cholinergic neurons were also reduced in db/db mice compared with those in m/m mice. Moreover, the db/db mice had significantly reduced levels of vasculogenesis/angiogenesis factors, vascular endothelial growth factor (VEGF), VEGF receptor type 2, platelet-derived growth factor-B, and PDGF receptor β, in the hippocampus. CTS and THA treatment reversed these neurochemical and histological alterations caused by diabetes. These results suggest that CTS ameliorates diabetes-induced cognitive deficits by protecting central cholinergic and VEGF/PDGF systems via Akt signaling pathway and that CTS exhibits the anxiolytic effect via

Neurocognitive Impairments in Deficit and Non-Deficit Schizophrenia and Their Relationships with Symptom Dimensions and Other Clinical Variables.

PubMed

Yu, Miao; Tang, XiaoWei; Wang, Xiang; Zhang, XiangRong; Zhang, XiaoBin; Sha, WeiWei; Yao, ShuQiao; Shu, Ni; Zhang, XiangYang; Zhang, ZhiJun

2015-01-01

Deficit schizophrenia (DS) has been proposed as a pathophysiologically distinct subgroup within schizophrenia. Earlier studies focusing on neurocognitive function of DS patients have yielded inconsistent findings ranging from substantial deficits to no significant difference relative to non-deficit schizophrenia patients (NDS). The present study investigated the severity and characteristic patterns of neurocognitive impairments in DS and NDS patients and their relationships with clinical variables. Attention, ideation fluency, cognitive flexibility and visuospatial memory function were assessed in 40 DS patients, 57 NDS patients, and 52 healthy controls by a comprehensive neuropsychological battery. Both schizophrenia subgroups had overall more severe cognitive impairments than controls while DS performed worse on every neuropsychological measure except the Stroop interference than the NDS patients with age and education as the covariates. Profile analysis found significantly different patterns of cognitive profiles between two patients group mainly due to their differences in attention and cognitive flexibility functions. Age, education, illness duration and negative symptoms were found to have the correlations with cognitive impairments in the NDS group, while only age and the negative symptoms were correlated with the cognitive impairments in the DS group. Multiple regression analyses revealed that sustained attention and cognitive flexibility were the core impaired cognitive domains mediating other cognitive functions in DS and NDS patients respectively. DS patients exemplified worse in almost all cognitive domains than NDS patients. Sustained attention and cognitive flexibility might be the key impaired cognitive domains for DS and NDS patients respectively. The present study suggested the DS as a specific subgroup of schizophrenia.

Neurocognitive Impairments in Deficit and Non-Deficit Schizophrenia and Their Relationships with Symptom Dimensions and Other Clinical Variables

PubMed Central

Zhang, XiangRong; Zhang, XiaoBin; Sha, WeiWei; Yao, ShuQiao; Shu, Ni; Zhang, XiangYang; Zhang, ZhiJun

2015-01-01

Background Deficit schizophrenia (DS) has been proposed as a pathophysiologically distinct subgroup within schizophrenia. Earlier studies focusing on neurocognitive function of DS patients have yielded inconsistent findings ranging from substantial deficits to no significant difference relative to non-deficit schizophrenia patients (NDS). The present study investigated the severity and characteristic patterns of neurocognitive impairments in DS and NDS patients and their relationships with clinical variables. Methods Attention, ideation fluency, cognitive flexibility and visuospatial memory function were assessed in 40 DS patients, 57 NDS patients, and 52 healthy controls by a comprehensive neuropsychological battery. Results Both schizophrenia subgroups had overall more severe cognitive impairments than controls while DS performed worse on every neuropsychological measure except the Stroop interference than the NDS patients with age and education as the covariates. Profile analysis found significantly different patterns of cognitive profiles between two patients group mainly due to their differences in attention and cognitive flexibility functions. Age, education, illness duration and negative symptoms were found to have the correlations with cognitive impairments in the NDS group, while only age and the negative symptoms were correlated with the cognitive impairments in the DS group. Multiple regression analyses revealed that sustained attention and cognitive flexibility were the core impaired cognitive domains mediating other cognitive functions in DS and NDS patients respectively. Conclusions DS patients exemplified worse in almost all cognitive domains than NDS patients. Sustained attention and cognitive flexibility might be the key impaired cognitive domains for DS and NDS patients respectively. The present study suggested the DS as a specific subgroup of schizophrenia. PMID:26381645

Acupuncture attenuates cognitive deficits and increases pyramidal neuron number in hippocampal CA1 area of vascular dementia rats.

PubMed

Li, Fang; Yan, Chao-Qun; Lin, Li-Ting; Li, Hui; Zeng, Xiang-Hong; Liu, Yi; Du, Si-Qi; Zhu, Wen; Liu, Cun-Zhi

2015-04-28

Decreased cognition is recognized as one of the most severe and consistent behavioral impairments in dementia. Experimental studies have reported that acupuncture may improve cognitive deficits, relieve vascular dementia (VD) symptoms, and increase cerebral perfusion and electrical activity. Multi-infarction dementia was modeled in rats with 3% microemboli saline suspension. Two weeks after acupuncture at Zusanli (ST36), all rats were subjected to a hidden platform trial to test their 3-day spatial memory using the Morris water maze test. To estimate the numbers of pyramidal neuron, astrocytes, and synaptic boutons in hippocampal CA1 area, we adopted an unbiased stereology method to accurately sample and measure the size of cells. We found that acupuncture at ST36 significantly decreased the escape latency of VD rats. In addition, acupuncture significantly increased the pyramidal neuron number in hippocampal CA1 area (P < 0.05) and tended to decrease the number of astrocytes (P = 0.063). However, there was no significant change in the synaptic bouton number of hippocampal CA1 area in any of the groups (P > 0.05). These findings suggest that acupuncture may improve cognitive deficits and increase pyramidal neuron number of hippocampal CA1 area in VD rats.

[Cognitive, linguistic, motoric, and social deficits in schoolstarters with behavioral disorders].

PubMed

Korsch, Franziska; Petermann, Ulrike; Schmidt, Sören; Petermann, Franz

2013-01-01

Studies show that ADHD, conduct disorders, and anxiety disorders are clinical disorders mostly diagnosed in schoolstarters. The preschool medical examination in Bremen was therefore extended by behavioral screenings. Based on their screening results from the SEU (health examination for school entry) 2011 in Bremen, 67 preschoolers were tested for behavioral disorders. Subsequently, children with behavioral or emotional symptoms (N = 56) were compared to symptomfree controls (N = 52) for their cognitive, motoric, linguistic, and social-emotional development. Psychosocial health was obtained through external assessment by the parents and kindergarten teachers. Results of the WPPSI-III, M-ABC-2, and ET 6-6 were included in the analysis. 32 children met the criteria for behavioral disorders. Children with behavioral or emotional symptoms showed significant lower scores on tests measuring cognitive, motoric, linguistic and emotional development compared to controls. Results suggest that there is necessity to screen all preschoolers for behavioral disorders before entering school. Because children with clinical or subclinical behavioral disorders showed major developmental deficits compared to children without behavioral symptoms, it is essential to conduct a multiple assessment on children with suspected behavioral disorders to ensure early developmental support and adequate interventional programs.

Development of a cognitive-behavioral intervention program to treat anxiety and social deficits in teens with high-functioning autism.

PubMed

White, Susan W; Albano, Anne Marie; Johnson, Cynthia R; Kasari, Connie; Ollendick, Thomas; Klin, Ami; Oswald, Donald; Scahill, Lawrence

2010-03-01

Anxiety is a common co-occurring problem among young people with autism spectrum disorders (ASD). Characterized by deficits in social interaction, communication problems, and stereotyped behavior and restricted interests, this group of disorders is more prevalent than previously realized. When present, anxiety may compound the social deficits of young people with ASD. Given the additional disability and common co-occurrence of anxiety in ASD, we developed a manual-based cognitive-behavioral treatment program to target anxiety symptoms as well as social skill deficits in adolescents with ASD [Multimodal Anxiety and Social Skills Intervention: MASSI]. In this paper, we describe the foundation, content, and development of MASSI. We also summarize data on treatment feasibility based on a pilot study that implemented the intervention.

Multifunctional neuroprotective effect of Withanone, a compound from Withania somnifera roots in alleviating cognitive dysfunction.

PubMed

Pandey, Anjali; Bani, Sarang; Dutt, Prabhu; Kumar Satti, Naresh; Avtar Suri, Krishan; Nabi Qazi, Ghulam

2018-02-01

Alzheimer's disease (AD) is a chronic disorder that slowly worsens and impairs the person's memory, learning, reasoning, judgment, communication and familiar tasks with loss of orientation. AD is characterized clinically by cognitive deficit and pathologically by the deposition of β amyloid plaques, neurofibrillary tangles, associated with degeneration of the cholinergic forebrain. Withanone (WS-2), a compound isolated from root extract of Withania somnifera at doses administered orally/day to wistar rats for duration of 21 days showed significant improvement in the cognitive skill by inhibiting amyloid β-42 and attenuated the elevated levels of pro-inflammatory cytokines like TNF alpha, IL-1 beta, IL-6, MCP-1, Nitric oxide, lipid peroxidation and both β- and γ- secretase enzymatic activity. Administration of WS-2 also significantly reversed the decline in acetyl choline and Glutathione (GSH) activity. None of the treatments that are available today alter the underlying causes of this terminal disease. Few preliminary clinical treatments have demonstrated that some plant medicines do ameliorate and improve memory and learning in patients with mild-to-moderate AD. WS-2 showed promise in AD treatment because of cognitive benefits and more importantly, mechanisms of action with respect to the fundamental pathophysiology of the disease, not limited to the inhibition of AChE, but also include the modification of Aβ processing, protection against oxidative stress and anti-inflammatory effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cognitive Deficits in Calsyntenin-2-deficient Mice Associated with Reduced GABAergic Transmission

PubMed Central

Lipina, Tatiana V; Prasad, Tuhina; Yokomaku, Daisaku; Luo, Lin; Connor, Steven A; Kawabe, Hiroshi; Wang, Yu Tian; Brose, Nils; Roder, John C; Craig, Ann Marie

2016-01-01

Calsyntenin-2 has an evolutionarily conserved role in cognition. In a human genome-wide screen, the CLSTN2 locus was associated with verbal episodic memory, and expression of human calsyntenin-2 rescues the associative learning defect in orthologous Caenorhabditis elegans mutants. Other calsyntenins promote synapse development, calsyntenin-1 selectively of excitatory synapses and calsyntenin-3 of excitatory and inhibitory synapses. We found that targeted deletion of calsyntenin-2 in mice results in a selective reduction in functional inhibitory synapses. Reduced inhibitory transmission was associated with a selective reduction of parvalbumin interneurons in hippocampus and cortex. Clstn2−/− mice showed normal behavior in elevated plus maze, forced swim test, and novel object recognition assays. However, Clstn2−/− mice were hyperactive in the open field and showed deficits in spatial learning and memory in the Morris water maze and Barnes maze. These results confirm a function for calsyntenin-2 in cognitive performance and indicate an underlying mechanism that involves parvalbumin interneurons and aberrant inhibitory transmission. PMID:26171716

Dynamic balance in children with attention-deficit hyperactivity disorder and its relationship with cognitive functions and cerebellum

PubMed Central

Goetz, Michal; Schwabova, Jaroslava Paulasova; Hlavka, Zdenek; Ptacek, Radek; Surman, Craig BH

2017-01-01

Background Attention-deficit hyperactivity disorder (ADHD) is linked to the presence of motor deficiencies, including balance deficits. The cerebellum serves as an integrative structure for balance control and is also involved in cognition, including timing and anticipatory regulation. Cerebellar development may be delayed in children and adolescents with ADHD, and inconsistent reaction time is commonly seen in ADHD. We hypothesized that dynamic balance deficits would be present in children with ADHD and they would correlate with attention and cerebellar functions. Methods Sixty-two children with ADHD and no other neurological conditions and 62 typically developing (TD) children were examined with five trials of the Phyaction Balance Board, an electronic balancing platform. Cerebellar clinical symptoms were evaluated using an international ataxia rating scale. Conners’ Continuous Performance Test was used to evaluate patterns of reaction. Results Children with ADHD had poorer performance on balancing tasks, compared to TD children (P<0.001). They exhibited significantly greater sway amplitudes than TD children (P<0.001) in all of the five balancing trials. The effect size of the difference between the groups increased continuously from the first to the last trial. Balance score in both groups was related to the variation in the reaction time, including reaction time standard error (r =0.25; P=0.0409, respectively, r =0.31; P=0.0131) and Variability of Standard Error (r =0.28; P=0.0252, respectively, r =0.41; P<0.001). The burden of cerebellar symptoms was strongly related to balance performance in both groups (r =0.50, P<0.001; r =0.49, P=0.001). Conclusion This study showed that ADHD may be associated with poor dynamic balance control. Furthermore, we showed that maintaining balance correlates with neuropsychological measures of consistency of reaction time. Balance deficits and impaired cognitive functioning could reflect a common cerebellar dysfunction in ADHD

Dynamic balance in children with attention-deficit hyperactivity disorder and its relationship with cognitive functions and cerebellum.

