Sachs, Gabriele; Schaffer, Markus; Winklbaur, Bernadette
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
Hasselbalch, Jacob; Knorr, Ulla; Hasselbalch, Steen Gregers; Gade, Anders; Kessing, Lars Vedel
Patients with unipolar depressive disorder may present with cognitive deficits in the remitted state, and the aim of the present study was to investigate whether cognitive deficits within specific cognitive domains are present....
SHEN Chao; BAO Wei-min; YANG Bo-jie; XIE Rong; CAO Xiao-yun; LUAN Shi-hai; MAO Ying
Objective To discuss the present status and progress of clinical research on the cognitive effects caused by different types of brain tumors and common treatments.Data sources The data used in this review were mainly from PubMed articles published in English from 1990 to Febuary 2012.Research terms were "cognitive deficits" or "cognitive dysfunction".Study selection Articals including any information about brain tumor related cognitive deficits were selected.Results It is widely accepted that brain tumors and related treatments can impair cognitive function across manydomains,and can impact on patients' quality of life.Tumor localization,lateralization,surgery,drugs,radiotherapy and chemotherapy are all thought to be important factors in this process.However,some conflicting findings regarding brain tumor-related cognitive deficits have been reported.It can be difficult to determine the mechanism of these treatments,such as chemotherapy,antibiotics,antiepileptics,and steroids.Future research is needed to clarify these potential treatment effects.Conclusions Cognitive function is important for patients with brain tumor.Much more focus has been paid on this field.It should be regarded as an important prognostic index for the patients with brain tumor,and neuropsychological tests should be used in regular examinations.
Lund, H; Jønsson, A; Andresen, Jesper Graubæk;
Objectives - Although disease load in multiple sclerosis (MS) often is based on T2 lesion volumes, the changes in T2 of normal appearing brain tissue (NABT) are rarely considered. By means of magnetic resonance, (MR) we retrospectively investigated whether T2 changes in NABT explain part of the...... Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Impairment Scale (MSIS). Voxel-wise T2 estimates and total T2 lesion volume were tested for correlations with eight cognitive domains, a general cognitive dysfunction factor (CDF), and the two clinical scales. Results - We found distinct...
Gadow, Kenneth D.
Research on the effects of stimulant drugs on attention and cognitive deficits in children with hyperactivity is reviewed. Topics covered include: attention and impulsivity, paired associate learning, school achievement, and drug induced attention and cognitive deficits. (CL)
Ni, Yu-Fei; Zhang, Wei; Bao, Xiao-Feng; Wang, Wei; Song, Lu; Jiang, Bo
Cognitive deficits are core symptoms of schizophrenia, but effective treatments are still lacking. Previous studies have reported that the brain-derived neurotrophic factor (BDNF) signaling is closely involved in learning and memory. Monosialotetrahexosylganglioside (GM1) is a ganglioside with wide-ranging pharmacologic effects that enhances the BDNF signaling cascade. This study aimed to assess the effects of GM1 on schizophrenia-related cognitive impairments. A brief disruption of N-methyl-D-aspartate receptors with MK801 was used to generate the animal model for cognitive deficits in schizophrenia. It was found that MK801-treated mice showed significant deficits in memory ability compared with control mice in different behavior tests, and this was accompanied by decreased hippocampal BDNF signaling pathway. Consecutive administration of GM1 fully restored the MK801-induced cognitive deficits and the impaired BDNF signaling in the hippocampus. Furthermore, a BDNF system inhibitor abolished the effects of GM1 in the MK801 model. Taken together, our results show that GM1 could reverse the MK801-induced cognitive deficits, suggesting a potential usefulness of GM1 in treating the schizophrenia-related cognitive impairments. PMID:26960162
Zeier, Joshua D.; Baskin-Sommers, Arielle R.; Newman, Joseph P.; Racer, Kristina Hiatt
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 compe...
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.
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…
Lesh, Tyler A.; Niendam, Tara A; Minzenberg, Michael J.; Carter, Cameron S.
Although schizophrenia is an illness that has been historically characterized by the presence of positive symptomatology, decades of research highlight the importance of cognitive deficits in this disorder. This review proposes that the theoretical model of cognitive control, which is based on contemporary cognitive neuroscience, provides a unifying theory for the cognitive and neural abnormalities underlying higher cognitive dysfunction in schizophrenia. To support this model, we outline con...
Zeier, Joshua D; Baskin-Sommers, Arielle R; Hiatt Racer, Kristina D; Newman, Joseph P
Antisociality has been linked to a variety of executive functioning deficits, including poor cognitive control. Surprisingly, cognitive control deficits are rarely found in psychopathic individuals, despite their notoriously severe and persistent antisocial behavior. In fact, primary (low-anxious) psychopathic individuals display superior performance on cognitive control-type tasks under certain circumstances. To clarify these seemingly contradictory findings, we administered a response competition (i.e., flanker) task to incarcerated offenders, who were assessed for Antisocial Personality Disorder (APD) symptoms and psychopathy. As hypothesized, APD related to poorer accuracy, especially on incongruent trials. Contrary to expectation, however, the same pattern of results was found in psychopathy. Additional analyses indicated that these effects of APD and psychopathy were associated with overlapping variance. The findings suggest that psychopathy and APD symptoms are both associated with deficits in cognitive control, and that this deficit relates to general antisociality as opposed to a specific antisocial syndrome. PMID:22452754
Loe, Irene M.; Feldman, Heidi M.; Yasui, Enami; Luna, Beatriz
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.
Vogel, Asmus; Stokholm, Jette; Gade, Anders;
In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective...
Full Text Available Neurocognitive deficits in schizophrenia 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 schizophrenia 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 schizophrenia 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.
Cognitive dysfunction is a core feature in schizophrenia and has a great impact on psychosocial functioning. Still it remains unclear, whether the different diagnostic subgroups have a specific cognitive profile. The topic of this research was to investigate the neurocognitive characteristics of deficit and non-deficit schizophrenia, and to examine if the two diagnostic subgroups have a qualitative difference in cognitive functioning. In Study 1., 275 patient and 130 healthy controls completed the WCST (Wisconsin Card Sorting Test). We performed an exploratory factor analytic study on the variables for the total group and each subgroups, then we assessed the ability of the factors to distinguish between the deficit, non deficit and control groups. In Study 2., I used the Kilroy-test to investigate procedural and context-dependent learning. 78 patients and 30 healthy controls completed the test, which has two phases: while the training phase is dominantly related to basal ganglia circuits, the context-dependent probe phase requires intact medial-temporal lobe functioning. Thus the two interactive memory systems can be examined separately within one test. Study 1.: Results of the exploratory factor analysis of the whole sample yielded two factors which together explained approximately 95% of the total variance. Comparison of the diagnostic groups on each of the factors revealed that both schizophrenia groups showed executive function impairment in comparison to controls. Deficit patients suffer from a more severe degree of impairment on the "General executive function" factor (conceptualization, flexibility, set shifting) than non-deficit patients. On the other hand, non-perseverative error type (factor 2.) seems to be less typical to deficit than to the non-deficit patients. Study 2.: Results revealed that deficit and non-deficit patients were similarly impaired on the probe phase compared with controls. However, the training phase was not compromised in non-deficit
Full Text Available In the first part of the article the authors present a set of the actual concepts explaining problems of cognitive functions and social cognition currently observed in patients with anorexia nervosa (AN. It is possible; through the neuroimaging research, to get better understanding of the brain specifics in these individuals. Even though, the AN remains a disease with very complex and multifactorial etiology which remains a huge medical challenge. Currently, popular is the view that takes into consideration the integrating role of the insula and subcortical structures (such as hippocampus, amygdala, thalamus in the regulation of cognitive and emotional processes in people suffering from AN. There is still an open problem, however, of the selection of therapeutic interventions targeting these deficits. The second part of the article presents the attempt to describe deficits in neurocognitive and social cognition in people with AN occurring prior to illness, during and after the recovery. Particular attention has been paid to the most frequently described in the literature – neuro- cognitive deficits such as rigidity of thinking, weak central coherence, and deficits in social cognition, including mental processes of perception and expression of emotions, disorders of the theory of mind (ToM and empathy. The results of previous studies, their scarcity in Poland, do not give a satisfactory answer to the question whether the above mentioned disorders are a feature of endophenotype or condition in an episode of the disease. Research point to the more permanent nature, which may be more resistant to therapeutic modifications.
Szczodry, O.; van der Staay, F.J.; Arndt, S.S.
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
Cohen, Alex S; McGovern, Jessica E; Dinzeo, Thomas J; Covington, Michael A
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
Kułakowska, Dorota; Biernacka, Katarzyna; Wilkos, Ewelina; Rybakowski, Filip; Kucharska-Pietura, Katarzyna
In the first part of the article the authors present a set of the actual concepts explaining problems of cognitive functions and social cognition currently observed in patients with anorexia nervosa (AN). It is possible; through the neuroimaging research, to get better understanding of the brain specifics in these individuals. Even though, the AN remains a disease with very complex and multifactorial etiology which remains a huge medical challenge. Currently, popular is the view that takes into consideration the integrating role of the insula and subcortical structures (such as hippocampus, amygdala, thalamus) in the regulation of cognitive and emotional processes in people suffering from AN. There is still an open problem, however, of the selection of therapeutic interventions targeting these deficits. The second part of the article presents the attempt to describe deficits in neurocognitive and social cognition in people with AN occurring prior to illness, during and after the recovery. Particular attention has been paid to the most frequently described in the literature--neurocognitive deficits such as rigidity of thinking, weak central coherence, and deficits in social cognition, including mental processes of perception and expression of emotions, disorders of the theory of mind (ToM) and empathy. The results of previous studies, their scarcity in Poland, do not give a satisfactory answer to the question whether the above mentioned disorders are a feature of endophenotype or condition in an episode of the disease. Research point to the more permanent nature, which may be more resistant to therapeutic modifications. PMID:25204093
J Gordon Millichap
Full Text Available Cognitive and behavioral features of Sturge-Weber syndrome, tuberous sclerosis, and neurofibromatosis are summarized by a literature review (113 references at the New York University, New York.
Cognition denotes a relatively high level of processing of specific information including thinking, memory, perception, motivation, skilled movements and language. Cognitive psychology has become an important discipline in the research of a number of psychiatric disorders, ranging from severe psychotic illness such as schizophrenia to relatively benign, yet significantly disabling, non-psychotic illnesses such as somatoform disorder. Research in the area of neurocognition has started unlockin...
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.
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…
McQuade, Julia D.; Tomb, Meghan; Hoza, Betsy; Waschbusch, Daniel A.; Hurt, Elizabeth A.; Vaughn, Aaron J.
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, working memory, broad attention, and cognitive fluency) compared to each other and to control children. Further, specific cognitive deficits emerged as p...
Woo, Young Sup; Rosenblat, Joshua D; Kakar, Ron; Bahk, Won-Myong; McIntyre, Roger S
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 cognit...
Grafman, J; Litvan, I; Massaquoi, S; Stewart, M; Sirigu, A; Hallett, M
We compared the performance of 12 patients with cerebellar atrophy (CA) and 12 normal controls matched for age and education on the Tower of Hanoi, a nine-problem task that requires cognitive planning. CA patients performed significantly worse than controls on this task despite no difference in planning and between-move pause times. A reanalysis of the data using just the subgroup of patients with pure cerebellar cortical atrophy (CCA) (N = 9) replicated the above results and also showed that CCA patients had significantly increased planning times compared with controls. Neither age, sex, education level, severity of dementia, word fluency, response time, memory, nor visuomotor procedural learning predicted CA or CCA performance. This deficit in cognitive planning suggests a functional link between the cerebellum, basal ganglia, and the frontal lobe concerning specific cognitive processes. However, the exact role of the cerebellum in cognitive planning remains undetermined. PMID:1641142
Strauss, M E
Schizophrenia is characterized by a variety of cognitive dysfunctions. Information-processing dysfunctions differ between clinical subtypes such that nonparanoid schizophrenia patients attend less than paranoid schizophrenia patients to connotative or contextual aspects of stimuli. The positive and negative symptom dimensions are also associated with distinct cognitive deficits. In general, positive symptoms are related to auditory-processing deficits and negative symptoms to visual/motor dysfunctions. The interaction of frontal and septohippocampal brain systems, and failures of information-processing automaticity and self-monitoring, have been proposed as the bases of positive symptoms. Negative symptoms are thought to arise from abnormalities in the complex interactions of frontal and striatal systems. Recent theoretical analyses have recommended a focus on the cognitive and neuropsychological analysis of specific symptoms (e.g., hallucinations and delusions) instead of on the more heterogeneous symptom clusters or dimensions. Studies of specific symptoms indicate that patients with hallucinations have deficits in discriminating the source of information. Delusions have been related to abnormal inference processes as well as abnormal perceptual experiences. Studies should now examine the links between information-processing abnormalities and symptoms over time, as the latter change, within the framework of explicit, disconfirmable theoretical models. PMID:8322033
V V Zakharov
Full Text Available Both mild and moderate cognitive impairments (CIs that cause no professional and social disadaptation have recently been of interest to physicians and investigators. Epidemiological surveys suggest that CIs not progressing to the manifestations of dementia are noted in the majority of elderly neurological outpatients. Both dementia and non-dementia CIs is a multietiological syndrome; the clinical features of these impairments are therewith determined by their cause. The most sensitive neuropsychological tests, such as the Montreal Cognitive Assessment (MoCA test should be used to diagnose non-dementia CIs. Moderate CIs are associated with the high risk of dementia (10—15% yearly. As of now, the generally accepted management protocol for patients with mild and moderate CIs has not worked out. However, drugs with neuroprotective properties are of first-priority in treating CIs, by taking into account the high risk of their progression.
Volkert, J; Schiele, M A; Kazmaier, Julia; Glaser, Friederike; Zierhut, K C; Kopf, J; Kittel-Schneider, S; Reif, A
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
Dramsdahl, Margaretha; Westerhausen, René; Haavik, Jan;
The objective of the present study was to investigate the ability of adults with Attention-Deficit/Hyperactivity Disorder (ADHD) to direct their attention and exert cognitive control in a forced instruction dichotic listening (DL) task. The performance of 29 adults with ADHD was compared with 58......-forced condition), or to focus and report either the right- or left-ear syllable (forced-right and forced-left condition). This procedure is presumed to tap distinct cognitive processes: perception (non-forced condition), orienting of attention (forced-right condition), and cognitive control (forced-left condition......). Adults with ADHD did not show significant impairment in the conditions tapping perception and attention orientation, but were significantly impaired in their ability to report the left-ear syllable during the forced-left instruction condition, whereas the control group showed the expected left...
Wiecki, Thomas V; Frank, Michael J
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
Kannan, Geetha; Pletnikov, Mikhail V.
Cognitive deficits are a core feature of schizophrenia. Epidemiological evidence indicates that microbial pathogens may contribute to cognitive impairment in patients with schizophrenia. Exposure to Toxoplasma gondii (T. gondii) has been associated with cognitive deficits in humans. However, the mechanisms whereby the parasite impacts cognition remain poorly understood. Animal models of T. gondii infection may aid in elucidating the underpinnings of cognitive dysfunction. Here, we (1) overvie...
Kally C O'Reilly
Full Text Available Despite substantial effort and immense need, the treatment options for major neuropsychiatric illnesses like schizophrenia are limited and largely ineffective at improving the most debilitating cognitive symptoms that are central to mental illness. These symptoms include cognitive control deficits, the inability to selectively use information that is currently relevant and ignore what is currently irrelevant. Contemporary attempts to accelerate progress are in part founded on an effort to reconceptualize neuropsychiatric illness as a disorder of neural development. This neurodevelopmental framework emphasizes abnormal neural circuits on the one hand, and on the other, it suggests there are therapeutic opportunities to exploit the developmental processes of excitatory neuron pruning, inhibitory neuron proliferation, elaboration of myelination, and other circuit refinements that extend through adolescence and into early adulthood. We have crafted a preclinical research program aimed at cognition failures that may be relevant to mental illness. By working with a variety of neurodevelopmental rodent models we strive to identify a common pathophysiology that underlies cognitive control failure as well as a common strategy for improving cognition in the face of neural circuit abnormalities. Here we review our work to characterize cognitive control deficits in rats with a neonatal ventral hippocampus lesion and rats that were exposed to Methylazoxymethanol acetate (MAM in utero. We review our findings as they pertain to early developmental processes, including neurogenesis, as well as the power of cognitive experience to refine neural circuit function within the mature and maturing brain’s cognitive circuitry.
Murray, Laura L.
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…
Stewart, Lynn A; Wilton, Geoff; Sapers, Jeremy
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. PMID:26341309
Holthausen, EAE; Wiersma, D; Sitskoorn, MM; Hijman, R; Dingemans, PM; Schene, AH; van den Bosch, RJ
Some schizophrenic patients do not show clinically relevant cognitive deficits. The question remains whether this represents the existence of an etiologically different subgroup, a general effect of disease severity or whether their cognitive deficits do not reach a clinical threshold due to a great
Nekovářová, Tereza; Stuchlík, Aleš; Valeš, Karel; Rambousek, Lukáš; Sumiyoshi, T.
New York: Nova Science Publisher, 2012 - (Sumiyoshi, T.), s. 291-319 ISBN 978-1-61942-459-3 R&D Projects: GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GA309/09/0286; GA ČR(CZ) GCP303/10/J032 Institutional research plan: CEZ:AV0Z50110509 Keywords : schizophrenia * cognitive deficits * animal models * behavior Subject RIV: FH - Neurology
Rivera-Flores, Gladys Wilma
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…
Researchers have argued against deficit-based explanations of students' troubles with mathematical sense-making, pointing instead to factors such as epistemology: students' beliefs about the nature of knowledge and learning can hinder them from activating and integrating productive knowledge they have. But such explanations run the risk of substituting an epistemological deficit for a concepts/skills deficit. Our analysis of an undergraduate engineering major avoids this "deficit trap" by incorporating multiple, context-dependent epistemological stances into his cognitive dynamics.
Full Text Available Sara Calderoni,1 Pamela Fantozzi,1 Sandra Maestro,1 Elena Brunori,1 Antonio Narzisi,1 Giulia Balboni,2 Filippo Muratori1,31Department of Child Neurology and Psychiatry, IRCCS Stella Maris Foundation, 2Department of Surgery, Medical, Molecular and Critical Area Pathology, University of Pisa, 3Department of Developmental Medicine, University of Pisa, Pisa, ItalyBackground: A growing, but conflicting body of literature suggests altered empathic abilities in subjects with anorexia nervosa-restricting type (AN-R. This study aims to characterize the cognitive and affective empathic profiles of adolescents with purely AN-R.Methods: As part of a standardized clinical and research protocol, the Interpersonal Reactivity Index (IRI, a valid and reliable self-reported instrument to measure empathy, was administered to 32 female adolescents with AN-R and in 41 healthy controls (HC comparisons, matched for age and gender. Correlational analyses were performed to evaluate the links between empathy scores and psychopathological measures.Results: Patients scored significantly lower than HC on cognitive empathy (CE, while they did not differ from controls on affective empathy (AE. The deficit in CE was not related to either disease severity nor was it related to associated psychopathology.Conclusion: These results, albeit preliminary, suggest that a dysfunctional pattern of CE capacity may be a stable trait of AN-R that should be taken into account not only for the clinical management, but also in preventive and therapeutic intervention.Keywords: anorexia nervosa-restricting type, cognitive empathy, affective empathy, female adolescents, Interpersonal Reactivity Index
Georgy, Gehan S; Nassar, Noha N; Mansour, Hanaa A; Abdallah, Dalaal M
Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ) on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i) vehicle- (ii) CBL- and (iii) STZ diabetic-control as well as (iv) STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%), which were associated by weight loss, elevated tumor necrosis factor (TNF)-α and decreased insulin growth factor (IGF)-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp)-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU), glycine, serotonin (5-HT) and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti-inflammatory, antioxidant and
Gehan S Georgy
Full Text Available Cerebrolysin (CBL, a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF, is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i vehicle- (ii CBL- and (iii STZ diabetic-control as well as (iv STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%, which were associated by weight loss, elevated tumor necrosis factor (TNF-α and decreased insulin growth factor (IGF-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU, glycine, serotonin (5-HT and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti
Full Text Available 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.
