Science.gov

Sample records for alleviate cognitive deficits

  1. The histone deacetylase inhibitor, sodium butyrate, alleviates cognitive deficits in pre-motor stage PD.

    PubMed

    Rane, Pallavi; Shields, Jessica; Heffernan, Meghan; Guo, Yin; Akbarian, Schahram; King, Jean A

    2012-06-01

    Parkinson's disease (PD) patients often times experience impairment in their cognitive abilities early on in the progression of the disease. The reported deficits appear to mainly involve functions that are associated with frontal lobe and frontal-striatal pathways subserving attentional set-shifting, working memory and executive function. The current study explored executive function deficits in a rat model of PD in the pre-motor deficit stage. The rats were lesioned with 12 μg of 6-hydroxydonpamine (6-OHDA) in the striatum in a two step process (10 μg/μl followed by 2 μg/μl) 48 hours apart. Executive function was tested at 3 weeks post-surgery using a rat analogue of Wisconsin card sorting test called the Extra Dimensional/Intra Dimensional (ED/ID) set-shifting task. The results demonstrated that performance by the pre-motor rat model of PD was equivalent to that of the control groups in the simple and the compound discriminations as well as the intra-dimensional set-shifting. However the PD group exhibited attentional set-shifting deficits similar to those observed in PD patients. Additionally, sodium butyrate, a short chain fatty acid derivative and inhibitor of class I and II histone deacetylase (HDACi), was tested as a potential therapeutic agent to mitigate the pre-motor cognitive deficits in PD. The results indicated that the sodium butyrate treatment not only effectively alleviated the set-shifting deficits, but also improved the attentional set formation in the treated rats.

  2. Inhibition of inflammation by astaxanthin alleviates cognition deficits in diabetic mice.

    PubMed

    Zhou, Xiaoyan; Zhang, Fang; Hu, Xiaotong; Chen, Jing; Wen, Xiangru; Sun, Ying; Liu, Yonghai; Tang, Renxian; Zheng, Kuiyang; Song, Yuanjian

    2015-11-01

    Neurons in the hippocampal and cortical functional regions are more susceptible to damage induced by hyperglycemia, which can result in severe spatial learning and memory impairment. Neuroprotection ameliorates cognitive impairment induced by hyperglycemia in diabetic encephalopathy (DE). Astaxanthin has been widely studied in diabetes mellitus and diabetic complications due to its hypoglycemic, antioxidant and anti-apoptotic effects. However, whether astaxanthin can alleviate cognition deficits induced by DE and its precise mechanisms remain undetermined. In this study, DE was induced by streptozotocin (STZ, 150 mg/kg) in ICR mice. We observed the effect of astaxanthin on cognition and investigated its potential mechanisms in DE mice. Results showed that astaxanthin treatment significantly decreased the latency and enhanced the distance and time spent in the target quadrant in the Morris water maze test. Furthermore, neuronal survival was significantly increased in the hippocampal CA3 region and the frontal cortex following treatment with astaxanthin. Meanwhile, immunoblotting was used to observe the nuclear translocation of nuclear factor-kappaB (NF-κB) p65 and the expression of tumor necrosis factor-α (TNF-α) in the hippocampus and frontal cortex. The results indicated that astaxanthin could inhibit NF-κB nuclear translocation and downregulate TNF-α expression in the hippocampus and frontal cortex. Overall, the present study implied that astaxanthin could improve cognition by protecting neurons against inflammation injury potentially through inhibiting the nuclear translocation of NF-κB and down-regulating TNF-α. PMID:26272354

  3. Bilobalide alleviates depression-like behavior and cognitive deficit induced by chronic unpredictable mild stress in mice.

    PubMed

    Wu, Ruiyong; Shui, Li; Wang, Siyang; Song, Zhenzhen; Tai, Fadao

    2016-10-01

    Bilobalide (BB), a unique constituent of Ginkgo biloba, has powerful neuroprotection and stress-alleviating properties. However, whether BB exerts a positive effect on depression and cognitive deficit induced by chronic stress is not known. The present study was designed to investigate the influence of BB on depression and cognitive impairments induced by chronic unpredictable mild stress (CUMS) in mice. During daily exposure to stressors for 5 consecutive weeks, mice were administered BB at the doses of 0, 3, or 6 mg/kg/day intraperitoneally. We replicated the finding that CUMS induced depression-like behavior and cognitive deficits as the CUMS+vehicle (VEH) group showed a significant increase in immobility in the tail suspension test, a decrease in the discrimination index of the novel object recognition task, and increased latency to platform and decreased number of platform crossings in the Morris water maze compared with the control+VEH group. Chronic administration of BB effectively reversed these alterations. In addition, the CUMS+VEH group showed significantly higher levels of baseline serum corticosterone than those of the control+VEH group and BB dose-dependently inhibited this effect. Our results suggest that BB may be useful for inhibition of depression-like behavior and cognitive deficits, and this protective effect was possibly exerted partly through an action on the hypothalamic-pituitary-adrenal axis. PMID:27509313

  4. Bilobalide alleviates depression-like behavior and cognitive deficit induced by chronic unpredictable mild stress in mice.

    PubMed

    Wu, Ruiyong; Shui, Li; Wang, Siyang; Song, Zhenzhen; Tai, Fadao

    2016-10-01

    Bilobalide (BB), a unique constituent of Ginkgo biloba, has powerful neuroprotection and stress-alleviating properties. However, whether BB exerts a positive effect on depression and cognitive deficit induced by chronic stress is not known. The present study was designed to investigate the influence of BB on depression and cognitive impairments induced by chronic unpredictable mild stress (CUMS) in mice. During daily exposure to stressors for 5 consecutive weeks, mice were administered BB at the doses of 0, 3, or 6 mg/kg/day intraperitoneally. We replicated the finding that CUMS induced depression-like behavior and cognitive deficits as the CUMS+vehicle (VEH) group showed a significant increase in immobility in the tail suspension test, a decrease in the discrimination index of the novel object recognition task, and increased latency to platform and decreased number of platform crossings in the Morris water maze compared with the control+VEH group. Chronic administration of BB effectively reversed these alterations. In addition, the CUMS+VEH group showed significantly higher levels of baseline serum corticosterone than those of the control+VEH group and BB dose-dependently inhibited this effect. Our results suggest that BB may be useful for inhibition of depression-like behavior and cognitive deficits, and this protective effect was possibly exerted partly through an action on the hypothalamic-pituitary-adrenal axis.

  5. Use of Cognitive Behavioral Therapy and Token Economy to Alleviate Dysfunctional Behavior in Children with Attention-Deficit Hyperactivity Disorder

    PubMed Central

    Coelho, Luzia Flavia; Barbosa, Deise Lima Fernandes; Rizzutti, Sueli; Muszkat, Mauro; Bueno, Orlando Francisco Amodeo; Miranda, Monica Carolina

    2015-01-01

    Medication has proved highly efficacious as a means of alleviating general symptoms of attention-deficit hyperactivity disorder (ADHD). However, many patients remain functionally impaired by inappropriate behavior. The present study analyzed the use of cognitive behavioral therapy (CBT) with the Token-Economy (TE) technique to alleviate problem behavior for 25 participants with ADHD, all children (19 boys, mean age 10.11) on long-term methylphenidate medication, who were given 20 CBT sessions with 10 weeks of TE introduced as of session 5. Their ten most acute problem behaviors were selected and written records kept. On weekdays, parents recorded each inappropriate behavior and provided a suitable model for their actions. At weekly sessions, problem behaviors were counted and incident-free participants rewarded with a token. To analyze improvement (less frequent problem behavior), a list of 11 behavioral categories was rated: inattention, impulsivity, hyperactivity, disorganization, disobeying rules and routines, poor self-care, verbal/physical aggression, low frustration tolerance, compulsive behavior, antisocial behavior, lacking in initiative and distraction. Two CBT specialists categorized behaviors and an ADHD specialist ruled on discrepancies. Statistical analyses used were Generalized Estimating Equations with Poisson distribution and autoregressive order correlation structure. In the course of the sessions, problematic behaviors decreased significantly in seven categories: impulsiveness, hyperactivity, disorganization, disobeying rules and routine, poor self-care, low frustration tolerance, compulsive behaviors, and antisocial behaviors. Caregiver attitudes to children’s inappropriate behavior were discussed and reshaped. As functional improvement was observed on applying TE for 10 weeks, this type of intervention may be useful as an auxiliary strategy combined with medication. PMID:26635642

  6. Use of Cognitive Behavioral Therapy and Token Economy to Alleviate Dysfunctional Behavior in Children with Attention-Deficit Hyperactivity Disorder.

    PubMed

    Coelho, Luzia Flavia; Barbosa, Deise Lima Fernandes; Rizzutti, Sueli; Muszkat, Mauro; Bueno, Orlando Francisco Amodeo; Miranda, Monica Carolina

    2015-01-01

    Medication has proved highly efficacious as a means of alleviating general symptoms of attention-deficit hyperactivity disorder (ADHD). However, many patients remain functionally impaired by inappropriate behavior. The present study analyzed the use of cognitive behavioral therapy (CBT) with the Token-Economy (TE) technique to alleviate problem behavior for 25 participants with ADHD, all children (19 boys, mean age 10.11) on long-term methylphenidate medication, who were given 20 CBT sessions with 10 weeks of TE introduced as of session 5. Their ten most acute problem behaviors were selected and written records kept. On weekdays, parents recorded each inappropriate behavior and provided a suitable model for their actions. At weekly sessions, problem behaviors were counted and incident-free participants rewarded with a token. To analyze improvement (less frequent problem behavior), a list of 11 behavioral categories was rated: inattention, impulsivity, hyperactivity, disorganization, disobeying rules and routines, poor self-care, verbal/physical aggression, low frustration tolerance, compulsive behavior, antisocial behavior, lacking in initiative and distraction. Two CBT specialists categorized behaviors and an ADHD specialist ruled on discrepancies. Statistical analyses used were Generalized Estimating Equations with Poisson distribution and autoregressive order correlation structure. In the course of the sessions, problematic behaviors decreased significantly in seven categories: impulsiveness, hyperactivity, disorganization, disobeying rules and routine, poor self-care, low frustration tolerance, compulsive behaviors, and antisocial behaviors. Caregiver attitudes to children's inappropriate behavior were discussed and reshaped. As functional improvement was observed on applying TE for 10 weeks, this type of intervention may be useful as an auxiliary strategy combined with medication.

  7. Enriched endogenous n-3 polyunsaturated fatty acids alleviate cognitive and behavioral deficits in a mice model of Alzheimer's disease.

    PubMed

    Wu, Kefeng; Gao, Xiang; Shi, Baoyan; Chen, Shiyu; Zhou, Xin; Li, Zhidong; Gan, Yuhong; Cui, Liao; Kang, Jing Xuan; Li, Wende; Huang, Ren

    2016-10-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accompanied by memory deficits and neuropsychiatric dysfunction. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have seemly therapeutic potential in AD, but the benefit of n-3 PUFAs is still in debates. Here, we employed a transgenic mice carry fat-1 gene to encode n-3 desaturase from Caenorhabditis elegans, which increase endogenous n-3 PUFAs by converting n-6 PUFAs to n-3 PUFAs crossed with amyloid precursor protein (APP) Tg mice to evaluate the protective effects of endogenous n-3 PUFAs on cognitive and behavioral deficits of APP Tg mice. We fed APP, APP/fat-1 and fat-1 mice with n-6 PUFAs rich diet. Brain tissues were collected at 3, 9 and 12 months for fatty acid and gene expression analysis, histology and protein assays. Morris Water Maze Test, open field test and elevated plus maze test were performed to measure the behavior capability. From the results, the expression of fat-1 transgene increased cortical n-3: n-6 PUFAs ratio and n-3 PUFAs concentrations, and sensorimotor dysfunction and cognitive deficits in AD were significantly less severe in APP/fat-1 mice with endogenous n-3 PUFAs than in APP mice controls. The protection against disturbance of spontaneous motor activity and cognitive deficits in AD was strongly correlated with increased n-3: n-6 PUFAs ratio and endogenous n-3 PUFAs, reduced APP generation, inhibited amyloid β peptide aggregation, suppressed nuclear factor-kappa B and astroglia activation, and reduced death of neurons in the cortex of APP/fat-1 mice compared with APP mice controls. In conclusion, our study demonstrates that an available medication with the maintenance of enriched n-3 PUFAs in the brain could slow down cognitive decline and prevent neuropsychological disorder in AD. PMID:27474225

  8. Ciproxifan, an H3 Receptor Antagonist, Alleviates Hyperactivity and Cognitive Deficits in the APPTg2576 Mouse Model of Alzheimer’s Disease

    PubMed Central

    Bardgett, Mark E.; Davis, Natasha N.; Schultheis, Patrick J.; Griffith, Molly S.

    2010-01-01

    Previous research has indicated that the blockade of H3-type histamine receptors may improve attention and memory in normal rodents. The purpose of this study was to determine if ciproxifan, an H3 receptor antagonist, could alleviate the hyperactivity and cognitive deficits observed in a transgenic mouse model (APPTg2576) of Alzheimer’s disease. APPTg2576 mice displayed significantly greater locomotor activity than wild-type mice, but APPTg2576 mice provided with daily ciproxifan treatment showed activity levels that did not differ from wild-type mice. In the swim maze, APPTg2576 mice exhibited significantly longer escape latencies, but the APPTg2576 mice treated daily with ciproxifan had latencies that were indistinguishable from controls. In probe trials conducted one hour after the last training trial, ciproxifan-treated APPTg2576 mice spent more time near the previous platform location and made more crossings of this area than did saline-treated APPTg2576 mice. APPTg2576 mice also demonstrated a significant impairment in the object recognition task that was reversed by acute treatment with ciproxifan (3.0 mg/kg). These data support the idea that modulation of H3 receptors represents a novel and viable therapeutic strategy in the treatment of Alzheimer’s disease. PMID:21073971

  9. Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease independent of brain amyloid deposition.

    PubMed

    Koivisto, Hennariikka; Grimm, Marcus O; Rothhaar, Tatjana L; Berkecz, Róbert; Lütjohann D, Dieter; Giniatullina, Rajsa; Takalo, Mari; Miettinen, Pasi O; Lahtinen, Hanna-Maija; Giniatullin, Rashid; Penke, Botond; Janáky, Tamás; Broersen, Laus M; Hartmann, Tobias; Tanila, Heikki

    2014-02-01

    Dietary fish oil, providing n3 polyunsaturated fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), associates with reduced dementia risk in epidemiological studies and reduced amyloid accumulation in Alzheimer mouse models. We now studied whether additional nutrients can improve the efficacy of fish oil in alleviating cognitive deficits and amyloid pathology in APPswe/PS1dE9 transgenic and wild-type mice. We compared four isocaloric (5% fat) diets. The fish oil diet differed from the control diet only by substituted fish oil. Besides fish oil, the plant sterol diet was supplemented with phytosterols, while the Fortasyn diet contained as supplements precursors and cofactors for membrane synthesis, viz. uridine-monophosphate; DHA and EPA; choline; folate; vitamins B6, B12, C and E; phospholipids and selenium. Mice began the special diets at 5 months and were sacrificed at 14 months after behavioral testing. Transgenic mice, fed with control chow, showed poor spatial learning, hyperactivity in exploring a novel cage and reduced preference to explore novel odors. All fish-oil-containing diets increased exploration of a novel odor over a familiar one. Only the Fortasyn diet alleviated the spatial learning deficit. None of the diets influenced hyperactivity in a new environment. Fish-oil-containing diets strongly inhibited β- and γ-secretase activity, and the plant sterol diet additionally reduced amyloid-β 1-42 levels. These data indicate that beneficial effects of fish oil on cognition in Alzheimer model mice can be enhanced by adding other specific nutrients, but this effect is not necessarily mediated via reduction of amyloid accumulation. PMID:24445040

  10. [Cognitive deficits in bipolar disorder].

    PubMed

    Sachs, Gabriele; Schaffer, Markus; Winklbaur, Bernadette

    2007-01-01

    Bipolar disorders are often associated with cognitive deficits which have an influence on social functioning and the course of the illness. These deficits have an impact on occupational ability and social integration. To date, specific cognitive domains have been found which characterize bipolar affective disorders. However, there is evidence of stable and lasting cognitive impairment in all phases of the disorder, including the remission phase, in the following domains: sustained attention, memory and executive functions (e.g. cognitive flexibility and problem solving). Although their cognitive deficits are comparable the deficits in patients with schizophrenia are more severe than those with bipolar disorder. Recent brain imaging findings indicate structural and functional abnormalities in the cortical and limbic networks of the brain in patients with bipolar disorder compared to healthy controls. Mood stabilizer and atypical antipsychotics may reduce cognitive deficits in certain domains (e.g. executive functions and word fluency) and may have a positive effect on quality of life and social functioning. PMID:17640495

  11. Physical exercise alleviates ADHD symptoms: regional deficits and development trajectory.

    PubMed

    Archer, Trevor; Kostrzewa, Richard M

    2012-02-01

    The heterogeneous, chronic, and proliferating aspect of attention deficit hyperactivity disorder (ADHD) and comorbidities covers heritability, cognitive, emotional, motor, and everyday behavioral domains that place individuals presenting the condition at some considerable disadvantage. Disruption of "typical developmental trajectories" in the manifestation of gene-environment interactive predispositions implies that ADHD children and adolescents may continue to perform at defective levels as adults with regard to academic achievement, occupational enterprises, and interpersonal relationships, despite the promise of pharmacotherapeutic treatments. Physical exercise provides a plethora of beneficial effects against stress, anxiety, depression, negative affect and behavior, poor impulse control, and compulsive behavior concomitant with improved executive functioning, working memory and positive affect, as well as improved conditions for relatives and care-givers. Brain-derived neurotrophic factor, an essential element in normal brain development that promotes health-associated behaviors and quality-of-life, though reduced in ADHD, is increased markedly by the intervention of regular physical exercise. Functional, regional, and biomarker deficits, as well as hypothalamic-pituitary-adrenal disruptions, have been improved through regular and carefully applied exercise programs. In view of the complications involving ADHD with co-morbidities, such as obesity, the influence of regular physical exercise has not been found negligible. Physical exercise bestows a propensity for eventual manifestation of "redifferentiated" developmental trajectories that may equip ADHD adults with a prognosis that is more adaptive functionally, independent of the applications of other therapeutic agents and treatments. PMID:21850535

  12. Physical exercise alleviates ADHD symptoms: regional deficits and development trajectory.

    PubMed

    Archer, Trevor; Kostrzewa, Richard M

    2012-02-01

    The heterogeneous, chronic, and proliferating aspect of attention deficit hyperactivity disorder (ADHD) and comorbidities covers heritability, cognitive, emotional, motor, and everyday behavioral domains that place individuals presenting the condition at some considerable disadvantage. Disruption of "typical developmental trajectories" in the manifestation of gene-environment interactive predispositions implies that ADHD children and adolescents may continue to perform at defective levels as adults with regard to academic achievement, occupational enterprises, and interpersonal relationships, despite the promise of pharmacotherapeutic treatments. Physical exercise provides a plethora of beneficial effects against stress, anxiety, depression, negative affect and behavior, poor impulse control, and compulsive behavior concomitant with improved executive functioning, working memory and positive affect, as well as improved conditions for relatives and care-givers. Brain-derived neurotrophic factor, an essential element in normal brain development that promotes health-associated behaviors and quality-of-life, though reduced in ADHD, is increased markedly by the intervention of regular physical exercise. Functional, regional, and biomarker deficits, as well as hypothalamic-pituitary-adrenal disruptions, have been improved through regular and carefully applied exercise programs. In view of the complications involving ADHD with co-morbidities, such as obesity, the influence of regular physical exercise has not been found negligible. Physical exercise bestows a propensity for eventual manifestation of "redifferentiated" developmental trajectories that may equip ADHD adults with a prognosis that is more adaptive functionally, independent of the applications of other therapeutic agents and treatments.

  13. [Cognitive deficit: another complication of diabetes mellitus?].

    PubMed

    Almeida-Pititto, Bianca de; Almada Filho, Clineu de M; Cendoroglo, Maysa S

    2008-10-01

    As the population getting older, the chronic diseases will be more prevalent as diabetes mellitus (DM) and diseases characterized by cognitive deficits, as dementia. Studies have already shown an association between DM and cardiovascular risk factors associated with cognitive impairment. Besides the vascular complications of DM, studies have proposed the role of hyperglycemia and advanced glycosilation end products (AGEP) causing oxidative stress and beta-amyloid protein brain deposition. Other factors have also been investigated, such as the role of insulinemia, genetic and IGF-1 (insulin-like growth factor-1). Some studies showed that good glucose control and intake of polyunsaturated fat, Omega-3 or anti-oxidative food can play a protector role against cognitive deficits. Improving knowledge about the association between DM and cognition and its physiopathology, can be essential for the prevention and treatment of cognitive impairment, leading to a beneficial impact on the quality of life of elderly patients with DM. PMID:19082295

  14. Cognitive deficits in post-stroke aphasia.

    PubMed

    Bonini, Milena V; Radanovic, Márcia

    2015-10-01

    The assessment of aphasics' cognitive performance is challenging and such patients are generally excluded from studies that describe cognitive deficits after stroke. We evaluated aphasics' performance in cognitive tasks compared to non-aphasic subjects. A sample of 47 patients (21 aphasics, 17 non-aphasics with left hemisphere lesions and 9 non-aphasics with right hemisphere lesions) performed cognitive tasks (attention, verbal and visual memory, executive functions, visuospatial skills and praxis). Aphasic patients performed poorer than all non-aphasics in Digit Span (p < 0.001), Clock-Drawing Test (p = 0.006), Verbal memory (p = 0.002), Visual Memory (p < 0.01), Verbal Fluency (p < 0.001), and Gesture Praxis (p < 0.001). Aphasia severity correlated with performance in Trail Making test part B (p = 0.004), Digit Span forward (p < 0.001) and backwards (p = 0.011), and Gesture Praxis (p = 0.002). Aphasia is accompanied by deficits not always easy to be evaluated by cognitive tests due to speech production and motor impairments. Assessment of cognitive functions in aphasics might contribute to optimize therapeutic intervention. PMID:26465401

  15. Neurocomputational models of motor and cognitive deficits in Parkinson's disease.

    PubMed

    Wiecki, Thomas V; Frank, Michael J

    2010-01-01

    We review the contributions of biologically constrained computational models to our understanding of motor and cognitive deficits in Parkinson's disease (PD). The loss of dopaminergic neurons innervating the striatum in PD, and the well-established role of dopamine (DA) in reinforcement learning (RL), enable neural network models of the basal ganglia (BG) to derive concrete and testable predictions. We focus in this review on one simple underlying principle - the notion that reduced DA increases activity and causes long-term potentiation in the indirect pathway of the BG. We show how this theory can provide a unified account of diverse and seemingly unrelated phenomena in PD including progressive motor degeneration as well as cognitive deficits in RL, decision making and working memory. DA replacement therapy and deep brain stimulation can alleviate some aspects of these impairments, but can actually introduce negative effects such as motor dyskinesias and cognitive impulsivity. We discuss these treatment effects in terms of modulation of specific mechanisms within the computational framework. In addition, we review neurocomputational interpretations of increased impulsivity in the face of response conflict in patients with deep-brain-stimulation.

  16. Neurocomputational models of motor and cognitive deficits in Parkinson's disease.

    PubMed

    Wiecki, Thomas V; Frank, Michael J

    2010-01-01

    We review the contributions of biologically constrained computational models to our understanding of motor and cognitive deficits in Parkinson's disease (PD). The loss of dopaminergic neurons innervating the striatum in PD, and the well-established role of dopamine (DA) in reinforcement learning (RL), enable neural network models of the basal ganglia (BG) to derive concrete and testable predictions. We focus in this review on one simple underlying principle - the notion that reduced DA increases activity and causes long-term potentiation in the indirect pathway of the BG. We show how this theory can provide a unified account of diverse and seemingly unrelated phenomena in PD including progressive motor degeneration as well as cognitive deficits in RL, decision making and working memory. DA replacement therapy and deep brain stimulation can alleviate some aspects of these impairments, but can actually introduce negative effects such as motor dyskinesias and cognitive impulsivity. We discuss these treatment effects in terms of modulation of specific mechanisms within the computational framework. In addition, we review neurocomputational interpretations of increased impulsivity in the face of response conflict in patients with deep-brain-stimulation. PMID:20696325

  17. Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats

    PubMed Central

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

    2016-01-01

    Objective(s): 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. Materials and Methods: 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. Results: 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. Conclusion: Our results showed that naringin may be a promising therapeutic agent for improving cognitive decline in DACD. PMID:27279986

  18. Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Xianchu; Mo, Yanzhi; Gong, Jingbo; Li, Zhuang; Peng, Huan; Chen, Jiaxue; Wang, Qichao; Ke, Zhaowen; Xie, Jingtao

    2016-04-01

    Previous research has indicated that Diabetes is a high risk of learning and memory deficits. Puerarin, an isoflavonoid extracted from Kudzu roots, has been reported to possess antioxidant, anti-inflammatory, anti-apoptotic and anti-diabetic properties which are useful in the treatment of various diseases. Recently, Puerarin was found to have the effects on learning and memory performances in humans and animal models. However, up to now, there is no detailed evidence on the effect of Puerarin on diabetes-associated cognitive decline (DACD). In this study, we designed to assess the effects of Puerarin on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model and exploring its potential mechanism. Diabetic rats were treated with Puerarin (100 mg/kg per d) for 7 days. The learning and memory function was evaluated by morris water maze test. The acetylcholinesterase (AChE), choline acetylase (ChAT), oxidative indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] and inflammatory cytokine (TNF-a, IL-1β and IL-6) were measured in hippocampus by using corresponding commercial kits. mRNA and Protein levels of Bcl-2 were analyzed by RT-PCR and Westernblot. The results showed that supplementation of Puerarin improved the learning and memory performances compared with the STZ group by the morris water maze test. In addition, Puerarin supplement significantly prevented AChE and MDA activities, increased ChAT and SOD activities, and alleviated the protein level of TNF-α, IL-1β and IL-6 in the hippocampus compared with the STZ group. Moreover, the pretreatment with Puerarin also significantly increased the Bcl-2 expression. It is concluded that Puerarin possesses neuroprotection to ameliorate cognitive deficits in streptozotocin-induced diabetic rats by anti-inflammatory, antioxidant and antiapototic effects. PMID:26686502

  19. [Treatment of cognitive deficits in schizophrenia. Part 2: Pharmacological strategies].

    PubMed

    Roesch-Ely, D; Pfueller, U; Mundt, C; Müller, U; Weisbrod, M

    2010-05-01

    Cognitive deficits in schizophrenia are a clinically relevant symptom dimension and one of the best predictors for functional outcome. Pharmacological treatment of cognitive deficits in schizophrenia is still a challenge. The objective of this article is to present a detailed review of the literature on strategies for the pharmacological treatment of cognitive deficits. It is not clear whether first-generation antipsychotics have a genuine positive influence on cognition. There is only sparse evidence for the positive effect of second-generation antipsychotics on cognitive processes. Furthermore it is not evident that second-generation antipsychotics are more beneficial than first-generation antipsychotics in the treatment of cognitive deficits. The add-on use of substances which directly influence cognitive processes, so-called cognition-enhancing drugs is more promising.

  20. A Multiple Deficit Model of Reading Disability and Attention-Deficit/Hyperactivity Disorder: Searching for Shared Cognitive Deficits

    ERIC Educational Resources Information Center

    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.

    2011-01-01

    Background: This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity. Methods: A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique…

  1. The 5-HT1A antagonist, WAY 100 635, alleviates cognitive impairments induced by dizocilpine (MK-801) in monkeys.

    PubMed

    Harder, J A; Ridley, R M

    2000-02-14

    Central glutamate neurotransmission is modulated by an upregulatory cholinergic influence and an inhibitory serotonergic influence. In Alzheimer's disease, cognitive decline is associated with loss of both glutamatergic and cholinergic neurones (Francis et al., 1992, Progress in Neurobiology 39, 517-545). While therapeutic strategies for alleviating this cognitive decline have concentrated on restoring cholinergic tone, we suggest that 5-HT1A antagonists also have the potential to alleviate the cognitive symptoms of Alzheimer's disease. Previous studies have shown that dizocilpine (MK-801), a glutamatergic antagonist acting at the NMDA receptor, produces learning impairments in the common marmoset, a non-human primate. Specifically, it impairs the acquisition of shape discrimination and visuospatial conditional tasks, at doses that do not affect locomotor behaviour or coordination (Harder et al., 1998, Society for Neuroscience Abstracts 23(1), 219). In the present study we investigated the effects of WAY 100 635, a 5-HT1A antagonist, on the cognitive deficits induced by dizocilpine. The number of trials required to learn each type of task under combined treatment with dizocilpine and WAY 100 635 was significantly lower than under dizocilpine treatment alone, and did not differ significantly from the number of trials required under saline, demonstrating that the cognitive effects of glutamatergic blockade can be overcome by treatment with a 5-HT1A antagonist.

  2. 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.

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  4. Oculomotor Performance Identifies Underlying Cognitive Deficits in Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Loe, Irene M.; Feldman, Heidi M.; Yasui, Enami; Luna, Beatriz

    2009-01-01

    The evaluation of the cognitive control in children with attention-deficit hyperactivity disorder through the use of oculomotor tests reveal that this group showed susceptibility to peripheral distractors and deficits in response inhibition. All subjects were found to have intact sensorimotor function and working memory.

  5. Cognitive Mapping Deficits in Schizophrenia: A Critical Overview

    PubMed Central

    Bose, Anushree; Agarwal, Sri Mahavir; Kalmady, Sunil V.; Venkatasubramanian, Ganesan

    2014-01-01

    Hippocampal deficits are an established feature of schizophrenia and are complementary with recent evidences of marked allocentric processing deficits being reported in this disorder. By “Cognitive mapping” we intend to refer to the concepts from the seminal works of O’Keefe and Nadel (1978) that led to the development of cognitive map theory of hippocampal function. In this review, we summarize emerging evidences and issues that indicate that “Cognitive mapping deficits” form one of the important cognitive aberrations in schizophrenia. The importance has been placed upon hippocampally mediated allocentric processing deficits and their role in pathology of schizophrenia, for spatial/representational cognitive deficits and positive symptoms in particular. It is modestly summarized that emerging evidences point toward a web of spatial and cognitive representation errors concurrent with pronounced hippocampal dysfunction. In general, it can be stated that there are clear and consistent evidences that favor the cognitive mapping theory in explaining certain deficits of schizophrenia and for drawing out a possible and promising endophenotype/biomarkers. Further research in this regard demands attention. PMID:24701005

  6. Cognitive control in alcohol use disorder: deficits and clinical relevance

    PubMed Central

    Wilcox, Claire E.; Dekonenko, Charlene J.; Mayer, Andrew R.; Bogenschutz, Michael P.; Turner, Jessica A.

    2014-01-01

    Cognitive control refers to the internal representation, maintenance, and updating of context information in the service of exerting control over thoughts and behavior. Deficits in cognitive control likely contribute to difficulty in maintaining abstinence in individuals with alcohol use disorders (AUD). In this article, we define three cognitive control processes in detail (response inhibition, distractor interference control, and working memory), review the tasks measuring performance in these areas, and summarize the brain networks involved in carrying out these processes. Next, we review evidence of deficits in these processes in AUD, including both metrics of task performance and functional neuroimaging. Finally, we explore the clinical relevance of these deficits by identifying predictors of clinical outcome and markers that appear to change (improve) with treatment. We observe that individuals with AUD experience deficits in some, but not all, metrics of cognitive control. Deficits in cognitive control may predict clinical outcome in AUD, but more work is necessary to replicate findings. It is likely that performance on tasks requiring cognitive control improves with abstinence, and with some psychosocial and medication treatments. Future work should clarify which aspects of cognitive control are most important to target during treatment of AUD. PMID:24361772

  7. A high cholesterol diet ameliorates hippocampus-related cognitive and pathological deficits in ovariectomized mice.

    PubMed

    Li, Liu; Xiao, Na; Yang, Xiaoxin; Gao, Junying; Ding, Jiong; Wang, Tong; Hu, Gang; Xiao, Ming

    2012-04-21

    Both sex hormone deficiency and hypercholesterolemia are related to cognitive decline or Alzheimer's disease. However, their interactive influence on the neurodegenerative progress is not clear. This study was designed to assess the effects of ovarian hormone depletion and high cholesterol diet alone or in combination on hippocampus-related cognitive and pathological deficits in adult female ICR mice. Depletion of ovarian hormones by ovariectomy for 9 weeks resulted in significant spatial learning and memory deficits as revealed by the water maze testing. Such cognitive alteration was accompanied with increases in neuron death and decreases in choline acetyltransferase activity and synaptopysin expression in the hippocampus. On the other hand, the high cholesterol diet (3% cholesterol plus normal chow) did not exacerbate, but slightly alleviated cognitive decline and significantly attenuated hippocampal pathological changes in ovariectomized mice. Moreover, ovariectomized mice fed high cholesterol had increased serum estrogen levels compared with those fed a normal chow. These results indicate that high cholesterol intake increases the sex hormone synthesis and in turn partially attenuates hippocampus-related cognitive and pathological deficits caused by ovariectomy.

  8. A high cholesterol diet ameliorates hippocampus-related cognitive and pathological deficits in ovariectomized mice.

    PubMed

    Li, Liu; Xiao, Na; Yang, Xiaoxin; Gao, Junying; Ding, Jiong; Wang, Tong; Hu, Gang; Xiao, Ming

    2012-04-21

    Both sex hormone deficiency and hypercholesterolemia are related to cognitive decline or Alzheimer's disease. However, their interactive influence on the neurodegenerative progress is not clear. This study was designed to assess the effects of ovarian hormone depletion and high cholesterol diet alone or in combination on hippocampus-related cognitive and pathological deficits in adult female ICR mice. Depletion of ovarian hormones by ovariectomy for 9 weeks resulted in significant spatial learning and memory deficits as revealed by the water maze testing. Such cognitive alteration was accompanied with increases in neuron death and decreases in choline acetyltransferase activity and synaptopysin expression in the hippocampus. On the other hand, the high cholesterol diet (3% cholesterol plus normal chow) did not exacerbate, but slightly alleviated cognitive decline and significantly attenuated hippocampal pathological changes in ovariectomized mice. Moreover, ovariectomized mice fed high cholesterol had increased serum estrogen levels compared with those fed a normal chow. These results indicate that high cholesterol intake increases the sex hormone synthesis and in turn partially attenuates hippocampus-related cognitive and pathological deficits caused by ovariectomy. PMID:22366266

  9. Premorbid Cognitive Deficits in Young Relatives of Schizophrenia Patients

    PubMed Central

    Keshavan, Matcheri S.; Kulkarni, Shreedhar; Bhojraj, Tejas; Francis, Alan; Diwadkar, Vaibhav; Montrose, Debra M.; Seidman, Larry J.; Sweeney, John

    2009-01-01

    Neurocognitive deficits in schizophrenia (SZ) are thought to be stable trait markers that predate the illness and manifest in relatives of patients. Adolescence is the age of maximum vulnerability to the onset of SZ and may be an opportune “window” to observe neurocognitive impairments close to but prior to the onset of psychosis. We reviewed the extant studies assessing neurocognitive deficits in young relatives at high risk (HR) for SZ and their relation to brain structural alterations. We also provide some additional data pertaining to the relation of these deficits to psychopathology and brain structural alterations from the Pittsburgh Risk Evaluation Program (PREP). Cognitive deficits are noted in the HR population, which are more severe in first-degree relatives compared to second-degree relatives and primarily involve psychomotor speed, memory, attention, reasoning, and social-cognition. Reduced general intelligence is also noted, although its relationship to these specific domains is underexplored. Premorbid cognitive deficits may be related to brain structural and functional abnormalities, underlining the neurobiological basis of this illness. Cognitive impairments might predict later emergence of psychopathology in at-risk subjects and may be targets of early remediation and preventive strategies. Although evidence for neurocognitive deficits in young relatives abounds, further studies on their structural underpinnings and on their candidate status as endophenotypes are needed. PMID:20300465

  10. A neurobiological approach to the cognitive deficits of psychiatric disorders.

    PubMed

    Etkin, Amit; Gyurak, Anett; O'Hara, Ruth

    2013-12-01

    Deficits in brain networks that support cognitive regulatory functions are prevalent in many psychiatric disorders. Findings across neuropsychology and neuroimaging point to broad-based impairments that cross traditional diagnostic boundaries. These dysfunctions are largely separate from the classical symptoms of the disorders, and manifest in regulatory problems in both traditional cognitive and emotional domains. As such, they relate to the capacity of patients to engage effectively in their daily lives and activity, often persist even in the face of symptomatically effective treatment, and are poorly targeted by current treatments. Advances in cognitive neuroscience now allow us to ground an understanding of these cognitive regulatory deficits in the function and interaction of key brain networks. This emerging neurobiological understanding furthermore points to several promising routes for novel neuroscience-informed treatments targeted more specifically at improving cognitive function in a range of psychiatric disorders.

  11. Social perception deficits, cognitive distortions, and empathy deficits in sex offenders: a brief review.

    PubMed

    Blake, Emily; Gannon, Theresa

    2008-01-01

    This literature review examines the differences between sex offenders and nonoffenders with regard to social perception skills, cognitive distortions, and empathy skills in order to investigate sex offenders' cognition. The literature on cognitive distortions is discussed, with reference to the confusion surrounding its definition, and the debate between cognitive distortions as offense-supportive beliefs or justifications is examined. In terms of social perception, particular reference is made to sex offenders' misinterpretations of women's social cues and the source of this deficit. The authors discuss possibilities for this deficit, including offense-supportive beliefs that are driven by underlying implicit theories or schemata held by offenders. The concept of empathy and its relation to both social perception skills and cognitive distortions is discussed, and the integration of these factors is represented in a new model.

  12. 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

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

    PubMed Central

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

    2016-01-01

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

  14. Swimming exercise alleviates the symptoms of attention-deficit hyperactivity disorder in spontaneous hypertensive rats.

    PubMed

    Ko, Il-Gyu; Kim, Sung-Eun; Kim, Tae-Woon; Ji, Eun-Sang; Shin, Mal-Soon; Kim, Chang-Ju; Hong, Min-Ha; Bahn, Geon Ho

    2013-08-01

    Attention-deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by inattention, hyperactivity and impulsivity. In the present study, we investigated the effects of swimming exercise on the symptoms of ADHD in correlation with the expression levels of dopamine and the dopamine D2 receptor. Adult male spontaneous hypertensive rats (SHRs) were used as animal models of ADHD and Wistar-Kyoto rats were used as controls. The activity, impulsivity and levels of non-aggressive and aggressive behaviors in rats were measured. The short-term memory in the animal models of ADHD was assessed using an open-field test. The social interaction test, elevated plus maze test and step-through avoidance test were additionally performed. The expression levels of tyrosine hydroxylase (TH), which catalyzes the rate‑limiting step of dopamine synthesis, and the dopamine D2 receptor in the prefrontal cortex, substantia nigra and striatum were evaluated. The expression levels of TH and the dopamine D2 receptor were detected using immunohistochemistry and western blotting, respectively. In ADHD rats, the activity, impulsivity and levels of non-aggressive and aggressive behaviors were higher than that in control rats. By contrast, short-term memory in ADHD rats deteriorated. Swimming exercise suppressed hyperactivity, impulsivity and non-aggressive and aggressive behaviors, and alleviated the short-term memory impairment observed in ADHD rats. The expression levels of TH and the dopamine D2 receptor were decreased and increased in ADHD rats, respectively, when compared with control rats. Swimming exercise enhanced the expression of TH and suppressed the expression of the dopamine D2 receptor in ADHD rats. In the present study, swimming exercise improved the symptoms of ADHD by upregulating the expression of dopamine and downregulating the expression of the dopamine D2 receptor. PMID:23779147

  15. Swimming exercise alleviates the symptoms of attention-deficit hyperactivity disorder in spontaneous hypertensive rats.

    PubMed

    Ko, Il-Gyu; Kim, Sung-Eun; Kim, Tae-Woon; Ji, Eun-Sang; Shin, Mal-Soon; Kim, Chang-Ju; Hong, Min-Ha; Bahn, Geon Ho

    2013-08-01

    Attention-deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by inattention, hyperactivity and impulsivity. In the present study, we investigated the effects of swimming exercise on the symptoms of ADHD in correlation with the expression levels of dopamine and the dopamine D2 receptor. Adult male spontaneous hypertensive rats (SHRs) were used as animal models of ADHD and Wistar-Kyoto rats were used as controls. The activity, impulsivity and levels of non-aggressive and aggressive behaviors in rats were measured. The short-term memory in the animal models of ADHD was assessed using an open-field test. The social interaction test, elevated plus maze test and step-through avoidance test were additionally performed. The expression levels of tyrosine hydroxylase (TH), which catalyzes the rate‑limiting step of dopamine synthesis, and the dopamine D2 receptor in the prefrontal cortex, substantia nigra and striatum were evaluated. The expression levels of TH and the dopamine D2 receptor were detected using immunohistochemistry and western blotting, respectively. In ADHD rats, the activity, impulsivity and levels of non-aggressive and aggressive behaviors were higher than that in control rats. By contrast, short-term memory in ADHD rats deteriorated. Swimming exercise suppressed hyperactivity, impulsivity and non-aggressive and aggressive behaviors, and alleviated the short-term memory impairment observed in ADHD rats. The expression levels of TH and the dopamine D2 receptor were decreased and increased in ADHD rats, respectively, when compared with control rats. Swimming exercise enhanced the expression of TH and suppressed the expression of the dopamine D2 receptor in ADHD rats. In the present study, swimming exercise improved the symptoms of ADHD by upregulating the expression of dopamine and downregulating the expression of the dopamine D2 receptor.

  16. Depression and Helplessness-Induced Cognitive Deficits in the Aged.

    ERIC Educational Resources Information Center

    Kennelly, Kevin J.; And Others

    To explore the effects of depression and learned helplessness on cognitive task deficits, 66 community-residing elderly adults were categorized as depressed or nondepressed based on Beck Depression Inventory scores. After a pre-test battery measuring short-term memory and components of crystallized/fluid intelligence, the subjects responded to a…

  17. 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…

  18. Management of Subtle Cognitive Communication Deficits.

    ERIC Educational Resources Information Center

    Milton, Sandra B.

    1988-01-01

    Traumatically head-injured individuals who reach the higher stages of recovery typically exhibit cognitive communication disorders. Patient management requires, among other considerations, a focus on functional communication competency, an ecologic-systematic perspective, and use of compensatory techniques. A case study applies this management…

  19. Empathy deficits and cognitive distortions in child molesters.

    PubMed

    Marshall, W L; Hamilton, K; Fernandez, Y

    2001-04-01

    An attempt was made to examine the thesis that the apparent empathy deficits in child molesters are simply another aspect of their self-serving tendency to distort information by, in this case, failing to recognize victim harm. Thirty-four child molesters were compared on a victim empathy measure and a measure of cognitive distortions, with 24 nonsex offenders and 28 nonoffending males. Child molesters displayed greater cognitive distortions than the other subjects and their greatest empathy deficits were toward their own victims. Consistent with the theory being examined it was found that the empathy scores of the child molesters toward their own victims were significantly correlated with the responses to the cognitive distortions scale. The results are discussed in terms of their implications for theory and practice.

  20. Treatment of Cognitive Deficits in Alzheimer's disease: A psychopharmacological review.

    PubMed

    Campos, Carlos; Rocha, Nuno Barbosa; Vieira, Renata Teles; Rocha, Susana A; Telles-Correia, Diogo; Paes, Flávia; Yuan, Tifei; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Machado, Sergio; Caixeta, Leonardo

    2016-03-01

    The growing and aging population has contributed to the increased prevalence of Alzheimer's disease (AD) and other types of dementia in the world. AD is a progressive and degenerative brain disease with an onset characterized by episodic memory impairments, although progressive deficits can be observed in several domains including language, executive functions, attention and working memory. The relationship between cognitive impairments and the topography and progression of brain neuropathology is well established. The pathophysiologic mechanisms and processes that underline the course of cognitive and clinical decline have been the theoretical support for the development of pharmacological treatments for AD. Cholinesterase inhibitors (ChEIs) and N-methyl-D-aspartate (NMDA) antagonists are the main drugs used in the management of global cognitive impairment and several studies also explore the effects of both in specific cognitive measures. Recent research trends also examine the effects of combination therapy using both compounds. This review aims to update practical recommendations for the treatment of global cognitive functioning and specific neurocognitive deficits in AD using ChEIs, NMDA antagonists and combination therapy with both drugs. PMID:26938815

  1. Evidence for distinct cognitive deficits after focal cerebellar lesions

    PubMed Central

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

    2004-01-01

    Objectives: 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. Methods: 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. Results: 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. Conclusions: 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." PMID:15489381

  2. 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

  3. 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

  4. Environmental enrichment restores cognitive deficits induced by prenatal maternal seizure.

    PubMed

    Xie, Tao; Wang, Wei-ping; Jia, Li-jing; Mao, Zhuo-feng; Qu, Zhen-zhen; Luan, Shao-qun; Kan, Min-chen

    2012-08-27

    Maternal seizure has adverse effects on brain histology as well as on learning and memory ability in progeny. An enriched environment (EE) is known to promote structural changes in the brain and improve cognitive and motor deficits following a variety of brain injuries. Whether EE treatment in early postnatal periods could restore cognitive impairment induced by prenatal maternal seizure is unknown. Adult female Sprague-Dawley rats were randomly separated into two groups and were injected intraperitoneally either saline or pentylenetetrazol (PTZ) for 30 days. Then the fully kindled rats and control animals were allowed to mate. PTZ administration was continued until delivery, while the control group received saline at the same time. After weaning at postnatal day 22, one-half of the male offspring in the control and in the prenatal maternal group were given the environmental enrichment treatment through all the experiments until they were tested. Morris water maze testing was performed at 8 weeks of age. Western blot and synaptic ultrastructure analysis were then performed. We found that EE treatment reversed spatial learning deficits induced by prenatal maternal seizure. An EE also reversed the changes in synaptic ultrastructure following prenatal maternal seizure. In addition, prenatal maternal seizure significantly decreased phosphorylation states of cAMP response element binding (CREB) in the hippocampus, whereas EE reversed this reduced expression. These findings suggest that EE treatment on early postnatal periods could be a potential therapy for improving cognitive deficits induced by prenatal maternal seizure.

  5. Cognitive deficits in bipolar disorder: from acute episode to remission.

    PubMed

    Volkert, J; Schiele, M A; Kazmaier, Julia; Glaser, Friederike; Zierhut, K C; Kopf, J; Kittel-Schneider, S; Reif, A

    2016-04-01

    Considerable evidence demonstrates that neuropsychological deficits are prevalent in bipolar disorder during both acute episodes and euthymia. However, it is less clear whether these cognitive disturbances are state- or trait-related. We here present the first longitudinal study employing a within-subject pre- and post-testing examining acutely admitted bipolar patients (BP) in depression or mania and during euthymia, aiming to identify cognitive performance from acute illness to remission. Cognitive performance was measured during acute episodes and repeated after at least 3 months of remission. To do so, 55 BP (35 depressed, 20 hypo-/manic) and 55 healthy controls (HC) were tested with a neuropsychological test battery (attention, working memory, verbal memory, executive functioning). The results showed global impairments in acutely ill BP compared to HC: depressed patients showed a characteristic psychomotor slowing, while manic patients had severe deficits in executive functioning. Twenty-nine remitted BP could be measured in the follow-up (dropout rate 48 %), whose cognitive functions partially recovered, whereas working memory and verbal memory were still impaired. However, we found that subthreshold depressive symptoms and persisting sleep disturbances in euthymic BP were associated with reduced speed, deficits in attention and verbal memory, while working memory was correlated with psychotic symptoms (lifetime). This result indicates working memory as trait related for a subgroup of BP with psychotic symptoms. In contrast, attention and verbal memory are negatively influenced by state factors like residual symptoms, which should be more considered as possible confounders in the search of cognitive endophenotypes in remitted BP. PMID:26611783

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

    PubMed

    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.

  7. Donepezil Improved Cognitive Deficits in a Patient With Neurosyphilis.

    PubMed

    Wu, Yi-Shan; Lane, Hsien-Yuan; Lin, Chieh-Hsin

    2015-01-01

    A large number of patients with neurosyphilis present dementia with a progressive course and psychiatric symptoms such as depression, mania, and psychosis. Despite prompt and proper antibiotic treatment, the recovery is often incomplete, especially when tissue damage has occurred. We reported a patient with persisted cognitive decline associated with neurosyphilis that improved substantially after donepezil therapy. A 43-year-old man manifested significant psychiatric symptoms such as mania, psychosis, and cognitive impairment due to neurosyphilis. Subsequently, the patient was treated with antipsychotics and donepezil concurrent with an adequate antibiotic treatment for neurosyphilis. During the 1-year follow-up, his rapid plasma reagin titer approached from 1:256 to 1:64. His Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale scores improved from 12 to 25 and 42.3 to 6.3, respectively, after a 6-month donepezil treatment. Donepezil was discontinued. Three months later, worsening of cognitive impairment (MMSE score, 23) was noted. After donepezil was started again for 3 months, his MMSE score improved to 26. Persistent cognitive impairment is commonly associated with neurosyphilis despite adequate penicillin treatment. Treatment of the cognitive impairment is important but difficult. Cholinergic pathways are considered as involving in the cognitive deficit induced by neurosyphilis and donepezil, a cholinesterase inhibitor, which may be useful for the improvement of cognition. In this case report, we described for the first time the successful use of donepezil in treating cognitive impairment associated with neurosyphilis. The role of cholinesterase inhibitors in the treatment of cognitive impairments caused by neurosyphilis needs further studies.

  8. Empathy deficits in Asperger syndrome: a cognitive profile.

    PubMed

    Shamay-Tsoory, S G; Tomer, R; Yaniv, S; Aharon-Peretz, J

    2002-01-01

    Although lack of empathy has been considered a central characteristic of Asperger syndrome, quantitative and qualitative assessments of empathy in this syndrome are lacking. We present two cases of adolescents with Asperger syndrome who show extreme deficits on measures of both cognitive and affective empathy. Analysis of their performance on tasks assessing cognitive and affective processing did not reveal significant impairment in executive functions, nor in their ability to recognize emotions or the ability to create a mental representation of another person's knowledge. However, both patients were unable to integrate the emotional content with mental representations and deduce the other person's emotional state. These results suggest that impaired empathy in individuals with Asperger syndrome may be due to impaired integration of the cognitive and affective facets of the other person's mental state. PMID:12119321

  9. 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,…

  10. 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

  11. Cognitive Deficits in Geriatric Depression: Clinical Correlates and Implications for Current and Future Treatment

    PubMed Central

    Morimoto, Sarah Shizuko; Alexopoulos, George S.

    2013-01-01

    Synopsis The purpose of this article is to identify the cognitive deficits commonly associated with geriatric depression, and describe their clinical significance. We then summarize the complex relationship between geriatric depression and dementia and discuss possible shared mechanisms. Last, we present evidence regarding whether the cognitive deficits in depression may be mitigated with medication or with computerized cognitive remediation. PMID:24229654

  12. 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…

  13. 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.

  14. Age-Related Cognitive Deficits In Rhesus Monkeys Mirror Human Deficits on an Automated Test Battery

    PubMed Central

    Nagahara, Alan H.; Bernot, Tim; Tuszynski, Mark H.

    2010-01-01

    Aged non-human primates are a valuable model for gaining insight into mechanisms underlying neural decline with aging and during the course of neurodegenerative disorders. Behavioral studies are a valuable component of aged primate models, but are difficult to perform, time consuming, and often of uncertain relevance to human cognitive measures. We now report findings from an automated cognitive test battery in aged primates using equipment that is identical, and tasks that are similar, to those employed in human aging and Alzheimer’s disease studies. Young (7.1 ± 0.8 years) and aged (23.0 ± 0.5 years) rhesus monkeys underwent testing on a modified version of the Cambridge Automated Neuropsychological Test Battery (CANTAB), examining cognitive performance on separate tasks that sample features of visuospatial learning, spatial working memory, discrimination learning, and skilled motor performance. We find selective cognitive impairments among aged subjects in visuospatial learning and spatial working memory, but not in delayed recall of previously learned discriminations. Aged monkeys also exhibit slower speed in skilled motor function. Thus, aged monkeys behaviorally characterized on a battery of automated tests reveal patterns of age-related cognitive impairment that mirror in quality and severity those of aged humans, and differ fundamentally from more severe patterns of deficits observed in Alzheimer’s Disease. PMID:18760505

  15. Early cognitive deficits in Swedish gene carriers of Huntington's disease.

    PubMed

    Robins Wahlin, Tarja-Brita; Lundin, Anders; Dear, Keith

    2007-01-01

    The primary focus of this study was to examine whether there is early neuropsychological impairment in presymptomatic Huntington's disease (HD). A broad neuropsychological assessment battery was administered to 24 asymptomatic gene carriers (HD+) and 31 noncarriers (HD-). The gene carriers revealed inferior cognitive functioning as compared with the noncarriers in memory and executive functions. When the gene carriers were assigned to 2 groups based on predicted years to onset (with 15 and over being HD+ late and under 15 being HD+ near), the HD+ near group performed significantly worse than the HD+ late group in all domains but ability to shift conceptually and visuospatial memory. Results suggest that early cognitive deficits are detectable prior to motor symptoms, first in memory functions and then in executive functions and perceptual motor speed. PMID:17201528

  16. Salidroside ameliorates arthritis-induced brain cognition deficits by regulating Rho/ROCK/NF-κB pathway.

    PubMed

    Zhu, Lingpeng; Chen, Tong; Chang, Xiayun; Zhou, Rui; Luo, Fen; Liu, Jingyan; Zhang, Kai; Wang, Yue; Yang, Ying; Long, Hongyan; Liu, Yu; Yan, Tianhua; Ma, Chunhua

    2016-04-01

    The prevalence of cognitive impairment in rheumatoid arthritis (RA) patients was increasingly serious nowadays. The purpose of the current study was to explore whether salidroside (Sal) could alleviate arthritis-induced cognition deficits and examine the relationship between the impairment and Rho/ROCK/NF-κB pathway. Collagen-induced arthritis (CIA) was established by the injection of chicken type II collagen (CII), complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA). Arthritic lesions of CIA rats were assessed by arthritis index score, swelling of paws and histological analysis. Cognitive deficits symptoms of CIA rats were monitored through Morris water maze test. The contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and serum were significantly reduced with salidroside (20 mg/kg, 40 mg/kg) treatment compared with those in the CIA group. In parallel, we demonstrated that the expressions of RhoA, ROCK1, ROCK2, p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ were enhanced accompanying the investigation arthritis-induced cognition deficits, which were remarkably down-regulated by salidroside and confirmed by the results obtained from western blot and immunohistochemistry. LC-MS/MS results ascertained that Sal could enter into the blood and brain tissues to exhibit the protective effect on arthritis-induced cognitive dysfunction. Therefore, it was assumed that Sal might be a potential therapeutic candidate to treat arthritis-induced brain cognition deficits through the regulation of Rho/ROCK/NF-κB signaling. PMID:26690894

  17. Anxiety modulates cognitive deficits in a perinatal glutathione deficit animal model of schizophrenia.

    PubMed

    Preissmann, D; Dépré, M; Schenk, F; Gisquet-Verrier, P

    2016-10-01

    In this study, we investigated long-term repercussion of early glutathione deficit by l-buthionine-(S,R)-sulfoximine (BSO) injections as a rat model of schizophrenia. BSO rats were tested through various behavioral tasks requiring animals to take into account previously delivered information. We showed that relative to controls, BSO rats (1) were less active and more anxious in an Elevated Plus Maze test, allowing us to split them into two subgroups with high and low anxiety levels; (2) demonstrated normal abilities of behavioral flexibility tested with a rat-adapted version of the Wisconsin Card Sorting Test (WCST), with even higher abilities in anxious BSO rats suggesting reduced interference of previously acquired rules; (3) did not forage normally in radial arm mazes and mainly used clockwise strategies; (4) exhibited a lack of habituation during a startle response task; and (5) showed a normal prepulse inhibition of the startle response (PPI) and a normal conditioned taste aversion (CTA). All these results indicate that early glutathione deficit provokes persistent changes in adulthood and improves the validity of this animal model of schizophrenia. They further suggest difficulties binding temporally separated events (WCST), except when the salience of this information is very strong (CTA). We propose that the transient glutathione deficit during cerebral development could alter a "cognitive binding" process in interaction with the emotional state that could possibly account for the disruption of integrative function that characterizes schizophrenia. PMID:27485658

  18. Anxiety modulates cognitive deficits in a perinatal glutathione deficit animal model of schizophrenia.

    PubMed

    Preissmann, D; Dépré, M; Schenk, F; Gisquet-Verrier, P

    2016-10-01

    In this study, we investigated long-term repercussion of early glutathione deficit by l-buthionine-(S,R)-sulfoximine (BSO) injections as a rat model of schizophrenia. BSO rats were tested through various behavioral tasks requiring animals to take into account previously delivered information. We showed that relative to controls, BSO rats (1) were less active and more anxious in an Elevated Plus Maze test, allowing us to split them into two subgroups with high and low anxiety levels; (2) demonstrated normal abilities of behavioral flexibility tested with a rat-adapted version of the Wisconsin Card Sorting Test (WCST), with even higher abilities in anxious BSO rats suggesting reduced interference of previously acquired rules; (3) did not forage normally in radial arm mazes and mainly used clockwise strategies; (4) exhibited a lack of habituation during a startle response task; and (5) showed a normal prepulse inhibition of the startle response (PPI) and a normal conditioned taste aversion (CTA). All these results indicate that early glutathione deficit provokes persistent changes in adulthood and improves the validity of this animal model of schizophrenia. They further suggest difficulties binding temporally separated events (WCST), except when the salience of this information is very strong (CTA). We propose that the transient glutathione deficit during cerebral development could alter a "cognitive binding" process in interaction with the emotional state that could possibly account for the disruption of integrative function that characterizes schizophrenia.

  19. 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.

  20. Modelling Alzheimer-like cognitive deficits in rats using biperiden as putative cognition impairer.

    PubMed

    Szczodry, Olga; van der Staay, Franz Josef; Arndt, Saskia S

    2014-11-01

    To enable the development of effective treatments for dementias such as Alzheimer's disease (AD), it is important to establish valid animal models of cognitive impairments. Scopolamine is widely used to induce cognitive deficits in animal models of AD, but also causes non-cognitive side effects. We assessed whether biperiden, a selective antagonist of M1 muscarinic receptors, which are predominantly expressed in brain areas involved in cognitive processes, causes cognitive deficits without inducing peripheral side-effects. Two different doses of biperiden (3 or 10mgkg(-1)) on the acquisition of a spatial cone field task were assessed in male Lister Hooded rats. This task measures, among others, spatial working (WM) - and reference memory (RM) simultaneously. Biperiden did not impair learning of the task. The animals reached asymptotic levels for all variables except reference memory and the number of rewards collected. However, the 10mgkg(-1) dose decreased the tendency of rats to use searching strategies to solve the task and made them slower to start searching and completing the task. In conclusion, though no effects on WM and RM performance were seen, the present study cannot conclude that biperiden acts as a more selective cognition impairer than scopolamine in other rats strains and/or other doses than those tested.