PubMed

Goetz, Michal; Schwabova, Jaroslava Paulasova; Hlavka, Zdenek; Ptacek, Radek; Surman, Craig Bh

2017-01-01

Attention-deficit hyperactivity disorder (ADHD) is linked to the presence of motor deficiencies, including balance deficits. The cerebellum serves as an integrative structure for balance control and is also involved in cognition, including timing and anticipatory regulation. Cerebellar development may be delayed in children and adolescents with ADHD, and inconsistent reaction time is commonly seen in ADHD. We hypothesized that dynamic balance deficits would be present in children with ADHD and they would correlate with attention and cerebellar functions. Sixty-two children with ADHD and no other neurological conditions and 62 typically developing (TD) children were examined with five trials of the Phyaction Balance Board, an electronic balancing platform. Cerebellar clinical symptoms were evaluated using an international ataxia rating scale. Conners' Continuous Performance Test was used to evaluate patterns of reaction. Children with ADHD had poorer performance on balancing tasks, compared to TD children ( P <0.001). They exhibited significantly greater sway amplitudes than TD children ( P <0.001) in all of the five balancing trials. The effect size of the difference between the groups increased continuously from the first to the last trial. Balance score in both groups was related to the variation in the reaction time, including reaction time standard error ( r =0.25; P =0.0409, respectively, r =0.31; P =0.0131) and Variability of Standard Error ( r =0.28; P =0.0252, respectively, r =0.41; P <0.001). The burden of cerebellar symptoms was strongly related to balance performance in both groups ( r =0.50, P <0.001; r =0.49, P =0.001). This study showed that ADHD may be associated with poor dynamic balance control. Furthermore, we showed that maintaining balance correlates with neuropsychological measures of consistency of reaction time. Balance deficits and impaired cognitive functioning could reflect a common cerebellar dysfunction in ADHD children.

Cognitive dysfunction in lower motor neuron disease: executive and memory deficits in progressive muscular atrophy.

PubMed

Raaphorst, Joost; de Visser, Marianne; van Tol, Marie-José; Linssen, Wim H J P; van der Kooi, Anneke J; de Haan, Rob J; van den Berg, Leonard H; Schmand, Ben

2011-02-01

In contrast with findings in amyotrophic lateral sclerosis (ALS), cognitive impairments have as yet not been shown in the lower motor neuron variant of motor neuron disease, progressive spinal muscular atrophy (PMA). The objective of this study was to investigate cognitive function in PMA and to compare the cognitive profile with that of ALS. In addition, visuospatial functions were assessed comprehensively; these tests are underrepresented in earlier neuropsychological investigations in ALS. 23 PMA and 30 ALS patients (vital capacity >70% of predicted value) underwent a neuropsychological assessment adapted to motor impairments: global cognitive and executive functioning, psychomotor speed, memory, language, attention and visuospatial skills. The results were compared with age, education and sex matched controls and with normative data. Compared with controls, PMA patients performed worse on attention/working memory (digit span backward), category fluency and the Mini-Mental State Examination. Compared with normative data, PMA patients most frequently showed impairment on three measures: letter-number sequencing, and immediate and delayed story recall. 17% of PMA patients showed cognitive impairment, defined as performance below 2 SDs from the mean of normative data on at least three neuropsychological tests. In ALS, similar but more extensive cognitive deficits were found. Visuospatial dysfunction was not found in PMA and ALS. 17% of PMA patients have executive and memory impairments. PMA with cognitive impairment adds a formerly unknown phenotype to the existing classification of motor neuron diseases.

Intrinsic motivation as a mediator between metacognition deficits and impaired functioning in psychosis.

PubMed

Luther, Lauren; Firmin, Ruth L; Vohs, Jenifer L; Buck, Kelly D; Rand, Kevin L; Lysaker, Paul H

2016-09-01

Poor functioning has long been observed in individuals with psychosis. Recent studies have identified metacognition - one's ability to form complex ideas about oneself and others and to use that information to respond to psychological and social challenges-as being an important determinant of functioning. However, the exact process by which deficits in metacognition lead to impaired functioning remains unclear. This study first examined whether low intrinsic motivation, or the tendency to pursue novel experiences and to engage in self-improvement, mediates the relationship between deficits in metacognition and impaired functioning. We then examined whether intrinsic motivation significantly mediated the relationship when controlling for age, education, symptoms, executive functioning, and social cognition. Mediation models were examined in a cross-sectional data set. One hundred and seventy-five individuals with a psychotic disorder completed interview-based measures of metacognition, intrinsic motivation, symptoms, and functioning and performance-based measures of executive functioning and social cognition. Analyses revealed that intrinsic motivation mediated the relationship between metacognition deficits and impaired functioning (95% CI of indirect effect [0.12-0.43]), even after controlling for the aforesaid variables (95% CI of indirect effect [0.04-0.29]). Results suggest that intrinsic motivation may be a mechanism that underlies the link between deficits in metacognition and impaired functioning and indicate that metacognition and intrinsic motivation may be important treatment targets to improve functioning in individuals with psychosis. The findings of this study suggest that deficits in metacognition may indirectly lead to impaired functioning through their effect on intrinsic motivation in individuals with psychosis. Psychological treatments that target deficits in both metacognition and intrinsic motivation may help to alleviate impaired functioning in

Selective activation of α7 nicotinic acetylcholine receptor by PHA-543613 improves Aβ25-35-mediated cognitive deficits in mice.

PubMed

Sadigh-Eteghad, S; Talebi, M; Mahmoudi, J; Babri, S; Shanehbandi, D

2015-07-09

Agonists of α7 nicotinic acetylcholine receptors (nAChRs) are currently being considered as therapeutic approaches for managing cognitive deficits in Alzheimer's disease (AD). Present study was designed to evaluate the effect of α7 nAChR selective activation by PHA-543613 (PHA) on beta-amyloid (Aβ)25-35-mediated cognitive deficits in mice. For this purpose, PHA (1mg/kg, i.p.), a selective α7 nAChR agonist, and galantamine (Gal) (3mg/kg, s.c.), an acetylcholine-esterase inhibitor (AChEI) effects on α7 nAChR were tested in Aβ25-35-received (intracerebroventricular, 10 nmol) mice model of AD. Methyllycaconitine (MLA) (1mg/kg, i.p.), a α7 nAChR antagonist, was used for receptor blockage effects evaluation. Working and reference memory in animals was assessed by the Morris water maze (MWM) task. The mRNA and protein levels of α7 subunit were analyzed by real-time PCR and Western blotting, respectively. PHA and Gal, ameliorate Aβ-impaired working and reference memory. However, Gal had less effect than PHA in this regard. Pretreatment with MLA reverses both Gal and PHA effects in MWM. PHA and Gal treatment prevent Aβ-induced α7 subunit protein reduction, but Gal has lesser effect than PHA. This effect blocked by pretreatment with MLA. In neither the pretreatment nor treatment group, the mRNA levels of nAChR α7 subunit were significantly changed. Therefore, α7 nAChR activation, reduces Aβ-induced cognitive deficits and increases the α7 protein level and subsequent neuron survival. However, blockage of receptor, increases Aβ toxicity and cognitive impairment and reduces the α7 nAChR protein level and flowing neuroprotection. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Propofol alleviates electroconvulsive shock-induced memory impairment by modulating proBDNF/mBDNF ratio in depressive rats.

PubMed

Zhang, Fan; Luo, Jie; Min, Su; Ren, Li; Qin, Peipei

2016-07-01

This study investigated the effects of propofol and electroconvulsive shock (ECS), the analogue of electroconvulsive therapy (ECT) in animals, on tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as well as the precursor of brain-derived neurotrophic factor (proBDNF)/mature BDNF (mBDNF) ratio in depressive rats. ECT is an effective treatment for depression, but can cause cognitive deficit. Some studies have indicated that propofol can ameliorate cognitive decline induced by ECT, but the underlying molecular mechanism is still unclear. Recent evidence has found that mBDNF and its precursor proBDNF are related to depression and cognitive function; they elicit opposite effects on cellular functions. Chronic unpredicted mild stress is widely used to induce depressive behaviors in rodents. This study found that the depression resulted in an increased expression of PAI-1 and upregulation of the proBDNF/mBDNF ratio, together with a decreased level of tPA, long-term potentiation (LTP) impairment, and cognitive decline. The proBDNF/mBDNF ratio was further upregulated after the ECS treatment in depressive rats, resulting in the deterioration of cognitive function and hippocampal LTP. Propofol alone did not reverse the changes in depressive rats, but when co-administered with ECS, it improved the cognitive function, alleviated the impairment of LTP, downregulated the proBDNF/mBDNF ratio, and increased the tPA expression. The results of this study suggest that propofol ameliorates cognitive decline induced by ECT, which was partly by modulating the proBDNF/mBDNF ratio and reversing the excessive changes in hippocampal synaptic plasticity, providing a new evidence for involving the proBDNF/mBDNF system in the progression and treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Detecting social-cognitive deficits after traumatic brain injury: An ALE meta-analysis of fMRI studies.

PubMed

Xiao, Hui; Jacobsen, Andre; Chen, Ziqian; Wang, Yang

2017-01-01

Traumatic brain injury (TBI) can result in significant social dysfunction, which is represented by impairment to social-cognitive abilities (i.e. social cognition, social attention/executive function and communication). This study is aimed to explore brain networks mediating the social dysfunction after TBI and its underlying mechanisms. We performed a quantitative meta-analysis using the activation likelihood estimation (ALE) approach on functional magnetic resonance imaging (fMRI) studies of social-cognitive abilities following TBI. Sixteen studies fulfilled the inclusion criteria resulting in a total of 190 patients with TBI and 206 controls enrolled in the ALE meta-analysis. The temporoparietal junction (TPJ) and the medial prefrontal cortex (mPFC) were the specific regions that social cognition predominantly engaged. The cingulate gyrus, frontal gyrus and inferior parietal lobule were the main regions related to social attention/executive functions. Communication dysfunction, especially related to language deficits, was found to show greater activation of the temporal gyrus and fusiform gyrus in TBI. The current ALE meta-analytic findings provide evidence that patients have significant social-cognitive disabilities following TBI. The relatively limited pool of literature and the varied fMRI results from published studies indicate that social-cognitive abilities following TBI is an area that would greatly benefit from further investigation.