Full Text Available Face-voice integration has been extensively explored among healthy participants during the last decades. Nevertheless, while binding alterations constitute a core feature of many psychiatric diseases and have been thoroughly investigated in schizophrenia and autism, these crossmodal processes have been little explored in other psychiatric populations, and notably in addictions. As an illustration, alcohol-dependence is associated with a wide range of psychological, cognitive and cerebral consequences, among which affective disturbances hold a crucial position. Indeed, it has been shown during the last decade that alcohol-dependent individuals present important emotional impairments, particularly in the decoding of affective faces and voices. In view of the role they play in the development and maintenance of alcohol-dependence, it appears crucial to deepen the understanding of these deficits, and notably to determine their evolution in more ecological settings. Indeed, these decoding deficits have up to now been exclusively explored in unimodal studies (i.e. focusing on one sensorial modality while in real life situations, emotional stimulations are most often multimodal. The central objective of the present paper is thus to present recent studies using an integrative approach combining behavioural, electrophysiological and neuroimaging techniques to explore the audio-visual integration of emotional stimuli in alcohol-dependence. These results, clearly showing that alcohol-dependence leads to altered crossmodal processing of affective faces and voices, constitute a first step towards a multidisciplinary exploration of crossmodal processing in psychiatry, extending to other stimulations, sensorial modalities and populations. Finally, the fundamental and clinical implications of this research perspective will also be underlined.
Maier, Larissa J; Wunderli, Michael D; Vonmoos, Matthias; Römmelt, Andreas T; Baumgartner, Markus R; Seifritz, Erich; Schaub, Michael P; Quednow, Boris B
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
Larissa J Maier
Full Text Available 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.
Kihara Michael; de Haan Michelle; Were Eugene O; Garrashi Harrun H; Neville Brian GR; Newton Charles RJC
Abstract Background Pneumococcal meningitis (PM) is a severe and life-threatening disease that is associated with cognitive impairment including learning difficulties, cognitive slowness, short-term memory deficits and poor academic performance. There are limited data on cognitive outcomes following exposure to PM from Africa mainly due to lack of culturally appropriate tools. We report cognitive processes of exposed children as measured by auditory and visual event-related potentials. Method...
Valdois, Sylviane; Bosse, Marie-Line; Tainturier, Marie-Josèphe
There is strong converging evidence suggesting that developmental dyslexia stems from a phonological processing deficit. However, this hypothesis has been challenged by the widely admitted heterogeneity of the dyslexic population, and by several reports of dyslexic individuals with no apparent phonological deficit. In this paper, we discuss the hypothesis that a phonological deficit may not be the only core deficit in developmental dyslexia and critically examine several alternative proposals...
J Gordon Millichap
The relationship between cognitive impairment, fine motor deficits, and T2-weighted MRI intensities in neurofibromatosis type 1 (NF1) was investigated in 100 patients and 100 healthy controls in a study at University Hospital of Munster, Germany.
Schulz, Kurt P.; Bédard, Anne-Claude V.; Jin Fan; Clerkin, Suzanne M.; Danai Dima; Newcorn, Jeffrey H.; Halperin, Jeffrey M.
Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD) across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functi...
Guillermo Gonzalez-Burgos; Fish, Kenneth N.; Lewis, David A.
Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, c...
Skagerlund, Kenny; Träff, Ulf
This study investigated if developmental dyscalculia (DD) in children with different profiles of mathematical deficits has the same or different cognitive origins. The defective approximate number system hypothesis and the access deficit hypothesis were tested using two different groups of children with DD (11-13 years old): a group with…
Denis, Isabelle; Guay, Marie-Claude; Foldes-Busque, Guillaume; BenAmor, Leila
Twenty-five percent of children with ADHD also have an anxiety disorder (AD). As per Quay and in light of Barkley's model, anxiety may have a protective effect on cognitive deficits and behaviors associated with ADHD. This study aimed to evaluate the effect of treating AD on cognitive deficits and behaviors associated with ADHD in children with both disorders. Twenty-four children with ADHD and AD were divided into two groups: treatment for AD, and wait list. Participants were assessed at pre-treatment, post-treatment, and 6-month follow-up with the ADIS-C, the CBCL, and neuropsychological measures. The results revealed a significant improvement in automatic response inhibition and flexibility, and a decrease in inattention/hyperactivity behaviors following the treatment for AD. No significant differences were observed in motor response inhibition, working memory, or attention deficits. The results do not seem to support Quay's hypothesis: treating AD did not exacerbate cognitive deficits and behaviors associated with ADHD in our sample. PMID:26323585
Mackenzie, Catherine; Green, Jan
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…
Background: Malaria infecting the central nervous system (CNS) affects over 575,000 children annually in sub-Saharan Africa leading to cognitive deficits. The effect of this form of malaria on everyday behaviour and academic achievement has not been investigated in Uganda. In addition, no interventions have been carried out for children whose cognitive functioning has been affected by CNS malaria. Main objective: To investigate the effectiveness of a rehabilitation program for cognitive de...
Rosenfeld, Andrew J.; Lieberman, Jeffrey A; Jarskog, L. Fredrik
Until recently, the social cognitive impairment in schizophrenia has been underappreciated and remains essentially untreated. Deficits in emotional processing, social perception and knowledge, theory of mind, and attributional bias may contribute to functional social cognitive impairments in schizophrenia. The amygdala has been implicated as a key component of social cognitive circuitry in both animal and human studies. In addition, structural and functional studies of schizophrenia reproduci...
Adler, Samantha M; Schmauss, Claudia
Studies showed that histone deacetylase (HDAC) inhibitors can reverse cognitive deficits found in neurodegenerative disorders and age-related memory decline. However, the role of HDACs in stress-induced cognitive deficits has not been investigated. In the stress-susceptible mouse strain Balb/c, early life stress triggers a persistent decrease in HDAC expression in the forebrain neocortex, including reduced expression of class I HDACs. The same mice show pronounced cognitive deficits in adulthood, namely deficits in working memory and attention set-shifting. Here we show that these mice also exhibit reduced association of HDAC1 with promotor III of the brain-derived neurotrophic factor (Bdnf) gene, and that cognitive testing leads to abnormally increased Bdnf mRNA expression. A pharmacological reduction of Bdnf-tropomyosine kinase B receptor signaling effectively reverses the cognitive deficits, indicating that enhanced transcriptional activation of the Bdnf gene contributes to their emergence. In contrast to Balb/c mice, C57Bl/6 mice only develop attention set-shifting deficits when raised by Balb/c foster mothers during the time the pups are exposed to early life stress. HDAC1 levels at Bdnf promotor III are unaltered in such C57Bl/6 mice, although they exhibit decreased levels of HDAC1 at the promotor of the early-growth response gene 2 (Egr2) and abnormally increased Egr2 mRNA expression after cognitive testing. Hence, contrary to the beneficial effects of HDAC inhibition in neurodegenerative diseases, the reduced HDAC1 levels at promotors of distinct plasticity-associated genes predispose animals exposed to early life stress to enhanced expression of these genes upon cognitive challenge, an effect that negatively influences cognitive task performance. PMID:27260837
Gehring, Karin; Roukema, Jan Anne; Sitskoorn, Margriet M
Research has demonstrated that patients with cancer experience cognitive deficits, often due to aggressive anticancer treatments. In this article, we critically review the interventional studies that have been conducted to investigate beneficial effects on cognitive function in cancer patients. Pharmacological agents that have been studied include psychostimulants, such as methylphenidate and modafinil, erythropoietin, and hormonal (supplement) treatments for patients who receive hormonal suppression therapy. In addition, several cognitive rehabilitation programs have been evaluated in cancer patients. Recently, the approach of physical exercise to treat cognitive deficits has received great interest, and findings from novel studies are keenly anticipated. Although, in general, the studies reviewed were well designed, future studies may wish to include larger sample sizes and pay more attention to the accurate assessment of cognitive function. PMID:22316373
Fagerlund, Birgitte; Pagsberg, A Katrine; Hemmingsen, Ralf
profile and severity of cognitive impairments in first-episode early onset psychotic patients who received the schizophrenia diagnosis to those diagnosed with other non-organic, non-affective psychotic disorders. The secondary purpose was to examine whether the profile of cognitive deficits, in terms of......Cognitive deficits have been found to be prevalent in early onset schizophrenia. Whether these deficits also characterise other early onset psychotic disorders to a similar degree is unclear, as very few comparative studies have been done. The primary purpose of this study was to compare the...... intelligence, executive functions, memory, attention and processing speed was global or specific. First-episode psychotic adolescents (N = 39) between the ages 11 and 17 years were included, 18 of whom were diagnosed with schizophrenia, and 21 with other non-organic, non-affective psychoses, using ICD-10...
Jonathan Williams; Eric Taylor
The underlying defects in ADHD (Attention Deficit/Hyperactivity Disorder) are not yet clear. The current paper tests three existing theories: State Regulation, Cognitive Deficit, and Temporal Difference (TD) learning. We present computational simulations of the Matching Familiar Figures Task and compare these with the experimental results reported by Sonuga- Barke (2002). The TD model contains four parameters: the learning rate, discounting for future rewards, br...
Mateou, Nicos H.; Zombanakis, George A.
This paper offers an alternative approach to policy modeling aiming at considering the question of the Greek current account deficit sustainability using Fuzzy Cognitive Maps (FCM). Given that the large Greek current account deficit figures reported during the past few years have become the source of increasing concern regarding its sustainability and bearing in mind the wide variety of views on this issue, we have chosen to resort to an entirely different technique compared to traditional po...
Skagerlund, Kenny; Träff, Ulf
This study investigated if developmental dyscalculia (DD) in children with different profiles of mathematical deficits has the same or different cognitive origins. The defective approximate number system hypothesis and the access deficit hypothesis were tested using two different groups of children with DD (11-13 years old): a group with arithmetic fact dyscalculia (AFD) and a group with general dyscalculia (GD). Several different aspects of number magnitude processing were assessed in these ...
Solomon, Marjorie; Ozonoff, Sally; Ursu, Stefan; Ravizza, Susan; Cummings, Neil; Ly, Stanford; Carter, Cameron
Executive functions deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive functions deficits in ASDs, and only one in adolescents. The current study examined cognitive control –the ability to maintain task context online to support adaptive functioning in the face of response competition—in 22 adolescents aged 12–18 with ...
Wu, Dong-mei [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Lu, Jun, E-mail: email@example.com [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Zhang, Yan-qiu [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zheng, Yuan-lin, E-mail: firstname.lastname@example.org [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Hu, Bin [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China); Cheng, Wei [School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, Jiangsu Province (China); Zhang, Zi-feng; Li, Meng-qiu [Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province (China)
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.
Fosco, Whitney D.; Hawk, Larry W.; Rosch, Keri S; Bubnik, Michelle G
Background Attention Deficit/Hyperactivity Disorder is associated with cognitive deficits and dysregulated motivation. Reinforcement improves cognitive performance, often to a greater degree among children with ADHD compared to typically-developing controls. The current study tests the degree to which cognitive (individual differences in baseline cognition) and/or motivational (individual differences in Sensitivity to Reward; SR) processes can account for diagnostic group differences in reinf...
Bikic, Aida; Leckman, J. F.; Lindschou, Jane; Ø. Christensen, Torben; Dalsgaard, Søren
BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by symptoms of inattention and impulsivity and/or hyperactivity and a range of cognitive dysfunctions. Pharmacological treatment may be beneficial; however, many affected individuals...... continue to have difficulties with cognitive functions despite medical treatment, and up to 30 % do not respond to pharmacological treatment. Inadequate medical compliance and the long-term effects of treatment make it necessary to explore nonpharmacological and supplementary treatments for ADHD. Treatment...... parts of cognition, mostly on the working memory or attention but with poor generalization of training on other cognitive functions and functional outcome. Children with ADHD have a variety of cognitive dysfunctions, and it is important that cognitive training target multiple cognitive functions...
Kerns, Kimberley A.; Don, Audrey; Mateer, Catherine A.; Streissguth, Ann P.
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…
Deshpande, Laxmikant S; Sun, David A; Sombati, Sompong; Baranova, Anya; Wilson, Margaret S; Attkisson, Elisa; Hamm, Robert J; DeLorenzo, Robert J
Traumatic brain injury (TBI) survivors often suffer from a post-traumatic syndrome with deficits in learning and memory. Calcium (Ca(2+)) has been implicated in the pathophysiology of TBI-induced neuronal death. However, the role of long-term changes in neuronal Ca(2+) function in surviving neurons and the potential impact on TBI-induced cognitive impairments are less understood. Here we evaluated neuronal death and basal free intracellular Ca(2+) ([Ca(2+)](i)) in acutely isolated rat CA3 hippocampal neurons using the Ca(2+) indicator, Fura-2, at seven and thirty days after moderate central fluid percussion injury. In moderate TBI, cognitive deficits as evaluated by the Morris Water Maze (MWM), occur after injury but resolve after several weeks. Using MWM paradigm we compared alterations in [Ca(2+)](i) and cognitive deficits. Moderate TBI did not cause significant hippocampal neuronal death. However, basal [Ca(2+)](i) was significantly elevated when measured seven days post-TBI. At the same time, these animals exhibited significant cognitive impairment (F(2,25)=3.43, p<0.05). When measured 30 days post-TBI, both basal [Ca(2+)](i) and cognitive functions had returned to normal. Pretreatment with MK-801 blocked this elevation in [Ca(2+)](i) and also prevented MWM deficits. These studies provide evidence for a link between elevated [Ca(2+)](i) and altered cognition. Since no significant neuronal death was observed, the alterations in Ca(2+) homeostasis in the traumatized, but surviving neurons may play a role in the pathophysiology of cognitive deficits that manifest in the acute setting after TBI and represent a novel target for therapeutic intervention following TBI. PMID:18583041
Bliksted, Vibeke Fuglsang; Fagerlund, Birgitte; Weed, Ethan;
BACKGROUND: Recent research has shown a significant impact of social cognitive domains on real world functioning and prognosis in schizophrenia. However, the correlations between specific aspects of social cognition, neurocognition, IQ and clinical symptoms remain unclear in first...... clinical symptoms. RESULTS: Data from 36 first-episode schizophrenia patients and 36 one to one matched healthy controls were analysed. Principal component analysis in the patient group was used to examine the variance contributed by different aspects of social cognition, neurocognition, and clinical...... symptoms. CONCLUSIONS: Complex aspects of social cognition explained 24% of the variance in the patient group. The other principal components consisted mainly of aspects of simple perception of theory of mind. Neurocognition and clinical symptoms only explained a minor proportion of the variance in the...
Kułakowska, Dorota; Biernacka, Katarzyna; Wilkos, Ewelina; Rybakowski, Filip; Kucharska-Pietura, Katarzyna
In the first part of the article the authors present a set of the actual concepts explaining problems of cognitive functions and social cognition currently observed in patients with anorexia nervosa (AN). It is possible; through the neuroimaging research, to get better understanding of the brain specifics in these individuals. Even though, the AN remains a disease with very complex and multifactorial etiology which remains a huge medical challenge. Currently, popular is the view that takes in...
Georgy, Gehan S.; Nassar, Noha N.; Mansour, Hanaa A.; Dalaal M. Abdallah
Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect...
Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte; Pagsberg, Anne Katrine;
Cognitive deficits in several domains have been demonstrated in early-onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early-onset schizo...... characterized by a broad and jagged profile of cognitive deficits. Deficits of attention and verbal recall of stories appear not to be accounted for by deficits in intelligence, and the severity of cognitive deficits seems independent from that of depressive symptoms.......Cognitive deficits in several domains have been demonstrated in early-onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early......-onset schizophrenia patients, assess the potential associations with depressive symptom severity, and examine whether cognitive deficits within several domains reflect intelligence impairments. This study compared attention, visual-construction, aspects of visual and verbal memory, and executive functions in chronic...
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.
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 asso...
Silva, Dina; Albers, Ulrike; Santana, Isabel; Vicente, Margarida; Martins, Isabel Pavão; Verdelho, Ana; Guerreiro, Manuela; de-Mendonça, Alexandre
Background Vitamin B12 deficiency is common in older people, and may be responsible for reversible dementia. Low serum vitamin B12 levels were also observed in patients with Mild Cognitive Impairment (MCI). It is not known whether patients with vitamin B12 deficiency have a distinctive profile of cognitive impairment different from the episodic memory deficit usually observed in MCI. Results From a cohort of 310 patients with MCI followed in a memory clinic in Lisbon, only 10 cases with vitam...
Sotiropoulos, I.; Catania, C; Pinto, Lucilia G.; Silva, Rui; Pollerberg, G. Elizabeth; Takashima, Akihiko; Sousa, Nuno; Almeida, O.F.X.
Stressful life experiences are likely tiological factors in sporadic forms of Alzheimer’s disease (AD). Many AD patients hypersecrete glucocorticoids (GCs), and their GC levels correlate with the rate of cognitive impairment and extent of neuronal atrophy. Severity of cognitive deficits in AD correlates strongly with levels of perphosphorylated forms of the cytoskeletal protein TAU, an essential mediator of the actions of amyloid Beta (ABeta ), another molecule with a key pathogenic role in ...
Blackman, Rachael K.; MacDonald, Angus W; Chafee, Matthew V
Cognitive deficits are at the crux of why many schizophrenia patients have poor functional outcomes. One of the cognitive symptoms experienced by schizophrenia patients is a deficit in context processing, the ability to use contextual information stored in working memory to adaptively respond to subsequent stimuli. As such, context processing can be thought of as the intersection between working memory and executive control. Although deficits in context processing have been extensively charac...
Debes, Frodi; Weihe, Pál; Grandjean, Philippe
Prenatal exposure to mercury has been associated with adverse effects on child neurodevelopment. The present study aims to determine the extent to which methylmercury-associated cognitive deficits persist into adult age. In a Faroese birth cohort originally formed in 1986-1987 (N = 1,022), prenatal...... concentration. Deficits were also present in all other tests applied, although most were not statistically significant. Structural equation models were developed to ascertain the possible differences in vulnerability of specific functional domains and the overall association with general intelligence. In models...... corresponds to about 2.2 IQ points at a 10-fold increased prenatal methylmercury exposure. Thus, although the cognitive deficits observed were smaller than at examinations at younger ages, maternal diets with contaminated seafood were associated with adverse effects in this birth cohort at age 22 years. The...
Preiss, M.; Kučerová, H.; Lukavský, Jiří; Štěpánková, H.; Šóš, P.; Kawaciuková, R.