  1. Potential Use of Nicotinic Receptor Agonists for the Treatment of Chemotherapy-Induced Cognitive Deficits.

    PubMed

    Philpot, Rex M

    2015-10-01

    Over the past several decades, research in both humans and animals has established the existence of persistent cognitive deficits resulting from exposure to chemotherapeutic agents. Nevertheless, there has been very little research addressing the treatment of chemotherapy-induced cognitive deficits and there is currently no approved treatment for this condition, often referred to as 'chemo-brain.' Several drugs that enhance cholinergic function and/or increase nicotinic acetylcholine receptor (nAChR) activity have been demonstrated to improve cognitive performance and/or reverse cognitive deficits in animals, findings that have led to the use of these compounds to treat the cognitive deficits present in a variety of disorders including attention deficit disorder, Alzheimer's disease, Parkinson's disease and schizophrenia. Although nAChR agonists have not been assessed for their efficacy in treating chemotherapy-induced cognitive deficits, these drugs have been shown to produce measureable increases in performance on several behavioral tasks known to be disrupted by exposure to chemotherapeutic agents. While the processes underlying chemotherapy-induced cognitive deficits may differ from those underlying other disorders, there appears to be a broad spectrum of application for the use of nAChR agonists to improve cognitive function. Therefore, studies examining the use of these drugs in the treatment of chemotherapy-induced cognitive deficits should be conducted as they may be of benefit for the treatment of 'chemo-brain.' PMID:25652578

  2. Cerebral lateralization and cognitive deficits after congenital hemiparesis.

    PubMed

    Kolk, Anneli; Talvik, Tiina

    2002-11-01

    The purpose of this study was to investigate whether and how handedness is related to the processes of cerebral lateralization and cognitive performance in children with congenital insult. Fifty-six children (31 males and 25 females) with congenital hemiparesis and 14 control subjects were investigated. Of these children, 32 had a left hemisphere lesion, and 24 children had a right hemisphere lesion. There were 30 right-handed, 23 left-handed, and three ambidextrous children in the study group. The neuropsychologic assessment was performed using the NEPSY (a developmental neuropsychological assessment of child development) test battery. We found that 41% of the hemiparetic children and 72% of the children with a left hemisphere lesion were left-handed. In children contralateral to lesion handedness (no evidence of interhemispheric transfer of functions), we found diffuse cognitive deficits with impaired language abilities and poor visuomotor and narrative memory processing. In contrast, children with ipsilateral to brain lesion handedness (interhemispheric transfer of functions) demonstrated minimal or moderate side-specific cognitive dysfunction. Right-handed children with a right hemisphere lesion had attention, spatial, and short-term memory problems; left-handed children with a left hemisphere lesion had receptive language and visuomotor difficulties. Handedness combined with neuropsychologic assessment is a reliable indicator of the processes of cerebral reorganization after early brain insult. PMID:12504203

  3. Cognitive Profiling in Chinese Developmental Dyslexia with Attention-Deficit/Hyperactivity Disorders

    ERIC Educational Resources Information Center

    Chan, Won Shing Raymond; Hung, Se Fong; Liu, Suet Nga; Lee, Cheuk Kiu Kathy

    2008-01-01

    The cognitive profiles of children with Developmental Reading Disorder (RD) and Attention-Deficit/Hyperactivity Disorders (ADHD) have been extensively studied in alphabetic language communities. Deficits in phonological processing and rapid naming have been implicated as core features of RD although whether the latter is a deficit specific to RD…

  4. 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…

  5. Offenders with Cognitive Deficits in a Canadian Prison Population: Prevalence, Profile, and Outcomes.

    PubMed

    Stewart, Lynn A; Wilton, Geoff; Sapers, Jeremy

    2016-01-01

    Impaired cognitive function has been associated with criminal behavior. In Canada it is unknown the extent to which this disorder affects federal inmates or its impact on key correctional outcomes. In this study, 488 incoming male offenders were assessed on the Cognistat, a neuropsychological screening tool. Twenty-five percent of offenders were found to have some level of cognitive deficit. Lower levels of educational achievement, unstable employment history, learning disability, serious alcohol problems, and symptoms of Attention Deficit Hyperactivity Disorder (ADHD) were significantly associated with the presence of cognitive deficits in this sample. Although there was a significant trend for offenders with cognitive deficits to have more admissions to segregation, level of cognitive deficit was not consistently related to rates of institutional charges or rates of completion of required correctional programs. On release, cognitive deficits were not related to returns to custody or returns to custody with an offence. These results indicate that while offenders with cognitive deficits may require assistance with educational upgrading and employment to improve their reintegration potential, they do not pose a particular management problem in the community after release relative to offenders without cognitive deficits.

  6. Models of cognitive deficit and statistical hypotheses: multiple sclerosis, an example.

    PubMed

    Ryan, L; Clark, C M; Klonoff, H; Paty, D

    1993-07-01

    The purpose of the current study was to describe four models of cognitive deficit and to outline the statistical hypotheses underlying each model. The four models of cognitive deficit were (a) specific deficit; (b) subgroup deficit; (c) a syndrome dissociation model; and (d) a global function dissociation model. Neuropsychological data are analyzed to examine each of these four models in a sample of mild Multiple Sclerosis (MS) patients. The results suggest that for these subjects and tests, the specific deficit model best fits the data. The results are reviewed initially in the context of MS. There follows a consideration of statistical caveats and finally, general applications of the proposed procedures. PMID:8354709

  7. Environmental enrichment to alleviate maze performance deficits in rats with microcephaly induced by X-irradiation

    SciTech Connect

    Shibagaki, M.; Seo, M.; Asano, T.; Kiyono, S. . Inst. for Developmental Research)

    1981-11-01

    Pregnant rats received 150 R of X-irradiation on day 17 of gestation. The male offspring were reared under environmentally enriched (EC), standard colony (SC) or impoverished conditions (IC) for 30 days after weaning. Then the Hebb-Williams maze test was carried out. The effects of X-irradiation and environment were both significant in initial, repetitive and total error scores and running time. Further analysis revealed that both EC-SC and EC-IC differences in initial, repetitive and total error scores were significant in X-irradiated animals, whereas only the EC-IC difference in initial and total error scores was significant in sham-irradiated control animals. Total protein, protein/g cortex, total benzodiazepine and muscarine cholinergic receptor bindings, and muscarinic cholinergic receptor binding/mg protein in the cerebral cortex were decreased in X-irradiated groups, compared to controls, but the effect of environment was not significant in these items. The results confirmed that environmental enrichment is a useful tool to alleviate the learning decrements in prenatally X-irradiated microcephalic rats.

  8. Quality of life and cognitive deficits after subarachnoid haemorrhage.

    PubMed

    Hütter, B O; Gilsbach, J M; Kreitschmann, I

    1995-01-01

    In a retrospective study of 58 patients after subarachnoid haemorrhage (SAH) with a late result either good (GOS = I) or fair (GOS = II), patients were examined 1-5 years after the acute event for their quality of life including a neuropsychological examination. Cognitive deficits were found in visual short-term memory (46%) and in the three parameters of a reaction-time task ranging from 31 to 65%. Further deficits were found in verbal long-term memory (28%), concentration (5-13%) and language (11%). The quality of life was reduced in the SAH patients according to a self-rating scale in motivation (50%), interests (47%), mental capacity (47%), free-time activities (52%), social relationships (39%), concentration (70%), fine motor co-ordination (25%) and sleep (47%). A further 77% of the patients reported more frequent headaches since their SAH. Depression was found in 30% of the SAH patients. Life-satisfaction was significantly reduced in 37%, whereas 48% of the SAH patients suffered from increased emotional lability and in 41% motivation was significantly reduced. Negative job consequences like loss of job or demotion were reported by 16% of the patients investigated and an additional 15% had been retired. PMID:7576273

  9. 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…

  10. Behavioral response inhibition in psychotic disorders: diagnostic specificity, familiality and relation to generalized cognitive deficit.

    PubMed

    Ethridge, Lauren E; Soilleux, Melanie; Nakonezny, Paul A; Reilly, James L; Hill, S Kristian; Keefe, Richard S E; Gershon, Elliot S; Pearlson, Godfrey D; Tamminga, Carol A; Keshavan, Matcheri S; Sweeney, John A

    2014-11-01

    Difficulty inhibiting context-inappropriate behavior is a common deficit in psychotic disorders. The diagnostic specificity of this impairment, its familiality, and its degree of independence from the generalized cognitive deficit associated with psychotic disorders remain to be clarified. Schizophrenia, schizoaffective and bipolar patients with history of psychosis (n=523), their available first-degree biological relatives (n=656), and healthy participants (n=223) from the multi-site B-SNIP study completed a manual Stop Signal task. A nonlinear mixed model was used to fit logistic curves to success rates on Stop trials as a function of parametrically varied Stop Signal Delay. While schizophrenia patients had greater generalized cognitive deficit than bipolar patients, their deficits were similar on the Stop Signal task. Further, only bipolar patients showed impaired inhibitory control relative to healthy individuals after controlling for generalized cognitive deficit. Deficits accounted for by the generalized deficit were seen in relatives of schizophrenia and schizoaffective patients, but not in relatives of bipolar patients. In clinically stable patients with psychotic bipolar disorder, impaired inhibitory behavioral control was a specific cognitive impairment, distinct from the generalized neuropsychological impairment associated with psychotic disorders. Thus, in bipolar disorder with psychosis, a deficit in inhibitory control may contribute to risk for impulsive behavior. Because the deficit was not familial in bipolar families and showed a lack of independence from the generalized cognitive deficit in schizophrenia spectrum disorders, it appears to be a trait related to illness processes rather than one tracking familial risk factors.

  11. Hyperforin alleviates mood deficits of adult rats suffered from early separation.

    PubMed

    Zhu, Minghui; Liu, Chunhua; Qin, Xuan; Yang, Zhuo

    2015-11-01

    In this study, we aimed to explore the effect of hyperforin (Hyp) on adult rats suffered from early separation. Wistar infant rats were randomly divided into three groups: control group (CON), early separation from parents group (ESP), and early separation from parents+treatment with 3mg/kg/day Hyp group (ESP+Hyp). Postnatal rats of ESP group and ESP+Hyp group were separated from their mothers for 6h every day on the 14th day after birth, and this separation lasted for 3 weeks, while rats of CON group had no separation. Hyperforin was intragastric administrated on the 21th day after birth, and lasted for 2 weeks in ESP+Hyp group. After separation, adult rats were evaluated by using the open field test (OFT), novelty suppressed feeding test (NSF) and forced swimming test (FST). In OFT, time spent in central grids was much shorter in ESP group compared with that of CON group. After treatment with hyperforin, time spent in central area was much longer compared with that of ESP group. In NSF, the feeding latency of ESP group was much longer than that of CON group. After treatment with hyperforin, the feeding latency was shorter compared with that of ESP group. In FST, score of ESP group was markedly higher than that of CON group. Interestingly, the score was obviously lower in ESP+Hyp group than that of ESP group. In conclusion, these results suggest that hyperforin is able to alleviate anxiety and remit depression in ESP rats. PMID:26420027

  12. Residual cognitive deficits 50 years after lead poisoning during childhood.

    PubMed Central

    White, R F; Diamond, R; Proctor, S; Morey, C; Hu, H

    1993-01-01

    The long term neurobehavioural consequences of childhood lead poisoning are not known. In this study adult subjects with a documented history of lead poisoning before age 4 and matched controls were examined with an abbreviated battery of neuropsychological tests including measures of attention, reasoning, memory, motor speed, and current mood. The subjects exposed to lead were inferior to controls on almost all of the cognitive tasks. This pattern of widespread deficits resembles that found in children evaluated at the time of acute exposure to lead rather than the more circumscribed pattern typically seen in adults exposed to lead. Despite having completed as many years of schooling as controls, the subjects exposed to lead were lower in lifetime occupational status. Within the exposed group, performance on the neuropsychological battery and occupational status were related, consistent with the presumed impact of limitations in neuropsychological functioning on everyday life. The results suggest that many subjects exposed to lead suffered acute encephalopathy in childhood which resolved into a chronic subclinical encephalopathy with associated cognitive dysfunction still evident in adulthood. These findings lend support to efforts to limit exposure to lead in childhood. PMID:8343422

  13. SNR Wall Effect Alleviation by Generalized Detector Employed in Cognitive Radio Networks.

    PubMed

    Shbat, Modar Safir; Tuzlukov, Vyacheslav

    2015-01-01

    The most commonly used spectrum sensing techniques in cognitive radio (CR) networks, such as the energy detector (ED), matched filter (MF), and others, suffer from the noise uncertainty and signal-to-noise ratio (SNR) wall phenomenon. These detectors cannot achieve the required signal detection performance regardless of the sensing time. In this paper, we explore a signal processing scheme, namely, the generalized detector (GD) constructed based on the generalized approach to signal processing (GASP) in noise, in spectrum sensing of CR network based on antenna array with the purpose to alleviate the SNR wall problem and improve the signal detection robustness under the low SNR. The simulation results confirm our theoretical issues and effectiveness of GD implementation in CR networks based on antenna array. PMID:26151216

  14. SNR Wall Effect Alleviation by Generalized Detector Employed in Cognitive Radio Networks

    PubMed Central

    Shbat, Modar Safir; Tuzlukov, Vyacheslav

    2015-01-01

    The most commonly used spectrum sensing techniques in cognitive radio (CR) networks, such as the energy detector (ED), matched filter (MF), and others, suffer from the noise uncertainty and signal-to-noise ratio (SNR) wall phenomenon. These detectors cannot achieve the required signal detection performance regardless of the sensing time. In this paper, we explore a signal processing scheme, namely, the generalized detector (GD) constructed based on the generalized approach to signal processing (GASP) in noise, in spectrum sensing of CR network based on antenna array with the purpose to alleviate the SNR wall problem and improve the signal detection robustness under the low SNR. The simulation results confirm our theoretical issues and effectiveness of GD implementation in CR networks based on antenna array. PMID:26151216

  15. SNR Wall Effect Alleviation by Generalized Detector Employed in Cognitive Radio Networks.

    PubMed

    Shbat, Modar Safir; Tuzlukov, Vyacheslav

    2015-07-03

    The most commonly used spectrum sensing techniques in cognitive radio (CR) networks, such as the energy detector (ED), matched filter (MF), and others, suffer from the noise uncertainty and signal-to-noise ratio (SNR) wall phenomenon. These detectors cannot achieve the required signal detection performance regardless of the sensing time. In this paper, we explore a signal processing scheme, namely, the generalized detector (GD) constructed based on the generalized approach to signal processing (GASP) in noise, in spectrum sensing of CR network based on antenna array with the purpose to alleviate the SNR wall problem and improve the signal detection robustness under the low SNR. The simulation results confirm our theoretical issues and effectiveness of GD implementation in CR networks based on antenna array.

  16. Alleviation of Communication Apprehension: An Individualized Approach.

    ERIC Educational Resources Information Center

    Watson, Arden K.

    Communication apprehension (CA) affects from 15% to 20% of the college population, indicating inherent problems of negative cognitive appraisal, conditioned anxiety, or skills deficits. Use of an individualized approach to the alleviation of CA has been shown to increase students' class interaction and to improve their verbal skills. During an…

  17. 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. PMID:27376853

  18. Pharmacological Cognitive Enhancement in Healthy Individuals: A Compensation for Cognitive Deficits or a Question of Personality?

    PubMed Central

    Maier, Larissa J.; Wunderli, Michael D.; Vonmoos, Matthias; Römmelt, Andreas T.; Baumgartner, Markus R.; Seifritz, Erich

    2015-01-01

    The ongoing bioethical debate on pharmacological cognitive enhancement (PCE) in healthy individuals is often legitimated by the assumption that PCE will widely spread and become desirable for the general public in the near future. This assumption was questioned as PCE is not equally save and effective in everyone. Additionally, it was supposed that the willingness to use PCE is strongly personality-dependent likely preventing a broad PCE epidemic. Thus, we investigated whether the cognitive performance and personality of healthy individuals with regular nonmedical methylphenidate (MPH) use for PCE differ from stimulant-naïve controls. Twenty-five healthy individuals using MPH for PCE were compared with 39 age-, sex-, and education-matched healthy controls regarding cognitive performance and personality assessed by a comprehensive neuropsychological test battery including social cognition, prosocial behavior, decision-making, impulsivity, and personality questionnaires. Substance use was assessed through self-report in an interview and quantitative hair and urine analyses. Recently abstinent PCE users showed no cognitive impairment but superior strategic thinking and decision-making. Furthermore, PCE users displayed higher levels of trait impulsivity, novelty seeking, and Machiavellianism combined with lower levels of social reward dependence and cognitive empathy. Finally, PCE users reported a smaller social network and exhibited less prosocial behavior in social interaction tasks. In conclusion, the assumption that PCE use will soon become epidemic is not supported by the present findings as PCE users showed a highly specific personality profile that shares a number of features with illegal stimulant users. Lastly, regular MPH use for PCE is not necessarily associated with cognitive deficits. PMID:26107846

  19. A perspective on psychosis in late life and deficits in social cognition.

    PubMed

    La Salvia, Elizabeth; Chemali, Zeina

    2011-01-01

    The etiology of new psychotic symptoms in late life, including subtle changes in cognition, is a controversial emerging area of study. The development of psychotic symptoms, particularly paranoia, is a common occurrence in late life, and the symptoms of cognitive dysfunction and psychosis are often prominent in dementia, schizophrenia, and mood disorders. This intermixing of symptoms has inescapably led to diagnostic confusion with regard to elderly patients with new-onset psychosis. The complex relationship among different domains of psychopathology makes it difficult to tease apart disorders of affect from psychosis, affect from cognition, and psychosis from cognition. It is therefore potentially useful to modify and expand our approach to how we conceptualize these patients. Emerging evidence suggests that those with dementia, psychotic disorders, and mood disorders suffer from growing cognitive deficits. The article suggests that deficits in social cognition, in particular, may be the unifying deficit that helps to explain why heterogeneous patients may develop paranoia and psychotic symptoms in late life.

  20. [The cognitive deficits in the late-life depression and their prognostic value for pharmacotherapy].

    PubMed

    Sołtys, Krzysztof; Bidzan, Leszek; Turczyński, Jacek; Łapin, Joanna

    2002-01-01

    The cognitive deficits in the late-life depression are considered as risk factor for presentation of dementia in the long-term prognosis. In this research we were looking for correlations between the cognitive deficits and depression, their influence for the short-term prognosis and the activity of daily living in the elderly. 90 patients with depression (ICD-10 criteria were used) were assessed with scales: MADRS, MMSE, ADAS, IADL. After 3 months the evaluation with clinical improvement scale was made. The results indicate for correlations between the cognitive deficits and intensity of depression. No influence of cognitive deficits level for the clinical improvement after 3 months was proved. The intensity of depression was connected with lower level of daily living activities (assessed with IADL). PMID:12647436

  1. Silicon improves seed germination and alleviates oxidative stress of bud seedlings in tomato under water deficit stress.

    PubMed

    Shi, Yu; Zhang, Yi; Yao, Hejin; Wu, Jiawen; Sun, Hao; Gong, Haijun

    2014-05-01

    The beneficial effects of silicon on plant growth and development under drought have been widely reported. However, little information is available on the effects of silicon on seed germination under drought. In this work, the effects of exogenous silicon (0.5 mM) on the seed germination and tolerance performance of tomato (Solanum lycopersicum L.) bud seedlings under water deficit stress simulated by 10% (w/v) polyethylene glycol (PEG-6000) were investigated in four cultivars ('Jinpengchaoguan', 'Zhongza No.9', 'Houpi L402' and 'Oubao318'). The results showed that the seed germination percentage was notably decreased in the four cultivars under water stress, and it was significantly improved by added silicon. Compared with the non-silicon treatment, silicon addition increased the activities of superoxide dismutase (SOD) and catalase (CAT), and decreased the production of superoxide anion (O2·) and hydrogen peroxide (H2O2) in the radicles of bud seedlings under water stress. Addition of silicon decreased the total phenol concentrations in radicles under water stress, which might contribute to the decrease of peroxidase (POD) activity, as observed in the in vivo and in vitro experiments. The decrease of POD activity might contribute to a less accumulation of hydroxyl radical (·OH) under water stress. Silicon addition also decreased the concentrations of malondialdehyde (MDA) in the radicles under stress, indicating decreased lipid peroxidation. These results suggest that exogenous silicon could improve seed germination and alleviate oxidative stress to bud seedling of tomato by enhancing antioxidant defense. The positive effects of silicon observed in a silicon-excluder also suggest the active involvement of silicon in biochemical processes in plants.

  2. Scutellarin Alleviates Behavioral Deficits in a Mouse Model of Multiple Sclerosis, Possibly Through Protecting Neural Stem Cells.

    PubMed

    Wang, Wei-Wei; Lu, Lin; Bao, Tian-Hao; Zhang, Hong-Miao; Yuan, Jing; Miao, Wei; Wang, Shu-Fen; Xiao, Zhi-Cheng

    2016-02-01

    Scutellarin, a flavonoid extracted from an herbal medication (Erigeron breviscapus Hand-Mazz), has been shown to protect neurons against damage and to promote neurogenesis, and thus has therapeutic potential in the treatment of a variety of neurodegenerative diseases. Since neural stem cells (NSCs) could differentiate into myelin-producing oligodendrocytes, we speculate that scutellarin could also be used to treat multiple sclerosis (MS). In the current study, we examined potential effects of scutellarin using a mouse model of MS. Briefly, adult C57BL/6 mice exposed to cuprizone (8 mg/day through diet, for 6 consecutive weeks) randomly received scutellarin (50 mg/kg/day) or vehicle for 10 consecutive days. In the scutellarin-treated group, rotarod testing at the end of the treatment showed significant improvement of motor function (increased time to fall); myelin basic protein (MBP) staining of the corpus callosum revealed decreased demyelination; TUNEL staining followed by Nestin or Sox2 staining revealed increased number of NSCs and decreased rate of NSC apoptosis in the subventricular zone (SVZ) of the lateral ventricles (LV). In a series of experiments using cultured NSCs subjected to cuprizone injury, we confirmed the protective effects of scutellarin. At 30 μM, scutellarin increased the commitment of NSCs to the oligodendrocyte and neuronal lineages, as evidenced by NG2 chondroitin sulfate proteoglycan (NG2) and doublecortin (DCX) staining. Differentiation into astrocytes (as revealed by glial fibrillary acidic protein (GFAP) staining) was decreased. Maturation of the NSCs committed to the oligodendrocyte lineage, as evidenced by oligodendrocyte marker O4 antibody (O4) staining and MBP staining, was also promoted by scutellarin. Further analysis revealed that scutellarin might suppress the phosphorylation of p38 in cuprizone-induced NSCs. In summary, scutellarin could alleviate motor deficits in a mouse model for MS, possibly by inhibiting NSC apoptosis and

  3. Scutellarin Alleviates Behavioral Deficits in a Mouse Model of Multiple Sclerosis, Possibly Through Protecting Neural Stem Cells.

    PubMed

    Wang, Wei-Wei; Lu, Lin; Bao, Tian-Hao; Zhang, Hong-Miao; Yuan, Jing; Miao, Wei; Wang, Shu-Fen; Xiao, Zhi-Cheng

    2016-02-01

    Scutellarin, a flavonoid extracted from an herbal medication (Erigeron breviscapus Hand-Mazz), has been shown to protect neurons against damage and to promote neurogenesis, and thus has therapeutic potential in the treatment of a variety of neurodegenerative diseases. Since neural stem cells (NSCs) could differentiate into myelin-producing oligodendrocytes, we speculate that scutellarin could also be used to treat multiple sclerosis (MS). In the current study, we examined potential effects of scutellarin using a mouse model of MS. Briefly, adult C57BL/6 mice exposed to cuprizone (8 mg/day through diet, for 6 consecutive weeks) randomly received scutellarin (50 mg/kg/day) or vehicle for 10 consecutive days. In the scutellarin-treated group, rotarod testing at the end of the treatment showed significant improvement of motor function (increased time to fall); myelin basic protein (MBP) staining of the corpus callosum revealed decreased demyelination; TUNEL staining followed by Nestin or Sox2 staining revealed increased number of NSCs and decreased rate of NSC apoptosis in the subventricular zone (SVZ) of the lateral ventricles (LV). In a series of experiments using cultured NSCs subjected to cuprizone injury, we confirmed the protective effects of scutellarin. At 30 μM, scutellarin increased the commitment of NSCs to the oligodendrocyte and neuronal lineages, as evidenced by NG2 chondroitin sulfate proteoglycan (NG2) and doublecortin (DCX) staining. Differentiation into astrocytes (as revealed by glial fibrillary acidic protein (GFAP) staining) was decreased. Maturation of the NSCs committed to the oligodendrocyte lineage, as evidenced by oligodendrocyte marker O4 antibody (O4) staining and MBP staining, was also promoted by scutellarin. Further analysis revealed that scutellarin might suppress the phosphorylation of p38 in cuprizone-induced NSCs. In summary, scutellarin could alleviate motor deficits in a mouse model for MS, possibly by inhibiting NSC apoptosis and

  4. 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.…

  5. The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus encephalitis: deficits in cognitive function.

    PubMed

    Griffin, William C; Middaugh, Lawrence D; Cook, Jennifer E; Tyor, William R

    2004-04-01

    The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus (HIV) encephalitis exhibits many of the histopathological and pathophysiological features of human HIV-associated dementia (HAD). Although deficits that may resemble HAD in humans have been reported for HIV-infected SCID mice, the cognitive deficit aspect of the model has very limited empirical support. Here, the authors report that HIV-infected SCID mice display cognitive deficits on a task requiring the animal to learn and remember the spatial relationship of cues in its environment in order to locate a submerged platform in a Morris water maze. The cognitive deficits manifest as longer latencies to locate the platform on the last day of the maze acquisition period and during a retention test 8 days later. Control experiments indicated that the poor performance by HIV-infected mice in comparison to controls was not due to impaired motor function or swimming ability, impaired visual acuity, or increased susceptibility to fatigue. Thus, the increased times required for HIV-infected mice to locate the submerged platform during the acquisition and memory tests likely reflect a cognitive deficit, rather than sensorimotor or emotional abnormalities. These behavioral deficits are associated with significant increases in astrogliosis and microgliosis in the HIV-infected mice. The results of this study strengthen the SCID mouse model of HIV encephalitis by definitively establishing cognitive deficits for the model in addition to its previously reported neuropathological features.

  6. Histone deacetylase inhibitor, trichostatin A, improves learning and memory in high-fat diet-induced cognitive deficits in mice.

    PubMed

    Sharma, Sorabh; Taliyan, Rajeev; Ramagiri, Shruti

    2015-05-01

    Metabolic syndrome is increasingly recognized for its effects on cognitive health. Recent studies have highlighted the role of histone deacetylases (HDACs) in metabolic syndrome and cognitive functions. The present study was designed to investigate the possible therapeutic role of a HDAC inhibitor, trichostatin A (TSA), in cognitive impairment associated with metabolic syndrome. To ascertain the mechanisms involved, we fed mice with high-fat diet (HFD) for 4 weeks and examined changes in behavioral and biochemical/oxidative stress markers. Mice subjected to HFD exhibited characteristic features of metabolic disorder, viz., hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and lower high-density lipoprotein (HDL) cholesterol levels. Moreover, these mice showed severe deficits in learning and memory as assessed by the Morris water maze and passive avoidance tasks along with elevated oxidative stress and inflammatory markers in brain homogenates. The observed changes occurred concurrently with reduced brain-derived neurotrophic factor (BDNF). In contrast, the mice treated with the HDAC inhibitor, TSA (0.5 and 1 mg/kg, i.p.), showed a significant and dose-dependent reduction in serum glucose, triglycerides, and total cholesterol along with improvement in HDL-cholesterol levels and learning and memory performance. TSA treatment also results in alleviation of oxidative stress and neuroinflammatory markers. Moreover, TSA significantly augmented the BDNF levels in HFD-fed mice. Thus, based upon these observations, it may be suggested that HDAC inhibition could be a novel therapeutic strategy to combat cognitive impairment associated with metabolic syndrome.

  7. 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

  8. 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

  9. Cognitive deficits in a mouse model of pre-manifest Parkinson's disease.

    PubMed

    Magen, Iddo; Fleming, Sheila M; Zhu, Chunni; Garcia, Eddie C; Cardiff, Katherine M; Dinh, Diana; De La Rosa, Krystal; Sanchez, Maria; Torres, Eileen Ruth; Masliah, Eliezer; Jentsch, J David; Chesselet, Marie-Françoise

    2012-03-01

    Early cognitive deficits are increasingly recognized in patients with Parkinson's disease (PD), and represent an unmet need for the treatment of PD. These early deficits have been difficult to model in mice, and their mechanisms are poorly understood. α-Synuclein is linked to both familial and sporadic forms of PD, and is believed to accumulate in brains of patients with PD before cell loss. Mice expressing human wild-type α-synuclein under the Thy1 promoter (Thy1-aSyn mice) exhibit broad overexpression of α-synuclein throughout the brain and dynamic alterations in dopamine release several months before striatal dopamine loss. We now show that these mice exhibit deficits in cholinergic systems involved in cognition, and cognitive deficits in domains affected in early PD. Together with an increase in extracellular dopamine and a decrease in cortical acetylcholine at 4-6 months of age, Thy1-aSyn mice made fewer spontaneous alternations in the Y-maze and showed deficits in tests of novel object recognition (NOR), object-place recognition, and operant reversal learning, as compared with age-matched wild-type littermates. These data indicate that cognitive impairments that resemble early PD manifestations are reproduced by α-synuclein overexpression in a murine genetic model of PD. With high power to detect drug effects, these anomalies provide a novel platform for testing improved treatments for these pervasive cognitive deficits.

  10. 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…

  11. Should Sluggish Cognitive Tempo Symptoms Be Included in the Diagnosis of Attention-Deficit/hyperactivity Disorder?

    ERIC Educational Resources Information Center

    Todd, Richard D.; Rasmussen, Erik R.; Wood, Catherine; Levy, Florence; Hay, David A.

    2004-01-01

    Objective: To determine the impact of including sluggish cognitive tempo items on the factor and latent class structure of attention-deficit/hyperactivity disorder (ADHD) subtypes in boys and girls. Method: Parent report of two sluggish cognitive tempo items on a population-based sample of 1,430 female twins and 1,414 male twins were analyzed…

  12. A controlled study of cognitive deficits in children with chronic Lyme disease.

    PubMed

    Tager, F A; Fallon, B A; Keilp, J; Rissenberg, M; Jones, C R; Liebowitz, M R

    2001-01-01

    Although neurologic Lyme disease is known to cause cognitive dysfunction in adults, little is known about its long-term sequelae in children. Twenty children with a history of new-onset cognitive complaints after Lyme disease were compared with 20 matched healthy control subjects. Each child was assessed with measures of cognition and psychopathology. Children with Lyme disease had significantly more cognitive and psychiatric disturbances. Cognitive deficits were still found after controlling for anxiety, depression, and fatigue. Lyme disease in children may be accompanied by long-term neuropsychiatric disturbances, resulting in psychosocial and academic impairments. Areas for further study are discussed.

  13. Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats

    PubMed Central

    Waterhouse, Uta; Roper, Vic E.; Brennan, Katharine A.

    2016-01-01

    ABSTRACT Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin) at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg) at one of three neurodevelopmental time periods [gestation days (GD) 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND) 60] and included: prepulse inhibition (PPI), latent inhibition (LI) and delayed non-matching to sample (DNMTS). Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously) were administered, and animals were re-tested in the same tasks (PND 110). Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11) resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI) and selective (LI) improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI) and induced a global enhancement of sensorimotor gating (PPI). PMID:27483346

  14. Characterization of cognitive deficits in mice with an alternating hemiplegia-linked mutation.

    PubMed

    Kirshenbaum, Greer S; Dachtler, James; Roder, John C; Clapcote, Steven J

    2015-12-01

    Cognitive impairment is a prominent feature in a range of different movement disorders. Children with Alternating Hemiplegia of Childhood are prone to developmental delay, with deficits in cognitive functioning becoming progressively more evident as they grow older. Heterozygous mutations of the ATP1A3 gene, encoding the Na+,K+-ATPase α3 subunit, have been identified as the primary cause of Alternating Hemiplegia. Heterozygous Myshkin mice have an amino acid change (I810N) in Na+,K+-ATPase α3 that is also found in Alternating Hemiplegia. To investigate whether Myshkin mice exhibit learning and memory deficits resembling the cognitive impairments of patients with Alternating Hemiplegia, we subjected them to a range of behavioral tests that interrogate various cognitive domains. Myshkin mice showed impairments in spatial memory, spatial habituation, locomotor habituation, object recognition, social recognition, and trace fear conditioning, as well as in the visible platform version of the Morris water maze. Increasing the duration of training ameliorated the deficit in social recognition but not in spatial habituation. The deficits of Myshkin mice in all of the learning and memory tests used are consistent with the cognitive impairment of the vast majority of AHC patients. These mice could thus help advance our understanding of the underlying neural mechanisms influencing cognitive impairment in patients with ATP1A3-related disorders.

  15. Characterization of Cognitive Deficits in Mice With an Alternating Hemiplegia-Linked Mutation

    PubMed Central

    2015-01-01

    Cognitive impairment is a prominent feature in a range of different movement disorders. Children with Alternating Hemiplegia of Childhood are prone to developmental delay, with deficits in cognitive functioning becoming progressively more evident as they grow older. Heterozygous mutations of the ATP1A3 gene, encoding the Na+,K+-ATPase α3 subunit, have been identified as the primary cause of Alternating Hemiplegia. Heterozygous Myshkin mice have an amino acid change (I810N) in Na+,K+-ATPase α3 that is also found in Alternating Hemiplegia. To investigate whether Myshkin mice exhibit learning and memory deficits resembling the cognitive impairments of patients with Alternating Hemiplegia, we subjected them to a range of behavioral tests that interrogate various cognitive domains. Myshkin mice showed impairments in spatial memory, spatial habituation, locomotor habituation, object recognition, social recognition, and trace fear conditioning, as well as in the visible platform version of the Morris water maze. Increasing the duration of training ameliorated the deficit in social recognition but not in spatial habituation. The deficits of Myshkin mice in all of the learning and memory tests used are consistent with the cognitive impairment of the vast majority of AHC patients. These mice could thus help advance our understanding of the underlying neural mechanisms influencing cognitive impairment in patients with ATP1A3-related disorders. PMID:26501181

  16. Reversing roles: a cognitive strategy for undoing memory deficits associated with token status.

    PubMed

    Saenz, D S; Lord, C G

    1989-05-01

    Tested whether having tokens (Ts) adopt the role of judge reduces cognitive deficits; examined several hypotheses to explain these deficits. In 3 experiments, Ss were asked to remember as many as possible of opinions exchanged in a group interaction with 3 actors. Experiment 1 demonstrated that judging majority members helped gender Ts improve their memory and ruled out self-denigration as a mediator of token deficits. Experiment 2 indicated that judging others was effective regardless of whether the others were said to know about it or not, ruling out insulation from evaluative scrutiny as a viable mediator for the judge role. Experiment 3 suggested the judge role restores completely the Ts, cognitive capacities and ruled out heightened responsibility as an explanation for the improved memory of judges. This work suggests that Ts may perform better if they can restructure cognitively their social environments.

  17. Spatial but not verbal cognitive deficits at age 3 years in persistently antisocial individuals.

    PubMed

    Raine, Adrian; Yaralian, Pauline S; Reynolds, Chandra; Venables, Peter H; Mednick, Sarnoff A

    2002-01-01

    Previous studies have repeatedly shown verbal intelligence deficits in adolescent antisocial individuals, but it is not known whether these deficits are in place prior to kindergarten or, alternatively, whether they are acquired throughout childhood. This study assesses whether cognitive deficits occur as early as age 3 years and whether they are specific to persistently antisocial individuals. Verbal and spatial abilities were assessed at ages 3 and 11 years in 330 male and female children, while antisocial behavior was assessed at ages 8 and 17 years. Persistently antisocial individuals (N = 47) had spatial deficits in the absence of verbal deficits at age 3 years compared to comparisons (N = 133), and also spatial and verbal deficits at age 11 years. Age 3 spatial deficits were independent of social adversity, early hyperactivity, poor test motivation, poor test comprehension, and social discomfort during testing, and they were found in females as well as males. Findings suggest that early spatial deficits contribute to persistent antisocial behavior whereas verbal deficits are developmentally acquired. An early-starter model is proposed whereby early spatial impairments interfere with early bonding and attachment, reflect disrupted right hemisphere affect regulation and expression, and predispose to later persistent antisocial behavior.

  18. Ursolic acid improves domoic acid-induced cognitive deficits in mice

    SciTech Connect

    Wu, Dong-mei; Lu, Jun; Zhang, Yan-qiu; Zheng, Yuan-lin; Hu, Bin; Cheng, Wei; Zhang, Zi-feng; Li, Meng-qiu

    2013-09-01

    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 cognitive 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.

  19. Cognitive Deficits in Nonretarded Adults with Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Kerns, Kimberley A.; Don, Audrey; Mateer, Catherine A.; Streissguth, Ann P.

    1997-01-01

    Sixteen nonretarded young adults with fetal alcohol syndrome were divided into two groups, one with average to above average IQ and one with borderline to low average IQ. Subjects in both groups manifested clear deficits on neuropsychological measures sensitive to complex attention, verbal learning, and executive function at a frequency and…

  20. A Mitochondrion-Targeted Antioxidant Ameliorates Isoflurane-Induced Cognitive Deficits in Aging Mice.

    PubMed

    Wu, Jing; Li, Huihui; Sun, Xiaoru; Zhang, Hui; Hao, Shuangying; Ji, Muhuo; Yang, Jianjun; Li, Kuanyu

    2015-01-01

    Isoflurane possesses neurotoxicity and can induce cognitive deficits, particularly in aging mammals. Mitochondrial reactive oxygen species (mtROS) have been linked to the early pathogenesis of this disorder. However, the role of mtROS remains to be evaluated due to a lack of targeted method to treat mtROS. Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic. We further investigated the possible mechanisms underlying the effects of SS-31 on hippocampal neuro-inflammation and apoptosis. The results showed that isoflurane induced hippocampus-dependent memory deficit, which was associated with mitochondrial dysfunction including reduced ATP contents, increased ROS levels, and mitochondrial swelling. Treatment with SS-31 significantly ameliorated isoflurane-induced cognitive deficits through the improvement of mitochondrial integrity and function. Mechanistically, SS-31 treatment suppressed pro-inflammatory responses by decreasing the levels of NF-κB, NLRP3, caspase 1, IL-1β, and TNF-α; and inhibited the apoptotic pathway by decreasing the Bax/Bcl-2 ratio, reducing the release of cytochrome C, and blocking the cleavage of caspase 3. Our results indicate that isoflurane-induced cognitive deficits may be attenuated by mitochondrion-targeted antioxidants, such as SS-31. Therefore, SS-31 may have therapeutic potentials in preventing injuries from oxidative stresses that contribute to anesthetic-induced neurotoxicity.

  1. Selective deficits in cognition and memory in high-functioning parkinsonian patients.

    PubMed

    Mohr, E; Juncos, J; Cox, C; Litvan, I; Fedio, P; Chase, T N

    1990-07-01

    To evaluate the profile and extent of cognitive deficits in Parkinson's disease, afflicted patients of exceptional professional distinction, who continue to function successfully in leadership positions, were compared neuropsychologically to neurologically normal individuals, matched for sex, age, education and professional standing. While patients showed relative preservation of verbal skills and higher executive function, they exhibited a significant reduction in episodic memory and visuospatial function. The observation of circumscribed impairment in this select group of Parkinsonian patients further implicates cognitive and memory deficits as consistent features of Parkinson's disease. PMID:2391526

  2. Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats.

    PubMed

    Pang, Y; Lin, S; Wright, C; Shen, J; Carter, K; Bhatt, A; Fan, L-W

    2016-03-24

    Protection of substantia nigra (SN) dopaminergic (DA) neurons by neurotrophic factors (NTFs) is one of the promising strategies in Parkinson's disease (PD) therapy. A major clinical challenge for NTF-based therapy is that NTFs need to be delivered into the brain via invasive means, which often shows limited delivery efficiency. The nose to brain pathway is a non-invasive brain drug delivery approach developed in recent years. Of particular interest is the finding that intranasal insulin improves cognitive functions in Alzheimer's patients. In vitro, insulin has been shown to protect neurons against various insults. Therefore, the current study was designed to test whether intranasal insulin could afford neuroprotection in the 6-hydroxydopamine (6-OHDA)-based rat PD model. 6-OHDA was injected into the right side of striatum to induce a progressive DA neuronal lesion in the ipsilateral SN pars compact (SNc). Recombinant human insulin was applied intranasally to rats starting from 24h post lesion, once per day, for 2 weeks. A battery of motor behavioral tests was conducted on day 8 and 15. The number of DA neurons in the SNc was estimated by stereological counting. Our results showed that 6-OHDA injection led to significant motor deficits and 53% of DA neuron loss in the ipsilateral side of injection. Treatment with insulin significantly ameliorated 6-OHDA-induced motor impairments, as shown by improved locomotor activity, tapered/ledged beam-walking performance, vibrissa-elicited forelimb-placing, initial steps, as well as methamphetamine-induced rotational behavior. Consistent with behavioral improvements, insulin treatment provided a potent protection of DA neurons in the SNc against 6-OHDA neurotoxicity, as shown by a 74.8% increase in tyrosine hydroxylase (TH)-positive neurons compared to the vehicle group. Intranasal insulin treatment did not affect body weight and blood glucose levels. In conclusion, our study showed that intranasal insulin provided strong

  3. Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats.

    PubMed

    Pang, Y; Lin, S; Wright, C; Shen, J; Carter, K; Bhatt, A; Fan, L-W

    2016-03-24

    Protection of substantia nigra (SN) dopaminergic (DA) neurons by neurotrophic factors (NTFs) is one of the promising strategies in Parkinson's disease (PD) therapy. A major clinical challenge for NTF-based therapy is that NTFs need to be delivered into the brain via invasive means, which often shows limited delivery efficiency. The nose to brain pathway is a non-invasive brain drug delivery approach developed in recent years. Of particular interest is the finding that intranasal insulin improves cognitive functions in Alzheimer's patients. In vitro, insulin has been shown to protect neurons against various insults. Therefore, the current study was designed to test whether intranasal insulin could afford neuroprotection in the 6-hydroxydopamine (6-OHDA)-based rat PD model. 6-OHDA was injected into the right side of striatum to induce a progressive DA neuronal lesion in the ipsilateral SN pars compact (SNc). Recombinant human insulin was applied intranasally to rats starting from 24h post lesion, once per day, for 2 weeks. A battery of motor behavioral tests was conducted on day 8 and 15. The number of DA neurons in the SNc was estimated by stereological counting. Our results showed that 6-OHDA injection led to significant motor deficits and 53% of DA neuron loss in the ipsilateral side of injection. Treatment with insulin significantly ameliorated 6-OHDA-induced motor impairments, as shown by improved locomotor activity, tapered/ledged beam-walking performance, vibrissa-elicited forelimb-placing, initial steps, as well as methamphetamine-induced rotational behavior. Consistent with behavioral improvements, insulin treatment provided a potent protection of DA neurons in the SNc against 6-OHDA neurotoxicity, as shown by a 74.8% increase in tyrosine hydroxylase (TH)-positive neurons compared to the vehicle group. Intranasal insulin treatment did not affect body weight and blood glucose levels. In conclusion, our study showed that intranasal insulin provided strong

  4. Static and Dynamic Cognitive Deficits in Childhood Preceding Adult Schizophrenia: A 30-Year Study

    PubMed Central

    Reichenberg, Abraham; Caspi, Avshalom; Harrington, HonaLee; Houts, Renate; Keefe, Richard S.E.; Murray, Robin M.; Poulton, Richie; Moffitt, Terrie E.

    2013-01-01

    Objective Premorbid cognitive deficits in schizophrenia are well documented and have been interpreted as supporting a neurodevelopmental etiological model. The authors investigated the following three unresolved questions about premorbid cognitive deficits: What is their developmental course? Do all premorbid cognitive deficits follow the same course? Are premorbid cognitive deficits specific to schizophrenia or shared by other psychiatric disorders? Methods Participants were members of a representative cohort of 1,037 males and females born between 1972 and 1973 in Dunedin, New Zealand. Cohort members underwent follow-up evaluations at specific intervals from age 3 to 32 years, with a 96% retention rate. Cognitive development was analyzed and compared in children who later developed schizophrenia or recurrent depression as well as in healthy comparison subjects. Results Children who developed adult schizophrenia exhibited developmental deficits (i.e., static cognitive impairments that emerge early and remain stable) on tests indexing verbal and visual knowledge acquisition, reasoning, and conceptualization. In addition, these children exhibited developmental lags (i.e., growth that is slower relative to healthy comparison subjects) on tests indexing processing speed, attention, visual-spatial problem solving ability, and working memory. These two premorbid cognitive patterns were not observed in children who later developed recurrent depression. Conclusions These findings suggest that the origins of schizophrenia include two interrelated developmental processes evident from childhood to early adolescence (ages 7–13 years). Children who will grow up to develop adult schizophrenia enter primary school struggling with verbal reasoning and lag further behind their peers in working memory, attention, and processing speed as they get older. PMID:20048021

  5. Environmental enrichment ameliorates phencyclidine-induced cognitive deficits.

    PubMed

    Saland, Samantha K; Rodefer, Joshua S

    2011-05-01

    Recent work has suggested that environmental enrichment during development can enhance aspects of learning and memory, however its effects on executive function and cognitive flexibility have not been well studied. The goal of this research was to evaluate whether environmental enrichment (EE) that included wheel running would improve cognitive performance in young male Long Evans rats that received subchronic administration of either phencyclidine (PCP) or saline. We used a sensitive extradimensional/intradimensional (ED/ID) test of cognitive flexibility similar to that used in humans and nonhuman primates for assessing executive function. PCP-treated rats demonstrated a selective impairment on ED shift (EDS) performance without significant impairment on other discrimination problems when compared to saline treated control animals. A separate group of animals that received PCP + EE demonstrated significantly improved performance on EDS and reversal learning problems, whereas the saline + EE group demonstrated a non-selective improvement in overall performance when compared to non-enriched saline controls. The saline + EE group demonstrated greater activity levels as measured by wheel running when compared to the PCP + EE group, but no significant associations were found between wheel running and cognitive performance. Together, these data suggest that EE that features wheel running may have promoted a general cognitive enhancement while also selectively acting upon neurobiological mechanisms that subserve executive function and cognitive flexibility in impaired animals. Development of novel treatment methodologies that target mechanisms underlying the ameliorative effects of EE in this model of cognitive impairment may be a useful tool in the development of new therapeutic strategies for disorders that feature cognitive dysfunction as a key symptom.

  6. Cognitive complaints of adults with attention deficit hyperactivity disorder.

    PubMed

    Fuermaier, Anselm B M; Tucha, Lara; Koerts, Janneke; Aschenbrenner, Steffen; Weisbrod, Matthias; Lange, Klaus W; Tucha, Oliver

    2014-01-01

    Executive dysfunction of adults with ADHD is often associated with poor self-awareness of problems, such as in emotional competence, emotional recognition, and driving competence. However, with regard to cognitive functioning, little is known about how adults with ADHD evaluate their own cognitive performance. A total of 77 adults with ADHD and 116 healthy adults were assessed with self-report scales measuring several aspects of cognition. Significance and effect sizes as well as the proportion of patients perceiving impairments were calculated. Further analysis was carried out on the frequency of patients perceiving various types of impairments. Adults with ADHD perceived themselves to have significant and severe dysfunction in all areas of cognition assessed as a group. Furthermore, the majority of patients reported multiple impairments in attention, memory and executive functioning. The present study demonstrated that adults with ADHD are aware of problems in cognitive functioning as shown by considerable perceived neuropsychological impairment in the majority of patients. Patients with ADHD tended to report cognitive impairments in multiple domains rather than impairments in specific functions.

  7. Subtle deficits of cognitive theory of mind in unaffected first-degree relatives of schizophrenia patients.

    PubMed

    Montag, Christiane; Neuhaus, Kathrin; Lehmann, Anja; Krüger, Katja; Dziobek, Isabel; Heekeren, Hauke R; Heinz, Andreas; Gallinat, Jürgen

    2012-04-01

    Alterations of theory of mind (ToM) and empathy were implicated in the formation of psychotic experiences, and deficits in psychosocial functioning of schizophrenia patients. Inspired by concepts of neurocognitive endophenotypes, the existence of a distinct, potentially neurobiologically based social-cognitive vulnerability marker for schizophrenia is a matter of ongoing debate. The fact that previous research on social-cognitive deficits in individuals at risk yielded contradictory results may partly be due to an insufficient differentiation between qualitative aspects of ToM. Thirty-four unaffected first-degree relatives of schizophrenia patients (21 parents, 8 siblings, 5 children; f/m: 30/4; mean age: 48.1 ± 12.7 years) and 34 controls subjects (f/m: 25/9; mean age: 45.9 ± 10.9 years) completed the 'Movie for the Assessment of Social Cognition'-a video-based ToM test-and an empathy questionnaire (Interpersonal Reactivity Index, IRI). Outcome parameters comprised (1) 'cognitive' versus 'emotional' ToM, (2) error counts representing 'undermentalizing' versus 'overmentalizing', (3) empathic abilities and (4) non-social neurocognition. MANCOVA showed impairments in cognitive but not emotional ToM in the relatives' group, when age, gender and neurocognition were controlled for. Relatives showed elevated error counts for 'undermentalizing' but not for 'overmentalizing'. No alterations were detected in self-rated dimensions of empathy. Of all measures of ToM and empathy, only the IRI subscale 'fantasy' was associated with measures of psychotic risk, i.e. a history of subclinical delusional ideation. The present study confirmed subtle deficits in cognitive, but not emotional ToM in first-degree relatives of schizophrenia patients, which were not explained by global cognitive deficits. Findings corroborate the assumption of distinct social-cognitive abilities as an intermediate phenotype for schizophrenia.

  8. 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

  9. 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.

  10. 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…

  11. Mitochondria-Targeted Peptide Reverses Mitochondrial Dysfunction and Cognitive Deficits in Sepsis-Associated Encephalopathy.

    PubMed

    Wu, Jing; Zhang, Mingqiang; Hao, Shuangying; Jia, Ming; Ji, Muhuo; Qiu, Lili; Sun, Xiaoyan; Yang, Jianjun; Li, Kuanyu

    2015-08-01

    Sepsis-associated encephalopathy (SAE) is associated with increased mortality, morbidity, and long-term cognitive impairments. Its pathophysiology remains to be determined and an effective pharmacologic treatment is lacking. The goal of this study was to investigate the effects of the mitochondria-targeted peptide SS-31 on mitochondrial function and cognitive deficits in SAE mice. C57BL/6 male mice were randomly divided into sham, sham + SS-31, cecal ligation and puncture (CLP), and CLP + SS-31 groups. Peptide SS-31 (5 mg/kg) was intraperitoneally administrated immediately after operation and afterwards once daily for six consecutive days. Surviving mice were subjected to behavioral tests and the hippocampus was collected for biochemical analysis 7 days after operation. The results showed that CLP resulted in high mortality rate and cognitive deficits, representative characteristics of SAE. A physiological mechanistic investigation revealed that mitochondrial function of hippocampus was severely impaired, coupled with reactive oxygen species (ROS) generation, triggering neuronal apoptosis and inflammation. Notably, administration of peptide SS-31 protected the integrity of mitochondria, reversed the mitochondrial dysfunction, inhibited the apoptosis resulting from the release of cytochrome c, diminished the response of inflammation, and ultimately reversed the behavior deficits in the SAE mice. In conclusion, our data demonstrate that daily treatment with mitochondria-targeted peptide SS-31 reduces mortality rate and ameliorates cognitive deficits, which is possibly through a mechanism of reversing mitochondrial dysfunction and partial inhibition of neuronal apoptosis and inflammation in the hippocampus of the SAE mice.

  12. The Relationship between Sluggish Cognitive Tempo, Subtypes of Attention-Deficit/Hyperactivity Disorder, and Anxiety Disorders

    ERIC Educational Resources Information Center

    Skirbekk, Benedicte; Hansen, Berit Hjelde; Oerbeck, Beate; Kristensen, Hanne

    2011-01-01

    The objective of the present study was to examine the relationship between sluggish cognitive tempo (SCT), subtypes of attention-deficit/hyperactivity disorder (ADHD), and anxiety disorders (AnxDs). One hundred and forty-one children (90 males, 51 females) aged 7-13 years were assigned to four groups, i.e., referred children with comorbid AnxDs…

  13. The Turner Syndrome: Cognitive Deficits, Affective Discrimination, and Behavior Problems.

    ERIC Educational Resources Information Center

    McCauley, Elizabeth; And Others

    1987-01-01

    The study attemped to link cognitive and social problems seen in girls with Turner syndrome by assessing the girls' ability to process affective cues. Seventeen 9- to 17-year-old girls diagnosed with Turner syndrome were compared to a matched control group on a task which required interpretation of affective intention from facial expression.…

  14. 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.

  15. 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

  16. 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.

  17. Finger agnosia and cognitive deficits in patients with Alzheimer's disease.

    PubMed

    Davis, Andrew S; Trotter, Jeffrey S; Hertza, Jeremy; Bell, Christopher D; Dean, Raymond S

    2012-01-01

    The purpose of this study was to examine the presence of finger agnosia in patients with Alzheimer's disease (AD) and to determine if level of finger agnosia was related to cognitive impairment. Finger agnosia is a sensitive measure of cerebral impairment and is associated with neurofunctional areas implicated in AD. Using a standardized and norm-referenced approach, results indicated that patients with AD evidenced significantly decreased performance on tests of bilateral finger agnosia compared with healthy age-matched controls. Finger agnosia was predictive of cognitive dysfunction on four of seven domains, including: Crystallized Language, Fluid Processing, Associative Learning, and Processing Speed. Results suggest that measures of finger agnosia, a short and simple test, may be useful in the early detection of AD.

  18. Tract-Specific Correlates of Neuropsychological Deficits in Patients with Subcortical Vascular Cognitive Impairment.

    PubMed

    Jung, Na-Yeon; Han, Cheol E; Kim, Hee Jin; Yoo, Sang Wook; Kim, Hee-Jong; Kim, Eun-Joo; Na, Duk L; Lockhart, Samuel N; Jagust, William J; Seong, Joon-Kyung; Seo, Sang Won

    2016-01-01

    The white matter tract-specific correlates of neuropsychological deficits are not fully established in patients with subcortical vascular cognitive impairment (SVCI), where white matter tract damage may be a critical factor in cognitive impairment. The purpose of this study is to investigate the tract-specific correlates of neuropsychological deficits in SVCI patients using tract-specific statistical analysis (TSSA). We prospectively recruited 114 SVCI patients, and 55 age-, gender-, and education-matched individuals with normal cognition (NC). All participants underwent diffusion weighted imaging and neuropsychological testing. We classified tractography results into fourteen major fiber tracts and analyzed group comparison and correlation with cognitive impairments. Relative to NC subjects, SVCI patients showed decreased fractional anisotropy values in bilateral anterior-thalamic radiation, cingulum, superior-longitudinal fasciculus, uncinate fasciculus, corticospinal tract, and left inferior-longitudinal fasciculus. Focal disruptions in specific tracts were associated with specific cognitive impairments. Our findings suggest that disconnection of specific white matter tracts, especially those neighboring and providing connections between gray matter regions important to certain cognitive functions, may contribute to specific cognitive impairments in SVCI. PMID:26836179

  19. Implicit cognition is impaired and dissociable in a head-injured group with executive deficits.

    PubMed

    Barker, L A; Andrade, J; Romanowski, C A J; Morton, N; Wasti, A

    2006-01-01

    Implicit or non-conscious cognition is traditionally assumed to be robust to pathology but Gomez-Beldarrain et al. recently showed deficits on a single implicit task after head injury. Laboratory research suggests that implicit processes dissociate. This study therefore examined implicit cognition in 20 head-injured patients and age- and IQ-matched controls using a battery of four implicit cognition tasks: a serial reaction time task (SRT), mere exposure effect task, automatic stereotype activation and hidden co-variation detection. Patients were assessed on an extensive neuropsychological battery, and MRI scanned. Inclusion criteria included impairment on at least one measure of executive function. The patient group was impaired relative to the control group on all the implicit cognition tasks except automatic stereotype activation. Effect size analyses using the control mean and standard deviation for reference showed further dissociations across patients and across implicit tasks. Patients impaired on implicit tasks had more cognitive deficits overall than those unimpaired, and a larger dysexecutive self/other discrepancy (DEX) score suggesting greater behavioural problems. Performance on the SRT task correlated with a composite measure of executive function. Head injury thus produced heterogeneous impairments in the implicit acquisition of new information. Implicit activation of existing knowledge structures appeared intact. Impairments in implicit cognition and executive function may interact to produce dysfunctional behaviour after head injury. Future comparisons of implicit and explicit cognition should use several measures of each function, to ensure that they measure the latent variable of interest. PMID:16436286

  20. Pyrroloquinoline quinone prevents MK-801-induced stereotypical behavior and cognitive deficits in mice.

    PubMed

    Zhou, Xingqin; Chen, Quancheng; Hu, Xindai; Mao, Shishi; Kong, Yanyan

    2014-01-01

    Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator, and nerve growth factor, prevents cognitive deficits associated with oxidative stress-induced neurodegeneration. Previous molecular imaging studies also demonstrate that PQQ binds to N-methyl D-aspartate (NMDA) receptors. In this study, we investigated the effects of PQQ on stereotypical behaviors and cognitive deficits induced by MK-801, a non-competitive NMDA antagonist used to model schizophrenia. Mice were given repeated injections of MK-801 (0.5mg/kg/d) and PQQ (0.2, 2.0, or 20 μg/kg/d) for 60 days. Behavior was evaluated using a variety of motor, social, and cognitive tests. We found that PQQ administration significantly attenuated MK-801-induced increases in stereotypical behavior and ataxia, suggesting a protective role of PQQ against MK-801-induced neuronal dysfunction and psychiatric disorders. Future studies are necessary to elucidate the underlying mechanisms of PQQ.

  1. Cognitive mechanisms underlying achievement deficits in children with mathematical learning disability.

    PubMed

    Geary, David C; Hoard, Mary K; Byrd-Craven, Jennifer; Nugent, Lara; Numtee, Chattavee

    2007-01-01

    Using strict and lenient mathematics achievement cutoff scores to define a learning disability, respective groups of children who are math disabled (MLD, n=15) and low achieving (LA, n=44) were identified. These groups and a group of typically achieving (TA, n=46) children were administered a battery of mathematical cognition, working memory, and speed of processing measures (M=6 years). The children with MLD showed deficits across all math cognition tasks, many of which were partially or fully mediated by working memory or speed of processing. Compared with the TA group, the LA children were less fluent in processing numerical information and knew fewer addition facts. Implications for defining MLD and identifying underlying cognitive deficits are discussed. PMID:17650142

  2. Identical neural risk factors predict cognitive deficit in dyslexia and schizophrenia.

    PubMed

    Leonard, Christiana M; Kuldau, John M; Maron, Leeza; Ricciuti, Nikki; Mahoney, Bryan; Bengtson, Michael; DeBose, Cheryl

    2008-03-01

    In previous work, the authors found that an anatomical risk index created from the combination of 7 neuroanatomical measures predicted reading and oral language skills in individuals with learning disabilities. Individuals with small auditory brain structures and reduced asymmetry had more deficits than those with large structures and exaggerated asymmetry. In the present study, the same anatomical index predicted reading and other cognitive abilities in 45 individuals with chronic schizophrenia. The anatomical risk index was significantly associated with broad cognitive ability (Pearson r = .53, p < .0001), reading comprehension (r = .58, p < .0001), and a measure of nonverbal reasoning (r = .39, p < .01), but not with age, parental socioeconomic status, symptom measures, alcohol use, or processing speed. These findings support the prediction that reduced size and asymmetry in temporal lobe auditory cortex and cerebellum may not be specific risk factors for schizophrenia but for cognitive deficits that characterize a broad spectrum of developmental disorders.

  3. Cognitive deficits induced by 56Fe radiation exposure

    NASA Technical Reports Server (NTRS)

    Shukitt-Hale, B.; Casadesus, G.; Cantuti-Castelvetri, I.; Rabin, B. M.; Joseph, J. A.

    2003-01-01

    Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Published by Elsevier Science Ltd on behalf of COSPAR.

  4. Cognitive deficits induced by 56Fe radiation exposure

    NASA Astrophysics Data System (ADS)

    Shukitt-Hale, B.; Casadesus, G.; Cantuti-Castelvetri, I.; Rabin, B. M.; Joseph, J. A.

    Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

  5. Cognitive deficits induced by 56Fe radiation exposure.

    PubMed

    Shukitt-Hale, B; Casadesus, G; Cantuti-Castelvetri, I; Rabin, B M; Joseph, J A

    2003-01-01

    Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

  6. Lateralized cognitive deficits in children following cerebellar lesions.

    PubMed

    Scott, R B; Stoodley, C J; Anslow, P; Paul, C; Stein, J F; Sugden, E M; Mitchell, C D

    2001-10-01

    The aim of this preliminary study was to examine the developing cognitive profiles of children with cerebellar tumours in a consecutive series of clinical patients. MRI and longitudinal intellectual profiles were obtained on seven children (two females, five males; mean age 3 years at diagnosis; mean age 7 years at first assessment). Tumours in three of the children were astrocytomas; of the remaining tumours, two were medulloblastomas, one low-grade glioma, and one ependymoma. In right-handed children, we observed an association between greater damage to right cerebellar structures and a plateauing in verbal and/or literacy skills. In contrast, greater damage to left cerebellar structures was associated with delayed or impaired non-verbal/spatial skills. Long-term cognitive development of the children studied tentatively supports a role for the cerebellum in learning/development. These findings suggest that lateralized cerebellar damage may selectively impair the development of cognitive functions subserved by the contralateral cerebral hemisphere and, in addition, that all children with cerebellar lesions in early childhood should routinely undergo long-term monitoring of their intellectual development. PMID:11665825

  7. Reading comprehension in children with ADHD: cognitive underpinnings of the centrality deficit.

    PubMed

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

    2013-04-01

    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 and Keenan, Annals of Dyslexia 59:99-113, 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.

  8. 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

  9. Testing sensory and cognitive explanations of the antisaccade deficit in schizophrenia.

    PubMed

    Leonard, Carly J; Robinson, Benjamin M; Kaiser, Samuel T; Hahn, Britta; McClenon, Clara; Harvey, Alex N; Luck, Steven J; Gold, James M

    2013-11-01

    Recent research has suggested that people with schizophrenia (PSZ) have sensory deficits, especially in the magnocellular pathway, and this has led to the proposal that dysfunctional sensory processing may underlie higher-order cognitive deficits. Here we test the hypothesis that the antisaccade deficit in PSZ reflects dysfunctional magnocellular processing rather than impaired cognitive processing, as indexed by working memory capacity. This is a plausible hypothesis because oculomotor regions have direct magnocellular inputs, and the stimuli used in most antisaccade tasks strongly activate the magnocellular visual pathway. In the current study, we examined both prosaccade and antisaccade performance in PSZ (N = 22) and matched healthy control subjects (HCS; N = 22) with Gabor stimuli designed to preferentially activate the magnocellular pathway, the parvocellular pathway, or both pathways. We also measured working memory capacity. PSZ exhibited impaired antisaccade performance relative to HCS across stimulus types, with impairment even for stimuli that minimized magnocellular activation. Although both sensory thresholds and working memory capacity were impaired in PSZ, only working memory capacity was correlated with antisaccade accuracy, consistent with a cognitive rather than sensory origin for the antisaccade deficit. PMID:24364614

  10. Evidence that aetiological risk factors for psychiatric disorders cause distinct patterns of cognitive deficits.

    PubMed

    Wallace, J; Marston, H M; McQuade, R; Gartside, S E

    2014-06-01

    Schizophrenia and bipolar disorder are associated with neurocognitive symptoms including deficits in attentional set shifting (changing attentional focus from one perceptual dimension to another) and reversal learning (learning a reversed stimulus/outcome contingency). Maternal infection during gestation and chronically flattened glucocorticoid rhythm are aetiological risk factors for schizophrenia and bipolar disorder. We hypothesised that these factors are causative in the neurocognitive deficits observed in schizophrenia and bipolar disorder. Here we used maternal immune activation (MIA) as a rat model of maternal infection, and sub-chronic low dose corticosterone treatment as a rat model of flattened glucocorticoid rhythm. For comparison we examined the effects of sub-chronic phencyclidine - a widely used rodent model of schizophrenia pathology. The effects of these three treatments on neurocognition were explored using the attentional set shifting task - a multistage test of executive functions. As expected, phencyclidine treatment selectively impaired set shifting ability. In contrast, MIA caused a marked and selective impairment of reversal learning. Corticosterone treatment impaired reversal learning but in addition also impaired rule abstraction and prevented the animals from forming an attentional set. The reversal learning deficits induced by MIA and corticosterone treatment were due to increases in non-perseverative rather than perseverative errors. Our data indicate that the cognitive deficits of schizophrenia and bipolar disorder may be explained by aetiological factors including maternal infection and glucocorticoid abnormalities and moreover suggest that the particular spectrum of cognitive deficits in individual patients may depend on the specific underlying aetiology of the disorder. PMID:24377755

  11. Cognitive and emotional deficits in chronic alcoholics: a role for the cerebellum?

    PubMed

    Fitzpatrick, Lauren E; Crowe, Simon F

    2013-08-01

    It is now widely accepted that in addition to motor coordination, the cerebellum is also involved in the modulation of cognitive and affective processes. Despite alcoholic cerebellar degeneration (ACD) being the most common form of cerebellar disorder, little systematic investigation of cerebellar-mediated cognitive and affective deficits has occurred in chronic alcoholics. Forty-nine chronic alcoholics and 29 healthy control participants underwent testing of cognitive and affective function, along with measurement of cerebellar ataxia using the International Cooperative Ataxia Rating Scale (Trouillas et al., Journal of the Neurological Sciences 145:205-11, 1997). The alcoholic group demonstrated significantly poorer performance as compared to the control group in a number of domains, including visuospatial and language skills, psychomotor speed, new learning and memory, executive functioning, and emotional regulation and affect processing. There were no differences between the alcoholic and control groups in immediate attention and working memory abilities. Years of heavy drinking and total period of abstinence were found to be the best predictors of cognitive and emotional function in the alcoholic group. After accounting for alcohol chronicity, there was still a relationship between the degree of clinical signs of ACD and some areas of cognitive and emotional functioning, including language, executive functioning, processing speed and affect processing. The results suggest that some of the cognitive and affective deficits observed in chronic alcoholics may be mediated, at least in part, by cerebellar dysfunction. These findings add support to the theory of disruption to bidirectional cerebro-cerebellar circuitry underlying cognitive and affective deficits in chronic alcoholics. PMID:23436003

  12. 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.

  13. Reactive oxygen species mediate cognitive deficits in experimental temporal lobe epilepsy

    PubMed Central

    Pearson, Jennifer N.; Rowley, Shane; Liang, Li-Ping; White, Andrew M.; Day, Brian J.; Patel, Manisha

    2016-01-01

    Cognitive dysfunction is an important comorbidity of temporal lobe epilepsy (TLE). However, no targeted therapies are available and the mechanisms underlying cognitive impairment, specifically deficits in learning and memory associated with TLE remain unknown. Oxidative stress is known to occur in the pathogenesis of TLE but its functional role remains to be determined. Here, we demonstrate that oxidative stress and resultant processes contribute to cognitive decline associated with epileptogenesis. Using a synthetic catalytic antioxidant, we show that pharmacological removal of reactive oxygen species (ROS) prevents 1) oxidative stress, 2) deficits in mitochondrial oxygen consumption rates, 3) hippocampal neuronal loss and 4) cognitive dysfunction without altering the intensity of the initial status epilepticus (SE) or epilepsy development in a rat model of SE-induced TLE. Moreover, the effects of the catalytic antioxidant on cognition persisted beyond the treatment period suggestive of disease-modification. The data implicate oxidative stress as a novel mechanism by which cognitive dysfunction can arise during epileptogenesis and suggest a potential disease-modifying therapeutic approach to target it. PMID:26184893

  14. Reactive oxygen species mediate cognitive deficits in experimental temporal lobe epilepsy.

    PubMed

    Pearson, Jennifer N; Rowley, Shane; Liang, Li-Ping; White, Andrew M; Day, Brian J; Patel, Manisha

    2015-10-01

    Cognitive dysfunction is an important comorbidity of temporal lobe epilepsy (TLE). However, no targeted therapies are available and the mechanisms underlying cognitive impairment, specifically deficits in learning and memory associated with TLE remain unknown. Oxidative stress is known to occur in the pathogenesis of TLE but its functional role remains to be determined. Here, we demonstrate that oxidative stress and resultant processes contribute to cognitive decline associated with epileptogenesis. Using a synthetic catalytic antioxidant, we show that pharmacological removal of reactive oxygen species (ROS) prevents 1) oxidative stress, 2) deficits in mitochondrial oxygen consumption rates, 3) hippocampal neuronal loss and 4) cognitive dysfunction without altering the intensity of the initial status epilepticus (SE) or epilepsy development in a rat model of SE-induced TLE. Moreover, the effects of the catalytic antioxidant on cognition persisted beyond the treatment period suggestive of disease-modification. The data implicate oxidative stress as a novel mechanism by which cognitive dysfunction can arise during epileptogenesis and suggest a potential disease-modifying therapeutic approach to target it.

  15. Reactive oxygen species mediate cognitive deficits in experimental temporal lobe epilepsy.

    PubMed

    Pearson, Jennifer N; Rowley, Shane; Liang, Li-Ping; White, Andrew M; Day, Brian J; Patel, Manisha

    2015-10-01

    Cognitive dysfunction is an important comorbidity of temporal lobe epilepsy (TLE). However, no targeted therapies are available and the mechanisms underlying cognitive impairment, specifically deficits in learning and memory associated with TLE remain unknown. Oxidative stress is known to occur in the pathogenesis of TLE but its functional role remains to be determined. Here, we demonstrate that oxidative stress and resultant processes contribute to cognitive decline associated with epileptogenesis. Using a synthetic catalytic antioxidant, we show that pharmacological removal of reactive oxygen species (ROS) prevents 1) oxidative stress, 2) deficits in mitochondrial oxygen consumption rates, 3) hippocampal neuronal loss and 4) cognitive dysfunction without altering the intensity of the initial status epilepticus (SE) or epilepsy development in a rat model of SE-induced TLE. Moreover, the effects of the catalytic antioxidant on cognition persisted beyond the treatment period suggestive of disease-modification. The data implicate oxidative stress as a novel mechanism by which cognitive dysfunction can arise during epileptogenesis and suggest a potential disease-modifying therapeutic approach to target it. PMID:26184893

  16. Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke.

    PubMed

    Li, Wen-Lei; Cai, Hui-Hui; Wang, Bin; Chen, Ling; Zhou, Qi-Gang; Luo, Chun-Xia; Liu, Na; Ding, Xin-Sheng; Zhu, Dong-Ya

    2009-01-01

    Cognitive deficits, including spatial memory impairment, are very common after ischemic stroke. Neurogenesis in the dentate gyrus (DG) contributes to forming spatial memory in the ischemic brain. Fluoxetine, a selective serotonin reuptake inhibitor, can enhance neurogenesis in the hippocampus in physiological situations and some neurological diseases. However, whether it has effects on ischemia-induced spatial cognitive impairment and hippocampal neurogenesis has not been determined. Here we report that fluoxetine treatment (10 mg kg(-1), i.p.) for 4 weeks promoted the survival of newborn cells in the ischemic hippocampus and, consequently, attenuated spatial memory impairment of mice after focal cerebral ischemia. Disrupting hippocampal neurogenesis blocked the beneficial effect of fluoxetine on ischemia-induced spatial cognitive impairment. These results suggest that chronic fluoxetine treatment benefits spatial cognitive function recovery following ischemic insult, and the improved cognitive function is associated with enhanced newborn cell survival in the hippocampus. Our results raise the possibility that fluoxetine can be used as a drug to treat poststroke spatial cognitive deficits.

  17. Interaction of Cognitive Distortions and Cognitive Deficits in the Formulation and Treatment of Obsessive-Compulsive Behaviours in a Woman with an Intellectual Disability

    ERIC Educational Resources Information Center

    Willner, Paul; Goodey, Rebecca

    2006-01-01

    Aims: This case study describes the formulation and cognitive-behavioural treatment (CBT) of obsessive-compulsive thoughts and behaviours in a woman with an intellectual disability. The report aimed to distinguish the cognitive deficits that reflect her disability from the cognitive distortions integral to her obsessive-compulsive disorder. Case…

  18. RPS23RG1 reduces Aβ oligomer-induced synaptic and cognitive deficits

    PubMed Central

    Yan, Li; Chen, Yaomin; Li, Wubo; Huang, Xiumei; Badie, Hedieh; Jian, Fan; Huang, Timothy; Zhao, Yingjun; Cohen, Stanley N.; Li, Limin; Zhang, Yun-wu; Luo, Huanmin; Tu, Shichun; Xu, Huaxi

    2016-01-01

    Alzheimer’s disease (AD) is the most common form of dementia in the elderly. It is generally believed that β-amyloidogenesis, tau-hyperphosphorylation, and synaptic loss underlie cognitive decline in AD. Rps23rg1, a functional retroposed mouse gene, has been shown to reduce Alzheimer’s β-amyloid (Aβ) production and tau phosphorylation. In this study, we have identified its human homolog, and demonstrated that RPS23RG1 regulates synaptic plasticity, thus counteracting Aβ oligomer (oAβ)-induced cognitive deficits in mice. The level of RPS23RG1 mRNA is significantly lower in the brains of AD compared to non-AD patients, suggesting its potential role in the pathogenesis of the disease. Similar to its mouse counterpart, human RPS23RG1 interacts with adenylate cyclase, activating PKA/CREB, and inhibiting GSK-3. Furthermore, we show that human RPS23RG1 promotes synaptic plasticity and offsets oAβ-induced synaptic loss in a PKA-dependent manner in cultured primary neurons. Overexpression of Rps23rg1 in transgenic mice consistently prevented oAβ-induced PKA inactivation, synaptic deficits, suppression of long-term potentiation, and cognitive impairment as compared to wild type littermates. Our study demonstrates that RPS23RG1 may reduce the occurrence of key elements of AD pathology and enhance synaptic functions to counteract oAβ-induced synaptic and cognitive deficits in AD. PMID:26733416

  19. Specific cognitive deficits are common in children with Duchenne muscular dystrophy.

    PubMed

    Wicksell, Rikard K; Kihlgren, Margareta; Melin, Lennart; Eeg-Olofsson, Orvar

    2004-03-01

    A neuropsychological assessment was conducted to study cognition, with emphasis on memory, information processing/learning ability, and executive functions in boys with Duchenne muscular dystrophy (DMD). A group of 20 boys with DMD, aged 7 to 14 years (mean age 9 years 5 months, SD 2 years 2 months), was contrasted with 17 normally developing age-matched comparison individuals, using specific neuropsychological tests (Block Span, Digit Span, Story Recall, Rey Auditory Verbal Learning Test, Rey Complex Figure Test, Spatial Learning Test, Verbal Fluency, Trail Making Test, Tower of London, Memory for Faces, and Raven's Coloured Progressive Matrices). The DMD group performed significantly worse on all aspects of memory, learning, and executive functions. There was no significant difference in general intellectual ability between the two groups. Analyses of group differences indicate that problems in short-term memory are the most apparent, suggesting specific cognitive deficits. The differences between the groups were similar for both verbal-auditory and visuospatial tests, thus contradicting the idea that cognitive deficits are related to type of stimulus presented. It is concluded from this study that short-term memory deficits might play a critical role in the cognitive impairment and intellectual development seen in those with DMD. PMID:14995084

  20. 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…

  1. A cognitive deficit induced in rats by chronic intermittent cold stress is reversed by chronic antidepressant treatment

    PubMed Central

    Danet, M.; Lapiz-Bluhm, S.; Morilak, David A.

    2010-01-01

    We have previously reported that 14-days of chronic intermittent cold (CIC) stress induced a cognitive deficit in reversal learning on the rat attentional set-shifting test. This effect may be related to dysregulation of 5-HT function in orbitofrontal cortex, as a model of cognitive dysfunction in depression. To test the ability of chronic antidepressant drug treatment to reverse the cognitive deficit induced by CIC, it was first necessary to assess the temporal characteristics of the CIC-induced cognitive deficit. Thus, in the first study, we assessed the duration of the cognitive deficit following 2-weeks CIC stress. Replicating previous experiments, CIC induced a reversal learning deficit tested 3 days after the last cold exposure. However, cognitive performance of CIC-stressed rats was no different from unstressed controls when tested 7, 14 or 21 days after termination of the stress treatment. We next compared behavior 3 days after 2-weeks CIC to that seen 3 days after 5-weeks CIC, and found similar deficits in reversal learning. Thus, in the final study, antidepressant drug treatment was initiated after 2-weeks of CIC stress, and was maintained for 3 weeks, concurrent with the continuation of CIC stress. Both chronic and acute treatment with the selective serotonin reuptake inhibitor, citalopram, but not the norepinephrine reuptake blocker, desipramine, reversed the cognitive deficit induced by CIC stress. Thus, this stress-induced cognitive deficit may be a useful model for cognitive deficits related to prefrontal cortical hypoactivity in depression, and for investigating neurobiological mechanisms underlying the beneficial effects of chronic antidepressant drug treatment. PMID:20149267

  2. 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.

  3. Levetiracetam might act as an efficacious drug to attenuate cognitive deficits of Alzheimer's disease.

    PubMed

    Xiao, Rong

    2016-01-01

    Levetiracetam is a homologue of piracetam with an a-ethyl side-chain substitution and it is a Food and Drug Administration (FDA) approved antiepileptic drug. Recently, several studies have found that levetiracetam was able to reduce seizure frequency in epileptic seizures patients without affecting their cognitive functions. In the present review, the effects of levetiracetam on cognitive improvement were summarized in epileptic seizures patients with or without Alzheimer's disease (AD), high-grade glioma (HGG) patients and amnestic mild cognitive impairment (aMCI) patients. In addition, levetiracetam was observed to improve the cognitive deficits in normal aged animals and the transgenic animal models with AD, suggesting that levetiracetam may be a better choice for the prevention or treatment of AD.

  4. Social Cognition Deficits and Psychopathic Traits in Young People Seeking Mental Health Treatment

    PubMed Central

    van Zwieten, Anita; Meyer, Johanna; Hermens, Daniel F.; Hickie, Ian B.; Hawes, David J.; Glozier, Nicholas; Naismith, Sharon L.; Scott, Elizabeth M.; Lee, Rico S. C.; Guastella, Adam J.

    2013-01-01

    Antisocial behaviours and psychopathic traits place an individual at risk for criminality, mental illness, substance dependence, and psychosocial dysfunction. Social cognition deficits appear to be associated with psychopathic traits and are believed to contribute to interpersonal dysfunction. Most research investigating the relationship of these traits with social cognition has been conducted either in children or adult forensic settings. We investigated whether psychopathic traits were associated with social cognition in 91 young people presenting for mental healthcare (aged between 15 and 25 years). Participants completed symptom severity measures, neuropsychological tests, the Reading the Mind in the Eyes Test of social cognition (RMET), and the Antisocial Process Screening Device (APSD) to assess psychopathic personality traits. Correlation analyses showed poorer social cognition was associated with greater psychopathic traits (r = −.36, p = .01). Interestingly, social cognition performance predicted unique variance in concurrent psychopathic personality traits above gender, IQ sustained attention, and working memory performance. These findings suggest that social cognitive impairments are associated with psychopathic tendencies in young people presenting for community mental healthcare. Research is needed to establish the directionality of this relationship and to determine whether social cognition training is an effective treatment amongst young people with psychopathic tendencies. PMID:23861799

  5. 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.

  6. GHB-Induced Cognitive Deficits During Adolescence and the Role of NMDA Receptor.

    PubMed

    Sircar, R; Wu, L-C; Reddy, K; Sircar, D; Basak, A K

    2011-03-01

    We have earlier reported that γ-hydroxybutyric acid (GHB) disrupts the acquisition of spatial learning and memory in adolescent rats. GHB is known to interact with several neurotransmitter systems that have been implicated in cognitive functioning. The N-methyl-D-aspartate receptor (NR) -type of glutamate receptor is considered to be an important target for spatial learning and memory. Molecular mechanisms governing the neuroadptations following repeated GHB treatment in adolecent rats remain unknown. We examined the role of NMDA receptor in adolescent GHB-induced cognitive deficit. Adolescent rats were administered with GHB on 6 consecutive days, and surface-expressed NMDA receptor subunits levels were measured. GHB significantly decreased NR1 levels in the frontal cortex. Adolescent GHB also significantly reduced cortical NR2A subunit levels. Our findings support the hypothesis that adolescent GHB-induced cogntive deficits are associated with neuroadaptations in glutamatergic transmission, particulaly NR functioning in the frontal cortex.

  7. Reelin supplementation recovers synaptic plasticity and cognitive deficits in a mouse model for Angelman syndrome.

    PubMed

    Hethorn, Whitney R; Ciarlone, Stephanie L; Filonova, Irina; Rogers, Justin T; Aguirre, Daniela; Ramirez, Raquel A; Grieco, Joseph C; Peters, Melinda M; Gulick, Danielle; Anderson, Anne E; L Banko, Jessica; Lussier, April L; Weeber, Edwin J

    2015-05-01

    The Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus-dependent learning and memory. A single direct in vivo application of Reelin enhances long-term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long-term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits. In this study, we investigated the effects of Reelin administration on synaptic plasticity and cognitive function in a mouse model of AS and demonstrated that bilateral, intraventricular injections of Reelin recover synaptic function and corresponding hippocampus-dependent associative and spatial learning and memory. Additionally, we describe alteration of the Reelin profile in tissue from both the AS mouse and post-mortem human brain. PMID:25864922

  8. GHB–Induced Cognitive Deficits During Adolescence and the Role of NMDA Receptor

    PubMed Central

    Sircar, R; Wu, L-C; Reddy, K; Sircar, D; Basak, A.K

    2011-01-01

    We have earlier reported that γ-hydroxybutyric acid (GHB) disrupts the acquisition of spatial learning and memory in adolescent rats. GHB is known to interact with several neurotransmitter systems that have been implicated in cognitive functioning. The N-methyl-D-aspartate receptor (NR) -type of glutamate receptor is considered to be an important target for spatial learning and memory. Molecular mechanisms governing the neuroadptations following repeated GHB treatment in adolecent rats remain unknown. We examined the role of NMDA receptor in adolescent GHB-induced cognitive deficit. Adolescent rats were administered with GHB on 6 consecutive days, and surface-expressed NMDA receptor subunits levels were measured. GHB significantly decreased NR1 levels in the frontal cortex. Adolescent GHB also significantly reduced cortical NR2A subunit levels. Our findings support the hypothesis that adolescent GHB-induced cogntive deficits are associated with neuroadaptations in glutamatergic transmission, particulaly NR functioning in the frontal cortex. PMID:21886597

  9. Reelin supplementation recovers synaptic plasticity and cognitive deficits in a mouse model for Angelman syndrome

    PubMed Central

    Hethorn, Whitney R; Ciarlone, Stephanie L; Filonova, Irina; Rogers, Justin T; Aguirre, Daniela; Ramirez, Raquel A; Grieco, Joseph C; Peters, Melinda M; Gulick, Danielle; Anderson, Anne E; L Banko, Jessica; Lussier, April L; Weeber, Edwin J

    2015-01-01

    The Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus-dependent learning and memory. A single direct in vivo application of Reelin enhances long-term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long-term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits. In this study, we investigated the effects of Reelin administration on synaptic plasticity and cognitive function in a mouse model of AS and demonstrated that bilateral, intraventricular injections of Reelin recover synaptic function and corresponding hippocampus-dependent associative and spatial learning and memory. Additionally, we describe alteration of the Reelin profile in tissue from both the AS mouse and post-mortem human brain. PMID:25864922

  10. Cognitive and neuropsychological characteristics of attention deficit hyperactivity disorder children receiving stimulant medications.

    PubMed

    Risser, M G; Bowers, T G

    1993-12-01

    10 children receiving stimulant medication for Attention Deficit Hyperactivity Disorder were compared to normal children on cognitive and neuropsychological dimensions in a pilot study. When compared with 10 normal children the ADHD children showed significant differences on cognitive measures, including the Wechsler Developmental Index, the Bender Visual-motor Gestalt Test, and the Benton Revised Visual Retention Test. Elevated levels of polyspike EEG activity were also noted for these children. Analysis suggested that ADHD children receiving stimulant medications may have persisting neuropsychological difficulty. Further research on the neuropsychological correlates of ADHD seems warranted.

  11. 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.

  12. 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. PMID:20594394

  13. The Energetic Value of Land-Based Foods in Western Hudson Bay and Their Potential to Alleviate Energy Deficits of Starving Adult Male Polar Bears

    PubMed Central

    Gormezano, Linda J.; Rockwell, Robert F.

    2015-01-01

    Climate change is predicted to expand the ice-free season in western Hudson Bay and when it grows to 180 days, 28–48% of adult male polar bears are projected to starve unless nutritional deficits can be offset by foods consumed on land. We updated a dynamic energy budget model developed by Molnar et al. to allow influx of additional energy from novel terrestrial foods (lesser snow geese, eggs, caribou) that polar bears currently consume as part of a mixed diet while on land. We calculated the units of each prey, alone and in combination, needed to alleviate these lethal energy deficits under conditions of resting or limited movement (2 km d-1) prior to starvation. We further considered the total energy available from each sex and age class of each animal prey over the period they would overlap land-bound polar bears and calculated the maximum number of starving adult males that could be sustained on each food during the ice-free season. Our results suggest that the net energy from land-based food, after subtracting costs of limited movement to obtain it, could eliminate all projected nutritional deficits of starving adult male polar bears and likely other demographic groups as well. The hunting tactics employed, success rates as well as behavior and abundance of each prey will determine the realized energetic values for individual polar bears. Although climate change may cause a phenological mismatch between polar bears and their historical ice-based prey, it may simultaneously yield a new match with certain land-based foods. If polar bears can transition their foraging behavior to effectively exploit these resources, predictions for starvation-related mortality may be overestimated for western Hudson Bay. We also discuss potential complications with stable-carbon isotope studies to evaluate utilization of land-based foods by polar bears including metabolic effects of capture-related stress and consuming a mixed diet. PMID:26061693

  14. The Energetic Value of Land-Based Foods in Western Hudson Bay and Their Potential to Alleviate Energy Deficits of Starving Adult Male Polar Bears.

    PubMed

    Gormezano, Linda J; Rockwell, Robert F

    2015-01-01

    Climate change is predicted to expand the ice-free season in western Hudson Bay and when it grows to 180 days, 28-48% of adult male polar bears are projected to starve unless nutritional deficits can be offset by foods consumed on land. We updated a dynamic energy budget model developed by Molnar et al. to allow influx of additional energy from novel terrestrial foods (lesser snow geese, eggs, caribou) that polar bears currently consume as part of a mixed diet while on land. We calculated the units of each prey, alone and in combination, needed to alleviate these lethal energy deficits under conditions of resting or limited movement (2 km d-1) prior to starvation. We further considered the total energy available from each sex and age class of each animal prey over the period they would overlap land-bound polar bears and calculated the maximum number of starving adult males that could be sustained on each food during the ice-free season. Our results suggest that the net energy from land-based food, after subtracting costs of limited movement to obtain it, could eliminate all projected nutritional deficits of starving adult male polar bears and likely other demographic groups as well. The hunting tactics employed, success rates as well as behavior and abundance of each prey will determine the realized energetic values for individual polar bears. Although climate change may cause a phenological mismatch between polar bears and their historical ice-based prey, it may simultaneously yield a new match with certain land-based foods. If polar bears can transition their foraging behavior to effectively exploit these resources, predictions for starvation-related mortality may be overestimated for western Hudson Bay. We also discuss potential complications with stable-carbon isotope studies to evaluate utilization of land-based foods by polar bears including metabolic effects of capture-related stress and consuming a mixed diet.

  15. The Energetic Value of Land-Based Foods in Western Hudson Bay and Their Potential to Alleviate Energy Deficits of Starving Adult Male Polar Bears.

    PubMed

    Gormezano, Linda J; Rockwell, Robert F

    2015-01-01

    Climate change is predicted to expand the ice-free season in western Hudson Bay and when it grows to 180 days, 28-48% of adult male polar bears are projected to starve unless nutritional deficits can be offset by foods consumed on land. We updated a dynamic energy budget model developed by Molnar et al. to allow influx of additional energy from novel terrestrial foods (lesser snow geese, eggs, caribou) that polar bears currently consume as part of a mixed diet while on land. We calculated the units of each prey, alone and in combination, needed to alleviate these lethal energy deficits under conditions of resting or limited movement (2 km d-1) prior to starvation. We further considered the total energy available from each sex and age class of each animal prey over the period they would overlap land-bound polar bears and calculated the maximum number of starving adult males that could be sustained on each food during the ice-free season. Our results suggest that the net energy from land-based food, after subtracting costs of limited movement to obtain it, could eliminate all projected nutritional deficits of starving adult male polar bears and likely other demographic groups as well. The hunting tactics employed, success rates as well as behavior and abundance of each prey will determine the realized energetic values for individual polar bears. Although climate change may cause a phenological mismatch between polar bears and their historical ice-based prey, it may simultaneously yield a new match with certain land-based foods. If polar bears can transition their foraging behavior to effectively exploit these resources, predictions for starvation-related mortality may be overestimated for western Hudson Bay. We also discuss potential complications with stable-carbon isotope studies to evaluate utilization of land-based foods by polar bears including metabolic effects of capture-related stress and consuming a mixed diet. PMID:26061693

  16. Self-perceived cognitive deficits and their relationship with internalized stigma and quality of life in patients with schizophrenia

    PubMed Central

    Shin, Yeon-Jeong; Joo, Yo-Han; Kim, Jong-Hoon

    2016-01-01

    Background We investigated self-perceived cognitive deficits and their relationship with internalized stigma and quality of life in patients with schizophrenia in order to shed light on the clinical correlates of subjective cognitive deficits in schizophrenia. Methods Seventy outpatients with schizophrenia were evaluated. Patients’ self-perceived cognitive deficits, internalized stigma, and subjective quality of life were assessed using the Scale to Investigate Cognition in Schizophrenia (SSTICS), the Internalized Stigma of Mental Illness Scale (ISMI), and the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4), respectively. Correlation and regression analyses controlling for the severity of symptoms of schizophrenia were performed, and a mediation analysis was conducted to examine the hypothesis that internalized stigma mediates the relationship between self-perceived cognitive deficits and subjective quality of life. Results Pearson’s partial correlation analysis showed significant correlations among the SSTICS, ISMI, and SQLS-R4 scores (P<0.01). Multiple regression analysis showed that the SSTICS and ISMI scores significantly predicted the SQLS-R4 score (P<0.01). Mediation analysis revealed that the strength of the association between the SSTICS and SQLS-R4 scores decreased from β=0.74 (P<0.01) to β=0.56 (P<0.01), when the ISMI score was statistically controlled. The Sobel test revealed that this difference was significant (P<0.01), indicating that internalized stigma partially mediated the relationship between self-perceived cognitive deficits and quality of life. Conclusion The present study indicates that self-perceived cognitive deficits are significantly associated with internalized stigma and quality of life. Furthermore, internalized stigma was identified as a partial mediator of the relationship between self-perceived cognitive deficits and quality of life. These findings suggest that clinicians should be aware that patients with

  17. Methodology and validity in the construction of computational models of cognitive deficits following brain damage.

    PubMed

    Mayall, K

    1998-05-01

    Over recent years, neural network models of several cognitive neuropsychological disorders have been developed. These include word recognition difficulties, face recognition difficulties, attentional deficits, visual processing impairments, semantic deficits, and aphasia. These models are useful in various ways. Firstly, they require detailed specifications of theories, and can focus attention on critical assumptions. Secondly, they can query alternative theories, and provide predictions which can be verified by testing patients. In this paper, issues relating both to the methodology and validity of attempts to model cognitive deficits using neural networks will be discussed, providing examples from several studies. Issues discussed will include the requirement for models to perform normally prior to damage, and to show potential effects of rehabilitation or partial recovery following damage. A single model should be able to incorporate multiple symptoms of a deficit and ideally also multiple syndromes when different lesions are introduced. The model must also be able to handle variability between patients with the same syndrome, and even with the same patient at different test sessions.

  18. Methodology and validity in the construction of computational models of cognitive deficits following brain damage.

    PubMed

    Mayall, K

    1998-05-01

    Over recent years, neural network models of several cognitive neuropsychological disorders have been developed. These include word recognition difficulties, face recognition difficulties, attentional deficits, visual processing impairments, semantic deficits, and aphasia. These models are useful in various ways. Firstly, they require detailed specifications of theories, and can focus attention on critical assumptions. Secondly, they can query alternative theories, and provide predictions which can be verified by testing patients. In this paper, issues relating both to the methodology and validity of attempts to model cognitive deficits using neural networks will be discussed, providing examples from several studies. Issues discussed will include the requirement for models to perform normally prior to damage, and to show potential effects of rehabilitation or partial recovery following damage. A single model should be able to incorporate multiple symptoms of a deficit and ideally also multiple syndromes when different lesions are introduced. The model must also be able to handle variability between patients with the same syndrome, and even with the same patient at different test sessions. PMID:9654377

  19. Luteolin protects against high fat diet-induced cognitive deficits in obesity mice.

    PubMed

    Liu, Yi; Fu, Xiaobin; Lan, Nuo; Li, Sai; Zhang, Jingzheng; Wang, Shuaishuai; Li, Cheng; Shang, Yanguo; Huang, Tonghui; Zhang, Ling

    2014-07-01

    The epidemic and experimental studies have confirmed that the obesity can lead to neuroinflammation, neurodegenerative diseases and adversely affect cognition. Despite the numerous elucidations on the impact of obesity on cognition decline, the contributors to the impairments in obesity remain unclear. Male C57BL/6J mice were fed either a control or high-fat diet (HFD) for 16 weeks and then randomized into four groups treated with their respective diets for 4 weeks including control diet (CD); control diet+luteolin (CDL); high-fat diet (HFD), high-fat diet+luteolin (HFDL). The dose of luteolin was 10mg/kg, oral. We showed that adding luteolin in high-fat diet can significantly reduce body weight gain, food intake and plasma cytokines as well as improving glucose metabolism of mice on HFD. Importantly, we showed that luteolin treatment had the effects of alleviating neuroinflammation, oxidative stress and neuronal insulin resistance in the mouse brain, restored blood adipocytokines level to normal. Furthermore, luteolin increased the level of brain-derived neurotrophic factor (BDNF), the action of synapsin I (SYP) and postsynaptic density protein 95 (PSD-95) in the cortex and hippocampus as to that the behavioral performance in Morris water maze (MWM) and step-through task were significantly improved. These results indicate a previously unrecognized potential of luteolin in alleviating obesity-induced cognitive impairment for type-2 diabetes mellitus and Alzheimer disease (AD).

  20. Rapamycin ester analog CCI-779/Temsirolimus alleviates tau pathology and improves motor deficit in mutant tau transgenic mice.

    PubMed

    Frederick, Christelle; Ando, Kunie; Leroy, Karelle; Héraud, Céline; Suain, Valérie; Buée, Luc; Brion, Jean-Pierre

    2015-01-01

    Neurofibrillary tangles are intracellular inclusions made of tau protein that accumulates in neurons in Alzheimer's disease (AD) and in other tauopathies. We have investigated the ability of the rapamycin ester CCI-779/Temsilorimus, a mTOR inhibitor with better stability and pharmacological properties compared to rapamycin, to interfere with the development of a motor phenotype and tau pathology in a mutant tau mouse model developing neurofibrillary tangles, by stimulation of mTOR dependent macroautophagy. Mutant tau mice (Tg30) were treated with CCI-779 before onset of motor signs for 7 months (from 5 to 12 months of age) or after the onset of motor signs for 2 months (from 10 to 12 months of age). End-point motor deficits were 50% lower in the group of Tg30 mice treated for 7 months. Inhibition of mTOR signaling and stimulation of macroautophagy in the brain of CCI-779 treated Tg30 mice was suggested by decreased phosphorylation of mTOR downstream signaling molecules p70S6 kinase and Akt and increased level of the autophagy markers Rab7 and LC3-II. CCI-779 treatment decreased the brain levels of Sarkosyl-insoluble tau and phosphotau inTg30 mice both after 2 months or 7 months of treatment. The density of neurofibrillary tangles was significantly decreased when treatment was started prior onset of motor signs. These results indicate that stimulation of mTOR dependent autophagy by CCI-779 compound is efficient to counteract the accumulation of abnormal tau when administered early or late in a tauopathy model and to improve a motor deficit when started before onset of motor signs.

  1. Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse.

    PubMed

    Bouët, Valentine; Freret, Thomas; Toutain, Jérôme; Divoux, Didier; Boulouard, Michel; Schumann-Bard, Pascale

    2007-02-01

    Whereas behavioral impairments after stroke are increasingly studied in the rat, little is known about the long-term functional consequences of focal ischemia in the mouse. To address this issue, Swiss mice underwent transient (60 min) intraluminal occlusion of the middle cerebral artery (MCAo) or sham surgery. Sensorimotor (chimney, accelerating rotarod, pole, corner, adhesive removal and staircase tests) and cognitive (passive avoidance and Morris water maze) performances were regularly assessed during 1 month, after which the final histological lesion was measured. Motor coordination and balance, assessed by the chimney and rotarod tests, were transiently altered by MCAo. Moreover, bradykinesia was evidenced by the pole test. The most striking and long-lasting (1 month) sensorimotor deficits were postural asymmetries on the corner test, bilateral skilled forepaw reaching deficits on the staircase test and a contralateral sensorimotor impairment on the adhesive removal test. MCAo animals showed normal spatial learning abilities on the Morris water maze test, but they displayed learning deficits measured by the passive avoidance test. This latter deficit was significantly correlated with both cortical and striatal damage. Our findings demonstrate the usefulness of three tests that had never been reported in the mouse after ischemia: the adhesive removal, staircase and pole tests, which showed deficits 1 month after ischemia and should therefore constitute meaningful tools in mice for assessing both neuroprotective and regenerative therapies in stroke preclinical studies.

  2. 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

  3. Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease.

    PubMed

    Siepel, Françoise J; Brønnick, Kolbjørn S; Booij, Jan; Ravina, Bernard M; Lebedev, Alexander V; Pereira, Joana B; Grüner, Renate; Aarsland, Dag

    2014-12-01

    Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross-sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single-photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [(123) I]FP-CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age-moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD. PMID:25284687

  4. 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. PMID:23841985

  5. The cognitive genetics of attention deficit hyperactivity disorder (ADHD): sustained attention as a candidate phenotype.

    PubMed

    Bellgrove, Mark A; Hawi, Ziarih; Gill, Michael; Robertson, Ian H

    2006-08-01

    Here we describe the application of cognitive genetics to the study of attention deficit hyperactivity disorder (ADHD). Cognitive genetics owes much to the pioneering work of cognitive neuropsychologists such as John Marshall, whose careful observations of cognitive dissociations between brain-lesioned patients greatly advanced the theoretical understanding of normal cognitive function. These theories have in turn helped to constrain linkages between candidate genes and cognitive processes and thus help to drive the relatively new field of cognitive genetics in a hypothesis-driven fashion. We examined the relationship between sustained attention deficits in ADHD and genetic variation in a catecholamine-related gene, dopamine beta hydroxylase (DbetaH). DBH encodes the enzyme that converts dopamine to noradrenaline and is crucial to catecholamine regulation. A polymorphism with the DBH gene has been associated with ADHD. In fifty-two children with ADHD, we examined whether variation in the Taq I DBH gene polymorphism was related to sustained attention performance. Participants performed the Sustained Attention to Response Test (SART). Performance on the SART discriminates ADHD from control children, and in imaging work, is associated with right frontoparietal activation. A significant effect of DBH genotype was found on SART performance measures. Children possessing two copies of the ADHD-associated risk allele (A2) had significantly poorer sustained attention than those ADHD children who did not possess this allele or a non-genotyped control group. The DBH gene may contribute to the susceptibility for ADHD, in part because of its varying effects on the development of brain mechanisms mediating sustained attention.

  6. Memantine in the prevention or alleviation of electroconvulsive therapy induces cognitive disorders: A placebo controlled trial.

    PubMed

    Abbasinazari, Mohammad; Adib-Eshgh, Ladan; Rostami, Azin; Beyraghi, Narges; Dabir, Shideh; Jafari, Reyhaneh

    2015-06-01

    The purpose of this study was to evaluate the effect of memantine administration on the adverse cognitive effects of electroconvulsive therapy (ECT). Forty patients diagnosed with a major depressive disorder for which ECT was indicated as a treatment for their current episode were randomly allocated to either the memantine (5mg/day) group or the placebo group. All patients underwent the same protocol for anaesthesia and ECT procedures. The patients received memantine or the placebo for the whole period of ECT treatment, starting the day before ECT and continuing until the fourth session of ECT. The Modified Mental State Examination (MMSE) was used for the assessment of cognition before and after the trial. Regarding MMSE and item 3 MMSE (related to recent memory), the memantine group scored significantly higher at the end of ECT sessions than the control group (P=0.02, P<0.001, respectively). Our data support the hypothesis that memantine may reduce cognitive impairment following ECT. Memantine could be both a safe and well-tolerated treatment for use with ECT.

  7. 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. PMID:27277154

  8. 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.

  9. 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.

  10. 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.

  11. 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. PMID:27384073

  12. 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. PMID:27555234

  13. Cognitive deficits associated with acquired amusia after stroke: a neuropsychological follow-up study.

    PubMed

    Särkämö, Teppo; Tervaniemi, Mari; Soinila, Seppo; Autti, Taina; Silvennoinen, Heli M; Laine, Matti; Hietanen, Marja

    2009-10-01

    Recent evidence on amusia suggests that our ability to perceive music might be based on the same neural resources that underlie other higher cognitive functions, such as speech perception and spatial processing. We studied the neural correlates of acquired amusia by performing extensive neuropsychological assessments on 53 stroke patients with a left or right hemisphere middle cerebral artery (MCA) stroke 1 week, 3 months, and 6 months after the stroke. In addition, structural magnetic resonance imaging (MRI) was performed on all patients 1 week and 6 months post-stroke. Based on their performance on a shortened version of the Montreal Battery of Evaluation of Amusia (MBEA), the patients were classified as amusic (n=32) or non-amusic (n=21). MRI results showed that the incidence of auditory cortex and frontal lobe damage was significantly higher in the amusic group than in the non-amusic group, but the two groups did not differ in respect to lesion laterality. Cognitively, amusia was associated with general deficits in working memory and learning, semantic fluency, executive functioning, and visuospatial cognition, as well as hemisphere-specific deficits in verbal comprehension, mental flexibility, and visuospatial attention (unilateral spatial neglect). Moreover, the recovery of music perception ability was related to the recovery of verbal learning, visuospatial perception and attention, and focused attention, especially in amusic patients. Together, these results suggest the ability to perceive music is closely linked to other higher cognitive functions.

  14. Future perspectives on the treatment of cognitive deficits and negative symptoms in schizophrenia

    PubMed Central

    Goff, Donald C

    2013-01-01

    Drug discovery based on classic models for cognitive impairment and negative symptoms of schizophrenia have met with only modest success. Because cognitive impairment and negative symptoms may result from disruptions in neurodevelopment, more complex developmental models that integrate environmental and genetic risk factors are needed. In addition, it has become clear that biochemical pathways involved in schizophrenia form complex, interconnected networks. Points at which risk factors converge, such as brain-derived neurotrophic factor (BDNF) and protein kinase B (AKT), and from which processes involved in neuroplasticity diverge, are of particular interest for pharmacologic interventions. This paper reviews elements of neurodevelopmental models for cognitive deficits and negative symptoms of schizophrenia with the aim of identifying potential targets for interventions. PMID:23737409

  15. 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

  16. Dexmedetomidine alleviates postoperative cognitive dysfunction by inhibiting neuron excitation in aged rats

    PubMed Central

    Xiong, Bo; Shi, Qiqing; Fang, Hao

    2016-01-01

    The perioperative stress response is one of the factors leading to postoperative cognitive dysfunction (POCD). Dexmedetomidine (Dex) can reduce the stress response and hippocampus neuroapoptosis, but its mechanism of action on POCD remains unknown. This study investigated the protective effect and possible mechanism of Dex on POCD in aged rats. Ninety-six aged male rats were randomly divided into four groups (n = 24 rats per group): a non-surgical control group, a surgical (model) group, a surgical group receiving a high dose of Dex (12 μg/kg), and a surgical group receiving a low dose of Dex (3 μg/kg). Cognitive function and neuronal apoptosis were evaluated after splenectomy. Compared with the control group, the model group had significantly longer escape latencies and fewer platform crossings in the Morris water-maze test. Immunohistochemistry showed that relaxin-3 and c-fos positive neurons in the hippocampus increased on postoperative days 1 and 3. Greater downregulation of the Bcl-2 protein and upregulation of Fas, caspase-8, and caspase-9 significantly increased neuroapoptosis in the model group. Compared with the model group, rats given Dex had (1) shorter escape latencies, (2) more platform crossings, (3) fewer relaxin-3 and c-fos positive neurons in the hippocampal CA1 area, (4) upregulation of Bcl-2, (5) downregulation of Fas, caspase-8, and caspase-9 proteins, and (6) decreased neuroapoptosis in the hippocampus. Thus, our data suggest that Dex may improve cognitive functioning in aged rats by inhibiting neural over-excitability. The mechanism may operate by restraining relaxin-3 and c-fos expression. PMID:27069541

  17. 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

  18. Cognitive deficits in patients with obsessive–compulsive disorder – electroencephalography correlates

    PubMed Central

    Kamaradova, Dana; Hajda, Miroslav; Prasko, Jan; Taborsky, Jiri; Grambal, Ales; Latalova, Klara; Ociskova, Marie; Brunovsky, Martin; Hlustik, Petr

    2016-01-01

    Background Obsessive–compulsive disorder (OCD) is associated with cognitive dysfunction. Although there are several studies focused on the neurobiology of OCD, little is known about the biological correlates of the cognitive deficit linked to this disorder. The aim of our study was to examine the association between cognitive impairment and current source density markers in patients with OCD. Methods Resting-state eyes-closed electroencephalography (EEG) data were recorded in 20 patients with OCD and 15 healthy controls who were involved in the study. Cortical EEG sources were estimated by standardized low-resolution electromagnetic tomography in seven frequency bands: delta (1.5–6 Hz), theta (6.5–8 Hz), alpha-1 (8.5–10 Hz), alpha-2 (10.5–12 Hz), beta-1 (12.5–18 Hz), beta-2 (18.5–21 Hz), and beta-3 (21.5–30 Hz). Cognitive performance was measured by the Trail-Making Test (versions A and B), Stroop CW Test, and D2 Test. Results Frontal delta and theta EEG sources showed significantly higher activity in the whole group of patients with OCD (N=20) than in control subjects (N=15). Subsequent analysis revealed that this excess of low-frequency activity was present only in the subgroup of eleven patients with cognitive impairment (based on the performance in the Trail-Making Test – A). The subgroup of patients with normal cognitive functions (N=9) did not differ in cortical EEG sources from healthy controls. Conclusion The present results suggest that frontal low-frequency cortical sources of resting-state EEG rhythms can distinguish groups of cognitively impaired and cognitively intact patients with OCD. Based on our results, future studies should consider whether the present methodological approach provides clinically useful information for the revelation of cognitive impairment in patients with OCD. PMID:27226716

  19. Mount Everest: a space analogue for speech monitoring of cognitive deficits and stress.

    PubMed

    Lieberman, Philip; Morey, Angie; Hochstadt, Jesse; Larson, Mara; Mather, Sandra

    2005-06-01

    In deep-space missions, the basal ganglia and hippocampus, subcortical structures of the brain that play critical roles in motor activity, cognition, and memory, will be vulnerable to damage from cosmic rays. These metabolically active structures are also sensitive to damage arising from the low oxygen content of air at extreme altitudes. We have, therefore, used Mount Everest as an analogue for deep space, where astronauts will be subject to danger and stress as well as neural damage. We can ethically obtain data because our climber-subjects already intend to climb Mt. Everest. We record speech and test cognitive and linguistic performance before, during, and after exposure to hypoxic conditions. From these data we have derived and validated computer-implemented acoustic voice measures that track slight as well as profound cognitive impairment. Vowel duration and speech motor sequencing errors increase as climbers ascend, reflecting degraded basal ganglia activity. These metrics detect deficits in language comprehension and the ability to change plans in changing circumstances. Preliminary analyses also reveal memory deficits reflecting hippocampal damage. Our speech metrics are unobtrusive and do not reveal the content of a verbal message; they could be derived automatically, allowing space crews to detect subtle motor and cognitive deficits and invoke countermeasures before performance is profoundly impaired. In future work we will be validating the voice metrics of stress in collaboration with the Dinges NSBRI laboratory study of task-induced stress. Our procedures can also be applied in general aviation and in the treatment of Parkinson's disease, Alzheimer's dementia, and other neurological disorders. PMID:15943213

  20. A Web-Based Training Program Using Cognitive Behavioral Therapy to Alleviate Psychological Distress Among Employees: Randomized Controlled Pilot Trial

    PubMed Central

    Tajima, Miyuki; Kimura, Risa; Sasaki, Norio; Somemura, Hironori; Ito, Yukio; Okanoya, June; Yamamoto, Megumi; Nakamura, Saki; Tanaka, Katsutoshi

    2014-01-01

    Background A number of psychoeducational programs based on cognitive behavioral therapy (CBT) to alleviate psychological distress have been developed for implementation in clinical settings. However, while these programs are considered critical components of stress management education in a workplace setting, they are required to be brief and simple to implement, which can hinder development. Objective The intent of the study was to examine the effects of a brief training program based on CBT in alleviating psychological distress among employees and facilitating self-evaluation of stress management skills, including improving the ability to recognize dysfunctional thinking patterns, transform dysfunctional thoughts to functional ones, cope with stress, and solve problems. Methods Of the 187 employees at an information technology company in Tokyo, Japan, 168 consented to participate in our non-blinded randomized controlled study. The training group received CBT group education by a qualified CBT expert and 1 month of follow-up Web-based CBT homework. The effects of this educational program on the psychological distress and stress management skills of employees were examined immediately after completion of training and then again after 6 months. Results Although the training group did exhibit lower mean scores on the Kessler-6 (K6) scale for psychological distress after 6 months, the difference from the control group was not significant. However, the ability of training group participants to recognize dysfunctional thinking was significantly improved both immediately after training completion and after 6 months. While the ability of participants to cope with stress was not significantly improved immediately after training, improvement was noted after 6 months in the training group. No notable improvements were observed in the ability of participants to transform thoughts from dysfunctional to functional or in problem-solving skills. A sub-analysis of participants who

  1. 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…

  2. 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…

  3. 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

  4. Cognitive Deficits Associated with Nav1.1 Alterations: Involvement of Neuronal Firing Dynamics and Oscillations

    PubMed Central

    Bender, Alex C.; Luikart, Bryan W.; Lenck-Santini, Pierre-Pascal

    2016-01-01

    Brain oscillations play a critical role in information processing and may, therefore, be essential to uncovering the mechanisms of cognitive impairment in neurological disease. In Dravet syndrome (DS), a mutation in SCN1A, coding for the voltage-gated sodium channel Nav1.1, is associated with severe cognitive impairment and seizures. While seizure frequency and severity do not correlate with the extent of impairment, the slowing of brain rhythms may be involved. Here we investigate the role of Nav1.1 on brain rhythms and cognition using RNA interference. We demonstrate that knockdown of Nav1.1 impairs fast- and burst-firing properties of neurons in the medial septum in vivo. The proportion of neurons that fired phase-locked to hippocampal theta oscillations was reduced, and medial septal regulation of theta rhythm was disrupted. During a working memory task, this deficit was characterized by a decrease in theta frequency and was negatively correlated with performance. These findings suggest a fundamental role for Nav1.1 in facilitating fast-firing properties in neurons, highlight the importance of precise temporal control of theta frequency for working memory, and imply that Nav1.1 deficits may disrupt information processing in DS via a dysregulation of brain rhythms. PMID:26978272

  5. 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

  6. Cognitive Deficits Associated with Nav1.1 Alterations: Involvement of Neuronal Firing Dynamics and Oscillations.

    PubMed

    Bender, Alex C; Luikart, Bryan W; Lenck-Santini, Pierre-Pascal

    2016-01-01

    Brain oscillations play a critical role in information processing and may, therefore, be essential to uncovering the mechanisms of cognitive impairment in neurological disease. In Dravet syndrome (DS), a mutation in SCN1A, coding for the voltage-gated sodium channel Nav1.1, is associated with severe cognitive impairment and seizures. While seizure frequency and severity do not correlate with the extent of impairment, the slowing of brain rhythms may be involved. Here we investigate the role of Nav1.1 on brain rhythms and cognition using RNA interference. We demonstrate that knockdown of Nav1.1 impairs fast- and burst-firing properties of neurons in the medial septum in vivo. The proportion of neurons that fired phase-locked to hippocampal theta oscillations was reduced, and medial septal regulation of theta rhythm was disrupted. During a working memory task, this deficit was characterized by a decrease in theta frequency and was negatively correlated with performance. These findings suggest a fundamental role for Nav1.1 in facilitating fast-firing properties in neurons, highlight the importance of precise temporal control of theta frequency for working memory, and imply that Nav1.1 deficits may disrupt information processing in DS via a dysregulation of brain rhythms. PMID:26978272

  7. 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.

  8. Characteristics of cognitive deficits and writing skills of Polish adults with developmental dyslexia.

    PubMed

    Bogdanowicz, Katarzyna Maria; Łockiewicz, Marta; Bogdanowicz, Marta; Pąchalska, Maria

    2014-07-01

    The present study was aimed at analysing cognitive deficits of dyslexic adults, and examining their written language skills in comparison with their peers. Our results confirm the presence of a certain profile of symptoms in adult dyslexics. We noticed deficits in: phonological (verbal) short-term memory, phonological awareness, rapid automatised naming (speed, self-corrections), visual perception and control, and visual-motor coordination. Moreover, the dyslexic participants, as compared with their nondyslexic peers, produced more word structure errors whilst writing an essay. However, there were no significant differences between the two groups in the length of the essay, the number of linguistic and punctuation errors, the number of adjectives, and stylistic devices.

  9. 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

  10. Deficits of cognitive restructuring in major depressive disorder: Measured by textual micro-counseling dialogues.

    PubMed

    Jiang, Nengzhi; Yu, Fei; Zhang, Wencai; Zhang, Jianxin

    2016-04-30

    Cognitive restructuring is an important strategy in cognitive behavioral therapy (CBT). The present study aimed to observe cognitive restructuring in major depressive disorder (MDD) patients using textual micro-counseling dialogue situations. A set of textual micro-counseling dialogues was used to trigger cognitive restructuring in 25 MDD patients and 27 healthy adults. The participants read descriptions ("problems") and explanations ("solutions") for psychologically distressing situations. High-, low-, and zero-restructuring solutions were randomly matched to the problems. The participants evaluated the adaptability and emotional valence of the problems and the insightfulness, adaptability, novelty, and emotional valence of the solutions. Insightfulness ratings for high-restructuring solutions were significantly higher relative to those of low-restructuring solutions in healthy adults, while adaptability ratings for low-restructuring solutions were significantly higher relative to those of high-restructuring solutions in MDD patients. Insightfulness ratings for the solutions were significantly predicted by novelty and adaptability in healthy adults and emotional valence in MDD patients. Lower insightfulness in high-restructuring solutions and higher adaptability in low-restructuring solutions in MDD patients may reflect deficits in cognitive control.

  11. Manganese exposure and cognitive deficits: A growing concern for manganese neurotoxicity⋆

    PubMed Central

    Roels, H.A.; Bowler, R.M.; Kim, Y.; Henn, B. Claus; 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

    2013-01-01

    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. PMID:22498092

  12. Prefrontal cognitive deficits in mice with altered cerebral cortical GABAergic interneurons

    PubMed Central

    Bissonette, Gregory B.; Bae, Mihyun H.; Suresh, Tejas; Jaffe, David E.; Powell, Elizabeth M.

    2013-01-01

    Alterations of inhibitory GABAergic neurons are implicated in multiple psychiatric and neurological disorders, including schizophrenia, autism and epilepsy. In particular, interneuron deficits in prefrontal areas, along with presumed decreased inhibition, have been reported in several human patients. The majority of forebrain GABAergic interneurons arise from a single subcortical source before migrating to their final regional destination. Factors that govern the interneuron populations have been identified, demonstrating that a single gene mutation may globally affect forebrain structures or a single area. In particular, mice lacking the urokinase plasminogen activator receptor (Plaur) gene have decreased GABAergic interneurons in frontal and parietal, but not caudal, cortical regions. Plaur assists in the activation of hepatocyte growth factor/scatter factor (HGF/SF), and several of the interneuron deficits are correlated with decreased levels of HGF/SF. In some cortical regions, the interneuron deficit can be remediated by endogenous overexpression of HGF/SF. In this study, we demonstrate decreased parvalbumin-expressing interneurons in the medial frontal cortex, but not in the hippocampus or basal lateral amygdala in the Plaur null mouse. The Plaur null mouse demonstrates impaired medial frontal cortical function in extinction of cued fear conditioning and the inability to form attentional sets. Endogenous HGF/SF overexpression increased the number of PV-expressing cells in medial frontal cortical areas to levels greater than found in wildtype mice, but did not remediate the behavioral deficits. These data suggest that proper medial frontal cortical function is dependent upon optimum levels of inhibition and that a deficit or excess of interneuron numbers impairs normal cognition. PMID:24211452

  13. Different storage and retrieval deficits in normal aging and mild cognitive impairment: a multinomial modeling analysis.

    PubMed

    Bröder, Arndt; Herwig, Andrea; Teipel, Stefan; Fast, Kristina

    2008-06-01

    The authors compared patients with mild cognitive impairment with healthy older adults and young control participants in a free recall test in order to locate potential qualitative differences in normal and pathological memory decline. Analysis with an extended multitrial version of W. H. Batchelder and D. M. Riefer's (1980) pair-clustering model revealed globally decelerated learning and an additional retrieval deficit in patients with mild cognitive impairment but not in healthy older adults. Results thus suggest differences in memory decline between normal and pathological aging that may be useful for the detection of risk groups for dementia, and they illustrate the value of model-based disentangling of processes and of multitrial tests for early detection of dementia.

  14. [The histaminergic system: a target for innovative treatments of cognitive deficits].

    PubMed

    Motawaj, Mouhammad; Burban, Aude; Davenas, Elisabeth; Gbahou, Florence; Faucard, Raphaël; Morisset, Séverine; Arrang, Jean-Michel

    2010-01-01

    The central effects of histamine are mediated by H(1), H(2) and H(3) receptors. The H(3) receptor inhibits histamine release in brain. Therefore, H(3) receptor inverse agonists, by suppressing this brake, enhance histamine neuron activity. The histaminergic system plays a major role in cognition and H(3) receptor inverse agonists are expected to be a potential therapeutics for cognitive deficits of Alzheimer's disease (AD). They are eagerly awaited inasmuch as other treatments of the disease, such as tacrine or memantine, also enhance, through different mechanisms, histaminergic neurotransmission. An important loss of histaminergic neurons has been observed in AD. In contrast, levels of the histamine metabolite in the CSF of AD patients show that their global activity is decreased by only 25%. This indicates that activating histamine neurons in AD can be envisaged.

  15. NEURONAL NICOTINIC RECEPTOR AGONISTS FOR THE TREATMENT OF ATTENTION-DEFICIT/HYPERACTIVITY DISORDER: FOCUS ON COGNITION

    PubMed Central

    Wilens, Timothy E.; Decker, Michael W.