Long-Term Post-Stroke Changes Include Myelin Loss, Specific Deficits in Sensory and Motor Behaviors and Complex Cognitive Impairment Detected Using Active Place Avoidance

PubMed Central

Li, Jie; Ooi, Evelyn; Bloom, Jonathan; Poon, Carrie; Lax, Daniel; Rosenbaum, Daniel M.; Barone, Frank C.

2013-01-01

Persistent neurobehavioral deficits and brain changes need validation for brain restoration. Two hours middle cerebral artery occlusion (tMCAO) or sham surgery was performed in male Sprague-Dawley rats. Neurobehavioral and cognitive deficits were measured over 10 weeks included: (1) sensory, motor, beam balance, reflex/abnormal responses, hindlimb placement, forepaw foot fault and cylinder placement tests, and (2) complex active place avoidance learning (APA) and simple passive avoidance retention (PA). Electroretinogram (ERG), hemispheric loss (infarction), hippocampus CA1 neuronal loss and myelin (Luxol Fast Blue) staining in several fiber tracts were also measured. In comparison to Sham surgery, tMCAO surgery produced significant deficits in all behavioral tests except reflex/abnormal responses. Acute, short lived deficits following tMCAO were observed for forelimb foot fault and forelimb cylinder placement. Persistent, sustained deficits for the whole 10 weeks were exhibited for motor (p<0.001), sensory (p<0.001), beam balance performance (p<0.01) and hindlimb placement behavior (p<0.01). tMCAO produced much greater and prolonged cognitive deficits in APA learning (maximum on last trial of 604±83% change, p<0.05) but only a small, comparative effect on PA retention. Hemispheric loss/atrophy was measured 10 weeks after tMCAO and cross-validated by two methods (e.g., almost identical % ischemic hemispheric loss of 33.4±3.5% for H&E and of 34.2±3.5% for TTC staining). No visual dysfunction by ERG and no hippocampus neuronal loss were detected after tMCAO. Fiber tract damage measured by Luxol Fast Blue myelin staining intensity was significant (p<0.01) in the external capsule and striatum but not in corpus callosum and anterior commissure. In summary, persistent neurobehavioral deficits were validated as important endpoints for stroke restorative research in the future. Fiber myelin loss appears to contribute to these long term behavioral dysfunctions and can be

Cognitive Rehabilitation in Bilateral Vestibular Patients: A Computational Perspective.

PubMed

Ellis, Andrew W; Schöne, Corina G; Vibert, Dominique; Caversaccio, Marco D; Mast, Fred W

2018-01-01

There is evidence that vestibular sensory processing affects, and is affected by, higher cognitive processes. This is highly relevant from a clinical perspective, where there is evidence for cognitive impairments in patients with peripheral vestibular deficits. The vestibular system performs complex probabilistic computations, and we claim that understanding these is important for investigating interactions between vestibular processing and cognition. Furthermore, this will aid our understanding of patients' self-motion perception and will provide useful information for clinical interventions. We propose that cognitive training is a promising way to alleviate the debilitating symptoms of patients with complete bilateral vestibular loss (BVP), who often fail to show improvement when relying solely on conventional treatment methods. We present a probabilistic model capable of processing vestibular sensory data during both passive and active self-motion. Crucially, in our model, knowledge from multiple sources, including higher-level cognition, can be used to predict head motion. This is the entry point for cognitive interventions. Despite the loss of sensory input, the processing circuitry in BVP patients is still intact, and they can still perceive self-motion when the movement is self-generated. We provide computer simulations illustrating self-motion perception of BVP patients. Cognitive training may lead to more accurate and confident predictions, which result in decreased weighting of sensory input, and thus improved self-motion perception. Using our model, we show the possible impact of cognitive interventions to help vestibular rehabilitation in patients with BVP.

Affective symptoms in schizophrenia are strongly associated with neurocognitive deficits indicating disorders in executive functions, visual memory, attention and social cognition.

PubMed

Kanchanatawan, Buranee; Thika, Supaksorn; Anderson, George; Galecki, Piotr; Maes, Michael

2018-01-03

The aim of this study was to assess the neurocognitive correlates of affective symptoms in schizophrenia. Towards this end, 40 healthy controls and 80 schizophrenia patients were investigated with six tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB), assessing spatial working memory, paired-association learning, one touch stocking, rapid visual information (RVP), emotional recognition test and intra/extradimensional set shifting. The Hamilton Depression (HDRS) and Anxiety (HAMA) Rating Scales and the Calgary Depression Scale for Schizophrenia (CDSS) as well as the Positive and Negative Syndrome Scale (PANSS) were also used. There were highly significant associations between all 6 CANTAB tests and HDRS, HAMA and CDSS (except RVP) scores. The most significant items associating with neurocognitive impairments in schizophrenia were self-depreciation (CDSS), fatigue, psychomotor retardation and agitation, psychic and somatic anxiety (HDRS), fears, cognitive symptoms, somatic-muscular, genito-urinary and autonomic symptoms and anxious behavior (HAMA). The selected HDRS and HAMA symptoms indicate fatigue, fears, anxiety, agitation, retardation, somatization and subjective cognitive complaints (SCC) and are therefore labeled "FAARS". Up to 28.8% of the variance in the 6 CANTAB measurements was explained by FAARS, which are better predictors of neurocognitive impairments than the PANSS negative subscale score. Neurocognitive deficits in schizophrenia are best predicted by FAARS combined with difficulties in abstract thinking. In conclusion, depression and anxiety symptoms accompanying the negative and positive symptoms of schizophrenia are associated with neurocognitive deficits indicating disorders in executive functions, attention, visual memory, and social cognition. Neurocognitive deficits in schizophrenia reflect difficulties in abstract thinking and FAARS, including subjective cognitive complaints. Copyright © 2017 Elsevier Inc. All rights

Therapies for Cognitive Deficits Associated With Chemotherapy for Breast Cancer: A Systematic Review of Objective Outcomes.

PubMed

Morean, Diane F; O'Dwyer, Linda; Cherney, Leora R

2015-10-01

To systematically review evidence of treatments for cognitive impairments experienced by at least 20% of all women who undergo chemotherapy for breast cancer. Searches of 5 databases (PubMed, Embase, Cochrane CENTRAL, PsycINFO, CINAHL), with no date or language restrictions, identified 1701 unique results. Search terms included breast cancer, chemotherapy, chemobrain, chemofog, and terms on cognition and language deficits. Included only peer-reviewed journal articles that described therapies for cognitive dysfunction in women undergoing (or who had undergone) chemotherapy for breast cancer and provided objective measurements of cognition or language. Data were extracted according to Cochrane recommendations, including characteristics of participants, interventions, outcomes, and studies. Quality assessment of all 12 eligible studies was performed using the Physiotherapy Evidence Database scale and treatment fidelity criteria. Screening, data extraction, and quality assessment reliability were performed. Six articles described interventions for cognition that took place during cancer treatment; 6, afterward. Five interventions were medical (including a strength-training program), 2 were restorative, and 5 were cognitive. Medicinal treatments were ineffective; restorative and exercise treatments had mixed results; cognitive therapy had success in varying cognitive domains. The domains most tested and most successfully treated were verbal memory, attention, and processing speed. Cognitive therapy protocols delivered after chemotherapy and aimed at improving verbal memory, attention, and processing speed hold the most promise. Future research is needed to clarify whether computerized cognitive training can be effective in treating this population, and to identify objective assessment tools that are sensitive to this disorder. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Attention-Deficit/Hyperactivity Disorder and Sluggish Cognitive Tempo throughout Childhood: Temporal Invariance and Stability from Preschool through Ninth Grade

ERIC Educational Resources Information Center

Leopold, Daniel R.; Christopher, Micaela E.; Burns, G. Leonard; Becker, Stephen P.; Olson, Richard K.; Willcutt, Erik G.

2016-01-01

Background: Although multiple cross-sectional studies have shown symptoms of sluggish cognitive tempo (SCT) and attention-deficit/hyperactivity disorder (ADHD) to be statistically distinct, studies have yet to examine the temporal stability and measurement invariance of SCT in a longitudinal sample. To date, only six studies have assessed SCT…

Effect of Atomoxetine on the Cognitive Functions in Treatment of Attention Deficit Hyperactivity Disorder in Children with Congenital Hypothyroidism: A Pilot Study.

PubMed

Yang, Rongwang; Gao, Weijia; Li, Rong; Zhao, Zhengyan

2015-04-19

With early initiation of thyroxine supplementation, children with congenital hypothyroidism (CH) retain some subtle deficits, such as attention and inhibitory control problems. This study assessed the effects of atomoxetine on cognitive functions in treatment of attention deficit hyperactivity disorder (ADHD) symptoms in children with CH. In a 6-month, open-labeled pilot study, 12 children were recruited and received atomoxetine. The measures of efficacy were scores on the Swanson, Nolan and Pelham Teacher and Parent Rating Scale, version IV (SNAP-IV) and Clinical Global Impression-Severity scale (CGI-S). The cognitive functions were evaluated with the Wechsler Intelligence Scale for Chinese Children, Digit Span, Wisconsin Card Sorting Test, and Stroop test. A statistically significant difference was found between the mean CGI-S and SNAP-IV scores before and after treatment (p < 0.01). All the indicators of cognitive functions at the endpoint were improved compared with those at baseline. No serious adverse events were reported. Atomoxetine appears to be useful in improving ADHD symptoms, as well as cognitive functions, in children with CH. Larger, randomized, double-blinded, clinical trials are required to replicate these results. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Impact of Education on Memory Deficits in Subclinical Depression

PubMed Central

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

2015-01-01

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

Pharmacotherapy of attention deficit in neurofibromatosis type 1: effects on cognition.

PubMed

Lidzba, Karen; Granstroem, Sofia; Leark, Robert A; Kraegeloh-Mann, Inge; Mautner, Victor-Felix

2014-08-01

 Attention deficit with or without hyperactivity (AD[H]D) is a common comorbidity of neurofibromatosis type 1 (NF 1). We tested the hypothesis that permanent medication with methylphenidate can improve cognitive functioning in children with NF 1 and comorbid AD(H)D.  We retrospectively analyzed data of a clinical sample of patients with NF 1 with or without AD(H)D, who underwent standardized neuropsychological diagnostics twice (age range: T1, 6-14 years; T2, 7-16 years; mean interval, 49.09 months). A total of 16 children without AD(H)D (nine females) were compared with 14 unmedicated children with AD(H)D (eight females) and to 13 medicated children with AD(H)D (two females). Effects of medication and attention on cognitive outcome (IQ) were tested by repeated measures analysis of covariance (rmANCOVA).  Medicated children with NF 1 improved significantly in full-scale IQ from T1 to T2 (IQ[T1] = 80.38, IQ[T2] = 98.38, confidence interval [diff]: -25.59 to -10.40, p < 0.0001), this effect was not evident for the other groups. With attention measures as covariates, the effect remained marginally significant.  Children and adolescents with NF 1 and comorbid AD(H)D may profit from MPH medication regarding general cognition. This effect could be specific for the group of patients with NF 1, and cannot be explained solely by improvements in attention. Controlled, prospective studies are warranted to corroborate our findings. Georg Thieme Verlag KG Stuttgart · New York.