Roč. 169, č. 3 (2009), s. 235-239. ISSN 0165-1781 R&D Projects: GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z70250504 Keywords : major depressive episode * remission * cognitive function Subject RIV: AN - Psychology Impact factor: 2.373, year: 2009
McCauley, Elizabeth; And Others
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.…
Cerebral blood flow pattern in Parkinson's disease was examined by 123I-IMP SPECT to determine whether the deficit in cognitive function is reflected in it. The patient group with Parkinson's disease showed deterioration in intelligence (Minimental state examination, Raven's Colored Progressive Matrices) and frontal lobe test (the Wisconsin Card Sorting Test). Though the uptake ratio of prefrontal area/occipital area in 123I-IMP SPECT study varied widely in the Parkinson's disease group compared to the normal control group, there was no significant difference in the mean. Selective depletion of frontal lobe blood flow was not confirmed in this study. There was no correlation between cerebral blood flow pattern and cognitive functions including frontal lobe function and intelligence. We concluded that the deficit in cognitive function was not reflected in the cerebral blood flow pattern in Parkinson's disease. (author)
Danet, M.; Lapiz-Bluhm, S.; Morilak, David A
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-ind...
Wang, Suo-bin; Jia, Jian-ping
Aim: Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait (the Chinese herb Kushen) and exhibits diverse pharmacological actions. In this work we investigated the effects of OMT on diabetes-associated cognitive decline (DACD) in a rat model of diabetes and explored the mechanisms of action. Methods: Male Wistar rats were injected with streptozotocin (65 mg/kg, ip) once to induce diabetes. The rats were then treated with vehicle or OMT (60 or 1...
Hort, J.; Laczó, J.; Vyhnálek, M.; Bojar, M.; Bureš, Jan; Vlček, Kamil
Roč. 104, č. 10 (2007), s. 4042-4047. ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA309/06/1231; GA MŠk(CZ) 1M0517; GA ČR(CZ) GA309/05/0693 Institutional research plan: CEZ:AV0Z50110509 Keywords : Mild cognitive impairment * spatial navigation * Alzheimer’s Disease Subject RIV: FH - Neurology Impact factor: 9.598, year: 2007
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.
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. Published by Elsevier Science Ltd on behalf of COSPAR.
Wallace, J; Marston, H M; McQuade, R; Gartside, S E
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
Sithisarn, Pongtip; Rojsanga, Piyanuch; Jarikasem, Siripen; Tanaka, Ken; Matsumoto, Kinzo
Acanthopanax trifoliatus is a plant that has been traditionally used in Thailand as a vegetable and a tonic. This study investigated effects of the aqueous extract of its leaves (ATL) on cognitive and emotional deficits using an olfactory bulbectomized mouse (OBX) model. OBX mice were treated daily with ATL (250 and 500 mg/kg, p.o.) 3 days after OBX. Antidementia drug tacrine (2.5 mg/kg/day) and antidepressant drug imipramine (10 mg/kg/day) were given i.p. as reference drugs. OBX significantl...
Willner, Paul; Goodey, Rebecca
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…
Alexander, Gregory E; Satalich, Timothy A; Shankle, W Rodman; Batchelder, William H
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. (PsycINFO Database Record PMID:26214016
Aarsen, Femke K; Paquier, Philippe F; Arts, Willem-Frans; Van Veelen, Marie-Lise; Michiels, Erna; Lequin, Maarten; Catsman-Berrevoets, Coriene E
PURPOSE To prospectively study cognitive deficits and predictors 3 years after diagnosis in a large series of pediatric patients treated for pilocytic astrocytoma (PA). PATIENTS AND METHODS Sixty-one of 67 children were grouped according to infratentorial, supratentorial midline, and supratentorial hemispheric site. Intelligence, memory, attention, language, visual-spatial, and executive functions were assessed. Included predictors were sex, age, relapse, diagnosis-assessment interval, hydrocephalus, kind of treatment, and tumor variables. Results All children with PA had problems with sustained attention and speed. In the infratentorial group, there also were deficits in verbal intelligence, visual-spatial memory, executive functioning, and naming. Verbal intelligence and verbal memory problems occurred in the brainstem tumor group. The supratentorial hemispheric tumor group had additional problems with selective attention and executive functioning, and the supratentorial midline tumor group displayed no extra impairments. More specifically, the dorsal supratentorial midline tumor group displayed problems with language and verbal memory. Predictors for lower cognitive functioning were hydrocephalus, radiotherapy, residual tumor size, and age; predictors for better functioning were chemotherapy or treatment of hydrocephalus. Almost 60% of children had problems with academic achievement, for which risk factors were relapse and younger age at diagnosis. CONCLUSION Despite normal intelligence at long-term follow-up, children treated for PA display invalidating cognitive impairments. Adequate treatment of hydrocephalus is important for a more favorable long-term cognitive outcome. Even children without initial severe deficits may develop cognitive impairments years after diagnosis, partly because of the phenomenon of growing into deficit, which has devastating implications for academic achievement and quality of life (QOL). PMID:19433687
Aharonovich, Efrat; Brooks, Adam C.; Nunes, Edward V.; Hasin, Deborah S.
Clinical variables that affect treatment outcome for marijuana dependent individuals are not yet well understood, including the effects of cognitive functioning. To address this, level of cognitive functioning and treatment outcome were investigated. Twenty marijuana-dependent outpatients were administered a neuropsychological battery at treatment entry. All patients received 12 weekly individual sessions of combined motivational enhancement therapy and cognitive behavioral therapy. The Wilco...
Maschio, Marta; Dinapoli, Loredana; Fabi, Alessandra; Giannarelli, Diana; Cantelmi, Tonino
The aim of this pilot observational study was to evaluate effect of cognitive rehabilitation training (RehabTr) on cognitive performances in patients with brain tumor-related epilepsy (BTRE) and cognitive disturbances. Medical inclusion criteria: patients (M/F) ≥ 18 years ≤ 75 with symptomatic seizures due to primary brain tumors or brain metastases in stable treatment with antiepileptic drugs; previous surgical resection or biopsy; >70 Karnofsky Performance Status; stable oncological disease. Eligible patients recruited from 100 consecutive patients with BTRE at first visit to our Center from 2011 to 2012. All recruited patients were administered battery of neuropsychological tests exploring various cognitive domains. Patients considered to have a neuropsychological deficit were those with at least one test score for a given domain indicative of impairment. Thirty patients out of 100 showed cognitive deficits, and were offered participation in RehabTr, of which 16 accepted (5 low grade glioma, 4 high grade glioma, 2 glioblastoma, 2 meningioma and 3 metastases) and 14 declined for various reasons. The RehabTr consisted of one weekly individual session of 1 h, for a total of 10 weeks, carried out by a trained psychologist. The functions trained were: memory, attention, visuo-spatial functions, language and reasoning by means of Training NeuroPsicologico (TNP(®)) software. To evaluate the effect of the RehabTr, the same battery of tests was administered directly after cognitive rehabilitation (T1), and at six-month follow-up (T2). Statistical analysis with Student T test for paired data showed that short-term verbal memory, episodic memory, fluency and long term visuo-spatial memory improved immediately after the T1 and remained stable at T2. At final follow-up all patients showed an improvement in at least one domain that had been lower than normal at baseline. Our results demonstrated a positive effect of rehabilitative training at different times, and, for
Full Text Available Objective: To evaluate the influence of environmental enrichment (EE on memory, cytokines, and brain-derived neurotrophic factor (BDNF in the brain of adult rats subjected to experimental pneumococcal meningitis during infancy. Methods: On postnatal day 11, the animals received either artificial cerebrospinal fluid (CSF or Streptococcus pneumoniae suspension intracisternally at 1 × 106 CFU/mL and remained with their mothers until age 21 days. Animals were divided into the following groups: control, control + EE, meningitis, and meningitis + EE. EE began at 21 days and continued until 60 days of age (adulthood. EE consisted of a large cage with three floors, ramps, running wheels, and objects of different shapes and textures. At 60 days, animals were randomized and subjected to habituation to the open-field task and the step-down inhibitory avoidance task. After the tasks, the hippocampus and CSF were isolated for analysis. Results: The meningitis group showed no difference in performance between training and test sessions of the open-field task, suggesting habituation memory impairment; in the meningitis + EE group, performance was significantly different, showing preservation of habituation memory. In the step-down inhibitory avoidance task, there were no differences in behavior between training and test sessions in the meningitis group, showing aversive memory impairment; conversely, differences were observed in the meningitis + EE group, demonstrating aversive memory preservation. In the two meningitis groups, IL-4, IL-10, and BDNF levels were increased in the hippocampus, and BDNF levels in the CSF. Conclusions: The data presented suggest that EE, a non-invasive therapy, enables recovery from memory deficits caused by neonatal meningitis.
Anita van Zwieten
Full Text Available 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.
Yang, Li-Chao; Guo, Han; Zhou, Hao; Suo, Da-Qin; Li, Wen-Jun; Zhou, Yu; Zhao, Yun; Yang, Wu-Shuang; Jin, Xin
Oleoylethanolamide (OEA) has been shown to have neuroprotective effects after acute cerebral ischemic injury. The aim of this study was to investigate the effects of chronic OEA treatment on ischemia-induced spatial cognitive impairments, electrophysiology behavior and hippocampal neurogenesis. Daily treatments of 30 mg/kg OEA significantly ameliorated spatial cognitive deficits and attenuated the inhibition of long-term potentiation (LTP) in the middle cerebral artery occlusion (MCAO) rat model. Moreover, OEA administration improved cognitive function in a manner associated with enhanced neurogenesis in the hippocampus. Further study demonstrated that treatment with OEA markedly increased the expressions of brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptors α (PPARα). Our data suggest that chronic OEA treatment can exert functional recovery of cognitive impairments and neuroprotective effects against cerebral ischemic insult in rats via triggering of neurogenesis in the hippocampus, which supports the therapeutic use of OEA for cerebral ischemia. PMID:25748831
UCL's former provost, Sir Derek Roberts, has been drafted in for a year to run the college. UCL is expected to have a 6 million pounds deficit this year and up to a 10 million pounds deficit next year. Sir Christopher Llewellyn-Smith took over at UCL nearly 4 years ago and decided then that the finanical situation was serious enough to warrant a reduction in the vast expansion policy undertaken by his predecessor (1 page).
Barry, Jeremy M; Tian, Chengju; Spinella, Anthony; Page, Matias; Holmes, Gregory L
Cognitive impairment is a common comorbidity in childhood epilepsy. Studies in rodents have demonstrated that frequent seizures during the first weeks of life result in impaired spatial cognition when the rats are tested as juvenile or adults. To determine if spatial cognitive deficits following early-life seizures are task-specific or similar across spatial tasks, we compared the effects of early-life seizures in two spatial assays: 1) the Morris water maze, a hippocampal-dependent task of spatial cognition and 2) the active avoidance task, a task that associates an aversive shock stimulus with a static spatial location that requires intact hippocampal-amygdala networks. Rats with early-life seizures tested as adults did not differ from control rats in the water maze. However, while animals with early-life seizures showed some evidence of learning the active avoidance task, they received significantly more shocks in later training trials, particularly during the second training day, than controls. One possibility for the performance differences between the tasks is that the active avoidance task requires multiple brain regions and that interregional communication could be affected by alterations in white matter integrity. However, there were no measurable group differences with regard to levels of myelination. The study suggests that elucidation of mild cognitive deficits seen following early-life seizures may be dependent on task features of active avoidance. PMID:27152463
Hou, Zonggang; Luo, Wei; Sun, Xuejun; Hao, Shuyu; Zhang, Ying; Xu, Feifan; Wang, Zhongcheng; Liu, Baiyun
Oxidative stress is the principal factor in traumatic brain injury (TBI) that initiates events that result in protracted neuronal dysfunction and remodeling. Importantly, antioxidants can protect the brain against oxidative damage and modulate the capacity of the brain to cope with synaptic dysfunction and cognitive impairment. However, no studies have investigated the effects of hydrogen-rich saline on cognitive deficits after TBI. In the present study, rats with fluid percussion injury (FPI) were used to investigate the protective effects of hydrogen-rich saline. The results showed that hydrogen-rich saline reduced the level of malondialdehyde (MDA) and elevated the level of silent information regulator 2 (Sir2). In addition, treatment with hydrogen-rich saline, which elevated the levels of molecules associated with brain-derived neurotropic factor (BDNF)-mediated synaptic plasticity, improved cognitive performance in the Morris water maze after mild TBI. These results suggest that hydrogen-rich saline can protect the brain against the deleterious effects of mild TBI on synaptic plasticity and cognition and that hydrogen-rich saline could be an effective therapeutic strategy for patients with cognitive deficits after TBI. PMID:22742936
Hebda-Bauer, Elaine K.; Luo, Jie; Watson, Stanley J.; Akil, Huda
Age-related changes in the hippocampus increase vulnerability to impaired learning and memory. Our goal is to understand how a genetic vulnerability to cognitive impairment can be modified by aging and sex. Mice with a mutation in the cAMP response element binding (CREB) protein gene (CREBαδ- deficient mice) have a mild cognitive impairment and show test condition-dependent learning and memory deficits. We tested 3 ages of CREBαδ- deficient and wild-type (WT) mice in 2 Morris water maze (MWM)...
Fagerlund, Birgitte; Pagsberg, A Katrine; Hemmingsen, Ralf
Cognitive deficits have been found to be prevalent in early onset schizophrenia. Whether these deficits also characterise other early onset psychotic disorders to a similar degree is unclear, as very few comparative studies have been done. The primary purpose of this study was to compare the...... intelligence, executive functions, memory, attention and processing speed was global or specific. First-episode psychotic adolescents (N = 39) between the ages 11 and 17 years were included, 18 of whom were diagnosed with schizophrenia, and 21 with other non-organic, non-affective psychoses, using ICD-10...... criteria. A healthy control group (N = 40) was included, matched on gender and age. Cognitive functions were assessed using WISC-III/R, the CANTAB battery, WCST, Trail Making B, fluency tasks, and Buschke's selective reminding task. A similar profile and level of impairment was found on measures of...
Kang, Sung-Han; Yum, Mi-sun; Kim, Eun-Hee; Kim, Hyo-won; Ko, Tae-Sung
Background and Purpose To determine how cognitive function is related to epilepsy classification and comorbid attention deficit hyperactivity disorder (ADHD) in children with newly diagnosed epilepsy of genetic or unknown etiology. Methods The medical records of children aged 6-16 years with newly diagnosed epilepsy of genetic or unknown etiology were reviewed retrospectively. The Korean Education Development Institute-Wechsler Intelligence Scale for Children and the Comprehensive Attention T...
Full Text Available 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 MRI 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 nonword. 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 deficit
Luisa Colucci,1,2 Massimiliano Bosco,2 Antonio Rosario Ziello,1,2 Raffaele Rea,1,2 Francesco Amenta,1 Angiola Maria Fasanaro21Centro di Ricerche Cliniche, Telemedicina e Telefarmacia, Università di Camerino, Camerino, 2Unità Valutazione Alzheimer, Naples, ItalyAbstract: 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 ...
Yerys, Benjamin E.; Wallace, Gregory L.; Sokoloff, Jennifer L.; Shook, Devon A.; James, Joette D.; Kenworthy, Lauren
Recent estimates suggest that over 30% of children with autism spectrum disorders (ASD) meet diagnostic criteria for attention deficit/hyperactivity disorder (ADHD), and another 20% of children with ASD exhibit subthreshold clinical ADHD symptoms. Presence of ADHD symptoms in the context of ASD could have a variety of effects on cognition, autistic traits, and adaptive/maladaptive behaviors including: exacerbating core ASD impairments; adding unique impairments specific to ADHD; producing new...
van der Vaart, Thijs
markdownabstractAbstract Neurofibromatosis type 1(NF1) is a common neurocutaneous disorder (birth incidence 1:2000) caused by heterozygous mutations in NF1, a gene on chromosome 17 encoding neurofibromin, which is a suppressor of the Ras pathway. Cognitive dysfunction and behavioural problems are common features of NF1 during childhood. Preclinical studies have shown that excessive inhibition by GABAergic interneurons leads to a deficit in synaptic plasticity, and that statins can reverse the...
Colucci, Luisa; Bosco, Massimiliano; Rosario Ziello, Antonio; Rea, Raffaele; Amenta, Francesco; Fasanaro, Angiola Maria
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 peri...
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
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 calcu...
Nicholas T Van Dam
Full Text Available Although amnestic mild cognitive impairment (aMCI; often considered a prodromal phase of Alzheimer's disease, AD is most recognized by its implications for decline in memory function, research suggests that deficits in attention are present early in aMCI and may be predictive of progression to AD. The present study used functional magnetic resonance imaging to examine differences in the brain during the attention network test between 8 individuals with aMCI and 8 neurologically healthy, demographically matched controls. While there were no significant behavioral differences between groups for the alerting and orienting functions, patients with aMCI showed more activity in neural regions typically associated with the networks subserving these functions (e.g., temporoparietal junction and posterior parietal regions, respectively. More importantly, there were both behavioral (i.e., greater conflict effect and corresponding neural deficits in executive control (e.g., less activation in the prefrontal and anterior cingulate cortices. Although based on a small number of patients, our findings suggest that deficits of attention, especially the executive control of attention, may significantly contribute to the behavioral and cognitive deficits of aMCI.
Cope, Z A; Powell, S B; Young, J W
Numerous psychiatric disorders whose cognitive dysfunction links to functional outcome have neurodevelopmental origins including schizophrenia, autism and bipolar disorder. Treatments are needed for these cognitive deficits, which require development using animal models. Models of neurodevelopmental disorders are as varied and diverse as the disorders themselves, recreating some but not all aspects of the disorder. This variety may in part underlie why purported procognitive treatments translated from these models have failed to restore functioning in the targeted patient populations. Further complications arise from environmental factors used in these models that can contribute to numerous disorders, perhaps only impacting specific domains, while diagnostic boundaries define individual disorders, limiting translational efficacy. The Research Domain Criteria project seeks to 'develop new ways to classify mental disorders based on behavioral dimensions and neurobiological measures' in hopes of facilitating translational research by remaining agnostic toward diagnostic borders derived from clinical presentation in humans. Models could therefore recreate biosignatures of cognitive dysfunction irrespective of disease state. This review highlights work within the field of neurodevelopmental models of psychiatric disorders tested in cross-species translational cognitive paradigms that directly inform this newly developing research strategy. By expounding on this approach, the hopes are that a fuller understanding of each model may be attainable in terms of the cognitive profile elicited by each manipulation. Hence, conclusions may begin to be drawn on the nature of cognitive neuropathology on neurodevelopmental and other disorders, increasing the chances of procognitive treatment development for individuals affected in specific cognitive domains. PMID:26667374
Siepel, Françoise J; Brønnick, Kolbjørn S; Booij, Jan; Ravina, Bernard M; Lebedev, Alexander V; Pereira, Joana B; Grüner, Renate; Aarsland, Dag
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
Kurt P. Schulz
Full Text Available Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functional magnetic resonance imaging while performing a face emotion go/no-go task. Event-related analyses contrasted activation and functional connectivity for cognitive control collapsed over face valence and tested for variations in activation for response execution and inhibition as a function of face valence. Probands with childhood ADHD made fewer correct responses and inhibitions overall than comparison subjects, but demonstrated comparable effects of face emotion on response execution and inhibition. The two groups showed similar frontotemporal activation for cognitive control collapsed across face valence, but differed in the functional connectivity of the right dorsolateral prefrontal cortex, with fewer interactions with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in probands than in comparison subjects. Further, valence-dependent activation for response execution was seen in the amygdala, ventral striatum, subgenual cingulate cortex, and orbitofrontal cortex in comparison subjects but not in probands. The findings point to functional anomalies in limbic networks for both the valence-dependent biasing of cognitive control and the valence-independent cognitive control of face emotion processing in probands with childhood ADHD. This limbic dysfunction could impact cognitive control in emotional contexts and may contribute to the social and emotional problems associated with ADHD.