    2010-01-01

    Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioral disorder in children and adolescents, and in about half of these patients, significant symptomology continues into adulthood. Although impulsivity and hyperactivity are the most salient features of ADHD, cognitive deficits, particularly impairments in attention and executive function, are an important component, particularly in adolescents and adults, with over 90% of adults seeking treatment for ADHD manifesting cognitive dysfunction. Currently available medications treat the core ADHD symptoms but typically do not adequately address cognitive aspects of ADHD, underscoring the need for new therapeutics. Dopamine and norepinephrine are hypothesized to be particularly important in ADHD, but there is emerging evidence that cholinergic neurotransmission, particularly involving neuronal nicotinic acetylcholine receptors (nAChRs), may play a role in the pathophysiology of ADHD. Nicotine has demonstrated procognitive effects in both humans and experimental animals and has produced signals of efficacy in small proof-of-concept adult ADHD trials. Although adverse effects associated with nicotine preclude its development as a therapeutic, a number of novel nAChR agonists with improved safety/tolerability profiles have been discovered. Of these, ABT-418 and ABT-089 have both demonstrated signals of efficacy in adults with ADHD. Notably, tolerability issues that might be expected of a nAChR agonist, such as nausea and emesis, were not observed at efficacious doses of ABT-089. Further understanding of the effects of novel neuronal nAChR agonists on specific aspects of cognitive functioning in ADHD is required to assess the full potential of this approach. PMID:17689498

  16. Cognitive deficits and ALA-D-inhibition in children exposed to multiple metals.

    PubMed

    do Nascimento, Sabrina N; Barth, Anelise; Göethel, Gabriela; Baierle, Marília; Charão, Mariele F; Brucker, Natália; Moro, Angela M; Bubols, Guilherme B; Sobreira, Johanna S; Sauer, Elisa; Rocha, Rafael; Gioda, Adriana; Dias, Ana Cristina; Salles, Jerusa F; Garcia, Solange C

    2015-01-01

    Children are especially vulnerable to adverse effects of multiple metals exposure. The aim of this study was to assess some metals concentrations such as lead (Pb), arsenic (As), chromium (Cr), manganese (Mn) and iron (Fe) in whole blood, serum, hair and drinking water samples using inductively coupled plasma-mass spectrometry (ICP-MS) in rural and urban children. In addition, evaluate the adverse effects of multiple metals exposure on cognitive function and δ-aminolevulinate dehydratase (ALA-D) activity. The cognitive ability assessment was performed by the Raven's Colored Progressive Matrices (RCPM) test. The ALA-D activity and ALA-D reactivation index (ALA-RE) activity with DTT and ZnCl2 also were determined. Forty-six rural children and 23 urban children were enrolled in this study. Rural children showed percentile IQ scores in the RCPM test significantly decreased in relation to urban children. According to multiple linear regression analysis, the Mn and Fe in hair may account for the cognitive deficits of children. Manganese and Fe in hair also were positively correlated with Mn and Fe in drinking water, respectively. These results suggest that drinking water is possibly a source of metals exposure in children. ALA-D activity was decreased and ALA-RE with DTT and ZnCl2 was increased in rural children in comparison to urban children. Moreover, ALA-D inhibition was correlated with Cr blood levels and ALA-RE/DDT and ALA-RE/ZnCl2 were correlated with levels of Cr and Hg in blood. Thus, our results indicated some adverse effects of children's exposure to multiple metals, such as cognitive deficits and ALA-D inhibition, mainly associated to Mn, Fe, Cr and Hg.

  17. Complexin 1 knockout mice exhibit marked deficits in social behaviours but appear to be cognitively normal.

    PubMed

    Drew, Cheney J G; Kyd, Rachel J; Morton, A Jennifer

    2007-10-01

    Complexins are presynaptic proteins that modulate neurotransmitter release. Abnormal expression of complexin 1 (Cplx1) is seen in several neurodegenerative and psychiatric disorders in which disturbed social behaviour is commonplace. These include Parkinsons's disease, Alzheimer's disease, schizophrenia, major depressive illness and bipolar disorder. We wondered whether changes in Cplx1 expression contribute to the psychiatric components of the diseases in which Cplx1 is dysregulated. To investigate this, we examined the cognitive and social behaviours of complexin 1 knockout mice (Cplx1(-/-)) mice. Cplx1(-/-) mice have a profound ataxia that limits their ability to perform co-ordinated motor tasks. Nevertheless, when we taught juvenile Cplx1(-/-) mice to swim, they showed no evidence of cognitive impairment in the two-choice swim tank. In contrast, although olfactory discrimination in Cplx1(-/-) mice was normal, Cplx1(-/-) mice failed in the social transmission of food preference task, another cognitive paradigm. This was due to abnormal social interactions rather than cognitive impairments, increased anxiety or neophobia. When we tested social behaviour directly, Cplx1(-/-) mice failed to demonstrate a preference for social novelty. Further, in a resident-intruder paradigm, male Cplx1(-/-) mice failed to show the aggressive behaviour that is typical of wild-type males towards an intruder mouse. Together our results show that in addition to the severe motor and exploratory deficits already described, Cplx1(-/-) mice have pronounced deficits in social behaviours. Abnormalities in complexin 1 levels in the brain may therefore contribute to the psycho-social aspects of human diseases in which this protein is dysregulated.

  18. Early detection of cognitive deficits in the 3xTg-AD mouse model of Alzheimer's disease.

    PubMed

    Stover, Kurt R; Campbell, Mackenzie A; Van Winssen, Christine M; Brown, Richard E

    2015-08-01

    Which behavioral test is the most sensitive for detecting cognitive deficits in the 3xTg-AD at 6.5 months of age? The 3xTg-AD mouse model of Alzheimer's disease (AD) has three transgenes (APPswe, PS1M146V, and Tau P301L) which cause the development of amyloid beta plaques, neurofibrillary tangles, and cognitive deficits with age. In order to determine which task is the most sensitive in the early detection of cognitive deficits, we compared male and female 3xTg-AD and B6129SF2 wildtype mice at 6.5 months of age on a test battery including spontaneous alternation in the Y-Maze, novel object recognition, spatial memory in the Barnes maze, and cued and contextual fear conditioning. The 3xTg-AD mice had impaired learning and memory in the Barnes maze but performed better than B6129SF2 wildtype mice in the Y-Maze and in contextual fear conditioning. Neither genotype demonstrated a preference in the novel object recognition task nor was there a genotype difference in cued fear conditioning but females performed better than males. From our results we conclude that the 3xTg-AD mice have mild cognitive deficits in spatial learning and memory and that the Barnes maze was the most sensitive test for detecting these cognitive deficits in 6.5-month-old mice.

  19. Cognitive heterogeneity in adult attention deficit/hyperactivity disorder: A systematic analysis of neuropsychological measurements.

    PubMed

    Mostert, Jeanette C; Onnink, A Marten H; Klein, Marieke; Dammers, Janneke; Harneit, Anais; Schulten, Theresa; van Hulzen, Kimm J E; Kan, Cornelis C; Slaats-Willemse, Dorine; Buitelaar, Jan K; Franke, Barbara; Hoogman, Martine

    2015-11-01

    Attention Deficit/Hyperactivity Disorder (ADHD) in childhood is associated with impaired functioning in multiple cognitive domains: executive functioning (EF), reward and timing. Similar impairments have been described for adults with persistent ADHD, but an extensive investigation of neuropsychological functioning in a large sample of adult patients is currently lacking. We systematically examined neuropsychological performance on tasks measuring EF, delay discounting, time estimation and response variability using univariate ANCOVA's comparing patients with persistent ADHD (N=133, 42% male, mean age 36) and healthy adults (N=132, 40% male, mean age 36). In addition, we tested which combination of variables provided the highest accuracy in predicting ADHD diagnosis. We also estimated for each individual the severity of neuropsychological dysfunctioning. Lastly, we investigated potential effects of stimulant medication and a history of comorbid major depressive disorder (MDD) on performance. Compared to healthy adults, patients with ADHD showed impaired EF, were more impulsive, and more variable in responding. However, effect sizes were small to moderate (range: 0.05-0.70) and 11% of patients did not show neuropsychological dysfunctioning. The best fitting model predicting ADHD included measures from distinct cognitive domains (82.1% specificity, 64.9% sensitivity). Furthermore, patients receiving stimulant medication or with a history of MDD were not distinctively impaired. To conclude, while adults with ADHD as a group are impaired on several cognitive domains, the results confirm that adult ADHD is neuropsychologically heterogeneous. This provides a starting point to investigate individual differences in terms of impaired cognitive pathways.

  20. Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats.

    PubMed

    Pintana, Hiranya; Sripetchwandee, Jirapas; Supakul, Luerat; Apaijai, Nattayaporn; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-12-01

    Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg(-1)·day(-1)) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

  1. 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.

  2. Cognitive heterogeneity in adult attention deficit/hyperactivity disorder: A systematic analysis of neuropsychological measurements.

    PubMed

    Mostert, Jeanette C; Onnink, A Marten H; Klein, Marieke; Dammers, Janneke; Harneit, Anais; Schulten, Theresa; van Hulzen, Kimm J E; Kan, Cornelis C; Slaats-Willemse, Dorine; Buitelaar, Jan K; Franke, Barbara; Hoogman, Martine

    2015-11-01

    Attention Deficit/Hyperactivity Disorder (ADHD) in childhood is associated with impaired functioning in multiple cognitive domains: executive functioning (EF), reward and timing. Similar impairments have been described for adults with persistent ADHD, but an extensive investigation of neuropsychological functioning in a large sample of adult patients is currently lacking. We systematically examined neuropsychological performance on tasks measuring EF, delay discounting, time estimation and response variability using univariate ANCOVA's comparing patients with persistent ADHD (N=133, 42% male, mean age 36) and healthy adults (N=132, 40% male, mean age 36). In addition, we tested which combination of variables provided the highest accuracy in predicting ADHD diagnosis. We also estimated for each individual the severity of neuropsychological dysfunctioning. Lastly, we investigated potential effects of stimulant medication and a history of comorbid major depressive disorder (MDD) on performance. Compared to healthy adults, patients with ADHD showed impaired EF, were more impulsive, and more variable in responding. However, effect sizes were small to moderate (range: 0.05-0.70) and 11% of patients did not show neuropsychological dysfunctioning. The best fitting model predicting ADHD included measures from distinct cognitive domains (82.1% specificity, 64.9% sensitivity). Furthermore, patients receiving stimulant medication or with a history of MDD were not distinctively impaired. To conclude, while adults with ADHD as a group are impaired on several cognitive domains, the results confirm that adult ADHD is neuropsychologically heterogeneous. This provides a starting point to investigate individual differences in terms of impaired cognitive pathways. PMID:26336867

  3. Homer1 mediates acute stress-induced cognitive deficits in the dorsal hippocampus.

    PubMed

    Wagner, Klaus V; Hartmann, Jakob; Mangold, Katharina; Wang, Xiao-Dong; Labermaier, Christiana; Liebl, Claudia; Wolf, Miriam; Gassen, Nils C; Holsboer, Florian; Rein, Theo; Müller, Marianne B; Schmidt, Mathias V

    2013-02-27

    In recent years, the glutamatergic system has been implicated in the development and treatment of psychiatric disorders. Glutamate signaling is processed by different receptors, including metabotropic glutamate receptors (mGluRs), which in turn interact with the scaffolding protein Homer1 to modulate downstream Ca(2+) signaling. Stress is a major risk factor for the incidence of psychiatric diseases, yet acute stress episodes may have diverging effects on individuals. Cognitive impairments have often been shown to occur after episodes of stress, however the specific role of mGluR5/Homer1 signaling in the interaction of stress and cognition has not yet been elucidated. In this study we show that a single episode of social defeat stress is sufficient to specifically induce cognitive impairments in mice 8 h after the stressor without affecting the animals' locomotion or anxiety levels. We also demonstrate that Homer1b/c levels as well as mGluR5/Homer1b/c interactions in the dorsal hippocampus are reduced up to 8 h after stress. Blockade of mGluR5 during the occurrence of social stress was able to rescue the cognitive impairments. In addition, a specific overexpression of Homer1b/c in the dorsal hippocampus also reversed the behavioral phenotype, indicating that both mGluR5 and Homer1b/c play a crucial role in the mediation of the stress effects. In summary, we could demonstrate that stress induces a cognitive deficit that is likely mediated by mGluR5/Homer1 signaling in the hippocampus. These findings help to reveal the underlying effects of cognitive impairments in patients suffering from stress-related psychiatric disorders.

  4. Pentamethylquercetin protects against diabetes-related cognitive deficits in diabetic Goto-Kakizaki rats.

    PubMed

    Li, Xian-Hui; Xin, Xin; Wang, Yan; Wu, Jian-zhao; Jin, Zhen-dong; Ma, Li-na; Nie, Chun-jie; Xiao, Xiao; Hu, Yan; Jin, Man-wen

    2013-01-01

    Diabetic patients have a signifiantly higher risk of developing all forms of dementia. Pentamethylquercetin (PMQ) has been proven to have potential as an anti-diabetic agent. Nevertheless, whether PMQ can improve diabetes-induced cognitive dysfunction has not been investigated. To address this, we evaluated the effectiveness and underlying mechanisms of PMQ for ameliorating diabetes-related cognitive dysfunction in vivo and in vitro. Our results showed that Goto-Kakizaki (GK) rats displayed impairment in their learning abilities and memory capabilities. Furthermore, GK rats reflected cognitive dysfunction in proportion to the intensity of insulin resistance index. In addition, dendritic spine density and the % cell viability significantly decreased in hippocampus neurons. High glucose conditions induced hippocampal neurons damage, inflicted dendritic spine dysontogenesis, and reduced Akt/cAMP response element-binding protein activation. Treatment with PMQ in GK rats significantly ameliorated cognitive deficits and neuronal damage and increased dendritic spine density, at least in part, by improving insulin resistance and metabolic disorders. Furthermore, PMQ significantly activated the Akt/cAMP response element-binding protein pathway and increased the expression of memory-related proteins in the downstream part of the Akt/cAMP response element-binding protein pathway, such as synaptophysin and glutamate receptor 1. In addition, PMQ inhibited high glucose-induced cellular toxicity. LY294002 appeared to partly inhibit PMQ-mediated protective effects in hippocampal neurons. The results suggest that insulin resistance could predominantly reduce Akt/cAMP response element-binding protein activation in the brain, which is associated with a higher risk of cognitive dysfunction. PMQ could provide a new potential option for the prevention of cognitive dysfunction in diabetes.

  5. Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin

    PubMed Central

    Ma, Ping; Liu, Xudong; Wu, Jiliang; Yan, Biao; Zhang, Yuchao; Lu, Yu; Wu, Yang; Liu, Chao; Guo, Junhui; Nanberg, Eewa; Bornehag, Carl-Gustaf; Yang, Xu

    2015-01-01

    Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a substitute for other plasticizers whose use is prohibited in certain products. In vivo studies on the neurotoxicity of DINP are however, limited. This work aims to investigate whether DINP causes neurobehavioral changes in mice and to provide useful advice on preventing the occurrence of these adverse effects. Behavioral analysis showed that oral administration of 20 or 200 mg/kg/day DINP led to mouse cognitive deficits and anxiety. Brain histopathological observations, immunohistochemistry assays (cysteine-aspartic acid protease 3 [caspase-3], glial fibrillary acidic protein [GFAP]), oxidative stress assessments (reactive oxygen species [ROS], glutathione [GSH], superoxide dismutase [SOD] activities, 8-hydroxy-2-deoxyguanosine [8-OH-dG] and DNA-protein crosslinks [DPC]), and assessment of inflammation (tumor necrosis factor alpha [TNF-а] and interleukin-1 beta [IL-1β]) of mouse brains showed that there were histopathological alterations in the brain and increased levels of oxidative stress, and inflammation for these same groups. However, some of these effects were blocked by administration of melatonin (50 mg/kg/day). Down-regulation of oxidative stress was proposed to explain the neuroprotective effects of melatonin. The data suggests that DINP could cause cognitive deficits and anxiety in mice, and that melatonin could be used to avoid these adverse effects. PMID:26424168

  6. Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease

    PubMed Central

    Holland, Philip R; Searcy, James L; Salvadores, Natalia; Scullion, Gillian; Chen, Guiquan; Lawson, Greig; Scott, Fiona; Bastin, Mark E; Ihara, Masafumi; Kalaria, Rajesh; Wood, Emma R; Smith, Colin; Wardlaw, Joanna M; Horsburgh, Karen

    2015-01-01

    Cerebral small vessel disease (SVD) is a major cause of age-related cognitive impairment and dementia. The pathophysiology of SVD is not well understood and is hampered by a limited range of relevant animal models. Here, we describe gliovascular alterations and cognitive deficits in a mouse model of sustained cerebral hypoperfusion with features of SVD (microinfarcts, hemorrhage, white matter disruption) induced by bilateral common carotid stenosis. Multiple features of SVD were determined on T2-weighted and diffusion-tensor magnetic resonance imaging scans and confirmed by pathologic assessment. These features, which were absent in sham controls, included multiple T2-hyperintense infarcts and T2-hypointense hemosiderin-like regions in subcortical nuclei plus increased cerebral atrophy compared with controls. Fractional anisotropy was also significantly reduced in several white matter structures including the corpus callosum. Investigation of gliovascular changes revealed a marked increase in microvessel diameter, vascular wall disruption, fibrinoid necrosis, hemorrhage, and blood–brain barrier alterations. Widespread reactive gliosis, including displacement of the astrocytic water channel, aquaporin 4, was observed. Hypoperfused mice also demonstrated deficits in spatial working and reference memory tasks. Overall, gliovascular disruption is a prominent feature of this mouse, which could provide a useful model for early-phase testing of potential SVD treatment strategies. PMID:25669904

  7. Cognitive and motivational deficits together with prefrontal oxidative stress in a mouse model for neuropsychiatric illness.

    PubMed

    Johnson, Alexander W; Jaaro-Peled, Hanna; Shahani, Neelam; Sedlak, Thomas W; Zoubovsky, Sandra; Burruss, Daniel; Emiliani, Francesco; Sawa, Akira; Gallagher, Michela

    2013-07-23

    Guided by features of molecular, cellular, and circuit dysfunction affecting the prefrontal cortex in clinical investigations, we targeted prefrontal cortex in studies of a model for neuropsychiatric illness using transgenic mice expressing a putative dominant-negative disrupted in schizophrenia 1 (DN-DISC1). We detected marked augmentation of GAPDH-seven in absentia homolog Siah protein binding in the DISC1 mice, a major hallmark of a nuclear GAPDH cascade that is activated in response to oxidative stress. Furthermore, deficits were observed in well-defined tests for the cognitive control of adaptive behavior using reversal learning and reinforcer devaluation paradigms. These deficits occurred even though DN-DISC1 mice showed intact performance in simple associative learning and normal responses in consumption of reward. In an additional series of assessments, motivational functions also were impoverished in DN-DISC1 mice, including tests of the dynamic modulation of reward value by effortful action, progressive ratio performance, and social behavior. Augmentation of an oxidative stress-associated cascade (e.g., a nuclear GAPDH cascade) points to an underlying condition that may contribute to the profile of cognitive and motivational impairments in DN-DISC1 mice by affecting the functional integrity of the prefrontal cortex and dysfunction within its connected networks. As such, this model should be useful for further preclinical research and drug discovery efforts relevant to the burden of prefrontal dysfunction in neuropsychiatric illness.

  8. Cognitive deficits and changes in gene expression of NMDA receptors after prenatal methylmercury exposure.

    PubMed Central

    Baraldi, Mario; Zanoli, Paola; Tascedda, Fabio; Blom, Joan M C; Brunello, Nicoletta

    2002-01-01

    Previous studies showed learning and memory deficit in adult rats that were prenatally exposed to methylmercury chloride (MMC) in an advanced stage of pregnancy (15 days). Under these conditions, the cognitive deficits found at 60 days of age paralleled particularly changes in the N-methyl-D-aspartate (NMDA) receptor characteristics. In the present study, we report the behavioral effects of a single oral dose of MMC (8 mg/kg) administered earlier at gestational day 8. The use of different learning and memory tests (passive avoidance, object recognition, water maze) showed a general cognitive impairment in the in utero-exposed rats tested at 60 days of age compared with matched controls. Considering the importance of the glutamatergic receptor system and its endogenous ligands in learning and memory process regulation, we surmised that MMC could affect the gene expression of NMDA receptor subtypes. The use of a sensitive RNase protection assay allowed the evaluation of gene expression of two families of NMDA receptors (NR-1 and NR-2 subtypes). The result obtained in 60-day-old rats prenatally exposed to MMC, showed increased mRNA levels of the NR-2B subunit in the hippocampus but not in the frontal cortex. The data suggest that the behavioral abnormalities of MMC-exposed rats might be ascribed to a neurotoxic effect of the metal that alters the gene expression of a specific NMDA receptor subunit in the hippocampus. PMID:12426146

  9. Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin.

    PubMed

    Ma, Ping; Liu, Xudong; Wu, Jiliang; Yan, Biao; Zhang, Yuchao; Lu, Yu; Wu, Yang; Liu, Chao; Guo, Junhui; Nanberg, Eewa; Bornehag, Carl-Gustaf; Yang, Xu

    2015-01-01

    Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a substitute for other plasticizers whose use is prohibited in certain products. In vivo studies on the neurotoxicity of DINP are however, limited. This work aims to investigate whether DINP causes neurobehavioral changes in mice and to provide useful advice on preventing the occurrence of these adverse effects. Behavioral analysis showed that oral administration of 20 or 200 mg/kg/day DINP led to mouse cognitive deficits and anxiety. Brain histopathological observations, immunohistochemistry assays (cysteine-aspartic acid protease 3 [caspase-3], glial fibrillary acidic protein [GFAP]), oxidative stress assessments (reactive oxygen species [ROS], glutathione [GSH], superoxide dismutase [SOD] activities, 8-hydroxy-2-deoxyguanosine [8-OH-dG] and DNA-protein crosslinks [DPC]), and assessment of inflammation (tumor necrosis factor alpha [TNF-а] and interleukin-1 beta [IL-1β]) of mouse brains showed that there were histopathological alterations in the brain and increased levels of oxidative stress, and inflammation for these same groups. However, some of these effects were blocked by administration of melatonin (50 mg/kg/day). Down-regulation of oxidative stress was proposed to explain the neuroprotective effects of melatonin. The data suggests that DINP could cause cognitive deficits and anxiety in mice, and that melatonin could be used to avoid these adverse effects. PMID:26424168

  10. 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

  11. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson’s Disease

    PubMed Central

    Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane

    2015-01-01

    Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson’s disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease. PMID:26571268

  12. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

    PubMed

    Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane; Amalric, Marianne; Kerkerian-Le Goff, Lydia

    2015-01-01

    Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease. PMID:26571268

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

    PubMed Central

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

    2014-01-01

    Objective: 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. Methods: 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. Results: 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. Conclusions: 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. PMID:24850492

  14. Phosphodiesterase-4D Knock-down in the Prefrontal Cortex Alleviates Chronic Unpredictable Stress-Induced Depressive-Like Behaviors and Memory Deficits in Mice

    PubMed Central

    Wang, Zhen-Zhen; Yang, Wei-Xing; Zhang, Yi; Zhao, Nan; Zhang, You-Zhi; Liu, Yan-Qin; Xu, Ying; Wilson, Steven P.; O'Donnell, James M.; Zhang, Han-Ting; Li, Yun-Feng

    2015-01-01

    Phosphodiesterase 4 (PDE4) has four isoforms (PDE4A-D) with at least 25 splice variants. PDE4 subtype nonselective inhibitors produce potent antidepressant-like and cognition-enhancing effects via increased intracellular cyclic AMP (cAMP) signaling in the brain. Our previous data have demonstrated that long-form PDE4Ds appear to be involved in these pharmacological properties of PDE4 inhibitors in the normal animals. However, it is not clear whether long-form PDE4Ds are critical for the behaviors and related cellular signaling/neuronal plasticity/neuroendocrine alterations in the depressed animals. In the present study, animals exposed to the chronic unpredictable stress (CUS), a rodent model of depression, exhibited elevated corticosterone, depressive-like behavior, memory deficits, accompanied with decreased cAMP-PKA-CREB and cAMP-ERK1/2-CREB signaling and neuroplasticity. These alterations induced by CUS were reversed by RNA interference (RNAi)-mediated prefrontal cortex long-form PDE4Ds (especially PDE4D4 and PDE4D5) knock-down, similar to the effects of the PDE4 subtype nonselective inhibitor rolipram. Furthermore, these effects of RNAi were not enhanced by rolipram. These data indicate a predominant role of long-form PDE4Ds in the pharmacotherapies of PDE4 inhibitors for depression and concomitant memory deficits. Long-form PDE4Ds, especially PDE4D4 and PDE4D5, appear to be the promising targets for the development of antidepressants with high therapeutic indices. PMID:26161529

  15. Cognitive Deficits in Long-Term Anabolic-Androgenic Steroid Users

    PubMed Central

    Kanayama, Gen; Kean, Joseph; Hudson, James I.; Pope, Harrison G.

    2012-01-01

    Background Millions of individuals worldwide have used anabolic-androgenic steroids (AAS) to gain muscle or improve athletic performance. Recently, in vitro investigations have suggested that supraphysiologic AAS doses cause apoptosis of neuronal cells. These findings raise the possibility, apparently still untested, that humans using high-dose AAS might eventually develop cognitive deficits. Methods We administered five cognitive tests from the computerized CANTAB battery (Pattern Recognition Memory, Verbal Recognition Memory, Paired Associates Learning, Choice Reaction Time, and Rapid Visual Information Processing) to 31 male AAS users and 13 non-AAS-using weightlifters age 29-55, recruited and studied in May 2012 in Middlesbrough, UK. Testers were blinded to participants’ AAS status and other historical data. Results Long-term AAS users showed no significant differences from nonusers on measures of response speed, sustained attention, and verbal memory. On visuospatial memory, however, AAS users performed significantly more poorly than nonusers, and within the user group, visuospatial performance showed a significant negative correlation with total lifetime AAS dose. These were large effects: on Pattern Recognition Memory, long-term AAS users underperformed nonusers by almost one standard deviation, based on normative population scores (adjusted mean difference in z-scores = 0.89; p = 0.036), and performance on this test declined markedly with increasing lifetime AAS dose (adjusted change in z-score = −0.13 per 100g of lifetime AAS dose; p = 0.002). These results remained stable in sensitivity analyses addressing potential confounding factors. Conclusions These preliminary findings raise the ominous possibility that long-term high-dose AAS exposure may cause cognitive deficits, notably in visuospatial memory. PMID:23253252

  16. Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice.

    PubMed

    Yabuki, Y; Ohizumi, Y; Yokosuka, A; Mimaki, Y; Fukunaga, K

    2014-02-14

    Nobiletin, a polymethoxylated flavonoid found in citrus fruit peel, reportedly improves memory impairment in rodent models. Here we report its effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor and cognitive deficits. Nobiletin administration (50mg/kg i.p.) for 2 consecutive weeks improved motor deficits seen in MPTP-induced Parkinson model mice by 2weeks, an effect that continued until 2weeks after drug withdrawal. Drug treatment promoted similar rescue of MPTP-induced cognitive impairment at equivalent time points. Nonetheless, nobiletin treatment did not block loss of dopaminergic neurons seen in the MPTP-treated mouse midbrain, nor did it rescue decreased tyrosine hydroxylase (TH) protein levels seen in the striatum or hippocampal CA1 region of these mice. Interestingly, nobiletin administration (50mg/kg i.p.) rescued reduced levels of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and phosphorylation at Thr-34 of dopamine- and cAMP-regulated phosphoprotein-32 (DARPP-32) in striatum and hippocampal CA1 to levels seen in sham-operated mice. Likewise, CaMKII- and cAMP kinase-dependent TH phosphorylation was significantly restored by nobiletin treatment. MPTP-induced reduction of dopamine contents in the striatum and hippocampal CA1 region was improved by nobiletin administration (50mg/kg i.p.). Acute intraperitoneal administration of nobiletin also enhanced dopamine release in striatum and hippocampal CA1, an effect partially inhibited by treatment with nifedipine (a L-type Ca(2+) channel inhibitor) or NNC 55-0396 (a T-type Ca(2+) channel inhibitor) and completely abolished by combined treatment with both. Overall, our study describes a novel nobiletin activity in brain and suggests that nobiletin rescues motor and cognitive dysfunction in MPTP-induced Parkinson model mice, in part by enhancing dopamine release.

  17. Early Cognitive Deficits in Type 2 Diabetes: A Population-Based Study.

    PubMed

    Marseglia, Anna; Fratiglioni, Laura; Laukka, Erika J; Santoni, Giola; Pedersen, Nancy L; Bäckman, Lars; Xu, Weili

    2016-06-15

    Evidence links type 2 diabetes to dementia risk. However, our knowledge on the initial cognitive deficits in diabetic individuals and the factors that might promote such deficits is still limited. This study aimed to identify the cognitive domains initially impaired by diabetes and the factors that play a role in this first stage. Within the population-based Swedish National Study on Aging and Care-Kungsholmen, 2305 cognitively intact participants aged ≥60 y were identified. Attention/working memory, perceptual speed, category fluency, letter fluency, semantic memory, and episodic memory were assessed. Diabetes (controlled and uncontrolled) and prediabetes were ascertained by clinicians, who also collected information on vascular disorders (hypertension, heart diseases, and stroke) and vascular risk factors (VRFs, including smoking and overweight/obesity). Data were analyzed with linear regression models. Overall, 196 participants (8.5%) had diabetes, of which 144 (73.5%) had elevated glycaemia (uncontrolled diabetes); 571 (24.8%) persons had prediabetes. In addition, diabetes, mainly uncontrolled, was related to lower performance in perceptual speed (β - 1.10 [95% CI - 1.98, - 0.23]), category fluency (β - 1.27 [95% CI - 2.52, - 0.03]), and digit span forward (β - 0.35 [95% CI - 0.54, - 0.17]). Critically, these associations were present only among APOEɛ4 non-carriers. The associations of diabetes with perceptual speed and category fluency were present only among participants with VRFs or vascular disorders. Diabetes, especially uncontrolled diabetes, is associated with poorer performance in perceptual speed, category fluency, and attention/primary memory. VRFs, vascular disorders, and APOE status play a role in these associations. PMID:27314527

  18. Attention-deficit hyperactivity disorder (ADHD) stimulant medications as cognitive enhancers

    PubMed Central

    Advokat, Claire; Scheithauer, Mindy

    2013-01-01

    Recent increases in attention deficit hyperactivity disorder (ADHD) diagnoses, and the escalation of stimulant prescriptions, has raised concern about diversion and abuse of stimulants, as well as the ethics of using these drugs as “cognitive enhancers.”Such concern appears misplaced in the face of substantial evidence that stimulant drugs do not improve the academic performance of ADHD-diagnosed students. Moreover, numerous studies have found little or no benefit of stimulants on neuropsychological tests of ADHD-diagnosed as well as normal, individuals. This paper examines the apparent paradox: why don't drugs that improve “attention,” produce better academic outcomes in ADHD-diagnosed students? We found that stimulant drugs significantly improved impairment of episodic memory in ADHD-diagnosed undergraduate students. Nevertheless, we also found consistent academic deficits between ADHD students and their non-ADHD counterparts, regardless of whether or not they used stimulant medications. We reviewed the current literature on the behavioral effects of stimulants, to try to find an explanation for these conflicting phenomena. Across a variety of behavioral tasks, stimulants have been shown to reduce emotional reactions to frustration, improve the ability to detect errors, and increase effortful behavior. However, all of these effects would presumably enhance academic performance. On the other hand, the drugs were also found to promote “risky behavior” and to increase susceptibility to environmental distraction. Such negative effects, including the use of drugs to promote wakefulness for last minute study, might explain the lack of academic benefit in the “real world,” despite their cognitive potential. Like many drugs, stimulants influence behavior in multiple ways, depending on the environmental contingencies. Depending on the circumstances, stimulants may, or may not, enhance cognition. PMID:23754970

  19. Attention-deficit hyperactivity disorder (ADHD) stimulant medications as cognitive enhancers.

    PubMed

    Advokat, Claire; Scheithauer, Mindy

    2013-01-01

    Recent increases in attention deficit hyperactivity disorder (ADHD) diagnoses, and the escalation of stimulant prescriptions, has raised concern about diversion and abuse of stimulants, as well as the ethics of using these drugs as "cognitive enhancers."Such concern appears misplaced in the face of substantial evidence that stimulant drugs do not improve the academic performance of ADHD-diagnosed students. Moreover, numerous studies have found little or no benefit of stimulants on neuropsychological tests of ADHD-diagnosed as well as normal, individuals. This paper examines the apparent paradox: why don't drugs that improve "attention," produce better academic outcomes in ADHD-diagnosed students? We found that stimulant drugs significantly improved impairment of episodic memory in ADHD-diagnosed undergraduate students. Nevertheless, we also found consistent academic deficits between ADHD students and their non-ADHD counterparts, regardless of whether or not they used stimulant medications. We reviewed the current literature on the behavioral effects of stimulants, to try to find an explanation for these conflicting phenomena. Across a variety of behavioral tasks, stimulants have been shown to reduce emotional reactions to frustration, improve the ability to detect errors, and increase effortful behavior. However, all of these effects would presumably enhance academic performance. On the other hand, the drugs were also found to promote "risky behavior" and to increase susceptibility to environmental distraction. Such negative effects, including the use of drugs to promote wakefulness for last minute study, might explain the lack of academic benefit in the "real world," despite their cognitive potential. Like many drugs, stimulants influence behavior in multiple ways, depending on the environmental contingencies. Depending on the circumstances, stimulants may, or may not, enhance cognition. PMID:23754970

  20. Early Cognitive Deficits in Type 2 Diabetes: A Population-Based Study

    PubMed Central

    Marseglia, Anna; Fratiglioni, Laura; Laukka, Erika J.; Santoni, Giola; Pedersen, Nancy L.; Bäckman, Lars; Xu, Weili

    2016-01-01

    Evidence links type 2 diabetes to dementia risk. However, our knowledge on the initial cognitive deficits in diabetic individuals and the factors that might promote such deficits is still limited. This study aimed to identify the cognitive domains initially impaired by diabetes and the factors that play a role in this first stage. Within the population-based Swedish National Study on Aging and Care–Kungsholmen, 2305 cognitively intact participants aged ≥60 y were identified. Attention/working memory, perceptual speed, category fluency, letter fluency, semantic memory, and episodic memory were assessed. Diabetes (controlled and uncontrolled) and prediabetes were ascertained by clinicians, who also collected information on vascular disorders (hypertension, heart diseases, and stroke) and vascular risk factors (VRFs, including smoking and overweight/obesity). Data were analyzed with linear regression models. Overall, 196 participants (8.5%) had diabetes, of which 144 (73.5%) had elevated glycaemia (uncontrolled diabetes); 571 (24.8%) persons had prediabetes. In addition, diabetes, mainly uncontrolled, was related to lower performance in perceptual speed (β – 1.10 [95% CI – 1.98, – 0.23]), category fluency (β – 1.27 [95% CI – 2.52, – 0.03]), and digit span forward (β – 0.35 [95% CI – 0.54, – 0.17]). Critically, these associations were present only among APOE ɛ4 non–carriers. The associations of diabetes with perceptual speed and category fluency were present only among participants with VRFs or vascular disorders. Diabetes, especially uncontrolled diabetes, is associated with poorer performance in perceptual speed, category fluency, and attention/primary memory. VRFs, vascular disorders, and APOE status play a role in these associations. PMID:27314527

  1. Cognitive Training at a Young Age Attenuates Deficits in the zQ175 Mouse Model of HD

    PubMed Central

    Curtin, Paul C. P.; Farrar, Andrew M.; Oakeshott, Stephen; Sutphen, Jane; Berger, Jason; Mazzella, Matthew; Cox, Kimberly; He, Dansha; Alosio, William; Park, Larry C.; Howland, David; Brunner, Daniela

    2016-01-01

    Huntington's Disease (HD) is a progressive neurodegenerative disorder that causes motor, cognitive, and psychiatric symptoms. In these experiments, we tested if operant training at an early age affected adult cognitive deficits in the zQ175 KI Het (zQ175) mouse model of HD. In Experiment 1 we trained zQ175 mice in a fixed-ratio/progressive ratio (FR/PR) task to assay learning and motivational deficits. We found pronounced deficits in response rates and task engagement in naïve adult zQ175 mice (32–33 weeks age), while deficits in zQ175 mice trained from 6–7 weeks age were either absent or less severe. When those mice were re-tested as adults, FR/PR performance deficits were absent or otherwise less severe than deficits observed in naïve adult zQ175 relative to wild type (WT) mice. In Experiment 2, we used a Go/No-go operant task to assess the effects of early cognitive testing on response inhibition deficits in zQ175 mice. We found that zQ175 mice that began testing at 7–8 weeks did not exhibit deficits in Go/No-go testing, but when re-tested at 28–29 weeks age exhibited an initial impairment that diminished with training. These transient deficits were nonetheless mild relative to deficits observed among adult zQ175 mice without prior testing experience. In Experiment 3 we trained mice in a two-choice visual discrimination test to evaluate cognitive flexibility. As in prior experiments, we found performance deficits were mild or absent in mice that started training at 6–9 weeks of age, while deficits in naive mice exposed to training at 28–29 weeks were severe. Re-testing mice at 28–29 weeks age, were previously trained starting at 6–9 weeks, revealed that deficits in learning and cognitive flexibility were absent or reduced relative to effects observed in naive adults. In Experiment 4, we tested working memory deficits with a delayed non-match to position (DNMTP) test. Mice with prior experience exhibited mild working memory deficits, with males

  2. Cognitive Training at a Young Age Attenuates Deficits in the zQ175 Mouse Model of HD.

    PubMed

    Curtin, Paul C P; Farrar, Andrew M; Oakeshott, Stephen; Sutphen, Jane; Berger, Jason; Mazzella, Matthew; Cox, Kimberly; He, Dansha; Alosio, William; Park, Larry C; Howland, David; Brunner, Daniela

    2015-01-01

    Huntington's Disease (HD) is a progressive neurodegenerative disorder that causes motor, cognitive, and psychiatric symptoms. In these experiments, we tested if operant training at an early age affected adult cognitive deficits in the zQ175 KI Het (zQ175) mouse model of HD. In Experiment 1 we trained zQ175 mice in a fixed-ratio/progressive ratio (FR/PR) task to assay learning and motivational deficits. We found pronounced deficits in response rates and task engagement in naïve adult zQ175 mice (32-33 weeks age), while deficits in zQ175 mice trained from 6-7 weeks age were either absent or less severe. When those mice were re-tested as adults, FR/PR performance deficits were absent or otherwise less severe than deficits observed in naïve adult zQ175 relative to wild type (WT) mice. In Experiment 2, we used a Go/No-go operant task to assess the effects of early cognitive testing on response inhibition deficits in zQ175 mice. We found that zQ175 mice that began testing at 7-8 weeks did not exhibit deficits in Go/No-go testing, but when re-tested at 28-29 weeks age exhibited an initial impairment that diminished with training. These transient deficits were nonetheless mild relative to deficits observed among adult zQ175 mice without prior testing experience. In Experiment 3 we trained mice in a two-choice visual discrimination test to evaluate cognitive flexibility. As in prior experiments, we found performance deficits were mild or absent in mice that started training at 6-9 weeks of age, while deficits in naive mice exposed to training at 28-29 weeks were severe. Re-testing mice at 28-29 weeks age, were previously trained starting at 6-9 weeks, revealed that deficits in learning and cognitive flexibility were absent or reduced relative to effects observed in naive adults. In Experiment 4, we tested working memory deficits with a delayed non-match to position (DNMTP) test. Mice with prior experience exhibited mild working memory deficits, with males zQ175 exhibiting

  3. Cognitive Training at a Young Age Attenuates Deficits in the zQ175 Mouse Model of HD.

    PubMed

    Curtin, Paul C P; Farrar, Andrew M; Oakeshott, Stephen; Sutphen, Jane; Berger, Jason; Mazzella, Matthew; Cox, Kimberly; He, Dansha; Alosio, William; Park, Larry C; Howland, David; Brunner, Daniela

    2015-01-01

    Huntington's Disease (HD) is a progressive neurodegenerative disorder that causes motor, cognitive, and psychiatric symptoms. In these experiments, we tested if operant training at an early age affected adult cognitive deficits in the zQ175 KI Het (zQ175) mouse model of HD. In Experiment 1 we trained zQ175 mice in a fixed-ratio/progressive ratio (FR/PR) task to assay learning and motivational deficits. We found pronounced deficits in response rates and task engagement in naïve adult zQ175 mice (32-33 weeks age), while deficits in zQ175 mice trained from 6-7 weeks age were either absent or less severe. When those mice were re-tested as adults, FR/PR performance deficits were absent or otherwise less severe than deficits observed in naïve adult zQ175 relative to wild type (WT) mice. In Experiment 2, we used a Go/No-go operant task to assess the effects of early cognitive testing on response inhibition deficits in zQ175 mice. We found that zQ175 mice that began testing at 7-8 weeks did not exhibit deficits in Go/No-go testing, but when re-tested at 28-29 weeks age exhibited an initial impairment that diminished with training. These transient deficits were nonetheless mild relative to deficits observed among adult zQ175 mice without prior testing experience. In Experiment 3 we trained mice in a two-choice visual discrimination test to evaluate cognitive flexibility. As in prior experiments, we found performance deficits were mild or absent in mice that started training at 6-9 weeks of age, while deficits in naive mice exposed to training at 28-29 weeks were severe. Re-testing mice at 28-29 weeks age, were previously trained starting at 6-9 weeks, revealed that deficits in learning and cognitive flexibility were absent or reduced relative to effects observed in naive adults. In Experiment 4, we tested working memory deficits with a delayed non-match to position (DNMTP) test. Mice with prior experience exhibited mild working memory deficits, with males zQ175 exhibiting

  4. Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy

    PubMed Central

    Choi, Kee-Hong; Wykes, Til; Kurtz, Matthew M.

    2013-01-01

    Background A growing number of studies have investigated the efficacy of novel, adjunctive pharmacotherapies for treatment of cognitive deficits in schizophrenia with conflicting results. Aims To investigate the comparative efficacy of these agents on cognition and symptoms in schizophrenia, and to identify promising cognitive domains and candidate medications that can be incorporated in treatment trials combined with cognitive remediation to maximise treatment effects. Method A total of 26 double-blind, placebo-controlled studies investigating medications targeted at cholinergic, glutamatergic or serotonergic receptor classes and with participants with schizophrenia or schizoaffective disorder were identified. Results Medications targeted at the cholinergic receptor class produced marginal improvements in verbal learning and memory (d = 0.23, P = 0.06), and donepezil, a specific type of cholinergic agonist, produced a moderate effect (d = 0.58) on spatial learning and memory. Cholinergic and glutamatergic agents produced moderate effect-size improvements on negative symptoms (d = 0.54 and d = 0.62 respectively), and small effect-size improvements on general symptoms (d = 0.46 and d = 0.41 respectively). Serotonergic agents produced small effect-size improvements in positive symptoms (d = 0.33). Conclusions Cholinergic medications produced marginal improvement in verbal learning and memory and moderate improvements on spatial learning and memory, although there was no evidence to support the use of glutamatergic or serotonergic medications as a stand-alone treatment for improving cognitive function. Cholinergic and glutamatergic agents improved negative and general symptoms, whereas serotenergic medications improved positive symptoms. PMID:23999481

  5. Time may not fully attenuate solvent-associated cognitive deficits in highly exposed workers

    PubMed Central

    Gutierrez, Laure-Anne; Okechukwu, Cassandra A.; Singh-Manoux, Archana; Amieva, Hélène; Goldberg, Marcel; Zins, Marie; Berr, Claudine

    2014-01-01

    Objective: To test the effects of lifetime occupational solvent exposure, as measured by dose and timing, on performance on multiple cognitive tests among retired French utility workers. Methods: A total of 2,143 retirees in the GAZEL cohort underwent cognitive testing in 2010. Lifetime exposure to chlorinated solvents, petroleum solvents, and benzene was assessed using a job exposure matrix. We modeled effects of lifetime solvent dose, timing of last exposure, and a combination of these metrics on risk for cognitive impairment. Results: Thirty-three percent of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. High exposure to solvents was significantly associated with poor cognition; for example, those highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination (risk ratio 1.18; 95% confidence interval 1.06, 1.31), the Digit Symbol Substitution Test (1.54; 1.31, 1.82), semantic fluency test (1.33; 1.14, 1.55), and the Trail Making Test B (1.49; 1.25, 1.77). Retirees at greatest risk for deficits had both high lifetime exposure to solvents and were last exposed 12 to 30 years before testing. Risk was somewhat elevated among those with high lifetime exposure who were last exposed 31 to 50 years before testing. Those with high, recent exposure exhibited impairment in almost all domains, including those not typically associated with solvent exposure. Conclusions: While risk of cognitive impairment among moderately exposed workers may attenuate with time, this may not be fully true for those with higher exposure. This has implications for physicians working with formerly solvent-exposed patients as well as for workplace exposure limit policies. PMID:24821933

  6. 16p11.2 Deletion mice display cognitive deficits in touchscreen learning and novelty recognition tasks

    PubMed Central

    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+/− 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. PMID:26572653

  7. 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

  8. 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.

  9. 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. PMID:26572653

  10. 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.

  11. Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies.

    PubMed

    Shrot, S; Katzav, A; Korczyn, A D; Litvinju, Y; Hershenson, R; Pick, C G; Blank, M; Zaech, J; Shoenfeld, Y; Sirota, P; Chapman, J

    2002-01-01

    The antiphospholipid (Hughes) syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI). Beta2-GPI immunized mice develop systemic manifestations of APS and we presently examined CNS manifestations in this APS model. Female BALB/c mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). A staircase test and a T-maze alternation test were performed to test behavior and cognition in independent groups of mice 6, 12 and 18 weeks following the immunization. The APS mice developed elevated levels of antibodies against negatively charged phospholipids and beta2-GPI. Neurological impairment was detected only 18 weeks after the induction of the APS and consisted of both cognitive (53 +/- 4 vs 71 +/- 3% correct choices in the T-maze alternation for APS vs control mice, P < 0.001) and behavioral changes (higher number of rears (18 +/- 2 vs 11 +/- 1, P < 0.006) and higher number of stairs climbed (12 +/- 2 vs 7 +/- 1, P < 0.02). This is the first report of cognitive deficits in this APS model and demonstrates the time course for the development of previously described behavioral changes. The mechanism involved in these CNS manifestations remains to be elucidated.

  12. Cognitive deficits induced by global cerebral ischaemia: prospects for transplant therapy.

    PubMed

    Hodges, H; Nelson, A; Virley, D; Kershaw, T R; Sinden, J D

    1997-04-01

    Global ischaemia induced by interruption of cerebral blood flow results in damage to vulnerable cells, notably in the CA1 and hilar hippocampal fields, and is frequently associated with memory deficits. This review examines cognitive deficits that occur in animal models of global ischaemia in rats and monkeys, the extent to which these deficits are associated with CA1 cell loss, and the evidence for functional recovery following transplants of foetal CA1 cells and grafts of conditionally immortalised precursor cells. In rats, impairments are seen most consistently in tasks of spatial learning and spatial working memory dependent on use of allocentric environmental cues. In monkeys, ischaemic deficits have been shown to a moderate extent in delayed object recognition tasks, but animals with a selective excitotoxic CA1 lesion show a profound impairment in conditional discrimination tasks, suggesting that these may be a more sensitive measure of ischaemic impairments. Several studies have reported correlational links between the extent of CA1 cell loss following two or four vessel occlusion (2 VO, 4 VO) in rats and behavioural impairments, but recent findings indicate that at intermediate levels of damage these relationships are weak and variable, and emerge clearly only when animals with maximal CA1 cell loss are included, suggesting that the deficits involve more than damage to the CA1 field. Nevertheless, ischaemic rats and CA1-lesioned marmosets with grafts of foetal CA1 cells show substantial improvements; in rats these are not found with grafts from other hippocampal fields. Conditionally immortalised cell lines and trophic grafts are currently being assessed for their functional potential in animal models, because clinical use of foetal cells will not be practicable. Recent findings suggest that an expanded population of neuroepithelial cells derived from the conditionally immortalised H-2Kb-tsA58 transgenic mouse improve spatial learning as effectively as CA1

  13. 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

  14. Stimulation of 5-HT2C receptors improves cognitive deficits induced by human tryptophan hydroxylase 2 loss of function mutation.

    PubMed

    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

    2014-04-01

    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-HT(2C) 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-HT(2) 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.

  15. Stress alleviates reduced expression of cell adhesion molecules (NCAM, L1), and deficits in learning and corticosterone regulation of apolipoprotein E knockout mice.

    PubMed

    Grootendorst, J; Oitzl, M S; Dalm, S; Enthoven, L; Schachner, M; de Kloet, E R; Sandi, C

    2001-11-01

    Cell adhesion molecules (CAMs) involved in synaptic changes underlying learning and memory processes, are implicated in the effect of stress on behavioural performance. The present study was designed to test the hypothesis that (i) expression of CAMs is apolipoprotein E- (apoE) genotype dependent and (ii) repeated exposure to stress modulates the synthesis of CAMs in an apoE-genotype dependent manner. Using ELISA we tested this hypothesis and measured expression of NCAM and L1 in different brain regions of naïve and stressed apolipoprotein E-knockout (apoE0/0) and C57Bl6 (wild-type) mice. Naïve apoE0/0 mice had elevated basal morning corticosterone and ACTH concentrations and decreased expression of NCAM and L1 compared to wild-type mice. Repeated exposure of mice to rats, as the common stressor, alleviated the reduction in expression of CAMs in apoE0/0 mice; seven days after the last rat exposure, expression of NCAM was increased in frontal brain and hippocampus whereas expression of L1 was increased in hippocampus and cerebellum. Rat stress attenuated the elevation of basal morning corticosterone concentration in apoE0/0 mice towards concentrations detected in wild-type mice. Moreover, rat stress improved learning and memory of apoE0/0 mice in the water maze. In conclusion, repeated exposure to stress eliminated apoE-genotype-related differences in expression of CAMs. Under these same conditions the differences in cognitive performance and corticosterone concentrations were abolished between wild type and apoE0/0 mice.

  16. Unrealistic representations of "the self": A cognitive neuroscience assessment of anosognosia for memory deficit.

    PubMed

    Berlingeri, Manuela; Ravasio, Alessandra; Cranna, Silvia; Basilico, Stefania; Sberna, Maurizio; Bottini, Gabriella; Paulesu, Eraldo

    2015-12-01

    Three cognitive components may play a crucial role in both memory awareness and in anosognosia for memory deficit (AMD): (1) a personal data base (PDB), i.e., a memory store that contains "semantic" representations about the self, (2) monitoring processes (MPs) and (3) an explicit evaluation system (EES), or comparator, that assesses and binds the representations stored in the PDB with information obtained from the environment. We compared both the behavior and the functional connectivity (as assessed by resting-state fMRI) of AMD patients with aware patients and healthy controls. We found that AMD is associated with an impoverished PDB, while MPs are necessary to successfully update the PDB. AMD was associated with reduced functional connectivity within both the default-mode network and in a network that includes the left lateral temporal cortex, the hippocampus and the insula. The reduced connectivity between the hippocampus and the insular cortex was correlated with AMD severity. PMID:26397037

  17. Current Status of Cognitive Behavioral Therapy for Adult Attention-Deficit Hyperactivity Disorder

    PubMed Central

    Knouse, Laura E.; Safren, Steven A.

    2010-01-01

    Synopsis Attention-deficit / hyperactivity disorder (ADHD) is a valid and impairing psychological disorder that persists into adulthood in a majority of cases and is associated with chronic functional impairment and increased rates of comorbidity. Cognitive-behavioral therapy (CBT) approaches for this disorder have emerged relatively recently, and available evidence from open and randomized controlled trials suggests that these approaches are promising in producing significant symptom reduction. A conceptual model of how CBT may work for ADHD is reviewed along with existing efficacy studies. A preliminary comparison of effect sizes across intervention packages suggests that targeted learning and practice of specific behavioral compensatory strategies may be a critical “active ingredient” in CBT for adult ADHD. The article concludes with a discussion of future directions and critical questions that must be addressed in this area of clinical research. PMID:20599129

  18. Negative attention bias and processing deficits during the cognitive reappraisal of unpleasant emotions in HIV+ women.

    PubMed

    McIntosh, Roger C; Tartar, Jaime L; Widmayer, Susan; Rosselli, Monica

    2015-01-01

    Deficits in emotional processing may be attributed to HIV disease or comorbid psychiatric disorders. Electrocortical markers of emotional attention, i.e., amplitude of the P2 and late positive potential (LPP), were compared between 26 HIV+ women and 25 healthy controls during an emotional regulation paradigm. HIV+ women showed early attention bias to negative stimuli indexed by greater P2 amplitude. In contrast, compared with the passive viewing of unpleasant images, HIV+ women demonstrated attenuation of the early and late LPP during positive reappraisal. This interaction remained significant after adjusting for individual differences in apathy, anxiety, and depression. Post hoc analyses implicated time since HIV diagnosis with LPP attenuation during positive reappraisal. Advancing HIV disease may disrupt neural generators associated with the cognitive reappraisal of emotions independent of psychiatric function. PMID:25541865

  19. Gray and White Matter Contributions to Cognitive Frontostriatal Deficits in Non-Demented Parkinson's Disease

    PubMed Central

    Price, Catherine C.; Tanner, Jared; Nguyen, Peter T.; Schwab, Nadine A.; Mitchell, Sandra; Slonena, Elizabeth; Brumback, Babette; Okun, Michael S.; Mareci, Thomas H.; Bowers, Dawn

    2016-01-01

    Objective This prospective investigation examined: 1) processing speed and working memory relative to other cognitive domains in non-demented medically managed idiopathic Parkinson’s disease, and 2) the predictive role of cortical/subcortical gray thickness/volume and white matter fractional anisotropy on processing speed and working memory. Methods Participants completed a neuropsychological protocol, Unified Parkinson’s Disease Rating Scale, brain MRI, and fasting blood draw to rule out vascular contributors. Within group a priori anatomical contributors included bilateral frontal thickness, caudate nuclei volume, and prefrontal white matter fractional anisotropy. Results Idiopathic Parkinson’s disease (n = 40; Hoehn & Yahr stages 1–3) and non-Parkinson’s disease ‘control’ peers (n = 40) matched on demographics, general cognition, comorbidity, and imaging/blood vascular metrics. Cognitively, individuals with Parkinson’s disease were significantly more impaired than controls on tests of processing speed, secondary deficits on working memory, with subtle impairments in memory, abstract reasoning, and visuoperceptual/spatial abilities. Anatomically, Parkinson’s disease individuals were not statistically different in cortical gray thickness or subcortical gray volumes with the exception of the putamen. Tract Based Spatial Statistics showed reduced prefrontal fractional anisotropy for Parkinson’s disease relative to controls. Within Parkinson’s disease, prefrontal fractional anisotropy and caudate nucleus volume partially explained processing speed. For controls, only prefrontal white matter was a significant contributor to processing speed. There were no significant anatomical predictors of working memory for either group. Conclusions Caudate nuclei volume and prefrontal fractional anisotropy, not frontal gray matter thickness, showed unique and combined significance for processing speed in Parkinson’s disease. Findings underscore the

  20. Methylphenidate improves the behavioral and cognitive deficits of neurogranin knockout mice.

    PubMed

    Huang, F L; Huang, K-P

    2012-10-01

    Neurogranin (Ng), a brain-specific calmodulin-binding protein, is expressed highly in hippocampus, and is important for cognitive function. Deletion of the Ng gene from mice caused attenuation of signal reaction cascade in hippocampus, impairments in learning and memory and high frequency stimulation-induced long-term potentiation (LTP). Environmental enrichment alone failed to improve cognitive function. In this study, behavioral testing revealed that Ng knockout (NgKO) mice were both hyperactive and socially withdrawn. Methylphenidate (MPH) was given to mice while they were also kept under an enrichment condition. MPH treatment reduced the hyperactivity of NgKO mice tested in both the open field and forced swim chamber. MPH improved their social abilities such that mice recognized and interacted better with novel subjects. The cognitive memories of MPH-treated mutants were improved in both water maze and contextual fear conditioning tests. High frequency stimulation-induced LTP of NgKO mice was also improved by MPH. The present treatment regimen, however, did not fully reverse the deficits of the mutant mice. In contrast, MPH exerted only a minimal effect on the wild type mice. At the cellular level, MPH increased the number of glial fibrillary acidic protein-positive cells in hippocampus, particularly within the dentate gyrus of NgKO mice. Therefore it will be of interest to determine the nature of MPH-mediated astrocyte activation and how it may modulate behavior in future studies. Taken together these NgKO mice may be useful for the development of better drug treatment to improve cognitive and behavioral impairments.

  1. 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.

  2. Cognitive deficits and striato-frontal dopamine release in Parkinson's disease.

    PubMed

    Sawamoto, Nobukatsu; Piccini, Paola; Hotton, Gary; Pavese, Nicola; Thielemans, Kris; Brooks, David J

    2008-05-01

    Idiopathic Parkinson's disease (PD) is often accompanied by a pattern of executive deficits similar to those found in patients with frontal lobe lesions. We investigated whether such cognitive deficits are attributable to frontal lobe dysfunction as a direct consequence of impaired mesocortical dopaminergic transmission or an indirect consequence of impaired nigrostriatal dopaminergic function. For this purpose, changes in synaptic dopamine levels during task performance were monitored using a marker of dopamine D2-receptor availability (11)C-raclopride (RAC) PET. During RAC PET, seven patients with early symptomatic PD and seven age-matched healthy controls performed two types of behavioural task, a spatial working memory task (SWT) and a visuomotor control task (VMT). The SWT involves an executive process which is known to be impaired by both frontal lobe lesions and PD while the VMT is a control test for the visuomotor component of the SWT. Parametric images of RAC binding potential during performance of each task were generated, and compared between the tasks using voxel-based statistical parametric mapping as well as region of interest analysis. In controls, RAC binding was reduced in the dorsal caudate during performance of the SWT compared with the VMT, compatible with increased levels of endogenous dopamine release due to the executive process. In PD patients, this RAC binding reduction was not observed. In contrast, RAC binding in the anterior cingulate cortex within the medial prefrontal cortex was reduced by a comparable level during the SWT both in controls and PD patients. Statistical comparisons between controls and PD patients confirmed significantly attenuated dopamine release in the dorsal caudate in PD, but preserved levels of medial prefrontal dopamine release. Our data suggest that executive deficits in early patients with PD are associated with impaired nigrostriatal dopaminergic function resulting in abnormal processing in the cortico

  3. 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

  4. Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease.

    PubMed

    Jankowsky, Joanna L; Melnikova, Tatiana; Fadale, Daniel J; Xu, Guilian M; Slunt, Hilda H; Gonzales, Victoria; Younkin, Linda H; Younkin, Steven G; Borchelt, David R; Savonenko, Alena V

    2005-05-25

    Epidemiological studies suggest that individuals with greater education or more cognitively demanding occupations have diminished risk of developing dementia. We wanted to test whether this effect could be recapitulated in rodents using environmental enrichment, a paradigm well documented to attenuate behavioral deficits induced by various pathological insults. Here, we demonstrate that learning and memory deficits observed in a transgenic mouse model of Alzheimer's disease can be ameliorated by enrichment. Female transgenic mice overexpressing amyloid precursor protein and/or presenilin-1 and nontransgenic controls were placed into enriched or standard cages at 2 months of age and tested for cognitive behavior after 6 months of differential housing. Enrichment significantly improved performance of all genotypes in the radial water maze and in the classic and repeated-reversal versions of the Morris water maze. However, enrichment did not benefit all genotypes equally. Mice overproducing amyloid-beta (Abeta), particularly those with amyloid deposits, showed weaker memory for the platform location in the classic Morris water maze and learned new platform positions in the repeated-reversals task less quickly than their nontransgenic cagemates. Nonetheless, enrichment normalized the performance of Abeta-overproducing mice to the level of standard-housed nontransgenic mice. Moreover, this functional preservation occurred despite increased neuritic plaque burden in the hippocampus of double-transgenic animals and elevated steady-state Abeta levels, because both endogenous and transgene-derived Abeta are increased in enriched animals. These results demonstrate that the generation of Abeta in vivo and its impact on the function of the nervous system can be strongly modulated by environmental factors.

  5. Cognition and the compassion deficit: the social psychology of helping behaviour in nursing.

    PubMed

    Paley, John

    2014-10-01

    This paper discusses compassion failure and compassion deficits in health care, using two major reports by Robert Francis in the UK as a point of reference. Francis enquired into events at the Mid Staffordshire Hospital between 2005 and 2009, events that unequivocally warrant the description 'appalling care'. These events prompted an intense national debate, along with proposals for significant changes in the regulation of nursing and nurse education. The circumstances are specific to the UK, but the issues are international. I suggest that social psychology provides numerous hints about the mechanisms that might have been involved at Mid Staffs and about the reasons why outsiders are blind to these mechanisms. However, there have been few references to social psychology in the post-Francis debate (the Francis Report itself makes no reference to it at all). It is an enormously valuable resource, and it has been overlooked. Drawing on the social psychology literature, I express scepticism about the idea that there was a compassion deficit among the Mid Staff nurses - the assumption that the appalling care had something to do with the character, attitudes, and values of nurses - and argue that the Francis Report's emphasis on a 'culture of compassion and caring in nurse recruitment, training and education' is misconceived. It was not a 'failure of compassion' that led to the events in Mid Staffs but an interlocking set of contextual factors that are known to affect social cognition. These factors cannot be corrected or compensated for by teaching ethics, empathy, and compassion to student nurses.

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

    PubMed Central

    Puccioni, Olga; Vallesi, Antonino

    2012-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. Cognitive deficits and emotion regulation strategies in patients with psychogenic nonepileptic seizures: a task-switching study.