A miRNA Signature for Cognitive Deficits and Alcohol Use Disorder in Persons Living with HIV/AIDS

PubMed Central

Wyczechowska, Dorota; Lin, Hui-Yi; LaPlante, Andrea; Jeansonne, Duane; Lassak, Adam; Parsons, Christopher H.; Molina, Patricia E.; Peruzzi, Francesca

2017-01-01

HIV-associated neurocognitive disorders (HAND) affects more than half of persons living with HIV-1/AIDS (PLWHA). Identification of biomarkers representing the cognitive status of PLWHA is a critical step for implementation of successful cognitive, behavioral and pharmacological strategies to prevent onset and progression of HAND. However, the presence of co-morbidity factors in PLWHA, the most common being substance abuse, can prevent the identification of such biomarkers. We have optimized a protocol to profile plasma miRNAs using quantitative RT-qPCR and found a miRNA signature with very good discriminatory ability to distinguish PLWHA with cognitive impairment from those without cognitive impairment. Here, we have evaluated this miRNA signature in PLWHA with alcohol use disorder (AUD) at LSU Health Sciences Center (LSUHSC). The results show that AUD is a potential confounding factor for the miRNAs associated with cognitive impairment in PLWHA. Furthermore, we have investigated the miRNA signature associated with cognitive impairment in an independent cohort of PLWHA using plasma samples from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) program. Despite differences between the two cohorts in socioeconomic status, AUD, and likely misuse of illicit or prescription drugs, we validated a miRNA signature for cognitive deficits found at LSUHSC in the CHARTER samples. PMID:29187813

Infrared thermometry for deficit irrigation of peach trees

USDA-ARS?s Scientific Manuscript database

Water shortage has been a major concern for crop production in the western states of the USA and other arid regions in the world. Deficit irrigation can be used in some cropping systems as a potential water saving strategy to alleviate water shortage, however, the margin of error in irrigation manag...

Cognition in multiple sclerosis

PubMed Central

Benedict, Ralph; Enzinger, Christian; Filippi, Massimo; Geurts, Jeroen J.; Hamalainen, Paivi; Hulst, Hanneke; Inglese, Matilde; Leavitt, Victoria M.; Rocca, Maria A.; Rosti-Otajarvi, Eija M.; Rao, Stephen

2018-01-01

Cognitive decline is recognized as a prevalent and debilitating symptom of multiple sclerosis (MS), especially deficits in episodic memory and processing speed. The field aims to (1) incorporate cognitive assessment into standard clinical care and clinical trials, (2) utilize state-of-the-art neuroimaging to more thoroughly understand neural bases of cognitive deficits, and (3) develop effective, evidence-based, clinically feasible interventions to prevent or treat cognitive dysfunction, which are lacking. There are obstacles to these goals. Our group of MS researchers and clinicians with varied expertise took stock of the current state of the field, and we identify several important practical and theoretical challenges, including key knowledge gaps and methodologic limitations related to (1) understanding and measurement of cognitive deficits, (2) neuroimaging of neural bases and correlates of deficits, and (3) development of effective treatments. This is not a comprehensive review of the extensive literature, but instead a statement of guidelines and priorities for the field. For instance, we provide recommendations for improving the scientific basis and methodologic rigor for cognitive rehabilitation research. Toward this end, we call for multidisciplinary collaborations toward development of biologically based theoretical models of cognition capable of empirical validation and evidence-based refinement, providing the scientific context for effective treatment discovery. PMID:29343470

A novel GLP-1/GIP/Gcg triagonist reduces cognitive deficits and pathology in the 3xTg mouse model of Alzheimer's disease.

PubMed

Li, Tian; Jiao, Juan-Juan; Hölscher, Christian; Wu, Mei-Na; Zhang, Jun; Tong, Jia-Qing; Dong, Xue-Fan; Qu, Xue-Song; Cao, Yue; Cai, Hong-Yan; Su, Qiang; Qi, Jin-Shun

2018-05-01

Type 2 diabetes mellitus (T2DM) is an important risk factor for Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been identified to be effective in T2DM treatment and neuroprotection. In this study, we further explored the effects of a novel unimolecular GLP-1/GIP/Gcg triagonist on the cognitive behavior and cerebral pathology in the 7-month-old triple transgenic mouse model of AD (3xTg-AD), and investigated its possible electrophysiological and molecular mechanisms. After chronic administration of the GLP-1/GIP/Gcg triagonist (10 nmol/kg bodyweight, once daily, i.p.) for 30 days, open field, Y maze and Morris water maze tests were performed, followed by in vivo electrophysiological recording, immunofluorescence and Western blotting experiments. We found that the chronic treatment with the triagonist could improve long-term spatial memory of 3xTg-AD mice in Morris water maze, as well as the working memory in Y maze task. The triagonist also alleviated the suppression of long-term potentiation (LTP) in the CA1 region of hippocampus. In addition, the triagonist significantly reduced hippocampal pathological damages, including amyloid-β (Aβ) and phosphorylated tau aggregates, and upregulated the expression levels of S133 p-CREB, T286 p-CAMKII and S9 p-GSK3β in the hippocampus of the 3xTg-AD mice. These results demonstrate for the first time that the novel GLP-1/GIP/Gcg triagonist is efficacious in ameliorating cognitive deficits and pathological damages of 3xTg-AD mice, suggesting that the triagonist might be potentially beneficial in the treatment of AD. © 2018 Wiley Periodicals, Inc.

Cognitive Control in Autism Spectrum Disorders

PubMed Central

Solomon, Marjorie; Ozonoff, Sally; Cummings, Neil; Carter, Cameron

2009-01-01

Cognitive control refers to the ability to flexibly allocate mental resources to guide thoughts and actions in light of internal goals. Given the behavioral inflexibility exhibited by individuals with autism spectrum disorders (ASDs), it would appear they experience cognitive control deficits. Cognitive correlates of this behavioral inflexibility have been elusive in previous investigations. Study goals were to investigate deficits in cognitive control in ASDs; to explore its developmental trajectory; and to test whether control deficits are related to symptoms of inflexible thoughts and/or behaviors, and attention symptoms. Thirty-one children and adolescents aged 8 to17 with ASDs and 32 age, IQ, and gender matched control subjects completed cognitive, diagnostic, and behavorial assessments, as well as a measure of cognitive control involving overcoming a prepotent response tendency. Compared with typically developing control subjects, individuals with ASDs exhibited deficits in cognitive control. Younger children with ASDs did not demonstrate age related improvements in cognitive control. Modest relationships between cognitive control, IQ, and attention problems were found for the sample. Only the relationship between cognitive control and Full Scale IQ survived correction for multiple comparisons. PMID:18093787

An Investigation of an Evaluation Method and Retraining Procedures for Emotionally Handicapped Children with Cognitive-Motor Deficits. Final Report.

ERIC Educational Resources Information Center

Rubin, Eli Z.; And Others

To assess the effects of specialized retraining of cognitive, perceptual, and motor (CPM) deficits, a battery of tests was prepared and used with 200 behaviorally maladjusted and 200 problem-free children. The composite score indicated that 40% of the maladjusted group manifested major dysfunction whereas none of the problem-free group…

High Suicide Risk after the Development of Cognitive and Working Memory Deficits Caused by Cannabis, Cocaine and Ecstasy Use

ERIC Educational Resources Information Center

Pompili, Maurizio; Lester, David; Girardi, Paolo; Tatarelli, Roberto

2007-01-01

We report the case of attempted suicide by a 30-year-old man who had significant cognitive deficits that developed after at least three years of polysubstance use with cannabis, methylenedioxymethamphetamine (MDMA, "ecstasy") and cocaine. The patient reported increasing difficulties in his professional and interpersonal life which may have been…

Frontal gamma noise power and cognitive domains in schizophrenia.

PubMed

Díez, Alvaro; Suazo, Vanessa; Casado, Pilar; Martín-Loeches, Manuel; Perea, María Victoria; Molina, Vicente

2014-01-30

The cognitive deficit profile is different among individuals with schizophrenia. We quantified the amount of electroencephalographic activity unlocked to stimuli onset (noise power) over frontal regions regarding deficit in cognitive domains. Forty-six patients with schizophrenia and 27 healthy controls underwent clinical, cognitive and electrophysiological assessments. Noise power studies may be considered complementary but not equivalent to induced power studies. We compared gamma and theta noise power magnitude during a P300 paradigm between subsets of patients divided according to cognitive deficit in key domains and controls. Patients displayed higher gamma noise power activity at Fz site and significantly lower performance in all cognitive domains when compared to controls. The subset of patients with cognitive deficit for working memory and problem solving/executive functions domains displayed significantly higher frontal-lateral noise power values in comparison to the subset of patients without cognitive deficit and controls. Patients with significant cognitive deficits in domains with greater frontal contribution are also characterized by an abnormally higher gamma band noise power over the frontal region. Our data may endorse various biological subsets within schizophrenia, characterized by the presence or absence of a significant cognitive deficit in frontal domains. © 2013 Published by Elsevier Ireland Ltd.

Virtual reality training to enhance behavior and cognitive function among children with attention-deficit/hyperactivity disorder: brief report.

PubMed

Shema-Shiratzky, Shirley; Brozgol, Marina; Cornejo-Thumm, Pablo; Geva-Dayan, Karen; Rotstein, Michael; Leitner, Yael; Hausdorff, Jeffrey M; Mirelman, Anat

2018-05-17

To examine the feasibility and efficacy of a combined motor-cognitive training using virtual reality to enhance behavior, cognitive function and dual-tasking in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Fourteen non-medicated school-aged children with ADHD, received 18 training sessions during 6 weeks. Training included walking on a treadmill while negotiating virtual obstacles. Behavioral symptoms, cognition and gait were tested before and after the training and at 6-weeks follow-up. Based on parental report, there was a significant improvement in children's social problems and psychosomatic behavior after the training. Executive function and memory were improved post-training while attention was unchanged. Gait regularity significantly increased during dual-task walking. Long-term training effects were maintained in memory and executive function. Treadmill-training augmented with virtual-reality is feasible and may be an effective treatment to enhance behavior, cognitive function and dual-tasking in children with ADHD.

Measuring disorganized speech in schizophrenia: automated analysis explains variance in cognitive deficits beyond clinician-rated scales.

PubMed

Minor, K S; Willits, J A; Marggraf, M P; Jones, M N; Lysaker, P H

2018-04-25

Conveying information cohesively is an essential element of communication that is disrupted in schizophrenia. These disruptions are typically expressed through disorganized symptoms, which have been linked to neurocognitive, social cognitive, and metacognitive deficits. Automated analysis can objectively assess disorganization within sentences, between sentences, and across paragraphs by comparing explicit communication to a large text corpus. Little work in schizophrenia has tested: (1) links between disorganized symptoms measured via automated analysis and neurocognition, social cognition, or metacognition; and (2) if automated analysis explains incremental variance in cognitive processes beyond clinician-rated scales. Disorganization was measured in schizophrenia (n = 81) with Coh-Metrix 3.0, an automated program that calculates basic and complex language indices. Trained staff also assessed neurocognition, social cognition, metacognition, and clinician-rated disorganization. Findings showed that all three cognitive processes were significantly associated with at least one automated index of disorganization. When automated analysis was compared with a clinician-rated scale, it accounted for significant variance in neurocognition and metacognition beyond the clinician-rated measure. When combined, these two methods explained 28-31% of the variance in neurocognition, social cognition, and metacognition. This study illustrated how automated analysis can highlight the specific role of disorganization in neurocognition, social cognition, and metacognition. Generally, those with poor cognition also displayed more disorganization in their speech-making it difficult for listeners to process essential information needed to tie the speaker's ideas together. Our findings showcase how implementing a mixed-methods approach in schizophrenia can explain substantial variance in cognitive processes.

A 12-week randomized controlled trial of twice-daily intranasal oxytocin for social cognitive deficits in people with schizophrenia.