Paul C.P. Curtin
Full Text Available 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
Titus, David J; Furones, Concepcion; Atkins, Coleen M; Dietrich, W Dalton
Mild elevations in core temperature can occur in individuals involved in strenuous activities that are risky for potentially sustaining a mild traumatic brain injury (mTBI) or concussion. Recently, we have discovered that mild elevations in brain temperature can significantly aggravate the histopathological consequences of mTBI. However, whether this exacerbation of brain pathology translates into behavioral deficits is unknown. Therefore, we investigated the behavioral consequences of elevating brain temperature to mildly hyperthermic levels prior to mTBI. Adult male Sprague Dawley rats underwent mild fluid-percussion brain injury or sham surgery while normothermic (37 °C) or hyperthermic (39 °C) and were allowed to recover for 7 days. Animals were then assessed for cognition using the water maze and cue and contextual fear conditioning. We found that mTBI alone at normothermia had no effect on long-term cognitive measures whereas mTBI animals that were hyperthermic for 15 min prior to and for 4h after brain injury were significantly impaired on long-term retention for both the water maze and fear conditioning. In contrast, hyperthermic mTBI animals cooled within 15 min to normothermia demonstrated no significant long-term cognitive deficits. Mild TBI irrespective of temperature manipulations resulted in significant short-term working memory deficits. Cortical atrophy and contusions were detected in all mTBI treatment groups and contusion volume was significantly less in hyperthermic mTBI animals that were cooled as compared to hyperthermic mTBI animals that remained hyperthermic. These results indicate that brain temperature is an important variable for mTBI outcome and that mildly elevated temperatures at the time of injury result in persistent cognitive deficits. Importantly, cooling to normothermia after mTBI prevents the development of long-term cognitive deficits caused by hyperthermia. Reducing temperature to normothermic levels soon after mTBI represents
Nakagawa, Yutaka; Chiba, Kenji
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
Harmon, Dominic C
PURPOSE: Cognitive deficit after coronary artery bypass surgery (CABG) has a high prevalence and is persistent. Meta-analysis of clinical trials demonstrates a decreased incidence of stroke after CABG when aprotinin is administrated perioperatively. We hypothesized that aprotinin administration would decrease the incidence of cognitive deficit after CABG. METHODS: Thirty-six ASA III-IV patients undergoing elective CABG were included in a prospective, randomized, single-blinded pilot study. Eighteen patients received aprotinin 2 x 10(6) KIU (loading dose), 2 x 10(6) KIU (added to circuit prime) and a continuous infusion of 5 x 10(5) KIU.hr(-1). A battery of cognitive tests was administered to patients and spouses (n = 18) the day before surgery, four days and six weeks postoperatively. RESULTS: Four days postoperatively new cognitive deficit (defined by a change in one or more cognitive domains using the Reliable Change Index method) was present in ten (58%) patients in the aprotinin group compared to 17 (94%) in the placebo group [95% confidence interval (CI) 0.10-0.62, P = 0.005); (P = 0.01)]. Six weeks postoperatively, four (23%) patients in the aprotinin group had cognitive deficit compared to ten (55%) in the placebo group (95% CI 0.80-0.16, P = 0.005); (P = 0.05). CONCLUSION: In this prospective pilot study, the incidence of cognitive deficit after CABG and cardiopulmonary bypass is decreased by the administration of high-dose aprotinin.
Kamaradova, Dana; Hajda, Miroslav; Prasko, Jan; Taborsky, Jiri; Grambal, Ales; Latalova, Klara; Ociskova, Marie; Brunovsky, Martin; Hlustik, Petr
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.
Full Text Available Background: Cognitive impairment is said to be a core feature of schizophrenia. Executive function is an important cognitive domain. Aim: This study was undertaken to assess cognitive impairment among Indian patients with schizophrenia (Sz or schizoaffective disorder (SzA, compared with their parents and unaffected individuals (controls. Settings and Design: Executive functions as measured by Trail-making Test (TMT, of patients and their parents were compared with controls. The patients were recruited from the Outpatients′ Department (OPD of a government hospital. Materials and Methods: Patients diagnosed as Sz or SzA (n=172 and their parents (n=196: families n=132, 119 fathers and 77 mothers participated. We also included 120 persons with no history of psychiatric illness. Cognitive function was assessed with the TMT. The Information Score of the Post Graduate Institute Battery of Brain Dysfunction test, developed in India for Indian subjects was used as a proxy for general fixed knowledge. Statistical Analysis: Logistic and linear regression was used to compare cognitive deficits of cases, parents and controls. Results: Cases and their parents took significantly more time than controls on Part B of the TMT. There were no statistically significant differences between cases and parents on any of the TMT parameters. Using regression analysis, the most significant correlates of all TMT parameters among cases were with occurrence of auditory hallucinations and current age. Conclusion: Cases, as well as their parents showed more cognitive impairment than controls on the TMT.
Maier, Larissa J.; Wunderli, Michael D; Vonmoos, Matthias; Römmelt, Andreas T.; Baumgartner, Markus R; Seifritz, Erich; Schaub, Michael P.; Quednow, Boris B.
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 p...
Maier, Larissa J.; Wunderli, Michael D.; Vonmoos, Matthias; Römmelt, Andreas T; Baumgartner, Markus R; Seifritz, Erich; Michael P Schaub; Quednow, Boris B.
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 p...
Pershing, Michelle L; Bortz, David M; Pocivavsek, Ana; Fredericks, Peter J; Jørgensen, Christinna Vangsgaard; Vunck, Sarah A; Leuner, Benedetta; Schwarcz, Robert; Bruno, John P
The levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha7 nicotinic acetylcholine receptors (α7nAChRs), are elevated in the brains of patients with schizophrenia (SZ). We reported that increases of brain KYNA in rats, through dietary exposure to its precursor kynurenine from...... prefrontally-mediated set-shifting task. These results highlight the deleterious impact of elevated KYNA levels during sensitive periods of early development, which model the pathophysiological and cognitive deficits seen in SZ....... embryonic day (ED)15 to postnatal day (PD) 21, result in neurochemical and cognitive deficits in adulthood. The present experiments focused on the effects of prenatal exposure to elevated kynurenine on measures of prefrontal excitability known to be impaired in SZ. Pregnant dams were fed a mash containing...... of the α7nAChR (22% and 17% reductions at PD2 and PD56-80), expression of mGluR2 (31% and 24% reductions at ED21 and PD56-80), dendritic spine density (11-14% decrease at PD56-80), subsensitive mesolimbic stimulation of glutamate release in PFC, and reversal/extra-dimensional shift deficits in the...
Erin M Gibson
Full Text Available 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.
Full Text Available Since the number and proportion of old people increases worldwide, health professionals and systems should be made aware and prepared to deal with their problems. Cognitive deficit and symptoms of depression are commom among the elderly, and may occur in relation to various risk factors such as health conditions and psychosocial variables. In order to study cognitive deficit and the presence of signs and symptoms of depression, 62 elderly community subjects enrolled at a Community Health Unit in Porto Alegre, southern Brazil, were interviewed. They were evaluated by means of the Mini Mental State Exam, the Montgomery-Asberg Depression rating scale, and a questionnaire on health conditions, living arrangements and social variables. Higher levels of symptoms of depression were observed among subjects exposed to major risk factors for cerebrovascular diseases (diabetes and coronary disease, while impaired cognitive performance was seen among individuals who could not count on the presence of a confidant (social network variable. The results suggest that the early identification of major risk groups among old people can help to prevent institutionalization and keep individuals in the community.
Cai, Chenxi; Yuan, Kai; Yin, Junsen; Feng, Dan; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Jin, Chenwang; Qin, Wei; Tian, Jie
Internet gaming disorder (IGD), identified in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Section III as a condition warranting more clinical research, may be associated with impaired cognitive control. Previous IGD-related studies had revealed structural abnormalities in the prefrontal cortex, an important part of prefrontal-striatal circuits, which play critical roles in cognitive control. However, little is known about the relationship between the striatal nuclei (caudate, putamen, and nucleus accumbens) volumes and cognitive control deficit in individuals with IGD. Twenty-seven adolescents with IGD and 30 age-, gender- and education-matched healthy controls participated in this study. The volume differences of the striatum were assessed by measuring subcortical volume in FreeSurfer. Meanwhile, the Stroop task was used to detect cognitive control deficits. Correlation analysis was used to investigate the relationship between striatal volumes and performance in the Stroop task as well as severity in IGD. Relative to controls, the IGD committed more incongruent condition response errors during the Stroop task and showed increased volumes of dorsal striatum (caudate) and ventral striatum (nucleus accumbens). In addition, caudate volume was correlated with Stroop task performance and nucleus accumbens (NAc) volume was associated with the internet addiction test (IAT) score in the IGD group. The increased volumes of the right caudate and NAc and their association with behavioral characteristics (i.e., cognitive control and severity) in IGD were detected in the present study. Our findings suggest that the striatum may be implicated in the underlying pathophysiology of IGD. PMID:25720356
Jiang, Nengzhi; Yu, Fei; Zhang, Wencai; Zhang, Jianxin
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. PMID:27086227
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
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 the 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 (9-11weeks) 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 arm 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
Knouse, Laura E.; Zvorsky, Ivori; Safren, Steven A.
Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) are at increased risk for depressive disorders but little is known about the potential cognitive and behavioral mechanisms of risk that could shape treatment. This study evaluated the degree to which cognitive-behavioral constructs associated with depression and its treatment—dysfunctional attitudes and cognitive-behavioral avoidance—accounted for variance in depressive symptoms and disorder in adults with ADHD. 77 adults clinically ...
Full Text Available Cognitive symptoms are core features of mental disorders but procognitive treatments are limited. We have proposed a ‘discoordination’ hypothesis that cognitive impairment results from aberrant coordination of neural activity. We reported that neonatal ventral hippocampus lesion (NVHL rats, an established neurodevelopmental model of schizophrenia, have abnormal neural synchrony and cognitive deficits in the active place avoidance task. During stillness, we observed that cortical local field potentials sometimes resembled epileptiform spike-wave discharges with higher prevalence in NVHL rats, indicating abnormal neural synchrony due perhaps to imbalanced excitation-inhibition coupling. Here, within the context of the hypothesis, we investigated whether attenuating abnormal neural synchrony will improve cognition in NVHL rats. We report that 1 interhippocampal synchrony in the theta and beta bands is correlated with active place avoidance performance; 2 the anticonvulsant ethosuximide attenuated the abnormal spike-wave activity, improved cognitive control, and reduced hyperlocomotion; 3 ethosuximide normalized the task-associated theta and beta synchrony between the two hippocampi but also increased synchrony between the medial prefrontal cortex and hippocampus above control levels; 4 the antipsychotic olanzapine was less effective at improving cognitive control and normalizing place avoidance-related inter-hippocampal neural synchrony, although it reduced hyperactivity; and 5 olanzapine caused an abnormal pattern of frequency-independent increases in neural synchrony, in both NVHL and control rats. These data suggest that normalizing aberrant neural synchrony can be beneficial and that drugs targeting the pathophysiology of abnormally coordinated neural activities may be a promising theoretical framework and strategy for developing treatments that improve cognition in neurodevelopmental disorders such as schizophrenia.
Damholdt, Malene Flensborg; Borghammer, Per; Larsen, Lars;
Olfactory dysfunction is a prodromal and prevalent nonmotor symptom of Parkinson's disease. Unlike olfactory dysfunction in Alzheimer's disease, it is believed to be unrelated to cognitive impairment. However, recent research has implicated cholinergic denervation in Parkinson's disease hyposmia...... and linked it to verbal memory. This research hypothesized that severe odor identification deficits may identify patients with Parkinson's disease at risk for cognitive impairment. The current study tested this hypothesis by comparing 24 functionally anosmic, nondemented patients with Parkinson......'s disease and 39 nonanosmic, nondemented patients with Parkinson's disease with 29 healthy control participants on composite scores of memory, processing speed, executive function, and language. The functionally anosmic group had significantly poorer visual and verbal memory than the nonanosmic group, which...
Zhou, Xiaoyan; Zhang, Fang; Hu, Xiaotong; Chen, Jing; Wen, Xiangru; Sun, Ying; Liu, Yonghai; Tang, Renxian; Zheng, Kuiyang; Song, Yuanjian
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
Sotiropoulos, Ioannis; Catania, Caterina; Pinto, Lucilia G; Silva, Rui; Pollerberg, G Elizabeth; Takashima, Akihiko; Sousa, Nuno; Almeida, Osborne F X
Stressful life experiences are likely etiological factors in sporadic forms of Alzheimer's disease (AD). Many AD patients hypersecrete glucocorticoids (GCs), and their GC levels correlate with the rate of cognitive impairment and extent of neuronal atrophy. Severity of cognitive deficits in AD correlates strongly with levels of hyperphosphorylated forms of the cytoskeletal protein TAU, an essential mediator of the actions of amyloid β (Aβ), another molecule with a key pathogenic role in AD. Our objective was to investigate the sequential interrelationships between these various pathogenic elements, in particular with respect to the mechanisms through which stress might precipitate cognitive decline. We thus examined whether stress, through the mediation of GCs, influences TAU hyperphosphorylation, a critical and early event in the cascade of processes leading to AD pathology. Results from healthy, wild-type, middle-aged rats show that chronic stress and GC induce abnormal hyperphosphorylation of TAU in the hippocampus and prefrontal cortex (PFC), with contemporaneous impairments of hippocampus- and PFC-dependent behaviors. Exogenous GC potentiated the ability of centrally infused Aβ to induce hyperphosphorylation of TAU epitopes associated with AD and cytoplasmic accumulation of TAU, while previous exposure to stress aggravated the biochemical and behavioral effects of GC in Aβ-infused animals. Thus, lifetime stress/GC exposure may have a cumulative impact on the onset and progress of AD pathology, with TAU hyperphosphorylation serving to transduce the negative effects of stress and GC on cognition. PMID:21613497
Wright, M Jerry; Taffe, Michael A
Although human alcoholics exhibit lasting cognitive deficits, it can be difficult to definitively rule out pre-alcohol performance differences. For example, individuals with a family history of alcoholism are at increased risk for alcoholism and are also behaviorally impaired. Animal models of controlled alcohol exposure permit balanced group assignment, thereby ruling out the effects of pre-existing differences. Periadolescent male rhesus macaques (N = 5) consumed alcohol during 200 drinking sessions (M-F) across a 10-month period (mean daily alcohol consumption: 1.38 g/kg/day). A control group (N = 5) consumed a fruit-flavored vehicle during the same period. Spatial working memory, visual discrimination learning and retention and response time behavioral domains were assessed with subtests of the Monkey CANTAB (CAmbridge Neuropsychological Test Automated Battery). Spatial working memory performance was impaired in the alcohol group after 120 drinking sessions (6 mo) in a manner that depended on retention interval. The chronic alcohol animals were also impaired in retaining a visual discrimination over 24 hrs when assessed 6-8 weeks after cessation of alcohol drinking. Finally, the presentation of distractors in the response time task impaired the response time and accuracy of the chronic alcohol group more than controls after 6 months of alcohol cessation. Chronic alcohol consumption over as little as 6 months produces cognitive deficits, with some domains still affected after acute (6-8 wks) and lasting (6 mo) discontinuation from drinking. Animals were matched on alcohol preference and behavioral performance prior to exposure, thus providing strong evidence for the causal role of chronic alcohol in these deficits. PMID:25018042
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.
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 varian...
Feng, Dan; Yuan, Kai; Li, Yangding; Cai, Chenxi; Yin, Junsen; Bi, Yanzhi; Cheng, Jiadong; Guan, Yanyan; Shi, Sha; Yu, Dahua; Jin, Chenwang; Lu, Xiaoqi; Qin, Wei; Tian, Jie
Tobacco use during later adolescence and young adulthood may cause serious neurophysiological changes; rationally, it is extremely important to study the relationship between brain dysfunction and behavioral performances in young adult smokers. Previous resting state studies investigated the neural mechanisms in smokers. Unfortunately, few studies focused on spontaneous activity differences between young adult smokers and nonsmokers from both intra-regional and inter-regional levels, less is known about the association between resting state abnormalities and behavioral deficits. Therefore, we used fractional amplitude of low frequency fluctuation (fALFF) and resting state functional connectivity (RSFC) to investigate the resting state spontaneous activity differences between young adult smokers and nonsmokers. A correlation analysis was carried out to assess the relationship between neuroimaging findings and clinical information (pack-years, cigarette dependence, age of onset and craving score) as well as cognitive control deficits measured by the Stroop task. Consistent with previous addiction findings, our results revealed the resting state abnormalities within frontostriatal circuits, i.e., enhanced spontaneous activity of the caudate and reduced functional strength between the caudate and anterior cingulate cortex (ACC) in young adult smokers. Moreover, the fALFF values of the caudate were correlated with craving and RSFC strength between the caudate and ACC was associated with the cognitive control impairments in young adult smokers. Our findings could lead to a better understanding of intrinsic functional architecture of baseline brain activity in young smokers by providing regional and brain circuit spontaneous neuronal activity properties as well as their association with cognitive control impairments. PMID:26164168
Braga-Neto, Pedro; Dutra, Lívia Almeida; Pedroso, José Luiz; Felício, André C; Alessi, Helena; Santos-Galduroz, Ruth F; Bertolucci, Paulo Henrique F; Castiglioni, Mário Luiz V; Bressan, Rodrigo Affonseca; de Garrido, Griselda Esther Jara; Barsottini, Orlando Graziani Povoas; Jackowski, Andrea
Cognitive and olfactory impairments have previously been demonstrated in patients with spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD)-SCA3/MJD. We investigated changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) imaging in a cohort of Brazilian patients with SCA3/MJD. The aim of the present study was to evaluate the correlation among rCBF, cognitive deficits, and olfactory dysfunction in SCA3/MJD. Twenty-nine genetically confirmed SCA3/MJD patients and 25 control subjects were enrolled in the study. The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. Psychiatric symptoms were evaluated by the Hamilton Anxiety Scale and Beck Depression Inventory. The neuropsychological assessment consisted of Spatial Span, Symbol Search, Picture Completion, the Stroop Color Word Test, Trail Making Test (TMT), and Phonemic Verbal Fluency. Subjects were also submitted to odor identification evaluation using the 16-item Sniffin' Sticks. SPECT was performed using ethyl cysteine dimer labeled with technetium-99m. SCA3/MJD patients showed reduced brain perfusion in the cerebellum, temporal, limbic, and occipital lobes compared to control subjects (pFDR <0.001). A significant positive correlation was found between the Picture Completion test and perfusion of the left parahippocampal gyrus and basal ganglia in the patient group as well as a negative correlation between the TMT part A and bilateral thalamus perfusion. The visuospatial system is affected in patients with SCA3/MJD and may be responsible for the cognitive deficits seen in this disease. PMID:22307858
Lennertz, Leonhard; An der Heiden, Wolfram; Kronacher, Regina; Schulze-Rauschenbach, Svenja; Maier, Wolfgang; Häfner, Heinz; Wagner, Michael
Most neuropsychological studies on schizophrenia suffer from sample selection bias, with male and chronic patients being overrepresented. This probably leads to an overestimation of cognitive impairments. The present study aimed to provide a less biased estimate of cognitive functions in schizophrenia using a population-representative catchment area sample. Schizophrenia patients (N = 89) from the prospective Mannheim ABC cohort were assessed 14 years after disease onset and first diagnosis, using a comprehensive neuropsychological test battery. A healthy control group (N = 90) was carefully matched according to age, gender, and geographic region (city, rural surrounds). The present sample was representative for the initial ABC cohort. In the comprehensive neuropsychological assessment, the schizophrenia patients were only moderately impaired as compared to the healthy control group (d = 0.56 for a general cognitive index, d = 0.42 for verbal memory, d = 0.61 for executive functions, d = 0.69 for attention). Only 33 % of the schizophrenia patients scored one standard deviation unit below the healthy control group in the general cognitive index. Neuropsychological performance did not correlate with measures of the clinical course including age at onset, number of hospital admissions, and time in paid work. Thus, in this population-representative sample of schizophrenia patients, neuropsychological deficits were less pronounced than expected from meta-analyses. In agreement with other epidemiological studies, this suggests a less devastating picture of cognition in schizophrenia. PMID:26233432
Full Text Available Abstract Background Cognition in children with anxiety disorders (ANX and comorbid Attention Deficit Disorder (ADHD has received little attention, potentially impacting clinical and academic interventions in this highly disabled group. This study examined several cognitive features relative to children with either pure condition and to normal controls. Methods One hundred and eight children ages 8–12 and parents were diagnosed by semi-structured parent interview and teacher report as having: ANX (any anxiety disorder except OCD or PTSD; n = 52, ADHD (n = 21, or ANX + ADHD (n = 35. All completed measures of academic ability, emotional perception, and working memory. Clinical subjects were compared to 35 normal controls from local schools. Results Groups did not differ significantly on age, gender, or estimated IQ. On analyses of variance, groups differed on academic functioning (Wide Range Achievement Test, p Conclusion Though requiring replication, findings suggest that ANX + ADHD relates to greater cognitive and academic vulnerability than ANX, but may relate to reduced perception of anger.