    PubMed

    Gul, Amara; Ahmad, Hira

    2014-03-01

    This study examined the task-switching ability and emotion regulation strategies in 72 patients with psychogenic nonepileptic seizures (PNES) and 72 healthy individuals, where participants categorized emotion and age dimensions among faces. Results demonstrated cognitive impairment in terms of the interrupted ability to switch between emotion and nonemotion face categorizations in patients with PNES. In contrast, healthy individuals exhibited efficient switching between these face categorizations. In patients with PNES, there was an asymmetric relationship between emotion and age tasks, while this asymmetry was absent in the healthy group. The results demonstrated that patients with PNES used expressive suppression to regulate their emotions more frequently than the control group. On the other hand, patients with PNES less frequently reappraised their cognitions than healthy individuals. Switching deficits in patients with PNES were positively correlated with expressive suppression but were negatively correlated with cognitive reappraisal. This is the first study demonstrating the presence of switching deficits in terms of inferior cognitive control of emotion in patients with PNES as compared to healthy individuals. The switching deficits are associated with emotion regulation strategies. These findings suggest that emotion regulation strategies are significant markers of switching deficits in patients with PNES.

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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…

  14. 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)

  15. Phloroglucinol Attenuates the Cognitive Deficits of the 5XFAD Mouse Model of Alzheimer’s Disease

    PubMed Central

    Ryu, Junghwa; Choi, Moon-Seok; Choi, Shinkyu; Chong, Young Hae; Hyun, Jin-Won; Chang, Moon-Jeong; Kim, Hye-Sun

    2015-01-01

    Alzheimer’s disease (AD) is the most common form of dementia among the elderly. Neuritic plaques whose primary component is amyloid beta peptide (Aβ) and neurofibrillary tangles which are composed of hyperphosphorylated tau, are known to be the neuropathological hallmarks of AD. In addition, impaired synaptic plasticity in neuronal networks is thought to be important mechanism underlying for the cognitive deficits observed in AD. Although various causative factors, including excitotoxicity, mitochondrial dysregulation and oxidative damage caused by Aβ, are involved in early onset of AD, fundamental therapeutics that can modify the progression of this disease are not currently available. In the present study, we investigated whether phloroglucinol (1, 3, 5—trihydroxybenzene), a component of phlorotannins, which are plentiful in Ecklonia cava, a marine brown alga species, displays therapeutic activities in AD. We found that phloroglucinol attenuates the increase in reactive oxygen species (ROS) accumulation induced by oligomeric Aβ1–42 (Aβ1–42) treatment in HT-22, hippocampal cell line. In addition, phloroglucinol was shown to ameliorate the reduction in dendritic spine density induced by Aβ1–42 treatment in rat primary hippocampal neuron cultures. We also found that the administration of phloroglucinol to the hippocampal region attenuated the impairments in cognitive dysfunction observed in 22-week-old 5XFAD (Tg6799) mice, which are used as an AD animal model. These results indicate that phloroglucinol displays therapeutic potential for AD by reducing the cellular ROS levels. PMID:26284625

  16. Estrogen receptor ligands counteract cognitive deficits caused by androgen deprivation in male rats.

    PubMed

    Lagunas, Natalia; Calmarza-Font, Isabel; Grassi, Daniela; Garcia-Segura, Luis M

    2011-04-01

    Androgen deprivation causes impairment of cognitive tasks in rodents and humans, and this deficit can be reverted by androgen replacement therapy. Part of the effects of androgens in the male may be mediated by their local metabolism to estradiol or 3-alpha androstanediol within the brain and the consequent activation of estrogen receptors. In this study we have assessed whether the administration of estradiol benzoate, the estrogen receptor β selective agonist diarylpropionitrile or the estrogen receptor α selective agonist propyl pyrazole triol affect performance of androgen-deprived male Wistar rats in the cross-maze test. In addition, we tested the effect of raloxifene and tamoxifen, two selective estrogen receptor modulators used in clinical practice. The behavior of the rats was assessed 2 weeks after orchidectomy or sham surgery. Orchidectomy impaired acquisition in the cross-maze test. Estradiol benzoate and the selective estrogen receptor β agonist significantly improved acquisition in the cross-maze test compared to orchidectomized animals injected with vehicle. Raloxifene and tamoxifen at a dose of 1mg/kg, but not at doses of 0.5 or 2mg/kg, also improved acquisition of orchidectomized animals. Our findings suggest that estrogenic compounds with affinity for estrogen receptor β and selective estrogen receptor modulators, such as raloxifene and tamoxifen, may represent good candidates to promote cognitive performance in androgen-deprived males.

  17. Phosphodiesterase Inhibition Rescues Chronic Cognitive Deficits Induced by Traumatic Brain Injury

    PubMed Central

    Titus, David J.; Sakurai, Atsushi; Kang, Yuan; Furones, Concepcion; Jergova, Stanislava; Santos, Rosmery; Sick, Thomas J.; Atkins, Coleen M.

    2013-01-01

    Traumatic brain injury (TBI) modulates several cell signaling pathways in the hippocampus critical for memory formation. Previous studies have found that the cAMP-protein kinase A signaling pathway is downregulated after TBI and that treatment with a phosphodiesterase (PDE) 4 inhibitor rolipram rescues the decrease in cAMP. In the present study, we examined the effect of rolipram on TBI-induced cognitive impairments. At 2 weeks after moderate fluid-percussion brain injury or sham surgery, adult male Sprague Dawley rats received vehicle or rolipram (0.03 mg/kg) 30 min before water maze acquisition or cue and contextual fear conditioning. TBI animals treated with rolipram showed a significant improvement in water maze acquisition and retention of both cue and contextual fear conditioning compared with vehicle-treated TBI animals. Cue and contextual fear conditioning significantly increased phosphorylated CREB levels in the hippocampus of sham animals, but not in TBI animals. This deficit in CREB activation during learning was rescued in TBI animals treated with rolipram. Hippocampal long-term potentiation was reduced in TBI animals, and this was also rescued with rolipram treatment. These results indicate that the PDE4 inhibitor rolipram rescues cognitive impairments after TBI, and this may be mediated through increased CREB activation during learning. PMID:23516287

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

    PubMed

    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

    2016-02-01

    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.

  19. Epileptiform activity and cognitive deficits in SNAP-25(+/-) mice are normalized by antiepileptic drugs.

    PubMed

    Corradini, Irene; Donzelli, Andrea; Antonucci, Flavia; Welzl, Hans; Loos, Maarten; Martucci, Roberta; De Astis, Silvia; Pattini, Linda; Inverardi, Francesca; Wolfer, David; Caleo, Matteo; Bozzi, Yuri; Verderio, Claudia; Frassoni, Carolina; Braida, Daniela; Clerici, Mario; Lipp, Hans-Peter; Sala, Mariaelvina; Matteoli, Michela

    2014-02-01

    Synaptosomal-associated protein of 25 kDa (SNAP-25) is a protein that participates in the regulation of synaptic vesicle exocytosis through the formation of the soluble NSF attachment protein receptor complex and modulates voltage-gated calcium channels activity. The Snap25 gene has been associated with schizophrenia, attention deficit hyperactivity disorder, and bipolar disorder, and lower levels of SNAP-25 have been described in patients with schizophrenia. We used SNAP-25 heterozygous (SNAP-25(+/-)) mice to investigate at which extent the reduction of the protein levels affects neuronal network function and mouse behavior. As interactions of genotype with the specific laboratory conditions may impact behavioral results, the study was performed through a multilaboratory study in which behavioral tests were replicated in at least 2 of 3 distinct European laboratories. Reductions of SNAP-25 levels were associated with a moderate hyperactivity, which disappeared in the adult animals, and with impaired associative learning and memory. Electroencephalographic recordings revealed the occurrence of frequent spikes, suggesting a diffuse network hyperexcitability. Consistently, SNAP-25(+/-) mice displayed higher susceptibility to kainate-induced seizures, paralleled by degeneration of hilar neurons. Notably, both EEG profile and cognitive defects were improved by antiepileptic drugs. These results indicate that reduction of SNAP-25 expression is associated to generation of epileptiform discharges and cognitive dysfunctions, which can be effectively treated by antiepileptic drugs.

  20. Effectiveness of nootropic drugs with cholinergic activity in treatment of cognitive deficit: a review

    PubMed Central

    Colucci, Luisa; Bosco, Massimiliano; Ziello, Antonio Rosario; Rea, Raffaele; Amenta, Francesco; Fasanaro, Angiola Maria

    2012-01-01

    Nootropics represent probably the first “smart drugs” used for the treatment of cognitive deficits. The aim of this paper is to verify, by a systematic analysis of the literature, the effectiveness of nootropics in this indication. The analysis was limited to nootropics with cholinergic activity, in view of the role played by acetylcholine in learning and memory. Acetylcholine was the first neurotransmitter identified in the history of neuroscience and is the main neurotransmitter of the peripheral, autonomic, and enteric nervous systems. We conducted a systematic review of the literature for the 5-year period 2006–2011. From the data reported in the literature, it emerges that nootropics may be an effective alternative for strengthening and enhancing cognitive performance in patients with a range of pathologies. Although nootropics, and specifically the cholinergic precursors, already have a long history behind them, according to recent renewal of interest, they still seem to have a significant therapeutic role. Drugs with regulatory indications for symptomatic treatment of Alzheimer’s disease, such as cholinesterase inhibitors and memantine, often have transient effects in dementia disorders. Nootropics with a cholinergic profile and documented clinical effectiveness in combination with cognate drugs such as cholinesterase inhibitors or alone in patients who are not suitable for these inhibitors should be taken into account and evaluated further. PMID:27186129

  1. Effectiveness of nootropic drugs with cholinergic activity in treatment of cognitive deficit: a review.

    PubMed

    Colucci, Luisa; Bosco, Massimiliano; Rosario Ziello, Antonio; Rea, Raffaele; Amenta, Francesco; Fasanaro, Angiola Maria

    2012-01-01

    Nootropics represent probably the first "smart drugs" used for the treatment of cognitive deficits. The aim of this paper is to verify, by a systematic analysis of the literature, the effectiveness of nootropics in this indication. The analysis was limited to nootropics with cholinergic activity, in view of the role played by acetylcholine in learning and memory. Acetylcholine was the first neurotransmitter identified in the history of neuroscience and is the main neurotransmitter of the peripheral, autonomic, and enteric nervous systems. We conducted a systematic review of the literature for the 5-year period 2006-2011. From the data reported in the literature, it emerges that nootropics may be an effective alternative for strengthening and enhancing cognitive performance in patients with a range of pathologies. Although nootropics, and specifically the cholinergic precursors, already have a long history behind them, according to recent renewal of interest, they still seem to have a significant therapeutic role. Drugs with regulatory indications for symptomatic treatment of Alzheimer's disease, such as cholinesterase inhibitors and memantine, often have transient effects in dementia disorders. Nootropics with a cholinergic profile and documented clinical effectiveness in combination with cognate drugs such as cholinesterase inhibitors or alone in patients who are not suitable for these inhibitors should be taken into account and evaluated further.

  2. Facilitative effects of bi-hemispheric tDCS in cognitive deficits of Parkinson disease patients.

    PubMed

    Leite, Jorge; Gonçalves, Oscar F; Carvalho, Sandra

    2014-02-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily characterized by motor symptoms such as tremor, rigidity, bradykinesia, stiffness, slowness and impaired equilibrium. Although the motor symptoms have been the focus in PD, slight cognitive deficits are commonly found in non-demented and non-depressed PD patients, even in early stages of the disease, which have been linked to the subsequent development of pathological dementia. Thus, strongly reducing the quality of life (QoL). Both levodopa therapy and deep brain stimulation (DBS) have yield controversial results concerning the cognitive symptoms amelioration in PD patients. That does not seems to be the case with transcranial direct current stimulation (tDCS), although better stimulation parameters are needed. Therefore we hypothesize that simultaneously delivering cathodal tDCS (or ctDCS), over the right prefrontal cortex delivered with anodal tDCS (or atDCS) to left prefrontal cortex could be potentially beneficial for PD patients, either by mechanisms of homeostatic plasticity and by increases in the extracellular dopamine levels over the striatum.

  3. Phloroglucinol Attenuates the Cognitive Deficits of the 5XFAD Mouse Model of Alzheimer's Disease.

    PubMed

    Yang, Eun-Jeong; Ahn, Sangzin; Ryu, Junghwa; Choi, Moon-Seok; Choi, Shinkyu; Chong, Young Hae; Hyun, Jin-Won; Chang, Moon-Jeong; Kim, Hye-Sun

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia among the elderly. Neuritic plaques whose primary component is amyloid beta peptide (Aβ) and neurofibrillary tangles which are composed of hyperphosphorylated tau, are known to be the neuropathological hallmarks of AD. In addition, impaired synaptic plasticity in neuronal networks is thought to be important mechanism underlying for the cognitive deficits observed in AD. Although various causative factors, including excitotoxicity, mitochondrial dysregulation and oxidative damage caused by Aβ, are involved in early onset of AD, fundamental therapeutics that can modify the progression of this disease are not currently available. In the present study, we investigated whether phloroglucinol (1, 3, 5-trihydroxybenzene), a component of phlorotannins, which are plentiful in Ecklonia cava, a marine brown alga species, displays therapeutic activities in AD. We found that phloroglucinol attenuates the increase in reactive oxygen species (ROS) accumulation induced by oligomeric Aβ1-42 (Aβ1-42) treatment in HT-22, hippocampal cell line. In addition, phloroglucinol was shown to ameliorate the reduction in dendritic spine density induced by Aβ1-42 treatment in rat primary hippocampal neuron cultures. We also found that the administration of phloroglucinol to the hippocampal region attenuated the impairments in cognitive dysfunction observed in 22-week-old 5XFAD (Tg6799) mice, which are used as an AD animal model. These results indicate that phloroglucinol displays therapeutic potential for AD by reducing the cellular ROS levels. PMID:26284625

  4. Oligodendrocyte and Interneuron Density in Hippocampal Subfields in Schizophrenia and Association of Oligodendrocyte Number with Cognitive Deficits

    PubMed Central

    Falkai, Peter; Steiner, Johann; Malchow, Berend; Shariati, Jawid; Knaus, Andreas; Bernstein, Hans-Gert; Schneider-Axmann, Thomas; Kraus, Theo; Hasan, Alkomiet; Bogerts, Bernhard; Schmitt, Andrea

    2016-01-01

    In schizophrenia, previous stereological post-mortem investigations of anterior, posterior, and total hippocampal subfields showed no alterations in total neuron number but did show decreased oligodendrocyte numbers in CA4, an area that corresponds to the polymorph layer of the dentate gyrus (DG). However, these investigations identified oligodendrocytes only on the basis of morphological criteria in Nissl staining and did not assess alterations of interneurons with immunohistochemical markers. Moreover, the association of findings in the posterior hippocampus with cognitive deficits remains unknown. On the basis of the available clinical records, we compared patients with definite and possible cognitive dysfunction; nine patients had evidence in their records of either definite (n = 4) or possible (n = 5) cognitive dysfunction. Additionally, we assessed the density of two oligodendrocyte subpopulations immunostained by the oligodendrocyte transcription factors Olig1 and Olig2 and of interneurons immunolabeled by parvalbumin. We investigated posterior hippocampal subregions in the post-mortem brains of the same schizophrenia patients (SZ; n = 10) and healthy controls (n = 10) we examined in our previously published stereological studies. Our stereological studies found that patients with definite cognitive deficits had decreased total/Nissl-stained oligodendrocyte numbers in the left (p = 0.014) and right (p = 0.050) CA4, left CA2/3 (p = 0.050), left CA1 (p = 0.027), and left (p = 0.050) and right (p = 0.014) subiculum of the anterior part of the hippocampus compared to patients with possible cognitive deficits. In the present study, we found no significant influence of definite cognitive deficits in the posterior part of the hippocampus, whereas in the entire hippocampus SZ with definite cognitive deficits showed decreased oligodendrocyte numbers in the left (p = 0.050) and right (p = 0.050) DG and left CA2/3 (p = 0.050). We did not find significant differences in

  5. Emotion Perception or Social Cognitive Complexity: What Drives Face Processing Deficits in Autism Spectrum Disorder?

    ERIC Educational Resources Information Center

    Walsh, Jennifer A.; Creighton, Sarah E.; Rutherford, M. D.

    2016-01-01

    Some, but not all, relevant studies have revealed face processing deficits among those with autism spectrum disorder (ASD). In particular, deficits are revealed in face processing tasks that involve emotion perception. The current study examined whether either deficits in processing emotional expression or deficits in processing social cognitive…

  6. Longitudinal characterization of motor and cognitive deficits in a model of penetrating ballistic-like brain injury.

    PubMed

    Shear, Deborah A; Lu, Xi-Chun May; Bombard, Matthew C; Pedersen, Rebecca; Chen, Zhiyong; Davis, Angela; Tortella, Frank C

    2010-10-01

    Traumatic brain injury (TBI) produces a wide range of motor and cognitive changes. While some neurological symptoms may respond to therapeutic intervention during the initial recovery period, others may persist for many years after the initial insult, and often have a devastating impact on quality of life for the TBI victim. The aim of the current study was to develop neurobehavioral testing parameters designed to provide a longitudinal assessment of neurofunctional deficits in a rodent model of penetrating ballistic-like brain injury (PBBI). We report here a series of experiments in which unilateral frontal PBBI was induced in rats, and motor/cognitive abilities were assessed using a battery of tests ranging from 30 min to 10 weeks post-injury. The results showed that PBBI produced consistent and significant (1) neurological deficits (neuroscore examination: 30 min to 10 weeks post-PBBI), (2) sensorimotor dysfunction in the contralateral forelimb (forelimb asymmetry task: 7 and 21 days), (3) motor dysfunction (balance beam task: 3-7 days; and fixed-speed rotarod task: 3-28 days), and (4) spatial learning deficits in the Morris water maze (MWM) task out to 10 weeks post-injury. Overall, the results of this study demonstrate that PBBI produces enduring motor and cognitive deficits, and identifies the optimal task and testing parameters for facilitating longitudinal screening of promising therapeutic interventions in this brain injury model.

  7. 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

  8. Characterization of cognitive deficits in a transgenic mouse model of Alzheimer's disease and effects of donepezil and memantine.

    PubMed

    Nagakura, Akira; Shitaka, Yoshitsugu; Yarimizu, Junko; Matsuoka, Nobuya

    2013-03-01

    Alzheimer's disease is characterized by a progressive decline in cognitive function and involves β-amyloid (Aβ) in its pathogenesis. To characterize cognitive deficits associated with Aβ accumulation, we analyzed PS1/APP mice overexpressing mutant presenilin-1 (PS1, M146L; line 6.2) and amyloid precursor protein (APP, K670N/M671L; line Tg2576), a mouse model of Alzheimer's disease with accelerated Aβ production. Age-dependent changes in working and spatial memory behaviors were investigated using Y-maze and Morris water maze tasks, respectively, in female PS1/APP mice at ages of 2, 4, 6, and 12 months. Significant deficits in working and spatial memory were observed from 4 and 6 months of age, respectively. Acute single-dose administrations of memantine, a low-to-moderate-affinity N-methyl-d-aspartate (NMDA) antagonist, showed improvements in working memory deficits at 4 months of age, whereas donepezil, an acetylcholinesterase (AChE) inhibitor, did not. However, both drugs improved spatial memory dysfunction at 6 months of age at therapeutically relevant doses. No age-related dramatic changes were observed in expression levels of several proteins relating to memory dysfunction and also the mechanisms of donepezil and memantine in the cerebral cortex of PS1/APP mice until 6 months of age. Taken together, these results suggest dysfunctions in cholinergic and/or glutamatergic transmissions may be involved in the cognitive deficits associated with Aβ toxicity. Since donepezil and memantine have been widely used for treating patients of Alzheimer's disease, these results also suggest that cognitive deficits in PS1/APP mice assessed in the Y-maze and Morris water maze tasks are a useful animal model for evaluating novel Alzheimer's disease therapeutics.

  9. Cognition and the compassion deficit: the social psychology of helping behaviour in nursing.

    PubMed

    Paley, John

    2014-10-01

    This paper discusses compassion failure and compassion deficits in health care, using two major reports by Robert Francis in the UK as a point of reference. Francis enquired into events at the Mid Staffordshire Hospital between 2005 and 2009, events that unequivocally warrant the description 'appalling care'. These events prompted an intense national debate, along with proposals for significant changes in the regulation of nursing and nurse education. The circumstances are specific to the UK, but the issues are international. I suggest that social psychology provides numerous hints about the mechanisms that might have been involved at Mid Staffs and about the reasons why outsiders are blind to these mechanisms. However, there have been few references to social psychology in the post-Francis debate (the Francis Report itself makes no reference to it at all). It is an enormously valuable resource, and it has been overlooked. Drawing on the social psychology literature, I express scepticism about the idea that there was a compassion deficit among the Mid Staff nurses - the assumption that the appalling care had something to do with the character, attitudes, and values of nurses - and argue that the Francis Report's emphasis on a 'culture of compassion and caring in nurse recruitment, training and education' is misconceived. It was not a 'failure of compassion' that led to the events in Mid Staffs but an interlocking set of contextual factors that are known to affect social cognition. These factors cannot be corrected or compensated for by teaching ethics, empathy, and compassion to student nurses. PMID:24447716

  10. Cluster analysis of cognitive deficits may mark heterogeneity in schizophrenia in terms of outcome and response to treatment

    PubMed Central

    Gilbert, Elsa; Mérette, Chantal; Jomphe, Valérie; Émond, Claudia; Rouleau, Nancie; Bouchard, Roch-Hugo; Roy, Marc-André; Paccalet, Thomas

    2016-01-01

    Cognitive impairments are central to schizophrenia, but their clinical utility for tagging heterogeneity in lifetime outcome and response to treatment is not conclusive. By exploiting four cognitive domains consistently showing large deficits in studies, we tested whether cluster analysis would define separate subsets of patients and then whether the disease heterogeneity marked by these clusters would be related to lifetime outcome and response to treatment. A total of 112 schizophrenia patients completed a neuropsychological evaluation. The PANSS, GAF-S and GAF-F were rated at the onset and endpoint of the illness trajectory. A blind judgment of the lifetime response to treatment was made. The first cluster presented near-normal cognitive performance. Two other clusters of severely impaired patients were identified: one generally impaired in the four cognitive domains and another selectively impaired in visual episodic memory and processing speed, each relating to a different lifetime evolution of disease and treatment response. Although the two impaired clusters were clinically indistinguishable in symptom severity and functioning at disease onset, patients with selective cognitive impairments demonstrated better improvement at outcome, whereas the generally impaired patients were more likely to be treatment refractory. The findings have implications for the management of patients and for clinical trials since particular combinations of cognitive deficits in patients would influence their treatment response. PMID:24173295

  11. Selective cognitive deficits in adult rats after prenatal exposure to inhaled ethanol.

    PubMed

    Oshiro, W M; Beasley, T E; McDaniel, K L; Taylor, M M; Evansky, P; Moser, V C; Gilbert, M E; Bushnell, P J

    2014-01-01

    Increased use of ethanol blends in gasoline suggests a need to assess the potential public health risks of exposure to these fuels. Ethanol consumed during pregnancy is a teratogen. However, little is known about the potential developmental neurotoxicity of ethanol delivered by inhalation, the most likely route of exposure from gasoline-ethanol fuel blends. We evaluated the potential cognitive consequences of ethanol inhalation by exposing pregnant Long Evans rats to clean air or ethanol vapor from gestational days 9-20, a critical period of neuronal development. Concentrations of inhaled ethanol (5000, 10,000, or 21,000 ppm for 6.5h/day) produced modeled peak blood ethanol concentrations (BECs) in exposed dams of 2.3, 6.8, and 192 mg/dL, respectively. In offspring, no dose-related impairments were observed on spatial learning or working memory in the Morris water maze or in operant delayed match-to-position tests. Two measures showed significant effects in female offspring at all ethanol doses: 1) impaired cue learning after trace fear conditioning, and 2) an absence of bias for the correct quadrant after place training during a reference memory probe in the Morris water maze. In choice reaction time tests, male offspring (females were not tested) from the 5000 and 10,000 ppm groups showed a transient increase in decision times. Also, male offspring from the 21,000 ppm group made more anticipatory responses during a preparatory hold period, suggesting a deficit in response inhibition. The increase in anticipatory responding during the choice reaction time test shows that inhaled ethanol yielding a peak BEC of ~200mg/dL can produce lasting effects in the offspring. The lack of a dose-related decrement in the effects observed in females on cue learning and a reference memory probe may reflect confounding influences in the exposed offspring possibly related to maternal care or altered anxiety levels in females. The surprising lack of more pervasive cognitive deficits

  12. 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

    2015-01-01

    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.

  13. Beneficial effects of asiaticoside on cognitive deficits in senescence-accelerated mice.

    PubMed

    Lin, Xing; Huang, Renbin; Zhang, Shijun; Wei, Ling; Zhuo, Lang; Wu, Xiaoyan; Tang, Aicun; Huang, Quanfang

    2013-06-01

    The effect of asiaticoside isolated from Hydrocotyle sibthorpioides (AHS) on the promotion of cognition in senescence-accelerated mice (SAMP) was evaluated. Six-month old male SAMP8 mice were orally administered 20, 40 or 80 mg/kg AHS daily for three months. SAMR1 mice were used as a "normal aging" control. The results showed that treatment with AHS significantly improved learning and memory abilities in behavioral tests. AHS-treated mice showed higher antioxidant enzyme activity and lower lipid oxidation in serum compared with untreated SAMP8 mice. Mechanistically, studies showed that AHS markedly reduced the content and deposition of β-amyloid peptide (Aβ) by inhibiting the expression of mRNA for amyloid protein precursor, β-site amyloid cleaving enzyme-1 and cathepsin B and promoting the expression of mRNA for neprilysin and insulin degrading enzyme. In addition, AHS significantly increased the expression of plasticity-related proteins including postsynaptic density-95, phosphor-N-methyl-D-aspartate receptor 1, phospho-calcium-calmodulin dependent kinase II, phospho-protein kinase A Catalyticβ subunit, protein kinase Cγ subunit, phospho-CREB and brain derived neurotrophic factor. Furthermore, AHS increased the levels of acetylcholine (Ach), but decreased cholinesterase (AchE) activity. These results demonstrated that AHS administration may prevent spatial learning and memory decline by scavenging free radicals, up-regulating the activity of antioxidant enzymes, decreasing the level of Aβ, ameliorating dysfunction in synaptic plasticity, and reversing abnormal changes in Ach level and AchE activity. Thus, AHS should be developed as a new drug to prevent age-related cognitive deficits.

  14. Sensation-to-Cognition Cortical Streams in Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Carmona, Susana; Hoekzema, Elseline; Castellanos, Francisco X.; García-García, David; Lage-Castellanos, Agustín; Dijk, Koene R.A.Van; Navas-Sánchez, Francisco J.; Martínez, Kenia; Desco, Manuel; Sepulcre, Jorge

    2015-01-01

    We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortex—visual, auditory, and somatosensory—we used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naïve children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD. PMID:25821110

  15. Sensation-to-cognition cortical streams in attention-deficit/hyperactivity disorder.

    PubMed

    Carmona, Susana; Hoekzema, Elseline; Castellanos, Francisco X; García-García, David; Lage-Castellanos, Agustín; Van Dijk, Koene R A; Navas-Sánchez, Francisco J; Martínez, Kenia; Desco, Manuel; Sepulcre, Jorge

    2015-07-01

    We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortex-visual, auditory, and somatosensory-we used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naïve children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD.

  16. Insulin Signaling Misregulation underlies Circadian and Cognitive Deficits in a Drosophila Fragile X Model

    PubMed Central

    Monyak, Rachel E.; Emerson, Danielle; Schoenfeld, Brian P.; Zheng, Xiangzhong; Chambers, Daniel B.; Rosenfelt, Cory; Langer, Steven; Hinchey, Paul; Choi, Catherine H.; McDonald, Thomas V.; Bolduc, Francois V.; Sehgal, Amita; McBride, Sean M.J.; Jongens, Thomas A.

    2016-01-01

    Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low IQ and a wide range of other symptoms including disordered sleep and autism. Although FXS is the most prevalent inherited cause of intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. Examination of the insulin-signaling (IS) pathway revealed elevated levels of Drosophila insulin-like peptide 2 (Dilp2) in the IPCs and elevated IS in the dfmr1 mutant brain. Consistent with a causal role for elevated IS in dfmr1 mutant phenotypes, expression of dfmr1 specifically in the IPCs reduced IS, and genetic reduction of the insulin pathway also led to amelioration of circadian and memory defects. Furthermore we showed that treatment with the FDA approved drug metformin also rescued memory. Finally, we showed that reduction of IS is required at different time points to rescue circadian behavior and memory. Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients. PMID:27090306

  17. Chronic behavioral and cognitive deficits in a rat survival model of paraoxon toxicity.

    PubMed

    Deshpande, Laxmikant S; Phillips, Kristin; Huang, Beverly; DeLorenzo, Robert J

    2014-09-01

    Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen for medical countermeasures against severe OP exposure. It is well known that the survivors of nerve gas and chronic OP exposure exhibit neurobehavioral deficits such as mood changes, depression, and memory impairments. In this study we investigated whether animals surviving severe POX exposure exhibited long-term neurological impairments. POX exposure produced overt signs of cholinergic toxicity. Rats were rescued using an optimized atropine, 2-PAM and diazepam therapy. Surviving rats were studied using established behavioral assays for identifying symptoms of depression and memory impairment 3-months after POX exposure. In the forced swim test, POX rats exhibited increased immobility time indicative of a despair-like state. In the sucrose preference test, POX rats consumed significantly less sucrose water indicating anhedonia-like condition. POX rats also displayed increased anxiety as characterized by significantly lower performance in the open arm of the elevated plus maze. Further, when tested with a novel object recognition paradigm, POX rats exhibited a negative discrimination ratio indicative of impaired recognition memory. The results indicate that this model of survival from severe POX exposure can be employed to study some of the molecular bases for OP-induced chronic behavioral and cognitive comorbidities and develop therapies for their treatment.

  18. Quantative EEG during baseline and various cognitive tasks in children with attention deficit/hyperactivity disorder.

    PubMed

    Bakhtadze, S; Janelidze, M

    2010-09-01

    It is known that attention deficit/hyperactivity disorder is a widely spread condition in school aged childhood population. Making of precise diagnosis is a serious problem of modern pediatric neurology. In spite of large amount of guidelines and questionnaires the unified consensus of diagnosis is still absent. Thus it is important to search additional diagnostic criteria which can help physicians to confirm ADHD. For this purposes we have used quantative EEG (QEEG) parameters. There are numerous papers regarding QEEG changes of ADHD children during baseline (resting with closed eyes, resting with opened eyes, photic stimulation, hyperventilation).But information concerning QEEG evidences during cognitive tasks is insufficient. For this purposes we have used QEEG during Raven test, reading and calculation in children with ADHD and control group. QEEG was carried out according to standard 10-20 electrode placement rule from the following derivations: F3, F4, C3, C4, P3, P4, O1, O2. We have observed that in controls fulfilling of Raven test is more difficult than reading. Thus they are eulectic but in ADHD children reading is more difficult than Raven test. Thus they are dyslexic. By means of alpha and delta bands analysis it became apparent that alpha band is inversely proportional to mental effort and delta band is directly proportional to mental activity. PMID:20972277

  19. Hypercholesterolemic diet applied to rat dams protects their offspring against cognitive deficits. Simulated neonatal anoxia model.

    PubMed

    Bohr, Iwo

    2004-09-30

    There is accumulating data suggesting a neuroprotective activity of cholesterol, especially in stroke and Alzheimer's disease (AD). In the present study, a protective activity of this lipid in simulated neonatal anoxia was investigated. Rats were subjected to high cholesterol by feeding their dams with a diet enriched with cholesterol. Half of these rats were subjected to anoxia. One and a half months later, the rats were tested for their ability to acquire a spatial memory, one group on the linear maze and the other on the Morris water maze. After these assessments, the level of total plasma cholesterol was measured. Rats from dams subjected to neonatal anoxia on standard diet performed worse than control rats in both types of behavioral experiments, whereas anoxic rats from dams were housed on hypercholesterolemic diet performed as control animals. It suggests that dietetic cholesterol applied by their dams protected rats against cognitive deficits elicited by neonatal anoxia. Furthermore, offspring of anoxic rats housed on standard diet had elevated levels of blood cholesterol in relation to control animals. Generally, anoxia affected the concentration of this lipid much stronger than hypercholesterolemic diet of their dams. It might mean that the anoxia-related rise of cholesterol could be involved in physiological phenomenon being an adaptive response to neurotoxic processes. This concept is discussed in relation to pathological mechanisms in AD.

  20. Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model

    PubMed Central

    Xu, Jiqing; de Winter, Fred; Farrokhi, Catherine; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Cook, Jonathan; Jin, Xin; Masliah, Eliezer; Lee, Kuo-Fen

    2016-01-01

    Several lines of evidence suggest that neuregulin 1 (NRG1) signaling may influence cognitive function and neuropathology in Alzheimer’s disease (AD). To test this possibility, full-length type I or type III NRG1 was overexpressed via lentiviral vectors in the hippocampus of line 41 AD mouse. Both type I and type III NRG1 improves deficits in the Morris water-maze behavioral task. Neuropathology was also significantly ameliorated. Decreased expression of the neuronal marker MAP2 and synaptic markers PSD95 and synaptophysin in AD mice was significantly reversed. Levels of Aβ peptides and plaques were markedly reduced. Furthermore, we showed that soluble ectodomains of both type I and type III NRG1 significantly increased expression of Aβ-degrading enzyme neprilysin (NEP) in primary neuronal cultures. Consistent with this finding, immunoreactivity of NEP was increased in the hippocampus of AD mice. These results suggest that NRG1 provides beneficial effects in candidate neuropathologic substrates of AD and, therefore, is a potential target for the treatment of AD. PMID:27558862

  1. Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer's disease pathogenesis.

    PubMed

    Zhu, Li; Zhong, Minghao; Elder, Gregory A; Sano, Mary; Holtzman, David M; Gandy, Sam; Cardozo, Christopher; Haroutunian, Vahram; Robakis, Nikolaos K; Cai, Dongming

    2015-09-22

    The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer's disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD.

  2. Cognitive-motivational deficits in ADHD: development of a classification system.

    PubMed

    Gupta, Rashmi; Kar, Bhoomika R; Srinivasan, Narayanan

    2011-01-01

    The classification systems developed so far to detect attention deficit/hyperactivity disorder (ADHD) do not have high sensitivity and specificity. We have developed a classification system based on several neuropsychological tests that measure cognitive-motivational functions that are specifically impaired in ADHD children. A total of 240 (120 ADHD children and 120 healthy controls) children in the age range of 6-9 years and 32 Oppositional Defiant Disorder (ODD) children (aged 9 years) participated in the study. Stop-Signal, Task-Switching, Attentional Network, and Choice Delay tests were administered to all the participants. Receiver operating characteristic (ROC) analysis indicated that percentage choice of long-delay reward best classified the ADHD children from healthy controls. Single parameters were not helpful in making a differential classification of ADHD with ODD. Multinominal logistic regression (MLR) was performed with multiple parameters (data fusion) that produced improved overall classification accuracy. A combination of stop-signal reaction time, posterror-slowing, mean delay, switch cost, and percentage choice of long-delay reward produced an overall classification accuracy of 97.8%; with internal validation, the overall accuracy was 92.2%. Combining parameters from different tests of control functions not only enabled us to accurately classify ADHD children from healthy controls but also in making a differential classification with ODD. These results have implications for the theories of ADHD.

  3. Smart Soup, a Traditional Chinese Medicine Formula, Ameliorates Amyloid Pathology and Related Cognitive Deficits

    PubMed Central

    Li, Xiaohang; Cui, Jin; Ding, Jianqing; Wang, Ying; Zeng, Xianglu; Ling, Yun; Shen, Xiaoheng; Chen, Shengdi; Huang, Chenggang; Pei, Gang

    2014-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe disease-modifying treatment and symptomatic intervention alternatives against AD. Smart Soup (SS), a Chinese medicine formula composed of Rhizoma Acori Tatarinowii (AT), Poria cum Radix Pini (PRP) and Radix Polygalae (RP), is a typical prescription against memory deficits. Here, we assessed the efficacy of SS against AD. Oral administration of SS ameliorated the cognitive impairment of AD transgenic mice, with reduced Aβ levels, retarded Aβ amyloidosis and reduced Aβ-induced gliosis and neuronal loss in the brains of AD mice. Consistently, SS treatment reduced amyloid-related locomotor dysfunctions and premature death of AD transgenic Drosophila. Mechanistic studies showed that RP reduced Aβ generation, whereas AT and PRP exerted neuroprotective effects against Aβ. Taken together, our study indicates that SS could be effective against AD, providing a practical therapeutic strategy against the disease. PMID:25386946

  4. Caffeine regulates frontocorticostriatal dopamine transporter density and improves attention and cognitive deficits in an animal model of attention deficit hyperactivity disorder.

    PubMed

    Pandolfo, Pablo; Machado, Nuno J; Köfalvi, Attila; Takahashi, Reinaldo N; Cunha, Rodrigo A

    2013-04-01

    Attention deficit hyperactivity disorder (ADHD) likely involves dopaminergic dysfunction in the frontal cortex and striatum, resulting in cognitive and motor abnormalities. Since both adenosine and dopamine modulation systems are tightly intertwined, we tested if caffeine (a non-selective adenosine receptor antagonist) attenuated the behavioral and neurochemical changes in adolescent spontaneously hypertensive rats (SHR, a validated ADHD animal model) compared to their control strain (Wistar Kyoto rats, WKY). SHR were hyperactive and had poorer performance in the attentional set-shifting and Y-maze paradigms and also displayed increased dopamine transporter (DAT) density and increased dopamine uptake in frontocortical and striatal terminals compared with WKY rats. Chronic caffeine treatment was devoid of effects in WKY rats while it improved memory and attention deficits and also normalized dopaminergic function in SHR. Additionally, we provide the first direct demonstration for the presence of adenosine A2A receptors (A2AR) in frontocortical nerve terminals, whose density was increased in SHR. These findings underscore the potential for caffeine treatment to normalize frontocortical dopaminergic function and to abrogate attention and cognitive changes characteristic of ADHD.

  5. Troxerutin protects against high cholesterol-induced cognitive deficits in mice.

    PubMed

    Lu, Jun; Wu, Dong-mei; Zheng, Zi-hui; Zheng, Yuan-lin; Hu, Bin; Zhang, Zi-feng

    2011-03-01

    -positive cells in the hippocampus. However, intra-cerebroventricular infusion of PI-103, a specific phosphoinositide 3-kinase 110α inhibitor, significantly inhibited the expression levels of phosphoinositide 3-kinase 110α and phosphoinositide 3-kinase downstream signalling in the hippocampus of mice co-treated with high cholesterol and troxerutin and vehicle control mice. These results suggest that troxerutin could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in type 2 diabetes mellitus and Alzheimer's disease.

  6. Asiaticoside attenuates diabetes-induced cognition deficits by regulating PI3K/Akt/NF-κB pathway.

    PubMed

    Yin, Zhujun; Yu, Haiyang; Chen, She; Ma, Chunhua; Ma, Xiao; Xu, Lixing; Ma, Zhanqiang; Qu, Rong; Ma, Shiping

    2015-10-01

    Diabetes-associated cognitive dysfunction, referred as "diabetic encephalopathy", has been confirmed in a great deal of literature. Current evidence support that oxidative stress, inflammation, energy metabolism imbalance, and aberrant insulin signaling are associated with cognition deficits induced by diabetes. The present study explore the effect of asiaticoside on the cognition behaviors, synapses, and oxidative stress in diabetic rats. Asiaticoside could markedly ameliorate the performance in the Morris Water Maze (decreased latency time and path length, and increased time spent in the target quadrant), which was correlated with its capabilities of suppressing oxidative stress, restoring Na(+)-K(+)-ATPase activity and protecting hippocampal synapses. In vitro, asiaticoside could up-regulate synaptic proteins expression via modulating Phosphoinositide 3-kinase (PI3K)/Protein Kinase B(AKT)/Nuclear Factor -kappa B (NF-κB)-mediated inflammatory pathway in SH-SY5Y cells incubated with high glucose chronically. In conclusion, asiaticoside had beneficial effects on the prevention and treatment of diabetes-associated cognitive deficits, which was involved in oxidative stress, PI3K/Akt/NF-κB pathway and synaptic function in the development of cognitive decline induced by diabetes.

  7. Hippocampal Aβ expression, but not phosphorylated tau, predicts cognitive deficits following repeated peripheral poly I:C administration.

    PubMed

    White, J D; Eimerbrink, M J; Hayes, H B; Hardy, A; Van Enkevort, E A; Peterman, J L; Chumley, M J; Boehm, G W

    2016-10-15

    Alzheimer's disease is marked by the accumulation of the amyloid-beta (Aβ) peptide, and increases in phosphorylation of the microtubule associated protein, tau. Changes in these proteins are considered responsible, in part, for the progressive neuronal degeneration and cognitive deficits seen in AD. We examined the effect of repeated consecutive peripheral poly I:C injections on cognitive deficits, central Aβ, and phosphorylated tau accumulation, following three treatment durations: 7, 14, and 21 days. Forty-eight hours after the final injection, animals were trained in a contextual fear-conditioning paradigm, and tested 24h later. Immediately after testing, the hippocampus was collected to quantify Aβ and phosphorylated tau accumulation. Results showed that, although poly I:C-induced Aβ was significantly elevated at all time points examined, poly I:C only disrupted cognition after 14 and 21 days of administration. Moreover, elevations in phosphorylated tau were not seen until the 14-day time point. Interestingly, phosphorylated tau expression then declined at the 21-day time point. Finally, we demonstrated that Aβ levels are a stronger predictor of cognitive dysfunction, explaining 37% of the variance, whereas phosphorylated tau levels only accounted for 0.2%. Taken together, these results support the hypothesis that inflammation-induced elevation in Aβ disrupts cognition, independently of phosphorylated tau, and suggest that long-term administration of poly I:C may provide a model to investigate the contribution of long-term inflammation toward the development of Alzheimer's-like pathology.

  8. Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway.

    PubMed

    Zhu, Yao-Feng; Li, Xian-Hui; Yuan, Zhi-Peng; Li, Chun-Yan; Tian, Rong-Bo; Jia, Wei; Xiao, Zhu-Ping

    2015-09-01

    Endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases including Alzheimer's disease (AD), in which dysregulation of double-stranded RNA-dependent protein kinase (PKR)-like ER-resident kinase (PERK) is considered to play a critical role. Allicin, a garlic extract, has been demonstrated a protective role in AD model. The present study was designed to investigate the possible protective effect of allicin on ER stress-induced cognitive deficits and underlying mechanisms in rats. In this study, 72h of lateral ventricular infusion of tunicamycin (TM), an ER stress stimulator, induced significant cognitive deficits. TM increased tau phosphorylation, Aβ42 deposit, and oxidative stress, and reduced antioxidative enzymes activity in the hippocampus. TM moderately elevated the expression of PERK and its downstream substrate nuclear factor erythroid-derived 2-like 2 (Nrf2) in the hippocampus. All these impaired changes by TM were significantly improved by allicin pretreatment. Allicin markedly increased PERK and Nrf2 expression in the hippocampus. Thus, our data demonstrate the protective role of allicin in ER stress-related cognitive deficits, and suggest that PERK/Nrf2 antioxidative signaling pathway underlies the action mechanism. PMID:26049013

  9. Cognitive deficits caused by a disease-mutation in the α3 Na(+)/K(+)-ATPase isoform.

    PubMed

    Holm, Thomas Hellesøe; Isaksen, Toke Jost; Glerup, Simon; Heuck, Anders; Bøttger, Pernille; Füchtbauer, Ernst-Martin; Nedergaard, Steen; Nyengaard, Jens Randel; Andreasen, Mogens; Nissen, Poul; Lykke-Hartmann, Karin

    2016-01-01

    The Na(+)/K(+)-ATPases maintain Na(+) and K(+) electrochemical gradients across the plasma membrane, a prerequisite for electrical excitability and secondary transport in neurons. Autosomal dominant mutations in the human ATP1A3 gene encoding the neuron-specific Na(+)/K(+)-ATPase α3 isoform cause different neurological diseases, including rapid-onset dystonia-parkinsonism (RDP) and alternating hemiplegia of childhood (AHC) with overlapping symptoms, including hemiplegia, dystonia, ataxia, hyperactivity, epileptic seizures, and cognitive deficits. Position D801 in the α3 isoform is a mutational hotspot, with the D801N, D801E and D801V mutations causing AHC and the D801Y mutation causing RDP or mild AHC. Despite intensive research, mechanisms underlying these disorders remain largely unknown. To study the genotype-to-phenotype relationship, a heterozygous knock-in mouse harboring the D801Y mutation (α3(+/D801Y)) was generated. The α3(+/D801Y) mice displayed hyperactivity, increased sensitivity to chemically induced epileptic seizures and cognitive deficits. Interestingly, no change in the excitability of CA1 pyramidal neurons in the α3(+/D801Y) mice was observed. The cognitive deficits were rescued by administration of the benzodiazepine, clonazepam, a GABA positive allosteric modulator. Our findings reveal the functional significance of the Na(+)/K(+)-ATPase α3 isoform in the control of spatial learning and memory and suggest a link to GABA transmission. PMID:27549929

  10. Cognitive deficits caused by a disease-mutation in the α3 Na+/K+-ATPase isoform

    PubMed Central

    Holm, Thomas Hellesøe; Isaksen, Toke Jost; Glerup, Simon; Heuck, Anders; Bøttger, Pernille; Füchtbauer, Ernst-Martin; Nedergaard, Steen; Nyengaard, Jens Randel; Andreasen, Mogens; Nissen, Poul; Lykke-Hartmann, Karin

    2016-01-01

    The Na+/K+-ATPases maintain Na+ and K+ electrochemical gradients across the plasma membrane, a prerequisite for electrical excitability and secondary transport in neurons. Autosomal dominant mutations in the human ATP1A3 gene encoding the neuron-specific Na+/K+-ATPase α3 isoform cause different neurological diseases, including rapid-onset dystonia-parkinsonism (RDP) and alternating hemiplegia of childhood (AHC) with overlapping symptoms, including hemiplegia, dystonia, ataxia, hyperactivity, epileptic seizures, and cognitive deficits. Position D801 in the α3 isoform is a mutational hotspot, with the D801N, D801E and D801V mutations causing AHC and the D801Y mutation causing RDP or mild AHC. Despite intensive research, mechanisms underlying these disorders remain largely unknown. To study the genotype-to-phenotype relationship, a heterozygous knock-in mouse harboring the D801Y mutation (α3+/D801Y) was generated. The α3+/D801Y mice displayed hyperactivity, increased sensitivity to chemically induced epileptic seizures and cognitive deficits. Interestingly, no change in the excitability of CA1 pyramidal neurons in the α3+/D801Y mice was observed. The cognitive deficits were rescued by administration of the benzodiazepine, clonazepam, a GABA positive allosteric modulator. Our findings reveal the functional significance of the Na+/K+-ATPase α3 isoform in the control of spatial learning and memory and suggest a link to GABA transmission. PMID:27549929

  11. Rosemary extract improves cognitive deficits in a rats model of repetitive mild traumatic brain injury associated with reduction of astrocytosis and neuronal degeneration in hippocampus.

    PubMed

    Song, Hai; Xu, Lincheng; Zhang, Rongping; Cao, Zhenzhen; Zhang, Huan; Yang, Li; Guo, Zeyun; Qu, Yongqiang; Yu, Jianyun

    2016-05-27

    In this study, we investigated whether Rosemary extract (RE) improved cognitive deficits in repetitive mild Traumatic brain injury (rmTBI) rats and its potential mechanisms. The present results showed that rmTBI caused cognitive deficits, such as increased latency to find platform and decreased time spent in target quadrant in Morris water maze (MWM). These behavioral alterations were accompanying with the increased neuronal degeneration and glial fibrillary acidic protein (GFAP)-positive cells, increased Reactive oxygen species (ROS) generation, decreased activity of Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Catalase (CAT), elevated protein level of IL-1β, IL-6 and TNF-α in hippocampus. Treatment with RE prevented these changes above. Our findings confirmed the effect of rosemary extract on improvement of cognitive deficits and suggested its mechanisms might be mediated by anti-oxidative and anti-inflammatory. Therefore, rosemary extract may be a potential treatment to improve cognitive deficits in rmTBI patients. PMID:27113205

  12. Rosemary extract improves cognitive deficits in a rats model of repetitive mild traumatic brain injury associated with reduction of astrocytosis and neuronal degeneration in hippocampus.

    PubMed

    Song, Hai; Xu, Lincheng; Zhang, Rongping; Cao, Zhenzhen; Zhang, Huan; Yang, Li; Guo, Zeyun; Qu, Yongqiang; Yu, Jianyun

    2016-05-27

    In this study, we investigated whether Rosemary extract (RE) improved cognitive deficits in repetitive mild Traumatic brain injury (rmTBI) rats and its potential mechanisms. The present results showed that rmTBI caused cognitive deficits, such as increased latency to find platform and decreased time spent in target quadrant in Morris water maze (MWM). These behavioral alterations were accompanying with the increased neuronal degeneration and glial fibrillary acidic protein (GFAP)-positive cells, increased Reactive oxygen species (ROS) generation, decreased activity of Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Catalase (CAT), elevated protein level of IL-1β, IL-6 and TNF-α in hippocampus. Treatment with RE prevented these changes above. Our findings confirmed the effect of rosemary extract on improvement of cognitive deficits and suggested its mechanisms might be mediated by anti-oxidative and anti-inflammatory. Therefore, rosemary extract may be a potential treatment to improve cognitive deficits in rmTBI patients.

  13. 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

  14. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats.

    PubMed

    Oshiro, W M; Beasley, T E; McDaniel, K L; Evansky, P A; Martin, S A; Moser, V C; Gilbert, M E; Bushnell, P J

    2015-01-01

    any choice reaction time measure. Finally, no response inhibition deficit was observed in a differential reinforcement of low rate (DRL) response schedule in males or females in the E15 or E85 experiments. In summary, prenatal exposure to these fuel blends produced few deficits in adult offspring on these cognitive tests. Significant effects found during a water maze probe trial and choice reaction time tests were observed at vapor concentrations of 6000 ppm or higher, a concentration that is 4-6 orders of magnitude higher than those associated with normal automotive fueling operations and garages. Similar effects were not consistently observed in a previous study of inhaled ethanol, and thus these effects cannot be attributed to the concentration of ethanol in the mixture.

  15. Insight into dopamine-dependent planning deficits in Parkinson's disease: A sharing of cognitive & sensory resources.

    PubMed

    Pieruccini-Faria, F; Jones, J A; Almeida, Q J

    2016-03-24

    Cognitive and sensorimotor processes are both needed for successful planning of footsteps during complex gait situations, but the interaction between these factors during motor planning, as well as their response to dopaminergic treatment is poorly understood in Parkinson's disease (PD). In the current study, we evaluated walking and gaze behaviors of individuals with PD while planning an approach toward an obstacle to be stepped over. The obstacle clearance task was completed both ON and OFF dopaminergic medication by individuals with Parkinson's disease (n=20) and compared to healthy age-matched control participants (n=19), as well as with and without an auditory digit monitoring dual task. In this novel protocol of synchronized gaze and gait data collection, each trial was split into an early and late phase prior to the obstacle, providing a unique opportunity to examine dopamine-dependent planning deficits in PD. Interestingly, only patients in the OFF medication state showed greater deceleration in the late phase (i.e., just before the obstacle) (F(1,37)=45.42, p<0.001), as well as an increase in step time variability (also in this late phase) with the additional demands of a dual task (F(2,74)=3.49, p=0.035). Only gait deceleration between approaching phases improved with dopaminergic treatment (F(1,18)=59.20; p<0.001). Although groups showed different walking behaviors, gaze behaviors were the same for all participants, in that they planned for the obstacle more so in the early phase (p<0.05), and fixations were reduced across participants with the presence of the dual task (p<0.001). Surprisingly, the gaze behavior of the PD OFF group showed no interactions with phase or condition suggesting that the deceleration and increased variability when approaching an obstacle is the result of a greater demand for online sensory feedback that cannot be compensated for with visual strategies. We conclude that dopamine influences planning by limiting sensorimotor

  16. 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.

  17. A reversal learning task detects cognitive deficits in a Dachshund model of late-infantile neuronal ceroid lipofuscinosis

    PubMed Central

    Sanders, Douglas N.; Kanazono, Shinichi; Wininger, Fred A.; Whiting, Rebecca E.H.; Flournoy, Camille A.; Coates, Joan R.; Castaner, Lani J.; O’Brien, Dennis P.; Katz, Martin L.

    2011-01-01

    The neuronal ceroid lipofuscinoses (NCLs) are autosomal recessive lysosomal storage diseases characterized by progressive neurodegeneration and by accumulation of autofluorescent storage material in the central nervous system and other tissues. One of the most prominent clinical signs of NCL is progressive decline in cognitive function. We previously described a frame shift mutation of TPP1 in miniature long-haired Dachshunds which causes an early-onset form of NCL analogous to classical late-infantile onset NCL (CLN2) in children. Dogs homozygous for the TPP1 mutation exhibit progressive neurological signs similar to those exhibited by human patients. In order to establish biomarkers for evaluating the efficacy of ongoing therapeutic studies in this canine model, we characterized phenotypic changes in 13 dogs through 9 months of age. Cognitive function was assessed using a T-maze reversal learning task. Cognitive dysfunction was detected in affected dogs as early as 6 months of age and worsened as the disease progressed. Physical and neurological examination, funduscopy, and electroretinography (ERG) were performed at regular intervals. Only changes in ERG responses revealed signs of disease progression earlier than the reversal learning task. In the later stages of the disease clinical signs of visual and motor deficits became evident. The visual and motor deficits were not severe enough to affect the performance of dogs in the T-maze. Declining performance on the reversal learning task is a sensitive measure of higher order cognitive dysfunction which can serve as a useful biomarker of disease progression. PMID:21745338

  18. Brain perfusion correlates of visuoperceptual deficits in Mild Cognitive Impairment and mild Alzheimer’s disease

    PubMed Central

    Alegret, Montserrat; Vinyes-Junqué, Georgina; Boada, Mercè; Martínez-Lage, Pablo; Cuberas, Gemma; Espinosa, Ana; Roca, Isabel; Hernández, Isabel; Valero, Sergi; Rosende-Roca, Maitée; Mauleón, Ana; Becker, James T.; Tárraga, Lluís

    2012-01-01

    Background Visuoperceptual processing is impaired early in the clinical course of Alzheimer’s disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in Mild Cognitive Impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal and prefrontal regions have been found in early AD and MCI patients. Objectives To confirm the role of the 15-OT in the diagnosis of MCI and AD, and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD and normal aging. Methods Forty-two AD, 42 MCI and 42 healthy elderly control (EC) subjects underwent a brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. Results 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Conclusion Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. PMID:20555146

  19. Role of nicotine on cognitive and behavioral deficits in sepsis-surviving rats.

    PubMed

    Leite, Franco B; Prediger, Rui D; Silva, Mônica V; de Sousa, João Batista; Carneiro, Fabiana P; Gasbarri, Antonella; Tomaz, Carlos; Queiroz, Amadeu J; Martins, Natália T; Ferreira, Vania M

    2013-04-24

    Sepsis and its complications are important causes of mortality in intensive care units and sepsis survivors may present long-term cognitive and emotional impairments, including memory deficits and anxiety symptoms. In the present study, we investigated whether repeated nicotine administration can affect the behavioral changes in sepsis-surviving rats. Male Wistar rats were divided in two groups: sham-operated and experimental sepsis induced by cecal ligation and puncture (CLP). The animals were injected subcutaneously with nicotine (0.1 mg/kg) or vehicle once a day during 1 week before and/or 1 week after sepsis induction. Thirty minutes after the last administration (i.e., 7 days after surgery), the animals were tested in the open field, elevated plus-maze and step-down inhibitory avoidance tasks. The repeated nicotine treatment did not affect the survival rate in the sepsis group (50%). Moreover, no significant changes on locomotor activity were observed in the sepsis group while the treatment with nicotine during 1 week after surgery reduced the locomotion of sepsis-surviving rats in the open field. It is important to note that both schedules of nicotine treatment (prior and/or after CLP) improved the sepsis-induced anxiogenic-like responses. Interestingly, nicotine was able to improve short- and long-term inhibitory avoidance memory impairments, observed in sepsis survivors, only when administered during 2 consecutive weeks (i.e., prior and after CLP). Taken together, these results indicate that repeated nicotine administration does not alter the survival rate in rats submitted to CLP and provide new evidence that nicotine can improve long-lasting memory impairments and anxiogenic-like responses in sepsis-surviving animals.

  20. Chronic behavioral and cognitive deficits in a rat survival model of paraoxon toxicity

    PubMed Central

    Deshpande, Laxmikant S.; Phillips, Kristin; Huang, Beverly; DeLorenzo, Robert J.

    2014-01-01

    Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen for medical countermeasures against severe OP exposure. It is well known that the survivors of nerve gas and chronic OP exposure exhibit neurobehavioral deficits such as mood changes, depression, and memory impairments. In this study we investigated whether animals surviving severe POX exposure exhibited long-term neurological impairments. POX exposure produced overt signs of cholinergic toxicity. Rats were rescued using an optimized atropine, 2-PAM and diazepam therapy. Surviving rats were studied using established behavioral assays for identifying symptoms of depression and memory impairment 3-months after POX exposure. In the forced swim test, POX rats exhibited increased immobility time indicative of a despair-like state. In the sucrose preference test, POX rats consumed significantly less sucrose water indicating anhedonia-like condition. POX rats also displayed increased anxiety as characterized by significantly lower performance in the open arm of the elevated plus maze. Further, when tested with a novel object recognition paradigm, POX rats exhibited a negative discrimination ratio indicative of impaired recognition memory. The results indicate that this model of survival from severe POX exposure can be employed to study some of the molecular bases for OP-induced chronic behavioral and cognitive comorbidities and develop therapies for their treatment. PMID:25172410

  1. Emotional face recognition deficit in amnestic patients with mild cognitive impairment: behavioral and electrophysiological evidence

    PubMed Central

    Yang, Linlin; Zhao, Xiaochuan; Wang, Lan; Yu, Lulu; Song, Mei; Wang, Xueyi

    2015-01-01

    Amnestic mild cognitive impairment (MCI) has been conceptualized as a transitional stage between healthy aging and Alzheimer’s disease. Thus, understanding emotional face recognition deficit in patients with amnestic MCI could be useful in determining progression of amnestic MCI. The purpose of this study was to investigate the features of emotional face processing in amnestic MCI by using event-related potentials (ERPs). Patients with amnestic MCI and healthy controls performed a face recognition task, giving old/new responses to previously studied and novel faces with different emotional messages as the stimulus material. Using the learning-recognition paradigm, the experiments were divided into two steps, ie, a learning phase and a test phase. ERPs were analyzed on electroencephalographic recordings. The behavior data indicated high emotion classification accuracy for patients with amnestic MCI and for healthy controls. The mean percentage of correct classifications was 81.19% for patients with amnestic MCI and 96.46% for controls. Our ERP data suggest that patients with amnestic MCI were still be able to undertake personalizing processing for negative faces, but not for neutral or positive faces, in the early frontal processing stage. In the early time window, no differences in frontal old/new effect were found between patients with amnestic MCI and normal controls. However, in the late time window, the three types of stimuli did not elicit any old/new parietal effects in patients with amnestic MCI, suggesting their recollection was impaired. This impairment may be closely associated with amnestic MCI disease. We conclude from our data that face recognition processing and emotional memory is impaired in patients with amnestic MCI. Such damage mainly occurred in the early coding stages. In addition, we found that patients with amnestic MCI had difficulty in post-processing of positive and neutral facial emotions. PMID:26347065

  2. 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.

  3. 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. PMID:26655189

  4. Motor, Visual and Emotional Deficits in Mice after Closed-Head Mild Traumatic Brain Injury Are Alleviated by the Novel CB2 Inverse Agonist SMM-189

    PubMed Central

    Reiner, Anton; Heldt, Scott A.; Presley, Chaela S.; Guley, Natalie H.; Elberger, Andrea J.; Deng, Yunping; D’Surney, Lauren; Rogers, Joshua T.; Ferrell, Jessica; Bu, Wei; Del Mar, Nobel; Honig, Marcia G.; Gurley, Steven N.; Moore, Bob M.