PubMed

Jarskog, L Fredrik; Pedersen, Cort A; Johnson, Jacqueline L; Hamer, Robert M; Rau, Shane W; Elliott, Tonya; Penn, David L

2017-07-01

Social cognition is impaired in people with schizophrenia and these deficits are strongly correlated with social functioning. Oxytocin is a hypothalamic peptide that contributes to maternal infant bonding and has diverse pro-social effects in adults. This study tested the hypothesis that 12weeks of intranasal oxytocin will improve social cognitive function in outpatients with schizophrenia and schizoaffective disorder. Sixty-eight eligible participants were randomized to oxytocin (24IU twice daily) or placebo. Social cognitive function was assessed using the Emotion Recognition-40, Brüne Theory of Mind, Reading the Mind in the Eyes test, Trustworthiness task and Ambiguous Intentions Hostility Questionnaire at baseline, 6weeks and 12weeks. In addition, social function was assessed using the Specific Levels of Functioning Scale and a role-play test, and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Fifty-five participants completed the 12-week trial. The study found no evidence for a differential advantage of oxytocin over placebo on social cognition. Among secondary outcomes, there was a modest advantage for oxytocin over placebo on a component of social functioning, although there was also evidence that the placebo group outperformed the oxytocin group on the role-play task. No between-group differences emerged on measures of psychopathology in pre-specified comparisons, but oxytocin showed significant within-group reduction in PANSS negative symptoms and significant between-group improvement in negative symptoms in the schizophrenia subgroup. Further testing is needed to clarify whether oxytocin has therapeutic potential for social cognitive deficits and/or negative symptoms in people with schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Electroencephalogram complexity analysis in children with attention-deficit/hyperactivity disorder during a visual cognitive task.

PubMed

Zarafshan, Hadi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Moeini, Mahdi; Malmir, Nastaran

2016-01-01

The aim of this study was to investigate electroencephalogram (EEG) dynamics using complexity analysis in children with attention-deficit/hyperactivity disorder (ADHD) compared with healthy control children when performing a cognitive task. Thirty 7-12-year-old children meeting Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) criteria for ADHD and 30 healthy control children underwent an EEG evaluation during a cognitive task, and Lempel-Ziv complexity (LZC) values were computed. There were no significant differences between ADHD and control groups on age and gender. The mean LZC of the ADHD children was significantly larger than healthy children over the right anterior and right posterior regions during the cognitive performance. In the ADHD group, complexity of the right hemisphere was higher than that of the left hemisphere, but the complexity of the left hemisphere was higher than that of the right hemisphere in the normal group. Although fronto-striatal dysfunction is considered conclusive evidence for the pathophysiology of ADHD, our arithmetic mental task has provided evidence of structural and functional changes in the posterior regions and probably cerebellum in ADHD.

[Subjective cognition in schizophrenia].

PubMed

Potvin, S; Aubin, G; Stip, E

2017-02-01

Given the extent, magnitude and functional significance of the neurocognitive deficits of schizophrenia, growing attention has been paid recently to patients' self-awareness of their own deficits. Thus far, the literature has shown either that patients fail to recognize their cognitive deficits or that the association between subjective and objective cognition is weak in schizophrenia. The reasons for this lack of consistency remain unexplained but may have to do, among others, with the influence of potential confounding clinical variables and the choice of the scale used to measure self-awareness of cognitive deficits. In the current study, we sought to examine the relationships between subjective and objective cognitive performance in schizophrenia, while controlling for the influence of sociodemographic and psychiatric variables. Eighty-two patients with a schizophrenia-spectrum disorder (DSM-IV criteria) were recruited. Patients' subjective cognitive complaints were evaluated with the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS), the most frequently used scale to measure self-awareness of cognitive deficits in schizophrenia. Neurocognition was evaluated with working memory, planning and visual learning tasks taken from Cambridge Neuropsychological Tests Automated Battery. The Stroop Color-Word test was also administered. Psychiatric symptoms were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. The relationships between subjective and objective cognition were evaluated with multivariate hierarchic linear regression analyses, taking into consideration potential confounders such as sociodemographic and psychiatric variables. Finally, a factor analysis of the SSTICS was performed. For the SSTICS total score, the regression analysis produced a model including two predictors, namely visual learning and Stoop interference performance, explaining a moderate portion of the variance

"SLC2A3" Single-Nucleotide Polymorphism and Duplication Influence Cognitive Processing and Population-Specific Risk for Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Merker, Sören; Reif, Andreas; Ziegler, Georg C.; Weber, Heike; Mayer, Ute; Ehlis, Ann-Christine; Conzelmann, Annette; Johansson, Stefan; Müller-Reible, Clemens; Nanda, Indrajit; Haaf, Thomas; Ullmann, Reinhard; Romanos, Marcel; Fallgatter, Andreas J.; Pauli, Paul; Strekalova, Tatyana; Jansch, Charline; Vasquez, Alejandro Arias; Haavik, Jan; Ribasés, Marta; Ramos-Quiroga, Josep Antoni; Buitelaar, Jan K.; Franke, Barbara; Lesch, Klaus-Peter

2017-01-01

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of…

Cognitive Flexibility and Its Relationship to Academic Achievement and Career Choice of College Students with and without Attention Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Kercood, Suneeta; Lineweaver, Tara T.; Frank, Colleen C.; Fromm, Erik D.

2017-01-01

The purpose of this study was to investigate the relationship between cognitive flexibility, academic skills, educational trajectories, and career goals of college students with and without Attention Deficit Hyperactivity Disorder (ADHD). Participants completed a demographic questionnaire, objective and subjective measures of cognitive…

The Relationship between Prenatal and Postnatal Exposure to Polychlorinated Biphenyls (PCBs) and Cognitive, Neuropsychological, and Behavioral Deficits: A Critical Appraisal

ERIC Educational Resources Information Center

Cicchetti, Domenic V.; Kaufman, Alan S.; Sparrow, Sara S.

2004-01-01

Our purpose in this report is to evaluate scientifically that body of literature relating the effects of prenatal and postnatal exposure to polychlorinated biphenyls (PCBs) upon neurobehavioral, health-related, and cognitive deficits in neonates, developing infants, children, and adults. The data derive from seven cohorts: six cohorts of mothers…

Amyloid β-Mediated Zn2+ Influx into Dentate Granule Cells Transiently Induces a Short-Term Cognitive Deficit

PubMed Central

Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A.; Bush, Ashley I.; Tamano, Haruna

2014-01-01

We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits. PMID:25536033

Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

PubMed

Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A; Bush, Ashley I; Tamano, Haruna

2014-01-01

We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.

Attention Deficit/Hyperactivity Disorder (ADHD) symptoms and cognitive skills of preschool children.

PubMed

Thomaidis, L; Choleva, A; Janikian, M; Bertou, G; Tsitsika, A; Giannakopoulos, G; Anagnostopoulos, D C

2017-01-01

Attention deficit/hyperactivity disorder (ADHD) constitutes a neurobehavioral disorder which may potentially adversely affect children's wellbeing and academic achievement. The onset of symptoms is present prior to 12 years of age, and often the symptoms are evident in the preschool years. In fact, it has been suggested that screening for ADHD symptoms may be initiated as early as four years of age. Preschool children with ADHD have been shown to present with poor pre-academic skills and might be at increased risk for numerous school-related problems, including functional impairment during elementary school years and persistent poor academic performance thereafter. Although preschool years are characterized by rapid cognitive growth, preschoolers with ADHD may present with poorer cognitive and neuropsychological functioning. Due to the early onset of ADHD symptoms, exploring the cognitive correlates of this condition among preschool children is thought to be of notable importance. The aim of the present study was to evaluate any association between ADHD symptoms and cognitive skills among preschool children. A cross-sectional study was conducted among a nationwide random sample of 4,480 preschool children. ADHD symptoms were assessed though interviews with parents and teachers based on DSM-IV-TR criteria. Cognitive skills were assessed through a standardized school readiness test (A' TEST). Among participants, the occurrence of ADHD symptoms was 4.6% (boys/girls: 3.4/1). The presence of ADHD symptoms among children was inversely associated with non-verbal and verbal cognitive skills; specifically, with abstract thinking (aOR 1.97, 95% CI 1.30-3.00), language (2.36, 1.55-3.59), critical reasoning (2.58, 1.84-3.62), visual perception (2.42, 1.38- 4.24), and visual motor skills (2.61, 1.91-3.55). Children with ADHD symptoms were five times as likely to have compromised organizational skills (4.92, 3.04-7.97). Abstract thinking was the least affected domain

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.

Targeting Neural Synchrony Deficits is Sufficient to Improve Cognition in a Schizophrenia-Related Neurodevelopmental Model

PubMed Central

Lee, Heekyung; Dvorak, Dino; Fenton, André A.

2014-01-01

Cognitive symptoms are core features of mental disorders but procognitive treatments are limited. We have proposed a “discoordination” hypothesis that cognitive impairment results from aberrant coordination of neural activity. We reported that neonatal ventral hippocampus lesion (NVHL) rats, an established neurodevelopmental model of schizophrenia, have abnormal neural synchrony and cognitive deficits in the active place avoidance task. During stillness, we observed that cortical local field potentials sometimes resembled epileptiform spike-wave discharges with higher prevalence in NVHL rats, indicating abnormal neural synchrony due perhaps to imbalanced excitation–inhibition coupling. Here, within the context of the hypothesis, we investigated whether attenuating abnormal neural synchrony will improve cognition in NVHL rats. We report that: (1) inter-hippocampal synchrony in the theta and beta bands is correlated with active place avoidance performance; (2) the anticonvulsant ethosuximide attenuated the abnormal spike-wave activity, improved cognitive control, and reduced hyperlocomotion; (3) ethosuximide not only normalized the task-associated theta and beta synchrony between the two hippocampi but also increased synchrony between the medial prefrontal cortex and hippocampus above control levels; (4) the antipsychotic olanzapine was less effective at improving cognitive control and normalizing place avoidance-related inter-hippocampal neural synchrony, although it reduced hyperactivity; and (5) olanzapine caused an abnormal pattern of frequency-independent increases in neural synchrony, in both NVHL and control rats. These data suggest that normalizing aberrant neural synchrony can be beneficial and that drugs targeting the pathophysiology of abnormally coordinated neural activities may be a promising theoretical framework and strategy for developing treatments that improve cognition in neurodevelopmental disorders such as schizophrenia. PMID:24592242

Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stress and cognitive deficit in experimental hypothyroidism.

PubMed

Pan, Tianrong; Zhong, Mingkui; Zhong, Xing; Zhang, Yanqing; Zhu, Defa

2013-04-01

Hypothyroidism has a variety of adverse effects on cognitive function. The treatment of levothyroxine alone cannot restore cognitive defects of hypothyroid patients. Antioxidant vitamin E supplementation could be useful in disturbances which are associated with oxidative stress and could effectively slow the progression of Alzheimer disease. Thus, the purpose of this study was to evaluate oxidative stress status of the serum and hippocampus in hypothyroidism and to examine the effects of levothyroxine replacement therapy with vitamin E supplementation on cognitive deficit. Sprague-Dawley rats were randomly divided into five groups: control group, PTU group, PTU + Vit E group, PTU + L-T4 group, and PTU + L-T4 + Vit E group. Serum and hippocampus malondialdehyde (MDA) levels were determined using the thiobarbituric-acid reactive substances method. Serum and hippocampus superoxide dismutase (SOD) levels were determined by measuring its ability to inhibit the photoreduction of nitroblue tetrazolium. Learning and memory was assessed by Morris water maze test. In the present study, we found that the rats of PTU + Vit E group spent less time to find the platform on days 2, 3, 4, and 5 than the PTU group. Moreover, the rats of PTU + L-T4 + Vit E group spent less time to find the platform on days 4 and 5 than the PTU + L-T4 group. The time spent in the target quadrants was measured in the probe test and no difference was observed in all groups. Oxidative damage has been observed in the serum and hippocampus of hypothyroidism rat. SOD levels of serum and hippocampus tissue were significantly increased and MDA levels were significantly decreased in the PTU + Vit E and PTU + L-T4 + Vit E groups than the PTU and PTU + L-T4 groups. Therefore, these findings indicate that levothyroxine replacement therapy with vitamin E supplementation may ameliorate cognitive deficit in PTU-induced hypothyroidism through the decrease of oxidative stress status.