Sanger, Maureen; Jordan, Lori; Pruthi, Sumit; Day, Matthew; Covert, Brittany; Merriweather, Brenda; Rodeghier, Mark; DeBaun, Michael; Kassim, Adetola
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. PMID:27167865
Haddon, Josephine E; George, David N; Grayson, Lois; McGowan, Christopher; Honey, Robert C; Killcross, Simon
The cognitive deficits observed in schizophrenia have been characterized as a failure to utilize task-setting information to guide behaviour, especially in situations in which there is response conflict. Recently, we have provided support for this account; high schizotypy individuals demonstrated inferior biconditional discrimination performance compared to low scorers, but were not impaired on a simple discrimination that did not require the use of task-setting cues. These results may, however, also be explained by the way in which individuals with high schizotypy process stimulus compounds. Here, we examine the initial approaches to solving biconditional and control discrimination tasks of participants with high and low schizotypy scores. In particular, we focus on performance during the first block of training trials to capture processing style before the acquisition of the discrimination tasks. Participants scoring highly on the introvertive anhedonia subscale (which has been allied to the negative and cognitive symptoms of schizophrenia) demonstrated better biconditional performance during the first block of training trials than did low-schizotypy individuals, consistent with a highly elemental approach to stimulus processing. Subsequent recognition tests confirmed this analysis demonstrating that the pattern of performance observed in participants with high schizotypy was associated with a failure to discriminate conjunctions of items that had been seen before from those that had not. These results suggest that the negative/cognitive symptoms of schizophrenia may reflect an extreme bias towards elemental, as opposed to configural, processing of stimulus conjunctions. PMID:24279945
Volkert, Julia; Haubner, J; Kazmaier, J; Glaser, F; Kopf, J; Kittel-Schneider, S; Reif, A
Previous studies have demonstrated impairments in attention, memory and executive functions in euthymic bipolar patients (BP) as well as their unaffected first-degree relatives, albeit in an attenuated form. Subsequently, cognitive deficits are discussed as a possible endophenotype of bipolar disorder. However, recent studies showed that only a subgroup of BP shows cognitive impairments. The aim of the present study was to investigate cognitive functioning in relatives compared to BP, to find out if the differentiation in a cognitive deficit vs. non-deficit subgroup is valid for relatives of BP, too. Therefore, the performance of 27 unaffected relatives of BP, 27 euthymic BP and 27 HC were compared using a neuropsychological test battery. The results showed that BP exhibited a reduced psychomotor speed and deficits in working memory compared to relatives and HC. Relatives performed significantly slower (psychomotor speed) as compared to HC (p = 0.024); performance in the other test measures lie between BP and HC. Furthermore, a detailed evaluation of the data indicated that only subgroups of BP and relatives exhibited cognitive impairments in the implemented tests. However, the deficit and non-deficit groups did not differ in sociodemographic and clinical variables from each other, possibly due to the small sample size. In conclusion, our results suggest that reduced psychomotor speed could serve as a potential endophenotype for bipolar disorder which should be investigated along the developmental trajectory of this disorder, also to examine whether abnormalities therein precede onset of the first mood episode. Furthermore, the division of relatives into subgroups aids in the identification of stable trait markers and high-risk bipolar groups and could enable early prevention strategies. As to that more research using distinct and homogeneous subgroups is necessary. PMID:27273092
Full Text Available Hae Kook Lee, Jong-Hyun Jeong, Na-Young Kim, Min-hyeon Park, Tae-Won Kim, Ho-Jun Seo, Hyun-Kook Lim, Seung-Chul Hong, Jin-Hee Han Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea Objectives: Attention-deficit hyperactivity disorder (ADHD is characterized by inattentive and impulsive behavior. Many ADHD patients reportedly have cognitive dysfunction and sleep problems, including longer sleep latency, lower sleep efficiency, and shorter total sleep time. The purpose of this study was to examine neurocognitive functions and nocturnal sleep parameters in patients with ADHD, using a cognitive function test and actigraphy.Methods: Subjects included 37 male patients with ADHD and 32 controls (7–12 years of age. For each participant, we determined intelligence quotient (IQ and administered the Matching Familiar Figures Test (MFFT and 72-hour actigraphy. The relationships between sleep parameters and cognitive functions were assessed.Results: ADHD patients significantly differed from controls in several cognitive functions and sleep variables. In the MFFT, response error rate (P<0.001 and error counts (P=0.003 were significantly increased in ADHD patients compared with control children. MFFT response latency was significantly shorter in ADHD patients than in controls (P<0.001. In addition, sleep latency (P=0.01, wake after sleep onset (WASO (P<0.001, and fragmentation index (P<0.001 were evaluated by actigraphy and found to be significantly increased in patients with ADHD compared with controls. However, no significant differences in total sleep time or sleep efficiency were observed. WASO and response error rates were positively correlated in patients with ADHD (rho =0.52, P=0.012. Furthermore, fragmentation index sleep variables were significantly positively correlated with response error (rho =0.44, P=0.008 and response latency rates (rho =0.4, P=0.018 in the MFFT. Reaction error rate was significantly
Scott Elizabeth M
Full Text Available Abstract Background Although major depression (MD is associated with high levels of disability, the relationships between cognitive dysfunction and self-rated disability are poorly understood. This study examined the relationships between self-rated disability in persons with MD and both self-rated and objectively-measured cognitive functioning. Methods Twenty-one persons with MD and 21 control participants underwent neuropsychological assessment and z-scores representing deviations from control performance were calculated and averaged across the domains of psychomotor speed, initial learning, memory retention and executive function. Self-ratings of cognitive deficits (SRCDs were reported on a 6-point scale for overall rating of cognitive change, speed of thinking, concentration, and short-term memory. Disability scores for self-rated physical, mental-health and functional (ie. days out of role disability were computed from the Brief-Disability Questionnaire and the SF-12 'mental component' subscale. Results Persons with MD had a mean age of 53.9 years (SD = 11.0, 76% female and had moderate to high depression severity (mean HDRS 21.7, sd = 4.4. As expected, depression severity was a strong predictor of physical (r = 0.7, p Conclusion While depression severity is associated with disability, the contributions of both self-rated and objectively-measured cognitive deficits are substantial and contribute uniquely and differentially to various forms of disability. Efforts directed at reducing cognitive deficits in depression may have the potential to reduce disability.
Xu, Jian; Chatterjee, Manavi; Baguley, Tyler D; Brouillette, Jonathan; Kurup, Pradeep; Ghosh, Debolina; Kanyo, Jean; Zhang, Yang; Seyb, Kathleen; Ononenyi, Chimezie; Foscue, Ethan; Anderson, George M; Gresack, Jodi; Cuny, Gregory D; Glicksman, Marcie A; Greengard, Paul; Lam, TuKiet T; Tautz, Lutz; Nairn, Angus C; Ellman, Jonathan A; Lombroso, Paul J
STEP (STriatal-Enriched protein tyrosine Phosphatase) is a neuron-specific phosphatase that regulates N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking, as well as ERK1/2, p38, Fyn, and Pyk2 activity. STEP is overactive in several neuropsychiatric and neurodegenerative disorders, including Alzheimer's disease (AD). The increase in STEP activity likely disrupts synaptic function and contributes to the cognitive deficits in AD. AD mice lacking STEP have restored levels of glutamate receptors on synaptosomal membranes and improved cognitive function, results that suggest STEP as a novel therapeutic target for AD. Here we describe the first large-scale effort to identify and characterize small-molecule STEP inhibitors. We identified the benzopentathiepin 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (known as TC-2153) as an inhibitor of STEP with an IC50 of 24.6 nM. TC-2153 represents a novel class of PTP inhibitors based upon a cyclic polysulfide pharmacophore that forms a reversible covalent bond with the catalytic cysteine in STEP. In cell-based secondary assays, TC-2153 increased tyrosine phosphorylation of STEP substrates ERK1/2, Pyk2, and GluN2B, and exhibited no toxicity in cortical cultures. Validation and specificity experiments performed in wild-type (WT) and STEP knockout (KO) cortical cells and in vivo in WT and STEP KO mice suggest specificity of inhibitors towards STEP compared to highly homologous tyrosine phosphatases. Furthermore, TC-2153 improved cognitive function in several cognitive tasks in 6- and 12-mo-old triple transgenic AD (3xTg-AD) mice, with no change in beta amyloid and phospho-tau levels. PMID:25093460
Kuntsi, J.; Wood, A.C.; Rijsdijk, F.; Johnson, K.A.; Andreou, P.; Albrecht, B.; Arias-Vasquez, A.; Buitelaar, J.K.; Mcloughlin, G.; Rommelse, N.N.J.; Sergeant, J.A.; Sonuga-Barke, E.J.S.; Uebel, H.; van der Meere, J.J.; Banaschewski, T.; Gill, M.; Manor, I.; Miranda, A.; Mulas, F.; Oades, R.D.; Roeyers, H.; Rothenberger, A.; Steinhausen, H.C.; Faraone, S.V.; Asherson, P.
Context Attention deficit hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots, or whether separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. Objective To determine, using a multivariate familial factor analysis approach, whether one or more familial factors underlie the slow and variable reaction times (RTs), impaired response inhibition and choice impulsivity that are associated with ADHD. Design An ADHD and control sibling-pair design. Setting Belgium, Germany, Ireland, Israel, Spain, Switzerland and the United Kingdom. Participants The sample consisted of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with ADHD combined subtype), and 345 control participants. Main Outcome Measures Performance on a four-choice RT task, a go/no-go inhibition task and a choice-delay task. Results The final model consisted of two familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98-100% of the familial influences on mean RT and RT variability. The second smaller factor, reflecting 12.5% of the familial variance of ADHD, captured 62-82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model, due to poor fit. Conclusions The findings suggest the existence of two familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the two cognitive impairments is consistent with recent theoretical models – a developmental model and an arousal-attention model – on two separable underlying processes in ADHD
Full Text Available This paper investigates the utility and efficacy of a novel eight-week cognitive rehabilitation programme developed to remediate attention deficits in adults who have sustained a traumatic brain injury (TBI, incorporating the use of both action video game playing and a compensatory skills programme. Thirty-one male TBI patients, aged 18–65 years, were recruited from 2 Australian brain injury units and allocated to either a treatment or waitlist (treatment as usual control group. Results showed improvements in the treatment group, but not the waitlist control group, for performance on the immediate trained task (i.e. the video game and in non-trained measures of attention and quality of life. Neither group showed changes to executive behaviours or self-efficacy. The strengths and limitations of the study are discussed, as are the potential applications and future implications of the research.
Full Text Available 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.
Full Text Available 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.
Full Text Available BACKGROUND: Deficits of the default mode network (DMN have been demonstrated in subjects with amnestic type mild cognitive impairment (aMCI who have a high risk of developing Alzheimer's disease (AD. However, no longitudinal study of this network has been reported in aMCI. Identifying links between development of DMN and aMCI progression would be of considerable value in understanding brain changes underpinning aMCI and determining risk of conversion to AD. METHODOLOGY/PRINCIPAL FINDINGS: Resting-state fMRI was acquired in aMCI subjects (n = 26 and controls (n = 18 at baseline and after approximately 20 months follow up. Independent component analysis was used to isolate the DMN in each participant. Differences in DMN between aMCI and controls were examined at baseline, and subsequent changes between baseline and follow-up were also assessed in the groups. Posterior cingulate cortex/precuneus (PCC/PCu hyper-functional connectivity was observed at baseline in aMCI subjects, while a substantial decrement of these connections was evident at follow-up in aMCI subjects, compared to matched controls. Specifically, PCC/PCu dysfunction was positively related to the impairments of episodic memory from baseline to follow up in aMCI group. CONCLUSIONS/SIGNIFICANCE: The patterns of longitudinal deficits of DMN may assist investigators to identify and monitor the development of aMCI.
Cicchetti, Domenic V.; Kaufman, Alan S.; Sparrow, Sara S.
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…
Jensen, Maria Høj; Glenthøj, Birte Yding; Nielsen, Mette Ødegaard;
are obtained using PANSS (Positive and Negative Symptom Scale). Results: Preliminary analyses show significant deficits in almost all cognitive domains assessed with effect sizes ranging between 0.5 to 1.2 standard deviations below the average of the healthy controls. The prevalence and profile of...
Yang, Mu; Lewis, Freeman C.; Sarvi, Michael S.; Foley, Gillian M.; Crawley, Jacqueline N.
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…
Pompili, Maurizio; Lester, David; Girardi, Paolo; Tatarelli, Roberto
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…
Titus, David J; Sakurai, Atsushi; Kang, Yuan; Furones, Concepcion; Jergova, Stanislava; Santos, Rosmery; Sick, Thomas J; Atkins, Coleen M
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
Tobe, Russell H; Corcoran, Cheryl M; Breland, Melissa; MacKay-Brandt, Anna; Klim, Casimir; Colcombe, Stanley J; Leventhal, Bennett L; Javitt, Daniel C
Impairment in social cognition, including emotion recognition, has been extensively studied in both Autism Spectrum Disorders (ASD) and Schizophrenia (SZ). However, the relative patterns of deficit between disorders have been studied to a lesser degree. Here, we applied a social cognition battery incorporating both auditory (AER) and visual (VER) emotion recognition measures to a group of 19 high-functioning individuals with ASD relative to 92 individuals with SZ, and 73 healthy control adult participants. We examined group differences and correlates of basic auditory processing and processing speed. Individuals with SZ were impaired in both AER and VER while ASD individuals were impaired in VER only. In contrast to SZ participants, those with ASD showed intact basic auditory function. Our finding of a dissociation between AER and VER deficits in ASD relative to Sz support modality-specific theories of emotion recognition dysfunction. Future studies should focus on visual system-specific contributions to social cognitive impairment in ASD. PMID:27131617
Full Text Available Recent increases in ADHD diagnoses, and the escalation of stimulant prescriptions, have 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 nonADHD 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.
Walsh, Jennifer A.; Creighton, Sarah E.; Rutherford, M. D.
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…
Full Text Available The frequency of ADHD in the aging population and its relationship to late-life cognitive decline has not been studied previously. To address this gap in our understanding, the Wender-Utah ADHD Rating scale (WURS was administered to 310 geriatric subjects with cognitive status ranging from normal cognition to mild cognitive impairment to overt dementia. The frequency of WURS-positive ADHD in this sample was 4.4%. WURS scores were not related to cognitive diagnoses, but did show nonlinear associations with tasks requiring sustained attention. The frequency of ADHD appears stable across generations and does not appear to be associated with MCI or dementia diagnoses. The association of attentional processing deficits and WURS scores in geriatric subjects could suggest that such traits remain stable throughout life. Caution should be considered when interpreting cognitive test profiles in the aging population that exhibit signs and symptoms of ADHD, as attentional deficits may not necessarily imply the existence of an underlying neurodegenerative disease state.
Nagakura, Akira; Shitaka, Yoshitsugu; Yarimizu, Junko; Matsuoka, Nobuya
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. PMID:23276665
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
Full Text Available Abstract Background Neurologic deficits after cardiac surgery are common complications. Aim of this prospective observational pilot study was to investigate the incidence of postoperative cognitive deficit (POCD after cardiac surgery, provided that relevant decrease of cerebral oxygen saturation (cSO2 is avoided during cardiopulmonary bypass. Methods cSO2 was measured by near infrared spectroscopy in 35 patients during cardiopulmonary bypass. cSO2 was kept above 80% of baseline and above 55% during anesthesia including cardiopulmonary bypass. POCD was tested by trail making test, digit symbol substitution test, Ray's auditorial verbal learning test, digit span test and verbal fluency test the day before and 5 days after surgery. POCD was defined as a decline in test performance that exceeded - 20% from baseline in two tests or more. Correlation of POCD with lowest cSO2 and cSO2 - threshold were determined explorative. Results POCD was observed in 43% of patients. Lowest cSO2 during cardiopulmonary bypass was significantly correlated with POCD (p = 0.015, r2 = 0.44, without Bonferroni correction. A threshold of 65% for cSO2 was able to predict POCD with a sensitivity of 86.7% and a specificity of 65.0% (p = 0.03, without Bonferroni correction. Conclusions Despite a relevant decrease of cerebral oxygen saturation was avoided in our pilot study during cardiopulmonary bypass, incidence of POCD was comparable to that reported in patients without monitoring. A higher threshold for cSO2 may be needed to reduce the incidence of POCD.