    2014-01-01

    We have developed a focal blast model of closed-head mild traumatic brain injury (TBI) in mice. As true for individuals that have experienced mild TBI, mice subjected to 50–60 psi blast show motor, visual and emotional deficits, diffuse axonal injury and microglial activation, but no overt neuron loss. Because microglial activation can worsen brain damage after a concussive event and because microglia can be modulated by their cannabinoid type 2 receptors (CB2), we evaluated the effectiveness of the novel CB2 receptor inverse agonist SMM-189 in altering microglial activation and mitigating deficits after mild TBI. In vitro analysis indicated that SMM-189 converted human microglia from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype. Studies in mice showed that daily administration of SMM-189 for two weeks beginning shortly after blast greatly reduced the motor, visual, and emotional deficits otherwise evident after 50–60 psi blasts, and prevented brain injury that may contribute to these deficits. Our results suggest that treatment with the CB2 inverse agonist SMM-189 after a mild TBI event can reduce its adverse consequences by beneficially modulating microglial activation. These findings recommend further evaluation of CB2 inverse agonists as a novel therapeutic approach for treating mild TBI. PMID:25561230

  5. Rats bred for helplessness exhibit positive reinforcement learning deficits which are not alleviated by an antidepressant dose of the MAO-B inhibitor deprenyl.

    PubMed

    Schulz, Daniela; Henn, Fritz A; Petri, David; Huston, Joseph P

    2016-08-01

    Principles of negative reinforcement learning may play a critical role in the etiology and treatment of depression. We examined the integrity of positive reinforcement learning in congenitally helpless (cH) rats, an animal model of depression, using a random ratio schedule and a devaluation-extinction procedure. Furthermore, we tested whether an antidepressant dose of the monoamine oxidase (MAO)-B inhibitor deprenyl would reverse any deficits in positive reinforcement learning. We found that cH rats (n=9) were impaired in the acquisition of even simple operant contingencies, such as a fixed interval (FI) 20 schedule. cH rats exhibited no apparent deficits in appetite or reward sensitivity. They reacted to the devaluation of food in a manner consistent with a dose-response relationship. Reinforcer motivation as assessed by lever pressing across sessions with progressively decreasing reward probabilities was highest in congenitally non-helpless (cNH, n=10) rats as long as the reward probabilities remained relatively high. cNH compared to wild-type (n=10) rats were also more resistant to extinction across sessions. Compared to saline (n=5), deprenyl (n=5) reduced the duration of immobility of cH rats in the forced swimming test, indicative of antidepressant effects, but did not restore any deficits in the acquisition of a FI 20 schedule. We conclude that positive reinforcement learning was impaired in rats bred for helplessness, possibly due to motivational impairments but not deficits in reward sensitivity, and that deprenyl exerted antidepressant effects but did not reverse the deficits in positive reinforcement learning. PMID:27163379

  6. Rats bred for helplessness exhibit positive reinforcement learning deficits which are not alleviated by an antidepressant dose of the MAO-B inhibitor deprenyl.

    PubMed

    Schulz, Daniela; Henn, Fritz A; Petri, David; Huston, Joseph P

    2016-08-01

    Principles of negative reinforcement learning may play a critical role in the etiology and treatment of depression. We examined the integrity of positive reinforcement learning in congenitally helpless (cH) rats, an animal model of depression, using a random ratio schedule and a devaluation-extinction procedure. Furthermore, we tested whether an antidepressant dose of the monoamine oxidase (MAO)-B inhibitor deprenyl would reverse any deficits in positive reinforcement learning. We found that cH rats (n=9) were impaired in the acquisition of even simple operant contingencies, such as a fixed interval (FI) 20 schedule. cH rats exhibited no apparent deficits in appetite or reward sensitivity. They reacted to the devaluation of food in a manner consistent with a dose-response relationship. Reinforcer motivation as assessed by lever pressing across sessions with progressively decreasing reward probabilities was highest in congenitally non-helpless (cNH, n=10) rats as long as the reward probabilities remained relatively high. cNH compared to wild-type (n=10) rats were also more resistant to extinction across sessions. Compared to saline (n=5), deprenyl (n=5) reduced the duration of immobility of cH rats in the forced swimming test, indicative of antidepressant effects, but did not restore any deficits in the acquisition of a FI 20 schedule. We conclude that positive reinforcement learning was impaired in rats bred for helplessness, possibly due to motivational impairments but not deficits in reward sensitivity, and that deprenyl exerted antidepressant effects but did not reverse the deficits in positive reinforcement learning.

  7. On the importance of cognitive profiling: A graphical modelling analysis of domain-specific and domain-general deficits after stroke.

    PubMed

    Massa, M Sofia; Wang, Naxian; Bickerton, Wa-Ling; Demeyere, Nele; Riddoch, M Jane; Humphreys, Glyn W

    2015-10-01

    Cognitive problems following stroke are typically analysed using either short but relatively uninformative general tests or through detailed but time consuming tests of domain specific deficits (e.g., in language, memory, praxis). Here we present an analysis of neuropsychological deficits detected using a screen designed to fall between other screens by being 'broad' (testing multiple cognitive abilities) but 'shallow' (sampling the abilities briefly, to be time efficient) - the BCoS. Assessment using the Birmingham Cognitive Screen (BCoS) enables the relations between 'domain specific' and 'domain general' cognitive deficits to be evaluated as the test generates an overall cognitive profile for individual patients. We analysed data from 287 patients tested at a sub-acute stage of stroke (<3 months). Graphical modelling techniques were used to investigate the associative structure and conditional independence between deficits within and across the domains sampled by BCoS (attention and executive functions, language, memory, praxis and number processing). The patterns of deficit within each domain conformed to existing cognitive models. However, these within-domain patterns underwent substantial change when the whole dataset was modelled, indicating that domain-specific deficits can only be understood in relation to linked changes in domain-general processes. The data point to the importance of using over-arching cognitive screens, measuring domain-general as well as domain-specific processes, in order to account for neuropsychological deficits after stroke. The paper also highlights the utility of using graphical modelling to understand the relations between cognitive components in complex datasets. PMID:26232552

  8. 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

  9. A Systematic Review of Psychological Interventions to Alleviate Cognitive and Psychosocial Problems in Children with Acquired Brain Injury

    ERIC Educational Resources Information Center

    Ross, Kimberley A.; Dorris, Liam; McMillan, Tom

    2011-01-01

    Aim: It is now generally accepted that paediatric acquired brain injury (ABI) can have an impact on a child's cognitive, social, and behavioural functioning. However, the lack of guidelines on effective interventions for the affected children and their families, particularly beyond the acute recovery phase, can limit access to effective support.…

  10. Experimental ‘Jet Lag’ Inhibits Adult Neurogenesis and Produces Long-Term Cognitive Deficits in Female Hamsters

    PubMed Central

    Gibson, Erin M.; Wang, Connie; Tjho, Stephanie; Khattar, Neera; Kriegsfeld, Lance J.

    2010-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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. PMID:21152025

  11. Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model.

    PubMed

    Ghoshal, A; Rook, J M; Dickerson, J W; Roop, G N; Morrison, R D; Jalan-Sakrikar, N; Lamsal, A; Noetzel, M J; Poslusney, M S; Wood, M R; Melancon, B J; Stauffer, S R; Xiang, Z; Daniels, J S; Niswender, C M; Jones, C K; Lindsley, C W; Conn, P J

    2016-01-01

    Schizophrenia patients exhibit deficits in signaling of the M1 subtype of muscarinic acetylcholine receptor (mAChR) in the prefrontal cortex (PFC) and also display impaired cortical long-term depression (LTD). We report that selective activation of the M1 mAChR subtype induces LTD in PFC and that this response is completely lost after repeated administration of phencyclidine (PCP), a mouse model of schizophrenia. Furthermore, discovery of a novel, systemically active M1 positive allosteric modulator (PAM), VU0453595, allowed us to evaluate the impact of selective potentiation of M1 on induction of LTD and behavioral deficits in PCP-treated mice. Interestingly, VU0453595 fully restored impaired LTD as well as deficits in cognitive function and social interaction in these mice. These results provide critical new insights into synaptic changes that may contribute to behavioral deficits in this mouse model and support a role for selective M1 PAMs as a novel approach for the treatment of schizophrenia.

  12. 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…

  13. Enhanced neural activity in frontal and cerebellar circuits after cognitive training in children with attention-deficit/hyperactivity disorder.

    PubMed

    Hoekzema, Elseline; Carmona, Susanna; Tremols, Virginia; Gispert, Joan Domingo; Guitart, Marc; Fauquet, Jordi; Rovira, Mariana; Bielsa, Anna; Soliva, Juan Carlos; Tomas, Xavier; Bulbena, Antonio; Ramos-Quiroga, Antoni; Casas, Miguel; Tobeña, Adolf; Vilarroya, Oscar

    2010-12-01

    The brain is a plastic entity that can undergo dynamic changes throughout the lifespan as a result of training. Attention-deficit/hyperactivity disorder (ADHD) is commonly treated with psychostimulant medication, and the prevalence of ADHD medication prescription is a topic of heated scientific debate. In addition, cognitive training is frequently provided to patients with ADHD. Although psychostimulant effects have been thoroughly investigated, no previous studies have assessed the neural effects of cognitive training in ADHD. We applied fMRI-paradigms of response inhibition and selective attention to chart the effects of a 10-day cognitive training program in 19 unmedicated ADHD children receiving either cognitive or control training. The two resulting longitudinal datasets were analyzed using whole-brain random-effects general linear models. Although we observed no increases of activity in the control group, both fMRI-datasets revealed enhanced activity after cognitive training in neural structures closely related to ADHD pathophysiology. On the inhibition paradigm, our results indicated increases in orbitofrontal, superior frontal, middle temporal, and inferior frontal cortex. The attentional task was characterized by increased activity in the cerebellum, which correlated with improvement on in-scanner measures of attention. Our findings provide preliminary evidence that cognitive training enhances activity in neural structures typically affected by the disorder. Similar results have been obtained following methylphenidate administration, suggesting that training of cognitive functions may mimic the effects of psychostimulant medication on the brain. These findings postulate a neural account for the potency of cognitive training in ADHD, and hold clinical implications, supporting the inclusion of training programs in standard ADHD-treatment. PMID:20336653

  14. Voluntary exercise ameliorates cognitive deficits in morphine dependent rats: the role of hippocampal brain-derived neurotrophic factor.

    PubMed

    Miladi-Gorji, Hossein; Rashidy-Pour, Ali; Fathollahi, Yaghoub; Akhavan, Maziar M; Semnanian, Saeed; Safari, Manouchehr

    2011-10-01

    Chronic exposure to opiates impairs spatial learning and memory. Given the well-known beneficial effects of voluntary exercise on cognitive functions, we investigated whether voluntary exercise would ameliorate the cognitive deficits that are induced by morphine dependence. If an effect of exercise was observed, we aimed to investigate the possible role of hippocampal brain-derived neurotrophic factor (BDNF) in the exercise-induced enhancement of learning and memory in morphine-dependent rats. The rats were injected with bi-daily doses (10mg/kg, at 12h intervals) of morphine over a period of 10 days of voluntary exercise. Following these injections, a water maze task was performed twice a day for five consecutive days, followed by a probe trial 2 days later. A specific BDNF inhibitor (TrkB-IgG chimera) was used to block the hippocampal BDNF action during the 10 days of voluntary exercise. We found that voluntary exercise blocked the ability of chronic morphine to impair spatial memory retention. A blockade of the BDNF action blunted the exercise-induced improvement of spatial memory in the dependent rats. Moreover, the voluntary exercise diminished the severity of the rats' dependency on morphine. This study demonstrates that voluntary exercise ameliorates, via a TrkB-mediated mechanism, the cognitive deficits that are induced by chronic morphine. Thus, voluntary exercise might be a potential method to ameliorate some of the deleterious behavioral consequences of the abuse of morphine and other opiates.

  15. Soluble Aβ levels correlate with cognitive deficits in the 12-month-old APPswe/PS1dE9 mouse model of Alzheimer's disease.

    PubMed

    Zhang, Wei; Hao, Jian; Liu, Rui; Zhang, Zhuo; Lei, Gesheng; Su, Changjun; Miao, Jianting; Li, Zhuyi

    2011-09-23

    Amyloid-beta peptide (Aβ) is believed to be central in the pathogenesis of Alzheimer's disease (AD) characterized by cognitive deficits. However, it remains uncertain which form(s) of Aβ pathology is responsible for the cognitive deficits in AD. In the present study, the cognitive deficits and the profiles of Aβ pathology were characterized in the 12-month-old APPswe/PS1dE9 double transgenic mice, and their correlations were examined. Compared with non-transgenic littermates, the middle-aged APPswe/PS1dE9 mice exhibited spatial learning and memory deficits in the water maze test and long-term contextual memory deficits in the step-down passive avoidance test. Among the middle-aged APPswe/PS1dE9 mice, hippocampal soluble Aβ1-40 and Aβ1-42 levels were highly correlated with spatial learning deficits and long-term contextual memory deficits, as well as cortical and hippocampal soluble Aβ1-40 and Aβ1-42 levels were strongly correlated with spatial memory deficits. By contrast, no significant correlations were observed between three measures of cognitive functions and amyloid plaque burden (total Aβ plaque load and fibrillar Aβ plaque load), total Aβ levels (Aβ1-40 and Aβ1-42), as well as insoluble Aβ levels (Aβ1-40 and Aβ1-42). Stepwise multiple regression analysis identified hippocampal soluble Aβ1-40 and Aβ1-42 levels as independent factors for predicting the spatial learning deficits and the long-term contextual memory deficits, as well as hippocampal and cortical soluble Aβ1-40 and Aβ1-42 levels as independent factors for predicting the spatial memory deficits in transgenic mice. These results demonstrate that cognitive deficits are highly related to the levels of soluble Aβ in middle-aged APPswe/PS1dE9 mice, in which soluble Aβ levels are only a tiny fraction of the amount of total Aβ levels. Consequently, our findings provide further evidence that soluble Aβ might primarily contribute to cognitive deficits in AD, suggesting that reducing

  16. Effect of exercise-induced neurogenesis on cognitive function deficit in a rat model of vascular dementia.

    PubMed

    Choi, Dong-Hee; Lee, Kyoung-Hee; Lee, Jongmin

    2016-04-01

    Chronic cerebral hypoperfusion (CCH) is strongly correlated with progressive cognitive decline in neurological diseases, such as vascular dementia (VaD) and Alzheimer's disease. Exercise can enhance learning and memory, and delay age-related cognitive decline. However, exercise-induced hippocampal neurogenesis in experimental animals submitted to CCH has not been investigated. The present study aimed to investigate whether hippocampal neurogenesis induced by exercise can improve cognitive deficit in a rat model of VaD. Male Wistar rats (age, 8 weeks; weight, 292±3.05 g; n=12-13/group) were subjected to bilateral common carotid artery occlusion (2VO) or sham‑surgery and each group was then subdivided randomly into no exercise and treadmill exercise groups. Exercise groups performed treadmill exercise daily at 15 m/min for 30 min for 4 weeks from the third to the seventh week after 2VO. It was demonstrated that the number of neural progenitor cells and mature neurons in the subgranular zone of 2VO rats was increased by exercise, and cognitive impairment in 2VO rats was attenuated by treadmill exercise. In addition, mature brain‑derived neurotrophic factor (BDNF) levels in the hippocampus were increased in the exercise groups. Thus the present study suggests that exercise delays cognitive decline by the enhancing neurogenesis and increasing BDNF expression in the context of VaD. PMID:26934837

  17. Effect of exercise-induced neurogenesis on cognitive function deficit in a rat model of vascular dementia

    PubMed Central

    CHOI, DONG-HEE; LEE, KYOUNG-HEE; LEE, JONGMIN

    2016-01-01

    Chronic cerebral hypoperfusion (CCH) is strongly correlated with progressive cognitive decline in neurological diseases, such as vascular dementia (VaD) and Alzheimer's disease. Exercise can enhance learning and memory, and delay age-related cognitive decline. However, exercise-induced hippocampal neurogenesis in experimental animals submitted to CCH has not been investigated. The present study aimed to investigate whether hippocampal neurogenesis induced by exercise can improve cognitive deficit in a rat model of VaD. Male Wistar rats (age, 8 weeks; weight, 292±3.05 g; n=12–13/group) were subjected to bilateral common carotid artery occlusion (2VO) or sham-surgery and each group was then subdivided randomly into no exercise and treadmill exercise groups. Exercise groups performed treadmill exercise daily at 15 m/min for 30 min for 4 weeks from the third to the seventh week after 2VO. It was demonstrated that the number of neural progenitor cells and mature neurons in the subgranular zone of 2VO rats was increased by exercise, and cognitive impairment in 2VO rats was attenuated by treadmill exercise. In addition, mature brain-derived neurotrophic factor (BDNF) levels in the hippocampus were increased in the exercise groups. Thus the present study suggests that exercise delays cognitive decline by the enhancing neurogenesis and increasing BDNF expression in the context of VaD. PMID:26934837

  18. Effect of exercise-induced neurogenesis on cognitive function deficit in a rat model of vascular dementia.

    PubMed

    Choi, Dong-Hee; Lee, Kyoung-Hee; Lee, Jongmin

    2016-04-01

    Chronic cerebral hypoperfusion (CCH) is strongly correlated with progressive cognitive decline in neurological diseases, such as vascular dementia (VaD) and Alzheimer's disease. Exercise can enhance learning and memory, and delay age-related cognitive decline. However, exercise-induced hippocampal neurogenesis in experimental animals submitted to CCH has not been investigated. The present study aimed to investigate whether hippocampal neurogenesis induced by exercise can improve cognitive deficit in a rat model of VaD. Male Wistar rats (age, 8 weeks; weight, 292±3.05 g; n=12-13/group) were subjected to bilateral common carotid artery occlusion (2VO) or sham‑surgery and each group was then subdivided randomly into no exercise and treadmill exercise groups. Exercise groups performed treadmill exercise daily at 15 m/min for 30 min for 4 weeks from the third to the seventh week after 2VO. It was demonstrated that the number of neural progenitor cells and mature neurons in the subgranular zone of 2VO rats was increased by exercise, and cognitive impairment in 2VO rats was attenuated by treadmill exercise. In addition, mature brain‑derived neurotrophic factor (BDNF) levels in the hippocampus were increased in the exercise groups. Thus the present study suggests that exercise delays cognitive decline by the enhancing neurogenesis and increasing BDNF expression in the context of VaD.

  19. Remission of Cognitive Deficits in Parkinson's Disease: Recovery from a Nonamnestic Mild Cognitive Impairment or Psychiatric Symptoms Remission?

    PubMed Central

    de Paula, Jonas Jardim; Cintra, Marco Túlio Gualberto; Miranda, Débora Marques; Bicalho, Maria Aparecida Camargos; Moares, Edgar Nunes; Malloy-Diniz, Leandro Fernandes

    2012-01-01

    Mild cognitive impairment is a clinical condition more frequent in patients with Parkinson's disease than in general population. The nonamnestic presentations, usually characterized by executive dysfunction, are most prevalent. We present a case report of a Parkinson's disease patient diagnosed with nonamnestic mild cognitive impairment that showed complete remission of cognitive symptoms after one year. We discuss the possible causes for the remission, focusing on the treatment of medical conditions such as a major depressive episode and vitamin B12 deficiency, in addition to the change of pharmacological treatment. In a third assessment, cognitive performance remained normal. The case report highlights the importance of controlling clinical comorbidities on the assessment and followup of mild cognitive impairment, especially on Parkinson's disease. PMID:23193494

  20. Over-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice.

    PubMed

    Zhang, Hui; Ma, Li; Yin, Yan-Ling; Dong, Lian-Qiang; Cheng, Gang-Ge; Ma, Ya-Qun; Li, Yun-Feng; Xu, Bai-Nan

    2016-09-01

    The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future.

  1. Mangiferin ameliorates aluminium chloride-induced cognitive dysfunction via alleviation of hippocampal oxido-nitrosative stress, proinflammatory cytokines and acetylcholinesterase level.

    PubMed

    Kasbe, Prajapati; Jangra, Ashok; Lahkar, Mangala

    2015-01-01

    Mangiferin is a phytochemical primarily present in the stem, leaves and bark of Mangifera indica. It offers neuroprotection mainly through inhibition of oxidative stress, and decreasing proinflammatory cytokines level in the brain. Aluminium has been reported to cause oxidative stress-associated damage in the brain. In the present investigation, protective effect of mangiferin against aluminium chloride (AlCl3)-induced neurotoxicity and cognitive impairment was studied in male Swiss albino mice. AlCl3 (100 mg/kg) was administered once daily through oral gavage for 42 days. Mangiferin (20 and 40 mg/kg, p.o.) was given to mice for last 21 days of the study. We found cognitive dysfunction in AlCl3-treated group, which was assessed by Morris water maze test, and novel object recognition test. AlCl3-treated group showed elevated level of oxidative stress markers, proinflammatory cytokines level and lowered hippocampal brain-derived neurotrophic factor (BDNF) content. Mangiferin (40 mg/kg) prevented the cognitive deficits, hippocampal BDNF depletion, and biochemical anomalies induced by AlCl3-treatment. In conclusion, our data demonstrated that mangiferin offers neuroprotection in AlCl3-induced neurotoxicity and it may be a potential therapeutic approach in the treatment of oxido-nitrosative stress and inflammation-associated neurotoxicity.

  2. Mangiferin ameliorates aluminium chloride-induced cognitive dysfunction via alleviation of hippocampal oxido-nitrosative stress, proinflammatory cytokines and acetylcholinesterase level.

    PubMed

    Kasbe, Prajapati; Jangra, Ashok; Lahkar, Mangala

    2015-01-01

    Mangiferin is a phytochemical primarily present in the stem, leaves and bark of Mangifera indica. It offers neuroprotection mainly through inhibition of oxidative stress, and decreasing proinflammatory cytokines level in the brain. Aluminium has been reported to cause oxidative stress-associated damage in the brain. In the present investigation, protective effect of mangiferin against aluminium chloride (AlCl3)-induced neurotoxicity and cognitive impairment was studied in male Swiss albino mice. AlCl3 (100 mg/kg) was administered once daily through oral gavage for 42 days. Mangiferin (20 and 40 mg/kg, p.o.) was given to mice for last 21 days of the study. We found cognitive dysfunction in AlCl3-treated group, which was assessed by Morris water maze test, and novel object recognition test. AlCl3-treated group showed elevated level of oxidative stress markers, proinflammatory cytokines level and lowered hippocampal brain-derived neurotrophic factor (BDNF) content. Mangiferin (40 mg/kg) prevented the cognitive deficits, hippocampal BDNF depletion, and biochemical anomalies induced by AlCl3-treatment. In conclusion, our data demonstrated that mangiferin offers neuroprotection in AlCl3-induced neurotoxicity and it may be a potential therapeutic approach in the treatment of oxido-nitrosative stress and inflammation-associated neurotoxicity. PMID:26004900

  3. Effects of the Cognition-Enhancing Agent ABT-239 on Fetal Ethanol-Induced Deficits in Dentate Gyrus Synaptic Plasticity

    PubMed Central

    Varaschin, Rafael K.; Akers, Katherine G.; Rosenberg, Martina J.; Hamilton, Derek A.

    2010-01-01

    Prenatal ethanol exposure causes deficits in hippocampal synaptic plasticity and learning. At present, there are no clinically effective pharmacotherapeutic interventions for these deficits. In this study, we examined whether the cognition-enhancing agent 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl) benzonitrile (ABT-239), a histamine H3 receptor antagonist, could ameliorate fetal ethanol-induced long-term potentiation (LTP) deficits. Long-Evans rat dams consumed a mean of 2.82 g/kg ethanol during a 4-h period each day. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, offspring litter size, and birth weights were not different between ethanol-consuming and control groups. A stimulating electrode was implanted in the entorhinal cortical perforant path, and a recording electrode was implanted in the dorsal dentate gyrus of urethane-anesthetized adult male offspring. Baseline input/output responses were not affected either by prenatal ethanol exposure or by 1 mg/kg ABT-239 administered 2 h before data collection. No differences were observed between prenatal treatment groups when a 10-tetanus train protocol was used to elicit LTP. However, LTP elicited by 3 tetanizing trains was markedly impaired by prenatal ethanol exposure compared with control. This fetal ethanol-induced LTP deficit was reversed by ABT-239. In contrast, ABT-239 did not enhance LTP in control offspring using the 3-tetanus train protocol. These results suggest that histamine H3 receptor antagonists may have utility for treating fetal ethanol-associated synaptic plasticity and learning deficits. Furthermore, the differential effect of ABT-239 in fetal alcohol offspring compared with controls raises questions about the impact of fetal ethanol exposure on histaminergic modulation of excitatory neurotransmission in affected offspring. PMID:20308329

  4. Small molecule LX2343 ameliorates cognitive deficits in AD model mice by targeting both amyloid β production and clearance

    PubMed Central

    Guo, Xiao-dan; Sun, Guang-long; Zhou, Ting-ting; Xu, Xin; Zhu, Zhi-yuan; Rukachaisirikul, Vatcharin; Hu, Li-hong; Shen, Xu

    2016-01-01

    Aim: 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. Methods: Cell-based assays for screening anti-amyloid compounds were established by assessing Aβ accumulation in HEK293-APPsw 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. Results: LX2343 (5–20 μmol/L) dose-dependently decreased Aβ accumulation in HEK293-APPsw 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 APPThr668 phosphorylation, thus inhibiting APP cleavage on one hand, and inhibiting BACE1 enzymatic activity with an IC50 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

  5. Cognitive deficits associated with blood lead concentrations <10 microg/dL in US children and adolescents.

    PubMed Central

    Lanphear, B P; Dietrich, K; Auinger, P; Cox, C

    2000-01-01

    OBJECTIVE: Lead is a confirmed neurotoxicant, but the lowest blood lead concentration associated with deficits in cognitive functioning and academic achievement is poorly defined. The purpose of the present study was to examine the relationship of relatively low blood lead concentrations-especially concentrations <10 micrograms per deciliter (microg/dL)--with performance on tests of cognitive functioning in a representative sample of US children and adolescents. METHODS: The authors used data from the Third National Health and Nutrition Examination Survey (NHANES III), conducted from 1988 to 1994, to assess the relationship between blood lead concentration and performance on tests of arithmetic skills, reading skills, nonverbal reasoning, and short-term memory among 4,853 children ages 6-16 years. RESULTS: The geometric mean blood lead concentration for children n the study sample was 1.9 microg/dL; 172 (2.1%) had blood lead concentrations > or =10 microg/dL. After adjustment for gender, race/ethnicity, poverty, region of the country, parent or caregiver's educational level, parent or caregiver's marital status parent, serum ferritin level, and serum cotinine level, the data showed an inverse relationship between blood lead concentration and scores on four measures of cognitive functioning. For every 1 microg/dL increase in blood lead concentration, there was a 0.7-point decrement in mean arithmetic scores, an approximately 1-point decrement in mean reading scores, a 0.1-point decrement in mean scores on a measure of nonverbal reasoning, and a 0.5-point decrement in mean scores on a measure of short-term memory. An inverse relationship between blood lead concentration and arithmetic and reading scores was observed for children with blood lead concentrations lower than 5.0 microg/dL. CONCLUSION: Deficits in cognitive and academic skills associated with lead exposure occur at blood lead concentrations lower than 5 microg/dL. PMID:11354334

  6. Serotonergic interaction between medial prefrontal cortex and mesotelencephalic DA system underlies cognitive and affective deficits in hemiparkinsonian rats.

    PubMed

    Petri, D; de Souza Silva, M A; Chao, O Y-H; Schnitzler, A; Huston, J P

    2015-10-29

    Parkinson's disease (PD) patients not only exhibit motor impairments, but also characteristic deficits in cognitive and affective functions. Such functions have consistently been associated with the medial prefrontal cortex (mPFC). To determine whether there is an interaction between the midbrain dopamine system (MDS) and the mPFC underlying the cognitive and emotional deficits seen in rats, we administered a disconnection procedure of these structures by applying lesions to the mPFC (N-methyl-d-aspartic acid (NMDA)) and the medial forebrain bundle (6-hydroxydopamine (6-OHDA)) either in the same or opposite hemispheres. The results indicate a functional interaction of the MDS and the mPFC: Disconnection effects on behavior were observed with respect to memory-, anxiety- and depression-related behaviors. A disconnection of the mPFC and MDS had promnestic, antidepressant- and anxiolytic-like effects. In order to determine whether this circuit between the mPFC and MDS involves serotonergic mechanisms, we also utilized serotonin-specific disconnections of the mPFC by applying the 5-HT-specific agent 5,7-dihydroxytryptamine (5,7-DHT) into the mPFC and 6-OHDA into the medial forebrain bundle, again either in the same or opposite hemispheres. The behavioral effects observed here resembled those incurred by the unspecific disconnection of the mPFC, demonstrating a significant contribution of serotonergic mechanisms to the interplay between the MDS and the mPFC. Taken together, these experiments provide evidence for an interaction of the MDS and the mPFC in the control of cognitive and affective processes known to be impaired in PD and point toward a prominent involvement of the serotonergic system. A disconnection of the mPFC and the MDS had promnestic, antidepressant- and anxiolytic-like behavioral effects. These findings may impact therapeutic approaches in the treatment of cognitive and neuropsychiatric symptoms seen in PD.

  7. Over-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice.

    PubMed

    Zhang, Hui; Ma, Li; Yin, Yan-Ling; Dong, Lian-Qiang; Cheng, Gang-Ge; Ma, Ya-Qun; Li, Yun-Feng; Xu, Bai-Nan

    2016-09-01

    The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future. PMID:27265418

  8. Comprehensive treatments for social cognitive deficits in schizophrenia: A critical review and effect-size analysis of controlled studies.

    PubMed

    Kurtz, Matthew M; Gagen, Emily; Rocha, Nuno B F; Machado, Sergio; Penn, David L

    2016-02-01

    Recent advances in psychosocial treatments for schizophrenia have targeted social cognitive deficits. A critical literature review and effect-size (ES) analysis was conducted to investigate the efficacy of comprehensive programs of social cognitive training in schizophrenia. Results revealed 16 controlled studies consisting of seven models of comprehensive treatment with only three of these treatment models investigated in more than one study. The effects of social cognitive training were reported in 11/15 studies that included facial affect recognition skills (ES=.84) and 10/13 studies that included theory-of-mind (ES=.70) as outcomes. Less than half (4/9) of studies that measured attributional style as an outcome reported effects of treatment, but effect sizes across studies were significant (ESs=.30-.52). The effect sizes for symptoms were modest, but, with the exception of positive symptoms, significant (ESs=.32-.40). The majority of trials were randomized (13/16), selected active control conditions (11/16) and included at least 30 participants (12/16). Concerns for this area of research include the absence of blinded outcome raters in more than 50% of trials and low rates of utilization of procedures for maintaining treatment fidelity. These findings provide preliminary support for the broader use of comprehensive social cognitive training procedures as a psychosocial intervention for schizophrenia.

  9. Odor identification deficit in mild cognitive impairment and Alzheimer's disease is associated with hippocampal and deep gray matter atrophy.

    PubMed

    Hagemeier, Jesper; Woodward, Matthew R; Rafique, Usama A; Amrutkar, Chaitanya V; Bergsland, Niels; Dwyer, Michael G; Benedict, Ralph; Zivadinov, Robert; Szigeti, Kinga

    2016-09-30

    Even in early stages, Alzheimer's disease (AD) is associated with olfactory deficit. We assess the association of volumetric differences in subcortical deep gray matter (DGM) structures and odor identification deficit (OID) in subjects with amnestic mild cognitive impairment (aMCI), AD and normal controls (NCs), and relate findings to the current gold standard right sided memory measure, visual reproduction. Eighty subjects (19 aMCI; 42 CE; 19 NC) were included in this study. We obtained olfactory testing and normalized structural brain volumes from 3T T1 MRI scans. Associations between MRI, olfactory- and memory impairment were studied using Pearson- and partial-correlation adjusted for age. AD patients had significantly higher olfactory deficits, lower visual reproduction scores, and reduced brain volumes (p<0.05). Within aMCI, OID was associated with lower right hippocampal- and left amygdala volume (p<0.05). In AD, OID was associated with bilaterally lower hippocampus and left amygdala volumes. In contrast, visual reproduction was associated with bilateral volume loss regardless of study group. OID is a more specific marker of early pathological right mesial-temporal involvement than the currently regarded gold standard of right sided-memory (visual reproduction). OID may be valuable in the longitudinal evaluation of disease modifying treatments in early disease course. PMID:27567325

  10. Metacognition-augmented cognitive remediation training reduces jumping to conclusions and overconfidence but not neurocognitive deficits in psychosis

    PubMed Central

    Moritz, Steffen; Thoering, Teresa; Kühn, Simone; Willenborg, Bastian; Westermann, Stefan; Nagel, Matthias

    2015-01-01

    The majority of patients with schizophrenia display neurocognitive deficits (e.g., memory impairment) as well as inflated cognitive biases (e.g., jumping to conclusions). Both cognitive domains are implicated in the pathogenesis of the disorder and are known to compromise functional outcome. At present, there is a dearth of effective treatment options. A total of 90 patients with schizophrenia were recruited online (a diagnosis of schizophrenia had been confirmed in a large subgroup during a previous hospital admission). Subsequent to a baseline assessment encompassing psychopathology, self-reported cognition as well as objective memory and reasoning tests, patients were randomized to one of three conditions: standard cognitive remediation (mybraintraining), metacognition-augmented cognition remediation (CR) condition (variant of mybraintraining which encouraged patients to reduce speed of decision-making and attenuate response confidence when participants made high-confidence judgements and hasty incorrect decisions) and a waitlist control group. Patients were retested after 6 weeks and again 3 months after the second assessment. Groups did not differ on psychopathology and neurocognitive parameters at any timepoint. However, at follow-up the metacognitive-augmented CR group displayed a significant reduction on jumping to conclusions and overconfidence. Treatment adherence correlated with a reduction of depression; gains in the training exercises from the standard mybraintraining condition were correlated with improved objective memory performance. The study suggests that metacognition-augmented CR may ameliorate cognitive biases but not neurocognition. The study ties in well with prior research showing that neurocognitive dysfunctions are rather resistant to change; the failure to detect significant improvement of CR or metacognition-augmented CR on psychopathology and neurocognition over time may partly be attributed to a number of methodological limitations of

  11. Metacognition-augmented cognitive remediation training reduces jumping to conclusions and overconfidence but not neurocognitive deficits in psychosis.

    PubMed

    Moritz, Steffen; Thoering, Teresa; Kühn, Simone; Willenborg, Bastian; Westermann, Stefan; Nagel, Matthias

    2015-01-01

    The majority of patients with schizophrenia display neurocognitive deficits (e.g., memory impairment) as well as inflated cognitive biases (e.g., jumping to conclusions). Both cognitive domains are implicated in the pathogenesis of the disorder and are known to compromise functional outcome. At present, there is a dearth of effective treatment options. A total of 90 patients with schizophrenia were recruited online (a diagnosis of schizophrenia had been confirmed in a large subgroup during a previous hospital admission). Subsequent to a baseline assessment encompassing psychopathology, self-reported cognition as well as objective memory and reasoning tests, patients were randomized to one of three conditions: standard cognitive remediation (mybraintraining), metacognition-augmented cognition remediation (CR) condition (variant of mybraintraining which encouraged patients to reduce speed of decision-making and attenuate response confidence when participants made high-confidence judgements and hasty incorrect decisions) and a waitlist control group. Patients were retested after 6 weeks and again 3 months after the second assessment. Groups did not differ on psychopathology and neurocognitive parameters at any timepoint. However, at follow-up the metacognitive-augmented CR group displayed a significant reduction on jumping to conclusions and overconfidence. Treatment adherence correlated with a reduction of depression; gains in the training exercises from the standard mybraintraining condition were correlated with improved objective memory performance. The study suggests that metacognition-augmented CR may ameliorate cognitive biases but not neurocognition. The study ties in well with prior research showing that neurocognitive dysfunctions are rather resistant to change; the failure to detect significant improvement of CR or metacognition-augmented CR on psychopathology and neurocognition over time may partly be attributed to a number of methodological limitations of

  12. A functional magnetic resonance imaging study of cognitive control and neurosensory deficits in mild traumatic brain injury.

    PubMed

    Mayer, Andrew R; Hanlon, Faith M; Dodd, Andrew B; Ling, Josef M; Klimaj, Stefan D; Meier, Timothy B

    2015-11-01

    Mild traumatic brain injury patients (mTBI) frequently report symptoms of increased distractability and sensory disturbances during mutisensory stimulation. These common post-concussive symptoms could putatively result from dysfunction within the cognitive control network (CCN; top-down) or from unisensory cortex (bottom-up) itself. Functional magnetic resonance imaging (fMRI) and high-resolution structural data were therefore prospectively collected during a multisensory (audio-visual) cognitive control task from 46 mTBI patients within 3 weeks of injury and 46 matched healthy controls (HC), with a subset of participants returning at 4 months. Multisensory stimuli were presented at two frequencies to manipulate cognitive and perceptual load. Patients self-reported more cognitive, emotional, somatic, vestibular and visual symptoms relative to HC, which improved, but did not entirely resolve, over the 4 month follow-up period. There were no group differences in behavior or functional activation during cognitive control (incongruent--congruent trials). In contrast, patients exhibited abnormal activation within different regions of visual cortex that depended on whether attention was focused on auditory or visual information streams. Patients also exhibited increased activation within bilateral inferior parietal lobules during higher cognitive/perceptual loads, suggesting a compensatory mechanism to achieve similar levels of behavioral performance. Functional abnormalities within the visual cortex and inferior parietal lobules were only partially resolved at 4 months post-injury, suggesting that neural abnormalities may take longer to resolve than behavioral measures used in most clinical settings. In summary, current results indicate that abnormalities within unisensory cortex (particularly visual areas) following mTBI, which likely contribute to deficits commonly reported during multisensory stimulation. PMID:26493161

  13. Caramiphen edisylate as adjunct to standard therapy attenuates soman-induced seizures and cognitive deficits in rats.

    PubMed

    Schultz, M K; Wright, L K M; de Araujo Furtado, M; Stone, M F; Moffett, M C; Kelley, N R; Bourne, A R; Lumeh, W Z; Schultz, C R; Schwartz, J E; Lumley, L A

    2014-01-01

    The progression of epileptiform activity following soman (GD) exposure is characterized by a period of excessive cholinergic activity followed by excessive glutamatergic activity resulting in status epilepticus, which may lead to neuropathological damage and behavioral deficits. Caramiphen edisylate is an anticholinergic drug with antiglutamatergic properties, which conceptually may be a beneficial therapeutic approach to the treatment of nerve agent exposure. In the present study, rats were exposed to 1.2 LD50 GD or saline, treated with atropine sulfate (2mg/kg, im) and HI-6 (93.6mg/kg, im) 1min after GD exposure, and monitored for seizure activity. Rats were treated with diazepam (10mg/kg, sc) and caramiphen (0, 20 or 100mg/kg, im) 30min after seizure onset. Following GD exposure, performance was evaluated using a battery of behavioral tests to assess motor coordination and function, sensorimotor gating, and cognitive function. Caramiphen as adjunct to diazepam treatment attenuated GD-induced seizure activity, neuropathological damage, and cognitive deficits compared to diazepam alone, but did not attenuate the GD-induced sensorimotor gating impairment. These findings show that physiological, behavioral, and neuropathological effects of GD exposure can be attenuated by treatment with caramiphen as an adjunct to therapy, even if administration is delayed to 30min after seizure onset.

  14. Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid.

    PubMed

    Liu, Xudong; Zhang, Yuchao; Li, Jinquan; Wang, Dong; Wu, Yang; Li, Yan; Lu, Zhisong; Yu, Samuel C T; Li, Rui; Yang, Xu

    2014-01-01

    Single-walled carbon nanotubes (SWCNTs) have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test), brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH]), inflammation (nuclear factor κB, tumor necrosis factor α, interleukin-1β), and apoptosis (cysteine-aspartic acid protease 3) in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of ascorbic acid. This work suggests SWCNTs could induce cognitive deficits and decreased locomotor activity, and provides a strategy to avoid the adverse effects. PMID:24596461

  15. Autologous transplantation of intestine-isolated glia cells improves neuropathology and restores cognitive deficits in β amyloid-induced neurodegeneration

    PubMed Central

    Esposito, Giuseppe; Sarnelli, Giovanni; Capoccia, Elena; Cirillo, Carla; Pesce, Marcella; Lu, Jie; Calì, Gaetano; Cuomo, Rosario; Steardo, Luca

    2016-01-01

    Alzheimer’s disease (AD) is characterized by chronic deposition of β-amyloid (Aβ) in the brain, progressive neurodegeneration and consequent cognitive and behavioral deficits that typify the disease. Astrocytes are pivotal in this process because they are activated in the attempt to digest Aβ which starts a neuroinflammatory response that further contributes to neurodegeneration. The intestine is a good source of astrocytes-like cells-referred to as enteric glial cells (EGCs). Here we show that the autologous transplantation of EGCs into the brain of Aβ-injected rats arrested the development of the disease after their engraftment. Transplanted EGCs showed anti-amyloidogenic activity, embanked Aβ-induced neuroinflammation and neurodegeneration, and released neutrophic factors. The overall result was the amelioration of the pathological hallmarks and the cognitive and behavioral deficits typical of Aβ-associated disease. Our data indicate that autologous EGCs transplantation may provide an efficient alternative for applications in cell-replacement therapies to treat neurodegeneration in AD. PMID:26940982

  16. Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid.

    PubMed

    Liu, Xudong; Zhang, Yuchao; Li, Jinquan; Wang, Dong; Wu, Yang; Li, Yan; Lu, Zhisong; Yu, Samuel C T; Li, Rui; Yang, Xu

    2014-01-01

    Single-walled carbon nanotubes (SWCNTs) have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test), brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH]), inflammation (nuclear factor κB, tumor necrosis factor α, interleukin-1β), and apoptosis (cysteine-aspartic acid protease 3) in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of ascorbic acid. This work suggests SWCNTs could induce cognitive deficits and decreased locomotor activity, and provides a strategy to avoid the adverse effects.

  17. 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

  18. Distinguishing between autism spectrum disorder and attention deficit hyperactivity disorder by using behavioral checklists, cognitive assessments, and neuropsychological test battery.

    PubMed

    Matsuura, Naomi; Ishitobi, Makoto; Arai, Sumiyoshi; Kawamura, Kaori; Asano, Mizuki; Inohara, Keisuke; Narimoto, Tadamasa; Wada, Yuji; Hiratani, Michio; Kosaka, Hirotaka

    2014-12-01

    Children with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share many common symptoms, including attention deficit, behavioral problems, and difficulties with social skills. The aim of this study was to distinguish between ASD and ADHD by identifying the characteristic features of both the disorders, by using multidimensional assessments, including screening behavioral checklists, cognitive assessments, and comprehensive neurological battery. After screening for comorbid disorders, we carefully selected age-, sex-, IQ-, and socio-economic status-matched children with typical development (TD). In the Wechsler Intelligence Scale for children, a lower score was observed for the ASD group than for the TD group in Picture concept, which is a subscale of perceptual reasoning. A lower score was shown by the ADHD group than by the TD group in the spatial working memory test in the Cambridge Neuropsychological Test Automated Battery (CANTAB(®)). Although ASD and ADHD have many similar symptoms, they can be differentiated by focusing on the behavioral and cognitive characteristics of executive function. PMID:25440561

  19. 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.

  20. Effectiveness of cognitive-functional (Cog-Fun) intervention with children with attention deficit hyperactivity disorder: a pilot study.

    PubMed

    Hahn-Markowitz, Jeri; Manor, Iris; Maeir, Adina

    2011-01-01

    The executive function (EF) deficits of children with attention deficit hyperactivity disorder (ADHD) hinder their performance of complex daily functions. Despite the existing evidence-based pharmacological interventions for ADHD symptoms, no intervention has yet been found that deals directly with EFs in daily tasks. Fourteen children and their parents participated in the Cognitive-Functional (Cog-Fun) program in occupational therapy, which is tailored to the executive dysfunction of ADHD and focuses on enabling cognitive strategies for occupational performance. The study included initial assessment of EFs (Behavior Rating Inventory of Executive Functions; Tower of London(DX)), occupational performance (Canadian Occupational Performance Measure), 10 sessions of Cog-Fun intervention with each child-parent dyad, and postintervention and 3-month follow-up assessments. We found significant improvements with medium to large effects on outcome measures after intervention, and most effects were maintained at follow-up. The findings warrant controlled studies examining the effectiveness of this intervention for children with ADHD. PMID:21834453

  1. Distinguishing between autism spectrum disorder and attention deficit hyperactivity disorder by using behavioral checklists, cognitive assessments, and neuropsychological test battery.

    PubMed

    Matsuura, Naomi; Ishitobi, Makoto; Arai, Sumiyoshi; Kawamura, Kaori; Asano, Mizuki; Inohara, Keisuke; Narimoto, Tadamasa; Wada, Yuji; Hiratani, Michio; Kosaka, Hirotaka

    2014-12-01

    Children with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share many common symptoms, including attention deficit, behavioral problems, and difficulties with social skills. The aim of this study was to distinguish between ASD and ADHD by identifying the characteristic features of both the disorders, by using multidimensional assessments, including screening behavioral checklists, cognitive assessments, and comprehensive neurological battery. After screening for comorbid disorders, we carefully selected age-, sex-, IQ-, and socio-economic status-matched children with typical development (TD). In the Wechsler Intelligence Scale for children, a lower score was observed for the ASD group than for the TD group in Picture concept, which is a subscale of perceptual reasoning. A lower score was shown by the ADHD group than by the TD group in the spatial working memory test in the Cambridge Neuropsychological Test Automated Battery (CANTAB(®)). Although ASD and ADHD have many similar symptoms, they can be differentiated by focusing on the behavioral and cognitive characteristics of executive function.

  2. FLZ Alleviates the Memory Deficits in Transgenic Mouse Model of Alzheimer’s Disease via Decreasing Beta-Amyloid Production and Tau Hyperphosphorylation

    PubMed Central

    Wang, Tao; Kong, Xiang-Chen; Tai, Wen-Jiao; Sun, Hua; Zhang, Dan

    2013-01-01

    Alzheimer’s disease (AD) is the most common cause of dementia worldwide and mainly characterized by the aggregated β-amyloid (Aβ) and hyperphosphorylated tau. FLZ is a novel synthetic derivative of natural squamosamide and has been proved to improve memory deficits in dementia animal models. In this study, we aimed to investigate the mechanisms of FLZ’s neuroprotective effect in APP/PS1 double transgenic mice and SH-SY5Y (APPwt/swe) cells. The results showed that treatment with FLZ significantly improved the memory deficits of APP/PS1 transgenic mice and decreased apoptosis of SH-SY5Y (APPwt/swe) cells. FLZ markedly attenuated Aβ accumulation and tau phosphorylation both in vivo and in vitro. Mechanistic study showed that FLZ interfered APP processing, i.e., FLZ decreased β-amyloid precursor protein (APP) phosphorylation, APP-carboxy-terminal fragment (APP-CTF) production and β-amyloid precursor protein cleaving enzyme 1 (BACE1) expression. These results indicated that FLZ reduced Aβ production through inhibiting amyloidogenic pathway. The mechanistic study about FLZ’s inhibitory effect on tau phosphorylation revealed t the involvement of Akt/glycogen synthase kinase 3β (GSK3β) pathway. FLZ treatment increased Akt activity and inhibited GSK3β activity both in vivo and in vitro. The inhibitory effect of FLZ on GSK3β activity and tau phosphorylation was suppressed by inhibiting Akt activity, indicating that Akt/GSK3β pathway might be the possible mechanism involved in the inhibitory effect of FLZ on tau hyperphosphorylation. These results suggested FLZ might be a potential anti-AD drug as it not only reduced Aβ production via inhibition amyloidogenic APP processing pathway, but also attenuated tau hyperphosphoylation mediated by Akt/GSK3β. PMID:24223757

  3. Effect of Acacia catechu (L.f.) Willd. on Oxidative Stress with Possible Implications in Alleviating Selected Cognitive Disorders.

    PubMed

    Saha, Manas Ranjan; Dey, Priyankar; Begum, Sainiara; De, Bratati; Chaudhuri, Tapas Kr; Sarker, Dilip De; Das, Abhaya Prasad; Sen, Arnab

    2016-01-01

    In human body, several categories of degenerative processes are largely determined by free radicals originating in cell. Free radicals are also known to have correlated with a variety of cognitive disorders (CDs) resulting in neuronal injury and eventually to death. Alzheimer's disease (AD) and Parkinson's disease (PD) are such kind of killer CDs that occur due to dysfunction of cholinergic and dopaminergic neurons. Plant parts of Ginkgo biloba, Bacopa monnieri etc. are being used for the treatment of cognitive disorders in several countries. The present study was aimed to explore the detailed antioxidant and anti-cholinesterase activity of Acaciacatechu leaf (ACL) over CDs. Gas chromatography-Mass spectroscopy (GC-MS) analysis and Nuclear Magnetic Resonance (NMR) were employed to identify the bioactive components present in ACL. Furthermore, the extract was evaluated to check the cytotoxic effects of ACL on normal cells. Amongst several antioxidant assays, DPPH assay, hydroxyl radical, nitric oxide radical and hypochlorous acid inhibitory activities were found to be greater in ACL than that of the respective standards while other assays exhibited a moderate or at per inhibitory activity with standards. Total phenolic and flavonoid content were also found to be present in decent amount. In addition, we found, a greater acetylcholinesterase (AChE) inhibitory activity of ACL when compared to other medicinally important plants, indicating its positive effect over CDs. Forty one bioactive components were explored through GC-MS. Of these, gallic acid, epicatechin, catechin, isoquercitrin etc. were found, which are potent antioxidant and a few of them have anti-neurodegenerative properties. Eventually, ACL was found to be nontoxic and safer to consume. Further studies with animal or human model however, would determine its efficacy as a potential anti-schizophrenic drug.

  4. Effect of Acacia catechu (L.f.) Willd. on Oxidative Stress with Possible Implications in Alleviating Selected Cognitive Disorders

    PubMed Central

    Saha, Manas Ranjan; Dey, Priyankar; Begum, Sainiara; De, Bratati; Chaudhuri, Tapas Kr.; Sarker, Dilip De; Das, Abhaya Prasad; Sen, Arnab

    2016-01-01

    In human body, several categories of degenerative processes are largely determined by free radicals originating in cell. Free radicals are also known to have correlated with a variety of cognitive disorders (CDs) resulting in neuronal injury and eventually to death. Alzheimer’s disease (AD) and Parkinson's disease (PD) are such kind of killer CDs that occur due to dysfunction of cholinergic and dopaminergic neurons. Plant parts of Ginkgo biloba, Bacopa monnieri etc. are being used for the treatment of cognitive disorders in several countries. The present study was aimed to explore the detailed antioxidant and anti-cholinesterase activity of Acaciacatechu leaf (ACL) over CDs. Gas chromatography-Mass spectroscopy (GC-MS) analysis and Nuclear Magnetic Resonance (NMR) were employed to identify the bioactive components present in ACL. Furthermore, the extract was evaluated to check the cytotoxic effects of ACL on normal cells. Amongst several antioxidant assays, DPPH assay, hydroxyl radical, nitric oxide radical and hypochlorous acid inhibitory activities were found to be greater in ACL than that of the respective standards while other assays exhibited a moderate or at per inhibitory activity with standards. Total phenolic and flavonoid content were also found to be present in decent amount. In addition, we found, a greater acetylcholinesterase (AChE) inhibitory activity of ACL when compared to other medicinally important plants, indicating its positive effect over CDs. Forty one bioactive components were explored through GC-MS. Of these, gallic acid, epicatechin, catechin, isoquercitrin etc. were found, which are potent antioxidant and a few of them have anti-neurodegenerative properties. Eventually, ACL was found to be nontoxic and safer to consume. Further studies with animal or human model however, would determine its efficacy as a potential anti-schizophrenic drug. PMID:26949964

  5. Effect of Acacia catechu (L.f.) Willd. on Oxidative Stress with Possible Implications in Alleviating Selected Cognitive Disorders.

    PubMed

    Saha, Manas Ranjan; Dey, Priyankar; Begum, Sainiara; De, Bratati; Chaudhuri, Tapas Kr; Sarker, Dilip De; Das, Abhaya Prasad; Sen, Arnab

    2016-01-01

    In human body, several categories of degenerative processes are largely determined by free radicals originating in cell. Free radicals are also known to have correlated with a variety of cognitive disorders (CDs) resulting in neuronal injury and eventually to death. Alzheimer's disease (AD) and Parkinson's disease (PD) are such kind of killer CDs that occur due to dysfunction of cholinergic and dopaminergic neurons. Plant parts of Ginkgo biloba, Bacopa monnieri etc. are being used for the treatment of cognitive disorders in several countries. The present study was aimed to explore the detailed antioxidant and anti-cholinesterase activity of Acaciacatechu leaf (ACL) over CDs. Gas chromatography-Mass spectroscopy (GC-MS) analysis and Nuclear Magnetic Resonance (NMR) were employed to identify the bioactive components present in ACL. Furthermore, the extract was evaluated to check the cytotoxic effects of ACL on normal cells. Amongst several antioxidant assays, DPPH assay, hydroxyl radical, nitric oxide radical and hypochlorous acid inhibitory activities were found to be greater in ACL than that of the respective standards while other assays exhibited a moderate or at per inhibitory activity with standards. Total phenolic and flavonoid content were also found to be present in decent amount. In addition, we found, a greater acetylcholinesterase (AChE) inhibitory activity of ACL when compared to other medicinally important plants, indicating its positive effect over CDs. Forty one bioactive components were explored through GC-MS. Of these, gallic acid, epicatechin, catechin, isoquercitrin etc. were found, which are potent antioxidant and a few of them have anti-neurodegenerative properties. Eventually, ACL was found to be nontoxic and safer to consume. Further studies with animal or human model however, would determine its efficacy as a potential anti-schizophrenic drug. PMID:26949964

  6. Assessment of cognitive and motor deficits in a marmoset model of stroke.

    PubMed

    Marshall, Jonathan W B; Ridley, Rosalind M

    2003-01-01

    The Stroke Therapy Academic Industry Roundtable noted the need for standardized, well-accepted primate models of stroke to help develop both neuroprotective and restorative therapies. One primate model has been developed using the marmoset, a small New World species of monkey, in which long-term functional deficits can be assessed. The surgery and postoperative care of the animals is described, as well as the behavioral tests used to quantify the postoperative disability. The types of deficits seen are illustrated by reference to some of the findings with neuroprotective treatments. Nevertheless, the long-term nature and consistency of the motor deficits make this model ideal for assessing the worth of restorative therapies.

  7. Cognitive and socio-emotional deficits in platelet-derived growth factor receptor-β gene knockout mice.

    PubMed

    Nguyen, Phuong Thi Hong; Nakamura, Tomoya; Hori, Etsuro; Urakawa, Susumu; Uwano, Teruko; Zhao, Juanjuan; Li, Ruixi; Bac, Nguyen Duy; Hamashima, Takeru; Ishii, Yoko; Matsushima, Takako; Ono, Taketoshi; Sasahara, Masakiyo; Nishijo, Hisao

    2011-01-01

    Platelet-derived growth factor (PDGF) is a potent mitogen. Extensive in vivo studies of PDGF and its receptor (PDGFR) genes have reported that PDGF plays an important role in embryogenesis and development of the central nervous system (CNS). Furthermore, PDGF and the β subunit of the PDGF receptor (PDGFR-β) have been reported to be associated with schizophrenia and autism. However, no study has reported on the effects of PDGF deletion on mice behavior. Here we generated novel mutant mice (PDGFR-β KO) in which PDGFR-β was conditionally deleted in CNS neurons using the Cre/loxP system. Mice without the Cre transgene but with floxed PDGFR-β were used as controls. Both groups of mice reached adulthood without any apparent anatomical defects. These mice were further examined by conducting several behavioral tests for spatial memory, social interaction, conditioning, prepulse inhibition, and forced swimming. The test results indicated that the PDGFR-β KO mice show deficits in all of these areas. Furthermore, an immunohistochemical study of the PDGFR-β KO mice brain indicated that the number of parvalbumin (calcium-binding protein)-positive (i.e., putatively γ-aminobutyric acid-ergic) neurons was low in the amygdala, hippocampus, and medial prefrontal cortex. Neurophysiological studies indicated that sensory-evoked gamma oscillation was low in the PDGFR-β KO mice, consistent with the observed reduction in the number of parvalbumin-positive neurons. These results suggest that PDGFR-β plays an important role in cognitive and socioemotional functions, and that deficits in this receptor may partly underlie the cognitive and socioemotional deficits observed in schizophrenic and autistic patients. PMID:21437241

  8. Cognitive and Emotional Components of Generalized Empathy Deficits in Child Molesters.

    ERIC Educational Resources Information Center

    Marshall, W. L.; Maric, Alexandra

    1996-01-01

    Two scales were used to measure the cognitive (Hogan's Empathy Scale) and emotional (Questionnaire Measure of Emotional Empathy) components of empathy. Results indicated that incarcerated child molesters (N=29) were, relative to nonoffenders, deficient in both the cognitive and emotional components of generalized empathy. Theoretical and treatment…

  9. Binge-like ingestion of a combination of an energy drink and alcohol leads to cognitive deficits and motivational changes.

    PubMed

    Takahashi, Tatiane T; Vendruscolo, Leandro F; Takahashi, Reinaldo N

    2015-09-01

    The combination of alcohol with an energy drink (ED) is believed to contribute to risky alcohol-drinking behaviors, such as binge drinking. However, the long-term effects on cognition and reward function that are caused by the repeated binge-like ingestion of alcohol and EDs are still poorly known. The present study examined the effects of a history of repeated exposure to alcohol and/or an ED on short-term memory and alcohol-seeking behavior. Male Wistar rats were given daily intragastric administration of alcohol (3.4g/kg) combined or not with an ED (10.71ml/kg) for 6 consecutive days. The rats were tested for locomotion 15min after the first intragastric treatment. Short-term memory was assessed in the novel object recognition and social discrimination tests 2-3days after the last intragastric administration. The rewarding effect of alcohol was tested 1-3weeks following the last intragastric administration in a conditioned place preference paradigm. The acute binge-like ingestion of alcohol decreased locomotor activity, whereas the combination of alcohol and an ED increased locomotion in the first minutes of assessment. Alcohol exposure produced cognitive deficits in both the object recognition and social discrimination tests, and adding the ED to the alcohol solution did not modify these effects. The combination of alcohol and the ED increased alcohol-induced conditioned place preference. Thus, a history of binge-like alcohol exposure combined with the ED caused subsequent cognitive deficits and increased alcohol seeking behavior, and such behavioral effects might contribute to the progression to alcohol abuse disorders.

  10. Regulation of hippocampal cGMP levels as a candidate to treat cognitive deficits in Huntington's disease.

    PubMed

    Saavedra, Ana; Giralt, Albert; Arumí, Helena; Alberch, Jordi; Pérez-Navarro, Esther

    2013-01-01

    Huntington's disease (HD) patients and mouse models show learning and memory impairment associated with hippocampal dysfunction. The neuronal nitric oxide synthase/3',5'-cyclic guanosine monophosphate (nNOS/cGMP) pathway is implicated in synaptic plasticity, and in learning and memory processes. Here, we examined the nNOS/cGMP pathway in the hippocampus of HD mice to determine whether it can be a good therapeutic target for cognitive improvement in HD. We analyzed hippocampal nNOS and phosphodiesterase (PDE) 5 and 9 levels in R6/1 mice, and cGMP levels in the hippocampus of R6/1, R6/2 and Hdh(Q7/Q111) mice, and of HD patients. We also investigated whether sildenafil, a PDE5 inhibitor, could improve cognitive deficits in R6/1 mice. We found that hippocampal cGMP levels were 3-fold lower in 12-week-old R6/1 mice, when they show deficits in object recognition memory and in passive avoidance learning. Consistent with hippocampal cGMP levels, nNOS levels were down-regulated, while there were no changes in the levels of PDE5 and PDE9 in R6/1 mice. A single intraperitoneal injection of sildenafil (3 mg/Kg) immediately after training increased cGMP levels, and improved memory in R6/1 mice, as assessed by using the novel object recognition and the passive avoidance test. Importantly, cGMP levels were also reduced in R6/2 mouse and human HD hippocampus. Therefore, the regulation of hippocampal cGMP levels can be a suitable treatment for cognitive impairment in HD. PMID:24040016

  11. Do Social and Cognitive Deficits Curtail Musical Understanding? Evidence from Autism and Down Syndrome

    ERIC Educational Resources Information Center

    Heaton, Pamela; Allen, Rory; Williams, Kerry; Cummins, Omar; Happe, Francesca

    2008-01-01

    Children with autism experience difficulties in understanding social affective cues, and it has been suggested that such deficits will generalize to music. In order to investigate this proposal, typically developing individuals and children with autism and Down syndrome were compared on tasks measuring perception of affective and movement states…

  12. Cognitive-Behavioral Depression Treatment for Mothers of Children with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Chronis, Andrea M.; Gamble, Stephanie A.; Roberts, John E.; Pelham, William E., Jr.