Deep Sleep and Parietal Cortex Gene Expression Changes Are Related to Cognitive Deficits with Age

PubMed Central

Buechel, Heather M.; Popovic, Jelena; Searcy, James L.; Porter, Nada M.; Thibault, Olivier; Blalock, Eric M.

2011-01-01

Background Age-related cognitive deficits negatively affect quality of life and can presage serious neurodegenerative disorders. Despite sleep disruption's well-recognized negative influence on cognition, and its prevalence with age, surprisingly few studies have tested sleep's relationship to cognitive aging. Methodology We measured sleep stages in young adult and aged F344 rats during inactive (enhanced sleep) and active (enhanced wake) periods. Animals were behaviorally characterized on the Morris water maze and gene expression profiles of their parietal cortices were taken. Principal Findings Water maze performance was impaired, and inactive period deep sleep was decreased with age. However, increased deep sleep during the active period was most strongly correlated to maze performance. Transcriptional profiles were strongly associated with behavior and age, and were validated against prior studies. Bioinformatic analysis revealed increased translation and decreased myelin/neuronal pathways. Conclusions The F344 rat appears to serve as a reasonable model for some common sleep architecture and cognitive changes seen with age in humans, including the cognitively disrupting influence of active period deep sleep. Microarray analysis suggests that the processes engaged by this sleep are consistent with its function. Thus, active period deep sleep appears temporally misaligned but mechanistically intact, leading to the following: first, aged brain tissue appears capable of generating the slow waves necessary for deep sleep, albeit at a weaker intensity than in young. Second, this activity, presented during the active period, seems disruptive rather than beneficial to cognition. Third, this active period deep sleep may be a cognitively pathologic attempt to recover age-related loss of inactive period deep sleep. Finally, therapeutic strategies aimed at reducing active period deep sleep (e.g., by promoting active period wakefulness and/or inactive period deep sleep) may

Scientific biography, cognitive deficits, and laboratory practice. James McKeen Cattell and early American experimental psychology, 1880-1904.

PubMed

Sokal, Michael M

2010-09-01

Despite widespread interest in individual life histories, few biographies of scientists make use of insights derived from psychology, another discipline that studies people, their thoughts, and their actions. This essay argues that recent theoretical work in psychology and tools developed for clinical psychological practice can help biographical historians of science create and present fuller portraits of their subjects' characters and temperaments and more nuanced analyses of how these traits helped shape their subjects' scientific work. To illustrate this thesis, the essay examines the early career of James McKeen Cattell--an influential late nineteenth- and early twentieth-century experimental psychologist--through a lens offered by psychology and argues that Cattell's actual laboratory practices derived from an "accommodation" to a long-standing "cognitive deficit." These practices in turn enabled Cattell to achieve more precise experimental results than could any of his contemporaries; and their students readily adopted them, along with their behavioral implications. The essay concludes that, in some ways, American psychology's early twentieth-century move toward a behavioral understanding of psychological phenomena can be traced to Cattell's personal cognitive deficit. It closes by reviewing several "remaining general questions" that this thesis suggests.

Relationship between cognitive and non-cognitive symptoms of delirium.

PubMed

Rajlakshmi, Aarya Krishnan; Mattoo, Surendra Kumar; Grover, Sandeep

2013-04-01

To study relationship between the cognitive and the non-cognitive symptoms of delirium. Eighty-four patients referred to psychiatry liaison services and met DSM-IVTR criteria of delirium were assessed using the Delirium Rating Scale Revised-1998 (DRSR-98) and Cognitive Test for Delirium (CTD). The mean DRS-R-98 severity score was 17.19 and DRS-R-98 total score was 23.36. The mean total score on CTD was 11.75. The mean scores on CTD were highest for comprehension (3.47) and lowest for vigilance (1.71). Poor attention was associated with significantly higher motor retardation and higher DRS-R-98 severity scores minus the attention scores. There were no significant differences between those with and without poor attention. Higher attention deficits were associated with higher dysfunction on all other domains of cognition on CTD. There was significant correlation between cognitive functions as assessed on CTD and total DRS-R-98 score, DRS-R-98 severity score and DRS-R-98 severity score without the attention item score. However, few correlations emerged between CTD domains and CTD total scores with cognitive symptom total score of DRS-R-98 (items 9-13) and non-cognitive symptom total score of DRS-R-98 (items 1-8). Our study suggests that in delirium, cognitive deficits are quite prevalent and correlate with overall severity of delirium. Attention deficit is a core symptom of delirium. Copyright © 2012 Elsevier B.V. All rights reserved.

Smaller than expected cognitive deficits in schizophrenia patients from the population-representative ABC catchment cohort.

PubMed

Lennertz, Leonhard; An der Heiden, Wolfram; Kronacher, Regina; Schulze-Rauschenbach, Svenja; Maier, Wolfgang; Häfner, Heinz; Wagner, Michael

2016-08-01

Most neuropsychological studies on schizophrenia suffer from sample selection bias, with male and chronic patients being overrepresented. This probably leads to an overestimation of cognitive impairments. The present study aimed to provide a less biased estimate of cognitive functions in schizophrenia using a population-representative catchment area sample. Schizophrenia patients (N = 89) from the prospective Mannheim ABC cohort were assessed 14 years after disease onset and first diagnosis, using a comprehensive neuropsychological test battery. A healthy control group (N = 90) was carefully matched according to age, gender, and geographic region (city, rural surrounds). The present sample was representative for the initial ABC cohort. In the comprehensive neuropsychological assessment, the schizophrenia patients were only moderately impaired as compared to the healthy control group (d = 0.56 for a general cognitive index, d = 0.42 for verbal memory, d = 0.61 for executive functions, d = 0.69 for attention). Only 33 % of the schizophrenia patients scored one standard deviation unit below the healthy control group in the general cognitive index. Neuropsychological performance did not correlate with measures of the clinical course including age at onset, number of hospital admissions, and time in paid work. Thus, in this population-representative sample of schizophrenia patients, neuropsychological deficits were less pronounced than expected from meta-analyses. In agreement with other epidemiological studies, this suggests a less devastating picture of cognition in schizophrenia.

Small molecule LX2343 ameliorates cognitive deficits in AD model mice by targeting both amyloid β production and clearance.

PubMed

Guo, Xiao-Dan; Sun, Guang-Long; Zhou, Ting-Ting; Xu, Xin; Zhu, Zhi-Yuan; Rukachaisirikul, Vatcharin; Hu, Li-Hong; Shen, Xu

2016-09-01

Streptozotocin (STZ) is widely used to induce oxidative damage and to impair glucose metabolism, apoptosis, and tau/Aβ pathology, eventually leading to cognitive deficits in both in vitro and in vivo models of Alzheimer's disease (AD). In this study, we constructed a cell-based platform using STZ to induce stress conditions mimicking the complicated pathologies of AD in vitro, and evaluated the anti-amyloid effects of a small molecule, N-(1,3-benzodioxol-5-yl)-2-[5-chloro-2-methoxy(phenylsulfonyl)anilino]acetamide (LX2343) in the amelioration of cognitive deficits in AD model mice. Cell-based assays for screening anti-amyloid compounds were established by assessing Aβ accumulation in HEK293-APP sw and CHO-APP cells, and Aβ clearance in primary astrocytes and SH-SY5Y cells after the cells were treated with STZ in the presence of the test compounds. Autophagic flux was observed using confocal laser scanning microscopy. APP/PS1 transgenic mice were administered LX2343 (10 mg·kg -1 ·d -1 , ip) for 100 d. After LX2343 administration, cognitive ability of the mice was evaluated using Morris water maze test, and senile plaques in the brains were detected using Thioflavine S staining. ELISA assay was used to evaluate Aβ and sAPPβ levels, while Western blot analysis was used to measure the signaling proteins in both cell and animal brains. LX2343 (5-20 μmol/L) dose-dependently decreased Aβ accumulation in HEK293-APP sw and CHO-APP cells, and promoted Aβ clearance in SH-SY5Y cells and primary astrocytes. The anti-amyloid effects of LX2343 were attributed to suppressing JNK-mediated APP Thr668 phosphorylation, thus inhibiting APP cleavage on one hand, and inhibiting BACE1 enzymatic activity with an IC 50 value of 11.43±0.36 μmol/L, on the other hand. Furthermore, LX2343 acted as a non-ATP competitive PI3K inhibitor to negatively regulate AKT/mTOR signaling, thus promoting autophagy, and increasing Aβ clearance. Administration of LX2343 in APP/PS1 transgenic mice

Detecting navigational deficits in cognitive aging and Alzheimer disease using virtual reality

PubMed Central

Cushman, Laura A.; Stein, Karen; Duffy, Charles J.

2008-01-01

Background: Older adults get lost, in many cases because of recognized or incipient Alzheimer disease (AD). In either case, getting lost can be a threat to individual and public safety, as well as to personal autonomy and quality of life. Here we compare our previously described real-world navigation test with a virtual reality (VR) version simulating the same navigational environment. Methods: Quantifying real-world navigational performance is difficult and time-consuming. VR testing is a promising alternative, but it has not been compared with closely corresponding real-world testing in aging and AD. We have studied navigation using both real-world and virtual environments in the same subjects: young normal controls (YNCs, n = 35), older normal controls (ONCs, n = 26), patients with mild cognitive impairment (MCI, n = 12), and patients with early AD (EAD, n = 14). Results: We found close correlations between real-world and virtual navigational deficits that increased across groups from YNC to ONC, to MCI, and to EAD. Analyses of subtest performance showed similar profiles of impairment in real-world and virtual testing in all four subject groups. The ONC, MCI, and EAD subjects all showed greatest difficulty in self-orientation and scene localization tests. MCI and EAD patients also showed impaired verbal recall about both test environments. Conclusions: Virtual environment testing provides a valid assessment of navigational skills. Aging and Alzheimer disease (AD) share the same patterns of difficulty in associating visual scenes and locations, which is complicated in AD by the accompanying loss of verbally mediated navigational capacities. We conclude that virtual navigation testing reveals deficits in aging and AD that are associated with potentially grave risks to our patients and the community. GLOSSARY AD = Alzheimer disease; EAD = early Alzheimer disease; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; ONC = older normal control; std

Effects of caffeine on behavioural and cognitive deficits in rats.

PubMed

Assis, Melissa S; Soares, Aluízio C; de Sousa, Dircilei N; Eudes-Filho, João; Faro, Lilian Rosana F; Carneiro, Fabiana P; da Silva, Mônica V; Motoyama, Andrea B; de Souza, Greice Maria R; Marchiori, Stéphanie; de Lima, Nadyelle T; Boëchat-Barros, Raphael; Ferreira, Vania M

2018-05-07

There are many studies that have sought to find drug therapies to prevent harm arising from sepsis. Such studies have represented a progress in the support to septic patients and also in the development of new pharmacological alternatives. Our interest was to investigate the caffeine effect on sepsis behavioural and memory impairments. Male rats were anaesthetized and the surgery was made to allow exposure of the cecum, which was then squeezed to extrude a small amount of faeces from the perforation site, which was later placed back into the peritoneal cavity. This procedure, which served to generate experimental sepsis, is herein referred to as ceccum ligation and perforation (CLP). The caffeine (10 mg/kg) was administered by gavage route, once daily, during 7 or 14 consecutive days to investigate the effects of acute or subchronic caffeine treatment on long-term behavioural and cognitive deficits induced by CLP. On the last day, one hour after caffeine administration, the animals were submitted to open-field, elevated plus-maze (EPM), forced swimming, and step-down inhibitory avoidance tests. The results showed that caffeine increased the percentage of open arm entries and open arm time in the EPM test, and reduced the immobility time when compared to the sham-operated group. The caffeine also increased the latency in the inhibitory avoidance test platform. Our results demonstrated that the caffeine improved behavioural changes and improved the neurocognitive deficits of sepsis-surviving animals. It is possible that blockage of the adenosine receptors may be responsible for the results here observed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Impact of Education on Memory Deficits in Subclinical Depression.