Huang, Pengcheng; Li, Cai; Fu, Tianli; Zhao, Dan; Yi, Zhen; Lu, Qing; Guo, Lianjun; Xu, Xulin
Chronic restraint stress (CRS) causes hippocampal neurodegeneration and hippocampus-dependent cognitive deficits. Flupirtine represents neuroprotective effects and we have previously shown that flupirtine can protect against memory impairment induced by acute stress. The present study aimed to investigate whether flupirtine could alleviate spatial learning and memory impairment and hippocampal apoptosis induced by CRS. CRS mice were restrained in well-ventilated Plexiglass tubes for 6h daily beginning from 10:00 to 16:00 for 21 consecutive days. Mice were injected with flupirtine (10mg/kg and 25mg/kg) or vehicle (10% DMSO) 30min before restraint stress for 21 days. After stressor cessation, the spatial learning and memory, dendritic spine density, injured neurons and the levels of Bcl-2, Bax, p-Akt, p-GSK-3β, p-Erk1/2 and synaptophysin of hippocampal tissues were examined. Our results showed that flupirtine significantly prevented spatial learning and memory impairment induced by CRS in the Morris water maze. In addition, flupirtine (10mg/kg and 25mg/kg) treatment alleviated neuronal apoptosis and the reduction of dendritic spine density and synaptophysin expression in the hippocampal CA1 region of CRS mice. Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3β, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice. These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3β and Erk1/2 signaling pathways. PMID:25869780
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
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
Full Text Available Background and Objectives: Little is known about the differences between patients managing depression on an outpatient basis as compared with hospitalized ones. This study investigated the performance of attention, executive function and verbal memory during remission from unipolar depressive episodes and compare patients with and without history of hospitalization. Methods: The sample of participants who had undergone one or more hospitalizations (hospitalized, N = 46 as well as in a sample without hospitalization (never hospitalized, N = 46 and controls (N = 92 were used. The Auditory Verbal Learning Test (AVLT and the Trail Making Test (TMT were administrated to test this hypothesis. Results and conclusion: The hospitalized sample had similar results in all four neuropsychological variables in comparison with the never hospitalized group, and both groups had some lower results in comparison with controls. In comparison with the controls, hospitalized sample had mean cognitive deficits of 34% (28-41%, the never hospitalized group had a mean of 20% (21-35%. Contrary to previous reports we have found no meaningful differences between the two patient groups.
Li, Yue; Stockton, Michael E; Bhuiyan, Ismat; Eisinger, Brian E; Gao, Yu; Miller, Jessica L; Bhattacharyya, Anita; Zhao, Xinyu
Fragile X syndrome, the most common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein (FMRP). However, the mechanism remains unclear, and effective treatment is lacking. We show that loss of FMRP leads to activation of adult mouse neural stem cells (NSCs) and a subsequent reduction in the production of neurons. We identified the ubiquitin ligase mouse double minute 2 homolog (MDM2) as a target of FMRP. FMRP regulates Mdm2 mRNA stability, and loss of FMRP resulted in elevated MDM2 mRNA and protein. Further, we found that increased MDM2 expression led to reduced P53 expression in adult mouse NSCs, leading to alterations in NSC proliferation and differentiation. Treatment with Nutlin-3, a small molecule undergoing clinical trials for treating cancer, specifically inhibited the interaction of MDM2 with P53, and rescued neurogenic and cognitive deficits in FMRP-deficient mice. Our data reveal a potential regulatory role for FMRP in the balance between adult NSC activation and quiescence, and identify a potential new treatment for fragile X syndrome. PMID:27122614
Xu, Jiqing; de Winter, Fred; Farrokhi, Catherine; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Cook, Jonathan; Jin, Xin; Masliah, Eliezer; Lee, Kuo-Fen
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
Gupta, Ayush; Elby, Andrew
Researchers have argued against deficit-based explanations of students' troubles with mathematical sense-making, pointing instead to factors such as epistemology: students' beliefs about the nature of knowledge and learning can hinder them from activating and integrating productive knowledge they have. But such explanations run the risk of substituting an epistemological deficit for a concepts/skills deficit. Our analysis of an undergraduate engineering major avoids this "deficit trap" by inc...
Maria E. Cottingham
Full Text Available We tested the notion that patients at high risk for progression to Alzheimer's disease (AD display relatively isolated memory deficits by assessing the relationship between memory and fluency performances in a sample of 92 geriatric subjects with cognitive complaints and normal to mild clinical presentations. Patient groups were formed on the basis of memory test scores. Patients with normal memory scores also performed normally on fluency tests, and their fluency scores were significantly higher than those of patients with low memory performances. Patients falling between these two groups in memory abilities also displayed intermediate level fluency performances. Whereas the normal memory group performed at equivalent levels on semantic and phonemic fluency tasks, both the impaired memory group and the intermediate group displayed relatively greater weaknesses in semantic fluency. This pattern is similar to that seen in AD. Since the impaired memory patients meet criteria for Amnestic Mild Cognitive Impairment, these findings suggest that memory deficits in “pre-clinical” AD are likely to be accompanied by fluency weaknesses, with semantic fluency weaknesses predominating.
White, J D; Eimerbrink, M J; Hayes, H B; Hardy, A; Van Enkevort, E A; Peterman, J L; Chumley, M J; Boehm, G W
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. PMID:27449203
Cognitive impairments are core psychopathological components of the symptomatic of schizophrenic patients. These dysfunctions are generally related to attention, executive functions and memory. This report provides information on the importance of using functional magnetic resonance imaging (fMRI) for the diagnostics and therapy monitoring of the different subtypes of cognitive dysfunctions. Furthermore, it describes the typical differences in the activation of individual brain regions between schizophrenic patients and healthy control persons. This information should be helpful in identifying the deficit profile of each patient and create an individual therapy plan. (orig.)
Serdar, Meray; Herz, Josephine; Kempe, Karina; Lumpe, Katharina; Reinboth, Barbara S; Sizonenko, Stéphane V; Hou, Xinlin; Herrmann, Ralf; Hadamitzky, Martin; Heumann, Rolf; Hansen, Wiebke; Sifringer, Marco; van de Looij, Yohan; Felderhoff-Müser, Ursula; Bendix, Ivo
Cerebral white matter injury is a leading cause of adverse neurodevelopmental outcome in prematurely born infants involving cognitive deficits in later life. Despite increasing knowledge about the pathophysiology of perinatal brain injury, therapeutic options are limited. In the adult demyelinating disease multiple sclerosis the sphingosine-1-phosphate (S1P) receptor modulating substance fingolimod (FTY720) has beneficial effects. Herein, we evaluated the neuroprotective potential of FTY720 in a neonatal model of oxygen-toxicity, which is associated with hypomyelination and impaired neuro-cognitive outcome. A single dose of FTY720 (1mg/kg) at the onset of neonatal hyperoxia (24h 80% oxygen on postnatal day 6) resulted in improvement of neuro-cognitive development persisting into adulthood. This was associated with reduced microstructural white matter abnormalities 4 months after the insult. In search of the underlying mechanisms potential non-classical (i.e. lymphocyte-independent) pathways were analysed shortly after the insult, comprising modulation of oxidative stress and local inflammatory responses as well as myelination, oligodendrocyte degeneration and maturation. Treatment with FTY720 reduced hyperoxia-induced oxidative stress, microglia activation and associated pro-inflammatory cytokine expression. In vivo and in vitro analyses further revealed that oxygen-induced hypomyelination is restored to control levels, which was accompanied by reduced oligodendrocyte degeneration and enhanced maturation. Furthermore, hyperoxia-induced elevation of S1P receptor 1 (S1P1) protein expression on in vitro cultured oligodendrocyte precursor cells was reduced by activated FTY720 and protection from degeneration is abrogated after selective S1P1 blockade. Finally, FTY720s' classical mode of action (i.e. retention of immune cells within peripheral lymphoid organs) was analysed demonstrating that FTY720 diminished circulating lymphocyte counts independent from hyperoxia
Vandana J. Rathod; Vyoma Shah; Jagatheesan Alagesan; Poongundran Paranthaman; Soundararajan P
Introduction: Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder. Cognitive behavior therapy is effective in children with ADHD. But data are lacking to prove efficacy of sensory integration therapy in treating the children with ADHD. Method: This multi-center experimental study was done at three physiotherapy colleges in India. 60 patients with ADHD are included in the study. They are randomly assigned into three different groups. Group A: 20 (subj...
Coelho, Luzia Flavia; Barbosa, Deise Lima Fernandes; Rizzutti, Sueli; Muszkat, Mauro; Bueno, Orlando Francisco Amodeo; Miranda, Monica Carolina
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...
Schirmbeck, Frederike; Rausch, Franziska; Englisch, Susanne; Eifler, Sarah; Esslinger, Christine; Meyer-Lindenberg, Andreas; Zink, Mathias
Background: Amongst schizophrenia patients, a large subgroup of up to 25% also suffers from comorbid obsessive-compulsive symptoms (OCSs). The association between comorbid OCSs in these patients and neuropsychological impairment remains unclear and somewhat contradictory. Longitudinal approaches investigating the stability of OCS-associated cognitive deficits are missing. Methods: Thirty-seven patients with schizophrenia and comorbid OCSs and 43 schizophrenia patients without OCS were assesse...
Passarotti, Alessandra M.; Sweeney, John A.; Pavuluri, Mani N.
This fMRI study investigates the neural bases of cognitive control of emotion processing in pediatric bipolar disorder (PBD) and attention deficit hyperactivity disorder (ADHD). Seventeen un-medicated PBD patients, 15 un-medicated ADHD patients, and 14 healthy controls (HC) (mean age = 13.78 ± 2.47) performed an emotional valence Stroop Task, requiring them to match the color of an emotionally valenced word to the color of either of two adjacent circles. Both patient groups responded signific...
Schmeichel, Brooke E.; Zemlan, Frank P.; Berridge, Craig W
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 u...
Cláudia eDrummond; Gabriel eCoutinho; Rochele ePaz Fonseca; Naima eAssunção; Alina eTeldeschi; Ricardo ede Oliveira-Souza; Jorge eMoll; Fernanda eTovar-Moll; Paulo eMattos
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 d...
Lanphear, B P; Dietrich, K.; Auinger, P; Cox, C
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 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, ...
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
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
Song, Hai; Xu, Lincheng; Zhang, Rongping; Cao, Zhenzhen; Zhang, Huan; Yang, Li; Guo, Zeyun; Qu, Yongqiang; Yu, Jianyun
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
Ott, Caroline Vintergaard; Vinberg, Maj; Kessing, Lars V; Miskowiak, Kamilla W
This is a secondary data analysis from our erythropoietin (EPO) trials. We examine (I) whether EPO improves speed of complex cognitive processing across bipolar and unipolar disorder, (II) if objective and subjective baseline cognitive impairment increases patients׳ chances of treatment-efficacy and (III) if cognitive improvement correlates with better subjective cognitive function, quality of life and socio-occupational capacity. Patients with unipolar or bipolar disorder were randomized to eight weekly EPO (N=40) or saline (N=39) infusions. Cognition, mood, quality of life and socio-occupational capacity were assessed at baseline (week 1), after treatment completion (week 9) and at follow-up (week 14). We used repeated measures analysis of covariance to investigate the effect of EPO on speed of complex cognitive processing. With logistic regression, we examined whether baseline cognitive impairment predicted treatment-efficacy. Pearson correlations were used to assess associations between objective and subjective cognition, quality of life and socio-occupational capacity. EPO improved speed of complex cognitive processing across affective disorders at weeks 9 and 14 (p≤0.05). In EPO-treated patients, baseline cognitive impairment increased the odds of treatment-efficacy on cognition at weeks 9 and 14 by a factor 9.7 (95% CI:1.2-81.1) and 9.9 (95% CI:1.1-88.4), respectively (p≤0.04). Subjective cognitive complaints did not affect chances of treatment-efficacy (p≥0.45). EPO-associated cognitive improvement correlated with reduced cognitive complaints but not with quality of life or socio-occupational function. As the analyses were performed post-hoc, findings are only hypothesis-generating. In conclusion, pro-cognitive effects of EPO occurred across affective disorders. Neuropsychological screening for cognitive dysfunction may be warranted in future cognition trials. PMID:27349944
Translational aspects of the novel object recognition task in rats abstinent following sub-chronic treatment with phencyclidine (PCP: effects of modafinil and relevance to cognitive deficits in schizophrenia?
John P Redrobe
Full Text Available Phencyclidine (PCP induces a behavioural syndrome in rodents that bears remarkable similarities to some of the core symptoms observed in schizophrenic patients, among those cognitive deficits. The successful alleviation of cognitive impairments associated with schizophrenia (CIAS has become a major focus of research efforts as they remain largely untreated. The aim of the present study was to investigate the effects of selected antipsychotic and cognition enhancing drugs, namely haloperidol, risperidone, donepezil, and modafinil in an animal model widely used in preclinical schizophrenia research. To this end, the novel object recognition (NOR task was applied to rats abstinent following sub-chronic treatment with PCP. Rats were administered either PCP (5 mg/kg, i.p. or vehicle twice a day for 7 days, followed by a 7-day washout period, before testing in NOR. Upon testing, vehicle-treated rats successfully discriminated between novel and familiar objects, an effect abolished in rats that had previously been exposed to PCP-treatment. Acute treatment with modafinil (64 mg/kg, p.o. ameliorated the PCP-induced deficit in novel object exploration, whereas haloperidol (0.1 mg/kg, s.c., risperidone (0.2 mg/kg, i.p. and donepezil (3 mg/kg, p.o. were without significant effect. Given the negligible efficacy of haloperidol and risperidone, and the contradictory data with donepezil to treat CIAS in the clinic, together with the promising preliminary pro-cognitive effects of modafinil in certain subsets of schizophrenic patients, the sub-chronic PCP-NOR abstinence paradigm may represent an attractive option for the identification of potential novel treatments for CIAS.
Hyo Geun Kim
Full Text Available 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.
Full Text Available Linlin Yang, Xiaochuan Zhao, Lan Wang, Lulu Yu, Mei Song, Xueyi Wang Department of Mental Health, The First Hospital of Hebei Medical University, Hebei Medical University Institute of Mental Health, Shijiazhuang, People’s Republic of China Abstract: 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
Duering, Marco; Gonik, Mariya; Malik, Rainer; Zieren, Nikola; Reyes, Sonia; Jouvent, Eric; Hervé, Dominique; Gschwendtner, Andreas; Opherk, Christian; Chabriat, Hugues; Dichgans, Martin
Patients with vascular cognitive impairment (VCI) commonly exhibit deficits in processing speed. This has been attributed to a disruption of frontal-subcortical neuronal circuits by ischemic lesions, but the exact mechanisms and underlying anatomical structures are poorly understood. We set out to identify a strategic brain network for processing speed by applying graph-based data-mining techniques to MRI lesion maps from patients with small vessel disease. We studied 235 patients with CADASIL, a genetic small vessel disease causing pure VCI. Using a probabilistic atlas in standard space we first determined the regional volumes of white matter hyperintensities (WMH) and lacunar lesions (LL) within major white matter tracts. Conditional dependencies between the regional lesion volumes and processing speed were then examined using Bayesian network analysis. Exploratory analysis identified a network of five imaging variables as the best determinant of processing speed. The network included LL in the left anterior thalamic radiation and the left cingulum as well as WMH in the left forceps minor, the left parahippocampal white matter and the left corticospinal tract. Together these variables explained 34% of the total variance in the processing speed score. Structural equation modeling confirmed the findings obtained from the Bayesian models. In summary, using graph-based models we identified a strategic brain network having the highest predictive value for processing speed in our cohort of patients with pure small vessel disease. Our findings confirm and extend previous results showing a role of frontal-subcortical neuronal circuits, in particular dorsolateral prefrontal and cingulate circuits, in VCI. PMID:23153965
Neill, Jo C; Grayson, Ben; Kiss, Béla; Gyertyán, István; Ferguson, Paul; Adham, Nika
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
Reimers, Tonny Solveig; Ehrenfels, Susanne; Mortensen, Erik Lykke; Schmiegelow, Marianne; Sønderkaer, Signe; Carstensen, Mads Henrik; Schmiegelow, Kjeld; Müller, Jørn
To describe cognitive function and to evaluate the association between potentially predictive factors and cognitive outcome in an unselected population of survivors of childhood brain tumors.......To describe cognitive function and to evaluate the association between potentially predictive factors and cognitive outcome in an unselected population of survivors of childhood brain tumors....
Vandana J Rathod
Full Text Available Introduction: Attention deficit hyperactivity disorder (ADHD is a neurobehavioral developmental disorder. Cognitive behavior therapy is effective in children with ADHD. But data are lacking to prove efficacy of sensory integration therapy in treating the children with ADHD. Method: This multi-center experimental study was done at three physiotherapy colleges in India. 60 patients with ADHD are included in the study. They are randomly assigned into three different groups. Group A: 20 (subjects receiving sensory integration therapy, group B: 20 (subjects receiving cognitive behavior therapy and group C: 20 (subjects receiving sensory integration therapy and cognitive behavior therapy. The outcome measure used is Conner’s Teacher Rating Scale before and after six months of intervention. Result: There was a significant decrease in scores of Conner’s Teacher Rating Scale (p<0.001 in children with ADHD who received sensory integration therapy and Cognitive Behavior Therapy alone and combined therapies of Sensory Integration Therapy and Cognitive Behavior Therapy. Conclusion: Combined therapies of Sensory Integration Therapy and Cognitive Behavior Therapy are effective in reducing symptoms of ADHD as assed by Conner’s Teacher Rating Scale.
Bikic, Aida; Leckman, James F; Lindschou, Jane;
of cognitive dysfunctions may prove particularly important because of the impact of these dysfunctions on the ability to cope with everyday life. Lately, several trials have shown promising results for cognitive computer training, often referred to as cognitive training, which focuses on particular...... parts of cognition, mostly on the working memory or attention but with poor generalization of training on other cognitive functions and functional outcome. Children with ADHD have a variety of cognitive dysfunctions, and it is important that cognitive training target multiple cognitive functions....... METHODS/DESIGN: This multicenter randomized clinical superiority trial aims to investigate the effect of "ACTIVATE™," a computer program designed to improve a range of cognitive skills and ADHD symptoms. A total of 122 children with ADHD, aged 6 to 13 years, will be randomized to an intervention or a...
Vukovic, Mile; Vuksanovic, Jasmina; Vukovic, Irena
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…
WEINSTEIN, CHERYL S.
Evidence continues to emerge that childhood symptoms of attention-deficit hyperactivity disorder (ADHD) persist into adulthood. These symptoms include motoric hyperactivity, restlessness, attention deficits, poor organizational skills, impulsivity, and memory impairment. Poor academic and work performance, frustration, humiliation, and shame are also components of adult ADHD. Psychotherapists are challenged to understand the meaning of the disorder and its ramifications in a...
Valdois, Sylviane; Bosse, Marie-Line; Tainturier, Marie-Josephe
There is strong converging evidence suggesting that developmental dyslexia stems from a phonological processing deficit. However, this hypothesis has been challenged by the widely admitted heterogeneity of the dyslexic population, and by several reports of dyslexic individuals with no apparent phonological deficit. In this paper, we discuss the…
Zhang, Wei; Hao, Jian; Liu, Rui; Zhang, Zhuo; Lei, Gesheng; Su, Changjun; Miao, Jianting; Li, Zhuyi
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
Full Text Available Acquired amusia is a common disorder after damage to the middle cerebral artery (MCA territory. However, its neurocognitive mechanisms, especially the relative contribution of perceptual and cognitive factors, are still unclear. We studied cognitive and auditory processing in the amusic brain by performing neuropsychological testing as well as magnetoencephalography (MEG measurements of frequency and duration discrimination using magnetic mismatch negativity (MMNm recordings. Fifty-three patients with a left (n = 24 or right (n = 29 hemisphere MCA stroke (MRI verified were investigated 1 week, 3 months, and 6 months after the stroke. Amusia was evaluated using the Montreal Battery of Evaluation of Amusia (MBEA. We found that amusia caused by right hemisphere damage (RHD, especially to temporal and frontal areas, was more severe than amusia caused by left hemisphere damage (LHD. Furthermore, the severity of amusia was found to correlate with weaker frequency MMNm responses only in amusic RHD patients. Additionally, within the RHD subgroup, the amusic patients who had damage to the auditory cortex (AC showed worse recovery on the MBEA as well as weaker MMNm responses throughout the 6-month follow-up than the non-amusic patients or the amusic patients without AC damage. Furthermore, the amusic patients both with and without AC damage performed worse than the non-amusic patients on tests of working memory, attention, and cognitive flexibility. These findings suggest domain-general cognitive deficits to be the primary mechanism underlying amusia without AC damage whereas amusia with AC damage is associated with both auditory and cognitive deficits.