    2006-01-01

    An adaptation of the Coping With Depression Course (CWDC) was evaluated in mothers of children with attention-deficit/hyperactivity disorder (ADHD), a population at risk for depression. Mothers were randomly assigned to receive the CWDC either immediately following an intensive summer treatment program targeting their child's behavior or after a…

  13. Systematic review of the relationship between amyloid-β levels and measures of transgenic mouse cognitive deficit in Alzheimer's disease.

    PubMed

    Foley, Avery M; Ammar, Zeena M; Lee, Robert H; Mitchell, Cassie S

    2015-01-01

    Amyloid-β (Aβ) is believed to directly affect memory and learning in Alzheimer's disease (AD). It is widely suggested that there is a relationship between Aβ40 and Aβ42 levels and cognitive performance. In order to explore the validity of this relationship, we performed a meta-analysis of 40 peer-reviewed, published AD transgenic mouse studies that quantitatively measured Aβ levels in brain tissue after assessing cognitive performance. We examined the relationship between Aβ levels (Aβ40, Aβ42, or the ratio of Aβ42 to Aβ40) and cognitive function as measured by escape latency times in the Morris water maze or exploratory preference percentage in the novel object recognition test. Our systematic review examined five mouse models (Tg2576, APP, PS1, 3xTg, APP(OSK)-Tg), gender, and age. The overall result revealed no statistically significant correlation between quantified Aβ levels and experimental measures of cognitive function. However, enough of the trends were of the same sign to suggest that there probably is a very weak qualitative trend visible only across many orders of magnitude. In summary, the results of the systematic review revealed that mice bred to show elevated levels of Aβ do not perform significantly worse in cognitive tests than mice that do not have elevated Aβ levels. Our results suggest two lines of inquiry: 1) Aβ is a biochemical "side effect" of the AD pathology; or 2) learning and memory deficits in AD are tied to the presence of qualitatively "high" levels of Aβ but are not quantitatively sensitive to the levels themselves.

  14. The heterogeneity of attention-deficit/hyperactivity disorder symptoms and conduct problems: Cognitive inhibition, emotion regulation, emotionality, and disorganized attachment.

    PubMed

    Forslund, Tommie; Brocki, Karin C; Bohlin, Gunilla; Granqvist, Pehr; Eninger, Lilianne

    2016-09-01

    This study examined the contributions of several important domains of functioning to attention-deficit/hyperactivity disorder (ADHD) symptoms and conduct problems. Specifically, we investigated whether cognitive inhibition, emotion regulation, emotionality, and disorganized attachment made independent and specific contributions to these externalizing behaviour problems from a multiple pathways perspective. The study included laboratory measures of cognitive inhibition and disorganized attachment in 184 typically developing children (M age = 6 years, 10 months, SD = 1.7). Parental ratings provided measures of emotion regulation, emotionality, and externalizing behaviour problems. Results revealed that cognitive inhibition, regulation of positive emotion, and positive emotionality were independently and specifically related to ADHD symptoms. Disorganized attachment and negative emotionality formed independent and specific relations to conduct problems. Our findings support the multiple pathways perspective on ADHD, with poor regulation of positive emotion and high positive emotionality making distinct contributions to ADHD symptoms. More specifically, our results support the proposal of a temperamentally based pathway to ADHD symptoms. The findings also indicate that disorganized attachment and negative emotionality constitute pathways specific to conduct problems rather than to ADHD symptoms. PMID:26895773

  15. Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits

    PubMed Central

    Aungst, Stephanie L; Kabadi, Shruti V; Thompson, Scott M; Stoica, Bogdan A; Faden, Alan I

    2014-01-01

    Repeated mild traumatic brain injury (mTBI) can cause sustained cognitive and psychiatric changes, as well as neurodegeneration, but the underlying mechanisms remain unclear. We examined histologic, neurophysiological, and cognitive changes after single or repeated (three injuries) mTBI using the rat lateral fluid percussion (LFP) model. Repeated mTBI caused substantial neuronal cell loss and significantly increased numbers of activated microglia in both ipsilateral and contralateral hippocampus on post-injury day (PID) 28. Long-term potentiation (LTP) could not be induced on PID 28 after repeated mTBI in ex vivo hippocampal slices from either hemisphere. N-Methyl-D-aspartate (NMDA) receptor-mediated responses were significantly attenuated after repeated mTBI, with no significant changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated responses. Long-term potentiation was elicited in slices after single mTBI, with potentiation significantly increased in ipsilateral versus contralateral hippocampus. After repeated mTBI, rats displayed cognitive impairments in the Morris water maze (MWM) and novel object recognition (NOR) tests. Thus, repeated mTBI causes deficits in the hippocampal function and changes in excitatory synaptic neurotransmission, which are associated with chronic neuroinflammation and neurodegeneration. PMID:24756076

  16. A global immune deficit in Alzheimer's disease and mild cognitive impairment disclosed by a novel data mining process.

    PubMed

    Gironi, Maira; Borgiani, Bruno; Farina, Elisabetta; Mariani, Enrica; Cursano, Cristina; Alberoni, Margherita; Nemni, Raffaello; Comi, Giancarlo; Buscema, Massimo; Furlan, Roberto; Grossi, Enzo

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia, while mild cognitive impairment (MCI) causes a slight but measurable decline in cognitive abilities. A person with MCI has an increased risk of developing AD or another dementia. Thus, it is of medical interest to develop predictive tools to assess this risk. A growing awareness exists that pro-oxidative state and neuro-inflammation are both involved in AD. However, the extent of this relationship is still a matter of debate. Due to the expected non-linear correlations between oxidative and inflammatory markers, traditional statistics is unsuitable to dissect their relationship with the disease. Artificial neural networks (ANNs) are computational models inspired by central nervous system networks, capable of machine learning and pattern recognition. The aim of this work was to disclose the relationship between immunological and oxidative stress markers in AD and MCI by the application of ANNs. Through a machine learning approach, we were able to construct an algorithm to classify MCI and AD with high accuracy. Such an instrument, requiring a small amount of immunological and oxidative-stress parameters, would be useful in the clinical practice. Moreover, applying an innovative non-linear mathematical technique, a global immune deficit was shown to be associated with cognitive impairment. Surprisingly, both adaptive and innate immunity were peripherally defective in AD and MCI patients. From this study, new pathogenetic aspects of these diseases could emerge.

  17. The heterogeneity of attention-deficit/hyperactivity disorder symptoms and conduct problems: Cognitive inhibition, emotion regulation, emotionality, and disorganized attachment.

    PubMed

    Forslund, Tommie; Brocki, Karin C; Bohlin, Gunilla; Granqvist, Pehr; Eninger, Lilianne

    2016-09-01

    This study examined the contributions of several important domains of functioning to attention-deficit/hyperactivity disorder (ADHD) symptoms and conduct problems. Specifically, we investigated whether cognitive inhibition, emotion regulation, emotionality, and disorganized attachment made independent and specific contributions to these externalizing behaviour problems from a multiple pathways perspective. The study included laboratory measures of cognitive inhibition and disorganized attachment in 184 typically developing children (M age = 6 years, 10 months, SD = 1.7). Parental ratings provided measures of emotion regulation, emotionality, and externalizing behaviour problems. Results revealed that cognitive inhibition, regulation of positive emotion, and positive emotionality were independently and specifically related to ADHD symptoms. Disorganized attachment and negative emotionality formed independent and specific relations to conduct problems. Our findings support the multiple pathways perspective on ADHD, with poor regulation of positive emotion and high positive emotionality making distinct contributions to ADHD symptoms. More specifically, our results support the proposal of a temperamentally based pathway to ADHD symptoms. The findings also indicate that disorganized attachment and negative emotionality constitute pathways specific to conduct problems rather than to ADHD symptoms.

  18. Visuo-cognitive skill deficits in Alzheimer's disease and Lewy body disease: A comparative analysis

    PubMed Central

    Li, Xuemei; Rastogi, Priyanka; Gibbons, Jeffrey A.; Chaudhury, Suprakash

    2014-01-01

    Dementia is a chronic neurodegenerative disorder characterized by progressive cognitive loss. Alzheimer's disease (AD) and the Lewy body disease are the two most common causes of age-related degenerative dementia. Visuo-cognitive skills are a combination of very different cognitive functions being performed by the visual system. These skills are impaired in both AD and dementia with Lewy bodies (DLB). The aim of this review is to evaluate various studies for these visuo-cognitive skills. An exhaustive internet search of all relevant medical databases was carried out using a series of key-word applications, including The Cochrane Library, MEDLINE, PSYCHINFO, EMBASE, CINAHL, AMED, SportDiscus, Science Citation Index, Index to Theses, ZETOC, PEDro and occupational therapy (OT) seeker and OT search. We reviewed all the articles until March 2013 with key words of: Visual skills visual cognition dementia AD, but the direct neurobiological etiology is difficult to establish., Dementia of Lewy body disease. Although most studies have used different tests for studying these abilities, in general, these tests evaluated the individual's ability of (1) visual recognition, (2) visual discrimination, (3) visual attention and (4) visuo-perceptive integration. Performance on various tests has been evaluated for assessing these skills. Most studies assessing such skills show that these skills are impaired in DLB as compared with AD. Visuo-cognitive skills are impaired more in DLB as compared with AD. These impairments have evident neuropathological correlations, but the direct neurobiological etiology is difficult to establish. PMID:24753653

  19. Gender differences in cognitive deficits in schizophrenia with and without diabetes.

    PubMed

    Zhang, Bao Hua; Han, Mei; Zhang, Xiang Yang; Hui, Li; Jiang, Shu Rong; Yang, Fu De; Tan, Yun Long; Wang, Zhi Ren; Li, Juan; Huang, Xu Feng

    2015-11-01

    This study investigated gender differences in cognition in schizophrenia with and without diabetes. Cognition was assessed in 263 individuals with schizophrenia with age range (40-68): 67 males and 34 females with schizophrenia with diabetes; and 125 males and 37 females with schizophrenia without diabetes according to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Fasting glucose, hemoglobin A1c (HbA1c) and lipid levels were measured. Results showed that male individuals performed worse on most cognitive tasks, especially attention, in schizophrenia with than without diabetes. This result was not observed in female individuals. Also, individuals of both genders showed higher fasting glucose and HbA1c in schizophrenia with than without diabetes. In schizophrenia with diabetes, males had significantly worse cognition than females in all cognitive domains. Higher HbA1c, lower high-density lipoprotein, and an earlier age of onset of schizophrenia were found in males compared with female individuals. HbA1c was negatively associated with attention and the RBANS total score for males but not for females. In schizophrenia without diabetes, males showed worse performance in immediate and delayed memory than females. This study support cognition was worse for males with schizophrenia irrespective of whether they have diabetes. However, diabetes exemplified the gender differences, especially in attention.

  20. Developing treatments for cognitive deficits in schizophrenia: The challenge of translation

    PubMed Central

    Young, J.W.; Geyer, M.A.

    2015-01-01

    Schizophrenia is a life-long debilitating mental disorder affecting tens of millions of people worldwide. The serendipitous discovery of antipsychotics focused pharmaceutical research on developing a better antipsychotic. Our understanding of the disorder has advanced however, with the knowledge that cognitive enhancers are required for patients in order to improve their everyday lives. Whilst antipsychotics treat psychosis, they do not enhance cognition and hence are not antischizophrenics. Developing pro-cognitive therapeutics has been extremely difficult however, especially when no approved treatment exists. In lieu of stumbling on an efficacious treatment, developing targeted compounds can be facilitated by understanding the neural mechanisms underlying altered cognitive functioning in patients. Equally importantly, these cognitive domains will need to be measured similarly in animals and humans so that novel targets can be tested prior to conducting expensive clinical trials. To date, the limited similarity of testing across species has resulted in a translational bottleneck. In this review, we emphasize that schizophrenia is a disorder characterized by abnormal cognitive behavior. Quantifying these abnormalities using tasks having cross-species validity would enable the quantification of comparable processes in rodents. This approach would increase the likelihood that the neural substrates underlying relevant behaviors will be conserved across species. Hence, we detail cross-species tasks which can be used to test the effects of manipulations relevant to schizophrenia and putative therapeutics. Such tasks offer the hope of providing a bridge between non-clinical and clinical testing that will eventually lead to treatments developed specifically for patients with deficient cognition. PMID:25516372

  1. [Neuropsychological treatment of cognitive deficits in substance abuse disorders, affective disorders, anxiety disorders and obsessive-compulsive disorders - current status and perspectives].

    PubMed

    Buschert, V C; Zwanzger, P; Brunnauer, A

    2015-05-01

    Neuropsychological treatment represents a promising therapeutic approach in the amelioration of cognitive deficits in many neuropsychiatric disorders. Cognitive impairment constitutes a core feature that often persists beyond psychopathological symptoms having a significant impact on psychosocial functioning. However, research interest and evidence of efficacy vary considerably between disease groups. Although neuropsychological treatment is frequently used in clinical practice, there are, with the exception of schizophrenia, relatively few studies on its effectiveness.

  2. Assessing Specific Cognitive Deficits Associated with Dementia in Older Adults with Down Syndrome: Use and Validity of the Arizona Cognitive Test Battery (ACTB)

    PubMed Central

    Sinai, Amanda; Hassiotis, Angela; Rantell, Khadija; Strydom, Andre

    2016-01-01

    Background Down syndrome is associated with specific cognitive deficits. Alongside this, older adults with Down syndrome are a high risk group for dementia. The Arizona Cognitive Test Battery (ACTB), a cognitive assessment battery specifically developed for use with individuals with Down syndrome, has been proposed for use as outcome measures for clinical trials in this population. It has not been validated in older adults with Down syndrome. This study aims to assess the use and validity of the ACTB in older adults with Down syndrome. Methods Participants with Down syndrome aged 45 and over were assessed using the ACTB, standard tabletop tests and informant ratings. Results Assessment outcomes of 49 participants were analysed. Of these, 19 (39%) had a diagnosis of dementia or possible dementia. Most participants were able to attempt most of the tasks, although some tasks had high floor effects (including CANTAB Intra-Extra Dimensional shift stages completed and Modified Dots Task). Of the ACTB tasks, statistically significant differences were observed between the dementia and no dementia groups on CANTAB Simple Reaction Time median latency, NEPSY Visuomotor Precision—Car and Motorbike and CANTAB Paired Associates Learning stages completed. No significant differences were observed for CANTAB Intra-Extra Dimensional Shift, Modified Dots Task, Finger Sequencing, NEPSY Visuomotor precision—Train and Car and CANTAB Paired Associates Learning first trial memory score. Several of the tasks in the ACTB can be used in older adults with Down syndrome and have mild to moderate concurrent validity when compared to tabletop tests and informant ratings, although this varies on a test by test basis. Conclusions Overall, scores for a number of tests in the ACTB were similar when comparing dementia and no dementia groups of older adults with Down syndrome, suggesting that it would not be an appropriate outcome measure of cognitive function for clinical trials of dementia

  3. Effects of a multicomponent behavioral intervention on impulsivity and cognitive deficits in adolescents with excess weight.

    PubMed

    Delgado-Rico, Elena; Río-Valle, Jacqueline S; Albein-Urios, Natalia; Caracuel, Alfonso; González-Jiménez, Emilio; Piqueras, María J; Brandi, Pilar; Ruiz-López, Isabel M; García-Rodríguez, Inmaculada; Martín-Matillas, Miguel; Delgado-Fernández, Manuel; Campoy, Cristina; Verdejo-García, Antonio

    2012-09-01

    The aim of this study was to explore the effects of a multidisciplinary behavioral intervention including cognitive behavioral therapy, structured physical activity, and dietary counseling on impulsive personality and cognitive skills and subsequent BMI loss in excess weight adolescents. Forty-two adolescents with excess weight (14 males and 28 females, range 12-17 years), as defined by the International Obesity Task Force Criteria, participated in our study. We used a longitudinal observational design with two assessments: before and after treatment. We collected baseline measures of impulsive personality (UPPS-P scale), cognitive performance (letter number sequencing, Stroop and Iowa gambling task), and biometric parameters. After 12 weeks of intervention, parallel measures were used to determine whether treatment-induced changes in impulsivity and cognition predicted changes in BMI. BMI showed a statistically significant reduction after treatment [from mean (SD) 29.36 (4.51) to 27.31 (4.41), Cohen's d=0.5]. Greater reductions in negative urgency (negative-emotion-driven impulsivity) and greater improvement in cognitive inhibitory control skills were associated with greater reductions in BMI. Because the design was correlational and lacked a control group, future studies should clarify whether these associations reflect a causal effect or just overlapping improvements associated with a third variable (e.g. increases in attention procurement or motivation). PMID:22785438

  4. Assessing schizophrenia-relevant cognitive and social deficits in mice: a selection of mouse behavioral tasks and potential therapeutic compounds.

    PubMed

    Lai, Wen-Sung; Chang, Chia-Yuan; Wong, Wan-Rong; Pei, Ju-Chun; Chen, Ya-Shan; Hung, Wei-Li

    2014-01-01

    Schizophrenia and other psychiatric disorders are generally diagnosed based on a collection of symptoms defined by a combination of an individual's feelings, perceptions, and behaviors. Many of these disorders are characterized by specific cognitive and social deficits. Although it is nearly impossible to recapitulate the full phenotypic spectrum of schizophrenia in mice, mouse models play an indispensable role in understanding the pathogenesis of this disorder and the development of new therapeutics. Genetic mouse models of schizophrenia and mouse behavioral tests provide a feasible approach for elucidating causal relationships between susceptibility gene(s) and schizophrenia-related symptoms. There has been a proliferation of studies characterizing basic behavioral phenotypes in mice. Since there is no way to completely model human psychiatric symptoms in mice, the major role of behavioral tests is to provide insights into underlying affected circuitry and pathophysiology. Given that the recovery of cognitive and social abilities significantly benefits functional outcomes, there has been an increasing interest in characterizing cognitive and social functions in mutant mice; however, these functions are not easy to measure. In this review, a selection of conventional behavioral tasks was briefly described and three specific behavioral tasks aimed at characterizing social communication, attentional function, and choice behavior in mice were highlighted. The choice of specific behavioral tasks during experimental planning should take into consideration a variety of factors, including their validity, reliability, sensitivity, utility, and specificity. Based upon the hypothetical hypofunction of N-methyl-D-aspartate receptor (NMDAR)-mediated signaling pathways in the involvement of cognitive and social impairments in schizophrenia, three NMDAR-related compounds/drugs, D-serine, sarcosine, and D-cycloserine, are discussed as an example.

  5. Beyond stimulus deprivation: iron deficiency and cognitive deficits in postinstitutionalized children.

    PubMed

    Doom, Jenalee R; Gunnar, Megan R; Georgieff, Michael K; Kroupina, Maria G; Frenn, Kristin; Fuglestad, Anita J; Carlson, Stephanie M

    2014-01-01

    Children adopted from institutions have been studied as models of the impact of stimulus deprivation on cognitive development (Nelson, Bos, Gunnar, & Sonuga-Barke, 2011), but these children may also suffer from micronutrient deficiencies (Fuglestad et al., 2008). The contributions of iron deficiency (ID) and duration of deprivation on cognitive functioning in children adopted from institutions between 17 and 36 months of age were examined. ID was assessed in 55 children soon after adoption, and cognitive functioning was evaluated 11-14.6 months postadoption when the children averaged 37.4 months old (SD = 4.9). ID at adoption and longer duration of institutional care independently predicted lower IQ scores and executive function (EF) performance. IQ did not mediate the association between ID and EF.

  6. Beyond Stimulus Deprivation: Iron Deficiency and Cognitive Deficits in Post-Institutionalized Children

    PubMed Central

    Doom, Jenalee R.; Gunnar, Megan R.; Georgieff, Michael K.; Kroupina, Maria G.; Frenn, Kristin; Fuglestad, Anita J.

    2014-01-01

    Children adopted from institutions have been studied as models of the impact of stimulus deprivation on cognitive development (Nelson et al., 2011), but these children may also suffer from micronutrient deficiencies (Fuglestad et al., 2008). The contributions of iron deficiency (ID) and duration of deprivation on cognitive functioning in children adopted from institutions between 17 and 36 months of age were examined. ID was assessed in 55 children soon after adoption, and cognitive functioning was evaluated 11–14.6 months post-adoption when the children averaged 37.4 months old (SD = 4.9). ID at adoption and longer duration of institutional care independently predicted lower IQ scores and executive function (EF) performance. IQ did not mediate the association between ID and EF. PMID:24597672

  7. The origins of repetitive thought in rumination: Separating cognitive style from deficits in inhibitory control over memory

    PubMed Central

    Fawcett, Jonathan M.; Benoit, Roland G.; Gagnepain, Pierre; Salman, Amna; Bartholdy, Savani; Bradley, Caroline; Chan, Daniel K.-Y.; Roche, Ayesha; Brewin, Chris R.; Anderson, Michael C.

    2015-01-01

    Background and objectives Rumination is a major contributor to the maintenance of affective disorders and has been linked to memory control deficits. However, ruminators often report intentionally engaging in repetitive thought due to its perceived benefits. Deliberate re-processing may lead to the appearance of a memory control deficit that is better explained as a difference in cognitive style. Methods Ninety-six undergraduate students volunteered to take part in a direct-suppression variant of the Think/No-Think paradigm after which they completed self-report measures of rumination and the degree to which they deliberately re-processed the to-be-suppressed items. Results We demonstrate a relation between rumination and impaired suppression-induced forgetting. This relation is robust even when controlling for deliberate re-processing of the to-be-suppressed items, a behavior itself related to both rumination and suppression. Therefore, whereas conscious fixation on to-be-suppressed items reduced memory suppression, it did not fully account for the relation between rumination and memory suppression. Limitations The current experiment employed a retrospective measure of deliberate re-processing in the context of an unscreened university sample; future research might therefore generalize our findings using an online measure of deliberate re-processing or within a clinical population. Conclusions We provide evidence that deliberate re-processing accounts for some – but not all – of the relation between rumination and suppression-induced forgetting. The present findings, observed in a paradigm known to engage top-down inhibitory modulation of mnemonic processing, provide the most theoretically focused evidence to date for the existence of a memory control deficit in rumination. PMID:25462596

  8. Working Memory Deficits in Neuronal Nitric Oxide Synthase Knockout Mice: Potential Impairments in Prefrontal Cortex Mediated Cognitive Function

    PubMed Central

    Zoubovsky, Sandra P.; Pogorelov, Vladimir M.; Taniguchi, Yu; Kim, Sun-Hong; Yoon, Peter; Nwulia, Evaristus; Sawa, Akira; Pletnikov, Mikhail V.; Kamiya, Atsushi

    2011-01-01

    Neuronal nitric oxide synthase (nNOS) forms nitric oxide (NO), which functions as a signaling molecule via S-nitrosylation of various proteins and regulation of soluble guanylate cyclase (cGC)/cyclic guanosine monophosphate (cGMP) pathway in the central nervous system. nNOS signaling regulates diverse cellular processes during brain development and molecular mechanisms required for higher brain function. Human genetics have identified nNOS and several downstream effectors of nNOS as risk genes for schizophrenia. Besides the disease itself, nNOS has also been associated with prefrontal cortical functioning, including cognition, of which disturbances are a core feature of schizophrenia. Although mice with genetic deletion of nNOS display various behavioral deficits, no studies have investigated prefrontal cortex-associated behaviors. Here, we report that nNOS knockout (KO) mice exhibit hyperactivity and impairments in contextual fear conditioning, results consistent with previous reports. nNOS KO mice also display mild impairments in object recognition memory. Most importantly, we report for the first time working memory deficits, potential impairments in prefrontal cortex mediated cognitive function in nNOS KO mice. Furthermore, we demonstrate Disrupted-in-Schizophrenia 1 (DISC1), another genetic risk factor for schizophrenia that plays roles for cortical development and prefrontal cortex functioning, including working memory, is a novel protein binding partner of nNOS in the developing cerebral cortex. Of note, genetic deletion of nNOS appears to increase the binding of DISC1 to NDEL1, regulating neurite outgrowth as previously reported. These results suggest that nNOS KO mice are useful tools in studying the role of nNOS signaling in cortical development and prefrontal cortical functioning. PMID:21539806

  9. Working memory deficits in neuronal nitric oxide synthase knockout mice: potential impairments in prefrontal cortex mediated cognitive function.

    PubMed

    Zoubovsky, Sandra P; Pogorelov, Vladimir M; Taniguchi, Yu; Kim, Sun-Hong; Yoon, Peter; Nwulia, Evaristus; Sawa, Akira; Pletnikov, Mikhail V; Kamiya, Atsushi

    2011-05-20

    Neuronal nitric oxide synthase (nNOS) forms nitric oxide (NO), which functions as a signaling molecule via S-nitrosylation of various proteins and regulation of soluble guanylate cyclase (cGC)/cyclic guanosine monophosphate (cGMP) pathway in the central nervous system. nNOS signaling regulates diverse cellular processes during brain development and molecular mechanisms required for higher brain function. Human genetics have identified nNOS and several downstream effectors of nNOS as risk genes for schizophrenia. Besides the disease itself, nNOS has also been associated with prefrontal cortical functioning, including cognition, of which disturbances are a core feature of schizophrenia. Although mice with genetic deletion of nNOS display various behavioral deficits, no studies have investigated prefrontal cortex-associated behaviors. Here, we report that nNOS knockout (KO) mice exhibit hyperactivity and impairments in contextual fear conditioning, results consistent with previous reports. nNOS KO mice also display mild impairments in object recognition memory. Most importantly, we report for the first time working memory deficits, potential impairments in prefrontal cortex mediated cognitive function in nNOS KO mice. Furthermore, we demonstrate Disrupted-in-Schizophrenia 1 (DISC1), another genetic risk factor for schizophrenia that plays roles for cortical development and prefrontal cortex functioning, including working memory, is a novel protein binding partner of nNOS in the developing cerebral cortex. Of note, genetic deletion of nNOS appears to increase the binding of DISC1 to NDEL1, regulating neurite outgrowth as previously reported. These results suggest that nNOS KO mice are useful tools in studying the role of nNOS signaling in cortical development and prefrontal cortical functioning. PMID:21539806

  10. Methanol extract of Ficus platyphylla ameliorates seizure severity, cognitive deficit and neuronal cell loss in pentylenetetrazole-kindled mice.

    PubMed

    Chindo, Ben A; Schröder, Helmut; Becker, Axel

    2015-01-15

    Decoctions of Ficus plathyphylla are used in Nigeria's folk medicine to manage epilepsy for many years and their efficacies are widely acclaimed among the rural communities of Northern Nigeria. In this study, we examined the ameliorative effects of the standardized methanol extract of Ficus platyphylla (FP) stem bark on seizure severity, cognitive deficit and neuronal cell loss in pentylenetetrazole-kindled mice. The (35)S-GTPγS, glutamate and γ-aminobutyric acid receptors binding properties of the extract were also evaluated. Male CD-1 mice were kindled with an initial subeffective dose of pentylenetetrazole (PTZ, 37.5mg/kg, i.p.) for a total of 13 convulsant injections and the treatment groups concurrently received FP (100 and 200mg/kg). Control animals received the same number of saline injections. Twenty-four h after kindling completion the animals' learning performance was tested in a two-way shuttle-box. The animals were challenged with another subeffective dose of PTZ (32.5mg/kg, i.p.) on day 7 after kindling completion. Animals were sacrificed a day after the challenged experiment and the brains were processed for histological investigation. FP ameliorates seizure severity, cognitive deficits and neuronal cell loss in PTZ kindled mice. Components of the extract showed affinity for GABAergic and glutamatergic receptors. Glutamate release was diminished and the (35)S-GTPγS binding assay revealed no intrinsic activity at glutamatergic receptors. Our results revealed that FP contains psychoactive secondary metabolites with anticonvulsant properties, thus supporting the isolation and development of the biologically active components of this medicinal plant as antiepileptic agents.

  11. Baduk (the Game of Go) Improved Cognitive Function and Brain Activity in Children with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Kim, Se Hee; Lee, Young Sik; Kim, Bung-Nyun; Cheong, Jae Hoon; Han, Sang Ho

    2014-01-01

    Objective Attention deficit hyperactivity disorder (ADHD) symptoms are associated with the deficit in executive functions. Playing Go involves many aspect of cognitive function and we hypothesized that it would be effective for children with ADHD. Methods Seventeen drug naïve children with ADHD and seventeen age and sex matched comparison subjects were participated. Participants played Go under the instructor's education for 2 hours/day, 5 days/week. Before and at the end of Go period, clinical symptoms, cognitive functions, and brain EEG were assessed with Dupaul's ADHD scale (ARS), Child depression inventory (CDI), digit span, the Children's Color Trails Test (CCTT), and 8-channel QEEG system (LXE3208, Laxtha Inc., Daejeon, Korea). Results There were significant improvements of ARS total score (z=2.93, p<0.01) and inattentive score (z=2.94, p<0.01) in children with ADHD. However, there was no significant change in hyperactivity score (z=1.33, p=0.18). There were improvement of digit total score (z=2.60, p<0.01; z=2.06, p=0.03), digit forward score (z=2.21, p=0.02; z=2.02, p=0.04) in both ADHD and healthy comparisons. In addition, ADHD children showed decreased time of CCTT-2 (z=2.21, p=0.03). The change of theta/beta right of prefrontal cortex during 16 weeks was greater in children with ADHD than in healthy comparisons (F=4.45, p=0.04). The change of right theta/beta in prefrontal cortex has a positive correlation with ARS-inattention score in children with ADHD (r=0.44, p=0.03). Conclusion We suggest that playing Go would be effective for children with ADHD by activating hypoarousal prefrontal function and enhancing executive function. PMID:24843369

  12. Deficits in narrative discourse elicited by visual stimuli are already present in patients with mild cognitive impairment

    PubMed Central

    Drummond, Cláudia; Coutinho, Gabriel; Fonseca, Rochele Paz; Assunção, Naima; Teldeschi, Alina; de Oliveira-Souza, Ricardo; Moll, Jorge; Tovar-Moll, Fernanda; Mattos, Paulo

    2015-01-01

    Language batteries used to assess the skills of elderly individuals, such as naming and semantic verbal fluency, present some limitations in differentiating healthy controls from patients with amnestic mild cognitive impairment (a-MCI). Deficits in narrative discourse occur early in dementia caused by Alzheimer's disease (AD), and the narrative discourse abilities of a-MCI patients are poorly documented. The present study sought to propose and evaluate parameters for investigating narrative discourse in these populations. After a pilot study of 30 healthy subjects who served as a preliminary investigation of macro- and micro-linguistic aspects, 77 individuals (patients with AD and a-MCI and a control group) were evaluated. The experimental task required the participants to narrate a story based on a sequence of actions visually presented. The Control and AD groups differed in all parameters except narrative time and the total number of words recalled. The a-MCI group displayed mild discursive difficulties that were characterized as an intermediate stage between the Control and AD groups' performances. The a-MCI and Control groups differed from the AD group with respect to global coherence, discourse type and referential cohesion. The a-MCI and AD groups were similar to one another but differed from the Control group with respect to the type of words recalled, the repetition of words in the same sentence, the narrative structure and the inclusion of irrelevant propositions in the narrative. The narrative parameter that best distinguished the three groups was the speech effectiveness index. The proposed task was able to reveal differences between healthy controls and groups with cognitive decline. According to our findings, patients with a-MCI already present narrative deficits that are characterized by mild discursive difficulties that are less severe than those found in patients with AD. PMID:26074814

  13. "I Know that You Know that I Know": Neural Substrates Associated with Social Cognition Deficits in DM1 Patients.

    PubMed

    Serra, Laura; Cercignani, Mara; Bruschini, Michela; Cipolotti, Lisa; Mancini, Matteo; Silvestri, Gabriella; Petrucci, Antonio; Bucci, Elisabetta; Antonini, Giovanni; Licchelli, Loretta; Spanò, Barbara; Giacanelli, Manlio; Caltagirone, Carlo; Meola, Giovanni; Bozzali, Marco

    2016-01-01

    Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in the Eyes" and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients' "Theory of Mind-network", which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients' success in life. PMID:27258100

  14. Deficits in narrative discourse elicited by visual stimuli are already present in patients with mild cognitive impairment.

    PubMed

    Drummond, Cláudia; Coutinho, Gabriel; Fonseca, Rochele Paz; Assunção, Naima; Teldeschi, Alina; de Oliveira-Souza, Ricardo; Moll, Jorge; Tovar-Moll, Fernanda; Mattos, Paulo

    2015-01-01

    Language batteries used to assess the skills of elderly individuals, such as naming and semantic verbal fluency, present some limitations in differentiating healthy controls from patients with amnestic mild cognitive impairment (a-MCI). Deficits in narrative discourse occur early in dementia caused by Alzheimer's disease (AD), and the narrative discourse abilities of a-MCI patients are poorly documented. The present study sought to propose and evaluate parameters for investigating narrative discourse in these populations. After a pilot study of 30 healthy subjects who served as a preliminary investigation of macro- and micro-linguistic aspects, 77 individuals (patients with AD and a-MCI and a control group) were evaluated. The experimental task required the participants to narrate a story based on a sequence of actions visually presented. The Control and AD groups differed in all parameters except narrative time and the total number of words recalled. The a-MCI group displayed mild discursive difficulties that were characterized as an intermediate stage between the Control and AD groups' performances. The a-MCI and Control groups differed from the AD group with respect to global coherence, discourse type and referential cohesion. The a-MCI and AD groups were similar to one another but differed from the Control group with respect to the type of words recalled, the repetition of words in the same sentence, the narrative structure and the inclusion of irrelevant propositions in the narrative. The narrative parameter that best distinguished the three groups was the speech effectiveness index. The proposed task was able to reveal differences between healthy controls and groups with cognitive decline. According to our findings, patients with a-MCI already present narrative deficits that are characterized by mild discursive difficulties that are less severe than those found in patients with AD.

  15. The use of mouse models to understand and improve cognitive deficits in Down syndrome

    PubMed Central

    Das, Ishita; Reeves, Roger H.

    2011-01-01

    Remarkable advances have been made in recent years towards therapeutics for cognitive impairment in individuals with Down syndrome (DS) by using mouse models. In this review, we briefly describe the phenotypes of mouse models that represent outcome targets for drug testing, the behavioral tests used to assess impairments in cognition and the known mechanisms of action of several drugs that are being used in preclinical studies or are likely to be tested in clinical trials. Overlaps in the distribution of targets and in the pathways that are affected by these diverse drugs in the trisomic brain suggest new avenues for DS research and drug development. PMID:21816951

  16. Cognitive performance deficits in a simulated climb of Mount Everest - Operation Everest II

    NASA Technical Reports Server (NTRS)

    Kennedy, R. S.; Dunlap, W. P.; Banderet, L. E.; Smith, M. G.; Houston, C. S.

    1989-01-01

    Cognitive function at simulated altitude was investigated in a repeated-measures within-subject study of performance by seven volunteers in a hypobaric chamber, in which atmospheric pressure was systematically lowered over a period of 40 d to finally reach a pressure equivalent to 8845 m, the approximate height of Mount Everest. The automated performance test system employed compact computer design; automated test administrations, data storage, and retrieval; psychometric properties of stability and reliability; and factorial richness. Significant impairments of cognitive function were seen for three of the five tests in the battery; on two tests, grammatical reasoning and pattern comparison, every subject showed a substantial decrement.

  17. Uncovering a clinical portrait of sluggish cognitive tempo within an evaluation for attention-deficit/hyperactivity disorder: A case study.

    PubMed

    Becker, Stephen P; Ciesielski, Heather A; Rood, Jennifer E; Froehlich, Tanya E; Garner, Annie A; Tamm, Leanne; Epstein, Jeffery N

    2016-01-01

    Despite the burgeoning scientific literature examining the sluggish cognitive tempo (SCT) construct, very little is known about the clinical presentation of SCT. In clinical cases where SCT is suspected, it is critical to carefully assess not only for attention-deficit/hyperactivity disorder (ADHD) but also for other comorbidities that may account for the SCT-related behaviors, especially internalizing symptoms and sleep problems. The current case study provides a clinical description of SCT in a 7-year-old girl, offering a real-life portrait of SCT while also providing an opportunity to qualitatively differentiate between SCT and ADHD, other psychopathologies (e.g. depression, anxiety), and potentially related domains of functioning (e.g. sleep, executive functioning [EF]). "Jessica" was described by herself, parents, and teacher as being much slower than her peers in completing schoolwork, despite standardized testing showing Jessica to have above average intelligence and academic achievement. Jessica's parents completed rating scales indicating high levels of SCT symptoms and daytime sleepiness, as well as mildly elevated EF deficits. More research is needed to determine how to best conceptualize, assess, and treat SCT, and Jessica's case underscores the importance of further work in this area. PMID:25326531

  18. Uncovering a clinical portrait of sluggish cognitive tempo within an evaluation for attention-deficit/hyperactivity disorder: A case study.

    PubMed

    Becker, Stephen P; Ciesielski, Heather A; Rood, Jennifer E; Froehlich, Tanya E; Garner, Annie A; Tamm, Leanne; Epstein, Jeffery N

    2016-01-01

    Despite the burgeoning scientific literature examining the sluggish cognitive tempo (SCT) construct, very little is known about the clinical presentation of SCT. In clinical cases where SCT is suspected, it is critical to carefully assess not only for attention-deficit/hyperactivity disorder (ADHD) but also for other comorbidities that may account for the SCT-related behaviors, especially internalizing symptoms and sleep problems. The current case study provides a clinical description of SCT in a 7-year-old girl, offering a real-life portrait of SCT while also providing an opportunity to qualitatively differentiate between SCT and ADHD, other psychopathologies (e.g. depression, anxiety), and potentially related domains of functioning (e.g. sleep, executive functioning [EF]). "Jessica" was described by herself, parents, and teacher as being much slower than her peers in completing schoolwork, despite standardized testing showing Jessica to have above average intelligence and academic achievement. Jessica's parents completed rating scales indicating high levels of SCT symptoms and daytime sleepiness, as well as mildly elevated EF deficits. More research is needed to determine how to best conceptualize, assess, and treat SCT, and Jessica's case underscores the importance of further work in this area.

  19. Disrupting the clustering of GABAA receptor α2 subunits in the frontal cortex leads to reduced γ-power and cognitive deficits

    PubMed Central

    Hines, Rochelle M.; Hines, Dustin J.; Houston, Catriona M.; Mukherjee, Jayanta; Haydon, Philip G.; Tretter, Verena; Smart, Trevor G.; Moss, Stephen J.

    2013-01-01

    In schizophrenia, cognitive dysfunction is highly predictive of poor patient outcomes and is not responsive to current medications. Postmortem studies have suggested that cognitive deficits in schizophrenia are correlated with modifications in the number and size of inhibitory synapses. To test if these modifications lead to cognitive deficits, we have created a dominant-negative virus [adeno-associated (AAV)-DN1] that disrupts the clustering of γ-aminobutyric acid type A receptors (GABAARs) at postsynaptic inhibitory specializations. When injected into the frontal cortex of mice, AAV-DN1 impairs GABAAR α2 subunit and GABA transporter 1 (GAT-1) clustering, but increases GABAAR α1 subunit clustering on the perisomatic region, with no influence on axon-initial segment clustering. Mice expressing AAV-DN1 have prepulse inhibition deficits and impairments in working memory. Significantly, these behavioral deficits are paralleled by a reduction in electroencephalography γ-power. Collectively, our study provides functional evidence revealing that GABAergic synapses in the prefrontal cortex directly contribute to cognition and γ-power. PMID:24043839

  20. Cognitive Performance Is Highly Sensitive to Prior Experience in Mice with a Learning and Memory Deficit: Failure Leads to More Failure

    ERIC Educational Resources Information Center

    Hebda-Bauer, Elaine K.; Watson, Stanley J.; Akil, Huda

    2005-01-01

    The impact of a previously successful or unsuccessful experience on the subsequent acquisition of a related task is not well understood. The nature of past experience may have even greater impact in individuals with learning deficits, as their cognitive processes can be easily disrupted. Mice with a targeted disruption of the [alpha] and [delta]…

  1. Randomized Controlled Trial of Osmotic-Release Methylphenidate with Cognitive-Behavioral Therapy in Adolescents with Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders

    ERIC Educational Resources Information Center

    Riggs, Paula D.; Winhusen, Theresa; Davies, Robert D.; Leimberger, Jeffrey D.; Mikulich-Gilbertson, Susan; Klein, Constance; Macdonald, Marilyn; Lohman, Michelle; Bailey, Genie L.; Haynes, Louise; Jaffee, William B.; Haminton, Nancy; Hodgkins, Candace; Whitmore, Elizabeth; Trello-Rishel, Kathlene; Tamm, Leanne; Acosta, Michelle C.; Royer-Malvestuto, Charlotte; Subramaniam, Geetha; Fishman, Marc; Holmes, Beverly W.; Kaye, Mary Elyse; Vargo, Mark A.; Woody, George E.; Nunes, Edward V.; Liu, David

    2011-01-01

    Objective: To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared with placebo for attention-deficit/hyperactivity disorder (ADHD), and the impact on substance treatment outcomes in adolescents concurrently receiving cognitive-behavioral therapy (CBT) for substance use disorders (SUD). Method: This was a…

  2. Learning to Read Against All Odds: Using Precision Reading to Enhance Literacy in Students with Cognitive Impairments, Extreme Academic Deficits, and Severe Social, Emotional, and Psychiatric Problems

    ERIC Educational Resources Information Center

    Freeze, Rick; Cook, Paula

    2005-01-01

    The purpose of this study was to assess the efficacy and practicality of precision reading, a constructive reading intervention, with students with cognitive impairments, extreme academic deficits in reading, and severe social, emotional, and psychiatric problems. As precision reading had shown promise with students with low achievement, learning…

  3. Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation

    PubMed Central

    Murray, Donna E; Durazzo, Timothy C; Schmidt, Thomas P; Abé, Christoph; Guydish, Joseph; Meyerhoff, Dieter J

    2016-01-01

    Objective Proton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence. Methods Single-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions. Results Compared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits. Conclusion The anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment. PMID:27695638

  4. Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation

    PubMed Central

    Murray, Donna E; Durazzo, Timothy C; Schmidt, Thomas P; Abé, Christoph; Guydish, Joseph; Meyerhoff, Dieter J

    2016-01-01

    Objective Proton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence. Methods Single-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions. Results Compared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits. Conclusion The anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment.

  5. Beyond Stimulus Deprivation: Iron Deficiency and Cognitive Deficits in Postinstitutionalized Children

    ERIC Educational Resources Information Center

    Doom, Jenalee R.; Gunnar, Megan R.; Georgieff, Michael K.; Kroupina, Maria G.; Frenn, Kristin; Fuglestad, Anita J.; Carlson, Stephanie M.

    2014-01-01

    Children adopted from institutions have been studied as models of the impact of stimulus deprivation on cognitive development (Nelson, Bos, Gunnar, & Sonuga-Barke, 2011), but these children may also suffer from micronutrient deficiencies (Fuglestad et al., 2008). The contributions of iron deficiency (ID) and duration of deprivation on…

  6. Cognitive Deficits Associated with Acquired Amusia after Stroke: A Neuropsychological Follow-Up Study

    ERIC Educational Resources Information Center

    Sarkamo, Teppo; Tervaniemi, Mari; Soinila, Seppo; Autti, Taina; Silvennoinen, Heli M.; Laine, Matti; Hietanen, Marja

    2009-01-01

    Recent evidence on amusia suggests that our ability to perceive music might be based on the same neural resources that underlie other higher cognitive functions, such as speech perception and spatial processing. We studied the neural correlates of acquired amusia by performing extensive neuropsychological assessments on 53 stroke patients with a…

  7. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    EPA Science Inventory

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  8. Investigating Metacognition, Cognition, and Behavioral Deficits of College Students with Acute Traumatic Brain Injuries

    ERIC Educational Resources Information Center

    Martinez, Sarah; Davalos, Deana

    2016-01-01

    Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…

  9. Cognitive Set Shifting Deficits and Their Relationship to Repetitive Behaviors in Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Miller, Haylie L.; Ragozzino, Michael E.; Cook, Edwin H.; Sweeney, John A.; Mosconi, Matthew W.

    2015-01-01

    The neurocognitive impairments associated with restricted and repetitive behaviors (RRBs) in autism spectrum disorder (ASD) are not yet clear. Prior studies indicate that individuals with ASD show reduced cognitive flexibility, which could reflect difficulty shifting from a previously learned response pattern or a failure to maintain a new…

  10. Prefrontal Cortex Cognitive Deficits in Children Treated Early and Continuously for PKU.

    ERIC Educational Resources Information Center

    Diamond, Adele; Prevor, Meredith B.; Druin, Donald P.; Callender, Glenda

    1997-01-01

    Hypothesized that elevated ratio of phenylalanine to tyrosine in blood of children with phenylketonuria uniquely affects cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in tyrosine. Found that children whose phenylalanine levels were three to five…

  11. Cognitive mediational deficits and the role of coping styles in pedophile and ephebophile Roman Catholic clergy.

    PubMed

    Ryan, Gregory P; Baerwald, Jeffrey P; McGlone, Gerard

    2008-01-01

    This study was designed to examine hypothesized differences between sex offending and nonoffending Roman Catholic clergy on cognitive mediation abilities as measured by the Rorschach Inkblot Test (H. Rorschach, 1921/1942). This study compared 78 priest pedophiles and 77 priest ephebophiles with 80 nonoffending priest controls on the Inkblot test using J. E. Exner's (2003) Comprehensive System. The three groups were compared on seven variables that constitute Exner's Cognitive Mediation cluster. Additionally, the groups' coping styles were compared to examine the interaction of coping style and cognitive mediational abilities. We found interactions between coping style and offending status across most of the cognitive variables indicating impairment in the mild to pathological ranges. Moreover, significantly higher unusual thinking styles (Xu%) and significantly lower conventional thinking styles (X+%) in offenders compared to nonoffenders. Those with an Extratensive style (n=31) showed significantly higher distorted thinking when compared to the Introversive (n=81), Ambitent (n=73), and Avoidant (n=50) coping styles. This study suggests that offenders display significantly higher distorted thinking styles than do nonoffenders. Possible reasons for these discrepancies and the role of coping styles in abusive behaviors were discussed.

  12. Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer’s Disease-Like Models

    PubMed Central

    Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

    2014-01-01

    Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer’s disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD. PMID:25009697

  13. Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer's Disease-Like Models.

    PubMed

    Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

    2014-05-01

    Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD. PMID:25009697

  14. Dimensions and Correlates of Attention Deficit/Hyperactivity Disorder and Sluggish Cognitive Tempo

    ERIC Educational Resources Information Center

    Garner, Annie A.; Marceaux, Janice; Mrug, Sylvie; Patterson, Cryshelle; Hodgens, Bart

    2010-01-01

    The present study examined Sluggish Cognitive Tempo (SCT) in relation to ADHD symptoms, clinical diagnosis, and multiple aspects of adjustment in a clinical sample. Parent and teacher reports were gathered for 322 children and adolescents evaluated for behavioral, emotional, and/or learning problems at a university clinic. Confirmatory factor…

  15. Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer's disease.

    PubMed

    Chonpathompikunlert, Pennapa; Wattanathorn, Jintanaporn; Muchimapura, Supaporn

    2010-03-01

    Recently, numerous medicinal plants possessing profound central nervous system effects and antioxidant activity have received much attention as food supplement to improve cognitive function against cognitive deficit condition including in Alzheimer's disease condition. Based on this information, the effect of piperine, a main active alkaloid in fruit of Piper nigrum, on memory performance and neurodegeneration in animal model of Alzheimer's disease have been investigated. Adult male Wistar rats (180-220 g) were orally given piperine at various doses ranging from 5, 10 and 20mg/kg BW at a period of 2 weeks before and 1 week after the intracerebroventricular administration of ethylcholine aziridinium ion (AF64A) bilaterally. The results showed that piperine at all dosage range used in this study significantly improved memory impairment and neurodegeneration in hippocampus. The possible underlying mechanisms might be partly associated with the decrease lipid peroxidation and acetylcholinesterase enzyme. Moreover, piperine also demonstrated the neurotrophic effect in hippocampus. However, further researches about the precise underlying mechanism are still required.

  16. Safflower yellow ameliorates cognition deficits and reduces tau phosphorylation in APP/PS1 transgenic mice.

    PubMed

    Ruan, Ying-Ying; Zhai, Wei; Shi, Xiao-Meng; Zhang, Lu; Hu, Yan-Li

    2016-10-01

    Alzheimer's disease (AD), the most common cause of dementia worldwide, is mainly characterized by the aggregated β-amyloid (Aβ) and hyperphosphorylated tau. Safflower yellow (SY) is a novel water extract of natural safflower and has been suggested to ameliorate memory deficits in several animal models of dementia. In this study, we aimed to investigate the effect and mechanism of SY on deficits of learning and memory and hyperphosphorylation of tau in APP/PS1 double transgenic mice. APP/PS1 mice were administered with SY (10, 30, 100 mg/kg) by oral gavage for three months at the age of six months. The ability of learning and memory was investigated using the step-down test and Morris water maze test, and protein level in the brain was evaluated using western blot. Here, we found that SY treatment can improve spatial learning and memory ability, and reduce tau hyperphosphorylation at Ser199, Thr205, Ser396, Ser404 sites in APP/PS1 mice. In addition, the activity the of cyclin-dependent kinase 5 (CDK-5) and glycogen synthase kinase 3β (GSK-3β), major kinases involved in tau phosphorylation, was siginificantly decreased in APP/PS1 mice by SY treatment. These results support SY can serve as a promising multitarget neuronal therapeutic agent for the treatment of AD.

  17. Safflower yellow ameliorates cognition deficits and reduces tau phosphorylation in APP/PS1 transgenic mice.

    PubMed

    Ruan, Ying-Ying; Zhai, Wei; Shi, Xiao-Meng; Zhang, Lu; Hu, Yan-Li

    2016-10-01

    Alzheimer's disease (AD), the most common cause of dementia worldwide, is mainly characterized by the aggregated β-amyloid (Aβ) and hyperphosphorylated tau. Safflower yellow (SY) is a novel water extract of natural safflower and has been suggested to ameliorate memory deficits in several animal models of dementia. In this study, we aimed to investigate the effect and mechanism of SY on deficits of learning and memory and hyperphosphorylation of tau in APP/PS1 double transgenic mice. APP/PS1 mice were administered with SY (10, 30, 100 mg/kg) by oral gavage for three months at the age of six months. The ability of learning and memory was investigated using the step-down test and Morris water maze test, and protein level in the brain was evaluated using western blot. Here, we found that SY treatment can improve spatial learning and memory ability, and reduce tau hyperphosphorylation at Ser199, Thr205, Ser396, Ser404 sites in APP/PS1 mice. In addition, the activity the of cyclin-dependent kinase 5 (CDK-5) and glycogen synthase kinase 3β (GSK-3β), major kinases involved in tau phosphorylation, was siginificantly decreased in APP/PS1 mice by SY treatment. These results support SY can serve as a promising multitarget neuronal therapeutic agent for the treatment of AD. PMID:27311611

  18. Cognitive deficits and brain myo-Inositol are early biomarkers of epileptogenesis in a rat model of epilepsy.

    PubMed

    Pascente, Rosaria; Frigerio, Federica; Rizzi, Massimo; Porcu, Luca; Boido, Marina; Davids, Joe; Zaben, Malik; Tolomeo, Daniele; Filibian, Marta; Gray, William P; Vezzani, Annamaria; Ravizza, Teresa

    2016-09-01

    One major unmet clinical need in epilepsy is the identification of therapies to prevent or arrest epilepsy development in patients exposed to a potential epileptogenic insult. The development of such treatments has been hampered by the lack of non-invasive biomarkers that could be used to identify the patients at-risk, thereby allowing to design affordable clinical studies. Our goal was to test the predictive value of cognitive deficits and brain astrocyte activation for the development of epilepsy following a potential epileptogenic injury. We used a model of epilepsy induced by pilocarpine-evoked status epilepticus (SE) in 21-day old rats where 60-70% of animals develop spontaneous seizures after around 70days, although SE is similar in all rats. Learning was evaluated in the Morris water-maze at days 15 and 65 post-SE, each time followed by proton magnetic resonance spectroscopy for measuring hippocampal myo-Inositol levels, a marker of astrocyte activation. Rats were video-EEG monitored for two weeks at seven months post-SE to detect spontaneous seizures, then brain histology was done. Behavioral and imaging data were retrospectively analysed in epileptic rats and compared with non-epileptic and control animals. Rats displayed spatial learning deficits within three weeks from SE. However, only epilepsy-prone rats showed accelerated forgetting and reduced learning rate compared to both rats not developing epilepsy and controls. These deficits were associated with reduced hippocampal neurogenesis. myo-Inositol levels increased transiently in the hippocampus of SE-rats not developing epilepsy while this increase persisted until spontaneous seizures onset in epilepsy-prone rats, being associated with a local increase in S100β-positive astrocytes. Neuronal cell loss was similar in all SE-rats. Our data show that behavioral deficits, together with a non-invasive marker of astrocyte activation, predict which rats develop epilepsy after an acute injury. These measures

  19. Cognitive deficits and brain myo-Inositol are early biomarkers of epileptogenesis in a rat model of epilepsy.

    PubMed

    Pascente, Rosaria; Frigerio, Federica; Rizzi, Massimo; Porcu, Luca; Boido, Marina; Davids, Joe; Zaben, Malik; Tolomeo, Daniele; Filibian, Marta; Gray, William P; Vezzani, Annamaria; Ravizza, Teresa

    2016-09-01

    One major unmet clinical need in epilepsy is the identification of therapies to prevent or arrest epilepsy development in patients exposed to a potential epileptogenic insult. The development of such treatments has been hampered by the lack of non-invasive biomarkers that could be used to identify the patients at-risk, thereby allowing to design affordable clinical studies. Our goal was to test the predictive value of cognitive deficits and brain astrocyte activation for the development of epilepsy following a potential epileptogenic injury. We used a model of epilepsy induced by pilocarpine-evoked status epilepticus (SE) in 21-day old rats where 60-70% of animals develop spontaneous seizures after around 70days, although SE is similar in all rats. Learning was evaluated in the Morris water-maze at days 15 and 65 post-SE, each time followed by proton magnetic resonance spectroscopy for measuring hippocampal myo-Inositol levels, a marker of astrocyte activation. Rats were video-EEG monitored for two weeks at seven months post-SE to detect spontaneous seizures, then brain histology was done. Behavioral and imaging data were retrospectively analysed in epileptic rats and compared with non-epileptic and control animals. Rats displayed spatial learning deficits within three weeks from SE. However, only epilepsy-prone rats showed accelerated forgetting and reduced learning rate compared to both rats not developing epilepsy and controls. These deficits were associated with reduced hippocampal neurogenesis. myo-Inositol levels increased transiently in the hippocampus of SE-rats not developing epilepsy while this increase persisted until spontaneous seizures onset in epilepsy-prone rats, being associated with a local increase in S100β-positive astrocytes. Neuronal cell loss was similar in all SE-rats. Our data show that behavioral deficits, together with a non-invasive marker of astrocyte activation, predict which rats develop epilepsy after an acute injury. These measures

  20. The study of social cognition with neuroimaging methods as a means to explore future directions of deficit evaluation in schizophrenia?

    PubMed

    Brunet-Gouet, Eric; Achim, Amélie M; Vistoli, Damien; Passerieux, Christine; Hardy-Baylé, Marie-Christine; Jackson, Philip L

    2011-11-30

    This article discusses the important advances in a recent field of science dealing with the brain processes implicated in understanding social situations and interacting with others. Many behavioral studies on schizophrenia have shown the impairment of these processes and their preferential relation with disorganization and negative syndromes. Brain imaging is a powerful method to identify brain systems participating in these processes in healthy subjects and will be used increasingly to study mental disorders such as schizophrenia. A few preliminary studies have opened this field of research and allowed for the drawing of some limited conclusions. We emphasize the importance of developing an integrated neurocognitive framework to account for the multifaceted nature of social cognition deficits in schizophrenia. Inspired by contemporary models of empathy and social cognition that identify different components such as shared representation, mentalizing, self/other distinction, we show how schizophrenia affects these components at the behavioral and functional levels. We also outline the interest of this model to understand putative abnormalities of contextual integration within the area of mentalization. Finally, we discuss how specialized measures of brain functions during the performance of these precisely defined mental processes might be used as outcome predictors. PMID:21185085

  1. Lignans from Schisandra chinensis ameliorate cognition deficits and attenuate brain oxidative damage induced by D-galactose in rats.

    PubMed

    Yan, Tingxu; Shang, Lei; Wang, Mengshi; Zhang, Chenning; Zhao, Xu; Bi, Kaishun; Jia, Ying

    2016-06-01

    The aim of this study was to explore the neuroprotective effects of active compounds from Schisandra chinensis (Trucz.) Baill. (Magnoliaceae) against the D-galactose (D-gal)-induced neurotoxicity in rat. The Wistar rats were subcutaneously injected with D-gal (150 mg/(kg day)) for six weeks and orally administered with water extract or 95 % ethanol extract (partitioned with petroleum ether (PE), chloroform (CF), ethyl acetate (EA) and n-Butanol (NB), respectively) of the fruits of Schisandra chinensis simultaneously. The alteration of cognitive functions was assessed by using Morris water maze and Step-down type passive avoidance test. The results demonstrated that PE fraction was the most effective fraction to ameliorate cognitive deficits. Further biochemical examination indicated that PE could attenuate the activities decreasing of superoxide dismutase (SOD), catalase (CAT), the total antioxidant (T-AOC) induced by D-gal, and maintain the normal levels of glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) in the serum, prefrontal cortex, striatum and hippocampus of the brain of related rat, selectively. Meanwhile, the compounds of PE fraction were also identified as mainly lignans, thus, these results suggest that lignans from the PE fraction of Schisandra chinensis represented a potential source of medicine for the treatment of the aging-associated neurodegenerative diseases.

  2. Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats

    PubMed Central

    Arteaga, Olatz; Revuelta, Miren; Urigüen, Leyre; Álvarez, Antonia; Montalvo, Haizea; Hilario, Enrique

    2015-01-01

    Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia. PMID:26544861

  3. Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats.

    PubMed

    Arteaga, Olatz; Revuelta, Miren; Urigüen, Leyre; Álvarez, Antonia; Montalvo, Haizea; Hilario, Enrique

    2015-01-01

    Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.

  4. A novel technique for the quantitative assessment of apraxic deficits: application to individuals with mild cognitive impairment.

    PubMed

    Crutch, Sebastian J; Rossor, Martin N; Warrington, Elizabeth K

    2007-09-01

    The purpose of this study was to apply two novel quantitative assessments of apraxia to issues surrounding the cognitive profile of individuals with mild cognitive impairment (MCI) who are at increased risk of Alzheimer's disease (AD). In particular, it was wished to determine whether such quantitative assessment techniques can detect minor degrees of impairment at a stage in the putative disease process before apraxia has become clinically obvious. A total of 23 individuals with MCI and 75 healthy controls were assessed on two 3-item sequential movement tasks involving either meaningful or meaningless actions. A traditional rating scale assessment of gesture-to-command was also administered. MCI patients took significantly longer than control subjects to complete the sequential movement tasks despite unimpaired performance on the traditional gesture production tasks. Furthermore, retrospective analyses revealed that, at the group level, only MCI patients who subsequently proceeded to a clinical diagnosis of AD were significantly slower than controls at the initial assessment. These findings provide the first evidence that the neuropsychological deficits associated with MCI may extend to the domain of praxic functions. Consequently, this work contributes to the growing literature questioning the clinical usefulness of the concept of MCI and the appropriateness of current diagnostic criteria for distinguishing this condition from mild AD.