PubMed

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

2015-08-01

Elevated depressive symptoms are associated with cognitive deficits, while higher education protects against cognitive decline. This study was conducted to test if education level moderates the relationship between depressive symptoms and cognitive function. Seventy-three healthy, dementia-free adults aged 18-81 completed neuropsychological tests, as well as depression and anxiety questionnaires. Controlling for age, sex, and state anxiety, we found a significant interaction of depressive symptoms and education for immediate and delayed verbal memory, such that those with a higher education level performed well regardless of depressive symptomatology, whereas those with lower education and high depressive symptoms had worse performance. No effects were found for executive functioning or processing speed. Results suggest that education protects against verbal memory deficits in individuals with elevated depressive symptoms. Further research on cognitive reserve in depression-related cognitive deficits and decline is needed to understand the mechanisms behind this phenomenon. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A glucose-caffeine 'energy drink' ameliorates subjective and performance deficits during prolonged cognitive demand.

PubMed

Kennedy, David O; Scholey, Andrew B

2004-06-01

Effects of a combination of caffeine and glucose were assessed in two double-blind, placebo-controlled, cross-over studies during extended performance of cognitively demanding tasks. In the first study, 30 participants received two drinks containing carbohydrate and caffeine (68 g/38 mg; 68 g/46 mg, respectively) and a placebo drink, in counter-balanced order, on separate days. In the second study 26 participants received a drink containing 60 g of carbohydrate and 33 mg of caffeine and a placebo drink. In both studies, participants completed a 10-min battery of tasks comprising 2-min versions of Serial 3s and Serial 7s subtraction tasks and a 5-min version of the Rapid Visual Information Processing task (RVIP), plus a rating of 'mental fatigue', once before the drink and six times in succession commencing 10 min after its consumption. In comparison to placebo, all three active drinks improved the accuracy of RVIP performance and both the drink with the higher level of caffeine in first study and the active drink in the second study resulted in lower ratings of mental fatigue. These results indicate that a combination of caffeine and glucose can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive demand.

The social-cognitive basis of personality disorders.

PubMed

Herpertz, Sabine C; Bertsch, Katja

2014-01-01

The review summarizes recent results on abnormalities in social cognition in patients with personality disorders that predispose them to develop dysfunctional interaction with others. The review starts with more basic social cognition processes, such as emotion recognition and reactions to social exclusion that are followed by more complex processes such as cognitive and affective empathy. The deficits in social cognition depend on the particular function that is investigated and is strongly associated with characteristic symptoms of particular personality disorders. Thus, patients with borderline personality disorder are hypersensitive for social threat, they show deficits in cognitive empathy and high emotion contagion, that is, they share emotions of others without properly discriminating between one's own feelings and those of others. Psychopaths are characterized by deficiency in facial fear recognition and emotional empathy similar to patients with narcissistic personality disorder. Studies on social cognition in cluster A and C personality disorders are sparse. Research indicates deficits in social cognition in patients with personality disorders, but more research is needed to investigate social cognition in cluster A and C personality disorders and to compare deficits in social cognitive functions across personality disorders.

ChAT-ChR2-EYFP mice have enhanced motor endurance but show deficits in attention and several additional cognitive domains.

PubMed

Kolisnyk, Benjamin; Guzman, Monica S; Raulic, Sanda; Fan, Jue; Magalhães, Ana C; Feng, Guoping; Gros, Robert; Prado, Vania F; Prado, Marco A M

2013-06-19

Acetylcholine (ACh) is an important neuromodulator in the nervous system implicated in many forms of cognitive and motor processing. Recent studies have used bacterial artificial chromosome (BAC) transgenic mice expressing channelrhodopsin-2 (ChR2) protein under the control of the choline acetyltransferase (ChAT) promoter (ChAT-ChR2-EYFP) to dissect cholinergic circuit connectivity and function using optogenetic approaches. We report that a mouse line used for this purpose also carries several copies of the vesicular acetylcholine transporter gene (VAChT), which leads to overexpression of functional VAChT and consequently increased cholinergic tone. We demonstrate that these mice have marked improvement in motor endurance. However, they also present severe cognitive deficits, including attention deficits and dysfunction in working memory and spatial memory. These results suggest that increased VAChT expression may disrupt critical steps in information processing. Our studies demonstrate that ChAT-ChR2-EYFP mice show altered cholinergic tone that fundamentally differentiates them from wild-type mice.

Magical ideation associated social cognition in adolescents: signs of a negative facial affect recognition deficit.

PubMed

Canli, Derya; Ozdemir, Hatice; Kocak, Orhan Murat

2015-08-01

Studies provide evidence for impaired social cognition in schizotypy and its association with negative symptoms. Cognitive features related to magical ideation - a component of the positive dimension of schizotypy - have been less investigated. We aimed to assess social cognitive functioning among adolescents with high magical ideation scores, mainly focusing on face and emotion recognition. 22 subjects with magical ideation scale scores above the cut off level and 22 controls with lowest scores from among 250 students screened with this scale were included in the study. A face and emotion recognition n-back test, the empathy quotient, theory of mind tests and the Physical Anhedonia Scale were applied to both magical ideation and control groups. The magical ideation group performed significantly worse than controls on both face and emotion recognition tests. Emotion recognition performance was found to be affected by memory load, with sadness, among emotions, revealing a difference between the two groups. Empathy and theory of mind tests did not distinguish the magical ideation group from controls. Our findings provide evidence for a deficit in negative emotion recognition affected by memory load associated with magical ideation in adolescents. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute cocaine induced deficits in cognitive performance in rhesus macaque monkeys treated with baclofen

PubMed Central

Porrino, Linda J.; Hampson, Robert E.; Opris, Ioan; Deadwyler, Samuel A.

2013-01-01

Rationale Acute and/or chronic exposure to cocaine can affect cognitive performance, which may influence rate of recovery during treatment. Objective Effects of the GABA-B receptor agonist baclofen were assessed for potency to reverse the negative influence of acute, pre-session, intravenous (IV) injection of cocaine on cognitive performance in Macaca mulatta nonhuman primates. Methods Animals were trained to perform a modified delayed match to sample (DMS) task incorporating two types of trials with varying degrees of cognitive load that had different decision requirements in order to correctly utilize information retained over the delay interval. The effects of cocaine (0.2, 0.4, and 0.6 mg/kg, IV) alone and in combination with baclofen (0.29 and 0.40 mg/kg, IV) were examined with respect to sustained performance levels. Brain metabolic activity during performance of the task was assessed using PET imaged uptake of [18F]-fluorodeoxyglucose. Results Acute cocaine injections produced a dose-dependent decline in DMS performance selective for trials of high cognitive load. The GABA-receptor agonist baclofen, co-administered with cocaine, reversed task performance back to nondrug (saline IV) control levels. Simultaneous assessment of PET-imaged brain metabolic activity in prefrontal cortex (PFC) showed alterations by cocaine compared to PFC metabolic activation in nondrug (saline, IV) control DMS sessions, but like performance, PFC activation was returned to control levels by baclofen (0.40 mg/kg, IV) injected with cocaine. Conclusions The results show that baclofen, administered at a relatively high dose, reversed the cognitive deficits produced by acute cocaine intoxication that may have implications for use in chronic drug exposure. PMID:22836369

Exogenous nitric oxide improves sugarcane growth and photosynthesis under water deficit.

PubMed

Silveira, Neidiquele M; Frungillo, Lucas; Marcos, Fernanda C C; Pelegrino, Milena T; Miranda, Marcela T; Seabra, Amedea B; Salgado, Ione; Machado, Eduardo C; Ribeiro, Rafael V

2016-07-01

Nitric oxide (NO)-mediated redox signaling plays a role in alleviating the negative impact of water stress in sugarcane plants by improving root growth and photosynthesis. Drought is an environmental limitation affecting sugarcane growth and yield. The redox-active molecule nitric oxide (NO) is known to modulate plant responses to stressful conditions. NO may react with glutathione (GSH) to form S-nitrosoglutathione (GSNO), which is considered the main reservoir of NO in cells. Here, we investigate the role of NO in alleviating the effects of water deficit on growth and photosynthesis of sugarcane plants. Well-hydrated plants were compared to plants under drought and sprayed with mock (water) or GSNO at concentrations ranging from 10 to 1000 μM. Leaf GSNO sprayed plants showed significant improvement of relative water content and leaf and root dry matter under drought compared to mock-sprayed plants. Additionally, plants sprayed with GSNO (≥ 100 μM) showed higher leaf gas exchange and photochemical activity as compared to mock-sprayed plants under water deficit and after rehydration. Surprisingly, a raise in the total S-nitrosothiols content was observed in leaves sprayed with GSH or GSNO, suggesting a long-term role of NO-mediated responses to water deficit. Experiments with leaf discs fumigated with NO gas also suggested a role of NO in drought tolerance of sugarcane plants. Overall, our data indicate that the NO-mediated redox signaling plays a role in alleviating the negative effects of water stress in sugarcane plants by protecting the photosynthetic apparatus and improving shoot and root growth.

Comparison of the Recovery Patterns of Language and Cognitive Functions in Patients with Post-Traumatic Language Processing Deficits and in Patients with Aphasia Following a Stroke

ERIC Educational Resources Information Center

Vukovic, Mile; Vuksanovic, Jasmina; Vukovic, Irena

2008-01-01

In this study we investigated the recovery patterns of language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke. The correlation of specific language functions and cognitive functions was analyzed in the acute phase and 6 months later. Significant recovery of the…

The paradox of cognitive flexibility in autism

PubMed Central

Geurts, Hilde M.; Corbett, Blythe; Solomon, Marjorie

2017-01-01

We present an overview of current literature addressing cognitive flexibility in autism spectrum disorders. Based on recent studies at multiple sites, using diverse methods and participants of different autism subtypes, ages and cognitive levels, no consistent evidence for cognitive flexibility deficits was found. Researchers and clinicians assume that inflexible everyday behaviors in autism are directly related to cognitive flexibility deficits as assessed by clinical and experimental measures. However, there is a large gap between the day-to-day behavioral flexibility and that measured with these cognitive flexibility tasks. To advance the field, experimental measures must evolve to reflect mechanistic models of flexibility deficits. Moreover, ecologically valid measures are required to be able to resolve the paradox between cognitive and behavioral inflexibility. PMID:19138551

[Effects of Cognitive Behavioral Therapy on Attention Deficit Hyperactivity Disorder among School-aged Children in Korea: A Meta-Analysis].

PubMed

Park, Wan-Ju; Park, Shin-Jeong; Hwang, Sung-Dong

2015-04-01

This study was a meta-analysis designed to identify effects of Cognitive Behavioral Therapy (CBT) interventions in alleviating main symptoms of Attention Deficit Hyperactivity Disorder (ADHD) among school-aged children in Korea. Examination of several databases including Research Information Sharing Service, Korean Studies Information Service System, Data Base Periodical Information Academic and hand-searched article references, resulted in identification of 1,298 studies done between 2000 and 2013 of which 21 met the inclusion criteria. Comprehensive Meta-Analysis version 2.0 was used to analyze effect sizes, explore possible causes of heterogeneity, and check publication bias with a funnel plot and its trim-and-fill analysis. Overall effect size of CBT intervention was large (g=1.08) along with each outcome of self-control (g=1.26), lack of attention (g=1.02), social skills (g=0.92), and hyperactivity (g=0.92). For heterogeneity, moderator analysis was performed, but no significant differences were found between the RCT (Randomized Controlled Trials) group and the NRCT (Non RCT) group. Also, meta-regression was performed using sample size, number of sessions, and length of session as predictors, but no statistically significant moderators were found. Finally, a funnel plot along with trim-and-fill analysis was produced to check for publication bias, but no significant bias was detected. Based on these findings, there is clear evidence that CBT intervention has significant positive effects on the main symptoms of school-aged children suffering ADHD. Further research is needed to target diverse age groups with ADHD along with more RCT studies to improve the effectiveness of the CBT intervention.