Särkämö, Teppo; Tervaniemi, Mari; Soinila, Seppo; Autti, Taina; Silvennoinen, Heli M; Laine, Matti; Hietanen, Marja; Pihko, Elina
Acquired amusia is a common disorder after damage to the middle cerebral artery (MCA) territory. However, its neurocognitive mechanisms, especially the relative contribution of perceptual and cognitive factors, are still unclear. We studied cognitive and auditory processing in the amusic brain by performing neuropsychological testing as well as magnetoencephalography (MEG) measurements of frequency and duration discrimination using magnetic mismatch negativity (MMNm) recordings. Fifty-three patients with a left (n = 24) or right (n = 29) hemisphere MCA stroke (MRI verified) were investigated 1 week, 3 months, and 6 months after the stroke. Amusia was evaluated using the Montreal Battery of Evaluation of Amusia (MBEA). We found that amusia caused by right hemisphere damage (RHD), especially to temporal and frontal areas, was more severe than amusia caused by left hemisphere damage (LHD). Furthermore, the severity of amusia was found to correlate with weaker frequency MMNm responses only in amusic RHD patients. Additionally, within the RHD subgroup, the amusic patients who had damage to the auditory cortex (AC) showed worse recovery on the MBEA as well as weaker MMNm responses throughout the 6-month follow-up than the non-amusic patients or the amusic patients without AC damage. Furthermore, the amusic patients both with and without AC damage performed worse than the non-amusic patients on tests of working memory, attention, and cognitive flexibility. These findings suggest domain-general cognitive deficits to be the primary mechanism underlying amusia without AC damage whereas amusia with AC damage is associated with both auditory and cognitive deficits. PMID:21152040
黄雅洁; 杨震; 汪明
对字母语言和非字母语言阅读障碍的认知缺陷的研究发现，语音意识缺陷均表现在两类语言中，但二者所存在的问题又有明显的不同。对字母语言而言，阅读障碍的根源问题是语音技能和快速自动命名缺陷；而对汉语来说，阅读障碍的主要缺陷则集中在正字法知识技能、快速命名、序列内隐记忆等方面。我国相关研究领域还存在很多不足和缺乏，应该建立完整的汉语阅读障碍理论和研究体系。%Researches on cognitive deficits of dyslexia in alphabetic languages and non-alphabetic languages claim that def-icits of phonological skills exist in both kinds of languages,while these deficits are apparently quite different from each other. Findings on dyslexic alphabetic readers suggest that the nature of dyslexia lies in deficits of phonological skills and rapid auto-matic naming.Chinese dyslexia,however,has different manifestations with reading disorders in alphabetic languages.The main deficits of Chinese reading disorders include orthographic skills deficiency,slower rapid automatic naming speed,and less implicit sequence learning.In China,studies in these fields are relatively scarce and insufficient;therefore,a comprehensive system of theory and research on Chinese dyslexia remains to be constructed.
Becker, Stephen P; Langberg, Joshua M
Previous research has failed to find a consistent relation between Sluggish Cognitive Tempo (SCT) and executive function (EF) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) when laboratory-based neuropsychological tasks of EF are used, whereas recent research with youth and adults suggests a significant relation between SCT and ratings of EF. The purpose of this study was to examine ADHD dimensions and SCT symptoms in relation to ratings of EF in adolescents with ADHD. Fifty-two adolescents (ages 12-16; 70 % male) participated in this study. Parents and teachers completed validated measures of SCT, ADHD symptoms, and EF in daily life. Adolescents' intelligence and academic achievement were also assessed. ADHD and SCT symptoms were significantly correlated with ratings of EF. Regression analyses demonstrated that, as hypothesized, ADHD hyperactive-impulsive symptoms were strongly associated with behavioral regulation EF deficits, with ADHD inattentive and SCT symptoms unrelated to behavioral regulation EF when hyperactive-impulsivity symptoms were included in the model. The parent-reported SCT Slow scale measuring motivation, initiative, and apathy predicted both parent- and teacher-reported metacognitive EF deficits above and beyond youth characteristics and ADHD symptoms. In contrast, teacher-reported ADHD inattention was most clearly associated with teacher-reported metacognitive EF deficits. This study provides preliminary evidence for the importance of SCT symptoms in relation to metacognitive EF deficits among adolescents with ADHD and the need to further investigate the overlap and distinctiveness of SCT/ADHD. Further research is needed to replicate and extend these findings. PMID:23443466
Full Text Available A sample of 30 subjects, 10 with Attention Deficit and Hyperactivity Disorder(ADHD and 20 non-ADHD children, statistically controlled byage, gender, academic grades and normal full scale intelligence quotient,was selected. To measure cognitive inhibitory control, a math problem solving ability test containing four problems for each level with verbal and numerical irrelevant content was administered. ADHD children exhibited significantly inferior performance in choosing correct answers (p = 0.011 with a large effect size (d = 1.00 and a significantly superior number of irrelevant answers (p = 0.004 with a very large effect size. In conclusion ADHD children showed a cognitive inhibitory control disorder, measured by math problem solving ability.
Wu, Jing; Zhang, Mingqiang; Li, Huihui; Sun, Xiaoru; Hao, Shuangying; Ji, Muhuo; Yang, Jianjun; Li, Kuanyu
Mitochondrial dysfunction has been linked to the earliest pathogenesis of isoflurane-induced cognitive impairments in developing or aging mammalian brain. However, its molecular mechanism is poorly understood and a pharmacologic treatment to rapidly reverse mitochondrial dysfunction is lacking. Fifteen-month-old male C57BL/6 mice were exposed to isoflurane for two hours following intraperitoneal administration of mitochondrion-targeted peptide SS-31 or vehicle with 30min interval. The hippocampus was immediately removed for biochemical assays and mitochondria isolation after inhalation. Behavioral tests were evaluated by the open field test and fear conditioning test 24h after the experiment. We showed that cognitive deficits induced by exposure of the aging mice to isoflurane were accompanied by mitochondrial dysfunction in hippocampus due to loss of the enzymatic activity of complex I. This loss resulted in the increase of reactive oxygen species production, decrease of ATP production and mitochondrial membrane potential, and opening of mitochondrial permeability transition pore. Further, we provided evidence that the BDNF signaling pathway was involved in this process to regulate synaptic plasticity-related proteins, for instance, downregulation of synapsin 1, PSD-95 and p-CREB, and upregulation of NR2A, NR2B, CaMKIIα and CaMKIIβ. Of note, the isoflurane-induced cognitive deficits were rescued by SS-31 through reversal of mitochondrial dysfunction, which facilitated the regulation of BDNF signaling including the expression reversal of aforementioned important synaptic-signaling proteins in aging mice. Our data demonstrate that reversing mitochondrial dysfunction by SS-31 enhances BDNF signaling pathway and synaptic plasticity, and provides protective effects on cognitive function, thereby support the notion that SS-31 may have therapeutic benefits for elderly humans undertaking anesthesia. PMID:26944333
Christman, Andrea L.; Vannorsdall, Tracy D.; Pearlson, Godfrey D.; Hill-Briggs, Felicia; Schretlen, David J.
Diabetes is associated with dementia in older adults, but it remains unclear whether nondemented adults with type 2 diabetes show subtle abnormalities across cognition, neuroanatomy, and everyday functioning. Using the Aging, Brain Imaging, and Cognition study sample of 301 community-dwelling, middle-aged and older adults, we conducted a secondary analysis on 28 participants with and 150 participants without diabetes. We analyzed brain magnetic resonance imaging data, cognitive test performan...
Doom, Jenalee R.; Gunnar, Megan R.; Georgieff, Michael K.; Kroupina, Maria G.; Frenn, Kristin; Fuglestad, Anita J.
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 functioni...
Eack, Shaun M.; Greeno, Catherine G.; Pogue-Geile, Michael F.; Newhill, Christina E.; HOGARTY, GERARD E; Keshavan, Matcheri S.
The emotion management subscale of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) has recently been recommended by the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia committee as the sole measure of social cognition for trials of cognitive enhancement in schizophrenia, yet the psychometric properties of this subscale and the larger instrument in schizophrenia patients have not been thoroughly examined. This research ...
Kurtz, Matthew M; Gagen, Emily; Rocha, Nuno B F; Machado, Sergio; Penn, David L
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. PMID:26437567
Matsuura, Naomi; Ishitobi, Makoto; Arai, Sumiyoshi; Kawamura, Kaori; Asano, Mizuki; Inohara, Keisuke; Narimoto, Tadamasa; Wada, Yuji; Hiratani, Michio; Kosaka, Hirotaka
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
Hahn-Markowitz, Jeri; Manor, Iris; Maeir, Adina
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
Gavrilova, S I; Kolykhalov, I V; Fedorova, Ia B; Kalyn, Ia B; Selezneva, N D; Samorodov, A V; Miasoedov, S N; Boksha, I S
The aim of the study was to predict treatment efficacy in patients with mild cognitive impairment (MCI) and to find the most reliable clinical tests for the prediction of dementia. Patients with amnestic MCI (n=53) were treated with cerebrolysin for three years and underwent regularly neurocognitive and clinical psychiatric tests. The data were analyzed using non-parametric statistics, cluster analysis, and linear discriminate analysis. The combination of statistical methods has enabled to predict the degree of cognitive impairment as well as the development of dementia. A "dementia risk group" with fast cognitive decline (i.e. the low efficacy of the treatment) was identified. The tests are ranked according to their predictive values. PMID:23612410
Davenport, Richard K.; And Others
According to transfer index testing, chimpanzees who had been reared in restricted laboratory environments for the first two years of life were inferior in cognitive skills to wild born control subjects. Findings are discussed in terms of the role of early experience in cognitive development. (DP)
Sharma, Sorabh; Taliyan, Rajeev
Insulin resistance has been reported as a strong risk factor for Alzheimer's disease. However the molecular mechanisms of association between these still remain elusive. Various studies have highlighted the involvement of histone deacetylases (HDACs) in insulin resistance and cognitive deficits. Thus, the present study was designed to investigate the possible neuroprotective role of HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) in insulin resistance induced cognitive impairment in mice. Mice were subjected to either normal pellet diet (NPD) or high fat diet (HFD) for 8 weeks. HFD fed mice were treated with SAHA at 25 and 50 mg/kg i.p. once daily for 2 weeks. Serum insulin, glucose, triglycerides, total cholesterol and HDL-cholesterol levels were measured. A battery of behavioral parameters was performed to assess cognitive functions. Level of tumour necrosis factor (TNF-α) was measured in hippocampus to assess neuroinflammation. To further explore the molecular mechanisms we measured the histone H3 acetylation and brain derived neurotrophic factor (BDNF) level. HFD fed mice exhibit characteristic features of insulin resistance. These mice also showed a severe deficit in learning and memory along with reduced histone H3 acetylation and BDNF levels. In contrast, the mice treated with SAHA showed significant and dose dependent improvement in insulin resistant condition. These mice also showed improved learning and memory performance. SAHA treatment ameliorates the HFD induced reduction in histone H3 acetylation and BDNF levels. Based upon these results, it could be suggested that HDAC inhibitors exert neuroprotective effects by increasing H3 acetylation and subsequently BDNF level. PMID:26805421
Full Text Available 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.
Sokhadze, Estate M; Tasman, Allan; Sokhadze, Guela E; El-Baz, Ayman S; Casanova, Manuel F
Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80 % of subjects with autism display "motor dyspraxia" or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N = 30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more
Heaton, Pamela; Allen, Rory; Williams, Kerry; Cummins, Omar; Happe, Francesca
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…
Ramsay, J. Russell; Rostain, Anthony L.
Attention-Deficit/Hyperactivity Disorder (ADHD) is a developmental syndrome that persists into adulthood for the majority of children with ADHD. Other individuals may not experience the full negative effects of undiagnosed ADHD until they face the demands of adult life. College counseling centers in particular are seeing a rise in the number of…
Foley, Avery M; Ammar, Zeena M; Lee, Robert H; Mitchell, Cassie S
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. PMID:25362040
Full Text Available BACKGROUND: The cue-related go/no-go switching task provides an experimental approach to study individual's flexibility in changing situations. Because Internet addiction disorder (IAD belongs to the compulsive-impulsive spectrum of disorders, it should present cognitive bias and executive functioning deficit characteristics of some of these types of disorders. Until now, no studies have been reported on cognitive bias and executive function involving mental flexibility and response inhibition in IAD. METHODOLOGY/PRINCIPAL FINDINGS: A total of 46 subjects who met the criteria of the modified Young's Diagnostic Questionnaire for Internet addiction (YDQ were recruited as an Internet game addiction (IGA group, along with 46 healthy control individuals. All participants performed the Internet game-shifting task. Using hit rate, RT, d' and C as the dependent measures, a three-way ANOVA (group × target × condition was performed. For hit rate, a significant effect of group, type of target and condition were found. The group-target interaction effect was significant. For RT, significant effects were revealed for group and type of target. The group-target interaction effect was significant. Comparisons of the means revealed that the slowing down of IGA relative to NIA was more pronounced when the target stimuli were neutral as opposed to Internet game-related pictures. In addition, the group-condition interaction effect was significant. For d', significant effects of group, type of target and condition were found. The group-target interaction effect was significant. For C, the type of target produced a significant effect. There was a positive correlation between the length of the addiction (number of years and the severity of the cognitive bias. CONCLUSIONS: IGA present cognitive biases towards information related to Internet gaming. These biases, as well as poor executive functioning skills (lower mental flexibility and response inhibition, might be
Aungst, Stephanie L; Kabadi, Shruti V; Thompson, Scott M; Stoica, Bogdan A; Faden, Alan I
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
Aungst, Stephanie L; Kabadi, Shruti V; Thompson, Scott M; Stoica, Bogdan A; Faden, Alan I
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
Forslund, Tommie; Brocki, Karin C; Bohlin, Gunilla; Granqvist, Pehr; Eninger, Lilianne
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
Eslinger, Paul J.; Moore, Peachie; Anderson, Chivon; Grossman, Murray
The authors investigated aspects of interpersonal sensitivity and perspective-taking in relation to empathy, social cognitions, and executive functioning in 26 frontotemporal dementia (FTD) patients. Behavioral-variant FTD (bvFTD) patients were significantly impaired on caregiver assessments of empathy, although self-ratings were normal. Progressive nonfluent aphasia and semantic-dementia samples were rarely abnormal. In bvFTD, empathy ratings were found to be correlated with social cognition...
Harrison, Fiona E.; Yu, S Sarah; Van Den Bossche, Kristen L; Li, Liying; May, James M.; McDonald, Michael P.
Oxidative stress is implicated in the cognitive deterioration associated with normal aging as well as neurodegenerative disorders such as Alzheimer’s and Parkinson's diseases. We investigated the effect of ascorbic acid (vitamin C) on oxidative stress, cognition and motor abilities in mice null for gulono-γ-lactone oxidase (Gulo). Gulo−/− mice are unable to synthesize ascorbic acid and depend on dietary ascorbic acid for survival. Gulo−/− mice were given supplements that provided them either ...
McClure, Margaret M.; Harvey, Philip D.; Goodman, Marianne; Triebwasser, Joseph; New, Antonia; Koenigsberg, Harold W.; Sprung, Larry J; Flory, Janine D.; Siever, Larry J.
Cognitive deficits observed in schizophrenia are also frequently found in individuals with other schizophrenia spectrum disorders, such as schizotypal personality disorder (SPD). Dopamine appears to be a particularly important modulator of cognitive processes such as those impaired in schizophrenia spectrum disorders. In a double-blind, placebo-controlled clinical trial, we administered pergolide, a dopamine agonist targeting D1 and D2 receptors, to 25 participants with SPD and assessed the e...
Young, J W; Geyer, M A
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. While 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
Corbett, Faye; Jefferies, Elizabeth; Burns, Alistair; Lambon Ralph, Matthew A
Executive control is impaired from the early stages of Alzheimer's Disease (AD) and this produces deregulated semantic cognition (Corbett, Jefferies, Burns, & Lambon Ralph, ; Perry, Watson, & Hodges, ). While control deficits should affect semantic retrieval across all modalities, previous studies have typically focused on verbal semantic tasks. Even when non-verbal semantic tasks have been used, these have typically employed simple picture-matching tasks, which may be influenced by abnormalities in covert naming. Therefore, in the present study, we examined 10 patients with AD on a battery of object-use tasks, in order to advance our understanding of the origins of non-verbal semantic deficits in this population. The AD patients' deficits were contrasted with previously published performance on the same tasks within two additional groups of patients, displaying either semantic degradation (semantic dementia) or deregulation of semantic retrieval (semantic aphasia; Corbett, Jefferies, Ehsan, & Lambon Ralph, ). While overall accuracy was comparable to the scores in both other groups, the AD patients' object-use impairment most closely resembled that observed in SA; they exhibited poorer performance on comprehension tasks that placed strong demands on executive control. A similar pattern was observed in the expressive domain: the AD and SA groups were relatively good at straightforward object use compared to executively demanding, mechanical puzzles. Error types also differed: while all patients omitted essential actions, the SA and AD groups' demonstrations also featured unrelated intrusions. An association between AD patients' object use and their scores on standard executive measures suggested that control deficits contributed to their non-verbal semantic deficits. Moreover, in a task specifically designed to manipulate executive demand, patients with AD (and SA) exhibited difficulty in thinking flexibly about the non-canonical uses of everyday objects, especially
Stergiakouli, E.; Langley, K; Williams, H.; Walters, J.; Williams, N. M.; Suren, S; Giegling, I; Wilkinson, L. S.; Owen, M J; O'Donovan, M.C.; Rujescu, D.; Thapar, A; Davies, W.
Deletions encompassing the X-linked STS gene (encoding steroid sulfatase) have been observed in subjects with neurodevelopmental disorders, including attention deficit hyperactivity disorder (ADHD). Recently, two single nucleotide polymorphisms (SNPs) within STS (rs12861247 and rs17268988) have been reported to be associated with ADHD risk and inattentive symptoms in ADHD, respectively. Using a UK sample of ADHD subjects (aged 5–18 years), we tested the hypothesis that rs12861247 is associate...
Boulanger, Marie; Collet, Denis; Cornet, Lidvine; Blairy, Sylvie
Schizophrenia is accompanied by deficit in autobiographical memories (AM). These impairments are correlated to difficulties in imagining specific events that might happen to them in the future (D’Argembeau, Raffard et Van-der-Linden, 2008). Previous study suggested that the specific autobiographical memory (past and future) may be improved by an AM remediation therapy (Blairy et al., accepted). The aim of the present study was to compare performances from individuals involved in an AM remedia...
Sinai, Amanda; Hassiotis, Angela; Rantell, Khadija; Strydom, Andre
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
Qi, Zhonghua; Xu, Yinghui; Liang, Zhanhua; Li, Sheng; Wang, Jie; Wei, Yi; Dong, Bin
Naringenin is a flavonoid polyphenolic compound, which facilitates the removal of free radicals, oxidative stress and inflammation. The present study aimed to obtain a better understanding of the effects of curcumin on the regulation of diabetes‑associated cognitive decline, and its underlying mechanisms. An experimental diabetes mellitus (DM) rat model was induced by streptozoticin (50 mg/kg). Following treatment with naringin (100 and 200 mg/kg) for 16 weeks, the body weight and blood glucose levels of the DM rats were measured. A morris water maze test was used to analyze the effects of naringin on the cognitive deficit of the DM rats. The levels of oxidative stress, proinflammatory factors, caspase‑3 and caspase‑9, and the protein expression of peroxisome proliferator‑activated receptor γ (PPARγ) were quantified in the DM rats using a commercially‑available kit and western blot assay, respectively. In addition, a GW9662 PPARγ inhibitor (0.3 mg/kg) was administered to the DM rats to determine whether PPARγ affected the effects of naringin on the cognitive deficit of the DM rats. The results demonstrated that naringin increased the body weight, blood glucose levels, and cognitive deficits of the DM rats. The levels of oxidative stress and proinflammatory factors in the naringin‑treated rats were significantly lower, compared with those of the DM rats. In addition, naringin activated the protein expression of PPARγ, and administration of the PPARγ inhibitor decreased the protein expression of PPARγ, and attenuated the effects of naringin on cognitive deficit. The results also demonstrated that naringin decreased the expression levels of caspase‑3 and caspase‑9 in the DM rats. These results suggested that naringin ameliorated cognitive deficits via oxidative stress, proinflammatory factors and the PPARγ signaling pathway in the type 2 diabetic rat model. Furthermore, oxidative stress, proinflammatory factors and PPARγ signaling may be
criteria was a minimum score of 23/30 in MMSE. Results: Compared with the healthy controls, patients revealed significantly lower scores in CVLT, GML-DR, and VFT. Furthermore, compared to healthy controls, patients showed significantly delayed recognition of “happiness” in EmoDiff40 and significantly worse performance on Reading the Mind in the Eyes Test, revised version II. Neuropsychological assessment demonstrated some statistically significant deficits in learning and remembering both verbal and visual material, long-term information storing, problem solving, and executive functions such as verbal fluency. Conclusion: Patients at early stage of unilateral thalamic stroke showed both neurocognitive and social cognitive deficits. Further research is needed to increase understanding about diagnosis, early treatment, and prognosis of patients with thalamic lesions. Keywords: social cognitive deficits, neurocognitive deficits, thalamic stroke, posterior, inferolateral, paramedian
Drummond, Cláudia; Coutinho, Gabriel; Fonseca, Rochele Paz; Assunção, Naima; Teldeschi, Alina; de Oliveira-Souza, Ricardo; Moll, Jorge; Tovar-Moll, Fernanda; Mattos, Paulo
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
Full Text Available 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 microlinguistic 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.
Full Text Available 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.
Becker, Stephen P; Ciesielski, Heather A; Rood, Jennifer E; Froehlich, Tanya E; Garner, Annie A; Tamm, Leanne; Epstein, Jeffery N
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
Diamond, Adele; Prevor, Meredith B.; Druin, Donald P.; Callender, Glenda
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…
Sarkamo, Teppo; Tervaniemi, Mari; Soinila, Seppo; Autti, Taina; Silvennoinen, Heli M.; Laine, Matti; Hietanen, Marja
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…
Ryan, Gregory P; Baerwald, Jeffrey P; McGlone, Gerard
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. PMID:18161043
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...
M.H.T. van der Vaart (Thijs)
markdownabstractAbstract Neurofibromatosis type 1(NF1) is a common neurocutaneous disorder (birth incidence 1:2000) caused by heterozygous mutations in NF1, a gene on chromosome 17 encoding neurofibromin, which is a suppressor of the Ras pathway. Cognitive dysfunction and behavioural problems are c
Doom, Jenalee R.; Gunnar, Megan R.; Georgieff, Michael K.; Kroupina, Maria G.; Frenn, Kristin; Fuglestad, Anita J.; Carlson, Stephanie M.
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…
José Evandro Marques Gomes
Full Text Available Introduction: the world population is ageing, and Brazil follows this tendency, which requires the reorganization of society for care provision to older people. In such tendency, an increasing number of cases of depression and dementia is observed in addition to their association with other chronic-degenerative diseases. Objective: to estimate the prevalence of depression and cognitive-deficit symptoms in a population aged 60 years and older, residing in a middle-sized city in São Paulo state and to associate the population with other more prevalent chronic degenerative diseases. Methods: cross-sectional study on 364 older people using the following instruments: socio-demographic and morbidity, Mini Mental State Examination, Yesavage Scale, the Activities of Daily Living Scale, and the Instrumental Activities of Daily Living (IADL Scale. The following were performed: statistical analyses of the instruments’ score frequencies; presentation and summarization of the variables; and the possible associations between depression/dementia by applying the X2 test followed by fitting of a logistic regression model for ordinal data. Results: the suspected depression was found in 44% (160, and cognitive deficit was observed in 38.7% (141 aged. About 75% of the individuals with suspicion of depression or cognitive deficit had at least another chronic pathology. It was possible to establish statistically significant associations between suspected depression and IADL (p<0.0001; OR=7.59; CI=3.361-7.139 and cognitive deficit and IADL (p=0.0007; OR=3.967; CI=1.788-8.799. No associations were found between age, marital status, schooling, placement in the work market, retirement or income. Conclusion: male and female older individuals are vulnerable to diseases, such as depression and dementia. On the other hand, depression symptoms and cognitive deficit were associated with the score of compromised older individuals, according to IADL.
Yan, Tingxu; Shang, Lei; Wang, Mengshi; Zhang, Chenning; Zhao, Xu; Bi, Kaishun; Jia, Ying
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
Passarotti, Alessandra M; Sweeney, John A; Pavuluri, Mani N
This fMRI study investigates the neural bases of cognitive control of emotion processing in pediatric bipolar disorder (PBD) and attention deficit hyperactivity disorder (ADHD). Seventeen un-medicated PBD patients, 15 un-medicated ADHD patients, and 14 healthy controls (HC) (mean age = 13.78 +/- 2.47) performed an emotional valence Stroop Task, requiring them to match the color of an emotionally valenced word to the color of either of two adjacent circles. Both patient groups responded significantly slower than HC, but there were no group differences in accuracy. A voxel-wise analysis of variance on brain activation revealed a significant interaction of group by word valence [F(2,41) = 4.44; p = .02]. Similar group differences were found for negative and positive words. For negative versus neutral words, both patient groups exhibited greater activation in dorsolateral prefrontal cortex (DLPFC) and parietal cortex relative to HC. The PBD group exhibited greater activation in ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) relative to HC. The ADHD group exhibited decreased VLPFC activation relative to HC and the PBD group. During cognitive control of emotion processing, PBD patients deployed the VLPFC to a greater extent than HC. The ADHD patients showed decreased VLPFC engagement relative to both HC and PBD patients. PMID:19849880
Campagna, Roberta; Brunelli, Laura; Airoldi, Luisa; Fanelli, Roberto; Hakansson, Helen; Heimeier, Rachel A; De Boever, Patrick; Boix, Jordi; Llansola, Marta; Felipo, Vicente; Pastorelli, Roberta
Developmental exposure to polychlorinated biphenyls (PCBs) has been associated with cognitive deficits in humans and laboratory animals by mechanisms that remain unknown. Recently, it has been shown that developmental exposure to 2,2',3,4,4',5'-hexachlorobiphenyl (PCB138), a food-relevant PCB congener, decreases the learning ability of young rats. The aim of this study was to characterize the effect of perinatal exposure to PCB138 on the brain proteome profile in young rats in order to gain insight into the mechanisms underlying PCB138 neurotoxicity. Comparison of the cerebellum proteome from 3-month-old unexposed and PCB138-exposed male offspring was performed using state-of-the-art label-free semiquantitative mass spectrometry method. Biological pathways associated with Ca(2+) homeostasis and androgen receptor signaling pathways were primarily disrupted. These perturbations may contribute toward a premature ageing-like proteome profile of the cerebellum that is triggered by PCB138 exposure in males. Our proteomic data provide insights into the phenomena that may be contributing to the PCB138 neurotoxicity effects observed in laboratory rodents and correlate with PCB exposure and decreased cognitive functions in humans. As such, this study highlights the importance of PCB138 as a risk factor in developmental neurotoxicity in laboratory rodents and humans. PMID:21673325
Arteaga, Olatz; Revuelta, Miren; Urigüen, Leyre; Álvarez, Antonia; Montalvo, Haizea; Hilario, Enrique
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
Brunet-Gouet, Eric; Achim, Amélie M; Vistoli, Damien; Passerieux, Christine; Hardy-Baylé, Marie-Christine; Jackson, Philip L
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
Yun LIAO; Rui WANG; Xi-can TANG
AIM: To study the effects of centrophenoxine (CPH, meclofenoxate) on chronic cerebral hypoperfusion induced deficits in rats. METHODS: Chronic hypoperfusion in rats was performed by permanent bilateral ligation of the common carotid arteries. Morris water maze was used to measure spatial memory performance. Spectrophotometrical techniques were used to assay SOD, GPx activities, MDA content, TXB2, and 6-keto-PGF1α levels. Morphological change was examined by HE staining. The expression of Bax and p53 protein were assayed by immunohistochemistry analysis. RESULTS: Chronic hypoperfusion in rats resulted in spatial memory impairments shown by longer escape latency and shorter time spent in the target quadrant. These behavioral dysfunction were accompanied by increase in SOD and GPx activities, the content of MDA, the levels of pro-inflammatory mediators (TXB2, 6-keto-PGF1α), overexpression of Bax and P53 protein, and delayed degeneration of neurons in cortex and hippocampus. Oral administration of CPH (100 mg/kg, once per day for 37 d) markedly improved the memory impairment, reduced the increase in antioxidant enzyme activities, MDA content and the levels of pro-inflammatory mediators to their normal levels, and attenuated neuronal damage. CONCLUSION: The abilities of CPH to attenuate memory deficits and neuronal damage after ischemia may be beneficial in cerebrovascular type dementia.
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
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
Strittmatter Stephen M
Full Text Available Abstract Background Alzheimer's Disease (AD is the most common of the conformational neurodegenerative disorders characterized by the conversion of a normal biological protein into a β-sheet-rich pathological isoform. In AD the normal soluble Aβ (sAβ forms oligomers and fibrils which assemble into neuritic plaques. The most toxic form of Aβ is thought to be oligomeric. A recent study reveals the cellular prion protein, PrPC, to be a receptor for Aβ oligomers. Aβ oligomers suppress LTP signal in murine hippocampal slices but activity remains when pretreated with the PrP monoclonal anti-PrP antibody, 6D11. We hypothesized that targeting of PrPC to prevent Aβ oligomer-related cognitive deficits is a potentially novel therapeutic approach. APP/PS1 transgenic mice aged 8 months were intraperitoneally (i.p. injected with 1 mg 6D11 for 5 days/week for 2 weeks. Two wild-type control groups were given either the same 6D11 injections or vehicle solution. Additional groups of APP/PS1 transgenic mice were given either i.p. injections of vehicle solution or the same dose of mouse IgG over the same period. The mice were then subjected to cognitive behavioral testing using a radial arm maze, over a period of 10 days. At the conclusion of behavioral testing, animals were sacrificed and brain tissue was analyzed biochemically or immunohistochemically for the levels of amyloid plaques, PrPC, synaptophysin, Aβ40/42 and Aβ oligomers. Results Behavioral testing showed a marked decrease in errors in 6D11 treated APP/PS1 Tg mice compared with the non-6D11 treated Tg groups (p C or Aβ oligomer levels. 6D11 treated APP/PS1 Tg mice had significantly greater synaptophysin immunoreactivity in the dentate gyrus molecular layer of the hippocampus compared to vehicle treated APP/PS1 Tg mice (p Conclusions Even short term treatment with monoclonal antibodies such as 6D11 or other compounds which block the binding of Aβ oligomers to PrPC can be used to treat
Radanov, B P; Dvorák, J; Valach, L
Fifty-one patients suffering from soft tissue injury of the cervical spine underwent clinical and psychometric examination. Clinical interview evaluated subjective complaints and formal testing of self-estimated cognitive impairment, divided attention, and speed of information processing. Results indicated at least two different syndromes: 1) the "cervicoencephalic syndrome," characterized by headache, fatigue, dizziness, poor concentration, disturbed accommodation, and impaired adaptation to light intensity; and 2) the "lower cervical spine syndrome," which is accompanied by cervical and cervicobrachial pain. When comparing patients with either of these two syndromes, those suffering from cervicoencephalic syndrome had significantly poorer results when tested for divided attention. Speed of information processing was reduced to a comparable extent in both syndromes. These findings were not related to the length of the post-traumatic interval. Reduced processing of working memory is assumed, which may account for more global cognitive problems as well as secondary neurotic reaction. PMID:1553581
Baker, Kate; Astle, Duncan E.; Scerif, Gaia; Barnes, Jessica; Smith, Jennie; Moffat, Georgina; Gillard, Jonathan; Baldeweg, Torsten; Raymond, F. Lucy
Objective Systematic investigation of individuals with intellectual disability after genetic diagnosis can illuminate specific phenotypes and mechanisms relevant to common neurodevelopmental disorders. We report the neurological, cognitive and neuroanatomical characteristics of nine males from three families with loss-of-function mutations in ZDHHC9 (OMIM #300799). Methods All known cases of X-linked intellectual disability (XLID) due to ZDHHC9 mutation in the United Kingdom were i...
Maimaiti, Shaniya; Anderson, Katie L; DeMoll, Chris; Brewer, Lawrence D; Rauh, Benjamin A; Gant, John C; Blalock, Eric M; Porter, Nada M; Thibault, Olivier
Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP. PMID:25659889
Braga-Neto, Pedro; Felicio, Andre C; Hoexter, Marcelo Q; Pedroso, José Luiz; Dutra, Lívia Almeida; Alessi, Helena; Minett, Thaís; Santos-Galduroz, Ruth F; da Rocha, Antônio José; Garcia, Lucas A L; Bertolucci, Paulo Henrique F; Bressan, Rodrigo A; Barsottini, Orlando Graziani Povoas
Cognitive and olfactory impairments have been demonstrated in patients with Machado-Joseph disease (MJD), and a possible relationship with dopaminergic dysfunction is implicated. However, there is still controversy regarding the pattern of striatal dopaminergic dysfunction in patients with MJD. In this study, we investigated whether these patients had different dopamine transporter (DAT) densities as compared to healthy subjects, and correlated these data with cognitive performance and sense of smell. Twenty-two MJD patients and 20 control subjects were enrolled. The neuropsychological assessment comprised the spatial span, symbol search, picture completion, stroop color word test, trail making test and phonemic verbal fluency test. The 16-item Sniffin' Sticks was used to evaluate odor identification. DAT imaging was performed using the SPECT radioligand [(99m)Tc]-TRODAT-1, alongside with Magnetic Resonance imaging. Patients with MJD showed significantly lower DAT density in the caudate (1.34 ± 0.27 versus 2.02 ± 0.50, p system involvement or of cerebellum neurodegeneration exerting a direct influence on cognitive and sensorial information processing in MJD. PMID:22575233
Full Text Available Abstract Background Chronic neuroinflammation is a hallmark of several neurological disorders associated with cognitive loss. Activated microglia and secreted factors such as tumor necrosis factor (TNF-α are key mediators of neuroinflammation and may contribute to neuronal dysfunction. Our study was aimed to evaluate the therapeutic potential of a novel analog of thalidomide, 3,6'-dithiothalidomide (DT, an agent with anti-TNF-α activity, in a model of chronic neuroinflammation. Methods Lipopolysaccharide or artificial cerebrospinal fluid was infused into the fourth ventricle of three-month-old rats for 28 days. Starting on day 29, animals received daily intraperitoneal injections of DT (56 mg/kg/day or vehicle for 14 days. Thereafter, cognitive function was assessed by novel object recognition, novel place recognition and Morris water maze, and animals were euthanized 25 min following water maze probe test evaluation. Results Chronic LPS-infusion was characterized by increased gene expression of the proinflammatory cytokines TNF-α and IL-1β in the hippocampus. Treatment with DT normalized TNF-α levels back to control levels but not IL-1β. Treatment with DT attenuated the expression of TLR2, TLR4, IRAK1 and Hmgb1, all genes involved in the TLR-mediated signaling pathway associated with classical microglia activation. However DT did not impact the numbers of MHC Class II immunoreactive cells. Chronic neuroinflammation impaired novel place recognition, spatial learning and memory function; but it did not impact novel object recognition. Importantly, treatment with DT restored cognitive function in LPS-infused animals and normalized the fraction of hippocampal neurons expressing the plasticity-related immediate-early gene Arc. Conclusion Our data demonstrate that the TNF-α synthesis inhibitor DT can significantly reverse hippocampus-dependent cognitive deficits induced by chronic neuroinflammation. These results suggest that TNF-α is a
Kaitlin L. Lansford
Full Text Available Hypokinetic dysarthria is a common manifestation of Parkinson's disease, which negatively influences quality of life. Behavioral techniques that aim to improve speech intelligibility constitute the bulk of intervention strategies for this population, as the dysarthria does not often respond vigorously to medical interventions. Although several case and group studies generally support the efficacy of behavioral treatment, much work remains to establish a rigorous evidence base. This absence of definitive research leaves both the speech-language pathologist and referring physician with the task of determining the feasibility and nature of therapy for intelligibility remediation in PD. The purpose of this paper is to introduce a novel framework for medical practitioners in which to conceptualize and justify potential targets for speech remediation. The most commonly targeted deficits (e.g., speaking rate and vocal loudness can be supported by this approach, as well as underutilized and novel treatment targets that aim at the listener's perceptual skills.
This paper discusses about the diagnosis and evaluation of brain higher functions, feature of their impairment induced by radiotherapy for brain tumor, and association of the impairment and neurogenesis in hippocampus (H). Radiation is one of important causes of cognitive impairment in patients with brain tumor: exempli gratia (e.g.) single irradiation of 2 Gy increases its risk. The impairment is usually diagnosed and evaluated with neuropsychological tests like mini-mental state examination (MMSE), authors' Ryudai version of the brief neuropsychological test battery, etc. The neurotoxicity of radiation is classified in acute effect caused by destruction of the blood brain barrier (BBB) appearing within 2 weeks after irradiation, early-late one of demyelination as a result of BBB rupture within 1-6 months after radiotherapy and late-late effect accompanying serious symptoms like necrosis of irradiated region at later than a few months to several years. Lowered neurogenic function in H and invasion of microglia cells are observed in autopsy specimen of the irradiated brain, and single X-irradiation at 5 or 10 Gy is known to result in the arrest of neurogenesis in the mouse H dentate gyrus. Lowered cognition by irradiation of H in clinical cases is particularly reported in children. Inflammatory biomarkers like cytokines are detected in the serum of irradiated patients as well as of animals. Although fMRI alone is not satisfactory to diagnose and evaluate the radiation-induced impairment, the imaging reveals the association of anatomically different regions in cognition through neural network. It has been recently shown that the impairment can be partially protected by planning the irradiation field so as to avoid H, by medication with donepezil, memantine, erythropoietin and indomethacin, and by hyperbaric oxygen therapy. (T.T.)
Stuchlík, Aleš; Sumiyoshi, T.
Roč. 8, - (2014), s. 444. ISSN 1662-5153 R&D Projects: GA ČR(CZ) GA14-03627S; GA ČR(CZ) GBP304/12/G069; GA MZd(CZ) NT13386; GA MŠk(CZ) LH14053 Grant ostatní: Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : cognition * neuropsychiatric disorders * animal models * clinical studies * preclinical studies Subject RIV: FH - Neurology Impact factor: 3.270, year: 2014