  5. Lignans from Schisandra chinensis ameliorate cognition deficits and attenuate brain oxidative damage induced by D-galactose in rats.

    PubMed

    Yan, Tingxu; Shang, Lei; Wang, Mengshi; Zhang, Chenning; Zhao, Xu; Bi, Kaishun; Jia, Ying

    2016-06-01

    The aim of this study was to explore the neuroprotective effects of active compounds from Schisandra chinensis (Trucz.) Baill. (Magnoliaceae) against the D-galactose (D-gal)-induced neurotoxicity in rat. The Wistar rats were subcutaneously injected with D-gal (150 mg/(kg day)) for six weeks and orally administered with water extract or 95 % ethanol extract (partitioned with petroleum ether (PE), chloroform (CF), ethyl acetate (EA) and n-Butanol (NB), respectively) of the fruits of Schisandra chinensis simultaneously. The alteration of cognitive functions was assessed by using Morris water maze and Step-down type passive avoidance test. The results demonstrated that PE fraction was the most effective fraction to ameliorate cognitive deficits. Further biochemical examination indicated that PE could attenuate the activities decreasing of superoxide dismutase (SOD), catalase (CAT), the total antioxidant (T-AOC) induced by D-gal, and maintain the normal levels of glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) in the serum, prefrontal cortex, striatum and hippocampus of the brain of related rat, selectively. Meanwhile, the compounds of PE fraction were also identified as mainly lignans, thus, these results suggest that lignans from the PE fraction of Schisandra chinensis represented a potential source of medicine for the treatment of the aging-associated neurodegenerative diseases. PMID:26847610

  6. Assessing windows of susceptibility to lead-induced cognitive deficits in Mexican children

    PubMed Central

    Braun, Joe M.; Hoffman, Elaine; Schwartz, Joel; Sanchez, Brisa; Schnaas, Lourdes; Mercado-Garcia, Adriana; Solano-Gonzalez, Maritsa; Bellinger, David C.; Lanphear, Bruce P.; Hu, Howard; Tellez-Rojo, Martha M.; Wright, Robert O.; Hernandez-Avila, Mauricio

    2013-01-01

    Background The identification of susceptible periods to Pb-induced decrements in childhood cognitive abilities remains elusive. Objective To draw inferences about windows of susceptibility using the pattern of associations between serial childhood blood lead (BPb) concentrations and children’s cognitive abilities at 4 years of age among 1035 mother–child pairs enrolled in 4 prospective birth cohorts from Mexico City. Methods Multiple longitudinally collected BPb measurements were obtained from children (1, 2, 3, and 4 years) between 1994 and 2007. Child cognitive abilities were assessed at 4 years using the general cognitive index (GCI) of the McCarthy Scales of Children’s Abilities. We used multivariable linear regression to estimate the change in cognitive abilities at 4 years of age with a 10 μg/dL increase in childhood BPb concentrations adjusting for maternal IQ, education, marital status, child sex, breastfeeding duration, and cohort. Results In separate models for each BPb measurement, 2 year BPb concentrations were most strongly associated with reduced GCI scores at 4 years after adjusting for confounders (β: −3.8; 95% confidence interval CI: −6.3, −1.4). Mutual adjustment for other BPb concentrations in a single model resulted in larger, but less precise estimate between 2 year BPb concentrations and GCI scores at 4 years of age (β: −7.1; 95% CI: −12, −2.0). The association between 2 year BPb and GCI was not heterogeneous (p = 0.89), but some BPb and GCI associations varied in magnitude and direction across the cohorts. Additional adjustment for child hemoglobin, birth weight, gestational age, gestational BPb concentrations, or test examiner did not change the pattern of associations. Conclusions Higher BPb concentrations at 2 years of age were most predictive of decreased cognitive abilities among these Mexico City children; however, the observed pattern may be due to exposure, outcome, or cohort related factors. These results may

  7. Cognitive and behavioural deficits associated with the orbitomedial prefrontal cortex in amyotrophic lateral sclerosis.

    PubMed

    Meier, Sandra L; Charleston, Alison J; Tippett, Lynette J

    2010-11-01

    Amyotrophic lateral sclerosis, a progressive disease affecting motor neurons, may variably affect cognition and behaviour. We tested the hypothesis that functions associated with orbitomedial prefrontal cortex are affected by evaluating the behavioural and cognitive performance of 18 participants with amyotrophic lateral sclerosis without dementia and 18 healthy, matched controls. We measured Theory of Mind (Faux Pas Task), emotional prosody recognition (Aprosodia Battery), reversal of behaviour in response to changes in reward (Probabilistic Reversal Learning Task), decision making without risk (Holiday Apartment Task) and aberrant behaviour (Neuropsychiatric Inventory). We also assessed dorsolateral prefrontal function, using verbal and written fluency and planning (One-touch Stockings of Cambridge), to determine whether impairments in tasks sensitive to these two prefrontal regions co-occur. The patient group was significantly impaired at identifying social faux pas, recognizing emotions and decision-making, indicating mild, but consistent impairment on most measures sensitive to orbitomedial prefrontal cortex. Significant levels of aberrant behaviour were present in 50% of patients. Patients were also impaired on verbal fluency and planning. Individual subject analyses involved computing classical dissociations between tasks sensitive to different prefrontal regions. These revealed heterogeneous patterns of impaired and spared cognitive abilities: 33% of participants had classical dissociations involving orbitomedial prefrontal tasks, 17% had classical dissociations involving dorsolateral prefrontal tasks, 22% had classical dissociations between tasks of both regions, and 28% had no classical dissociations. These data indicate subtle changes in behaviour, emotional processing, decision-making and altered social awareness, associated with orbitomedial prefrontal cortex, may be present in a significant proportion of individuals with amyotrophic lateral sclerosis

  8. Striatal Activity is Associated with Deficits of Cognitive Control and Aberrant Salience for Patients with Schizophrenia

    PubMed Central

    Ceaser, Alan E.; Barch, Deanna M.

    2016-01-01

    A recent meta-analysis has shown that a large dopamine abnormality exists in the striatum when comparing patients with schizophrenia and controls, and this abnormality is thought to contribute to aberrant salience assignment (or a misattribution of relevance to irrelevant stimuli). This abnormality may also disrupt striatal contributions to cognitive control processing. We examined the relationship between striatal involvement in cognition and aberrant salience symptoms using a task of cognitive control that involves updating, interference control, and simple maintenance. The current study included a sample of 22 patients with schizophrenia and 20 healthy controls and used a slow event-related fMRI design. We predicted that (1) aberrant salience symptoms would be greater for patient's, (2) patients would demonstrate increased errors during interference control trials, given that patients may be inappropriately assigning salience to distracters, and (3) striatal activity during those errors would be correlated with aberrant salience symptoms. We found a trend toward a significant difference between patients and controls on aberrant salience symptoms, and a significant difference between groups on select task conditions. During interference control trials, patients were more likely to inappropriately encode distracters. For patients, both prefrontal and striatal activity was significantly greater when patients inappropriately identified the distracter as correct compared to activity during distracter rejection. During updating, patient prefrontal and striatal activity was significantly lower for incorrect than correct updating trials. Finally, as predicted, for patients the increase of activity during incorrect distracter trials was positively correlated with aberrant salience symptoms, but only for the striatal region. These relationships may have implications for treatments that improve cognitive function and reduce symptom expression. PMID:26869912

  9. A link between vascular damage and cognitive deficits after whole-brain radiation therapy for cancer: A clue to other types of dementia?

    PubMed

    Yamada, Maki K

    2016-01-01

    Whole brain radiation therapy for the treatment of tumors can sometimes cause cognitive impairment. Memory deficits were noted in up to 50% of treated patients over a short period of several months. In addition, an increased rate of dementia in young patients has been noted over the longer term, i.e. years. A deficit in neurogenesis after irradiation has been postulated to be the main cause of cognitive decline in patients, but recent data on irradiation therapy for limited parts of the brain appear to indicate other possibilities. Irradiation can directly damage various types of cells other than neuronal stem cells. However, this paper will focus on injury to brain vasculature leading to cognitive decline since vessels represent a better therapeutic target for drug development than other cells in the brain because of the blood-brain barrier. PMID:27087553

  10. Dysregulated peripheral endocannabinoid system signaling is associated with cognitive deficits in first-episode psychosis.

    PubMed

    Bioque, Miquel; Cabrera, Bibiana; García-Bueno, Borja; Mac-Dowell, Karina S; Torrent, Carla; Saiz, Pilar A; Parellada, Mara; González-Pinto, Ana; Lobo, Antonio; Leza, Juan C; Bernardo, Miguel

    2016-04-01

    Among etiological explanations for psychosis, several hypotheses involving alterations on the immune/inflammatory system have been proposed. The endocannabinoid system (ECS) is an endogenous neuroprotective, anti-inflammatory system that modulates cognitive processes. Its altered expression has been associated with psychotic disorders. 73 patients with a first episode of psychoses (FEP) and 67 healthy controls were recruited in 5 university centers in Spain. The protein expression of the main peripheral ECS components was determined in peripheral blood mononuclear cells. The cognition function was assessed following the MATRICS consensus. After controlling for potential confounding factors, working memory statistically correlated to the peripheral N-acyl phosphatidylethanolamine phospholipase expression (p = 0.039). The short-term verbal memory correlated to the Diacylglycerol lipase (p = 0.043) and the fatty acid amide hydrolase (p = 0.026) expression. Finally, attention measures correlated to the Monoacylglycerol lipase expression, by means of the CPT-II commissions (p = 0.036) and detectability (p = 0.026) scores. The ECS may regulate the activation of key mediators in immune and inflammatory responses that may be involved in the primary neuronal stress phenomenon that occurs from the onset of psychotic illness. This study points a relationship between the ECS and the cognitive function in early psychosis and suggests the use of some of the ECS elements as biomarkers and/or pharmacological targets for FEP. PMID:26783729

  11. Ondansetron and arecoline prevent scopolamine-induced cognitive deficits in the marmoset.

    PubMed

    Carey, G J; Costall, B; Domeney, A M; Gerrard, P A; Jones, D N; Naylor, R J; Tyers, M B

    1992-05-01

    The cognitive-enhancing potential of the 5-hydroxytryptamine (5-HT) selective 5-HT3 receptor antagonist, ondansetron, was investigated in a model of cognitive impairment induced by the muscarinic receptor antagonist, scopolamine. For this purpose, marmosets were trained in an object discrimination task utilizing the Wisconsin General Test Apparatus. Administration of scopolamine (0.01-0.04 mg/kg, SC) caused a dose-dependent impairment in the acquisition of the object discrimination task in that marmosets required more trials to reach criterion, made more errors, and took longer to choose the objects. Administration of arecoline (0.06-0.1 mg/kg, SC) or 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol- 1-yl)methyl]-4H-carbazol-4-one,HCl.2H2O (ondansetron) (0.1-1 micrograms/kg, SC) prevented the scopolamine-induced impairment in task acquisition in that the performance of marmosets was indistinguishable from that of saline-treated animals and was significantly better than that following scopolamine/saline. From these studies, we conclude that ondansetron prevents impairment in the cognitive performance of marmosets induced by administration of scopolamine.

  12. Dysregulated peripheral endocannabinoid system signaling is associated with cognitive deficits in first-episode psychosis.

    PubMed

    Bioque, Miquel; Cabrera, Bibiana; García-Bueno, Borja; Mac-Dowell, Karina S; Torrent, Carla; Saiz, Pilar A; Parellada, Mara; González-Pinto, Ana; Lobo, Antonio; Leza, Juan C; Bernardo, Miguel

    2016-04-01

    Among etiological explanations for psychosis, several hypotheses involving alterations on the immune/inflammatory system have been proposed. The endocannabinoid system (ECS) is an endogenous neuroprotective, anti-inflammatory system that modulates cognitive processes. Its altered expression has been associated with psychotic disorders. 73 patients with a first episode of psychoses (FEP) and 67 healthy controls were recruited in 5 university centers in Spain. The protein expression of the main peripheral ECS components was determined in peripheral blood mononuclear cells. The cognition function was assessed following the MATRICS consensus. After controlling for potential confounding factors, working memory statistically correlated to the peripheral N-acyl phosphatidylethanolamine phospholipase expression (p = 0.039). The short-term verbal memory correlated to the Diacylglycerol lipase (p = 0.043) and the fatty acid amide hydrolase (p = 0.026) expression. Finally, attention measures correlated to the Monoacylglycerol lipase expression, by means of the CPT-II commissions (p = 0.036) and detectability (p = 0.026) scores. The ECS may regulate the activation of key mediators in immune and inflammatory responses that may be involved in the primary neuronal stress phenomenon that occurs from the onset of psychotic illness. This study points a relationship between the ECS and the cognitive function in early psychosis and suggests the use of some of the ECS elements as biomarkers and/or pharmacological targets for FEP.

  13. A Selective Dopamine Reuptake Inhibitor Improves Prefrontal Cortex-Dependent Cognitive Function: Potential Relevance to Attention Deficit Hyperactivity Disorder

    PubMed Central

    Schmeichel, Brooke E.; Zemlan, Frank P.; Berridge, Craig W.

    2012-01-01

    Drugs used to treat attention deficit hyperactivity disorder (ADHD) improve prefrontal cortex (PFC)-dependent cognitive function. The majority of ADHD-related treatments act either as dual norepinephrine (NE) and dopamine (DA) reuptake inhibitors (psychostimulants) or selective NE reuptake inhibitors (SNRIs). Certain benztropine analogs act as highly selective DA reuptake inhibitors while lacking the reinforcing actions, and thus abuse potential, of psychostimulants. To assess the potential use of these compounds in the treatment of ADHD, we examined the effects of a well-characterized benztropine analog, AHN 2-005, on performance of rats in a PFC-dependent delayed-alternation task of spatial working memory. Similar to that seen with all drugs currently approved for ADHD, AHN 2-005 dose-dependently improved performance in this task. Clinically-relevant doses of psychostimulants and SNRIs elevate NE and DA preferentially in the PFC. Despite the selectivity of this compound for the DA transporter, additional microdialysis studies demonstrated that a cognition-enhancing dose of AHN 2-005 that lacked locomotor activating effects increased extracellular levels of both DA and NE in the PFC. AHN 2-005 produced a larger increase in extracellular DA in the nucleus accumbens, although the magnitude of this was well below that seen with motor activating doses of psychostimulants. Collectively, these observations suggest that benztropine analogs may be efficacious in the treatment of ADHD or other disorders associated with PFC dysfunction. These studies provide a strong rationale for future research focused on the neural mechanisms contributing to the cognition-enhancing actions and the potential clinical utility of AHN 2-005 and related compounds. PMID:22796428

  14. Measuring Specific, Rather than Generalized, Cognitive Deficits and Maximizing Between-Group Effect Size in Studies of Cognition and Cognitive Change

    PubMed Central

    Silverstein, Steven M.

    2008-01-01

    While cognitive impairment in schizophrenia is easy to demonstrate, it has been much more difficult to measure a specific cognitive process unconfounded by the influence of other cognitive processes and noncognitive factors (eg, sedation, low motivation) that affect test scores. With the recent interest in the identification of neurophysiology-linked cognitive probes for clinical trials, the issue of isolating specific cognitive processes has taken on increased importance. Recent advances in research design and psychometric theory regarding cognition research in schizophrenia demonstrate the importance of (1) maximizing between-group differences via reduction of measurement error during both test development and subsequent research and (2) the development and use of process-specific tasks in which theory-driven performance indices are derived across multiple conditions. Use of these 2 strategies can significantly advance both our understanding of schizophrenia and measurement sensitivity for clinical trials. Novel data-analytic strategies for analyzing change across multiple conditions and/or multiple time points also allow for increased reliability and greater measurement sensitivity than traditional strategies. Following discussion of these issues, trade-offs inherent to attempts to address psychometric issues in schizophrenia research are reviewed. Finally, additional considerations for maximizing sensitivity and real-world significance in clinical trials are discussed. PMID:18468987

  15. Regional cerebral blood flow and cognitive deficits in chronic lyme disease.

    PubMed

    Fallon, Brian A; Keilp, John; Prohovnik, Isak; Heertum, Ronald Van; Mann, J John

    2003-01-01

    This study examined brain functioning in patients with Lyme encephalopathy. Eleven patients underwent neuropsychological tests and Xenon(133)-regional cerebral blood flow (rCBF) studies, using an external detector system. Each rCBF scan was age- and sex-matched to two archival, normal controls. While few differences were noted on gray-matter flow indices (ISI, fg), Lyme patients demonstrated significant flow reductions in white matter index (k(2)) (p=.004), particularly in the posterior temporal and parietal lobes bilaterally (p=.003). Flow reductions in white matter areas were significantly associated with deficits in memory (r=.66, p=.027) and visuospatial organization (r=.62, p=.041). Results suggest that Lyme encephalopathy may be a disease primarily affecting the cerebral white matter.

  16. Cognitive deficits and posttraumatic stress disorder in children: A diagnostic dilemma illustrated through a case study.

    PubMed

    Malarbi, Stephanie; Muscara, Frank; Stargatt, Robyn

    2016-01-01

    Studies investigating the neuropsychological functioning of children who experience trauma have predominantly focused on maltreated populations. This article presents a case study that details the longitudinal outcome of a girl who experienced a motor vehicle accident at 5 years of age. It highlights the clinical relevance of research investigating the neuropsychological impact of single-incident trauma on children. It illustrates difficulties clinicians face in discriminating between the effects of developmental delay, traumatic brain injury, attention-deficit/hyperactivity disorder, trauma, and posttraumatic stress symptoms or posttraumatic stress disorder, especially in children with compensable injuries. The state of the current literature is discussed, and directions for future research are provided. PMID:26418173

  17. Treadmill exercise slows cognitive deficits in aging rats by antioxidation and inhibition of amyloid production.

    PubMed

    Yu, Feng; Xu, Bo; Song, Chenghui; Ji, Liu; Zhang, Xianliang

    2013-04-17

    Chronic administration of D-galactose simulates the changes in natural senescence and accelerates aging in animal models and has been used in aging research. The present study was undertaken to investigate the molecular mechanisms underlying the effects of exercise on learning and memory in rats with D-galactose-induced aging. The learning and memory performance in aging rats, either after exercise or without exercise, was assessed with the Morris water maze test. The effect of treadmill exercise on the expression of amyloid-β 42 and two key enzymes involved in processing of the β-amyloid precursor protein, a disintegrase and metalloprotease domain 17 and β-site amyloid precursor protein-cleaving enzyme 1, in the hippocampi of rats were monitored using real-time quantitative PCR. Moreover, oxidative stress-associated changes, including changes in superoxide dismutase activity and malondialdehyde content, in the hippocampi were assessed after exercise. Our results showed that treadmill exercise significantly improved learning and memory performance in aging rats. The behavioral changes were likely induced by repression of amyloid-β 42 protein levels, through the upregulation of a disintegrase and metalloprotease domain 17 mRNA and downregulation of β-site amyloid precursor protein-cleaving enzyme 1 mRNA, and a concomitant increase in superoxide dismutase activity and decrease in malondialdehyde content, in rat hippocampi. Our data suggest that exercise may be an effective therapy for alleviating learning and memory decline due to aging or the onset of neurodegenerative diseases.

  18. Transgenerational effects of adolescent nicotine exposure in rats: Evidence for cognitive deficits in adult female offspring.

    PubMed

    Renaud, Samantha M; Fountain, Stephen B

    2016-01-01

    This study investigated whether adolescent nicotine exposure in one generation of rats would impair the cognitive capacity of a subsequent generation. Male and female rats in the parental F0 generation were given twice-daily i.p. injections of either 1.0mg/kg nicotine or an equivalent volume of saline for 35days during adolescence on postnatal days 25-59 (P25-59). After reaching adulthood, male and female nicotine-exposed rats were paired for breeding as were male and female saline control rats. Only female offspring were used in this experiment. Half of the offspring of F0 nicotine-exposed breeders and half of the offspring of F0 saline control rats received twice-daily i.p. injections of 1.0mg/kg nicotine during adolescence on P25-59. The remainder of the rats received twice-daily saline injections for the same period. To evaluate transgenerational effects of nicotine exposure on complex cognitive learning abilities, F1 generation rats were trained to perform a highly structured serial pattern in a serial multiple choice (SMC) task. Beginning on P95, rats in the F1 generation were given either 4days of massed training (20patterns/day) followed by spaced training (10 patterns/day) or only spaced training. Transgenerational effects of adolescent nicotine exposure were observed as greater difficulty in learning a "violation element" of the pattern, which indicated that rats were impaired in the ability to encode and remember multiple sequential elements as compound or configural cues. The results indicated that for rats that received massed training, F1 generation rats with adolescent nicotine exposure whose F0 generation parents also experienced adolescent nicotine exposure showed poorer learning of the violation element than rats that experienced adolescent nicotine exposure only in the F1 generation. Thus, adolescent nicotine exposure in one generation of rats produced a cognitive impairment in the next generation.

  19. Deficits in episodic memory retrieval reveal impaired default mode network connectivity in amnestic mild cognitive impairment

    PubMed Central

    Dunn, Cameron J.; Duffy, Shantel L; Hickie, Ian B; Lagopoulos, Jim; Lewis, Simon J.G.; Naismith, Sharon L.; Shine, James M.

    2014-01-01

    Amnestic mild cognitive impairment (aMCI) is believed to represent a transitional stage between normal healthy ageing and the development of dementia. In particular, aMCI patients have been shown to have higher annual transition rates to Alzheimer's Disease (AD) than individuals without cognitive impairment. Despite intensifying interest investigating the neuroanatomical basis of this transition, there remain a number of questions regarding the pathophysiological process underlying aMCI itself. A number of recent studies in aMCI have shown specific impairments in connectivity within the default mode network (DMN), which is a group of regions strongly related to episodic memory capacities. However to date, no study has investigated the integrity of the DMN between patients with aMCI and those with a non-amnestic pattern of MCI (naMCI), who have cognitive impairment, but intact memory storage systems. In this study, we contrasted the DMN connectivity in 24 aMCI and 33 naMCI patients using seed-based resting state fMRI. The two groups showed no statistical difference in their DMN intra-connectivity. However when connectivity was analysed according to performance on measures of episodic memory retrieval, the two groups were separable, with aMCI patients demonstrating impaired functional connectivity between the hippocampal formation and the posterior cingulate cortex. We provide evidence that this lack of connectivity is driven by impaired communication from the posterior cingulate hub and does not simply represent hippocampal atrophy, suggesting that posterior cingulate degeneration is the driving force behind impaired DMN connectivity in aMCI. PMID:24634833

  20. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder

    PubMed Central

    Severance, Emily G; Gressitt, Kristin L; Stallings, Catherine R; Katsafanas, Emily; Schweinfurth, Lucy A; Savage, Christina L; Adamos, Maria B; Sweeney, Kevin M; Origoni, Andrea E; Khushalani, Sunil; Leweke, F Markus; Dickerson, Faith B; Yolken, Robert H

    2016-01-01

    Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case–control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case–control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04–9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007–0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009–0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of

  1. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder.

    PubMed

    Severance, Emily G; Gressitt, Kristin L; Stallings, Catherine R; Katsafanas, Emily; Schweinfurth, Lucy A; Savage, Christina L; Adamos, Maria B; Sweeney, Kevin M; Origoni, Andrea E; Khushalani, Sunil; Leweke, F Markus; Dickerson, Faith B; Yolken, Robert H

    2016-01-01

    Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case-control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case-control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04-9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007-0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009-0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of gut

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. Effects of a Novel Cognition-Enhancing Agent on Fetal Ethanol-Induced Learning Deficits

    PubMed Central

    Savage, Daniel D.; Rosenberg, Martina J.; Wolff, Christina R.; Akers, Katherine G.; El-Emawy, Ahmed; Staples, Miranda C.; Varaschin, Rafael K.; Wright, Carrie A.; Seidel, Jessica L.; Caldwell, Kevin K.; Hamilton, Derek A.

    2013-01-01

    Background Drinking during pregnancy has been associated with learning disabilities in affected offspring. At present, there are no clinically effective pharmacotherapeutic interventions for these learning deficits. Here, we examined the effects of ABT-239, a histamine H3 receptor antagonist, on fetal ethanol-induced fear conditioning and spatial memory deficits. Methods and Results Long-Evans rat dams stably consumed a mean of 2.82 g ethanol/kg during a 4-hour period each day during pregnancy. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, litter size and birth weights were not different between the ethanol-consuming and control groups. Female adult offspring from the control and fetal alcohol-exposed (FAE) groups received saline or 1 mg ABT-239/kg 30 minutes prior to fear conditioning training. Three days later, freezing time to the context was significantly reduced in saline-treated FAE rats compared to control. Freezing time in ABT-239-treated FAE rats was not different than that in controls. In the spatial navigation study, adult male offspring received a single injection of saline or ABT-239 30 minutes prior to 12 training trials on a fixed platform version of the Morris Water Task. All rats reached the same performance asymptote on Trials 9 to 12 on Day 1. However, 4 days later, first-trial retention of platform location was significantly worse in the saline-treated FAE rats compared control offspring. Retention by ABT-239-treated FAE rats was similar to that by controls. ABT-239’s effect on spatial memory retention in FAE rats was dose dependent. Conclusions These results suggest that ABT-239 administered prior to training can improve retention of acquired information by FAE offspring on more challenging versions of hippocampal-sensitive learning tasks. Further, the differential effects of ABT-239 in FAE offspring compared to controls raises questions about the impact of fetal ethanol exposure

  5. Cognitive mapping deficits in schizophrenia: Evidence from clinical correlates of visuospatial transformations.

    PubMed

    Agarwal, Sri Mahavir; Danivas, Vijay; Amaresha, Anekal C; Shivakumar, Venkataram; Kalmady, Sunil V; Bose, Anushree; Narayanaswamy, Janardhanan C; Venkatasubramanian, Ganesan

    2015-08-30

    The 'cognitive mapping' component of spatial cognition, namely - the allocentric/egocentric function and its relation to symptoms in schizophrenia is relatively unexplored. In this study, we compared schizophrenia patients (N=44) to demographically-matched healthy controls (N=43) using computer-administered visuospatial transformation tasks with egocentric and allocentric components and analyzed their correlation with symptoms. Significant diagnosis X task-type interaction effect was seen on task accuracy. Patients performed significantly worse than controls in the allocentric letter rotation task (LRT) but not in the egocentric people rotation task (PRT). Accuracy in the LRT was significantly lesser than in PRT among patients but not among controls. Patients were significantly slower as compared to controls in both tasks. Both groups took longer to perform PRT as compared to LRT. LRT accuracy showed significant negative correlation with total positive symptoms as well as negative symptoms scores. Angle of rotation, perspective (front-facing/back-facing), orientation (mirrored/normal), and stimulus type (letter/number) were found to significantly influence performance in both groups of subjects. The present data support the finding that there is a differential impairment of allocentric abilities in schizophrenia patients. Further systematic research in this area may facilitate better understanding of schizophrenia pathogenesis. PMID:26162664

  6. Scopolamine induced deficits in a battery of rat cognitive tests: comparisons of sensitivity and specificity.

    PubMed

    Hodges, Donald Bartholomew; Lindner, Mark D; Hogan, John B; Jones, Kelly M; Markus, Etan J

    2009-05-01

    Despite much research, the cognitive effects of scopolamine hydrobromide, a cholinergic antagonist, remain controversial. Scopolamine affects multiple systems each of which can impact behavior. One way to tease apart the effects of the drug is to determine the effects of low scopolamine doses on different abilities. The present experiments compared the effects of low doses of scopolamine on a single group of rats conducting a battery of behavioral tasks: Morris water maze, radial arm maze, delayed non-matching to position tasks, and fixed ratio 5 bar pressing. The behavioral battery ranged from tasks having little cognitive demand to those thought to be based more on attention and spatial-working memory. Control experiments using additional groups of rats assessing peripheral versus central effects were conducted with both liquid and dry reinforcement and with methyl scopolamine. Furthermore, the 5-choice serial reaction time test assessed scopolamine effects on attention. The data show a wide spectrum of central and peripheral cholinergic involvement. The central effects include attention and motor initiation, both of which impact and interact with the mnemonic function of acetylcholine. These results show that a limited disruption of the central cholinergic system can have profound effects on attention and/or psychomotor control before any measurable mnemonic disruption.

  7. Cognitive Deficits in Healthy Elderly Population With "Normal" Scores on the Mini-Mental State Examination.

    PubMed

    Votruba, Kristen L; Persad, Carol; Giordani, Bruno

    2016-05-01

    This study investigated whether healthy older adults with Mini-Mental State Examination (MMSE) scores above 23 exhibit cognitive impairment on neuropsychological tests. Participants completed the MMSE and a neuropsychological battery including tests of 10 domains. Results were compared to published normative data. On neuropsychological testing, participants performed well on measures of naming and recall but showed mild to moderate impairment in working memory and processing speed and marked impairment in inhibition, sustained attention, and executive functioning. Almost everyone (91%) scored at least 1 standard deviation (SD) below the mean in at least 1 domain. The median number of domains in which individuals scored below 1 SD was 3.0 of 10.0, whereas over 21% scored below 1 SD in 5 domains or more. With the strictest of definitions for impairment, 20% of this population scored below 2.0 SDs below the norm in at least 2 domains, a necessary condition for a diagnosis of dementia. The finding that cognitive impairment, particularly in attention and executive functioning, is found in healthy older persons who perform well on the MMSE has clinical and research implications in terms of emphasizing normal variability in performance and early identification of possible impairment. PMID:26850856

  8. 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

  9. 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.

  10. 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. PMID:26107664

  11. 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.

  12. 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. PMID:27258418

  13. A Randomized, Placebo-Controlled Study Investigating the Nicotinic α7 Agonist, RG3487, for Cognitive Deficits in Schizophrenia

    PubMed Central

    Umbricht, Daniel; Keefe, Richard SE; Murray, Stephen; Lowe, David A; Porter, Richard; Garibaldi, George; Santarelli, Luca

    2014-01-01

    Effective treatments for cognitive impairment associated with schizophrenia (CIAS) remain an unmet need. Nicotinic α7 receptor agonists may be effective in CIAS. This 8-week (week 1, inpatient; weeks 2–8, outpatient), double-blind, randomized study used Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) guidelines to investigate the nicotinic α7 partial agonist RG3487 (formerly MEM3454) in CIAS; 215 patients with chronic stable schizophrenia received placebo or RG3487 (5, 15, or 50 mg) added to ongoing treatment with risperidone, paliperidone, or aripiprazole. Primary end point was baseline to week 8 change in MATRICS Consensus Cognitive Battery (MCCB) composite t-score. Secondary outcomes were change in MCCB domain and negative symptom assessment (NSA) scores. The study did not allow for evaluation of nonsmokers. Each RG3487 dose was evaluated using a mixed-effects model repeated measures approach. Mean (SD) baseline MCCB composite t-score was 28.3 (12.0). No significant effect on MCCB composite t-scores was observed with RG3487 (adjusted mean difference (SE) vs placebo: 5 mg: 0.11 (1.39); 15 mg: −1.95 (1.39); 50 mg: −1.13 (1.37); p=0.2–0.9). RG3487 did not improve MCCB domain scores. In a post hoc analysis of patients with moderate negative symptoms, 5 and 50 mg RG3487 vs placebo significantly improved NSA total (−4.45 (p=0.04) and −4.75 (p=0.02), respectively) and global (−0.39 (p=0.04) and −0.55 (p=0.003), respectively) scores. The MCCB did not lead to higher than expected patient withdrawal. RG3487 was generally well tolerated. In patients with stable schizophrenia, RG3487 did not improve cognitive deficits, as assessed by the MCCB; however, in patients with moderate negative symptoms, a post hoc analysis revealed significant improvement of negative symptoms. PMID:24549101

  14. Edaravone injection ameliorates cognitive deficits in rat model of Alzheimer's disease.

    PubMed

    Yang, Rui; Wang, Qingjun; Li, Fang; Li, Jian; Liu, Xuewen

    2015-11-01

    Oxidative stress plays important role in the pathogenesis of Alzheimer's disease (AD). Edaravone is a potent free radical scavenger that exerts antioxidant effects. Therefore, in this study we aimed to investigate neuroprotective effects of edaravone for AD. Wistar rats were randomly divided into three groups (n = 15): control group, model group, and treatment group, which were injected with phosphate buffered saline, Aβ1-40, and Aβ1-40 together with 5 mg/kg edaravone, respectively, into the right hippocampal dentate gyrus. Spatial learning and memory of the rats were examined by Morris water maze test. 4-Hydroxynonenal (4-HNE) level in rat hippocampus was analyzed by immunohistochemistry. Acetylcholinesterase (AChE) and choline acetylase (ChAT) activities were assayed by commercial kits. We found that edaravone ameliorated spatial learning and memory deficits in the rats. 4-HNE level in the hippocampus as well as AChE and ChAT activities in the hippocampus was significantly lower in treatment group than in model group. In conclusion, edaravone may be developed as a novel agent for the treatment of AD for improving cholinergic system and protecting neurons from oxidative toxicity.

  15. "Presemantic" cognition in semantic dementia: six deficits in search of an explanation.

    PubMed

    Patterson, Karalyn; Lambon Ralph, Matthew A; Jefferies, Elizabeth; Woollams, Anna; Jones, Roy; Hodges, John R; Rogers, Timothy T

    2006-02-01

    On the basis of a theory about the role of semantic knowledge in the recognition and production of familiar words and objects, we predicted that patients with semantic dementia would reveal a specific pattern of impairment on six different tasks typically considered "pre-" or "non-" semantic: reading aloud, writing to dictation, inflecting verbs, lexical decision, object decision, and delayed copy drawing. The prediction was that all tasks would reveal a frequency-by-typicality interaction, with patients performing especially poorly on lower-frequency items with atypical structure (e.g., words with an atypical spelling-to-sound relationship; objects with an atypical feature for their class, such as the hump on a camel, etc). Of 84 critical observations (14 patients performing 6 tasks), this prediction was correct in 84/84 cases; and a single component in a factor analysis accounted for 87% of the variance across seven measures: each patient's degree of impairment on atypical items in the six experimental tasks and a separate composite score reflecting his or her degree of semantic impairment. Errors also consistently conformed to the predicted pattern for both expressive and receptive tasks, with responses reflecting residual knowledge about the typical surface structure of each domain. We argue that these results cannot be explained as associated but unrelated deficits but instead are a principled consequence of a primary semantic impairment.

  16. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology.

    PubMed

    Frautschy, S A; Hu, W; Kim, P; Miller, S A; Chu, T; Harris-White, M E; Cole, G M

    2001-01-01

    Both oxidative damage and inflammation have been implicated in age-related neurodegenerative diseases including Alzheimer's Disease (AD). The yellow curry spice, curcumin, has both antioxidant and anti-inflammatory activities which confer significant protection against neurotoxic and genotoxic agents. We used 22 month Sprague-Dawley (SD) rats to compare the effects of the conventional NSAID, ibuprofen, and curcumin for their ability to protect against amyloid beta-protein (Abeta)-induced damage. Lipoprotein carrier-mediated, intracerebroventricular infusion of Abeta peptides induced oxidative damage, synaptophysin loss, a microglial response and widespread Abeta deposits. Dietary curcumin (2000 ppm), but not ibuprofen, suppressed oxidative damage (isoprostane levels) and synaptophysin loss. Both ibuprofen and curcumin reduced microgliosis in cortical layers, but curcumin increased microglial labeling within and adjacent to Abeta-ir deposits. In a second group of middle-aged female SD rats, 500 ppm dietary curcumin prevented Abeta-infusion induced spatial memory deficits in the Morris Water Maze and post-synaptic density (PSD)-95 loss and reduced Abeta deposits. Because of its low side-effect profile and long history of safe use, curcumin may find clinical application for AD prevention.

  17. [Cognitive-behavioural guidance interventions in adolescents with attention deficit hyperactivity disorder].

    PubMed

    Valls-Llagostera, Cristina; Vidal, Raquel; Abad, Alfonso; Corrales, Montse; Richarte, Vanesa; Casas, Miguel; Ramos-Quiroga, Josep A

    2015-02-25

    Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) es un trastorno del neurodesarrollo que se puede manifestar a lo largo de la vida. Un 50-70% de los niños diagnosticados presenta el trastorno en la adolescencia. Los jovenes con TDAH tienen elevadas tasas de comorbilidad con otros trastornos psiquiatricos y una elevada afectacion funcional. Objetivo. Revisar la bibliografia de las intervenciones cognitivo-conductuales que se han aplicado al tratamiento del TDAH en la adolescencia. Desarrollo. Se revisan los estudios sobre tratamiento psicologico, clasificando las intervenciones en: tratamientos psicosociales, tratamiento en mindfulness y tratamiento cognitivo-conductual (individual y en formato de grupo). Se revisa el unico estudio publicado sobre terapia cognitivo-conductual para adolescentes con TDAH, asi como un nuevo protocolo de intervencion en formato de grupo diseñado en el Hospital Universitari Vall d'Hebron. Conclusiones. Aunque recientemente se ha incrementado el numero de publicaciones sobre el tratamiento psicologico del TDAH en el adolescente, se requiere un desarrollo mayor de protocolos de intervencion y estudios sobre la eficacia/efectividad de estos.

  18. Double-blind, randomized sham controlled study of deep-TMS add-on treatment for negative symptoms and cognitive deficits in schizophrenia.

    PubMed

    Rabany, Liron; Deutsch, Lisa; Levkovitz, Yechiel

    2014-07-01

    Negative symptoms and cognitive deficits are considered core symptoms of schizophrenia, yet treatment for them remains inadequate. Deep-transcranial magnetic stimulation (TMS) is a novel technology that enables non-invasive stimulation of deep layers of the prefrontal cortex. Preliminary evidence suggests that deep-TMS could be effective in the treatment of negative symptoms and cognitive deficits. The current study is the first double-blind, randomized sham-controlled study to examine the feasibility of deep-TMS add-on treatment for negative symptoms and cognitive deficits in schizophrenia. Twenty daily H1 deep-TMS treatments (20Hz, 120% MT) were delivered, in a double-blind, randomized sham-controlled design (n=30). Extensive clinical and cognitive assessments were carried out throughout the study and for an additional one month follow-up period. The results indicate that at the end of the treatment period, negative symptoms (as indicated by the Scale for the Assessment of Negative Symptoms (SANS)) significantly reduced in the TMS group (-7.7), but not in the sham group (-1.9). Differences between the groups were not statistically significant.

  19. Efficacy of social cognition remediation programs targeting facial affect recognition deficits in schizophrenia: a review and consideration of high-risk samples and sex differences.

    PubMed

    Statucka, Marta; Walder, Deborah J

    2013-04-30

    Schizophrenia patients suffer from significant social functioning deficits. Social cognition, particularly facial affect recognition (FAR), is an important predictor of functional outcome. Recently, investigators developed numerous social cognition remediation programs targeting FAR deficits with the goal of improving social functioning and quality of life in schizophrenia patients. This article builds on Horan et al.'s (2008) comprehensive review and Kurtz and Richardson's (2012) meta-analysis of a broad range of social cognition remediations, by systematically reviewing efficacy of empirically based remediations in schizophrenia specifically targeting FAR (across 23 studies), and their potential functional benefits. We describe each FAR-based social cognition remediation program, which may aid clinical scientists and clinicians in selecting programs for further study and practice. We critically evaluate limitations of FAR remediation programs and applications. Our review concludes FAR remediation programs are strongly efficacious in improving FAR performance and functional status in schizophrenia. Importantly, we provide rationale for and recommend that future research consider (as yet underexplored) sexual dimorphisms in FAR remediation effects, and examine FAR remediation in clinical high-risk for psychosis populations. The goal is to mitigate deficits, perhaps hinder illness onset, and individually tailor treatments across the psychosis continuum in a way that maximally aids those in greatest need.

  20. Cognitive Set Shifting Deficits and Their Relationship to Repetitive Behaviors in Autism Spectrum Disorder

    PubMed Central

    Miller, Haylie L.; Ragozzino, Michael E.; Cook, Edwin H.; Sweeney, John A.; Mosconi, Matthew W.

    2015-01-01

    The neurocognitive impairments associated with restricted and repetitive behaviors (RRBs) in autism spectrum disorder (ASD) are not yet clear. Prior studies indicate that individuals with ASD show reduced cognitive flexibility, which could reflect difficulty shifting from a previously learned response pattern or a failure to maintain a new response set. We examined different error types on a test of set-shifting completed by 60 individuals with ASD and 55 age- and nonverbal IQ-matched controls. Individuals with ASD were able to initially shift sets, but they exhibited difficulty maintaining new response sets. Difficulty with set maintenance was related to increased severity of RRBs. General difficulty maintaining new response sets and a heightened tendency to revert to old preferences may contribute to RRBs. PMID:25234483

  1. Toxoplasmosis Infection and Cognitive Deficit after Electroconvulsive Treatment (ECT), Is There a Connection?

    PubMed Central

    E. Berg, John

    2012-01-01

    Electroconvulsive treatment (ECT) has developed over 70 years to a modern, effective way of lifting depressive moods. Memory loss and visual acuity after electroconvulsive treatment is the only remaining relevant criticism of the treatment modality when considering the overall rate of remission from this treatment compared to all other treatment modalities. A depressive state impedes memory, and memory improves on several qualities of cognition after treatment. However, the comparison of a person’s memory ability from the months before depression started to the level after a course of ECT is never performed, for obvious reasons. Some infectious diseases are known to influence memory negatively through effects on the dopamine receptors. More specifically, former toxoplasmosis infection may be a factor. Preliminary data on titres of toxoplasma IgG may indicate a connection to the development of long-standing memory problems after ECT. PMID:24600630

  2. Prevention of Hippocampal Neuronal Damage and Cognitive Function Deficits in Vascular Dementia by Dextromethorphan.

    PubMed

    Xu, Xiaofeng; Zhang, Bin; Lu, Kaili; Deng, Jiangshan; Zhao, Fei; Zhao, Bing-Qiao; Zhao, Yuwu

    2016-07-01

    Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD. PMID:26887382

  3. Disentangling the effects of Tourette syndrome and attention deficit hyperactivity disorder on cognitive and behavioral phenotypes.

    PubMed

    Rizzo, Renata; Curatolo, Paolo; Gulisano, Mariangela; Virzì, Marina; Arpino, Carla; Robertson, Mary M

    2007-08-01

    Eighty participants (62 males; 18 females; age range: 6-16 years) took part in the study, comprising four groups of 20 subjects each: TS-only, ADHD-only, TS+ADHD, controls. The age distributions, did not differ significantly among the four groups. The severity of symptoms, assessed by the TSGS, did not differ significantly between the two TS groups. Standardised measures were used throughout. The "cases" (i.e. TS-only, TS+ADHD, ADHD-only) were significantly different from controls on most measures of behavior. There were also differences amongst the various clinical subgroups, with, in general, TS-only participants being similar to controls with regards to both "total behavior" ratings and cognitive testing results. A diagnosis of ADHD, either or its own or in association with TS, was associated with greater maladaptive behavior and worse cognitive functioning. With regards to affective symptoms and anxiety, the three clinical groups did not differ from each other, but each of them was more affected than the control group. One finding in our study which differed from previous literature was that TS-only patients were rated as more "delinquent" than controls by their parents: possible reasons for this are discussed. Oppositional defiant disorder (ODD) was seen in a few (2,3,3 ODD patients in each clinical group), but as numbers were small no statistics were undertaken. Family histories were in accord with both TS and ADHD being genetic disorders, but sharing an overlap in only some cases. The "additive effect" hypothesis is discussed in detail in the light of our results and recent literature.

  4. Peripheral Immune Cell Populations Associated with Cognitive Deficits and Negative Symptoms of Treatment-Resistant Schizophrenia

    PubMed Central

    Turner, Lorinda; Mustafa, Syed; Hatton, Alex; Smith, Kenneth G. C.; Lyons, Paul A.; Bullmore, Edward T.

    2016-01-01

    Background Hypothetically, psychotic disorders could be caused or conditioned by immunological mechanisms. If so, one might expect there to be peripheral immune system phenotypes that are measurable in blood cells as biomarkers of psychotic states. Methods We used multi-parameter flow cytometry of venous blood to quantify and determine the activation state of 73 immune cell subsets for 18 patients with chronic schizophrenia (17 treated with clozapine), and 18 healthy volunteers matched for age, sex, BMI and smoking. We used multivariate methods (partial least squares) to reduce dimensionality and define populations of differentially co-expressed cell counts in the cases compared to controls. Results Schizophrenia cases had increased relative numbers of NK cells, naïve B cells, CXCR5+ memory T cells and classical monocytes; and decreased numbers of dendritic cells (DC), HLA-DR+ regulatory T-cells (Tregs), and CD4+ memory T cells. Likewise, within the patient group, more severe negative and cognitive symptoms were associated with decreased relative numbers of dendritic cells, HLA-DR+ Tregs, and CD4+ memory T cells. Motivated by the importance of central nervous system dopamine signalling for psychosis, we measured dopamine receptor gene expression in separated CD4+ cells. Expression of the dopamine D3 (DRD3) receptor was significantly increased in clozapine-treated schizophrenia and covaried significantly with differentiated T cell classes in the CD4+ lineage. Conclusions Peripheral immune cell populations and dopaminergic signalling are disrupted in clozapine-treated schizophrenia. Immuno-phenotypes may provide peripherally accessible and mechanistically specific biomarkers of residual cognitive and negative symptoms in this treatment-resistant subgroup of patients. PMID:27244229

  5. Cognitive deficits and disruption of neurogenesis in a mouse model of apolipoprotein E4 domain interaction.

    PubMed

    Adeosun, Samuel O; Hou, Xu; Zheng, Baoying; Stockmeier, Craig; Ou, Xiaoming; Paul, Ian; Mosley, Thomas; Weisgraber, Karl; Wang, Jun Ming

    2014-01-31

    Apolipoprotein E4 (apoE4) allele is the major genetic risk factor for sporadic Alzheimer disease (AD) due to the higher prevalence and earlier onset of AD in apoE4 carriers. Accumulating data suggest that the interaction between the N- and the C-terminal domains in the protein may be the main pathologic feature of apoE4. To test this hypothesis, we used Arg-61 mice, a model of apoE4 domain interaction, by introducing the domain interaction feature of human apoE4 into native mouse apoE. We carried out hippocampus-dependent learning and memory tests and related cellular and molecular assays on 12- and 3-month-old Arg-61 and age-matched background C57BL/6J mice. Learning and memory task performance were impaired in Arg-61 mice at both old and young ages compared with C57BL/6J mice. Surprisingly, young Arg-61 mice had more mitotic doublecortin-positive cells in the subgranular zone; mRNA levels of brain-derived neurotrophic factor (BDNF) and TrkB were also higher in 3-month-old Arg-61 hippocampus compared with C57BL/6J mice. These early-age neurotrophic and neurogenic (proliferative) effects in the Arg-61 mouse may be an inadequate compensatory but eventually detrimental attempt by the system to "repair" itself. This is supported by the higher cleaved caspase-3 levels in the young animals that not only persisted, but increased in old age, and the lower levels of doublecortin at old age in the hippocampus of Arg-61 mice. These results are consistent with human apoE4-dependent cognitive and neuro-pathologic changes, supporting the principal role of domain interaction in the pathologic effect of apoE4. Domain interaction is, therefore, a viable therapeutic/prophylactic target for cognitive impairment and AD in apoE4 subjects.

  6. Abnormal Functional Connectivity of Amygdala in Late-Onset Depression Was Associated with Cognitive Deficits

    PubMed Central

    Yue, Yingying; Yuan, Yonggui; Hou, Zhenghua; Jiang, Wenhao; Bai, Feng; Zhang, Zhijun

    2013-01-01

    Background Major depressive disorder (MDD) is associated with decreased function of cortico-limbic circuits, which play important roles in the pathogenesis of MDD. Abnormal functional connectivity (FC) with the amygdala, which is involved in cortico-limbic circuits, has also been observed in MDD. However, little is known about connectivity alterations in late-onset depression (LOD) or whether disrupted connectivity is correlated with cognitive impairment in LOD. Methods and Results A total of twenty-two LOD patients and twenty-two matched healthy controls (HC) underwent neuropsychological tests and resting state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) and FC with bilateral amygdala seeds were used to analyze blood oxygen level-dependent fMRI data between two groups. Compared with HC, LOD patients showed decreased ReHo in the right middle frontal gyrus and left superior frontal gyrus. In the LOD group, the left amygdala had decreased FC with the right middle frontal gyrus and the left superior frontal gyrus in the amygdala positive network, and it had increased FC with the right post-central gyrus in the amygdala negative network. However, significantly reduced FC with the right amygdala was observed in the right middle occipital gyrus in the amygdala negative network. Further correlative analyses revealed that decreased FC between the amygdala and the right middle occipital gyrus was negatively correlated with the verbal fluency test (VFT, r = −0.485, P = 0.022) and the digit span test (DST, r = −0.561, P = 0.007). Conclusions Our findings of reduced activity of the prefrontal gyrus and abnormal FC with the bilateral amygdala may be key markers of cognitive dysfunction in LOD patients. PMID:24040385

  7. The beneficial effects of leptin on REM sleep deprivation-induced cognitive deficits in mice.

    PubMed

    Chang, Hsiao-Fu; Su, Chun-Lin; Chang, Chih-Hua; Chen, Yu-Wen; Gean, Po-Wu

    2013-05-17

    Leptin, a 167 amino acid peptide, is synthesized predominantly in the adipose tissues and plays a key role in the regulation of food intake and body weight. Recent studies indicate that leptin receptor is expressed with high levels in many brain regions that may regulate synaptic plasticity. Here we show that deprivation of rapid eye movement (REMD) sleep resulted in impairment of both cue and contextual fear memory. In parallel, surface expression of GluR1 was reduced in the amygdala. Intraperitoneal injection of leptin to the REMD mice rescued memory impairment and reversed surface GluR1 reduction. Using whole-cell recording to evaluate the synaptic function of the thalamus-lateral amygdala (LA) pathway, we found a decrease in frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) concomitant with reduced AMPA/NMDA ratios in the REMD mice. By contrast, paired-pulse facilitation (PPF) was increased. The effects of REMD on mEPSCs and AMPA/NMDA ratio could be reversed by leptin treatment, whereas on PPR it could not. Phosphatase and tensin homolog (PTEN), a dual protein/lipid phosphatase, down-regulates the effect of the PI-3 kinase pathway. Fear conditioning increased whereas REMD led to a decrease in the phosphorylated states of PTEN, Akt, and glycogen synthase kinase-3β (GSK3β), and the effects of REMD were reversed by leptin. These results suggest that both pre- and postsynaptic functions of the thalamus-LA pathway were altered by fear conditioning and REMD in opposite directions. Leptin treatment reversed REMD-induced memory deficits primarily by a postsynaptic action by restoring surface expression of GluR1 without affecting PPR.

  8. Academic, Behavioral, and Cognitive Effects of OROS® Methylphenidate on Older Children with Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Wigal, Sharon B.; Wigal, Tim; Schuck, Sabrina; Brams, Matthew; Williamson, David; Armstrong, Robert B.

    2011-01-01

    Abstract Objective To assess the effect of Osmotic-Release Oral System (OROS) methylphenidate (MPH) on a variety of measures evaluating academic performance, cognition, and social behavior in children with attention-deficit/hyperactivity disorder (ADHD). Methods This double-blind, randomized, placebo-controlled, crossover laboratory school study enrolled 78 children aged 9–12 years with ADHD who responded to OROS MPH. After determining individualized OROS MPH dosing (18–54 mg/day), 71 subjects received blinded treatment (OROS MPH or placebo then vice versa) on each of 2 laboratory school days, separated by 1 week. Primary efficacy was measured by Permanent Product Measure of Performance at 4 hours after study drug administration. Results Treatment with OROS MPH resulted in statistically significant improvement in Permanent Product Measure of Performance and Swanson, Kotkin, Agler, M-Flynn, and Pelham scores, measures of response time, and of working memory compared to placebo. Other measures did not meet all pre-established criteria for significance (maintenance of the overall type I error rate at 5%). Adverse events were consistent with previous reports of stimulant medications used in the management of ADHD. There were no discontinuations due to adverse events, and no serious adverse events or deaths. Conclusions OROS MPH dosed to reduce core symptoms of ADHD to within the normal range also improved performance on a variety of academic tasks in school-aged children compared to placebo. Adverse effects reported were consistent with prior studies. Clinical Trial Registry Information Double-Blind, Randomized, Placebo-Controlled, Crossover Study Evaluating the Academic, Behavioral and Cognitive Effects of Concerta on Older Children with ADHD, URL: http://clinicaltrials.gov/ct2/show/NCT00799409, unique identifier: NCT00799409. PMID:21488750

  9. Cannabinoid receptor 1 gene polymorphisms and marijuana misuse interactions on white matter and cognitive deficits in schizophrenia.

    PubMed

    Ho, Beng-Choon; Wassink, Thomas H; Ziebell, Steven; Andreasen, Nancy C

    2011-05-01

    Marijuana exposure during the critical period of adolescent brain maturation may disrupt neuro-modulatory influences of endocannabinoids and increase schizophrenia susceptibility. Cannabinoid receptor 1 (CB1/CNR1) is the principal brain receptor mediating marijuana effects. No study to-date has systematically investigated the impact of CNR1 on quantitative phenotypic features in schizophrenia and inter-relationships with marijuana misuse. We genotyped 235 schizophrenia patients using 12 tag single nucleotide polymorphisms (tSNPs) that account for most of CB1 coding region genetic variability. Patients underwent a high-resolution anatomic brain magnetic resonance scan and cognitive assessment. Almost a quarter of the sample met DSM marijuana abuse (14%) or dependence (8%) criteria. Effects of CNR1 tSNPs and marijuana abuse/dependence on brain volumes and neurocognition were assessed using ANCOVA, including co-morbid alcohol/non-marijuana illicit drug misuse as covariates. Significant main effects of CNR1 tSNPs (rs7766029, rs12720071, and rs9450898) were found in white matter (WM) volumes. Patients with marijuana abuse/dependence had smaller fronto-temporal WM volumes than patients without heavy marijuana use. More interestingly, there were significant rs12720071 genotype-by-marijuana use interaction effects on WM volumes and neurocognitive impairment; suggestive of gene-environment interactions for conferring phenotypic abnormalities in schizophrenia. In this comprehensive evaluation of genetic variants distributed across the CB1 locus, CNR1 genetic polymorphisms were associated with WM brain volume variation among schizophrenia patients. Our findings suggest that heavy cannabis use in the context of specific CNR1 genotypes may contribute to greater WM volume deficits and cognitive impairment, which could in turn increase schizophrenia risk.

  10. An Anti-β-Amyloid Vaccine for Treating Cognitive Deficits in a Mouse Model of Down Syndrome.

    PubMed

    Belichenko, Pavel V; Madani, Rime; Rey-Bellet, Lorianne; Pihlgren, Maria; Becker, Ann; Plassard, Adeline; Vuillermot, Stephanie; Giriens, Valérie; Nosheny, Rachel L; Kleschevnikov, Alexander M; Valletta, Janice S; Bengtsson, Sara K S; Linke, Gordon R; Maloney, Michael T; Hickman, David T; Reis, Pedro; Granet, Anne; Mlaki, Dorin; Lopez-Deber, Maria Pilar; Do, Long; Singhal, Nishant; Masliah, Eliezer; Pearn, Matthew L; Pfeifer, Andrea; Muhs, Andreas; Mobley, William C

    2016-01-01

    In Down syndrome (DS) or trisomy of chromosome 21, the β-amyloid (Aβ) peptide product of the amyloid precursor protein (APP) is present in excess. Evidence points to increased APP gene dose and Aβ as playing a critical role in cognitive difficulties experienced by people with DS. Particularly, Aβ is linked to the late-life emergence of dementia as associated with neuropathological markers of Alzheimer's disease (AD). At present, no treatment targets Aβ-related pathogenesis in people with DS. Herein we used a vaccine containing the Aβ 1-15 peptide embedded into liposomes together with the adjuvant monophosphoryl lipid A (MPLA). Ts65Dn mice, a model of DS, were immunized with the anti-Aβ vaccine at 5 months of age and were examined for cognitive measures at 8 months of age. The status of basal forebrain cholinergic neurons and brain levels of APP and its proteolytic products were measured. Immunization of Ts65Dn mice resulted in robust anti-Aβ IgG titers, demonstrating the ability of the vaccine to break self-tolerance. The vaccine-induced antibodies reacted with Aβ without detectable binding to either APP or its C-terminal fragments. Vaccination of Ts65Dn mice resulted in a modest, but non-significant reduction in brain Aβ levels relative to vehicle-treated Ts65Dn mice, resulting in similar levels of Aβ as diploid (2N) mice. Importantly, vaccinated Ts65Dn mice showed resolution of memory deficits in the novel object recognition and contextual fear conditioning tests, as well as reduction of cholinergic neuron atrophy. No treatment adverse effects were observed; vaccine did not result in inflammation, cellular infiltration, or hemorrhage. These data are the first to show that an anti-Aβ immunotherapeutic approach may act to target Aβ-related pathology in a mouse model of DS. PMID:27023444

  11. Modulation of Rho GTPases rescues brain mitochondrial dysfunction, cognitive deficits and aberrant synaptic plasticity in female mice modeling Rett syndrome.

    PubMed

    De Filippis, Bianca; Valenti, Daniela; Chiodi, Valentina; Ferrante, Antonella; de Bari, Lidia; Fiorentini, Carla; Domenici, Maria Rosaria; Ricceri, Laura; Vacca, Rosa Anna; Fabbri, Alessia; Laviola, Giovanni

    2015-06-01

    Rho GTPases are molecules critically involved in neuronal plasticity and cognition. We have previously reported that modulation of brain Rho GTPases by the bacterial toxin CNF1 rescues the neurobehavioral phenotype in MeCP2-308 male mice, a model of Rett syndrome (RTT). RTT is a rare X-linked neurodevelopmental disorder and a genetic cause of intellectual disability, for which no effective therapy is available. Mitochondrial dysfunction has been proposed to be involved in the mechanism of the disease pathogenesis. Here we demonstrate that modulation of Rho GTPases by CNF1 rescues the reduced mitochondrial ATP production via oxidative phosphorylation in the brain of MeCP2-308 heterozygous female mice, the condition which more closely recapitulates that of RTT patients. In RTT mouse brain, CNF1 also restores the alterations in the activity of the mitochondrial respiratory chain (MRC) complexes and of ATP synthase, the molecular machinery responsible for the majority of cell energy production. Such effects were achieved through the upregulation of the protein content of those MRC complexes subunits, which were defective in RTT mouse brain. Restored mitochondrial functionality was accompanied by the rescue of deficits in cognitive function (spatial reference memory in the Barnes maze), synaptic plasticity (long-term potentiation) and Tyr1472 phosphorylation of GluN2B, which was abnormally enhanced in the hippocampus of RTT mice. Present findings bring into light previously unknown functional mitochondrial alterations in the brain of female mice modeling RTT and provide the first evidence that RTT brain mitochondrial dysfunction can be rescued by modulation of Rho GTPases.

  12. Effect of EEG Biofeedback on Cognitive Flexibility in Children with Attention Deficit Hyperactivity Disorder With and Without Epilepsy.

    PubMed

    Bakhtadze, Sophia; Beridze, Maia; Geladze, Nana; Khachapuridze, Nana; Bornstein, Natan

    2016-03-01

    Attention deficit hyperactivity disorder (ADHD) is one of the most common developmental disorders in school-aged children. Symptoms consistent with ADHD have been observed in 8-77 % of children with epilepsy. Researchers have been motivated to search for alternative forms of treatment because 30 % of patients with ADHD cannot be treated by psychostimulants. Several studies support the use of a multimodal treatment approach that includes neurofeedback (NF) for the long-term management of ADHD. These studies have shown that NF provides a sustained effect, even without concurrent treatment with stimulants. We aimed to assess cognitive flexibility in ADHD children with and without temporal lobe epilepsy (TLE), and to evaluate the effects of NF on cognitive flexibility in these groups of children. We prospectively evaluated 69 patients with ADHD aged 9-12 years. The control group was 26 ADHD children without TLE who received no treatment. The first experimental group comprised 18 children with ADHD. The second experimental group comprised 25 age-matched ADHD children with TLE. This group was further divided in two subgroups. One subgroup compri