Effects of Concord grape juice on cognitive and motor deficits in aging.

PubMed

Shukitt-Hale, Barbara; Carey, Amanda; Simon, Laura; Mark, David A; Joseph, James A

2006-03-01

Animals and humans show increased motor and cognitive declines with aging that are thought to be due to increased susceptibility to the long-term effects of oxidative stress and inflammation. Previous findings have suggested that reversals in these age-related declines might be accomplished by increasing the dietary intake of polyphenolics found in fruits and vegetables, especially those identified as being high in antioxidant and anti-inflammatory activities. We investigated the beneficial effects of two concentrations of Concord grape juice (10% and 50%) compared with a calorically matched placebo for their effectiveness in reversing age-related deficits in behavioral and neuronal functions in aged Fischer 344 rats. Rats that drank the 10% grape juice from age 19 to 21 mo had improvements in oxotremorine enhancement of K+-evoked release of dopamine from striatal slices and in cognitive performance on the Morris water maze, and the 50% grape juice produced improvements in motor function. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, polyphenolics in foods may be beneficial in reversing the course of neuronal and behavioral aging, possibly through a multiplicity of direct and indirect effects that can affect a variety of neuronal parameters.

Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer's Disease.

PubMed

Huang, Shichao; Mao, Jianxin; Ding, Kan; Zhou, Yue; Zeng, Xianglu; Yang, Wenjuan; Wang, Peipei; Zhao, Cun; Yao, Jian; Xia, Peng; Pei, Gang

2017-01-10

Promoting neurogenesis is a promising strategy for the treatment of cognition impairment associated with Alzheimer's disease (AD). Ganoderma lucidum is a revered medicinal mushroom for health-promoting benefits in the Orient. Here, we found that oral administration of the polysaccharides and water extract from G. lucidum promoted neural progenitor cell (NPC) proliferation to enhance neurogenesis and alleviated cognitive deficits in transgenic AD mice. G. lucidum polysaccharides (GLP) also promoted self-renewal of NPC in cell culture. Further mechanistic study revealed that GLP potentiated activation of fibroblast growth factor receptor 1 (FGFR1) and downstream extracellular signal-regulated kinase (ERK) and AKT cascades. Consistently, inhibition of FGFR1 effectively blocked the GLP-promoted NPC proliferation and activation of the downstream cascades. Our findings suggest that GLP could serve as a regenerative therapeutic agent for the treatment of cognitive decline associated with neurodegenerative diseases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The Nature and Consequences of Cognitive Deficits among Tobacco Smokers with HIV: A Comparison to Tobacco Smokers without HIV

PubMed Central

Harrison, Joseph D.; Dochney, Jessica A.; Blazekovic, Sonja; Leone, Frank; Metzger, David; Frank, Ian; Gross, Robert; Hole, Anita; Mounzer, Karam; Siegel, Steven; Schnoll, Robert A.; Ashare, Rebecca L.

2017-01-01

HIV-infected smokers lose more years of life to tobacco-related disease than HIV. Since neurocognitive deficits are common among those with HIV and are associated with smoking persistence, these deficits may be a unique barrier to smoking cessation among HIV-infected smokers. Documenting unique differences in and correlates of cognition among HIV-infected smokers is a critical step towards developing a population-specific tobacco cessation treatment. We compared neurocognitive function between HIV-infected (n=103) and HIV-uninfected smokers (n=70), accounting for demographic and smoking-related variables. We also evaluated whether HIV-related health outcomes (e.g., CD4 count, viral load, depression ratings, quality of life [QoL]) and HAART adherence were associated with cognition. Participants completed neurocognitive tasks (N-back and Continuous Performance Task [CPT]) measuring working memory, attention, and processing speed, and intra-individual variability. Stepwise regression models were conducted and validated with resampling techniques. HIV-infected smokers performed worse than HIV-uninfected smokers on working memory, processing speed, and intra-individual variability (all p<0.01). ROC analysis for the model including cognitive measures demonstrated 85% area under the curve, which indicates “good prediction” for distinguishing between HIV-infected and HIV-uninfected smokers. This was a significant improvement over the model including demographic and smoking-related variables only (p=0.0003). Among HIV-infected smokers, neurocognitive performance was negatively associated with QoL and depression ratings. Smoking cessation interventions for HIV-infected smokers should consider cognitive neurorehabilitation as a potential strategy to decrease the likelihood of nicotine relapse and decrease tobacco-related morbidity in this population. PMID:28429289

Designing websites for persons with cognitive deficits: Design and usability of a psychoeducational intervention for persons with severe mental illness.

PubMed Central

Rotondi, Armando J.; Sinkule, Jennifer; Haas, Gretchen L.; Spring, Michael B.; Litschge, Christine M.; Newhill, Christina E.; Ganguli, Rohan; Anderson, Carol M.

2013-01-01

The purpose of this study was to develop an understanding of the design elements that influence the ability of persons with severe mental illness (SMI) and cognitive deficits to use a website, and to use this knowledge to design a web-based telehealth application to deliver a psychoeducation program to persons with schizophrenia and their families. Usability testing was conducted with 98 persons with SMI. First, individual website design elements were tested. Based on these results, theoretical website design models were used to create several alternative websites. These designs were tested for their ability to facilitate use by persons with SMI. The final website design is presented. The results indicate that commonly prescribed design models and guidelines produce websites that are poorly suited and confusing to persons with SMI. Our findings suggest an alternative model that should be considered when designing websites and other telehealth interventions for this population. Implications for future studies addressing the characteristics of accessible designs for persons with SMI and cognitive deficits are discussed. PMID:26321884

Chotosan (Diaoteng San)-induced improvement of cognitive deficits in senescence-accelerated mouse (SAMP8) involves the amelioration of angiogenic/neurotrophic factors and neuroplasticity systems in the brain

PubMed Central

2011-01-01

Background Chotosan (CTS, Diaoteng San), a Kampo medicine (ie Chinese medicine) formula, is reportedly effective in the treatment of patients with cerebral ischemic insults. This study aims to evaluate the therapeutic potential of CTS in cognitive deficits and investigates the effects and molecular mechanism(s) of CTS on learning and memory deficits and emotional abnormality in an animal aging model, namely 20-week-old senescence-accelerated prone mice (SAMP8), with and without a transient ischemic insult (T2VO). Methods Age-matched senescence-resistant inbred strain mice (SAMR1) were used as control. SAMP8 received T2VO (T2VO-SAMP8) or sham operation (sham-SAMP8) at day 0. These SAMP8 groups were administered CTS (750 mg/kg, p.o.) or water daily for three weeks from day 3. Results Compared with the control group, both sham-SAMP8 and T2VO-SAMP8 groups exhibited cognitive deficits in the object discrimination and water maze tests and emotional abnormality in the elevated plus maze test. T2VO significantly exacerbated spatial cognitive deficits of SAMP8 elucidated by the water maze test. CTS administration ameliorated the cognitive deficits and emotional abnormality of sham- and T2VO-SAMP8 groups. Western blotting and immunohistochemical studies revealed a marked decrease in the levels of phosphorylated forms of neuroplasticity-related proteins, N-methyl-D-aspartate receptor 1 (NMDAR1), Ca2+/calmodulin-dependent protein kinase II (CaMKII), cyclic AMP responsive element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the frontal cortices of sham-SAMP8 and T2VO-SAMP8. Moreover, these animal groups showed significantly reduced levels of vasculogenesis/angiogenesis factors, vascular endothelial growth factor (VEGF), VEGF receptor type 2 (VEGFR2), platelet-derived growth factor-A (PDGF-A) and PDGF receptor α (PDGFRα). CTS treatment reversed the expression levels of these factors down-regulated in the brains of sham- and T2VO-SAMP8. Conclusion

Cognitive skill learning and schizophrenia: implications for cognitive remediation.

PubMed

Michel, L; Danion, J M; Grangé, D; Sandner, G

1998-10-01

The ability to acquire a motor and cognitive skill was investigated in 26 patients with schizophrenia and 26 normal participants using repeated testing on the Tower of Toronto puzzle. Seven patients with defective performance were retested using additional trials and immediate feedback designed to facilitate problem solving. A component analysis of performance was used based on J. R. Anderson's (1987) model of cognitive skill learning. Patients exhibited a performance deficit on both motor and cognitive skills. However, their acquisition rate was similar to that of normal participants on most parameters, indicating that skill learning suffered little or no impairment. Performance deficit was accounted for by poor problem-solving ability, explicit memory, and general intellectual capacities. It was remediable in some, but not all, patients. Remediation failure was also related to severe defects of cognitive functions.

The genesis of cognitive and behavioral deficits in premature graduates of intensive care.

PubMed

Perlman, J M

2003-04-01

Increased survival of very low birth weight infants including those born at the cutting edge of viability is associated with substantial cognitive and behavioral deficits at follow-up that has extended into school age and adolescence. These problems have occurred as common in the presence or absence of neurosonographic abnormalities. Factors/events that may predispose to these problems include medical complications of prematurity i.e. chronic lung disease, recurrent episodes of apnea and bradycardia, transient hypothyroxinemia of prematurity, hyperbilirubinemia, nutritional deficiencies, medications used to treat such conditions i.e. glucorticoids, theophylline etc. and stress associated with prolonged hospitalization. With regard to the latter, attachment to multiple devices that limits infant provider interactions, high noise levels and constant light levels are considered to be of particular importance. Experimental evidence is presented that demonstrates the value of positive interactions between the subject and provider with regard to neurobehavioral outcome. Some suggested interventions include reducing noise levels and displacing it with music, modulating light exposure and enhancing infant parent interactions such as kangaroo care. Finally the important postnatal role of social influences on cognitive and behavioral outcomes is discussed.

Protective effect of stilbenes containing extract-fraction from Cajanus cajan L. on Abeta(25-35)-induced cognitive deficits in mice.

PubMed

Ruan, Can-Jun; Si, Jian-Yong; Zhang, Li; Chen, Di-Hua; Du, Guan-Hua; Su, Lan

2009-12-25

Cajanus cajan (L.) is a traditional Chinese herb medicine which contains a lot of potential active components. In the present study, we identified the effects of the stilbenes containing extract-fraction from C. cajan L. (sECC) on Abeta(25-35)-induced cognitive deficits, oxidative stress and cholinergic dysfunction in mice. Mice were treated with sECC (100 and 200mg/kg/d) for 1-week, and then received a single intracerebroventricular (i.c.v.) injection of Abeta(25-35) (5mug/mice). Behavioral changes and neuron apoptosis in mice were evaluated using Morris water maze and TUNEL tests. Furthermore, superoxide dismutase (SOD), choline acetyl transferase (ChAT) and acetylcholine esterase (AchE) activity in hippocampus and cortex were analyzed by spectrophotometric method. The data showed that consumption of sECC (200mg/kg) significantly ameliorated the cognitive deficits and neuron apoptosis caused by i.c.v. injection of Abeta(25-35). At the same time, the decreased SOD and ChAT activity in hippocampus and cortex were markedly increased by sECC (200mg/kg). sECC has no effect on AchE activity in hippocampus and cortex. These findings suggest that sECC may be a potential candidate for the development of therapeutic agents to manage cognitive impairment associated with Alzheimer's disease (AD) through increasing the activity of ChAT and anti-oxidative mechanism.

Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure.